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- Wallabag.it! - Save to Instapaper - Save to Pocket -
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- arXiv:2412.03210v1 Announce Type: cross
-Abstract: While deep learning models can learn human-like features at earlier levels, which suggests their utility in modeling human vision, few attempts exist to incorporate these features by design. Current approaches mostly optimize all parameters blindly, only constraining minor architectural aspects. This paper demonstrates how parametrizing neural network layers enables more biologically-plausible operations while reducing trainable parameters and improving interpretability. We constrain operations to functional forms present in human vision, optimizing only these functions' parameters rather than all convolutional tensor elements independently. We present two parametric model versions: one with hand-chosen biologically plausible parameters, and another fitted to human perception experimental data. We compare these with a non-parametric version. All models achieve comparable state-of-the-art results, with parametric versions showing orders of magnitude parameter reduction for minimal performance loss. The parametric models demonstrate improved interpretability and training behavior. Notably, the model fitted to human perception, despite biological initialization, converges to biologically incorrect results. This raises scientific questions and highlights the need for diverse evaluation methods to measure models' humanness, rather than assuming task performance correlates with human-like behavior.
+ Science, Volume 386, Issue 6726, December 2024.
- in arXiv: Quantitative Biology: Neurons and Cognition on 2024-12-05 05:00:00 UTC.
+
in Science on 2024-12-06 08:00:00 UTC.
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- arXiv:2411.16582v2 Announce Type: replace
-Abstract: This paper introduces a novel approach for modelling time-varying connectivity in neuroimaging data, focusing on the slow fluctuations in synaptic efficacy that mediate neuronal dynamics. Building on the framework of Dynamic Causal Modelling (DCM), we propose a method that incorporates temporal basis functions into neural models, allowing for the explicit representation of slow parameter changes. This approach balances expressivity and computational efficiency by modelling these fluctuations as a Gaussian process, offering a middle ground between existing methods that either strongly constrain or excessively relax parameter fluctuations. We validate the ensuing model through simulations and real data from an auditory roving oddball paradigm, demonstrating its potential to explain key aspects of brain dynamics. This work aims to equip researchers with a robust tool for investigating time-varying connectivity, particularly in the context of synaptic modulation and its role in both healthy and pathological brain function.
+ Science, Volume 386, Issue 6726, December 2024.
- in arXiv: Quantitative Biology: Neurons and Cognition on 2024-12-05 05:00:00 UTC.
+
in Science on 2024-12-06 08:00:00 UTC.
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- arXiv:2408.16347v2 Announce Type: replace-cross
-Abstract: Stereoelectroencephalography (SEEG) is an invasive surgical procedure to record the electrical activities in cortical brain regions, aiming at identifying the Epileptogenic Zone (EZ) in patients with drug-resistant epilepsy. To improve the accuracy of the EZ definition, SEEG analysis can be supported by computational tools, among which the Epileptogenic Index (EI) represents the most common solution. However, the scientific community has still not found an agreement on which quantitative biomarkers can characterize the cortical sites within the EZ. In this work, we design a new algorithm, named Desynchronization Index (DI), to assist neurophysiologists in SEEG interpretation. Our algorithm estimates the effective connectivity between cortical sites and hypothesizes that the EZ is identified by those sites getting abnormally desynchronized from the network during the seizure generation. We test the proposed method over a SEEG dataset of 10 seizures, comparing its accuracy in terms of EZ definition against the EI algorithm and clinical ground truth. Our results indicate that the DI algorithm underscores specific connectivity dynamics that can hardly be identified with a pure visual analysis, increasing sensitivity in detecting epileptogenic cortical sites.
+ Science, Volume 386, Issue 6726, December 2024.
- in arXiv: Quantitative Biology: Neurons and Cognition on 2024-12-05 05:00:00 UTC.
+
in Science on 2024-12-06 08:00:00 UTC.
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- arXiv:2412.01110v2 Announce Type: replace-cross
-Abstract: Statistical physics provides tools for analyzing high-dimensional problems in machine learning and theoretical neuroscience. These calculations, particularly those using the replica method, often involve lengthy derivations that can obscure physical interpretation. We give concise, non-replica derivations of several key results and highlight their underlying similarities. Specifically, we introduce a cavity approach to analyzing high-dimensional learning problems and apply it to three cases: perceptron classification of points, perceptron classification of manifolds, and kernel ridge regression. These problems share a common structure -- a bipartite system of interacting feature and datum variables -- enabling a unified analysis. For perceptron-capacity problems, we identify a symmetry that allows derivation of correct capacities through a na\"ive method. These results match those obtained through the replica method.
+ Science, Volume 386, Issue 6726, December 2024.
- in arXiv: Computer Science: Neural and Evolutionary Computing on 2024-12-05 05:00:00 UTC.
+
in Science on 2024-12-06 08:00:00 UTC.
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- arXiv:2412.02702v1 Announce Type: new
-Abstract: In prior research, we analyzed the backwards swimming motion of mosquito larvae, parameterized it, and replicated it in a Computational Fluid Dynamics (CFD) model. Since the parameterized swimming motion is copied from observed larvae, it is not necessarily the most efficient locomotion for the model of the swimmer. In this project, we further optimize this copied solution for the swimmer model. We utilize Reinforcement Learning to guide local parameter updates. Since the majority of the computation cost arises from the CFD model, we additionally train a deep learning model to replicate the forces acting on the swimmer model. We find that this method is effective at performing local search to improve the parameterized swimming locomotion.
+ Science, Volume 386, Issue 6726, December 2024.
- in arXiv: Computer Science: Neural and Evolutionary Computing on 2024-12-05 05:00:00 UTC.
+
in Science on 2024-12-06 08:00:00 UTC.
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- arXiv:2412.02884v1 Announce Type: new
-Abstract: This project investigates factors that influence the perceived helpfulness of Amazon product reviews through machine learning techniques. After extensive feature analysis and correlation testing, we identified key metadata characteristics that serve as strong predictors of review helpfulness. While we initially explored natural language processing approaches using TextBlob for sentiment analysis, our final model focuses on metadata features that demonstrated more significant correlations, including the number of images per review, reviewer's historical helpful votes, and temporal aspects of the review.
- The data pipeline encompasses careful preprocessing and feature standardization steps to prepare the input for model training. Through systematic evaluation of different feature combinations, we discovered that metadata elements we choose using a threshold provide reliable signals when combined for predicting how helpful other Amazon users will find a review. This insight suggests that contextual and user-behavioral factors may be more indicative of review helpfulness than the linguistic content itself.
+ arXiv:2412.03628v1 Announce Type: new
+Abstract: Long duration spaceflight missions can affect the cognitive and behavioral activities of astronauts due to changes in gravity. The microgravity significantly impacts the central nervous system physiology which causes the degradation in the performance and lead to potential risk in the space exploration. The aim of this study was to evaluate functional connectivity at simulated space conditions using an unloading harness system to mimic the body-weight distribution related to Earth, Mars, and International Space Station. A unity model with six directional arrows to imagine six different motor imagery tasks associated with arms and legs were designed for the Oculus Rift S virtual reality headset for testing. An Electroencephalogram (EEG) and functional near infrared spectroscopy (fNIRS) signals were recorded from 10 participants in the distributed weight conditions related to Earth, Mars, and International Space station using the g.Nautilus fNIRS system at sampling rate of 500 Hz. The magnitude squared coherence were estimated from left vs right hemisphere of the brain that represents functional connectivity. The EEG coherence was the higher which shows the strong functional connectivity and fNIRS coherence was lower shows weak functional connectivity between left vs right hemisphere of the brain, during all the tasks and trials irrespective of the simulated space conditions. Further analysis of functional connectivity needed between the intra-regions of the brain.
- in arXiv: Computer Science: Neural and Evolutionary Computing on 2024-12-05 05:00:00 UTC.
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in arXiv: Quantitative Biology: Neurons and Cognition on 2024-12-06 05:00:00 UTC.
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- arXiv:2412.02894v1 Announce Type: new
-Abstract: Mathematical modeling is a powerful tool for describing, predicting, and understanding complex phenomena exhibited by real-world systems. However, identifying the equations that govern a system's dynamics from experimental data remains a significant challenge without a definitive solution. In this study, evolutionary computing techniques are presented to estimate the governing equations of a dynamical system using time-series data. The main approach is to propose polynomial equations with unknown coefficients, and subsequently perform a parametric estimation using genetic algorithms. Some of the main contributions of the present study are an adequate modification of the genetic algorithm to remove terms with minimal contributions, and a mechanism to escape local optima during the search. To evaluate the proposed method, we applied it to three dynamical systems: a linear model, a nonlinear model, and the Lorenz system. Our results demonstrate a reconstruction with an Integral Square Error below 0.22 and a coefficient of determination R-squared of 0.99 for all systems, indicating successful reconstruction of the governing dynamic equations.
+ arXiv:2412.04172v1 Announce Type: new
+Abstract: Neurons depend on two interdependent mechanisms-homeostasis and neuromodulation-to maintain robust and adaptable functionality. Homeostasis stabilizes neuronal activity by adjusting ionic conductances, whereas neuromodulation dynamically modifies ionic properties in response to external signals. Combining these mechanisms in conductance-based models often produces unreliable outcomes, particularly when sharp neuromodulation interferes with homeostatic tuning. This study explores how a biologically inspired neuromodulation controller can harmonize with homeostasis to ensure reliable neuronal function. Using computational models of stomatogastric ganglion and dopaminergic neurons, we demonstrate that controlled neuromodulation preserves neuronal firing patterns while maintaining intracellular calcium levels. Unlike sharp neuromodulation, the neuromodulation controller integrates activity-dependent feedback through mechanisms mimicking G-protein-coupled receptor cascades. The interaction between these controllers critically depends on the existence of an intersection in conductance space, representing a balance between target calcium levels and neuromodulated firing patterns. Maximizing neuronal degeneracy enhances the likelihood of such intersections, enabling robust modulation and compensation for channel blockades. We further show that this controller pairing extends to network-level activity, reliably modulating central pattern generators in crustaceans. These findings suggest that targeting neuromodulation pathways-rather than ion channels directly-may offer safer pharmacological strategies to manage neuronal dysfunctions. This study highlights the complementary roles of homeostasis and neuromodulation, proposing a unified control framework for maintaining robust and adaptive neural activity under physiological and pathological conditions.
- in arXiv: Computer Science: Neural and Evolutionary Computing on 2024-12-05 05:00:00 UTC.
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in arXiv: Quantitative Biology: Neurons and Cognition on 2024-12-06 05:00:00 UTC.
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- arXiv:2412.03013v1 Announce Type: new
-Abstract: In recent years, multimodal multiobjective optimization algorithms (MMOAs) based on evolutionary computation have been widely studied. However, existing MMOAs are mainly tested on benchmark function sets such as the 2019 IEEE Congress on Evolutionary Computation test suite (CEC 2019), and their performance on real-world problems is neglected. In this paper, two types of real-world multimodal multiobjective optimization problems in feature selection and location selection respectively are formulated. Moreover, four real-world datasets of Guangzhou, China are constructed for location selection. An investigation is conducted to evaluate the performance of seven existing MMOAs in solving these two types of real-world problems. An analysis of the experimental results explores the characteristics of the tested MMOAs, providing insights for selecting suitable MMOAs in real-world applications.
+ arXiv:2412.04191v1 Announce Type: new
+Abstract: Humans can perform exquisite sensorimotor skills, both individually and in teams, from athletes performing rhythmic gymnastics to everyday tasks like carrying a cup of coffee. The "predictive brain" framework suggests that mastering these tasks relies on predictive mechanisms, raising the question of how we deploy such predictions for real-time control and coordination. This review highlights two lines of research: one showing that during the control of complex objects people make the interaction with 'tools' predictable; the second one examines dyadic coordination showing that people make their behavior predictable for their partners. These studies demonstrate that to achieve sophisticated motor skills, we play "prediction tricks": we select subspaces of predictable solutions and make sensorimotor interactions more predictable and legible by and for others. This synthesis underscores the critical role of predictability in optimizing control strategies across various contexts and establishes a link between predictive processing and closed-loop control theories of behavior.
- in arXiv: Computer Science: Neural and Evolutionary Computing on 2024-12-05 05:00:00 UTC.
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in arXiv: Quantitative Biology: Neurons and Cognition on 2024-12-06 05:00:00 UTC.
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- arXiv:2412.03128v1 Announce Type: new
-Abstract: The study of plasticity in spiking neural networks is an active area of research. However, simulations that involve complex plasticity rules, dense connectivity/high synapse counts, complex neuron morphologies, or extended simulation times can be computationally demanding. The BrainScaleS-2 neuromorphic architecture has been designed to address this challenge by supporting "hybrid" plasticity, which combines the concepts of programmability and inherently parallel emulation. In particular, observables that are expensive in numerical simulation, such as per-synapse correlation measurements, are implemented directly in the synapse circuits. The evaluation of the observables, the decision to perform an update, and the magnitude of an update, are all conducted in a conventional program that runs simultaneously with the analog neural network. Consequently, these systems can offer a scalable and flexible solution in such cases. While previous work on the platform has already reported on the use of different kinds of plasticity, the descriptions for the spiking neural network experiment topology and protocol, and the plasticity algorithm have not been connected. In this work, we introduce an integrated framework for describing spiking neural network experiments and plasticity rules in a unified high-level experiment description language for the BrainScaleS-2 platform and demonstrate its use.
+ arXiv:2412.03613v1 Announce Type: cross
+Abstract: We prove a principle of linearized stability for traveling wave solutions to neural field equations posed on the real line. Additionally, we provide the existence of a finite dimensional invariant center manifold close to a traveling wave, this allows to study bifurcations of traveling waves. Finally, the spectral properties of the modulated traveling waves are investigated. Numerical schemes for the computation of modulated traveling waves are provided. We then apply these results and methods to study a neural field model in a inhibitory stabilized regime. We showcase Fold, Hopf and Bodgdanov-Takens bifurcations of traveling pulses. Additionally, we continue the modulated traveling pulses as function of the time scale ratio of the two neural populations and show numerical evidences for snaking of modulated traveling pulses.
- in arXiv: Computer Science: Neural and Evolutionary Computing on 2024-12-05 05:00:00 UTC.
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in arXiv: Quantitative Biology: Neurons and Cognition on 2024-12-06 05:00:00 UTC.
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- arXiv:2412.03129v1 Announce Type: new
-Abstract: Spiking neural networks (SNNs) emulated on dedicated neuromorphic accelerators promise to offer energy-efficient signal processing. However, the neuromorphic advantage over traditional algorithms still remains to be demonstrated in real-world applications. Here, we describe an intensity-modulation, direct-detection (IM/DD) task that is relevant to high-speed optical communication systems used in data centers. Compared to other machine learning-inspired benchmarks, the task offers several advantages. First, the dataset is inherently time-dependent, i.e., there is a time dimension that can be natively mapped to the dynamic evolution of SNNs. Second, small-scale SNNs can achieve the target accuracy required by technical communication standards. Third, due to the small scale and the defined target accuracy, the task facilitates the optimization for real-world aspects, such as energy efficiency, resource requirements, and system complexity.
+ arXiv:2412.04366v1 Announce Type: cross
+Abstract: Artificial intelligence (AI) systems capable of generating creative outputs are reshaping our understanding of creativity. This shift presents an opportunity for creativity researchers to reevaluate the key components of the creative process. In particular, the advanced capabilities of AI underscore the importance of studying the internal processes of creativity. This paper explores the neurobiological machinery that underlies these internal processes and describes the experiential component of creativity. It is concluded that although the products of artificial and human creativity can be similar, the internal processes are different. The paper also discusses how AI may negatively affect the internal processes of human creativity, such as the development of skills, the integration of knowledge, and the diversity of ideas.
- in arXiv: Computer Science: Neural and Evolutionary Computing on 2024-12-05 05:00:00 UTC.
+
in arXiv: Quantitative Biology: Neurons and Cognition on 2024-12-06 05:00:00 UTC.
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- arXiv:2412.03250v1 Announce Type: new
-Abstract: The integration of Large Language Models (LLMs) with evolutionary computation (EC) has introduced a promising paradigm for automating the design of metaheuristic algorithms. However, existing frameworks, such as the Large Language Model Evolutionary Algorithm (LLaMEA), often lack precise control over mutation mechanisms, leading to inefficiencies in solution space exploration and potentially suboptimal convergence. This paper introduces a novel approach to mutation control within LLM-driven evolutionary frameworks, inspired by theory of genetic algorithms. Specifically, we propose dynamic mutation prompts that adaptively regulate mutation rates, leveraging a heavy-tailed power-law distribution to balance exploration and exploitation. Experiments using GPT-3.5-turbo and GPT-4o models demonstrate that GPT-3.5-turbo fails to adhere to the specific mutation instructions, while GPT-4o is able to adapt its mutation based on the prompt engineered dynamic prompts. Further experiments show that the introduction of these dynamic rates can improve the convergence speed and adaptability of LLaMEA, when using GPT-4o. This work sets the starting point for better controlled LLM-based mutations in code optimization tasks, paving the way for further advancements in automated metaheuristic design.
+ arXiv:2112.14334v2 Announce Type: replace
+Abstract: In physics we often use very simple models to describe systems with many degrees of freedom, but it is not clear why or how this success can be transferred to the more complex biological context. We consider models for the joint distribution of many variables, as with the combinations of spiking and silence in large networks of neurons. In this probabilistic framework, we argue that simple models are possible if the mutual information between two halves of the system is consistently sub--extensive, and if this shared information is compressible. These conditions are not met generically, but they are met by real world data such as natural images and the activity in a population of retinal output neurons. We introduce compression strategies that combine the information bottleneck with an iteration scheme inspired by the renormalization group, and find that the number of parameters needed to describe the distribution of joint activity scales with the square of the number of neurons, even though the interactions are not well approximated as pairwise. Our results also show that this shared information is essentially equal to the information that individual neurons carry about natural visual inputs, which has surprising implications for the neural code.
- in arXiv: Computer Science: Neural and Evolutionary Computing on 2024-12-05 05:00:00 UTC.
+
in arXiv: Quantitative Biology: Neurons and Cognition on 2024-12-06 05:00:00 UTC.
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- arXiv:2412.02843v1 Announce Type: cross
-Abstract: \emph{Batch normalization} is a successful building block of neural network architectures. Yet, it is not well understood. A neural network layer with batch normalization comprises three components that affect the representation induced by the network: \emph{recentering} the mean of the representation to zero, \emph{rescaling} the variance of the representation to one, and finally applying a \emph{non-linearity}. Our work follows the work of Hadi Daneshmand, Amir Joudaki, Francis Bach [NeurIPS~'21], which studied deep \emph{linear} neural networks with only the rescaling stage between layers at initialization. In our work, we present an analysis of the other two key components of networks with batch normalization, namely, the recentering and the non-linearity. When these two components are present, we observe a curious behavior at initialization. Through the layers, the representation of the batch converges to a single cluster except for an odd data point that breaks far away from the cluster in an orthogonal direction. We shed light on this behavior from two perspectives: (1) we analyze the geometrical evolution of a simplified indicative model; (2) we prove a stability result for the aforementioned~configuration.
+ arXiv:2406.01107v3 Announce Type: replace
+Abstract: Normative models of brain structure estimate the effects of covariates such as age and sex using large samples of healthy controls. These models can then be applied to e.g. smaller clinical cohorts to distinguish disease effects from other covariates. However, these advanced statistical modelling approaches can be difficult to access, and processing large healthy cohorts is computationally demanding. Thus, accessible platforms with pre-trained normative models are needed.
+ We present such a platform for brain morphology analysis as an open-source web application (https://cnnplab.shinyapps.io/BrainMoNoCle/), with six key features: (i) user-friendly web interface, (ii) individual and group outputs, (iii) multi-site analysis, (iv) regional and whole-brain analysis, (v) integration with existing tools, and (vi) featuring multiple morphology metrics.
+ Using a diverse sample of 3,276 healthy controls across 21 sites, we pre-trained normative models on various metrics. We validated the models with a small sample of individuals with bipolar disorder, showing outputs that aligned closely with existing literature only after applying our normative modelling. Using a cohort of people with temporal lobe epilepsy, we showed that individual-level abnormalities were in line with seizure lateralisation. Finally, with the ability to investigate multiple morphology measures in the same framework, we found that biological covariates are better explained in specific morphology measures, and for applications, only some measures are sensitive to the disease process.
+ Our platform offers a comprehensive framework to analyse brain morphology in clinical and research settings. Validations confirm the superiority of normative models and the advantage of investigating a range of brain morphology metrics together.
- in arXiv: Computer Science: Neural and Evolutionary Computing on 2024-12-05 05:00:00 UTC.
+
in arXiv: Quantitative Biology: Neurons and Cognition on 2024-12-06 05:00:00 UTC.
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- arXiv:2406.08534v2 Announce Type: replace
-Abstract: This paper addresses the optimization of container unloading and loading operations at ports, integrating quay-crane dual-cycling with dockyard rehandle minimization. We present a unified model encompassing both operations: ship container unloading and loading by quay crane, and the other is reducing dockyard rehandles while loading the ship. We recognize that optimizing one aspect in isolation can lead to suboptimal outcomes due to interdependencies. Specifically, optimizing unloading sequences for minimal operation time may inadvertently increase dockyard rehandles during loading and vice versa. To address this NP-hard problem, we propose a hybrid genetic algorithm (GA) QCDC-DR-GA comprising one-dimensional and two-dimensional GA components. Our model, QCDC-DR-GA, consistently outperforms four state-of-the-art methods in maximizing dual cycles and minimizing dockyard rehandles. Compared to those methods, it reduced 15-20% of total operation time for large vessels. Statistical validation through a two-tailed paired t-test confirms the superiority of QCDC-DR-GA at a 5% significance level. The approach effectively combines QCDC optimization with dockyard rehandle minimization, optimizing the total unloading-loading time. Results underscore the inefficiency of separately optimizing QCDC and dockyard rehandles. Fragmented approaches, such as QCDC Scheduling Optimized by bi-level GA and GA-ILSRS (Scenario 2), show limited improvement compared to QCDC-DR-GA. As in GA-ILSRS (Scenario 1), neglecting dual-cycle optimization leads to inferior performance than QCDC-DR-GA. This emphasizes the necessity of simultaneously considering both aspects for optimal resource utilization and overall operational efficiency.
+ arXiv:2411.05712v2 Announce Type: replace-cross
+Abstract: When trained on large-scale object classification datasets, certain artificial neural network models begin to approximate core object recognition (COR) behaviors and neural response patterns in the primate visual ventral stream (VVS). While recent machine learning advances suggest that scaling model size, dataset size, and compute resources improve task performance, the impact of scaling on brain alignment remains unclear. In this study, we explore scaling laws for modeling the primate VVS by systematically evaluating over 600 models trained under controlled conditions on benchmarks spanning V1, V2, V4, IT and COR behaviors. We observe that while behavioral alignment continues to scale with larger models, neural alignment saturates. This observation remains true across model architectures and training datasets, even though models with stronger inductive bias and datasets with higher-quality images are more compute-efficient. Increased scaling is especially beneficial for higher-level visual areas, where small models trained on few samples exhibit only poor alignment. Finally, we develop a scaling recipe, indicating that a greater proportion of compute should be allocated to data samples over model size. Our results suggest that while scaling alone might suffice for alignment with human core object recognition behavior, it will not yield improved models of the brain's visual ventral stream with current architectures and datasets, highlighting the need for novel strategies in building brain-like models.
- in arXiv: Computer Science: Neural and Evolutionary Computing on 2024-12-05 05:00:00 UTC.
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in arXiv: Quantitative Biology: Neurons and Cognition on 2024-12-06 05:00:00 UTC.
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- arXiv:2408.17245v2 Announce Type: replace
-Abstract: Spiking Neural Networks (SNNs) seek to mimic the spiking behavior of biological neurons and are expected to play a key role in the advancement of neural computing and artificial intelligence. The conversion of Artificial Neural Networks (ANNs) to SNNs is the most widely used training method, which ensures that the resulting SNNs perform comparably to ANNs on large-scale datasets. The efficiency of these conversion-based SNNs is often determined by the neural coding schemes. Current schemes typically use spike count or timing for encoding, which is linearly related to ANN activations and increases the required number of time steps. To address this limitation, we propose a novel Canonic Signed Spike (CSS) coding scheme. This method incorporates non-linearity into the encoding process by weighting spikes at each step of neural computation, thereby increasing the information encoded in spikes. We identify the temporal coupling phenomenon arising from weighted spikes and introduce negative spikes along with a Ternary Self-Amplifying (TSA) neuron model to mitigate the issue. A one-step silent period is implemented during neural computation, achieving high accuracy with low latency. We apply the proposed methods to directly convert full-precision ANNs and evaluate performance on CIFAR-10 and ImageNet datasets. Our experimental results demonstrate that the CSS coding scheme effectively compresses time steps for coding and reduces inference latency with minimal conversion loss.
+ arXiv:2406.16453v2 Announce Type: replace-cross
+Abstract: The Wilson-Cowan model for metapopulation, a Neural Mass Network Model, treats different subcortical regions of the brain as connected nodes, with connections representing various types of structural, functional, or effective neuronal connectivity between these regions. Each region comprises interacting populations of excitatory and inhibitory cells, consistent with the standard Wilson-Cowan model. By incorporating stable attractors into such a metapopulation model's dynamics, we transform it into a learning algorithm capable of achieving high image and text classification accuracy. We test it on MNIST and Fashion MNIST, in combination with convolutional neural networks, on CIFAR-10 and TF-FLOWERS, and, in combination with a transformer architecture (BERT), on IMDB, always showing high classification accuracy. These numerical evaluations illustrate that minimal modifications to the Wilson-Cowan model for metapopulation can reveal unique and previously unobserved dynamics.
- in arXiv: Computer Science: Neural and Evolutionary Computing on 2024-12-05 05:00:00 UTC.
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in arXiv: Computer Science: Neural and Evolutionary Computing on 2024-12-06 05:00:00 UTC.
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- arXiv:2412.00295v2 Announce Type: replace
-Abstract: This paper explores the representational structure of linear Simple Cycle Reservoirs (SCR) operating at the edge of stability. We view SCR as providing in their state space feature representations of the input-driving time series. By endowing the state space with the canonical dot-product, we ``reverse engineer" the corresponding kernel (inner product) operating in the original time series space. The action of this time-series kernel is fully characterized by the eigenspace of the corresponding metric tensor. We demonstrate that when linear SCRs are constructed at the edge of stability, the eigenvectors of the time-series kernel align with the Fourier basis. This theoretical insight is supported by numerical experiments.
+ arXiv:2406.03054v2 Announce Type: replace
+Abstract: Networks of interconnected neurons communicating through spiking signals offer the bedrock of neural computations. Our brains spiking neural networks have the computational capacity to achieve complex pattern recognition and cognitive functions effortlessly. However, solving real-world problems with artificial spiking neural networks (SNNs) has proved to be difficult for a variety of reasons. Crucially, scaling SNNs to large networks and processing large-scale real-world datasets have been challenging, especially when compared to their non-spiking deep learning counterparts. The critical operation that is needed of SNNs is the ability to learn distributed representations from data and use these representations for perceptual, cognitive and memory operations. In this work, we introduce a novel SNN that performs unsupervised representation learning and associative memory operations leveraging Hebbian synaptic and activity-dependent structural plasticity coupled with neuron-units modelled as Poisson spike generators with sparse firing (~1 Hz mean and ~100 Hz maximum firing rate). Crucially, the architecture of our model derives from the neocortical columnar organization and combines feedforward projections for learning hidden representations and recurrent projections for forming associative memories. We evaluated the model on properties relevant for attractor-based associative memories such as pattern completion, perceptual rivalry, distortion resistance, and prototype extraction.
- in arXiv: Computer Science: Neural and Evolutionary Computing on 2024-12-05 05:00:00 UTC.
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in arXiv: Computer Science: Neural and Evolutionary Computing on 2024-12-06 05:00:00 UTC.
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- arXiv:2407.05650v2 Announce Type: replace-cross
-Abstract: Nets, cooperative networks of neurons, have been proposed as format for the representation of sensory signals, as physical implementation of the Gestalt phenomenon and as solution to the neural binding problem, while the direct interaction between nets by structure-sensitive matching has been proposed as basis for object-global operations such as object detection. The nets are flexibly composed of overlapping net fragments, which are learned from statistical regularities of sensory input. We here present the cooperative network architecture (CNA), a concrete model that learns such net structure to represent input patterns and deals robustly with noise, deformation, and out-of-distribution data, thus laying the groundwork for a novel neural architecture.
+ arXiv:2412.03676v1 Announce Type: new
+Abstract: We introduce JPC, a JAX library for training neural networks with Predictive Coding. JPC provides a simple, fast and flexible interface to train a variety of PC networks (PCNs) including discriminative, generative and hybrid models. Unlike existing libraries, JPC leverages ordinary differential equation solvers to integrate the gradient flow inference dynamics of PCNs. We find that a second-order solver achieves significantly faster runtimes compared to standard Euler integration, with comparable performance on a range of tasks and network depths. JPC also provides some theoretical tools that can be used to study PCNs. We hope that JPC will facilitate future research of PC. The code is available at https://github.com/thebuckleylab/jpc.
- in arXiv: Computer Science: Neural and Evolutionary Computing on 2024-12-05 05:00:00 UTC.
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in arXiv: Computer Science: Neural and Evolutionary Computing on 2024-12-06 05:00:00 UTC.
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- arXiv:2410.08026v2 Announce Type: replace-cross
-Abstract: Kolmogorov-Arnold Network (KAN) is a network structure recently proposed by Liu et al. (2024) that offers improved interpretability and a more parsimonious design in many science-oriented tasks compared to multi-layer perceptrons. This work provides a rigorous theoretical analysis of KAN by establishing generalization bounds for KAN equipped with activation functions that are either represented by linear combinations of basis functions or lying in a low-rank Reproducing Kernel Hilbert Space (RKHS). In the first case, the generalization bound accommodates various choices of basis functions in forming the activation functions in each layer of KAN and is adapted to different operator norms at each layer. For a particular choice of operator norms, the bound scales with the $l_1$ norm of the coefficient matrices and the Lipschitz constants for the activation functions, and it has no dependence on combinatorial parameters (e.g., number of nodes) outside of logarithmic factors. Moreover, our result does not require the boundedness assumption on the loss function and, hence, is applicable to a general class of regression-type loss functions. In the low-rank case, the generalization bound scales polynomially with the underlying ranks as well as the Lipschitz constants of the activation functions in each layer. These bounds are empirically investigated for KANs trained with stochastic gradient descent on simulated and real data sets. The numerical results demonstrate the practical relevance of these bounds.
+ arXiv:2412.03858v1 Announce Type: new
+Abstract: Expensive optimization problems (EOPs) are prevalent in real-world applications, where the evaluation of a single solution requires a significant amount of resources. In our study of surrogate-assisted evolutionary algorithms (SAEAs) in EOPs, we discovered an intriguing phenomenon. Because only a limited number of solutions are evaluated in each iteration, relying solely on these evaluated solutions for evolution can lead to reduced disparity in successive populations. This, in turn, hampers the reproduction operators' ability to generate superior solutions, thereby reducing the algorithm's convergence speed. To address this issue, we propose a strategic approach that incorporates high-quality, un-evaluated solutions predicted by surrogate models during the selection phase. This approach aims to improve the distribution of evaluated solutions, thereby generating a superior next generation of solutions. This work details specific implementations of this concept across various reproduction operators and validates its effectiveness using multiple surrogate models. Experimental results demonstrate that the proposed strategy significantly enhances the performance of surrogate-assisted evolutionary algorithms. Compared to mainstream SAEAs and Bayesian optimization algorithms, our approach incorporating the un-evaluated solution strategy shows a marked improvement.
- in arXiv: Computer Science: Neural and Evolutionary Computing on 2024-12-05 05:00:00 UTC.
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in arXiv: Computer Science: Neural and Evolutionary Computing on 2024-12-06 05:00:00 UTC.
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+ arXiv:2412.03981v1 Announce Type: new
+Abstract: We consider the issue of intensification/diversification balance in the context of a memetic algorithm for the multiobjective optimization of investment portfolios with cardinality constraints. We approach this issue in this work by considering the selective application of knowledge-augmented operators (local search and a memory of elite solutions) based on the search epoch in which the algorithm finds itself, hence alternating between unbiased search (guided uniquely by the built-in search mechanics of the algorithm) and focused search (intensified by the use of the problem-aware operators). These operators exploit Sharpe index (a measure of the relationship between return and risk) as a source of problem knowledge. We have conducted a sensibility analysis to determine in which phases of the search the application of these operators leads to better results. Our findings indicate that the resulting algorithm is quite robust in terms of parameterization from the point of view of this problem-specific indicator. Furthermore, it is shown that not only can other non-memetic counterparts be outperformed, but that there is a range of parameters in which the MA is also competitive when not better in terms of standard multiobjective performance indicators.
- in Journal of Neuroscience on 2024-12-04 17:29:55 UTC.
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in arXiv: Computer Science: Neural and Evolutionary Computing on 2024-12-06 05:00:00 UTC.
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- Area TE is required for normal learning of visual categories based on perceptual similarity. To evaluate whether category learning changes neural activity in area TE, we trained two monkeys (both male) implanted with multielectrode arrays to categorize natural images of cats and dogs. Neural activity during a passive viewing task was compared pre- and post-training. After the category training, the accuracy of abstract category decoding improved. Single units became more category selective, the proportion of single units with category selectivity increased, and units sustained their category-specific responses for longer. Visual category learning thus appears to enhance category separability in area TE by driving changes in the stimulus selectivity of individual neurons and by recruiting more units to the active network.
+ arXiv:2412.04184v1 Announce Type: new
+Abstract: Accurate modeling of eye gaze dynamics is essential for advancement in human-computer interaction, neurological diagnostics, and cognitive research. Traditional generative models like Markov models often fail to capture the complex temporal dependencies and distributional nuance inherent in eye gaze trajectories data. This study introduces a GAN framework employing LSTM and CNN generators and discriminators to generate high-fidelity synthetic eye gaze velocity trajectories. We conducted a comprehensive evaluation of four GAN architectures: CNN-CNN, LSTM-CNN, CNN-LSTM, and LSTM-LSTM trained under two conditions: using only adversarial loss and using a weighted combination of adversarial and spectral losses. Our findings reveal that the LSTM-CNN architecture trained with this new loss function exhibits the closest alignment to the real data distribution, effectively capturing both the distribution tails and the intricate temporal dependencies. The inclusion of spectral regularization significantly enhances the GANs ability to replicate the spectral characteristics of eye gaze movements, leading to a more stable learning process and improved data fidelity. Comparative analysis with an HMM optimized to four hidden states further highlights the advantages of the LSTM-CNN GAN. Statistical metrics show that the HMM-generated data significantly diverges from the real data in terms of mean, standard deviation, skewness, and kurtosis. In contrast, the LSTM-CNN model closely matches the real data across these statistics, affirming its capacity to model the complexity of eye gaze dynamics effectively. These results position the spectrally regularized LSTM-CNN GAN as a robust tool for generating synthetic eye gaze velocity data with high fidelity.
- in Journal of Neuroscience on 2024-12-04 17:29:55 UTC.
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in arXiv: Computer Science: Neural and Evolutionary Computing on 2024-12-06 05:00:00 UTC.
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- Although neurons release neurotransmitter before contact, the role for this release in synapse formation remains unclear. Cortical synapses do not require synaptic vesicle release for formation (Verhage et al., 2000; Sando et al., 2017; Sigler et al., 2017; Held et al., 2020), yet glutamate clearly regulates glutamate receptor trafficking (Roche et al., 2001; Nong et al., 2004) and induces spine formation (Engert and Bonhoeffer, 1999; Maletic-Savatic et al., 1999; Toni et al., 1999; Kwon and Sabatini, 2011; Oh et al., 2016). Using rat and murine culture systems to dissect molecular mechanisms, we found that glutamate rapidly decreases synapse density specifically in young cortical neurons in a local and calcium-dependent manner through decreasing N-methyl-d-aspartate receptor (NMDAR) transport and surface expression as well as cotransport with neuroligin (NL1). Adhesion between NL1 and neurexin 1 protects against this glutamate-induced synapse loss. Major histocompatibility I (MHCI) molecules are required for the effects of glutamate in causing synapse loss through negatively regulating NL1 levels in both sexes. Thus, like acetylcholine at the neuromuscular junction, glutamate acts as a dispersal signal for NMDARs and causes rapid synapse loss unless opposed by NL1-mediated trans-synaptic adhesion. Together, glutamate, MHCI, and NL1 mediate a novel form of homeostatic plasticity in young neurons that induces rapid changes in NMDARs to regulate when and where nascent glutamatergic synapses are formed.
+ arXiv:2412.03843v1 Announce Type: cross
+Abstract: Autonomous Driving Systems (ADSs) rely on Deep Neural Networks, allowing vehicles to navigate complex, open environments. However, the unpredictability of these scenarios highlights the need for rigorous system-level testing to ensure safety, a task usually performed with a simulator in the loop. Though one important goal of such testing is to detect safety violations, there are many undesirable system behaviors, that may not immediately lead to violations, that testing should also be focusing on, thus detecting more subtle problems and enabling a finer-grained analysis. This paper introduces Cooperative Co-evolutionary MEtamorphic test Generator for Autonomous systems (CoCoMEGA), a novel automated testing framework aimed at advancing system-level safety assessments of ADSs. CoCoMEGA combines Metamorphic Testing (MT) with a search-based approach utilizing Cooperative Co-Evolutionary Algorithms (CCEA) to efficiently generate a diverse set of test cases. CoCoMEGA emphasizes the identification of test scenarios that present undesirable system behavior, that may eventually lead to safety violations, captured by Metamorphic Relations (MRs). When evaluated within the CARLA simulation environment on the Interfuser ADS, CoCoMEGA consistently outperforms baseline methods, demonstrating enhanced effectiveness and efficiency in generating severe, diverse MR violations and achieving broader exploration of the test space. These results underscore CoCoMEGA as a promising, more scalable solution to the inherent challenges in ADS testing with a simulator in the loop. Future research directions may include extending the approach to additional simulation platforms, applying it to other complex systems, and exploring methods for further improving testing efficiency such as surrogate modeling.
- in Journal of Neuroscience on 2024-12-04 17:29:55 UTC.
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in arXiv: Computer Science: Neural and Evolutionary Computing on 2024-12-06 05:00:00 UTC.
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- While humans typically saccade every ~250 ms in natural settings, studies on vision tend to prevent or restrict eye movements. As it takes ~50 ms to initiate and execute a saccade, this leaves only ~200 ms to identify the fixated object and select the next saccade goal. How much detail can be derived about parafoveal objects in this short time interval, during which foveal processing and saccade planning both occur? Here, we had male and female human participants freely explore a set of natural images while we recorded magnetoencephalography and eye movements. Using multivariate pattern analysis, we demonstrate that future parafoveal images could be decoded at the feature and category level with peak decoding at ~110 and ~165 ms, respectively, while the decoding of fixated objects at the feature and category level peaked at ~100 and ~145 ms. The decoding of features and categories was contingent on the objects being saccade goals. In sum, we provide insight on the neuronal mechanism of presaccadic attention by demonstrating that feature- and category-specific information of foveal and parafoveal objects can be extracted in succession within a ~200 ms intersaccadic interval. These findings rule out strict serial or parallel processing accounts but are consistent with a pipeline mechanism in which foveal and parafoveal objects are processed in parallel but at different levels in the visual hierarchy.
+ arXiv:2412.04008v1 Announce Type: cross
+Abstract: This paper explores the potential of conversion-based neuromorphic algorithms for highly accurate and energy-efficient single-snapshot multidimensional harmonic retrieval (MHR). By casting the MHR problem as a sparse recovery problem, we devise the currently proposed, deep-unrolling-based Structured Learned Iterative Shrinkage and Thresholding (S-LISTA) algorithm to solve it efficiently using complex-valued convolutional neural networks with complex-valued activations, which are trained using a supervised regression objective. Afterward, a novel method for converting the complex-valued convolutional layers and activations into spiking neural networks (SNNs) is developed. At the heart of this method lies the recently proposed Few Spikes (FS) conversion, which is extended by modifying the neuron model's parameters and internal dynamics to account for the inherent coupling between real and imaginary parts in complex-valued computations. Finally, the converted SNNs are mapped onto the SpiNNaker2 neuromorphic board, and a comparison in terms of estimation accuracy and power efficiency between the original CNNs deployed on an NVIDIA Jetson Xavier and the SNNs is being conducted. The measurement results show that the converted SNNs achieve almost five-fold power efficiency at moderate performance loss compared to the original CNNs.
- in Journal of Neuroscience on 2024-12-04 17:29:55 UTC.
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in arXiv: Computer Science: Neural and Evolutionary Computing on 2024-12-06 05:00:00 UTC.
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- Behaving as desired requires selecting the appropriate behavior and inhibiting the selection of inappropriate behavior. This inhibitory function involves multiple processes, such as reactive and proactive inhibition, instead of a single process. In this study, two male macaque monkeys were required to perform a task in which they had to sequentially select (accept) or refuse (reject) a choice. Neural activity was recorded from the anterior striatum, which is considered to be involved in behavioral inhibition, focusing on the distinction between proactive and reactive inhibitions. We identified neurons with significant activity changes during the rejection of bad objects. Cluster analysis revealed three distinct groups, of which only one showed increased activity during object rejection, suggesting its involvement in proactive inhibition. This activity pattern was consistent irrespective of the rejection method, indicating a role beyond saccadic suppression. Furthermore, minimal activity changes during the fixation task indicated that these neurons were not primarily involved in reactive inhibition. In conclusion, these findings suggest that the anterior striatum plays a crucial role in cognitive control and orchestrates goal-directed behavior through proactive inhibition, which may be critical in understanding the mechanisms of behavioral inhibition dysfunction that occur in patients with basal ganglia disease.
