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- Wallabag.it! - Save to Instapaper - Save to Pocket -
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- Science, Volume 385, Issue 6715, September 2024.
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+PTZ-induced seizures caused short-term changes in glial gene expression, with more significant alterations observed in astroglial genes compared to microglial genes.
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+The changes were directed toward the neuroprotective profile of A2 cell activation.
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+ABSTRACT
+Astrocytes and microglia can adopt two distinct phenotypes in various pathological processes: neurotoxic A1/M1 and neuroprotective A2/M2. Recent evidence suggests that these cells play a significant role in epileptogenesis. The objective of this study was to characterize the phenotype of astrocytes and microglial cells in the hippocampus and temporal cortex of young male Wistar rats at 3 h, 1, 3, and 7 days after pentylenetetrazole-induced seizures. RT-qPCR was employed to examine the expression of glial genes (Gfap, Aif1, Slc1a1, Slc1a2, Slc1a3, Itpr2, Gdnf, Bdnf, Fgf2, Tgfb, Il1b, Tnf, Il1rn, Lcn2, S100a10, Nlrp3, Arg1). The most notable alterations in the expression of glial genes were observed on the first day following seizures in the temporal cortex. An increase in the expression of the Gfap, Slc1a2, Slc1a1, Il1b, Tnfa, Bdnf, and Fgf2 genes, and the A2 astrocyte condition marker S100a10, was observed. An increase in the expression of the Gfap and Slc1a2 genes was observed in the hippocampus on the first day after seizures. However, in contrast to the changes observed in the cortex, the changes in the hippocampus were opposite for the Il1rn, Bdnf, Tgfb, and Arg1 genes. Nevertheless, the alterations in GFAP and EAAT2 protein levels were not corroborated by Western blot analysis. Conversely, a more comprehensive immunohistochemical analysis confirmed an augmentation in the number of GFAP-positive cells in the hippocampus 1 day after seizures. Based on the presented evidence, we can conclude that a single convulsive seizure episode in 3-week-old rats results in transient astroglial activation and polarization to a neuroprotective phenotype (A2).
- in Science on 2024-09-20 07:00:00 UTC.
+
in Journal of Neuroscience Research on 2024-09-21 07:03:57 UTC.
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- Science, Volume 385, Issue 6715, September 2024.
+ Brain Sciences, Vol. 14, Pages 943: The Effect of Social Information Processing, Self-Regulation and Metacognition on Theory of Mind: Path Analysis
+ Brain Sciences doi: 10.3390/brainsci14090943
+ Authors:
+ Canan Keleş Ertürk
+ Kezban Tepeli
+
+ Objectives: The main purpose of the current study was to examine the effects of social information processing, self-regulation, and metacognition variables on ToM using path analysis. Methods: For this purpose, path analysis was conducted for the model established according to the relationships between the variables. Theory of mind task battery (ToMTB), Metacognitive Knowledge Interview (McKI), Schultz Test of Emotion Processing—Preliminary Version (STEP-P), and self-regulation scale were administered to 310 children aged 3–5 years. Results: The results show that social information processing (except STEP-P.P.B, one of the sub-dimensions of the STEP-P scale) has a significant effect on ToM through metacognition and self-regulation. Conclusions: In this context, it can be said that social information processing, metacognition, and self-regulation are effective in the development of ToM.
- in Science on 2024-09-20 07:00:00 UTC.
+
in Brain Sciences on 2024-09-21 00:00:00 UTC.
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- Science, Volume 385, Issue 6715, September 2024.
+ Brain Sciences, Vol. 14, Pages 942: Biostasis: A Roadmap for Research in Preservation and Potential Revival of Humans
+ Brain Sciences doi: 10.3390/brainsci14090942
+ Authors:
+ Andrew T. McKenzie
+ Brian Wowk
+ Anton Arkhipov
+ Borys Wróbel
+ Nathan Cheng
+ Emil F. Kendziorra
+
+ Human biostasis, the preservation of a human when all other contemporary options for extension of quality life are exhausted, offers the speculative potential for survival via continuation of life in the future. While provably reversible preservation, also known as suspended animation, is not yet possible for humans, the primary justification for contemporary biostasis is the preservation of the brain, which is broadly considered the seat of memories, personality, and identity. By preserving the information contained within the brain’s structures, it may be possible to resuscitate a healthy whole individual using advanced future technologies. There are numerous challenges in biostasis, including inadequacies in current preservation techniques, methods to evaluate the quality of preservation, and potential future revival technologies. In this report, we describe a roadmap that attempts to delineate research directions that could improve the field of biostasis, focusing on optimizing preservation protocols and establishing metrics for querying preservation quality, as well as pre- and post-cardiac arrest factors, stabilization strategies, and methods for long-term preservation. We acknowledge the highly theoretical nature of future revival technologies and the importance of achieving high-fidelity brain preservation to maximize the potential of future repair technologies. We plan to update the research roadmap biennially. Our goal is to encourage multidisciplinary communication and collaboration in this field.
- in Science on 2024-09-20 07:00:00 UTC.
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in Brain Sciences on 2024-09-21 00:00:00 UTC.
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- Science, Volume 385, Issue 6715, September 2024.
+ Brain Sciences, Vol. 14, Pages 941: Effectiveness of Two Models of Telerehabilitation in Improving Recovery from Subacute Upper Limb Disability after Stroke: Robotic vs. Non-Robotic
+ Brain Sciences doi: 10.3390/brainsci14090941
+ Authors:
+ Arianna Pavan
+ Alessio Fasano
+ Stefania Lattanzi
+ Laura Cortellini
+ Valeria Cipollini
+ Sabina Insalaco
+ Maria Cristina Mauro
+ Marco Germanotta
+ Irene Giovanna Aprile
+
+ Background/Objectives: Finding innovative digital solutions is fundamental to ensure prompt and continuous care for patients with chronic neurological disorders, whose demand for rehabilitation also in home-based settings is steadily increasing. The aim is to verify the safety and the effectiveness of two telerehabilitation (TR) models in improving recovery from subacute upper limb (UL) disability after stroke, with and without a robotic device. Methods: One hundred nineteen subjects with subacute post-stroke UL disability were assessed for eligibility. Of them, 30 patients were enrolled in the study and randomly assigned to either the Robotic Group (RG), undergoing a 20-session TR program, using a robotic device, or the Non-Robotic Group (NRG), undergoing a 20-session TR program without robotics. Clinical evaluations were measured at baseline (T0) and post-intervention (T1, 5 weeks after baseline), and included assessments of quality of life, motor skills, and clinical/functional status. The primary outcome measure was the World Health Organization Disability Assessment Schedule 2.0, evaluating the change in perceived disability. Results: Statistical analysis shows that patients of both groups improved significantly over time in all domains analyzed (mean decrease from baseline in the WHODAS 2.0 of 6.09 ± 2.62% for the NRG, and of 0.76 ± 2.21% for the RG), with a greater improvement of patients in the NRG in motor (Fugl-Meyer Assessment Upper Extremity—motor function, Box and Block Test) and cognitive skills (Trail Making Test-A). Conclusions: This study highlights the potential of TR programs to transform stroke rehabilitation by enhancing accessibility and patient-centered care, promoting autonomy, improving adherence, and leading to better outcomes and quality of life for stroke survivors.
- in Science on 2024-09-20 07:00:00 UTC.
+
in Brain Sciences on 2024-09-21 00:00:00 UTC.
