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-Different factors determining Motor Execution and Motor Imagery performance in a serial reaction time task with intrinsic variability
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+PERIPHERAL CHEMORECEPTOR, A NEW PLAYER IN METABOLIC SENSING DURING PHYSICAL EXERTION: A HYPOTHETICAL SCENARIO
- arXiv:2412.05319v1 Announce Type: new -Abstract: Motor imagery corresponds to the mental practice of simulating visual and kinesthetic aspects of a given motor task. This practice shares a similar neural substrate and correlated temporal scale with motor execution. Besides that, it can lead to performance improvements in the actual execution of the imagined task. Therefore it is important to understand functional differences and equivalences between motor imagery and motor execution. To tackle that we employed a finger-tapping serial reaction time task in two groups of participants, a Motor Execution (n=10) and a Motor imagery (n=10). The sequence of stimuli defining the task had 750 items composed of three distinct auditory stimuli. Also, this sequence had some intrinsic variability making some of the next items unpredictable. Each auditory stimulus was mapped to a single right hand finger in the Motor Imagery group. The Motor imagery group indicated the end of the imagination with a single response using the left hand. The results show improvement in performance of the Motor Imagery group throughout the task and that the duration of the motor imagery, indirectly measured by reaction times, are influenced by distinct factors than those of Motor Execution. + Journal of Neurophysiology, Ahead of Print.-
in arXiv: Quantitative Biology: Neurons and Cognition on 2024-12-10 05:00:00 UTC. +
in Journal of Neurophysiology on 2024-12-11 07:18:19 UTC.
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-Statistical Mechanics of Support Vector Regression
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+Center of mass states render multi-joint torques throughout standing balance recovery
- arXiv:2412.05439v1 Announce Type: cross -Abstract: A key problem in deep learning and computational neuroscience is relating the geometrical properties of neural representations to task performance. Here, we consider this problem for continuous decoding tasks where neural variability may affect task precision. Using methods from statistical mechanics, we study the average-case learning curves for $\varepsilon$-insensitive Support Vector Regression ($\varepsilon$-SVR) and discuss its capacity as a measure of linear decodability. Our analysis reveals a phase transition in the training error at a critical load, capturing the interplay between the tolerance parameter $\varepsilon$ and neural variability. We uncover a double-descent phenomenon in the generalization error, showing that $\varepsilon$ acts as a regularizer, both suppressing and shifting these peaks. Theoretical predictions are validated both on toy models and deep neural networks, extending the theory of Support Vector Machines to continuous tasks with inherent neural variability. + Journal of Neurophysiology, Ahead of Print.-
in arXiv: Quantitative Biology: Neurons and Cognition on 2024-12-10 05:00:00 UTC. +
in Journal of Neurophysiology on 2024-12-11 06:11:03 UTC.
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-Not All Errors Are Equal: Investigation of Speech Recognition Errors in Alzheimer's Disease Detection
+Primary visual cortex contributes to color constancy by predicting rather than discounting the illuminant: evidence from a computational study
- arXiv:2412.06332v1 Announce Type: cross -Abstract: Automatic Speech Recognition (ASR) plays an important role in speech-based automatic detection of Alzheimer's disease (AD). However, recognition errors could propagate downstream, potentially impacting the detection decisions. Recent studies have revealed a non-linear relationship between word error rates (WER) and AD detection performance, where ASR transcriptions with notable errors could still yield AD detection accuracy equivalent to that based on manual transcriptions. This work presents a series of analyses to explore the effect of ASR transcription errors in BERT-based AD detection systems. Our investigation reveals that not all ASR errors contribute equally to detection performance. Certain words, such as stopwords, despite constituting a large proportion of errors, are shown to play a limited role in distinguishing AD. In contrast, the keywords related to diagnosis tasks exhibit significantly greater importance relative to other words. These findings provide insights into the interplay between ASR errors and the downstream detection model. + arXiv:2412.07102v1 Announce Type: new +Abstract: Color constancy (CC) is an important ability of the human visual system to stably perceive the colors of objects despite considerable changes in the color of the light illuminating them. While increasing evidence from the field of neuroscience supports that multiple levels of the visual system contribute to the realization of CC, how the primary visual cortex (V1) plays role in CC is not fully resolved. In specific, double-opponent (DO) neurons in V1 have been thought to contribute to realizing a degree of CC, but the computational mechanism is not clear. We build an electrophysiologically based V1 neural model to learn the color of the light source from a natural image dataset with the ground truth illuminants as the labels. Based on the qualitative and quantitative analysis of the responsive properties of the learned model neurons, we found that both the spatial structures and color weights of the receptive fields of the learned model neurons are quite similar to those of the simple and DO neurons recorded in V1. Computationally, DO cells perform more robustly than the simple cells in V1 for illuminant prediction. Therefore, this work provides computational evidence supporting that V1 DO neurons serve to realize color constancy by encoding the illuminant,which is contradictory to the common hypothesis that V1 contributes to CC by discounting the illuminant using its DO cells. This evidence is expected to not only help resolve the visual mechanisms of CC, but also provide inspiration to develop more effective computer vision models. -in arXiv: Quantitative Biology: Neurons and Cognition on 2024-12-10 05:00:00 UTC. +
in arXiv: Quantitative Biology: Neurons and Cognition on 2024-12-11 05:00:00 UTC.
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-Convolution goes higher-order: a biologically inspired mechanism empowers image classification
+QuantFormer: Learning to Quantize for Neural Activity Forecasting in Mouse Visual Cortex
- arXiv:2412.06740v1 Announce Type: cross -Abstract: We propose a novel approach to image classification inspired by complex nonlinear biological visual processing, whereby classical convolutional neural networks (CNNs) are equipped with learnable higher-order convolutions. Our model incorporates a Volterra-like expansion of the convolution operator, capturing multiplicative interactions akin to those observed in early and advanced stages of biological visual processing. We evaluated this approach on synthetic datasets by measuring sensitivity to testing higher-order correlations and performance in standard benchmarks (MNIST, FashionMNIST, CIFAR10, CIFAR100 and Imagenette). Our architecture outperforms traditional CNN baselines, and achieves optimal performance with expansions up to 3rd/4th order, aligning remarkably well with the distribution of pixel intensities in natural images. Through systematic perturbation analysis, we validate this alignment by isolating the contributions of specific image statistics to model performance, demonstrating how different orders of convolution process distinct aspects of visual information. Furthermore, Representational Similarity Analysis reveals distinct geometries across network layers, indicating qualitatively different modes of visual information processing. Our work bridges neuroscience and deep learning, offering a path towards more effective, biologically inspired computer vision models. It provides insights into visual information processing and lays the groundwork for neural networks that better capture complex visual patterns, particularly in resource-constrained scenarios. + arXiv:2412.07264v1 Announce Type: new +Abstract: Understanding complex animal behaviors hinges on deciphering the neural activity patterns within brain circuits, making the ability to forecast neural activity crucial for developing predictive models of brain dynamics. This capability holds immense value for neuroscience, particularly in applications such as real-time optogenetic interventions. While traditional encoding and decoding methods have been used to map external variables to neural activity and vice versa, they focus on interpreting past data. In contrast, neural forecasting aims to predict future neural activity, presenting a unique and challenging task due to the spatiotemporal sparsity and complex dependencies of neural signals. Existing transformer-based forecasting methods, while effective in many domains, struggle to capture the distinctiveness of neural signals characterized by spatiotemporal sparsity and intricate dependencies. To address this challenge, we here introduce QuantFormer, a transformer-based model specifically designed for forecasting neural activity from two-photon calcium imaging data. Unlike conventional regression-based approaches, QuantFormerreframes the forecasting task as a classification problem via dynamic signal quantization, enabling more effective learning of sparse neural activation patterns. Additionally, QuantFormer tackles the challenge of analyzing multivariate signals from an arbitrary number of neurons by incorporating neuron-specific tokens, allowing scalability across diverse neuronal populations. Trained with unsupervised quantization on the Allen dataset, QuantFormer sets a new benchmark in forecasting mouse visual cortex activity. It demonstrates robust performance and generalization across various stimuli and individuals, paving the way for a foundational model in neural signal prediction. -in arXiv: Quantitative Biology: Neurons and Cognition on 2024-12-10 05:00:00 UTC. +
in arXiv: Quantitative Biology: Neurons and Cognition on 2024-12-11 05:00:00 UTC.
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-An image-computable model of speeded decision-making
+Gradient Diffusion: Enhancing Multicompartmental Neuron Models for Gradient-Based Self-Tuning and Homeostatic Control
- arXiv:2403.16382v2 Announce Type: replace -Abstract: Evidence accumulation models (EAMs) are the dominant framework for modeling response time (RT) data from speeded decision-making tasks. While providing a good quantitative description of RT data in terms of abstract perceptual representations, EAMs do not explain how the visual system extracts these representations in the first place. To address this limitation, we introduce the visual accumulator model (VAM), in which convolutional neural network models of visual processing and traditional EAMs are jointly fitted to trial-level RTs and raw (pixel-space) visual stimuli from individual subjects in a unified Bayesian framework. Models fitted to large-scale cognitive training data from a stylized flanker task captured individual differences in congruency effects, RTs, and accuracy. We find evidence that the selection of task-relevant information occurs through the orthogonalization of relevant and irrelevant representations, demonstrating how our framework can be used to relate visual representations to behavioral outputs. Together, our work provides a probabilistic framework for both constraining neural network models of vision with behavioral data and studying how the visual system extracts representations that guide decisions. + arXiv:2412.07327v1 Announce Type: new +Abstract: Realistic brain models contain many parameters. Traditionally, gradient-free methods are used for estimating these parameters, but gradient-based methods offer many advantages including scalability. However, brain models are tied to existing brain simulators, which do not support gradient calculation. Here we show how to extend -- within the public interface of such simulators -- these neural models to also compute the gradients with respect to their parameters. We demonstrate that the computed gradients can be used to optimize a biophysically realistic multicompartmental neuron model with the gradient-based Adam optimizer. Beyond tuning, gradient-based optimization could lead the way towards dynamics learning and homeostatic control within simulations. -in arXiv: Quantitative Biology: Neurons and Cognition on 2024-12-10 05:00:00 UTC. +
in arXiv: Quantitative Biology: Neurons and Cognition on 2024-12-11 05:00:00 UTC.
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-Poisson Variational Autoencoder
+Investigation of in vitro neuronal activity processing using a CMOS-integrated ZrO2-based memristive crossbar
- arXiv:2405.14473v2 Announce Type: replace-cross -Abstract: Variational autoencoders (VAEs) employ Bayesian inference to interpret sensory inputs, mirroring processes that occur in primate vision across both ventral (Higgins et al., 2021) and dorsal (Vafaii et al., 2023) pathways. Despite their success, traditional VAEs rely on continuous latent variables, which deviates sharply from the discrete nature of biological neurons. Here, we developed the Poisson VAE (P-VAE), a novel architecture that combines principles of predictive coding with a VAE that encodes inputs into discrete spike counts. Combining Poisson-distributed latent variables with predictive coding introduces a metabolic cost term in the model loss function, suggesting a relationship with sparse coding which we verify empirically. Additionally, we analyze the geometry of learned representations, contrasting the P-VAE to alternative VAE models. We find that the P-VAE encodes its inputs in relatively higher dimensions, facilitating linear separability of categories in a downstream classification task with a much better (5x) sample efficiency. Our work provides an interpretable computational framework to study brain-like sensory processing and paves the way for a deeper understanding of perception as an inferential process. + arXiv:2412.07340v1 Announce Type: new +Abstract: The influence of the epileptiform neuronal activity on the response of a CMOS-integrated ZrO2-based memristive crossbar and its conductivity was studied. Epileptiform neuronal activity was obtained in vitro in the hippocampus slices of laboratory mice using 4-aminopyridine experimental model. Synaptic plasticity of the memristive crossbar induced by epileptiform neuronal activity pulses was detected. Qualitatively, the results obtained in the case of normal (without pathologies) and epileptiform neuronal activity with and without noise coincide. For quantitative analysis, the value of the relative change in synaptic weight has been calculated for such important biological mechanisms of synapses as paired-pulse facilitation/depression, post-tetanic potentiation/depression, and long-term potentiation/depression. It has been shown that average value of the relative change in synaptic weight and its are smaller mainly in the case of epileptiform neuronal activity pulses. An effect of the influence of noise included in the neuronal activity was found, which consists in the fact that the current response of the memristive crossbar is smaller in the presence of noise. The results of this study can be used in the development of new generation hardware-implemented computing devices with high performance and energy efficiency for the tasks of restorative medicine and robotics. In particular, using these results, neurohybrid devices can be developed for processing epileptiform activity in real time and for its suppression. -in arXiv: Quantitative Biology: Neurons and Cognition on 2024-12-10 05:00:00 UTC. +
in arXiv: Quantitative Biology: Neurons and Cognition on 2024-12-11 05:00:00 UTC.
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-Computational models of learning and synaptic plasticity
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+Periodic solutions for a pair of delay-coupled excitable theta neurons
- arXiv:2412.05501v1 Announce Type: cross -Abstract: Many mathematical models of synaptic plasticity have been proposed to explain the diversity of plasticity phenomena observed in biological organisms. These models range from simple interpretations of Hebb's postulate, which suggests that correlated neural activity leads to increases in synaptic strength, to more complex rules that allow bidirectional synaptic updates, ensure stability, or incorporate additional signals like reward or error. At the same time, a range of learning paradigms can be observed behaviorally, from Pavlovian conditioning to motor learning and memory recall. Although it is difficult to directly link synaptic updates to learning outcomes experimentally, computational models provide a valuable tool for building evidence of this connection. In this chapter, we discuss several fundamental learning paradigms, along with the synaptic plasticity rules that might be used to implement them. + arXiv:2412.06804v1 Announce Type: cross +Abstract: We consider a pair of identical theta neurons in the excitable regime, each coupled to the other via a delayed Dirac delta function with the same delay. This simple network can support different periodic solutions, and we concentrate on two important types: those for which the neurons are perfectly synchronous, and those where the neurons are exactly half a period out of phase and fire alternatingly. Owing to the specific type of pulsatile feedback, we are able to determine these solutions and their stability analytically. More specifically, (infinitely many) branches of periodic solutions of either type are created at saddle-node bifurcations, and they gain stability at symmetry-breaking bifurcations when their period as a function of delay is at its minimum. We also determine the respective branches of symmetry-broken periodic solutions and show that they are all unstable. We demonstrate by considering smoothed pulse-like coupling that the special case of the Dirac delta function can be seen as a sort of normal form: the basic structure of the different periodic solutions of the two theta neurons is preserved, but there may be additional changes of stability along the different branches. -in arXiv: Computer Science: Neural and Evolutionary Computing on 2024-12-10 05:00:00 UTC. +
in arXiv: Quantitative Biology: Neurons and Cognition on 2024-12-11 05:00:00 UTC.
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-Dynamical similarity analysis uniquely captures how computations develop in RNNs
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+Speaker effects in spoken language comprehension
- arXiv:2410.24070v3 Announce Type: replace-cross -Abstract: Methods for analyzing representations in neural systems have become a popular tool in both neuroscience and mechanistic interpretability. Having measures to compare how similar activations of neurons are across conditions, architectures, and species, gives us a scalable way of learning how information is transformed within different neural networks. In contrast to this trend, recent investigations have revealed how some metrics can respond to spurious signals and hence give misleading results. To identify the most reliable metric and understand how measures could be improved, it is going to be important to identify specific test cases which can serve as benchmarks. Here we propose that the phenomena of compositional learning in recurrent neural networks (RNNs) allows us to build a test case for dynamical representation alignment metrics. By implementing this case, we show it enables us to test whether metrics can identify representations which gradually develop throughout learning and probe whether representations identified by metrics are relevant to computations executed by networks. By building both an attractor- and RNN-based test case, we show that the new Dynamical Similarity Analysis (DSA) is more noise robust and identifies behaviorally relevant representations more reliably than prior metrics (Procrustes, CKA). We also show how test cases can be used beyond evaluating metrics to study new architectures. Specifically, results from applying DSA to modern (Mamba) state space models, suggest that, in contrast to RNNs, these models may not exhibit changes to their recurrent dynamics due to their expressiveness. Overall, by developing test cases, we show DSA's exceptional ability to detect compositional dynamical motifs, thereby enhancing our understanding of how computations unfold in RNNs. + arXiv:2412.07238v1 Announce Type: cross +Abstract: The identity of a speaker significantly influences spoken language comprehension by affecting both perception and expectation. This review explores speaker effects, focusing on how speaker information impacts language processing. We propose an integrative model featuring the interplay between bottom-up perception-based processes driven by acoustic details and top-down expectation-based processes driven by a speaker model. The acoustic details influence lower-level perception, while the speaker model modulates both lower-level and higher-level processes such as meaning interpretation and pragmatic inferences. We define speaker-idiosyncrasy and speaker-demographics effects and demonstrate how bottom-up and top-down processes interact at various levels in different scenarios. This framework contributes to psycholinguistic theory by offering a comprehensive account of how speaker information interacts with linguistic content to shape message construction. We suggest that speaker effects can serve as indices of a language learner's proficiency and an individual's characteristics of social cognition. We encourage future research to extend these findings to AI speakers, probing the universality of speaker effects across humans and artificial agents. -in arXiv: Computer Science: Neural and Evolutionary Computing on 2024-12-10 05:00:00 UTC. +
in arXiv: Quantitative Biology: Neurons and Cognition on 2024-12-11 05:00:00 UTC.
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-A Robust Clustering Framework Combining Minimum Description Length and Genetic Optimization
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+How EEG preprocessing shapes decoding performance
- arXiv:2412.05305v1 Announce Type: new -Abstract: Clustering algorithms are fundamental in data analysis, enabling the organization of data into meaningful groups. However, individual clustering methods often face limitations and biases, making it challenging to develop a universal solution for diverse datasets. To address this, we propose a novel clustering framework that combines the Minimum Description Length (MDL) principle with a genetic optimization algorithm. This approach begins with an ensemble clustering solution as a baseline, which is refined using MDL-based evaluation functions and optimized with a genetic algorithm. By leveraging the MDL principle, the method adapts to the intrinsic properties of datasets, minimizing dependence on input clusters and ensuring a data-driven process. The proposed method was evaluated on thirteen benchmark datasets using four validation metrics: accuracy, normalized mutual information (NMI), Fisher score, and adjusted Rand index (ARI). Results show that the method consistently outperforms traditional clustering algorithms, achieving higher accuracy, greater stability, and reduced biases. Its adaptability makes it a reliable tool for clustering complex and varied datasets. This study demonstrates the potential of combining MDL and genetic optimization to create a robust and versatile clustering framework, advancing the field of data analysis and offering a scalable solution for diverse applications. + arXiv:2410.14453v2 Announce Type: replace +Abstract: EEG preprocessing varies widely between studies, but its impact on classification performance remains poorly understood. To address this gap, we analyzed seven experiments with 40 participants drawn from the public ERP CORE dataset. We systematically varied key preprocessing steps, such as filtering, referencing, baseline interval, detrending, and multiple artifact correction steps. Then we performed trial-wise binary classification (i.e., decoding) using neural networks (EEGNet), or time-resolved logistic regressions. Our findings demonstrate that preprocessing choices influenced decoding performance considerably. All artifact correction steps reduced decoding performance across all experiments and models, while higher high-pass filter cutoffs consistently enhanced decoding. For EEGNet, baseline correction further improved performance, and for time-resolved classifiers, linear detrending and lower low-pass filter cutoffs were beneficial. Other optimal preprocessing choices were specific for each experiment. The current results underline the importance of carefully selecting preprocessing steps for EEG-based decoding. If not corrected, artifacts facilitate decoding but compromise conclusive interpretation. -in arXiv: Computer Science: Neural and Evolutionary Computing on 2024-12-10 05:00:00 UTC. +
in arXiv: Quantitative Biology: Neurons and Cognition on 2024-12-11 05:00:00 UTC.
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-Trimming Down Large Spiking Vision Transformers via Heterogeneous Quantization Search
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+Policy consequences of the new neuroeconomic framework
- arXiv:2412.05505v1 Announce Type: new -Abstract: Spiking Neural Networks (SNNs) are amenable to deployment on edge devices and neuromorphic hardware due to their lower dissipation. Recently, SNN-based transformers have garnered significant interest, incorporating attention mechanisms akin to their counterparts in Artificial Neural Networks (ANNs) while demonstrating excellent performance. However, deploying large spiking transformer models on resource-constrained edge devices such as mobile phones, still poses significant challenges resulted from the high computational demands of large uncompressed high-precision models. In this work, we introduce a novel heterogeneous quantization method for compressing spiking transformers through layer-wise quantization. Our approach optimizes the quantization of each layer using one of two distinct quantization schemes, i.e., uniform or power-of-two quantification, with mixed bit resolutions. Our heterogeneous quantization demonstrates the feasibility of maintaining high performance for spiking transformers while utilizing an average effective resolution of 3.14-3.67 bits with less than a 1% accuracy drop on DVS Gesture and CIFAR10-DVS datasets. It attains a model compression rate of 8.71x-10.19x for standard floating-point spiking transformers. Moreover, the proposed approach achieves a significant energy reduction of 5.69x, 8.72x, and 10.2x while maintaining high accuracy levels of 85.3%, 97.57%, and 80.4% on N-Caltech101, DVS-Gesture, and CIFAR10-DVS datasets, respectively. + arXiv:2409.07373v2 Announce Type: replace-cross +Abstract: Current theories of decision making suggest that the neural circuits in mammalian brains (including humans) computationally combine representations of the past (memory), present (perception), and future (agentic goals) to take actions that achieve the needs of the agent. How information is represented within those neural circuits changes what computations are available to that system which changes how agents interact with their world to take those actions. We argue that the computational neuroscience of decision making provides a new microeconomic framework (neuroeconomics) that offers new opportunities to construct policies that interact with those decision-making systems to improve outcomes. After laying out the computational processes underlying decision making in mammalian brains, we present four applications of this logic with policy consequences: (1) precommitment to avoid falling into the trap of sunk costs, (2) media consequences for changes in housing prices after a disaster, (3) contingency management as a treatment for addiction, and (4) how social interactions underlie the success (and failure) of microfinance institutions. -in arXiv: Computer Science: Neural and Evolutionary Computing on 2024-12-10 05:00:00 UTC. +
in arXiv: Quantitative Biology: Neurons and Cognition on 2024-12-11 05:00:00 UTC.
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-Towards 3D Acceleration for low-power Mixture-of-Experts and Multi-Head Attention Spiking Transformers
+SpikeFI: A Fault Injection Framework for Spiking Neural Networks
- arXiv:2412.05540v1 Announce Type: new -Abstract: Spiking Neural Networks(SNNs) provide a brain-inspired and event-driven mechanism that is believed to be critical to unlock energy-efficient deep learning. The mixture-of-experts approach mirrors the parallel distributed processing of nervous systems, introducing conditional computation policies and expanding model capacity without scaling up the number of computational operations. Additionally, spiking mixture-of-experts self-attention mechanisms enhance representation capacity, effectively capturing diverse patterns of entities and dependencies between visual or linguistic tokens. However, there is currently a lack of hardware support for highly parallel distributed processing needed by spiking transformers, which embody a brain-inspired computation. This paper introduces the first 3D hardware architecture and design methodology for Mixture-of-Experts and Multi-Head Attention spiking transformers. By leveraging 3D integration with memory-on-logic and logic-on-logic stacking, we explore such brain-inspired accelerators with spatially stackable circuitry, demonstrating significant optimization of energy efficiency and latency compared to conventional 2D CMOS integration. + arXiv:2412.06795v1 Announce Type: new +Abstract: Neuromorphic computing and spiking neural networks (SNNs) are gaining traction across various artificial intelligence (AI) tasks thanks to their potential for efficient energy usage and faster computation speed. This comparative advantage comes from mimicking the structure, function, and efficiency of the biological brain, which arguably is the most brilliant and green computing machine. As SNNs are eventually deployed on a hardware processor, the reliability of the application in light of hardware-level faults becomes a concern, especially for safety- and mission-critical applications. In this work, we propose SpikeFI, a fault injection framework for SNNs that can be used for automating the reliability analysis and test generation. SpikeFI is built upon the SLAYER PyTorch framework with fault injection experiments accelerated on a single or multiple GPUs. It has a comprehensive integrated neuron and synapse fault model library, in accordance to the literature in the domain, which is extendable by the user if needed. It supports: single and multiple faults; permanent and transient faults; specified, random layer-wise, and random network-wise fault locations; and pre-, during, and post-training fault injection. It also offers several optimization speedups and built-in functions for results visualization. SpikeFI is open-source and available for download via GitHub at https://github.com/SpikeFI. -in arXiv: Computer Science: Neural and Evolutionary Computing on 2024-12-10 05:00:00 UTC. +
in arXiv: Computer Science: Neural and Evolutionary Computing on 2024-12-11 05:00:00 UTC.
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-Training neural networks without backpropagation using particles
+Reinforcement learning-enhanced genetic algorithm for wind farm layout optimization
- arXiv:2412.05667v1 Announce Type: new -Abstract: Neural networks are a group of neurons stacked together in multiple layers to mimic the biological neurons in a human brain. Neural networks have been trained using the backpropagation algorithm based on gradient descent strategy for several decades. Several variants have been developed to improve the backpropagation algorithm. The loss function for the neural network is optimized through backpropagation, but several local minima exist in the manifold of the constructed neural network. We obtain several solutions matching the minima. The gradient descent strategy cannot avoid the problem of local minima and gets stuck in the minima due to the initialization. Particle swarm optimization (PSO) was proposed to select the best local minima among the search space of the loss function. The search space is limited to the instantiated particles in the PSO algorithm, and sometimes it cannot select the best solution. In the proposed approach, we overcome the problem of gradient descent and the limitation of the PSO algorithm by training individual neurons separately, capable of collectively solving the problem as a group of neurons forming a network. + arXiv:2412.06803v1 Announce Type: new +Abstract: A reinforcement learning-enhanced genetic algorithm (RLGA) is proposed for wind farm layout optimization (WFLO) problems. While genetic algorithms (GAs) are among the most effective and accessible methods for WFLO, their performance and convergence are highly sensitive to parameter selections. To address the issue, reinforcement learning (RL) is introduced to dynamically select optimal parameters throughout the GA process. To illustrate the accuracy and efficiency of the proposed RLGA, we evaluate the WFLO problem for four layouts (aligned, staggered, sunflower, and unstructured) under unidirectional uniform wind, comparing the results with those from the GA. RLGA achieves similar results to GA for aligned and staggered layouts and outperforms GA for sunflower and unstructured layouts, demonstrating its efficiency. The sunflower and unstructured layouts' complexity highlights RLGA's robustness and efficiency in tackling complex problems. To further validate its capabilities, we investigate larger wind farms with varying turbine placements ($\Delta x = \Delta y = 5D$ and 2$D$, where $D$ is the wind turbine diameter) under three wind conditions: unidirectional, omnidirectional, and non-uniform, presenting greater challenges. The proposed RLGA is about three times more efficient than GA, especially for complex problems. This improvement stems from RL's ability to adjust parameters, avoiding local optima and accelerating convergence. -in arXiv: Computer Science: Neural and Evolutionary Computing on 2024-12-10 05:00:00 UTC. +
in arXiv: Computer Science: Neural and Evolutionary Computing on 2024-12-11 05:00:00 UTC.
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-Neural network interpretability with layer-wise relevance propagation: novel techniques for neuron selection and visualization
+Multi-Objective Communication Optimization for Temporal Continuity in Dynamic Vehicular Networks
- arXiv:2412.05686v1 Announce Type: new -Abstract: Interpreting complex neural networks is crucial for understanding their decision-making processes, particularly in applications where transparency and accountability are essential. This proposed method addresses this need by focusing on layer-wise Relevance Propagation (LRP), a technique used in explainable artificial intelligence (XAI) to attribute neural network outputs to input features through backpropagated relevance scores. Existing LRP methods often struggle with precision in evaluating individual neuron contributions. To overcome this limitation, we present a novel approach that improves the parsing of selected neurons during LRP backward propagation, using the Visual Geometry Group 16 (VGG16) architecture as a case study. Our method creates neural network graphs to highlight critical paths and visualizes these paths with heatmaps, optimizing neuron selection through accuracy metrics like Mean Squared Error (MSE) and Symmetric Mean Absolute Percentage Error (SMAPE). Additionally, we utilize a deconvolutional visualization technique to reconstruct feature maps, offering a comprehensive view of the network's inner workings. Extensive experiments demonstrate that our approach enhances interpretability and supports the development of more transparent artificial intelligence (AI) systems for computer vision applications. This advancement has the potential to improve the trustworthiness of AI models in real-world machine vision applications, thereby increasing their reliability and effectiveness. + arXiv:2412.07011v1 Announce Type: new +Abstract: Vehicular Ad-hoc Networks (VANETs) operate in highly dynamic environments characterized by high mobility, time-varying channel conditions, and frequent network disruptions. Addressing these challenges, this paper presents a novel temporal-aware multi-objective robust optimization framework, which for the first time formally incorporates temporal continuity into the optimization of dynamic multi-hop VANETs. The proposed framework simultaneously optimizes communication delay, throughput, and reliability, ensuring stable and consistent communication paths under rapidly changing conditions. A robust optimization model is formulated to mitigate performance degradation caused by uncertainties in vehicular density and channel fluctuations. To solve the optimization problem, an enhanced Non-dominated Sorting Genetic Algorithm II (NSGA-II) is developed, integrating dynamic encoding, elite inheritance, and adaptive constraint handling to efficiently balance trade-offs among conflicting objectives. Simulation results demonstrate that the proposed framework achieves significant improvements in reliability, delay reduction, and throughput enhancement, while temporal continuity effectively stabilizes communication paths over time. This work provides a pioneering and comprehensive solution for optimizing VANET communication, offering critical insights for robust and efficient strategies in intelligent transportation systems. -in arXiv: Computer Science: Neural and Evolutionary Computing on 2024-12-10 05:00:00 UTC. +
in arXiv: Computer Science: Neural and Evolutionary Computing on 2024-12-11 05:00:00 UTC.
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-Spiking Neural Networks for Radio Frequency Interference Detection in Radio Astronomy
+MO-IOHinspector: Anytime Benchmarking of Multi-Objective Algorithms using IOHprofiler
- arXiv:2412.06124v1 Announce Type: new -Abstract: Spiking Neural Networks (SNNs) promise efficient spatio-temporal data processing owing to their dynamic nature. This paper addresses a significant challenge in radio astronomy, Radio Frequency Interference (RFI) detection, by reformulating it as a time-series segmentation task inherently suited for SNN execution. Automated RFI detection systems capable of real-time operation with minimal energy consumption are increasingly important in modern radio telescopes. We explore several spectrogram-to-spike encoding methods and network parameters, applying first-order leaky integrate-and-fire SNNs to tackle RFI detection. To enhance the contrast between RFI and background information, we introduce a divisive normalisation-inspired pre-processing step, which improves detection performance across multiple encoding strategies. Our approach achieves competitive performance on a synthetic dataset and compelling results on real data from the Low-Frequency Array (LOFAR) instrument. To our knowledge, this work is the first to train SNNs on real radio astronomy data successfully. These findings highlight the potential of SNNs for performing complex time-series tasks, paving the way for efficient, real-time processing in radio astronomy and other data-intensive fields. + arXiv:2412.07444v1 Announce Type: new +Abstract: Benchmarking is one of the key ways in which we can gain insight into the strengths and weaknesses of optimization algorithms. In sampling-based optimization, considering the anytime behavior of an algorithm can provide valuable insights for further developments. In the context of multi-objective optimization, this anytime perspective is not as widely adopted as in the single-objective context. In this paper, we propose a new software tool which uses principles from unbounded archiving as a logging structure. This leads to a clearer separation between experimental design and subsequent analysis decisions. We integrate this approach as a new Python module into the IOHprofiler framework and demonstrate the benefits of this approach by showcasing the ability to change indicators, aggregations, and ranking procedures during the analysis pipeline. -in arXiv: Computer Science: Neural and Evolutionary Computing on 2024-12-10 05:00:00 UTC. +
in arXiv: Computer Science: Neural and Evolutionary Computing on 2024-12-11 05:00:00 UTC.
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-Learnable Evolutionary Multi-Objective Combinatorial Optimization via Sequence-to-Sequence Model
+Inverting Visual Representations with Detection Transformers
- arXiv:2412.06140v1 Announce Type: new -Abstract: Recent advances in learnable evolutionary algorithms have demonstrated the importance of leveraging population distribution information and historical evolutionary trajectories. While significant progress has been made in continuous optimization domains, combinatorial optimization problems remain challenging due to their discrete nature and complex solution spaces. To address this gap, we propose SeqMO, a novel learnable multi-objective combinatorial optimization method that integrates sequence-to-sequence models with evolutionary algorithms. Our approach divides approximate Pareto solution sets based on their objective values' distance to the Pareto front, and establishes mapping relationships between solutions by minimizing objective vector angles in the target space. This mapping creates structured training data for pointer networks, which learns to predict promising solution trajectories in the discrete search space. The trained model then guides the evolutionary process by generating new candidate solutions while maintaining population diversity. Experiments on the multi-objective travel salesman problem and the multi-objective quadratic assignment problem verify the effectiveness of the algorithm. Our code is available at: \href{https://github.com/jiaxianghuang/SeqMO}{https://github.com/jiaxianghuang/SeqMO}. + arXiv:2412.06534v1 Announce Type: cross +Abstract: Understanding the mechanisms underlying deep neural networks in computer vision remains a fundamental challenge. While many prior approaches have focused on visualizing intermediate representations within deep neural networks, particularly convolutional neural networks, these techniques have yet to be thoroughly explored in transformer-based vision models. In this study, we apply the approach of training inverse models to reconstruct input images from intermediate layers within a Detection Transformer, showing that this approach is efficient and feasible for transformer-based vision models. Through qualitative and quantitative evaluations of reconstructed images across model stages, we demonstrate critical properties of Detection Transformers, including contextual shape preservation, inter-layer correlation, and robustness to color perturbations, illustrating how these characteristics emerge within the model's architecture. Our findings contribute to a deeper understanding of transformer-based vision models. The code for reproducing our experiments will be made available at github.com/wiskott-lab/inverse-detection-transformer. -in arXiv: Computer Science: Neural and Evolutionary Computing on 2024-12-10 05:00:00 UTC. +
in arXiv: Computer Science: Neural and Evolutionary Computing on 2024-12-11 05:00:00 UTC.
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-Flexible and Scalable Deep Dendritic Spiking Neural Networks with Multiple Nonlinear Branching
+Covered Forest: Fine-grained generalization analysis of graph neural networks
- arXiv:2412.06355v1 Announce Type: new -Abstract: Recent advances in spiking neural networks (SNNs) have a predominant focus on network architectures, while relatively little attention has been paid to the underlying neuron model. The point neuron models, a cornerstone of deep SNNs, pose a bottleneck on the network-level expressivity since they depict somatic dynamics only. In contrast, the multi-compartment models in neuroscience offer remarkable expressivity by introducing dendritic morphology and dynamics, but remain underexplored in deep learning due to their unaffordable computational cost and inflexibility. To combine the advantages of both sides for a flexible, efficient yet more powerful model, we propose the dendritic spiking neuron (DendSN) incorporating multiple dendritic branches with nonlinear dynamics. Compared to the point spiking neurons, DendSN exhibits significantly higher expressivity. DendSN's flexibility enables its seamless integration into diverse deep SNN architectures. To accelerate dendritic SNNs (DendSNNs), we parallelize dendritic state updates across time steps, and develop Triton kernels for GPU-level acceleration. As a result, we can construct large-scale DendSNNs with depth comparable to their point SNN counterparts. Next, we comprehensively evaluate DendSNNs' performance on various demanding tasks. By modulating dendritic branch strengths using a context signal, catastrophic forgetting of DendSNNs is substantially mitigated. Moreover, DendSNNs demonstrate enhanced robustness against noise and adversarial attacks compared to point SNNs, and excel in few-shot learning settings. Our work firstly demonstrates the possibility of training bio-plausible dendritic SNNs with depths and scales comparable to traditional point SNNs, and reveals superior expressivity and robustness of reduced dendritic neuron models in deep learning, thereby offering a fresh perspective on advancing neural network design. + arXiv:2412.07106v1 Announce Type: cross +Abstract: The expressive power of message-passing graph neural networks (MPNNs) is reasonably well understood, primarily through combinatorial techniques from graph isomorphism testing. However, MPNNs' generalization abilities -- making meaningful predictions beyond the training set -- remain less explored. Current generalization analyses often overlook graph structure, limit the focus to specific aggregation functions, and assume the impractical, hard-to-optimize $0$-$1$ loss function. Here, we extend recent advances in graph similarity theory to assess the influence of graph structure, aggregation, and loss functions on MPNNs' generalization abilities. Our empirical study supports our theoretical insights, improving our understanding of MPNNs' generalization properties. -in arXiv: Computer Science: Neural and Evolutionary Computing on 2024-12-10 05:00:00 UTC. +
in arXiv: Computer Science: Neural and Evolutionary Computing on 2024-12-11 05:00:00 UTC.
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-UAV Virtual Antenna Array Deployment for Uplink Interference Mitigation in Data Collection Networks
+ConfigX: Modular Configuration for Evolutionary Algorithms via Multitask Reinforcement Learning
- arXiv:2412.06456v1 Announce Type: new -Abstract: Unmanned aerial vehicles (UAVs) have gained considerable attention as a platform for establishing aerial wireless networks and communications. However, the line-of-sight dominance in air-to-ground communications often leads to significant interference with terrestrial networks, reducing communication efficiency among terrestrial terminals. This paper explores a novel uplink interference mitigation approach based on the collaborative beamforming (CB) method in multi-UAV network systems. Specifically, the UAV swarm forms a UAV-enabled virtual antenna array (VAA) to achieve the transmissions of gathered data to multiple base stations (BSs) for data backup and distributed processing. However, there is a trade-off between the effectiveness of CB-based interference mitigation and the energy conservation of UAVs. Thus, by jointly optimizing the excitation current weights and hover position of UAVs as well as the sequence of data transmission to various BSs, we formulate an uplink interference mitigation multi-objective optimization problem (MOOP) to decrease interference affection, enhance transmission efficiency, and improve energy efficiency, simultaneously. In response to the computational demands of the formulated problem, we introduce an evolutionary computation method, namely chaotic non-dominated sorting genetic algorithm II (CNSGA-II) with multiple improved operators. The proposed CNSGA-II efficiently addresses the formulated MOOP, outperforming several other comparative algorithms, as evidenced by the outcomes of the simulations. Moreover, the proposed CB-based uplink interference mitigation approach can significantly reduce the interference caused by UAVs to non-receiving BSs. + arXiv:2412.07507v1 Announce Type: cross +Abstract: Recent advances in Meta-learning for Black-Box Optimization (MetaBBO) have shown the potential of using neural networks to dynamically configure evolutionary algorithms (EAs), enhancing their performance and adaptability across various BBO instances. However, they are often tailored to a specific EA, which limits their generalizability and necessitates retraining or redesigns for different EAs and optimization problems. To address this limitation, we introduce ConfigX, a new paradigm of the MetaBBO framework that is capable of learning a universal configuration agent (model) for boosting diverse EAs. To achieve so, our ConfigX first leverages a novel modularization system that enables the flexible combination of various optimization sub-modules to generate diverse EAs during training. Additionally, we propose a Transformer-based neural network to meta-learn a universal configuration policy through multitask reinforcement learning across a designed joint optimization task space. Extensive experiments verify that, our ConfigX, after large-scale pre-training, achieves robust zero-shot generalization to unseen tasks and outperforms state-of-the-art baselines. Moreover, ConfigX exhibits strong lifelong learning capabilities, allowing efficient adaptation to new tasks through fine-tuning. Our proposed ConfigX represents a significant step toward an automatic, all-purpose configuration agent for EAs. -in arXiv: Computer Science: Neural and Evolutionary Computing on 2024-12-10 05:00:00 UTC. +
in arXiv: Computer Science: Neural and Evolutionary Computing on 2024-12-11 05:00:00 UTC.
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-STONet: A novel neural operator for modeling solute transport in micro-cracked reservoirs
+Competition on Dynamic Optimization Problems Generated by Generalized Moving Peaks Benchmark (GMPB)
- arXiv:2412.05576v1 Announce Type: cross -Abstract: In this work, we develop a novel neural operator, the Solute Transport Operator Network (STONet), to efficiently model contaminant transport in micro-cracked reservoirs. The model combines different networks to encode heterogeneous properties effectively. By predicting the concentration rate, we are able to accurately model the transport process. Numerical experiments demonstrate that our neural operator approach achieves accuracy comparable to that of the finite element method. The previously introduced Enriched DeepONet architecture has been revised, motivated by the architecture of the popular multi-head attention of transformers, to improve its performance without increasing the compute cost. The computational efficiency of the proposed model enables rapid and accurate predictions of solute transport, facilitating the optimization of reservoir management strategies and the assessment of environmental impacts. The data and code for the paper will be published at https://github.com/ehsanhaghighat/STONet. + arXiv:2106.06174v4 Announce Type: replace +Abstract: The Generalized Moving Peaks Benchmark (GMPB) is a tool for generating continuous dynamic optimization problem instances with controllable dynamic and morphological characteristics. GMPB has been used in recent Competitions on Dynamic Optimization at prestigious conferences, such as the IEEE Congress on Evolutionary Computation (CEC). This dynamic benchmark generator can create a wide variety of landscapes, ranging from simple unimodal to highly complex multimodal configurations and from symmetric to asymmetric forms. It also supports diverse surface textures, from smooth to highly irregular, and can generate varying levels of variable interaction and conditioning. This document provides an overview of GMPB, emphasizing how its parameters can be adjusted to produce landscapes with customizable characteristics. The MATLAB implementation of GMPB is available on the EDOLAB Platform. -in arXiv: Computer Science: Neural and Evolutionary Computing on 2024-12-10 05:00:00 UTC. +
in arXiv: Computer Science: Neural and Evolutionary Computing on 2024-12-11 05:00:00 UTC.
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-LLMs as Debate Partners: Utilizing Genetic Algorithms and Adversarial Search for Adaptive Arguments
+Symbolic Regression with a Learned Concept Library
- arXiv:2412.06229v1 Announce Type: cross -Abstract: This paper introduces DebateBrawl, an innovative AI-powered debate platform that integrates Large Language Models (LLMs), Genetic Algorithms (GA), and Adversarial Search (AS) to create an adaptive and engaging debating experience. DebateBrawl addresses the limitations of traditional LLMs in strategic planning by incorporating evolutionary optimization and game-theoretic techniques. The system demonstrates remarkable performance in generating coherent, contextually relevant arguments while adapting its strategy in real-time. Experimental results involving 23 debates show balanced outcomes between AI and human participants, with the AI system achieving an average score of 2.72 compared to the human average of 2.67 out of 10. User feedback indicates significant improvements in debating skills and a highly satisfactory learning experience, with 85% of users reporting improved debating abilities and 78% finding the AI opponent appropriately challenging. The system's ability to maintain high factual accuracy (92% compared to 78% in human-only debates) while generating diverse arguments addresses critical concerns in AI-assisted discourse. DebateBrawl not only serves as an effective educational tool but also contributes to the broader goal of improving public discourse through AI-assisted argumentation. The paper discusses the ethical implications of AI in persuasive contexts and outlines the measures implemented to ensure responsible development and deployment of the system, including robust fact-checking mechanisms and transparency in decision-making processes. + arXiv:2409.09359v3 Announce Type: replace-cross +Abstract: We present a novel method for symbolic regression (SR), the task of searching for compact programmatic hypotheses that best explain a dataset. The problem is commonly solved using genetic algorithms; we show that we can enhance such methods by inducing a library of abstract textual concepts. Our algorithm, called LaSR, uses zero-shot queries to a large language model (LLM) to discover and evolve concepts occurring in known high-performing hypotheses. We discover new hypotheses using a mix of standard evolutionary steps and LLM-guided steps (obtained through zero-shot LLM queries) conditioned on discovered concepts. Once discovered, hypotheses are used in a new round of concept abstraction and evolution. We validate LaSR on the Feynman equations, a popular SR benchmark, as well as a set of synthetic tasks. On these benchmarks, LaSR substantially outperforms a variety of state-of-the-art SR approaches based on deep learning and evolutionary algorithms. Moreover, we show that LaSR can be used to discover a novel and powerful scaling law for LLMs. -in arXiv: Computer Science: Neural and Evolutionary Computing on 2024-12-10 05:00:00 UTC. +
in arXiv: Computer Science: Neural and Evolutionary Computing on 2024-12-11 05:00:00 UTC.
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-Object Detection using Event Camera: A MoE Heat Conduction based Detector and A New Benchmark Dataset
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+Anti-obesity compounds, Semaglutide and LiPR, do not change the proportion of human and mouse POMC+ neurons
- arXiv:2412.06647v1 Announce Type: cross -Abstract: Object detection in event streams has emerged as a cutting-edge research area, demonstrating superior performance in low-light conditions, scenarios with motion blur, and rapid movements. Current detectors leverage spiking neural networks, Transformers, or convolutional neural networks as their core architectures, each with its own set of limitations including restricted performance, high computational overhead, or limited local receptive fields. This paper introduces a novel MoE (Mixture of Experts) heat conduction-based object detection algorithm that strikingly balances accuracy and computational efficiency. Initially, we employ a stem network for event data embedding, followed by processing through our innovative MoE-HCO blocks. Each block integrates various expert modules to mimic heat conduction within event streams. Subsequently, an IoU-based query selection module is utilized for efficient token extraction, which is then channeled into a detection head for the final object detection process. Furthermore, we are pleased to introduce EvDET200K, a novel benchmark dataset for event-based object detection. Captured with a high-definition Prophesee EVK4-HD event camera, this dataset encompasses 10 distinct categories, 200,000 bounding boxes, and 10,054 samples, each spanning 2 to 5 seconds. We also provide comprehensive results from over 15 state-of-the-art detectors, offering a solid foundation for future research and comparison. The source code of this paper will be released on: https://github.com/Event-AHU/OpenEvDET + Anti-obesity medications (AOMs) have become one of the most prescribed drugs in human medicine. While AOMs are known to impact adult neurogenesis in the hypothalamus, their effects on the functional maturation of hypothalamic neurons remain unexplored. Given that AOMs target neurons in the Medial Basal Hypothalamus (MBH), which play a crucial role in regulating energy homeostasis, we hypothesized that AOMs might influence the functional maturation of these neurons, potentially rewiring the MBH. To investigate this, we exposed hypothalamic neurons derived from human induced pluripotent stem cells (hiPSCs) to Semaglutide and lipidized prolactin-releasing peptide (LiPR), two anti-obesity compounds. Contrary to our expectations, treatment with Semaglutide or LiPR during neuronal maturation did not affect the proportion of anorexigenic, Pro-opiomelanocortin-expressing (POMC+) neurons. Additionally, LiPR did not alter the morphology of POMC+ neurons or the expression of selected genes critical for the metabolism or development of anorexigenic neurons. Furthermore, LiPR did not impact the proportion of adult-generated POMC+ neurons in the mouse MBH. Taken together, these results suggest that AOMs do not influence the functional maturation of anorexigenic hypothalamic neurons. -in arXiv: Computer Science: Neural and Evolutionary Computing on 2024-12-10 05:00:00 UTC. +
in bioRxiv: Neuroscience on 2024-12-11 00:00:00 UTC.
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-SpiKernel: A Kernel Size Exploration Methodology for Improving Accuracy of the Embedded Spiking Neural Network Systems
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+SegCSR: Weakly-Supervised Cortical Surfaces Reconstruction from Brain Ribbon Segmentations
- arXiv:2404.01685v3 Announce Type: replace -Abstract: Spiking Neural Networks (SNNs) can offer ultra-low power/energy consumption for machine learning-based application tasks due to their sparse spike-based operations. Currently, most of the SNN architectures need a significantly larger model size to achieve higher accuracy, which is not suitable for resource-constrained embedded applications. Therefore, developing SNNs that can achieve high accuracy with acceptable memory footprint is highly needed. Toward this, we propose SpiKernel, a novel methodology that improves the accuracy of SNNs through kernel size exploration. Its key steps include (1) investigating the impact of different kernel sizes on the accuracy, (2) devising new sets of kernel sizes, (3) generating SNN architectures using neural architecture search based on the selected kernel sizes, and (4) analyzing the accuracy-memory trade-offs for SNN model selection. The experimental results show that our SpiKernel achieves higher accuracy than state-of-the-art works (i.e., 93.24% for CIFAR10, 70.84% for CIFAR100, and 62% for TinyImageNet) with less than 10M parameters and up to 4.8x speed-up of searching time, thereby making it suitable for embedded applications. + Deep learning-based cortical surface reconstruction (CSR) methods heavily rely on pseudo ground truth (pGT) generated by conventional CSR pipelines as supervision, leading to dataset-specific challenges and lengthy training data preparation. We propose a new approach for reconstructing multiple cortical surfaces using weak supervision from brain MRI ribbon segmentations. Our approach initializes a midthickness surface and then deforms it inward and outward to form the inner (white matter) and outer (pial) cortical surfaces, respectively, by jointly learning diffeomorphic flows to align the surfaces with the boundaries of the cortical ribbon segmentation maps. Specifically, a boundary surface loss drives the initialization surface to the target inner and outer boundaries, and an inter-surface normal consistency loss regularizes the pial surface in challenging deep cortical sulci. Additional regularization terms are utilized to enforce surface smoothness and topology. Evaluated on two large-scale brain MRI datasets, our weakly-supervised method achieves comparable or superior CSR accuracy and regularity to existing supervised deep learning alternatives. -in arXiv: Computer Science: Neural and Evolutionary Computing on 2024-12-10 05:00:00 UTC. +
in bioRxiv: Neuroscience on 2024-12-11 00:00:00 UTC.
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-Guiding a Diffusion Model with a Bad Version of Itself
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+A decision-theoretic model of multistability: perceptual switches as internal actions
- arXiv:2406.02507v2 Announce Type: replace-cross -Abstract: The primary axes of interest in image-generating diffusion models are image quality, the amount of variation in the results, and how well the results align with a given condition, e.g., a class label or a text prompt. The popular classifier-free guidance approach uses an unconditional model to guide a conditional model, leading to simultaneously better prompt alignment and higher-quality images at the cost of reduced variation. These effects seem inherently entangled, and thus hard to control. We make the surprising observation that it is possible to obtain disentangled control over image quality without compromising the amount of variation by guiding generation using a smaller, less-trained version of the model itself rather than an unconditional model. This leads to significant improvements in ImageNet generation, setting record FIDs of 1.01 for 64x64 and 1.25 for 512x512, using publicly available networks. Furthermore, the method is also applicable to unconditional diffusion models, drastically improving their quality. + Perceptual multistability has been studied for centuries using a diverse collection of approaches. Insights derived from this phenomenon range from core principles of information processing, such as perceptual inference, to high-level concerns, such as visual awareness. The dominant computational explanations of perceptual multistability are based on the Helmholtzian view of perception as inverse inference. However, these approaches struggle to account for the crucial role played by value, e.g., with percepts paired with reward dominating for longer periods than unpaired ones. In this study, we formulate perceptual multistability in terms of dynamic, value-based, choice, employing the formalism of a partially observable Markov decision process (POMDP). We use binocular rivalry as an example, considering different explicit and implicit sources of reward (and punishment) for each percept. The resulting values are time-dependent and influenced by novelty as a form of exploration. The solution of the POMDP is the optimal perceptual policy, and we show that this can replicate and explain several characteristics of binocular rivalry, ranging from classic hallmarks such as apparently spontaneous random switches with approximately gamma-distributed dominance periods to more subtle aspects such as the rich temporal dynamics of perceptual switching rates. Overall, our decision-theoretic perspective on perceptual multistability not only accounts for a wealth of unexplained data, but also opens up modern conceptions of internal reinforcement learning in service of understanding perceptual phenomena, and sensory processing more generally. -in arXiv: Computer Science: Neural and Evolutionary Computing on 2024-12-10 05:00:00 UTC. +
in bioRxiv: Neuroscience on 2024-12-11 00:00:00 UTC.
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-Reducing ADC Front-end Costs During Training of On-sensor Printed Multilayer Perceptrons
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+Brain Sciences, Vol. 14, Pages 1240: The “Reading the Mind in Films” Task: A Pilot Study on Complex Emotion and Mental State Recognition for the Italian Adaptation in Adults with and Without Autism Spectrum Conditions
- arXiv:2411.08674v3 Announce Type: replace-cross -Abstract: Printed electronics technology offers a cost-effectiveand fully-customizable solution to computational needs beyondthe capabilities of traditional silicon technologies, offering ad-vantages such as on-demand manufacturing and conformal, low-cost hardware. However, the low-resolution fabrication of printedelectronics, which results in large feature sizes, poses a challengefor integrating complex designs like those of machine learn-ing (ML) classification systems. Current literature optimizes onlythe Multilayer Perceptron (MLP) circuit within the classificationsystem, while the cost of analog-to-digital converters (ADCs)is overlooked. Printed applications frequently require on-sensorprocessing, yet while the digital classifier has been extensivelyoptimized, the analog-to-digital interfacing, specifically the ADCs,dominates the total area and energy consumption. In this work,we target digital printed MLP classifiers and we propose thedesign of customized ADCs per MLP's input which involvesminimizing the distinct represented numbers for each input,simplifying thus the ADC's circuitry. Incorporating this ADCoptimization in the MLP training, enables eliminating ADC levelsand the respective comparators, while still maintaining highclassification accuracy. Our approach achieves 11.2x lower ADCarea for less than 5% accuracy drop across varying MLPs. +Brain Sciences, Vol. 14, Pages 1240: The “Reading the Mind in Films” Task: A Pilot Study on Complex Emotion and Mental State Recognition for the Italian Adaptation in Adults with and Without Autism Spectrum Conditions
+Brain Sciences doi: 10.3390/brainsci14121240
+Authors: + Raffaele Simone Scuotto + Sofia Bonfanti + Paola Ricciardelli +
+Background/Objectives: The present pilot study tested and reports the Italian adaptation of the Reading the Mind in Film test (RMF), an ecological test for assessing, in Italian adults with and without Autism Spectrum Condition (ASC), complex emotion and mental state recognition in natural settings and everyday situations. Method: A sample of young adults with Autism Spectrum Condition (with ASC; n = 22), attending a filmmaking course at a post-diploma school (Scuola Futuro Lavoro) took part in the study and was compared with a control group of neurotypical university students (without ASC; n = 22). All participants underwent individual testing and completed the Italian version of the Autism Questionnaire before performing the Italian version of both the RMF task and the Reading the Mind in the Eyes Test (RMET). The latter, widely used to evaluate the ability to detect what someone else is thinking or feeling from the eye region. Results: The findings of the control group were in line with the original study, demonstrating the validity and reliability of the translation and the dubbing procedure of the RMF test. However, no main significant differences in performance were found between the two groups. Conclusions: Such results suggest that taking a course in film and video making may have helped the autistic students learn how to recognize mental states.
-in arXiv: Computer Science: Neural and Evolutionary Computing on 2024-12-10 05:00:00 UTC. +
in Brain Sciences on 2024-12-11 00:00:00 UTC.
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-FabuLight-ASD: Unveiling Speech Activity via Body Language
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+Procaine Regulates the STAT3/CCL5 Axis and Inhibits Microglia M1 Polarization to Alleviate Complete Freunds Adjuvant Rats Pain Behavior
- arXiv:2411.13674v2 Announce Type: replace-cross -Abstract: Active speaker detection (ASD) in multimodal environments is crucial for various applications, from video conferencing to human-robot interaction. This paper introduces FabuLight-ASD, an advanced ASD model that integrates facial, audio, and body pose information to enhance detection accuracy and robustness. Our model builds upon the existing Light-ASD framework by incorporating human pose data, represented through skeleton graphs, which minimises computational overhead. Using the Wilder Active Speaker Detection (WASD) dataset, renowned for reliable face and body bounding box annotations, we demonstrate FabuLight-ASD's effectiveness in real-world scenarios. Achieving an overall mean average precision (mAP) of 94.3%, FabuLight-ASD outperforms Light-ASD, which has an overall mAP of 93.7% across various challenging scenarios. The incorporation of body pose information shows a particularly advantageous impact, with notable improvements in mAP observed in scenarios with speech impairment, face occlusion, and human voice background noise. Furthermore, efficiency analysis indicates only a modest increase in parameter count (27.3%) and multiply-accumulate operations (up to 2.4%), underscoring the model's efficiency and feasibility. These findings validate the efficacy of FabuLight-ASD in enhancing ASD performance through the integration of body pose data. FabuLight-ASD's code and model weights are available at https://github.com/knowledgetechnologyuhh/FabuLight-ASD. +Neuropathic pain (NP) caused by sciatic nerve injury can significantly impact the quality of life of patients. The M1 phenotype of microglia has been reported to promote the progression of NP. Procaine is a lipid-soluble local anesthetic drug that exerts narcotic analgesic effects. Nevertheless, the detailed effect of procaine in NP is not clear. In order to explore the role of procaine in the polarization of NP microglia, HAPI cells were exposed to LPS to polarize into M1 type. In addition, the number of the M1 phenotype of HAPI cells was assessed using flow cytometry. The binding site between CCL5 and STAT3 was explored using the dual luciferase assay. Furthermore, in vivo experiments were applied for testing the impact of procaine on NP. LPS significantly inhibited HAPI cell viability, which was reversed by procaine. Consistently, procaine alleviated LPS-induced upregulation of inflammatory factors. Additionally, it significantly inhibited HAPI cell M1 polarization induced by LPS. Meanwhile, overexpression of STAT3 was able to promote HAPI cells M1 polarization through binding with the CCL5 promoter region and activating the PI3K/Akt signaling. Procaine could alleviate the painful behavior of complete Freund's adjuvant (CFA) rats by modulating the STAT3/CCL5 axis and inhibiting microglia M1 polarization. In conclusion, procaine alleviated the painful behavior of CFA rats via regulating the STAT3/CCL5 axis and inhibiting microglia M1 polarization. Hence, the research might provide a novel agent for NP treatment.
-in arXiv: Computer Science: Neural and Evolutionary Computing on 2024-12-10 05:00:00 UTC. +
in eNeuro on 2024-12-10 17:30:20 UTC.