+ arXiv:2412.04034v1 Announce Type: cross
+Abstract: Temporal Graph Learning (TGL) is crucial for capturing the evolving nature of stock markets. Traditional methods often ignore the interplay between dynamic temporal changes and static relational structures between stocks. To address this issue, we propose the Dynamic Graph Representation with Contrastive Learning (DGRCL) framework, which integrates dynamic and static graph relations to improve the accuracy of stock trend prediction. Our framework introduces two key components: the Embedding Enhancement (EE) module and the Contrastive Constrained Training (CCT) module. The EE module focuses on dynamically capturing the temporal evolution of stock data, while the CCT module enforces static constraints based on stock relations, refined within contrastive learning. This dual-relation approach allows for a more comprehensive understanding of stock market dynamics. Our experiments on two major U.S. stock market datasets, NASDAQ and NYSE, demonstrate that DGRCL significantly outperforms state-of-the-art TGL baselines. Ablation studies indicate the importance of both modules. Overall, DGRCL not only enhances prediction ability but also provides a robust framework for integrating temporal and relational data in dynamic graphs. Code and data are available for public access.
- in Journal of Neuroscience on 2024-12-04 17:29:55 UTC.
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in arXiv: Computer Science: Neural and Evolutionary Computing on 2024-12-06 05:00:00 UTC.
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- There is mounting evidence that the cerebellum impacts hippocampal functioning, but the impact of the cerebellum on hippocampal interneurons remains obscure. Using miniscopes in freely behaving male and female mice, we found optogenetic stimulation of Purkinje cells alters the calcium activity of a large percentage of CA1 interneurons. This includes both increases and decreases in activity. Remarkably, this bidirectional impact occurs in a coordinated fashion, in line with interneurons’ functional properties. Specifically, CA1 interneurons activated by cerebellar stimulation are commonly locomotion-active, while those inhibited by cerebellar stimulation are commonly rest-active interneurons. We additionally found that subsets of CA1 interneurons show altered activity during object investigations. Importantly, these interneurons also show coordinated modulation by cerebellar stimulation: CA1 interneurons that are activated by cerebellar stimulation are more likely to be activated, rather than inhibited, during object investigations, while interneurons that show decreased activity during cerebellar stimulation show the opposite profile. We examined two different stimulation locations (IV/V vermis or simplex) and two different stimulation approaches (7 Hz or a single 1 s light pulse)—in all cases, the cerebellum induces similar coordinated CA1 interneuron changes congruent with an explorative state. Overall, our data show that CA1 interneurons are impacted by cerebellar manipulation in a bidirectional and coordinated fashion and are therefore likely to play an important role in cerebello–hippocampal communication.
+ arXiv:2412.02482v2 Announce Type: replace-cross
+Abstract: In modern deep neural networks, the learning dynamics of the individual neurons is often obscure, as the networks are trained via global optimization. Conversely, biological systems build on self-organized, local learning, achieving robustness and efficiency with limited global information. We here show how self-organization between individual artificial neurons can be achieved by designing abstract bio-inspired local learning goals. These goals are parameterized using a recent extension of information theory, Partial Information Decomposition (PID), which decomposes the information that a set of information sources holds about an outcome into unique, redundant and synergistic contributions. Our framework enables neurons to locally shape the integration of information from various input classes, i.e. feedforward, feedback, and lateral, by selecting which of the three inputs should contribute uniquely, redundantly or synergistically to the output. This selection is expressed as a weighted sum of PID terms, which, for a given problem, can be directly derived from intuitive reasoning or via numerical optimization, offering a window into understanding task-relevant local information processing. Achieving neuron-level interpretability while enabling strong performance using local learning, our work advances a principled information-theoretic foundation for local learning strategies.
- in Journal of Neuroscience on 2024-12-04 17:29:55 UTC.
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in arXiv: Computer Science: Neural and Evolutionary Computing on 2024-12-06 05:00:00 UTC.
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- Animal vocalizations and human speech are typically characterized by a complex spectrotemporal structure, composed of multiple harmonics, and patterned as temporally organized sequences. However, auditory research often employed simple artificial acoustic stimuli or their combinations. Here we addressed the question of whether the neuronal responses to natural echolocation call sequences can be predicted by manipulated sequences of incomplete constituents at the midbrain inferior colliculus (IC). We characterized the extracellular single-unit activity of IC neurons in the great roundleaf bat, Hipposideros armiger (both sexes), using natural call sequences, various manipulated sequences of incomplete vocalizations, and pure tones. We report that approximately two-thirds of IC neurons exhibited a harmonic interaction. Neurons with high harmonic interactions exhibited greater selectivity to natural call sequences, and the degree of harmonic interaction was robust to the natural amplitude variations between call harmonics. For 81% of the IC neurons, the responses to the natural echolocation call sequence could not be predicted by altered sequences of missing call components. Surprisingly, nearly 70% of the neurons that showed a harmonic interaction were characterized by a single excitatory response peak as revealed by pure tones. Our results suggest that prevalent harmonic processing has already emerged in the auditory midbrain IC in the echolocating bat.
+ 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.
- in Journal of Neuroscience on 2024-12-04 17:29:55 UTC.
+
in eNeuro on 2024-12-05 17:30:15 UTC.
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- Mutations in SYNGAP1, a protein enriched at glutamatergic synapses, cause intellectual disability associated with epilepsy, autism spectrum disorder, and sensory dysfunctions. Several studies showed that Syngap1 regulates the time course of forebrain glutamatergic synapse maturation; however, the developmental role of Syngap1 in inhibitory GABAergic neurons is less clear. GABAergic neurons can be classified into different subtypes based on their morphology, connectivity, and physiological properties. Whether Syngap1 expression specifically in parvalbumin (PV)-expressing and somatostatin (SST)-expressing interneurons, which are derived from the medial ganglionic eminence (MGE), plays a role in the emergence of distinct brain functions remains largely unknown. We used genetic strategies to generate Syngap1 haploinsufficiency in (1) prenatal interneurons derived from the medial ganglionic eminence, (2) in postnatal PV cells, and (3) in prenatal SST interneurons. We further performed in vivo recordings and behavioral assays to test whether and how these different genetic manipulations alter brain function and behavior in mice of either sex. Mice with prenatal-onset Syngap1 haploinsufficiency restricted to Nkx2.1-expressing neurons show abnormal cortical oscillations and increased entrainment induced by 40 Hz auditory stimulation but lack stimulus-specific adaptation. This latter phenotype was reproduced in mice with Syngap1 haploinsufficiency restricted to PV, but not SST, interneurons. Prenatal-onset Syngap1 haploinsufficiency in Nkx2.1-expressing neurons led to impaired social behavior and inability to extinguish fear memories; however, neither postnatal PV- nor prenatal SST-specific mutant mice show these phenotypes. We speculate that Syngap1 haploinsufficiency in prenatal/perinatal PV interneurons may contribute to cortical activity and cognitive alterations associated with Syngap1 mutations.
+ 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.
- in Journal of Neuroscience on 2024-12-04 17:29:55 UTC.
+
in F1000Research on 2024-12-05 14:54:58 UTC.
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- In a real-world environment, the brain must integrate information from multiple sensory modalities, including the auditory and olfactory systems. However, little is known about the neuronal circuits governing how odors influence and modulate sound processing. Here, we investigated the mechanisms underlying auditory–olfactory integration using anatomical, electrophysiological, and optogenetic approaches, focusing on the auditory cortex as a key locus for cross-modal integration. First, retrograde and anterograde viral tracing strategies revealed a direct projection from the piriform cortex to the auditory cortex. Next, using in vivo electrophysiological recordings of neuronal activity in the auditory cortex of awake male or female mice, we found that odors modulate auditory cortical responses to sound. Finally, we used in vivo optogenetic manipulations during electrophysiology to demonstrate that olfactory modulation in the auditory cortex, specifically, odor-driven enhancement of sound responses, depends on direct input from the piriform cortex. Together, our results identify a novel role of piriform-to-auditory cortical circuitry in shaping olfactory modulation in the auditory cortex, shedding new light on the neuronal mechanisms underlying auditory–olfactory integration.
+ 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.
- in Journal of Neuroscience on 2024-12-04 17:29:55 UTC.
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in F1000Research on 2024-12-05 14:20:38 UTC.
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- Single-photon optogenetics enables precise, cell-type–specific modulation of neuronal circuits, making it a crucial tool in neuroscience. Its miniaturization in the form of fully implantable wide-field stimulator arrays enables long-term interrogation of cortical circuits and bears promise for brain–machine interfaces for sensory and motor function restoration. However, achieving selective activation of functional cortical representations poses a challenge, as studies show that targeted optogenetic stimulation results in activity spread beyond one functional domain. While recurrent network mechanisms contribute to activity spread, here we demonstrate with detailed simulations of isolated pyramidal neurons from cats of unknown sex that already neuron morphology causes a complex spread of optogenetic activity at the scale of one cortical column. Since the shape of a neuron impacts its optogenetic response, we find that a single stimulator at the cortical surface recruits a complex spatial distribution of neurons that can be inhomogeneous and vary with stimulation intensity and neuronal morphology across layers. We explore strategies to enhance stimulation precision, finding that optimizing stimulator optics may offer more significant improvements than the preferentially somatic expression of the opsin through genetic targeting. Our results indicate that, with the right optical setup, single-photon optogenetics can precisely activate isolated neurons at the scale of functional cortical domains spanning several hundred micrometers.
+ 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.
- in Journal of Neuroscience on 2024-12-04 17:29:55 UTC.
+
in PLoS Computational Biology on 2024-12-05 14:00:00 UTC.
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+ by Gene J. Yu, Federico Ranieri, Vincenzo Di Lazzaro, Marc A. Sommer, Angel V. Peterchev, Warren M. Grill
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+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.
- in Journal of Neuroscience on 2024-12-04 17:29:55 UTC.
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in PLoS Computational Biology on 2024-12-05 14:00:00 UTC.
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- The cortex immediately surrounding a brain ischemic lesion, the peri-infarct cortex (PIC), harbors a large part of the potential to recover lost functions. However, our understanding of the neurophysiological conditions in which synaptic plasticity operates remains limited. Here we hypothesized that the chronic imbalance between excitation and inhibition of the PIC prevents the normalization of the gamma rhythm, a waveband of neural oscillations thought to orchestrate action potential trafficking. Probing the local field potential activity of the forelimb primary sensory cortex (S1FL) located in the PIC of male adult mice, we found a constant, deep reduction of low-gamma oscillation power (L-gamma; 30–50 Hz) precisely during the critical time window for recovery (1–3 weeks after stroke). The collapse of L-gamma power negatively correlated with behavioral progress in affected forelimb use. Mapping astrocyte reactivity and GABA-like immunoreactivity in the PIC revealed a parallel high signal, which gradually increased when approaching the lesion. Increasing tonic inhibition with local infusion of GABA or by blocking its recapture reduced L-gamma oscillation power in a magnitude similar to stroke. Conversely, the negative allosteric modulation of tonic GABA conductance using L655,708 or the gliopeptide ODN rescued the L-gamma power of the PIC. Altogether the present data point out that the chronic excess of ambient GABA in the PIC limits the generation of L-gamma oscillations in the repairing cortex and suggests that rehabilitative interventions aimed at normalizing low-gamma power within the critical period of stroke recovery could optimize the restitution of lost functions.
+ 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.
- in Journal of Neuroscience on 2024-12-04 17:29:55 UTC.
+
in PLoS Computational Biology on 2024-12-05 14:00:00 UTC.
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- In the anterior area of the mouth, the interdental papilla is important for dental hygiene and appearance. When it disappears, unpleasant “black triangles” form, which affects patients’ self-confidence in their smiles and makes oral hygiene more difficult. The loss of interdental papilla is caused by several variables such as tooth shape, periodontal disease, and aging. Although surgical treatments have been utilized to restore or retain missing papilla, their predictability remains unknown. In response, researchers have investigated non-invasive procedures, such as the use of fillers such as hyaluronic acid (HA). Owing to its capacity to increase tissue volume and bind water, HA, a naturally occurring polysaccharide with special rheological qualities, has become a popular choice for use as a dermal filler. It shows promise when used to cure interdental papilla loss; the effects usually last for six–12 months. This review article explores the development and history of papilla rebuilding methods, emphasizing hyaluronic acid as a cutting-edge and successful method for regaining both periodontal health and aesthetics.
+ 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%.
- in F1000Research on 2024-12-04 15:34:29 UTC.
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in PLoS Computational Biology on 2024-12-05 14:00:00 UTC.
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- The splenic localization of hydatid cysts is extremely rare. A 50-year-old obese female who consults with a painful and febrile syndrome of the right hypochondrium. Abdominal ultrasound and a CT scan computed tomography revealed a complete situs inversus, a mass of the right hypochondrium measuring 152 mm with membrane detachment, and infiltration of the surrounding fat, evoking a type II complicated splenic hydatic cyst. The patient was operated on in an emergency via midline laparotomy. Exploration revealed situs inversus, an angiant cyst of the spleen. Exposition of the splenic pedicle is difficult. The samples were then infected. Total splenectomy was performed. The postoperative period was unproblematic, and the patient was discharged with antibiotic and antiparasitic treatment and habitual vaccination.
+ 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.
- in F1000Research on 2024-12-04 15:24:57 UTC.
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in PLoS Biology on 2024-12-05 14:00:00 UTC.
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- Abstract* Background This study examines the influence of auxiliary lighting configurations and artificial surface textures on the quality of 3D models generated using Structure from Motion (SfM) in an indoor laboratory setting. Method Experiments were conducted by capturing images of concrete, metal, and wooden specimens at a one-meter distance. Various lighting setups, including vertical and adjacent auxiliary lighting models, were tested to determine their impact on model accuracy. In addition, complex artificial textures, such as checkerboard patterns, were applied to the specimens to assess their effect on 3D model precision. Results Our results demonstrate that optimal lighting and artificial textures significantly enhance the accuracy of 3D models, especially for materials with uniform textures, such as painted metal. For materials with more varied textures, such as concrete and wood, improvements were notable but less pronounced. The combination of auxiliary lighting and artificial textures improved model quality by approximately 40% for high-texture materials and up to 60% for uniform-texture materials. Furthermore, the study highlights the role of image file formats in the SfM process. While RAW images stored in TIFF format offered a slight advantage over lossless JPEG in terms of model accuracy, the difference may not be substantial enough to justify the larger file size in situations where submillimeter precision is not required. Conclusions Overall, our findings emphasize the importance of tailored lighting and texturing strategies for achieving high-precision 3D models in SfM applications. These results are particularly relevant for structural testing and other applications that demand high-fidelity 3D reconstructions, providing a foundation for more accurate and reliable models.
+ by Kota Ishibashi, Yuichi Shichino, Peixun Han, Kimi Wakabayashi, Mari Mito, Toshifumi Inada, Seisuke Kimura, Shintaro Iwasaki, Yuichiro Mishima
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+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.
- in F1000Research on 2024-12-04 15:12:23 UTC.
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in PLoS Biology on 2024-12-05 14:00:00 UTC.
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- Olive (Olea europaea Linaeus 1753) is one of the valuable fruit trees and very important edible oil plant in the world. The chloroplast (cp) genome of an olive tree (Olea europaea) from the southern Peruvian arid coast was obtained for the first time. Genomic DNA of high quality was used to generate librarieswith Illumina Hiseq paired-end methods. The cp genome is 155,886 pb in length and contains a large single-copy region (LSC) of 86,610 pb and a small single copy region (SSC) of 17,790 pb separated by two inverted repeat (IR) regions (25,741bp). The cp genome of olive contains 124 genes that consists of 80 protein-coding genes, 36 tRNA, eight rRNA. Phylogenetic analysis showed this olive tree is sister to O. europaea subsp. maroccana (Oleeae tribe). This study presents the first overview of the chloroplast genome organization and phylogenetics of O. europaea, offering valuable insights for genetic and evolutionary research in the genus Olea.
+ by Grant Kinsler, Yuping Li, Gavin Sherlock, Dmitri A. Petrov
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+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.
- in F1000Research on 2024-12-04 15:02:23 UTC.
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in PLoS Biology on 2024-12-05 14:00:00 UTC.
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- Background Cardiovascular disease (CVD) is a leading cause of death worldwide. Ischemic heart disease is a major cause of morbidity and mortality. Lack of blood supply to the brain can cause tissue death if any of the cerebral veins, carotid arteries, or vertebral arteries are blocked. An ischemic stroke describes this type of event. One of the byproducts of methionine metabolism, the demethylation of methionine, is homocysteine, an amino acid that contains sulfur. During myocardial ischemia, the plasma level of homocysteine (Hcy) increases and plays a role in many methylation processes. Hyperhomocysteinemia has only recently been recognized as a major contributor to the increased risk of cardiovascular disease (CVD) owing to its effects on atherothrombosis and improvement of oxidative stress-induced endothelial dysfunction, joining the ranks of other known risk factors such as hyperlipidemia, hypertension, diabetes, and advanced age. Objective The purpose of this study was to determine whether there is a relationship between elevated serum total homocysteine (tHcy) levels and an increased risk of coronary artery disease (CAD) in an Iraqi population of patients with ischemic heart disease. Methods This study was conducted at Madinat al-Imamain Al Kadhmain Hospital’s Cardiology Department in Baghdad, Iraq. The study lasted for six months and was designed as an observational case-control study from November 1, 2023, to April 1, 2024. Results Cases and controls had similar characteristics but differed significantly in serum homocysteine concentration. The mean homocysteine level in case group was 40.21±14.47 mmol/L and 9.23±2.41 mmol/L in control group with p value <0.001. Conclusion In young individuals, hyperhomocysteinemia is positively associated with coronary artery, even when other traditional risk factors are not present.
+ 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
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+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.
- in F1000Research on 2024-12-04 14:48:31 UTC.
+
in PLoS Biology on 2024-12-05 14:00:00 UTC.
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- by Niloufar Abhari, Caroline Colijn, Arne Mooers, Paul Tupper
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-Diversity plays an important role in various domains, including conservation, whether it describes diversity within a population or diversity over a set of species. While various strategies for measuring among-species diversity have emerged (e.g. Phylogenetic Diversity (PD), Split System Diversity (SSD) and entropy-based methods), extensions to populations are rare. An understudied problem is how to assess the diversity of a collection of populations where each has its own internal diversity. Relying solely on measures that treat each population as a monomorphic lineage (like a species) can be misleading. To address this problem, we present four population-level diversity assessment approaches: Pooling, Averaging, Pairwise Differencing, and Fixing. These approaches can be used to extend any diversity measure that is primarily defined for a group of individuals to a collection of populations. We then apply the approaches to two measures of diversity that have been used in conservation—Heterozygosity (Het) and Split System Diversity (SSD)—across a dataset comprising SNP data for 50 anadromous Atlantic salmon populations. We investigate agreement and disagreement between these measures of diversity when used to identify optimal sets of populations for conservation, on both the observed data, and randomized and simulated datasets. The similarity and differences of the maximum-diversity sets as well as the pairwise correlations among our proposed measures emphasize the need to clearly define what aspects of biodiversity we aim to both measure and optimize, to ensure meaningful and effective conservation decisions.
+ 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.
- in PLoS Computational Biology on 2024-12-04 14:00:00 UTC.
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in F1000Research on 2024-12-05 13:56:58 UTC.
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- by Henri Schmidt, Benjamin J. Raphael
-Motivation DNA sequencing of multiple bulk samples from a tumor provides the opportunity to investigate tumor heterogeneity and reconstruct a phylogeny of a patient’s cancer. However, since bulk DNA sequencing of tumor tissue measures thousands of cells from a heterogeneous mixture of distinct sub-populations, accurate reconstruction of the tumor phylogeny requires simultaneous deconvolution of cancer clones and inference of ancestral relationships, leading to a challenging computational problem. Many existing methods for phylogenetic reconstruction from bulk sequencing data do not scale to large datasets, such as recent datasets containing upwards of ninety samples with dozens of distinct sub-populations.
Results We develop an approach to reconstruct phylogenetic trees from multi-sample bulk DNA sequencing data by separating the reconstruction problem into two parts: a structured regression problem for a fixed tree T, and an optimization over tree space. We derive an algorithm for the regression sub-problem by exploiting the unique, combinatorial structure of the matrices appearing within the problem. This algorithm has both asymptotic and empirical improvements over linear programming (LP) approaches to the problem. Using our algorithm for this regression sub-problem, we develop fastBE, a simple method for phylogenetic inference from multi-sample bulk DNA sequencing data. We demonstrate on simulated data with hundreds of samples and upwards of a thousand distinct sub-populations that fastBE outperforms existing approaches in terms of reconstruction accuracy, sample efficiency, and runtime. Owing to its scalability, fastBE enables both phylogenetic reconstruction directly from indvidual mutations without requiring the clustering of mutations into clones, as well as a new phylogeny constrained mutation clustering algorithm. On real data from fourteen B-progenitor acute lymphoblastic leukemia patients, fastBE infers mutation phylogenies with fewer violations of a widely used evolutionary constraint and better agreement to the observed mutational frequencies. Using our phylogeny constrained mutation clustering algorithm, we also find mutation clusters with lower distortion compared to state-of-the-art approaches. Finally, we show that on two patient-derived colorectal cancer models, fastBE infers mutation phylogenies with less violation of a widely used evolutionary constraint compared to existing methods.
+ 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.
- in PLoS Computational Biology on 2024-12-04 14:00:00 UTC.
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in F1000Research on 2024-12-05 12:15:52 UTC.
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- by Max Grogan, Kyle P. Blum, Yufei Wu, J. Alex Harston, Lee E. Miller, A. Aldo Faisal
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-Proprioception is one of the least understood senses, yet fundamental for the control of movement. Even basic questions of how limb pose is represented in the somatosensory cortex are unclear. We developed a topographic variational autoencoder with lateral connectivity (topo-VAE) to compute a putative cortical map from a large set of natural movement data. Although not fitted to neural data, our model reproduces two sets of observations from monkey centre-out reaching: 1. The shape and velocity dependence of proprioceptive receptive fields in hand-centered coordinates despite the model having no knowledge of arm kinematics or hand coordinate systems. 2. The distribution of neuronal preferred directions (PDs) recorded from multi-electrode arrays. The model makes several testable predictions: 1. Encoding across the cortex has a blob-and-pinwheel-type geometry of PDs. 2. Few neurons will encode just a single joint. Our model provides a principled basis for understanding of sensorimotor representations, and the theoretical basis of neural manifolds, with applications to the restoration of sensory feedback in brain-computer interfaces and the control of humanoid robots.
+ 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.
- in PLoS Computational Biology on 2024-12-04 14:00:00 UTC.
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in F1000Research on 2024-12-05 11:59:33 UTC.
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- by Malthe S. Nordentoft, Naoya Takahashi, Mathias S. Heltberg, Mogens H. Jensen, Rune N. Rasmussen, Athanasia Papoutsi
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-During neuronal activity, the extracellular concentration of potassium ions ([K+]o) increases substantially above resting levels, yet it remains unclear what role these [K+]o changes play in the dendritic integration of synaptic inputs. We here used mathematical formulations and biophysical modeling to explore the role of synaptic activity-dependent K+ changes in dendritic segments of a visual cortex pyramidal neuron, receiving inputs tuned to stimulus orientation. We found that the spatial arrangement of inputs dictates the magnitude of [K+]o changes in the dendrites: Dendritic segments receiving similarly tuned inputs can attain substantially higher [K+]o increases than segments receiving diversely tuned inputs. These [K+]o elevations in turn increase dendritic excitability, leading to more robust and prolonged dendritic spikes. Ultimately, these local effects amplify the gain of neuronal input–output transformations, causing higher orientation-tuned somatic firing rates without compromising orientation selectivity. Our results suggest that local, activity-dependent [K+]o changes in dendrites may act as a “volume knob” that determines the impact of synaptic inputs on feature-tuned neuronal firing.
+ 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.
- in PLoS Biology on 2024-12-04 14:00:00 UTC.
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in F1000Research on 2024-12-05 11:25:27 UTC.
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- Background Fuzzy sets and ideals play a significant role in the study of algebraic structures, particularly in the context of pseudo-TM algebras, which are non-commutative generalizations of MV-algebras. However, the concept of fuzzy pseudo-ideals within these algebras has not been extensively explored. This paper introduces fuzzy pseudo-ideals in pseudo-TM algebras and investigates their key properties, contributing to the broader understanding of fuzzy algebraic structures. Methods We define fuzzy pseudo-ideals in the framework of pseudo-TM algebras and investigate their properties using level sets. The paper employs techniques from algebraic logic and set theory to characterize fuzzy pseudo-ideals and their interactions with homomorphism’s and Cartesian products. Several theorems are developed to establish the closure of fuzzy pseudo-ideals under intersection, and their relationships with homomorphism’s and Cartesian products are explored. Results The main findings include a comprehensive characterization of fuzzy pseudo-ideals in pseudo-TM algebras, both in terms of their algebraic structure and their behavior under intersections. We also show how these fuzzy pseudo-ideals interact with homomorphism’s and Cartesian products. Concrete examples are provided to illustrate the theoretical results, demonstrating the applicability of the concepts to real-world algebraic problems. Conclusions This research enhances the theoretical understanding of fuzzy sets and ideals within pseudo-TM algebras, offering new insights into their properties and interrelationships. The results pave the way for future work, particularly in extending the concepts to fuzzy pseudo-strong ideals and fuzzy pseudo-TM ideals. These extensions could further advance the study of fuzzy algebraic structures, contributing to the broader field of algebraic logic and fuzzy set theory.
+ 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.
- in F1000Research on 2024-12-04 10:43:46 UTC.
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in F1000Research on 2024-12-05 11:23:59 UTC.
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- Background Fenugreek, or Trigonella foenum-graecum L, is an edible and medicinal plant of the Fabaceae family. Fenugreek seeds are rich in proteins, lipids, and essential nutrients, and they also contain various phytochemicals, including flavonoids, steroidal saponins, coumarin, and alkaloids such as trigonelline. Trigonelline (TG) is a bioactive plant alkaloid initially extracted from fenugreek seeds. A substantial portion of fenugreek’s health benefits may rely on the presence of TG. This study addresses the critical need for a fast, green, and economical method that overcomes inefficiencies, high solvent usage, and sensitivity limitations in the quantification of TG. Methods Fenugreek seeds from various origins were extracted using three green solvents: acetone (ACt), ethanol (EtOH), and water (H2O). The UPLC-MS/MS method was developed and validated using a green mobile phase of H2O: EtOH, and an r2-value of 0.999 in the linearity range of 0.1-500 ppb was adopted. The method was validated with an accuracy of 98.6% for trace analysis of TG using a small amount (10 mg) of fenugreek samples from five different origins. Results The average extract yield was 5.36 mg/100 mg with a standard deviation (SD) of 6.3, with the highest extract yield observed in H2O. The ESI (+ve) of the UPLC-MS/MS resulted in the fragmentation pattern (m/z) 138→94.10→92.05→78.20. The TG quantification revealed an average TG concentration of 181.4 ppb (SD = 176.4), with the highest amount of TG in H2O extract (mean = 392.7, SD = 132.4 ppb), followed by EtOH (mean = 91.9, SD = 83.3 ppb) and ACt (mean = 59.5, SD = 30.9 ppb). The TG amount observed in the validation step substantiated the efficiency and reproducibility of the developed method. Conclusions The method may be used as an effective tool for a green, rapid, economical, and eco-friendly extraction and quantification of TG in diverse matrices of pharmaceutical, cosmeceutical, herbal, and food products.
+ 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.
- in F1000Research on 2024-12-04 10:40:53 UTC.
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- Science Advances, Volume 10, Issue 49, December 2024.
+ 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.
- in Science Advances on 2024-12-04 08:00:00 UTC.
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- Science Advances, Volume 10, Issue 49, December 2024.
+ Science, Volume 386, Issue 6726, December 2024.
- in Science Advances on 2024-12-04 08:00:00 UTC.
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- Science Advances, Volume 10, Issue 49, December 2024.
+ Science, Volume 386, Issue 6726, December 2024.
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- Science Advances, Volume 10, Issue 49, December 2024.
+ Science, Volume 386, Issue 6726, Page 1100-1100, December 2024.
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- Science Advances, Volume 10, Issue 49, December 2024.
+ Science, Volume 386, Issue 6726, Page 1098-1099, December 2024.
- in Science Advances on 2024-12-04 08:00:00 UTC.
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- Science Advances, Volume 10, Issue 49, December 2024.
+ Science, Volume 386, Issue 6726, Page 1146-1153, December 2024.
- in Science Advances on 2024-12-04 08:00:00 UTC.
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- Science Advances, Volume 10, Issue 49, December 2024.
+ Science, Volume 386, Issue 6726, Page 1173-1178, December 2024.
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- Science Advances, Volume 10, Issue 49, December 2024.
+ Science, Volume 386, Issue 6726, Page 1154-1161, December 2024.
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- Science Advances, Volume 10, Issue 49, December 2024.
+ Science, Volume 386, Issue 6726, Page 1123-1128, December 2024.
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- Science Advances, Volume 10, Issue 49, December 2024.
+ Science, Volume 386, Issue 6726, Page 1117-1122, December 2024.
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- Science Advances, Volume 10, Issue 49, December 2024.
+ Science, Volume 386, Issue 6726, Page 1161-1168, December 2024.
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- Science Advances, Volume 10, Issue 49, December 2024.
+ Science, Volume 386, Issue 6726, Page 1141-1146, December 2024.
- in Science Advances on 2024-12-04 08:00:00 UTC.
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- Science Advances, Volume 10, Issue 49, December 2024.
+ Science, Volume 386, Issue 6726, Page 1112-1117, December 2024.
- in Science Advances on 2024-12-04 08:00:00 UTC.
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- Science Advances, Volume 10, Issue 49, December 2024.
+ Science, Volume 386, Issue 6726, Page 1128-1134, December 2024.
- in Science Advances on 2024-12-04 08:00:00 UTC.
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- Science Advances, Volume 10, Issue 49, December 2024.
+ Science, Volume 386, Issue 6726, Page 1135-1141, December 2024.
- in Science Advances on 2024-12-04 08:00:00 UTC.
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- Science Advances, Volume 10, Issue 49, December 2024.
+ Science, Volume 386, Issue 6726, Page 1182-1182, December 2024.
- in Science Advances on 2024-12-04 08:00:00 UTC.
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- Science Advances, Volume 10, Issue 49, December 2024.
+ Science, Volume 386, Issue 6726, Page 1105-1106, December 2024.
- in Science Advances on 2024-12-04 08:00:00 UTC.
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- Science Advances, Volume 10, Issue 49, December 2024.
+ Science, Volume 386, Issue 6726, Page 1091-1092, December 2024.
- in Science Advances on 2024-12-04 08:00:00 UTC.
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- Science Advances, Volume 10, Issue 49, December 2024.
+ Science, Volume 386, Issue 6726, Page 1094-1095, December 2024.
- in Science Advances on 2024-12-04 08:00:00 UTC.
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- Science Advances, Volume 10, Issue 49, December 2024.
+ Science, Volume 386, Issue 6726, Page 1090-1091, December 2024.
- in Science Advances on 2024-12-04 08:00:00 UTC.
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- Science Advances, Volume 10, Issue 49, December 2024.
+ Science, Volume 386, Issue 6726, Page 1093-1094, December 2024.
- in Science Advances on 2024-12-04 08:00:00 UTC.
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- Science Advances, Volume 10, Issue 49, December 2024.
+ Science, Volume 386, Issue 6726, Page 1103-1103, December 2024.
- in Science Advances on 2024-12-04 08:00:00 UTC.
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- Science Advances, Volume 10, Issue 49, December 2024.
+ Science, Volume 386, Issue 6726, Page 1102-1103, December 2024.
- in Science Advances on 2024-12-04 08:00:00 UTC.
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- Science Advances, Volume 10, Issue 49, December 2024.
+ Science, Volume 386, Issue 6726, Page 1081-1081, December 2024.
- in Science Advances on 2024-12-04 08:00:00 UTC.
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- Science Advances, Volume 10, Issue 49, December 2024.
+ Science, Volume 386, Issue 6726, Page 1078-1079, December 2024.
- in Science Advances on 2024-12-04 08:00:00 UTC.
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- Science Advances, Volume 10, Issue 49, December 2024.
+ Science, Volume 386, Issue 6726, Page 1080-1081, December 2024.
- in Science Advances on 2024-12-04 08:00:00 UTC.
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- Science Advances, Volume 10, Issue 49, December 2024.
+ Science, Volume 386, Issue 6726, Page 1082-1082, December 2024.
- in Science Advances on 2024-12-04 08:00:00 UTC.
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- Science Advances, Volume 10, Issue 49, December 2024.
+ Science, Volume 386, Issue 6726, Page 1083-1083, December 2024.
- in Science Advances on 2024-12-04 08:00:00 UTC.
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- Science Advances, Volume 10, Issue 49, December 2024.
+ Science, Volume 386, Issue 6726, Page 1084-1085, December 2024.
- in Science Advances on 2024-12-04 08:00:00 UTC.
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- Science Advances, Volume 10, Issue 49, December 2024.
+ Science, Volume 386, Issue 6726, Page 1085-1086, December 2024.
- in Science Advances on 2024-12-04 08:00:00 UTC.
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- Science Advances, Volume 10, Issue 49, December 2024.
+ Science, Volume 386, Issue 6726, Page 1087-1089, December 2024.
- in Science Advances on 2024-12-04 08:00:00 UTC.
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- Lopes-Bastos et al. report that melanoma in zebrafish initiates without telomerase (or ALT) activation. However, in late progression, telomerase becomes essential for sustained tumor growth. Tumors that fail to re-activate telomerase slow down growth and even regress. This occurs due to tumor-autonomous (genomic instability) and non-tumor-autonomous (immune response) mechanisms.
+ Science, Volume 386, Issue 6726, Page 1073-1073, December 2024.
- in Cell Reports: Current Issue on 2024-12-04 00:00:00 UTC.
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- Revenu et al. show the function of myosin 1b (Myo1b) in intestinal epithelia. In human cells, MYO1B is part of the UNC45A interactome and contributes to lumenogenesis by modulating spindle orientation in vitro. In zebrafish Myo1b is important for intestinal epithelium folding during the development of the intestinal bulb.
+ Science, Volume 386, Issue 6726, Page 1179-1179, December 2024.
- in Cell Reports: Current Issue on 2024-12-04 00:00:00 UTC.
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- Coren et al. show that in skeletal muscles, fibroblasts diversify into distinct subpopulations during embryonic development. These subpopulations reside in distinct niches, entail different dynamics and transcriptomes, and exert opposing effects on myogenic differentiation. This diversification process is dependent on muscle contraction in the embryo.
+ Science, Volume 386, Issue 6726, Page 1096-1097, December 2024.
- in Cell Reports: Current Issue on 2024-12-04 00:00:00 UTC.
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- Ariura et al. performed a comprehensive analysis of Piwi-associated RNAs to decipher the targeting rules of Drosophila Piwi. These rules explain how Piwi distinguishes TEs from mRNAs and reveal that transcriptional and post-transcriptional silencing is controlled by surprisingly similar rules despite vastly different modes of repression.
+ Science, Volume 386, Issue 6726, Page 1104-1106, December 2024.
- in Cell Reports: Current Issue on 2024-12-04 00:00:00 UTC.
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- Brain rhythms can facilitate neural communication for the maintenance of brain function. Beta rhythms (13–35 Hz) have been proposed to serve multiple domains of human ability, including motor control, cognition, memory, and emotion, but the overarching organisational principles remain unknown. To uncover the circuit architecture of beta oscillations, we leverage normative brain data, analysing over 30 hr of invasive brain signals from 1772 channels from cortical areas in epilepsy patients, to demonstrate that beta is the most distributed cortical brain rhythm. Next, we identify a shared brain network from beta-dominant areas with deeper brain structures, like the basal ganglia, by mapping parametrised oscillatory peaks to whole-brain functional and structural MRI connectomes. Finally, we show that these networks share significant overlap with dopamine uptake as indicated by positron emission tomography. Our study suggests that beta oscillations emerge in cortico-subcortical brain networks that are modulated by dopamine. It provides the foundation for a unifying circuit-based conceptualisation of the functional role of beta activity beyond the motor domain and may inspire an extended investigation of beta activity as a feedback signal for closed-loop neurotherapies for dopaminergic disorders.
+ Science, Volume 386, Issue 6726, Page 1102-1102, December 2024.
- in eLife on 2024-12-04 00:00:00 UTC.
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- Signaling through the platelet-derived growth factor receptor alpha (PDGFRα) plays a critical role in craniofacial development. Phosphatidylinositol 3-kinase (PI3K)/Akt is the primary effector of PDGFRα signaling during mouse skeletal development. We previously demonstrated that Akt phosphorylates the RNA-binding protein serine/arginine-rich splicing factor 3 (Srsf3) downstream of PI3K-mediated PDGFRα signaling in mouse embryonic palatal mesenchyme (MEPM) cells, leading to its nuclear translocation. We further showed that ablation of Srsf3 in the murine neural crest lineage results in severe midline facial clefting and widespread alternative RNA splicing (AS) changes. Here, we demonstrated via enhanced UV-crosslinking and immunoprecipitation of MEPM cells that PDGF-AA stimulation leads to preferential binding of Srsf3 to exons and loss of binding to canonical Srsf3 CA-rich motifs. Through the analysis of complementary RNA-seq data, we showed that Srsf3 activity results in the preferential inclusion of exons with increased GC content and lower intron to exon length ratio. We found that Srsf3 activity downstream of PDGFRα signaling leads to retention of the receptor in early endosomes and increases in downstream PI3K-mediated Akt signaling. Taken together, our findings reveal that growth factor-mediated phosphorylation of an RNA-binding protein underlies gene expression regulation necessary for mammalian craniofacial development.
+ Science, Volume 386, Issue 6726, Page 1102-1102, December 2024.
- in eLife on 2024-12-04 00:00:00 UTC.
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- As the early step of food ingestion, the swallow is under rigorous sensorimotor control. Nevertheless, the mechanisms underlying swallow control at a molecular and circuitry level remain largely unknown. Here, we find that mutation of the mechanotransduction channel genes nompC, Tmc, or piezo impairs the regular pumping rhythm of the cibarium during feeding of the fruit fly Drosophila melanogaster. A group of multi-dendritic mechanosensory neurons, which co-express the three channels, wrap the cibarium and are crucial for coordinating the filling and emptying of the cibarium. Inhibition of them causes difficulty in food emptying in the cibarium, while their activation leads to difficulty in cibarium filling. Synaptic and functional connections are detected between the pharyngeal mechanosensory neurons and the motor circuit that controls swallow. This study elucidates the role of mechanosensation in swallow, and provides insights for a better understanding of the neural basis of food swallow.
+ In Box 2 in the print and online PDF versions of the article, there was a mistake in the indexing of one of the matrices. Specifically, both instances of the equation Wjkli = DkjiDlji should read instead as: Wjkli = DkjiDkli, were k is the index of the dendritic compartment, and j and l are indices of the connected neurons. The authors apologize for this oversight.
- in eLife on 2024-12-04 00:00:00 UTC.
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in Trends in Neurosciences: In press on 2024-12-05 00:00:00 UTC.
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- Since its inception, the concept of neurodiversity has been defined in a number of different ways, which can cause confusion among those hoping to educate themselves about the topic. Learning about neurodiversity can also be challenging because there is a lack of well-curated, appropriately contextualized information on the topic. To address such barriers, we present an annotated reading list that was developed collaboratively by a neurodiverse group of researchers. The nine themes covered in the reading list are: the history of neurodiversity; ways of thinking about neurodiversity; the importance of lived experience; a neurodiversity paradigm for autism science; beyond deficit views of ADHD; expanding the scope of neurodiversity; anti-ableism; the need for robust theory and methods; and integration with open and participatory work. We hope this resource can support readers in understanding some of the key ideas and topics within neurodiversity, and that it can further orient researchers towards more rigorous, destigmatizing, accessible, and inclusive scientific practices.
+ Raingeval et al. characterize the insertion of the ONSEN transposon in the intron of a flowering repressor, which allows the plant to accelerate its life cycle in response to stress. They show the insertion was positively selected in a herbicide-intense environment demonstrating its role in adaptation to the local environment.
- in eLife on 2024-12-04 00:00:00 UTC.
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in Cell Reports: Current Issue on 2024-12-05 00:00:00 UTC.
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- Although the αC-β4 loop is a stable feature of all protein kinases, the importance of this motif as a conserved element of secondary structure, as well as its links to the hydrophobic architecture of the kinase core, has been underappreciated. We first review the motif and then describe how it is linked to the hydrophobic spine architecture of the kinase core, which we first discovered using a computational tool, local spatial Pattern (LSP) alignment. Based on NMR predictions that a mutation in this motif abolishes the synergistic high-affinity binding of ATP and a pseudo substrate inhibitor, we used LSP to interrogate the F100A mutant. This comparison highlights the importance of the αC-β4 loop and key residues at the interface between the N- and C-lobes. In addition, we delved more deeply into the structure of the apo C-subunit, which lacks ATP. While apo C-subunit showed no significant changes in backbone dynamics of the αC-β4 loop, we found significant differences in the side chain dynamics of K105. The LSP analysis suggests disruption of communication between the N- and C-lobes in the F100A mutant, which would be consistent with the structural changes predicted by the NMR spectroscopy.
+ Zhao et al. report that IL-17A inhibits anti-tumor immune responses by expanding highly immunosuppressive LYVE-1+ tissue-resident TAMs. Mechanistically, IL-17A activates CEBPβ, an identified OPN transcription factor, stimulating tumor cell production of OPN, which interacts with its receptor LYVE-1, leading to the proliferation of LYVE-1+ TAMs.
- in eLife on 2024-12-04 00:00:00 UTC.
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in Cell Reports: Current Issue on 2024-12-05 00:00:00 UTC.
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- Climatic warming can shift community composition driven by the colonization-extinction dynamics of species with different thermal preferences; but simultaneously, habitat fragmentation can mediate species’ responses to warming. As this potential interactive effect has proven difficult to test empirically, we collected data on birds over 10 years of climate warming in a reservoir subtropical island system that was formed 65 years ago. We investigated how the mechanisms underlying climate-driven directional change in community composition were mediated by habitat fragmentation. We found thermophilization driven by increasing warm-adapted species and decreasing cold-adapted species in terms of trends in colonization rate, extinction rate, occupancy rate and population size. Critically, colonization rates of warm-adapted species increased faster temporally on smaller or less isolated islands; cold-adapted species generally were lost more quickly temporally on closer islands. This provides support for dispersal limitation and microclimate buffering as primary proxies by which habitat fragmentation mediates species range shift. Overall, this study advances our understanding of biodiversity responses to interacting global change drivers.