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- arXiv:2409.12593v1 Announce Type: new
-Abstract: Educational multimedia has become increasingly important in modern learning environments because of its cost-effectiveness and ability to overcome the temporal and spatial limitations of traditional methods. However, the complex cognitive processes involved in multimedia learning pose challenges in understanding its neural mechanisms. This study employs network neuroscience to investigate how multimedia design principles influence the underlying neural mechanisms by examining interactions among various brain regions. Two distinct multimedia programs were constructed using identical auditory content but differing visual designs: one adhered to five guidelines for optimizing multimedia instruction, referred to as principal multimedia, while the other intentionally violated these guidelines, referred to as non-principal multimedia. Cortical functional brain networks were then extracted from EEG data to evaluate local and global information processing across the two conditions. Network measurements revealed that principal networks exhibited more efficient local information processing, whereas non-principal networks demonstrated enhanced global information processing and hub formation. Network modularity analysis also indicated two distinct modular organizations, with modules in non-principal networks displaying higher integration and lower segregation than those in principal networks, aligning with initial findings. These observations suggest that the brain may employ compensatory mechanisms to enhance learning and manage cognitive load despite less effective instructional designs.
+ Some visual neurons in the dragonfly (Hemicordulia tau) optic lobe respond to small, moving targets, likely underlying their fast pursuit of prey and conspecifics. In response to repetitive targets presented at short intervals, the spiking activity of these "small target motion detector" (STMD) neurons diminishes over time. Previous experiments limited this adaptation by including intertrial rest periods of varying durations. However, the characteristics of this effect have never been quantified. Here, using extracellular recording techniques lasting for several hours, we quantified both the spatial and temporal properties of STMD adaptation. We found that the time course of adaptation was variable across STMD units. In any one STMD, a repeated series led to more rapid adaptation, a minor accumulative effect more akin to habituation. Following an adapting stimulus, responses recovered quickly, though the rate of recovery decreased nonlinearly over time. We found that the region of adaptation is highly localized, with targets displaced by ~2.5° eliciting a naive response. Higher frequencies of target stimulation converged to lower levels of sustained response activity. We determined that adaptation itself is a target-tuned property, not elicited by moving bars or luminance flicker. As STMD adaptation is a localized phenomenon, dependent on recent history, it is likely to play an important role in closed-loop behavior where a target is foveated in a localized region for extended periods of the pursuit duration.
- in arXiv: Quantitative Biology: Neurons and Cognition on 2024-09-20 04:00:00 UTC.
+
in eNeuro on 2024-09-20 16:30:24 UTC.
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- arXiv:2409.12562v1 Announce Type: cross
-Abstract: Selective attention enables humans to efficiently process visual stimuli by enhancing important locations or objects and filtering out irrelevant information. Locating visual attention is a fundamental problem in neuroscience with potential applications in brain-computer interfaces. Conventional paradigms often use synthetic stimuli or static images, but visual stimuli in real life contain smooth and highly irregular dynamics. In this study, we show that these irregular dynamics in natural videos can be decoded from electroencephalography (EEG) signals to perform selective visual attention decoding. To this end, we propose an experimental paradigm in which participants attend to one of two superimposed videos, each showing a center-aligned person performing a stage act. We then train a stimulus-informed decoder to extract EEG signal components that are correlated with the motion patterns of the attended object, and show that this decoder can be used on unseen data to detect which of both objects is attended. Eye movements are also found to be correlated to the motion patterns in the attended video, despite the spatial overlap between the target and the distractor. We further show that these eye movements do not dominantly drive the EEG-based decoding and that complementary information exists in EEG and gaze data. Moreover, our results indicate that EEG also captures information about unattended objects. To our knowledge, this study is the first to explore EEG-based selective visual attention decoding on natural videos, opening new possibilities for experiment design in related fields.
+ Chemotherapy-related cognitive impairments (CRCIs) encompass cognitive deficits in memory, attention, and executive function that arise during and following chemotherapy. CRCI symptoms are predominantly reported by female cancer patients but also occur in males. These impairments may involve reduced estradiol levels, which then increases vulnerability to the impact of tumors and chemotherapy on cognition. This study utilized the MMTV-PyVT mouse model of breast cancer to test the hypothesis that impaired ovarian function and associated estradiol levels play a critical role in CRCI susceptibility. Mice were either ovariectomized (OVX) or underwent sham surgery. The OVX group then received supplemental estradiol (E2) ad libitum in the drinking water to maintain physiological hormone levels. After tumor development, mice were trained in the Morris water maze to assess spatial memory, and subsequently, they received weekly injections of either saline or a combination of cyclophosphamide (CYP; 66.7 mg/kg, i.v.) and doxorubicin (DOX; 6.7 mg/kg, i.v.) for 4 weeks. Spatial memory was reassessed 10 d and then 35 d, after the final injections. Results demonstrated a significant disruption of normal ovarian cycling in sham-operated mice treated with CYP + DOX, as well as significant spatial memory impairments when compared with OVX mice supplemented with E2. This study suggests that chemotherapy-induced ovarian damage and the consequent drop in circulating estrogens significantly contribute to vulnerability to CRCIs, underscoring the importance of estradiol in mitigating CRCI risks.
- in arXiv: Quantitative Biology: Neurons and Cognition on 2024-09-20 04:00:00 UTC.
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in eNeuro on 2024-09-20 16:30:24 UTC.
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- arXiv:2308.06578v5 Announce Type: replace
-Abstract: Just like electrical engineers understand how microprocessors execute programs in terms of how transistor currents are affected by their inputs, neuroscientists want to understand behavior production in terms of how neuronal outputs are affected by their inputs and internal states. This dependency of neuronal outputs on inputs can be described by a state-dependent input-output (IO)-function. However, to reliably identify these IO-functions, we need to perturb each input and combinations of inputs while observing all the outputs. Here, we argue that such completeness is possible in C. elegans; a complete description that goes all the way from the activity of every neuron to predict behavior. The established and growing toolkit of optophysiology can non-invasively capture and control every neuron's activity and scale to countless experiments. The information from many such experiments can be pooled while capturing the inter-individual variability because neuronal identity and function are largely conserved across individuals. Just like electrical engineers use transistor IO-functions to simulate program execution, we argue that neuronal IO-functions could be used to simulate the impressive breadth of brain states and behaviors of C. elegans.
+ Learning to solve a new problem involves identifying the operating rules, which can be accelerated if known rules generalize in the new context. We ask how prior experience affects learning a new rule that is distinct from known rules. We examined how rats learned a new spatial navigation task after having previously learned tasks with different navigation rules. The new task differed from the previous tasks in spatial layout and navigation rule. We found that experience history did not impact overall performance. However, by examining navigation choice sequences in the new task, we found experience-dependent differences in exploration patterns during early stages of learning, as well as differences in the types of errors made during stable performance. The differences were consistent with the animals adopting experience-dependent memory strategies to discover and implement the new rule. Our results indicate prior experience shapes the strategies for solving novel problems, and the impact of prior experience remains persistent.
- in arXiv: Quantitative Biology: Neurons and Cognition on 2024-09-20 04:00:00 UTC.
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in eNeuro on 2024-09-20 16:30:24 UTC.
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- arXiv:2403.19001v3 Announce Type: replace-cross
-Abstract: Shape plays an important role in computer graphics, offering informative features to convey an object's morphology and functionality. Shape analysis in brain imaging can help interpret structural and functionality correlations of the human brain. In this work, we investigate the shape of the brain's 3D white matter connections and its potential predictive relationship to human cognitive function. We reconstruct brain connections as sequences of 3D points using diffusion magnetic resonance imaging (dMRI) tractography. To describe each connection, we extract 12 shape descriptors in addition to traditional dMRI connectivity and tissue microstructure features. We introduce a novel framework, Shape--fused Fiber Cluster Transformer (SFFormer), that leverages a multi-head cross-attention feature fusion module to predict subject-specific language performance based on dMRI tractography. We assess the performance of the method on a large dataset including 1065 healthy young adults. The results demonstrate that both the transformer-based SFFormer model and its inter/intra feature fusion with shape, microstructure, and connectivity are informative, and together, they improve the prediction of subject-specific language performance scores. Overall, our results indicate that the shape of the brain's connections is predictive of human language function.