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-UGGT1-mediated reglucosylation of N-glycan competes with ER-associated degradation of unstable and misfolded glycoproteins
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+The Overexpression of eIF4E Decreases Oxytocin Levels and Induces Social Cognitive Behavioral Disorders in Mice
- How the fate (folding versus degradation) of glycoproteins is determined in the endoplasmic reticulum (ER) is an intriguing question. Monoglucosylated glycoproteins are recognized by lectin chaperones to facilitate their folding, whereas glycoproteins exposing well-trimmed mannoses are subjected to glycoprotein ER-associated degradation (gpERAD); we have elucidated how mannoses are sequentially trimmed by EDEM family members (George et al., 2020; 2021 eLife). Although reglucosylation by UGGT was previously reported to have no effect on substrate degradation, here we directly tested this notion using cells with genetically disrupted UGGT1/2. Strikingly, the results showed that UGGT1 delayed the degradation of misfolded substrates and unstable glycoproteins including ATF6α. An experiment with a point mutant of UGGT1 indicated that the glucosylation activity of UGGT1 was required for the inhibition of early glycoprotein degradation. These and overexpression-based competition experiments suggested that the fate of glycoproteins is determined by a tug-of-war between structure formation by UGGT1 and degradation by EDEMs. We further demonstrated the physiological importance of UGGT1, since ATF6α cannot function properly without UGGT1. Thus, our work strongly suggests that UGGT1 is a central factor in ER protein quality control via the regulation of both glycoprotein folding and degradation. +Overexpression of the eukaryotic initiation factor 4E (eIF4E) gene has been associated with excessive stereotypic behaviors and reduced sociability, which manifest as autism-like social cognitive deficits. However, the precise mechanisms by which eIF4E overexpression insufficiently induces these autism-like behaviors and the specific brain regions implicated remain insufficiently understood. Oxytocin (OXT), a neurotransmitter known for its role in social behavior, has been proposed to modulate certain autism-related symptoms by influencing microglial function and attenuating neuroinflammation. Nonetheless, the contributions of the hippocampus and oxytocin in the content of eIF4E overexpression-induced autistic behaviors remain elucidated. To investigate this issue, researchers utilized the three-chamber social interaction test, the open-field test, and the Morris water maze to evaluate the social cognitive behaviors of the two groups of mice. Additionally, ELISA, immunofluorescence, Western blotting, and qRT-PCR were employed to quantify oxytocin levels and assess hippocampal microglial activation. The results indicate that overexpression of eIF4E in mice is associated with significant impairments in social cognition, alongside pronounced marked hyperactivation of hippocampal microglia.
-in eLife on 2024-12-10 00:00:00 UTC. +
in eNeuro on 2024-12-10 17:30:20 UTC.
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-Paracrine rescue of MYR1-deficient Toxoplasma gondii mutants reveals limitations of pooled in vivo CRISPR screens
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+Phenotypic and genetic extended spectrum beta lactamase profiles of bacterial isolates from ICU in tertiary level hospital in Kenya [version 2; peer review: 2 approved with reservations]
- Toxoplasma gondii is an intracellular parasite that subverts host cell functions via secreted virulence factors. Up to 70% of parasite-controlled changes in the host transcriptome rely on the MYR1 protein, which is required for the translocation of secreted proteins into the host cell. Mice infected with MYR1 knock-out (KO) strains survive infection, supporting a paramount function of MYR1-dependent secreted proteins in Toxoplasma virulence and proliferation. However, we have previously shown that MYR1 mutants have no growth defect in pooled in vivo CRISPR-Cas9 screens in mice, suggesting that the presence of parasites that are wild-type at the myr1 locus in pooled screens can rescue the phenotype. Here, we demonstrate that MYR1 is not required for the survival in IFN-γ-activated murine macrophages, and that parasites lacking MYR1 are able to expand during the onset of infection. While ΔMYR1 parasites have restricted growth in single-strain murine infections, we show that the phenotype is rescued by co-infection with wild-type (WT) parasites in vivo, independent of host functional adaptive immunity or key pro-inflammatory cytokines. These data show that the major function of MYR1-dependent secreted proteins is not to protect the parasite from clearance within infected cells. Instead, MYR-dependent proteins generate a permissive niche in a paracrine manner, which rescues ΔMYR1 parasites within a pool of CRISPR mutants in mice. Our results highlight an important limitation of otherwise powerful in vivo CRISPR screens and point towards key functions for MYR1-dependent Toxoplasma-host interactions beyond the infected cell. + Background Bacterial infections in the Intensive Care Units are a threat to the lives of critically ill patients. Their vulnerable immunity predisposes them to developing bacteria-associated sepsis, deteriorating their already fragile health. In the face of increasing antibiotics resistance, the problem of bacterial infection in ICU is worsening. Surveillance of bacterial infections in ICUs and drug resistance will help to understand the magnitude of the problem it poses and inform response strategies. We assessed bacterial infections in ICU setting by identifying prevalent Gram-negative bacterial species and characterized their antibiotic susceptibility patterns. Methods Cross-sectional samples collected from Kenyatta National Hospital ICU between January and June 2021 were cultured and phenotypic identification of culture-positive samples performed using VITEK 2. Antibiotic susceptibility patterns were determined based on Antimicrobial Susceptibility Testing (AST) results. Cephalosporin-resistant Gram-negative bacteria were assessed by PCR to detect the presence of ESBL genes including ( bla CTX-M, bla SHV, bla TEM, bla OXA) Results and discussion Out of the 168 Gram-negative isolates, Acinetobacter baumanii was the most abundant (35%). Other isolates that were present at frequencies more than 15% are Klebsiella pneumoniae and Escherichia. coli. A. baumaniii is known to be a notorious bacterium in ICU due to its multidrug resistance nature. Indeed, A. baumanii isolates from Kenyatta National Hospital showed significantly high level of phenotypic resistance. Concordant with the high level of phenotypic resistance, we found high carriage of the ESBL genes among the isolates analysed in this study. Moreover, majority of isolates harboured all the four ESBL genes. Conclusion A high rate of phenotypic and genetic resistance was detected among the tested isolates. Resistance to cephalosporins was primarily driven by acquisition of the ESBL genes. The high prevalence rate of ESBL genes in ICU bacterial isolates shown in this study has a important implication for ICU patient management and general antibiotics use. -in eLife on 2024-12-10 00:00:00 UTC. +
in F1000Research on 2024-12-10 16:08:09 UTC.
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-Tau Accumulation Induces Microglial State Alterations in Alzheimer's Disease Model Mice
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+Upholding dignity during a pandemic via Twitter [version 2; peer review: 1 approved, 2 approved with reservations]
-Unique microglial states have been identified in Alzheimer's disease (AD) model mice and postmortem AD brains. Although it has been well documented that amyloid-β accumulation induces the alteration of microglial states, the relationship between tau pathology and microglial states remains incompletely understood because of a lack of suitable AD models. In the present study, we generated a novel AD model mouse by the intracerebral administration of tau purified from human brains with primary age-related tauopathy into App knock-in mice with humanized tau. Immunohistochemical analyses revealed that Dectin-1-positive disease-associated microglia were increased in the AD model mice after tau accumulation in the brain. We then performed single-nucleus RNA sequencing on the AD model mice to evaluate the differences in microglial states with and without tau propagation and accumulation. By taking advantage of spatial transcriptomics and existing single-cell RNA sequencing datasets, we showed for the first time that tau propagation and accumulation induce a disease-associated microglial phenotype at the expense of an age-related nonhomeostatic counterpart (namely, white matter-associated microglia) in an AD model mouse brain. Future work using spatial transcriptomics at single-cell resolution will pave the way for a more appropriate interpretation of microglial alterations in response to tau pathology in the AD brain.
+ Background This article investigates how people invoked the concept of dignity on Twitter (X) during the first year of the COVID-19 pandemic, with a secondary focus on mentions of dignity in the context of older adults and ageing. Methods We report the results of a study that combines text analytic and interpretive approaches to analyze word clusters and dignity-based themes in a cross-national sample of 1,946 original Twitter (X) messages posted in 2020. Results The study finds that dignity discourse on Twitter advances five major themes: (a) recognizing dignity as a fundamental right, (b) upholding the dignity of essential workers, (c) preserving the dignity of at-risk populations, (d) preventing cascading disasters that exacerbate dignity’s decline, and (e) attending to death, dignity, and the sanctity of life. Conclusions Within the discourse, dignity emerged as a right and a policy target (improving or maximizing dignity in various groups). Further, the posts focusing on older adults and dignity demonstrated that the impacts of COVID-19 disproportionately impacted older adults, particularly those with greater care needs and financial insecurity or lower socioeconomic status. -in eNeuro on 2024-12-09 17:30:13 UTC. +
in F1000Research on 2024-12-10 16:04:45 UTC.
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-Dissociable Effects of Urgency and Evidence Accumulation during Reaching Revealed by Dynamic Multisensory Integration
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+Partner violence in healthcare settings on breastfeeding mothers: a scientometric analysis [version 2; peer review: 1 approved with reservations]
-When making perceptual decisions, humans combine information across sensory modalities dependent on their respective uncertainties. However, it remains unknown how the brain integrates multisensory feedback during movement and which factors besides sensory uncertainty influence sensory contributions. We performed two reaching experiments on healthy adults to investigate whether movement corrections to combined visual and mechanical perturbations scale with visual uncertainty. To describe the dynamics of multimodal feedback responses, we further varied movement time and visual feedback duration during the movement. The results of our first experiment show that the contribution of visual feedback decreased with uncertainty. Additionally, we observed a transient phase during which visual feedback responses were stronger during faster movements. In a follow-up experiment, we found that the contribution of vision increased more quickly during slow movements when we presented the visual feedback for a longer time. Muscle activity corresponding to these visual responses exhibited modulations with sensory uncertainty and movement speed ca. 100 ms following the onset of the visual feedback. Using an optimal feedback control model, we show that the increased response to visual feedback during fast movements can be explained by an urgency-dependent increase in control gains. Further, the fact that a longer viewing duration increased the visual contributions suggests that the brain accumulates sensory information over time to estimate the state of the arm during reaching. Our results provide additional evidence concerning the link between reaching control and decision-making, both of which appear to be influenced by sensory evidence accumulation and response urgency.
+ Background Partner violence is a significant issue affecting women’s health, particularly their breastfeeding practices in healthcare settings. Despite a considerable body of research on this topic, there is a need for a systematic overview of the existing literature to explore its thematic and structural developments. Methods This scientometric analysis covers a period of 45 years (1977-2022) and identifies 415 peer-reviewed articles published in English before 2023 from the Scopus database. The articles were included if they engaged with themes related to partner violence, healthcare settings, breastfeeding, and mothers, using predefined search terms and filters. Bibliometric data were decoded and visualized using VOSviewer and RStudio to analyze and visualize the scientific dialogue, trends, patterns, and networks in the literature regarding partner violence and its impact on breastfeeding mothers in healthcare settings. Results A total of 415 articles were identified, revealing key trends in research on partner violence and breastfeeding in healthcare settings. Seven pivotal clusters emerged: domestic violence and screening, nursing and substance abuse, pregnancy and depression, breastfeeding and HIV, childbirth and quality of care during the COVID-19 pandemic, nurses’ role in women’s Health, and Women’s Health and Violence. These clusters reflect key thematic areas, emphasizing the multifaceted nature of the research, with a particular focus on mental health, reproductive health, and the role of healthcare providers. Emerging themes, such as the impact of COVID-19 and HIV on breastfeeding practices, further highlight the evolving research priorities. Conclusions This analysis provides a panoramic overview of the existing literature, revealing intricate thematic structures and collaboration networks within the research on partner violence and breastfeeding mothers in healthcare settings. The study not only sheds light on the historical and current states of research but also pinpoints potential future directions, thereby assisting scholars and policymakers in navigating and prioritizing subsequent investigative endeavors. -in eNeuro on 2024-12-09 17:30:13 UTC. +
in F1000Research on 2024-12-10 15:25:54 UTC.
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-Oxygen as obturation biomaterial in endodontic treatment: development of novel membranous dental restoration system [version 3; peer review: 1 approved, 2 approved with reservations]
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+Developmental and Adult Striatal Patterning of Nociceptin Ligand Marks Striosomal Population With Direct Dopamine Projections
- Complexities in obturation and difficulties in disinfection represent significant issues that render endodontic treatment notably time-consuming. A new perspective is essential to reduce both working time and address these two challenges. To date, none of the established techniques for root canal obturation can assure a perfect seal. Solid materials are not easily manipulated to hermetically fill the intricate branches of the root canal system. Concurrently, anaerobic and facultative anaerobic bacteria, particularly Enterococcus faecalis, are predominant in discussions surrounding endodontic infections. Numerous studies have demonstrated that achieving complete disinfection of Enterococcus faecalis is exceedingly difficult, even with the use of irrigating solutions that possess strong antibacterial properties. Under anaerobic conditions, the invasion efficiency of facultative anaerobes is heightened. If irrigation and disinfection fail to entirely eliminate anaerobes and facultative anaerobes, a novel strategy is required to address the bacteria that persist within the root canal. Oxygen can easily permeate the root canal system, eradicate anaerobes, and inhibit facultative anaerobes from becoming pathogenic. Therefore, employing oxygen as a biomaterial for obturation following appropriate cleaning and shaping procedures is anticipated to address the two primary endodontic issues. This article aims to explore a new potential concept for a dental restoration system that utilizes an oxygen-permeable membrane to reduce the time required for endodontic treatment. The membrane is positioned at the orifice of a duct designed to connect the entire root canal system with ambient air outside the restoration. The function of the membrane is somewhat analogous to the masks used during the COVID-19 pandemic, as it allows for the circulation of oxygen while preventing the passage of fluids, debris, and microorganisms. We hypothesize that the oxygen circulating within the root canal system will also function as a continuously renewing antimicrobial agent. +
+Hueske, Stine, Yoshida, et al. identify striatal neurons with a developmental expression of the Pnoc gene, dorsal striosomes, and ventral clusters, expressing Drd1, and directly projecting to nigral dopamine neurons. + +
++
ABSTRACT
+Circuit influences on the midbrain dopamine system are crucial to adaptive behavior and cognition. Recent developments in the study of neuropeptide systems have enabled high-resolution investigations of the intersection of neuromodulatory signals with basal ganglia circuitry, identifying the nociceptin/orphanin FQ (N/OFQ) endogenous opioid peptide system as a prospective regulator of striatal dopamine signaling. Using a prepronociceptin-Cre reporter mouse line, we characterized highly selective striosomal patterning of Pnoc mRNA expression in mouse dorsal striatum, reflecting the early developmental expression of Pnoc. In the ventral striatum, Pnoc expression in the nucleus accumbens core was grouped in clusters akin to the distribution found in striosomes. We found that PnoctdTomato reporter cells largely comprise a population of dopamine receptor D1 (Drd1) expressing medium spiny projection neurons localized in dorsal striosomes, known to be unique among striatal projection neurons for their direct innervation of midbrain dopamine neurons. These findings provide a new understanding of the intersection of the N/OFQ system among basal ganglia circuits with particular implications for developmental regulation or wiring of striato-nigral circuits.
-in F1000Research on 2024-12-09 16:59:52 UTC. +
in Journal of Comparative Neurology on 2024-12-10 15:06:56 UTC.
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-Towards an Integrated Performance Management and Measurement System for healthcare organisations: a case study in Montreal [version 2; peer review: 1 approved, 3 approved with reservations]
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+Irx3/5 Null Deletion in Mice Blocks Cochlea‐Saccule Segregation and Disrupts the Auditory Tonotopic Map
- This study proposes an approach for developing or improving performance management and measurement systems (PMMSs) for healthcare organisations. First, data is collected to analyse and understand the current organisation’s performance management system. Second, the SWOT (Strengths, Weaknesses, Opportunities, Threats) method is used to identify the main aspects of the performance management system to be improved. Third, based on the scientific literature and SWOT analysis, BSC principles are integrated to this performance management system to better align the organisation’s performance objectives and indicators with its strategy. Finally, we develop a performance indicator structure and select indicators to be used as well as how these indicators could be integrated and shared with higher hierarchical levels in the organisation by using AHP (Analytic Hierarchy Process). Our approach is applied to the CIUSSS du Centre-Sud-de-l’île-de-Montreal (CCSMTL), a large healthcare network, in the province of Québec, Canada. +
+Deletion mutant of Irx3/5 shows the cochlear base fused with the saccule, whereas in wild-type mice, the saccule is separated from the base by the ductus reuniens. Irx3 and Irx5 are potential evolutionary branch-point genes necessary for balance-sound segregation. + +
++
ABSTRACT
+A gene cadre orchestrates the normal development of sensory and non-sensory cells in the inner ear, segregating the cochlea with a distinct tonotopic sound frequency map, similar brain projection, and five vestibular end-organs. However, the role of genes driving the ear development is largely unknown. Here, we show double deletion of the Iroquois homeobox 3 and 5 transcription factors (Irx3/5 DKO) leads to the fusion of the saccule and the cochlear base. The overlying otoconia and tectorial membranes are absent in the Irx3/5 DKO inner ear, and the primary auditory neurons project fibers to both the saccule and cochlear hair cells. The central neuronal projections from the cochlear apex-base contour are not fully segregated into a dorsal and ventral innervation in the Irx3/5 DKO cochlear nucleus, obliterating the characteristic tonotopic auditory map. Additionally, Irx3/5 deletion reveals a pronounced cochlear-apex-vestibular “vestibular-cochlear” nerve (VCN) bilateral connection that is less noticeable in wild-type control mice. Moreover, the incomplete segregation of apex and base projections that expands fibers to connect with vestibular nuclei. The results suggest the mammalian cochlear apex is a derived lagena reminiscent of sarcopterygians. Thus, Irx3 and 5 are potential evolutionary branch-point genes necessary for balance-sound segregation, which fused into a saccule-cochlea organization.
-in F1000Research on 2024-12-09 16:57:44 UTC. +
in Journal of Comparative Neurology on 2024-12-10 11:34:46 UTC.
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-Differential quantification of alternative splicing events on spliced pangenome graphs
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+Only severe Injuries are effectively reduced by muscles' injury prevention protocols in football players: A systematic review [version 2; peer review: 1 approved, 1 approved with reservations]
-by Simone Ciccolella, Davide Cozzi, Gianluca Della Vedova, Stephen Njuguna Kuria, Paola Bonizzoni, Luca Denti
- -Pangenomes are becoming a powerful framework to perform many bioinformatics analyses taking into account the genetic variability of a population, thus reducing the bias introduced by a single reference genome. With the wider diffusion of pangenomes, integrating genetic variability with transcriptome diversity is becoming a natural extension that demands specific methods for its exploration. In this work, we extend the notion of spliced pangenomes to that of annotated spliced pangenomes; this allows us to introduce a formal definition of Alternative Splicing (AS) events on a graph structure. To investigate the usage of graph pangenomes for the quantification of AS events across conditions, we developed pantas, the first pangenomic method for the detection and differential analysis of AS events from short RNA-Seq reads. A comparison with state-of-the-art linear reference-based approaches proves that pantas achieves competitive accuracy, making spliced pangenomes effective for conducting AS events quantification and opening future directions for the analysis of population-based transcriptomes. + Background Muscle injuries are the most frequent in football and may lead to the end of a player’s career. Many studies have evaluated the effectiveness of prevention programs for all injury types. Few studies have evaluated the effects of exercise on muscle injuries. The aim of this study is to report, through a systematic review of research of high level of proof (randomized controlled trial) the efficacy of preventive programs for muscle injuries for football players. Methods A documentary search was conducted in October 2022 from three databases: Medline via its PubMed interface, Google Scholar, and COCHRANE databases. We only included original articles published between October 2012 and October 2022 with a high level of evidence. The research was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria. The target population consisted of professional and semi-professional footballers. The intervention in question was structured injury preventive protocols, including specific training or pre-established protocols such as the FIFA 11+ program, compared to each other or with regular training sessions. The main outcomes were the incidence rates of muscle injuries and severe injury in each group, as well as the time loss to injury. Results Seven randomized controlled trials with a high level of evidence confirmed using the PEDRO scale were included. There were 3815 male professional football players. There was heterogeneity in the age, hours of exposure, and duration of the intervention. The prevention protocols used were FIFA 11+, bounding exercises, NHE, and stretching exercises. Structured exercises significantly reduce the severity of muscle injury and, consequently, time loss to injury. Discussion Despite the diversity of prevention programs, teams still lack standardized programs. Structured exercises, such as FIFA 11+ and bounding exercises, which combine strengthening, body kinesthesic awareness, and neuromuscular control, reduce the incidence and severity of muscle injury. FIFA 11+ is the first and most complete structured program, but lacks some exercises, such as adductor strengthening. Conclusion This review showed the interest in structured exercises in reducing severity and time loss to injury in professional football players. It shows that effective MI prevention program should combine variable structured programs taking into consideration risk evaluation. Registration This review was registered on 8/17/2023 in the International Prospective Register of Systematic Reviews under the reference code CRD42023452202. -in PLoS Computational Biology on 2024-12-09 14:00:00 UTC. +
in F1000Research on 2024-12-10 10:32:37 UTC.
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-Preserving friendships in school contacts: An algorithm to construct synthetic temporal networks for epidemic modelling
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+Preliminary Evidence of Human Plasmodium in Domestic Animals from a Malaria-Endemic Region in Indonesia [version 4; peer review: 1 approved, 1 approved with reservations, 1 not approved]
-by Lucille Calmon, Elisabetta Colosi, Giulia Bassignana, Alain Barrat, Vittoria Colizza
- -High-resolution temporal data on contacts between hosts provide crucial information on the mixing patterns underlying infectious disease transmission. Publicly available data sets of contact data are however typically recorded over short time windows with respect to the duration of an epidemic. To inform models of disease transmission, data are thus often repeated several times, yielding synthetic data covering long enough timescales. Looping over short term data to approximate contact patterns on longer timescales can lead to unrealistic transmission chains because of the deterministic repetition of all contacts, without any renewal of the contact partners of each individual between successive periods. Real contacts indeed include a combination of regularly repeated contacts (e.g., due to friendship relations) and of more casual ones. In this paper, we propose an algorithm to longitudinally extend contact data recorded in a school setting, taking into account this dual aspect of contacts and in particular the presence of repeated contacts due to friendships. To illustrate the interest of such an algorithm, we then simulate the spread of SARS-CoV-2 on our synthetic contacts using an agent-based model specific to the school setting. We compare the results with simulations performed on synthetic data extended with simpler algorithms to determine the impact of preserving friendships in the data extension method. Notably, the preservation of friendships does not strongly affect transmission routes between classes in the school but leads to different infection pathways between individual students. Our results moreover indicate that gathering contact data during two days in a population is sufficient to generate realistic synthetic contact sequences between individuals in that population on longer timescales. The proposed tool will allow modellers to leverage existing contact data, and contributes to the design of optimal future field data collection. + Background In Indonesia, malaria incidence is at a high rate despite maximum preventive efforts. Therefore, this study aims to determine the possibility of a Plasmodium reservoir among domestic animals in malaria-endemic areas. Methods Animal blood was collected using EDTA tubes, then smeared and stained with Giemsa for Plasmodium microscopic identification. About 10 μl of blood was dropped on to a filter paper to capture Plasmodium DNA. Nested PCR was used for parasite molecular detection, while Plasmodium species were identified using the sequenced DNA. Results A total of 208 and 62 animal blood samples were collected from Gaura village, West Sumba and Fakfak village, West Papua, Indonesia respectively. In total, 32 samples from Gaura contained P. falciparum or P. vivax, while the Plasmodium percentage in buffalo, horse, goat, and dogs were 20.7%, 14.3%, 5.8%, 16.7%, respectively. P. knowlesi was not found in any of the samples, and no other species were detected in 18 pig blood samples. Conclusion The human Plasmodium DNA in domestic animals within malaria-endemic regions suggests a potential link to the persistence and high prevalence of malaria in these areas. While the findings suggest a potential role of domestic animals in malaria transmission, they remain preliminary and do not definitively establish domestic animals as reservoirs. Further research is necessary to confirm these findings and to better understand the contribution of domestic animals to the transmission dynamics of malaria. -in PLoS Computational Biology on 2024-12-09 14:00:00 UTC. +
in F1000Research on 2024-12-10 10:29:33 UTC.
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-Federated privacy-protected meta- and mega-omics data analysis in multi-center studies with a fully open-source analytic platform
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+Automated Neuroprognostication Via Machine Learning in Neonates with Hypoxic‐Ischemic Encephalopathy
-by Xavier Escriba-Montagut, Yannick Marcon, Augusto Anguita-Ruiz, Demetris Avraam, Jose Urquiza, Andrei S. Morgan, Rebecca C. Wilson, Paul Burton, Juan R. Gonzalez
- -The importance of maintaining data privacy and complying with regulatory requirements is highlighted especially when sharing omic data between different research centers. This challenge is even more pronounced in the scenario where a multi-center effort for collaborative omics studies is necessary. OmicSHIELD is introduced as an open-source tool aimed at overcoming these challenges by enabling privacy-protected federated analysis of sensitive omic data. In order to ensure this, multiple security mechanisms have been included in the software. This innovative tool is capable of managing a wide range of omic data analyses specifically tailored to biomedical research. These include genome and epigenome wide association studies and differential gene expression analyses. OmicSHIELD is designed to support both meta- and mega-analysis, so that it offers a wide range of capabilities for different analysis designs. We present a series of use cases illustrating some examples of how the software addresses real-world analyses of omic data. +Objectives
+Neonatal hypoxic-ischemic encephalopathy is a serious neurologic condition associated with death or neurodevelopmental impairments. Magnetic resonance imaging (MRI) is routinely used for neuroprognostication, but there is substantial subjectivity and uncertainty about neurodevelopmental outcome prediction. We sought to develop an objective and automated approach for the analysis of newborn brain MRI to improve the accuracy of prognostication.
+Methods
+We created an anatomic MRI template from a sample of 286 infants treated with therapeutic hypothermia, and labeled the deep gray-matter structures. We extracted quantitative information, including shape-related information, and information represented by complex patterns (radiomic measures), from each of these structures in all infants. We then trained an elastic net model to use either only these measures, only the infants’ demographic and laboratory data, or both, to predict neurodevelopmental outcomes, as measured by the Bayley Scales of Infant and Toddler Development at 18 months of age.
+Results
+Among those infants for whom Bayley scores were available for cognitive, language, and motor outcomes, we found sets of MRI-based measures that could predict their Bayley scores with correlations that were greater than the correlations based on only the demographic and laboratory data, explained more of the variance in the observed scores, and generated a smaller error; predictions based on the combination of the demographic-laboratory and MRI-based measures were similar or marginally better.
+Interpretation
+Our findings show that machine learning models using MRI-based measures can predict neurodevelopmental outcomes in neonates with hypoxic-ischemic encephalopathy across all neurodevelopmental domains and across the full spectrum of outcomes. ANN NEUROL 2024
-in PLoS Computational Biology on 2024-12-09 14:00:00 UTC. +
in Annals of Neurology on 2024-12-10 10:14:17 UTC.
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-Oscillatory dynamics of Rac1 activity in Dictyostelium discoideum amoebae
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+Letter on Intramedullary Spinal Cord Abscess: Acupuncture Is the Real Infected Villain?
-by Marko Šoštar, Maja Marinović, Vedrana Filić, Nenad Pavin, Igor Weber
- -Small GTPases of the Rho family play a central role in the regulation of cell motility by controlling the remodeling of the actin cytoskeleton. In the amoeboid cells of Dictyostelium discoideum, the active form of the Rho GTPase Rac1 regulates actin polymerases at the leading edge and actin filament bundling proteins at the posterior cortex of polarized cells. We monitored the spatiotemporal dynamics of Rac1 and its effector DGAP1 in vegetative amoebae using specific fluorescent probes. We observed that plasma membrane domains enriched in active Rac1 not only exhibited stable polarization, but also showed rotations and oscillations, whereas DGAP1 was depleted from these regions. To simulate the observed dynamics of the two proteins, we developed a mass-conserving reaction-diffusion model based on the circulation of Rac1 between the membrane and the cytoplasm coupled with its activation by GEFs, deactivation by GAPs and interaction with DGAP1. Our theoretical model accurately reproduced the experimentally observed dynamic patterns, including the predominant anti-correlation between active Rac1 and DGAP1. Significantly, the model predicted a new colocalization regime of these two proteins in polarized cells, which we confirmed experimentally. In summary, our results improve the understanding of Rac1 dynamics and reveal how the occurrence and transitions between different regimes depend on biochemical reaction rates, protein levels and cell size. This study not only expands our knowledge of the behavior of Rac1 GTPases in D. discoideum amoebae but also demonstrates how specific modes of interaction between Rac1 and its effector DGAP1 lead to their counterintuitively anti-correlated dynamics. + -in PLoS Computational Biology on 2024-12-09 14:00:00 UTC. +
in Annals of Neurology on 2024-12-10 10:09:41 UTC.
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-Quantitative perturbation-phenotype maps reveal nonlinear responses underlying robustness of PAR-dependent asymmetric cell division
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+Coat stiffening can explain invagination of clathrin-coated membranes
-by Nelio T. L. Rodrigues, Tom Bland, KangBo Ng, Nisha Hirani, Nathan W. Goehring
- -A key challenge in the development of an organism is to maintain robust phenotypic outcomes in the face of perturbation. Yet, it is often unclear how such robust outcomes are encoded by developmental networks. Here, we use the Caenorhabditis elegans zygote as a model to understand sources of developmental robustness during PAR polarity-dependent asymmetric cell division. By quantitatively linking alterations in protein dosage to phenotype in individual embryos, we show that spatial information in the zygote is read out in a highly nonlinear fashion and, as a result, phenotypes are highly canalized against substantial variation in input signals. Our data point towards robustness of the conserved PAR polarity network that renders polarity axis specification resistant to variations in both the strength of upstream symmetry-breaking cues and PAR protein dosage. Analogously, downstream pathways involved in cell size and fate asymmetry are robust to dosage-dependent changes in the local concentrations of PAR proteins, implying nontrivial complexity in translating PAR concentration profiles into pathway outputs. We propose that these nonlinear signal-response dynamics between symmetry-breaking, PAR polarity, and asymmetric division modules effectively insulate each individual module from variation arising in others. This decoupling helps maintain the embryo along the correct developmental trajectory, thereby ensuring that asymmetric division is robust to perturbation. Such modular organization of developmental networks is likely to be a general mechanism to achieve robust developmental outcomes. +Author(s): Felix Frey and Ulrich S. Schwarz
Clathrin-mediated endocytosis is the main pathway used by eukaryotic cells to take up extracellular material, but the dominant physical mechanisms driving this process are still elusive. Recently, several high-resolution imaging techniques have been used on different cell lines to measure the geomet…
[Phys. Rev. E 110, 064403] Published Tue Dec 10, 2024
-in PLoS Biology on 2024-12-09 14:00:00 UTC. +
in Physical Review E: Biological physics on 2024-12-10 10:00:00 UTC.
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-Incentives for pregnant mothers during antenatal care for better maternal and neonatal health outcomes in low and middle income countries: A Systematic Review and Meta-Analysis [version 1; peer review: awaiting peer review]
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+Supraspinal Plasticity of Axonal Projections From the Motor Cortex After Spinal Cord Injury in Macaques
- Background Universal access to maternal, newborn, and child healthcare is essential for achieving Sustainable Development Goal 3, but the effectiveness of various incentive-based programs for pregnant mothers in low- and middle-income countries (LMICs) remains uncertain. Objective of this systematic review was to determine if incentive-based interventions influenced maternal and neonatal health outcomes. Methods We conducted a search in various databases from inception. All incentive-based interventional studies conducted on pregnant women in LMICs were included. Evidence from the included trials was synthesized using risk ratios (RRs) to compare the outcomes between groups receiving incentives and not receiving incentives. The meta-analysis was conducted using random-effects model. We assessed the quality of the included studies using the Cochrane Risk of Bias 2.0 tool and reviewed the collected data to determine its suitability for meta-analysis. This study is registered in PROSPERO (CRD42021247681). Results Of the 3,897 records that were identified, 11 met eligibility criteria, all of which exhibited varying degrees of risk of bias, ranging from high to some concerns. Analysis of maternal outcomes across studies revealed no significant differences in the likelihood of delivering at a healthcare facility (RR 1.13, 95% CI: 0.86 to 1.47) and in frequency of prenatal care (RR 0.99, 95% CI: 0.88 to 1.12) between intervention and control groups. However, high levels of statistical heterogeneity were observed for both outcomes indicating variability among study results. Similarly, analysis of tetanus vaccine coverage showed no significant difference between groups (RR 1.00, 95% CI: 0.92 to 1.08), with moderate statistical heterogeneity observed. Conclusion The maternal and neonatal outcomes examined in this review did not have any significant differences in intervention group when compared to the control group. The interventions to address maternal health concerns need to follow a multifactorial approach. There is a need for extensive primary research studies in the future. +
+We investigated the reorganization of motor circuits in macaque monkeys following spinal cord injury. Our results showed that projections from the contralesional (affected) motor cortex (M1) to the putamen (Pu), lateral reticular nucleus (LRN), and pontine nucleus (Pn) on the normally nondominant side increased compared to those from the ipsilesional (unaffected) M1. Such reorganization of the corticofugal fibers might be used for the recruitment of the cortico-basal ganglia loop and cortico-cerebellar loop involving the M1 on the ipsilesional side. + +
++
ABSTRACT
+During recovery following spinal cord injury in the macaque, the sensorimotor cortex on the same side as the injury (ipsilesional, unaffected) becomes activated and plays a role in guiding movements of the affected hand. Effective regulation of these movements by the ipsilesional sensorimotor cortex would depend not only on its ability to send motor commands directly to target muscles but also on coordinated functioning with higher-level motor planning systems such as the cortico-basal ganglia and cortico-cerebellar loops. In this study, using anterograde viral tracers, we analyzed the axonal trajectories of corticofugal fibers from the contralesional (affected) primary motor cortex (M1) at the brainstem level in two macaque monkeys with sub-hemisection spinal cord injury at the mid-cervical level. They showed considerable recovery of grasping movements after injury. We found an increase in axonal projections from the contralesional M1 to the contralateral putamen, ipsilateral lateral reticular nucleus, and contralateral pontine nucleus compared to projections from the ipsilesional (unaffected) M1. We propose that these increased projections from the contralesional M1 to the striatum and precerebellar nuclei on the nondominant side may function to recruit the ipsilesional M1 through the cortico-basal ganglia and cortico-cerebellar loops to control hand movements on the affected side during recovery.
-in F1000Research on 2024-12-09 10:44:20 UTC. +
in Journal of Comparative Neurology on 2024-12-10 08:03:24 UTC.
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-Viral interactions with host factors (TIM-1, TAM -receptors, Glut-1) are related to the disruption of glucose and ascorbate transport and homeostasis, causing the haemorrhagic manifestations of viral haemorrhagic fevers. [version 6; peer review: 1 approve
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+Anxiety‐Like Behaviors in Mice Unmasked: Revealing Sex Differences in Anxiety Using a Novel Light‐Heat Conflict Test
- The haemorrhagic features of viral haemorrhagic fevers may be caused by common patterns of metabolic disturbances of the glucose and ascorbate homeostasis. Haemorrhages and vasculature disfunctions are a clinical feature not only of viral haemorrhagic fevers, but also in scurvy, diabetes and thrombotic microangiopathic haemolytic anaemia. Interestingly, the expression of glucose and ascorbate transporter Glut-1 on the erythrocyte membrane is associated with the inability to synthesize ascorbate and is restricted to that very species that are susceptible to filoviruses (primates, humans and fruit bats). Glut-1 may play a pivotal role in haemorrhagic fever pathogenesis. TIM-1 and TAM receptors have been recognized to enhance entry of Ebola, Lassa and Dengue viruses and viral interferences with TIM-1 could disturb its function, disturbing the expression of Glut-1. In those species not able to synthesize ascorbate and expressing Glut-1 on erythrocytes virus could interact with Glut-1 or other functionally related protein, and the influx of glucose into the cells would be severely impaired. As a consequence, transient hyperglycemia and a marked oxidative stress coupled with the high levels of glucose in plasma would be established, and then promote the activation of NF–κB transcription, exacerbating a pro-inflammatory response mediated by cytokines and chemokines: The inability to synthesize ascorbate is an Achilles Heel when trying to counteract the oxidative stress. +
+Tests for mouse anxiety-related behavior do not reliably recapitulate sex differences in human anxiety. The TIDAL conflict test comprises one dark plate that heats to uncomfortable temperatures, and one illuminated-isothermic plate. Female mice persist on the dark-heated plate longer than males; thus, TIDAL reveals clinically relevant sex differences in anxiety-related behavior.
++
ABSTRACT
+Anxiety and chronic pain afflict hundreds of millions worldwide. Anxiety and pain are more prevalent in females compared to males. Unfortunately, robust sex differences in human anxiety are not recapitulated in rodent tests, and results from rodent pain studies frequently fail to translate clinically. Therefore, there is a need to develop tests that reflect the differential salience of anxiety or pain-related stimuli between the sexes. Accordingly, here we introduce the Thermal Increments Dark–Light (TIDAL) conflict test. The TIDAL test places an anxiety-relevant stimulus (dark vs. illuminated chamber) in conflict with a heat-related stimulus (incrementally heated vs. isothermic chamber); mice freely explore both apparatus chambers. Here, we aim to determine whether the TIDAL conflict test reveals in mice underappreciated sex differences in anxiety and/or heat sensitivity. We establish in four distinct experiments that females on the TIDAL conflict test persist substantially longer on the dark-heated plate, suggesting that female mice exhibit elevated anxiety-like behavior. Mice more strongly prefer the heated-dark plate on the TIDAL conflict test compared to control thermal place preference with both chambers illuminated. We also reveal that an anxiety-relieving drug, paroxetine, reduces mouse preference for the heating dark plate, supporting the validity of the TIDAL test. Therefore, our new TIDAL conflict test reliably unmasks the relative salience of anxiety (vs. heat sensitivity): mice that are female exhibit robust anxiety-like behaviors not consistently observed in classical tests. Future studies should incorporate TIDAL and other conflict tests to better understand rodent behavior and to identify mechanisms underlying anxiety and pain.
-in F1000Research on 2024-12-09 10:15:10 UTC. +
in Journal of Neuroscience Research on 2024-12-10 05:28:43 UTC.
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-Out-of-Pocket Expenditure (OOPE) on Selected Surgeries in the Obstetrics and Gynaecology Department incurred by Ayushman Bharat Pradhan Mantri Jan Arogya Yojana (AB-PMJAY), Private Health Insurance and Uninsured Patients in a Tertiary Care Teaching Hospi
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+Correction to “What Do Brain Oscillations Tell About the Human Sense of Smell?”
- Introduction OOPE for healthcare services is a major concern within the Indian healthcare system. 30% of the population remains uninsured despite increasing health insurance coverage. For obstetrics and gynaecology (OBG) patients financial obstacles like OOPE can delay access to health care, evaluating spending patterns can inform policies to enhance accessibility, affordability and equitable health. Methodology A retrospective study was conducted at a tertiary care teaching hospital in Karnataka state of India to analyze OOPE for 905 OBG patients who underwent Cesarean Section(C-Section), Laparoscopic Hysterectomy, Laparoscopic Cystectomy, Laparoscopic Myomectomy and Laparoscopic Assisted Vaginal Hysterectomy (LAVH). These were the top five most performed obstetrics and gynecology surgeries in the tertiary care teaching hospital between January 2023 and July 2023. Data was collected across AB-PMJAY, private health insurance, uninsured patients and analyzed using descriptive statistics (mean, median) and the Shapiro-Wilk test for data normality. Results The study analyzed OOPE across 905 OBG patients. Findings show AB-PMJAY provided full coverage with zero OOPE for all surgeries. Though private health insurance reduced OOPE compared to uninsured patients under private health insurance still faced significant financial burden. Variations existed in minimum and maximum OOPE and percentage of OOPE across different private insurances. All the uninsured patients incurred 100% OOPE, with a median OOPE of Rs. 33,257 (405.67 USD) to Rs. 57,053 (695.76 USD) and a mean OOPE of Rs. 39,848 (485.95 USD) to Rs. 60,687 (740 USD) across the surgeries. Discussion Findings of the study show that AB-PMJAY is highly effective in reducing OOPE and enhancing financial risk protection for OBG patients. Patients covered by private health insurance incurred less OOPE, yet the burden remained considerable. High OOPE rates for uninsured patients (100%) and private health insurance (38.15%) compared to 0% OOPE in AB-PMJAY emphasizes the need for the continued expansion of AB-PMJAY. + -in F1000Research on 2024-12-09 10:12:50 UTC. +
in Journal of Neuroscience Research on 2024-12-10 05:24:14 UTC.
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-Natural disaster and medication preparedness among elderly: a scoping review [version 1; peer review: awaiting peer review]
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+Deconstructing the neural circuit underlying social hierarchy in mice
- Introduction The increasing number of older people and their vulnerability to disaster and medication preparedness as the primary elements of disaster mitigation are necessary to reduce the impact of a disaster. Nevertheless, research on natural disasters and medication preparedness in the elderly population is still lacking. This review aimed to explore all reported research and publications related to natural disasters and medication preparedness among the elderly. Methods A scoping review was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Extension for Scoping Reviews (PRISMA-ScR). A literature search was conducted using the following four databases: Scopus, PubMed, Sage, and Google Scholar. Screening was conducted using the following criteria: articles written in English, open access, and published between 2020 and 2024. Articles must discuss natural disasters and medication preparedness. In the data search, we input several keywords that include “elderly,” “natural disaster,” “preparedness,” and “medication.” Snowballing was then conducted to find articles on preparedness interventions. Data extraction and analysis were then performed. Results and conclusion The findings from this literature review are the majority of studies showing that most elderly people are not well prepared in facing disasters; however, through various programs that have been implemented by either the government or community, the elderly show more preparation when they encounter any natural disaster. + Xin et al. find that in the dorsomedial prefrontal cortex (dmPFC), layer 2/3 neurons projecting to the anterior basolateral amygdala promote losing, whereas layer 5 neurons projecting to the dorsal raphe nucleus and periaqueductal gray promote winning. Moreover, the lose-related pathway inhibits the win-related pathways through local GABAergic interneurons. -in F1000Research on 2024-12-09 10:12:04 UTC. +
in Neuron: In press on 2024-12-10 00:00:00 UTC.
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-Types of refractive errors in a sample of Iraqi children with Intermittent exotropia [version 2; peer review: 1 not approved]
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+The next phase of biomolecular condensate research
- Background One of the most common strabismus types in children is intermittent exotropia, which predominantly occurs in children between the ages of 2 to 4 years. It may affect visual development and often coexists with refractive errors. Unlike esotropia, which usually links to hyperopia, intermittent exotropia might have a different relationship with refractive errors and thus lead to myopia. Methods In this cross-sectional retrospective study from August 2021 to December 2023, 179 patients diagnosed with intermittent exotropia were recruited via an outpatient clinic of Najah Al-Quraishi, Baghdad, Iraq. The refractive errors were compared by autorefractometry and retinoscopy after cycloplegic dilation. Data analysis was constructed under the use of IBM SPSS V.26 for the determination of emmetropia, myopia, and hyperopia prevalence. Results Among the 179 patients, emmetropia was the most commonly observed refractive status, present in 68 patients (38%). Low hyperopia and low myopia were also common, with 64 and 40, respectively. A limited number of patients had moderate/high myopia and moderate/high hyperopia; in detail, the prevalence was following: 5% of patients had moderate myopia, while 0.5% of patients suffered from high myopia; symmetrically, 5% were moderate to high hyperopia. From the data collected, a trend emerged for a low refractive error and symmetric refractive error in both eyes. Conclusion Contrasted to prior conventional wisdom about refractive error in strabismus, it established the greater incidence of emmetropia in patients with intermittent exotropia. The findings call for specific management strategies to be applied in this population. + The Cell Reports team recently attended the Keystone Symposia on Biological Condensates. The meeting was a great opportunity to learn about the latest developments in this exciting area. In this Voices piece, we asked three researchers in the field how the landscape of biomolecular condensate research is evolving. They emphasize the need for new theoretical frameworks and experimental approaches. They discuss the complex nature of biomolecular condensates formed via phase separation, their emergent properties, and the implications for cellular function and disease. -in F1000Research on 2024-12-09 10:08:49 UTC. +
in Cell Reports: Current Issue on 2024-12-10 00:00:00 UTC.
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-Neurodiversity in Saudi Arabia: Towards quality education and reduced inequalities [version 2; peer review: 2 approved with reservations]
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+Complexity of synovial fluid-derived monocyte-macrophage-lineage cells in knee osteoarthritis
- Traditional educational frameworks in Saudi Arabia have historically adopted a deficit-based approach to special education, potentially overlooking the benefits of neurodiversity. As global educational paradigms shift toward inclusive practices, examining the alignment of Saudi special education laws with neurodiversity principles becomes crucial. This content analysis study aimed to explore the existing literature on special education in Saudi Arabia to ascertain whether the laws and policies support or hinder the practice of neurodiversity, a concept that is gaining international recognition but remains nascent in Saudi Arabia. A systematic literature search was performed in Web of Science and Scopus, yielding 21 relevant studies after screening and application of inclusion criteria. A content analysis was conducted, focusing on the categorization of data relevant to special education laws and their implications for neurodiversity. The analysis identified seven key categories, including Implementation of Inclusive education and transition services, that reflect the current state of special education laws in relation to neurodiversity. A conceptual model was developed, illustrating the potential of special education laws to both support and impede neurodiversity in Saudi Arabia and potentially worldwide. + Mikulkova et al. functionally characterized four subpopulations within the synovial fluid-derived monocyte-macrophage lineage in knee osteoarthritis (KOA). Abundant inactive myeloid dendritic cells (type cDC2) were linked to early KOA and mild pain, whereas less common macrophages, monocyte-like cells, and cDC1 dendritic cells revealed new insights into the disease. -in F1000Research on 2024-12-09 10:07:14 UTC. +
in Cell Reports: Current Issue on 2024-12-10 00:00:00 UTC.
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-Mapping evidence of postgraduate research supervision experiences at higher education institutions in Africa: A scoping review protocol [version 1; peer review: awaiting peer review]
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+Restricting lysine normalizes toxic catabolites associated with ALDH7A1 deficiency in cells and mice
- Background The evolving landscape of the African higher education sector necessitated by global higher education reforms and the need for research informed responses to address contextual challenges is partly dependent on effective postgraduate research supervision. A wide range of postgraduate research supervision models and practices are documented globally. In the African context, the experiences of postgraduate research supervision are not clearly understood from the experiences of all stakeholders. Aim The proposed scoping review aims to map evidence on the range of postgraduate research supervision experiences at higher education institutions in Africa. Methods The methodological framework proposed by Arksey and O’Malley will be used to conduct the review. Relevant articles will be sourced from different electronic data bases namely; ERIC, Web of Science, EbscoHost and Scopus. A combination of search terms and Boolean operators will be used to obtain the relevant articles based on the inclusion criteria stipulated within the Population, Context and Concept (PCC) framework of study identification for this review. Results Studies reporting on postgraduate research supervision experiences from the perspective of academics, students and support staff in the African higher education context will be included. The results may also provide insights postgraduate supervision experiences from varying postgraduate research disciplines. Conclusion The findings will provide consolidated empirical evidence on experiences of postgraduate supervision in the African higher education context, thereby providing holistic insight on postgraduate research supervision practices, models currently used, implementation challenges and highlight research gaps. This may inform recommendations that advance knowledge within this field, particularly in the African higher education context. + Johal et al. show that ALDH7A1-deficient cells and mice accumulate lysine metabolites via the saccharopine pathway, which are thought to cause seizures in patients with pyridoxine-dependent epilepsy (PDE). They explore two therapeutic strategies to reduce pathogenic lysine metabolite accumulation, including inhibiting lysine transport or enzymatically depleting lysine. -in F1000Research on 2024-12-09 10:05:05 UTC. +
in Cell Reports: Current Issue on 2024-12-10 00:00:00 UTC.
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-Platelet-rich plasma as a potential therapy of cystocele: a systematic review and meta-analysis [version 1; peer review: awaiting peer review]
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+Legionella uses host Rab GTPases and BAP31 to create a unique ER niche
- Abstract Background Platelet-rich plasma (PRP) therapy, is known for its regenerative properties. PRP may be able to help with cystocele cases. This review aims to explore how it might be applied to urogynecological cases, particularly those involving cystocele. Methods The present systematic review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guideline 2020, Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guideline. The present systematic review was registered with PROSPERO with the registered number CRD42023414366. PubMed, Science Direct, Epistemonikos, COCHRANE, Google Scholar, and ProQuest were among the databases we searched. “(PRP OR Platelet-Rich Plasma) AND (Cystocele OR Anterior Pelvic Organ Prolapse)” from January 2007 to December 2022. Based on the PICO framework (Population = Patients with Cystocele; Intervention = Reconstruction with platelet-rich plasma injection; Compare = Reconstruction only; Outcome: Recurrency of Cystocele), four investigators (AMS, PMA, EAU, RSD, and AH) independently assessed eligibility by titles and abstracts. Using the Joanna Briggs Institute Critical Appraisal tool, each author evaluated full-text articles based on the kind of articles they had received. When consensus could not be obtained, disagreements were settled by involving the supervisors (EF, EMK, and BS). Results A total of 8,924 studies were identified. After removing duplicates and applying eligibility criteria, two articles were included, encompassing 65 patients. In two studies, PRP injections were found and administered post-anterior colporrhaphy at the pubovesical fascia. According to these two trials, women who had anterior colporrhaphy and PRP injections required fewer reoperations. Conclusion PRP has the potential to be a good alternative treatment to prevent cystocele recurrence. However, it cannot be generalized to large populations due to the small number of findings. Further studies with large samples examining the efficacy and safety of the therapy are needed to prove it. + Chadha et al. demonstrate that Legionella pneumophila manipulates host cell membranes to form the Legionella-containing vacuole (LCV), which is distinct from the host rough ER. This transition is driven by host proteins BAP31, GTPases Rab10 and Rab4, and the Legionella effector Lpg1152. -in F1000Research on 2024-12-09 10:03:29 UTC. +
in Cell Reports: Current Issue on 2024-12-10 00:00:00 UTC.
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-Complications following miniplate insertion in maxillofacial fractures: a systematic review [version 1; peer review: awaiting peer review]
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+Multi-conflict islands are a widespread trend within Serratia spp.
- Background Maxillofacial fractures, frequently arising from road traffic incidents, falls, and acts of interpersonal aggression, are a considerable public health issue, exhibiting diverse epidemiological patterns according to demographic factors. The application of miniplates for fracture stabilization is a recognized technique, with innovative methods such as 3D plate systems emerging. Nonetheless, consequences including infections and hardware malfunctions persist. This systematic review seeks to present current evidence regarding the complications linked to miniplate placement in maxillofacial fractures over the last ten years. Methods A systematic review was performed in accordance with PRISMA principles. Databases such as the Cochrane Library, PubMed, and Scopus were examined from September 2014 to September 2024. Studies documenting problems related to miniplate placement were included, without language constraints. The ROBINS-I tool was utilized for non-randomized studies, whereas the Cochrane risk of bias tool was applied to randomized controlled trials. Results From 2,289 initially found studies, 56 satisfied the inclusion criteria. Among these, 28 employed interventional designs, whilst the remaining 28 were observational research. The predominant problems documented in several investigations encompassed infection, wound dehiscence, malocclusion, paraesthesia, malunion/non-union, segment movement, hardware failure, and palpable hardware. Advanced methodologies such as 3D plate systems and locking mechanisms were linked to diminished complication rates. Conclusion This systematic analysis presents a decade of updated research about problems associated with miniplate placement in maxillofacial fractures. Novel methodologies such as 3D plate systems and locking mechanisms demonstrate promise in mitigating problems relative to conventional techniques. These findings can facilitate informed decision-making in clinical practice. Additional study utilizing standardized outcomes and prospective designs is essential to enhance comprehension of the long-term effects of miniplate utilization. + Cummins, Songra et al. identify three Serratia defense islands co-localizing anti-phage systems, virulence factors, and anti-bacterial factors. These islands provide a resource for discovering previously unreported systems, including four newly identified anti-phage systems (SDIC1–4). Notably, SDIC1 and SDIC4 exhibit distinct mechanisms, with SDIC1 using ubiquitination to inhibit its toxin in a TA-like manner. -in F1000Research on 2024-12-09 10:02:12 UTC. +
in Cell Reports: Current Issue on 2024-12-10 00:00:00 UTC.
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-Does Brand Attitude Complement Influencer Credibility in Shaping Purchase Intention of Indian GenZ Consumers? [version 2; peer review: 1 approved]
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+Mapping functional elements of the DNA damage response through base editor screens
- Introduction The social media landscape has undergone radical changes and has revolutionized consumer perspectives, purchasing habits, and behaviours. Amidst this emerging trend is the rise of influencer marketing and its impact on the purchase intentions of followers. The objective is to explore the characteristics of influencers that contribute to their credibility. This research aims to explore the role of consumers’ attitude toward brands on their intention to adopt brands endorsed by influencers. Methods This cross-sectional research was undertaken among GenZ in the urban landscape of India. Data collected was analyzed using SmartPLS4 software. Findings Trust, expertise, and similarity were the significant antecedents of the formation of influencer credibility. Attractiveness did not have a significant influence on influencer credibility. A complementary partial mediation of Attitude towards a brand is observed in the association between influencer credibility and the purchase intention of followers. Attitude towards the video also had a significant positive influence on purchase intention. Conclusion The study found that Gen Z places little importance on an influencer’s attractiveness, as it has no significant impact on credibility. However, attitude toward the brand strongly influenced purchase intention and partially mediated the relationship between influencer credibility and purchase intention. + Pan et al. employ CRISPR-mediated base editing in pooled screens to investigate the functional lysine residues and genes affecting the DNA damage response. They identify the K494 mutation in C17orf53, which increases cisplatin sensitivity, and emphasize STK35 as a novel gene involved in DNA repair, offering insights for cancer therapy. -in F1000Research on 2024-12-09 09:59:25 UTC. +
in Cell Reports: Current Issue on 2024-12-10 00:00:00 UTC.
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-SYSTEMATIC LITERATURE REVIEW: SERVANT LEADERSHIP IN PUBLIC SECTORS [version 1; peer review: awaiting peer review]
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+Adiponectin receptor 1-mediated basolateral amygdala-prelimbic cortex circuit regulates methamphetamine-associated memory
- Servant leadership delivers important reforms to the increasingly complex public utility system. This systematic review seeks to incorporate the latest six years of articles on geographic divisions, conceptual definitions, measuring techniques, theoretical frameworks, and nomological networks (antecedents, mediators, outcomes, and moderators) in the public sector. The risk of bias was evaluated using the Cochrane Risk of Bias Tool and ROBINS-I, and employing automated techniques such as Rayyan for screening. Using PRISMA’s review approach, this comprehensive synthesis of 51 relevant public sector-specific conceptual and empirical studies across six academic electronic databases (Taylor & Francis, Sage, Scopus, Springer Link, Web of Science, and Wiley) shows that servant leadership is critical for establishing a prosocial workforce. This review discovered that the global construct of servant leadership (SL-7) scale has been the most often utilised measure of servant leadership in public sector-specific studies recently. Social exchange theory remains the predominant explanation for the impact of servant leadership on specific variables. The findings also illustrate a generally positive influence of servant leadership. Moreover, this review provides limitations and suggestions for future studies by summarising elements that have received less attention. + Chen et al. reveal the critical roles of AdipoR1 in the BLA that regulate methamphetamine (MA) reward memory and show that AdipoR1 signaling is modulated by physical exercise as an alternative intervention strategy for MA addiction, presenting a potential target for managing MA use disorders. -in F1000Research on 2024-12-09 09:57:29 UTC. +
in Cell Reports: Current Issue on 2024-12-10 00:00:00 UTC.
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-Trends in Smart Restaurant Research: Bibliometric Review and Research Agenda [version 1; peer review: awaiting peer review]
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+Prolonged cell cycle arrest in response to DNA damage in yeast requires the maintenance of DNA damage signaling and the spindle assembly checkpoint
- Background The automation of processes and services has transformed various industries, including the restaurant sector. Technologies such as the Internet of Things (IoT), machine learning, Radio Frequency Identification (RFID), and big data have been increasingly adopted to enhance service delivery, improve user experiences, and enable data traceability. By collecting user feedback and analyzing sentiments, these technologies facilitate decision-making and offer predictive insights into future food preferences. This study aims to explore current research trends in intelligent restaurants, focusing on technological applications that improve service and decision-making. Methods A bibliometric analysis was conducted in accordance with the PRISMA-2020 guidelines. A total of 94 academic documents were reviewed from the Scopus and Web of Science databases, focusing on publications related to intelligent restaurant systems, particularly involving IoT and automation technologies. Results The analysis revealed that the United States, India, and China have contributed the most to the field, with a particular emphasis on China’s implementation of IoT architecture and robotics in restaurant settings. Chinese restaurant innovations, particularly in robotics, are among the most frequently cited in the literature. The study identifies these countries as leading the research in the intelligent restaurant domain. Conclusions Technologies such as IoT, machine learning, RFID, and big data are driving advancements in restaurant automation, enhancing service efficiency and user experience. The United States, India, and China are leading research in this area, with China standing out for its application of robotics and IoT in restaurants. This research provides a foundation for future studies aimed at improving predictive models for food selection and service optimization. + Cells evoke the DNA damage checkpoint (DDC) to inhibit mitosis in the presence of DNA double-strand breaks (DSBs) to allow more time for DNA repair. In budding yeast, a single irreparable DSB is sufficient to activate the DDC and induce cell cycle arrest prior to anaphase for about 12–15 hr, after which cells ‘adapt’ to the damage by extinguishing the DDC and resuming the cell cycle. While activation of the DNA damage-dependent cell cycle arrest is well understood, how it is maintained remains unclear. To address this, we conditionally depleted key DDC proteins after the DDC was fully activated and monitored changes in the maintenance of cell cycle arrest. Degradation of Ddc2ATRIP, Rad9, Rad24, or Rad53CHK2 results in premature resumption of the cell cycle, indicating that these DDC factors are required both to establish and maintain the arrest. Dun1 is required for the establishment, but not the maintenance, of arrest, whereas Chk1 is required for prolonged maintenance but not for initial establishment of the mitotic arrest. When the cells are challenged with two persistent DSBs, they remain permanently arrested. This permanent arrest is initially dependent on the continuous presence of Ddc2, Rad9, and Rad53; however, after 15 hr these proteins become dispensable. Instead, the continued mitotic arrest is sustained by spindle assembly checkpoint (SAC) proteins Mad1, Mad2, and Bub2 but not by Bub2’s binding partner Bfa1. These data suggest that prolonged cell cycle arrest in response to 2 DSBs is achieved by a handoff from the DDC to specific components of the SAC. Furthermore, the establishment and maintenance of DNA damage-induced cell cycle arrest require overlapping but different sets of factors. -in F1000Research on 2024-12-09 09:55:55 UTC. +
in eLife on 2024-12-10 00:00:00 UTC.