+ Wang et al. demonstrate the function of the ATAC complex as a negative regulator of the transcriptional program governing the autophagy-lysosome pathway by modulating the stability of the transcription factors TFE3 and TFEB. Mechanistically, the ATAC complex directly ubiquitinates TFE3 through its E3 ligase activity and prompts TFE3’s proteasome-dependent degradation.
- in eLife on 2024-12-04 00:00:00 UTC.
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in Cell Reports: Current Issue on 2024-12-05 00:00:00 UTC.
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- Recent studies have shown that, in human cancer cells, the tetrameric Shieldin complex (comprising REV7, SHLD1, SHLD2, and SHLD3) facilitates non-homologous end-joining (NHEJ) while blocking homologous recombination (HR). Surprisingly, several eukaryotic species lack SHLD1, SHLD2, and SHLD3 orthologs, suggesting that Rev7 may leverage an alternative mechanism to regulate the double-strand break (DSB) repair pathway choice. Exploring this hypothesis, we discovered that Saccharomyces cerevisiae Rev7 physically interacts with the Mre11–Rad50–Xrs2 (MRX) subunits, impedes G-quadruplex DNA synergized HU-induced toxicity, and facilitates NHEJ, while antagonizing HR. Notably, we reveal that a 42-amino acid C-terminal fragment of Rev7 binds to the subunits of MRX complex, protects rev7∆ cells from G-quadruplex DNA-HU-induced toxicity, and promotes NHEJ by blocking HR. By comparison, the N-terminal HORMA domain, a conserved protein–protein interaction module, was dispensable. We further show that the full-length Rev7 impedes Mre11 nuclease and Rad50’s ATPase activities without affecting the latter’s ATP-binding ability. Combined, these results provide unanticipated insights into the functional interaction between the MRX subunits and Rev7 and highlight a previously unrecognized mechanism by which Rev7 facilitates DSB repair via NHEJ, and attenuation of HR, by blocking Mre11 nuclease and Rad50’s ATPase activities in S. cerevisiae.
+ Socha et al. find that visual stimuli in nasal directions trigger an arousal-related pupil response, which impacts the activity of dorsal lateral geniculate nucleus boutons measured in the primary visual cortex, affecting measurements of visual tuning. The over-representation of responses preferring nasal directions is not present under anesthesia, suggesting that the effect is linked to changes in arousal levels triggered by visual stimuli, which modulate thalamic visual inputs to the cortex.
- in eLife on 2024-12-04 00:00:00 UTC.
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in Cell Reports: Current Issue on 2024-12-05 00:00:00 UTC.
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- Experience-based plasticity of the human cortex mediates the influence of individual experience on cognition and behavior. The complete loss of a sensory modality is among the most extreme such experiences. Investigating such a selective, yet extreme change in experience allows for the characterization of experience-based plasticity at its boundaries. Here, we investigated information processing in individuals who lost vision at birth or early in life by probing the processing of braille letter information. We characterized the transformation of braille letter information from sensory representations depending on the reading hand to perceptual representations that are independent of the reading hand. Using a multivariate analysis framework in combination with functional magnetic resonance imaging (fMRI), electroencephalography (EEG), and behavioral assessment, we tracked cortical braille representations in space and time, and probed their behavioral relevance. We located sensory representations in tactile processing areas and perceptual representations in sighted reading areas, with the lateral occipital complex as a connecting ‘hinge’ region. This elucidates the plasticity of the visually deprived brain in terms of information processing. Regarding information processing in time, we found that sensory representations emerge before perceptual representations. This indicates that even extreme cases of brain plasticity adhere to a common temporal scheme in the progression from sensory to perceptual transformations. Ascertaining behavioral relevance through perceived similarity ratings, we found that perceptual representations in sighted reading areas, but not sensory representations in tactile processing areas are suitably formatted to guide behavior. Together, our results reveal a nuanced picture of both the potentials and limits of experience-dependent plasticity in the visually deprived brain.
+ Sieu et al. report that impaired auditory responsiveness in a mouse temporal lobe seizure model is related to depressed cortical arousal and acetylcholine release. Slow changes in cortical slow waves, multiunit activity, and acetylcholine relate to impaired responsiveness in seizures, whereas fast changes relate to decreased responses to individual stimuli.
- in eLife on 2024-12-04 00:00:00 UTC.
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in Cell Reports: Current Issue on 2024-12-05 00:00:00 UTC.
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- Early-life stress (ELS), such as parental neglect or abuse, predisposes an individual to develop mental disorders. Disease hallmarks include heightened amygdala reactivity and impaired prefrontal cortex-amygdala functional interactions, already during childhood and adolescence. However, which cellular and circuit mechanisms underlie these hallmarks, as well as the altered developmental trajectory of prefrontal-amygdala networks, is poorly understood. Here we performed simultaneous in vivo local-field potential and multi-unit recordings under light urethane anaesthesia in the medial prefrontal cortex (mPFC) and basolateral amygdala (BLA) of male and female juvenile or adolescent mice, exposed to a resource scarcity model of ELS. We find a developmentally transient low-theta (3-5 Hz) oscillatory hypercoupling within mPFC-BLA networks in juvenile ELS males which seems to result from a precocious development of coupling strength after ELS. In the mPFC, neuronal spiking activity was decreased in juvenile males and the local theta entrainment of spike firing disrupted. In BLA, both sexes showed an increase in firing activity in a subpopulation of neurons after ELS, also confirmed by an increase in deltaFosB-positive neurons in BLA, which we identified to be non-GABAergic. Directed interactions, i.e. the ability to entrain spike firing in mPFC to the theta rhythm in BLA and vice versa, were also impaired predominantly in juvenile males after ELS, while females showed a milder phenotype. These early sex-dependent impairments in the functional development of prefrontal-amygdala circuits may promote abnormal fear learning and anxiety after ELS and may predispose to a disease phenotype later on.
+ Amyloid β (Aβ) forms aggregates in the Alzheimer’s disease brain and is well known for its pathological roles. Recent studies show that it also regulates neuronal physiology in the healthy brain. Whether Aβ also regulates glial physiology in the normal brain, however, has remained unclear. In this article, we describe the discovery of a novel signaling pathway activated by the monomeric form of Aβ in vitro that plays essential roles in the regulation of microglial activity and the assembly of neocortex during mouse development in vivo. We find that activation of this pathway depends on the function of amyloid precursor and the heterotrimeric G protein regulator Ric8a in microglia and inhibits microglial immune activation at transcriptional and post-transcriptional levels. Genetic disruption of this pathway during neocortical development results in microglial dysregulation and excessive matrix proteinase activation, leading to basement membrane degradation, neuronal ectopia, and laminar disruption. These results uncover a previously unknown function of Aβ as a negative regulator of brain microglia and substantially elucidate the underlying molecular mechanisms. Considering the prominence of Aβ and neuroinflammation in the pathology of Alzheimer’s disease, they also highlight a potentially overlooked role of Aβ monomer depletion in the development of the disease.
- in bioRxiv: Neuroscience on 2024-12-04 00:00:00 UTC.
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- Half of all newborn neurons in the developing brain are removed via efferocytosis - the phagocytic clearance of apoptotic cells. Microglia are brain-resident professional phagocytes that play important roles in neural circuit development including as primary effectors of efferocytosis. While the mechanisms through which microglia recognize potential phagocytic cargo are widely studied, the lysosomal mechanisms that are necessary for efficient digestion are less well defined. Here we show that the lysosomal protease cathepsin B promotes microglial efferocytosis of neurons and restricts the accumulation of apoptotic cells during brain development. We show that cathepsin B is microglia-specific and enriched in brain regions where neuronal turnover is high in both zebrafish and mouse. Myeloid-specific cathepsin B knockdown in zebrafish led to dysmorphic microglia containing undigested dead cells, as well as an accumulation of dead cells in surrounding tissue. These effects where phenocopied in mice globally deficient for Ctsb using markers for apoptosis. We also observed behavioral impairments in both models. Live imaging studies in zebrafish revealed deficits in phagolysosomal fusion and acidification, and live imaging of cultured mouse microglia reveal delayed phagocytosis consistent with impairments in digestion and resolution of phagocytosis rather than initial uptake. These data reveal a novel role for microglial cathepsin B in mediating neuronal efferocytosis during typical brain development.
+ The cell wall of human fungal pathogens plays critical roles as an architectural scaffold and as a target and modulator of the host immune response. Although the cell wall of the pathogenic yeast Candida albicans is intensively studied, one of the major fibrillar components in its cell wall, β-1,6-glucan, has been largely neglected. Here, we show that β-1,6-glucan is essential for bilayered cell wall organization, cell wall integrity, and filamentous growth. For the first time, we show that β-1,6-glucan production compensates the defect in mannan elongation in the outer layer of the cell wall. In addition, β-1,6-glucan dynamics are also coordinated by host environmental stimuli and stresses with wall remodeling, where the regulation of β-1,6-glucan structure and chain length is a crucial process. As we point out that β-1,6-glucan is exposed at the yeast surface and modulate immune response, β-1,6-glucan must be considered a key factor in host–pathogen interactions.
- in bioRxiv: Neuroscience on 2024-12-04 00:00:00 UTC.
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- Cholinergic interneurons of the dorsomedial striatum may play a role in social hierarchy dynamics. A social hierarchy is an organization of individuals by rank that occurs in social animals. Establishing a new social hierarchy involves flexible behavior in deciding whether to be a winner or loser, experience of winning or losing, and stabilization of rank. The neural circuits underlying such flexible behavior have yet to be fully understood, but previous research indicates that cholinergic interneurons in the dorsomedial striatum play a role in behavioral flexibility. We used the dominance tube test to measure ranking within group housed mice, before and after between-cage competitions using the same test. We found that the experience of winning or losing against mice from different cages not only contributes to new social hierarchies among the competitors, but also causally influences the subsequent social hierarchy among their cage mates in the home cage - supporting the hypothesis of winner-loser effects on later social ranking. To test the hypothesis that cholinergic interneurons contribute to social hierarchy dynamics, we made a selective lesion of cholinergic interneurons in the dorsomedial striatum. The lesion did not prevent social hierarchy formation among pairs of similarly ranked individuals from different cages. However, it reduced the loser effect of external competition on the subsequent home-cage rankings in dominant mice. In light of these results we suggest that cholinergic interneurons in dorsomedial striatum increase the flexibility of social hierarchy dynamics.
+ The brain predicts regularities in sensory inputs at multiple complexity levels, with neuronal mechanisms that remain elusive. Here, we monitored auditory cortex activity during the local-global paradigm, a protocol nesting different regularity levels in sound sequences. We observed that mice encode local predictions based on stimulus occurrence and stimulus transition probabilities, because auditory responses are boosted upon prediction violation. This boosting was due to both short-term adaptation and an adaptation-independent surprise mechanism resisting anesthesia. In parallel, and only in wakefulness, VIP interneurons responded to the omission of the locally expected sound repeat at the sequence ending, thus providing a chunking signal potentially useful for establishing global sequence structure. When this global structure was violated, by either shortening the sequence or ending it with a locally expected but globally unexpected sound transition, activity slightly increased in VIP and PV neurons, respectively. Hence, distinct cellular mechanisms predict different regularity levels in sound sequences.
- in bioRxiv: Neuroscience on 2024-12-04 00:00:00 UTC.
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in eLife on 2024-12-05 00:00:00 UTC.
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- The neural bases of narcissistic and antisocial traits are still under debate. One intriguing question is whether these traits are encoded within the so-called triple network e.g. the default mode (DMN), salience (SN), and fronto-parietal (FPN) networks, and whether these traits affect the same networks in a similar manner. Connectome-based analyses were conducted on resting-state scans from 183 participants, examining regional and global graph-theoretic metrics in the DMN, SN, and FPN, with the visual and sensorimotor networks as controls. Our findings revealed a clear involvement of the triple network in narcissistic and antisocial traits, confirming a shared neural substrate for the two traits. Both traits were negatively predicted by the anterior cingulate cortex of the SN, possibly indicating less awareness of dangers and more proneness to engage in risky behaviors. Additionally, both traits were positively predicted by the lateral prefrontal cortex of the FPN, suggesting augmented strategic thinking to manipulate others and increased planning skills to achieve personal goals. Besides similarities, there were also some differences. Specific hubs of the DMN were positively associated with narcissism but negatively related with antisocials, possibly explaining their differences in self-reflection and thinking about the self, largely present in the former, but usually reduced in the latter. These results extend previous findings on the involvement of the triple network in personality disorders and suggest both common and different mechanisms underlying narcissistic and antisocial traits. As such, these findings could pave the way for developing potential biomarkers of personality pathology and identify neurostimulation intervention targets.
+ Multisensory integration (MSI) combines information from multiple sensory modalities to create a coherent perception of the world. In contexts where sensory information is limited or equivocal, it also allows animals to integrate individually ambiguous stimuli into a clearer or more accurate percept and, thus, react with a more adaptive behavioral response. Although responses to multisensory stimuli have been described at the neuronal and behavioral levels, a causal or direct link between these two is still missing. In this study, we studied the integration of audiovisual inputs in the Mauthner cell, a command neuron necessary and sufficient to trigger a stereotypical escape response in fish. We performed intracellular recordings in adult goldfish while presenting a diverse range of stimuli to determine which stimulus properties affect their integration. Our results show that stimulus modality, intensity, temporal structure, and interstimulus delay affect input summation. Mechanistically, we found that the distinct decay dynamics of FFI triggered by auditory and visual stimuli can account for certain aspects of input integration. Altogether, this is a rare example of the characterization of MSI in a cell with clear behavioral relevance, providing both phenomenological and mechanistic insights into how MSI depends on stimulus properties.
- in bioRxiv: Neuroscience on 2024-12-04 00:00:00 UTC.
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- Humans across cultures show an outstanding capacity to perceive, learn, and produce musical rhythms. These skills rely on mapping the infinite space of possible rhythmic sensory inputs onto a finite set of internal rhythm categories. What are the brain processes underlying rhythm categorization? We used electroencephalography (EEG) to measure brain activity as human participants listened to a continuum of rhythmic sequences characterized by repeating patterns of two inter-onset intervals. Using frequency and representational similarity analyses, we show that brain activity does not merely track the temporal structure of rhythmic inputs, but, instead, automatically produces categorical representation of rhythms. Surprisingly, despite this automaticity, these rhythm categories do not arise in the earliest stages of the ascending auditory pathway, but show strong similarity between implicit neural and overt behavioral responses. Together, these results and methodological advances constitute a critical step towards understanding the biological roots and diversity of musical behaviors across cultures.
+ Language is acquired and processed in complex and dynamic naturalistic contexts, involving the simultaneous processing of connected speech, faces, bodies, objects, etc. How words and their associated concepts are encoded in the brain during real-world processing is still unknown. Here, the representational structure of concrete and abstract concepts was investigated during movie watching to address the extent to which brain responses dynamically change depending on visual context. First, across contexts, concrete and abstract concepts are shown to encode different experience-based information in separable sets of brain regions. However, these differences are reduced when multimodal context is considered. Specifically, the response profile of abstract words becomes more concrete-like when these are processed in visual scenes highly related to their meaning. Conversely, when the visual context is unrelated to a given concrete word, the activation pattern resembles more that of abstract conceptual processing. These results suggest that while concepts generally encode habitual experiences, the underlying neurobiological organisation is not fixed but depends dynamically on available contextual information.
- in bioRxiv: Neuroscience on 2024-12-04 00:00:00 UTC.
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- Medial ganglionic eminence-derived inhibitory GABAergic pallial interneurons (MGE-pINs) are essential regulators of cortical circuits; their dysfunction is associated with numerous neurological disorders. We developed human (h) MGE-pINs from pluripotent stem cells for the treatment of drug-resistant epilepsy. Here, we analyzed xenografted hMGE-pINs over the lifespan of host mice using single nuclei RNA sequencing. Comparative transcriptomics against endogenous human brain datasets revealed that 97% of grafted cells developed into somatostatin (SST) and parvalbumin (PVALB) subtypes, including populations that exhibit selective vulnerability in Alzheimer's disease. Transplanted hMGE-pINs demonstrated rapid emergence of subclass features, progressing through distinct transcriptional states sequentially involving neuronal migration, synapse organization, and membrane maturation. We present molecular, electrophysiological, and morphological data that collectively confirm the derivation of diverse bona-fide human SST and PVALB subtypes, providing a high-fidelity model to study human MGE-pIN development and functional maturation as well as a compositional atlas for regenerative cell therapy applications.
+ Despite their importance in a wide range of living organisms, self-cleaving ribozymes in the human genome are few and poorly studied. Here, we performed deep mutational scanning and covariance analysis of two previously proposed self-cleaving ribozymes (LINE-1 and OR4K15). We found that the regions essential for ribozyme activities are made of two short segments, with a total of 35 and 31 nucleotides only. The discovery makes them the simplest known self-cleaving ribozymes. Moreover, the essential regions are circular permutated with two nearly identical catalytic internal loops, supported by two stems of different lengths. These two self-cleaving ribozymes, which are shaped like lanterns, are similar to the catalytic regions of the twister sister ribozymes in terms of sequence and secondary structure. However, the nucleotides at the cleavage site have shown that mutational effects on two twister sister-like (TS-like) ribozymes are different from the twister sister ribozyme. The discovery of TS-like ribozymes reveals a ribozyme class with the simplest and, perhaps, the most primitive structure needed for self-cleavage.
- in bioRxiv: Neuroscience on 2024-12-04 00:00:00 UTC.
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- Purpose: The aim of this study was to test whether oral administration of nicotinamide riboside (NR), the nicotinamide adenine dinucleotide (NAD+) precursors, protect retina ganglion cells (RGCs) from neurodegeneration in DBA/2J (D2) mice, which is a widely used mouse model of age-related inherited glaucoma. Method: Oral NR or NAM administration (NR low dose: 1150mg/kg; NR high dose: 4200mg/kg; NAM low dose group: 500mg/kg; NAM high dose: 2000mg/kg of body weight per day) essentially started when D2 mice were 4 or 9 months old and continued up to 12 months old. Control cohort identically received food/water without NAM or NR. Intraocular pressure (IOP) was measured every month until experiment completion. Pattern electroretinography (PERG) was recorded. Retinas were harvested for whole mount immunofluorescence staining with RGCs marker Brn3a and imaged by fluorescent confocal microscopy. Optic nerves were harvested for axon staining and quantification. Retinal NAD+ levels were enzymatically assayed. Results: NR oral supplementary treatment started at 4 months old robustly increased retinal NAD+ levels in D2 mice (NRHigh vs. vehicle: 273.7{+/-}23.59% vs. 108.70{+/-}12.10%, p<0.001). In aged vehicle group (12 months old), there was significantly diminution of the P1 and N2 components of PERG response compare with naïve group (naïve vs. vehicle: P1: 7.82{+/-} 0.70uV vs 1.63{+/-} 0.17uV, p<0.0001; N2: -13.29{+/-} 0.83uV 2 vs. -3.22{+/-} 0.27uV, p<0.0001; Kruskal-Wallis test with Dunn's multiple comparison test). NR treatment preserved aged D2 visual function when mice were 9 and 12 months old. In addition, long-term NR high dose treatment significantly protected against total RGCs loss and optic nerve atrophy (RGC: NRHigh vs. vehicle: 1412{+/-}62.00vs 475.2{+/-}94.68 cells/field, p<0.00001; axon numbers: NRHigh vs. vehicle: 23990{+/-}1159 vs 8573{+/-}1160, n=41-53, p<0.0001). Furthermore, long-term NR supplementation prevent iris depigmentation and delayed IOP elevation. Conclusion: NR oral supplementary treatment significantly preserved RGC and axon numbers, potentially preserves retinal function via elevated retinal NAD+ level in aged D2 mice. Interestingly, NR treatment also prevented iris atrophy, delayed IOP elevation associated with this glaucoma model. NR oral supplementation thus treated several aspects of murine pigment dispersion glaucoma. Given parallels between this model and glaucoma in human, out data indicate that NR is worth exploring as a therapeutic candidate in treatment of glaucoma.
+ Here, we sequenced rearranged TCRβ and TCRα chain sequences in CD4+CD8+ double positive (DP), CD4+CD8- single positive (SP4) and CD4-CD8+ (SP8) thymocyte populations from the foetus and young adult mouse. We found that life-stage had a greater impact on TCRβ and TCRα gene segment usage than cell-type. Foetal repertoires showed bias towards 3’TRAV and 5’TRAJ rearrangements in all populations, whereas adult repertoires used more 5’TRAV gene segments, suggesting that progressive TCRα rearrangements occur less frequently in foetal DP cells. When we synchronised young adult DP thymocyte differentiation by hydrocortisone treatment the new recovering DP thymocyte population showed more foetal-like 3’TRAV and 5’TRAJ gene segment usage. In foetus we identified less influence of MHC-restriction on α-chain and β-chain combinatorial VxJ usage and CDR1xCDR2 (V region) usage in SP compared to adult, indicating weaker impact of MHC-restriction on the foetal TCR repertoire. The foetal TCRβ repertoire was less diverse, less evenly distributed, with fewer non-template insertions, and all foetal populations contained more clonotypic expansions than adult. The differences between the foetal and adult thymus TCR repertoires are consistent with the foetal thymus producing αβT-cells with properties and functions that are distinct from adult T-cells: their repertoire is less governed by MHC-restriction, with preference for particular gene segment usage, less diverse with more clonotypic expansions, and more closely encoded by genomic sequence.
- in bioRxiv: Neuroscience on 2024-12-04 00:00:00 UTC.
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- Spiking activity along synaptic circuits linking primary somatosensory (S1) and motor (M1) areas is fundamental for sensorimotor integration in cortex. Circuits along the ascending somatosensory pathway through mouse hand/forelimb S1 and M1 were recently described in detail (Yamawaki et al., 2021). Here, we characterize the peripherally evoked spiking dynamics in these two cortical areas in the same system. Brief (5 ms) optogenetic photostimulation of the hand generated short (~25 ms) barrages of activity first in S1 (onset latency 15 ms) then M1 (10 ms later). The estimated propagation speed was 20-fold faster from hand to S1 than from S1 to M1. Response amplitudes in M1 were strongly attenuated to approximately a third of those in S1. Responses were typically triphasic, with suppression and rebound following the initial peak. Parvalbumin (PV) inhibitory interneurons were involved in each phase, accounting for three-quarters of the initial spikes generated in S1, and their selective photostimulation sufficed to evoke suppression and rebound in both S1 and M1. Partial silencing of S1 by PV activation during hand stimulation reduced the M1 sensory responses. These results provide quantitative measures of spiking dynamics of cortical activity along the hand/forelimb-related transcortical loop; demonstrate a prominent and mechanistic role for PV neurons in each phase of the response; and, support a conceptual model in which somatosensory signals reach S1 via high-speed subcortical circuits to generate characteristic barrages of cortical activity, then reach M1 via densely polysynaptic corticocortical circuits to generate a similar but delayed and attenuated profile of activity.
+ Primary and secondary neurulation – processes that form the spinal cord – are incompletely understood in humans, largely due to the challenge of accessing neurulation-stage embryos (3–7 weeks post-conception). Here, we describe findings from 108 human embryos, spanning Carnegie stages (CS) 10–18. Primary neurulation is completed at the posterior neuropore with neural plate bending that is similar, but not identical, to the mouse. Secondary neurulation proceeds from CS13 with formation of a single lumen as in mouse, not coalescence of multiple lumens as in chick. There is no evidence of a ‘transition zone’ from primary to secondary neurulation. Secondary neural tube ‘splitting’ occurs in 60% of proximal human tail regions. A somite is formed every 7 hr in human, compared with 2 hr in mice and a 5 hr ‘segmentation clock’ in human organoids. Termination of axial elongation occurs after down-regulation of WNT3A and FGF8 in the CS15 embryonic tailbud, with a ‘burst’ of apoptosis that may remove neuro-mesodermal progenitors. Hence, the main differences between human and mouse/rat spinal neurulation relate to timing. Investigators are now attempting to recapitulate neurulation events in stem cell-derived organoids, and our results provide ‘normative data’ for interpretation of such research findings.
- in bioRxiv: Neuroscience on 2024-12-04 00:00:00 UTC.
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- Obsessive-compulsive (OC) tendencies involve intrusive thoughts and rigid, repetitive behaviours that also manifest at the subclinical level in the general population. The neurocognitive factors driving the development and persistence of the excessive presence of these tendencies remain highly elusive, though emerging theories emphasize the role of implicit information processing. Despite various empirical studies on distinct neurocognitive processes, the incidental retrieval of environmental structures in dynamic and noisy environments, such as probabilistic learning, has received relatively little attention. In this study, we aimed to unravel potential individual differences in implicit probabilistic learning and the updating of predictive representations related to OC tendencies in the general population. We conducted two independent online experiments (NStudy1 = 164, NStudy2 = 257) with young adults. Probabilistic learning was assessed using a reliable implicit visuomotor probabilistic learning task, which involved sequences with second-order non-adjacent dependencies. Our findings revealed that even among individuals displaying a broad spectrum of OC tendencies within a non-clinical population, implicit probabilistic learning remained remarkably robust. Furthermore, the results highlighted effective updating capabilities of predictive representations, which were not influenced by OC tendencies. These results offer new insights into individual differences in probabilistic learning and updating in relation to OC tendencies, contributing to theoretical, methodological, and practical approaches for understanding the maladaptive behavioural manifestations of OC disorder and subclinical tendencies.
+ The environmental challenges the human malaria parasite, Plasmodium falciparum, faces during its progression into its various lifecycle stages warrant the use of effective and highly regulated access to chromatin for transcriptional regulation. Microrchidia (MORC) proteins have been implicated in DNA compaction and gene silencing across plant and animal kingdoms. Accumulating evidence has shed light on the role MORC protein plays as a transcriptional switch in apicomplexan parasites. In this study, using the CRISPR/Cas9 genome editing tool along with complementary molecular and genomics approaches, we demonstrate that PfMORC not only modulates chromatin structure and heterochromatin formation throughout the parasite erythrocytic cycle, but is also essential to the parasite survival. Chromatin immunoprecipitation followed by deep sequencing (ChIP-seq) experiments suggests that PfMORC binds to not only sub-telomeric regions and genes involved in antigenic variation but may also play a role in modulating stage transition. Protein knockdown experiments followed by chromatin conformation capture (Hi-C) studies indicate that downregulation of PfMORC impairs key histone marks and induces the collapse of the parasite heterochromatin structure leading to its death. All together these findings confirm that PfMORC plays a crucial role in chromatin structure and gene regulation, validating this factor as a strong candidate for novel antimalarial strategies.
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- Temporal integration is crucial for auditory perception, yet the mechanisms underlying its role are not fully elucidated. This study examines the perceptual discrimination of click trains with varied temporal configurations to determine if they can be perceived as distinct auditory objects, potentially introducing a novel dimension to sound perception. In humans, psychological experiments using a delayed match-to-sample task revealed that participants could distinctly discriminate between click trains with different temporal configurations, suggesting that temporal configuration significantly influences auditory perception. This was supported by electroencephalogram (EEG) recordings showing robust mismatch negativity (MMN) signals, indicating that the auditory system differentiates standard from deviant sounds based on their temporal characteristics. Parallel electrocorticography (ECoG) studies in rats demonstrated similar discriminatory abilities, suggesting a cross-species consistency. Neuronal recordings showed pronounced stimulus-specific adaptation (SSA) in the primary auditory cortex (A1) but minimal SSA in lower auditory areas such as the inferior colliculus (IC) and medial geniculate body (MGB), indicating that A1 uniquely integrates temporal features and discriminates complex temporal patterns. This research advances our understanding of how temporal configurations are processed in the auditory system and suggests a new feature of sound perception.
+ The coordination of cell cycle progression and flagellar synthesis is a complex process in motile bacteria. In γ-proteobacteria, the localization of the flagellum to the cell pole is mediated by the SRP-type GTPase FlhF. However, the mechanism of action of FlhF, and its relationship with the cell pole landmark protein HubP remain unclear. In this study, we discovered a novel protein called FipA that is required for normal FlhF activity and function in polar flagellar synthesis. We demonstrated that membrane-localized FipA interacts with FlhF and is required for normal flagellar synthesis in Vibrio parahaemolyticus, Pseudomonas putida, and Shewanella putrefaciens, and it does so independently of the polar localization mediated by HubP. FipA exhibits a dynamic localization pattern and is present at the designated pole before flagellar synthesis begins, suggesting its role in licensing flagellar formation. This discovery provides insight into a new pathway for regulating flagellum synthesis and coordinating cellular organization in bacteria that rely on polar flagellation and FlhF-dependent localization.
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- Deep brain stimulation [DBS] is an effective treatment for many brain disorders, has a favourable adverse effect profile, and can be particularly effective for individuals with treatment resistant symptoms. DBS is, however, inaccessible for most individuals, is extremely expensive, and is not considered suitable for children and adolescents. For these reasons, non-invasive alternatives to DBS, such as transcranial magnetic stimulation [TMS], are increasingly being sought to treat brain health conditions. Unfortunately, current TMS approaches exhibit large intra- and inter-subject variability in their efficacy, which limits their use clinically. One likely reason for this is that TMS is invariably delivered without reference to ongoing brain activity (i.e., open loop). We propose that the efficacy of stimulation might be improved, and the variability of its effects reduced, if stimulation could be synchronised with ongoing brain activity. To investigate this, we used transcranial alternating current stimulation (tACS) to induce entrainment of brain activity at two frequencies (=10 Hz and {beta}=20 Hz), and we delivered single pulse TMS that was temporally aligned with the phase of each tACS oscillation. To investigate the effects of tACS-phase-aligned TMS we measured motor-evoked potentials (MEPs). Our findings confirm that for -tACS and {beta}-tACS both corticospinal excitability and inter-trial variability varied as a function of tACS phase. Importantly, however, the tACS phase angle that produced maximum TMS-evoked excitability was different for -tACS and {beta}-tACS; coinciding with the negative peak (trough) for -tACS and the positive peak (peak) for {beta}-tACS. These findings confirm that aligning non-invasive brain stimulation to ongoing brain activity may increase the efficacy of TMS and reduce the variability of its effects. However, our results illustrate that the optimal phase of the tACS cycle at which to deliver TMS may vary for different tACS frequencies.
+ The gut-brain axis mediates bidirectional signaling between the intestine and the nervous system and is critical for organism-wide homeostasis. Here, we report the identification of a peptidergic endocrine circuit in which bidirectional signaling between neurons and the intestine potentiates the activation of the antioxidant response in Caenorhabditis elegans in the intestine. We identify an FMRF-amide-like peptide, FLP-2, whose release from the intestine is necessary and sufficient to activate the intestinal oxidative stress response by promoting the release of the antioxidant FLP-1 neuropeptide from neurons. FLP-2 secretion from the intestine is positively regulated by endogenous hydrogen peroxide (H2O2) produced in the mitochondrial matrix by sod-3/superoxide dismutase, and is negatively regulated by prdx-2/peroxiredoxin, which depletes H2O2 in both the mitochondria and cytosol. H2O2 promotes FLP-2 secretion through the DAG and calcium-dependent protein kinase C family member pkc-2 and by the SNAP25 family member aex-4 in the intestine. Together, our data demonstrate a role for intestinal H2O2 in promoting inter-tissue antioxidant signaling through regulated neuropeptide-like protein exocytosis in a gut-brain axis to activate the oxidative stress response.
- in bioRxiv: Neuroscience on 2024-12-04 00:00:00 UTC.
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in eLife on 2024-12-05 00:00:00 UTC.
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- Epilepsy is typically characterized by excessive neuronal excitability, manifesting as seizures and interictal epileptiform discharges (IEDs) in the EEG. However, the dynamics of excitation and inhibition (E/I balance) remain poorly understood. Here, we leverage the aperiodic exponent of the EEG power spectrum - a marker indicative of synaptic inhibition - to investigate shifts in E/I balance during antiseizure medication (ASM) tapering in patients with mesial temporal lobe epilepsy (TLE). We analyzed EEG data from 28 TLE patients and 25 controls with non-epileptic episodes (NEE) undergoing presurgical video EEG monitoring. Unexpectedly, TLE patients showed a localized increase in the aperiodic exponent in the ipsilesional temporal lobe during ASM tapering, absent in controls. This inhibition increase correlated with seizure latency and predicted seizure occurrence. Intracranial recordings from 10 TLE patients revealed higher aperiodic exponents in the lateral temporal cortex compared to the hippocampus, suggesting stronger inhibition in the lateral cortex. Notably, hippocampal IEDs triggered transient inhibitory responses in the lateral cortex, accompanied by increased high-frequency activity and disrupted hippocampus-to-lateral connectivity. These findings suggest that TLE likely involves complex inhibitory mechanisms beyond the epileptic focus in the interictal period, with neocortical inhibition potentially containing epileptic activity, and offers a new tool to map epileptic brain regions.
+ Entorhinal grid cells implement a spatial code with hexagonal periodicity, signaling the position of the animal within an environment. Grid maps of cells belonging to the same module share spacing and orientation, only differing in relative two-dimensional spatial phase, which could result from being part of a two-dimensional attractor guided by path integration. However, this architecture has the drawbacks of being complex to construct and rigid, path integration allowing for no deviations from the hexagonal pattern such as the ones observed under a variety of experimental manipulations. Here, we show that a simpler one-dimensional attractor is enough to align grid cells equally well. Using topological data analysis, we show that the resulting population activity is a sample of a torus, while the ensemble of maps preserves features of the network architecture. The flexibility of this low dimensional attractor allows it to negotiate the geometry of the representation manifold with the feedforward inputs, rather than imposing it. More generally, our results represent a proof of principle against the intuition that the architecture and the representation manifold of an attractor are topological objects of the same dimensionality, with implications to the study of attractor networks across the brain.
- in bioRxiv: Neuroscience on 2024-12-04 00:00:00 UTC.
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- In this protocol, we introduce a sparse driver system for cell-type specific single-cell labeling and manipulation in Drosophila, enabling complete and simultaneous expression of multiple transgenes in the same cells. The system precisely controls expression probability and sparsity via mutant FRT sites with reduced recombination efficiency and tunable FLP levels adjusted by heat-shock durations. We demonstrate that this generalizable toolkit enables tunable sparsity, multi-color staining, single-cell trans-synaptic tracing, single-cell manipulation, and in vivo analysis of cell-autonomous gene function.
+ Hematopoietic dysfunction has been associated with a reduction in the number of active precursors. However, precursor quantification at homeostasis and under diseased conditions is constrained by the scarcity of available methods. To address this issue, we optimized a method for quantifying a wide range of hematopoietic precursors. Assuming the random induction of a stable label in precursors following a binomial distribution, estimates depend on the inverse correlation between precursor numbers and the variance of precursor labeling among independent samples. Experimentally validated to cover the full dynamic range of hematopoietic precursors in mice (1–105), we utilized this approach to demonstrate that thousands of precursors, which emerge after modest expansion during fetal-to-adult transition, contribute to native and perturbed hematopoiesis. We further estimated the number of precursors in a mouse model of Fanconi Anemia, showcasing how repopulation deficits can be classified as autologous (cell proliferation) and non-autologous (lack of precursor). Our results support an accessible and reliable approach for precursor quantification, emphasizing the contemporary perspective that native hematopoiesis is highly polyclonal.
- in bioRxiv: Neuroscience on 2024-12-04 00:00:00 UTC.
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in eLife on 2024-12-05 00:00:00 UTC.
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- Objectives: Our working memory (WM) is susceptible to errors influenced by various sources. Recent research has illuminated the intricate relationship between emotional valence and working memory performance. This study aims to comprehensively investigate memory recall biases across different emotional categories. Method: To explore this relationship, we designed and implemented a delayed-reproduction facial emotion n-back task. Participants were tasked with recalling the emotional valence of target faces across various n-back conditions, selecting their responses from a continuum of 19 morphed faces ranging from sad to happy. Results: Our findings indicate that participants generally exhibit a negativity bias, struggling more with happy faces. Interestingly, they also perceive happy faces as less happy and sad faces as less sad, suggesting both positive and negative reappraisal in their emotional valence perception. This underscores the complex interplay between emotional valence and cognitive performance. Notably, recall of neutral images remained stable and was unaffected by preceding emotional contexts. Conclusion: These findings demonstrate that emotional content in working memory significantly impacts errors during WM tasks, with more emotionally charged faces leading to a greater drift toward the lower valence axis. This highlights the need for further exploration of how emotional factors influence cognitive processes in working memory.
+ Damage to the synapses connecting hair cells to the auditory nerve leads to undetected hearing impairments.
- in bioRxiv: Neuroscience on 2024-12-04 00:00:00 UTC.
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in eLife on 2024-12-05 00:00:00 UTC.
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+http://biorxiv.org/cgi/content/short/2024.12.02.626512v1?rss=1
+">Octopamine signals coordinate the spatial pattern of presynaptic machineries in the Drosophila mushroom bodies
- Human visual perception in natural conditions involves multiple fixations within single objects. While traditional studies focus on transient neural responses to initial stimuli, this study investigates how object-category representations evolve across sequential fixations on an object. Using electroencephalography (EEG) and eye-tracking, we analyzed fixation-related potentials (FRPs) and applied multivariate pattern analysis (MVPA) to decode neural representations of faces and watches during prolonged viewing. Results revealed robust category-selective responses, including the N170 component, at stimulus onset, with sustained representations persisting throughout object presentation. Temporal signal deconvolution showed that subsequent fixations did not re-evoke the N170 but elicited transient occipital responses, likely reflecting low-level category differences. These findings underscore the dynamic interplay between transient and sustained neural processes during naturalistic vision and highlight the importance of disentangling overlapping neural signals during free viewing.
+ Neurons possess numerous synaptic terminals. Presynaptic structures in a single motor neuron exhibit heterogeneity that associated with distinct characters of synaptic vesicle release. However, such heterogeneity is scarcely reported in the central nervous system, and its regulatory mechanism remain unknown. Here, we explored the intracellular diversity of presynaptic structures within the Kenyon cells of the Drosophila mushroom bodies. Applying the CRISPR/Cas9-mediated split-GFP tagging, we devised cell-type specific fluorescent labeling of the endogenous active zone scaffold protein, Bruchpilot (Brp). Morphometry of individual Brp clusters revealed heterogenous accumulations among the axon terminal compartments. Mechanistically, the localized octopaminergic signaling along Kenyon cell terminals regulate the Brp heterogeneity via Octbeta2R and cAMP signaling. We further found that acute food deprivation reduced the compartmental heterogeneity of Brp accumulation in an octopaminergic signaling-dependent manner. These findings are consistent with the mushroom body functions in integrating the signals of changing physiological states.
- in bioRxiv: Neuroscience on 2024-12-04 00:00:00 UTC.
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in bioRxiv: Neuroscience on 2024-12-05 00:00:00 UTC.
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+http://biorxiv.org/cgi/content/short/2024.12.02.626511v1?rss=1
+">Synapse profiling of identified neurons in the Drosophila brain
- We investigate how respiration influences cognition by examining the interaction between respiratory phase and task-related brain activity during two visual categorization tasks. While prior research shows that cognitive performance varies along the respiratory cycle, the underlying neurophysiological mechanisms remain poorly understood. Though some studies have shown that large-scale neural activity reflecting changes in the excitation-inhibition balance is co-modulated with the respiratory cycle, it remains unclear whether respiration directly shapes the quality by which task-relevant sensory information is encoded. We address this gap by applying single-trial multivariate analyses to EEG data obtained in humans, allowing us to track how respiration modulates the sensory evidence in this neurophysiological signal. Confirming previous studies, our data show that participant's performance varies with the respiratory phase prior and during a trial. Importantly, they also suggest that respiration directly influences the sensory evidence carried by parieto-occipital processes emerging around 300 to 200 ms prior to participant's responses. Hence, respiration and sensory-cognitive processes are not only highly intertwined but respiration directly facilitates the representation of behaviourally-relevant signals in the brain.
+ Synapses are highly heterogeneous even within a single motor neuron in Drosophila melanogaster. In the central nervous system (CNS), the degree of stereotypy in the synaptic structure of specific neurons across individuals remains largely unexplored, due to the significant effort required to analyze multiple brain samples. Utilizing the split-GFP fluorescence-tagging, we achieved endogenous labeling of the presynaptic active zone (AZ) scaffold protein Bruchpilot (Brp) in a cell-type-specific manner. This strategy allowed us to devise a high-throughput quantification pipeline to characterize and compare cell-type-specific AZ structures across individuals. We found that multiple structural parameters such as Brp localization and AZ size revealed significant intracellular synaptic heterogeneity and cell-type-dependent stereotypy in the mushroom body (MB) circuit. Furthermore, we found that the AZ organization can be surprisingly local, even at the neighboring AZ level. These findings therefore suggest multi-level organizations of AZs, from neighboring synapses to across individuals.
- in bioRxiv: Neuroscience on 2024-12-04 00:00:00 UTC.
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in bioRxiv: Neuroscience on 2024-12-05 00:00:00 UTC.