+ Previous physiological and psychophysical studies have explored whether feedback to the cochlea from the efferent system influences forward masking. The present work proposes that the limited growth-of-masking (GOM) observed in auditory nerve (AN) fibers may have been misunderstood; namely, that this limitation may be due to the influence of anesthesia on the efferent system. Building on the premise that the unanesthetized AN may exhibit GOM similar to more central nuclei, the present computational modeling study demonstrates that feedback from the medial olivocochlear (MOC) efferents may contribute to GOM observed physiologically in onset-type neurons in both the cochlear nucleus and inferior colliculus (IC). Additionally, the computational model of MOC efferents used here generates a decrease in masking with longer masker-signal delays similar to that observed in IC physiology and in psychophysical studies. An advantage of this explanation over alternative physiological explanations (e.g., that forward masking requires inhibition from the superior paraolivary nucleus) is that this theory can explain forward masking observed in the brainstem, early in the ascending pathway. For explaining psychoacoustic results, one strength of this model is that it can account for the lack of elevation in thresholds observed when masker level is randomly varied from interval-to-interval, a result that is difficult to explain using the conventional temporal window model of psychophysical forward masking. Future directions for evaluating the efferent mechanism as a contributing mechanism for psychoacoustic results are discussed.
- in arXiv: Quantitative Biology: Neurons and Cognition on 2024-09-20 04:00:00 UTC.
+
in eNeuro on 2024-09-20 16:30:24 UTC.
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- arXiv:2404.08647v2 Announce Type: replace-cross
-Abstract: In pursuit of neuromorphic (brain-inspired) devices, memristors (memory-resistors) have emerged as effective components for emulating neuronal circuitry. Here we formally define a class of Simple Volatile Memristors (SVMs) based on a simple conductance equation of motion from which we build a simple mathematical theory on the dynamics of isolated SVMs and SVM-based spiking circuits. Notably, SVMs include various fluidic iontronic devices that have recently garnered significant interest due to their unique quality of operating within the same medium as the brain. Specifically we show that symmetric SVMs produce non self-crossing current-voltage hysteresis loops, while asymmetric SVMs produce self-crossing loops. Additionally, we derive a general expression for the enclosed area in a loop, providing a relation between the voltage frequency and the SVM memory timescale. These general results are shown to materialise in physical finite-element calculations of microfluidic memristors. An SVM-based circuit has been proposed that exhibits all-or-none and tonic neuronal spiking. We generalise and analyse this spiking circuit, characterising it as a two-dimensional dynamical system. Moreover, we demonstrate that stochastic effects can induce novel neuronal firing modes absent in the deterministic case. Through our analysis, the circuit dynamics are well understood, while retaining its explicit link with the physically plausible underlying system.
+ Background The process of preparing a scientific manuscript is intricate, encompassing several critical stages, including pre-writing, research development, drafting, peer review, editing, publication, dissemination, and access. Among these, the peer review process (PRP) stands out as a pivotal component requiring seamless collaboration among editors, reviewers, and authors. Reviewers play a crucial role in assessing the manuscript’s quality and providing constructive feedback, which authors must adeptly navigate to enhance their work and meet journal standards. This process can often appear daunting and time-consuming, as authors are required to address numerous comments and requested changes. Authors are encouraged to perceive reviewers as consultants rather than adversaries, viewing their critiques as opportunities for improvement rather than personal attacks. Methods Opinion article. Aim To equip authors with practical strategies for engaging effectively in the PRP and improving their publication acceptance rates. Results Key guidelines include thoroughly understanding and prioritizing feedback, maintaining professionalism, and systematically addressing each comment. In cases of significant disagreement or misunderstanding, authors have the option to refer the issue to the editor. Crafting a well-organized and scientific “response to reviews” along with the revised manuscript can substantially increase the likelihood of acceptance. Best practices for writing an effective response to reviews include expressing gratitude, addressing major revisions first, seeking opinions from co-authors and colleagues, and adhering strictly to journal guidelines. Emphasizing the importance of planning responses, highlighting changes in the revised manuscript, and conducting a final review ensures all corrections are properly documented. Conclusion By following these guidelines, authors can enhance their manuscripts’ quality, foster positive relationships with reviewers, and ultimately contribute to scholarly advancement.
- in arXiv: Quantitative Biology: Neurons and Cognition on 2024-09-20 04:00:00 UTC.
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in F1000Research on 2024-09-20 15:17:42 UTC.
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- arXiv:2409.12846v1 Announce Type: cross
-Abstract: The tensor brain has been introduced as a computational model for perception and memory. We provide an overview of the tensor brain model, including recent developments. The tensor brain has two major layers: the representation layer and the index layer. The representation layer is a model for the subsymbolic global workspace from consciousness research. The state of the representation layer is the cognitive brain state. The index layer contains symbols for concepts, time instances, and predicates. In a bottom-up operation, the cognitive brain state is encoded by the index layer as symbolic labels. In a top-down operation, symbols are decoded and written to the representation layer. This feeds to earlier processing layers as embodiment. The top-down operation became the basis for semantic memory. The embedding vector of a concept forms the connection weights between its index and the representation layer. The embedding is the signature or ``DNA'' of a concept, which is decoded by the brain when its index is activated. It integrates all that is known about a concept from different experiences, modalities, and symbolic decodings. Although being computational, it has been suggested that the tensor brain might be related to the actual operation of the brain. The sequential nature of symbol generation might have been a prerequisite to the generation of natural language. We describe an attention mechanism and discuss multitasking by multiplexing. We emphasize the inherent multimodality of the tensor brain. Finally, we discuss embedded and symbolic reasoning.
+ by Rekha Gopalan-Nair, Aurore Coissac, Ludovic Legrand, Céline Lopez-Roques, Yann Pécrix, Céline Vandecasteele, Olivier Bouchez, Xavier Barlet, Anne Lanois, Alain Givaudan, Julien Brillard, Stéphane Genin, Alice Guidot
+
+Adaptation is usually explained by beneficial genetic mutations that are transmitted from parents to offspring and become fixed in the adapted population. However, genetic mutation analysis alone is not sufficient to fully explain the adaptive processes, and several studies report the existence of nongenetic (or epigenetic) inheritance that can enable adaptation to new environments. In the present work, we tested the hypothesis of the role of DNA methylation, a form of epigenetic modification, in adaptation of the plant pathogen Ralstonia pseudosolanacearum to the host during experimental evolution. Using SMRT-seq technology, we analyzed the methylomes of 31 experimentally evolved clones obtained after serial passages on 5 different plant species during 300 generations. Comparison with the methylome of the ancestral clone revealed a list of 50 differential methylated sites (DMSs) at the GTWWAC motif. Gene expression analysis of the 39 genes targeted by these DMSs revealed limited correlation between differential methylation and differential expression of the corresponding genes. Only 1 gene showed a correlation, the RSp0338 gene encoding the EpsR regulator protein. The MSRE-qPCR technology, used as an alternative approach for DNA methylation analysis, also found the 2 DMSs upstream RSp0338. Using site-directed mutagenesis, we demonstrated the contribution of these 2 DMSs in host adaptation. As these DMSs appeared very early in the experimental evolution, we hypothesize that such fast epigenetic changes can allow rapid adaptation to the plant stem environment. In addition, we found that the change in DNA methylation upstream RSp0338 remains stable at least for 100 generations outside the host and thus can contribute to long-term adaptation to the host plant. To our knowledge, this is the first study showing a direct link between bacterial epigenetic variation and adaptation to a new environment.
- in arXiv: Computer Science: Neural and Evolutionary Computing on 2024-09-20 04:00:00 UTC.
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in PLoS Biology on 2024-09-20 14:00:00 UTC.