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-The first mitochondrial genome of Haemagogus equinus from Jamaica [version 1; peer review: awaiting peer review]
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+Molecular, cellular, and developmental organization of the mouse vomeronasal organ at single cell resolution
- In the Americas, the expansion in incidence of arboviral infections including Mayaro virus (MAYV) has drawn attention to the resurgence of viruses associated with understudied arthropods. Mosquitoes belonging to the genus Haemagogus are generally geographically restricted to the forests of Central and South America and the Caribbean and are the known sylvan vectors for yellow fever virus and emerging MAYV. With an established population in Jamaica, Haemagogus equinus has been reported to be well-adapted to oviposition in artificial containers close to human populations. Its role in arboviral transmission however is not fully understood. Given the dearth of genetic information and the difficulty in morphologically identifying cryptic features in species belonging to this genus, we report the first mitochondrial genome of Hg. equinus. Using a genome skimming approach, two Hg. equinus mosquito specimens were sequenced using the Illumina Novaseq 6000 platform. A representative mitogenome of 16,471 bp, 80.7% AT and 37 genes was assembled using NOVOplasty. Phylogenetic analysis placed Hg. equinus in the Albomaculatus section of the Haemagogus subgenus supporting previously described taxonomic studies. + We have generated single cell transcriptomic atlases of vomeronasal organs (VNO) from juvenile and adult mice. Combined with spatial molecular imaging, we uncover a distinct, previously unidentified class of cells that express the vomeronasal receptors (VRs) and a population of canonical olfactory sensory neurons in the VNO. High-resolution trajectory and cluster analyses reveal the lineage relationship, spatial distribution of cell types, and a putative cascade of molecular events that specify the V1r, V2r, and OR lineages from a common stem cell population. The expression of vomeronasal and olfactory receptors follow power law distributions, but there is high variability in average expression levels between individual receptor and cell types. Substantial co-expression is found between receptors across clades, from different classes, and between olfactory and VRs, with nearly half from pairs located on the same chromosome. Interestingly, the expression of V2r, but not V1r, genes is associated with various transcription factors, suggesting distinct mechanisms of receptor choice associated with the two cell types. We identify association between transcription factors, surface axon guidance molecules, and individual VRs, thereby uncovering a molecular code that guides the specification of the vomeronasal circuitry. Our study provides a wealth of data on the development and organization of the accessory olfactory system at both cellular and molecular levels to enable a deeper understanding of vomeronasal system function. -in F1000Research on 2024-12-09 09:54:14 UTC. +
in eLife on 2024-12-10 00:00:00 UTC.
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-Life Cycle Assessment of Microalgae-Based Products for Carbon Dioxide Utilization in Thailand: Biofertilizer, Fish Feed, and Biodiesel [version 1; peer review: awaiting peer review]
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+Male rats emit aversive 44-kHz ultrasonic vocalizations during prolonged Pavlovian fear conditioning
- Background Microalgae-based products offer a sustainable solution for food, fuel, and agricultural inputs, presenting environmental benefits and economic opportunities. A comprehensive assessment is needed to understand their potential in supporting sustainability goals, considering the complex interplay between production methods, energy sources, and environmental impacts. Methods This study evaluated the environmental impacts of three microalgae-derived products – biodiesel, fish feed, and biofertilizer – through a comprehensive life cycle assessment. Nine scenarios were explored comparing three electricity profiles (current Thai mix, 50% renewable/50% current mix hybrid, 100% renewable) across the three products. The assessment evaluated environmental impacts and potential economic benefits of transitioning to these microalgae-based alternatives. Results and discussion All products demonstrated potential for significant environmental benefits under increased renewable energy scenarios. Fish feed consistently exhibited the lowest environmental impacts across all categories examined, showing substantial improvements with increased renewable energy use. With an annual demand of 0.4 million tonnes, fish feed could generate USD 560 million in revenue and reduce CO2 emissions by 1.1 million tonnes. Fulfilling the projected biodiesel demand of 4,015 million liters per year through microalgae production could yield approximately USD 3.5 billion in revenue and reduce CO2 emissions by 30 million tonnes compared to conventional fossil-based diesel. Additionally, algal biofertilizer production could meet a 5 million tonnes annual demand, offering USD 2 billion in revenue while reducing CO2 emissions by 6 million tonnes yearly. Collectively, these products could offset 37 million tonnes of CO2, representing about 14% of Thailand’s total CO2 emissions, contributing significantly to the country’s Nationally Determined Contribution (NDC) target of 20-30% greenhouse gas emissions reduction. Conclusion Transitioning to microalgae-based products could transform the aquaculture, energy, and agricultural sectors, potentially supporting the national climate change mitigation goals, if implemented. + Rats are believed to communicate their emotional state by emitting two distinct types of ultrasonic vocalizations. The first is long ‘22-kHz’ vocalizations (>300 ms, <32-kHz) with constant frequency, signaling aversive states, and the second is short ‘50-kHz’ calls (<150 ms, >32 kHz), often frequency-modulated, in appetitive situations. Here, we describe aversive vocalizations emitted at a higher pitch by male Wistar and spontaneously hypertensive rats (SHR) in an intensified aversive state – prolonged fear conditioning. These calls, which we named ‘44-kHz’ vocalizations, are long (>150 ms), generally at a constant frequency (usually within 35–50-kHz range) and have an overall spectrographic image similar to 22-kHz calls. Some 44-kHz vocalizations are comprised of both 22-kHz-like and 44-kHz-like elements. Furthermore, two separate clustering methods confirmed that these 44-kHz calls can be separated from other vocalizations. We observed 44-kHz calls to be associated with freezing behavior during fear conditioning training, during which they constituted up to 19.4% of all calls and most of them appeared next to each other forming uniform groups of vocalizations (bouts). We also show that some of rats’ responses to the playback of 44-kHz calls were more akin to that of aversive calls, for example, heart rate changes, whereas other responses were at an intermediate level between aversive and appetitive calls. Our results suggest that rats have a wider vocal repertoire than previously believed, and current definitions of major call types may require reevaluation. We hope that future investigations of 44-kHz calls in rat models of human diseases will contribute to expanding our understanding and therapeutic strategies related to human psychiatric conditions. -in F1000Research on 2024-12-09 09:52:49 UTC. +
in eLife on 2024-12-10 00:00:00 UTC.
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-Molecular docking and dynamics studies to identify novel active compounds targeting potential breast cancer receptor proteins from an indigenous herb Euphorbia thymifolia Linn [version 3; peer review: 1 approved]
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+Ligand-coupled conformational changes in a cyclic nucleotide-gated ion channel revealed by time-resolved transition metal ion FRET
- Background Breast cancer has become the most prevalent disease and its incidence has almost doubled in the Indian population. This increased burden demands new targeted therapies with novel compounds either synthetically produced or derived from indigenous plants, which could be a promising approach for the development of drugs. Euphorbia thymifolia L is a widely growing tropical herb that has been reported to have various ethnopharmacological properties. Although Euphorbia genus is reported to have anticancer properties, E. thymifolia is not reported to have anticancer properties to date. Therefore, the aim of the present study was to screen the phytoconstituents and identify the active compounds present in the methanolic extract of E. thymifolia (ME.ET) as ligands to inhibit human cancer cell lines with special reference to potential protein targets implicated in breast cancer using an In-silico approach. Methods ME.ET was subjected to GC-MS analysis to screen the phytoconstituents, and the identified compounds were docked with protein targets such as extracellular signal-regulated kinases (ERK1), a serine/threonine kinase-1(AKT1), human epidermal growth factor 2 (HER2), estrogen receptor (ER), maternal embryonic leucine zipper kinase (MELK), polo-like kinase-1(PLK1), and protein tyrosine kinase (PTK6). Compounds with good docking scores were further subjected to dynamic studies to understand the protein ligand binding stability, ligand pathway calculation, and molecular mechanics energies combined with Poisson-Boltzmann (MM/PBSA) calculations using the Schrodinger suite. Results GC-MS analysis revealed the presence of 245 phytoconstituents, 219 of which were unique. When subjected to docking, these phytocompounds, namely 3,6,9,12-tetraoxatetradecane-1,14-diyl dibenzoate (TTDB) and succinic acid, 2-(dimethylamino) ethyl 4-isopropylphenyl ester (SADPE), showed good docking scores. Molecular dynamics studies showed a high affinity and low binding energy for TTDB with HER2, ERK1, and SADPE with ER. Conclusions Hence, in this study, we identified two lead compounds in E.thymifolia linn. Further invitro and invivo anticancer studies can be performed to confirm these results and to understand the molecular mechanism by which they exhibit anticancer activity against breast cancer. + Cyclic nucleotide-binding domain (CNBD) ion channels play crucial roles in cellular-signaling and excitability and are regulated by the direct binding of cyclic adenosine- or guanosine-monophosphate (cAMP, cGMP). However, the precise allosteric mechanism governing channel activation upon ligand binding, particularly the energetic changes within domains, remains poorly understood. The prokaryotic CNBD channel SthK offers a valuable model for investigating this allosteric mechanism. In this study, we investigated the conformational dynamics and energetics of the SthK C-terminal region using a combination of steady-state and time-resolved transition metal ion Förster resonance energy transfer (tmFRET) experiments. We engineered donor-acceptor pairs at specific sites within a SthK C-terminal fragment by incorporating a fluorescent noncanonical amino acid donor and metal ion acceptors. Measuring tmFRET with fluorescence lifetimes, we determined intramolecular distance distributions in the absence and presence of cAMP or cGMP. The probability distributions between conformational states without and with ligand were used to calculate the changes in free energy (ΔG) and differences in free energy change (ΔΔG) in the context of a simple four-state model. Our findings reveal that cAMP binding produces large structural changes, with a very favorable ΔΔG. In contrast to cAMP, cGMP behaved as a partial agonist and only weakly promoted the active state. Furthermore, we assessed the impact of protein oligomerization and ionic strength on the structure and energetics of the conformational states. This study demonstrates the effectiveness of time-resolved tmFRET in determining the conformational states and the ligand-dependent energetics of the SthK C-terminal region. -in F1000Research on 2024-12-09 09:51:53 UTC. +
in eLife on 2024-12-10 00:00:00 UTC.
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-Is publishing gold open-access worth it? An assessment of hybrid and gold open-access publishing models of medical journals on their impact [version 1; peer review: awaiting peer review]
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+SLAM/SAP signaling regulates discrete γδ T cell developmental checkpoints and shapes the innate-like γδ TCR repertoire
- Background Hybrid and gold open-access (OA) are the most common publishing models. The latter requires fees to allow full-text visibility upon publishing, whereas hybrid journals offer the option to publish gold OA or for free (subscription-based) where only users with access can get the full-text. We aimed to evaluate the impact of the publishing model and other factors on medical journals’ impact. Methods A sample of hybrid and gold OA medical journals indexed in Web of Science (WOS) and Scopus were included. The effect of the publishing model and other factors on journals’ impact factor (IF), CiteScore, quartile, and number of citations was assessed. Results 402 journals were included, 201 in each group. Hybrid and gold OA journals had a median age of 32 and 21 years, respectively (P<0.001). The median publishing cost in gold OA journals was $2,690, and 46.3% of them publish continuously. Publishing model, journal’s age, being of an organization/society, and EMBASE indexation didn’t affect IF, CiteScore, number of citations, and WOS quartile (P>0.05). However, gold OA model wasn’t significantly associated with Q1 ranking in Scopus (OR, 0.49; 95% CI, 0.25-0.94; P=0.032), which indicates that hybrid journals were more likely to have such ranking. Conclusion These findings indicate that gold OA publishing doesn’t necessarily result in higher impact, which contradicts the claim that such model enhances citations. Therefore, authors can continue to publish in hybrid journals without being concerned about getting cited. Gold OA journals are encouraged to reduce their fees to facilitate global research access. + During thymic development, most γδ T cells acquire innate-like characteristics that are critical for their function in tumor surveillance, infectious disease, and tissue repair. The mechanisms, however, that regulate γδ T cell developmental programming remain unclear. Recently, we demonstrated that the SLAM/SAP signaling pathway regulates the development and function of multiple innate-like γδ T cell subsets. Here, we used a single-cell proteogenomics approach to identify SAP-dependent developmental checkpoints and to define the SAP-dependent γδ TCR repertoire in mice. SAP deficiency resulted in both a significant loss of an immature Gzma+Blk+Etv5+Tox2+ γδT17 precursor population and a significant increase in Cd4+Cd8+Rorc+Ptcra+Rag1+ thymic γδ T cells. SAP-dependent diversion of embryonic day 17 thymic γδ T cell clonotypes into the αβ T cell developmental pathway was associated with a decreased frequency of mature clonotypes in neonatal thymus, and an altered γδ TCR repertoire in the periphery. Finally, we identify TRGV4/TRAV13-4(DV7)-expressing T cells as a novel, SAP-dependent Vγ4 γδT1 subset. Together, the data support a model in which SAP-dependent γδ/αβ T cell lineage commitment regulates γδ T cell developmental programming and shapes the γδ TCR repertoire. -in F1000Research on 2024-12-09 09:49:04 UTC. +
in eLife on 2024-12-10 00:00:00 UTC.
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-Long‐Term Potentiation: The Accidental Discovery
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+Value construction through sequential sampling explains serial dependencies in decision making
-ABSTRACT
-Long-term potentiation (LTP), is a type of synaptic plasticity now considered essential for learning and memory. Here I tell the story of how I accidentally discovered in 1966 in the laboratory of Per Andersen in Oslo, Norway, because I was not looking for it. It just emerged. I recount how I came to work with Per and why my result was not immediately followed up. Then, in 1968 Tim Bliss joined the lab and, on his urging, from 1968 to 1969 we did the experiments that resulted in Bliss and Lømo, 1973. I explain why I think the experiments later failed in Oslo, and for a few years also in Tim's lab in London, before it became a readily observable phenomenon. I also describe how Tony Gardner-Medwin and I in 1971 failed to reproduce the results that Tim and I had obtained 2 years earlier in the same lab and the same type of anesthetized rabbit preparation. I tell how this failure caused me to leave the LTP field and, instead, continue exploring mechanisms of nerve–muscle interactions, which I had studied with much success during my postdoc period in London from 1969 to 1971. I reflect on Donald Hebb's influence on LTP studies and on my experience when after many years of neglect, I became interested in LTP and the hippocampus anew and started to write about it, though without doing lab experiments. Finally, I report briefly on the experiments I am doing now in retirement, studying how the nervous system regulates body temperature through varying amounts of muscle tone.
+ Deciding between a pair of familiar items is thought to rely on a comparison of their subjective values. When the values are similar, decisions take longer, and the choice may be inconsistent with stated value. These regularities are thought to be explained by the same mechanism of noisy evidence accumulation that leads to perceptual errors under conditions of low signal to noise. However, unlike perceptual decisions, subjective values may vary with internal states (e.g. desires, priorities) that change over time. This raises the possibility that the apparent stochasticity of choice reflects changes in value rather than mere noise. We hypothesized that these changes would manifest in serial dependencies across decision sequences. We analyzed data from a task in which participants chose between snack items. We developed an algorithm, Reval, that revealed significant fluctuations of the subjective values of items within an experimental session. The dynamic values predicted choices and response times more accurately than stated values. The dynamic values also furnished a superior account of the BOLD signal in ventromedial prefrontal cortex. A novel bounded-evidence accumulation model with temporally correlated evidence samples supports the idea that revaluation reflects the dynamic construction of subjective value during deliberation, which in turn influences subsequent decisions. -in Hippocampus on 2024-12-09 07:49:13 UTC. +
in eLife on 2024-12-10 00:00:00 UTC.
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-Adult Neurogenesis in the Human Dentate Gyrus
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+Semantic relatedness proactively benefits learning, memory, and interdependence across episodes
-ABSTRACT
-In the adult dentate gyrus of the hippocampus there are neuronal stem cells that give rise to immature neurons and subsequently to mature functional granule neurons. The rate of proliferation, differentiation, and survival is regulated intrinsically and extrinsically. For example, Wnt, BMP, TLX, and BDNF all regulate adult neurogenesis intrinsically, while exercise, environmental enrichment, stress, and epilepsy are some of the extrinsic factors that regulate adult neurogenesis. A clearer picture is emerging for the functional role of these newly born neurons in behavior, demonstrating that adult neurogenesis plays a role in recognizing events, places, objects, or people as unique when comparing options that are very similar, but that these newly born cells play little role in recognition when differences are greater. Most of the research on adult neurogenesis is conducted in experimental mammals, including mice and rats. The first evidence for adult neurogenesis in humans was reported in 1998, when postmortem brains from cancer patients injected with bromodeoxyuridine (BrdU) were examined and cells were found that had divided and differentiated into mature neurons. Subsequently, additional evidence using other techniques has confirmed human adult neurogenesis. Additional in vivo live reports will be needed to monitor the effects of changes in human adult neurogenesis with age and disease.
+ Over the past century of memory research, the interplay between initial and later-learned information in determining long-term memory retention has been of central interest. A likely factor for determining whether initial and later memories interfere with or strengthen each other is semantic relatedness. Relatedness has been shown to retroactively boost initial memory and increase the interdependence between earlier and more recent experiences in memory. Here, we investigated the converse relationship of how relatedness proactively affects later memory for paired associates. In five experiments (N=1000 total), we varied the relatedness between initial and later cues, initial and later targets, or both. Across experiments and conditions, relatedness profoundly benefited later-learned memories – in some conditions, low relatedness reliably produced proactive interference (versus a control condition) while high relatedness produced proactive facilitation within the same experiment. Additionally, relatedness also accelerated learning and increased interdependence between initial and later-learned pairs. In sum, we demonstrate the robust effects of relatedness in scaffolding memory for recently learned information and creating strong integrative links with prior experiences. -in Hippocampus on 2024-12-09 07:48:40 UTC. +
in eLife on 2024-12-10 00:00:00 UTC.
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-Spatial organizations of heterochromatin underpin nuclear structural integrity of ventricular cardiomyocytes against mechanical stress
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+A novel image segmentation method based on spatial autocorrelation identifies A-type potassium channel clusters in the thalamus
- Cardiomyocytes exhibit characteristic prominent spatial organizations of heterochromatin (SOH). Fujiwara et al. found that the replacement of endogenous H2B with H2B-mCherry disrupts SOH, leading to extreme elongation of ventricular cardiomyocyte nuclei, resulting in severe heart failure, demonstrating that SOH play a structural role in maintaining nuclear shape against mechanical stress. + Unsupervised segmentation in biological and non-biological images is only partially resolved. Segmentation either requires arbitrary thresholds or large teaching datasets. Here, we propose a spatial autocorrelation method based on Local Moran’s I coefficient to differentiate signal, background, and noise in any type of image. The method, originally described for geoinformatics, does not require a predefined intensity threshold or teaching algorithm for image segmentation and allows quantitative comparison of samples obtained in different conditions. It utilizes relative intensity as well as spatial information of neighboring elements to select spatially contiguous groups of pixels. We demonstrate that Moran’s method outperforms threshold-based method in both artificially generated as well as in natural images especially when background noise is substantial. This superior performance can be attributed to the exclusion of false positive pixels resulting from isolated, high intensity pixels in high noise conditions. To test the method’s power in real situation, we used high power confocal images of the somatosensory thalamus immunostained for Kv4.2 and Kv4.3 (A-type) voltage-gated potassium channels in mice. Moran’s method identified high-intensity Kv4.2 and Kv4.3 ion channel clusters in the thalamic neuropil. Spatial distribution of these clusters displayed strong correlation with large sensory axon terminals of subcortical origin. The unique association of the special presynaptic terminals and a postsynaptic voltage-gated ion channel cluster was confirmed with electron microscopy. These data demonstrate that Moran’s method is a rapid, simple image segmentation method optimal for variable and high noise conditions. -in Cell Reports: Current Issue on 2024-12-09 00:00:00 UTC. +
in eLife on 2024-12-10 00:00:00 UTC.
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-Cytokines reprogram airway sensory neurons in asthma
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+Tissue-resident natural killer cells support survival in pancreatic cancer through promotion of cDC1-CD8 T activity
- Nociceptor neurons play multiple roles in asthma by exacerbating inflammation and bronchial hypersensitivity and triggering mucus metaplasia. Crosson et al. characterize a distinct subset of NPY1R-expressing sensory neurons that innervate the lung and describe their transcriptional and functional reprogramming by the asthma-driving cytokine IL-13. + The immunosuppressive microenvironment in pancreatic ductal adenocarcinoma (PDAC) prevents tumor control and strategies to restore anti-cancer immunity (i.e. by increasing CD8 T-cell activity) have had limited success. Here, we demonstrate how inducing localized physical damage using ionizing radiation (IR) unmasks the benefit of immunotherapy by increasing tissue-resident natural killer (trNK) cells that support CD8 T activity. Our data confirms that targeting mouse orthotopic PDAC tumors with IR together with CCR5 inhibition and PD1 blockade reduces E-cadherin positive tumor cells by recruiting a hypoactive NKG2D-ve NK population, phenotypically reminiscent of trNK cells, that supports CD8 T-cell involvement. We show an equivalent population in human single-cell RNA sequencing (scRNA-seq) PDAC cohorts that represents immunomodulatory trNK cells that could similarly support CD8 T-cell levels in a cDC1-dependent manner. Importantly, a trNK signature associates with survival in PDAC and other solid malignancies revealing a potential beneficial role for trNK in improving adaptive anti-tumor responses and supporting CCR5 inhibitor (CCR5i)/αPD1 and IR-induced damage as a novel therapeutic approach. -in Cell Reports: Current Issue on 2024-12-09 00:00:00 UTC. +
in eLife on 2024-12-10 00:00:00 UTC.
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-Spinal microcircuits go through multiphasic homeostatic compensations in a mouse model of motoneuron degeneration
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+Lipid discovery enabled by sequence statistics and machine learning
- Through in vitro and in vivo electrophysiology and super-resolution microscopy, Nascimento et al. identify early-stage alterations in pre-motor spinal recurrent inhibition and monosynaptic Ia excitation in the mSOD1 mouse model of ALS. The authors describe that such changes are multiphasic across disease progression, thus providing insights into disease pathophysiology. + Bacterial membranes are complex and dynamic, arising from an array of evolutionary pressures. One enzyme that alters membrane compositions through covalent lipid modification is MprF. We recently identified that Streptococcus agalactiae MprF synthesizes lysyl-phosphatidylglycerol (Lys-PG) from anionic PG, and a novel cationic lipid, lysyl-glucosyl-diacylglycerol (Lys-Glc-DAG), from neutral glycolipid Glc-DAG. This unexpected result prompted us to investigate whether Lys-Glc-DAG occurs in other MprF-containing bacteria, and whether other novel MprF products exist. Here, we studied protein sequence features determining MprF substrate specificity. First, pairwise analyses identified several streptococcal MprFs synthesizing Lys-Glc-DAG. Second, a restricted Boltzmann machine-guided approach led us to discover an entirely new substrate for MprF in Enterococcus, diglucosyl-diacylglycerol (Glc2-DAG), and an expanded set of organisms that modify glycolipid substrates using MprF. Overall, we combined the wealth of available sequence data with machine learning to model evolutionary constraints on MprF sequences across the bacterial domain, thereby identifying a novel cationic lipid. -in Cell Reports: Current Issue on 2024-12-09 00:00:00 UTC. +
in eLife on 2024-12-10 00:00:00 UTC.
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-Polarised moonlight guides nocturnal bull ants home
+UGGT1-mediated reglucosylation of N-glycan competes with ER-associated degradation of unstable and misfolded glycoproteins
- For the first time in any animal, we show that nocturnal bull ants use the exceedingly dim polarisation pattern produced by the moon for overnight navigation. The sun or moon can provide directional information via their position; however, they can often be obstructed by clouds, canopy, or the horizon. Despite being hidden, these bodies can still provide compass information through the polarised light pattern they produce/reflect. Sunlight produces polarised light patterns across the overhead sky as it enters the atmosphere, and solar polarised light is a well-known compass cue for navigating animals. Moonlight produces an analogous pattern, albeit a million times dimmer than sunlight. Here, we show evidence that polarised moonlight forms part of the celestial compass of navigating nocturnal ants. Nocturnal bull ants leave their nest at twilight and rely heavily on the overhead solar polarisation pattern to navigate. Yet many foragers return home overnight when the sun cannot guide them. We demonstrate that these bull ants use polarised moonlight to navigate home during the night, by rotating the overhead polarisation pattern above homing ants, who alter their headings in response. Furthermore, these ants can detect this cue throughout the lunar month, even under crescent moons, when polarised light levels are at their lowest. Finally, we show the long-term incorporation of this moonlight pattern into the ants’ path integration system throughout the night for homing, as polarised sunlight is incorporated throughout the day. + How the fate (folding versus degradation) of glycoproteins is determined in the endoplasmic reticulum (ER) is an intriguing question. Monoglucosylated glycoproteins are recognized by lectin chaperones to facilitate their folding, whereas glycoproteins exposing well-trimmed mannoses are subjected to glycoprotein ER-associated degradation (gpERAD); we have elucidated how mannoses are sequentially trimmed by EDEM family members (George et al., 2020; 2021 eLife). Although reglucosylation by UGGT was previously reported to have no effect on substrate degradation, here we directly tested this notion using cells with genetically disrupted UGGT1/2. Strikingly, the results showed that UGGT1 delayed the degradation of misfolded substrates and unstable glycoproteins including ATF6α. An experiment with a point mutant of UGGT1 indicated that the glucosylation activity of UGGT1 was required for the inhibition of early glycoprotein degradation. These and overexpression-based competition experiments suggested that the fate of glycoproteins is determined by a tug-of-war between structure formation by UGGT1 and degradation by EDEMs. We further demonstrated the physiological importance of UGGT1, since ATF6α cannot function properly without UGGT1. Thus, our work strongly suggests that UGGT1 is a central factor in ER protein quality control via the regulation of both glycoprotein folding and degradation. -in eLife on 2024-12-09 00:00:00 UTC. +
in eLife on 2024-12-10 00:00:00 UTC.
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-Pharmacologically inducing regenerative cardiac cells by small molecule drugs
+Paracrine rescue of MYR1-deficient Toxoplasma gondii mutants reveals limitations of pooled in vivo CRISPR screens
- Adult mammals, unlike some lower organisms, lack the ability to regenerate damaged hearts through cardiomyocytes (CMs) dedifferentiation into cells with regenerative capacity. Developing conditions to induce such naturally unavailable cells with potential to proliferate and differentiate into CMs, that is, regenerative cardiac cells (RCCs), in mammals will provide new insights and tools for heart regeneration research. In this study, we demonstrate that a two-compound combination, CHIR99021 and A-485 (2C), effectively induces RCCs from human embryonic stem cell-derived TNNT2+ CMs in vitro, as evidenced by lineage tracing experiments. Functional analysis shows that these RCCs express a broad spectrum of cardiogenesis genes and have the potential to differentiate into functional CMs, endothelial cells, and smooth muscle cells. Importantly, similar results were observed in neonatal rat CMs both in vitro and in vivo. Remarkably, administering 2C in adult mouse hearts significantly enhances survival and improves heart function post-myocardial infarction. Mechanistically, CHIR99021 is crucial for the transcriptional and epigenetic activation of genes essential for RCC development, while A-485 primarily suppresses H3K27Ac and particularly H3K9Ac in CMs. Their synergistic effect enhances these modifications on RCC genes, facilitating the transition from CMs to RCCs. Therefore, our findings demonstrate the feasibility and reveal the mechanisms of pharmacological induction of RCCs from endogenous CMs, which could offer a promising regenerative strategy to repair injured hearts. + Toxoplasma gondii is an intracellular parasite that subverts host cell functions via secreted virulence factors. Up to 70% of parasite-controlled changes in the host transcriptome rely on the MYR1 protein, which is required for the translocation of secreted proteins into the host cell. Mice infected with MYR1 knock-out (KO) strains survive infection, supporting a paramount function of MYR1-dependent secreted proteins in Toxoplasma virulence and proliferation. However, we have previously shown that MYR1 mutants have no growth defect in pooled in vivo CRISPR-Cas9 screens in mice, suggesting that the presence of parasites that are wild-type at the myr1 locus in pooled screens can rescue the phenotype. Here, we demonstrate that MYR1 is not required for the survival in IFN-γ-activated murine macrophages, and that parasites lacking MYR1 are able to expand during the onset of infection. While ΔMYR1 parasites have restricted growth in single-strain murine infections, we show that the phenotype is rescued by co-infection with wild-type (WT) parasites in vivo, independent of host functional adaptive immunity or key pro-inflammatory cytokines. These data show that the major function of MYR1-dependent secreted proteins is not to protect the parasite from clearance within infected cells. Instead, MYR-dependent proteins generate a permissive niche in a paracrine manner, which rescues ΔMYR1 parasites within a pool of CRISPR mutants in mice. Our results highlight an important limitation of otherwise powerful in vivo CRISPR screens and point towards key functions for MYR1-dependent Toxoplasma-host interactions beyond the infected cell. -in eLife on 2024-12-09 00:00:00 UTC. +
in eLife on 2024-12-10 00:00:00 UTC.
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-Endogenous oligomer formation underlies DVL2 condensates and promotes Wnt/β-catenin signaling
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+Collablots: Quantification of collagen VI levels and its structural disorganisation in cell cultures from patients with collagen VI-related dystrophies
- Activation of the Wnt/β-catenin pathway crucially depends on the polymerization of dishevelled 2 (DVL2) into biomolecular condensates. However, given the low affinity of known DVL2 self-interaction sites and its low cellular concentration, it is unclear how polymers can form. Here, we detect oligomeric DVL2 complexes at endogenous protein levels in human cell lines, using a biochemical ultracentrifugation assay. We identify a low-complexity region (LCR4) in the C-terminus whose deletion and fusion decreased and increased the complexes, respectively. Notably, LCR4-induced complexes correlated with the formation of microscopically visible multimeric condensates. Adjacent to LCR4, we mapped a conserved domain (CD2) promoting condensates only. Molecularly, LCR4 and CD2 mediated DVL2 self-interaction via aggregating residues and phenylalanine stickers, respectively. Point mutations inactivating these interaction sites impaired Wnt pathway activation by DVL2. Our study discovers DVL2 complexes with functional importance for Wnt/β-catenin signaling. Moreover, we provide evidence that DVL2 condensates form in two steps by pre-oligomerization via high-affinity interaction sites, such as LCR4, and subsequent condensation via low-affinity interaction sites, such as CD2. + Aims: This study aims to develop a quantitative method for assessing collagen VI expression in cell cultures, which is crucial for the diagnosis and treatment of collagen VI-related dystrophies. Methods: We developed a combined in-cell western (ICW) and on-cell western (OCW) assay, that we have called 'collablot' to quantify collagen VI and its organisation in the extracellular matrix of cell cultures from patients and healthy controls. To optimise it, we optimised cell density and the protocols to induce collagen expression in cultures, as well as the cell fixation and permeabilisation methods. This was completed with a thorough selection of collagen antibodies and a collagen hybridising peptide (CHP). We then used collablots to compare cultures from patients and controls and evaluate therapeutic interventions in the cultures. Results: Collablots enabled the quantification of collagen VI expression in both control and patient cells, aligning with immunocytochemistry findings and detecting variations in collagen VI expression following treatment of the cultures. Additionally, CHP analysis revealed a marked increase in collagen network disruption in patients compared to the controls. Conclusions: The collablot assay represents an optimal method for quantifying collagen VI expression and its organisation in culture and assessing the effect of therapies. -in eLife on 2024-12-09 00:00:00 UTC. +
in bioRxiv: Neuroscience on 2024-12-10 00:00:00 UTC.
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-How vision shapes the paths we choose
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+Relaxation selective Intravoxel Incoherent Motion Imaging of Microvascular Perfusion and Fluid Compartments in the Human Choroid Plexus
- A mathematical model can predict the path walkers take through a rugged landscape, including the tendency of people to avoid paths that are too steep, even if it means going farther. + The choroid plexus (ChP) plays an important role in the glymphatic system of the human brain as the primary source of the cerebrospinal fluid (CSF) production. Development of a non-invasive imaging technique is crucial for studying its function and age-related neurofluid dynamics. This study developed a relaxation-selective intravoxel incoherent motion (IVIM) technique to assess tissue and fluid compartments in the ChP in a prospective cross-sectional study involving 83 middle-aged to elderly participants (age: 61.5{+/-}17.1 years old) and 15 young controls (age: 30.7{+/-}2.9 years old). Using a 3T MRI scanner, IVIM, FLAIR-IVIM, LongTE-IVIM, and VASO-LongTE-IVIM were employed to measure diffusivity and volume fractions of fluid compartments and evaluate aging effects on microvascular perfusion and interstitial fluid (ISF). FLAIR-IVIM identified an additional ISF compartment with free-water-like diffusivity (2.4{+/-}0.9 x10-3 mm2/s). Older adults exhibited increased ChP volume (2320{+/-} 812 mm3 vs 1470{+/-}403 mm3, p=0.0017), reduced perfusion (6.5 {+/-}4.7 vs 3.6{+/-}2.9 x10-3 mm2/s, p=0.0088), decreased ISF volume fraction (0.58{+/-}0.09 vs 0.67 {+/-}0.06, p=0.0042), and lower tissue diffusivity (1.16{+/-}0.14 vs 1.29{+/-} 0.17x10-3 mm2/s, p=0.031) compared to younger adults. Relaxation-selective IVIM may offers enhanced specificity for characterizing age-related changes in ChP structure and fluid dynamics. -in eLife on 2024-12-09 00:00:00 UTC. +
in bioRxiv: Neuroscience on 2024-12-10 00:00:00 UTC.
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-Complex aneuploidy triggers autophagy and p53-mediated apoptosis and impairs the second lineage segregation in human preimplantation embryos
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+Comparable neural and behavioural performance in dominant and non-dominant hands during grasping tasks
- About 70% of human cleavage stage embryos show chromosomal mosaicism, falling to 20% in blastocysts. Chromosomally mosaic human blastocysts can implant and lead to healthy new-borns with normal karyotypes. Studies in mouse embryos and human gastruloids showed that aneuploid cells are eliminated from the epiblast by p53-mediated apoptosis while being tolerated in the trophectoderm. These observations suggest a selective loss of aneuploid cells from human embryos, but the underlying mechanisms are not yet fully understood. Here, we investigated the cellular consequences of aneuploidy in a total of 125 human blastocysts. RNA-sequencing of trophectoderm cells showed activated p53 pathway and apoptosis proportionate to the level of chromosomal imbalance. Immunostaining corroborated that aneuploidy triggers proteotoxic stress, autophagy, p53-signaling, and apoptosis independent from DNA damage. Total cell numbers were lower in aneuploid embryos, due to a decline both in trophectoderm and in epiblast/primitive endoderm cell numbers. While lower cell numbers in trophectoderm may be attributed to apoptosis, aneuploidy impaired the second lineage segregation, particularly primitive endoderm formation. This might be reinforced by retention of NANOG. Our findings might explain why fully aneuploid embryos fail to further develop and we hypothesize that the same mechanisms lead to the removal of aneuploid cells from mosaic embryos. + Hand dominance has long been associated with differences in neural control and motor performance, with the dominant hand typically exhibiting better coordination in reaching tasks. However, the extent to which this dominance influences performance in finger force control remains unclear. This study aimed to examine the behavioural and neural features of the dominant and non dominant hands during grasping and lifting tasks in healthy young adults, focusing on the synergy index, EEG band power, and EEG EMG coherence as key measures. Twenty right handed adults (mean age = 26.95, STD = 2.68) participated in this study. Participants engaged in an experimental task where they grasped a handle for the initial five seconds, followed by lifting and holding it for an additional five seconds. There were two task conditions: fixed (thumb platform secured) and free (thumb platform movable). They performed 25 trials with both the dominant and non-dominant hands in the two task conditions, with the order of trials and hands block randomized to eliminate potential order effects. Contrary to the dynamic dominance hypothesis, we found statistical equivalence in the synergy index, EEG band power, and EEG EMG coherence between the dominant and non-dominant hands across both fixed and free task conditions. These findings suggest that both hands are capable of achieving similar levels of performance in tasks emphasizing steady state force maintenance, despite the typical advantages of the dominant hand in other motor tasks. While task-dependent modulations in behavioural and neural features were observed due to changes in friction, these adjustments were non different between the dominant and non dominant hands. -in eLife on 2024-12-09 00:00:00 UTC. +
in bioRxiv: Neuroscience on 2024-12-10 00:00:00 UTC.
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-Unified bursting strategies in ectopic and endogenous even-skipped expression patterns
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+Accelerated amyloid deposition in SARS-CoV-2 infected mouse models of Alzheimer's disease
- Transcription often occurs in bursts as gene promoters switch stochastically between active and inactive states. Enhancers can dictate transcriptional activity in animal development through the modulation of burst frequency, duration, or amplitude. Previous studies observed that different enhancers can achieve a wide range of transcriptional outputs through the same strategies of bursting control. For example, in Berrocal et al., 2020, we showed that despite responding to different transcription factors, all even-skipped enhancers increase transcription by upregulating burst frequency and amplitude while burst duration remains largely constant. These shared bursting strategies suggest that a unified molecular mechanism constraints how enhancers modulate transcriptional output. Alternatively, different enhancers could have converged on the same bursting control strategy because of natural selection favoring one of these particular strategies. To distinguish between these two scenarios, we compared transcriptional bursting between endogenous and ectopic gene expression patterns. Because enhancers act under different regulatory inputs in ectopic patterns, dissimilar bursting control strategies between endogenous and ectopic patterns would suggest that enhancers adapted their bursting strategies to their trans-regulatory environment. Here, we generated ectopic even-skipped transcription patterns in fruit fly embryos and discovered that bursting strategies remain consistent in endogenous and ectopic even-skipped expression. These results provide evidence for a unified molecular mechanism shaping even-skipped bursting strategies and serve as a starting point to uncover the realm of strategies employed by other enhancers. + Familial Alzheimer's disease (AD) involving known AD causing genes accounts for a small fraction of cases, the vast majority are sporadic. Neuroinflammation, secondary to viral infection, has been suggested as an initiating or accelerating factor. In this work we tested the hypothesis that SARS-CoV-2 (SCV2) viral infection accelerates the development of AD pathology in mouse models of AD. We profiled transcriptomic changes using transgenic APP/PSEN1 and P301S mouse models that develop AD pathology and k18hACE2 mice that express the humanized ACE2 receptor used by SCV2 to enter cells. This study identified the interferon and chemokine responses constituting key shared pathways between SCV2 infection and the development of AD pathology. Two transgenic mouse models of AD: APP/PSEN1 (develops amyloid pathology) and 3xTg AD (develops both amyloid and tau pathology) were crossed with k18-hACE2 mice to generate hybrid hACE2-3xTg and hACE2-APP/PSEN1 mice. Neuroinflammation and amyloid deposition in the brain of infected mice were imaged in vivo using molecular MRI (mMRI) probes and confirmed postmortem by histopathology. Results show that 11-14-month-old SCV2 infected hACE2-3xTg mice exhibit neuroinflammation 10 days post infection and 4-5-month-old hACE2-APP/PS1 hybrid mice develop amyloid deposits, while age-matched uninfected mice exhibit neither phenotype. This suggests that SCV2 infection could induce or accelerate AD when risk factors are present. -in eLife on 2024-12-09 00:00:00 UTC. +
in bioRxiv: Neuroscience on 2024-12-10 00:00:00 UTC.
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-Decoding contextual influences on auditory perception from primary auditory cortex
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+Emergence of Sparse Coding, Balance and Decorrelation from a Biologically-Grounded Spiking Neural Network Model of Learning in the Primary Visual Cortex
- Perception can be highly dependent on stimulus context, but whether and how sensory areas encode the context remains uncertain. We used an ambiguous auditory stimulus – a tritone pair – to investigate the neural activity associated with a preceding contextual stimulus that strongly influenced the tritone pair’s perception: either as an ascending or a descending step in pitch. We recorded single-unit responses from a population of auditory cortical cells in awake ferrets listening to the tritone pairs preceded by the contextual stimulus. We find that the responses adapt locally to the contextual stimulus, consistent with human MEG recordings from the auditory cortex under the same conditions. Decoding the population responses demonstrates that cells responding to pitch-changes are able to predict well the context-sensitive percept of the tritone pairs. Conversely, decoding the individual pitch representations and taking their distance in the circular Shepard tone space predicts the opposite of the percept. The various percepts can be readily captured and explained by a neural model of cortical activity based on populations of adapting, pitch and pitch-direction cells, aligned with the neurophysiological responses. Together, these decoding and model results suggest that contextual influences on perception may well be already encoded at the level of the primary sensory cortices, reflecting basic neural response properties commonly found in these areas. + Many computational studies attempt to address the question of information representation in biological neural networks using an explicit optimization based on an objective function. These approaches begin with principles of information representation that are expected to be found in the network and from which learning rules can be derived. This study approaches the question from the opposite direction; beginning with a model built upon the experimentally observed properties of neural responses, homeostasis, and synaptic plasticity. The known properties of information representation are then expected to emerge from this substrate. A spiking neural model of the primary visual cortex (V1) was investigated. Populations of both inhibitory and excitatory leaky integrate-and-fire neurons with recurrent connections were provided with spiking input from simulated ON and OFF neurons of the lateral geniculate nucleus. This network was provided with natural image stimuli as input. All synapses underwent learning using spike-timing-dependent plasticity learning rules. A homeostatic rule adjusted the weights and thresholds of each neuron based on target homeostatic spiking rates and mean synaptic input values. These experimentally grounded rules resulted in a number of the expected properties of information representation. The network showed a temporally sparse spike response to inputs and this was associated with a sparse code with Gabor-like receptive fields. The network was balanced at both slow and fast time scales; increased excitatory input was balanced by increased inhibition. This balance was associated with decorrelated firing that was observed as population sparseness. This population sparseness was both the cause and result of the decorrelation of receptive fields. These observed emergent properties (balance, temporal sparseness, population sparseness, and decorrelation) indicate that the network is implementing expected principles of information processing: efficient coding, information maximization ('infomax'), and a lateral or single-layer form of predictive coding. These emergent features of the network were shown to be robust to randomized jitter of the values of key simulation parameters. -in eLife on 2024-12-09 00:00:00 UTC. +
in bioRxiv: Neuroscience on 2024-12-10 00:00:00 UTC.
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-Cross-species alignment along the chronological axis reveals evolutionary effect on structural development of the human brain
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+Comparative analysis of neural decoding algorithms for brain-machine interfaces
- Disentangling the evolution mysteries of the human brain has always been an imperative endeavor in neuroscience. Although many previous comparative studies revealed genetic, brain structural and connectivity distinctness between human and other nonhuman primates, the brain evolutional mechanism is still largely unclear. Here, we proposed to embed the brain anatomy of human and macaque in the developmental chronological axis to construct cross-species predictive model to quantitatively characterize brain evolution using two large public human and macaque datasets. We observed that applying the trained models within-species could well predict the chronological age. Interestingly, we found the model trained in macaque showed a higher accuracy in predicting the chronological age of human than the model trained in human in predicting the chronological age of macaque. The cross-application of the trained model introduced an individual brain cross-species age gap index to quantify the cross-species discrepancy along the temporal axis of brain development and was found to be associated with the behavioral performance in visual acuity test and picture vocabulary test in human. Taken together, our study situated the cross-species brain development along the chronological axis, which highlighted the disproportionately anatomical development in human brain to extend our understanding of the potential evolutionary effects. + Accurate neural decoding of brain dynamics remains a significant and open challenge in brain-machine interfaces. While various signal processing, feature extraction, and classification algorithms have been proposed, a systematic comparison of these is lacking. Accordingly, here we conducted one of the largest comparative studies evaluating different combinations of state-of-the-art algorithms for motor neural decoding to find the optimal combination. We studied three signal processing methods (i.e., artifact subspace reconstruction, surface Laplacian filtering, and data normalization), four feature extractors (i.e., common spatial patterns, independent component analysis, short-time Fourier transform, and no feature extraction), and four machine learning classifiers (i.e., support vector machine, linear discriminant analysis, convolutional neural networks, and long short-term memory networks). Using a large-scale EEG dataset, we optimized each combination for individual subjects (i.e., resulting in 672 total experiments) and evaluated performance based on classification accuracy. We also compared the computational and memory storage requirements, which are important for real-time embedded computing. Our comparative analysis provides novel insights that help inform the design of next-generation neural decoding algorithms for brain-machine interfaces used to interact with and control robots and computers. -in eLife on 2024-12-09 00:00:00 UTC. +
in bioRxiv: Neuroscience on 2024-12-10 00:00:00 UTC.
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-The identification of extensive samples of motor units in human muscles reveals diverse effects of neuromodulatory inputs on the rate coding
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+Insights into Dentatorubral-Pallidoluysian Atrophy from a new Drosophila model of disease
- Movements are performed by motoneurons transforming synaptic inputs into an activation signal that controls muscle force. The control signal emerges from interactions between ionotropic and neuromodulatory inputs to motoneurons. Critically, these interactions vary across motoneuron pools and differ between muscles. To provide the most comprehensive framework to date of motor unit activity during isometric contractions, we identified the firing activity of extensive samples of motor units in the tibialis anterior (129 ± 44 per participant; n=8) and the vastus lateralis (130 ± 63 per participant; n=8) muscles during isometric contractions of up to 80% of maximal force. From this unique dataset, the rate coding of each motor unit was characterised as the relation between its instantaneous firing rate and the applied force, with the assumption that the linear increase in isometric force reflects a proportional increase in the net synaptic excitatory inputs received by the motoneuron. This relation was characterised with a natural logarithm function that comprised two stages. The initial stage was marked by a steep acceleration of firing rate, which was greater for low- than medium- and high-threshold motor units. The second stage comprised a linear increase in firing rate, which was greater for high- than medium- and low-threshold motor units. Changes in firing rate were largely non-linear during the ramp-up and ramp-down phases of the task, but with significant prolonged firing activity only evident for medium-threshold motor units. Contrary to what is usually assumed, our results demonstrate that the firing rate of each motor unit can follow a large variety of trends with force across the pool. From a neural control perspective, these findings indicate how motor unit pools use gain control to transform inputs with limited bandwidths into an intended muscle force. + Dentatorubral-pallidoluysian atrophy (DRPLA) is a neurodegenerative disorder that presents with ataxia, dementia and epilepsy. As a member of the polyglutamine family of diseases, DRPLA is caused by abnormal CAG triplet expansion beyond 48 repeats in the protein-coding region of ATROPHIN 1 (ATN1), a transcriptional co-repressor. To better understand DRPLA, we generated new Drosophila lines that express full-length, human ATN1 with a normal (Q7) or pathogenic (Q88) repeat. Expression of ATN1 is toxic, with the polyglutamine-expanded version being consistently more problematic than wild-type ATN1. Fly motility, longevity and internal structures are negatively impacted by pathogenic ATN1. RNA-seq identified altered protein quality control and immune pathways in the presence of pathogenic ATN1. Based on these data, we conducted genetic experiments that confirmed the role of protein quality control components that ameliorate or exacerbate ATN1 toxicity. Hsc70-3, a chaperone, arose as a likely suppressor of toxicity. VCP (a proteasome-related AAA ATPase), Rpn11 (a proteasome-related deubiquitinase) and select DnaJ proteins (co-chaperones) were inconsistently protective, depending on the tissues where they were expressed. Lastly, informed by RNA-seq data that exercise-related genes may also be involved in this model of DRPLA, we conducted short-term exercise, which improved overall fly motility. This new model of DRPLA will prove important to understanding this understudied disease and will help to identify therapeutic targets for it. -in eLife on 2024-12-09 00:00:00 UTC. +
in bioRxiv: Neuroscience on 2024-12-10 00:00:00 UTC.
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-Efficient value synthesis in the orbitofrontal cortex explains how loss aversion adapts to the ranges of gain and loss prospects
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+Tactile stimulations reduce or promote the segregation of auditory streams: psychophysics and modelling
- Is irrational behavior the incidental outcome of biological constraints imposed on neural information processing? In this work, we consider the paradigmatic case of gamble decisions, where gamble values integrate prospective gains and losses. Under the assumption that neurons have a limited firing response range, we show that mitigating the ensuing information loss within artificial neural networks that synthetize value involves a specific form of self-organized plasticity. We demonstrate that the ensuing efficient value synthesis mechanism induces value range adaptation. We also reveal how the ranges of prospective gains and/or losses eventually determine both the behavioral sensitivity to gains and losses and the information content of the network. We test these predictions on two fMRI datasets from the OpenNeuro.org initiative that probe gamble decision-making but differ in terms of the range of gain prospects. First, we show that peoples' loss aversion eventually adapts to the range of gain prospects they are exposed to. Second, we show that the strength with which the orbitofrontal cortex (in particular: Brodmann area 11) encodes gains and expected value also depends upon the range of gain prospects. Third, we show that, when fitted to participant’s gambling choices, self-organizing artificial neural networks generalize across gain range contexts and predict the geometry of information content within the orbitofrontal cortex. Our results demonstrate how self-organizing plasticity aiming at mitigating information loss induced by neurons’ limited response range may result in value range adaptation, eventually yielding irrational behavior. + Auditory stream segregation plays a crucial role in understanding the auditory scene. This study investigates the role of tactile stimulation in auditory stream segregation through psychophysics experiments and a computational model of audio-tactile interactions. We examine how tactile pulses, synchronized with specific tones in a sequence of interleaved high- and low-frequency tones (ABA- triplets), influence the likelihood of perceiving integrated or segregated auditory streams. Our findings reveal that tactile pulses synchronized with specific tones enhance perceptual segregation, while pulses synchronized with both tones promote integration. Based on these findings, we developed a dynamical model that captures interactions between auditory and tactile neural circuits, including recurrent excitation, mutual inhibition, adaptation, and noise. The proposed model shows excellent agreement with the experiment. Model predictions are validated through psychophysics experiments. In the model, we assume that selective tactile stimulation dynamically modulates the tonotopic organization within the auditory cortex. This modulation facilitates segregation by reinforcing specific tonotopic responses through single-tone synchronization while smoothing neural activity patterns with dual-tone alignment to promote integration. The model offers a robust computational framework for exploring cross-modal effects on stream segregation and predicts neural behaviour under varying tactile conditions. Our findings imply that cross-modal synchronization, with carefully timed tactile cues, could improve auditory perception with potential applications in auditory assistive technologies aimed at enhancing speech recognition in noisy settings. -in eLife on 2024-12-09 00:00:00 UTC. +
in bioRxiv: Neuroscience on 2024-12-10 00:00:00 UTC.
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-Analysis of foothold selection during locomotion using terrain reconstruction
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+A subset of human choroid plexus epithelial cells exhibit mitochondrial eccentricity and distinct expression of the pigmentation-associated enzyme TYRP1
- Relatively little is known about the way vision is used to guide locomotion in the natural world. What visual features are used to choose paths in natural complex terrain? To answer this question, we measured eye and body movements while participants walked in natural outdoor environments. We incorporated measurements of the three-dimensional (3D) terrain structure into our analyses and reconstructed the terrain along the walker’s path, applying photogrammetry techniques to the eye tracker’s scene camera videos. Combining these reconstructions with the walker’s body movements, we demonstrate that walkers take terrain structure into account when selecting paths through an environment. We find that they change direction to avoid taking steeper steps that involve large height changes, instead of choosing more circuitous, relatively flat paths. Our data suggest walkers plan the location of individual footholds and plan ahead to select flatter paths. These results provide evidence that locomotor behavior in natural environments is controlled by decision mechanisms that account for multiple factors, including sensory and motor information, costs, and path planning. + For decades, ultrastructural evaluation of epithelial cells in diverse organ systems has demonstrated the existence of two subtypes identified by stark differences in cytoplasmic electron density -- so-called light and dark epithelial cells. Choroid plexus (CP) epithelial cells are key regulators of CSF homeostasis and are one of many specialized epithelial linings that exhibit this bimodal phenotype. Despite longstanding acknowledgement, it has been difficult to assess the potential significance of adult human light and dark CP epithelial cells due to a lack of characterization beyond electron microscopy (EM). We present the first transcriptomic analysis of adult human CP epithelial cells and denote the existence of four epithelial subpopulations, one of which is defined by elevated expression of TYRP1 -- a melanocyte-associated tyrosine-related protein involved in cellular pigmentation and proliferation. TYRP1-high cells also downregulate genes related to cilia function (which is consistent with observations of dark cell identity in organoids) and upregulate genes associated with pathways related to cell cycling, stress, and iron regulation. Our data provide an explanation of the molecular underpinning of adult human light and dark cell identity and serve as a resource for investigations of epithelial heterogeneity in the CP and other organs where dark cells are found. -in eLife on 2024-12-09 00:00:00 UTC. +
in bioRxiv: Neuroscience on 2024-12-10 00:00:00 UTC.
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Dysregulated calcium signaling in the aged macaque entorhinal cortex associated with tau hyperphosphorylation.
+http://biorxiv.org/cgi/content/short/2024.12.05.627067v1?rss=1 +">Gabapentin's Effect on Human Dorsal Root Ganglia: Donor-Specific Electrophysiological and Transcriptomic Profiles - Tau pathology in sporadic Alzheimer's disease (AD) follows a distinct pattern, beginning in the entorhinal cortex (ERC) and spreading to interconnected brain regions. Early-stage tau pathology, characterized by soluble phosphorylated tau, is difficult to study in human brains post-mortem due to rapid dephosphorylation. Rhesus macaques, which naturally develop age-related tau pathology resembling human AD, provide an ideal model for investigating early tau etiology. This study examines the molecular processes underlying tau pathology in the macaque ERC, focusing on calcium and inflammatory signaling pathways. Our findings reveal age-related decreases in PDE4 phosphodiesterases that hydrolyze cAMP and increases in calpain-2 and GCPII that occur in parallel with early-stage tau hyperphosphorylation at multiple epitopes (pS214-tau, pT181-tau, pT217-tau). These findings suggest that dysregulated calcium signaling in ERC, beginning in middle-age, primes tau for hyperphosphorylation, potentially driving the early stages of AD, advancing our understanding of how ERC vulnerabilities contribute to neurodegeneration in AD. + Neuropathic pain affects approximately 10% of the adult population and is commonly treated with gabapentin (GBP), a repurposed anticonvulsant drug. Despite its widespread clinical use, GBPs efficacy varies significantly among patients, highlighting the need to better understand its functional and molecular impacts on human pain-sensing neurons. In this study, we characterized the electrophysiological and transcriptomic effects of GBP on primary sensory neurons derived from the dorsal root ganglia (DRG) of ethically consented human donors. Using patch-clamp electrophysiology, we demonstrated that GBP treatment reduced neuronal excitability, with more pronounced effects in multi-firing vs. single-firing neuronal subtypes. Notably, significant donor-specific variability was observed in electrophysiological responsiveness to GBP treatment in vitro. RNA sequencing of DRG tissue from the GBP-responsive donor revealed differences in the transcriptome-wide expression of genes associated with ion transport, synaptic transmission, inflammation, and immune response relative to non-responsive donors. Cross-transcriptomic analyses further showed that GBP treatment counteracted these altered processes, rescuing aberrant gene expression at the pathway level and for several key genes. This study provides a comprehensive electrophysiological and transcriptomic profile of the effects of GBP on human DRG neurons. These findings enhance our understanding of GBPs mechanistic actions on peripheral sensory neurons and could help optimize its clinical use for neuropathic pain management. -in bioRxiv: Neuroscience on 2024-12-09 00:00:00 UTC. +
in bioRxiv: Neuroscience on 2024-12-10 00:00:00 UTC.
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Egocentric perception of walking environments using an interactive vision-language system
+http://biorxiv.org/cgi/content/short/2024.12.05.626723v1?rss=1 +">Aging and the Spectral Properties of Brain Hemodynamics - Large language models can provide a more detailed contextual understanding of a scene beyond what computer vision alone can provide, which have implications for robotics and embodied intelligence. In this study, we developed a novel multimodal vision-language system for egocentric visual perception, with an initial focus on real-world walking environments. We trained a number of state-of-the-art transformer-based vision-language models that use causal language modelling on our custom dataset of 43,055 image-text pairs for few-shot image captioning. We then designed a new speech synthesis model and a user interface to convert the generated image captions into speech for audio feedback to users. Our system also uniquely allows for feedforward user prompts to personalize the generated image captions. Our system is able to generate detailed captions with an average length of 10 words while achieving a high ROUGE-L score of 43.9% and a low word error rate of 28.1% with an end-to-end processing time of 2.2 seconds. Overall, our new multimodal vision-language system can generate accurate and detailed descriptions of natural scenes, which can be further augmented by user prompts. This innovative feature allows our image captions to be personalized to the individual and immediate needs and preferences of the user, thus optimizing the closed-loop interactions between the human and generative AI models for understanding and navigating of real-world environments. + Cerebral glucose metabolism (CMRGlc) systematically decreases with advancing age. We sought to identify correlates of decreased CMRGlc in the spectral properties of fMRI signals imaged in the task-free state. We analyzed lifespan resting-state fMRI data acquired in 455 healthy adults (ages 18-87 years) and cerebral metabolic data acquired in a separate cohort of 94 healthy adults (ages 25-45 years, 65-85 years). We characterized the spectral properties of the fMRI data in terms of the relative predominance of slow vs. fast activity using the spectral slope (SS) measure. We found that the relative proportion of fast activity increases with advancing age (SS flattening) across most cortical regions. The regional distribution of spectral slope was topographically correlated with CMRGlc in young adults. Notably, whereas most older adults maintained a youthful pattern of SS topography, a distinct subset of older adults significantly diverged from the youthful pattern. This subset of older adults also diverged from the youthful pattern of CMRGlc metabolism. This divergent pattern was associated with T2-weighted signal changes in frontal lobe white matter, an independent marker of small vessel disease. These findings suggest that BOLD signal spectral slope flattening may represent a biomarker of age-associated neurometabolic pathology. -in bioRxiv: Neuroscience on 2024-12-09 00:00:00 UTC. +
in bioRxiv: Neuroscience on 2024-12-10 00:00:00 UTC.
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Divalent siRNA for prion disease
+http://biorxiv.org/cgi/content/short/2024.12.05.627043v1?rss=1 +">Multi-omic characterization of human sural nerves acrosspolyneuropathies - Pharmacologic lowering of PrP expression is efficacious against prion disease in animal models and is now being tested clinically. 50% lowering of PrP increases both survival time and healthy life in prion-infected mice, but does not prevent symptom onset nor halt disease progression. Additional drug candidates should seek to reduce PrP expression to even lower levels. Divalent siRNA is a novel oligonucleotide drug modality with promising potency, durability, and biodistribution data in preclinical models, inspiring us to seek in this technology a new drug candidate for prion disease. Here, we first identify a tool compound against the mouse PrP gene and establish the efficacy of PrP-lowering divalent siRNA in prion-infected mice. We then introduce humanized transgenic mouse lines harboring the full non-coding sequence of the human PrP gene as tools for identifying human sequence-targeted drugs. We identify a highly potent siRNA sequence against the human PrP gene and determine that a chemical scaffold incorporating extended nucleic acid and a 3' antisense tail unmatched to the RNA target yields superior potency. We nominate PrP-lowering divalent siRNA 2439-s4 as a new drug candidate for human prion disease. + Diseases of peripheral nerves termed polyneuropathies (PNPs) are common, mechanistically heterogeneous, and challenging to diagnose. Here, we integrated single nuclei transcriptomics of peripheral nerves from 33 human PNP patients and four controls (365,708 nuclei) with subcellular spatial transcriptomics. We identified novel and human-specific nerve cell type markers including unexpectedly heterogeneous perineurial fibroblasts. All PNPs shared a loss of myelinating and an increase in repair Schwann cells and endoneurial lipid-associated macrophages. Transcriptional changes affected multiple cells outside of the endoneurium across PNPs, suggesting PNPs as pan-nerve diseases. Spatially, PNPs showed a previously unknown perineurial hyperplasia and fibrotic dispersion and this was most pronounced in immune-mediated PNPs. Single cell transcriptomics supported the differential diagnosis of PNPs with potential for future unbiased diagnostic classification. -in bioRxiv: Neuroscience on 2024-12-09 00:00:00 UTC. +
in bioRxiv: Neuroscience on 2024-12-10 00:00:00 UTC.