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- Brain Sciences, Vol. 14, Pages 1226: Determining the Predictors of Recurrence or Regrowth Following Spinal Astrocytoma Resection: A Systematic Review and Meta-Analysis
- Brain Sciences doi: 10.3390/brainsci14121226
- Authors:
- Harry Hoang
- Amine Mellal
- Milad Dulloo
- Ryan T. Nguyen
- Neil Nazar Al-Saidi
- Hamzah Magableh
- Alexis Cailleteau
- Abdul Karim Ghaith
- Victor Gabriel El-Hajj
- Adrian Elmi-Terander
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- Background/Objectives: Spinal astrocytomas (SA) represent 30&ndash;40% of all intramedullary spinal cord tumors (IMSCTs) and present significant clinical challenges due to their aggressive behavior and potential for recurrence. We aimed to pool the evidence on SA and investigate predictors of regrowth or recurrence after surgical resection. Methods: A systematic review and meta-analysis were conducted on peer-reviewed human studies from several databases covering the field of SA. Data were collected including sex, age, tumor location, extent of resection, histopathological diagnosis, and adjuvant therapy to identify predictors of SA recurrence. Recurrence was defined as failure of local tumor control or regrowth after treatment. Results: A total of 53 studies with 1365 patients were included in the meta-analysis. A postoperative deterioration in neurological outcomes, as assessed by the modified McCormick scale, was noted in most of the patients. The overall recurrence rate amounted to 41%. On meta-analysis, high-grade WHO tumors were associated with higher odds of recurrence (OR = 2.65; 95% CI: 1.87, 3.76; p = 0.001). Similarly, GTR was associated with lower odds of recurrence compared to STR (OR = 0.33; 95% CI: 0.18, 0.60; p = 0.0003). Sex (p = 0.5848) and tumor location (p = 0.3693) did not show any significant differences in the odds of recurrence. Intraoperative neurophysiological monitoring was described in 8 studies and adjuvant radiotherapy in 41 studies. Conclusions: The results highlight the significant importance of tumor grade and extent of resection in patient prognosis. The role of adjuvant radiotherapy remains unclear, with most studies suggesting no differences in outcomes, with limitations due to potential confounders.
+ Language and consequently the ability to transmit and spread complex information is unique to the human species. The disruptive event of the introduction of large language models has shown that the ability to process language alone leads to incredible abilities and, to some extent, to intelligence. However, how language is processed in the human brain remains elusive. Many insights originate from fMRI studies, as the high spatial resolution of fMRI devices provides valid information about where things happen. Nevertheless, the limited temporal resolution prevents us from gaining a deep understanding on the underlying mechanisms. In this study, we performed combined EEG and MEG measurements in 29 healthy right-handed human subjects during the presentation of continuous speech. We compared the evoked potentials (ERPs and ERFs) for different word types in source space and sensor space across the whole brain. We found characteristic spatio-temporal patterns for different word types (nouns, verbs) especially at latencies of 300 ms to 1 s. This is further emphasized by the fact that we observe these effects in two pre-defined sub-samples of the data set (exploration and validation sample). We expect this study to be the starting point for further evaluations of semantic and syntactic processing in the brain.
- in Brain Sciences on 2024-12-04 00:00:00 UTC.
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in bioRxiv: Neuroscience on 2024-12-05 00:00:00 UTC.
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- Climate change significantly affects smallholder farmers, whose livelihoods are closely tied to the environment. This study explores factors influencing the adoption of climate-smart agriculture (CSA) practices and their impact on crop productivity among small-scale farmers in Nyimba District, Zambia. Data were collected from 194 households across 12 villages, and logistic regression and propensity score matching analyses were employed to identify key factors and evaluate CSA’s effects on crop yields. Findings revealed that CSA adoption is influenced by factors such as education level, household size, fertilizer use, age, gender, farming experience, livestock ownership, income, farmland size, marital status, and access to climate-related information. CSA adopters experienced a 20.20% increase in overall crop yields compared to non-adopters, with a 21.50% increase in maize yields specifically. The study underscores the need for targeted interventions to support CSA adoption through education, improved dissemination of climate information, and access to critical resources such as improved seeds and financial services. This research offers insights for policymakers and extension services to develop evidence-based strategies enhancing resilience and productivity among smallholder farmers in response to climate challenges.
+ In this study we investigated the neural processing of auditory stimuli of varying complexity: a non-linguistic (pure tone), a simple linguistic (phoneme) and a complex linguistic (word) stimulus. We recorded brain activity of 30 healthy, right-handed participants using magnetoencephalography (MEG), and compared the resulting evoked fields (ERFs) in source space in three different time intervals, i.e. early (0-250ms), mid (250-500ms) and late (500-750ms) responses. Our results reveal a bilateral activation during early response and right-lateralized activation in the mid-phase for all stimuli. Hoewever, the late response exhibited lateralization variations. The pure tone predominantly activated the right hemisphere, consistent with pitch processing theories. The phoneme primarily engaged the left hemisphere, supporting its role in phonemic processing. Notably, the word elicited activation in both hemispheres, reflecting phonemic processing on the left and stress patterns on the right. These findings highlight the intricate interplay between temporal processing and hemispheric lateralization in speech perception, emphasizing the importance of stimulus complexity and temporal dynamics in understanding auditory and speech processing.
- in F1000Research on 2024-12-03 16:24:56 UTC.
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in bioRxiv: Neuroscience on 2024-12-05 00:00:00 UTC.
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- by Elif Köksal-Ersöz, Pascal Benquet, Fabrice Wendling
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-Neuroplasticity refers to functional and structural changes in brain regions in response to healthy and pathological activity. Activity dependent plasticity induced by epileptic activity can involve healthy brain regions into the epileptogenic network by perturbing their excitation/inhibition balance. In this article, we present a new neural mass model, which accounts for neuroplasticity, for investigating the possible mechanisms underlying the epileptogenic network expansion. Our multiple-timescale model is inspired by physiological calcium-mediated synaptic plasticity and pathological extrasynaptic N-methyl-D-aspartate (NMDA) dependent plasticity dynamics. The model highlights that synaptic plasticity at excitatory connections and structural changes in the inhibitory system can transform a healthy region into a secondary epileptic focus under recurrent seizures and interictal activity occurring in the primary focus. Our results suggest that the latent period of this transformation can provide a window of opportunity to prevent the expansion of epileptogenic networks, formation of an epileptic focus, or other comorbidities associated with epileptic activity.
+ Brain Sciences, Vol. 14, Pages 1227: Impact of Cognitive VR vs. Traditional Training on Emotional Self-Efficacy and Cognitive Function in Patients with Multiple Sclerosis: A Retrospective Study Focusing on Gender Differences
+ Brain Sciences doi: 10.3390/brainsci14121227
+ Authors:
+ Maria Grazia Maggio
+ Alessandra Benenati
+ Federica Impellizzeri
+ Amelia Rizzo
+ Martina Barbera
+ Antonino Cannavò
+ Vera Gregoli
+ Giovanni Morone
+ Francesco Chirico
+ Angelo Quartarone
+ Rocco Salvatore Calabrò
+
+ Background and aim: While conventional MS rehabilitation primarily addresses physical and cognitive symptoms, recent advances in VR technology offer immersive environments that facilitate both emotional and cognitive skill development. The purpose of this study is to evaluate the impact of VR-based training on emotional self-efficacy in multiple sclerosis (MS) patients and examine its association with cognitive function improvement. Additionally, this study aims to explore potential gender differences in these outcomes, hypothesizing that gender may influence the effectiveness of VR-based rehabilitation, which could inform more tailored approaches for emotional and cognitive rehabilitation in MS. Method: The present retrospective study analyzed data from 43 MS patients undergoing cognitive and behavioral rehabilitation at the IRCCS Centro Neurolesi &ldquo;Bonino Pulejo&rdquo; in Italy, comparing a VR intervention group (VR-G) and a control group receiving traditional rehabilitation. Emotional self-efficacy, depression, and anxiety were assessed, alongside cognitive function pre- and post-intervention. Results: Findings indicate that the VR-G showed significant improvements in managing negative emotions, reduced depressive and anxiety symptoms, and enhanced cognitive performance, particularly in verbal learning and working memory. Gender-based analysis revealed a trend suggesting that females in the VR-G may exhibit greater improvements in positive emotional self-efficacy, although this difference did not reach statistical significance. Spearman&rsquo;s correlation highlighted associations between emotional self-efficacy and cognitive gains, supporting the potential of VR to foster both emotional and cognitive resilience. Conclusions: These findings suggest that VR training may provide a tailored approach for MS rehabilitation, enhancing therapeutic outcomes by integrating emotional and cognitive training in an immersive setting. Further research should investigate long-term effects and neurophysiological correlates of VR training to optimize MS rehabilitation.
- in PLoS Computational Biology on 2024-12-03 14:00:00 UTC.
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in Brain Sciences on 2024-12-05 00:00:00 UTC.
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- by Ikram Mahmoudi, Chloé Quignot, Carla Martins, Jessica Andreani
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-Protein-RNA interactions play a critical role in many cellular processes and pathologies. However, experimental determination of protein-RNA structures is still challenging, therefore computational tools are needed for the prediction of protein-RNA interfaces. Although evolutionary pressures can be exploited for structural prediction of protein-protein interfaces, and recent deep learning methods using protein multiple sequence alignments have radically improved the performance of protein-protein interface structural prediction, protein-RNA structural prediction is lagging behind, due to the scarcity of structural data and the flexibility involved in these complexes. To study the evolution of protein-RNA interface structures, we first identified a large and diverse dataset of 2,022 pairs of structurally homologous interfaces (termed structural interologs). We leveraged this unique dataset to analyze the conservation of interface contacts among structural interologs based on the properties of involved amino acids and nucleotides. We uncovered that 73% of distance-based contacts and 68% of apolar contacts are conserved on average, and the strong conservation of these contacts occurs even in distant homologs with sequence identity below 20%. Distance-based contacts are also much more conserved compared to what we had found in a previous study of homologous protein-protein interfaces. In contrast, hydrogen bonds, salt bridges, and π-stacking interactions are very versatile in pairs of protein-RNA interologs, even for close homologs with high interface sequence identity. We found that almost half of the non-conserved distance-based contacts are linked to a small proportion of interface residues that no longer make interface contacts in the interolog, a phenomenon we term “interface switching out”. We also examined possible recovery mechanisms for non-conserved hydrogen bonds and salt bridges, uncovering diverse scenarios of switching out, change in amino acid chemical nature, intermolecular and intramolecular compensations. Our findings provide insights for integrating evolutionary signals into predictive protein-RNA structural modeling methods.
+
- in PLoS Computational Biology on 2024-12-03 14:00:00 UTC.
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in Journal of Neuroscience on 2024-12-04 17:29:55 UTC.
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- by Adam J. Kucharski
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-Ongoing influenza H5N1 outbreaks highlight the need for timely, scalable interventions that draw on lessons from COVID-19. In particular, successful pandemic preparedness requires early outbreak management, including effective responses targeting spillovers before there is evidence of human-to-human transmission.
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-Ongoing influenza H5N1 outbreaks highlight the need for timely, scalable interventions that draw on lessons from COVID-19. This Perspective discussed that successful pandemic preparedness requires early outbreak management, including effective responses targeting spillovers before evidence of human-to-human transmission exists.
+ Area TE is required for normal learning of visual categories based on perceptual similarity. To evaluate whether category learning changes neural activity in area TE, we trained two monkeys (both male) implanted with multielectrode arrays to categorize natural images of cats and dogs. Neural activity during a passive viewing task was compared pre- and post-training. After the category training, the accuracy of abstract category decoding improved. Single units became more category selective, the proportion of single units with category selectivity increased, and units sustained their category-specific responses for longer. Visual category learning thus appears to enhance category separability in area TE by driving changes in the stimulus selectivity of individual neurons and by recruiting more units to the active network.
- in PLoS Biology on 2024-12-03 14:00:00 UTC.
+
in Journal of Neuroscience on 2024-12-04 17:29:55 UTC.
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- by Corson N. Areshenkoff, Anouk J. de Brouwer, Daniel J. Gale, Joseph Y. Nashed, Jonathan Smallwood, J. Randall Flanagan, Jason P. Gallivan
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-Sensorimotor learning is supported by multiple competing processes that operate concurrently, making it a challenge to elucidate their neural underpinnings. Here, using human functional MRI, we identify 3 distinct axes of connectivity between the motor cortex and other brain regions during sensorimotor adaptation. These 3 axes uniquely correspond to subjects’ degree of implicit learning, performance errors and explicit strategy use, and involve different brain networks situated at increasing levels of the cortical hierarchy. We test the generalizability of these neural axes to a separate form of motor learning known to rely mainly on explicit processes and show that it is only the Explicit neural axis, composed of higher-order areas in transmodal cortex, that predicts learning in this task. Together, our study uncovers multiple distinct patterns of functional connectivity with motor cortex during sensorimotor adaptation, the component processes that these patterns support, and how they generalize to other forms of motor learning.
+ Although neurons release neurotransmitter before contact, the role for this release in synapse formation remains unclear. Cortical synapses do not require synaptic vesicle release for formation (Verhage et al., 2000; Sando et al., 2017; Sigler et al., 2017; Held et al., 2020), yet glutamate clearly regulates glutamate receptor trafficking (Roche et al., 2001; Nong et al., 2004) and induces spine formation (Engert and Bonhoeffer, 1999; Maletic-Savatic et al., 1999; Toni et al., 1999; Kwon and Sabatini, 2011; Oh et al., 2016). Using rat and murine culture systems to dissect molecular mechanisms, we found that glutamate rapidly decreases synapse density specifically in young cortical neurons in a local and calcium-dependent manner through decreasing N-methyl-d-aspartate receptor (NMDAR) transport and surface expression as well as cotransport with neuroligin (NL1). Adhesion between NL1 and neurexin 1 protects against this glutamate-induced synapse loss. Major histocompatibility I (MHCI) molecules are required for the effects of glutamate in causing synapse loss through negatively regulating NL1 levels in both sexes. Thus, like acetylcholine at the neuromuscular junction, glutamate acts as a dispersal signal for NMDARs and causes rapid synapse loss unless opposed by NL1-mediated trans-synaptic adhesion. Together, glutamate, MHCI, and NL1 mediate a novel form of homeostatic plasticity in young neurons that induces rapid changes in NMDARs to regulate when and where nascent glutamatergic synapses are formed.
- in PLoS Biology on 2024-12-03 14:00:00 UTC.
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in Journal of Neuroscience on 2024-12-04 17:29:55 UTC.
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- by Simon Dellicour, Paul Bastide, Pauline Rocu, Denis Fargette, Olivier J. Hardy, Marc A. Suchard, Stéphane Guindon, Philippe Lemey
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-Genomic data collected from viral outbreaks can be exploited to reconstruct the dispersal history of viral lineages in a two-dimensional space using continuous phylogeographic inference. These spatially explicit reconstructions can subsequently be used to estimate dispersal metrics that can be informative of the dispersal dynamics and the capacity to spread among hosts. Heterogeneous sampling efforts of genomic sequences can however impact the accuracy of phylogeographic dispersal metrics. While the impact of spatial sampling bias on the outcomes of continuous phylogeographic inference has previously been explored, the impact of sampling intensity (i.e., sampling size) when aiming to characterise dispersal patterns through continuous phylogeographic reconstructions has not yet been thoroughly evaluated. In our study, we use simulations to evaluate the robustness of 3 dispersal metrics — a lineage dispersal velocity, a diffusion coefficient, and an isolation-by-distance (IBD) signal metric — to the sampling intensity. Our results reveal that both the diffusion coefficient and IBD signal metrics appear to be the most robust to the number of samples considered for the phylogeographic reconstruction. We then use these 2 dispersal metrics to compare the dispersal pattern and capacity of various viruses spreading in animal populations. Our comparative analysis reveals a broad range of IBD patterns and diffusion coefficients mostly reflecting the dispersal capacity of the main infected host species but also, in some cases, the likely signature of rapid and/or long-distance dispersal events driven by human-mediated movements through animal trade. Overall, our study provides key recommendations for the use of lineage dispersal metrics to consider in future studies and illustrates their application to compare the spread of viruses in various settings.
+ While humans typically saccade every ~250 ms in natural settings, studies on vision tend to prevent or restrict eye movements. As it takes ~50 ms to initiate and execute a saccade, this leaves only ~200 ms to identify the fixated object and select the next saccade goal. How much detail can be derived about parafoveal objects in this short time interval, during which foveal processing and saccade planning both occur? Here, we had male and female human participants freely explore a set of natural images while we recorded magnetoencephalography and eye movements. Using multivariate pattern analysis, we demonstrate that future parafoveal images could be decoded at the feature and category level with peak decoding at ~110 and ~165 ms, respectively, while the decoding of fixated objects at the feature and category level peaked at ~100 and ~145 ms. The decoding of features and categories was contingent on the objects being saccade goals. In sum, we provide insight on the neuronal mechanism of presaccadic attention by demonstrating that feature- and category-specific information of foveal and parafoveal objects can be extracted in succession within a ~200 ms intersaccadic interval. These findings rule out strict serial or parallel processing accounts but are consistent with a pipeline mechanism in which foveal and parafoveal objects are processed in parallel but at different levels in the visual hierarchy.
- in PLoS Biology on 2024-12-03 14:00:00 UTC.
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in Journal of Neuroscience on 2024-12-04 17:29:55 UTC.
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- by Benedict G. Hogan, Mary Caswell Stoddard
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-Hyperspectral imaging—a technique that combines the high spectral resolution of spectrophotometry with the high spatial resolution of photography—holds great promise for the study of animal coloration. However, applications of hyperspectral imaging to questions about the ecology and evolution of animal color remain relatively rare. The approach can be expensive and unwieldy, and we lack user-friendly pipelines for capturing and analyzing hyperspectral data in the context of animal color. Fortunately, costs are decreasing and hyperspectral imagers are improving, particularly in their sensitivity to wavelengths (including ultraviolet) visible to diverse animal species. To highlight the potential of hyperspectral imaging for animal coloration studies, we developed a pipeline for capturing, sampling, and analyzing hyperspectral data (here, in the 325 nm to 700 nm range) using avian museum specimens. Specifically, we used the pipeline to characterize the plumage colors of the King bird-of-paradise (Cicinnurus regius), Magnificent bird-of-paradise (C. magnificus), and their putative hybrid, the King of Holland’s bird-of-paradise (C. magnificus x C. regius). We also combined hyperspectral data with 3D digital models to supplement hyperspectral images of each specimen with 3D shape information. Using visual system-independent methods, we found that many plumage patches on the hybrid King of Holland’s bird-of-paradise are—to varying degrees—intermediate relative to those of the parent species. This was true of both pigmentary and structurally colored plumage patches. Using visual system-dependent methods, we showed that only some of the differences in plumage patches among the hybrid and its parent species would be perceivable by birds. Hyperspectral imaging is poised to become the gold standard for many animal coloration applications: comprehensive reflectance data—across the entire surface of an animal specimen—can be obtained in a matter of minutes. Our pipeline provides a practical and flexible roadmap for incorporating hyperspectral imaging into future studies of animal color.
+ Behaving as desired requires selecting the appropriate behavior and inhibiting the selection of inappropriate behavior. This inhibitory function involves multiple processes, such as reactive and proactive inhibition, instead of a single process. In this study, two male macaque monkeys were required to perform a task in which they had to sequentially select (accept) or refuse (reject) a choice. Neural activity was recorded from the anterior striatum, which is considered to be involved in behavioral inhibition, focusing on the distinction between proactive and reactive inhibitions. We identified neurons with significant activity changes during the rejection of bad objects. Cluster analysis revealed three distinct groups, of which only one showed increased activity during object rejection, suggesting its involvement in proactive inhibition. This activity pattern was consistent irrespective of the rejection method, indicating a role beyond saccadic suppression. Furthermore, minimal activity changes during the fixation task indicated that these neurons were not primarily involved in reactive inhibition. In conclusion, these findings suggest that the anterior striatum plays a crucial role in cognitive control and orchestrates goal-directed behavior through proactive inhibition, which may be critical in understanding the mechanisms of behavioral inhibition dysfunction that occur in patients with basal ganglia disease.
- in PLoS Biology on 2024-12-03 14:00:00 UTC.
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in Journal of Neuroscience on 2024-12-04 17:29:55 UTC.
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- by Neha Malhotra, Sangmi Oh, Peter Finin, Jessica Medrano, Jenna Andrews, Michael Goodwin, Tovah E. Markowitz, Justin Lack, Helena I. M. Boshoff, Clifton Earl Barry III
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-Mycobacterial species in nature are found in abundance in sphagnum peat bogs where they compete for nutrients with a variety of microorganisms including fungi. We screened a collection of fungi isolated from sphagnum bogs by co-culture with Mycobacterium tuberculosis (Mtb) to look for inducible expression of antitubercular agents and identified 5 fungi that produced cidal antitubercular agents upon exposure to live Mtb. Whole genome sequencing of these fungi followed by fungal RNAseq after Mtb exposure allowed us to identify biosynthetic gene clusters induced by co-culture. Three of these fungi induced expression of patulin, one induced citrinin expression and one induced the production of nidulalin A. The biosynthetic gene clusters for patulin and citrinin have been previously described but the genes involved in nidulalin A production have not been described before. All 3 of these potent electrophiles react with thiols and treatment of Mtb cells with these agents followed by Mtb RNAseq showed that these natural products all induce profound thiol stress suggesting a rapid depletion of mycothiol. The induction of thiol-reactive mycotoxins through 3 different systems in response to exposure to Mtb suggests that fungi have identified this as a highly vulnerable target in a similar microenvironment to that of the caseous human lesion.
+ There is mounting evidence that the cerebellum impacts hippocampal functioning, but the impact of the cerebellum on hippocampal interneurons remains obscure. Using miniscopes in freely behaving male and female mice, we found optogenetic stimulation of Purkinje cells alters the calcium activity of a large percentage of CA1 interneurons. This includes both increases and decreases in activity. Remarkably, this bidirectional impact occurs in a coordinated fashion, in line with interneurons’ functional properties. Specifically, CA1 interneurons activated by cerebellar stimulation are commonly locomotion-active, while those inhibited by cerebellar stimulation are commonly rest-active interneurons. We additionally found that subsets of CA1 interneurons show altered activity during object investigations. Importantly, these interneurons also show coordinated modulation by cerebellar stimulation: CA1 interneurons that are activated by cerebellar stimulation are more likely to be activated, rather than inhibited, during object investigations, while interneurons that show decreased activity during cerebellar stimulation show the opposite profile. We examined two different stimulation locations (IV/V vermis or simplex) and two different stimulation approaches (7 Hz or a single 1 s light pulse)—in all cases, the cerebellum induces similar coordinated CA1 interneuron changes congruent with an explorative state. Overall, our data show that CA1 interneurons are impacted by cerebellar manipulation in a bidirectional and coordinated fashion and are therefore likely to play an important role in cerebello–hippocampal communication.
- in PLoS Biology on 2024-12-03 14:00:00 UTC.
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in Journal of Neuroscience on 2024-12-04 17:29:55 UTC.
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-In the subacute period (i.e., 6 - 12 weeks) following injury, mild traumatic brain injury (mTBI) patients show increased bilateral medial thalamus and right intralaminar volume, when compared to trauma control patients.
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-ABSTRACT
-Structural vulnerability of the thalamus remains underinvestigated in mild traumatic brain injury (mTBI), and few studies have addressed its constituent nuclei using robust segmentation methods. This study aimed to investigate thalamic subnuclei volume in the subacute period following mTBI. Trauma control (TC) and mTBI patients aged 18–60 years old completed a magnetic resonance imaging (MRI) protocol including both high resolution structural (T1w) and diffusion-weighted sequences at 6–12 weeks following injury (mean: 57 days; SD 11). Each thalamus was segmented into its constituent subnuclei, which were grouped into eight lateralized subregions. Volumes of the subregions were calculated. Neurite Orientation Dispersion and Density (NODDI) maps with parameters optimized for gray matter were computed for the same subregions. Group differences in subregion volumes and NODDI parameters were investigated using Bayesian linear modeling, with age, sex, and estimated intracranial volume included as covariates. Comparisons of mTBI (n = 39) and TC (n = 28) groups revealed evidence of relatively increased gray matter volume in the mTBI group for the bilateral medial and right intralaminar subregions (BF10 > 3). Of the subregions which showed volume differences, there was no evidence for differences in NODDI metrics between groups. This study demonstrates that in the subacute period following mTBI, there is evidence of increased volume in specific thalamic subregions. Putative mechanisms underpinning the increased volume observed here are disordered remyelination or myelin debris yet to be cleared.
+ Animal vocalizations and human speech are typically characterized by a complex spectrotemporal structure, composed of multiple harmonics, and patterned as temporally organized sequences. However, auditory research often employed simple artificial acoustic stimuli or their combinations. Here we addressed the question of whether the neuronal responses to natural echolocation call sequences can be predicted by manipulated sequences of incomplete constituents at the midbrain inferior colliculus (IC). We characterized the extracellular single-unit activity of IC neurons in the great roundleaf bat, Hipposideros armiger (both sexes), using natural call sequences, various manipulated sequences of incomplete vocalizations, and pure tones. We report that approximately two-thirds of IC neurons exhibited a harmonic interaction. Neurons with high harmonic interactions exhibited greater selectivity to natural call sequences, and the degree of harmonic interaction was robust to the natural amplitude variations between call harmonics. For 81% of the IC neurons, the responses to the natural echolocation call sequence could not be predicted by altered sequences of missing call components. Surprisingly, nearly 70% of the neurons that showed a harmonic interaction were characterized by a single excitatory response peak as revealed by pure tones. Our results suggest that prevalent harmonic processing has already emerged in the auditory midbrain IC in the echolocating bat.
- in Journal of Neuroscience Research on 2024-12-03 13:35:14 UTC.
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-ABSTRACT
-Neurologic music therapy (NMT) represents a groundbreaking, interdisciplinary approach that combines the therapeutic properties of music with neuroscientific principles to treat a range of neurological and psychiatric conditions. This interdisciplinary approach, increasingly recognized in clinical and research settings, leverages advances in neuroimaging to explore how music affects the structure and activity of the brain. This review provides an in-depth exploration of the multifaceted effects of NMT on brain function, highlighting its role in promoting neuroplastic changes and enhancing cognitive, emotional and motor functions in diverse patient groups. This review consolidates current knowledge on NMT and provides insights into how music affects brain structure and function and the mechanisms of action. The article then discusses the application and research results of NMT in various diseases such as stroke, Alzheimer's disease and Parkinson's disease. Its potential in personalizing therapeutic interventions and its ability to improve treatment access and effectiveness in various settings are highlighted.
+ Mutations in SYNGAP1, a protein enriched at glutamatergic synapses, cause intellectual disability associated with epilepsy, autism spectrum disorder, and sensory dysfunctions. Several studies showed that Syngap1 regulates the time course of forebrain glutamatergic synapse maturation; however, the developmental role of Syngap1 in inhibitory GABAergic neurons is less clear. GABAergic neurons can be classified into different subtypes based on their morphology, connectivity, and physiological properties. Whether Syngap1 expression specifically in parvalbumin (PV)-expressing and somatostatin (SST)-expressing interneurons, which are derived from the medial ganglionic eminence (MGE), plays a role in the emergence of distinct brain functions remains largely unknown. We used genetic strategies to generate Syngap1 haploinsufficiency in (1) prenatal interneurons derived from the medial ganglionic eminence, (2) in postnatal PV cells, and (3) in prenatal SST interneurons. We further performed in vivo recordings and behavioral assays to test whether and how these different genetic manipulations alter brain function and behavior in mice of either sex. Mice with prenatal-onset Syngap1 haploinsufficiency restricted to Nkx2.1-expressing neurons show abnormal cortical oscillations and increased entrainment induced by 40 Hz auditory stimulation but lack stimulus-specific adaptation. This latter phenotype was reproduced in mice with Syngap1 haploinsufficiency restricted to PV, but not SST, interneurons. Prenatal-onset Syngap1 haploinsufficiency in Nkx2.1-expressing neurons led to impaired social behavior and inability to extinguish fear memories; however, neither postnatal PV- nor prenatal SST-specific mutant mice show these phenotypes. We speculate that Syngap1 haploinsufficiency in prenatal/perinatal PV interneurons may contribute to cortical activity and cognitive alterations associated with Syngap1 mutations.
- in Journal of Neuroscience Research on 2024-12-03 12:55:18 UTC.
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- Background Ischemic stroke is a primary contributor to both mortality and disability on a global scale. The triglyceride-glucose index (TyG index), which measures insulin resistance, has been found as a possible predictor of outcomes of cerebrovascular events. Objective To examine the correlation between TyG index and outcomes in patients diagnosed with ischemic stroke. Methods This retrospective analysis of 200 patients diagnosed with ischemic stroke was carried out at the department of medicine, Khyber Teaching Hospital, Peshawar between 1st August 2022 and 31st December 2023. Triglyceride/glucose ratio was determined using the formula TyG = ln [Fasting triglycerides (mg/dl)/Fasting glucose (mg/dl)]/2. Patients were categorized into two Group A (TyG index < 8.8) and Group B (TyG index > 8.8). Demographic data, clinical features, and stroke outcomes, such as death and functional status (assessed by the modified Rankin Scale [mRS]), were compared between the two groups. Results Group A contained (112) patients and Group B (88). Both Group A and Group B had 51.8% (n=58) and 51.1% (n=45) male patients respectively. The mean age of patients in Group A was 65.4 ± 10.2 years and 67.1 ± 11.5 years in group B. 30-day mortality in group A was 8.0% (n=9) and 18.2% (n=16) in group B (p value 0.03). The median mRS score at 3 months in group A was 2.5 versus 3.5 in group B (p value = 0.02). Patients in Group B had longer hospital stay (10.5 ± 3.1days vs. 8.2 ± 2.4days, p = 0.01) and higher frequency of major adverse cardiovascular events (MACE) (15% vs. 7%, p = 0.05). Conclusion In ischemic stroke patients, 30-day mortality was more common with TyG index >8.8 and the modified Rankin Scale (mRS) functional status at 3 months was better in TyG index <8.8.
+ In a real-world environment, the brain must integrate information from multiple sensory modalities, including the auditory and olfactory systems. However, little is known about the neuronal circuits governing how odors influence and modulate sound processing. Here, we investigated the mechanisms underlying auditory–olfactory integration using anatomical, electrophysiological, and optogenetic approaches, focusing on the auditory cortex as a key locus for cross-modal integration. First, retrograde and anterograde viral tracing strategies revealed a direct projection from the piriform cortex to the auditory cortex. Next, using in vivo electrophysiological recordings of neuronal activity in the auditory cortex of awake male or female mice, we found that odors modulate auditory cortical responses to sound. Finally, we used in vivo optogenetic manipulations during electrophysiology to demonstrate that olfactory modulation in the auditory cortex, specifically, odor-driven enhancement of sound responses, depends on direct input from the piriform cortex. Together, our results identify a novel role of piriform-to-auditory cortical circuitry in shaping olfactory modulation in the auditory cortex, shedding new light on the neuronal mechanisms underlying auditory–olfactory integration.
- in F1000Research on 2024-12-03 12:09:38 UTC.
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- Abstract* Background Glioblastoma multiforme (GBM) is the most aggressive and lethal form of brain cancer, and is characterized by rapid progression and poor patient survival. Genetic mutations play a significant role in cancer development and recurrence. This study investigated the role of Mucin 19 (MUC19), a member of the mucin family that has been implicated in cancer progression. We aimed to assess whether MUC19 mutations are associated with a worse prognosis in patients with GBM and explore its potential as a therapeutic target. Methods Data from 16 independent GBM patient datasets were retrieved from the cBioPortal for Cancer Genomics, comprising over 5,600 patients. These patients were categorized into two groups based on their survival status: living and deceased. Clinical attributes, including mutation frequencies and survival outcomes, were analyzed to identify significant genetic alterations in the deceased group. MUC19 is one of the most prominent mutations. To functionally investigate the role of MUC19, we conducted RNA interference (RNAi) experiments using A172 glioblastoma cells. Small interfering RNA (siRNA) specific to MUC19 (siMUC19) was used to knock down MUC19 expression, whereas the negative control group was treated with non-targeting siRNA. The effects on cell viability, proliferation, and MUC19 expression were also assessed. Results Our analysis identified 10 significantly mutated genes in deceased GBM patients, with MUC19 showing the most prominent association with poor outcome. siRNA-mediated knockdown of MUC19 resulted in a significant reduction in cell growth and viability compared to the control group, supporting its role in GBM progression. Conclusion MUC19 plays a significant role in GBM progression, and its suppression leads to reduced tumor cell growth. These findings suggest that MUC19 may be a promising therapeutic target for improving outcomes in patients with GBM. Further research is needed to explore its potential in clinical settings.
+ Single-photon optogenetics enables precise, cell-type–specific modulation of neuronal circuits, making it a crucial tool in neuroscience. Its miniaturization in the form of fully implantable wide-field stimulator arrays enables long-term interrogation of cortical circuits and bears promise for brain–machine interfaces for sensory and motor function restoration. However, achieving selective activation of functional cortical representations poses a challenge, as studies show that targeted optogenetic stimulation results in activity spread beyond one functional domain. While recurrent network mechanisms contribute to activity spread, here we demonstrate with detailed simulations of isolated pyramidal neurons from cats of unknown sex that already neuron morphology causes a complex spread of optogenetic activity at the scale of one cortical column. Since the shape of a neuron impacts its optogenetic response, we find that a single stimulator at the cortical surface recruits a complex spatial distribution of neurons that can be inhomogeneous and vary with stimulation intensity and neuronal morphology across layers. We explore strategies to enhance stimulation precision, finding that optimizing stimulator optics may offer more significant improvements than the preferentially somatic expression of the opsin through genetic targeting. Our results indicate that, with the right optical setup, single-photon optogenetics can precisely activate isolated neurons at the scale of functional cortical domains spanning several hundred micrometers.
- in F1000Research on 2024-12-03 11:59:19 UTC.
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in Journal of Neuroscience on 2024-12-04 17:29:55 UTC.
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- Objective
-Given the high disease and cost burden of ischemic stroke, evaluating the clinical efficacy and cost-effectiveness of new approaches to prevent and treat ischemic stroke is critical. Effective ischemic stroke management depends on timely administration of thrombolytics after stroke onset. This study evaluates the cost-effectiveness associated with the use of mobile stroke units (MSUs) to expedite tissue plasminogen activator (tPA) administration, as compared with standard management through emergency medical services (EMS).
-Methods
-This study is a prospective, multicenter, alternating-week, cluster-controlled trial of MSU versus EMS. One-year and life-time cost-effectiveness analyses, using the incremental cost-effectiveness ratio (ICER) method, were performed from the perspective of CMS's Medicare. Quality-adjusted life years (QALYs) estimated using patient-reported EQ-5D-5L data were used as the effectiveness measure. Health care utilizations were converted to costs using average national Medicare reimbursements. ICERs excluding patients with pre-existing disability, and limited to stroke-related costs were also calculated.
-Results
-The first-year ICER for all tPA-eligible patients using total cost differences between MSU and EMS groups was $238,873/QALY; for patients without pre-existing disability was $61,199/QALY. The lifetime ICERs for all tPA-eligible patients and for those without pre-existing disability were $94,710 and $31,259/QALY, respectively. All ICERs were lower when restricted to stroke-related costs and were highly dependent on the number of patients treated per year in an MSU.
-Interpretation
-MSUs' cost-effectiveness is borderline if we consider total first-year costs and outcomes in all tPA-eligible patients. MSUs are cost-effective to highly cost-effective when calculations are based on patients without pre-existing disability, patients' lifetime horizon, stroke-related costs, and more patients treated per year in an MSU. ANN NEUROL 2024
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- in Annals of Neurology on 2024-12-03 11:44:40 UTC.
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in Journal of Neuroscience on 2024-12-04 17:29:55 UTC.
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- Background This study investigates the influence of perceived follower–leader congruence in basic moral behaviors, as defined by the morality-as-cooperation theory (MAC), on the perceived level of ethical leadership. Although important for the leadership theory and practice, this association is scarcely covered by the literature. Methods The study employed a mixed-methods approach, consisting of a one-site quantitative survey in Phase 1 carried out in a Russophone logistics company, and a follow-up series of semi-structured interviews within the same population in Phase 2. Results The results of Phase 1 showed a moderate positive correlation (r(54) = [.34;.64], p < .05) between perceived congruence in each MAC element and the perceived level of ethical leadership, whereas the findings from Phase 2 demonstrated that this association is causal. Moreover, the research unexpectedly revealed that the influence of the congruence in care for kin, heroism, and deference is mediated by the congruence in loyalty to the group and reciprocity, with the significance level at p < .05 for all indirect effects. The study also found a moderating role of duration of leader’s moral behavior observation by followers. Conclusions This research advances ethical leadership literature by applying the MAC theory to studying the antecedents of the perceived leaders’ ethicality and revealing the mediating role of some basic moral values in assessing a leader’s ethicality. Besides, the study contributes to the cross-cultural validity of both MAC and ethical leadership theories by testing the respective instruments in a Russophone organization.
+ The cortex immediately surrounding a brain ischemic lesion, the peri-infarct cortex (PIC), harbors a large part of the potential to recover lost functions. However, our understanding of the neurophysiological conditions in which synaptic plasticity operates remains limited. Here we hypothesized that the chronic imbalance between excitation and inhibition of the PIC prevents the normalization of the gamma rhythm, a waveband of neural oscillations thought to orchestrate action potential trafficking. Probing the local field potential activity of the forelimb primary sensory cortex (S1FL) located in the PIC of male adult mice, we found a constant, deep reduction of low-gamma oscillation power (L-gamma; 30–50 Hz) precisely during the critical time window for recovery (1–3 weeks after stroke). The collapse of L-gamma power negatively correlated with behavioral progress in affected forelimb use. Mapping astrocyte reactivity and GABA-like immunoreactivity in the PIC revealed a parallel high signal, which gradually increased when approaching the lesion. Increasing tonic inhibition with local infusion of GABA or by blocking its recapture reduced L-gamma oscillation power in a magnitude similar to stroke. Conversely, the negative allosteric modulation of tonic GABA conductance using L655,708 or the gliopeptide ODN rescued the L-gamma power of the PIC. Altogether the present data point out that the chronic excess of ambient GABA in the PIC limits the generation of L-gamma oscillations in the repairing cortex and suggests that rehabilitative interventions aimed at normalizing low-gamma power within the critical period of stroke recovery could optimize the restitution of lost functions.
- in F1000Research on 2024-12-03 10:37:16 UTC.
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- Endometriosis is a benign, estrogen-dependent, persistent chronic inflammatory heterogeneous condition that features fibrotic adhesions caused by periodic bleeding. The characteristic ectopic lesions are marked by a widely spread dense fibrotic interstitium comprising of fibroblasts, myofibroblasts, collagen fibers, extracellular proteins, inflammatory cells, and active angiogenesis. Fibrosis is now recognized as a critical component of endometriosis because of which current treatments, such as hormonal therapy and surgical excision of lesions are largely ineffective with severe side effects, high recurrence rates, and significant morbidity. The symptoms include dysmenorrhea (cyclic or noncyclic), dyspareunia, abdominal discomfort, and infertility. The significant lack of knowledge regarding the underlying root causes, etiology, and complex pathogenesis of this debilitating condition, hinders early diagnosis and implement effective therapeutic approaches with minimal side effects presenting substantial hurdles in endometriosis management. Emerging research offer a close relationship between endometriosis and fibrosis, which is believed to be tightly linked to pain, a primary contributor to the deterioration of the patient’s quality of life. However, the underlying pathophysiological cellular and molecular signaling pathways behind endometriosis-associated fibrosis are poorly addressed. The available experimental disease models have tremendous challenges in reproducing the human characteristics of the disease limiting the treatment effectiveness. Future translational research on the topic has been hindered by the lack of an adequate fibrotic model of endometriosis emphasizing the necessity of etiological exploration. This review article focuses on recent developments in the field and highlight the necessity for novel fibrotic models for early diagnosis, a better understanding the disease’s etiology and develop effective anti-fibrotic treatments. By addressing these knowledge gaps, we want to open fresh avenues for a thorough investigation and extended research in the field of endometriosis.
+ In the anterior area of the mouth, the interdental papilla is important for dental hygiene and appearance. When it disappears, unpleasant “black triangles” form, which affects patients’ self-confidence in their smiles and makes oral hygiene more difficult. The loss of interdental papilla is caused by several variables such as tooth shape, periodontal disease, and aging. Although surgical treatments have been utilized to restore or retain missing papilla, their predictability remains unknown. In response, researchers have investigated non-invasive procedures, such as the use of fillers such as hyaluronic acid (HA). Owing to its capacity to increase tissue volume and bind water, HA, a naturally occurring polysaccharide with special rheological qualities, has become a popular choice for use as a dermal filler. It shows promise when used to cure interdental papilla loss; the effects usually last for six–12 months. This review article explores the development and history of papilla rebuilding methods, emphasizing hyaluronic acid as a cutting-edge and successful method for regaining both periodontal health and aesthetics.
- in F1000Research on 2024-12-03 10:27:27 UTC.
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in F1000Research on 2024-12-04 15:34:29 UTC.
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- Author(s): Quirine J. S. Braat, Cornelis Storm, and Liesbeth M. C. Janssen
Collectively migrating clusters of tumor cells can spread cancer more effectively than single cells, yet the mechanisms driving their formation remain unclear. Using a computational model, this study investigates how cell-cell alignment and the presence of nonmotile cells within a densely packed tumor environment impact clustering dynamics. The study offers new insights into the physical drivers of early-stage metastasis.
[Phys. Rev. E 110, 064401] Published Tue Dec 03, 2024
+ The splenic localization of hydatid cysts is extremely rare. A 50-year-old obese female who consults with a painful and febrile syndrome of the right hypochondrium. Abdominal ultrasound and a CT scan computed tomography revealed a complete situs inversus, a mass of the right hypochondrium measuring 152 mm with membrane detachment, and infiltration of the surrounding fat, evoking a type II complicated splenic hydatic cyst. The patient was operated on in an emergency via midline laparotomy. Exploration revealed situs inversus, an angiant cyst of the spleen. Exposition of the splenic pedicle is difficult. The samples were then infected. Total splenectomy was performed. The postoperative period was unproblematic, and the patient was discharged with antibiotic and antiparasitic treatment and habitual vaccination.
- in Physical Review E: Biological physics on 2024-12-03 10:00:00 UTC.
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in F1000Research on 2024-12-04 15:24:57 UTC.