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- arXiv:2409.12567v1 Announce Type: new
-Abstract: Neuronal damage, in the form of both brain and spinal cord injuries, is one of the major causes of disability and death in young adults worldwide. One way to assess the direct damage occurring after a mechanical insult is the simulation of the neuronal cells functional deficits following the mechanical event. In this study, we use a coupled mechanical electrophysiological model with several free parameters that are required to be calibrated against experimental results. The calibration is carried out by means of an evolutionary algorithm (differential evolution, DE) that needs to evaluate each configuration of parameters on six different damage cases, each of them taking several minutes to compute. To minimise the simulation time of the parameter tuning for the DE, the stretch of one unique fixed-diameter axon with a simplified triggering process is used to speed up the calculations. The model is then leveraged for the parameter optimization of the more realistic bundle of independent axons, an impractical configuration to run on a single processor computer. To this end, we have developed a parallel implementation based on OpenMP that runs on a multi-processor taking advantage of all the available computational power. The parallel DE algorithm obtains good results, outperforming the best effort achieved by published manual calibration, in a fraction of the time. While not being able to fully capture the experimental results, the resulting nerve model provides a complex averaging framework for nerve damage simulation able to simulate gradual axonal functional alteration in a bundle.
+ Background The interaction between Streptococcus mutans (S. mutans) and Veillonella species (Veillonella spp.) is unclear. This study aims to investigate the interaction between S. mutans and Veillonella spp. on caries development using systematic review. Methods This systematic review was accorded to the guideline of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Three electronic databases, namely PubMed, Embase, and the Cochrane library, were used to conduct a systematic search for eligible studies from their inception until July 18, 2023. PROSPERO registration number was No. CRD42023445968. Results We initially identified 4,774 articles. After eliminating duplicates and irrelevant articles, 11 studies met the inclusion criteria. The studies revealed important aspects of the relationship between S. mutans and Veillonellae spp. in dental caries. One significant finding is that Veillonellae spp. can affect the acid production capacity of S. mutans. Some studies indicate that Veillonellae spp. can inhibit the acid production by S. mutans, potentially reducing the cariogenic process. Another aspect is the competition for substrates. Veillonellae spp. utilize lactic acid, which is a by product of S. mutans metabolism, as a source of carbon. This metabolic interaction may decrease the availability of lactic acid for S. mutans, potentially influencing its cariogenic potential. Conclusions This systematic review highlights the emerging evidence on the interaction between S. mutans and Veillonellae spp. in dental caries. The findings suggest that Veillonellae spp. can modulate the acid production, and substrate competition of S. mutans, potentially influencing the cariogenic process.
- in arXiv: Computer Science: Neural and Evolutionary Computing on 2024-09-20 04:00:00 UTC.
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in F1000Research on 2024-09-20 13:52:57 UTC.
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- arXiv:2409.12335v1 Announce Type: cross
-Abstract: The foundations of deep learning are supported by the seemingly opposing perspectives of approximation or learning theory. The former advocates for large/expressive models that need not generalize, while the latter considers classes that generalize but may be too small/constrained to be universal approximators. Motivated by real-world deep learning implementations that are both expressive and statistically reliable, we ask: "Is there a class of neural networks that is both large enough to be universal but structured enough to generalize?"
- This paper constructively provides a positive answer to this question by identifying a highly structured class of ReLU multilayer perceptions (MLPs), which are optimal function approximators and are statistically well-behaved. We show that any $L$-Lipschitz function from $[0,1]^d$ to $[-n,n]$ can be approximated to a uniform $Ld/(2n)$ error on $[0,1]^d$ with a sparsely connected $L$-Lipschitz ReLU MLP of width $\mathcal{O}(dn^d)$, depth $\mathcal{O}(\log(d))$, with $\mathcal{O}(dn^d)$ nonzero parameters, and whose weights and biases take values in $\{0,\pm 1/2\}$ except in the first and last layers which instead have magnitude at-most $n$. Unlike previously known "large" classes of universal ReLU MLPs, the empirical Rademacher complexity of our class remains bounded even when its depth and width become arbitrarily large. Further, our class of MLPs achieves a near-optimal sample complexity of $\mathcal{O}(\log(N)/\sqrt{N})$ when given $N$ i.i.d. normalized sub-Gaussian training samples.
- We achieve this by avoiding the standard approach to constructing optimal ReLU approximators, which sacrifices regularity by relying on small spikes. Instead, we introduce a new construction that perfectly fits together linear pieces using Kuhn triangulations and avoids these small spikes.
+ Background Kimono is being reevaluated for its sustainability aspects, such as having fewer offcuts in the production process due to its structural differences from Western-style clothes and its high reusability due to the adaptability to individuals’ body shapes. On the other hand, once a common attire for daily wear in Japan, kimono has transitioned to being worn only on special events and the kimono-related industry has also shrunk. To stimulate demand for kimono, it is essential to familiarize younger generations with its potential as daily wear. Methods A questionnaire survey on perceptions of kimono was conducted among two groups in Japan: 211 college students and 50 kimono enthusiasts. The questionnaire included demographic questions and psychometric scales, primarily focusing on their kimono experiences, challenges associated with wearing kimono, their perceptions of kimono and Western-style clothes, and their attitudes towards kimono. Results The results revealed that a majority of students had worn kimono before, though they found it difficult to move while wearing it. In contrast, kimono enthusiasts evaluated it as easier to move, hard to become disheveled, and casual. They also rated the ease of wearing Western-style clothes lower compared to students, and this tendency intensified with the length of enthusiast experience. Furthermore, the findings indicated that enthusiasts regarded the kimono more as daily wear compared to students, while still deriving enjoyment from it as formal attire in special events. Conclusions These results suggest that the cognition that Western-style clothes are easy to move and kimono is not may change with experiences. Therefore, providing opportunities for people in Japan to acquire how to wear kimono in comfortable ways possibly impacts their perceptions of kimono.
- in arXiv: Computer Science: Neural and Evolutionary Computing on 2024-09-20 04:00:00 UTC.
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in F1000Research on 2024-09-20 13:41:22 UTC.
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- arXiv:2409.12632v1 Announce Type: cross
-Abstract: Clustering algorithms rely on complex optimisation processes that may be difficult to comprehend, especially for individuals who lack technical expertise. While many explainable artificial intelligence techniques exist for supervised machine learning, unsupervised learning -- and clustering in particular -- has been largely neglected. To complicate matters further, the notion of a ``true'' cluster is inherently challenging to define. These facets of unsupervised learning and its explainability make it difficult to foster trust in such methods and curtail their adoption. To address these challenges, we propose a new, model-agnostic technique for explaining clustering algorithms with counterfactual statements. Our approach relies on a novel soft-scoring method that captures the spatial information utilised by clustering models. It builds upon a state-of-the-art Bayesian counterfactual generator for supervised learning to deliver high-quality explanations. We evaluate its performance on five datasets and two clustering algorithms, and demonstrate that introducing soft scores to guide counterfactual search significantly improves the results.
+ Background Active venous leg ulcer (VLU) is the most severe manifestation of chronic venous disease which not only affects patients’ health, but also decreases the quality of life, and delivers economic burdens. Treatment of superficial venous reflux with early endovenous laser ablation (EVLA) has been associated with reducing ulcer recurrence levels and promoting faster VLU healing. We reported three cases of patients with active VLU undergoing EVLA with different approaches. Case illustration Three patients came with complaint of leg ulcer, diagnosed with C6sEpAsdPr, with venous clinical severity scores (VCSS) of 15, 23, and 22 respectively. Severe great saphenous veins (GSV) reflux was found in all patients by duplex ultrasound examination. The second patient had undergone above-the-knee EVLA. All patients underwent EVLA using 1470-nano meter wavelength laser device and ELVeS radial fiber (Biolitec, Bonn, Germany). The laser energy protocol used was 6 W linear endovenous energy density (LEED) 50 J/cm for proximal until media ATK GSV ablation, 5 W LEED 40 J/cm for media ATK until proximal below-the-knee (BTK) GSV, and 2 W LEED 20 J/cm for proximal until distal BTK GSV. The third patient was also treated with EVLA for small saphenous vein severe reflux. Follow-up until 6 months post-EVLA showed significant healing of the ulcer with 14, 16, and 17 VCSS reduction consecutively without any complication. Conclusion We’ve reported three cases of patients with active VLU undergoing EVLA until BTK with significant results. The EVLA of GSV until BTK where there is still significant reflux is safe and provides satisfactory results in patients with VLU.