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Multi-scale parameterization of neural rhythmicity with lagged Hilbert autocoherence
+http://biorxiv.org/cgi/content/short/2024.12.05.627046v1?rss=1 +">Grid cells anticipate the animal's future movement - Analysis of neural activity in different frequency bands is ubiquitous in systems and cognitive neuroscience. Recent analytical breakthroughs and theoretical developments rely on phase maintenance of oscillatory signals without considering whether or not this assumption is met. Lagged (auto)coherence, the coherence between a signal and itself at increasing temporal delays, has been proposed as a way to quantify the rhythmicity, or periodicity, of a signal. However, current Fourier-based lagged autocoherence algorithms suffer from poor spectral accuracy and resolution, aliasing effects that become more pronounced at higher frequencies, and conflation with amplitude covariation, especially in frequency ranges in which the signal power is low. We introduce a continuous lagged autocoherence metric, lagged Hilbert autocoherence, that addresses these shortcomings by using multiplication in the frequency domain for precise bandpass filtering, instantaneous analytic signals via the Hilbert transform, and thresholding using the amplitude covariation of surrogate data generated by an autoregressive model. We show that this version of lagged coherence yields vastly higher spectral accuracy and resolution than lagged Fourier autocoherence, and that this unlocks additional, increasingly fine grained applications. This includes examination of: 1) frequency-specific differences in rhythmicity between conditions, 2) changes in signal rhythmicity during learning, and 3) the relationship between frequency-specific rhythmicity and behavior, trial-by-trial. Lagged Hilbert autocoherence thus offers a significant toolset advancement for analysis of neurophysiological rhythmicity. + Grid cells in the rodent medial entorhinal cortex preferentially fire spikes when the animal is within certain regions of space. When experimental data are averaged over time, spatial firing fields become apparent. If these firing fields represented only the current position of the animal, a grid cell's firing should not depend on whether the animal is running into or out of a firing field. Yet many grid cells are sensitive to the animal's direction of motion relative to the firing-field center. Such apparent egocentric ''inbound-outbound tuning'' could be a sign of prospective encoding of future position, but it is unclear whether grid cells code ahead in space or in time. To investigate this question, we decided to undo the inbound-outbound modulation by shifting all spikes within a given firing field by a fixed distance in space or in time. For grid-cell data recorded in mice, optimizing in space requires a forward shift of around 2.5 cm, whereas optimizing in time yielded a forward shift of about 170 ms. In either case the firing-field sizes decrease. Minimizing just the field size yields somewhat smaller shifts (roughly 1.8 cm and around 115 ms ahead). Jointly optimizing along the temporal and spatial dimension reveals a continuum of flat inbound-outbound tuning curves and a shallow minimum for field sizes, located at about 2.3 cm and 35 ms. These findings call into question a purely spatial or purely temporal interpretation of grid-cell firing fields and inbound- outbound tuning. -in bioRxiv: Neuroscience on 2024-12-09 00:00:00 UTC. +
in bioRxiv: Neuroscience on 2024-12-10 00:00:00 UTC.
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One Hundred Neural Networks and Brains Watching Videos: Lessons from Alignment
+http://biorxiv.org/cgi/content/short/2024.12.09.627581v1?rss=1 +">Modulation of Purkinje Cell Inhibition by Stem Cell Factor - What can we learn from comparing video models to human brains, arguably the most efficient and effective video processing systems in existence? Our work takes a step towards answering this question by performing the first large-scale benchmarking of deep video models on representational alignment to the human brain, using publicly available models and a recently released video brain imaging (fMRI) dataset. We disentangle four factors of variation in the models (temporal modeling, classification task, architecture, and training dataset) that affect alignment to the brain, which we measure by conducting Representational Similarity Analysis across multiple brain regions and model layers. We show that temporal modeling is key for alignment to brain regions involved in early visual processing, while a relevant classification task is key for alignment to higher-level regions. Moreover, we identify clear differences between the brain scoring patterns across layers of CNNs and Transformers, and reveal how training dataset biases transfer to alignment with functionally selective brain areas. Additionally, we uncover a negative correlation of computational complexity to brain alignment. Measuring a total of 99 neural networks and 10 human brains watching videos, we aim to forge a path that widens our understanding of temporal and semantic video representations in brains and machines, ideally leading towards more efficient video models and more mechanistic explanations of processing in the human brain. + Target derived factors influence the specification, maintenance, and modulation of synaptic connectivity. The transmembrane protein, Kit Ligand, and Kit receptor tyrosine kinase are differentially expressed in connected neurons. In development and postnatal periods, these proteins maintain connectivity between cerebellar Purkinje cells (PC) that express Kit Ligand, and presynaptic Molecular Layer Interneurons (MLI) expressing Kit. In this study, it is demonstrated that Stem Cell Factor (SCF), the active extracellular domain of Kit Ligand, produces a potent potentiation of inhibition upon Purkinje Cells. The SCF enhancement of inhibition required presynaptic Kit, produced long term suppression of PC firing, and was associated with a specific potentiation of basket cells of the MLI1 subtype. It is posited that SCF exerts a postsynaptic effect involving enhanced sensitivity of somatic PC GABAA receptors. This work demonstrates that the SCF/Kit axis modulates synaptic function in adult tissue. -in bioRxiv: Neuroscience on 2024-12-09 00:00:00 UTC. +
in bioRxiv: Neuroscience on 2024-12-10 00:00:00 UTC.
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Modelling inter-shot variability for robust temporal sub-sampling of dynamic, GABA-edited MR spectroscopy data
+http://biorxiv.org/cgi/content/short/2024.12.07.627361v1?rss=1 +">GABAergic neurons from the ventral tegmental area represent and regulate force vectors - Variability between individual transients in an MRS acquisition presents a challenge for reliable quantification, particularly in functional scenarios where discrete subsets of the available transients may be compared. The current study aims to develop and validate a model for removing unwanted variance from GABA-edited MRS data, whilst preserving variance of potential interest - such as metabolic response to a functional task. A linear model is used to describe sources of variance in the system: intrinsic, periodic variance associated with phase cycling and spectral editing, and abrupt changes associated with subject movement. We broadly hypothesize that modelling these factors appropriately will improve spectral quality and reduce variance in quantification outcomes, without introducing bias to the estimates. We additionally anticipate that the models will improve (or at least maintain) sensitivity to functional changes, outperforming established methods in this regard. In vivo GABA-edited MRS data (203 subjects from the publicly available Big GABA collection) were sub-sampled strategically to assess individual components of the model, benchmarked against the uncorrected case and against established approaches such as spectral improvement by Fourier thresholding (SIFT). Changes in metabolite concentration and lineshape simulating response to a functional task were synthesized, and sensitivity to such changes was assessed. Composite models yielded improved SNR and reduced variability of GABA+ estimates compared to the uncorrected case in all scenarios, with performance for individual model components varying. Similarly, while some model components in isolation led to increased variability in estimates, no bias was observed in these or in the composite models. While SIFT yielded the greatest reductions in unwanted variance, the resultant data were substantially less sensitive to synthetic functional changes. We conclude that the modelling presented is effective at reducing unwanted variance, whilst retaining temporal dynamics of interest for functional MRS applications, and recommend its inclusion in fMRS processing pipelines. + The ventral tegmental area (VTA), a midbrain region associated with motivated behaviors, consists predominantly of dopaminergic (DA) neurons and GABAergic (GABA) neurons. Previous work has suggested that VTA GABA neurons provide a reward prediction, which is used in computing a reward prediction error. In this study, using in vivo electrophysiology and continuous quantification of force exertion in head-fixed mice, we discovered distinct populations of VTA GABA neurons that exhibited precise force tuning independently of learning, reward prediction, and outcome valence. Their activity usually preceded force exertion, and selective optogenetic manipulations of these neurons systematically modulated force exertion without influencing reward prediction. Together, these findings show that VTA GABA neurons continuously regulate force vectors during motivated behavior. -in bioRxiv: Neuroscience on 2024-12-09 00:00:00 UTC. +
in bioRxiv: Neuroscience on 2024-12-10 00:00:00 UTC.
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Transcriptomic changes in retinal ganglion cell types associated with the disruption of cholinergic retinal waves
+http://biorxiv.org/cgi/content/short/2024.12.05.627057v1?rss=1 +">In Search of Transcriptomic Correlates of Neuronal Firing-Rate Adaptation across Subtypes, Regions and Species: A Patch-seq Analysis - In the early stages of retinal development, a form of correlated activity known as retinal waves causes periodic depolarizations of immature retinal ganglion cells (RGCs). Retinal waves are crucial for refining visual maps in the brain's retinofugal targets and for the development of retinal circuits underlying feature detection, such as direction selectivity. Yet, how waves alter gene expression in immature RGCs is poorly understood, particularly at the level of the many distinct types of RGCs that underlie the retinas ability to encode diverse visual features. We performed single-cell RNA sequencing on RGCs isolated at the end of the first postnatal week from wild-type (WT) mice and {beta}2KO mice, which lack the {beta}2 subunit of the nicotinic acetylcholine receptor, leading to the disruption of cholinergic retinal waves. Statistical comparisons of RGC transcriptomes between the two conditions reveal a weak impact of retinal waves on RGC diversity, indicating that retinal waves do not influence the molecular programs that instruct RGC differentiation and maturation. Although wave-dependent gene expression changes are modest in the global sense, we identified ~238 genes that are significantly altered in select subsets of RGC types. We focused on one gene, Kcnk9, which encodes the two-pore domain leak channel potassium channel TASK3. Kcnk9, which is highly enriched in RGCs, was strongly downregulated in {beta}2KO. We validated this result using in situ hybridization and performed whole-cell recording to demonstrate a significant decrease in the leak conductance in {beta}2KO RGCs. Our dataset provides a useful resource for identifying potential targets of spontaneous activity-dependent regulation of neurodevelopment in the retina. + Can the transcriptomic profile of a neuron predict its physiological properties? Using a Patch-seq dataset of the primary visual cortex, we addressed this question by focusing on spike rate adaptation (SRA), a well-known phenomenon that depends on small conductance calcium (Ca)-dependent potassium (SK) channels. We first show that in parvalbumin-expressing (PV) and somatostatin-expressing (SST) interneurons (INs), expression levels of genes encoding the ion channels underlying action potential generation are correlated with the half-width (HW) of spikes. Surprisingly, the SK encoding gene is not correlated with the degree of SRA (dAdap). Instead, genes that encode proteins upstream from the SK current are correlated with dAdap, a finding validated by a different dataset from the mouse's primary motor cortex that includes pyramidal cells and interneurons, as well as physiological datasets from multiple regions of macaque monkeys. Finally, we construct a minimal model to reproduce observed heterogeneity across cells, with testable predictions. -in bioRxiv: Neuroscience on 2024-12-09 00:00:00 UTC. +
in bioRxiv: Neuroscience on 2024-12-10 00:00:00 UTC.
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EEG data quality in large scale field studies in India and Tanzania
+http://biorxiv.org/cgi/content/short/2024.12.09.627541v1?rss=1 +">Gender-specific Single Transcript Level Atlas of Vasopressin and its Receptor (AVPR1a) in the Mouse Brain - There is a growing imperative to understand the neurophysiological impact of our rapidly changing and diverse technological, social, chemical, and physical environments. To untangle the multidimensional and interacting effects requires data at scale across diverse populations, taking measurement out of a controlled lab environment and into the field. Electroencephalography (EEG), which has correlates with various environmental factors as well as cognitive and mental health outcomes, has the advantage of both portability and cost-effectiveness for this purpose. However, with numerous field researchers spread across diverse locations, data quality issues and researcher idle time due to insufficient participants can quickly become unmanageable and expensive problems. In programs we have established in India and Tanzania, we demonstrate that with appropriate training, structured teams, and daily automated analysis and feedback on data quality, non-specialists can reliably collect EEG data alongside various survey and assessments with consistently high throughput and quality. Over a 30-week period, research teams were able to maintain an average of 25.6 subjects per week, collecting data from a diverse sample of 7,933 participants ranging from Hadzabe hunter-gatherers to office workers. Furthermore, data quality, computed on the first 2,400 records using two common methods, PREP and FASTER, was comparable to benchmark datasets from controlled lab conditions. Altogether this resulted in a cost per subject of under $50, a fraction of the cost typical of such data collection, opening up the possibility for large-scale programs particularly in low- and middle-income countries. + Vasopressin (AVP), a nonapeptide synthesized predominantly by magnocellular hypothalamic neurons, is conveyed to the posterior pituitary via the pituitary stalk, where AVP is secreted into the circulation. Known to regulate blood pressure and water homeostasis, it also modulates diverse social behaviors, such as pair-bonding, social recognition and cognition in mammals including humans. Importantly, AVP modulates social behaviors in a gender-specific manner, perhaps, due to gender differences in the distribution in the brain of AVP and its main receptor AVPR1a. There is a corpus of integrative studies for the expression of AVP and AVPR1a in various brain regions, and their functions in modulating central and peripheral actions. In order to purposefully address sexually dimorphic and novel roles of AVP on central and peripheral functions through its AVPR1a, we utilized RNAscope to map Avp and Avpr1a single transcript expression in the mouse brain. As the most comprehensive atlas of AVP and AVPR1a in the mouse brain, this compendium highlights the importance of newly identified AVP/AVPR1a neuronal nodes that may stimulate further functional studies. -in bioRxiv: Neuroscience on 2024-12-09 00:00:00 UTC. +
in bioRxiv: Neuroscience on 2024-12-10 00:00:00 UTC.
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Brain responses vary in duration - modelingstrategies and challenges
+http://biorxiv.org/cgi/content/short/2024.12.09.627642v1?rss=1 +">Spatial organization of multisensory convergence in mouse isocortex - Typically, event-related brain responses are calculated invariant to the underlying event duration, even in cases where event durations observably vary: with reaction times, fixation durations, word lengths, or varying stimulus durations. Additionally, an often co-occurring consequence of differing event durations is a variable overlap of the responses to subsequent events. While the problem of overlap e.g. in fMRI and EEG is successfully addressed using linear deconvolution, it is unclear whether deconvolution and duration covariate modeling can be jointly used, as both are dependent on the same inter-event-distance variability. Here, we first show that failing to explicitly account for event durations can lead to spurious results and thus are important to consider. Next, we propose and compare several methods based on multiple regression to explicitly account for stimulus durations. Using simulations, we find that non-linear spline regression of the duration effect outperforms other candidate approaches. Finally, we show that non-linear event duration modeling is compatible with linear overlap correction in time, making it a flexible and appropriate tool to model overlapping brain signals. This allows us to reconcile the analysis of stimulus responses with e.g. condition-biased reaction times, condition-biased stimulus duration, or fixation-related activity with condition-biased fixation durations. While in this paper we focus on EEG analyses, these findings generalize to LFPs, fMRI BOLD-responses, pupil dilation responses, and other overlapping signals. + The diverse functions of different cortical areas are thought to arise from their distinct groups of inputs. However, additional organizing principles may exist in the spatial structure of converging inputs. We investigated spatial convergence patterns of projections from primary sensory areas to other areas throughout the mouse isocortex. We used a large tract tracing dataset to estimate the dimension of the space into which topographical connections from multiple modalities converged within each other cortical area. We call this measure the topography dimension (TD). TD is higher for areas that receive inputs of similar strength from multiple sensory modalities, and lower when multiple inputs terminate in register with one another. Across the isocortex, TD varied by a factor of ~4. TD was positively correlated with hierarchy score, an independent measure that is based on laminar connection patterns. Furthermore, TD (an anatomical measure) was significantly related to several measures of neural activity. In particular, higher TD was associated with higher neural activity dimension, lower population sparseness, and lower lifetime sparseness of spontaneous activity, independent of an area's hierarchical position. Finally, we analyzed factors that limited TD and found that linear correlations among projections from different areas typically had little impact, while diversity of connection strengths, both between different projections onto the same area, and within projections across different parts of an area, limited TD substantially. This analysis revealed additional intricacy of cortical networks, beyond areas' sets of connections and hierarchical organization. We propose a means of approximating this organization in deep-network models. -in bioRxiv: Neuroscience on 2024-12-09 00:00:00 UTC. +
in bioRxiv: Neuroscience on 2024-12-10 00:00:00 UTC.
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Trial-by-trial inter-areal interactions in visual cortex in the presence or absence of visual stimulation
+http://biorxiv.org/cgi/content/short/2024.12.09.627520v1?rss=1 +">Dysfunctional oscillatory bursting patterns underlie working memory deficits in adolescents with ADHD - State-of-the-art computational models of vision largely focus on fitting trial-averaged spike counts to visual stimuli using overparameterized neural networks. However, a computational model of the visual cortex should predict the dynamic responses of neurons in single trials across different experimental conditions. In this study, we investigated trial-by-trial inter-areal interactions in the visual cortex by predicting neuronal activity in one area based on activity in another, distinguishing between stimulus-driven and non-stimulus-driven shared variability. We analyzed two datasets: calcium imaging from mouse V1 layers 2/3 and 4, and extracellular neurophysiological recordings from macaque V1 and V4. Our results show that neuronal activity can be predicted bidirectionally between L2/3 and L4 in mice, and between V1 and V4 in macaques, with the latter interaction exhibiting directional asymmetry. The predictability of neuronal responses varied with the type of visual stimulus, yet responses could also be predicted in the absence of visual stimulation. In mice, we observed a bimodal distribution of neurons, with some neurons primarily driven by visual inputs and others showing predictable activity during spontaneous activity despite lacking consistent visually evoked responses. Predictability also depended on intrinsic neuronal properties, receptive field overlap, and the relative timing of activity across areas. Our findings highlight the presence of both stimulus- and non-stimulus-related components in interactions between visual areas across diverse contexts and underscore the importance of non-visual shared variability between visual regions in both mice and macaques. + Identifying neural markers of clinical symptom fluctuations is prerequisite to developing more precise brain-targeted treatments in psychiatry. We have recently shown that working memory (WM) in healthy adults is dependent on the rise and fall interplay between alpha/beta and gamma bursts within frontoparietal regions, and that deviations in these patterns lead to WM performance errors. However, it is not known whether such bursting deviations underlie clinically relevant WM-related symptoms or clinical status in individuals with WM deficits. In adolescents (n=27) with attention deficit hyperactivity disorder (ADHD), we investigated WM-related dynamics between alpha/beta and gamma bursts in relation to clinical status fluctuations. Participants repeatedly completed a visual Sternberg spatial working memory task during EEG recording as part of their participation in two research studies (n=224 person-sessions). Source localizing EEG data to each structural MRI, the rate and volume of alpha, beta, and gamma bursts were examined within the dorsolateral prefrontal cortex (DLPFC) and posterior parietal cortex (PPC). Alpha/beta and gamma bursts at the DLPFC and PPC displayed complimentary roles in WM processes. Alpha/beta bursting decreased during stimuli encoding and increased during the delay, while gamma bursting was elevated during encoding and decreased during the delay. Deviations in bursting patterns were associated with WM errors and clinical symptoms. We conclude that dysfunctional alpha/beta and gamma burst dynamics within the frontoparietal region underlie both intra-individual WM performance and WM symptom fluctuations in adolescents with ADHD. Such burst dynamics reflect a novel target and biomarker for WM-related treatment development. -in bioRxiv: Neuroscience on 2024-12-09 00:00:00 UTC. +
in bioRxiv: Neuroscience on 2024-12-10 00:00:00 UTC.
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A subset of mouse hippocampus CA1 pyramidal neurons learns sparse synaptic input patterns.
+http://biorxiv.org/cgi/content/short/2024.12.09.626634v1?rss=1 +">The impact of sex differences on perceived pain intensity in pain protocol standardization - Synaptic plasticity in the hippocampus is fundamental to learning and memory, yet few studies examine how pattern learning occurs across multiple synapses. Such cross-synapse learning is fundamental to emergent properties of pattern discrimination and generalisation, which depend on assumptions about independence of plasticity and linearity of summation. We used sparse optogenetic spatiotemporal pattern stimulation in the CA3 coupled with postsynaptic depolarization to elicit plasticity on CA1 pyramidal neurons, and found that 'trained' patterns were selectively strengthened, but only in a subset of postsynaptic cells. Increased resting membrane potential and background mini-EPSP rates were predictive of learner cells. Summation following plasticity became more linear in learners compared to non-learners, consistent with the observed elevated post-stimulus hyperpolarization on non-learner cells. Thus our exploration of biologically plausible sparse activity supports pattern-selective learning, but in a heterogeneous manner modulated by both cell-intrinsic and network features. + Background: Sex differences have been widely demonstrated in both acute and chronic pain. Sex differences may have wider impact on research design and analysis than already established. This study addresses an important methodological aspect with regards to how sex differences could influence the design of standardized experimental pain protocols used to characterize an individuals pain response. Methods: This study addresses sex differences of perceived pain at tonic heat pain threshold (HPT). Participants used a computerized visual analogue scale (CoVAS) to continually rated subjective pain intensity during tonic HPT. Metrics (Mean, Standard Deviation, Maximum) were extracted from the CoVAS to characterize perceived pain. Results: Female participants rated pain intensity at HPT significantly lower than male participants across all extracted metrics used to characterize the coVAS rating. The effect of sex on the mean and standard deviation of pain intensity ratings at HPT was medium, while the effect size of sex on the maximum pain intensity rating at HPT was large. Conclusion: The significant sex differences in perceived pain intensity at HPT indicates that methods of standardization to a specific pain intensity merit sex-specific consideration. Additionally, these observed sex differences underscore the necessity for sex specific design across both pre-clinical and clinical studies of pain. -in bioRxiv: Neuroscience on 2024-12-09 00:00:00 UTC. +
in bioRxiv: Neuroscience on 2024-12-10 00:00:00 UTC.
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A Comparative Study of Muscular, Vestibular, and Haptic Stimulation on Dream Incorporation
+http://biorxiv.org/cgi/content/short/2024.12.06.625641v1?rss=1 +">Hormetic curve of dietary mono- and disaccharide content determines weight gain, gut microbiota composition and cognitive ability in mice - The connection between the dreamed body and the real physical body remains a subject of ongoing investigation. This study explored how the dreamed body responds to somatosensory stimulation of the physical body, aiming to shed light on the sensory processes that shape our dreaming experiences. We employed a novel within-subject design to compare the incorporation of three different types of bodily stimuli; electrical muscular, galvanic vestibular, and haptic vibration, into dream content, alongside a control sham condition for each stimulus. In total, 24 participants spent one adaptation night, followed by three consecutive test nights in the sleep laboratory. REM awakenings, after sham or stimulation periods, were carried out for dream report collection. In total, 165 dream reports were collected across conditions. While dream incorporation was observed across the three stimulation methods, it occurred equally in both the stimulation and sham conditions for all three modalities. These findings highlight broader methodological challenges in dream incorporation research and raise concerns about potential confounding factors affecting the interpretation of results. Future research with larger sample sizes is needed to detect smaller effect sizes and fully understand the influence of these somatosensory stimuli on dream content. This study employed a rigorous experimental approach to exploring dream incorporation and addressed many methodological challenges in this area. We further suggest areas of improvement to optimize dream incorporation of different sensory modalities. + Hormesis is defined as dose response phenomenon characterized by low-dose stimulation and high-dose inhibition (Calabrese & Mattson, 2017). To date, low doses of several stressors (intermittent fasting, caloric restriction or selected phytochemicals) have been shown to exert beneficial effects on health (Martin et al., 2006). In the present study, we aimed to determine hormetic factors in a series of diets used in mice. We found that animals fed high-sugar diet (HSD) or high-fat diet (HFD) containing relatively high amounts of mono- and disaccharides become obese compared to animals fed standard diet (STAND) or ketogenic diet (KD) containing low doses of these compounds. Underlying the observed metabolic phenotype may be changes in the composition of the intestinal microbiota, showing u-shaped features in selected species. It is noteworthy that a short-term dietary regimen of several weeks resulted in difficulties in achieving effective scores on a complex cognitive test based on spatial procedural acquisition in the HSD and HFD groups. Our data identify dietary mono- and disaccharide content (commonly known as sugars) as a critical hormetic factor with beneficial/harmful effects at multiple levels of body function. -in bioRxiv: Neuroscience on 2024-12-09 00:00:00 UTC. +
in bioRxiv: Neuroscience on 2024-12-10 00:00:00 UTC.
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Cognitive Dynamics of Verb-Particle Constructions: An Eye-Tracking Study
+http://biorxiv.org/cgi/content/short/2024.12.05.625471v1?rss=1 +">Brain-body circuit by which midbrain dopamine neuronal activity modulates splenic immunity - This study investigates the cognitive processing of verb-particle constructions (VPCs) using eye-tracking data analysis method to explore how English native speakers process different types of the sequence NP-verb-particle-NP during reading tasks. While previous research has focused on phrasal verbs, our study extends this examination to include patterns with prepositions, aiming to identify distinct cognitive engagement patterns and processing efficiencies associated with each. We employed the Provo Corpus to analyse eye movements while participants read sentences containing these constructions. we focused on metrics such as first fixation duration, gaze duration, go-past times, and total reading times. Our findings indicate similarities in the lexical verbs, and significant differences in particles, indicating how these two types of constructions are processed, with phrasal verbs sometimes processed more efficiently than the prepositional counterparts. This suggests that phrasal verbs might be more deeply entrenched in the linguistic repertoire of native speakers, possibly functioning as single lexical units. This research contributes to the understanding of complex structures processing and the cognitive mechanisms that support it, offering insights that could influence linguistic theory and language education. + Midbrain dopamine neurons are integral to central nervous system function, yet their influence on peripheral immunity remains underexplored. This study identifies a neural circuit connecting midbrain dopamine neurons to the spleen through the dorsal vagal complex (DVC) and celiac ganglion. Using DAT:Cre mice and Cre-dependent viral tracers, we demonstrated that midbrain dopamine neurons project to the DVC, where they form synapses and modulate neuronal activity. Electrophysiological recordings revealed that DVC neurons express D1-like and D2-like dopamine receptors, responding to dopamine with altered excitability. Chemogenetic activation of midbrain dopamine neurons induced dopamine release in the DVC and increased cFos expression in both the DVC and celiac ganglion, indicating enhanced neuronal activity along this circuit. Anterograde multi-transsynaptic tracing confirmed connectivity from the midbrain to the spleen via the celiac ganglion. Activation of this circuit resulted in reduced spleen weight as well as a significant decrease in naive CD4+ T-cell populations without affecting total T-cell numbers. These findings unveil a functional midbrain-DVC-celiac ganglion-spleen pathway, through which midbrain dopamine neurons modulate splenic immunity. This novel insight into the neural regulation of the immune system has important implications for diseases involving altered dopamine neurotransmission, highlighting potential targets for immunotherapeutic interventions. -in bioRxiv: Neuroscience on 2024-12-09 00:00:00 UTC. +
in bioRxiv: Neuroscience on 2024-12-10 00:00:00 UTC.
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Time-of-day related fluctuations of self-belief formation
+http://biorxiv.org/cgi/content/short/2024.12.05.626994v1?rss=1 +">The effect of illumination cues on color constancy in simultaneous identification of illumination and reflectance changes - Time of day influences a variety of human cognitive processes, including attention, executive functions and memory formation, as well as affective experiences and mood. However, circadian modulations of self-related learning and belief formation, which are highly affected by emotional states, remain poorly understood. Here, we present results from exploratory post-hoc analyses on data aggregated from five studies assessing the formation of self-related ability beliefs. A total of N=242 healthy participants completed a validated learning task at different times of the day, during which they continuously received feedback on their performance. Computational modeling was applied to quantify participants' learning behavior during the task. Results suggest an association between time-of-day and self-belief formation, showing that participants who were tested in the evening (7:00-9:59 p.m.) updated their self-beliefs more strongly in response to the received feedback compared to those tested in the afternoon (1:00-3:59 p.m.). Evidence from additional models indicated that these differences were driven by non-linear, rhythmic changes in self-belief formation across different times of the day. Future studies should systematically examine within-subject fluctuations in self-belief formation across the day and address the influence of individual factors such as chronotype, age, mood and sleep quality. Understanding circadian modulations of self-related belief formation could contribute to optimized interventions for conditions characterized by maladaptive self-beliefs, such as depression, as well as in academic contexts. + To provide a stable percept of the surface color of objects, the visual system needs to account for variation in illumination chromaticity. This ability is called color constancy. The details of how the visual system disambiguates effects of illumination and reflectance on the light reaching the eye are still unclear. Here we asked how independent illumination and reflectance judgments are of each other, whether color constancy depends on explicitly identifying the illumination chromaticity, and what kinds of contextual cues support this identification. We studied the simultaneous identification of illumination and reflectance changes with realistically rendered, abstract 3D-scenes. Observers were tasked to identify both of these changes between sequentially presented stimuli. The stimuli included a central object whose reflectance could vary, and a background that only varied due to changes in illumination chromaticity. We manipulated the visual cues available in the background: local contrast and specular highlights. Identification of illumination and reflectance changes was not independent: While reflectance changes were rarely mis-identified as illumination changes, illumination changes clearly biased reflectance judgments. However, correct identification of reflectance changes was also not fully dependent on correctly identifying the illumination change: Only when there was no illumination change in the stimulus did it lead to better color constancy, that is, correctly identifying the reflectance change. Discriminability of illumination changes did not vary based on available visual cues, but discriminability of reflectance changes was improved with local contrast, and to a lesser extent with specular highlights, in the stimulus. We conclude that a failure of color constancy does not depend on a failure to identify illumination changes, but additional visual cues still improve color constancy through better disambiguation of illumination and reflectance changes. -in bioRxiv: Neuroscience on 2024-12-09 00:00:00 UTC. +
in bioRxiv: Neuroscience on 2024-12-10 00:00:00 UTC.
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Effects of Spatial Constraints of Inhibitory Connectivity on the Dynamical Development of Criticality in Spiking Networks
+http://biorxiv.org/cgi/content/short/2024.12.06.626968v1?rss=1 +">Multi-omic integration with human DRG proteomics highlights TNFα signalling as a relevant sexually dimorphic pathway - Neural systems are hypothesized to operate near criticality, enhancing their capacity for optimal information processing, transmission and storage capabilities. Criticality has typically been studied in spiking neural networks and related systems organized in random or full connectivity, with the balance of excitation and inhibition being a key determinant of the critical point of the system. However, given that neurons in the brain are spatially distributed, with their distances significantly influencing connectivity and signal timing, it is unclear how the spatial organization of excitatory and inhibitory connectivity influences the network's self-organization towards criticality. Here, we systematically constrain the distance and density of inhibitory connectivity in two-dimensional spiking networks and allow synaptic weights to self-organize with activity-dependent excitatory and inhibitory plasticity in the presence of a low level of stochastic intrinsic activity. We then investigate the relationship between inhibitory connectivity, synaptic weights, and the resulting network activity during and after development. We find that networks with longer-range inhibitory synapses tend towards more supercritical behavior compared to networks with a similar number of shorter-range inhibitory synapses. We show that this distance dependence is a consequence of weaker long-range synapses after development due to the presence of synaptic delays, which shift most spike pairs outside of the potentiation window of the inhibitory learning rule. + The peripheral nervous system has been widely implicated in pathological conditions that exhibit distinct clinical presentations in men and women, most notably in chronic pain disorders. Here, we explored this sexual dimorphism at a molecular level. We expanded the available omics landscape in the PNS to include quantitative proteomics of the human dorsal root ganglia (hDRG) and nerve. Using data-independent acquisition mass spectrometry, we uncovered an extensive protein landscape, validated against tissue-specific differences between the nerve and hDRG. Using a combination of multi-omic analyses and in vitro functional support, we then examined sex-differences, highlighting TNF signalling as a relevant sexually dimorphic pathway in males. These results support a functional sexually dimorphism in the periphery, which is of particular importance to sensory- and pain-related clinical translation. -in bioRxiv: Neuroscience on 2024-12-09 00:00:00 UTC. +
in bioRxiv: Neuroscience on 2024-12-10 00:00:00 UTC.
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Caliber of sensory axons in vivo varies spatially and temporally and is influenced by the cellular microenvironment
+http://biorxiv.org/cgi/content/short/2024.12.09.627564v1?rss=1 +">Cannabinoid inhibition of mechanosensitive K+ channels - Cell shape is crucial to cell function, particularly in neurons. The cross-sectional diameter, also known as caliber, of axons and dendrites is an important parameter of neuron shape, best appreciated for its influence on the speed of action potential propagation. Most studies of axon caliber focus on cell-wide regulation and assume that caliber is static. Here, we have investigated local variation and dynamics of axon caliber in the peripheral axons of zebrafish touch-sensing neurons at embryonic stages, prior to sex determination. To obtain absolute measurements of caliber in vivo, we paired sparse membrane labeling with super-resolution microscopy of neurons in live fish. We found that axon segments had varicose or "pearled" morphologies, and thus vary in caliber along their length, consistent with reports from mammalian systems. Sister axon segments originating from the most proximal branch point in the axon arbor had average calibers that were largely independent of each other. Axon caliber tapered across the branch point, suggesting that action potential conductance may be favored in these afferent axons. Caliber was dynamic on the time-scale of minutes, and this dynamicity changed over the course of development. By measuring the caliber of axons adjacent to dividing epithelial cells, we found that the cellular microenvironment is one of potentially multiple drivers of axon caliber variation across space and time. Our findings raise the possibility that spatial and temporal variation in axon caliber could significantly influence neuronal physiology. + Cannabidiol (CBD) is a prominent non-psychoactive small molecule produced by cannabis plants used clinically as an antiepileptic. Here, we show CBD and other cannabinoids are potent inhibitors of mechanosensitive two-pore domain K+ (K2P) channels, including TRAAK and TREK-1 that contribute to spike propagation in myelinated axons. Five TRAAK mutations that cause epilepsy or the neurodevelopmental syndrome FHEIG (facial dysmorphism, hypertrichosis, epilepsy, intellectual/developmental delay, and gingival overgrowth) retain sensitivity to cannabinoid inhibition. A cryo-EM structure reveals CBD binds in the intracellular cavity of TREK-1 to sterically block ion conduction. These results show that cannabinoids and endogenous lipids compete for a common binding site to inhibit channel activity, identify mechanosensitive K2Ps as potential physiological targets of CBD, and suggest cannabinoids could counter gain-of-function in TRAAK channelopathies. -in bioRxiv: Neuroscience on 2024-12-09 00:00:00 UTC. +
in bioRxiv: Neuroscience on 2024-12-10 00:00:00 UTC.
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Top-down attention and Alzheimer's pathology impact cortical selectivity during learning,influencing episodic memory in older adults
+http://biorxiv.org/cgi/content/short/2024.12.09.627587v1?rss=1 +">Competition between glycine and GABAA receptors for gephyrin controls their equilibrium populations at inhibitory synapses - Human aging affects the ability to remember new experiences, in part, because of altered neural function during memory formation. One potential contributor to age-related memory decline is diminished neural selectivity -- i.e., a decline in the differential response of cortical regions to preferred vs. non-preferred stimuli during event perception -- yet the factors driving variability in neural selectivity with age remain unclear. We examined the impact of top-down attention and preclinical Alzheimer's disease (AD) pathology on neural selectivity during memory encoding in 156 cognitively unimpaired older participants who underwent fMRI while performing a word-face and word-scene associative memory task. Neural selectivity in face- and place-selective cortical regions was greater during events that were later remembered compared to forgotten. Critically, neural selectivity during learning positively scaled with memory-related variability in top-down attention, whereas selectivity negatively related to early AD pathology, evidenced by elevated plasma pTau181. Path analysis revealed that neural selectivity at encoding mediated the effects of age, top-down attention, and pTau181 on associative memory. Collectively, these data reveal multiple pathways that contribute to memory differences among older adults -- AD-independent reductions in top-down attention and AD-related pathology alter the precision of cortical representations of events during experience, with consequences for remembering. + Glycine and GABA receptors are ligand-gated chloride channels that mediate inhibitory neurotransmission throughout the central nervous system. The receptors co-localise widely at inhibitory synapses in the spinal cord and in the brainstem due to their interaction with an overlapping binding site of the synaptic scaffold protein gephyrin, pointing to a direct competition between the different receptor types. We have put this hypothesis to the test using single molecule approaches to measure receptor-gephyrin interactions in cells and in vitro. We explored the effects of receptor competition at inhibitory synapses in living neurons by measuring the change in the accumulation and effective stabilisation energy of glycine receptors in the presence of interfering GABA receptor complexes through single molecule tracking and diffusion analysis. Secondly, using molecular tweezers, we quantified the thermodynamic properties of receptor-gephyrin binding, demonstrating direct and reversible competition through the addition of interacting peptides in solution. The relatively low affinity of GABA receptor subunits for gephyrin compared to the glycine receptor raises interesting questions about the role of this competition in synaptic plasticity. We hypothesize that GABA and glycine receptor competition constitutes a molecular system designed to reconcile synapse stability and plasticity at mixed inhibitory synapses. -in bioRxiv: Neuroscience on 2024-12-09 00:00:00 UTC. +
in bioRxiv: Neuroscience on 2024-12-10 00:00:00 UTC.
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FTO (fat-mass and obesity-associated protein) deficiency aggravates age-dependent depression-like behaviors and cognitive impairment
+http://biorxiv.org/cgi/content/short/2024.12.08.627337v1?rss=1 +">Mobile Human Brain Imaging using Functional Ultrasound - Background: The demethylase fat mass and obesity-related protein (FTO) is strongly associated with depression. Aging is a risk factor for synaptic plasticity damage in the brain and leads to neurocognitive dysfunctions. However, whether FTO is associated with susceptibility to depression in different age groups remains unknown. Methods: We subjected 3- and 12-month-old C57BL/6J male mice to 6 weeks of chronic unpredictable mild stress (CUMS) and 3 weeks of hippocampal injection of FTO knockdown adeno-associated virus 9 shRNA (FTO-KD AAV9). Finally, 36 male mice in each 3-month-old and 12-month-old groups were divided into three groups (n=12): Sham, CUMS, and FTO-KD. After 6 weeks, we assessed behavioral deficits (depressive and anxiety-like behaviors and cognitive impairment) by behavioral tests and hippocampal neuronal damage (dendritic spine density, neuronal atrophy, and expression of proteins associated with synaptic plasticity) by molecular biochemical experiments. Results: The results showed that 12-month-old C57BL/6J mice were more likely to develop depression-like behavior and spatial learning and memory impairment induced by CUMS than 3-month-old mice. Chronic stress-induced depression-like behavior and cognitive impairment worsened after the FTO-KD intervention. In the hippocampus of 3- and 12-month-old mice, CUMS induced the downregulation of FTO, nerve growth factor (NGF), reelin, and synaptic plasticity-related proteins. It also caused abnormal BDNF-TrkB signaling, reduced density of dendritic spines, and an increased number of neuronal pyknotic nuclei, leading to neuronal disarray, which was more significant in 12-month-old animals. FTO deficiency accelerated neuronal damage in the hippocampus of 12-month-old CUMS mice. Conclusions: This study provides rodent evidence that FTO deficiency may increase the susceptibility to depression in older adults by impairing hippocampal neuronal function and neuronal synaptic plasticity in an age-dependent manner. This suggests that the development of FTO activators may be an effective treatment for depression in older adults. + Imagine being able to study the human brain in real-world scenarios while the subject displays natural behaviors such as locomotion, social interaction, or spatial navigation. The advent of ultrafast ultrasound imaging brings us closer to this goal with functional Ultrasound imaging (fUSi), a new mobile neuroimaging technique. Here, we present real-time fUSi monitoring of brain activity during walking in a subject with a clinically approved sonolucent skull implant. Our approach utilizes personalized 3D-printed fUSi-helmets for stability, optical tracking for cross-modal validation with fMRI, advanced signal processing to estimate hemodynamic responses and facial tracking of a lick licking paradigm. These combined efforts allowed us to show consistent fUSi signals over 20 months, even during high-motion activities like walking. These results demonstrate the feasibility of fUSi for monitoring brain activity in real-world contexts, marking an important milestone for fUSi-based insights in clinical and neuroscientific research. -in bioRxiv: Neuroscience on 2024-12-09 00:00:00 UTC. +
in bioRxiv: Neuroscience on 2024-12-10 00:00:00 UTC.
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-Lymphatic drainage of cerebrospinal fluid using lymph node seeker 64Cu-labeled Gram-negative bacterial extracellular vesicles PET
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+Impact of working memory training on brain network plasticity and genetic associations: insights from individual differences
- Cerebrospinal fluid (CSF) is drained into the systemic lymphatics via paravertebral lymph nodes. Superficial and deep cervical lymph nodes collect CSF in mice, but the exact and quantified routes are unknown. Recently, we simultaneously visualized cervical, sacral and iliac lymph nodes via serial imaging on the intrathecal [64Cu]Cu-albumin positron emission tomography. Paravertebral lymph nodes might act as sentinels to monitor the CSF, brain, and spinal cord. We used 64Cu-labeled Escherichia coli extracellular vesicles, outer membrane vesicles (OMVs), as lymph node seekers for intrathecal administration with an optimized volume/rate and quantified the differential amounts of various paravertebral lymph nodes along the axis of the brain and spinal cord in mice. The quantified results revealed 77.3% in superficial and deep cervical lymph nodes, 11.4% in abdominal/pelvic lymph nodes and 11.3% in sacral lymph nodes. Click-labeled [64Cu]Cu-OMVs were drained to reach and stop at the lymph nodes on serial quantification. The cervical lymph nodes drained most of the OMV-laden CSF, which is proportional to the surface areas of the brain (70%) and spinal cord in mice. We propose that all paravertebral lymph nodes monitor the segmental regions of the brain and spinal cord as immediate sentinel lymph nodes against the central nervous system. +in bioRxiv: Neuroscience on 2024-12-09 00:00:00 UTC. +
in Cerebral Cortex on 2024-12-10 00:00:00 UTC.
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-Parkinson's disease-associated Pink1 loss disrupts vesicle trafficking in ensheathing glia causing dopaminergic neuron synapse loss
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+Brain Sciences, Vol. 14, Pages 1239: Clearing Amyloid-Beta by Astrocytes: The Role of Rho GTPases Signaling Pathways as Potential Therapeutic Targets
- Parkinson's disease (PD) is commonly associated with the loss of dopaminergic neurons in the substantia nigra, but many other cell types are affected even before neuron loss occurs. Recent studies have linked oligodendrocytes to early stages of PD, though their precise role is still unclear. Pink1 is mutated in familial PD and through unbiased single-cell sequencing of the entire brain of Drosophila Pink1 models, we observed significant gene deregulation in ensheathing glia (EG); cells that share functional similarities with oligodendrocytes. We found that the loss of Pink1 leads to the activation of EG, similar to the reactive response of EG seen upon nerve injury. Using cell-type specific transcriptomics, we identified deregulated genes in EG as potential functional modifiers. Specifically, downregulating two trafficking factors, Rab7 and Vps13, also mutated in PD, or the direct regulators of Rab7, Mon1 and Ccz1, specifically in EG was sufficient to rescue neuronal function and protect against dopaminergic synapse loss. Our findings demonstrate that Pink1 loss in neurons triggers an injury response in EG, and that Pink1 loss in EG in turn disrupts neuronal function. Vesicle trafficking components, which regulate membrane interactions between organelles within EG, play a crucial role in maintaining neuronal health and preventing dopaminergic synapse loss. Our work highlights the essential role of glial support cells in the pathogenesis of PD and identifies vesicle trafficking within these cells as a key point of convergence in disease progression. +Brain Sciences, Vol. 14, Pages 1239: Clearing Amyloid-Beta by Astrocytes: The Role of Rho GTPases Signaling Pathways as Potential Therapeutic Targets
+Brain Sciences doi: 10.3390/brainsci14121239
+Authors: + Gyeongah Park + Zhen Jin + Hui Lu + Jianyang Du +
+Astrocytes, vital support cells in the central nervous system (CNS), are crucial for maintaining neuronal health. In neurodegenerative diseases such as Alzheimer&rsquo;s disease (AD), astrocytes play a key role in clearing toxic amyloid-&beta; (A&beta;) peptides. A&beta;, a potent neuroinflammatory trigger, stimulates astrocytes to release excessive glutamate and inflammatory factors, exacerbating neuronal dysfunction and death. Recent studies underscore the role of Rho GTPases&mdash;particularly RhoA, Rac1, and Cdc42&mdash;in regulating A&beta; clearance and neuroinflammation. These key regulators of cytoskeletal dynamics and intracellular signaling pathways function independently through distinct mechanisms but may converge to modulate inflammatory responses. Their influence on astrocyte structure and function extends to regulating endothelin-converting enzyme (ECE) activity, which modulates vasoactive peptides such as endothelin-1 (ET-1). Through these processes, Rho GTPases impact vascular permeability and neuroinflammation, contributing to AD pathogenesis by affecting both A&beta; clearance and cerebrovascular interactions. Understanding the interplay between Rho GTPases and the cerebrovascular system provides fresh insights into AD pathogenesis. Targeting Rho GTPase signaling pathways in astrocytes could offer a promising therapeutic approach to mitigate neuroinflammation, enhance A&beta; clearance, and slow disease progression, ultimately improving cognitive outcomes in AD patients.
-in bioRxiv: Neuroscience on 2024-12-09 00:00:00 UTC. +
in Brain Sciences on 2024-12-10 00:00:00 UTC.
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-Behavior-relevant periodized neural representation of acoustic but not tactile rhythm in humans
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+Tau Accumulation Induces Microglial State Alterations in Alzheimer's Disease Model Mice
- Music makes people move. This human propensity to coordinate movement with the rhythm of music requires multiscale temporal integration, allowing fast sensory events composing rhythmic input to be mapped onto slower internal templates such as periodic beats. Relatedly, beat perception has been shown to involve a selective enhancement of the beat periodicities in the neural response to rhythm. However, the extent to which this ability to move to the beat, and the related periodized neural representation, are shared across the senses beyond audition remains unknown. Here we addressed this question using acoustic and tactile rhythms, while recording separately the electroencephalography (EEG) responses and finger tapping to these rhythms in healthy volunteers. Consistent with previous studies, EEG responses to the acoustic rhythm featured significant enhancement of the beat, and this periodized neural representation was specifically concentrated within a low-frequency range below 15 Hz. In contrast, the same rhythm conveyed with tactile inputs elicited responses over a broader frequency range, up to 25Hz, with no significant periodization, and resulted in less stable tapping. Together, these findings indicate that low-frequency neural activity preferentially supports behavior-relevant internal representation of rhythmic input. However, this neural representation is not necessarily shared across the senses, as well as the ability to move to the beat, corroborating multimodal differences in beat perception. This low-frequency neural representation may thus reflect a process of multiscale temporal integration allowing the auditory system to go beyond mere tracking of onset timing and support higher-level internal representation and motor entrainment to rhythm. +Unique microglial states have been identified in Alzheimer's disease (AD) model mice and postmortem AD brains. Although it has been well documented that amyloid-β accumulation induces the alteration of microglial states, the relationship between tau pathology and microglial states remains incompletely understood because of a lack of suitable AD models. In the present study, we generated a novel AD model mouse by the intracerebral administration of tau purified from human brains with primary age-related tauopathy into App knock-in mice with humanized tau. Immunohistochemical analyses revealed that Dectin-1-positive disease-associated microglia were increased in the AD model mice after tau accumulation in the brain. We then performed single-nucleus RNA sequencing on the AD model mice to evaluate the differences in microglial states with and without tau propagation and accumulation. By taking advantage of spatial transcriptomics and existing single-cell RNA sequencing datasets, we showed for the first time that tau propagation and accumulation induce a disease-associated microglial phenotype at the expense of an age-related nonhomeostatic counterpart (namely, white matter-associated microglia) in an AD model mouse brain. Future work using spatial transcriptomics at single-cell resolution will pave the way for a more appropriate interpretation of microglial alterations in response to tau pathology in the AD brain.
-in bioRxiv: Neuroscience on 2024-12-09 00:00:00 UTC. +
in eNeuro on 2024-12-09 17:30:13 UTC.
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-Repetition of Rhythmic Patterns Fosters Neural Representation of Musical Meter
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+Dissociable Effects of Urgency and Evidence Accumulation during Reaching Revealed by Dynamic Multisensory Integration
- Music often entails perception of periodic pulses (hereafter meter) which serve as an internal temporal reference to coordinate movements to music. Crucially, meter perception arises even when the musical rhythm only weakly cues meter periodicities (i.e., syncopated rhythms). However, syncopated rhythms are often looped in music, suggesting that repetition of rhythmic patterns may facilitate meter perception by providing periodic cues at a slower, supra-second timescale. Here, we tested this hypothesis by recording separately electroencephalographic (EEG) and behavioral responses (finger tapping) while participants listened to different syncopated rhythmic sequences. These sequences either consisted of a repeated pattern (repetition of 4.8 and 9.6-s patterns) or were generated without repetition. EEG responses showed overall periodization of the rhythmic input, at periodicities corresponding to those expressed as the meter in behavioral responses, and in contrast with the weak cues to these periodicities in the rhythmic inputs. Most importantly, pattern repetition strengthened this neural representation of the meter, demonstrating that supra-second periodicities in the rhythmic input further enhance sub-second periodicities in neural activity. These findings thus highlight the multiscale nature of temporal processes at stake in processing musical rhythm, and, more generally, complex rhythmic inputs involved in interpersonal interaction and communication. +When making perceptual decisions, humans combine information across sensory modalities dependent on their respective uncertainties. However, it remains unknown how the brain integrates multisensory feedback during movement and which factors besides sensory uncertainty influence sensory contributions. We performed two reaching experiments on healthy adults to investigate whether movement corrections to combined visual and mechanical perturbations scale with visual uncertainty. To describe the dynamics of multimodal feedback responses, we further varied movement time and visual feedback duration during the movement. The results of our first experiment show that the contribution of visual feedback decreased with uncertainty. Additionally, we observed a transient phase during which visual feedback responses were stronger during faster movements. In a follow-up experiment, we found that the contribution of vision increased more quickly during slow movements when we presented the visual feedback for a longer time. Muscle activity corresponding to these visual responses exhibited modulations with sensory uncertainty and movement speed ca. 100 ms following the onset of the visual feedback. Using an optimal feedback control model, we show that the increased response to visual feedback during fast movements can be explained by an urgency-dependent increase in control gains. Further, the fact that a longer viewing duration increased the visual contributions suggests that the brain accumulates sensory information over time to estimate the state of the arm during reaching. Our results provide additional evidence concerning the link between reaching control and decision-making, both of which appear to be influenced by sensory evidence accumulation and response urgency.
-in bioRxiv: Neuroscience on 2024-12-09 00:00:00 UTC. +
in eNeuro on 2024-12-09 17:30:13 UTC.
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-Meta-prediction extends human cortical and subcortical reward learning
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+Oxygen as obturation biomaterial in endodontic treatment: development of novel membranous dental restoration system [version 3; peer review: 1 approved, 2 approved with reservations]
- Human reward learning is constrained by environmental structure. Stable environments facilitate reward prediction but limit learning experiences[1-8], while uncertain environments hinder predictability and learnability[9-12]. We propose a novel framework extending these boundaries through "meta-prediction" - predicting human prediction. The meta-prediction entwines two Bellman equations: one for human prediction and the other for predicting the prediction error of the former. The framework pretrains computational models imitating individuals' reward prediction (specification), then generates new tasks to extremize the models' prediction errors (generalization). Simulations with 82 subjects' data generated subject-independent task design across four scenarios without compromising learnability. In an independent fMRI experiment with 49 participants, meta-prediction guides behavior and neural activities in the ventral striatum, lateral prefrontal, and insular cortex, the areas encoding prediction errors. We also demonstrated that meta-prediction can generate complex tasks compositionally to discern human reward learning bias. Our framework redefines the role of tasks in cognitive science and AI. + Complexities in obturation and difficulties in disinfection represent significant issues that render endodontic treatment notably time-consuming. A new perspective is essential to reduce both working time and address these two challenges. To date, none of the established techniques for root canal obturation can assure a perfect seal. Solid materials are not easily manipulated to hermetically fill the intricate branches of the root canal system. Concurrently, anaerobic and facultative anaerobic bacteria, particularly Enterococcus faecalis, are predominant in discussions surrounding endodontic infections. Numerous studies have demonstrated that achieving complete disinfection of Enterococcus faecalis is exceedingly difficult, even with the use of irrigating solutions that possess strong antibacterial properties. Under anaerobic conditions, the invasion efficiency of facultative anaerobes is heightened. If irrigation and disinfection fail to entirely eliminate anaerobes and facultative anaerobes, a novel strategy is required to address the bacteria that persist within the root canal. Oxygen can easily permeate the root canal system, eradicate anaerobes, and inhibit facultative anaerobes from becoming pathogenic. Therefore, employing oxygen as a biomaterial for obturation following appropriate cleaning and shaping procedures is anticipated to address the two primary endodontic issues. This article aims to explore a new potential concept for a dental restoration system that utilizes an oxygen-permeable membrane to reduce the time required for endodontic treatment. The membrane is positioned at the orifice of a duct designed to connect the entire root canal system with ambient air outside the restoration. The function of the membrane is somewhat analogous to the masks used during the COVID-19 pandemic, as it allows for the circulation of oxygen while preventing the passage of fluids, debris, and microorganisms. We hypothesize that the oxygen circulating within the root canal system will also function as a continuously renewing antimicrobial agent. -in bioRxiv: Neuroscience on 2024-12-09 00:00:00 UTC. +
in F1000Research on 2024-12-09 16:59:52 UTC.
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-The neuroreceptors and transporters underlying spontaneous brain activity
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+Towards an Integrated Performance Management and Measurement System for healthcare organisations: a case study in Montreal [version 2; peer review: 1 approved, 3 approved with reservations]
- Identifying the neuromodulators driving brain activity is critical for understanding communication, cognition, and neuropathology. Neuromodulators act through neuroreceptors and transporters and crucially, operate in a coordinated manner. However, in vivo methods in humans that can identify the neuromodulators driving brain activity remain limited. Here, we address this limitation using a neuroreceptor-based framework, enabling the identification of neuroreceptors and transporters underlying spontaneous brain activity. The framework utilizes cortical density maps of 19 neuroreceptors and transporters derived from Positron Emission Tomography (PET). Across four datasets (Ntotal = 314), our framework reconstructs spontaneous brain activity and functional connectivity (FC) from BOLD signals measured by functional MRI (fMRI), achieving an average accuracy of RBOLD = 0.58 +/- 0.05 and RFC = 0.62 +/- 0.02. Notably, our analysis reveals that the excitation-inhibition balance is maintained by two distinct modules of neuroreceptors and transporters exhibiting regional density differences across the cortex. The frameworks validity is supported by its ability to recover neuroreceptors and transporter's, 5-HT1a, 5-HT1b, 5-HT2a, and D2, known to bind lysergic acid diethylamide (LSD), and D2, 5-HT1a, 5-HT2a, and NET mediating the effects of Modafinil. Furthermore, the framework identified mechanistic links between neuroreceptors, transporters, and altered brain activity in schizophrenia, bipolar disorder, and ADHD. Finally, neuroreceptor-based reconstruction outperformed models based on structural connectivity and cortical folding geometry. Together, these findings underscore the potential of this neuroreceptor-based framework to advance our understanding of neuromodulatory mechanisms across diverse brain states and conditions. + This study proposes an approach for developing or improving performance management and measurement systems (PMMSs) for healthcare organisations. First, data is collected to analyse and understand the current organisation’s performance management system. Second, the SWOT (Strengths, Weaknesses, Opportunities, Threats) method is used to identify the main aspects of the performance management system to be improved. Third, based on the scientific literature and SWOT analysis, BSC principles are integrated to this performance management system to better align the organisation’s performance objectives and indicators with its strategy. Finally, we develop a performance indicator structure and select indicators to be used as well as how these indicators could be integrated and shared with higher hierarchical levels in the organisation by using AHP (Analytic Hierarchy Process). Our approach is applied to the CIUSSS du Centre-Sud-de-l’île-de-Montreal (CCSMTL), a large healthcare network, in the province of Québec, Canada. -in bioRxiv: Neuroscience on 2024-12-09 00:00:00 UTC. +
in F1000Research on 2024-12-09 16:57:44 UTC.
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-Brain Sciences, Vol. 14, Pages 1238: Long-Term Real-World Experience with Safinamide in Patients with Parkinson’s Disease
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+Differential quantification of alternative splicing events on spliced pangenome graphs
-Brain Sciences, Vol. 14, Pages 1238: Long-Term Real-World Experience with Safinamide in Patients with Parkinson’s Disease
-Brain Sciences doi: 10.3390/brainsci14121238
-Authors: - Anna Planas-Ballvé - Núria Caballol Pons - Alejandro Peral Quirós - Isabel Gómez Ruiz - Marta Balagué Marmaña - Alexander J. Velázquez Ballester - Dolors Lozano Moreno - Asunción Ávila Rivera -
-Introduction: Randomized clinical trials should be complemented with data from real-world studies. We report our long-term experience with safinamide in a movement disorders unit. Methods: This retrospective study included patients with Parkinson&rsquo;s disease (PD) treated with safinamide in our unit from February 2016 to May 2022 under routine clinical practice. Assessments included the Hoehn and Yahr (HY) stage, unified Parkinson&rsquo;s disease rating scale (UPDRS) part III score, levodopa equivalent daily dose (LEDD), LEDD for dopamine agonists, and safinamide treatment discontinuation. Results: We included 180 patients with a median age of 74 years (IQR 11), and the majority (90.6%) had an HY stage of &le;2. After a median follow-up of 40 months (IQR 34), 14 patients discontinued treatment with safinamide (7.8%, 95% CI 4.7 to 12.6). Among the 166 patients who remained on safinamide, the UPDRS III score was stable (10 (IQR 9) vs. 9 (IQR 13), p = 0.455). The LEDD significantly increased from a median of 300 mg to 500 mg (p &lt; 0.001), whereas the LEDD for dopamine agonists did not significantly increase. A subgroup of 89 patients who did not require dopamine agonists during follow-up showed stable UPDRS III score (10 (IQR 7) vs. 9 (IQR 14); p = 0.923), with a significant LEDD increase (300 mg to 400 mg, p &lt; 0.001). Conclusions: Our results support the long-term effectiveness and tolerability of safinamide in patients with PD in clinical practice.