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- Author(s): Boris Kheyfets and Sergei Mukhin
An analytically solvable model of unsaturated lipid bilayer is derived by introducing finite bending angle of the unsaturated bond relative to straight part of the lipid chain considered previously in our model of semiflexible strings. It is found that the lateral pressure profile of unsaturated lip…
[Phys. Rev. E 110, 064402] Published Tue Dec 03, 2024
+ Abstract* Background This study examines the influence of auxiliary lighting configurations and artificial surface textures on the quality of 3D models generated using Structure from Motion (SfM) in an indoor laboratory setting. Method Experiments were conducted by capturing images of concrete, metal, and wooden specimens at a one-meter distance. Various lighting setups, including vertical and adjacent auxiliary lighting models, were tested to determine their impact on model accuracy. In addition, complex artificial textures, such as checkerboard patterns, were applied to the specimens to assess their effect on 3D model precision. Results Our results demonstrate that optimal lighting and artificial textures significantly enhance the accuracy of 3D models, especially for materials with uniform textures, such as painted metal. For materials with more varied textures, such as concrete and wood, improvements were notable but less pronounced. The combination of auxiliary lighting and artificial textures improved model quality by approximately 40% for high-texture materials and up to 60% for uniform-texture materials. Furthermore, the study highlights the role of image file formats in the SfM process. While RAW images stored in TIFF format offered a slight advantage over lossless JPEG in terms of model accuracy, the difference may not be substantial enough to justify the larger file size in situations where submillimeter precision is not required. Conclusions Overall, our findings emphasize the importance of tailored lighting and texturing strategies for achieving high-precision 3D models in SfM applications. These results are particularly relevant for structural testing and other applications that demand high-fidelity 3D reconstructions, providing a foundation for more accurate and reliable models.
- in Physical Review E: Biological physics on 2024-12-03 10:00:00 UTC.
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in F1000Research on 2024-12-04 15:12:23 UTC.
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- Journal of Neurophysiology, Ahead of Print.
+ Olive (Olea europaea Linaeus 1753) is one of the valuable fruit trees and very important edible oil plant in the world. The chloroplast (cp) genome of an olive tree (Olea europaea) from the southern Peruvian arid coast was obtained for the first time. Genomic DNA of high quality was used to generate librarieswith Illumina Hiseq paired-end methods. The cp genome is 155,886 pb in length and contains a large single-copy region (LSC) of 86,610 pb and a small single copy region (SSC) of 17,790 pb separated by two inverted repeat (IR) regions (25,741bp). The cp genome of olive contains 124 genes that consists of 80 protein-coding genes, 36 tRNA, eight rRNA. Phylogenetic analysis showed this olive tree is sister to O. europaea subsp. maroccana (Oleeae tribe). This study presents the first overview of the chloroplast genome organization and phylogenetics of O. europaea, offering valuable insights for genetic and evolutionary research in the genus Olea.
- in Journal of Neurophysiology on 2024-12-03 03:41:04 UTC.
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in F1000Research on 2024-12-04 15:02:23 UTC.
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- Journal of Neurophysiology, Ahead of Print.
+ Background Cardiovascular disease (CVD) is a leading cause of death worldwide. Ischemic heart disease is a major cause of morbidity and mortality. Lack of blood supply to the brain can cause tissue death if any of the cerebral veins, carotid arteries, or vertebral arteries are blocked. An ischemic stroke describes this type of event. One of the byproducts of methionine metabolism, the demethylation of methionine, is homocysteine, an amino acid that contains sulfur. During myocardial ischemia, the plasma level of homocysteine (Hcy) increases and plays a role in many methylation processes. Hyperhomocysteinemia has only recently been recognized as a major contributor to the increased risk of cardiovascular disease (CVD) owing to its effects on atherothrombosis and improvement of oxidative stress-induced endothelial dysfunction, joining the ranks of other known risk factors such as hyperlipidemia, hypertension, diabetes, and advanced age. Objective The purpose of this study was to determine whether there is a relationship between elevated serum total homocysteine (tHcy) levels and an increased risk of coronary artery disease (CAD) in an Iraqi population of patients with ischemic heart disease. Methods This study was conducted at Madinat al-Imamain Al Kadhmain Hospital’s Cardiology Department in Baghdad, Iraq. The study lasted for six months and was designed as an observational case-control study from November 1, 2023, to April 1, 2024. Results Cases and controls had similar characteristics but differed significantly in serum homocysteine concentration. The mean homocysteine level in case group was 40.21±14.47 mmol/L and 9.23±2.41 mmol/L in control group with p value <0.001. Conclusion In young individuals, hyperhomocysteinemia is positively associated with coronary artery, even when other traditional risk factors are not present.
- in Journal of Neurophysiology on 2024-12-03 02:51:03 UTC.
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in F1000Research on 2024-12-04 14:48:31 UTC.
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- Journal of Neurophysiology, Ahead of Print.
+ by Niloufar Abhari, Caroline Colijn, Arne Mooers, Paul Tupper
+
+Diversity plays an important role in various domains, including conservation, whether it describes diversity within a population or diversity over a set of species. While various strategies for measuring among-species diversity have emerged (e.g. Phylogenetic Diversity (PD), Split System Diversity (SSD) and entropy-based methods), extensions to populations are rare. An understudied problem is how to assess the diversity of a collection of populations where each has its own internal diversity. Relying solely on measures that treat each population as a monomorphic lineage (like a species) can be misleading. To address this problem, we present four population-level diversity assessment approaches: Pooling, Averaging, Pairwise Differencing, and Fixing. These approaches can be used to extend any diversity measure that is primarily defined for a group of individuals to a collection of populations. We then apply the approaches to two measures of diversity that have been used in conservation—Heterozygosity (Het) and Split System Diversity (SSD)—across a dataset comprising SNP data for 50 anadromous Atlantic salmon populations. We investigate agreement and disagreement between these measures of diversity when used to identify optimal sets of populations for conservation, on both the observed data, and randomized and simulated datasets. The similarity and differences of the maximum-diversity sets as well as the pairwise correlations among our proposed measures emphasize the need to clearly define what aspects of biodiversity we aim to both measure and optimize, to ensure meaningful and effective conservation decisions.
- in Journal of Neurophysiology on 2024-12-03 02:01:23 UTC.
+
in PLoS Computational Biology on 2024-12-04 14:00:00 UTC.
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- Journal of Neurophysiology, Volume 132, Issue 6, Page 1823-1836, December 2024.
+ by Henri Schmidt, Benjamin J. Raphael
+Motivation DNA sequencing of multiple bulk samples from a tumor provides the opportunity to investigate tumor heterogeneity and reconstruct a phylogeny of a patient’s cancer. However, since bulk DNA sequencing of tumor tissue measures thousands of cells from a heterogeneous mixture of distinct sub-populations, accurate reconstruction of the tumor phylogeny requires simultaneous deconvolution of cancer clones and inference of ancestral relationships, leading to a challenging computational problem. Many existing methods for phylogenetic reconstruction from bulk sequencing data do not scale to large datasets, such as recent datasets containing upwards of ninety samples with dozens of distinct sub-populations.
Results We develop an approach to reconstruct phylogenetic trees from multi-sample bulk DNA sequencing data by separating the reconstruction problem into two parts: a structured regression problem for a fixed tree T, and an optimization over tree space. We derive an algorithm for the regression sub-problem by exploiting the unique, combinatorial structure of the matrices appearing within the problem. This algorithm has both asymptotic and empirical improvements over linear programming (LP) approaches to the problem. Using our algorithm for this regression sub-problem, we develop fastBE, a simple method for phylogenetic inference from multi-sample bulk DNA sequencing data. We demonstrate on simulated data with hundreds of samples and upwards of a thousand distinct sub-populations that fastBE outperforms existing approaches in terms of reconstruction accuracy, sample efficiency, and runtime. Owing to its scalability, fastBE enables both phylogenetic reconstruction directly from indvidual mutations without requiring the clustering of mutations into clones, as well as a new phylogeny constrained mutation clustering algorithm. On real data from fourteen B-progenitor acute lymphoblastic leukemia patients, fastBE infers mutation phylogenies with fewer violations of a widely used evolutionary constraint and better agreement to the observed mutational frequencies. Using our phylogeny constrained mutation clustering algorithm, we also find mutation clusters with lower distortion compared to state-of-the-art approaches. Finally, we show that on two patient-derived colorectal cancer models, fastBE infers mutation phylogenies with less violation of a widely used evolutionary constraint compared to existing methods.
- in Journal of Neurophysiology on 2024-12-03 01:38:55 UTC.
+
in PLoS Computational Biology on 2024-12-04 14:00:00 UTC.
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- Journal of Neurophysiology, Volume 132, Issue 6, Page 1820-1822, December 2024.
+ by Max Grogan, Kyle P. Blum, Yufei Wu, J. Alex Harston, Lee E. Miller, A. Aldo Faisal
+
+Proprioception is one of the least understood senses, yet fundamental for the control of movement. Even basic questions of how limb pose is represented in the somatosensory cortex are unclear. We developed a topographic variational autoencoder with lateral connectivity (topo-VAE) to compute a putative cortical map from a large set of natural movement data. Although not fitted to neural data, our model reproduces two sets of observations from monkey centre-out reaching: 1. The shape and velocity dependence of proprioceptive receptive fields in hand-centered coordinates despite the model having no knowledge of arm kinematics or hand coordinate systems. 2. The distribution of neuronal preferred directions (PDs) recorded from multi-electrode arrays. The model makes several testable predictions: 1. Encoding across the cortex has a blob-and-pinwheel-type geometry of PDs. 2. Few neurons will encode just a single joint. Our model provides a principled basis for understanding of sensorimotor representations, and the theoretical basis of neural manifolds, with applications to the restoration of sensory feedback in brain-computer interfaces and the control of humanoid robots.
- in Journal of Neurophysiology on 2024-12-03 01:38:54 UTC.
+
in PLoS Computational Biology on 2024-12-04 14:00:00 UTC.
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- The dorsal striatum is instrumental in regulating motor control and goal-directed behaviors. The classical description of the two output pathways of the dorsal striatum highlights their antagonistic control over actions. However, recent experimental evidence implicates both pathways and their coordinated activities during actions. In this review, we examine the different models proposed for striatal encoding of actions during self-paced behaviors and how they can account for evidence harvested during goal-directed behaviors. We also discuss how the activation of striatal ensembles can be reshaped and reorganized to support the formation of instrumental learning and behavioral flexibility. Future work integrating these considerations may resolve controversies regarding the control of actions by striatal networks.
+ by Malthe S. Nordentoft, Naoya Takahashi, Mathias S. Heltberg, Mogens H. Jensen, Rune N. Rasmussen, Athanasia Papoutsi
+
+During neuronal activity, the extracellular concentration of potassium ions ([K+]o) increases substantially above resting levels, yet it remains unclear what role these [K+]o changes play in the dendritic integration of synaptic inputs. We here used mathematical formulations and biophysical modeling to explore the role of synaptic activity-dependent K+ changes in dendritic segments of a visual cortex pyramidal neuron, receiving inputs tuned to stimulus orientation. We found that the spatial arrangement of inputs dictates the magnitude of [K+]o changes in the dendrites: Dendritic segments receiving similarly tuned inputs can attain substantially higher [K+]o increases than segments receiving diversely tuned inputs. These [K+]o elevations in turn increase dendritic excitability, leading to more robust and prolonged dendritic spikes. Ultimately, these local effects amplify the gain of neuronal input–output transformations, causing higher orientation-tuned somatic firing rates without compromising orientation selectivity. Our results suggest that local, activity-dependent [K+]o changes in dendrites may act as a “volume knob” that determines the impact of synaptic inputs on feature-tuned neuronal firing.
- in Trends in Neurosciences: In press on 2024-12-03 00:00:00 UTC.
+
in PLoS Biology on 2024-12-04 14:00:00 UTC.
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- Zhao et al. report the identification and characterization of immunosuppressive neutrophils within human and mouse glioma tumors. The presence of such disease-specific suppressive granulocytes (DSSGs) correlates with glioma grades and poor clinical outcomes. Blockage of DSSGs, which partly originate from the skull bone marrow and meninges, strongly delays tumor progression.
+
+Using histologic and transcriptomic analysis, we found that co-expression of the transcription factors Lmx1b and Phox2b identifies glutamatergic neurons in the nucleus of the solitary tract (NTS), except for a caudal-ventral band of neurons that include Gcg-expressing neurons, which produce glucagon-like peptide 1 (GLP-1). The Lmx1b+Phox2b macropopulation includes subpopulations with distinct distributions expressing Grp, Hsd11b2, Npff, Pdyn, Pou3f1, Sctr, Th, and other markers. This information improves our understanding of the organization and distribution of neurons in this vital brain region.
+
+
+
+ABSTRACT
+The nucleus of the solitary tract (NTS) receives visceral information and regulates appetitive, digestive, and cardiorespiratory systems. Within the NTS, diverse processes operate in parallel to sustain life, but our understanding of their cellular composition is incomplete. Here, we integrate histologic and transcriptomic analysis to identify and compare molecular features that distinguish neurons in this brain region. Most glutamatergic neurons in the NTS and area postrema co-express the transcription factors Lmx1b and Phox2b, except for a ventral band of neurons in the far-caudal NTS, which include the Gcg-expressing neurons that produce glucagon-like peptide 1 (GLP-1). GABAergic interneurons intermingle through the Lmx1b+Phox2b macropopulation, and dense clusters of GABAergic neurons surround the NTS. The Lmx1b+Phox2b macropopulation includes subpopulations with distinct distributions expressing Grp, Hsd11b2, Npff, Pdyn, Pou3f1, Sctr, Th, and other markers. These findings highlight Lmx1b–Phox2b co-expression as a common feature of glutamatergic neurons in the NTS and improve our understanding of the organization and distribution of neurons in this critical brain region.
- in Cell Reports: Current Issue on 2024-12-03 00:00:00 UTC.
+
in Journal of Comparative Neurology on 2024-12-04 10:52:58 UTC.
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- Sadeghi et al. show that signaling pathways initiated by mutant EGFR, unlike the ligand-activated wild-type EGFR, are associated with defective autophosphorylation of the receptor. The distinctive autophosphorylation patterns on mutant EGFR lead to selective activation of PKCα, which promotes anchorage-independent growth and survival in an mTORC1-dependent manner.
+ Background Fuzzy sets and ideals play a significant role in the study of algebraic structures, particularly in the context of pseudo-TM algebras, which are non-commutative generalizations of MV-algebras. However, the concept of fuzzy pseudo-ideals within these algebras has not been extensively explored. This paper introduces fuzzy pseudo-ideals in pseudo-TM algebras and investigates their key properties, contributing to the broader understanding of fuzzy algebraic structures. Methods We define fuzzy pseudo-ideals in the framework of pseudo-TM algebras and investigate their properties using level sets. The paper employs techniques from algebraic logic and set theory to characterize fuzzy pseudo-ideals and their interactions with homomorphism’s and Cartesian products. Several theorems are developed to establish the closure of fuzzy pseudo-ideals under intersection, and their relationships with homomorphism’s and Cartesian products are explored. Results The main findings include a comprehensive characterization of fuzzy pseudo-ideals in pseudo-TM algebras, both in terms of their algebraic structure and their behavior under intersections. We also show how these fuzzy pseudo-ideals interact with homomorphism’s and Cartesian products. Concrete examples are provided to illustrate the theoretical results, demonstrating the applicability of the concepts to real-world algebraic problems. Conclusions This research enhances the theoretical understanding of fuzzy sets and ideals within pseudo-TM algebras, offering new insights into their properties and interrelationships. The results pave the way for future work, particularly in extending the concepts to fuzzy pseudo-strong ideals and fuzzy pseudo-TM ideals. These extensions could further advance the study of fuzzy algebraic structures, contributing to the broader field of algebraic logic and fuzzy set theory.
- in Cell Reports: Current Issue on 2024-12-03 00:00:00 UTC.
+
in F1000Research on 2024-12-04 10:43:46 UTC.
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- Elancheliyan et al. demonstrate that the prohibitin complex is critical for biogenesis of the TIMM17A- and TIMM17B-containing TIM23 translocases. A regulatory protein, OCIAD1, differently controls the levels of both translocase variants. The authors propose a regulatory axis that controls the levels of the TIM23 complex in human cells.
+ Background Fenugreek, or Trigonella foenum-graecum L, is an edible and medicinal plant of the Fabaceae family. Fenugreek seeds are rich in proteins, lipids, and essential nutrients, and they also contain various phytochemicals, including flavonoids, steroidal saponins, coumarin, and alkaloids such as trigonelline. Trigonelline (TG) is a bioactive plant alkaloid initially extracted from fenugreek seeds. A substantial portion of fenugreek’s health benefits may rely on the presence of TG. This study addresses the critical need for a fast, green, and economical method that overcomes inefficiencies, high solvent usage, and sensitivity limitations in the quantification of TG. Methods Fenugreek seeds from various origins were extracted using three green solvents: acetone (ACt), ethanol (EtOH), and water (H2O). The UPLC-MS/MS method was developed and validated using a green mobile phase of H2O: EtOH, and an r2-value of 0.999 in the linearity range of 0.1-500 ppb was adopted. The method was validated with an accuracy of 98.6% for trace analysis of TG using a small amount (10 mg) of fenugreek samples from five different origins. Results The average extract yield was 5.36 mg/100 mg with a standard deviation (SD) of 6.3, with the highest extract yield observed in H2O. The ESI (+ve) of the UPLC-MS/MS resulted in the fragmentation pattern (m/z) 138→94.10→92.05→78.20. The TG quantification revealed an average TG concentration of 181.4 ppb (SD = 176.4), with the highest amount of TG in H2O extract (mean = 392.7, SD = 132.4 ppb), followed by EtOH (mean = 91.9, SD = 83.3 ppb) and ACt (mean = 59.5, SD = 30.9 ppb). The TG amount observed in the validation step substantiated the efficiency and reproducibility of the developed method. Conclusions The method may be used as an effective tool for a green, rapid, economical, and eco-friendly extraction and quantification of TG in diverse matrices of pharmaceutical, cosmeceutical, herbal, and food products.
- in Cell Reports: Current Issue on 2024-12-03 00:00:00 UTC.
+
in F1000Research on 2024-12-04 10:40:53 UTC.
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- Hartley et al. generate Spp1-Cre and Ecel1-Cre mouse lines targeting genetically segregated thalamoreticular subnetworks to identify diverse differences in physiology and brain-wide synaptic inputs to the TRN. They further demonstrate how dysfunction of the FO and HO TRN subnetworks contributes to distinct cortical sensory processing deficits typical of psychiatric endophenotypes.
+ Science Advances, Volume 10, Issue 49, December 2024.
- in Cell Reports: Current Issue on 2024-12-03 00:00:00 UTC.
+
in Science Advances on 2024-12-04 08:00:00 UTC.
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- This study investigates the effects of two parathyroid hormone (PTH) analogs, rhPTH(1-34) and dimeric R25CPTH(1-34), on bone regeneration and osseointegration in a postmenopausal osteoporosis model using beagle dogs. Twelve osteoporotic female beagles were subjected to implant surgeries and assigned to one of three groups: control, rhPTH(1-34), or dimeric R25CPTH(1-34). Bone regeneration and osseointegration were evaluated after 10 weeks using micro-computed tomographic (micro-CT), histological analyses, and serum biochemical assays. Results showed that the rhPTH(1-34) group demonstrated superior improvements in bone mineral density, trabecular architecture, and osseointegration compared to controls, while the dimeric R25CPTH(1-34) group exhibited similar, though slightly less pronounced, anabolic effects. Histological and TRAP assays indicated both PTH analogs significantly enhanced bone regeneration, especially in artificially created bone defects. The findings suggest that both rhPTH(1-34) and dimeric R25CPTH(1-34) hold potential as therapeutic agents for promoting bone regeneration and improving osseointegration around implants in osteoporotic conditions, with implications for their use in bone-related pathologies and reconstructive surgeries.
+ Science Advances, Volume 10, Issue 49, December 2024.
- in eLife on 2024-12-03 00:00:00 UTC.
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in Science Advances on 2024-12-04 08:00:00 UTC.
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- Complex structural and functional changes occurring in typical and atypical development necessitate multidimensional approaches to better understand the risk of developing psychopathology. Here, we simultaneously examined structural and functional brain network patterns in relation to dimensions of psychopathology in the Adolescent Brain Cognitive Development dataset. Several components were identified, recapitulating the psychopathology hierarchy, with the general psychopathology (p) factor explaining most covariance with multimodal imaging features, while the internalizing, externalizing, and neurodevelopmental dimensions were each associated with distinct morphological and functional connectivity signatures. Connectivity signatures associated with the p factor and neurodevelopmental dimensions followed the sensory-to-transmodal axis of cortical organization, which is related to the emergence of complex cognition and risk for psychopathology. Results were consistent in two separate data subsamples and robust to variations in analytical parameters. Although model parameters yielded statistically significant brain-behavior associations in unseen data, generalizability of the model was rather limited for all three latent components (r change from within- to out-of-sample statistics: LC1within=0.36, LC1out=0.03; LC2within=0.34, LC2out=0.05; LC3within=0.35, LC3out=0.07). Our findings help in better understanding biological mechanisms underpinning dimensions of psychopathology, and could provide brain-based vulnerability markers.
+ Science Advances, Volume 10, Issue 49, December 2024.
- in eLife on 2024-12-03 00:00:00 UTC.
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in Science Advances on 2024-12-04 08:00:00 UTC.
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- Although HIV-1 integration sites favor active transcription units in the human genome, high-resolution analysis of individual HIV-1 integration sites has shown that the virus can integrate into a variety of host genomic locations, including non-genic regions. The invisible infection by HIV-1 integrating into non-genic regions, challenging the traditional understanding of HIV-1 integration site selection, is more problematic because they are selected for preservation in the host genome during prolonged antiretroviral therapies. Here, we showed that HIV-1 integrates its viral genome into the vicinity of R-loops, a genomic structure composed of DNA-RNA hybrids. VSV-G-pseudotyped HIV-1 infection initiates the formation of R-loops in both genic and non-genic regions of the host genome and preferentially integrates into R-loop-rich regions. Using a HeLa cell model that can independently control transcriptional activity and R-loop formation, we demonstrated that the exogenous formation of R-loops directs HIV-1 integration-targeting sites. We also found that HIV-1 integrase proteins physically bind to the host genomic R-loops. These findings provide novel insights into the mechanisms underlying retroviral integration and the new strategies for antiretroviral therapy against HIV-1 latent infection.
+ Science Advances, Volume 10, Issue 49, December 2024.
- in eLife on 2024-12-03 00:00:00 UTC.
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in Science Advances on 2024-12-04 08:00:00 UTC.
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- Chronic high-fat feeding triggers metabolic dysfunction including obesity, insulin resistance, and diabetes. How high-fat intake first triggers these pathophysiological states remains unknown. Here, we identify an acute microglial metabolic response that rapidly translates intake of high-fat diet (HFD) to a surprisingly beneficial effect on metabolism and spatial/learning memory. High-fat intake rapidly increases palmitate levels in cerebrospinal fluid and triggers a wave of microglial metabolic activation characterized by mitochondrial membrane activation and fission as well as metabolic skewing toward aerobic glycolysis. These effects are detectable throughout the brain and can be detected within as little as 12 hr of HFD exposure. In vivo, microglial ablation and conditional DRP1 deletion show that the microglial metabolic response is necessary for the acute effects of HFD. 13C-tracing experiments reveal that in addition to processing via β-oxidation, microglia shunt a substantial fraction of palmitate toward anaplerosis and re-release of bioenergetic carbons into the extracellular milieu in the form of lactate, glutamate, succinate, and intriguingly, the neuroprotective metabolite itaconate. Together, these data identify microglia as a critical nutrient regulatory node in the brain, metabolizing away harmful fatty acids and liberating the same carbons as alternate bioenergetic and protective substrates for surrounding cells. The data identify a surprisingly beneficial effect of short-term HFD on learning and memory.
+ Science Advances, Volume 10, Issue 49, December 2024.
- in eLife on 2024-12-03 00:00:00 UTC.
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in Science Advances on 2024-12-04 08:00:00 UTC.
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- Over the last three decades, human genetics has gone from dissecting high-penetrance Mendelian diseases to discovering the vast and complex genetic etiology of common human diseases. In tackling this complexity, scientists have discovered the importance of numerous genetic processes – most notably functional regulatory elements – in the development and progression of these diseases. Simultaneously, scientists have increasingly used multiplex assays of variant effect to systematically phenotype the cellular consequences of millions of genetic variants. In this article, we argue that the context of genetic variants – at all scales, from other genetic variants and gene regulation to cell biology to organismal environment – are critical components of how we can employ genomics to interpret these variants, and ultimately treat these diseases. We describe approaches to extend existing experimental assays and computational approaches to examine and quantify the importance of this context, including through causal analytic approaches. Having a unified understanding of the molecular, physiological, and environmental processes governing the interpretation of genetic variants is sorely needed for the field, and this perspective argues for feasible approaches by which the combined interpretation of cellular, animal, and epidemiological data can yield that knowledge.
+ Science Advances, Volume 10, Issue 49, December 2024.
- in eLife on 2024-12-03 00:00:00 UTC.
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in Science Advances on 2024-12-04 08:00:00 UTC.
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- Overactivity of the sympathetic nervous system is a hallmark of aging. The cellular mechanisms behind this overactivity remain poorly understood, with most attention paid to likely central nervous system components. In this work, we hypothesized that aging also affects the function of motor neurons in the peripheral sympathetic ganglia. To test this hypothesis, we compared the electrophysiological responses and ion-channel activity of neurons isolated from the superior cervical ganglia of young (12 weeks), middle-aged (64 weeks), and old (115 weeks) mice. These approaches showed that aging does impact the intrinsic properties of sympathetic motor neurons, increasing spontaneous and evoked firing responses. A reduction of M current emerged as a major contributor to age-related hyperexcitability. Thus, it is essential to consider the effect of aging on motor components of the sympathetic reflex as a crucial part of the mechanism involved in sympathetic overactivity.
+ Science Advances, Volume 10, Issue 49, December 2024.
- in eLife on 2024-12-03 00:00:00 UTC.
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in Science Advances on 2024-12-04 08:00:00 UTC.
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- The functional effects of an RNA can arise from complex three-dimensional folds known as tertiary structures. However, predicting the tertiary structure of an RNA and whether an RNA adopts distinct tertiary conformations remains challenging. To address this, we developed BASH MaP, a single-molecule dimethyl sulfate (DMS) footprinting method and DAGGER, a computational pipeline, to identify alternative tertiary structures adopted by different molecules of RNA. BASH MaP utilizes potassium borohydride to reveal the chemical accessibility of the N7 position of guanosine, a key mediator of tertiary structures. We used BASH MaP to identify diverse conformational states and dynamics of RNA G-quadruplexes, an important RNA tertiary motif, in vitro and in cells. BASH MaP and DAGGER analysis of the fluorogenic aptamer Spinach reveals that it adopts alternative tertiary conformations which determine its fluorescence states. BASH MaP thus provides an approach for structural analysis of RNA by revealing previously undetectable tertiary structures.
+ Science Advances, Volume 10, Issue 49, December 2024.
- in eLife on 2024-12-03 00:00:00 UTC.
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in Science Advances on 2024-12-04 08:00:00 UTC.
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- Studying the fecal microbiota of wild baboons helps provide new insight into the factors that influence biological aging.
+ Science Advances, Volume 10, Issue 49, December 2024.
- in eLife on 2024-12-03 00:00:00 UTC.
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in Science Advances on 2024-12-04 08:00:00 UTC.
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- During oncogene-induced senescence there are striking changes in the organisation of heterochromatin in the nucleus. This is accompanied by activation of a pro-inflammatory gene expression programme - the senescence associated secretory phenotype (SASP) - driven by transcription factors such as NF-κB. The relationship between heterochromatin re-organisation and the SASP has been unclear. Here we show that TPR, a protein of the nuclear pore complex basket required for heterochromatin re-organisation during senescence, is also required for the very early activation of NF-κB signalling during the stress-response phase of oncogene-induced senescence. This is prior to activation of the SASP and occurs without affecting NF-κB nuclear import. We show that TPR is required for the activation of innate immune signalling at these early stages of senescence and we link this to the formation of heterochromatin-enriched cytoplasmic chromatin fragments thought to bleb off from the nuclear periphery. We show that HMGA1 is also required for cytoplasmic chromatin fragment formation. Together these data suggest that re-organisation of heterochromatin is involved in altered structural integrity of the nuclear periphery during senescence, and that this can lead to activation of cytoplasmic nucleic acid sensing, NF-κB signalling, and activation of the SASP.
+ Science Advances, Volume 10, Issue 49, December 2024.
- in eLife on 2024-12-03 00:00:00 UTC.
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in Science Advances on 2024-12-04 08:00:00 UTC.
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- In amniotes, head motions and tilt are detected by two types of vestibular hair cells (HCs) with strikingly different morphology and physiology. Mature type I HCs express a large and very unusual potassium conductance, gK,L, which activates negative to resting potential, confers very negative resting potentials and low input resistances, and enhances an unusual non-quantal transmission from type I cells onto their calyceal afferent terminals. Following clues pointing to KV1.8 (Kcna10) in the Shaker K channel family as a candidate gK,L subunit, we compared whole-cell voltage-dependent currents from utricular HCs of KV1.8-null mice and littermate controls. We found that KV1.8 is necessary not just for gK,L but also for fast-inactivating and delayed rectifier currents in type II HCs, which activate positive to resting potential. The distinct properties of the three KV1.8-dependent conductances may reflect different mixing with other KV subunits that are reported to be differentially expressed in type I and II HCs. In KV1.8-null HCs of both types, residual outwardly rectifying conductances include KV7 (Knq) channels. Current clamp records show that in both HC types, KV1.8-dependent conductances increase the speed and damping of voltage responses. Features that speed up vestibular receptor potentials and non-quantal afferent transmission may have helped stabilize locomotion as tetrapods moved from water to land.
+ Science Advances, Volume 10, Issue 49, December 2024.
- in eLife on 2024-12-03 00:00:00 UTC.
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in Science Advances on 2024-12-04 08:00:00 UTC.
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- Brain Sciences, Vol. 14, Pages 1225: Middle and Long Latency Cutaneous Reflexes During the Stance Phase of Gait in Individuals with and Without Chronic Ankle Instability
- Brain Sciences doi: 10.3390/brainsci14121225
- Authors:
- Leif P. Madsen
- Annalee M. H. Friedman
- Carrie L. Docherty
- Koichi Kitano
- David M. Koceja
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- Background/objectives: Lower limb cutaneous reflex amplitudes can modulate across gait, which helps humans adjust rhythmic motor outputs to maintain balance in an ever-changing environment. Preliminary evidence suggests people who suffer from repetitive ankle sprains and residual feelings of giving way demonstrate altered cutaneous reflex patterns in the gastrocnemius. However, before cutaneous reflex assessment can be implemented as a clinical outcome measure, there is a need to substantiate these early findings by measuring reflex amplitudes across longer latency periods and exploring the variability of reflexes within each subject. Methods: Forty-eight subjects with and without chronic ankle instability (CAI) walked on a treadmill at 4 km/h while activity of the lateral gastrocnemius (LG) was measured via surface electromyography. Non-noxious stimulations were elicited randomly to the ipsilateral sural nerve at the mid-stance phase of gait, and reflex amplitudes were calculated offline by comparing muscle activity during unstimulated and stimulated gait cycles. Two primary outcome measures were compared between groups at the middle latency (MLR: 80&ndash;120 ms) and late latency (LLR: 120&ndash;150 ms) time windows: (1) average reflex amplitudes and (2) standard deviation of reflex amplitudes for each subject across 10 trials. Results: Both groups demonstrated an equal amount of LG inhibition at the MLR and LG facilitation at the LLR. However, subjects with CAI showed significantly higher variability in LLR amplitude across trials than healthy controls. Conclusions: Increased variability of cutaneous reflex amplitudes may relate to symptoms associated with CAI. These findings suggest that reflex variability following sural nerve stimulation could serve as an objective measure to track treatment progress in patients with CAI, offering clinicians a new tool for conducting rehabilitation assessments in a controlled environment.
+ Science Advances, Volume 10, Issue 49, December 2024.
- in Brain Sciences on 2024-12-03 00:00:00 UTC.
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in Science Advances on 2024-12-04 08:00:00 UTC.
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- Brain Sciences, Vol. 14, Pages 1224: A Review of the Consequences of Gut Microbiota in Neurodegenerative Disorders and Aging
- Brain Sciences doi: 10.3390/brainsci14121224
- Authors:
- Amanda A. Menezes
- Zahoor A. Shah
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- Age-associated alterations in the brain lead to cognitive deterioration and neurodegenerative disorders (NDDs). This review with a particular focus on Alzheimer&rsquo;s disease (AD), emphasizes the burgeoning significance of the gut microbiota (GMB) in neuroinflammation and its impact on the gut&ndash;brain axis (GBA), a communication conduit between the gut and the central nervous system (CNS). Changes in the gut microbiome, including diminished microbial diversity and the prevalence of pro-inflammatory bacteria, are associated with AD pathogenesis. Promising therapies, such as fecal microbiota transplantation (FMT), probiotics, and prebiotics, may restore gut health and enhance cognitive performance. Clinical data remain insufficient, necessitating further research to elucidate causes, enhance therapy, and consider individual variances. This integrative approach may yield innovative therapies aimed at the GMB to improve cognitive function and brain health in older people.
+ Science Advances, Volume 10, Issue 49, December 2024.
- in Brain Sciences on 2024-12-03 00:00:00 UTC.
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- Brain Sciences, Vol. 14, Pages 1223: Cerebrospinal Fluid Leak Prevention in Intradural Spine Surgery: A Long Series Analysis of Closure with Non-Penetrating Titanium Clips
- Brain Sciences doi: 10.3390/brainsci14121223
- Authors:
- Leonardo Anselmi
- Carla Daniela Anania
- Maria Cleofe Ubezio
- Generoso Farinaro
- Donato Creatura
- Alessandro Ortolina
- Massimo Tomei
- Ali Baram
- Maurizio Fornari
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- Background/Objectives: Postoperative cerebrospinal fluid (CSF) fistulas remain a significant concern in spinal neurosurgery, particularly following dural closure. The incidence of dural tears during spinal surgery is estimated between 1.6% and 10%. While direct suturing remains the gold standard, it has a failure rate of 5&ndash;10%. Various materials and techniques have been used to enhance dural closure. This study aims to assess the effectiveness of non-penetrating titanium clips (AnastoClip&reg;) for dural closure in intradural spinal lesion surgeries. Methods: A prospective analysis was conducted on 272 patients who were operated on for intradural spinal lesions from August 2017 to December 2023. Dural closure was performed using non-penetrating titanium clips with sealant, and, in select cases, autologous grafts. Postoperative care included early mobilization and routine MRI to assess outcomes. A comparative analysis was performed with a cohort of 81 patients treated with traditional sutures. Results: Among the 272 patients, postoperative CSF leaks occurred in 32 cases (11.76%), requiring various management approaches. Thirteen cases required surgical revision, while others resolved with external lumbar drainage or fluid aspiration. Compared to the suture group, which had a fistula rate of 23.46%, the titanium clip group had a significantly lower fistula rate. Logistic regression analysis did not find statistically significant associations between fistula risk and clinical factors. Conclusions: Non-penetrating titanium clips provide an effective alternative to sutures for dural closure, reducing CSF leak rates. They preserve dural integrity, reduce operative time, and avoid imaging artifacts, making them a viable advancement in spinal surgery with outcomes comparable to, or better than, traditional techniques.
+ Science Advances, Volume 10, Issue 49, December 2024.
- in Brain Sciences on 2024-12-03 00:00:00 UTC.
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- Background Several scholars defined the concepts of fuzzy soft set theory and their application on decision-making problem. Based on this concept, researchers defined the generalised fuzzy soft set and its applications. However, to the best of the author’s knowledge, the generalised fuzzy soft set has not been dealing with in the generalised fuzzy soft code set. In this paper, we introduce the notion of generalised fuzzy soft code set and its application. Methods The theory of fuzzy soft sets and its application, generalised fuzzy soft sets and fuzzy codes in different years were studied with various researchers. To derive a generalised fuzzy soft code set, we apply the concepts of generalised fuzzy soft set and a new view of fuzzy codes and its application. A new aspect of this paper is to introduce the definition of generalised fuzzy soft code sets and its application on medical diagnosis and decision-makings. Results Generalised fuzzy soft code is the most powerful and effective extension of fuzzy soft sets that deal with the choice’s parameterized values. It is an extended model of fuzzy soft sets and a new mathematical tool with significant advantages for handling uncertain information and is proposed by combining the concept of fuzzy soft sets and fuzzy code sets. This paper introduces the concept of generalised fuzzy soft code and its properties. Conclusions In this study, we combine generalised fuzzy soft set and a different approach to coding theory to introduce generalisation of fuzzy soft codes. The paper also considers the relation between generalised fuzzy soft code and its application. We discussed the matrix representation of generalised fuzzy soft code. Furthermore, a demonstration example illustrates how the strategy could be effectively applied to various problems.
+ Science Advances, Volume 10, Issue 49, December 2024.
- in F1000Research on 2024-12-02 15:40:23 UTC.
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- Background To supplement the extant literature on the economics of employing persons of disability, the present study explores the challenges and opportunities companies face with the employment of people with disabilities. Despite legal frameworks and growing awareness, individuals with disabilities often face significant barriers to securing meaningful employment. Misconceptions about their capabilities and concerns over potential costs persist, overshadowing evidence of economic and social benefits. This study explores these dynamics, emphasizing the potential advantages of inclusive hiring practices for organizations. Methods Semi-structured expert interviews were conducted with HR managers from five South Tyrolean companies across diverse industries. Participants were selected based on criteria such as company size (minimum 35 employees) and HR management experience (at least 3 years). Interviews focused on exploring workplace adjustments, employment motivations, challenges, and barriers, generating qualitative insights into inclusion practices. Results The study identified several advantages of employing individuals with disabilities, including low turnover rates, increased employee motivation, and a positive workplace atmosphere. Most companies incurred minimal costs for workplace adjustments. Challenges included insufficient understanding among staff, difficulty matching job roles with capabilities, and bureaucratic obstacles. The experts also noted a lack of job applications from individuals with disabilities, potentially due to low confidence or family overprotection. Conclusions Employing people with disabilities can be economically profitable and is not limited to social aspects alone. Existing barriers can often be dismantled without significant financial or time investment, with obstacles being readily overcome. This article contributes to a better understanding of challenges and opportunities of employing staff with disabilities and demonstrates the conditions under which economic benefits emerge for companies. The findings are discussed from an economical and social/cultural perspective with practical implications for human resource practice and operation management.
+ Science Advances, Volume 10, Issue 49, December 2024.
- in F1000Research on 2024-12-02 15:30:04 UTC.
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- Backround/Objectives We investigated a technique that facilitates the coiling of a regular straight catheter (with integral stylet) behind the sciatic nerve in an ultrasound (US) regional anaesthesia simulator, and then applied our findings to a series of orthopedic-trauma patients. Methods We conducted a randomized study of two methods of perineural catheter advancement in a sciatic nerve block Blue Phantom simulator. Two groups of twenty catheters each (method A and method B) were evaluated under real-time ultrasound imaging. The needle in-plane/nerve in-short-axis technique was applied. In method A the catheter was advanced beyond the needle tip with the integral stylet extending along its entire length; in method B the catheter was advanced after its integral stylet was retracted by 6 cm, thus providing flexibility to the catheter’s distal end. Additionally, to assess the procedural effectiveness of method B coiling technique, a pilot study was conducted examining 25 perineural catheters coiled underneath the sciatic nerve in trauma-orthopaedic patients to document any catheter tip displacement from their initial position (for 36 hours postoperatively). Results In the simulation study, method B led to a significantly higher percentage (18/20:90%) of coiled catheters than method A (3/20:15%). Two coiled catheters of method B were found kinked/obstructed. In our patients, after catheter insertion, the distal end of 2/25 (8%) coiled catheters was obstructed. One perineural catheter was dislodged. For the remaining 22 (88%) catheters, ultrasound imaging demonstrated that local anaesthetic infusion made contact with the sciatic nerve, indicating no displacement of the catheter’s distal end postoperatively. Conclusion Regular straight perineural catheters can be coiled if their integral stylet is partially retracted. This coiling method offers extra catheter length adjacent to the nerve structure which potentially mitigates catheter tip displacement. Trial registration clinicaltrials.gov, registration No: NCT06568510, 23/08/2024, registration URL: https://clinicaltrials.gov/study/NCT06568510?intr=coiling%20of%20echogenic%20sciatic%20nerve&rank=1#study-overview
+ Science Advances, Volume 10, Issue 49, December 2024.
- in F1000Research on 2024-12-02 15:27:20 UTC.
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- Background Livelihood diversification involves households earning through various economic activities, such as non-farm businesses, entrepreneurship, and off-farm jobs, improving sustainability, resilience, risk sharing, employment opportunities, and reducing poverty and food insecurity. However, little research has been done on the status, factors and relation of livelihood diversification and food security. This study explores the relationship between food security and livelihood diversification in the Chencha district of southern Ethiopia, focusing on determinants and their connection with household food security. Methods Quantitative and qualitative data were collected from 303 randomly selected households using surveys, key informant interviews, focus group discussions, and observations. Data were analyzed by using descriptive statistics, Herfindahl-Hirschman Index, Ordered probit regression and Pearson’s correlation coefficient. Results The result revealed that subsistence farming (52.1%) and weaving (38.6%) activities were reported as the primary and secondary main income sources of households. A majority of households (90.7%) diversified their livelihood. Based on income share, non-farm, on-farm, and off-farm income sources contributed, 72.96%, 25.3%, and 1.74% of total household income, respectively. Formal employment, weaving, barber/hairdresser, cattle production and sale, cereal production, and vegetable production (Potato) were highly paying livelihood activities in order. Households who combined on-farm, off-farm, and non-farm have gained far larger mean income followed by on-farm and non-farm strategies. Ordered Probit model results showed that landholding size, livestock holding size, and access to farmer training center (FTC) have positively affected the extent of livelihood diversification. Positive association was found between livelihood diversification and the food security status of households. Conclusion thus, the majority of weaving-based livelihood groups diversify their livelihood activities to on-farm, off-farm, and non-farm activities. Hence, supporting the weaving activity and motivating females’ participation, increasing other livelihood options, and modernizing the system with appropriate training, education, and market linkage seems inevitable.