- in arXiv: Computer Science: Neural and Evolutionary Computing on 2024-09-20 04:00:00 UTC.
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in F1000Research on 2024-09-20 13:01:54 UTC.
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- arXiv:2409.12769v1 Announce Type: cross
-Abstract: Spiking Neural Networks (SNNs) have recently gained significant interest in on-chip learning in embedded devices and emerged as an energy-efficient alternative to conventional Artificial Neural Networks (ANNs). However, to extend SNNs to a Federated Learning (FL) setting involving collaborative model training, the communication between the local devices and the remote server remains the bottleneck, which is often restricted and costly. In this paper, we first explore the inherent robustness of SNNs under noisy communication in FL. Building upon this foundation, we propose a novel Federated Learning with Top-K Sparsification (FLTS) algorithm to reduce the bandwidth usage for FL training. We discover that the proposed scheme with SNNs allows more bandwidth savings compared to ANNs without impacting the model's accuracy. Additionally, the number of parameters to be communicated can be reduced to as low as 6 percent of the size of the original model. We further improve the communication efficiency by enabling dynamic parameter compression during model training. Extensive experiment results demonstrate that our proposed algorithms significantly outperform the baselines in terms of communication cost and model accuracy and are promising for practical network-efficient FL with SNNs.
+ Understanding the nature of life and its propensity for reproduction has long been a question that humans aspire to answer. Reproduction, a defining characteristic of life, fundamentally involves the replication of genetic material, be it DNA or RNA. The driving force behind this replication process has always intrigued scientists. In recent years, theories involving selfish genes, the RNA world, and entropic forces have been proposed by some scholars. These theories seem to suggest that life, as we know it, exists solely in Earth’s environment and is based on a single type of genetic material, either DNA or RNA. However, if we broaden our definition of life to include any replicable molecules, we might be able to transcend traditional thought. This could potentially enhance our understanding of the impetus behind DNA replication and provide deeper insights into the essence of life.
- in arXiv: Computer Science: Neural and Evolutionary Computing on 2024-09-20 04:00:00 UTC.
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in F1000Research on 2024-09-20 12:54:33 UTC.
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- arXiv:2409.12913v1 Announce Type: cross
-Abstract: We study feedforward neural networks with inputs from a topological vector space (TVS-FNNs). Unlike traditional feedforward neural networks, TVS-FNNs can process a broader range of inputs, including sequences, matrices, functions and more. We prove a universal approximation theorem for TVS-FNNs, which demonstrates their capacity to approximate any continuous function defined on this expanded input space.
+ Author(s): Xiaowen Chen and William Bialek
Animal behavior occurs on timescales much longer than the response times of individual neurons. In many cases, it is plausible that these long timescales emerge from the recurrent dynamics of electrical activity in networks of neurons. In linear models, timescales are set by the eigenvalues of a dyn…
[Phys. Rev. E 110, 034407] Published Fri Sep 20, 2024
- in arXiv: Computer Science: Neural and Evolutionary Computing on 2024-09-20 04:00:00 UTC.
+
in Physical Review E: Biological physics on 2024-09-20 10:00:00 UTC.
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- arXiv:2304.12751v5 Announce Type: replace-cross
-Abstract: Network alignment (NA) is the task of discovering node correspondences across multiple networks. Although NA methods have achieved remarkable success in a myriad of scenarios, their effectiveness is not without additional information such as prior anchor links and/or node features, which may not always be available due to privacy concerns or access restrictions. To tackle this challenge, we propose Grad-Align+, a novel NA method built upon a recent state-of-the-art NA method, the so-called Grad-Align, that gradually discovers a part of node pairs until all node pairs are found. In designing Grad-Align+, we account for how to augment node features in the sense of performing the NA task and how to design our NA method by maximally exploiting the augmented node features. To achieve this goal, Grad-Align+ consists of three key components: 1) centrality-based node feature augmentation (CNFA), 2) graph neural network (GNN)-aided embedding similarity calculation alongside the augmented node features, and 3) gradual NA with similarity calculation using aligned cross-network neighbor-pairs (ACNs). Through comprehensive experiments, we demonstrate that Grad-Align+ exhibits (a) the superiority over benchmark NA methods, (b) empirical validations as well as our theoretical findings to see the effectiveness of CNFA, (c) the influence of each component, (d) the robustness to network noises, and (e) the computational efficiency.
+ Background Better affordability of data plans and an increase in “budget” smartphones have resulted in an exponential rise in internet and smartphone users. The ease of access to sexually explicit material (SEM) coupled with adolescents’ impulsivity makes them prone to excessive SEM exposure and may affect the development of sexuality via the perceived realism of such content. This study was done to study the influence between problematic smartphone usage (PSU) and sexuality development among late adolescent boys. Methods One hundred and thirty-four adolescents aged 18-19 years, studying in a medical university, participated in this cross-sectional study. Smartphone Addiction Scale – short version (SAS-SV) to evaluate PSU and a content validated semi-structured proforma to evaluate gender identity, sexual orientation, sources of information on pubertal changes, and exposure to pornographic content was used. We expressed results as proportion and summary measures (Mean±SD), Chi-square test to find influence between PSU and adolescent sexuality development. Results We found a 45.5% prevalence of PSU. Among study participants, 88% were attracted to the opposite sex, 6% were attracted to the same-sex, and 6% were attracted to both sexes. Three per cent of participants liked wearing clothes of the opposite sex, 7.5% wanted to be members of the opposite sex, whereas 10.4% were not comfortable with their genitalia. They obtained information regarding pubertal changes from friends (85) and media (78). Many had exposure to pornographic content (90%), with the youngest being nine years old. Conclusion Nearly half of the late adolescents have PSU. Pornographic contents are accessed through Smartphones.
- in arXiv: Computer Science: Neural and Evolutionary Computing on 2024-09-20 04:00:00 UTC.
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in F1000Research on 2024-09-20 09:10:56 UTC.
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- arXiv:2407.00449v2 Announce Type: replace-cross
-Abstract: Fully tensorial theory of hypercomplex neural networks is given. It allows neural networks to use arithmetic based on arbitrary algebras. The key point is to observe that algebra multiplication can be represented as a rank three tensor and use this tensor in every algebraic operation. This approach is attractive for neural network libraries that support effective tensorial operations. It agrees with previous implementations for four-dimensional algebras.
+ Science, Volume 385, Issue 6715, September 2024.
- in arXiv: Computer Science: Neural and Evolutionary Computing on 2024-09-20 04:00:00 UTC.
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in Science on 2024-09-20 07:00:00 UTC.
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- arXiv:2409.10739v2 Announce Type: replace-cross
-Abstract: Our research combines an Evolutionary Algorithm (EA) with a Quantum Approximate Optimization Algorithm (QAOA) to update the ansatz parameters, in place of traditional gradient-based methods, and benchmark on the Max-Cut problem. We demonstrate that our Evolutionary-QAOA (E-QAOA) pairing performs on par or better than a COBYLA-based QAOA in terms of solution accuracy and variance, for $d$-3 regular graphs between 4 and 26 nodes, using both $max\_count$ and Conditional Value at Risk (CVaR) for fitness function evaluations. Furthermore, we take our algorithm one step further and present a novel approach by presenting a multi-population EA distributed on two QPUs, which evolves independent and isolated populations in parallel, classically communicating elite individuals. Experiments were conducted on both simulators and IBM quantum hardware, and we investigated the relative performance accuracy and variance.
+ Science, Volume 385, Issue 6715, September 2024.
- in arXiv: Computer Science: Neural and Evolutionary Computing on 2024-09-20 04:00:00 UTC.
+
in Science on 2024-09-20 07:00:00 UTC.