+by Simone Ciccolella, Davide Cozzi, Gianluca Della Vedova, Stephen Njuguna Kuria, Paola Bonizzoni, Luca Denti
+ +Pangenomes are becoming a powerful framework to perform many bioinformatics analyses taking into account the genetic variability of a population, thus reducing the bias introduced by a single reference genome. With the wider diffusion of pangenomes, integrating genetic variability with transcriptome diversity is becoming a natural extension that demands specific methods for its exploration. In this work, we extend the notion of spliced pangenomes to that of annotated spliced pangenomes; this allows us to introduce a formal definition of Alternative Splicing (AS) events on a graph structure. To investigate the usage of graph pangenomes for the quantification of AS events across conditions, we developed pantas, the first pangenomic method for the detection and differential analysis of AS events from short RNA-Seq reads. A comparison with state-of-the-art linear reference-based approaches proves that pantas achieves competitive accuracy, making spliced pangenomes effective for conducting AS events quantification and opening future directions for the analysis of population-based transcriptomes. -in Brain Sciences on 2024-12-09 00:00:00 UTC. +
in PLoS Computational Biology on 2024-12-09 14:00:00 UTC.
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-Brain Sciences, Vol. 14, Pages 1237: Noninvasive Brain Stimulation for Improving Cognitive Deficits and Clinical Symptoms in Attention-Deficit/Hyperactivity Disorder: A Systematic Review and Meta-Analysis
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+Preserving friendships in school contacts: An algorithm to construct synthetic temporal networks for epidemic modelling
-Brain Sciences, Vol. 14, Pages 1237: Noninvasive Brain Stimulation for Improving Cognitive Deficits and Clinical Symptoms in Attention-Deficit/Hyperactivity Disorder: A Systematic Review and Meta-Analysis
-Brain Sciences doi: 10.3390/brainsci14121237
-Authors: - Yao Yin - Xueke Wang - Tingyong Feng -
-Objective: Noninvasive brain stimulation (NIBS) is a promising complementary treatment for attention-deficit/hyperactivity disorder (ADHD). However, its efficacy varies due to diverse participant profiles and methodologies. This meta-analysis, registered with PROSPERO (CRD42023457269), seeks to assess NIBS efficacy in improving cognitive deficits and clinical symptoms in individuals with ADHD. Methods: We systematically searched five databases (October 2024) for randomized controlled trials focusing on cognitive functions and clinical symptoms in individuals meeting the DSM/ICD criteria for ADHD. A meta-analytical synthesis was conducted using RevMan 5.4.1. Results: Meta-analyses found significant improvement in inhibitory control, working memory, and inattention in active transcranial direct current stimulation (tDCS) groups compared with sham groups. Conversely, repetitive transcranial magnetic stimulation (rTMS) did not demonstrate significant therapeutic benefits for ADHD symptoms. Additionally, four transcranial random noise stimulation (tRNS) and three transcranial alternating current stimulation (tACS) studies demonstrated promising improvements in executive functions and the alleviation of ADHD symptoms. Conclusions: The findings from this meta-analysis highlight NIBS as a promising adjunctive therapy for managing ADHD, advancing both theoretical knowledge and practical treatment options in this field.
+by Lucille Calmon, Elisabetta Colosi, Giulia Bassignana, Alain Barrat, Vittoria Colizza
+ +High-resolution temporal data on contacts between hosts provide crucial information on the mixing patterns underlying infectious disease transmission. Publicly available data sets of contact data are however typically recorded over short time windows with respect to the duration of an epidemic. To inform models of disease transmission, data are thus often repeated several times, yielding synthetic data covering long enough timescales. Looping over short term data to approximate contact patterns on longer timescales can lead to unrealistic transmission chains because of the deterministic repetition of all contacts, without any renewal of the contact partners of each individual between successive periods. Real contacts indeed include a combination of regularly repeated contacts (e.g., due to friendship relations) and of more casual ones. In this paper, we propose an algorithm to longitudinally extend contact data recorded in a school setting, taking into account this dual aspect of contacts and in particular the presence of repeated contacts due to friendships. To illustrate the interest of such an algorithm, we then simulate the spread of SARS-CoV-2 on our synthetic contacts using an agent-based model specific to the school setting. We compare the results with simulations performed on synthetic data extended with simpler algorithms to determine the impact of preserving friendships in the data extension method. Notably, the preservation of friendships does not strongly affect transmission routes between classes in the school but leads to different infection pathways between individual students. Our results moreover indicate that gathering contact data during two days in a population is sufficient to generate realistic synthetic contact sequences between individuals in that population on longer timescales. The proposed tool will allow modellers to leverage existing contact data, and contributes to the design of optimal future field data collection. -in Brain Sciences on 2024-12-09 00:00:00 UTC. +
in PLoS Computational Biology on 2024-12-09 14:00:00 UTC.
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-Brain Sciences, Vol. 14, Pages 1236: Interoceptive Awareness and Female Orgasm Frequency and Satisfaction
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+Federated privacy-protected meta- and mega-omics data analysis in multi-center studies with a fully open-source analytic platform
-Brain Sciences, Vol. 14, Pages 1236: Interoceptive Awareness and Female Orgasm Frequency and Satisfaction
-Brain Sciences doi: 10.3390/brainsci14121236
-Authors: - Emily Dixon - Giulia L. Poerio - Gerulf Rieger - Megan Klabunde -
-Background: The female orgasm is a highly understudied phenomenon that is linked to both wellbeing and relationship satisfaction in women. Although orgasm has been associated with interoception&mdash;the sense of the physiological condition of the body&mdash;very few studies have directly examined the influence that interoception has on orgasm. Objectives: This study investigates how the subjective experience of one&rsquo;s interoceptive capacities (called interoceptive awareness) is associated with self-reported orgasm frequency and satisfaction in people who identify as women. Methods: In a dataset of 318 women, orgasm frequency and satisfaction were both rated significantly higher for solitary as compared to partnered sexual experiences. Results: Analysis of how dimensions of interoceptive awareness correlated with orgasm frequency and satisfaction showed that (1) &lsquo;Noticing&rsquo; predicted orgasm frequency (but not satisfaction) across both solitary and partnered interactions, (2) &lsquo;Attention Regulation&rsquo; predicted greater frequency and satisfaction of solitary orgasm (but not partnered interactions), and (3) &lsquo;Body Trusting&rsquo; predicted orgasm satisfaction (but not frequency) across both solitary and partnered contexts. Conclusions: Findings underscore the importance of moving beyond orgasmic dysfunction research by investigating how interoception is associated with healthy&mdash;and potentially even optimal&mdash;orgasmic functioning in women.
+by Xavier Escriba-Montagut, Yannick Marcon, Augusto Anguita-Ruiz, Demetris Avraam, Jose Urquiza, Andrei S. Morgan, Rebecca C. Wilson, Paul Burton, Juan R. Gonzalez
+ +The importance of maintaining data privacy and complying with regulatory requirements is highlighted especially when sharing omic data between different research centers. This challenge is even more pronounced in the scenario where a multi-center effort for collaborative omics studies is necessary. OmicSHIELD is introduced as an open-source tool aimed at overcoming these challenges by enabling privacy-protected federated analysis of sensitive omic data. In order to ensure this, multiple security mechanisms have been included in the software. This innovative tool is capable of managing a wide range of omic data analyses specifically tailored to biomedical research. These include genome and epigenome wide association studies and differential gene expression analyses. OmicSHIELD is designed to support both meta- and mega-analysis, so that it offers a wide range of capabilities for different analysis designs. We present a series of use cases illustrating some examples of how the software addresses real-world analyses of omic data. -in Brain Sciences on 2024-12-09 00:00:00 UTC. +
in PLoS Computational Biology on 2024-12-09 14:00:00 UTC.
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-Brain Sciences, Vol. 14, Pages 1235: Comparative Evaluation of Major Robotic Systems in Microanastomosis Procedures: A Systematic Review of Current Capabilities and Future Potential
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+Oscillatory dynamics of Rac1 activity in Dictyostelium discoideum amoebae
-Brain Sciences, Vol. 14, Pages 1235: Comparative Evaluation of Major Robotic Systems in Microanastomosis Procedures: A Systematic Review of Current Capabilities and Future Potential
-Brain Sciences doi: 10.3390/brainsci14121235
-Authors: - Delia Cannizzaro - Matteo Scalise - Chiara Zancanella - Stefano Paulli - Stefano Peron - Roberto Stefini -
-Background/Objectives: Robotic-assisted surgery has revolutionised modern medicine, enabling greater precision and control, particularly in microsurgical procedures. This systematic review evaluates the current state of robotic-assisted surgery across various specialties, focusing on four major robotic systems: Symani, Da Vinci, ZEUS, and MUSA. Methods: The review systematically analyses the effectiveness of these systems in performing vascular, lymphatic, and nervous anastomoses, comparing key metrics such as procedure time, success rates, and learning curves against manual techniques. It includes 48 studies, highlighting the technological capabilities and limitations of these systems in direct comparisons. Results: Results indicate that while robotic procedures often take longer than manual methods, significant improvements in efficiency are observed as surgeons gain experience. Conclusions: Overall, this study provides insights into the future potential of robotic-assisted surgery and highlights areas that require further research. It ultimately aims to promote the application of robotic systems in cranial neurosurgery, with a particular focus on advancing neurovascular techniques, such as microsuturing for bypass procedures.
+by Marko Šoštar, Maja Marinović, Vedrana Filić, Nenad Pavin, Igor Weber
+ +Small GTPases of the Rho family play a central role in the regulation of cell motility by controlling the remodeling of the actin cytoskeleton. In the amoeboid cells of Dictyostelium discoideum, the active form of the Rho GTPase Rac1 regulates actin polymerases at the leading edge and actin filament bundling proteins at the posterior cortex of polarized cells. We monitored the spatiotemporal dynamics of Rac1 and its effector DGAP1 in vegetative amoebae using specific fluorescent probes. We observed that plasma membrane domains enriched in active Rac1 not only exhibited stable polarization, but also showed rotations and oscillations, whereas DGAP1 was depleted from these regions. To simulate the observed dynamics of the two proteins, we developed a mass-conserving reaction-diffusion model based on the circulation of Rac1 between the membrane and the cytoplasm coupled with its activation by GEFs, deactivation by GAPs and interaction with DGAP1. Our theoretical model accurately reproduced the experimentally observed dynamic patterns, including the predominant anti-correlation between active Rac1 and DGAP1. Significantly, the model predicted a new colocalization regime of these two proteins in polarized cells, which we confirmed experimentally. In summary, our results improve the understanding of Rac1 dynamics and reveal how the occurrence and transitions between different regimes depend on biochemical reaction rates, protein levels and cell size. This study not only expands our knowledge of the behavior of Rac1 GTPases in D. discoideum amoebae but also demonstrates how specific modes of interaction between Rac1 and its effector DGAP1 lead to their counterintuitively anti-correlated dynamics. -in Brain Sciences on 2024-12-09 00:00:00 UTC. +
in PLoS Computational Biology on 2024-12-09 14:00:00 UTC.
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-Using FoxP2 to Distinguish Direct and Indirect Basal Ganglia Pathways for Vocal Learning in Songbirds
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+Quantitative perturbation-phenotype maps reveal nonlinear responses underlying robustness of PAR-dependent asymmetric cell division
- Vocal learning in songbirds provides a powerful experimental model for motor skill learning. The cortico-basal ganglia pathways that mediate vocal learning in zebra finches (Taeniopygia guttata) are localized in two parallel circuits. These circuits traverse a cortical region (LMAN), a specialized region of the basal ganglia essential for vocal learning (Area X), and a region of dorsomedial thalamus (DLM). Area X, which contains both striatal and pallidal neurons, includes functional analogs of mammalian direct and indirect pathways that may have opposing effects and thereby increase or inhibit thalamic activity respectively. Direct pallidal neurons of Area X send inhibitory projections to DLM, whereas indirect pallidal neurons form intrinsic connections onto DLM-projecting neurons. We used tract-tracing techniques to label direct pallidal Area X[->]DLM projection neurons and immunohistochemical techniques to label neurons expressing the transcription factor FoxP2 in adult and juvenile male zebra finches. Our results showed that DLM-projecting neurons in Area X did not express FoxP2 in either adults or juveniles. We also observed a population of large neurons that expressed FoxP2 but were not retrogradely-labeled from DLM. A marker of striatal neurons (DARPP-32) did not co-localize with FoxP2 in most of these large neurons, providing evidence that they may form a class of putative indirect pallidal neurons. Our findings offer FoxP2 as a possible marker for indirect pallidal neurons and support the existence of different subpopulations of neurons that likely correspond to direct and indirect pathways within Area X. +by Nelio T. L. Rodrigues, Tom Bland, KangBo Ng, Nisha Hirani, Nathan W. Goehring
+ +A key challenge in the development of an organism is to maintain robust phenotypic outcomes in the face of perturbation. Yet, it is often unclear how such robust outcomes are encoded by developmental networks. Here, we use the Caenorhabditis elegans zygote as a model to understand sources of developmental robustness during PAR polarity-dependent asymmetric cell division. By quantitatively linking alterations in protein dosage to phenotype in individual embryos, we show that spatial information in the zygote is read out in a highly nonlinear fashion and, as a result, phenotypes are highly canalized against substantial variation in input signals. Our data point towards robustness of the conserved PAR polarity network that renders polarity axis specification resistant to variations in both the strength of upstream symmetry-breaking cues and PAR protein dosage. Analogously, downstream pathways involved in cell size and fate asymmetry are robust to dosage-dependent changes in the local concentrations of PAR proteins, implying nontrivial complexity in translating PAR concentration profiles into pathway outputs. We propose that these nonlinear signal-response dynamics between symmetry-breaking, PAR polarity, and asymmetric division modules effectively insulate each individual module from variation arising in others. This decoupling helps maintain the embryo along the correct developmental trajectory, thereby ensuring that asymmetric division is robust to perturbation. Such modular organization of developmental networks is likely to be a general mechanism to achieve robust developmental outcomes. -in bioRxiv: Neuroscience on 2024-12-08 00:00:00 UTC. +
in PLoS Biology on 2024-12-09 14:00:00 UTC.
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-Parallel and converging multisensory cascades in the Drosophila connectome
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+Incentives for pregnant mothers during antenatal care for better maternal and neonatal health outcomes in low and middle income countries: A Systematic Review and Meta-Analysis [version 1; peer review: awaiting peer review]
- Connectomes are network maps of synaptic connectivity. A key functional role of any connectome is to constrain inter-neuronal signaling and to sculpt the flow of activity patterns across the nervous system. Connectomes therefore play a central role in the rapid tranmission of information about an organism's environment from sensory neurons to higher-order neurons for action planning and ultimately to effectors. Here, we use an abstract model of activity spread to investigate the connectome's role in shaping sensory cascades. Our model allows us to simulate the signaling pathways from sensors to the rest of brain, mapping the similarity of these pathways between different sensory modalities and identifying convergence zones--neurons that are activated simultaneously by different sensory modalities. Further, we considered two multisensory integration scenarios -- a cooperative case where different sensory modalities interacted to "speed up" (reduce) neurons' activation times and a competitive "winner take all" case, where different sensory streams vied for the same neural territory. Finally, we use a data-driven algorithm to partition neurons into different classes based on their behavior during the cascade simulations. Our work helps underscore the role of "simple" models for enriching connectome data, while offering a data-driven classification of neurons based on their joint connectional/dynamical properties. + Background Universal access to maternal, newborn, and child healthcare is essential for achieving Sustainable Development Goal 3, but the effectiveness of various incentive-based programs for pregnant mothers in low- and middle-income countries (LMICs) remains uncertain. Objective of this systematic review was to determine if incentive-based interventions influenced maternal and neonatal health outcomes. Methods We conducted a search in various databases from inception. All incentive-based interventional studies conducted on pregnant women in LMICs were included. Evidence from the included trials was synthesized using risk ratios (RRs) to compare the outcomes between groups receiving incentives and not receiving incentives. The meta-analysis was conducted using random-effects model. We assessed the quality of the included studies using the Cochrane Risk of Bias 2.0 tool and reviewed the collected data to determine its suitability for meta-analysis. This study is registered in PROSPERO (CRD42021247681). Results Of the 3,897 records that were identified, 11 met eligibility criteria, all of which exhibited varying degrees of risk of bias, ranging from high to some concerns. Analysis of maternal outcomes across studies revealed no significant differences in the likelihood of delivering at a healthcare facility (RR 1.13, 95% CI: 0.86 to 1.47) and in frequency of prenatal care (RR 0.99, 95% CI: 0.88 to 1.12) between intervention and control groups. However, high levels of statistical heterogeneity were observed for both outcomes indicating variability among study results. Similarly, analysis of tetanus vaccine coverage showed no significant difference between groups (RR 1.00, 95% CI: 0.92 to 1.08), with moderate statistical heterogeneity observed. Conclusion The maternal and neonatal outcomes examined in this review did not have any significant differences in intervention group when compared to the control group. The interventions to address maternal health concerns need to follow a multifactorial approach. There is a need for extensive primary research studies in the future. -in bioRxiv: Neuroscience on 2024-12-08 00:00:00 UTC. +
in F1000Research on 2024-12-09 10:44:20 UTC.
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-Biological Database Mining for LLM-Driven Alzheimer's Disease Drug Repurposing
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+Spontaneous Pneumocephalus Due to Skull Base Defect and Spinal Cerebrospinal Fluid‐Venous Fistula
- INTRODUCTION: The synergy of structured knowledge and large language models (LLMs) may contribute to identifying drugs for Alzheimer disease (AD) drug repurposing (DR). This paper developed a software pipeline that uses LLMs to translate knowledge stored in natural language (such as in scientific texts) to an applicable DR information structure. METHODS: AD-related entries in Gene Ontology and DrugBank were integrated into a Knowledge Graph database to inform LLM prompts. Based on the biological process impact, the LLM provided a suitability rating for DR, taking into account the inhibitory effect of drugs on AD driving processes.. RESULTS: Drugs with a high potential for DR were identified and manually reviewed, also considering adverse effects. Ripretinib and Pertuzumab (both kinase inhibitors) had the highest DR applicable rating across all iterations. DISCUSSION: We propose retrospective analyses, considering the high-rated drugs and their effect on AD patients as a starting point for further (prospective) research. + -in bioRxiv: Neuroscience on 2024-12-08 00:00:00 UTC. +
in Annals of Neurology on 2024-12-09 10:33:50 UTC.
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-Lifespan trajectory of chimpanzee brains characterized by magnetic resonance imaging histology
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+Critical Care Decisions After Large Core Cerebral Infarctions: A Secondary Analysis From the SELECT2 Trial
- Chimpanzee brain maturation provides an invaluable framework for understanding the evolution of the human brain. We performed ultra-high resolution quantitative magnetic resonance imaging (qMRI) with histological validation on post mortem brains from captive and wild chimpanzees with a broad age range. We mapped developmental myelination and age-related iron accumulation across regions and layers of the neocortex. Compared to humans, chimpanzees showed more myelination and iron deposition in motor and premotor cortices, while the auditory cortex was more strongly myelinated in humans. Our model suggests that chimpanzees' cortical myelination was largely completed by the age of nine years, while iron accumulation continued throughout the lifespan. The regions with highest adult levels of myelin and iron took the longest to mature, challenging the widespread assumption that highly myelinated regions complete their development first. The reported maps and developmental curves provide a foundation for comparative neuroscience research and understanding of human brain evolution. +Objective
+Among patients with large vessel occlusion (LVO) and large ischemic cores, critical decisions often need to be made about decompressive hemicraniectomy (DHC) or early withdrawal of life-sustaining therapy (WLST). In this study, we aimed to evaluate utilization of DHC and early WLST and factors associated with them in patients with large strokes from the SELECT2 trial.
+Methods
+We analyzed the entire SELECT2 trial population, which randomized 352 patients with stroke due to LVO and large ischemic cores to endovascular thrombectomy (EVT) or medical management. We used the as-treated principle to compare the use of DHC and early WLST within 7 days after randomization. We further assessed functional outcomes (modified Rankin Score) after these decisions.
+Results
+Of 352 patients enrolled in this study, 55 received DHC and 81 transitioned to early WLST. Patients treated with EVT were as likely to undergo DHC (16% vs 15%, adjusted relative risk [aRR] = 1.19, 95% CI:0.75–1.88, p = 0.46) or WLST (22% vs 24%, aRR = 0.94, 95% CI: 0.66–1.34, p = 0.72) as those given medical management. DHC was used more frequently in younger patients and WLST more in older patients. EVT efficacy was maintained after adjusting for DHC (adjusted generalized odds ratio [aGenOR] = 1.68, 95% CI: 1.24–2.11, p < 0.001), with no interaction between DHC and treatment (p-interaction = 0.93). At 1 year, 21% of DHC-treated patients were ambulatory; the outcomes were universally poor after early WLST.
+Interpretation
+In the SELECT2 trial of patients with large ischemic core, DHC was performed in ~1 of 6 patients and early WLST in ~1 of 5 patients, without differences based on treatment with EVT or medical management, nor successful reperfusion. DHC or WLST did not detract from thrombectomy treatment benefit. Additionally, ~20% of patients achieved independent ambulation despite receiving DHC by the 1-year follow-up. The similar distribution of these critical care decisions provides reassurance that the overall trial outcomes were not biased by open-label treatment allocation. ANN NEUROL 2024
-in bioRxiv: Neuroscience on 2024-12-08 00:00:00 UTC. +
in Annals of Neurology on 2024-12-09 10:33:48 UTC.
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-HCN1 channels in GABAergic amygdalar neurons underpin male-biased aggressive behaviors
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+Viral interactions with host factors (TIM-1, TAM -receptors, Glut-1) are related to the disruption of glucose and ascorbate transport and homeostasis, causing the haemorrhagic manifestations of viral haemorrhagic fevers. [version 6; peer review: 1 approve
- Aggression behaviors typically vary between sexes, but the molecular mechanisms driving these disparities in neural coding are unclear. We found that aggression selectively activates GABAergic neurons in the posterior substantia innominata (pSI), an extend amygdala region critical for aggressive behaviors in both sexes of mice, with males exhibiting higher neuronal activity during the attack. Utilizing single-nucleus RNA sequencing, we characterized the diverse molecular landscape of pSI neurons, revealing significant differences in ion channels and hormone regulator genes that may underpin sex-specific aggression. Male GABAergic pSI neurons exhibited remarkable hyperexcitability due to increased Ih currents. Strikingly, modulating HCN1 expression not only adjusted this hyperexcitability but also influenced sexual dimorphism in aggression: silencing HCN1 in the GABAergic pSI neurons reduced male aggression, while its overexpression markedly heightened aggression in females. Furthermore, testosterone was shown to intensify aggression by upregulating HCN1 and remodeling pSI circuits. These findings provide detailed sex-specific molecular mechanisms underlying social behaviors. + The haemorrhagic features of viral haemorrhagic fevers may be caused by common patterns of metabolic disturbances of the glucose and ascorbate homeostasis. Haemorrhages and vasculature disfunctions are a clinical feature not only of viral haemorrhagic fevers, but also in scurvy, diabetes and thrombotic microangiopathic haemolytic anaemia. Interestingly, the expression of glucose and ascorbate transporter Glut-1 on the erythrocyte membrane is associated with the inability to synthesize ascorbate and is restricted to that very species that are susceptible to filoviruses (primates, humans and fruit bats). Glut-1 may play a pivotal role in haemorrhagic fever pathogenesis. TIM-1 and TAM receptors have been recognized to enhance entry of Ebola, Lassa and Dengue viruses and viral interferences with TIM-1 could disturb its function, disturbing the expression of Glut-1. In those species not able to synthesize ascorbate and expressing Glut-1 on erythrocytes virus could interact with Glut-1 or other functionally related protein, and the influx of glucose into the cells would be severely impaired. As a consequence, transient hyperglycemia and a marked oxidative stress coupled with the high levels of glucose in plasma would be established, and then promote the activation of NF–κB transcription, exacerbating a pro-inflammatory response mediated by cytokines and chemokines: The inability to synthesize ascorbate is an Achilles Heel when trying to counteract the oxidative stress. -in bioRxiv: Neuroscience on 2024-12-08 00:00:00 UTC. +
in F1000Research on 2024-12-09 10:15:10 UTC.
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-Ventral tegmental area GABA neurons integrate positive and negative valence
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+Out-of-Pocket Expenditure (OOPE) on Selected Surgeries in the Obstetrics and Gynaecology Department incurred by Ayushman Bharat Pradhan Mantri Jan Arogya Yojana (AB-PMJAY), Private Health Insurance and Uninsured Patients in a Tertiary Care Teaching Hospi
- Ventral tegmental area (VTA) dopamine (DA) neurons are classically linked to Pavlovian reward learning and reinforcement. Intermingled VTA GABA neurons are positioned to regulate dopaminergic and striatal systems, but we lack critical insight into how this population contributes to conditioned motivation in different learning contexts. Recording DA and GABA neurons across multiple conditioning paradigms, we found that GABA neurons not only actively encode appetitive and aversive cues and outcomes separately, but uniquely integrate salient events of both valences to guide reward seeking. + Introduction OOPE for healthcare services is a major concern within the Indian healthcare system. 30% of the population remains uninsured despite increasing health insurance coverage. For obstetrics and gynaecology (OBG) patients financial obstacles like OOPE can delay access to health care, evaluating spending patterns can inform policies to enhance accessibility, affordability and equitable health. Methodology A retrospective study was conducted at a tertiary care teaching hospital in Karnataka state of India to analyze OOPE for 905 OBG patients who underwent Cesarean Section(C-Section), Laparoscopic Hysterectomy, Laparoscopic Cystectomy, Laparoscopic Myomectomy and Laparoscopic Assisted Vaginal Hysterectomy (LAVH). These were the top five most performed obstetrics and gynecology surgeries in the tertiary care teaching hospital between January 2023 and July 2023. Data was collected across AB-PMJAY, private health insurance, uninsured patients and analyzed using descriptive statistics (mean, median) and the Shapiro-Wilk test for data normality. Results The study analyzed OOPE across 905 OBG patients. Findings show AB-PMJAY provided full coverage with zero OOPE for all surgeries. Though private health insurance reduced OOPE compared to uninsured patients under private health insurance still faced significant financial burden. Variations existed in minimum and maximum OOPE and percentage of OOPE across different private insurances. All the uninsured patients incurred 100% OOPE, with a median OOPE of Rs. 33,257 (405.67 USD) to Rs. 57,053 (695.76 USD) and a mean OOPE of Rs. 39,848 (485.95 USD) to Rs. 60,687 (740 USD) across the surgeries. Discussion Findings of the study show that AB-PMJAY is highly effective in reducing OOPE and enhancing financial risk protection for OBG patients. Patients covered by private health insurance incurred less OOPE, yet the burden remained considerable. High OOPE rates for uninsured patients (100%) and private health insurance (38.15%) compared to 0% OOPE in AB-PMJAY emphasizes the need for the continued expansion of AB-PMJAY. -in bioRxiv: Neuroscience on 2024-12-08 00:00:00 UTC. +
in F1000Research on 2024-12-09 10:12:50 UTC.
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-Brain Sciences, Vol. 14, Pages 1234: Advancing Neuropsychological Rehabilitation in Primary Progressive Aphasia Based on Principles of Cognitive Neuroscience: A Scoping Review and Systematic Analysis of the Data
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+Natural disaster and medication preparedness among elderly: a scoping review [version 1; peer review: awaiting peer review]
-Brain Sciences, Vol. 14, Pages 1234: Advancing Neuropsychological Rehabilitation in Primary Progressive Aphasia Based on Principles of Cognitive Neuroscience: A Scoping Review and Systematic Analysis of the Data
-Brain Sciences doi: 10.3390/brainsci14121234
-Authors: - Evgenia Gkintoni - Emilia Michou -
-Background/Objectives: This systematic review of neuropsychological rehabilitation strategies for primary progressive aphasia will consider recent developments in cognitive neuroscience, especially neuroimaging techniques such as EEG and fMRI, to outline how these tools might be integrated into clinical practice to maximize treatment outcomes. Methods: A systematic search of peer-reviewed literature from the last decade was performed following the PRISMA guidelines across multiple databases. A total of 63 studies were included, guided by predefined inclusion and exclusion criteria, with a focus on cognitive and language rehabilitation in PPA, interventions guided by neuroimaging, and mechanisms of neuroplasticity. Results: Integration of neuroimaging techniques contributes to the increase in the efficacy of interventions with critical information about the neural mechanisms underlying language deficits in the aphasias. Traditional rehabilitation strategies, technology-assisted interventions, and non-invasive brain stimulation techniques hold considerable promise for language improvement. Neuroimaging was also found to be necessary in subtype-specific differentiation toward tailoring therapeutic intervention. Evidence also shows that directed and sustained interventions using neuroplasticity can have long-term effects in managing the symptoms of PPA. Conclusions: The present review underlines the necessity of including cognitive neuroscience techniques within neuropsychological rehabilitation to enhance therapeutic outcomes in PPA. In addition, neuroimaging modalities such as EEG and fMRI are also of great importance in understanding the underlying neurobiology of language disturbances and guiding tailored interventions. Long-term benefits of these approaches should be evaluated, including their applicability in routine clinical practice.
+ Introduction The increasing number of older people and their vulnerability to disaster and medication preparedness as the primary elements of disaster mitigation are necessary to reduce the impact of a disaster. Nevertheless, research on natural disasters and medication preparedness in the elderly population is still lacking. This review aimed to explore all reported research and publications related to natural disasters and medication preparedness among the elderly. Methods A scoping review was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Extension for Scoping Reviews (PRISMA-ScR). A literature search was conducted using the following four databases: Scopus, PubMed, Sage, and Google Scholar. Screening was conducted using the following criteria: articles written in English, open access, and published between 2020 and 2024. Articles must discuss natural disasters and medication preparedness. In the data search, we input several keywords that include “elderly,” “natural disaster,” “preparedness,” and “medication.” Snowballing was then conducted to find articles on preparedness interventions. Data extraction and analysis were then performed. Results and conclusion The findings from this literature review are the majority of studies showing that most elderly people are not well prepared in facing disasters; however, through various programs that have been implemented by either the government or community, the elderly show more preparation when they encounter any natural disaster. -in Brain Sciences on 2024-12-08 00:00:00 UTC. +
in F1000Research on 2024-12-09 10:12:04 UTC.
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-Brain Sciences, Vol. 14, Pages 1233: Psychiatric Disorders and Cognitive Fluctuations in Parkinson’s Disease: Changing Approaches in the First Decades of the 21st Century
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+Types of refractive errors in a sample of Iraqi children with Intermittent exotropia [version 2; peer review: 2 not approved]
-Brain Sciences, Vol. 14, Pages 1233: Psychiatric Disorders and Cognitive Fluctuations in Parkinson’s Disease: Changing Approaches in the First Decades of the 21st Century
-Brain Sciences doi: 10.3390/brainsci14121233
-Authors: - Marco Onofrj - Matteo Alessandro De Rosa - Mirella Russo - Paola Ajdinaj - Dario Calisi - Astrid Thomas - Stefano Luca Sensi -
-Parkinson&rsquo;s Disease (PD) is a multifaceted neurodegenerative disorder characterized, in addition to the well-recognized motor disturbances, by a complex interplay between cognitive and psychiatric manifestations. We dissect the complex landscape of PD-related psychiatric symptoms, taking into account the impact of functional neurological disorders, somatic delusions, impulse control disorders, and conditions within the bipolar spectrum. The newer entities of somatoform and functional neurological disorders, as well as preexisting bipolar spectrum disorders, are analyzed in detail. Moreover, we emphasize the need for a holistic understanding of PD, wherein the cognitive and psychiatric dimensions are valued alongside motor symptoms. Such an approach aims to facilitate early detection and personalized interventions, and enhance the overall quality of life for individuals suffering from this neurodegenerative disorder.
+ Background One of the most common strabismus types in children is intermittent exotropia, which predominantly occurs in children between the ages of 2 to 4 years. It may affect visual development and often coexists with refractive errors. Unlike esotropia, which usually links to hyperopia, intermittent exotropia might have a different relationship with refractive errors and thus lead to myopia. Methods In this cross-sectional retrospective study from August 2021 to December 2023, 179 patients diagnosed with intermittent exotropia were recruited via an outpatient clinic of Najah Al-Quraishi, Baghdad, Iraq. The refractive errors were compared by autorefractometry and retinoscopy after cycloplegic dilation. Data analysis was constructed under the use of IBM SPSS V.26 for the determination of emmetropia, myopia, and hyperopia prevalence. Results Among the 179 patients, emmetropia was the most commonly observed refractive status, present in 68 patients (38%). Low hyperopia and low myopia were also common, with 64 and 40, respectively. A limited number of patients had moderate/high myopia and moderate/high hyperopia; in detail, the prevalence was following: 5% of patients had moderate myopia, while 0.5% of patients suffered from high myopia; symmetrically, 5% were moderate to high hyperopia. From the data collected, a trend emerged for a low refractive error and symmetric refractive error in both eyes. Conclusion Contrasted to prior conventional wisdom about refractive error in strabismus, it established the greater incidence of emmetropia in patients with intermittent exotropia. The findings call for specific management strategies to be applied in this population. -in Brain Sciences on 2024-12-08 00:00:00 UTC. +
in F1000Research on 2024-12-09 10:08:49 UTC.
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-Behavioral Consequences of Hippocampal 5‐HT7 Receptors Blockade in Stressed Rats
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+Neurodiversity in Saudi Arabia: Towards quality education and reduced inequalities [version 2; peer review: 2 approved with reservations]
-ABSTRACT
-Serotonin (5-HT) has long been involved in response to stress and its effect may be, in part, mediated by 5-HT1a and 5-HT7 receptor subtypes in different brain structures. Both pre- and post-synaptic activation of 5-HT1a receptor, respectively, in the rat median raphe nucleus (MnRN) and hippocampus, lead to adaptation to acute inescapable stressors such as restraint and forced swim. 5-HT7 receptor (5HT7r), a stimulatory G-protein coupled receptor, has also been investigated as a possible candidate for mediating stress response. In the MnRN, activation of 5-HT7r has antidepressant effects, while in the hippocampus, 5HT7r mRNA expression is increased after exposure to restraint stress, but the functional significance of these receptors remains to be determined. Therefore, the aim of this study was to investigate whether blockade of hippocampal 5HT7r would prevent and/or attenuate the behavioral effects of stress. Male adult Wistar rats with bilateral cannulas aimed at the dorsal hippocampus were restrained for 2 h and tested in the elevated plus maze (EPM) 24 h later. SB 258741 (3 nmoles/0.5 μL/side; selective 5HT7r antagonist) was administered bilateraly into the hippocampus according to the experimental protocol: immediately before or after stress, or 24 h after it (immediately before the test). In a second experiment, rats were exposed to 15 min. of forced swim, and tested 24 h later. Intra-hippocampal treatment was performed as described for the restraint stress protocol. We found that blockade of hippocampal 5-HT7r immediately after, but not before, the exposure to restraint or forced swim attenuated stress-induced behavioral changes. Similar results were obtained when SB was administered before the test in previously stressed rats. Our data suggest that activation of hippocampal 5-HT7r is crucial for the consolidation and retrieval of aversive stimulus-related memories, such as those caused by a stressful experience, probably through mechanisms involving stress-induced changes in 5-HT7r expression.
+ Traditional educational frameworks in Saudi Arabia have historically adopted a deficit-based approach to special education, potentially overlooking the benefits of neurodiversity. As global educational paradigms shift toward inclusive practices, examining the alignment of Saudi special education laws with neurodiversity principles becomes crucial. This content analysis study aimed to explore the existing literature on special education in Saudi Arabia to ascertain whether the laws and policies support or hinder the practice of neurodiversity, a concept that is gaining international recognition but remains nascent in Saudi Arabia. A systematic literature search was performed in Web of Science and Scopus, yielding 21 relevant studies after screening and application of inclusion criteria. A content analysis was conducted, focusing on the categorization of data relevant to special education laws and their implications for neurodiversity. The analysis identified seven key categories, including Implementation of Inclusive education and transition services, that reflect the current state of special education laws in relation to neurodiversity. A conceptual model was developed, illustrating the potential of special education laws to both support and impede neurodiversity in Saudi Arabia and potentially worldwide. -in Hippocampus on 2024-12-07 15:08:51 UTC. +
in F1000Research on 2024-12-09 10:07:14 UTC.
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-Explicit Memory, Implicit Memory, and the Hippocampus: Insights From Early Neuroimaging Studies
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+Mapping evidence of postgraduate research supervision experiences at higher education institutions in Africa: A scoping review protocol [version 1; peer review: awaiting peer review]
-ABSTRACT
-During the 1980s and 1990s, much memory research focused on the differential role of the hippocampus in various forms of memory. My work on the distinction between explicit and implicit memory led me to become involved in several early neuroimaging studies that made use of cognitive paradigms to investigate the conditions in which hippocampal activity does and does not occur, and to address the theoretical implications of these findings. Here, I summarize two such projects and some of the personal backstory associated with them.
+ Background The evolving landscape of the African higher education sector necessitated by global higher education reforms and the need for research informed responses to address contextual challenges is partly dependent on effective postgraduate research supervision. A wide range of postgraduate research supervision models and practices are documented globally. In the African context, the experiences of postgraduate research supervision are not clearly understood from the experiences of all stakeholders. Aim The proposed scoping review aims to map evidence on the range of postgraduate research supervision experiences at higher education institutions in Africa. Methods The methodological framework proposed by Arksey and O’Malley will be used to conduct the review. Relevant articles will be sourced from different electronic data bases namely; ERIC, Web of Science, EbscoHost and Scopus. A combination of search terms and Boolean operators will be used to obtain the relevant articles based on the inclusion criteria stipulated within the Population, Context and Concept (PCC) framework of study identification for this review. Results Studies reporting on postgraduate research supervision experiences from the perspective of academics, students and support staff in the African higher education context will be included. The results may also provide insights postgraduate supervision experiences from varying postgraduate research disciplines. Conclusion The findings will provide consolidated empirical evidence on experiences of postgraduate supervision in the African higher education context, thereby providing holistic insight on postgraduate research supervision practices, models currently used, implementation challenges and highlight research gaps. This may inform recommendations that advance knowledge within this field, particularly in the African higher education context. -in Hippocampus on 2024-12-07 15:08:43 UTC. +
in F1000Research on 2024-12-09 10:05:05 UTC.
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-Inhibition of Bone Morphogenetic Protein Signaling Prevents Tau Pathology in iPSC Derived Neurons and PS19 Mice
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+Platelet-rich plasma as a potential therapy of cystocele: a systematic review and meta-analysis [version 1; peer review: awaiting peer review]
-Objective
-Many neurodegenerative disorders share a common pathologic feature involving the deposition of abnormal tau protein in the brain (tauopathies). This suggests that there may be some shared pathophysiologic mechanism(s). The largest risk factor for the majority of these disorders is aging, suggesting involvement of the aging process in the shared pathophysiology. We test the hypothesis that an increase in bone morphogenetic protein (BMP) signaling that occurs during aging contributes to the onset and progression of tauopathies.
-Methods
-Human induced pluripotent stem cell (iPSC)-derived neurons from patients with Alzheimer's disease (AD) were used to investigate the effects of BMP signaling on tau phosphorylation and release and the mechanisms underlying these effects. Wildtype mice were used to examine effects of BMP signaling in vivo. P301S (PS19) mice were examined for the effects of BMP signaling in a model of tauopathy.
-Results
-Here, we show that BMP signaling, mediated by non-canonical p38 signaling, increases tau phosphorylation and release of p-tau in human iPSC-derived AD neurons. Further, there is an interaction between BMP signaling and apolipoprotein E4 (ApoE4) that significantly increases tau phosphorylation and release compared with ApoE3 neurons. Inhibiting BMP signaling reduces the changes in tau in the cultured human neurons, and it limits tau pathology and prevents cognitive decline in PS19 mice.
-Interpretation
-Our study suggests that the age-related increase in BMP signaling may participate in the onset and progression of tau pathology. Thus, therapeutic interventions that reduce BMP signaling in the aging brain could potentially slow or prevent development of diseases involving tau hyperphosphorylation. ANN NEUROL 2024
+ Abstract Background Platelet-rich plasma (PRP) therapy, is known for its regenerative properties. PRP may be able to help with cystocele cases. This review aims to explore how it might be applied to urogynecological cases, particularly those involving cystocele. Methods The present systematic review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guideline 2020, Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guideline. The present systematic review was registered with PROSPERO with the registered number CRD42023414366. PubMed, Science Direct, Epistemonikos, COCHRANE, Google Scholar, and ProQuest were among the databases we searched. “(PRP OR Platelet-Rich Plasma) AND (Cystocele OR Anterior Pelvic Organ Prolapse)” from January 2007 to December 2022. Based on the PICO framework (Population = Patients with Cystocele; Intervention = Reconstruction with platelet-rich plasma injection; Compare = Reconstruction only; Outcome: Recurrency of Cystocele), four investigators (AMS, PMA, EAU, RSD, and AH) independently assessed eligibility by titles and abstracts. Using the Joanna Briggs Institute Critical Appraisal tool, each author evaluated full-text articles based on the kind of articles they had received. When consensus could not be obtained, disagreements were settled by involving the supervisors (EF, EMK, and BS). Results A total of 8,924 studies were identified. After removing duplicates and applying eligibility criteria, two articles were included, encompassing 65 patients. In two studies, PRP injections were found and administered post-anterior colporrhaphy at the pubovesical fascia. According to these two trials, women who had anterior colporrhaphy and PRP injections required fewer reoperations. Conclusion PRP has the potential to be a good alternative treatment to prevent cystocele recurrence. However, it cannot be generalized to large populations due to the small number of findings. Further studies with large samples examining the efficacy and safety of the therapy are needed to prove it. -in Annals of Neurology on 2024-12-07 12:09:55 UTC. +
in F1000Research on 2024-12-09 10:03:29 UTC.
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-Prophylactic Fetal Creatine Supplementation Improves Post‐Asphyxial EEG Recovery and Reduces Seizures in Fetal Sheep: Implications for Hypoxic–Ischemic Encephalopathy
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+Complications following miniplate insertion in maxillofacial fractures: a systematic review [version 1; peer review: awaiting peer review]
-Objective
-Hypoxic–ischemic encephalopathy (HIE) is a major cause of perinatal brain injury. Creatine is a dietary supplement that can increase intracellular phosphocreatine to improve the provision of intracellular adenosine triphosphate (ATP) to meet the increase in metabolic demand of oxygen deprivation. Here, we assessed prophylactic fetal creatine supplementation in reducing acute asphyxia-induced seizures, disordered electroencephalography (EEG) activity and cerebral inflammation and cell death histopathology.
-Methods
-Fetal sheep (118 ± 1 days’ gestational age [dGA]; 0.8 gestation) were implanted with electrodes to continuously record EEG and nuchal electromyogram activity. At 121 dGA, fetuses were randomly assigned to sham control (i.v. saline infusion without umbilical cord occlusion [UCO]; SalCon), continuous i.v. creatine infusion (6 mg/kg/h; CrUCO) or isovolumetric saline (SalUCO) followed by UCO at 128 ± 2 dGA that lasted until the mean arterial blood pressure reached 19 mmHg. Brain tissue was collected for histopathology after 72 hours of recovery.
-Results
-Creatine supplementation had no effects on basal systemic or neurological physiology. UCO duration did not differ between CrUCO and SalUCO. After reperfusion, CrUCO fetuses had improved EEG power and frequency recovery and reduced electrographic seizure incidence (SalUCO, 86% vs CrUCO, 29%) and burden. At 72 hours after UCO, cell death in the cerebral cortex and astrogliosis in the periventricular white matter were reduced in CrUCO fetuses compared with SalUCO.
-Interpretation
-Creatine supplementation reduced post-asphyxial seizures and improved EEG recovery. Improvements in functional recovery with creatine were associated with regional reductions in cell death and astrogliosis. Prophylactic creatine treatment has the potential to mitigate functional indices of HIE in the late gestation fetal brain. ANN NEUROL 2024
+ Background Maxillofacial fractures, frequently arising from road traffic incidents, falls, and acts of interpersonal aggression, are a considerable public health issue, exhibiting diverse epidemiological patterns according to demographic factors. The application of miniplates for fracture stabilization is a recognized technique, with innovative methods such as 3D plate systems emerging. Nonetheless, consequences including infections and hardware malfunctions persist. This systematic review seeks to present current evidence regarding the complications linked to miniplate placement in maxillofacial fractures over the last ten years. Methods A systematic review was performed in accordance with PRISMA principles. Databases such as the Cochrane Library, PubMed, and Scopus were examined from September 2014 to September 2024. Studies documenting problems related to miniplate placement were included, without language constraints. The ROBINS-I tool was utilized for non-randomized studies, whereas the Cochrane risk of bias tool was applied to randomized controlled trials. Results From 2,289 initially found studies, 56 satisfied the inclusion criteria. Among these, 28 employed interventional designs, whilst the remaining 28 were observational research. The predominant problems documented in several investigations encompassed infection, wound dehiscence, malocclusion, paraesthesia, malunion/non-union, segment movement, hardware failure, and palpable hardware. Advanced methodologies such as 3D plate systems and locking mechanisms were linked to diminished complication rates. Conclusion This systematic analysis presents a decade of updated research about problems associated with miniplate placement in maxillofacial fractures. Novel methodologies such as 3D plate systems and locking mechanisms demonstrate promise in mitigating problems relative to conventional techniques. These findings can facilitate informed decision-making in clinical practice. Additional study utilizing standardized outcomes and prospective designs is essential to enhance comprehension of the long-term effects of miniplate utilization. -in Annals of Neurology on 2024-12-07 11:50:08 UTC. +
in F1000Research on 2024-12-09 10:02:12 UTC.
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-NORSE, FIRES, and a Polygenic Trickle of Autoimmunity
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+Does Brand Attitude Complement Influencer Credibility in Shaping Purchase Intention of Indian GenZ Consumers? [version 2; peer review: 1 approved]
- + Introduction The social media landscape has undergone radical changes and has revolutionized consumer perspectives, purchasing habits, and behaviours. Amidst this emerging trend is the rise of influencer marketing and its impact on the purchase intentions of followers. The objective is to explore the characteristics of influencers that contribute to their credibility. This research aims to explore the role of consumers’ attitude toward brands on their intention to adopt brands endorsed by influencers. Methods This cross-sectional research was undertaken among GenZ in the urban landscape of India. Data collected was analyzed using SmartPLS4 software. Findings Trust, expertise, and similarity were the significant antecedents of the formation of influencer credibility. Attractiveness did not have a significant influence on influencer credibility. A complementary partial mediation of Attitude towards a brand is observed in the association between influencer credibility and the purchase intention of followers. Attitude towards the video also had a significant positive influence on purchase intention. Conclusion The study found that Gen Z places little importance on an influencer’s attractiveness, as it has no significant impact on credibility. However, attitude toward the brand strongly influenced purchase intention and partially mediated the relationship between influencer credibility and purchase intention. -in Annals of Neurology on 2024-12-07 11:47:44 UTC. +
in F1000Research on 2024-12-09 09:59:25 UTC.
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-Some Memories of Stalking the Seahorse
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+SYSTEMATIC LITERATURE REVIEW: SERVANT LEADERSHIP IN PUBLIC SECTORS [version 1; peer review: awaiting peer review]
-ABSTRACT
-Early influences that led to the development of the cognitive map theory of hippocampal function, and the multiple trace theory, are discussed. Some details are provided, many are left out.
+ Servant leadership delivers important reforms to the increasingly complex public utility system. This systematic review seeks to incorporate the latest six years of articles on geographic divisions, conceptual definitions, measuring techniques, theoretical frameworks, and nomological networks (antecedents, mediators, outcomes, and moderators) in the public sector. The risk of bias was evaluated using the Cochrane Risk of Bias Tool and ROBINS-I, and employing automated techniques such as Rayyan for screening. Using PRISMA’s review approach, this comprehensive synthesis of 51 relevant public sector-specific conceptual and empirical studies across six academic electronic databases (Taylor & Francis, Sage, Scopus, Springer Link, Web of Science, and Wiley) shows that servant leadership is critical for establishing a prosocial workforce. This review discovered that the global construct of servant leadership (SL-7) scale has been the most often utilised measure of servant leadership in public sector-specific studies recently. Social exchange theory remains the predominant explanation for the impact of servant leadership on specific variables. The findings also illustrate a generally positive influence of servant leadership. Moreover, this review provides limitations and suggestions for future studies by summarising elements that have received less attention. -in Hippocampus on 2024-12-07 09:53:14 UTC. +
in F1000Research on 2024-12-09 09:57:29 UTC.
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-Vimentin modulates regulatory T cell receptor-ligand interactions at distal pole complex, leading to dysregulated host response to viral pneumonia
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+Trends in Smart Restaurant Research: Bibliometric Review and Research Agenda [version 1; peer review: awaiting peer review]
- The type III intermediate filament protein vimentin serves as a molecular switch in regulatory T cells. Ma et al. show that Treg-specific deletion of vimentin increases Helios+IL-18R+ Tregs, suppresses inflammatory immune cells, and enhances tissue repair, protecting the host from influenza A virus-induced lung injury and mortality. + Background The automation of processes and services has transformed various industries, including the restaurant sector. Technologies such as the Internet of Things (IoT), machine learning, Radio Frequency Identification (RFID), and big data have been increasingly adopted to enhance service delivery, improve user experiences, and enable data traceability. By collecting user feedback and analyzing sentiments, these technologies facilitate decision-making and offer predictive insights into future food preferences. This study aims to explore current research trends in intelligent restaurants, focusing on technological applications that improve service and decision-making. Methods A bibliometric analysis was conducted in accordance with the PRISMA-2020 guidelines. A total of 94 academic documents were reviewed from the Scopus and Web of Science databases, focusing on publications related to intelligent restaurant systems, particularly involving IoT and automation technologies. Results The analysis revealed that the United States, India, and China have contributed the most to the field, with a particular emphasis on China’s implementation of IoT architecture and robotics in restaurant settings. Chinese restaurant innovations, particularly in robotics, are among the most frequently cited in the literature. The study identifies these countries as leading the research in the intelligent restaurant domain. Conclusions Technologies such as IoT, machine learning, RFID, and big data are driving advancements in restaurant automation, enhancing service efficiency and user experience. The United States, India, and China are leading research in this area, with China standing out for its application of robotics and IoT in restaurants. This research provides a foundation for future studies aimed at improving predictive models for food selection and service optimization. -in Cell Reports: Current Issue on 2024-12-07 00:00:00 UTC. +
in F1000Research on 2024-12-09 09:55:55 UTC.
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-Brain Sciences, Vol. 14, Pages 1232: Changing the Paradigm for Tractography Segmentation in Neurosurgery: Validation of a Streamline-Based Approach
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+The first mitochondrial genome of Haemagogus equinus from Jamaica [version 1; peer review: awaiting peer review]
-Brain Sciences, Vol. 14, Pages 1232: Changing the Paradigm for Tractography Segmentation in Neurosurgery: Validation of a Streamline-Based Approach
-Brain Sciences doi: 10.3390/brainsci14121232
-Authors: - Silvio Sarubbo - Laura Vavassori - Luca Zigiotto - Francesco Corsini - Luciano Annicchiarico - Umberto Rozzanigo - Paolo Avesani -
-In glioma surgery, maximizing the extent of resection while preserving cognitive functions requires an understanding of the unique architecture of the white matter (WM) pathways of the single patient and of their spatial relationship with the tumor. Tractography enables the reconstruction of WM pathways, and bundle segmentation allows the identification of critical connections for functional preservation. This study evaluates the effectiveness of a streamline-based approach for bundle segmentation on a clinical dataset as compared to the traditional ROI-based approach. We performed bundle segmentation of the arcuate fasciculus, of its indirect anterior and posterior segments, and of the inferior fronto-occipital fasciculus in the healthy hemisphere of 25 high-grade glioma patients using both ROI- and streamline-based approaches. ROI-based segmentation involved manually delineating ROIs on MR anatomical images in Trackvis (V0.6.2.1). Streamline-based segmentations were performed in Tractome, which integrates clustering algorithms with the visual inspection and manipulation of streamlines. Shape analysis was conducted on each bundle. A paired t-test was performed on the irregularity measurement to compare segmentations achieved with the two approaches. Qualitative differences were evaluated through visual inspection. Streamline-based segmentation consistently yielded significantly lower irregularity scores (p &lt; 0.001) compared to ROI-based segmentation for all the examined bundles, indicating more compact and accurate bundle reconstructions. Qualitative assessment identified common biases in ROI-based segmentations, such as the inclusion of anatomically implausible streamlines or streamlines with undesired trajectories. Streamline-based bundle segmentation with Tractome provides reliable and more accurate reconstructions compared to the ROI-based approach. By directly manipulating streamlines rather than relying on voxel-based ROI delineations, Tractome allows us to discern and discard implausible or undesired streamlines and to identify the course of WM bundles even when the anatomy is distorted by the lesion. These features make Tractome a robust tool for bundle segmentation in clinical contexts.
+ In the Americas, the expansion in incidence of arboviral infections including Mayaro virus (MAYV) has drawn attention to the resurgence of viruses associated with understudied arthropods. Mosquitoes belonging to the genus Haemagogus are generally geographically restricted to the forests of Central and South America and the Caribbean and are the known sylvan vectors for yellow fever virus and emerging MAYV. With an established population in Jamaica, Haemagogus equinus has been reported to be well-adapted to oviposition in artificial containers close to human populations. Its role in arboviral transmission however is not fully understood. Given the dearth of genetic information and the difficulty in morphologically identifying cryptic features in species belonging to this genus, we report the first mitochondrial genome of Hg. equinus. Using a genome skimming approach, two Hg. equinus mosquito specimens were sequenced using the Illumina Novaseq 6000 platform. A representative mitogenome of 16,471 bp, 80.7% AT and 37 genes was assembled using NOVOplasty. Phylogenetic analysis placed Hg. equinus in the Albomaculatus section of the Haemagogus subgenus supporting previously described taxonomic studies. -in Brain Sciences on 2024-12-07 00:00:00 UTC. +
in F1000Research on 2024-12-09 09:54:14 UTC.
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-Brain Sciences, Vol. 14, Pages 1231: Therapeutic Approach to Primary Tic Disorders and Associated Psychiatric Comorbidities
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+Life Cycle Assessment of Microalgae-Based Products for Carbon Dioxide Utilization in Thailand: Biofertilizer, Fish Feed, and Biodiesel [version 1; peer review: awaiting peer review]
-Brain Sciences, Vol. 14, Pages 1231: Therapeutic Approach to Primary Tic Disorders and Associated Psychiatric Comorbidities
-Brain Sciences doi: 10.3390/brainsci14121231
-Authors: - Irene Berzosa-Gonzalez - Saul Martinez-Horta - Jesus Pérez-Pérez - Jaime Kulisevsky - Javier Pagonabarraga -
-Background/Objectives: The treatment of tics and psychiatric comorbidities is crucial when they affect the patient&rsquo;s well-being and relationships. However, the optimal pharmacological treatment (PT) tailored to each patient&rsquo;s phenotype remains unclear. The primary objective of this study is to describe the clinical characteristics and treatment received for tics and psychiatric comorbidities in our cohort of children and adult patients with tic disorders. Additionally, a further aim was to quantify the severity of tics, comorbidities and overall severity, and the overall clinical changes observed during the follow-up. Methods: Retrospective descriptive study of patients with tic disorders under follow-up at our Tic Functional Unit from January 2022 to March 2024. Two independent neurologists retrospectively applied the Clinical Global Impression of Change (CGI-C) and the Clinical Global Impression of Severity (CGI-S) scales at baseline and at last assessment. Results: A total of 36 individuals were included (63.8% males, median age = 18 years, IQR 19): 94.4% with Tourette syndrome (TS), 2.8% with chronic tic disorder (CTD), and 2.8% with provisional tic disorder (PTD). A total of 86% had at least one psychiatric comorbidity, the most common being obsessive&ndash;compulsive symptomatology (OCS) (52%), anxiety (52%), and attention deficit hyperactivity disorder (ADHD) (35%). At last assessment, 26 patients (72.2%) were on undergoing PT for tics and 3 were receiving additional botulinum toxin. The most used medication for tics were aripiprazole (46.2%) and clonazepam (46.2%), and for psychiatric comorbidities, SSRIs (42.9%), methylphenidate (19%), and benzodiazepines (57.1%). Overall improvement according to the CGI-C scale was mild (CGI-C 3). Children and adolescents showed greater improvement than adults (CGI-C 2 vs. 3; p = 0.005). Aripiprazole and clonazepam produced similar outcomes in reducing CGI-C. Conclusions: We observed a favorable clinical course in patients treated with aripiprazole and clonazepam, which appear to be better than that obtained with other treatments. We consider that clonazepam may be useful as a first-line monotherapy and as an adjuvant for both tics and comorbidities in selected cases.
+ Background Microalgae-based products offer a sustainable solution for food, fuel, and agricultural inputs, presenting environmental benefits and economic opportunities. A comprehensive assessment is needed to understand their potential in supporting sustainability goals, considering the complex interplay between production methods, energy sources, and environmental impacts. Methods This study evaluated the environmental impacts of three microalgae-derived products – biodiesel, fish feed, and biofertilizer – through a comprehensive life cycle assessment. Nine scenarios were explored comparing three electricity profiles (current Thai mix, 50% renewable/50% current mix hybrid, 100% renewable) across the three products. The assessment evaluated environmental impacts and potential economic benefits of transitioning to these microalgae-based alternatives. Results and discussion All products demonstrated potential for significant environmental benefits under increased renewable energy scenarios. Fish feed consistently exhibited the lowest environmental impacts across all categories examined, showing substantial improvements with increased renewable energy use. With an annual demand of 0.4 million tonnes, fish feed could generate USD 560 million in revenue and reduce CO2 emissions by 1.1 million tonnes. Fulfilling the projected biodiesel demand of 4,015 million liters per year through microalgae production could yield approximately USD 3.5 billion in revenue and reduce CO2 emissions by 30 million tonnes compared to conventional fossil-based diesel. Additionally, algal biofertilizer production could meet a 5 million tonnes annual demand, offering USD 2 billion in revenue while reducing CO2 emissions by 6 million tonnes yearly. Collectively, these products could offset 37 million tonnes of CO2, representing about 14% of Thailand’s total CO2 emissions, contributing significantly to the country’s Nationally Determined Contribution (NDC) target of 20-30% greenhouse gas emissions reduction. Conclusion Transitioning to microalgae-based products could transform the aquaculture, energy, and agricultural sectors, potentially supporting the national climate change mitigation goals, if implemented. -in Brain Sciences on 2024-12-07 00:00:00 UTC. +
in F1000Research on 2024-12-09 09:52:49 UTC.