+ Science Advances, Volume 10, Issue 49, December 2024.
- in F1000Research on 2024-12-02 15:05:36 UTC.
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- Background Prosthodontics significantly impacts oral health-related quality of life, especially oral comfort, functions, aesthetics, and overall well-being. This discipline is grounded in a solid academic and evidence-based understanding of fundamental principles for managing dental diseases and aims to restore the health of teeth and supporting tissues and compensate missing ones. Dental education is evolving quickly with the rise of digital dentistry, especially in prosthodontics. Integrating augmented reality simulations and haptic feedback has significantly advanced this transformation. This systematic review protocol intends to determine the effectiveness of haptic simulators in prosthodontics training during preclinical dental education. Methods An exhaustive search strategy will be employed, exploring PubMed, Scopus, EBSCO, Web of Science and Cochrane Central to select relevant studies, thereby enhancing the robustness of the review findings. Boolean operators (AND,OR) were utilized to assemble MeSH terms and relevant keywords. Titles and abstracts screening to identify studies that satisfy the eligibility criteria was followed by the quality and risk of bias assessment for the selected studies, via the Cochrane Collaboration’s tool and the Newcastle-Ottawa Scale (NOS). Data will be collected via standard form. Reviewers disagreement will be solved throughout debate, or by referring to a third opinion. This protocol will adhere the recommendations appointed by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Discussion The outcomes of this systematic review are highly significant for dental education exploring the importance of enhancing haptic simulation during preclinic prosthetic training. Recognizing the strengths and weaknesses of virtual reality (VR) in relation to traditional preclinical training methods is crucial for developing effective educational strategies. This understanding can lead to enhanced training outcomes and increased student satisfaction, which in turn contributes to improved quality of clinical prosthetic services. Systematic review registration PROSPERO: CRD42024603681 (Registered on 30/10/2024).
+ Science Advances, Volume 10, Issue 49, December 2024.
- in F1000Research on 2024-12-02 15:04:27 UTC.
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-Spinal and vagal afferents project to all layers of the rat atrium, with distinct patterns in each layer. In the epicardium, spinal afferents make close contacts with cardiac ganglionic neurons and adipose tissue, whereas vagal afferents selectively form pericellular terminal structures around small intensely fluorescent (SIF) cells. In the myocardium, spinal afferents display a range of axonal projections, from simple to complex branching patterns, whereas vagal afferents form specialized intramuscular endings. In the endocardium, some spinal afferents branch into free nerve endings, whereas vagal afferents form many distinct “flower-sprays” and end-net terminals.
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-ABSTRACT
-The spinal afferent innervation of the heart helps to regulate cardiac functions by sending sensory information through the dorsal root ganglia (DRG) to the brain. However, the distribution and morphology of spinal afferents in the heart are not well characterized due to tracer selections, the surgical access to upper thoracic DRGs, and the thickness of the heart tissues. In this study, we injected tracer dextran biotin (DB) into the left DRGs (C8-T3) of male Sprague–Dawley rats (3–5 months). After 16 days, flat-mounts of the whole left and right atria were prepared and diaminobenzidine stained. Then, the DB-labeled axons in the tissues were imaged, traced, and digitized using the Neurolucida system. Our results showed that the DB-labeled axons from left DRGs entered the left precaval vein and projected to the left and right atria, with predominant projection in the left atrial wall. DB-labeled varicose axons were observed in different layers, mostly in the epicardium and myocardium, but much less in the endocardium. In those layers, these spinal afferent axons branched out into simple to complex terminal arborizations, forming close appositions with cardiac muscles, intrinsic cardiac ganglia, blood vessels, and fat tissue. This work, for the first time, characterized cardiac spinal afferent distribution of the rat atria using anterograde tracing, which will provide the foundation for future studies of topographical cardiac spinal afferent innervation and remodeling in heart disease models.
+ Science Advances, Volume 10, Issue 49, December 2024.
- in Journal of Comparative Neurology on 2024-12-02 14:39:36 UTC.
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- by Michiel Vanslambrouck, Wim Thiels, Jef Vangheel, Casper van Bavel, Bart Smeets, Rob Jelier
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-During morphogenesis, cells precisely generate forces that drive cell shape changes and cellular motion. These forces predominantly arise from contractility of the actomyosin cortex, allowing for cortical tension, protrusion formation, and cell division. Image-based force inference can derive such forces from microscopy images, without complicated and time-consuming experimental set-ups. However, current methods do not account for common effects, such as physical confinement and local force generation. Here we propose a force-inference method based on a biophysical model of cell shape, and assess relative cellular surface tension, adhesive tension between cells, as well as cytokinesis and protrusion formation. We applied our method on fluorescent microscopy images of the early C. elegans embryo. Predictions for cell surface tension at the 7-cell stage were validated by measurements using cortical laser ablation. Our non-invasive method facilitates the accurate tracking of force generation, and offers many new perspectives for studying morphogenesis.
+ Science Advances, Volume 10, Issue 49, December 2024.
- in PLoS Computational Biology on 2024-12-02 14:00:00 UTC.
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- by Adrián F. Amil, Albert Albesa-González, Paul F. M. J. Verschure
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-Theta-band oscillations (3–8 Hz) in the mammalian hippocampus organize the temporal structure of cortical inputs, resulting in a phase code that enables rhythmic input sampling for episodic memory formation and spatial navigation. However, it remains unclear what evolutionary pressures might have driven the selection of theta over higher-frequency bands that could potentially provide increased input sampling resolution. Here, we address this question by introducing a theoretical framework that combines the efficient coding and neural oscillatory sampling hypotheses, focusing on the information rate (bits/s) of phase coding neurons. We demonstrate that physiologically realistic noise levels create a trade-off between the speed of input sampling, determined by oscillation frequency, and encoding precision in rodent hippocampal neurons. This speed-precision trade-off results in a maximum information rate of ∼1–2 bits/s within the theta frequency band, thus confining the optimal oscillation frequency to the low end of the spectrum. We also show that this framework accounts for key hippocampal features, such as the preservation of the theta band along the dorsoventral axis despite physiological gradients, and the modulation of theta frequency and amplitude by running speed. Extending the analysis beyond the hippocampus, we propose that theta oscillations could also support efficient stimulus encoding in the visual cortex and olfactory bulb. More broadly, our framework lays the foundation for studying how system features, such as noise, constrain the optimal sampling frequencies in both biological and artificial brains.
+ Science Advances, Volume 10, Issue 49, December 2024.
- in PLoS Computational Biology on 2024-12-02 14:00:00 UTC.
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- by Nisha Ann Viswan, Alexandre Tribut, Manvel Gasparyan, Ovidiu Radulescu, Upinder S. Bhalla
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-Biological signalling systems are complex, and efforts to build mechanistic models must confront a huge parameter space, indirect and sparse data, and frequently encounter multiscale and multiphysics phenomena. We present HOSS, a framework for Hierarchical Optimization of Systems Simulations, to address such problems. HOSS operates by breaking down extensive systems models into individual pathway blocks organized in a nested hierarchy. At the first level, dependencies are solely on signalling inputs, and subsequent levels rely only on the preceding ones. We demonstrate that each independent pathway in every level can be efficiently optimized. Once optimized, its parameters are held constant while the pathway serves as input for succeeding levels. We develop an algorithmic approach to identify the necessary nested hierarchies for the application of HOSS in any given biochemical network. Furthermore, we devise two parallelizable variants that generate numerous model instances using stochastic scrambling of parameters during initial and intermediate stages of optimization. Our results indicate that these variants produce superior models and offer an estimate of solution degeneracy. Additionally, we showcase the effectiveness of the optimization methods for both abstracted, event-based simulations and ODE-based models.
+ Science Advances, Volume 10, Issue 49, December 2024.
- in PLoS Computational Biology on 2024-12-02 14:00:00 UTC.
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- by Meng Yuan, Seppe Goovaerts, Michiel Vanneste, Harold Matthews, Hanne Hoskens, Stephen Richmond, Ophir D. Klein, Richard A. Spritz, Benedikt Hallgrimsson, Susan Walsh, Mark D. Shriver, John R. Shaffer, Seth M. Weinberg, Hilde Peeters, Peter Claes
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-Human facial shape, while strongly heritable, involves both genetic and structural complexity, necessitating precise phenotyping for accurate assessment. Common phenotyping strategies include simplifying 3D facial features into univariate traits such as anthropometric measurements (e.g., inter-landmark distances), unsupervised dimensionality reductions (e.g., principal component analysis (PCA) and auto-encoder (AE) approaches), and assessing resemblance to particular facial gestalts (e.g., syndromic facial archetypes). This study provides a comparative assessment of these strategies in genome-wide association studies (GWASs) of 3D facial shape. Specifically, we investigated inter-landmark distances, PCA and AE-derived latent dimensions, and facial resemblance to random, extreme, and syndromic gestalts within a GWAS of 8,426 individuals of recent European ancestry. Inter-landmark distances exhibit the highest SNP-based heritability as estimated via LD score regression, followed by AE dimensions. Conversely, resemblance scores to extreme and syndromic facial gestalts display the lowest heritability, in line with expectations. Notably, the aggregation of multiple GWASs on facial resemblance to random gestalts reveals the highest number of independent genetic loci. This novel, easy-to-implement phenotyping approach holds significant promise for capturing genetically relevant morphological traits derived from complex biomedical imaging datasets, and its applications extend beyond faces. Nevertheless, these different phenotyping strategies capture different genetic influences on craniofacial shape. Thus, it remains valuable to explore these strategies individually and in combination to gain a more comprehensive understanding of the genetic factors underlying craniofacial shape and related traits.
+ Science Advances, Volume 10, Issue 49, December 2024.
- in PLoS Computational Biology on 2024-12-02 14:00:00 UTC.
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- by Yuqian Liu, Yan Chen, Huanwen Wu, Xuanping Zhang, Yuqi Wang, Xin Yi, Zhiyong Liang, Jiayin Wang
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-Microsatellite instability (MSI) is an important genomic biomarker for cancer diagnosis and treatment, and sequencing-based approaches are often applied to identify MSI because of its fastness and efficiency. These approaches, however, may fail to identify MSI on one or more sub-clones for certain cancers with a high degree of heterogeneity, leading to erroneous diagnoses and unsuitable treatments. Besides, the computational cost of identifying sub-clonal MSI can be exponentially increased when multiple sub-clones with different length distributions share MSI status. Herein, this paper proposes “scMSI”, an accurate and efficient estimation of sub-clonal MSI to identify the microsatellite status. scMSI is an integrative Bayesian method to deconvolute the mixed-length distribution of sub-clones by a novel alternating iterative optimization procedure based on a subtle generative model. During the process of deconvolution, the optimized division of each sub-clone is attained by a heuristic algorithm, aligning with clone proportions that adhere optimally to the sample’s clonal structure. To evaluate the performance, 16 patients diagnosed with endometrial cancer, exhibiting positive responses to the treatment despite having negative MSI status based on sequencing-based approaches, were considered. Excitingly, scMSI reported MSI on sub-clones successfully, and the findings matched the conclusions on immunohistochemistry. In addition, testing results on a series of experiments with simulation datasets concerning a variety of impact factors demonstrated the effectiveness and superiority of scMSI in detecting MSI on sub-clones over existing approaches. scMSI provides a new way of detecting MSI for cancers with a high degree of heterogeneity.
+ Science Advances, Volume 10, Issue 49, December 2024.
- in PLoS Computational Biology on 2024-12-02 14:00:00 UTC.
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- by Mark A. Orloff, Dongil Chung, Xiaosi Gu, Xingchao Wang, Zhixian Gao, Guiding Song, Chandana Tatineni, Shuai Xu, Brooks Casas, Pearl H. Chiu
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-When making risky choices in social contexts, humans typically combine social information with individual preferences about the options at stake. It remains unknown how such decisions are made when these preferences are inaccessible or disrupted, as might be the case for individuals confronting novel options or experiencing cognitive impairment. Thus, we examined participants with lesions in insular or dorsal anterior cingulate cortex, key regions implicated in risky decision-making, as they played a gambling task where choices were made both alone and after observing others’ choices. Participants in both lesion groups showed disrupted use of standard utility-based computations about risky options. For socially situated decisions, these participants showed increased conformity with the choices of others, independent from social utility-based computations. These findings suggest that in social contexts, following others’ choices may be a heuristic for decision-making when utility-based risk processing is disrupted.
+ Science Advances, Volume 10, Issue 49, December 2024.
- in PLoS Computational Biology on 2024-12-02 14:00:00 UTC.
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- by Lalit Pandey, Donsuk Lee, Samantha M. W. Wood, Justin N. Wood
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-How do newborns learn to see? We propose that visual systems are space-time fitters, meaning visual development can be understood as a blind fitting process (akin to evolution) in which visual systems gradually adapt to the spatiotemporal data distributions in the newborn’s environment. To test whether space-time fitting is a viable theory for learning how to see, we performed parallel controlled-rearing experiments on newborn chicks and deep neural networks (DNNs), including CNNs and transformers. First, we raised newborn chicks in impoverished environments containing a single object, then simulated those environments in a video game engine. Second, we recorded first-person images from agents moving through the virtual animal chambers and used those images to train DNNs. Third, we compared the viewpoint-invariant object recognition performance of the chicks and DNNs. When DNNs received the same visual diet (training data) as chicks, the models developed common object recognition skills as chicks. DNNs that used time as a teaching signal—space-time fitters—also showed common patterns of successes and failures across the test viewpoints as chicks. Thus, DNNs can learn object recognition in the same impoverished environments as newborn animals. We argue that space-time fitters can serve as formal scientific models of newborn visual systems, providing image-computable models for studying how newborns learn to see from raw visual experiences.
+ Science Advances, Volume 10, Issue 49, December 2024.
- in PLoS Computational Biology on 2024-12-02 14:00:00 UTC.
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- by Jan Stasinski, Halgurd Taher, Jil Mona Meier, Michael Schirner, Dionysios Perdikis, Petra Ritter
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-Simulations of large-scale brain dynamics are often impacted by overexcitation resulting from heavy-tailed structural network distributions, leading to biologically implausible simulation results. We implement a homeodynamic plasticity mechanism, known from other modeling work, in the widely used Jansen-Rit neural mass model for The Virtual Brain (TVB) simulation framework. We aim at heterogeneously adjusting the inhibitory coupling weights to reach desired dynamic regimes in each brain region. We show that, by using this dynamic approach, we can control the target activity level to obtain biologically plausible brain simulations, including post-synaptic potentials and blood-oxygen-level-dependent functional magnetic resonance imaging (fMRI) activity. We demonstrate that the derived dynamic Feedback Inhibitory Control (dFIC) can be used to enable increased variability of model dynamics. We derive the conditions under which the simulated brain activity converges to a predefined target level analytically and via simulations. We highlight the benefits of dFIC in the context of fitting the TVB model to static and dynamic measures of fMRI empirical data, accounting for global synchronization across the whole brain. The proposed novel method helps computational neuroscientists, especially TVB users, to easily “tune” brain models to desired dynamical regimes depending on the specific requirements of each study. The presented method is a steppingstone towards increased biological realism in brain network models and a valuable tool to better understand their underlying behavior.
+ Science Advances, Volume 10, Issue 49, December 2024.
- in PLoS Computational Biology on 2024-12-02 14:00:00 UTC.
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- by Maciej Majka, Nils B. Becker, Pieter Rein ten Wolde, Marcin Zagorski, Thomas R. Sokolowski
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-Gene expression patterns in developing organisms are established by groups of cross-regulating target genes that are driven by morphogen gradients. As development progresses, morphogen activity is reduced, leaving the emergent pattern without stabilizing positional cues and at risk of rapid deterioration due to the inherently noisy biochemical processes at the cellular level. But remarkably, gene expression patterns remain spatially stable and reproducible over long developmental time spans in many biological systems. Here we combine spatial-stochastic simulations with an enhanced sampling method (Non-Stationary Forward Flux Sampling) and a recently developed stability theory to address how spatiotemporal integrity of a gene expression pattern is maintained in developing tissue lacking morphogen gradients. Using a minimal embryo model consisting of spatially coupled biochemical reactor volumes, we study a prototypical stripe pattern in which weak cross-repression between nearest neighbor expression domains alternates with strong repression between next-nearest neighbor domains, inspired by the gap gene system in the Drosophila embryo. We find that tuning of the weak repressive interactions to an optimal level can prolong stability of the expression patterns by orders of magnitude, enabling stable patterns over developmentally relevant times in the absence of morphogen gradients. The optimal parameter regime found in simulations of the embryo model closely agrees with the predictions of our coarse-grained stability theory. To elucidate the origin of stability, we analyze a reduced phase space defined by two measures of pattern asymmetry. We find that in the optimal regime, intact patterns are protected via restoring forces that counteract random perturbations and give rise to a metastable basin. Together, our results demonstrate that metastable attractors can emerge as a property of stochastic gene expression patterns even without system-wide positional cues, provided that the gene regulatory interactions shaping the pattern are optimally tuned.
+ Science Advances, Volume 10, Issue 49, December 2024.
- in PLoS Computational Biology on 2024-12-02 14:00:00 UTC.
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- by Anna N. Osiecka, Przemysław Bryndza, Elodie F. Briefer, Katarzyna Wojczulanis-Jakubas
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-How well does the information contained in vocal signals travel through the environment? To assess the efficiency of information transfer in little auk (Alle alle, an Arctic seabird) calls over distance, we selected two of the social call types with the highest potential for individuality coding. Using available recordings of known individuals, we calculated the apparent source levels, with apparent maximum peak sound pressure level (ASPL) of 63 dB re 20 μPa at 1 m for both call types. Further, we created a sound attenuation model using meteorological data collected in the vicinity of the little auk colony in Hornsund, Spitsbergen. Using this model, we modelled the calls to reflect higher frequency filtering and sound level loss occurring during spherical spreading in perfect local conditions, down to the putative hearing threshold of the species, calculated to equal ASPL of signals “propagated” to roughly one kilometre. Those modelled calls were then used in a permuted discriminant function analysis, support vector machine models, and linear models of Beecher’s information statistic, to investigate whether transmission loss will affect the retention of individual information of the signal. Calls could be correctly classified to individuals above chance level independently of the distance, down to and over the putative physiological hearing threshold. Interestingly, the information capacity of the signal did not decrease with its filtering and attenuation. While this study touches on signal properties purely and cannot provide evidence of the actual use by the animals, it shows that little auk signals can theoretically travel long distances with negligible information loss, and supports the hypothesis that vocalisations could facilitate long-distance communication in the species.
+ Science Advances, Volume 10, Issue 49, December 2024.
- in PLoS Computational Biology on 2024-12-02 14:00:00 UTC.
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in Science Advances on 2024-12-04 08:00:00 UTC.
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- by Roy Novoselsky, Yotam Harnik, Oran Yakubovsky, Corine Katina, Yishai Levin, Keren Bahar Halpern, Niv Pencovich, Ido Nachmany, Shalev Itzkovitz
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-The intestinal epithelium is a polarized monolayer of cells, with an apical side facing the lumen and a basal side facing the blood stream. In mice, both proteins and mRNAs have been shown to exhibit global basal-apical polarization; however, polarization in the human intestine has not been systematically explored. Here, we employed laser-capture microdissection to isolate apical and basal epithelial segments from intestinal tissues of 8 individuals and performed RNA sequencing and mass-spectrometry proteomics. We find a substantial polarization of mRNA molecules that largely overlaps polarization patterns observed in mice. This mRNA polarization remains consistent across different zones of the intestinal villi and is generally correlated with the polarization of proteins. Our protein analysis exposes streamlined intracellular nutrient transport and processing and reveals that mitochondria and ribosomes are less polarized in humans compared to mice. Our study provides a resource for understanding human intestinal epithelial biology.
+ Science Advances, Volume 10, Issue 49, December 2024.
- in PLoS Biology on 2024-12-02 14:00:00 UTC.
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in Science Advances on 2024-12-04 08:00:00 UTC.
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- by Xiaoyu Tian, Hanyu Wang, Song Liu, Wei Liu, Kaiyue Zhang, Xiaohan Gao, Qingchao Li, Huijie Zhao, Liangran Zhang, Peiwei Liu, Min Liu, Youjun Wang, Xueliang Zhu, Rutao Cui, Jun Zhou
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-Production of melanin pigments is a protective mechanism of the skin against ultraviolet (UV)-induced damage and carcinogenesis. However, the molecular basis for melanogenesis is still poorly understood. Herein, we demonstrate a critical interplay between the primary cilium and the melanocortin 1 receptor (MC1R) signaling. Our data show that UV and α-melanocyte-stimulating hormone (α-MSH) trigger cilium formation in human melanocytes and melanoma cells. Deficiency of MC1R or the presence of its red hair color (RHC) variations significantly attenuates the UV/α-MSH-induced ciliogenesis. Further investigation reveals that MC1R enters the cilium upon UV/α-MSH stimulation, which is facilitated by the interaction of MC1R with the BBSome and the palmitoylation of MC1R. MC1R interacts with the BBSome through the second and third intercellular loops, which contain the common RHC variant alleles (R151C and R160W). These RHC variants of MC1R exhibit attenuated ciliary localization, and enforced ciliary localization of these variants elevates melanogenesis. Ciliary MC1R triggers a sustained cAMP signaling and selectively stimulates Sox9, which appears to up-regulate melanogenesis-related genes as the transcriptional cofactor for MITF. These findings reveal a previously unrecognized nexus between MC1R and cilia and suggest an important mechanism for RHC variant-related pigmentary defects.
+ Carling et al. report that late-onset Alzheimer’s disease (LOAD) risk alleles drive cellular senescence, a hallmark of aging, in a tau- and sex-dependent manner. Mechanistic insights into interactions among genetic risk, biological aging, and sex differences in LOAD are presented.
- in PLoS Biology on 2024-12-02 14:00:00 UTC.
+
in Neuron: Current Issue on 2024-12-04 00:00:00 UTC.
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- by Xitong Chen, Stephanie C. Leach, Juniper Hollis, Dillan Cellier, Kai Hwang
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-Cognitive flexibility relies on hierarchically structured task representations that organize task contexts, relevant environmental features, and subordinate decisions. Despite ongoing interest in the human thalamus, its role in cognitive control has been understudied. This study explored thalamic representation and thalamocortical interactions that contribute to hierarchical cognitive control in humans. We found that several thalamic nuclei, including the anterior, mediodorsal, ventrolateral, and pulvinar nuclei, exhibited stronger evoked responses when subjects switch between task contexts. Decoding analysis revealed that thalamic activity encodes task contexts within the hierarchical task representations. To determine how thalamocortical interactions contribute to task representations, we developed a thalamocortical functional interaction model to predict task-related cortical representation. This data-driven model outperformed comparison models, particularly in predicting activity patterns in cortical regions that encode context representations. Collectively, our findings highlight the significant contribution of thalamic activity and thalamocortical interactions for contextually guided hierarchical cognitive control.
+ In this issue of Neuron, Chiappa et al. describe how neural networks can be trained to perform complex hand motor skills. A key to their approach is curriculum learning, breaking learning into stages, leading to good control.
- in PLoS Biology on 2024-12-02 14:00:00 UTC.
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in Neuron: Current Issue on 2024-12-04 00:00:00 UTC.
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- by János Brunner, Antónia Arszovszki, Gergely Tarcsay, János Szabadics
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-Active conductances tune the kinetics of axonal action potentials (APs) to support specialized functions of neuron types. However, the temporal characteristics of voltage signals strongly depend on the size of neuronal structures, as capacitive and resistive effects slow down voltage discharges in the membranes of small elements. Axonal action potentials are particularly sensitive to these inherent biophysical effects because of the large diameter variabilities within individual axons, potentially implying bouton size-dependent synaptic effects. However, using direct patch-clamp recordings and voltage imaging in small hippocampal axons in acute slices from rat brains, we demonstrate that AP shapes remain uniform within the same axons, even across an order of magnitude difference in caliber. Our results show that smaller axonal structures have more Kv1 potassium channels that locally re-accelerate AP repolarization and contribute to size-independent APs, while they do not preclude the plasticity of AP shapes. Thus, size-independent axonal APs ensure consistent digital signals for each synapse within axons of same types.
+ John Hopfield’s model on collective computation linked the recall of memories with interactions and dynamics associated with disordered magnetic systems. Insights from Hopfield’s work catalyzed formulations that link the dynamics and emergent properties of recurrently connected generic neurons with the functional properties and signaling observed from brain circuits.
- in PLoS Biology on 2024-12-02 14:00:00 UTC.
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in Neuron: Current Issue on 2024-12-04 00:00:00 UTC.
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- by Rosanna C. T. Wright, A. Jamie Wood, Michael J. Bottery, Katie J. Muddiman, Steve Paterson, Ellie Harrison, Michael A. Brockhurst, James P. J. Hall
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-Plasmids are important vectors of horizontal gene transfer in microbial communities but can impose a burden on the bacteria that carry them. Such plasmid fitness costs are thought to arise principally from conflicts between chromosomal- and plasmid-encoded molecular machineries, and thus can be ameliorated by compensatory mutations (CMs) that reduce or resolve the underlying causes. CMs can arise on plasmids (i.e., plaCM) or on chromosomes (i.e., chrCM), with contrasting predicted effects upon plasmid success and subsequent gene transfer because plaCM can also reduce fitness costs in plasmid recipients, whereas chrCM can potentially ameliorate multiple distinct plasmids. Here, we develop theory and a novel experimental system to directly compare the ecological effects of plaCM and chrCM that arose during evolution experiments between Pseudomonas fluorescens SBW25 and its sympatric mercury resistance megaplasmid pQBR57. We show that while plaCM was predicted to succeed under a broader range of parameters in mathematical models, chrCM dominated in our experiments, including conditions with numerous recipients, due to a more efficacious mechanism of compensation, and advantages arising from transmission of costly plasmids to competitors (plasmid “weaponisation”). We show analytically the presence of a mixed Rock-Paper-Scissors (RPS) regime for CMs, driven by trade-offs with horizontal transmission, that offers one possible explanation for the observed failure of plaCM to dominate even in competition against an uncompensated plasmid. Our results reveal broader implications of plasmid-bacterial evolution for plasmid ecology, demonstrating the importance of specific compensatory mutations for resistance gene spread. One consequence of the superiority of chrCM over plaCM is the likely emergence in microbial communities of compensated bacteria that can act as “hubs” for plasmid accumulation and dissemination.
+ Lopes-Bastos et al. report that melanoma in zebrafish initiates without telomerase (or ALT) activation. However, in late progression, telomerase becomes essential for sustained tumor growth. Tumors that fail to re-activate telomerase slow down growth and even regress. This occurs due to tumor-autonomous (genomic instability) and non-tumor-autonomous (immune response) mechanisms.
- in PLoS Biology on 2024-12-02 14:00:00 UTC.
+
in Cell Reports: Current Issue on 2024-12-04 00:00:00 UTC.
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- by Sarah Wettstadt, Francisco J. Marcos-Torres, Joaquín R. Otero-Asman, Alicia García-Puente, Álvaro Ortega, María A. Llamas
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-Competitive bacteria like the human pathogen Pseudomonas aeruginosa can acquire iron from different iron carriers, which are usually internalized via outer membrane TonB-dependent receptors (TBDRs). Production of TBDRs is promoted by the presence of the substrate. This regulation often entails a signal transfer pathway known as cell-surface signaling (CSS) that involves the TBDR itself that also functions as transducer (and is thus referred to as TBDT), a cytoplasmic membrane-bound anti-σ factor, and an extracytoplasmic function σ (σECF) factor. TBDTs contain an extra N-terminal domain known as signaling domain (SD) required for the signal transfer activity of these receptors. In the current CSS model, presence of the signal allows the interaction between the TBDT and the anti-σ factor in the periplasm, promoting the proteolysis of the anti-σ factor and in turn the σECF-dependent transcription of response genes, including the TBDT gene. However, recent evidence shows that σECF activity does not depend on this interaction, suggesting that the contact between these 2 proteins fulfills a different role. Using the P. aeruginosa Fox CSS system as model, we show here that the SD of the FoxA TBDT already interacts with the C-terminal domain of the FoxR anti-σ factor in absence of the signal. This interaction protects FoxR from proteolysis in turn preventing transcription of σFoxI-dependent genes. By structural modeling of the FoxR/FoxASD interaction, we have identified the interaction sites between these 2 proteins and provide the molecular details of this interaction. We furthermore show that to exert this protective role, FoxA undergoes proteolytic cleavage, denoting a change in the paradigm of the current CSS model.
+ Revenu et al. show the function of myosin 1b (Myo1b) in intestinal epithelia. In human cells, MYO1B is part of the UNC45A interactome and contributes to lumenogenesis by modulating spindle orientation in vitro. In zebrafish Myo1b is important for intestinal epithelium folding during the development of the intestinal bulb.
- in PLoS Biology on 2024-12-02 14:00:00 UTC.
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in Cell Reports: Current Issue on 2024-12-04 00:00:00 UTC.
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- by Xin Yuan, Hailiang Li, Fang Guo
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-Organisms detect temperature signals through peripheral neurons, which relay them to central circadian networks to drive adaptive behaviors. Despite recent advances in Drosophila research, how circadian circuits integrate temperature cues with circadian signals to regulate sleep/wake patterns remains unclear. In this study, we used the FlyWire brain electron microscopy connectome to map neuronal connections, identifying lateral posterior neurons LPNs as key nodes for integrating temperature information into the circadian network. LPNs receive input from both circadian and temperature-sensing neurons, promoting sleep behavior. Through connectome analysis, genetic manipulation, and behavioral assays, we demonstrated that LPNs, downstream of thermo-sensitive anterior cells (ACs), suppress activity-promoting lateral dorsal neurons LNds via the AstC pathway, inducing sleep Disrupting LPN-LNd communication through either AstCR1 RNAi in LNds or in an AstCR1 mutant significantly impairs the heat-induced reduction in the evening activity peak. Conversely, optogenetic calcium imaging and behavioral assays revealed that cold-activated LNds subsequently stimulate LPNs through NPF-NPFR signaling, establishing a negative feedback loop. This feedback mechanism limits LNd activation to appropriate levels, thereby fine-tuning the evening peak increase at lower temperatures. In conclusion, our study constructed a comprehensive connectome centered on LPNs and identified a novel peptidergic circadian feedback circuit that coordinates temperature and circadian signals, offering new insights into the regulation of sleep patterns in Drosophila.
+ Coren et al. show that in skeletal muscles, fibroblasts diversify into distinct subpopulations during embryonic development. These subpopulations reside in distinct niches, entail different dynamics and transcriptomes, and exert opposing effects on myogenic differentiation. This diversification process is dependent on muscle contraction in the embryo.
- in PLoS Biology on 2024-12-02 14:00:00 UTC.
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in Cell Reports: Current Issue on 2024-12-04 00:00:00 UTC.
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- by Jonathan M. Werner, Jesse Gillis
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-Human neural organoids offer an exciting opportunity for studying inaccessible human-specific brain development; however, it remains unclear how precisely organoids recapitulate fetal/primary tissue biology. We characterize field-wide replicability and biological fidelity through a meta-analysis of single-cell RNA-sequencing data for first and second trimester human primary brain (2.95 million cells, 51 data sets) and neural organoids (1.59 million cells, 173 data sets). We quantify the degree primary tissue cell type marker expression and co-expression are recapitulated in organoids across 10 different protocol types. By quantifying gene-level preservation of primary tissue co-expression, we show neural organoids lie on a spectrum ranging from virtually no signal to co-expression indistinguishable from primary tissue, demonstrating a high degree of variability in biological fidelity among organoid systems. Our preserved co-expression framework provides cell type-specific measures of fidelity applicable to diverse neural organoids, offering a powerful tool for uncovering unifying axes of variation across heterogeneous neural organoid experiments.
+ Ariura et al. performed a comprehensive analysis of Piwi-associated RNAs to decipher the targeting rules of Drosophila Piwi. These rules explain how Piwi distinguishes TEs from mRNAs and reveal that transcriptional and post-transcriptional silencing is controlled by surprisingly similar rules despite vastly different modes of repression.
- in PLoS Biology on 2024-12-02 14:00:00 UTC.
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in Cell Reports: Current Issue on 2024-12-04 00:00:00 UTC.
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- ABSTRACT
-Evidence from neurophysiological and genetic studies demonstrates that activity sparsity—the proportion of neurons that are active at a given time in a population—systematically varies across the canonical trisynaptic circuit of the hippocampus. Recent work has also shown that sparsity varies across the hippocampal dorsoventral (long) axis, wherein activity is sparser in ventral than dorsal regions. While the hippocampus has a critical role in long-term memory (LTM), whether sparsity across the trisynaptic circuit and hippocampal long axis is task-dependent or invariant remains unknown. Importantly, representational sparsity has significant implications for neural computation and theoretical models of learning and memory within and beyond the hippocampus. Here we used functional molecular imaging to quantify sparsity in the rat hippocampus during performance of the Morris water task (MWT) and contextual fear discrimination (CFD) – two popular and distinct assays of LTM. We found that activity sparsity is highly reliable across memory tasks, wherein activity increases sequentially across the trisynaptic circuit (DG < CA3 < CA1) and decreases across the long axis (ventral<dorsal). These results have important implications for models of hippocampal function and suggest that activity sparsity is a preserved property in the hippocampal system across cognitive settings.
+ Although the αC-β4 loop is a stable feature of all protein kinases, the importance of this motif as a conserved element of secondary structure, as well as its links to the hydrophobic architecture of the kinase core, has been underappreciated. We first review the motif and then describe how it is linked to the hydrophobic spine architecture of the kinase core, which we first discovered using a computational tool, local spatial Pattern (LSP) alignment. Based on NMR predictions that a mutation in this motif abolishes the synergistic high-affinity binding of ATP and a pseudo substrate inhibitor, we used LSP to interrogate the F100A mutant. This comparison highlights the importance of the αC-β4 loop and key residues at the interface between the N- and C-lobes. In addition, we delved more deeply into the structure of the apo C-subunit, which lacks ATP. While apo C-subunit showed no significant changes in backbone dynamics of the αC-β4 loop, we found significant differences in the side chain dynamics of K105. The LSP analysis suggests disruption of communication between the N- and C-lobes in the F100A mutant, which would be consistent with the structural changes predicted by the NMR spectroscopy.
- in Hippocampus on 2024-12-02 11:15:51 UTC.
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in eLife on 2024-12-04 00:00:00 UTC.
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- Background The COVID-19 pandemic has generated significant impacts on the forestry sector. Employment layoffs have led to an increase in return migration, resulting in additional labor supply and heightened family economic burdens. This research employs the Theory of Planned Behaviour (TPB) framework to examine and predict sustainable forest management practices among families managing customary forests and village forests in Bali. Methods Purposive sampling was used to collect data from 71 managers of customary forests and village forests in Tenganan and Wanagiri. Partial least square-structural equation modelling (PLS-SEM) was used to analyze the acquired data. Results The findings demonstrated that TPB can explain the sustainable forest management. The incorporation of an additional construct, Tri Hita Karana (THK), enhanced the model’s predictive power for both managerial intentions and behaviors in sustainable forest management. Specifically, THK influences management intentions through the mediation of attitudes, subjective norms, and perceived behavioral control. Conclusions This study established that THK, a fundamental value system in Balinese society, serves an antecedent predictor of behavioral intentions toward sustainable forest management. The relationship between THK and sustainable forest management intentions is mediated by attitudes, subjective norms, and perceived behavioral control. This research makes significant theoretical and managerial contributions. First, it validates the established TPB framework within the context of COVID-19’s impact in Bali. Additionally, it provides scholars with insights for identifying other potential constructs that may influence forest land managers’ behavior.
+ Brain rhythms can facilitate neural communication for the maintenance of brain function. Beta rhythms (13–35 Hz) have been proposed to serve multiple domains of human ability, including motor control, cognition, memory, and emotion, but the overarching organisational principles remain unknown. To uncover the circuit architecture of beta oscillations, we leverage normative brain data, analysing over 30 hr of invasive brain signals from 1772 channels from cortical areas in epilepsy patients, to demonstrate that beta is the most distributed cortical brain rhythm. Next, we identify a shared brain network from beta-dominant areas with deeper brain structures, like the basal ganglia, by mapping parametrised oscillatory peaks to whole-brain functional and structural MRI connectomes. Finally, we show that these networks share significant overlap with dopamine uptake as indicated by positron emission tomography. Our study suggests that beta oscillations emerge in cortico-subcortical brain networks that are modulated by dopamine. It provides the foundation for a unifying circuit-based conceptualisation of the functional role of beta activity beyond the motor domain and may inspire an extended investigation of beta activity as a feedback signal for closed-loop neurotherapies for dopaminergic disorders.
- in F1000Research on 2024-12-02 09:16:48 UTC.
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in eLife on 2024-12-04 00:00:00 UTC.
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- Background The emergence of artificial intelligence presents both potential for growth and challenges for the financial industry. This study examines the impact of artificial intelligence (AI) on the South African fintech industry, focusing on its transformative nature. Method A purposive sampling technique was used to select 76 participants from the banking sector. Furthermore, the participants were divided into focus groups and interviewed. The thematic analysis conducted in this study revealed eight critical themes that encapsulated the myriad challenges and opportunities faced by industry professionals. From navigating the ever-changing regulatory environment to embracing technological advancements, addressing shifting customer expectations, and cultivating organisational agility and resilience, the financial industry grapples with a complex interplay of factors that demand strategic foresight, adaptability, and a commitment to continuous learning and innovation. Conclusions The results demonstrate that AI is propelling innovation, improving operational efficiency, and transforming customer experience in the finance industry. Nevertheless, substantial impediments have arisen in the form of issues over data protection, talent recruiting, and regulatory ambiguity.
+ Since its inception, the concept of neurodiversity has been defined in a number of different ways, which can cause confusion among those hoping to educate themselves about the topic. Learning about neurodiversity can also be challenging because there is a lack of well-curated, appropriately contextualized information on the topic. To address such barriers, we present an annotated reading list that was developed collaboratively by a neurodiverse group of researchers. The nine themes covered in the reading list are: the history of neurodiversity; ways of thinking about neurodiversity; the importance of lived experience; a neurodiversity paradigm for autism science; beyond deficit views of ADHD; expanding the scope of neurodiversity; anti-ableism; the need for robust theory and methods; and integration with open and participatory work. We hope this resource can support readers in understanding some of the key ideas and topics within neurodiversity, and that it can further orient researchers towards more rigorous, destigmatizing, accessible, and inclusive scientific practices.
- in F1000Research on 2024-12-02 08:57:32 UTC.
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in eLife on 2024-12-04 00:00:00 UTC.
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- Background The purpose of the study was to assess the obstacles faced by diabetes patients in their self-care and determine the factors associated with these obstacles. The management of diabetes mellitus (DM) extends beyond the clinician’s efforts, with the responsibility of the care also being shared by the patient to achieve better treatment outcomes and prevent complications. Self-care management is the most important part of DM treatment, which includes diet, regular exercise, blood glucose monitoring, medication and foot care. Methods A facility-based cross-sectional study was conducted among 107 type 2 DM patients aged >18 years using the Diabetes Obstacles Questionnaire-30. Patients scoring a mean response score >3 were considered to have an obstacle. We included age, gender, socioeconomic status (SES), duration of DM and blood glucose levels as factors for regression analysis and a P value <0.05 was considered to be statistically significant. Results A large majority (64.5%, n = 69) of our participants were aged above 55 years and belonged to lower socio-economic status (65.4%, n = 70). Family history of DM was present in 41% (n=44) of the participants. The median duration of DM among the participant was 10 (4 – 7) years. In our study, the participants faced obstacles for two items in the domains: Support from Friends & Family (mean score: 3.73) and Knowledge of the Disease (mean score: 3.58). A multinominal regression analysis revealed SES was predictive of participants who could not understand information from literature with a P. value of 0.002 (OR: 3.65, CI: 1.60-8.338). Conclusion The two major obstacles to self-management practices that were identified were in the domains of Support from Friends and Family, and Knowledge of the Disease. Socioeconomic status was identified to be a predictive factor associated with the participants who are not able to understand information from the literature.
+ Experience-based plasticity of the human cortex mediates the influence of individual experience on cognition and behavior. The complete loss of a sensory modality is among the most extreme such experiences. Investigating such a selective, yet extreme change in experience allows for the characterization of experience-based plasticity at its boundaries. Here, we investigated information processing in individuals who lost vision at birth or early in life by probing the processing of braille letter information. We characterized the transformation of braille letter information from sensory representations depending on the reading hand to perceptual representations that are independent of the reading hand. Using a multivariate analysis framework in combination with functional magnetic resonance imaging (fMRI), electroencephalography (EEG), and behavioral assessment, we tracked cortical braille representations in space and time, and probed their behavioral relevance. We located sensory representations in tactile processing areas and perceptual representations in sighted reading areas, with the lateral occipital complex as a connecting ‘hinge’ region. This elucidates the plasticity of the visually deprived brain in terms of information processing. Regarding information processing in time, we found that sensory representations emerge before perceptual representations. This indicates that even extreme cases of brain plasticity adhere to a common temporal scheme in the progression from sensory to perceptual transformations. Ascertaining behavioral relevance through perceived similarity ratings, we found that perceptual representations in sighted reading areas, but not sensory representations in tactile processing areas are suitably formatted to guide behavior. Together, our results reveal a nuanced picture of both the potentials and limits of experience-dependent plasticity in the visually deprived brain.
- in F1000Research on 2024-12-02 08:56:42 UTC.