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- arXiv:2409.11430v2 Announce Type: replace-cross
-Abstract: The widespread deployment of products powered by machine learning models is raising concerns around data privacy and information security worldwide. To address this issue, Federated Learning was first proposed as a privacy-preserving alternative to conventional methods that allow multiple learning clients to share model knowledge without disclosing private data. A complementary approach known as Fully Homomorphic Encryption (FHE) is a quantum-safe cryptographic system that enables operations to be performed on encrypted weights. However, implementing mechanisms such as these in practice often comes with significant computational overhead and can expose potential security threats. Novel computing paradigms, such as analog, quantum, and specialized digital hardware, present opportunities for implementing privacy-preserving machine learning systems while enhancing security and mitigating performance loss. This work instantiates these ideas by applying the FHE scheme to a Federated Learning Neural Network architecture that integrates both classical and quantum layers.
+ Science, Volume 385, Issue 6715, September 2024.
- in arXiv: Computer Science: Neural and Evolutionary Computing on 2024-09-20 04:00:00 UTC.
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in Science on 2024-09-20 07:00:00 UTC.
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- Background The use of chemical pesticides without proper health literacy (HL) and necessary pesticide protective behaviors (PPB) can result in adverse effects on human health. Methods This study aims to determine if there is a correlation between HL and PPB among farmers in the Nakhon Ratchasima province, using a random sample of 464 farmers. Structured interviews consisted of three parts: 1. General information, 2. Health literacy (including knowledge, understanding, and other sub-aspects), and 3. Protective behaviors against chemical exposure. Each part of the questionnaire had a reliability index of 0.60 or higher. The reliability of the 2nd and 3rd parts of the questionnaire were as follows: sub-sections of part 2 had a Kuder-Richardson (KR-20) coefficient of 0.79 and Cronbach’s alpha (α) coefficient of 0.85-0.86, while part 3 had an α of 0.88. Risk of chemical exposure was assessed using a Cholinesterase Reactive Paper test administered by a finger-prick blood test. Data was analyzed using the Spearman correlation and binary logistic regression. The study was reviewed by the Human Research Ethics Committee with the approval date: August 9, 2021, and expiry date: August 9, 2022. Results Most participants had moderate levels of overall HL (48.8%) and PPB (44.6%). There was a statistically significant positive correlation between HL and PPB (rs(478) = 0.70, p<.005). Logistic regression analysis demonstrated that HL had a statistically significant positive association with PPB (p<.001, OR = 6.57, 95% CI 3.95, 10.94) and was associated with blood cholinesterase levels. Conclusions These findings highlight the need for increased health literacy among farmers in Thailand to ensure correct protective behaviors against chemical exposure and reduce the adverse effects of pesticide exposure on human health.
+ Science, Volume 385, Issue 6715, September 2024.
- in F1000Research on 2024-09-19 16:42:51 UTC.
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in Science on 2024-09-20 07:00:00 UTC.
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- Background Organizations recognized the importance of workplace inclusion. However, up to date, few organizations had developed strategic initiatives to improve workplace diversity. This research examines the impact of awareness of inclusion, inclusive leadership, psychosocial capital, and meaningful engagement on employee’s inclusion in the context of Malaysia. Methods The study employed a quantitative survey approach and collected data through a questionnaire survey administered to 204 participants. Descriptive analysis, reliability analysis and multiple linear regression analysis were utilized to explore the relationships between the independent and dependent variables. Results The findings indicate a significant correlation between awareness of inclusion and psychosocial capital with employee’s inclusion. However, no significant correlations were found between inclusive leadership and meaningful engagement with employee’s inclusion. These results underscore the importance of fostering an inclusive culture and nurturing psychosocial support to enhance employee’s inclusion experiences in the workplace. Conclusion This study contributes to the knowledge by being one of the pioneer research in Malaysia that provides insights into the factors influencing employee’s inclusion in Malaysia. The findings is important for organizations, particularly small and medium enterprise in Malaysia to promote employee inclusion in a multi-racial diversity society.
+ Science Advances, Volume 10, Issue 38, September 2024.
- in F1000Research on 2024-09-19 16:25:26 UTC.
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in Science Advances on 2024-09-20 07:00:00 UTC.
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- Shade selection is one of the most important factors that determines the satisfaction of the patient with the dental prosthesis and thus the overall success of the treatment. Conventional methods of shade selection require the presence of existing teeth or past dental/photographic records. In the absence of these, shade selection becomes challenging and must be done subjectively and arbitrarily based on the patient’s age and sex. This study aims to assess the prevalence, satisfaction, and preference of tooth shades, investigating their correlation with age, sex, and skin shade in a diverse sample of 120 participants. Methods A total of 120 participants, evenly distributed among 60 males and 60 females, were surveyed. Participants were categorized into age groups (n=15) and asked about their satisfaction with existing tooth shades and their preferences. Results The most common existing tooth shade was Value 2 (52.5%). Statistical analysis using Chi-square tests revealed that Value 2 was the most desired shade among males and females alike, particularly in the age group of 41 to 50 years (p < 0.001). Shade 2L1.5 was the most prevalent (n=26), with Value 2 (59.16%) being the most sought-after shade, followed by Shade 2L1.5 (n=21), Shade 2M1 (n=18), Shade 1M1 (n=15), and Shade 2R1.5 (n=14). Existing tooth shades of Value 0 were the least common. The highest satisfaction with existing shades was observed in males aged 41 to 50 (n=15), followed by males aged 51 to 60 (n=14) and females aged 31 to 40 (n=12) and 41 to 50 (n=12). Significant differences in satisfaction were noted among males (p < 0.001). Conclusions This study reveals a consistent and strong preference among both males and females for tooth shades classified as Value 2, following the VITA Tooth-Guide 3D Master shade guide. This universal preference suggests the relevance and acceptance of this shade category across diverse patient groups.
+ Science Advances, Volume 10, Issue 38, September 2024.
- in F1000Research on 2024-09-19 16:22:41 UTC.
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in Science Advances on 2024-09-20 07:00:00 UTC.
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- Background Glioblastoma (GBM) is a clinically challenging primary brain tumor with poor survival outcome despite surgical resection and intensive chemoradiation. The metabolic heterogeneity of GBM can become biomarkers for treatment response, resistance, and outcome prediction. The aim of the study is to investigate metabolic distinctions between primary and recurrent GBM tissue and patient plasma to establish feasibility for metabolic profiling. Methods A single-center cohort study analyzed tissue and blood samples from 15 patients with GBM using untargeted metabolomic/lipidomic assays. Metabolomic, lipidomic, and biogenic amine analyses were conducted on GBM tissue and patient plasma at diagnosis and recurrence using untargeted mass spectrometry. The study utilized a small but longitudinally collected cohort to evaluate alteration in metabolites, lipids, and biogenic amines between specimens at diagnosis and recurrence. Results Exploratory analysis revealed significant alteration in metabolites, lipids, and biogenic amines between diagnostic and recurrent states in both tumor and plasma specimens. Notable metabolites differed at recurrence, including N-alpha-methylhistamine, glycerol-3-phosphate, phosphocholine, and succinic acid in tissue, and indole-3-acetate, and urea in plasma. Principal component analysis revealed distinct metabolomic profiles between tumor tissue and patient plasma. Distinct metabolic profiles were observed in GBM tissue and patient plasma at recurrence, demonstrating the feasibility of using metabolomic methodologies for longitudinal studies. One patient exhibited a unique tumor resistance signature at diagnosis, possibly indicating a high-risk metabolomic phenotype. Conclusions In this small cohort, the findings suggest the potential of metabolomic signatures of GBM tissue and patient plasma for risk stratification, outcome prediction, and the development of novel adjuvant metabolic-targeting therapies. The findings suggest metabolic discrepancies at diagnosis and recurrence in tissue and plasma, highlighting potential implications for evaluation of clinical response. The identification of significant changes in metabolite abundance emphasizes the need for larger studies using targeted metabolomics to validate and further explore these profiles.
+ Science Advances, Volume 10, Issue 38, September 2024.
- in F1000Research on 2024-09-19 16:19:17 UTC.
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in Science Advances on 2024-09-20 07:00:00 UTC.