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-Brain Sciences, Vol. 14, Pages 1230: The Endocannabinoid Activity Remodulation for Psychosis Liability in Youth (EARLY) Study: An Open-Label Feasibility Trial of Ultramicronized Palmitoylethanolamide Oral Supplementation for Individuals at Clinical High R
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+Molecular docking and dynamics studies to identify novel active compounds targeting potential breast cancer receptor proteins from an indigenous herb Euphorbia thymifolia Linn [version 3; peer review: 1 approved]
-Brain Sciences, Vol. 14, Pages 1230: The Endocannabinoid Activity Remodulation for Psychosis Liability in Youth (EARLY) Study: An Open-Label Feasibility Trial of Ultramicronized Palmitoylethanolamide Oral Supplementation for Individuals at Clinical High Risk of Psychosis
-Brain Sciences doi: 10.3390/brainsci14121230
-Authors: - Riccardo Bortoletto - Marco Garzitto - Fabiana Piscitelli - Stefano Fornasaro - Claudia Scipioni - Orietta Sepulcri - Martina Fabris - Francesco Curcio - Matteo Balestrieri - Marco Colizzi -
-To date, no psychotropic medication has been shown to effectively halt progression to psychosis among individuals at Clinical HighRisk of psychosis (CHR), fueling the search for novel therapeutic agents. Recent evidence supports Palmitoylethanolamide (PEA) signaling as a potential psychosis biomarker, also indicating a therapeutic role for its supplementation in the treatment of psychotic disorders. Nonetheless, the effect of sustained PEA intake in CHR subjects has not explored so far. We will assess the feasibility of enrolling 20 CHR young adults presenting with attenuated psychotic symptoms (APSs) in a 12-week, open-label, investigator-initiated, proof-of-concept, single-arm trial of ultramicronized-PEA (um-PEA) at a dose of 600 mg/day. Once having completed the 12-week phase, participants will be asked to enter a 24-week extension phase of the study. We will examine um-PEA&rsquo;s ability to reduce APSs and psychic distress, um-PEA&rsquo;s safety and tolerability, and the biological basis of um-PEA&rsquo;s effect in terms of modulation of inflammatory response, endocannabinoid (eCB) signaling, and microbiome composition. Our trial aims to address an unmet clinical need in CHR subjects, providing an initial solid basis for the development of future studies evaluating the efficacy and tolerability of PEA supplementation in this group of patients.
+ Background Breast cancer has become the most prevalent disease and its incidence has almost doubled in the Indian population. This increased burden demands new targeted therapies with novel compounds either synthetically produced or derived from indigenous plants, which could be a promising approach for the development of drugs. Euphorbia thymifolia L is a widely growing tropical herb that has been reported to have various ethnopharmacological properties. Although Euphorbia genus is reported to have anticancer properties, E. thymifolia is not reported to have anticancer properties to date. Therefore, the aim of the present study was to screen the phytoconstituents and identify the active compounds present in the methanolic extract of E. thymifolia (ME.ET) as ligands to inhibit human cancer cell lines with special reference to potential protein targets implicated in breast cancer using an In-silico approach. Methods ME.ET was subjected to GC-MS analysis to screen the phytoconstituents, and the identified compounds were docked with protein targets such as extracellular signal-regulated kinases (ERK1), a serine/threonine kinase-1(AKT1), human epidermal growth factor 2 (HER2), estrogen receptor (ER), maternal embryonic leucine zipper kinase (MELK), polo-like kinase-1(PLK1), and protein tyrosine kinase (PTK6). Compounds with good docking scores were further subjected to dynamic studies to understand the protein ligand binding stability, ligand pathway calculation, and molecular mechanics energies combined with Poisson-Boltzmann (MM/PBSA) calculations using the Schrodinger suite. Results GC-MS analysis revealed the presence of 245 phytoconstituents, 219 of which were unique. When subjected to docking, these phytocompounds, namely 3,6,9,12-tetraoxatetradecane-1,14-diyl dibenzoate (TTDB) and succinic acid, 2-(dimethylamino) ethyl 4-isopropylphenyl ester (SADPE), showed good docking scores. Molecular dynamics studies showed a high affinity and low binding energy for TTDB with HER2, ERK1, and SADPE with ER. Conclusions Hence, in this study, we identified two lead compounds in E.thymifolia linn. Further invitro and invivo anticancer studies can be performed to confirm these results and to understand the molecular mechanism by which they exhibit anticancer activity against breast cancer. -in Brain Sciences on 2024-12-07 00:00:00 UTC. +
in F1000Research on 2024-12-09 09:51:53 UTC.
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-Brain Sciences, Vol. 14, Pages 1229: EEG Oscillations as Neuroplastic Markers of Neural Compensation in Spinal Cord Injury Rehabilitation: The Role of Slow-Frequency Bands
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+Is publishing gold open-access worth it? An assessment of hybrid and gold open-access publishing models of medical journals on their impact [version 1; peer review: awaiting peer review]
-Brain Sciences, Vol. 14, Pages 1229: EEG Oscillations as Neuroplastic Markers of Neural Compensation in Spinal Cord Injury Rehabilitation: The Role of Slow-Frequency Bands
-Brain Sciences doi: 10.3390/brainsci14121229
-Authors: - Guilherme J. M. Lacerda - Lucas Camargo - Marta Imamura - Lucas M. Marques - Linamara Battistella - Felipe Fregni -
-Background: Spinal cord injury (SCI) affects approximately 250,000 to 500,000 individuals annually. Current therapeutic interventions predominantly focus on mitigating the impact of physical and neurological impairments, with limited functional recovery observed in many patients. Electroencephalogram (EEG) oscillations have been investigated in this context of rehabilitation to identify effective markers for optimizing rehabilitation treatments. Methods: We performed an exploratory cross-sectional study assessing the baseline EEG resting state of 86 participants with SCI as part of the Deficit of Inhibitory as a Marker of Neuroplasticity in Rehabilitation Cohort Study (DEFINE). Results: Our multivariate models demonstrated a positive correlation between frontal delta asymmetry and depression symptoms, while the frontal alpha asymmetry band and anxiety symptoms were negatively correlated. Theta oscillations were negatively associated with motor-evoked potential (MEP), whereas alpha oscillations were positively associated with MEP in all regions of interest and with CPM response as a negative correlation. Based on the potential role of lower-frequency oscillations in exerting a salutogenic compensatory effect, detrimental clinical and neurophysiological markers, such as depression and lower ME, likely induce slow oscillatory rhythms. Alpha oscillations may indicate a more salutogenic state, often associated with various cognitive functions, such as attention and memory processing. Conclusions: These results show an attempt by the CNS to reorganize and restore function despite the disruption caused by SCI. Indeed, this finding also challenges the notion that low-frequency EEG rhythms are associated with cortical lesions. These results may contribute to the development of rehabilitation strategies and potentially improve the clinical outcomes of patients with SCI.
+ Background Hybrid and gold open-access (OA) are the most common publishing models. The latter requires fees to allow full-text visibility upon publishing, whereas hybrid journals offer the option to publish gold OA or for free (subscription-based) where only users with access can get the full-text. We aimed to evaluate the impact of the publishing model and other factors on medical journals’ impact. Methods A sample of hybrid and gold OA medical journals indexed in Web of Science (WOS) and Scopus were included. The effect of the publishing model and other factors on journals’ impact factor (IF), CiteScore, quartile, and number of citations was assessed. Results 402 journals were included, 201 in each group. Hybrid and gold OA journals had a median age of 32 and 21 years, respectively (P<0.001). The median publishing cost in gold OA journals was $2,690, and 46.3% of them publish continuously. Publishing model, journal’s age, being of an organization/society, and EMBASE indexation didn’t affect IF, CiteScore, number of citations, and WOS quartile (P>0.05). However, gold OA model wasn’t significantly associated with Q1 ranking in Scopus (OR, 0.49; 95% CI, 0.25-0.94; P=0.032), which indicates that hybrid journals were more likely to have such ranking. Conclusion These findings indicate that gold OA publishing doesn’t necessarily result in higher impact, which contradicts the claim that such model enhances citations. Therefore, authors can continue to publish in hybrid journals without being concerned about getting cited. Gold OA journals are encouraged to reduce their fees to facilitate global research access. -in Brain Sciences on 2024-12-07 00:00:00 UTC. +
in F1000Research on 2024-12-09 09:49:04 UTC.
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-Efficacy and Safety of Platelet-rich Plasma in the Management of Lumbar Disc Herniation: A Systematic Review and Meta-analysis [version 1; peer review: awaiting peer review]
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+Long‐Term Potentiation: The Accidental Discovery
- Background Lumbar radicular discomfort is often induced by mechanical compression of the nerve root and inflammatory reactions. Platelet-rich plasma (PRP) is an efficacious therapy modality, albeit ongoing controversies regarding its effectiveness, and it possesses the advantage of minimal side effects. Therefore, we conducted the current systematic review and meta-analysis to investigate the efficacy and safety of PRP in the treatment of lumbar disc herniation (LDH). Methods We conducted our database searching on PubMed, Scopus, and Web of Science from inception till August 2024 to look for articles that fulfil our aim. The search strategy was based on three main keywords: “Platelet-rich plasma” AND “Lumbar” AND “Hernia*”. We conducted the pooled analysis of continuous variables using mean difference (MD) and we used pooled odds ratio (OR) for dichotomous variables with 95% confidence intervals (CI). Results The use of PRP was statistically significant associated with reduced visual analogue scale (VAS) compared with no PRP with MD of -0.44 (95%CI:-0.76, -0.11, p=0.008), and Oswestry Disability Index (ODI) with MD of -5.36 (95%CI: -8.25, -2.48, p=0.0003). However, no significant difference was observed regarding Japanese Orthopedic Association (JOA) with MD of 2.52 (95%CI:-0.8, 5.84, p=0.14) with non-significant heterogeneity. PRP was also associated with reduced risk of complications with OR of 0.22 (95%CI:0.07, 0.68, p=0.009) and non-significant heterogeneity. Conclusion PRP use in patients with LDH is associated with positive outcomes presented in reduction of pain, and disability (decrease in ODI scale) in addition to being safe with less incidence of complications compared with patients not receiving PRP. +ABSTRACT
+Long-term potentiation (LTP), is a type of synaptic plasticity now considered essential for learning and memory. Here I tell the story of how I accidentally discovered in 1966 in the laboratory of Per Andersen in Oslo, Norway, because I was not looking for it. It just emerged. I recount how I came to work with Per and why my result was not immediately followed up. Then, in 1968 Tim Bliss joined the lab and, on his urging, from 1968 to 1969 we did the experiments that resulted in Bliss and Lømo, 1973. I explain why I think the experiments later failed in Oslo, and for a few years also in Tim's lab in London, before it became a readily observable phenomenon. I also describe how Tony Gardner-Medwin and I in 1971 failed to reproduce the results that Tim and I had obtained 2 years earlier in the same lab and the same type of anesthetized rabbit preparation. I tell how this failure caused me to leave the LTP field and, instead, continue exploring mechanisms of nerve–muscle interactions, which I had studied with much success during my postdoc period in London from 1969 to 1971. I reflect on Donald Hebb's influence on LTP studies and on my experience when after many years of neglect, I became interested in LTP and the hippocampus anew and started to write about it, though without doing lab experiments. Finally, I report briefly on the experiments I am doing now in retirement, studying how the nervous system regulates body temperature through varying amounts of muscle tone.
-in F1000Research on 2024-12-06 16:58:18 UTC. +
in Hippocampus on 2024-12-09 07:49:13 UTC.
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-Case Report: Case report : Mindfulness training led to catharsis and mindfulness-to-meaning in a patient with social anxiety disorder comorbid with persistent depressive disorder (Dysthymia) [version 1; peer review: awaiting peer review]
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+Adult Neurogenesis in the Human Dentate Gyrus
- Background The use of mindfulness in the treatment of anxiety and depression is becoming more and more widespread, but there are few reports that it has fundamentally changed patients’ sense of life. Case Presentation This report showed 9 year’s progress of treatment for Social Anxiety Disorder and Persistent Depressive Disorder in a 41-year-old female patient experiencing a long-term painful married life with a reckless husband and controlling mother-in-law. During the past 25 months, she received 180 sessions of mindfulness training, resulting in complete remission of the anxiety and depression symptoms. After the 30th session she experienced an episode of the catharsis during the mindfulness training and experienced what can be called Mindfulness-To-Meaning, which is characterized by durable eudaimonic well-being in the face of adversity. Conclusions The psychological mechanisms that supported arriving at Mindfulness-To-Meaning are delineated as: Heightened (1) awareness which promoted (2) verbalization of the primary theme of suppression, in which the stress was (3) appraised metacognitively. Then (4) decentering permitted integrating this painful theme into a new adaptive self and world view, which resulted in (5) emotional catharsis, or release. Furthermore (6) positive appraisal of this experience enhanced awareness and led to the experience of (7) Mindfulness-To-Meaning. +ABSTRACT
+In the adult dentate gyrus of the hippocampus there are neuronal stem cells that give rise to immature neurons and subsequently to mature functional granule neurons. The rate of proliferation, differentiation, and survival is regulated intrinsically and extrinsically. For example, Wnt, BMP, TLX, and BDNF all regulate adult neurogenesis intrinsically, while exercise, environmental enrichment, stress, and epilepsy are some of the extrinsic factors that regulate adult neurogenesis. A clearer picture is emerging for the functional role of these newly born neurons in behavior, demonstrating that adult neurogenesis plays a role in recognizing events, places, objects, or people as unique when comparing options that are very similar, but that these newly born cells play little role in recognition when differences are greater. Most of the research on adult neurogenesis is conducted in experimental mammals, including mice and rats. The first evidence for adult neurogenesis in humans was reported in 1998, when postmortem brains from cancer patients injected with bromodeoxyuridine (BrdU) were examined and cells were found that had divided and differentiated into mature neurons. Subsequently, additional evidence using other techniques has confirmed human adult neurogenesis. Additional in vivo live reports will be needed to monitor the effects of changes in human adult neurogenesis with age and disease.
-in F1000Research on 2024-12-06 16:54:17 UTC. +
in Hippocampus on 2024-12-09 07:48:40 UTC.
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-Predictors of mortality for blunt trauma patients in intensive care: A retrospective cohort study [version 5; peer review: 2 approved]
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+Spatial organizations of heterochromatin underpin nuclear structural integrity of ventricular cardiomyocytes against mechanical stress
- Background Major trauma places substantial demand on critical care services, is a leading cause of death in under 40-year-olds and causes significant morbidity and mortality across all age groups. Various factors influence patient outcome and predefining these could allow prognostication. The aim of this study was to identify predictors of mortality from major trauma in intensive care. Methods This was a retrospective study of adult trauma patients admitted to general intensive care between January 2018 and December 2019. We assessed the impact on mortality of patient demographics, patterns of injury, injury scores (Glasgow Coma Score (GCS), Charlson’s comorbidity index (CCI), Acute Physiology and Health Evaluation II (APACHE II), Injury Severity Score (ISS) and Probability of Survival Score (Ps19)), number of surgeries and mechanism of injury using logistic regression. Results A total of 414 patients were included with a median age of 54 years (IQR 34–72). Overall mortality was 18.6%. The most common mechanism of injury was traffic collision (46%). Non-survivors were older, had higher ISS scores with lower GCS on admission and lower probability of survival scores. Factors independently predictive of mortality were age 70-80 (OR 3.267, p = 0.029), age >80 (OR 27.043, p < 0.001) and GCS < 15 (OR 8.728, p < 0.001). Ps19 was the best predictor of mortality (p <0.001 for each score category), with an AUROC of 0.90. Conclusions The significant mortality predictors were age, fall from <2 metres, injury of head or limbs, GCS <15 and Ps19. Contrary to previous studies, CCI and APACHE II did not significantly predict mortality. Although Ps19 was found to be the best current prognostic score, trauma prognostication would benefit from a single validated scoring system incorporating both physiological variables and injury patterns. + Cardiomyocytes exhibit characteristic prominent spatial organizations of heterochromatin (SOH). Fujiwara et al. found that the replacement of endogenous H2B with H2B-mCherry disrupts SOH, leading to extreme elongation of ventricular cardiomyocyte nuclei, resulting in severe heart failure, demonstrating that SOH play a structural role in maintaining nuclear shape against mechanical stress. -in F1000Research on 2024-12-06 16:45:07 UTC. +
in Cell Reports: Current Issue on 2024-12-09 00:00:00 UTC.
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-Recent Advances in Biopesticide Research and Development with a Focus on Microbials [version 3; peer review: 2 approved]
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+Cytokines reprogram airway sensory neurons in asthma
- Biopesticides are pest control products derived from natural sources such as microbes, macro-organisms (insects and pathogens), plant extracts, and certain minerals. Many biopesticides are considered environmentally safe and can complement or substitute conventional chemical pesticides. They can also be highly specific or broad spectrum with a unique mode of action controlling a wide range of pest species. Due to their target-specificity and low to no environmental residuality, biopesticides conform to the 3 pillars of Climate-Smart Agriculture, the Sustainable Development Goals, and, ultimately, the Paris Agreement. This review focuses largely on microbial biopesticides derived from fungi, bacteria, viruses, and nematodes. It discusses (i) the various microbial biopesticide formulations, (ii) the mode of microbial biopesticide action, (iii) the factors that affect the potential efficacy of biopesticides, (iv) challenges to the adoption of microbial biopesticides, and (v) the role of microbial biopesticides in Integrated Pest Management programs. Finally, advancements in application techniques, as well as future research directions and gaps, are highlighted. + Nociceptor neurons play multiple roles in asthma by exacerbating inflammation and bronchial hypersensitivity and triggering mucus metaplasia. Crosson et al. characterize a distinct subset of NPY1R-expressing sensory neurons that innervate the lung and describe their transcriptional and functional reprogramming by the asthma-driving cytokine IL-13. -in F1000Research on 2024-12-06 16:37:01 UTC. +
in Cell Reports: Current Issue on 2024-12-09 00:00:00 UTC.
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-Study anti-viral drugs for their efficiency against multiple SARS CoV-2 drug targets within molecular docking, molecular quantum similarity, and chemical reactivity indices frameworks [version 2; peer review: 2 approved with reservations]
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+Spinal microcircuits go through multiphasic homeostatic compensations in a mouse model of motoneuron degeneration
- The study focused on drug discovery for COVID-19, emphasizing the challenges posed by the pandemic and the importance of understanding the virus’s biology. The research utilized molecular docking and quantum similarity analyses to explore potential ligands for SARS-CoV-2 RNA-dependent RNA polymerase. Docking Results Docking outcomes for various ligands, including Oseltamivir, Prochloraz, Valacyclovir, Baricitinib, Molnupiravir, Penciclovir, Famciclovir, Lamivudine, and Nitazoxanide, were presented. Interactions between ligands and specific residues in the RNA-dependent RNA polymerase were analyzed. Reactivity Descriptors Global parameters, such as electronic chemical potential, chemical hardness, global softness, and global electrophilicity, were computed for the ligands. For the local reactivity descriptors, the Fukui Functions were used. Fukui functions, representing electrophilic and nucleophilic sites, were calculated for selected ligands (Valacyclovir and Penciclovir). Nucleophilic character assignments for specific molecular regions were discussed, providing insights into potential charge-donating interactions. Results and Discussion Challenges in COVID-19 drug discovery, such as virus mutability, rapid evolution, and resource limitations, were summarized. Progress in vaccine development and the need for ongoing research to address variants and breakthrough cases were emphasized. Overlap Operator Analysis Higher MQSM between Lamivudine and Molnupiravir (0.5742) indicates structural and electronic similarity. Lowest MQSM between Oseltamivir and Prochloraz (0.2233) implies structural dissimilarity. Coulomb Operator Analysis Higher MQSM between Lamivudine and Molnupiravir (0.9178) suggests both structural and electronic similarity. Lowest MQSM between Baricitinib and Famciclovir (0.6001) indicates greater structural diversity. Measurements above 0.5 in Table 3 suggest electronic similarity, emphasizing the electronic aspects in molecular analysis. In this sense, it study employed a multi-faceted approach combining molecular docking, quantum similarity analyses, and chemical reactivity assessments to explore potential drug candidates for COVID-19. The findings provide valuable insights into ligand interactions, reactivity patterns, and the challenges associated with drug discovery in the context of the global pandemic. + Through in vitro and in vivo electrophysiology and super-resolution microscopy, Nascimento et al. identify early-stage alterations in pre-motor spinal recurrent inhibition and monosynaptic Ia excitation in the mSOD1 mouse model of ALS. The authors describe that such changes are multiphasic across disease progression, thus providing insights into disease pathophysiology. -in F1000Research on 2024-12-06 16:10:13 UTC. +
in Cell Reports: Current Issue on 2024-12-09 00:00:00 UTC.
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-Women’s representation in higher leadership positions in Ethiopia in the last three decades since 1991 [version 2; peer review: 2 approved]
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+Efficient value synthesis in the orbitofrontal cortex explains how loss aversion adapts to the ranges of gain and loss prospects
- Gender equality in decision-making positions is crucial to achieving the goals of good governance, peace, democracy, and inclusive/sustainable development. The major aim of this research article is to investigate the representation trend of women in higher decision-making positions over the last thirty years, since 1991. The federal three organs of government (law formulating, law enforcing, and law interpreting bodies) were the focus of this research. This research is a mixed type of research that inculcates both qualitative and quantitative data types. Secondary data sources from relevant government institutions were mostly used. The data was analyzed through content analysis of documents and presented via descriptive data presenting techniques. The research findings reveal that although women’s representation in positions of decision-making has advanced considerably in recent years, the empirical data throughout the previous thirty years demonstrated the underrepresentation of women in higher leadership positions within the Ethiopian federal government. Furthermore, Women never held certain higher-level government leadership positions, such as the Prime Minister position, which seems to be forbidden for women. Women made up 23%, 19%, 19%, and 24% of the House of Peoples Representatives (HPR), the House of Federation (HoF), ministerial posts, and judicial bodies, respectively over the last three decades. Women are visibly underrepresented in the executive positions as compared to others. Thus, substantial policy and practical initiatives are needed to remove institutional, social, and economic barriers to boost women’s advanced visibility in senior leadership roles. + Is irrational behavior the incidental outcome of biological constraints imposed on neural information processing? In this work, we consider the paradigmatic case of gamble decisions, where gamble values integrate prospective gains and losses. Under the assumption that neurons have a limited firing response range, we show that mitigating the ensuing information loss within artificial neural networks that synthetize value involves a specific form of self-organized plasticity. We demonstrate that the ensuing efficient value synthesis mechanism induces value range adaptation. We also reveal how the ranges of prospective gains and/or losses eventually determine both the behavioral sensitivity to gains and losses and the information content of the network. We test these predictions on two fMRI datasets from the OpenNeuro.org initiative that probe gamble decision-making but differ in terms of the range of gain prospects. First, we show that peoples' loss aversion eventually adapts to the range of gain prospects they are exposed to. Second, we show that the strength with which the orbitofrontal cortex (in particular: Brodmann area 11) encodes gains and expected value also depends upon the range of gain prospects. Third, we show that, when fitted to participant’s gambling choices, self-organizing artificial neural networks generalize across gain range contexts and predict the geometry of information content within the orbitofrontal cortex. Our results demonstrate how self-organizing plasticity aiming at mitigating information loss induced by neurons’ limited response range may result in value range adaptation, eventually yielding irrational behavior. -in F1000Research on 2024-12-06 16:08:18 UTC. +
in eLife on 2024-12-09 00:00:00 UTC.
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-Factors contributing to persistent shoulder pain after arthroscopic rotator cuff repair: Protocol for a scoping review [version 2; peer review: 1 approved, 1 approved with reservations]
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+Polarised moonlight guides nocturnal bull ants home
- Introduction Rotator cuff (RC) tears are the most common and disabling musculoskeletal ailments among patients with shoulder pain. Although most individuals show improvement in function and pain following arthroscopic rotator cuff repair (ARCR), a subgroup of patients continue to suffer from persistent shoulder pain following the surgical procedure. Identifying these factors is important in planning preoperative management to improve patient outcomes. Objective This scoping review aims to identify biological factors, psychological factors, and social determinants of health contributing to the development of persistent pain in individuals after the ARCR procedure. Inclusion criteria All prospective and retrospective longitudinal studies reporting the risk factors contributing to persistent pain three months or longer after the ARCR surgery will be considered for this scoping review. Methods Our review will adhere to the Joanna Briggs Institute (JBI) scoping review methodology. Four electronic databases PubMed, CINAHL, Embase, and Scopus will be searched for studies in the English language. Additional studies can be found by conducting a citation analysis of the included studies. Title and abstract screening will be performed by two independent reviewers following the inclusion criteria, a third reviewer will be consulted about any differences. Next, full-text screening will be conducted, and the remaining search results will be reviewed to extract data, as well as to synthesize findings from all research. An overview of findings will be depicted in tabular format accompanied by a narrative summary of various factors contributing to persistent pain. + For the first time in any animal, we show that nocturnal bull ants use the exceedingly dim polarisation pattern produced by the moon for overnight navigation. The sun or moon can provide directional information via their position; however, they can often be obstructed by clouds, canopy, or the horizon. Despite being hidden, these bodies can still provide compass information through the polarised light pattern they produce/reflect. Sunlight produces polarised light patterns across the overhead sky as it enters the atmosphere, and solar polarised light is a well-known compass cue for navigating animals. Moonlight produces an analogous pattern, albeit a million times dimmer than sunlight. Here, we show evidence that polarised moonlight forms part of the celestial compass of navigating nocturnal ants. Nocturnal bull ants leave their nest at twilight and rely heavily on the overhead solar polarisation pattern to navigate. Yet many foragers return home overnight when the sun cannot guide them. We demonstrate that these bull ants use polarised moonlight to navigate home during the night, by rotating the overhead polarisation pattern above homing ants, who alter their headings in response. Furthermore, these ants can detect this cue throughout the lunar month, even under crescent moons, when polarised light levels are at their lowest. Finally, we show the long-term incorporation of this moonlight pattern into the ants’ path integration system throughout the night for homing, as polarised sunlight is incorporated throughout the day. -in F1000Research on 2024-12-06 16:05:45 UTC. +
in eLife on 2024-12-09 00:00:00 UTC.
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-Hepatic GPx1 and GIT1 expression altered by ethanol exposure during third trimester-equivalent development [version 2; peer review: 1 approved with reservations]
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+Complex aneuploidy triggers autophagy and p53-mediated apoptosis and impairs the second lineage segregation in human preimplantation embryos
- Background Ethanol (EtOH) exposure throughout gestation and breastfeeding leads to multiple adverse outcomes in the hepatic system. Under oxidative stress, alterations in the liver are related to the inhibition of induced nitric oxide synthase activity in sinusoidal cells as a consequence of low expression of G-protein-coupled receptor (GPCR)-kinase interacting (GIT1). Here, we hypothesized that both glutathione peroxidase 1 (GPx1) and GIT1 could be altered by EtOH exposure during the third trimester of human equivalent development. Methods We exposed rats during the third trimester equivalent [postnatal days (PD) 2-8] to moderate levels of maternal EtOH (20%). GPx1 and GIT1 expression was detected by western blotting, and the antioxidant activity of glutathione peroxidase GPx and the concentration of hepatic carbonyl groups (CG were determined by spectrophotometry. Serum biochemistry parameters such as alanine aminotransferase (ALT), glucose (gluc), cholesterol (chol), and triglycerides (TG) were also measured. Results We found that ethanol decreased both GIT1 and GPx1 selenoprotein expression, affecting GPx antioxidant activity and increasing protein oxidation. Conclusions These results demonstrate for the first time that the GPx antioxidant system altered by EtOH exposure during the third trimester of development is related to a parallel decrease in GIT1 expression [1]. + About 70% of human cleavage stage embryos show chromosomal mosaicism, falling to 20% in blastocysts. Chromosomally mosaic human blastocysts can implant and lead to healthy new-borns with normal karyotypes. Studies in mouse embryos and human gastruloids showed that aneuploid cells are eliminated from the epiblast by p53-mediated apoptosis while being tolerated in the trophectoderm. These observations suggest a selective loss of aneuploid cells from human embryos, but the underlying mechanisms are not yet fully understood. Here, we investigated the cellular consequences of aneuploidy in a total of 125 human blastocysts. RNA-sequencing of trophectoderm cells showed activated p53 pathway and apoptosis proportionate to the level of chromosomal imbalance. Immunostaining corroborated that aneuploidy triggers proteotoxic stress, autophagy, p53-signaling, and apoptosis independent from DNA damage. Total cell numbers were lower in aneuploid embryos, due to a decline both in trophectoderm and in epiblast/primitive endoderm cell numbers. While lower cell numbers in trophectoderm may be attributed to apoptosis, aneuploidy impaired the second lineage segregation, particularly primitive endoderm formation. This might be reinforced by retention of NANOG. Our findings might explain why fully aneuploid embryos fail to further develop and we hypothesize that the same mechanisms lead to the removal of aneuploid cells from mosaic embryos. -in F1000Research on 2024-12-06 16:02:54 UTC. +
in eLife on 2024-12-09 00:00:00 UTC.
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-An open label, single arm, pilot study to evaluate the safety, tolerability, and efficacy of daily fluconazole 150 mg in subjects suffering from Tinea cruris and Tinea corporis [version 2; peer review: 1 approved with reservations, 1 not approved]
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+How vision shapes the paths we choose
- Background Dermatophytes are the most common superficial fungal infections worldwide and are treated with prescribed regimens of terbinafine and itraconazole, or with weekly doses of fluconazole. Dermatologists are increasingly encountering treatment failures, and experts suggest that standard treatment regimens are not applicable anymore. We planned an open-label study to evaluate the results of fluconazole 150 mg daily for 8 weeks in patients with tinea cruris and tinea corporis. Methods Patients were enrolled from the La’Mer Clinic, Mumbai, India. We included adult subjects with uncomplicated dermatophytosis confirmed by microscopic examination of skin scrapings. Pregnancy, poor renal function, and recent exposure to anti-fungal therapy were exclusion criteria. Patients were reviewed on days 14, 28 and 56. The treating doctor scored the severity of erythema, scaling, and pruritus on a four-point scale: absent, mild, moderate, and severe. Of 107 subjects screened, 100 were finally included in the study. Eleven were lost to follow up and one subject withdrew consent. Results The site of disease was body alone in 29, groin alone in 7, and both body and groin in 64 cases. At 5 weeks, 98%, 100%, and 97% of patients had no scaling, erythema, and pruritus, respectively. Skin scrapings showed 100% mycological cure. In one patient the alanine transaminase level rose from 54.9 to 100.2 U/L, and qualified as a grade 1 adverse event not requiring intervention. No other significant adverse events were noted. Conclusions Our results suggest that fluconazole 150 mg daily for eight weeks effectively treats dermatophytosis. This regimen is safe and well-tolerated even in patients with co-morbidities. Fluconazole is about eight times less expensive than itraconazole or terbinafine and may be the preferred therapy. Registration The trial was registered with Clinical Trials Registry, India (Registration number CTRI/2020/06/026110) on 24 June 2020. FDC Company, India, provided financial support for the study. + A mathematical model can predict the path walkers take through a rugged landscape, including the tendency of people to avoid paths that are too steep, even if it means going farther. -in F1000Research on 2024-12-06 15:54:43 UTC. +
in eLife on 2024-12-09 00:00:00 UTC.
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-Role modeling and Snack Choices of young adults: The mediating role of meal planning [version 1; peer review: awaiting peer review]
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+Analysis of foothold selection during locomotion using terrain reconstruction
- Objective This study aimed to examine the mediating role of meal planning in the relationship between role modeling and snack choice. Methods and Measures The study was correlational and quantitative in nature. The study selected a sample of 403 university students. We collected data through interviews using a questionnaire. We analyzed the data using SPSS 23.0.0.0 (IBM Corp; 1989, 2015) (Build 1607) and AMOS 23.0.0 (IBM Corp; 1983, 2015) (Build 1607) software for correlational and Confirmatory factor tests. We used the bootstrapping technique to test for the mediation effect of meal planning. Results Meal planning had a full mediation effect between role modeling and snack choice. This means that Role modeling had a significant influence on meal planning, meal planning had a significant influence on snack choice, and role modeling had no significant influence on snack choice. Conclusion when young people admire other people’s eating habits it leads them to plan their meals and choose similar snacks to their role models. Future studies should consider studying the effect that role models’ proximity has on snack choices among young people in other contexts. + Relatively little is known about the way vision is used to guide locomotion in the natural world. What visual features are used to choose paths in natural complex terrain? To answer this question, we measured eye and body movements while participants walked in natural outdoor environments. We incorporated measurements of the three-dimensional (3D) terrain structure into our analyses and reconstructed the terrain along the walker’s path, applying photogrammetry techniques to the eye tracker’s scene camera videos. Combining these reconstructions with the walker’s body movements, we demonstrate that walkers take terrain structure into account when selecting paths through an environment. We find that they change direction to avoid taking steeper steps that involve large height changes, instead of choosing more circuitous, relatively flat paths. Our data suggest walkers plan the location of individual footholds and plan ahead to select flatter paths. These results provide evidence that locomotor behavior in natural environments is controlled by decision mechanisms that account for multiple factors, including sensory and motor information, costs, and path planning. -in F1000Research on 2024-12-06 15:51:26 UTC. +
in eLife on 2024-12-09 00:00:00 UTC.
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-Incidence and predictive factors of hyperventilation syndrome in patients after COVID 19 pneumonia: a prospective cohort study [version 1; peer review: awaiting peer review]
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+Endogenous oligomer formation underlies DVL2 condensates and promotes Wnt/β-catenin signaling
- Background This study investigates the incidence and predictive factors of Hyperventilation Syndrome (HVS) in patients after COVID 19 pneumonia, addressing the clinical overlap between these conditions. Methods A one-month prospective study was conducted, tracking survivors of COVID-19 pneumonia. Patients were evaluated for ongoing clinical status, including HVS and post-traumatic syndrome disorder (PTSD), using clinical questionnaires, mMRC, Post-COVID-19 Functional Status (PCFS) Score, Nijmegen score, and PTSD Checklist for DSM-5 questionnaire. Results Our study included 222 patients (median age: 57 years, male predominance 62.6%). Somatic comorbidities, primarily metabolic disorders, were reported in 71.2% of cases. The majority had severe or critical infection forms (78.4%), and 91.9% experienced acute symptoms, with 86.5% having three or more symptom clusters. At one month follow-up, dyspnea (52.9%) and asthenia (21.7%) persisted. Functional limitations (PCFS Grade > 2) were observed in 19.6% of patients. The overall incidence of HVS was 158 per 1000 patients, and PTSD was 445 per 1000 patients. Multivariate logistic regression identified cognitive impairment (acute phase), persistent weight loss (post-COVID-19 phase), PCFS grade > 2, and PTSD as independent factors for developing HVS, with relative risks (RRs) of 3.47 (95%CI [1.48-8.31]; p = 0.004), 11.87 (95%CI [1.25-112.88]; p = 0.031), 3.24 (95%CI [1.34-7.86]; p = 0.009), and 5.98 (95%CI [2.27-15.77]; p < 0.001), respectively. Conclusion HVS is prevalent in the post-COVID-19 phase, affecting 15.6 % of survivors. Identified predictive factors suggest the convergence of psychosomatic pathophysiological mechanisms. Further research is crucial for a detailed understanding of these mechanisms in long COVID-19 patients. + Activation of the Wnt/β-catenin pathway crucially depends on the polymerization of dishevelled 2 (DVL2) into biomolecular condensates. However, given the low affinity of known DVL2 self-interaction sites and its low cellular concentration, it is unclear how polymers can form. Here, we detect oligomeric DVL2 complexes at endogenous protein levels in human cell lines, using a biochemical ultracentrifugation assay. We identify a low-complexity region (LCR4) in the C-terminus whose deletion and fusion decreased and increased the complexes, respectively. Notably, LCR4-induced complexes correlated with the formation of microscopically visible multimeric condensates. Adjacent to LCR4, we mapped a conserved domain (CD2) promoting condensates only. Molecularly, LCR4 and CD2 mediated DVL2 self-interaction via aggregating residues and phenylalanine stickers, respectively. Point mutations inactivating these interaction sites impaired Wnt pathway activation by DVL2. Our study discovers DVL2 complexes with functional importance for Wnt/β-catenin signaling. Moreover, we provide evidence that DVL2 condensates form in two steps by pre-oligomerization via high-affinity interaction sites, such as LCR4, and subsequent condensation via low-affinity interaction sites, such as CD2. -in F1000Research on 2024-12-06 15:21:44 UTC. +
in eLife on 2024-12-09 00:00:00 UTC.
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-Safety and efficacy of Dexmedetomidine in preoperative and postoperative settings during transsphenoidal resection of pituitary Adenoma: A systematic review and meta-analysis of randomized controlled trials [version 1; peer review: awaiting peer review]
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+Cross-species alignment along the chronological axis reveals evolutionary effect on structural development of the human brain
- Background Pituitary adenoma, a benign tumor of the pituitary gland, represents 10-15% of intracranial tumors. Although non-cancerous, its size and location can cause significant health issues, including hormonal imbalances and compression of nearby structures like the optic chiasm, leading to conditions such as Cushing’s disease, acromegaly, and visual disturbances. The prevalence ranges from 46 to 95 per 100,000 individuals. This study evaluates the effectiveness and safety of dexmedetomidine versus placebo in patients undergoing transsphenoidal resection of pituitary adenomas. Methods A systematic review and meta-analysis following PRISMA guidelines included 10 RCTs with 633 patients. English-language RCTs were sourced from PubMed, Scopus, Web of Science, Google Scholar, and Cochrane Library. Risk of bias was assessed using the ROB2 tool, and statistical analyses were performed using RevMan 5.3. Results Dexmedetomidine significantly reduced heart rate after intubation (MD: -6.61 bpm, 95% CI: -8.98 to -4.24, p < 0.00001) and post-extubation (MD: -6.77 bpm, 95% CI: -8.59 to -4.96, p < 0.00001). Mean arterial pressure decreased after intubation (MD: -10.49 mmHg, 95% CI: -12.73 to -8.26, p < 0.00001) and post-extubation (MD: -12.97 mmHg, 95% CI: -14.37 to -11.57, p < 0.00001). Dexmedetomidine also reduced surgical duration (SMD: -0.23, 95% CI: -0.41 to -0.05, p = 0.01), blood loss (MD: -109.49 mL, 95% CI: -152.60 to -66.38, p < 0.00001), propofol dose (SMD: -1.04, 95% CI: -1.72 to -0.37, p = 0.002), extubation time (SMD: -0.70, 95% CI: -0.93 to -0.47, p < 0.00001), and postoperative nausea and vomiting (OR: 0.45, 95% CI: 0.25 to 0.80, p = 0.007). Conclusions Dexmedetomidine enhances perioperative outcomes in transsphenoidal resection of pituitary adenomas, supporting its use as an effective anesthetic adjunct. + Disentangling the evolution mysteries of the human brain has always been an imperative endeavor in neuroscience. Although many previous comparative studies revealed genetic, brain structural and connectivity distinctness between human and other nonhuman primates, the brain evolutional mechanism is still largely unclear. Here, we proposed to embed the brain anatomy of human and macaque in the developmental chronological axis to construct cross-species predictive model to quantitatively characterize brain evolution using two large public human and macaque datasets. We observed that applying the trained models within-species could well predict the chronological age. Interestingly, we found the model trained in macaque showed a higher accuracy in predicting the chronological age of human than the model trained in human in predicting the chronological age of macaque. The cross-application of the trained model introduced an individual brain cross-species age gap index to quantify the cross-species discrepancy along the temporal axis of brain development and was found to be associated with the behavioral performance in visual acuity test and picture vocabulary test in human. Taken together, our study situated the cross-species brain development along the chronological axis, which highlighted the disproportionately anatomical development in human brain to extend our understanding of the potential evolutionary effects. -in F1000Research on 2024-12-06 14:56:43 UTC. +
in eLife on 2024-12-09 00:00:00 UTC.
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-Dose-dependent interaction of parasites with tiers of host defense predicts “wormholes” that prolong infection at intermediate inoculum sizes
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+Pharmacologically inducing regenerative cardiac cells by small molecule drugs
-by Andrea L. Graham, Roland R. Regoes
- -Immune responses are induced by parasite exposure and can in turn reduce parasite burden. Despite such apparently simple rules of engagement, key drivers of within-host dynamics, including dose-dependence of defense and infection duration, have proven difficult to predict. Here, we model how varied inoculating doses interact with multi-tiered host defenses at a site of inoculation, by confronting barrier, innate, and adaptive tiers with replicating and non-replicating parasites across multiple orders of magnitude of dose. We find that, in general, intermediate parasite doses generate infections of longest duration because they are sufficient in number to breach barrier defenses, but insufficient to strongly induce subsequent tiers of defense. These doses reveal “wormholes” in defense from which parasites might profit: Deviation from the hypothesis of independent action, which postulates that each parasite has an independent probability of establishing infection, may therefore be widespread. Interestingly, our model predicts local maxima of duration at two doses–one for each tier transition. While some empirical evidence is consistent with nonlinear dose-dependencies, testing the predicted dynamics will require finer-scale dose variation than experiments usually incorporate. Our results help explain varied infection establishment and duration among differentially-exposed hosts and elucidate evolutionary pressures that shape both virulence and defense. + Adult mammals, unlike some lower organisms, lack the ability to regenerate damaged hearts through cardiomyocytes (CMs) dedifferentiation into cells with regenerative capacity. Developing conditions to induce such naturally unavailable cells with potential to proliferate and differentiate into CMs, that is, regenerative cardiac cells (RCCs), in mammals will provide new insights and tools for heart regeneration research. In this study, we demonstrate that a two-compound combination, CHIR99021 and A-485 (2C), effectively induces RCCs from human embryonic stem cell-derived TNNT2+ CMs in vitro, as evidenced by lineage tracing experiments. Functional analysis shows that these RCCs express a broad spectrum of cardiogenesis genes and have the potential to differentiate into functional CMs, endothelial cells, and smooth muscle cells. Importantly, similar results were observed in neonatal rat CMs both in vitro and in vivo. Remarkably, administering 2C in adult mouse hearts significantly enhances survival and improves heart function post-myocardial infarction. Mechanistically, CHIR99021 is crucial for the transcriptional and epigenetic activation of genes essential for RCC development, while A-485 primarily suppresses H3K27Ac and particularly H3K9Ac in CMs. Their synergistic effect enhances these modifications on RCC genes, facilitating the transition from CMs to RCCs. Therefore, our findings demonstrate the feasibility and reveal the mechanisms of pharmacological induction of RCCs from endogenous CMs, which could offer a promising regenerative strategy to repair injured hearts. -in PLoS Computational Biology on 2024-12-06 14:00:00 UTC. +
in eLife on 2024-12-09 00:00:00 UTC.
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-Large scale paired antibody language models
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+Decoding contextual influences on auditory perception from primary auditory cortex
-by Henry Kenlay, Frédéric A. Dreyer, Aleksandr Kovaltsuk, Dom Miketa, Douglas Pires, Charlotte M. Deane
- -Antibodies are proteins produced by the immune system that can identify and neutralise a wide variety of antigens with high specificity and affinity, and constitute the most successful class of biotherapeutics. With the advent of next-generation sequencing, billions of antibody sequences have been collected in recent years, though their application in the design of better therapeutics has been constrained by the sheer volume and complexity of the data. To address this challenge, we present IgBert and IgT5, the best performing antibody-specific language models developed to date which can consistently handle both paired and unpaired variable region sequences as input. These models are trained comprehensively using the more than two billion unpaired sequences and two million paired sequences of light and heavy chains present in the Observed Antibody Space dataset. We show that our models outperform existing antibody and protein language models on a diverse range of design and regression tasks relevant to antibody engineering. This advancement marks a significant leap forward in leveraging machine learning, large scale data sets and high-performance computing for enhancing antibody design for therapeutic development. + Perception can be highly dependent on stimulus context, but whether and how sensory areas encode the context remains uncertain. We used an ambiguous auditory stimulus – a tritone pair – to investigate the neural activity associated with a preceding contextual stimulus that strongly influenced the tritone pair’s perception: either as an ascending or a descending step in pitch. We recorded single-unit responses from a population of auditory cortical cells in awake ferrets listening to the tritone pairs preceded by the contextual stimulus. We find that the responses adapt locally to the contextual stimulus, consistent with human MEG recordings from the auditory cortex under the same conditions. Decoding the population responses demonstrates that cells responding to pitch-changes are able to predict well the context-sensitive percept of the tritone pairs. Conversely, decoding the individual pitch representations and taking their distance in the circular Shepard tone space predicts the opposite of the percept. The various percepts can be readily captured and explained by a neural model of cortical activity based on populations of adapting, pitch and pitch-direction cells, aligned with the neurophysiological responses. Together, these decoding and model results suggest that contextual influences on perception may well be already encoded at the level of the primary sensory cortices, reflecting basic neural response properties commonly found in these areas. -in PLoS Computational Biology on 2024-12-06 14:00:00 UTC. +
in eLife on 2024-12-09 00:00:00 UTC.
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-OneNet—One network to rule them all: Consensus network inference from microbiome data
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+The identification of extensive samples of motor units in human muscles reveals diverse effects of neuromodulatory inputs on the rate coding
-by Camille Champion, Raphaëlle Momal, Emmanuelle Le Chatelier, Mathilde Sola, Mahendra Mariadassou, Magali Berland
- -Modeling microbial interactions as sparse and reproducible networks is a major challenge in microbial ecology. Direct interactions between the microbial species of a biome can help to understand the mechanisms through which microbial communities influence the system. Most state-of-the art methods reconstruct networks from abundance data using Gaussian Graphical Models, for which several statistically grounded and computationnally efficient inference approaches are available. However, the multiplicity of existing methods, when applied to the same dataset, generates very different networks. In this article, we present OneNet, a consensus network inference method that combines seven methods based on stability selection. This resampling procedure is used to tune a regularization parameter by computing how often edges are selected in the networks. We modified the stability selection framework to use edge selection frequencies directly and combine them in the inferred network to ensure that only reproducible edges are included in the consensus. We demonstrated on synthetic data that our method generally led to slightly sparser networks while achieving much higher precision than any single method. We further applied the method to gut microbiome data from liver-cirrothic patients and demonstrated that the resulting network exhibited a microbial guild that was meaningful in terms of human health. + Movements are performed by motoneurons transforming synaptic inputs into an activation signal that controls muscle force. The control signal emerges from interactions between ionotropic and neuromodulatory inputs to motoneurons. Critically, these interactions vary across motoneuron pools and differ between muscles. To provide the most comprehensive framework to date of motor unit activity during isometric contractions, we identified the firing activity of extensive samples of motor units in the tibialis anterior (129 ± 44 per participant; n=8) and the vastus lateralis (130 ± 63 per participant; n=8) muscles during isometric contractions of up to 80% of maximal force. From this unique dataset, the rate coding of each motor unit was characterised as the relation between its instantaneous firing rate and the applied force, with the assumption that the linear increase in isometric force reflects a proportional increase in the net synaptic excitatory inputs received by the motoneuron. This relation was characterised with a natural logarithm function that comprised two stages. The initial stage was marked by a steep acceleration of firing rate, which was greater for low- than medium- and high-threshold motor units. The second stage comprised a linear increase in firing rate, which was greater for high- than medium- and low-threshold motor units. Changes in firing rate were largely non-linear during the ramp-up and ramp-down phases of the task, but with significant prolonged firing activity only evident for medium-threshold motor units. Contrary to what is usually assumed, our results demonstrate that the firing rate of each motor unit can follow a large variety of trends with force across the pool. From a neural control perspective, these findings indicate how motor unit pools use gain control to transform inputs with limited bandwidths into an intended muscle force. -in PLoS Computational Biology on 2024-12-06 14:00:00 UTC. +
in eLife on 2024-12-09 00:00:00 UTC.
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-Not just a garbage truck: No-go decay plays a role during embryo development in zebrafish
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+Unified bursting strategies in ectopic and endogenous even-skipped expression patterns
-by Alana R. Plastrik, Hani S. Zaher
- -In eukaryotes, defective mRNAs that impede the movement of the ribosome are subject to rapid decay via no-go decay (NGD). In this issue of PLOS Biology, Ishibashi and colleagues expand on the role of NGD and reveal new endogenous targets for the process in zebrafish. + Transcription often occurs in bursts as gene promoters switch stochastically between active and inactive states. Enhancers can dictate transcriptional activity in animal development through the modulation of burst frequency, duration, or amplitude. Previous studies observed that different enhancers can achieve a wide range of transcriptional outputs through the same strategies of bursting control. For example, in Berrocal et al., 2020, we showed that despite responding to different transcription factors, all even-skipped enhancers increase transcription by upregulating burst frequency and amplitude while burst duration remains largely constant. These shared bursting strategies suggest that a unified molecular mechanism constraints how enhancers modulate transcriptional output. Alternatively, different enhancers could have converged on the same bursting control strategy because of natural selection favoring one of these particular strategies. To distinguish between these two scenarios, we compared transcriptional bursting between endogenous and ectopic gene expression patterns. Because enhancers act under different regulatory inputs in ectopic patterns, dissimilar bursting control strategies between endogenous and ectopic patterns would suggest that enhancers adapted their bursting strategies to their trans-regulatory environment. Here, we generated ectopic even-skipped transcription patterns in fruit fly embryos and discovered that bursting strategies remain consistent in endogenous and ectopic even-skipped expression. These results provide evidence for a unified molecular mechanism shaping even-skipped bursting strategies and serve as a starting point to uncover the realm of strategies employed by other enhancers. -in PLoS Biology on 2024-12-06 14:00:00 UTC. +
in eLife on 2024-12-09 00:00:00 UTC.
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-Regulatory networks may evolve to favor adaptive foresight
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+Brain Sciences, Vol. 14, Pages 1238: Long-Term Real-World Experience with Safinamide in Patients with Parkinson’s Disease
-by Alejandro Couce
- -Pleiotropy—a single mutation altering many traits—has long been seen as hindering adaptation. A new study in PLOS Biology offers a striking counterexample, suggesting that regulatory networks may evolve to ensure mutations are simultaneously beneficial in correlated environments. - -Pleiotropy (a single mutation altering many traits) has long been seen as hindering adaptation. A new study in PLOS Biology offers a striking counterexample, suggesting that regulatory networks may evolve to ensure mutations are simultaneously beneficial in correlated environments. +Brain Sciences, Vol. 14, Pages 1238: Long-Term Real-World Experience with Safinamide in Patients with Parkinson’s Disease
+Brain Sciences doi: 10.3390/brainsci14121238
+Authors: + Anna Planas-Ballvé + Núria Caballol Pons + Alejandro Peral Quirós + Isabel Gómez Ruiz + Marta Balagué Marmaña + Alexander J. Velázquez Ballester + Dolors Lozano Moreno + Asunción Ávila Rivera +
+Introduction: Randomized clinical trials should be complemented with data from real-world studies. We report our long-term experience with safinamide in a movement disorders unit. Methods: This retrospective study included patients with Parkinson&rsquo;s disease (PD) treated with safinamide in our unit from February 2016 to May 2022 under routine clinical practice. Assessments included the Hoehn and Yahr (HY) stage, unified Parkinson&rsquo;s disease rating scale (UPDRS) part III score, levodopa equivalent daily dose (LEDD), LEDD for dopamine agonists, and safinamide treatment discontinuation. Results: We included 180 patients with a median age of 74 years (IQR 11), and the majority (90.6%) had an HY stage of &le;2. After a median follow-up of 40 months (IQR 34), 14 patients discontinued treatment with safinamide (7.8%, 95% CI 4.7 to 12.6). Among the 166 patients who remained on safinamide, the UPDRS III score was stable (10 (IQR 9) vs. 9 (IQR 13), p = 0.455). The LEDD significantly increased from a median of 300 mg to 500 mg (p &lt; 0.001), whereas the LEDD for dopamine agonists did not significantly increase. A subgroup of 89 patients who did not require dopamine agonists during follow-up showed stable UPDRS III score (10 (IQR 7) vs. 9 (IQR 14); p = 0.923), with a significant LEDD increase (300 mg to 400 mg, p &lt; 0.001). Conclusions: Our results support the long-term effectiveness and tolerability of safinamide in patients with PD in clinical practice.
-in PLoS Biology on 2024-12-06 14:00:00 UTC. +
in Brain Sciences on 2024-12-09 00:00:00 UTC.
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-Gene transfer between fungal species triggers repeated coffee wilt disease outbreaks
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+Brain Sciences, Vol. 14, Pages 1237: Noninvasive Brain Stimulation for Improving Cognitive Deficits and Clinical Symptoms in Attention-Deficit/Hyperactivity Disorder: A Systematic Review and Meta-Analysis
-by Brenda D. Wingfield, Michael J. Wingfield
- -Two outbreaks of coffee wilt disease have devastated African coffee production. A PLOS Biology study suggests that horizontal gene transfer via large Starship transposons between 2 fungal species played a key role in the repeated emergence of the disease. - -Two outbreaks of coffee wilt disease have devastated African coffee production. A PLOS Biology study suggests that horizontal gene transfer via Starships between two fungal strains played a key role in the repeated emergence of the disease. +Brain Sciences, Vol. 14, Pages 1237: Noninvasive Brain Stimulation for Improving Cognitive Deficits and Clinical Symptoms in Attention-Deficit/Hyperactivity Disorder: A Systematic Review and Meta-Analysis
+Brain Sciences doi: 10.3390/brainsci14121237
+Authors: + Yao Yin + Xueke Wang + Tingyong Feng +
+Objective: Noninvasive brain stimulation (NIBS) is a promising complementary treatment for attention-deficit/hyperactivity disorder (ADHD). However, its efficacy varies due to diverse participant profiles and methodologies. This meta-analysis, registered with PROSPERO (CRD42023457269), seeks to assess NIBS efficacy in improving cognitive deficits and clinical symptoms in individuals with ADHD. Methods: We systematically searched five databases (October 2024) for randomized controlled trials focusing on cognitive functions and clinical symptoms in individuals meeting the DSM/ICD criteria for ADHD. A meta-analytical synthesis was conducted using RevMan 5.4.1. Results: Meta-analyses found significant improvement in inhibitory control, working memory, and inattention in active transcranial direct current stimulation (tDCS) groups compared with sham groups. Conversely, repetitive transcranial magnetic stimulation (rTMS) did not demonstrate significant therapeutic benefits for ADHD symptoms. Additionally, four transcranial random noise stimulation (tRNS) and three transcranial alternating current stimulation (tACS) studies demonstrated promising improvements in executive functions and the alleviation of ADHD symptoms. Conclusions: The findings from this meta-analysis highlight NIBS as a promising adjunctive therapy for managing ADHD, advancing both theoretical knowledge and practical treatment options in this field.
-in PLoS Biology on 2024-12-06 14:00:00 UTC. +
in Brain Sciences on 2024-12-09 00:00:00 UTC.
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-Longitudinal Imaging Biomarkers Correlate with Progressive Motor Deficit in the Mouse Model of Charlevoix‐Saguenay Ataxia
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+Brain Sciences, Vol. 14, Pages 1236: Interoceptive Awareness and Female Orgasm Frequency and Satisfaction
-Objective
-In autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) disease, severity and age of onset vary greatly, hindering to objectively measure and predict clinical progression. Thickening of the retinal nerve fiber layer is distinctive of ARSACS patients, as assessed by optical coherence tomography, whereas conventional brain magnetic resonance imaging findings include both supratentorial and infratentorial changes. Because longitudinal imaging studies in ARSACS patients are not available to define these changes as biomarkers of disease progression, we aimed to address this issue in the ARSACS mouse model.
-Methods
-We performed longitudinal retinal OCT and brain MRI in the Sacs -−/− ARSACS mouse model, alongside motor and coordination assessment in the beam walking test. We also investigated visual function and the molecular mechanisms underlying RNFL increased thickness by histology and immunofluorescence.
-Results
-We demonstrated that RNFL thickening by OCT gradually increases in the early stages of pathology in the Sacs -−/− mouse model, reflecting the progression of motor impairment, and later reaches a plateau when thinning of the posterior corpus callosum becomes detectable by MRI. Mechanistically, we unveiled that RNFL thickening is associated with aberrant accumulation of non-phosphorylated neurofilament H and glial fibrillary acidic protein. We also uncovered mild signs of myelin pathology coherent with increased latency of visual evoked potentials, and altered retinal activation by photopic electroretinography.
-Interpretation
-We show that both RNFL thickening and MRI changes may represent biomarkers of disease progression in the Sacs -−/− mouse model. Our data gathers knowledge instrumental to clinical studies, holding potential as readout for treatment efficacy. ANN NEUROL 2024
+Brain Sciences, Vol. 14, Pages 1236: Interoceptive Awareness and Female Orgasm Frequency and Satisfaction
+Brain Sciences doi: 10.3390/brainsci14121236
+Authors: + Emily Dixon + Giulia L. Poerio + Gerulf Rieger + Megan Klabunde +
+Background: The female orgasm is a highly understudied phenomenon that is linked to both wellbeing and relationship satisfaction in women. Although orgasm has been associated with interoception&mdash;the sense of the physiological condition of the body&mdash;very few studies have directly examined the influence that interoception has on orgasm. Objectives: This study investigates how the subjective experience of one&rsquo;s interoceptive capacities (called interoceptive awareness) is associated with self-reported orgasm frequency and satisfaction in people who identify as women. Methods: In a dataset of 318 women, orgasm frequency and satisfaction were both rated significantly higher for solitary as compared to partnered sexual experiences. Results: Analysis of how dimensions of interoceptive awareness correlated with orgasm frequency and satisfaction showed that (1) &lsquo;Noticing&rsquo; predicted orgasm frequency (but not satisfaction) across both solitary and partnered interactions, (2) &lsquo;Attention Regulation&rsquo; predicted greater frequency and satisfaction of solitary orgasm (but not partnered interactions), and (3) &lsquo;Body Trusting&rsquo; predicted orgasm satisfaction (but not frequency) across both solitary and partnered contexts. Conclusions: Findings underscore the importance of moving beyond orgasmic dysfunction research by investigating how interoception is associated with healthy&mdash;and potentially even optimal&mdash;orgasmic functioning in women.
-in Annals of Neurology on 2024-12-06 12:00:18 UTC. +
in Brain Sciences on 2024-12-09 00:00:00 UTC.
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-CORRECTION to “RETRACTION: Hippocampus of Ames Dwarf Mice is Resistant to β‐Amyloid‐Induced Tau Hyperphosphorylation and Changes in Apoptosis‐Regulatory Protein Levels”
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+Brain Sciences, Vol. 14, Pages 1235: Comparative Evaluation of Major Robotic Systems in Microanastomosis Procedures: A Systematic Review of Current Capabilities and Future Potential
- +Brain Sciences, Vol. 14, Pages 1235: Comparative Evaluation of Major Robotic Systems in Microanastomosis Procedures: A Systematic Review of Current Capabilities and Future Potential
+Brain Sciences doi: 10.3390/brainsci14121235
+Authors: + Delia Cannizzaro + Matteo Scalise + Chiara Zancanella + Stefano Paulli + Stefano Peron + Roberto Stefini +
+Background/Objectives: Robotic-assisted surgery has revolutionised modern medicine, enabling greater precision and control, particularly in microsurgical procedures. This systematic review evaluates the current state of robotic-assisted surgery across various specialties, focusing on four major robotic systems: Symani, Da Vinci, ZEUS, and MUSA. Methods: The review systematically analyses the effectiveness of these systems in performing vascular, lymphatic, and nervous anastomoses, comparing key metrics such as procedure time, success rates, and learning curves against manual techniques. It includes 48 studies, highlighting the technological capabilities and limitations of these systems in direct comparisons. Results: Results indicate that while robotic procedures often take longer than manual methods, significant improvements in efficiency are observed as surgeons gain experience. Conclusions: Overall, this study provides insights into the future potential of robotic-assisted surgery and highlights areas that require further research. It ultimately aims to promote the application of robotic systems in cranial neurosurgery, with a particular focus on advancing neurovascular techniques, such as microsuturing for bypass procedures.