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- Airway macrophages (AM) are the predominant immune cell in the lung and play a crucial role in preventing infection, making them a target for host directed therapy. Macrophage effector functions are associated with cellular metabolism. A knowledge gap remains in understanding metabolic reprogramming and functional plasticity of distinct human macrophage subpopulations, especially in lung resident AM. We examined tissue-resident AM and monocyte-derived macrophages (MDM; as a model of blood derived macrophages) in their resting state and after priming with IFN-γ or IL-4 to model the Th1/Th2 axis in the lung. Human macrophages, regardless of origin, had a strong induction of glycolysis in response to IFN-γ or upon stimulation. IFN-γ significantly enhanced cellular energetics in both AM and MDM by upregulating both glycolysis and oxidative phosphorylation. Upon stimulation, AM do not decrease oxidative phosphorylation unlike MDM which shift to ‘Warburg’-like metabolism. IFN-γ priming promoted cytokine secretion in AM. Blocking glycolysis with 2-deoxyglucose significantly reduced IFN-γ driven cytokine production in AM, indicating that IFN-γ induces functional plasticity in human AM, which is mechanistically mediated by glycolysis. Directly comparing responses between macrophages, AM were more responsive to IFN-γ priming and dependent on glycolysis for cytokine secretion than MDM. Interestingly, TNF production was under the control of glycolysis in AM and not in MDM. MDM exhibited glycolysis-dependent upregulation of HLA-DR and CD40, whereas IFN-γ upregulated HLA-DR and CD40 on AM independently of glycolysis. These data indicate that human AM are functionally plastic and respond to IFN-γ in a manner distinct from MDM. These data provide evidence that human AM are a tractable target for inhalable immunomodulatory therapies for respiratory diseases.
+ Recent studies have shown that, in human cancer cells, the tetrameric Shieldin complex (comprising REV7, SHLD1, SHLD2, and SHLD3) facilitates non-homologous end-joining (NHEJ) while blocking homologous recombination (HR). Surprisingly, several eukaryotic species lack SHLD1, SHLD2, and SHLD3 orthologs, suggesting that Rev7 may leverage an alternative mechanism to regulate the double-strand break (DSB) repair pathway choice. Exploring this hypothesis, we discovered that Saccharomyces cerevisiae Rev7 physically interacts with the Mre11–Rad50–Xrs2 (MRX) subunits, impedes G-quadruplex DNA synergized HU-induced toxicity, and facilitates NHEJ, while antagonizing HR. Notably, we reveal that a 42-amino acid C-terminal fragment of Rev7 binds to the subunits of MRX complex, protects rev7∆ cells from G-quadruplex DNA-HU-induced toxicity, and promotes NHEJ by blocking HR. By comparison, the N-terminal HORMA domain, a conserved protein–protein interaction module, was dispensable. We further show that the full-length Rev7 impedes Mre11 nuclease and Rad50’s ATPase activities without affecting the latter’s ATP-binding ability. Combined, these results provide unanticipated insights into the functional interaction between the MRX subunits and Rev7 and highlight a previously unrecognized mechanism by which Rev7 facilitates DSB repair via NHEJ, and attenuation of HR, by blocking Mre11 nuclease and Rad50’s ATPase activities in S. cerevisiae.
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- Hungry animals consistently show a desire to obtain food. Even a brief sensory detection of food can trigger bursts of physiological and behavioral changes. However, the underlying mechanisms by which the sensation of food triggers the acute behavioral response remain elusive. We have previously shown in Drosophila that hunger drives a preference for low temperature. Because Drosophila is a small ectotherm, a preference for low temperature implies a low body temperature and a low metabolic rate. Here, we show that taste-sensing triggers a switch from a low to a high temperature preference in hungry flies. We show that taste stimulation by artificial sweeteners or optogenetics triggers an acute warm preference, but is not sufficient to reach the fed state. Instead, nutrient intake is required to reach the fed state. The data suggest that starvation recovery is controlled by two components: taste-evoked and nutrient-induced warm preferences, and that taste and nutrient quality play distinct roles in starvation recovery. Animals are motivated to eat based on time of day or hunger. We found that clock genes and hunger signals profoundly control the taste-evoked warm preferences. Thus, our data suggest that the taste-evoked response is one of the critical layers of regulatory mechanisms representing internal energy homeostasis and metabolism.
+ Signaling through the platelet-derived growth factor receptor alpha (PDGFRα) plays a critical role in craniofacial development. Phosphatidylinositol 3-kinase (PI3K)/Akt is the primary effector of PDGFRα signaling during mouse skeletal development. We previously demonstrated that Akt phosphorylates the RNA-binding protein serine/arginine-rich splicing factor 3 (Srsf3) downstream of PI3K-mediated PDGFRα signaling in mouse embryonic palatal mesenchyme (MEPM) cells, leading to its nuclear translocation. We further showed that ablation of Srsf3 in the murine neural crest lineage results in severe midline facial clefting and widespread alternative RNA splicing (AS) changes. Here, we demonstrated via enhanced UV-crosslinking and immunoprecipitation of MEPM cells that PDGF-AA stimulation leads to preferential binding of Srsf3 to exons and loss of binding to canonical Srsf3 CA-rich motifs. Through the analysis of complementary RNA-seq data, we showed that Srsf3 activity results in the preferential inclusion of exons with increased GC content and lower intron to exon length ratio. We found that Srsf3 activity downstream of PDGFRα signaling leads to retention of the receptor in early endosomes and increases in downstream PI3K-mediated Akt signaling. Taken together, our findings reveal that growth factor-mediated phosphorylation of an RNA-binding protein underlies gene expression regulation necessary for mammalian craniofacial development.
- in eLife on 2024-12-02 00:00:00 UTC.
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- Riboswitches represent a class of non-coding RNA that possess the unique ability to specifically bind ligands and, in response, regulate gene expression. A recent report unveiled a type of riboswitch, known as the guanidine-IV riboswitch, which responds to guanidine levels to regulate downstream genetic transcription. However, the precise molecular mechanism through which the riboswitch senses its target ligand and undergoes conformational changes remain elusive. This gap in understanding has impeded the potential applications of this riboswitch. To bridge this knowledge gap, our study investigated the conformational dynamics of the guanidine-IV riboswitch RNA upon ligand binding. We employed single-molecule fluorescence resonance energy transfer (smFRET) to dissect the behaviors of the aptamer, terminator, and full-length riboswitch. Our findings indicated that the aptamer portion exhibited higher sensitivity to guanidine compared to the terminator and full-length constructs. Additionally, we utilized Position-specific Labelling of RNA (PLOR) combined with smFRET to observe, at the single-nucleotide and single-molecule level, the structural transitions experienced by the guanidine-IV riboswitch during transcription. Notably, we discovered that the influence of guanidine on the riboswitch RNA’s conformations was significantly reduced after the transcription of 88 nucleotides. Furthermore, we proposed a folding model for the guanidine-IV riboswitch in the absence and presence of guanidine, thereby providing insights into its ligand-response mechanism.
+ As the early step of food ingestion, the swallow is under rigorous sensorimotor control. Nevertheless, the mechanisms underlying swallow control at a molecular and circuitry level remain largely unknown. Here, we find that mutation of the mechanotransduction channel genes nompC, Tmc, or piezo impairs the regular pumping rhythm of the cibarium during feeding of the fruit fly Drosophila melanogaster. A group of multi-dendritic mechanosensory neurons, which co-express the three channels, wrap the cibarium and are crucial for coordinating the filling and emptying of the cibarium. Inhibition of them causes difficulty in food emptying in the cibarium, while their activation leads to difficulty in cibarium filling. Synaptic and functional connections are detected between the pharyngeal mechanosensory neurons and the motor circuit that controls swallow. This study elucidates the role of mechanosensation in swallow, and provides insights for a better understanding of the neural basis of food swallow.
- in eLife on 2024-12-02 00:00:00 UTC.
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- Pain is heavily modulated by expectations. Whereas the integration of expectations with sensory information has been examined in some detail, little is known about how positive and negative expectations are generated and their neural dynamics from generation over anticipation to the integration with sensory information. The present preregistered study employed a novel paradigm to induce positive and negative expectations on a trial-by-trial basis and examined the neural mechanisms using combined EEG-fMRI measurements (n=50). We observed substantially different neural representations between the anticipatory and the actual pain period. In the anticipation phase i.e., before the nociceptive input, the insular cortex, dorsolateral prefrontal cortex (DLPFC), and anterior cingulate cortex (ACC) showed increased activity for directed expectations regardless of their valence. Interestingly, a differentiation between positive and negative expectations within the majority of areas only occurred after the arrival of nociceptive information. FMRI-informed EEG analyses could reliably track the temporal sequence of processing showing an early effect in the DLPFC, followed by the anterior insula and late effects in the ACC. The observed effects indicate the involvement of different expectation-related subprocesses, including the transformation of visual information into a value signal that is maintained and differentiated according to its valence only during stimulus processing.
+ Climatic warming can shift community composition driven by the colonization-extinction dynamics of species with different thermal preferences; but simultaneously, habitat fragmentation can mediate species’ responses to warming. As this potential interactive effect has proven difficult to test empirically, we collected data on birds over 10 years of climate warming in a reservoir subtropical island system that was formed 65 years ago. We investigated how the mechanisms underlying climate-driven directional change in community composition were mediated by habitat fragmentation. We found thermophilization driven by increasing warm-adapted species and decreasing cold-adapted species in terms of trends in colonization rate, extinction rate, occupancy rate and population size. Critically, colonization rates of warm-adapted species increased faster temporally on smaller or less isolated islands; cold-adapted species generally were lost more quickly temporally on closer islands. This provides support for dispersal limitation and microclimate buffering as primary proxies by which habitat fragmentation mediates species range shift. Overall, this study advances our understanding of biodiversity responses to interacting global change drivers.
- in eLife on 2024-12-02 00:00:00 UTC.
+
in eLife on 2024-12-04 00:00:00 UTC.
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+http://biorxiv.org/cgi/content/short/2024.12.04.626305v1?rss=1
+">Early-life stress impairs development of functional interactions and neuronal activity within prefrontal-amygdala networks in vivo
- AbstractBasal ganglia disease has been reported as a post-infection sequela of several viruses, with documentation of this phenomenon from the H1N1 Spanish flu to the recent COVID-19 (SARS-CoV-2) pandemic. SARS-CoV-2 infection leads to multisystem deficits, including those affecting the nervous system. Here, we investigated whether a SARS-CoV-2 infection alone increases the susceptibility to develop parkinsonian phenotypes in C57BL/6J mice expressing the human ACE2 receptor, or in addition to two well-known toxin exposures, MPTP and paraquat. Additionally, we examined mice carrying a G2019S mutation in the LRRK2 gene. We also examined if vaccination with either an mRNA- or protein-based vaccine can alter any observed neuropathology. We find that the infection with the WA-1/2020 (alpha) or omicron B1.1.529 strains in ACE2 and G2019S LRRK2 mice both synergize with a subtoxic exposure to the mitochondrial toxin MPTP to induce neurodegeneration and neuroinflammation in the substantia nigra. This synergy appears toxin-dependent since we do not observe this following exposure to the direct redox-inducing compound paraquat. This synergistic neurodegeneration and neuroinflammation is rescued in WT mice that were vaccinated using either mRNA- and protein- based vaccines directed against the Spike protein of the SARS-CoV-2 virus. However, in the G2019S LRRK2 mutant mice, we find that only the protein-based vaccine but not the mRNA- based vaccine resulted in a rescue of the SARS-CoV-2 mediated neuropathology. Taken together, our results highlight the role of both environmental exposures and familial background on the development of parkinsonian pathology secondary to viral infection and the benefit of vaccines in reducing these risks.
+ Early-life stress (ELS), such as parental neglect or abuse, predisposes an individual to develop mental disorders. Disease hallmarks include heightened amygdala reactivity and impaired prefrontal cortex-amygdala functional interactions, already during childhood and adolescence. However, which cellular and circuit mechanisms underlie these hallmarks, as well as the altered developmental trajectory of prefrontal-amygdala networks, is poorly understood. Here we performed simultaneous in vivo local-field potential and multi-unit recordings under light urethane anaesthesia in the medial prefrontal cortex (mPFC) and basolateral amygdala (BLA) of male and female juvenile or adolescent mice, exposed to a resource scarcity model of ELS. We find a developmentally transient low-theta (3-5 Hz) oscillatory hypercoupling within mPFC-BLA networks in juvenile ELS males which seems to result from a precocious development of coupling strength after ELS. In the mPFC, neuronal spiking activity was decreased in juvenile males and the local theta entrainment of spike firing disrupted. In BLA, both sexes showed an increase in firing activity in a subpopulation of neurons after ELS, also confirmed by an increase in deltaFosB-positive neurons in BLA, which we identified to be non-GABAergic. Directed interactions, i.e. the ability to entrain spike firing in mPFC to the theta rhythm in BLA and vice versa, were also impaired predominantly in juvenile males after ELS, while females showed a milder phenotype. These early sex-dependent impairments in the functional development of prefrontal-amygdala circuits may promote abnormal fear learning and anxiety after ELS and may predispose to a disease phenotype later on.
- in bioRxiv: Neuroscience on 2024-12-02 00:00:00 UTC.
+
in bioRxiv: Neuroscience on 2024-12-04 00:00:00 UTC.
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+http://biorxiv.org/cgi/content/short/2024.12.03.626596v1?rss=1
+">Microglial cathepsin B promotes neuronal efferocytosis during brain development
- Temporal integration, the process by which the auditory system combines sound information over a curtain period to form a coherent auditory object, is essential for coherent auditory perception, yet its neural mechanisms remain underexplored. We use a "transitional click train" paradigm, which concatenates two click trains with slightly differing inter-click intervals (ICIs), to investigate temporal integration in the human cortex. Using a 64-channel electroencephalogram (EEG), we recorded responses from 42 healthy participants exposed to regular and irregular transitional click trains and conducted change detection tasks. Regular transitional click trains elicited significant change responses in the human cortex, indicative of temporal integration, whereas irregular trains did not. These neural responses were modulated by ICI length, ICI contrast, and regularity. Behavioral data mirrored EEG findings, showing enhanced detection for regular conditions compared to irregular conditions and pure tones. Furthermore, variations in change responses were associated with decision-making processes. Temporal continuity was critical, as introducing gaps between click trains diminished both behavioral and neural responses. In clinical assessments, 22 coma patients exhibited diminished or absent change responses, effectively distinguishing them from healthy individuals. Our findings identify distinct neural markers of temporal integration and highlight the potential of transitional click trains for clinical diagnostics.
+ Half of all newborn neurons in the developing brain are removed via efferocytosis - the phagocytic clearance of apoptotic cells. Microglia are brain-resident professional phagocytes that play important roles in neural circuit development including as primary effectors of efferocytosis. While the mechanisms through which microglia recognize potential phagocytic cargo are widely studied, the lysosomal mechanisms that are necessary for efficient digestion are less well defined. Here we show that the lysosomal protease cathepsin B promotes microglial efferocytosis of neurons and restricts the accumulation of apoptotic cells during brain development. We show that cathepsin B is microglia-specific and enriched in brain regions where neuronal turnover is high in both zebrafish and mouse. Myeloid-specific cathepsin B knockdown in zebrafish led to dysmorphic microglia containing undigested dead cells, as well as an accumulation of dead cells in surrounding tissue. These effects where phenocopied in mice globally deficient for Ctsb using markers for apoptosis. We also observed behavioral impairments in both models. Live imaging studies in zebrafish revealed deficits in phagolysosomal fusion and acidification, and live imaging of cultured mouse microglia reveal delayed phagocytosis consistent with impairments in digestion and resolution of phagocytosis rather than initial uptake. These data reveal a novel role for microglial cathepsin B in mediating neuronal efferocytosis during typical brain development.
- in bioRxiv: Neuroscience on 2024-12-02 00:00:00 UTC.
+
in bioRxiv: Neuroscience on 2024-12-04 00:00:00 UTC.
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+http://biorxiv.org/cgi/content/short/2024.12.04.626719v1?rss=1
+">Cholinergic interneurons of the dorsomedial striatum mediate winner-loser effects on social hierarchy dynamics in male mice.
- Recent research has demonstrated significant aberrant activation of the innate immune system in ALS model systems due to mutations in SOD1, TARDBP and C9orf72 through stimulation of the TBK1-IRF3 pathway. This pathway can be activated, for example, by cGAS-STING-dependent sensing of cytosolic DNA that accumulates as a result of chronic DNA damage and defective mitochondria, both of which have been identified as early pathology in FUS-ALS spinal motor neurons (sMNs). Therefore, we analysed innate immune pathways in isogenic and non-isogenic FUSmut iPSC-derived sMNs, which revealed upregulation of interferon-stimulated genes (ISGs) and activation of the TBK1-IRF3 pathway in FUSmut sMNs. Notably, we found evidence for accumulation of cytosolic dsRNA and its sensor RIG-I in FUS-ALS. RIG-I, but not MDA5, was found to be significantly upregulated in FUSmut sMNs, and siRNA-mediated knockdown abolished the increased IFN1 activation in FUSmut sMNs. In post-mortem analysis, RIG-I was highly expressed in the remaining -MNs. IFN treatment of FUSwt sMNs phenocopied the axonal degeneration of FUSmut sMNs. Mechanistically, DNA damage induction did not increase ISG expression, but dsRNA was increased in the mitochondria of FUSmut sMNs. Mitochondrial transcription, a known source of dsRNA, was found to be upregulated in compartmental axonal RNAseq analysis and its inhibition reduced ISGs in FUS-ALS sMNs. Furthermore, the JAK-STAT inhibitor ruxolitinib alleviated the upregulated ISG expression and reversed the axonal degeneration of sMNs. Finally, we analysed ISG expression in peripheral blood samples from 18 FUS-ALS patients, eight of whom had a significantly elevated interferon signature. Blood ISGs correlated with disease progression rate and negatively with disease duration. RIG-I-mediated innate immune activation in sMNs may be an interesting novel individualised biomarker-driven therapeutic target in (FUS-) ALS.
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-A one-sentence summary of your paperRIG-I-I-mediated innate immune activation is found in FUS-ALS spinal motor neurons caused by cytosolic dsRNA accumulation due to mitochondrial transcriptional activation and is amenable to JAK-STAT inhibition and might thus be an interesting novel individualized biomarker-driven therapeutic approach in (FUS-) ALS
+ Cholinergic interneurons of the dorsomedial striatum may play a role in social hierarchy dynamics. A social hierarchy is an organization of individuals by rank that occurs in social animals. Establishing a new social hierarchy involves flexible behavior in deciding whether to be a winner or loser, experience of winning or losing, and stabilization of rank. The neural circuits underlying such flexible behavior have yet to be fully understood, but previous research indicates that cholinergic interneurons in the dorsomedial striatum play a role in behavioral flexibility. We used the dominance tube test to measure ranking within group housed mice, before and after between-cage competitions using the same test. We found that the experience of winning or losing against mice from different cages not only contributes to new social hierarchies among the competitors, but also causally influences the subsequent social hierarchy among their cage mates in the home cage - supporting the hypothesis of winner-loser effects on later social ranking. To test the hypothesis that cholinergic interneurons contribute to social hierarchy dynamics, we made a selective lesion of cholinergic interneurons in the dorsomedial striatum. The lesion did not prevent social hierarchy formation among pairs of similarly ranked individuals from different cages. However, it reduced the loser effect of external competition on the subsequent home-cage rankings in dominant mice. In light of these results we suggest that cholinergic interneurons in dorsomedial striatum increase the flexibility of social hierarchy dynamics.
- in bioRxiv: Neuroscience on 2024-12-02 00:00:00 UTC.
+
in bioRxiv: Neuroscience on 2024-12-04 00:00:00 UTC.
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+http://biorxiv.org/cgi/content/short/2024.12.03.626524v1?rss=1
+">Narcissistic and Antisocial Personality Traits are both encoded in the Triple Network: Connectomics evidence
- BACKGROUNDEarly-life stress (ELS) arising from physical and emotional abuse disrupts normal brain development and impairs hypothalamic-pituitary-adrenal axis function, increasing the risk of psychopathological disorders and compulsive behaviors in adulthood. However, the underlying neural mechanisms remain unclear. The brainstem nucleus incertus (NI) is a highly stress-sensitive locus, involved in behavioral activation and stress-induced reward (food/alcohol) seeking, but its sensitivity to ELS remains unexplored.
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-METHODSWe used neonatal maternal separation stress in rats as a model for ELS and examined its impact on stress-related mRNA and neuropeptide expression in the NI, using fluorescent in situ hybridization and immunohistochemistry, respectively. Using whole-cell, patch-clamp recordings we determined the influence of ELS on the synaptic activity, excitability, and electrophysiological properties of NI neurons. Using c-Fos protein expression we also assessed the impact of ELS on the sensitivity of NI neurons to acute restraint stress in adulthood.
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-RESULTSELS weakened the acute stress responsiveness of NI neurons, and caused dendritic shrinkage, impaired synaptic transmission and altered electrophysiological properties of NI neurons in a cell-type-specific manner. Additionally, ELS increased the expression of mRNA encoding corticotropin-releasing hormone receptor type 1 and the nerve-growth factor receptor, TrkA in adult NI.
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-CONCLUSIONSThe multiple, cell-type specific changes in the expression of neuropeptides and molecules associated with stress and substance abuse in the NI, as well as impairments in NI neuron morphology and electrophysiology caused by early-life stress and observed in the adult brain, may contribute to the increased susceptibility to stress and compulsive behaviors observed in individuals with a history of ELS.
+ The neural bases of narcissistic and antisocial traits are still under debate. One intriguing question is whether these traits are encoded within the so-called triple network e.g. the default mode (DMN), salience (SN), and fronto-parietal (FPN) networks, and whether these traits affect the same networks in a similar manner. Connectome-based analyses were conducted on resting-state scans from 183 participants, examining regional and global graph-theoretic metrics in the DMN, SN, and FPN, with the visual and sensorimotor networks as controls. Our findings revealed a clear involvement of the triple network in narcissistic and antisocial traits, confirming a shared neural substrate for the two traits. Both traits were negatively predicted by the anterior cingulate cortex of the SN, possibly indicating less awareness of dangers and more proneness to engage in risky behaviors. Additionally, both traits were positively predicted by the lateral prefrontal cortex of the FPN, suggesting augmented strategic thinking to manipulate others and increased planning skills to achieve personal goals. Besides similarities, there were also some differences. Specific hubs of the DMN were positively associated with narcissism but negatively related with antisocials, possibly explaining their differences in self-reflection and thinking about the self, largely present in the former, but usually reduced in the latter. These results extend previous findings on the involvement of the triple network in personality disorders and suggest both common and different mechanisms underlying narcissistic and antisocial traits. As such, these findings could pave the way for developing potential biomarkers of personality pathology and identify neurostimulation intervention targets.
- in bioRxiv: Neuroscience on 2024-12-02 00:00:00 UTC.
+
in bioRxiv: Neuroscience on 2024-12-04 00:00:00 UTC.
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+http://biorxiv.org/cgi/content/short/2024.12.04.626390v1?rss=1
+">Revealing rhythm categorization in human brain activity
- functional connectivity (FC) measurements are important for robust and reproducible findings, yet pediatric functional magnetic resonance imaging (fMRI) faces unique challenges due to head motion and bias toward shorter scans. Passive viewing conditions during fMRI offer advantages for scanning pediatric populations, but FC reliability under these conditions remains underexplored. Here, we used precision fMRI data collected across three passive viewing conditions to directly compare FC reliability profiles between 25 pre-adolescent children and 25 adults, with each participant providing over 2.8 hours of data over four sessions. We found that FC test-retest correlations increased asymptotically with scan length, with children requiring nearly twice the post-censored scan time (24.6 minutes) compared to adults (14.4 minutes) to achieve comparable reliability, and that this effect was only partly attributable to head motion. Reliability differences between lower-motion adults and higher-motion children were spatially non-uniform and largest in ventral anterior temporal and frontal regions. While averaging features within functional networks improved intraclass correlation coefficient (ICC) reliability, values for higher-motion children remained in the poor-to-fair ICC range even with 48 minutes of total scan time. Viewing conditions with greater engagement reduced head motion in children but had lower FC reliability compared to less engaging low-demand videos, suggesting complex state- or condition-related trade-offs. These findings have important implications for developmental neuroimaging study design, particularly for higher motion pediatric populations.
+ Humans across cultures show an outstanding capacity to perceive, learn, and produce musical rhythms. These skills rely on mapping the infinite space of possible rhythmic sensory inputs onto a finite set of internal rhythm categories. What are the brain processes underlying rhythm categorization? We used electroencephalography (EEG) to measure brain activity as human participants listened to a continuum of rhythmic sequences characterized by repeating patterns of two inter-onset intervals. Using frequency and representational similarity analyses, we show that brain activity does not merely track the temporal structure of rhythmic inputs, but, instead, automatically produces categorical representation of rhythms. Surprisingly, despite this automaticity, these rhythm categories do not arise in the earliest stages of the ascending auditory pathway, but show strong similarity between implicit neural and overt behavioral responses. Together, these results and methodological advances constitute a critical step towards understanding the biological roots and diversity of musical behaviors across cultures.
- in bioRxiv: Neuroscience on 2024-12-02 00:00:00 UTC.
+
in bioRxiv: Neuroscience on 2024-12-04 00:00:00 UTC.
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+http://biorxiv.org/cgi/content/short/2024.12.03.626662v1?rss=1
+">Human stem cell-derived GABAergic interneuron development reveals early emergence of subtype diversity followed by gradual electrochemical maturation
- Making decisions based on noisy sensory information is a crucial function of the brain. Various decisions take each sensory signals uncertainty into account. Here, we investigated whether perceptual inferences rely on accurate estimates of sensory uncertainty. Participants completed a set of auditory, visual, and audiovisual spatial as well as temporal tasks. We fitted Bayesian observer models of each task to every participants complete dataset. Crucially, in some model variants the uncertainty estimates employed for perceptual inferences were independent of the actual uncertainty associated with the sensory signals. Model comparisons and analysis of the best-fitting parameters revealed that, in unimodal and bimodal contexts, participants perceptual decisions relied on overconfident estimates of auditory spatial and audiovisual temporal uncertainty. These findings challenge the ubiquitous assumption that human behavior optimally accounts for sensory uncertainty regardless of sensory domain.
+ Medial ganglionic eminence-derived inhibitory GABAergic pallial interneurons (MGE-pINs) are essential regulators of cortical circuits; their dysfunction is associated with numerous neurological disorders. We developed human (h) MGE-pINs from pluripotent stem cells for the treatment of drug-resistant epilepsy. Here, we analyzed xenografted hMGE-pINs over the lifespan of host mice using single nuclei RNA sequencing. Comparative transcriptomics against endogenous human brain datasets revealed that 97% of grafted cells developed into somatostatin (SST) and parvalbumin (PVALB) subtypes, including populations that exhibit selective vulnerability in Alzheimer's disease. Transplanted hMGE-pINs demonstrated rapid emergence of subclass features, progressing through distinct transcriptional states sequentially involving neuronal migration, synapse organization, and membrane maturation. We present molecular, electrophysiological, and morphological data that collectively confirm the derivation of diverse bona-fide human SST and PVALB subtypes, providing a high-fidelity model to study human MGE-pIN development and functional maturation as well as a compositional atlas for regenerative cell therapy applications.
- in bioRxiv: Neuroscience on 2024-12-02 00:00:00 UTC.
+
in bioRxiv: Neuroscience on 2024-12-04 00:00:00 UTC.
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+http://biorxiv.org/cgi/content/short/2024.12.03.626460v1?rss=1
+">Oral supplementation with Nicotinamide Riboside treatment protects RGCs in DBA/2J mouse model
- We demonstrate here that astrocytes in the striatum interact with striatal dopamine in bidirectional signaling with dopamine release actively driving surges in astrocytic Ca++, which in turn modulate and reduce subsequent dopamine release. These Ca++ surges accurately predict behavioral state changes from task-engaged to task-disengaged states, but fail to predict detailed action parameters. We propose that interactions between striatal astrocytes and dopamine are strong candidates to modulate nigro-striato-nigral loop function underlying on-going behavioral state dynamics.
+ Purpose: The aim of this study was to test whether oral administration of nicotinamide riboside (NR), the nicotinamide adenine dinucleotide (NAD+) precursors, protect retina ganglion cells (RGCs) from neurodegeneration in DBA/2J (D2) mice, which is a widely used mouse model of age-related inherited glaucoma. Method: Oral NR or NAM administration (NR low dose: 1150mg/kg; NR high dose: 4200mg/kg; NAM low dose group: 500mg/kg; NAM high dose: 2000mg/kg of body weight per day) essentially started when D2 mice were 4 or 9 months old and continued up to 12 months old. Control cohort identically received food/water without NAM or NR. Intraocular pressure (IOP) was measured every month until experiment completion. Pattern electroretinography (PERG) was recorded. Retinas were harvested for whole mount immunofluorescence staining with RGCs marker Brn3a and imaged by fluorescent confocal microscopy. Optic nerves were harvested for axon staining and quantification. Retinal NAD+ levels were enzymatically assayed. Results: NR oral supplementary treatment started at 4 months old robustly increased retinal NAD+ levels in D2 mice (NRHigh vs. vehicle: 273.7{+/-}23.59% vs. 108.70{+/-}12.10%, p<0.001). In aged vehicle group (12 months old), there was significantly diminution of the P1 and N2 components of PERG response compare with naïve group (naïve vs. vehicle: P1: 7.82{+/-} 0.70uV vs 1.63{+/-} 0.17uV, p<0.0001; N2: -13.29{+/-} 0.83uV 2 vs. -3.22{+/-} 0.27uV, p<0.0001; Kruskal-Wallis test with Dunn's multiple comparison test). NR treatment preserved aged D2 visual function when mice were 9 and 12 months old. In addition, long-term NR high dose treatment significantly protected against total RGCs loss and optic nerve atrophy (RGC: NRHigh vs. vehicle: 1412{+/-}62.00vs 475.2{+/-}94.68 cells/field, p<0.00001; axon numbers: NRHigh vs. vehicle: 23990{+/-}1159 vs 8573{+/-}1160, n=41-53, p<0.0001). Furthermore, long-term NR supplementation prevent iris depigmentation and delayed IOP elevation. Conclusion: NR oral supplementary treatment significantly preserved RGC and axon numbers, potentially preserves retinal function via elevated retinal NAD+ level in aged D2 mice. Interestingly, NR treatment also prevented iris atrophy, delayed IOP elevation associated with this glaucoma model. NR oral supplementation thus treated several aspects of murine pigment dispersion glaucoma. Given parallels between this model and glaucoma in human, out data indicate that NR is worth exploring as a therapeutic candidate in treatment of glaucoma.
- in bioRxiv: Neuroscience on 2024-12-02 00:00:00 UTC.
+
in bioRxiv: Neuroscience on 2024-12-04 00:00:00 UTC.
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+http://biorxiv.org/cgi/content/short/2024.12.02.626335v1?rss=1
+">Cortical dynamics in hand/forelimb S1 and M1 evoked by brief photostimulation of the mouses hand
- Rumination, characterized by recurrent and repetitive thinking, is closely associated with mental disorders such as depression. However, the neural mechanisms underlying this mental state remain poorly understood. In this study, we use a relatively novel neuroimaging analysis method-Brain Entropy (BEN) to quantitatively assess the irregularity, disorder, and complexity of brain activity, providing new insights into the neural mechanisms of rumination.
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-We utilized a publicly available MRI dataset from three different scanners. The dataset included 41 healthy adult participants who completed identical fMRI tasks on IPCASGE, PKUGE, and PKUSIEMENS scanners. The time interval between the two visits was 22.0 {+/-} 14.6 days. The fMRI session included four runs: resting state, sad memory, rumination, and distraction. Whole brain voxel-wise BEN differences of task state and resting state, rumination and sad memory, distraction and sad memory, and rumination and distraction were tested and overlap regions after thresholded (p<0.05) across the three scanners were identified as exhibiting significant differences.
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-The results demonstrate distinct alterations in BEN across mental states. Compared to the sad memory condition, decreased BEN was found in the visual cortex (VC) during rumination and decreased BEN in the posterior cingulate cortex/precuneus (PCC/PCu) during distraction. However, when compared to distraction, rumination showed increased BEN in the PCC/PCu. These findings suggest that rumination involves heightened internal focus and reduced processing of external environmental information. This study highlights BEN as a valuable metric for elucidating the neural mechanisms underlying rumination and its role in depression.
+ Spiking activity along synaptic circuits linking primary somatosensory (S1) and motor (M1) areas is fundamental for sensorimotor integration in cortex. Circuits along the ascending somatosensory pathway through mouse hand/forelimb S1 and M1 were recently described in detail (Yamawaki et al., 2021). Here, we characterize the peripherally evoked spiking dynamics in these two cortical areas in the same system. Brief (5 ms) optogenetic photostimulation of the hand generated short (~25 ms) barrages of activity first in S1 (onset latency 15 ms) then M1 (10 ms later). The estimated propagation speed was 20-fold faster from hand to S1 than from S1 to M1. Response amplitudes in M1 were strongly attenuated to approximately a third of those in S1. Responses were typically triphasic, with suppression and rebound following the initial peak. Parvalbumin (PV) inhibitory interneurons were involved in each phase, accounting for three-quarters of the initial spikes generated in S1, and their selective photostimulation sufficed to evoke suppression and rebound in both S1 and M1. Partial silencing of S1 by PV activation during hand stimulation reduced the M1 sensory responses. These results provide quantitative measures of spiking dynamics of cortical activity along the hand/forelimb-related transcortical loop; demonstrate a prominent and mechanistic role for PV neurons in each phase of the response; and, support a conceptual model in which somatosensory signals reach S1 via high-speed subcortical circuits to generate characteristic barrages of cortical activity, then reach M1 via densely polysynaptic corticocortical circuits to generate a similar but delayed and attenuated profile of activity.
- in bioRxiv: Neuroscience on 2024-12-02 00:00:00 UTC.
+
in bioRxiv: Neuroscience on 2024-12-04 00:00:00 UTC.
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+http://biorxiv.org/cgi/content/short/2024.12.03.626598v1?rss=1
+">Individual differences in probabilistic learning and updating predictive representations in individuals with obsessive-compulsive tendencies
- Activity-dependent synaptic accumulation of AMPA receptors (AMPARs) and subsequent long-term synaptic strengthening underlie different forms of learning and memory. The AMPAR subunit GluA1 amino-terminal domain is essential for synaptic docking of AMPAR during LTP, but the precise mechanisms involved are not fully understood. Using unbiased proteomics, we identified the epilepsy and intellectual disability-associated VGCC auxiliary subunit 2{delta}1 as a candidate extracellular AMPAR slot. Presynaptic 2{delta}1 deletion in CA3 affects synaptic AMPAR incorporation during long-term potentiation, but not basal synaptic transmission, at CA1 synapses. Consistently, mice lacking 2{delta}1 in CA3 display a specific impairment in CA1-dependent spatial memory, but not in memory tests involving other cortical regions. Decreased seizure susceptibility in mice lacking 2{delta}1 in CA3 suggests a regulation of circuit excitability by 2{delta}1/AMPAR interactions. Our study sheds light on the regulation of activity-dependent AMPAR trafficking, and highlights the synaptic organizing roles of 2{delta}1.
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-Significance statementActivity-dependent accumulation of AMPA receptors (AMPARs) at excitatory synapses and subsequent synaptic strengthening underlies long-term potentiation (LTP), forms of learning and memory, and some epilepsies. The "slot model" posits that postsynaptic scaffolding contain "slots" for AMPAR complexes, and that increased synaptic activity augments the availability of slots to accommodate more receptors, thereby strengthening synapses and enabling LTP. The presence of the GluA1 AMPAR subunit amino-terminal domain (ATD) has recently emerged as an additional requirement for LTP. Here we identify the auxiliary voltage-gated calcium channel subunit 2{delta}1 as a GluA1 ATD interacting protein and provide evidence supporting a role for 2{delta}1 as an extracellular AMPAR slot regulating activity dependent synaptic AMPAR clustering, excitability, and cognitive function.
+ Obsessive-compulsive (OC) tendencies involve intrusive thoughts and rigid, repetitive behaviours that also manifest at the subclinical level in the general population. The neurocognitive factors driving the development and persistence of the excessive presence of these tendencies remain highly elusive, though emerging theories emphasize the role of implicit information processing. Despite various empirical studies on distinct neurocognitive processes, the incidental retrieval of environmental structures in dynamic and noisy environments, such as probabilistic learning, has received relatively little attention. In this study, we aimed to unravel potential individual differences in implicit probabilistic learning and the updating of predictive representations related to OC tendencies in the general population. We conducted two independent online experiments (NStudy1 = 164, NStudy2 = 257) with young adults. Probabilistic learning was assessed using a reliable implicit visuomotor probabilistic learning task, which involved sequences with second-order non-adjacent dependencies. Our findings revealed that even among individuals displaying a broad spectrum of OC tendencies within a non-clinical population, implicit probabilistic learning remained remarkably robust. Furthermore, the results highlighted effective updating capabilities of predictive representations, which were not influenced by OC tendencies. These results offer new insights into individual differences in probabilistic learning and updating in relation to OC tendencies, contributing to theoretical, methodological, and practical approaches for understanding the maladaptive behavioural manifestations of OC disorder and subclinical tendencies.
- in bioRxiv: Neuroscience on 2024-12-02 00:00:00 UTC.
+
in bioRxiv: Neuroscience on 2024-12-04 00:00:00 UTC.
-
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+http://biorxiv.org/cgi/content/short/2024.12.02.626513v1?rss=1
+">Temporal Configuration as a New Feature of Sound: Psychological and Neurophysiological Evidence, Cross-species Consistency and Underlying Neuronal Mechanisms
- A detailed analysis of pain-related behaviors in rodents is essential for exploring both the mechanisms of pain and evaluating analgesic efficacy. With the advancement of pose-estimation tools, automatic single-camera video animal behavior pipelines are growing and integrating rapidly into quantitative behavioral research. However, current existing algorithms do not consider an animals body-part contact intensity with- and distance from- the surface, a critical nuance for measuring certain pain-related responses like paw withdrawals ( flinching) with high accuracy and interpretability. Quantifying these bouts demands a high degree of attention to body part movement and currently relies on laborious and subjective human visual assessment. Here, we introduce a supervised machine learning algorithm, ARBEL: Automated Recognition of Behavior Enhanced with Light, that utilizes a combination of pose estimation together with a novel light-based analysis of body part pressure and distance from the surface, to automatically score pain-related behaviors in freely moving mice in three dimensions. We show the utility and accuracy of this algorithm for capturing a range of pain-related behavioral bouts using a bottom-up animal behavior platform, and its application for robust drug-screening. It allows for rapid objective pain behavior scoring over extended periods with high precision. This open-source algorithm is adaptable for detecting diverse behaviors across species and experimental platforms.
+ Temporal integration is crucial for auditory perception, yet the mechanisms underlying its role are not fully elucidated. This study examines the perceptual discrimination of click trains with varied temporal configurations to determine if they can be perceived as distinct auditory objects, potentially introducing a novel dimension to sound perception. In humans, psychological experiments using a delayed match-to-sample task revealed that participants could distinctly discriminate between click trains with different temporal configurations, suggesting that temporal configuration significantly influences auditory perception. This was supported by electroencephalogram (EEG) recordings showing robust mismatch negativity (MMN) signals, indicating that the auditory system differentiates standard from deviant sounds based on their temporal characteristics. Parallel electrocorticography (ECoG) studies in rats demonstrated similar discriminatory abilities, suggesting a cross-species consistency. Neuronal recordings showed pronounced stimulus-specific adaptation (SSA) in the primary auditory cortex (A1) but minimal SSA in lower auditory areas such as the inferior colliculus (IC) and medial geniculate body (MGB), indicating that A1 uniquely integrates temporal features and discriminates complex temporal patterns. This research advances our understanding of how temporal configurations are processed in the auditory system and suggests a new feature of sound perception.
- in bioRxiv: Neuroscience on 2024-12-02 00:00:00 UTC.
+
in bioRxiv: Neuroscience on 2024-12-04 00:00:00 UTC.
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+http://biorxiv.org/cgi/content/short/2024.12.03.626574v1?rss=1
+">An investigation of the effects of α and β-frequency neural entrainment using tACS on phase-aligned TMS-evoked corticospinal excitability
- SignificanceBehavior regulates dural and cerebral vessels, with spontaneous locomotion inducing dural vessel constriction and increasing stimulus-evoked cerebral hemodynamic responses. It is vital to investigate the function of different vascular network components, surrounding and within the brain, to better understand the role of the neurovascular unit in health and neurodegeneration.
-
-AimWe characterized locomotion-induced hemodynamic responses across vascular compartments of the whisker barrel cortex: artery, vein, parenchyma, draining and meningeal vein.
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-ApproachUsing 2D-OIS, hemodynamic responses during locomotion were recorded in 9-12-month-old awake mice: wild-type, Alzheimers disease (AD), atherosclerosis or mixed (atherosclerosis/AD) models. Within somatosensory cortex, responses were taken from pial vessels inside the whisker barrel region ([WBR]: "whisker artery" and "whisker vein"), a large vein from the sagittal sinus adjacent to the WBR (draining vein), and meningeal vessels from the dura mater (which do not penetrate cortical tissue).
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-ResultsWe demonstrate that locomotion evokes an initial decrease in total hemoglobin (HbT) within the draining vein before the increase in HbT within WBR vessels. The locomotion event size influences the magnitude of the HbT increase in the pial vessels of the WBR, but not of the early HbT decrease within the draining veins. Following locomotion onset, an early HbT decrease was also observed in the overlying meningeal vessels, which unlike within the cortex did not go on to exceed baseline HbT levels during the remainder of the locomotion response. We show that locomotion-induced hemodynamic responses are altered in disease in the draining vein and whisker artery, suggesting this could be an important neurodegeneration biomarker.
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-ConclusionThis initial reduction in HbT within the draining and meningeal veins potentially serves as a space saving mechanism, allowing for large increases in cortical HbT associated with locomotion. Given this mechanism is impacted by disease it may provide an important target for vascular-based therapeutic interventions.