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- Background Primary cam morphology, an acquired bony prominence at the head-neck junction of the femur, is highly prevalent in athlete populations, and causally associated with femoroacetabular impingement syndrome and early hip osteoarthritis. Experts agreed on key elements for primary cam morphology and a prioritised research agenda for the field. This research agenda will require higher-quality research to achieve meaningful progress on the aetiology, prognosis and treatment of primary cam morphology in athletes. Aim To explore stakeholders’ perspectives of high-quality research in the research field of primary cam morphology and its natural history. Methods Grounded in interpretive description, we used semi-structured interviews to explore stakeholders’ perspectives of high-quality research in the primary cam morphology research field. The framework for INcreasing QUality In patient-orientated academic clinical REsearch (INQUIRE) informed the interview guide. Audio-recorded interviews were transcribed and analysed using thematic analysis. We recruited a heterogenous and purposive maximum variation sample, drawing from a network of research contacts. Results Fifteen individuals, several with multiple perspectives on research quality in the field, participated. Exploring stakeholders’ perspectives on research quality through an established research quality framework (INQUIRE) illuminated areas for immediate action for research communities in the field of primary cam morphology and its natural history. We crafted five action inviting themes: research communities should: partner with athletes/patients; champion equity, diversity and inclusion; collaborate with one another; pursue open science; and nurture young scholars. Conclusion The findings of this study could inform concrete actions by research communities to pursue higher quality research—more research value and less waste—in the field of primary cam morphology and its natural history. Although the five action-inviting themes reflect contemporary trends in research, and could therefore be transferable to other areas of research, their practical application remains context- and field-specific.
+ Science Advances, Volume 10, Issue 38, September 2024.
- in F1000Research on 2024-09-19 15:05:56 UTC.
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in Science Advances on 2024-09-20 07:00:00 UTC.
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- Background Ruptured abdominal aortic aneurysm (rAAA) is commonly fatal, with an overall mortality rate of nearly 90%, and the risk of subsequent rupture remains high, especially in large aneurysm diameters or progressive disease. Unfavorable neck anatomy in EVAR is linked to early graft failure and long-term complications. Recently, a novel multiple stiff wire (MSW) technique has been developed to overcome the challenges of hostile neck anatomy without introducing additional devices and procedural complexity. It has also been feasible in a series of elective cases. In this case, we report the first-ever utilization of the MSW technique in an emergency case of an acute contained rAAA with a conical-shaped, severely angulated neck who underwent Endovascular Aortic Repair (EVAR). Case presentation A 61-year-old man came with intermittent sharp stomach pain radiating to his back since three weeks ago. Physical examination showed elevated blood pressure and anemic conjunctiva. Laboratory examinations showed anemia, leukocytosis, elevated D-dimer level, high creatinine level, and low eGFR. CT-Scan Angiography (CTA) revealed severely hostile anatomy, a conical-shaped abdominal aorta aneurysm with a length of 13.2 cm and a maximum diameter of 9.3 cm with angulation of 90.1°. The patient was diagnosed with Ruptured AAA with a conical-shaped, severely angulated neck. Endovascular Aortic Repair (EVAR) management with MSW technique was planned for him. After four days, The patient was discharged in a clinically stable condition with optimal medical treatment and education. Conclusion The endovascular approach could be performed in emergency settings and has been proven to reduce length of stay, mortality, and morbidity rates. In this case, the endovascular approach with the MSW technique showed promising results for the patient.
+ Science Advances, Volume 10, Issue 38, September 2024.
- in F1000Research on 2024-09-19 14:49:08 UTC.
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in Science Advances on 2024-09-20 07:00:00 UTC.
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- Background Traditional optimization methods often struggle to balance global exploration and local refinement, particularly in complex real-world problems. To address this challenge, we introduce a novel hybrid optimization strategy that integrates the Nelder-Mead (NM) technique and the Genetic Algorithm (GA), named the Genetic and Nelder-Mead Algorithm (GANMA). This hybrid approach aims to enhance performance across various benchmark functions and parameter estimation tasks. Methods GANMA combines the global search capabilities of GA with the local refinement strength of NM. It is first tested on 15 benchmark functions commonly used to evaluate optimization strategies. The effectiveness of GANMA is also demonstrated through its application to parameter estimation problems, showcasing its practical utility in real-world scenarios. Results GANMA outperforms traditional optimization methods in terms of robustness, convergence speed, and solution quality. The hybrid algorithm excels across different function landscapes, including those with high dimensionality and multimodality, which are often encountered in real-world optimization issues. Additionally, GANMA improves model accuracy and interpretability in parameter estimation tasks, enhancing both model fitting and prediction. Conclusions GANMA proves to be a flexible and powerful optimization method suitable for both benchmark optimization and real-world parameter estimation challenges. Its capability to efficiently explore parameter spaces and refine solutions makes it a promising tool for scientific, engineering, and economic applications. GANMA offers a valuable solution for improving model performance and effectively handling complex optimization problems.
+ Science Advances, Volume 10, Issue 38, September 2024.
- in F1000Research on 2024-09-19 14:47:04 UTC.
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in Science Advances on 2024-09-20 07:00:00 UTC.
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- by Diego A. Forero, Walter H. Curioso, Wei Wang
+ Science Advances, Volume 10, Issue 38, September 2024.
- in PLoS Computational Biology on 2024-09-19 14:00:00 UTC.
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in Science Advances on 2024-09-20 07:00:00 UTC.
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- by Wilson Wen Bin Goh, Mohammad Neamul Kabir, Sehwan Yoo, Limsoon Wong
-Author summary: Artificial Intelligence (AI) and Machine Learning (ML) models are increasingly deployed on biomedical and health data to shed insights on biological mechanism, predict disease outcomes, and support clinical decision-making. However, ensuring model validity is challenging. The 10 quick tips described here discuss useful practices on how to check AI/ML models from 2 perspectives—the user and the developer.
+ Science Advances, Volume 10, Issue 38, September 2024.
- in PLoS Computational Biology on 2024-09-19 14:00:00 UTC.
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in Science Advances on 2024-09-20 07:00:00 UTC.
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- by Sofia Batista Leite, Matthew A. Brooke, Annamaria Carusi, Andy Collings, Pierre Deceuninck, Jean-François Dechamp, Bronwen Dekker, Elisa De Ranieri, Emma Ganley, Annalisa Gastaldello, Fanglian He, Marcel LaFlamme, Ingrid Langezaal, James Morris, David Pamies, Monica Piergiovanni, Bernd Pulverer, David Sadler, Caroline Shamu, Vivian Siegel, Marco Straccia, Tracey L. Weissgerber
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-Detailed method descriptions are essential for reproducibility, research evaluation, and effective data reuse. We summarize the key recommendations for life sciences researchers and research institutions described in the European Commission PRO-MaP report.
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-Essential details about study methods are often missing from academic research papers in the life sciences, which can adversely affect reproducibility, undermine trust and impair researchers’ ability to reuse methods and data. This Perspective article describes PRO-MaP (Promoting Reusable and Open Methods And Protocols), which aims to increase and improve the reporting of detailed, structured and open methods and reusable step-by-step protocols in the life sciences.
+ Science Advances, Volume 10, Issue 38, September 2024.
- in PLoS Biology on 2024-09-19 14:00:00 UTC.
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in Science Advances on 2024-09-20 07:00:00 UTC.