-in Hippocampus on 2024-12-06 12:00:15 UTC. +
in Brain Sciences on 2024-12-09 00:00:00 UTC.
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-Antimicrobial effect of silver diamine fluoride (SDF) in arresting dentine caries of permanent teeth: A Systematic review [version 1; peer review: awaiting peer review]
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+Brain Sciences, Vol. 14, Pages 1234: Advancing Neuropsychological Rehabilitation in Primary Progressive Aphasia Based on Principles of Cognitive Neuroscience: A Scoping Review and Systematic Analysis of the Data
- Background Silver diamine fluoride (SDF) is recognized for its potent antibacterial properties and is commonly used in dentistry to treat carious lesions. This review aims to evaluate the antimicrobial effect of SDF on dentine caries in permanent teeth. The objective is to provide a comprehensive analysis of the existing literature to assess the efficacy of SDF in combating cariogenic flora within dentin lesions. Materials and Methods A systematic electronic search was conducted using Google Scholar, Cochrane Library, and PubMed databases to identify relevant studies published between January 2010 and September 2022. The search strategy focused on retrieving in vitro and in vivo studies assessing the antimicrobial effect of SDF on dentinal caries. The inclusion criteria encompassed studies that compared SDF with other antimicrobial agents, such as sodium fluoride varnish, potassium iodide, silver nitrate, chlorhexidine, plasma jet, and deionized water. The Cochrane Collaboration assessment tool was employed to evaluate the risk of bias in the included studies. Results Nine studies met the inclusion criteria, consisting of seven in vitro and in situ studies investigating the antimicrobial effect of SDF on dentinal caries, and two in vitro and in vivo studies examining its antibacterial effect on root caries. These studies collectively demonstrated the promising antimicrobial potential of SDF against cariogenic flora present in dentin lesions. However, variations in study design, methodology, and outcome measures were observed across the included studies. Conclusion The review underscores the significant antimicrobial efficacy of SDF in combating cariogenic bacteria within dentin lesions of permanent teeth. Despite the promising findings, there remains a lack of comprehensive understanding regarding the precise characteristics and mechanisms underlying the antimicrobial action of SDF, particularly concerning nano-silver. Future research, including long-term clinical trials, is warranted to elucidate optimal dosage regimens and therapeutic approaches for the routine application of SDF in managing dental caries. +Brain Sciences, Vol. 14, Pages 1234: Advancing Neuropsychological Rehabilitation in Primary Progressive Aphasia Based on Principles of Cognitive Neuroscience: A Scoping Review and Systematic Analysis of the Data
+Brain Sciences doi: 10.3390/brainsci14121234
+Authors: + Evgenia Gkintoni + Emilia Michou +
+Background/Objectives: This systematic review of neuropsychological rehabilitation strategies for primary progressive aphasia will consider recent developments in cognitive neuroscience, especially neuroimaging techniques such as EEG and fMRI, to outline how these tools might be integrated into clinical practice to maximize treatment outcomes. Methods: A systematic search of peer-reviewed literature from the last decade was performed following the PRISMA guidelines across multiple databases. A total of 63 studies were included, guided by predefined inclusion and exclusion criteria, with a focus on cognitive and language rehabilitation in PPA, interventions guided by neuroimaging, and mechanisms of neuroplasticity. Results: Integration of neuroimaging techniques contributes to the increase in the efficacy of interventions with critical information about the neural mechanisms underlying language deficits in the aphasias. Traditional rehabilitation strategies, technology-assisted interventions, and non-invasive brain stimulation techniques hold considerable promise for language improvement. Neuroimaging was also found to be necessary in subtype-specific differentiation toward tailoring therapeutic intervention. Evidence also shows that directed and sustained interventions using neuroplasticity can have long-term effects in managing the symptoms of PPA. Conclusions: The present review underlines the necessity of including cognitive neuroscience techniques within neuropsychological rehabilitation to enhance therapeutic outcomes in PPA. In addition, neuroimaging modalities such as EEG and fMRI are also of great importance in understanding the underlying neurobiology of language disturbances and guiding tailored interventions. Long-term benefits of these approaches should be evaluated, including their applicability in routine clinical practice.
-in F1000Research on 2024-12-06 10:46:56 UTC. +
in Brain Sciences on 2024-12-08 00:00:00 UTC.
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-Comments about the comparative bulk RNA sequencing between palmoplantar pustulosis and dyshidrotic palmoplantar eczema [version 1; peer review: awaiting peer review]
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+Brain Sciences, Vol. 14, Pages 1233: Psychiatric Disorders and Cognitive Fluctuations in Parkinson’s Disease: Changing Approaches in the First Decades of the 21st Century
- This correspondence discusses the recent findings by Straalen et al., highlighting molecular similarities and distinctions between palmoplantar pustulosis (PPP) and dyshidrotic palmoplantar eczema (DPE). The study emphasizes shared proinflammatory pathways and T-cell–related gene upregulation while detailing unique features such as neutrophil involvement in PPP and lipid antigen processing in DPE. We elaborate on histopathological differences, especially intraepidermal vesicle formation in PPP linked to IL–1–mediated pathways and the absence of hyaluronan expression, contrasting with Th2 cytokines-driven spongiosis in DPE. By addressing IL-4, hyaluronan synthases, and keratinocyte adhesion molecules, this correspondence aims to deepen understanding of PPP and DPE pathophysiology. +Brain Sciences, Vol. 14, Pages 1233: Psychiatric Disorders and Cognitive Fluctuations in Parkinson’s Disease: Changing Approaches in the First Decades of the 21st Century
+Brain Sciences doi: 10.3390/brainsci14121233
+Authors: + Marco Onofrj + Matteo Alessandro De Rosa + Mirella Russo + Paola Ajdinaj + Dario Calisi + Astrid Thomas + Stefano Luca Sensi +
+Parkinson&rsquo;s Disease (PD) is a multifaceted neurodegenerative disorder characterized, in addition to the well-recognized motor disturbances, by a complex interplay between cognitive and psychiatric manifestations. We dissect the complex landscape of PD-related psychiatric symptoms, taking into account the impact of functional neurological disorders, somatic delusions, impulse control disorders, and conditions within the bipolar spectrum. The newer entities of somatoform and functional neurological disorders, as well as preexisting bipolar spectrum disorders, are analyzed in detail. Moreover, we emphasize the need for a holistic understanding of PD, wherein the cognitive and psychiatric dimensions are valued alongside motor symptoms. Such an approach aims to facilitate early detection and personalized interventions, and enhance the overall quality of life for individuals suffering from this neurodegenerative disorder.
-in F1000Research on 2024-12-06 09:59:49 UTC. +
in Brain Sciences on 2024-12-08 00:00:00 UTC.
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-A compilation of histidine kinase genes in Enterobacter hormaechei strain HCF3 isolated from the North West Province of South Africa [version 1; peer review: awaiting peer review]
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+Behavioral Consequences of Hippocampal 5‐HT7 Receptors Blockade in Stressed Rats
- This study investigates the histidine kinase (HK) gene repertoire of Enterobacter hormaechei strain HCF3, isolated from fresh cow dung in Mogosane Village, Northwest Province, South Africa. Histidine kinases are critical components of bacterial two-component signal transduction systems, enabling bacteria to sense and adapt to diverse environmental conditions. Given the growing concern over antimicrobial resistance (AMR) associated with E. hormaechei, this research elucidates the genetic components that facilitate its environmental adaptability. After isolating the strain, genomic sequencing using Illumina technology, resulting in high-quality sequence data, was conducted. The assembled genome was meticulously annotated and deposited in the National Center for Biotechnology Information (NCBI) under BioProject number PRJNA991313, with additional accession numbers for raw reads (JAUOLV000000000.1) and BioSample (SAMN36292742). Histidine kinase genes were identified based on conserved domains, particularly HisKA and HATPase. This led to compiling a comprehensive HK gene catalogue with locus tags, protein accession numbers, and functional annotations. To validate the HK gene set of E. hormaechei HCF3, we conducted a rigorous comparative analysis with other strains. This revealed that strain HCF1 contains 21 histidine kinase genes, HCF2 has 25, while HCF4 has 19. These findings underscore the diversity and conservation of HK genes across different Enterobacter species, providing a new perspective on their evolutionary significance. The assembled dataset provides valuable insights into the signalling pathways of E. hormaechei, highlighting the potential roles of HKs in environmental sensing, adaptation, and pathogenicity. Furthermore, this research lays the groundwork for future studies on the applications of these genes in agriculture and biotechnology, offering new avenues for understanding and managing E. hormaechei in various ecological contexts. +ABSTRACT
+Serotonin (5-HT) has long been involved in response to stress and its effect may be, in part, mediated by 5-HT1a and 5-HT7 receptor subtypes in different brain structures. Both pre- and post-synaptic activation of 5-HT1a receptor, respectively, in the rat median raphe nucleus (MnRN) and hippocampus, lead to adaptation to acute inescapable stressors such as restraint and forced swim. 5-HT7 receptor (5HT7r), a stimulatory G-protein coupled receptor, has also been investigated as a possible candidate for mediating stress response. In the MnRN, activation of 5-HT7r has antidepressant effects, while in the hippocampus, 5HT7r mRNA expression is increased after exposure to restraint stress, but the functional significance of these receptors remains to be determined. Therefore, the aim of this study was to investigate whether blockade of hippocampal 5HT7r would prevent and/or attenuate the behavioral effects of stress. Male adult Wistar rats with bilateral cannulas aimed at the dorsal hippocampus were restrained for 2 h and tested in the elevated plus maze (EPM) 24 h later. SB 258741 (3 nmoles/0.5 μL/side; selective 5HT7r antagonist) was administered bilateraly into the hippocampus according to the experimental protocol: immediately before or after stress, or 24 h after it (immediately before the test). In a second experiment, rats were exposed to 15 min. of forced swim, and tested 24 h later. Intra-hippocampal treatment was performed as described for the restraint stress protocol. We found that blockade of hippocampal 5-HT7r immediately after, but not before, the exposure to restraint or forced swim attenuated stress-induced behavioral changes. Similar results were obtained when SB was administered before the test in previously stressed rats. Our data suggest that activation of hippocampal 5-HT7r is crucial for the consolidation and retrieval of aversive stimulus-related memories, such as those caused by a stressful experience, probably through mechanisms involving stress-induced changes in 5-HT7r expression.
-in F1000Research on 2024-12-06 09:58:25 UTC. +
in Hippocampus on 2024-12-07 15:08:51 UTC.
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-A new genome sequence resource for five invasive fruit flies of agricultural concern: Ceratitis capitata, C. quilicii, C. rosa, Zeugodacus cucurbitae and Bactrocera zonata (Diptera, Tephritidae) [version 1; peer review: awaiting peer review]
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+Explicit Memory, Implicit Memory, and the Hippocampus: Insights From Early Neuroimaging Studies
- Here, we present novel high quality genome assemblies for five invasive tephritid species of agricultural concern: Ceratitis capitata, C. quilicii, C. rosa, Zeugodacus cucurbitae and Bactrocera zonata (read depths between 65 and 78x). Three assemblies (C. capitata, C. quilicii and Z. cucurbitae) were scaffolded with chromosome conformation data and annotated using RNAseq reads. For some species this is the first reference genome available (B. zonata, C. quilicii and C. rosa), for others we have published improved annotated genomes (C. capitata and Z. cucurbitae). Together, the new references provide an important resource to advance research on genetic techniques for population control, develop rapid species identification methods, and explore eco-evolutionary studies. +ABSTRACT
+During the 1980s and 1990s, much memory research focused on the differential role of the hippocampus in various forms of memory. My work on the distinction between explicit and implicit memory led me to become involved in several early neuroimaging studies that made use of cognitive paradigms to investigate the conditions in which hippocampal activity does and does not occur, and to address the theoretical implications of these findings. Here, I summarize two such projects and some of the personal backstory associated with them.
-in F1000Research on 2024-12-06 09:55:12 UTC. +
in Hippocampus on 2024-12-07 15:08:43 UTC.
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-Diagnosis of brain death in wistar rats at different levels of death induction [version 1; peer review: awaiting peer review]
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+Inhibition of Bone Morphogenetic Protein Signaling Prevents Tau Pathology in iPSC Derived Neurons and PS19 Mice
- Objective This study aimed to evaluate hematologic, biochemical, and gasometric parameters in Wistar rats to better understand brain death parameters and reduce early misdiagnoses. Methods Fifteen adult male Wistar rats (Rattus norvergicus; HanUnib: WH) were randomly distributed into three groups of five animals: the control group (G0) with evaluation performed before brain death, and two groups (G1 and G2) with brain death induced at different times: immediately after induction (G1) and one hour after induction (G2). Venous and arterial blood samples were taken to perform complete blood count, biochemical, and blood gas assays. Samples were taken at specific times based on the group each rat belonged to. Results Statistically significant mean values were observed (P<0,05) for segmented cells (G1>G2 and G0>G2), monocytes (G2>G1 and G0>G1), creatinine (G2>G0), aspartate aminotransferase (G1>G0), potassium (G2>G0), and bicarbonate (G0>G1). Discussion Furthermore, brain death showed a unique response in each organism, complicating its precise determination even more. +Objective
+Many neurodegenerative disorders share a common pathologic feature involving the deposition of abnormal tau protein in the brain (tauopathies). This suggests that there may be some shared pathophysiologic mechanism(s). The largest risk factor for the majority of these disorders is aging, suggesting involvement of the aging process in the shared pathophysiology. We test the hypothesis that an increase in bone morphogenetic protein (BMP) signaling that occurs during aging contributes to the onset and progression of tauopathies.
+Methods
+Human induced pluripotent stem cell (iPSC)-derived neurons from patients with Alzheimer's disease (AD) were used to investigate the effects of BMP signaling on tau phosphorylation and release and the mechanisms underlying these effects. Wildtype mice were used to examine effects of BMP signaling in vivo. P301S (PS19) mice were examined for the effects of BMP signaling in a model of tauopathy.
+Results
+Here, we show that BMP signaling, mediated by non-canonical p38 signaling, increases tau phosphorylation and release of p-tau in human iPSC-derived AD neurons. Further, there is an interaction between BMP signaling and apolipoprotein E4 (ApoE4) that significantly increases tau phosphorylation and release compared with ApoE3 neurons. Inhibiting BMP signaling reduces the changes in tau in the cultured human neurons, and it limits tau pathology and prevents cognitive decline in PS19 mice.
+Interpretation
+Our study suggests that the age-related increase in BMP signaling may participate in the onset and progression of tau pathology. Thus, therapeutic interventions that reduce BMP signaling in the aging brain could potentially slow or prevent development of diseases involving tau hyperphosphorylation. ANN NEUROL 2024
-in F1000Research on 2024-12-06 09:29:13 UTC. +
in Annals of Neurology on 2024-12-07 12:09:55 UTC.
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-Programming tissue-sensing T cells that deliver therapies to the brain
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+Prophylactic Fetal Creatine Supplementation Improves Post‐Asphyxial EEG Recovery and Reduces Seizures in Fetal Sheep: Implications for Hypoxic–Ischemic Encephalopathy
- Science, Volume 386, Issue 6726, December 2024.+
Objective
+Hypoxic–ischemic encephalopathy (HIE) is a major cause of perinatal brain injury. Creatine is a dietary supplement that can increase intracellular phosphocreatine to improve the provision of intracellular adenosine triphosphate (ATP) to meet the increase in metabolic demand of oxygen deprivation. Here, we assessed prophylactic fetal creatine supplementation in reducing acute asphyxia-induced seizures, disordered electroencephalography (EEG) activity and cerebral inflammation and cell death histopathology.
+Methods
+Fetal sheep (118 ± 1 days’ gestational age [dGA]; 0.8 gestation) were implanted with electrodes to continuously record EEG and nuchal electromyogram activity. At 121 dGA, fetuses were randomly assigned to sham control (i.v. saline infusion without umbilical cord occlusion [UCO]; SalCon), continuous i.v. creatine infusion (6 mg/kg/h; CrUCO) or isovolumetric saline (SalUCO) followed by UCO at 128 ± 2 dGA that lasted until the mean arterial blood pressure reached 19 mmHg. Brain tissue was collected for histopathology after 72 hours of recovery.
+Results
+Creatine supplementation had no effects on basal systemic or neurological physiology. UCO duration did not differ between CrUCO and SalUCO. After reperfusion, CrUCO fetuses had improved EEG power and frequency recovery and reduced electrographic seizure incidence (SalUCO, 86% vs CrUCO, 29%) and burden. At 72 hours after UCO, cell death in the cerebral cortex and astrogliosis in the periventricular white matter were reduced in CrUCO fetuses compared with SalUCO.
+Interpretation
+Creatine supplementation reduced post-asphyxial seizures and improved EEG recovery. Improvements in functional recovery with creatine were associated with regional reductions in cell death and astrogliosis. Prophylactic creatine treatment has the potential to mitigate functional indices of HIE in the late gestation fetal brain. ANN NEUROL 2024
-in Science on 2024-12-06 08:00:00 UTC. +
in Annals of Neurology on 2024-12-07 11:50:08 UTC.
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-Engineering synthetic suppressor T cells that execute locally targeted immunoprotective programs
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+NORSE, FIRES, and a Polygenic Trickle of Autoimmunity
- Science, Volume 386, Issue 6726, December 2024.+ -
in Science on 2024-12-06 08:00:00 UTC. +
in Annals of Neurology on 2024-12-07 11:47:44 UTC.
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-Ecological erosion and expanding extinction risk of sharks and rays
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+Some Memories of Stalking the Seahorse
- Science, Volume 386, Issue 6726, December 2024.+
ABSTRACT
+Early influences that led to the development of the cognitive map theory of hippocampal function, and the multiple trace theory, are discussed. Some details are provided, many are left out.
-in Science on 2024-12-06 08:00:00 UTC. +
in Hippocampus on 2024-12-07 09:53:14 UTC.
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-Dissecting the hydrogen bond network of water: Charge transfer and nuclear quantum effects
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+Vimentin modulates regulatory T cell receptor-ligand interactions at distal pole complex, leading to dysregulated host response to viral pneumonia
- Science, Volume 386, Issue 6726, December 2024.+ The type III intermediate filament protein vimentin serves as a molecular switch in regulatory T cells. Ma et al. show that Treg-specific deletion of vimentin increases Helios+IL-18R+ Tregs, suppresses inflammatory immune cells, and enhances tissue repair, protecting the host from influenza A virus-induced lung injury and mortality. -
in Science on 2024-12-06 08:00:00 UTC. +
in Cell Reports: Current Issue on 2024-12-07 00:00:00 UTC.
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-Imperfect wound healing sets the stage for chronic diseases
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+Brain Sciences, Vol. 14, Pages 1232: Changing the Paradigm for Tractography Segmentation in Neurosurgery: Validation of a Streamline-Based Approach
- Science, Volume 386, Issue 6726, December 2024.+
Brain Sciences, Vol. 14, Pages 1232: Changing the Paradigm for Tractography Segmentation in Neurosurgery: Validation of a Streamline-Based Approach
+Brain Sciences doi: 10.3390/brainsci14121232
+Authors: + Silvio Sarubbo + Laura Vavassori + Luca Zigiotto + Francesco Corsini + Luciano Annicchiarico + Umberto Rozzanigo + Paolo Avesani +
+In glioma surgery, maximizing the extent of resection while preserving cognitive functions requires an understanding of the unique architecture of the white matter (WM) pathways of the single patient and of their spatial relationship with the tumor. Tractography enables the reconstruction of WM pathways, and bundle segmentation allows the identification of critical connections for functional preservation. This study evaluates the effectiveness of a streamline-based approach for bundle segmentation on a clinical dataset as compared to the traditional ROI-based approach. We performed bundle segmentation of the arcuate fasciculus, of its indirect anterior and posterior segments, and of the inferior fronto-occipital fasciculus in the healthy hemisphere of 25 high-grade glioma patients using both ROI- and streamline-based approaches. ROI-based segmentation involved manually delineating ROIs on MR anatomical images in Trackvis (V0.6.2.1). Streamline-based segmentations were performed in Tractome, which integrates clustering algorithms with the visual inspection and manipulation of streamlines. Shape analysis was conducted on each bundle. A paired t-test was performed on the irregularity measurement to compare segmentations achieved with the two approaches. Qualitative differences were evaluated through visual inspection. Streamline-based segmentation consistently yielded significantly lower irregularity scores (p &lt; 0.001) compared to ROI-based segmentation for all the examined bundles, indicating more compact and accurate bundle reconstructions. Qualitative assessment identified common biases in ROI-based segmentations, such as the inclusion of anatomically implausible streamlines or streamlines with undesired trajectories. Streamline-based bundle segmentation with Tractome provides reliable and more accurate reconstructions compared to the ROI-based approach. By directly manipulating streamlines rather than relying on voxel-based ROI delineations, Tractome allows us to discern and discard implausible or undesired streamlines and to identify the course of WM bundles even when the anatomy is distorted by the lesion. These features make Tractome a robust tool for bundle segmentation in clinical contexts.
-in Science on 2024-12-06 08:00:00 UTC. +
in Brain Sciences on 2024-12-07 00:00:00 UTC.
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-Transcription-coupled changes in genomic region proximities during transcriptional bursting
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+Brain Sciences, Vol. 14, Pages 1231: Therapeutic Approach to Primary Tic Disorders and Associated Psychiatric Comorbidities
- Science Advances, Volume 10, Issue 49, December 2024.+
Brain Sciences, Vol. 14, Pages 1231: Therapeutic Approach to Primary Tic Disorders and Associated Psychiatric Comorbidities
+Brain Sciences doi: 10.3390/brainsci14121231
+Authors: + Irene Berzosa-Gonzalez + Saul Martinez-Horta + Jesus Pérez-Pérez + Jaime Kulisevsky + Javier Pagonabarraga +
+Background/Objectives: The treatment of tics and psychiatric comorbidities is crucial when they affect the patient&rsquo;s well-being and relationships. However, the optimal pharmacological treatment (PT) tailored to each patient&rsquo;s phenotype remains unclear. The primary objective of this study is to describe the clinical characteristics and treatment received for tics and psychiatric comorbidities in our cohort of children and adult patients with tic disorders. Additionally, a further aim was to quantify the severity of tics, comorbidities and overall severity, and the overall clinical changes observed during the follow-up. Methods: Retrospective descriptive study of patients with tic disorders under follow-up at our Tic Functional Unit from January 2022 to March 2024. Two independent neurologists retrospectively applied the Clinical Global Impression of Change (CGI-C) and the Clinical Global Impression of Severity (CGI-S) scales at baseline and at last assessment. Results: A total of 36 individuals were included (63.8% males, median age = 18 years, IQR 19): 94.4% with Tourette syndrome (TS), 2.8% with chronic tic disorder (CTD), and 2.8% with provisional tic disorder (PTD). A total of 86% had at least one psychiatric comorbidity, the most common being obsessive&ndash;compulsive symptomatology (OCS) (52%), anxiety (52%), and attention deficit hyperactivity disorder (ADHD) (35%). At last assessment, 26 patients (72.2%) were on undergoing PT for tics and 3 were receiving additional botulinum toxin. The most used medication for tics were aripiprazole (46.2%) and clonazepam (46.2%), and for psychiatric comorbidities, SSRIs (42.9%), methylphenidate (19%), and benzodiazepines (57.1%). Overall improvement according to the CGI-C scale was mild (CGI-C 3). Children and adolescents showed greater improvement than adults (CGI-C 2 vs. 3; p = 0.005). Aripiprazole and clonazepam produced similar outcomes in reducing CGI-C. Conclusions: We observed a favorable clinical course in patients treated with aripiprazole and clonazepam, which appear to be better than that obtained with other treatments. We consider that clonazepam may be useful as a first-line monotherapy and as an adjuvant for both tics and comorbidities in selected cases.
-in Science Advances on 2024-12-06 08:00:00 UTC. +
in Brain Sciences on 2024-12-07 00:00:00 UTC.
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-Structural and molecular properties of mumps virus inclusion bodies
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+Brain Sciences, Vol. 14, Pages 1230: The Endocannabinoid Activity Remodulation for Psychosis Liability in Youth (EARLY) Study: An Open-Label Feasibility Trial of Ultramicronized-Palmitoylethanolamide Oral Supplementation in Clinical High-Risk State for Ps
- Science Advances, Volume 10, Issue 49, December 2024.+
Brain Sciences, Vol. 14, Pages 1230: The Endocannabinoid Activity Remodulation for Psychosis Liability in Youth (EARLY) Study: An Open-Label Feasibility Trial of Ultramicronized-Palmitoylethanolamide Oral Supplementation in Clinical High-Risk State for Psychosis
+Brain Sciences doi: 10.3390/brainsci14121230
+Authors: + Riccardo Bortoletto + Marco Garzitto + Fabiana Piscitelli + Stefano Fornasaro + Claudia Scipioni + Orietta Sepulcri + Martina Fabris + Francesco Curcio + Matteo Balestrieri + Marco Colizzi +
+To date, no psychotropic medication has shown to effectively halt progression to psychosis among individuals at Clinical High-Risk for psychosis (CHR), fueling the search for novel therapeutic agents. Recent evidence supports Palmitoylethanolamide (PEA) signaling as a potential psychosis biomarker, also indicating a therapeutic role for its supplementation in the treatment of psychotic disorders. Nonetheless, the effect of sustained PEA intake in CHR subjects has never been explored so far. We will assess the feasibility of enrolling 20 CHR young adults presenting with attenuated psychotic symptoms (APS) in a 12-week, open-label, investigator-initiated, proof-of-concept, single-arm trial of ultramicronized-PEA (um-PEA) 600 mg/day. Once completed the 12-week phase, participants will be proposed to enter a 24-week extension phase of the study. We will examine um-PEA ability to reduce APS and psychic distress, um-PEA safety and tolerability, and the biological basis of um-PEA effect in terms of modulation of inflammatory response, endocannabinoid (eCB) signaling, and microbiome composition. Our trial aims to address an unmet clinical need in CHR subjects, providing an initial solid basis for the development of future studies evaluating the efficacy and tolerability of PEA supplementation in this group of patients.
-in Science Advances on 2024-12-06 08:00:00 UTC. +
in Brain Sciences on 2024-12-07 00:00:00 UTC.
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-Heat disproportionately kills young people: Evidence from wet-bulb temperature in Mexico
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+Brain Sciences, Vol. 14, Pages 1229: EEG Oscillations as Neuroplastic Markers of Neural Compensation in Spinal Cord Injury Rehabilitation: The Role of Slow-Frequency Bands
- Science Advances, Volume 10, Issue 49, December 2024.+
Brain Sciences, Vol. 14, Pages 1229: EEG Oscillations as Neuroplastic Markers of Neural Compensation in Spinal Cord Injury Rehabilitation: The Role of Slow-Frequency Bands
+Brain Sciences doi: 10.3390/brainsci14121229
+Authors: + Guilherme J. M. Lacerda + Lucas Camargo + Marta Imamura + Lucas M. Marques + Linamara Battistella + Felipe Fregni +
+Background: Spinal cord injury (SCI) affects approximately 250,000 to 500,000 individuals annually. Current therapeutic interventions predominantly focus on mitigating the impact of physical and neurological impairments, with limited functional recovery observed in many patients. Electroencephalogram (EEG) oscillations have been investigated in this context of rehabilitation to identify effective markers for optimizing rehabilitation treatments. Methods: We performed an exploratory cross-sectional study assessing the baseline EEG resting state of 86 participants with SCI as part of the Deficit of Inhibitory as a Marker of Neuroplasticity in Rehabilitation Cohort Study (DEFINE). Results: Our multivariate models demonstrated a positive correlation between frontal delta asymmetry and depression symptoms, while the frontal alpha asymmetry band and anxiety symptoms were negatively correlated. Theta oscillations were negatively associated with motor-evoked potential (MEP), whereas alpha oscillations were positively associated with MEP in all regions of interest and with CPM response as a negative correlation. Based on the potential role of lower-frequency oscillations in exerting a salutogenic compensatory effect, detrimental clinical and neurophysiological markers, such as depression and lower ME, likely induce slow oscillatory rhythms. Alpha oscillations may indicate a more salutogenic state, often associated with various cognitive functions, such as attention and memory processing. Conclusions: These results show an attempt by the CNS to reorganize and restore function despite the disruption caused by SCI. Indeed, this finding also challenges the notion that low-frequency EEG rhythms are associated with cortical lesions. These results may contribute to the development of rehabilitation strategies and potentially improve the clinical outcomes of patients with SCI.
-in Science Advances on 2024-12-06 08:00:00 UTC. +
in Brain Sciences on 2024-12-07 00:00:00 UTC.
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-Size-dependent guest-memory switching of the flexible and robust adsorption characteristics of layered metal-organic frameworks
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+Efficacy and Safety of Platelet-rich Plasma in the Management of Lumbar Disc Herniation: A Systematic Review and Meta-analysis [version 1; peer review: awaiting peer review]
- Science Advances, Volume 10, Issue 49, December 2024.+ Background Lumbar radicular discomfort is often induced by mechanical compression of the nerve root and inflammatory reactions. Platelet-rich plasma (PRP) is an efficacious therapy modality, albeit ongoing controversies regarding its effectiveness, and it possesses the advantage of minimal side effects. Therefore, we conducted the current systematic review and meta-analysis to investigate the efficacy and safety of PRP in the treatment of lumbar disc herniation (LDH). Methods We conducted our database searching on PubMed, Scopus, and Web of Science from inception till August 2024 to look for articles that fulfil our aim. The search strategy was based on three main keywords: “Platelet-rich plasma” AND “Lumbar” AND “Hernia*”. We conducted the pooled analysis of continuous variables using mean difference (MD) and we used pooled odds ratio (OR) for dichotomous variables with 95% confidence intervals (CI). Results The use of PRP was statistically significant associated with reduced visual analogue scale (VAS) compared with no PRP with MD of -0.44 (95%CI:-0.76, -0.11, p=0.008), and Oswestry Disability Index (ODI) with MD of -5.36 (95%CI: -8.25, -2.48, p=0.0003). However, no significant difference was observed regarding Japanese Orthopedic Association (JOA) with MD of 2.52 (95%CI:-0.8, 5.84, p=0.14) with non-significant heterogeneity. PRP was also associated with reduced risk of complications with OR of 0.22 (95%CI:0.07, 0.68, p=0.009) and non-significant heterogeneity. Conclusion PRP use in patients with LDH is associated with positive outcomes presented in reduction of pain, and disability (decrease in ODI scale) in addition to being safe with less incidence of complications compared with patients not receiving PRP. -
in Science Advances on 2024-12-06 08:00:00 UTC. +
in F1000Research on 2024-12-06 16:58:18 UTC.
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-Sex-dimorphic tumor growth is regulated by tumor microenvironmental and systemic signals
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+Case Report: Case report : Mindfulness training led to catharsis and mindfulness-to-meaning in a patient with social anxiety disorder comorbid with persistent depressive disorder (Dysthymia) [version 1; peer review: awaiting peer review]
- Science Advances, Volume 10, Issue 49, December 2024.+ Background The use of mindfulness in the treatment of anxiety and depression is becoming more and more widespread, but there are few reports that it has fundamentally changed patients’ sense of life. Case Presentation This report showed 9 year’s progress of treatment for Social Anxiety Disorder and Persistent Depressive Disorder in a 41-year-old female patient experiencing a long-term painful married life with a reckless husband and controlling mother-in-law. During the past 25 months, she received 180 sessions of mindfulness training, resulting in complete remission of the anxiety and depression symptoms. After the 30th session she experienced an episode of the catharsis during the mindfulness training and experienced what can be called Mindfulness-To-Meaning, which is characterized by durable eudaimonic well-being in the face of adversity. Conclusions The psychological mechanisms that supported arriving at Mindfulness-To-Meaning are delineated as: Heightened (1) awareness which promoted (2) verbalization of the primary theme of suppression, in which the stress was (3) appraised metacognitively. Then (4) decentering permitted integrating this painful theme into a new adaptive self and world view, which resulted in (5) emotional catharsis, or release. Furthermore (6) positive appraisal of this experience enhanced awareness and led to the experience of (7) Mindfulness-To-Meaning. -
in Science Advances on 2024-12-06 08:00:00 UTC. +
in F1000Research on 2024-12-06 16:54:17 UTC.
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-Laser-induced adhesives with excellent adhesion enhancement and reduction capabilities for transfer printing of microchips
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+Predictors of mortality for blunt trauma patients in intensive care: A retrospective cohort study [version 5; peer review: 2 approved]
- Science Advances, Volume 10, Issue 49, December 2024.+ Background Major trauma places substantial demand on critical care services, is a leading cause of death in under 40-year-olds and causes significant morbidity and mortality across all age groups. Various factors influence patient outcome and predefining these could allow prognostication. The aim of this study was to identify predictors of mortality from major trauma in intensive care. Methods This was a retrospective study of adult trauma patients admitted to general intensive care between January 2018 and December 2019. We assessed the impact on mortality of patient demographics, patterns of injury, injury scores (Glasgow Coma Score (GCS), Charlson’s comorbidity index (CCI), Acute Physiology and Health Evaluation II (APACHE II), Injury Severity Score (ISS) and Probability of Survival Score (Ps19)), number of surgeries and mechanism of injury using logistic regression. Results A total of 414 patients were included with a median age of 54 years (IQR 34–72). Overall mortality was 18.6%. The most common mechanism of injury was traffic collision (46%). Non-survivors were older, had higher ISS scores with lower GCS on admission and lower probability of survival scores. Factors independently predictive of mortality were age 70-80 (OR 3.267, p = 0.029), age >80 (OR 27.043, p < 0.001) and GCS < 15 (OR 8.728, p < 0.001). Ps19 was the best predictor of mortality (p <0.001 for each score category), with an AUROC of 0.90. Conclusions The significant mortality predictors were age, fall from <2 metres, injury of head or limbs, GCS <15 and Ps19. Contrary to previous studies, CCI and APACHE II did not significantly predict mortality. Although Ps19 was found to be the best current prognostic score, trauma prognostication would benefit from a single validated scoring system incorporating both physiological variables and injury patterns. -
in Science Advances on 2024-12-06 08:00:00 UTC. +
in F1000Research on 2024-12-06 16:45:07 UTC.
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-An extragenital cell population contributes to urethra closure during mouse penis development
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+Recent Advances in Biopesticide Research and Development with a Focus on Microbials [version 3; peer review: 2 approved]
- Science Advances, Volume 10, Issue 49, December 2024.+ Biopesticides are pest control products derived from natural sources such as microbes, macro-organisms (insects and pathogens), plant extracts, and certain minerals. Many biopesticides are considered environmentally safe and can complement or substitute conventional chemical pesticides. They can also be highly specific or broad spectrum with a unique mode of action controlling a wide range of pest species. Due to their target-specificity and low to no environmental residuality, biopesticides conform to the 3 pillars of Climate-Smart Agriculture, the Sustainable Development Goals, and, ultimately, the Paris Agreement. This review focuses largely on microbial biopesticides derived from fungi, bacteria, viruses, and nematodes. It discusses (i) the various microbial biopesticide formulations, (ii) the mode of microbial biopesticide action, (iii) the factors that affect the potential efficacy of biopesticides, (iv) challenges to the adoption of microbial biopesticides, and (v) the role of microbial biopesticides in Integrated Pest Management programs. Finally, advancements in application techniques, as well as future research directions and gaps, are highlighted. -
in Science Advances on 2024-12-06 08:00:00 UTC. +
in F1000Research on 2024-12-06 16:37:01 UTC.
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-Metasurface spectrometers beyond resolution-sensitivity constraints
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+Study anti-viral drugs for their efficiency against multiple SARS CoV-2 drug targets within molecular docking, molecular quantum similarity, and chemical reactivity indices frameworks [version 2; peer review: 2 approved with reservations]
- Science Advances, Volume 10, Issue 49, December 2024.+ The study focused on drug discovery for COVID-19, emphasizing the challenges posed by the pandemic and the importance of understanding the virus’s biology. The research utilized molecular docking and quantum similarity analyses to explore potential ligands for SARS-CoV-2 RNA-dependent RNA polymerase. Docking Results Docking outcomes for various ligands, including Oseltamivir, Prochloraz, Valacyclovir, Baricitinib, Molnupiravir, Penciclovir, Famciclovir, Lamivudine, and Nitazoxanide, were presented. Interactions between ligands and specific residues in the RNA-dependent RNA polymerase were analyzed. Reactivity Descriptors Global parameters, such as electronic chemical potential, chemical hardness, global softness, and global electrophilicity, were computed for the ligands. For the local reactivity descriptors, the Fukui Functions were used. Fukui functions, representing electrophilic and nucleophilic sites, were calculated for selected ligands (Valacyclovir and Penciclovir). Nucleophilic character assignments for specific molecular regions were discussed, providing insights into potential charge-donating interactions. Results and Discussion Challenges in COVID-19 drug discovery, such as virus mutability, rapid evolution, and resource limitations, were summarized. Progress in vaccine development and the need for ongoing research to address variants and breakthrough cases were emphasized. Overlap Operator Analysis Higher MQSM between Lamivudine and Molnupiravir (0.5742) indicates structural and electronic similarity. Lowest MQSM between Oseltamivir and Prochloraz (0.2233) implies structural dissimilarity. Coulomb Operator Analysis Higher MQSM between Lamivudine and Molnupiravir (0.9178) suggests both structural and electronic similarity. Lowest MQSM between Baricitinib and Famciclovir (0.6001) indicates greater structural diversity. Measurements above 0.5 in Table 3 suggest electronic similarity, emphasizing the electronic aspects in molecular analysis. In this sense, it study employed a multi-faceted approach combining molecular docking, quantum similarity analyses, and chemical reactivity assessments to explore potential drug candidates for COVID-19. The findings provide valuable insights into ligand interactions, reactivity patterns, and the challenges associated with drug discovery in the context of the global pandemic. -
in Science Advances on 2024-12-06 08:00:00 UTC. +
in F1000Research on 2024-12-06 16:10:13 UTC.
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-Gene acquisition by giant transposons primes eukaryotes for rapid evolution via horizontal gene transfer
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+Women’s representation in higher leadership positions in Ethiopia in the last three decades since 1991 [version 2; peer review: 2 approved]
- Science Advances, Volume 10, Issue 49, December 2024.+ Gender equality in decision-making positions is crucial to achieving the goals of good governance, peace, democracy, and inclusive/sustainable development. The major aim of this research article is to investigate the representation trend of women in higher decision-making positions over the last thirty years, since 1991. The federal three organs of government (law formulating, law enforcing, and law interpreting bodies) were the focus of this research. This research is a mixed type of research that inculcates both qualitative and quantitative data types. Secondary data sources from relevant government institutions were mostly used. The data was analyzed through content analysis of documents and presented via descriptive data presenting techniques. The research findings reveal that although women’s representation in positions of decision-making has advanced considerably in recent years, the empirical data throughout the previous thirty years demonstrated the underrepresentation of women in higher leadership positions within the Ethiopian federal government. Furthermore, Women never held certain higher-level government leadership positions, such as the Prime Minister position, which seems to be forbidden for women. Women made up 23%, 19%, 19%, and 24% of the House of Peoples Representatives (HPR), the House of Federation (HoF), ministerial posts, and judicial bodies, respectively over the last three decades. Women are visibly underrepresented in the executive positions as compared to others. Thus, substantial policy and practical initiatives are needed to remove institutional, social, and economic barriers to boost women’s advanced visibility in senior leadership roles. -
in Science Advances on 2024-12-06 08:00:00 UTC. +
in F1000Research on 2024-12-06 16:08:18 UTC.
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-Optimal repetitive readout of single solid-state spins determined by Fisher information
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+Factors contributing to persistent shoulder pain after arthroscopic rotator cuff repair: Protocol for a scoping review [version 2; peer review: 1 approved, 1 approved with reservations]
- Science Advances, Volume 10, Issue 49, December 2024.+ Introduction Rotator cuff (RC) tears are the most common and disabling musculoskeletal ailments among patients with shoulder pain. Although most individuals show improvement in function and pain following arthroscopic rotator cuff repair (ARCR), a subgroup of patients continue to suffer from persistent shoulder pain following the surgical procedure. Identifying these factors is important in planning preoperative management to improve patient outcomes. Objective This scoping review aims to identify biological factors, psychological factors, and social determinants of health contributing to the development of persistent pain in individuals after the ARCR procedure. Inclusion criteria All prospective and retrospective longitudinal studies reporting the risk factors contributing to persistent pain three months or longer after the ARCR surgery will be considered for this scoping review. Methods Our review will adhere to the Joanna Briggs Institute (JBI) scoping review methodology. Four electronic databases PubMed, CINAHL, Embase, and Scopus will be searched for studies in the English language. Additional studies can be found by conducting a citation analysis of the included studies. Title and abstract screening will be performed by two independent reviewers following the inclusion criteria, a third reviewer will be consulted about any differences. Next, full-text screening will be conducted, and the remaining search results will be reviewed to extract data, as well as to synthesize findings from all research. An overview of findings will be depicted in tabular format accompanied by a narrative summary of various factors contributing to persistent pain. -
in Science Advances on 2024-12-06 08:00:00 UTC. +
in F1000Research on 2024-12-06 16:05:45 UTC.
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-Dynamic silicone hydrogel gauze coatings with dual anti-blood adhesion mechanism for rapid hemostasis and minimal secondary damage
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+Hepatic GPx1 and GIT1 expression altered by ethanol exposure during third trimester-equivalent development [version 2; peer review: 1 approved with reservations]
- Science Advances, Volume 10, Issue 49, December 2024.+ Background Ethanol (EtOH) exposure throughout gestation and breastfeeding leads to multiple adverse outcomes in the hepatic system. Under oxidative stress, alterations in the liver are related to the inhibition of induced nitric oxide synthase activity in sinusoidal cells as a consequence of low expression of G-protein-coupled receptor (GPCR)-kinase interacting (GIT1). Here, we hypothesized that both glutathione peroxidase 1 (GPx1) and GIT1 could be altered by EtOH exposure during the third trimester of human equivalent development. Methods We exposed rats during the third trimester equivalent [postnatal days (PD) 2-8] to moderate levels of maternal EtOH (20%). GPx1 and GIT1 expression was detected by western blotting, and the antioxidant activity of glutathione peroxidase GPx and the concentration of hepatic carbonyl groups (CG were determined by spectrophotometry. Serum biochemistry parameters such as alanine aminotransferase (ALT), glucose (gluc), cholesterol (chol), and triglycerides (TG) were also measured. Results We found that ethanol decreased both GIT1 and GPx1 selenoprotein expression, affecting GPx antioxidant activity and increasing protein oxidation. Conclusions These results demonstrate for the first time that the GPx antioxidant system altered by EtOH exposure during the third trimester of development is related to a parallel decrease in GIT1 expression [1]. -
in Science Advances on 2024-12-06 08:00:00 UTC. +
in F1000Research on 2024-12-06 16:02:54 UTC.
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-Experimental demonstration of the equivalence of entropic uncertainty with wave-particle duality
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+An open label, single arm, pilot study to evaluate the safety, tolerability, and efficacy of daily fluconazole 150 mg in subjects suffering from Tinea cruris and Tinea corporis [version 2; peer review: 1 approved with reservations, 1 not approved]
- Science Advances, Volume 10, Issue 49, December 2024.+ Background Dermatophytes are the most common superficial fungal infections worldwide and are treated with prescribed regimens of terbinafine and itraconazole, or with weekly doses of fluconazole. Dermatologists are increasingly encountering treatment failures, and experts suggest that standard treatment regimens are not applicable anymore. We planned an open-label study to evaluate the results of fluconazole 150 mg daily for 8 weeks in patients with tinea cruris and tinea corporis. Methods Patients were enrolled from the La’Mer Clinic, Mumbai, India. We included adult subjects with uncomplicated dermatophytosis confirmed by microscopic examination of skin scrapings. Pregnancy, poor renal function, and recent exposure to anti-fungal therapy were exclusion criteria. Patients were reviewed on days 14, 28 and 56. The treating doctor scored the severity of erythema, scaling, and pruritus on a four-point scale: absent, mild, moderate, and severe. Of 107 subjects screened, 100 were finally included in the study. Eleven were lost to follow up and one subject withdrew consent. Results The site of disease was body alone in 29, groin alone in 7, and both body and groin in 64 cases. At 5 weeks, 98%, 100%, and 97% of patients had no scaling, erythema, and pruritus, respectively. Skin scrapings showed 100% mycological cure. In one patient the alanine transaminase level rose from 54.9 to 100.2 U/L, and qualified as a grade 1 adverse event not requiring intervention. No other significant adverse events were noted. Conclusions Our results suggest that fluconazole 150 mg daily for eight weeks effectively treats dermatophytosis. This regimen is safe and well-tolerated even in patients with co-morbidities. Fluconazole is about eight times less expensive than itraconazole or terbinafine and may be the preferred therapy. Registration The trial was registered with Clinical Trials Registry, India (Registration number CTRI/2020/06/026110) on 24 June 2020. FDC Company, India, provided financial support for the study. -
in Science Advances on 2024-12-06 08:00:00 UTC. +
in F1000Research on 2024-12-06 15:54:43 UTC.
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-Charting the transcriptomic landscape of primary and metastatic cancers in relation to their origin and target normal tissues
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+Role modeling and Snack Choices of young adults: The mediating role of meal planning [version 1; peer review: awaiting peer review]
- Science Advances, Volume 10, Issue 49, December 2024.+ Objective This study aimed to examine the mediating role of meal planning in the relationship between role modeling and snack choice. Methods and Measures The study was correlational and quantitative in nature. The study selected a sample of 403 university students. We collected data through interviews using a questionnaire. We analyzed the data using SPSS 23.0.0.0 (IBM Corp; 1989, 2015) (Build 1607) and AMOS 23.0.0 (IBM Corp; 1983, 2015) (Build 1607) software for correlational and Confirmatory factor tests. We used the bootstrapping technique to test for the mediation effect of meal planning. Results Meal planning had a full mediation effect between role modeling and snack choice. This means that Role modeling had a significant influence on meal planning, meal planning had a significant influence on snack choice, and role modeling had no significant influence on snack choice. Conclusion when young people admire other people’s eating habits it leads them to plan their meals and choose similar snacks to their role models. Future studies should consider studying the effect that role models’ proximity has on snack choices among young people in other contexts. -
in Science Advances on 2024-12-06 08:00:00 UTC. +
in F1000Research on 2024-12-06 15:51:26 UTC.
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-Antidepressant use in spatial social networks
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+Incidence and predictive factors of hyperventilation syndrome in patients after COVID 19 pneumonia: a prospective cohort study [version 1; peer review: awaiting peer review]
- Science Advances, Volume 10, Issue 49, December 2024.+ Background This study investigates the incidence and predictive factors of Hyperventilation Syndrome (HVS) in patients after COVID 19 pneumonia, addressing the clinical overlap between these conditions. Methods A one-month prospective study was conducted, tracking survivors of COVID-19 pneumonia. Patients were evaluated for ongoing clinical status, including HVS and post-traumatic syndrome disorder (PTSD), using clinical questionnaires, mMRC, Post-COVID-19 Functional Status (PCFS) Score, Nijmegen score, and PTSD Checklist for DSM-5 questionnaire. Results Our study included 222 patients (median age: 57 years, male predominance 62.6%). Somatic comorbidities, primarily metabolic disorders, were reported in 71.2% of cases. The majority had severe or critical infection forms (78.4%), and 91.9% experienced acute symptoms, with 86.5% having three or more symptom clusters. At one month follow-up, dyspnea (52.9%) and asthenia (21.7%) persisted. Functional limitations (PCFS Grade > 2) were observed in 19.6% of patients. The overall incidence of HVS was 158 per 1000 patients, and PTSD was 445 per 1000 patients. Multivariate logistic regression identified cognitive impairment (acute phase), persistent weight loss (post-COVID-19 phase), PCFS grade > 2, and PTSD as independent factors for developing HVS, with relative risks (RRs) of 3.47 (95%CI [1.48-8.31]; p = 0.004), 11.87 (95%CI [1.25-112.88]; p = 0.031), 3.24 (95%CI [1.34-7.86]; p = 0.009), and 5.98 (95%CI [2.27-15.77]; p < 0.001), respectively. Conclusion HVS is prevalent in the post-COVID-19 phase, affecting 15.6 % of survivors. Identified predictive factors suggest the convergence of psychosomatic pathophysiological mechanisms. Further research is crucial for a detailed understanding of these mechanisms in long COVID-19 patients. -
in Science Advances on 2024-12-06 08:00:00 UTC. +
in F1000Research on 2024-12-06 15:21:44 UTC.
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-Epitope-focused immunogens targeting the hepatitis C virus glycoproteins induce broadly neutralizing antibodies
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+Safety and efficacy of Dexmedetomidine in preoperative and postoperative settings during transsphenoidal resection of pituitary Adenoma: A systematic review and meta-analysis of randomized controlled trials [version 1; peer review: awaiting peer review]
- Science Advances, Volume 10, Issue 49, December 2024.+ Background Pituitary adenoma, a benign tumor of the pituitary gland, represents 10-15% of intracranial tumors. Although non-cancerous, its size and location can cause significant health issues, including hormonal imbalances and compression of nearby structures like the optic chiasm, leading to conditions such as Cushing’s disease, acromegaly, and visual disturbances. The prevalence ranges from 46 to 95 per 100,000 individuals. This study evaluates the effectiveness and safety of dexmedetomidine versus placebo in patients undergoing transsphenoidal resection of pituitary adenomas. Methods A systematic review and meta-analysis following PRISMA guidelines included 10 RCTs with 633 patients. English-language RCTs were sourced from PubMed, Scopus, Web of Science, Google Scholar, and Cochrane Library. Risk of bias was assessed using the ROB2 tool, and statistical analyses were performed using RevMan 5.3. Results Dexmedetomidine significantly reduced heart rate after intubation (MD: -6.61 bpm, 95% CI: -8.98 to -4.24, p < 0.00001) and post-extubation (MD: -6.77 bpm, 95% CI: -8.59 to -4.96, p < 0.00001). Mean arterial pressure decreased after intubation (MD: -10.49 mmHg, 95% CI: -12.73 to -8.26, p < 0.00001) and post-extubation (MD: -12.97 mmHg, 95% CI: -14.37 to -11.57, p < 0.00001). Dexmedetomidine also reduced surgical duration (SMD: -0.23, 95% CI: -0.41 to -0.05, p = 0.01), blood loss (MD: -109.49 mL, 95% CI: -152.60 to -66.38, p < 0.00001), propofol dose (SMD: -1.04, 95% CI: -1.72 to -0.37, p = 0.002), extubation time (SMD: -0.70, 95% CI: -0.93 to -0.47, p < 0.00001), and postoperative nausea and vomiting (OR: 0.45, 95% CI: 0.25 to 0.80, p = 0.007). Conclusions Dexmedetomidine enhances perioperative outcomes in transsphenoidal resection of pituitary adenomas, supporting its use as an effective anesthetic adjunct. -
in Science Advances on 2024-12-06 08:00:00 UTC. +
in F1000Research on 2024-12-06 14:56:43 UTC.
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-Magnetic kirigami dome metasheet with high deformability and stiffness for adaptive dynamic shape-shifting and multimodal manipulation
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+Dose-dependent interaction of parasites with tiers of host defense predicts “wormholes” that prolong infection at intermediate inoculum sizes
- Science Advances, Volume 10, Issue 49, December 2024.+
by Andrea L. Graham, Roland R. Regoes
+ +Immune responses are induced by parasite exposure and can in turn reduce parasite burden. Despite such apparently simple rules of engagement, key drivers of within-host dynamics, including dose-dependence of defense and infection duration, have proven difficult to predict. Here, we model how varied inoculating doses interact with multi-tiered host defenses at a site of inoculation, by confronting barrier, innate, and adaptive tiers with replicating and non-replicating parasites across multiple orders of magnitude of dose. We find that, in general, intermediate parasite doses generate infections of longest duration because they are sufficient in number to breach barrier defenses, but insufficient to strongly induce subsequent tiers of defense. These doses reveal “wormholes” in defense from which parasites might profit: Deviation from the hypothesis of independent action, which postulates that each parasite has an independent probability of establishing infection, may therefore be widespread. Interestingly, our model predicts local maxima of duration at two doses–one for each tier transition. While some empirical evidence is consistent with nonlinear dose-dependencies, testing the predicted dynamics will require finer-scale dose variation than experiments usually incorporate. Our results help explain varied infection establishment and duration among differentially-exposed hosts and elucidate evolutionary pressures that shape both virulence and defense. -in Science Advances on 2024-12-06 08:00:00 UTC. +
in PLoS Computational Biology on 2024-12-06 14:00:00 UTC.
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-Inhibitors of malaria parasite cyclic nucleotide phosphodiesterases block asexual blood-stage development and mosquito transmission
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+Large scale paired antibody language models
- Science Advances, Volume 10, Issue 49, December 2024.+
by Henry Kenlay, Frédéric A. Dreyer, Aleksandr Kovaltsuk, Dom Miketa, Douglas Pires, Charlotte M. Deane
+ +Antibodies are proteins produced by the immune system that can identify and neutralise a wide variety of antigens with high specificity and affinity, and constitute the most successful class of biotherapeutics. With the advent of next-generation sequencing, billions of antibody sequences have been collected in recent years, though their application in the design of better therapeutics has been constrained by the sheer volume and complexity of the data. To address this challenge, we present IgBert and IgT5, the best performing antibody-specific language models developed to date which can consistently handle both paired and unpaired variable region sequences as input. These models are trained comprehensively using the more than two billion unpaired sequences and two million paired sequences of light and heavy chains present in the Observed Antibody Space dataset. We show that our models outperform existing antibody and protein language models on a diverse range of design and regression tasks relevant to antibody engineering. This advancement marks a significant leap forward in leveraging machine learning, large scale data sets and high-performance computing for enhancing antibody design for therapeutic development. -in Science Advances on 2024-12-06 08:00:00 UTC. +
in PLoS Computational Biology on 2024-12-06 14:00:00 UTC.
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-Ultrathin rubbery bio-optoelectronic stimulators for untethered cardiac stimulation
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+OneNet—One network to rule them all: Consensus network inference from microbiome data
- Science Advances, Volume 10, Issue 49, December 2024.+
by Camille Champion, Raphaëlle Momal, Emmanuelle Le Chatelier, Mathilde Sola, Mahendra Mariadassou, Magali Berland
+ +Modeling microbial interactions as sparse and reproducible networks is a major challenge in microbial ecology. Direct interactions between the microbial species of a biome can help to understand the mechanisms through which microbial communities influence the system. Most state-of-the art methods reconstruct networks from abundance data using Gaussian Graphical Models, for which several statistically grounded and computationnally efficient inference approaches are available. However, the multiplicity of existing methods, when applied to the same dataset, generates very different networks. In this article, we present OneNet, a consensus network inference method that combines seven methods based on stability selection. This resampling procedure is used to tune a regularization parameter by computing how often edges are selected in the networks. We modified the stability selection framework to use edge selection frequencies directly and combine them in the inferred network to ensure that only reproducible edges are included in the consensus. We demonstrated on synthetic data that our method generally led to slightly sparser networks while achieving much higher precision than any single method. We further applied the method to gut microbiome data from liver-cirrothic patients and demonstrated that the resulting network exhibited a microbial guild that was meaningful in terms of human health. -in Science Advances on 2024-12-06 08:00:00 UTC. +
in PLoS Computational Biology on 2024-12-06 14:00:00 UTC.
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-Neuronal circuit mechanisms of competitive interaction between action-based and coincidence learning
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+Not just a garbage truck: No-go decay plays a role during embryo development in zebrafish
- Science Advances, Volume 10, Issue 49, December 2024.+
by Alana R. Plastrik, Hani S. Zaher
+ +In eukaryotes, defective mRNAs that impede the movement of the ribosome are subject to rapid decay via no-go decay (NGD). In this issue of PLOS Biology, Ishibashi and colleagues expand on the role of NGD and reveal new endogenous targets for the process in zebrafish. -in Science Advances on 2024-12-06 08:00:00 UTC. +
in PLoS Biology on 2024-12-06 14:00:00 UTC.
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-Plankton food web structure and productivity under ocean alkalinity enhancement
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+Regulatory networks may evolve to favor adaptive foresight
- Science Advances, Volume 10, Issue 49, December 2024.+
by Alejandro Couce
+ +Pleiotropy—a single mutation altering many traits—has long been seen as hindering adaptation. A new study in PLOS Biology offers a striking counterexample, suggesting that regulatory networks may evolve to ensure mutations are simultaneously beneficial in correlated environments. + +Pleiotropy (a single mutation altering many traits) has long been seen as hindering adaptation. A new study in PLOS Biology offers a striking counterexample, suggesting that regulatory networks may evolve to ensure mutations are simultaneously beneficial in correlated environments. -in Science Advances on 2024-12-06 08:00:00 UTC. +
in PLoS Biology on 2024-12-06 14:00:00 UTC.
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-X-ray–induced acoustic computed tomography: 3D X-ray absorption imaging from a single view
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+Gene transfer between fungal species triggers repeated coffee wilt disease outbreaks
- Science Advances, Volume 10, Issue 49, December 2024.+
by Brenda D. Wingfield, Michael J. Wingfield
+ +Two outbreaks of coffee wilt disease have devastated African coffee production. A PLOS Biology study suggests that horizontal gene transfer via large Starship transposons between 2 fungal species played a key role in the repeated emergence of the disease. + +Two outbreaks of coffee wilt disease have devastated African coffee production. A PLOS Biology study suggests that horizontal gene transfer via Starships between two fungal strains played a key role in the repeated emergence of the disease. -in Science Advances on 2024-12-06 08:00:00 UTC. +
in PLoS Biology on 2024-12-06 14:00:00 UTC.
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-Erratum for the Research Resource: “Harmonized cross-species cell atlases of trigeminal and dorsal root ganglia” by S. Bhuiyan et al.
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+Longitudinal Imaging Biomarkers Correlate with Progressive Motor Deficit in the Mouse Model of Charlevoix‐Saguenay Ataxia
- Science Advances, Volume 10, Issue 49, December 2024.+
Objective
+In autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) disease, severity and age of onset vary greatly, hindering to objectively measure and predict clinical progression. Thickening of the retinal nerve fiber layer is distinctive of ARSACS patients, as assessed by optical coherence tomography, whereas conventional brain magnetic resonance imaging findings include both supratentorial and infratentorial changes. Because longitudinal imaging studies in ARSACS patients are not available to define these changes as biomarkers of disease progression, we aimed to address this issue in the ARSACS mouse model.