+ Deep brain stimulation [DBS] is an effective treatment for many brain disorders, has a favourable adverse effect profile, and can be particularly effective for individuals with treatment resistant symptoms. DBS is, however, inaccessible for most individuals, is extremely expensive, and is not considered suitable for children and adolescents. For these reasons, non-invasive alternatives to DBS, such as transcranial magnetic stimulation [TMS], are increasingly being sought to treat brain health conditions. Unfortunately, current TMS approaches exhibit large intra- and inter-subject variability in their efficacy, which limits their use clinically. One likely reason for this is that TMS is invariably delivered without reference to ongoing brain activity (i.e., open loop). We propose that the efficacy of stimulation might be improved, and the variability of its effects reduced, if stimulation could be synchronised with ongoing brain activity. To investigate this, we used transcranial alternating current stimulation (tACS) to induce entrainment of brain activity at two frequencies (=10 Hz and {beta}=20 Hz), and we delivered single pulse TMS that was temporally aligned with the phase of each tACS oscillation. To investigate the effects of tACS-phase-aligned TMS we measured motor-evoked potentials (MEPs). Our findings confirm that for -tACS and {beta}-tACS both corticospinal excitability and inter-trial variability varied as a function of tACS phase. Importantly, however, the tACS phase angle that produced maximum TMS-evoked excitability was different for -tACS and {beta}-tACS; coinciding with the negative peak (trough) for -tACS and the positive peak (peak) for {beta}-tACS. These findings confirm that aligning non-invasive brain stimulation to ongoing brain activity may increase the efficacy of TMS and reduce the variability of its effects. However, our results illustrate that the optimal phase of the tACS cycle at which to deliver TMS may vary for different tACS frequencies.
- in bioRxiv: Neuroscience on 2024-12-02 00:00:00 UTC.
+
in bioRxiv: Neuroscience on 2024-12-04 00:00:00 UTC.
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+http://biorxiv.org/cgi/content/short/2024.11.30.626179v1?rss=1
+">Temporal Lobe Epilepsy is dominated by Region Specific Interictal Cortical Inhibition
- Early life stress (ELS) has profound implications for developmental trajectories, yet the neural mechanisms underlying its long-term effects remain incompletely understood. In the present study, we examined whether interindividual similarity in ELS exposure aligns with similarity in neural representations and behavioral task performance in early adulthood. Leveraging a 20-year longitudinal dataset of Finnish families, we evaluated 87 young adults who underwent functional magnetic resonance imaging (fMRI) during an emotional go/no-go task. Intersubject representational similarity analysis (IS-RSA) was used to assess the associations between pairwise similarities in prospectively or retrospectively measured ELS, neural representations in 360 cortical regions, and task performance. We incorporated multidimensional scaling and Procrustes alignment to visualize interindividual differences in representational spaces. Prospective ELS, but not Retrospective ELS, was significantly associated with neural representational similarity across 40 cortical regions, including the anterior insula, frontal operculum, and anterior cingulate cortex. Higher Prospective ELS was also linked to reduced detection sensitivity, mediated by neural responses to angry facial expressions. These findings highlight the systematic and chronic effects of more moderate ELS on brain development and emphasize the value of prospective measurements and advanced similarity analyses in capturing the nuanced influences of ELS. By integrating spatial and shape analytical techniques, the present study provides new insights into the long-term neurobiological correlates of ELS and introduces novel methodological tools for neurodevelopmental research.
+ Epilepsy is typically characterized by excessive neuronal excitability, manifesting as seizures and interictal epileptiform discharges (IEDs) in the EEG. However, the dynamics of excitation and inhibition (E/I balance) remain poorly understood. Here, we leverage the aperiodic exponent of the EEG power spectrum--a marker indicative of synaptic inhibition--to investigate shifts in E/I balance during antiseizure medication (ASM) tapering in patients with mesial temporal lobe epilepsy (TLE). We analyzed EEG data from 28 TLE patients and 25 controls with non-epileptic episodes (NEE) undergoing presurgical video EEG monitoring. Unexpectedly, TLE patients showed a localized increase in the aperiodic exponent in the ipsilesional temporal lobe during ASM tapering, absent in controls. This inhibition increase correlated with seizure latency and predicted seizure occurrence. Intracranial recordings from 10 TLE patients revealed higher aperiodic exponents in the lateral temporal cortex compared to the hippocampus, suggesting stronger inhibition in the lateral cortex. Notably, hippocampal IEDs triggered transient inhibitory responses in the lateral cortex, accompanied by increased high-frequency activity and disrupted hippocampus-to-lateral connectivity. These findings suggest that TLE likely involves complex inhibitory mechanisms beyond the epileptic focus in the interictal period, with neocortical inhibition potentially containing epileptic activity, and offers a new tool to map epileptic brain regions.
- in bioRxiv: Neuroscience on 2024-12-02 00:00:00 UTC.
+
in bioRxiv: Neuroscience on 2024-12-04 00:00:00 UTC.
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+http://biorxiv.org/cgi/content/short/2024.12.02.626507v1?rss=1
+">The sparse driver system for in vivo single-cell labeling and manipulation in Drosophila
- The human ability to maintain adequate movement quality despite muscle fatigue is of critical importance to master physically demanding activities of daily life and for retaining independence following motor impairments. Many real-life situations call for asymmetrical activation of extremity muscles leading to unilateral manifestations of muscle fatigue. Repeated unilateral handgrip contractions at submaximal force have been shown to be associated with neural dynamics in both contralateral and ipsilateral cortical motor areas and improved response times of the contralateral, unfatigued homologue in a button-press task. However, it remains unclear whether the observed improvement in contralateral response latency translates into higher-level benefits in movement quality.
+ In this protocol, we introduce a sparse driver system for cell-type specific single-cell labeling and manipulation in Drosophila, enabling complete and simultaneous expression of multiple transgenes in the same cells. The system precisely controls expression probability and sparsity via mutant FRT sites with reduced recombination efficiency and tunable FLP levels adjusted by heat-shock durations. We demonstrate that this generalizable toolkit enables tunable sparsity, multi-color staining, single-cell trans-synaptic tracing, single-cell manipulation, and in vivo analysis of cell-autonomous gene function.
+
+For details on the use and execution of this protocol, please refer to Xu et al. 2024.
-To investigate this, 30 healthy participants underwent unilateral handgrip fatiguing tasks at 5%, 50%, and 75% of maximum voluntary contraction (MVC) force. Subsequently, bimanual movement quality was assessed in an object-hit task using a Kinarm robot.
+GRAPHICAL ABSTRACT
-The protocol at 50% and 75% of MVC elicited clear signs of muscle fatigue compared to the control condition (5%) measured by a decline in force, post-exercise deterioration in MVC, characteristic changes in surface electromyography magnitudes, and increases in ratings of perceived exertion. No change was observed on kinematic measures in the object-hit task for both arms indicating that unilateral handgrip fatigue did not elicit measurable effects on higher-level movement quality on the ipsilateral or contralateral homologue. Previously reported improvements on contralateral response latency were not found to translate into advanced movement quality benefits.
+O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=193 SRC="FIGDIR/small/626507v1_ufig1.gif" ALT="Figure 1">
+View larger version (77K):
+org.highwire.dtl.DTLVardef@db89c3org.highwire.dtl.DTLVardef@131793dorg.highwire.dtl.DTLVardef@10ebc69org.highwire.dtl.DTLVardef@73aec2_HPS_FORMAT_FIGEXP M_FIG C_FIG
- in bioRxiv: Neuroscience on 2024-12-02 00:00:00 UTC.
+
in bioRxiv: Neuroscience on 2024-12-04 00:00:00 UTC.
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+http://biorxiv.org/cgi/content/short/2024.12.01.626217v1?rss=1
+">Emotional content effects the precision of visual working memory
- Task knowledge is encoded hierarchically such that complex tasks are composed of simpler tasks. This compositional organization also supports generalization to facilitate learning of related but novel complex tasks. To study how the brain implements composition and generalization in hierarchical task learning, we trained human participants on two complex tasks that shared a simple task and tested them on a novel complex task whose composition could be inferred via the shared simple task. Behaviorally, we observed faster learning of the novel complex task than control tasks (i.e., behavioral generalization effect). Using electroencephalogram (EEG) data, we could decode the constituent simple tasks when a complex task was performed (i.e., EEG composition effect). Crucially, the shared simple task, although not part of the novel complex task, could be reliably decoded from the novel complex task. The decoding strength was also correlated with EEG composition effect and behavioral generalization effect. The findings demonstrate how generalization in task learning is implemented via task reinstatement.
+ ObjectivesOur working memory (WM) is susceptible to errors influenced by various sources. Recent research has illuminated the intricate relationship between emotional valence and working memory performance. This study aims to comprehensively investigate memory recall biases across different emotional categories.
+
+MethodTo explore this relationship, we designed and implemented a delayed-reproduction facial emotion n-back task. Participants were tasked with recalling the emotional valence of target faces across various n-back conditions, selecting their responses from a continuum of 19 morphed faces ranging from sad to happy.
-Significance StatementHumans can generalize knowledge of existing tasks to accelerate the learning of new tasks. We hypothesize that generalization is achieved by decomposing a complex task into simple (sub)tasks and reusing the simple tasks to infer the structure of a new complex task and build it. Using electroencephalogram data, we showed that constituent simple tasks can be decoded from of humans learning new complex tasks. Crucially, when the structure of a new complex task can be inferred from simple tasks, the simple tasks can be decoded from the new complex task, even when they are not part of the new complex task. These findings demonstrate the importance of the reinstatement of simple tasks in task learning through generalization.
+ResultsOur findings indicate that participants generally exhibit a negativity bias, struggling more with happy faces. Interestingly, they also perceive happy faces as less happy and sad faces as less sad, suggesting both positive and negative reappraisal in their emotional valence perception. This underscores the complex interplay between emotional valence and cognitive performance. Notably, recall of neutral images remained stable and was unaffected by preceding emotional contexts.
+
+ConclusionThese findings demonstrate that emotional content in working memory significantly impacts errors during WM tasks, with more emotionally charged faces leading to a greater drift toward the lower valence axis. This highlights the need for further exploration of how emotional factors influence cognitive processes in working memory.
- in bioRxiv: Neuroscience on 2024-12-02 00:00:00 UTC.
+
in bioRxiv: Neuroscience on 2024-12-04 00:00:00 UTC.
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+
- Brain Sciences, Vol. 14, Pages 1222: At the Frontiers of Neurorehabilitation, Series II: Advancing Neurorehabilitation Through Patient-Centered Undogmatic Innovative Approaches
- Brain Sciences doi: 10.3390/brainsci14121222
- Authors:
- Hélène Viruega
- Manuel Gaviria
-
- At the Frontiers of Neurorehabilitation: Series II [...]
+ Human visual perception in natural conditions involves multiple fixations within single objects. While traditional studies focus on transient neural responses to initial stimuli, this study investigates how object-category representations evolve across sequential fixations on an object. Using electroencephalography (EEG) and eye-tracking, we analyzed fixation-related potentials (FRPs) and applied multivariate pattern analysis (MVPA) to decode neural representations of faces and watches during prolonged viewing. Results revealed robust category-selective responses, including the N170 component, at stimulus onset, with sustained representations persisting throughout object presentation. Temporal signal deconvolution showed that subsequent fixations did not re-evoke the N170 but elicited transient occipital responses, likely reflecting low-level differences. These findings underscore the dynamic interplay between transient and sustained neural processes during naturalistic vision and highlight the importance of disentangling overlapping neural signals during free viewing.
- in Brain Sciences on 2024-12-02 00:00:00 UTC.
+
in bioRxiv: Neuroscience on 2024-12-04 00:00:00 UTC.
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+
- Chun et al. characterize the transition of tumor-infiltrating CD8+ T cell populations that are distinguished by asialo-ganglio-N-tetraosylceramide (asGM1) expression. They show that, while both in situ Flt3L expression and PD-1 inhibition promote the transition with acquisition of effector functions via IL-12, the former induces TCR repertoire diversification.
+ We investigate how respiration influences cognition by examining the interaction between respiratory phase and task-related brain activity during two visual categorization tasks. While prior research shows that cognitive performance varies along the respiratory cycle, the underlying neurophysiological mechanisms remain poorly understood. Though some studies have shown that large-scale neural activity reflecting changes in the excitation-inhibition balance is co-modulated with the respiratory cycle, it remains unclear whether respiration directly shapes the quality by which task-relevant sensory information is encoded. We address this gap by applying single-trial multivariate analyses to EEG data obtained in humans, allowing us to track how respiration modulates the sensory evidence in this neurophysiological signal. Confirming previous studies, our data show that participants performance varies with the respiratory phase prior and during a trial. Importantly, they also suggest that respiration directly influences the sensory evidence carried by parieto-occipital processes emerging around 300 to 200 ms prior to participants responses. Hence, respiration and sensory-cognitive processes are not only highly intertwined but respiration directly facilitates the representation of behaviourally-relevant signals in the brain.
- in Cell Reports: Current Issue on 2024-11-30 00:00:00 UTC.
+
in bioRxiv: Neuroscience on 2024-12-04 00:00:00 UTC.
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- Li et al. report a time-dependent production of sex pheromone in male Bactrocera dorsalis, which is correlated with the level of glucose in the rectum. The expression of GLA, a transcription factor (BDTF), and a pigment-dispersing factor (PDF) in the rectum are responsible for the production of glucose.
+ Abstract
Research shows that the brain regions that subserve our ability to remember the past are also involved in imagining the future. Given this similarity in brain activity, it remains unclear how brain activity distinguishes imagination from memory. In the current work, we scanned participants using functional magnetic resonance imaging before and after they performed a highly unique and elaborate activity wherein they went skydiving for the first time in their lives. Multivariate pattern analysis, Bayesian inference, and a tightly controlled experimental design were used to identify the neural activity that differentiates between memory and imagination of the same events. The results showed that large swaths of the default mode network exhibited identical patterns of activity in recollection and imagination; several frontal areas were involved in imagination (but not in recollection). Representational similarity analysis revealed that the left ventral precuneus exhibited different patterns of memory and imagination. Further examination revealed that this subarea may be especially important for recollection of specific episodes. These results advance our understanding of how the critical distinction between the past and future might be manifested in the brain.
- in Cell Reports: Current Issue on 2024-11-30 00:00:00 UTC.
+
in Cerebral Cortex on 2024-12-04 00:00:00 UTC.
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- Ke et al. present cryo-EM structures of FFAR1 and FFAR2, revealing the structural basis for endogenous ligand selectivity and activation, with a potential allosteric binding pocket identified in FFAR2. These findings suggest new avenues for selective FFAR modulation in metabolic therapies.
+ Abstract
A social scene is particularly informative when people are distinguishable. To understand somebody amid a “cocktail party” chatter, we automatically index their voice. This ability is underpinned by parallel processing of vocal spectral contours from speech sounds, but it has not yet been established how this occurs in the brain’s cortex. We investigate single-trial neural tracking of slow frequency modulations in speech using electroencephalography. Participants briefly listened to unfamiliar single speakers, and in addition, they performed a cocktail party comprehension task. Quantified through stimulus reconstruction methods, robust tracking was found in neural responses to slow (delta-theta range) modulations of frequency contours in the fourth and fifth formant band, equivalent to the 3.5–5 KHz audible range. The spectral spacing between neighboring instantaneous frequency contours (ΔF), which also yields indexical information from the vocal tract, was similarly decodable. Moreover, EEG evidence of listeners’ spectral tracking abilities predicted their chances of succeeding at selective listening when faced with two-speaker speech mixtures. In summary, the results indicate that the communicating brain can rely on locking of cortical rhythms to major changes led by upper resonances of the vocal tract. Their corresponding articulatory mechanics hence continuously issue a fundamental credential for listeners to target in real time.
- in Cell Reports: Current Issue on 2024-11-30 00:00:00 UTC.
+
in Cerebral Cortex on 2024-12-04 00:00:00 UTC.
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- Bodart-Santos et al. show that Sepp1 is a key regulator of ATP-induced secretion of EVs by microglia. Sepp1-deficient microglia show impairment in expression of genes associated with EV biogenesis machinery and display increased lysosomal activity. Downregulation of Sepp1 halts hypersecretion of EVs by amyloid plaque-associated MGnD microglia.
+ Abstract
Salient emotional visual cues receive prioritized processing in human visual cortex. To what extent emotional facilitation relies on preattentional stimulus processing preceding semantic analysis remains controversial. Making use of steady-state visual evoke potentials frequency-tagged to meaningful complex emotional scenes and their scrambled versions, presented in a 4-Hz rapid serial visual presentation fashion, the current study tested temporal dynamics of semantic and emotional cue processing. The neural dynamics of bottom-up capture of attention driven by concrete images were analyzed under a passive-viewing-like scenario and in a competitive context, where a concurrent foreground task realized with a random dot kinematogram flickering at 15 Hz enabled the concurrent monitoring of top-down selective attention. Aligned with the semantic primacy hypothesis, the steady-state visual evoke potentials’ results provide evidence of an initial rapid capture of attention driven by objecthood, followed by heightened deployment of attentional resources to emotional scenes that remained stable for the entire stimulation period. We replicated previous findings in which emotional distractors first prompt visuocortical facilitation, followed by suppression of a concurrent foreground task. Modeling this time-delayed competition process fit the data better than a time-invariant trade-off between concurrent cues as assumed by most models of selective attention.
- in Cell Reports: Current Issue on 2024-11-30 00:00:00 UTC.
+
in Cerebral Cortex on 2024-12-04 00:00:00 UTC.
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- Brain Sciences, Vol. 14, Pages 1221: Identity and Temporal Fragmentation in Borderline Personality Disorder: A Systematic Review
- Brain Sciences doi: 10.3390/brainsci14121221
- Authors:
- Ilaria Faggioli
- Cecilia Maria Esposito
- Giovanni Stanghellini
-
- Background: Borderline Personality Disorder (BPD) is a prevalent psychopathological condition, affecting 0.7&ndash;2.7% of the general population. Given the known link between identity formation and the temporal, metacognitive, and narrative processes that contribute to its coherence, the aim of the present systematic review is to synthesize the current literature about the relationship between identity diffusion and lived time in adult patients with BPD. This would enhance knowledge and treatments, leading to a better understanding of the implications of time processes on identity diffusion in BPD. Methods: According to PRISMA guidelines, the main databases were consulted, and specific eligibility criteria were applied. The selection leads to the inclusion of 15 articles, investigating through integrated techniques the lived time, memory, self-reported narratives, and metacognition in BPD subjects. Results: A general agreement among researchers was found, confirming greater difficulty for BPD subjects in producing autobiographical stories, logically and temporally integrated, characterized by positive content. Functional and structural alterations were detected to explain narrative incoherence, as well as symptoms such as emotional dysregulation and cognitive biases. Conclusions: The difficulty for BPD subjects in producing a coherent personal narrative has been interpreted as a correlation of anomalies in autobiographical memories and consequently identities, which were equally compromised by the experience of discontinuity in the temporal structure. This would confirm the hypothesis of the temporal fragmentation of the self in BPD. Although some limitations have been encountered, we suggest that the understanding of identity diffusion and lived time in BPD subjects could represent a useful guide for further research.
+ The Editors of Cerebral Cortex would like to thank the following partial list of the over 1141 reviewers who have contributed their time and expertise to the journal in 2024.
- in Brain Sciences on 2024-11-30 00:00:00 UTC.
+
in Cerebral Cortex on 2024-12-04 00:00:00 UTC.
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+
- Brain Sciences, Vol. 14, Pages 1220: CAR-T Cells for the Treatment of Central Nervous System Tumours: Known and Emerging Neurotoxicities
- Brain Sciences doi: 10.3390/brainsci14121220
+ Brain Sciences, Vol. 14, Pages 1226: Determining the Predictors of Recurrence or Regrowth Following Spinal Astrocytoma Resection: A Systematic Review and Meta-Analysis
+ Brain Sciences doi: 10.3390/brainsci14121226
Authors:
- Leonardo Palazzo
- Valentina Pieri
- Giulia Berzero
- Massimo Filippi
+ Harry Hoang
+ Amine Mellal
+ Milad Dulloo
+ Ryan T. Nguyen
+ Neil Nazar Al-Saidi
+ Hamzah Magableh
+ Alexis Cailleteau
+ Abdul Karim Ghaith
+ Victor Gabriel El-Hajj
+ Adrian Elmi-Terander
- The advent of chimeric antigen receptor (CAR)-T cells has recently changed the prognosis of relapsing/refractory diffuse large B-cell lymphomas, showing response rates as high as 60 to 80%. Common toxicities reported in the pivotal clinical trials include the cytokine release syndrome (CRS) and the Immune effector Cell-Associated Neurotoxicity Syndrome (ICANS), a stereotyped encephalopathy related to myeloid cell activation and blood&ndash;brain barrier dysfunction, presenting with a distinctive cascade of dysgraphia, aphasia, disorientation, attention deficits, vigilance impairment, motor symptoms, seizures, and diffuse brain oedema. The tremendous oncological efficacy of CAR-T cells observed in systemic B-cell malignancies is leading to their growing use in patients with primary or secondary central nervous system (CNS) lymphomas and in patients with solid tumours, including several CNS cancers. Early studies conducted in adult and paediatric patients with solid CNS tumours reported a distinct profile of neurotoxicity referred to as Tumour inflammation-associated neurotoxicity (TIAN), corresponding to local inflammation at the tumour site manifesting with focal neurological deficits or mechanical complications (e.g., obstructive hydrocephalus). The present review summarises available data on the efficacy and safety of CAR-T cells for solid and haematological CNS malignancies, emphasising known and emerging phenotypes, ongoing challenges, and future perspectives.
+ Background/Objectives: Spinal astrocytomas (SA) represent 30&ndash;40% of all intramedullary spinal cord tumors (IMSCTs) and present significant clinical challenges due to their aggressive behavior and potential for recurrence. We aimed to pool the evidence on SA and investigate predictors of regrowth or recurrence after surgical resection. Methods: A systematic review and meta-analysis were conducted on peer-reviewed human studies from several databases covering the field of SA. Data were collected including sex, age, tumor location, extent of resection, histopathological diagnosis, and adjuvant therapy to identify predictors of SA recurrence. Recurrence was defined as failure of local tumor control or regrowth after treatment. Results: A total of 53 studies with 1365 patients were included in the meta-analysis. A postoperative deterioration in neurological outcomes, as assessed by the modified McCormick scale, was noted in most of the patients. The overall recurrence rate amounted to 41%. On meta-analysis, high-grade WHO tumors were associated with higher odds of recurrence (OR = 2.65; 95% CI: 1.87, 3.76; p = 0.001). Similarly, GTR was associated with lower odds of recurrence compared to STR (OR = 0.33; 95% CI: 0.18, 0.60; p = 0.0003). Sex (p = 0.5848) and tumor location (p = 0.3693) did not show any significant differences in the odds of recurrence. Intraoperative neurophysiological monitoring was described in 8 studies and adjuvant radiotherapy in 41 studies. Conclusions: The results highlight the significant importance of tumor grade and extent of resection in patient prognosis. The role of adjuvant radiotherapy remains unclear, with most studies suggesting no differences in outcomes, with limitations due to potential confounders.
- in Brain Sciences on 2024-11-30 00:00:00 UTC.
+
in Brain Sciences on 2024-12-04 00:00:00 UTC.
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- Brain Sciences, Vol. 14, Pages 1219: Advances in the Study of Anticipatory Postural Adjustments
- Brain Sciences doi: 10.3390/brainsci14121219
- Authors:
- William P. Berg
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- Postural stability is critical to the execution of almost any voluntary movement [...]
+ Climate change significantly affects smallholder farmers, whose livelihoods are closely tied to the environment. This study explores factors influencing the adoption of climate-smart agriculture (CSA) practices and their impact on crop productivity among small-scale farmers in Nyimba District, Zambia. Data were collected from 194 households across 12 villages, and logistic regression and propensity score matching analyses were employed to identify key factors and evaluate CSA’s effects on crop yields. Findings revealed that CSA adoption is influenced by factors such as education level, household size, fertilizer use, age, gender, farming experience, livestock ownership, income, farmland size, marital status, and access to climate-related information. CSA adopters experienced a 20.20% increase in overall crop yields compared to non-adopters, with a 21.50% increase in maize yields specifically. The study underscores the need for targeted interventions to support CSA adoption through education, improved dissemination of climate information, and access to critical resources such as improved seeds and financial services. This research offers insights for policymakers and extension services to develop evidence-based strategies enhancing resilience and productivity among smallholder farmers in response to climate challenges.
- in Brain Sciences on 2024-11-30 00:00:00 UTC.
+
in F1000Research on 2024-12-03 16:24:56 UTC.
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- Brain Sciences, Vol. 14, Pages 1218: Circadian Intervention Improves Parkinson’s Disease and May Slow Disease Progression: A Ten Year Retrospective Study
- Brain Sciences doi: 10.3390/brainsci14121218
- Authors:
- Gregory Willis
- Takuyuki Endo
- Murray Waldman
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- Background: The involvement of the circadian system in the etiology and treatment of Parkinson&rsquo;s disease (PD) is becoming an increasingly important topic. The prodromal symptoms of PD include insomnia, fatigue, depression and sleep disturbance which herald the onset of the primary symptoms of bradykinesia, tremor and rigidity while robbing patients of their quality of life. Light treatment (LT) has been implemented for modifying circadian function in PD but few studies have examined its use in a protracted term that characterizes PD itself. Methods: The present exploratory study monitors the effect of LT over a 10 year course of PD in the context of ongoing circadian function. Results: Improvement in circadian based symptoms were seen soon after LT commenced and continued for the duration of the study. Improvement in motor function was more subtle and was not distinguishable until 1.2 years after commencing treatment. Improvement in most motor and prodromal symptoms remained in steady state for the duration of the study as long as patients were compliant with daily use. Conclusions: The sequence of improvement in prodromal symptoms and motor function seen here parallels the slow, incremental repair process mimicking the protracted degenerative sequelae of PD that extends over decades. This process also emulates the slow incremental improvement characterizing the reparative course seen with circadian symptoms in other disorders that improve with LT. Recent findings from epidemiological work suggest that early disruption of circadian rhythmicity is associated with increased risk of PD and the present findings are consistent with that hypothesis. It is concluded that intervening in circadian function with LT presents a minimally invasive method that is compatible with internal timing that slows the degenerative process of PD.
+ by Elif Köksal-Ersöz, Pascal Benquet, Fabrice Wendling
+
+Neuroplasticity refers to functional and structural changes in brain regions in response to healthy and pathological activity. Activity dependent plasticity induced by epileptic activity can involve healthy brain regions into the epileptogenic network by perturbing their excitation/inhibition balance. In this article, we present a new neural mass model, which accounts for neuroplasticity, for investigating the possible mechanisms underlying the epileptogenic network expansion. Our multiple-timescale model is inspired by physiological calcium-mediated synaptic plasticity and pathological extrasynaptic N-methyl-D-aspartate (NMDA) dependent plasticity dynamics. The model highlights that synaptic plasticity at excitatory connections and structural changes in the inhibitory system can transform a healthy region into a secondary epileptic focus under recurrent seizures and interictal activity occurring in the primary focus. Our results suggest that the latent period of this transformation can provide a window of opportunity to prevent the expansion of epileptogenic networks, formation of an epileptic focus, or other comorbidities associated with epileptic activity.
- in Brain Sciences on 2024-11-30 00:00:00 UTC.
+
in PLoS Computational Biology on 2024-12-03 14:00:00 UTC.
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- Brain Sciences, Vol. 14, Pages 1217: Effects of Route Complexity and Lighting on Route Following in Alzheimer’s Disease and Posterior Cortical Atrophy
- Brain Sciences doi: 10.3390/brainsci14121217
- Authors:
- Amelia M. Carton
- Chris Frost
- Teresa Poole
- Biao Yang
- Ian D. McCarthy
- Tatsuto Suzuki
- Catherine Holloway
- Robin Serougne
- Derrick Boampong
- Mary Pat Sullivan
- Nick Tyler
- Sebastian Crutch
- Keir X. X. Yong
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- Objective: Visual processing deficits arising in dementia are associated with particular functional disability. This study aimed to investigate the effects of the built environment on mobility and navigation in people with dementia-related visual loss. Methods: Participants with posterior cortical atrophy (PCA; &ldquo;visual-variant Alzheimer&rsquo;s&rdquo;; n = 11), typical Alzheimer&rsquo;s disease (tAD; N = 10), and controls (n = 13) repeatedly walked down routes within a simplified real-world setting. Participant groups were of comparable age and gender. Routes were of different complexity (straight, U-shaped, and S-shaped), overhead lighting levels (low and high) and with or without a dynamic LED (light-emitting diode) cue (trial n = 24). Ratios of walking times for each experimental condition (each complex route vs the straight route, high lighting vs low, and LED cue vs no cue) were compared between participant groups. Kinematic measures were produced from a total of 10,813 steps using wearable inertial measurement units (IMUs). Results: The walking time ratios relating to route complexity were higher in the PCA group than in controls: 30.3% (95% CI [13.5%, 49.5%] higher for U-shaped vs straight and 31.9% [21.1%, 55.3%] for S-shaped vs straight, averaged over other conditions). The analogous results relating to route complexity for the tAD group were intermediate between those for the PCA and control groups. There was no evidence that walking time ratios differed according to lighting level or the presence of the LED cue. Conclusions: Findings contribute to evidence-based design for dementia-friendly environments, emphasizing consequences of environmental complexity for functional independence and mobility in people with dementia-related visual loss. Findings inform recommendations for environmental design to support the independence of individuals with dementia.
+ by Ikram Mahmoudi, Chloé Quignot, Carla Martins, Jessica Andreani
+
+Protein-RNA interactions play a critical role in many cellular processes and pathologies. However, experimental determination of protein-RNA structures is still challenging, therefore computational tools are needed for the prediction of protein-RNA interfaces. Although evolutionary pressures can be exploited for structural prediction of protein-protein interfaces, and recent deep learning methods using protein multiple sequence alignments have radically improved the performance of protein-protein interface structural prediction, protein-RNA structural prediction is lagging behind, due to the scarcity of structural data and the flexibility involved in these complexes. To study the evolution of protein-RNA interface structures, we first identified a large and diverse dataset of 2,022 pairs of structurally homologous interfaces (termed structural interologs). We leveraged this unique dataset to analyze the conservation of interface contacts among structural interologs based on the properties of involved amino acids and nucleotides. We uncovered that 73% of distance-based contacts and 68% of apolar contacts are conserved on average, and the strong conservation of these contacts occurs even in distant homologs with sequence identity below 20%. Distance-based contacts are also much more conserved compared to what we had found in a previous study of homologous protein-protein interfaces. In contrast, hydrogen bonds, salt bridges, and π-stacking interactions are very versatile in pairs of protein-RNA interologs, even for close homologs with high interface sequence identity. We found that almost half of the non-conserved distance-based contacts are linked to a small proportion of interface residues that no longer make interface contacts in the interolog, a phenomenon we term “interface switching out”. We also examined possible recovery mechanisms for non-conserved hydrogen bonds and salt bridges, uncovering diverse scenarios of switching out, change in amino acid chemical nature, intermolecular and intramolecular compensations. Our findings provide insights for integrating evolutionary signals into predictive protein-RNA structural modeling methods.
- in Brain Sciences on 2024-11-30 00:00:00 UTC.
+
in PLoS Computational Biology on 2024-12-03 14:00:00 UTC.
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- Brain Sciences, Vol. 14, Pages 1216: Sex Differences in Processing Emotional Speech Prosody: Preliminary Findings from a Multi-Feature Oddball Study
- Brain Sciences doi: 10.3390/brainsci14121216
- Authors:
- Chieh Kao
- Yang Zhang
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- Background/Objectives: Emotional prosody, the intonation and rhythm of speech that conveys emotions, is vital for speech communication as it provides essential context and nuance to the words being spoken. This study explored how listeners automatically process emotional prosody in speech, focusing on different neural responses for the prosodic categories and potential sex differences. Methods: The pilot data here involved 11 male and 11 female adult participants (age range: 18&ndash;28). A multi-feature oddball paradigm was used, in which participants were exposed to sequences of non-repeating English words with emotional (angry, happy, sad) or neutral prosody while watching a silent movie. Results: Both mismatch negativity (MMN) and P3a components were observed, indicating automatic perceptual grouping and neural sensitivity to emotional variations in speech. Women showed stronger MMN to angry than sad prosody, while men showed stronger MMN to angry than happy prosody. Happy prosody elicited the strongest P3a, but only in men. Conclusions: The findings challenge the notion that all facets of emotion processing are biased toward female superiority. However, these results from 22 young adult native English speakers should be interpreted with caution, as data from a more adequate sample size are needed to test the generalizability of the findings. Combined with results from studies on children and elderly adults, these preliminary data underscore the need to explore the complexities of emotional speech processing mechanisms to account for category and sex differences across the lifespan in a longitudinal perspective.
+ by Adam J. Kucharski
+
+Ongoing influenza H5N1 outbreaks highlight the need for timely, scalable interventions that draw on lessons from COVID-19. In particular, successful pandemic preparedness requires early outbreak management, including effective responses targeting spillovers before there is evidence of human-to-human transmission.
+
+Ongoing influenza H5N1 outbreaks highlight the need for timely, scalable interventions that draw on lessons from COVID-19. This Perspective discussed that successful pandemic preparedness requires early outbreak management, including effective responses targeting spillovers before evidence of human-to-human transmission exists.
- in Brain Sciences on 2024-11-30 00:00:00 UTC.
+
in PLoS Biology on 2024-12-03 14:00:00 UTC.
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- Brain Sciences, Vol. 14, Pages 1215: Methodology and Experimental Protocol for Fatigue Analysis in Suggestopedia Teachers
- Brain Sciences doi: 10.3390/brainsci14121215
- Authors:
- Gagandeep Kaur
- Borislava Kostova
- Paulina Tsvetkova
- Anna Lekova
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- Background: Among all professions, teaching is significantly affected by psycho-social risks with approximately 33.33% of educators reporting work-related fatigue. Suggestopedia, an effective pedagogical approach developed in Bulgaria, claims to induce positive psychological and cognitive benefits in both teachers and students. In order to gather scientific evidence, given the above statement, we designed a methodology to detect fatigue in Suggestopedia teachers based on neurocognitive analysis and psychological assessment. Methods: An increase in the EEG theta and alpha band powers is considered among the most reliable markers of fatigue. The proposed methodology introduces a robust framework for fatigue analysis. Initially, the changes in EEG band powers using the resting state EEG activity before and after teaching are measured. Subsequently, validated psychological questionnaires are used to gain subjective feedback on fatigue. The study participants include a control group (traditional teachers) and the test group (suggestopedia teachers) to assess whether suggestopedia practice mitigates fatigue among teachers. Observations: In a pilot study, the EEG data was analyzed by evaluating the interrelations between EEG bands and the alpha&ndash;beta ratio. The results of the proposed study are expected to provide comprehensive analysis for the fatigue levels of teachers. In future research, our goal is to position the described methodology as a robust approach for evaluating cognitive and emotional states.
+ by Corson N. Areshenkoff, Anouk J. de Brouwer, Daniel J. Gale, Joseph Y. Nashed, Jonathan Smallwood, J. Randall Flanagan, Jason P. Gallivan
+
+Sensorimotor learning is supported by multiple competing processes that operate concurrently, making it a challenge to elucidate their neural underpinnings. Here, using human functional MRI, we identify 3 distinct axes of connectivity between the motor cortex and other brain regions during sensorimotor adaptation. These 3 axes uniquely correspond to subjects’ degree of implicit learning, performance errors and explicit strategy use, and involve different brain networks situated at increasing levels of the cortical hierarchy. We test the generalizability of these neural axes to a separate form of motor learning known to rely mainly on explicit processes and show that it is only the Explicit neural axis, composed of higher-order areas in transmodal cortex, that predicts learning in this task. Together, our study uncovers multiple distinct patterns of functional connectivity with motor cortex during sensorimotor adaptation, the component processes that these patterns support, and how they generalize to other forms of motor learning.
- in Brain Sciences on 2024-11-30 00:00:00 UTC.
+
in PLoS Biology on 2024-12-03 14:00:00 UTC.
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- In Peru, insect consumption, as a nutritional complement or as the main source in the diet, is limited to the regions of our the central jungle where Atta sexdens ants are consumed. An energy bar based on Andean grains with Atta sexdens ant flour was formulated. The ants were obtained from the department of San Martin, district of Rioja, province of Rioja. Four different formulations were prepared with different Atta sexdens ant flour concentrations: 15%, 20%, 25%, and 30%. Moisture, total fat, ash, proteins, fiber, carbohydrates, instrumental texture, and organoleptic analysis (taste, texture, and color) were performed. The developed cereal energy bar presented a 10 g protein content in 100 g of the final product. Acceptability was evaluated in adolescents and young adult populations. The developed cereal bars presented a high protein content, adequate organoleptic properties and high acceptability. However, this must be considered in the context of the rising cost of protein-rich foods.
+ by Simon Dellicour, Paul Bastide, Pauline Rocu, Denis Fargette, Olivier J. Hardy, Marc A. Suchard, Stéphane Guindon, Philippe Lemey
+
+Genomic data collected from viral outbreaks can be exploited to reconstruct the dispersal history of viral lineages in a two-dimensional space using continuous phylogeographic inference. These spatially explicit reconstructions can subsequently be used to estimate dispersal metrics that can be informative of the dispersal dynamics and the capacity to spread among hosts. Heterogeneous sampling efforts of genomic sequences can however impact the accuracy of phylogeographic dispersal metrics. While the impact of spatial sampling bias on the outcomes of continuous phylogeographic inference has previously been explored, the impact of sampling intensity (i.e., sampling size) when aiming to characterise dispersal patterns through continuous phylogeographic reconstructions has not yet been thoroughly evaluated. In our study, we use simulations to evaluate the robustness of 3 dispersal metrics — a lineage dispersal velocity, a diffusion coefficient, and an isolation-by-distance (IBD) signal metric — to the sampling intensity. Our results reveal that both the diffusion coefficient and IBD signal metrics appear to be the most robust to the number of samples considered for the phylogeographic reconstruction. We then use these 2 dispersal metrics to compare the dispersal pattern and capacity of various viruses spreading in animal populations. Our comparative analysis reveals a broad range of IBD patterns and diffusion coefficients mostly reflecting the dispersal capacity of the main infected host species but also, in some cases, the likely signature of rapid and/or long-distance dispersal events driven by human-mediated movements through animal trade. Overall, our study provides key recommendations for the use of lineage dispersal metrics to consider in future studies and illustrates their application to compare the spread of viruses in various settings.
- in F1000Research on 2024-11-29 18:49:56 UTC.
+
in PLoS Biology on 2024-12-03 14:00:00 UTC.
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- Background Pathological response of liver metastases (LM) from colorectal carcinoma (CRC) to neoadjuvant therapy is a known prognostic factor associated with recurrence and survival. The aim of this study was to compare the performance of two prognostic scores in patients who underwent surgery for colorectal cancer liver metastases (CRCLM), specifically in stage IV disease. Methods We conducted a study on patients with stage IV colorectal cancer who received preoperative chemotherapy (CT) followed by liver metastasis (LM) resection between 2015 and 2021. Among these patients, 57% had synchronous metastases (diagnosed at the same time as the primary tumor), while the remaining cases were metachronous (diagnosed after the primary tumor). Pathological response was evaluated using both the Rubbia-Brandt tumor regression grade (TRG) and the Blazer scoring system. We then assessed the performance of these two prognostic scores based on homogeneity (using the likelihood ratio, LR+), monotonicity, and discriminative ability (using the area under the receiver operating characteristic [ROC] curve, AUC). Results 70 cases were included in the study. Mean age was 56 years. The sex ratio (males/females) was 2.2. Forty patients were stage IV (57%) with synchronous all CRCLMs. The overall survival, all stages combined, was 85.5% at 12 months, 41.7% at 24 months and 19.3% at 36 months. The median survival was better in case of major response (TRG1/TRG2) evaluated at 40.1 and 41.1 months after diagnosis. In cases of partial response (TRG3), the median survival was 32.1 months. In cases with no response (TRG4/TRG5), survival was estimated at 29.9 and 18.5 months. The Rubbia-Brandt TRG had the highest LR+ (10.95). The LR+ of the Rubbia-Brandt score was greater than 10, so it was a test with very strong contribution. The LR+ of the Blazer score was between 5 and 10, it was a test with strong contribution. The Rubbia-Brandt TRG had the highest linearity value (10.73). With a higher AUC of the ROC curve (0.8), the Rubbia-Brandt TRG was better at predicting survival than the Blazer score. Conclusion Surgical resection is the gold standard for CRCLM, with improved prognosis from neoadjuvant chemotherapy. Pathological response to CT is a key prognostic factor, and the Rubbia Brandt TRG system enhances survival predictivity when combined with ypTN stage.
+ by Benedict G. Hogan, Mary Caswell Stoddard
+
+Hyperspectral imaging—a technique that combines the high spectral resolution of spectrophotometry with the high spatial resolution of photography—holds great promise for the study of animal coloration. However, applications of hyperspectral imaging to questions about the ecology and evolution of animal color remain relatively rare. The approach can be expensive and unwieldy, and we lack user-friendly pipelines for capturing and analyzing hyperspectral data in the context of animal color. Fortunately, costs are decreasing and hyperspectral imagers are improving, particularly in their sensitivity to wavelengths (including ultraviolet) visible to diverse animal species. To highlight the potential of hyperspectral imaging for animal coloration studies, we developed a pipeline for capturing, sampling, and analyzing hyperspectral data (here, in the 325 nm to 700 nm range) using avian museum specimens. Specifically, we used the pipeline to characterize the plumage colors of the King bird-of-paradise (Cicinnurus regius), Magnificent bird-of-paradise (C. magnificus), and their putative hybrid, the King of Holland’s bird-of-paradise (C. magnificus x C. regius). We also combined hyperspectral data with 3D digital models to supplement hyperspectral images of each specimen with 3D shape information. Using visual system-independent methods, we found that many plumage patches on the hybrid King of Holland’s bird-of-paradise are—to varying degrees—intermediate relative to those of the parent species. This was true of both pigmentary and structurally colored plumage patches. Using visual system-dependent methods, we showed that only some of the differences in plumage patches among the hybrid and its parent species would be perceivable by birds. Hyperspectral imaging is poised to become the gold standard for many animal coloration applications: comprehensive reflectance data—across the entire surface of an animal specimen—can be obtained in a matter of minutes. Our pipeline provides a practical and flexible roadmap for incorporating hyperspectral imaging into future studies of animal color.
- in F1000Research on 2024-11-29 18:42:06 UTC.
+
in PLoS Biology on 2024-12-03 14:00:00 UTC.