+Methods
+We performed longitudinal retinal OCT and brain MRI in the Sacs +−/− ARSACS mouse model, alongside motor and coordination assessment in the beam walking test. We also investigated visual function and the molecular mechanisms underlying RNFL increased thickness by histology and immunofluorescence.
+Results
+We demonstrated that RNFL thickening by OCT gradually increases in the early stages of pathology in the Sacs +−/− mouse model, reflecting the progression of motor impairment, and later reaches a plateau when thinning of the posterior corpus callosum becomes detectable by MRI. Mechanistically, we unveiled that RNFL thickening is associated with aberrant accumulation of non-phosphorylated neurofilament H and glial fibrillary acidic protein. We also uncovered mild signs of myelin pathology coherent with increased latency of visual evoked potentials, and altered retinal activation by photopic electroretinography.
+Interpretation
+We show that both RNFL thickening and MRI changes may represent biomarkers of disease progression in the Sacs +−/− mouse model. Our data gathers knowledge instrumental to clinical studies, holding potential as readout for treatment efficacy. ANN NEUROL 2024
-in Science Advances on 2024-12-06 08:00:00 UTC. +
in Annals of Neurology on 2024-12-06 12:00:18 UTC.
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-Outside one’s comfort zone: Interactions between motor adaptation and executive functions
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+CORRECTION to “RETRACTION: Hippocampus of Ames Dwarf Mice is Resistant to β‐Amyloid‐Induced Tau Hyperphosphorylation and Changes in Apoptosis‐Regulatory Protein Levels”
- Journal of Neurophysiology, Ahead of Print.+ -
in Journal of Neurophysiology on 2024-12-06 04:30:26 UTC. +
in Hippocampus on 2024-12-06 12:00:15 UTC.
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-Estimating descending activation patterns from EMG in fast and slow movements using a model of the stretch reflex
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+Antimicrobial effect of silver diamine fluoride (SDF) in arresting dentine caries of permanent teeth: A Systematic review [version 1; peer review: awaiting peer review]
- Journal of Neurophysiology, Ahead of Print.+ Background Silver diamine fluoride (SDF) is recognized for its potent antibacterial properties and is commonly used in dentistry to treat carious lesions. This review aims to evaluate the antimicrobial effect of SDF on dentine caries in permanent teeth. The objective is to provide a comprehensive analysis of the existing literature to assess the efficacy of SDF in combating cariogenic flora within dentin lesions. Materials and Methods A systematic electronic search was conducted using Google Scholar, Cochrane Library, and PubMed databases to identify relevant studies published between January 2010 and September 2022. The search strategy focused on retrieving in vitro and in vivo studies assessing the antimicrobial effect of SDF on dentinal caries. The inclusion criteria encompassed studies that compared SDF with other antimicrobial agents, such as sodium fluoride varnish, potassium iodide, silver nitrate, chlorhexidine, plasma jet, and deionized water. The Cochrane Collaboration assessment tool was employed to evaluate the risk of bias in the included studies. Results Nine studies met the inclusion criteria, consisting of seven in vitro and in situ studies investigating the antimicrobial effect of SDF on dentinal caries, and two in vitro and in vivo studies examining its antibacterial effect on root caries. These studies collectively demonstrated the promising antimicrobial potential of SDF against cariogenic flora present in dentin lesions. However, variations in study design, methodology, and outcome measures were observed across the included studies. Conclusion The review underscores the significant antimicrobial efficacy of SDF in combating cariogenic bacteria within dentin lesions of permanent teeth. Despite the promising findings, there remains a lack of comprehensive understanding regarding the precise characteristics and mechanisms underlying the antimicrobial action of SDF, particularly concerning nano-silver. Future research, including long-term clinical trials, is warranted to elucidate optimal dosage regimens and therapeutic approaches for the routine application of SDF in managing dental caries. -
in Journal of Neurophysiology on 2024-12-06 04:20:50 UTC. +
in F1000Research on 2024-12-06 10:46:56 UTC.
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-Impact of different muscle lengthening amplitudes combined with electrical nerve stimulation on torque production
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+Comments about the comparative bulk RNA sequencing between palmoplantar pustulosis and dyshidrotic palmoplantar eczema [version 1; peer review: awaiting peer review]
- Journal of Neurophysiology, Ahead of Print.+ This correspondence discusses the recent findings by Straalen et al., highlighting molecular similarities and distinctions between palmoplantar pustulosis (PPP) and dyshidrotic palmoplantar eczema (DPE). The study emphasizes shared proinflammatory pathways and T-cell–related gene upregulation while detailing unique features such as neutrophil involvement in PPP and lipid antigen processing in DPE. We elaborate on histopathological differences, especially intraepidermal vesicle formation in PPP linked to IL–1–mediated pathways and the absence of hyaluronan expression, contrasting with Th2 cytokines-driven spongiosis in DPE. By addressing IL-4, hyaluronan synthases, and keratinocyte adhesion molecules, this correspondence aims to deepen understanding of PPP and DPE pathophysiology. -
in Journal of Neurophysiology on 2024-12-06 04:12:35 UTC. +
in F1000Research on 2024-12-06 09:59:49 UTC.
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-Differential behavioral engagement of inhibitory interneuron subtypes in the zebra finch brain
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+A compilation of histidine kinase genes in Enterobacter hormaechei strain HCF3 isolated from the North West Province of South Africa [version 1; peer review: awaiting peer review]
- Hozhabri et al. characterize GABAergic interneuron diversity in a zebra finch circuit critical for courtship song production, using population recordings during behavior and single-cell transcriptomics. They begin to assign distinct network functions to molecularly identified cell types, revealing that parvalbumin and somatostatin interneurons are differentially recruited for separate network roles. + This study investigates the histidine kinase (HK) gene repertoire of Enterobacter hormaechei strain HCF3, isolated from fresh cow dung in Mogosane Village, Northwest Province, South Africa. Histidine kinases are critical components of bacterial two-component signal transduction systems, enabling bacteria to sense and adapt to diverse environmental conditions. Given the growing concern over antimicrobial resistance (AMR) associated with E. hormaechei, this research elucidates the genetic components that facilitate its environmental adaptability. After isolating the strain, genomic sequencing using Illumina technology, resulting in high-quality sequence data, was conducted. The assembled genome was meticulously annotated and deposited in the National Center for Biotechnology Information (NCBI) under BioProject number PRJNA991313, with additional accession numbers for raw reads (JAUOLV000000000.1) and BioSample (SAMN36292742). Histidine kinase genes were identified based on conserved domains, particularly HisKA and HATPase. This led to compiling a comprehensive HK gene catalogue with locus tags, protein accession numbers, and functional annotations. To validate the HK gene set of E. hormaechei HCF3, we conducted a rigorous comparative analysis with other strains. This revealed that strain HCF1 contains 21 histidine kinase genes, HCF2 has 25, while HCF4 has 19. These findings underscore the diversity and conservation of HK genes across different Enterobacter species, providing a new perspective on their evolutionary significance. The assembled dataset provides valuable insights into the signalling pathways of E. hormaechei, highlighting the potential roles of HKs in environmental sensing, adaptation, and pathogenicity. Furthermore, this research lays the groundwork for future studies on the applications of these genes in agriculture and biotechnology, offering new avenues for understanding and managing E. hormaechei in various ecological contexts. -in Neuron: In press on 2024-12-06 00:00:00 UTC. +
in F1000Research on 2024-12-06 09:58:25 UTC.
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-Protein nanoparticle vaccines induce potent neutralizing antibody responses against MERS-CoV
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+A new genome sequence resource for five invasive fruit flies of agricultural concern: Ceratitis capitata, C. quilicii, C. rosa, Zeugodacus cucurbitae and Bactrocera zonata (Diptera, Tephritidae) [version 1; peer review: awaiting peer review]
- Efficacious vaccines developed during the SARS-CoV-2 pandemic provide templates for other betacoronavirus vaccines. Chao et al. describe the development of protein nanoparticle immunogens displaying MERS-CoV antigens. The vaccines elicit neutralizing antibody responses and protection during viral challenge. This study extends a successful vaccine modality for sarbecoviruses to the merbecovirus subgenus. + Here, we present novel high quality genome assemblies for five invasive tephritid species of agricultural concern: Ceratitis capitata, C. quilicii, C. rosa, Zeugodacus cucurbitae and Bactrocera zonata (read depths between 65 and 78x). Three assemblies (C. capitata, C. quilicii and Z. cucurbitae) were scaffolded with chromosome conformation data and annotated using RNAseq reads. For some species this is the first reference genome available (B. zonata, C. quilicii and C. rosa), for others we have published improved annotated genomes (C. capitata and Z. cucurbitae). Together, the new references provide an important resource to advance research on genetic techniques for population control, develop rapid species identification methods, and explore eco-evolutionary studies. -in Cell Reports: Current Issue on 2024-12-06 00:00:00 UTC. +
in F1000Research on 2024-12-06 09:55:12 UTC.
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-Microglia degrade Alzheimer’s amyloid-beta deposits extracellularly via digestive exophagy
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+Diagnosis of brain death in wistar rats at different levels of death induction [version 1; peer review: awaiting peer review]
- Jacquet et al. shows that microglia use digestive exophagy to engage large Aβ deposits that cannot be phagocytosed, forming acidic extracellular compartments on the aggregates into which lysosomal enzymes are exocytosed. The PI3K-AKT pathway modulates this process. Microglia also exocytose intralysosomal undigested fibrillar Aβ toward extracellular aggregates, potentially contributing to plaque growth. + Objective This study aimed to evaluate hematologic, biochemical, and gasometric parameters in Wistar rats to better understand brain death parameters and reduce early misdiagnoses. Methods Fifteen adult male Wistar rats (Rattus norvergicus; HanUnib: WH) were randomly distributed into three groups of five animals: the control group (G0) with evaluation performed before brain death, and two groups (G1 and G2) with brain death induced at different times: immediately after induction (G1) and one hour after induction (G2). Venous and arterial blood samples were taken to perform complete blood count, biochemical, and blood gas assays. Samples were taken at specific times based on the group each rat belonged to. Results Statistically significant mean values were observed (P<0,05) for segmented cells (G1>G2 and G0>G2), monocytes (G2>G1 and G0>G1), creatinine (G2>G0), aspartate aminotransferase (G1>G0), potassium (G2>G0), and bicarbonate (G0>G1). Discussion Furthermore, brain death showed a unique response in each organism, complicating its precise determination even more. -in Cell Reports: Current Issue on 2024-12-06 00:00:00 UTC. +
in F1000Research on 2024-12-06 09:29:13 UTC.
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-Lineage-specific intersection of endothelin and GDNF signaling in enteric nervous system development
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+Programming tissue-sensing T cells that deliver therapies to the brain
- Two major ligand-receptor signaling axes – endothelin Edn3 and its receptor Ednrb, and glial-derived neurotrophic factor (GDNF) and its receptor Ret – are required for migration of enteric nervous system (ENS) progenitors to the hindgut. Mutations in either component cause colonic aganglionosis, also called Hirschsprung disease. Here, we have used Wnt1Cre and Pax2Cre in mice to show that these driver lines label distinct ENS lineages during progenitor migration and in their terminal hindgut fates. Both Cre lines result in Hirschsprung disease when combined with conditional Ednrb or conditional Ret alleles. In vitro explant assays and analysis of lineage-labeled mutant embryos show that GDNF but not Edn3 is a migration cue for cells of both lineages. Instead, Edn3-Ednrb function is required in both for GDNF responsiveness albeit in different ways: by expanding the Ret+ population in the Pax2Cre lineage, and by supporting Ret function in Wnt1Cre-derived cells. Our results demonstrate that two distinct lineages of progenitors give rise to the ENS, and that these divergently utilize endothelin signaling to support migration to the hindgut. + Science, Volume 386, Issue 6726, December 2024.-
in eLife on 2024-12-06 00:00:00 UTC. +
in Science on 2024-12-06 08:00:00 UTC.
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-Increased inflammatory signature in myeloid cells of non-small cell lung cancer patients with high clonal hematopoiesis burden
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+Engineering synthetic suppressor T cells that execute locally targeted immunoprotective programs
- Clonal hematopoiesis of indeterminate potential (CHIP) allows estimation of clonal dynamics and documentation of somatic mutations in the hematopoietic system. Recent studies utilizing large cohorts of the general population and patients have revealed significant associations of CHIP burden with age and disease status, including in cancer and chronic diseases. An increasing number of cancer patients are treated with immune checkpoint inhibitors (ICIs), but the association of ICI response in non-small cell lung cancer (NSCLC) patients with CHIP burden remains to be determined. We collected blood samples from 100 metastatic NSCLC patients before and after ICI for high-depth sequencing of the CHIP panel and 63 samples for blood single-cell RNA sequencing. Whole exome sequencing was performed in an independent replication cohort of 180 patients. The impact of CHIP status on the immunotherapy response was not significant. However, metastatic lung cancer patients showed higher CHIP prevalence (44/100 for patients vs. 5/42 for controls; p = 0.01). In addition, lung squamous cell carcinoma (LUSC) patients showed increased burden of larger clones compared to lung adenocarcinoma (LUAD) patients (8/43 for LUSC vs. 2/50 for LUAD; p = 0.04). Furthermore, single-cell RNA-seq analysis of the matched patients showed significant enrichment of inflammatory pathways mediated by NF-κB in myeloid clusters of the severe CHIP group. Our findings suggest minimal involvement of CHIP mutation and clonal dynamics during immunotherapy but a possible role of CHIP as an indicator of immunologic response in NSCLC patients. + Science, Volume 386, Issue 6726, December 2024.-
in eLife on 2024-12-06 00:00:00 UTC. +
in Science on 2024-12-06 08:00:00 UTC.
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-A cryo-electron tomography study of ciliary rootlet organization
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+Ecological erosion and expanding extinction risk of sharks and rays
- Ciliary rootlets are striated bundles of filaments that connect the base of cilia to internal cellular structures. Rootlets are critical for the sensory and motile functions of cilia. However, the mechanisms underlying these functions remain unknown, in part due to a lack of structural information of rootlet organization. In this study, we obtain 3D reconstructions of membrane-associated and purified rootlets from mouse retina using cryo-electron tomography. We show that flexible protrusions on the rootlet surface, which emanate from the cross-striations, connect to intracellular membranes. In purified rootlets, the striations were classified into amorphous (A)-bands, associated with accumulations on the rootlet surface, and discrete (D)-bands corresponding to punctate lines of density that run through the rootlet. These striations connect a flexible network of longitudinal filaments. Subtomogram averaging suggests the filaments consist of two intertwined coiled coils. The rootlet’s filamentous architecture, with frequent membrane-connecting cross-striations, lends itself well for anchoring large membranes in the cell. + Science, Volume 386, Issue 6726, December 2024.-
in eLife on 2024-12-06 00:00:00 UTC. +
in Science on 2024-12-06 08:00:00 UTC.
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-The cation channel mechanisms of subthreshold inward depolarizing currents in the mice VTA dopaminergic neurons and their roles in the chronic-stress-induced depression-like behavior
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+Dissecting the hydrogen bond network of water: Charge transfer and nuclear quantum effects
- The slow-intrinsic-pacemaker dopaminergic (DA) neurons originating in the ventral tegmental area (VTA) are implicated in various mood- and emotion-related disorders, such as anxiety, fear, stress and depression. Abnormal activity of projection-specific VTA DA neurons is the key factor in the development of these disorders. Here, we describe the crucial role of the NALCN and TRPC6, non-selective cation channels in mediating the subthreshold inward depolarizing current and driving the firing of action potentials of VTA DA neurons in physiological conditions. Furthermore, we demonstrate that down-regulation of TRPC6 protein expression in the VTA DA neurons likely contributes to the reduced activity of projection-specific VTA DA neurons in chronic mild unpredictable stress (CMUS) depressive mice. In consistent with these, selective knockdown of TRPC6 channels in the VTA DA neurons conferred mice with depression-like behavior. This current study suggests down-regulation of TRPC6 expression/function is involved in reduced VTA DA neuron firing and chronic stress-induced depression-like behavior of mice. + Science, Volume 386, Issue 6726, December 2024.-
in eLife on 2024-12-06 00:00:00 UTC. +
in Science on 2024-12-06 08:00:00 UTC.
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-Reversing protonation of weakly basic drugs greatly enhances intracellular diffusion and decreases lysosomal sequestration
+- Wallabag.it! - Save to Instapaper - Save to Pocket -
+Imperfect wound healing sets the stage for chronic diseases
- For drugs to be active they have to reach their targets. Within cells this requires crossing the cell membrane, and then free diffusion, distribution, and availability. Here, we explored the in-cell diffusion rates and distribution of a series of small molecular fluorescent drugs, in comparison to proteins, by microscopy and fluorescence recovery after photobleaching (FRAP). While all proteins diffused freely, we found a strong correlation between pKa and the intracellular diffusion and distribution of small molecule drugs. Weakly basic, small-molecule drugs displayed lower fractional recovery after photobleaching and 10- to-20-fold slower diffusion rates in cells than in aqueous solutions. As, more than half of pharmaceutical drugs are weakly basic, they, are protonated in the cell cytoplasm. Protonation, facilitates the formation of membrane impermeable ionic form of the weak base small molecules. This results in ion trapping, further reducing diffusion rates of weakly basic small molecule drugs under macromolecular crowding conditions where other nonspecific interactions become more relevant and dominant. Our imaging studies showed that acidic organelles, particularly the lysosome, captured these molecules. Surprisingly, blocking lysosomal import only slightly increased diffusion rates and fractional recovery. Conversely, blocking protonation by N-acetylated analogues, greatly enhanced their diffusion and fractional recovery after FRAP. Based on these results, N-acetylation of small molecule drugs may improve the intracellular availability and distribution of weakly basic, small molecule drugs within cells. + Science, Volume 386, Issue 6726, December 2024.-
in eLife on 2024-12-06 00:00:00 UTC. +
in Science on 2024-12-06 08:00:00 UTC.
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-Modulation of RNA processing genes during sleep-dependent memory
+- Wallabag.it! - Save to Instapaper - Save to Pocket -
+Transcription-coupled changes in genomic region proximities during transcriptional bursting
- Memory consolidation in Drosophila can be sleep-dependent or sleep-independent, depending on the availability of food. The anterior posterior (ap) alpha′/beta′ (α′/β′) neurons of the mushroom body (MB) are required for sleep-dependent memory consolidation in flies fed after training. These neurons are also involved in the increase of sleep after training, suggesting a coupling of sleep and memory. To better understand the mechanisms underlying sleep and memory consolidation initiation, we analyzed the transcriptome of ap α′/β′ neurons 1 hr after appetitive memory conditioning. A small number of genes, enriched in RNA processing functions, were differentially expressed in flies fed after training relative to trained and starved flies or untrained flies. Knockdown of each of these differentially expressed genes in the ap α′/β′ neurons revealed notable sleep phenotypes for Polr1F and Regnase-1, both of which decrease in expression after conditioning. Knockdown of Polr1F, a regulator of ribosome RNA transcription, in adult flies promotes sleep and increases pre-ribosome RNA expression as well as overall translation, supporting a function for Polr1F downregulation in sleep-dependent memory. Conversely, while constitutive knockdown of Regnase-1, an mRNA decay protein localized to the ribosome, reduces sleep, adult specific knockdown suggests that effects of Regnase-1 on sleep are developmental in nature. We further tested the role of each gene in memory consolidation. Knockdown of Polr1F does not affect memory, which may be expected from its downregulation during memory consolidation. Regnase-1 knockdown in ap α′/β′ neurons impairs all memory, including short-term, implicating Regnase-1 in memory, but leaving open the question of why it is downregulated during sleep-dependent memory. Overall, our findings demonstrate that the expression of RNA processing genes is modulated during sleep-dependent memory and, in the case of Polr1F, this modulation likely contributes to increased sleep. + Science Advances, Volume 10, Issue 49, December 2024.-
in eLife on 2024-12-06 00:00:00 UTC. +
in Science Advances on 2024-12-06 08:00:00 UTC.
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-Maternal obesity may disrupt offspring metabolism by inducing oocyte genome hyper-methylation via increased DNMTs
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+Structural and molecular properties of mumps virus inclusion bodies
- Maternal obesity has deleterious effects on the process of establishing oocyte DNA methylation; yet the underlying mechanisms remain unclear. Here, we found that maternal obesity disrupted the genomic methylation of oocytes using a high-fat diet (HFD) induced mouse model, at least a part of which was transmitted to the F2 oocytes and livers via females. We further examined the metabolome of serum and found that the serum concentration of melatonin was reduced. Exogenous melatonin treatment significantly reduced the hyper-methylation of HFD oocytes, and the increased expression of DNMT3a and DNMT1 in HFD oocytes was also decreased. These suggest that melatonin may play a key role in the disrupted genomic methylation in the oocytes of obese mice. To address how melatonin regulates the expression of DNMTs, the function of melatonin was inhibited or activated upon oocytes. Results revealed that melatonin may regulate the expression of DNMTs via the cAMP/PKA/CREB pathway. These results suggest that maternal obesity induces genomic methylation alterations in oocytes, which can be partly transmitted to F2 in females, and that melatonin is involved in regulating the hyper-methylation of HFD oocytes by increasing the expression of DNMTs via the cAMP/PKA/CREB pathway. + Science Advances, Volume 10, Issue 49, December 2024.-
in eLife on 2024-12-06 00:00:00 UTC. +
in Science Advances on 2024-12-06 08:00:00 UTC.
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-Identification of suitable target/E3 ligase pairs for PROTAC development using a rapamycin-induced proximity assay (RiPA)
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+Heat disproportionately kills young people: Evidence from wet-bulb temperature in Mexico
- The development of proteolysis targeting chimeras (PROTACs), which induce the degradation of target proteins by bringing them into proximity with cellular E3 ubiquitin ligases, has revolutionized drug development. While the human genome encodes more than 600 different E3 ligases, current PROTACs use only a handful of them, drastically limiting their full potential. Furthermore, many PROTAC development campaigns fail because the selected E3 ligase candidates are unable to induce degradation of the particular target of interest. As more and more ligands for novel E3 ligases are discovered, the chemical effort to identify the best E3 ligase for a given target is exploding. Therefore, a genetic system to identify degradation-causing E3 ligases and suitable target/E3 ligase pairs is urgently needed. Here, we used the well-established dimerization of the FKBP12 protein and FRB domain by rapamycin to bring the target protein WDR5 into proximity with candidate E3 ligases. Strikingly, this rapamycin-induced proximity assay (RiPA) revealed that VHL, but not Cereblon, is able to induce WDR5 degradation - a finding previously made by PROTACs, demonstrating its predictive power. By optimizing the steric arrangement of all components and fusing the target protein with a minimal luciferase, RiPA can identify the ideal E3 for any target protein of interest in living cells, significantly reducing and focusing the chemical effort in the early stages of PROTAC development. + Science Advances, Volume 10, Issue 49, December 2024.-
in eLife on 2024-12-06 00:00:00 UTC. +
in Science Advances on 2024-12-06 08:00:00 UTC.
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-Single-nucleus transcriptomics reveal the differentiation trajectories of periosteal skeletal/stem progenitor cells in bone regeneration
+- Wallabag.it! - Save to Instapaper - Save to Pocket -
+Size-dependent guest-memory switching of the flexible and robust adsorption characteristics of layered metal-organic frameworks
- Bone regeneration is mediated by skeletal stem/progenitor cells (SSPCs) that are mainly recruited from the periosteum after bone injury. The composition of the periosteum and the steps of SSPC activation and differentiation remain poorly understood. Here, we generated a single-nucleus atlas of the periosteum at steady state and of the fracture site during the early stages of bone repair (https://fracture-repair-atlas.cells.ucsc.edu). We identified periosteal SSPCs expressing stemness markers (Pi16 and Ly6a/SCA1) and responding to fracture by adopting an injury-induced fibrogenic cell (IIFC) fate, prior to undergoing osteogenesis or chondrogenesis. We identified distinct gene cores associated with IIFCs and their engagement into osteogenesis and chondrogenesis involving Notch, Wnt, and the circadian clock signaling, respectively. Finally, we show that IIFCs are the main source of paracrine signals in the fracture environment, suggesting a crucial paracrine role of this transient IIFC population during fracture healing. Overall, our study provides a complete temporal topography of the early stages of fracture healing and the dynamic response of periosteal SSPCs to injury, redefining our knowledge of bone regeneration. + Science Advances, Volume 10, Issue 49, December 2024.-
in eLife on 2024-12-06 00:00:00 UTC. +
in Science Advances on 2024-12-06 08:00:00 UTC.
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-Brain Sciences, Vol. 14, Pages 1228: The Impact of Intraoperative CT-Based Navigation in Congenital Craniovertebral Junction Anomalies: New Concepts of Treatment
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+Sex-dimorphic tumor growth is regulated by tumor microenvironmental and systemic signals
-Brain Sciences, Vol. 14, Pages 1228: The Impact of Intraoperative CT-Based Navigation in Congenital Craniovertebral Junction Anomalies: New Concepts of Treatment
-Brain Sciences doi: 10.3390/brainsci14121228
-Authors: - Giorgio Cracchiolo - Ali Baram - Gabriele Capo - Zefferino Rossini - Marco Riva - Andrea Fanti - Mario De Robertis - Maurizio Fornari - Federico Pessina - Carlo Brembilla -
-Background: Congenital craniovertebral junction anomalies (CCVJAs) encompass a diverse range of conditions characterized by distorted anatomy and significant variation in the pathways of neurovascular structures. This study aims to assess the safety and feasibility of tailoring posterior fixation for CCVJAs through intraoperative CT-based navigation. Methods: An in-depth retrospective analysis was conducted on eight patients diagnosed with CCVJAs (excluding Arnold&ndash;Chiari malformation). These patients underwent posterior fixation/arthrodesis facilitated by intraoperative CT-based navigation. The analysis included an examination of the fixation strategies, complication rates, length of stay, post-operative complications, and success of arthrodesis. Additionally, a comprehensive literature review was undertaken to contextualize and compare our findings. Results: Patients undergoing CVJ posterior fixation with intraoperative CT-based navigation exhibited a flawless record, devoid of complications related to the damage to neurovascular structures, as well as any instances of screw misposition, pullout, or breakage (0 out of 36 total screws). Furthermore, the entire cohort demonstrated a 100% arthrodesis rate. None of the patients required treatment with an occipital plate. Conclusions: The incorporation of intraoperative CT-based navigation proves to be an invaluable asset in executing CVJ posterior fixation within the context of CCVJAs. This technology facilitates the customization of posterior constructs, a crucial adaptation required to navigate the anatomical challenges posed by these anomalies. The secure placement of screws into the occipital condyles, made possible by navigation, has proven highly effective in achieving CVJ fixation, obviating the need for an occipital plate. This technological leap represents a significant advancement, enhancing the safety, precision, and overall outcomes for patients undergoing this surgical procedure, while concurrently reducing the necessity for more invasive and morbid interventions.
+ Science Advances, Volume 10, Issue 49, December 2024.-
in Brain Sciences on 2024-12-06 00:00:00 UTC. +
in Science Advances on 2024-12-06 08:00:00 UTC.
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-Neural Encoding of Direction and Distance across Reference Frames in Visually Guided Reaching
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+Laser-induced adhesives with excellent adhesion enhancement and reduction capabilities for transfer printing of microchips
-Goal-directed actions require transforming sensory information into motor plans defined across multiple parameters and reference frames. Substantial evidence supports the encoding of target direction in gaze- and body-centered coordinates within parietal and premotor regions. However, how the brain encodes the equally critical parameter of target distance remains less understood. Here, using Bayesian pattern component modeling of fMRI data during a delayed reach-to-target task, we dissociated the neural encoding of both target direction and the relative distances between target, gaze, and hand at early and late stages of motor planning. This approach revealed independent representations of direction and distance along the human dorsomedial reach pathway. During early planning, most premotor and superior parietal areas encoded a target’s distance in single or multiple reference frames and encoded its direction. In contrast, distance encoding was magnified in gaze- and body-centric reference frames during late planning. These results emphasize a flexible and efficient human central nervous system that achieves goals by remapping sensory information related to multiple parameters, such as distance and direction, in the same brain areas.
+ Science Advances, Volume 10, Issue 49, December 2024.-
in eNeuro on 2024-12-05 17:30:15 UTC. +
in Science Advances on 2024-12-06 08:00:00 UTC.
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-Postoperative complications across different cervical spine surgical procedures: a systematic review and meta-analysis [version 1; peer review: awaiting peer review]
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+An extragenital cell population contributes to urethra closure during mouse penis development
- Background Surgical procedures on the cervical spine are frequently performed to treat spinal diseases such as degenerative disc degeneration, trauma, tumors, and infections. However, postoperative complications are a cause for concern, and the surgical procedure with the lowest complication risk still unknown. Methods A comprehensive literature search was carried out in different databases from the beginning of the study to January 2024. Observational studies that reported the incidence of postoperative complications following anterior cervical discectomy and fusion (ACDF), posterior cervical foraminotomy (PCF), laminoplasty, laminectomy with fusion, and corpectomy were included in the review. Outcomes like reoperation rates, infections, and nerve injuries were analyzed using random-effects models, with ORs (ORs) and 95% confidence intervals (CIs). Results 13 studies with 22,874 patients were included. ACDF was associated with higher complication rates versus PCF (OR 1.84, 95% CI 1.31 to 2.60) and laminoplasty (OR 2.85, 95% CI 1.84 to 4.41). Laminectomy with fusion showed greater pseudarthrosis (OR 2.57, 95% CI 1.35 to 4.90) and reoperation rates (OR 2.46, 95% CI 1.36 to 4.43) than ACDF. No differences were detected between other procedures. Conclusion Complications risk significantly differs based on surgical strategy and technique, with ACDF potentially having higher rates compared to less invasive methods. + Science Advances, Volume 10, Issue 49, December 2024.-
in F1000Research on 2024-12-05 14:54:58 UTC. +
in Science Advances on 2024-12-06 08:00:00 UTC.
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-Enter the Matrix: Fibroblast-immune cell interactions shape extracellular matrix deposition in health and disease. [version 2; peer review: 1 approved, 1 approved with reservations]
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+Metasurface spectrometers beyond resolution-sensitivity constraints
- Fibroblasts, non-hematopoietic cells of mesenchymal origin, are tissue architects which regulate the topography of tissues, dictate tissue resident cell types, and drive fibrotic disease. Fibroblasts regulate the composition of the extracellular matrix (ECM), a 3-dimensional network of macromolecules that comprise the acellular milieu of tissues. Fibroblasts can directly and indirectly regulate immune responses by secreting ECM and ECM-bound molecules to shape tissue structure and influence organ function. In this review, we will highlight recent studies which elucidate the mechanisms by which fibroblast-derived ECM factors (e.g., collagens, fibrillar proteins) regulate ECM architecture and subsequent immune responses, with a focus on macrophages. As examples of fibroblast-derived ECM proteins, we examine Collagen Triple Helix Repeat Containing 1 (CTHRC1) and Transforming Growth Factor-β-inducible protein (TGFBI), also known as BIGH3. We address the need for investigation into how diverse fibroblast populations coordinate immune responses by modulating ECM, including the fibroblast-ECM-immune axis and the precise molecular mediators and pathways which regulate these processes. Finally, we will outline how novel research identifying key regulators of ECM deposition is critical for therapeutic development for fibrotic diseases and cancer. + Science Advances, Volume 10, Issue 49, December 2024.-
in F1000Research on 2024-12-05 14:20:38 UTC. +
in Science Advances on 2024-12-06 08:00:00 UTC.
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-Whole brain functional connectivity: Insights from next generation neural mass modelling incorporating electrical synapses
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+Gene acquisition by giant transposons primes eukaryotes for rapid evolution via horizontal gene transfer
-by Michael Forrester, Sammy Petros, Oliver Cattell, Yi Ming Lai, Reuben D. O’Dea, Stamatios Sotiropoulos, Stephen Coombes
- -The ready availability of brain connectome data has both inspired and facilitated the modelling of whole brain activity using networks of phenomenological neural mass models that can incorporate both interaction strength and tract length between brain regions. Recently, a new class of neural mass model has been developed from an exact mean field reduction of a network of spiking cortical cell models with a biophysically realistic model of the chemical synapse. Moreover, this new population dynamics model can naturally incorporate electrical synapses. Here we demonstrate the ability of this new modelling framework, when combined with data from the Human Connectome Project, to generate patterns of functional connectivity (FC) of the type observed in both magnetoencephalography and functional magnetic resonance neuroimaging. Some limited explanatory power is obtained via an eigenmode description of frequency-specific FC patterns, obtained via a linear stability analysis of the network steady state in the neigbourhood of a Hopf bifurcation. However, direct numerical simulations show that empirical data is more faithfully recapitulated in the nonlinear regime, and exposes a key role of gap junction coupling strength in generating empirically-observed neural activity, and associated FC patterns and their evolution. Thereby, we emphasise the importance of maintaining known links with biological reality when developing multi-scale models of brain dynamics. As a tool for the study of dynamic whole brain models of the type presented here we further provide a suite of C++ codes for the efficient, and user friendly, simulation of neural mass networks with multiple delayed interactions. + Science Advances, Volume 10, Issue 49, December 2024.-
in PLoS Computational Biology on 2024-12-05 14:00:00 UTC. +
in Science Advances on 2024-12-06 08:00:00 UTC.
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-Circuits and mechanisms for TMS-induced corticospinal waves: Connecting sensitivity analysis to the network graph
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+Optimal repetitive readout of single solid-state spins determined by Fisher information
-by Gene J. Yu, Federico Ranieri, Vincenzo Di Lazzaro, Marc A. Sommer, Angel V. Peterchev, Warren M. Grill
- -Transcranial magnetic stimulation (TMS) is a non-invasive, FDA-cleared treatment for neuropsychiatric disorders with broad potential for new applications, but the neural circuits that are engaged during TMS are still poorly understood. Recordings of neural activity from the corticospinal tract provide a direct readout of the response of motor cortex to TMS, and therefore a new opportunity to model neural circuit dynamics. The study goal was to use epidural recordings from the cervical spine of human subjects to develop a computational model of a motor cortical macrocolumn through which the mechanisms underlying the response to TMS, including direct and indirect waves, could be investigated. An in-depth sensitivity analysis was conducted to identify important pathways, and machine learning was used to identify common circuit features among these pathways. Sensitivity analysis identified neuron types that preferentially contributed to single corticospinal waves. Single wave preference could be predicted using the average connection probability of all possible paths between the activated neuron type and L5 pyramidal tract neurons (PTNs). For these activations, the total conduction delay of the shortest path to L5 PTNs determined the latency of the corticospinal wave. Finally, there were multiple neuron type activations that could preferentially modulate a particular corticospinal wave. The results support the hypothesis that different pathways of circuit activation contribute to different corticospinal waves with participation of both excitatory and inhibitory neurons. Moreover, activation of both afferents to the motor cortex as well as specific neuron types within the motor cortex initiated different I-waves, and the results were interpreted to propose the cortical origins of afferents that may give rise to certain I-waves. The methodology provides a workflow for performing computationally tractable sensitivity analyses on complex models and relating the results to the network structure to both identify and understand mechanisms underlying the response to acute stimulation. + Science Advances, Volume 10, Issue 49, December 2024.-
in PLoS Computational Biology on 2024-12-05 14:00:00 UTC. +
in Science Advances on 2024-12-06 08:00:00 UTC.
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-Modelling the effectiveness of antiviral treatment strategies to prevent household transmission of acute respiratory viruses
+- Wallabag.it! - Save to Instapaper - Save to Pocket -
+Dynamic silicone hydrogel gauze coatings with dual anti-blood adhesion mechanism for rapid hemostasis and minimal secondary damage
-by Hind Zaaraoui, Clarisse Schumer, Xavier Duval, Bruno Hoen, Lulla Opatowski, Jérémie Guedj
- -Households are a major driver of transmission of acute respiratory viruses, such as SARS-CoV-2 or Influenza. Until now antiviral treatments have mostly been used as a curative treatment in symptomatic individuals. During an outbreak, more aggressive strategies involving pre- or post-exposure prophylaxis (PrEP or PEP) could be employed to further reduce the risk of severe disease but also prevent transmission to household contacts. In order to understand the effectiveness of such strategies and the factors that may modulate them, we developed a multi-scale model that follows the infection at both the individual-level (viral dynamics) and the population-level (transmission dynamics) in households. Using a simulation study we explored different antiviral treatment strategies, evaluating their effectiveness on reducing the transmission risk and the virological burden in households for a range of virus characteristics (e.g., secondary attack rate—SAR, or time to peak viral load). We found that when the index case can be identified and treated before symptom onset, both transmission and virological burden are reduced by > 75% for most SAR values and time to peak viral load, with minimal benefit to treat additionally household contacts. While treatment initiated after index symptom onset does not reduce the risk of transmission, it can still reduce the virological burden in the household, a proxy for severe disease and subsequent transmission risk outside the household. In that case optimal strategies involve treatment of both index case and household contacts as PEP, with efficacy > 50% when peak viral load occurs after symptom onset, and 30-50% otherwise. In all the considered cases, antiviral treatment strategies were optimal for SAR ranging 20-60%, and for larger household sizes. This study highlights the opportunity of antiviral drug-based interventions in households during an outbreak to minimize viral transmission and disease burden. + Science Advances, Volume 10, Issue 49, December 2024.-
in PLoS Computational Biology on 2024-12-05 14:00:00 UTC. +
in Science Advances on 2024-12-06 08:00:00 UTC.
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-Public surface disinfection every 2 hours can reduce the infection risk of norovirus in airports up to 83%
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+Experimental demonstration of the equivalence of entropic uncertainty with wave-particle duality
-by Nan Zhang, Linan Zhuang, Marco-Felipe King, Hua Qian, Min Zhu
- -Norovirus, primarily transmitted via fomite route, poses a significant threat to global public health and the economy. Airports, as critical transportation hubs connecting people from around the world, has high potential risk of norovirus transmission due to large number of public surfaces. A total of 21.3 hours of video episodes were recorded across nine functional areas at the airport, capturing 25,925 touches. A surface transmission model based on a Markov chain was developed. Using the beta-Poisson dose-response model, the infection risk of norovirus and the effectiveness of various interventions in different airports’ areas were quantified. Without any preventive measures, restaurants at airports exhibited the highest risk of norovirus transmission, with an infection probability of 8.8×10−3% (95% CI, 1.5×10−3% -2.1×10−2%). This means approximately 4.6 (95% CI, 0.8–10.9) out of 51,494 passengers who entered the restaurants would be infected by an infected passenger. Comparing with no surface disinfection, disinfecting public surfaces every 2 hours can reduce the risk of norovirus infection per visit to the airport by 83.2%. In contrast, comparing with no hand washing, handwashing every 2 hours can reduce the infection risk per visit to the airport by only 2.0%, making public surface disinfection significantly more effective than handwashing. If the mask-wearing rate increases from 0% to 50%, the infection risk of norovirus would be decreased by 48.0% (95% CI, 43.5–52.3%). Furthermore, using antimicrobial copper/copper-nickel alloy coatings for most public surfaces could reduce the infection risk by 15.9%-99.2%. + Science Advances, Volume 10, Issue 49, December 2024.-
in PLoS Computational Biology on 2024-12-05 14:00:00 UTC. +
in Science Advances on 2024-12-06 08:00:00 UTC.
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-Copy number variants underlie major selective sweeps in insecticide resistance genes in Anopheles arabiensis
+- Wallabag.it! - Save to Instapaper - Save to Pocket -
+Charting the transcriptomic landscape of primary and metastatic cancers in relation to their origin and target normal tissues
-by Eric R. Lucas, Sanjay C. Nagi, Bilali Kabula, Bernard Batengana, William Kisinza, Alexander Egyir-Yawson, John Essandoh, Sam Dadzie, Joseph Chabi, Arjen E. Van’t Hof, Emily J. Rippon, Dimitra Pipini, Nicholas J. Harding, Naomi A. Dyer, Chris S. Clarkson, Alistair Miles, David Weetman, Martin J. Donnelly
- -To keep ahead of the evolution of resistance to insecticides in mosquitoes, national malaria control programmes must make use of a range of insecticides, both old and new, while monitoring resistance mechanisms. The outdoor-biting malaria vector Anopheles arabiensis is of increasing concern for malaria transmission because it is apparently less susceptible to many indoor control interventions, yet knowledge of its mechanisms of resistance remains limited. Furthermore, comparatively little is known in general about resistance to non-pyrethroid insecticides such as pirimiphos-methyl (PM), which are crucial for effective control in the context of globally high resistance to pyrethroids. We performed a genome-wide association study to determine the molecular mechanisms of resistance to the pyrethroid deltamethrin (commonly used in bednets) and PM (widespread use for indoor spraying), in An. arabiensis from 2 regions in Tanzania. Genomic regions of positive selection in these populations were largely driven by copy number variants (CNVs) in gene families involved in metabolic resistance. We found evidence of a new gene cluster involved in resistance to PM, identifying a strong selective sweep tied to a CNV in the carboxylesterase genes Coeae2g - Coeae6g. Using complementary data from another malaria vector, An. coluzzii, in Ghana, we show that copy number at this locus is significantly associated with PM resistance. Similarly, for deltamethrin, resistance was strongly associated with a novel CNV allele in the Cyp6aa / Cyp6p cluster (Cyp6aap_Dup33). Against this background of metabolic resistance, resistance caused by mutations in the insecticide target sites was very rare or absent. Mutations in the pyrethroid target site Vgsc were at very low frequency in Tanzania, yet combining these samples with 3 An. arabiensis individuals from West Africa revealed a startling evolutionary diversity, with up to 5 independent origins of Vgsc-995 mutations found within just 8 haplotypes. Thus, despite having been first recorded over 10 years ago, Vgsc resistance mutations in Tanzanian An. arabiensis have remained at stable low frequencies. Overall, our results provide a new copy number marker for monitoring resistance to PM in malaria mosquitoes, and reveal the complex picture of resistance patterns in An. arabiensis. + Science Advances, Volume 10, Issue 49, December 2024.-
in PLoS Biology on 2024-12-05 14:00:00 UTC. +
in Science Advances on 2024-12-06 08:00:00 UTC.
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-Translation of zinc finger domains induces ribosome collision and Znf598-dependent mRNA decay in zebrafish
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+Antidepressant use in spatial social networks
-by Kota Ishibashi, Yuichi Shichino, Peixun Han, Kimi Wakabayashi, Mari Mito, Toshifumi Inada, Seisuke Kimura, Shintaro Iwasaki, Yuichiro Mishima
- -Quality control of translation is crucial for maintaining cellular and organismal homeostasis. Obstacles in translation elongation induce ribosome collision, which is monitored by multiple sensor mechanisms in eukaryotes. The E3 ubiquitin ligase Znf598 recognizes collided ribosomes, triggering ribosome-associated quality control (RQC) to rescue stalled ribosomes and no-go decay (NGD) to degrade stall-prone mRNAs. However, the impact of RQC and NGD on maintaining the translational homeostasis of endogenous mRNAs has remained unclear. In this study, we investigated the endogenous substrate mRNAs of NGD during the maternal-to-zygotic transition (MZT) of zebrafish development. RNA-Seq analysis of zebrafish znf598 mutant embryos revealed that Znf598 down-regulates mRNAs encoding the C2H2-type zinc finger domain (C2H2-ZF) during the MZT. Reporter assays and disome profiling indicated that ribosomes stall and collide while translating tandem C2H2-ZFs, leading to mRNA degradation by Znf598. Our results suggest that NGD maintains the quality of the translatome by mitigating the risk of ribosome collision at the abundantly present C2H2-ZF sequences in the vertebrate genome. + Science Advances, Volume 10, Issue 49, December 2024.-
in PLoS Biology on 2024-12-05 14:00:00 UTC. +
in Science Advances on 2024-12-06 08:00:00 UTC.
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-A high-resolution two-step evolution experiment in yeast reveals a shift from pleiotropic to modular adaptation
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+Epitope-focused immunogens targeting the hepatitis C virus glycoproteins induce broadly neutralizing antibodies
-by Grant Kinsler, Yuping Li, Gavin Sherlock, Dmitri A. Petrov
- -Evolution by natural selection is expected to be a slow and gradual process. In particular, the mutations that drive evolution are predicted to be small and modular, incrementally improving a small number of traits. However, adaptive mutations identified early in microbial evolution experiments, cancer, and other systems often provide substantial fitness gains and pleiotropically improve multiple traits at once. We asked whether such pleiotropically adaptive mutations are common throughout adaptation or are instead a rare feature of early steps in evolution that tend to target key signaling pathways. To do so, we conducted barcoded second-step evolution experiments initiated from 5 first-step mutations identified from a prior yeast evolution experiment. We then isolated hundreds of second-step mutations from these evolution experiments, measured their fitness and performance in several growth phases, and conducted whole genome sequencing of the second-step clones. Here, we found that while the vast majority of mutants isolated from the first-step of evolution in this condition show patterns of pleiotropic adaptation—improving both performance in fermentation and respiration growth phases—second-step mutations show a shift towards modular adaptation, mostly improving respiration performance and only rarely improving fermentation performance. We also identified a shift in the molecular basis of adaptation from genes in cellular signaling pathways towards genes involved in respiration and mitochondrial function. Our results suggest that the genes in cellular signaling pathways may be more likely to provide large, adaptively pleiotropic benefits to the organism due to their ability to coherently affect many phenotypes at once. As such, these genes may serve as the source of pleiotropic adaptation in the early stages of evolution, and once these become exhausted, organisms then adapt more gradually, acquiring smaller, more modular mutations. + Science Advances, Volume 10, Issue 49, December 2024.-
in PLoS Biology on 2024-12-05 14:00:00 UTC. +
in Science Advances on 2024-12-06 08:00:00 UTC.
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-Horizontal transfers between fungal Fusarium species contributed to successive outbreaks of coffee wilt disease
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+Magnetic kirigami dome metasheet with high deformability and stiffness for adaptive dynamic shape-shifting and multimodal manipulation
-by Lily D. Peck, Theo Llewellyn, Bastien Bennetot, Samuel O’Donnell, Reuben W. Nowell, Matthew J. Ryan, Julie Flood, Ricardo C. Rodríguez de la Vega, Jeanne Ropars, Tatiana Giraud, Pietro D. Spanu, Timothy G. Barraclough
- -Outbreaks of fungal diseases have devastated plants and animals throughout history. Over the past century, the repeated emergence of coffee wilt disease caused by the fungal pathogen Fusarium xylarioides severely impacted coffee production across sub-Saharan Africa. To improve the disease management of such pathogens, it is crucial to understand their genetic structure and evolutionary potential. We compared the genomes of 13 historic strains spanning 6 decades and multiple disease outbreaks to investigate population structure and host specialisation. We found that F. xylarioides comprised at least 4 distinct lineages: 1 host-specific to Coffea arabica, 1 to C. canephora var. robusta, and 2 historic lineages isolated from various Coffea species. The presence/absence of large genomic regions across populations, the higher genetic similarities of these regions between species than expected based on genome-wide divergence and their locations in different loci in genomes across populations showed that horizontal transfers of effector genes from members of the F. oxysporum species complex contributed to host specificity. Multiple transfers into F. xylarioides populations matched different parts of the F. oxysporum mobile pathogenicity chromosome and were enriched in effector genes and transposons. Effector genes in this region and other carbohydrate-active enzymes important in the breakdown of plant cell walls were shown by transcriptomics to be highly expressed during infection of C. arabica by the fungal arabica strains. Widespread sharing of specific transposons between F. xylarioides and F. oxysporum, and the correspondence of a putative horizontally transferred regions to a Starship (large mobile element involved in horizontal gene transfers in fungi), reinforce the inference of horizontal transfers and suggest that mobile elements were involved. Our results support the hypothesis that horizontal gene transfers contributed to the repeated emergence of coffee wilt disease. + Science Advances, Volume 10, Issue 49, December 2024.-
in PLoS Biology on 2024-12-05 14:00:00 UTC. +
in Science Advances on 2024-12-06 08:00:00 UTC.
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-Addressing common inferential mistakes when failing to reject the null-hypothesis [version 1; peer review: awaiting peer review]
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+Inhibitors of malaria parasite cyclic nucleotide phosphodiesterases block asexual blood-stage development and mosquito transmission
- Failure to reject a null hypothesis may lead to erroneous conclusions regarding the absence of an association or inadequate statistical power. Because an estimate (and its variance) can never be exactly zero, traditional statistical tests cannot conclusively demonstrate the absence of an association. Instead, estimates of accuracy should be used to identify settings in which an association and its variability are sufficiently small to be clinically acceptable, directly providing information on safety and efficacy. Post-hoc power calculations should be avoided, as they offer no additional information beyond statistical tests and p-values. Furthermore, post-hoc power calculations can be misleading because of an inability to distinguish between results based on insufficient sample size and results that reflect clinically irrelevant differences. Most multiple testing procedures unrealistically assume that all positive results are false positives. However, in applied settings, results typically represent a mix of true and false positives. This implies that multiplicity corrections do not effectively differentiate between true and false positives. Instead, considering the distributions of p-values and the proportion of significant results can help to identify bodies of evidence unlikely to be driven by false-positive results. In conclusion, rather than attempting to categorize results as true or false, medical research should embrace established statistical methods that focus on estimation accuracy, replication, and consistency. + Science Advances, Volume 10, Issue 49, December 2024.-
in F1000Research on 2024-12-05 13:56:58 UTC. +
in Science Advances on 2024-12-06 08:00:00 UTC.
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-Impact of contingent rewards and punishments on employee performance: the interplay of employee engagement [version 2; peer review: 1 approved, 1 approved with reservations]
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+Ultrathin rubbery bio-optoelectronic stimulators for untethered cardiac stimulation
- Background This paper investigated the connection between transactional leadership styles, contingent rewards, punishments, and employee performance while emphasizing employee engagement’s mediating role. Existing research has predominantly focused on isolated associations between contingent rewards, punishment, and employee performance, leaving gaps in the empirical exploration of these mediating mechanisms. To address this research gap, our study has introduced a conceptual framework to understand the multifaceted connection between contingent rewards, punishment, and their effects on employee performance, with a specific emphasis on the mediating function of employee engagement. Methods We involved 273 full-time non-clinical healthcare professionals employed in NABH-accredited hospitals in Jharkhand, India. A structured survey instrument was employed for data collection from the specific survey participants, with the investigation of the research hypotheses conducted through the application of partial least squares-structural equation modeling (PLS-SEM). Results Preliminary findings suggested that contingent rewards and punishment do not directly influence employee performance. Instead, our study highlighted the critical mediating role of employee engagement, particularly its dimensions of Vigor, absorption, and dedication. Conclusions This research has underscored rewards and punishments as essential tools for influencing employee behaviour, motivation, and performance. Employee engagement, as a multifaceted construct, not only benefits individual employees but also significantly impacts overall organizational performance and success. + Science Advances, Volume 10, Issue 49, December 2024.-
in F1000Research on 2024-12-05 12:15:52 UTC. +
in Science Advances on 2024-12-06 08:00:00 UTC.
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-Effect of preoperative hair removal vs. no removal on surgical site infections: a systematic review and meta-analysis [version 1; peer review: awaiting peer review]
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+Neuronal circuit mechanisms of competitive interaction between action-based and coincidence learning
- Background The practice of preoperative hair removal has been debated regarding its role in Surgical Site Infection (SSI) prevention. This study aimed to compare the different hair removing modalities and investigate the effect of preoperative hair removal on SSI rates. Methods A systematic review and meta-analysis were conducted according to PRISMA guidelines. Three databases—PubMed, Web of Science, and Cochrane Library—were searched for relevant studies comparing preoperative hair removal to no hair removal. Studies eligible for inclusion were randomized controlled trials (RCTs) and cohort studies reporting SSI rates. Odds ratios, mean differences, and p-values were analyzed using a random effect model. Results Seventeen studies involving 5,407 patients were included. No statistically significant difference in SSI rates was found between the hair removal and no removal groups (OR = 1.066, 95% CI 0.646–1.758, p = 0.803). When comparing clipping to no hair removal, there was no significant difference (OR = 0.967, 95% CI 0.642–1.455, p = 0.870). Razor shaving was associated with higher skin damage and slightly increased SSI risk compared to clipping but not statistically significant (OR = 0.749, 95% CI 0.346–1.623, p = 0.464). Depilatory creams, however, were favored over razor shaving (OR = 3.235, 95% CI 1.543–6.785, p = 0.002), as they were linked to less skin damage and easier application. Conclusion Preoperative hair removal does not significantly impact SSI rates. Clipping appears to be a safer alternative to shaving, while depilatory creams show promise as an effective, less damaging option. + Science Advances, Volume 10, Issue 49, December 2024.-
in F1000Research on 2024-12-05 11:59:33 UTC. +
in Science Advances on 2024-12-06 08:00:00 UTC.
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-The Awareness of Dental Erosion and Its Causes and Protective Factors Among a General Adult Population of Trinidad and Tobago [version 1; peer review: awaiting peer review]
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+Plankton food web structure and productivity under ocean alkalinity enhancement
- Introduction Given the worldwide prevalence of tooth wear and wear related to dental erosion a baseline understanding of the knowledge of populations related to erosive wear is required to maximize public health campaigns developed to address this condition. This research investigated the awareness of dental erosion, its causes, and protective factors among the general adult population of Trinidad and Tobago. Methods An anonymous de-novo questionnaire, developed using Google Forms and aligned with the CHERRIES framework for web-based surveys, was subjected to face validity to ensure the inclusion of content relevant to erosive tooth wear and clarity of items intended for a general population. The questionnaire was deployed on social media platforms (Facebook) and groups (WhatsApp Community Groups) specific to groups in Trinidad and Tobago for four months. Data was entered into SPSS (Version 29) and analyzed using cross-tabulations and Chi-squared tests. Results Of the 210 respondents, 39.2% had previously been diagnosed with tooth wear, 43.1 % believed they could identify erosive wear and 42.1% believed they could differentiate between predominantly erosive wear and dental caries. Sixty-two point nine percent of respondents identified sensitivity as a symptom of erosive tooth wear. Chi-squared tests on cross-tabulated data showed significant relationships between age and GERD causing erosive wear (p=0.03), heartburn causing erosive wear (p=0.049), eating disorders causing erosive wear (p=0.009), disorders with excessive vomiting causing erosive wear (p=0.005), excessive wine consumption (p=0.004). There were no significant statistical significances for cross-tabulated data on sex and the responses on causative factors. Conclusions Respondents were generally knowledgeable about the various types of foods, beverages, and medical conditions that may cause dental erosion but were unfamiliar with other factors that may influence erosion or protect against dental erosion. + Science Advances, Volume 10, Issue 49, December 2024.-
in F1000Research on 2024-12-05 11:25:27 UTC. +
in Science Advances on 2024-12-06 08:00:00 UTC.
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-Network and sentiment analysis of Enron emails [version 1; peer review: awaiting peer review]
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+X-ray–induced acoustic computed tomography: 3D X-ray absorption imaging from a single view
- Background The objective of the research was to analyze e-mails exchanged at Enron, a power company that declared bankruptcy in 2001 following an investigation into unethical operations regarding their financials. Methods Like other researchers, we identify the “most important” employees and detect “communities” using network science methods. In addition, because previous work required that 10 e-mails be sent and received for an e-mail relationship to exist, we analyzed the effect of different “thresholds” on the results. We also performed sentiment analyses on the e-mails to evaluate whether sentiment changed over time. Results We find that the “importance” of a person depends on the centrality measure used; while the communities we detected resembled the formal organizational structure of the company. In addition, we found that centrality results were very dependent on the “threshold” used. Finally, analysis of email sentiment over time = do not give insight into the financial wellbeing of Enron. Conclusion Our results provide insight into how information flowed through Enron, who the key employees were, and e-mail sentiment before and after the crisis. + Science Advances, Volume 10, Issue 49, December 2024.-
in F1000Research on 2024-12-05 11:23:59 UTC. +
in Science Advances on 2024-12-06 08:00:00 UTC.
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-Case Report: Large mediastino-abdominal hydatid cyst extending through the Larrey's hiatus: A rare case report [version 1; peer review: awaiting peer review]
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+Erratum for the Research Resource: “Harmonized cross-species cell atlases of trigeminal and dorsal root ganglia” by S. Bhuiyan et al.
- Background The extension of hydatid liver cysts into the mediastinum through diaphragmatic hiatus is extremely rare. In this report, we describe a rare case of a hydatid liver cyst with mediastinal extension through Larrey’s hiatus, emphasizing the surgical strategy for successful treatment. In this report, we present the first documented case of a hydatid liver cyst extending into the mediastinum through Larrey’s hiatus. Case presentation We report the case of a 65-year-old male who presented with right-upper-quadrant and left-sided chest pain evolving for two months. Physical examination showed dullnes in the epigastric region. A thoraco-abdominal CT scan, revealed a 13 cm mediastino-abdominal hydatid cyst, centered on the left liver lobe with extension into the mediastinum through the Larray’s diaphragmatic hiatus. The patient underwent surgical management. Both thoracic and visceral surgeons were involved. The surgical management involved both thoracic and visceral surgeons. A Makuuchi incision allowed resection of the hydatid liver cyst. The mediastinal portion of the cyst, resting on the pericardium was aspirated through Larrey’s hiatus, followed by irrigation with a scolicidal solution. The postoperative course was uneventful. Conclusion Transmediastinal hydatid liver cysts are rare and should be operated on in close collaboration between visceral and thoracic surgeons to prevent complications. + Science Advances, Volume 10, Issue 49, December 2024.-
in F1000Research on 2024-12-05 09:46:19 UTC. +
in Science Advances on 2024-12-06 08:00:00 UTC.
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-Comment regarding “Positive SARS-CoV-2 RT-qPCR of a nasal swab spot after 30 days of conservation on filter paper at room temperature” [version 1; peer review: awaiting peer review]
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+Outside one’s comfort zone: Interactions between motor adaptation and executive functions
- The diagnostic and therapeutic approaches towards the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic were a global challenge, and the reverse transcription polymerase chain reaction of virus RNA isolated from nasopharyngeal swabs has become a common tool to confirm the clinical diagnosis of coronavirus disease 2019. Available evidence suggests, that Whatman™ Flinders Technology Associates™ (FTA) cards are a reliable option for the safe transport and storage of viral RNA pathogens. In 2021 FTA cards were shown to be suitable for the stable preservation of SARS-CoV-2 RNA derived from nasopharyngeal swabs even at elevated storage temperatures. Subsequently, another study identified Whatman filter paper to be a cheaper alternative with respect to the stable storage SARS-CoV-2 RNA at room temperature. This correspondence is meant to discuss the performance of both FTA cards and filter paper also scrutinizing performance calculations and respective evaluations. + Journal of Neurophysiology, Ahead of Print.-
in F1000Research on 2024-12-05 09:44:36 UTC. +
in Journal of Neurophysiology on 2024-12-06 04:30:26 UTC.