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- by Chonprakun Thagun, Masaki Odahara, Yutaka Kodama, Keiji Numata
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-Plastids are pivotal target organelles for comprehensively enhancing photosynthetic and metabolic traits in plants via plastid engineering. Plastidial proteins predominantly originate in the nucleus and must traverse membrane-bound multiprotein translocons to access these organelles. This import process is meticulously regulated by chloroplast-targeting peptides (cTPs). Whereas many cTPs have been employed to guide recombinantly expressed functional proteins to chloroplasts, there is a critical need for more efficient cTPs. Here, we performed a comprehensive exploration and comparative assessment of an advanced suite of cTPs exhibiting superior targeting capabilities. We employed a multifaceted approach encompassing computational prediction, in planta expression, fluorescence tracking, and in vitro chloroplast import studies to identify and analyze 88 cTPs associated with Arabidopsis thaliana mutants with phenotypes linked to chloroplast function. These polypeptides exhibited distinct abilities to transport green fluorescent protein (GFP) to various compartments within leaf cells, particularly chloroplasts. A highly efficient cTP derived from Arabidopsis plastid ribosomal protein L35 (At2g24090) displayed remarkable effectiveness in chloroplast localization. This cTP facilitated the activities of chloroplast-targeted RNA-processing proteins and metabolic enzymes within plastids. This cTP could serve as an ideal transit peptide for precisely targeting biomolecules to plastids, leading to advancements in plastid engineering.
+ Science Advances, Volume 10, Issue 38, September 2024.
- in PLoS Biology on 2024-09-19 14:00:00 UTC.
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in Science Advances on 2024-09-20 07:00:00 UTC.
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-High nicotine dose induces anxiety-like behavior in mice in the Open Field Test, alongside oxidative stress, proinflammatory cytokine secretion, and brain-derived neurotrophic factor (BDNF) reduction in brain regions. Cannabidiol acts as an anxiolytic, exhibiting antioxidant activities, reducing cytokines, and normalizing BDNF levels.
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-ABSTRACT
-High doses of nicotine administered to rodents serve as a model for studying anxiety and test compounds' potential anxiolytic effects. At these doses, anxiety in rodents is accompanied by disruption of brain-derived neurotrophic factor (BDNF). The endocannabinoids and nicotine modulate several central nervous system processes via their specific receptors, impacting locomotion, anxiety, memory, nociception, and reward. Cannabidiol (CBD), an active ingredient of Cannabis sativa L., is devoid of psychoactive actions and has gained attention for its anxiolytic, antioxidant, and anti-inflammatory properties, among others. This work aims to examine the potential anxiety-reducing properties of CBD in a well-established experimental mouse model of anxiety-like behavior induced by high doses of nicotine on male C57BL/6 mice. In this context, the open-field behavioral test was specially conducted to assess CBD's effects on anxiety-like behavior and locomotion. Brain neuronal plasticity, modulated by BDNF, along with a diverse array of blood's metabolic markers, was examined as a means of evaluating systemic toxicity under various treatments. Finally, oxidative stress was evaluated through the measurement of glutathione (GSH), superoxide dismutase (SOD), and malondialdehyde (MDA), while pro-inflammatory cytokine assessments were conducted to evaluate redox status and immune system function. Our research suggests that CBD shows potential in reducing anxiety-like behaviors induced by high doses of nicotine, by mitigating changes in BDNF protein levels in cerebral hemispheres and cerebellum. At the same time, CBD targets specific liver enzymes, maintains tissue's systemic toxicity (i.e., renal, kidney, and pancreatic), balances redox status (SOD, GSH, and MDA), and regulates the secretion of pro-inflammatory cytokines (TNF-alpha and IL-6).
+ Science Advances, Volume 10, Issue 38, September 2024.
- in Journal of Neuroscience Research on 2024-09-19 11:54:37 UTC.
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in Science Advances on 2024-09-20 07:00:00 UTC.
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- Author(s): Ian Braga, Emmanuel Pereira, and Lucas Wardil
Here, we derive stochastic adaptive dynamics from the microscopic death-birth process by explicitly modeling the trait variation from offspring to parent in each reproductive event, thereby accounting for a highly polymorphic population. This generalization enables the construction of a quantitative…
[Phys. Rev. E 110, L032401] Published Thu Sep 19, 2024
+ Science Advances, Volume 10, Issue 38, September 2024.
- in Physical Review E: Biological physics on 2024-09-19 10:00:00 UTC.
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in Science Advances on 2024-09-20 07:00:00 UTC.
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- Background Major depressive disorder (MDD) and schizophrenia are linked to accelerated aging leading to reduced lifespan, health span and cognitive decline. Cellular senescence, in which cells lose proliferative capacity and develop a senescence-associated secretory phenotype (SASP), plays a role in this process. Emerging research suggests that the senolytic regimen of dasatinib+quercetin (D+Q) reduces senescent cells, potentially mitigating age-related health and cognitive decline. This pilot study aims to assess the feasibility and safety of D+Q in older adults with schizophrenia, schizoaffective disorder, and treatment-resistant depression (TRD). Methods This single-center study will recruit 30 participants total aged 50 years or older with schizophrenia/schizoaffective disorder or 60 years or older with TRD; the difference in age limits is because individuals with schizophrenia are biologically about 10 years older than general population owing to metabolic burden. Each participant will receive two consecutive days of 100 mg oral dasatinib plus 1250 mg oral quercetin at baseline and weeks one through three, (i.e., two days on, five days off) along with lifestyle risk management education. Questionnaires and assessments will measure health and cognitive function as well as psychiatric function at baseline, week 10, and one year. Magnetic Resonance Imaging (MRI) will measure structural and functional brain health at baseline and 10 weeks. Blood sampling for SASP testing will occur at seven time points: baseline, weeks one through four, week 10, and one year. Conclusion This pilot aims to evaluate the safety and feasibility of the senolytic regimen and D+Q’s potential to counteract accelerated aging in adults with schizophrenia/schizoaffective disorder and TRD. Trial registration Dasatinib Plus Quercetin for Accelerated Aging in Mental Disorders is registered on ClinicalTrials.gov: NCT05838560; posted May 1, 2023.
+ Science Advances, Volume 10, Issue 38, September 2024.
- in F1000Research on 2024-09-19 09:43:15 UTC.
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in Science Advances on 2024-09-20 07:00:00 UTC.
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- Biopesticides are pest control products derived from natural sources such as microbes, macro-organisms (insects and pathogens), plant extracts, and certain minerals. Many biopesticides are considered environmentally safe and can complement or substitute conventional chemical pesticides. They can also be highly specific or broad spectrum with a unique mode of action controlling a wide range of pest species. Due to their target-specificity and low to no environmental residuality, biopesticides conform to the 3 pillars of Climate-Smart Agriculture, the Sustainable Development Goals, and ultimately, the Paris Agreement. This review focuses largely on microbial biopesticides derived from fungi, bacteria, viruses, and nematodes. It discusses (i) the various microbial biopesticide formulations, (ii) the mode of microbial biopesticide action, (iii) the factors that affect the potential efficacy of biopesticides, (iv) challenges to the adoption of microbial biopesticides, and (v) the role of microbial biopesticides in Integrated Pest Management programs. Finally, advancements in application techniques, as well as future research directions and gaps are highlighted.
+ Science Advances, Volume 10, Issue 38, September 2024.
- in F1000Research on 2024-09-19 09:40:49 UTC.
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in Science Advances on 2024-09-20 07:00:00 UTC.
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- Science, Volume 385, Issue 6715, September 2024.
+ Science Advances, Volume 10, Issue 38, September 2024.
- in Science on 2024-09-19 07:00:00 UTC.
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in Science Advances on 2024-09-20 07:00:00 UTC.
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- Science, Volume 385, Issue 6715, Page 1282-1282, September 2024.
+ Science Advances, Volume 10, Issue 38, September 2024.
- in Science on 2024-09-19 05:59:01 UTC.
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in Science Advances on 2024-09-20 07:00:00 UTC.
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- Science, Volume 385, Issue 6715, Page 1281-1281, September 2024.
+ Science Advances, Volume 10, Issue 38, September 2024.
- in Science on 2024-09-19 05:59:01 UTC.
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in Science Advances on 2024-09-20 07:00:00 UTC.
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- Science, Volume 385, Issue 6715, Page 1331-1337, September 2024.
+ Science Advances, Volume 10, Issue 38, September 2024.
- in Science on 2024-09-19 05:59:01 UTC.
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in Science Advances on 2024-09-20 07:00:00 UTC.
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- Science, Volume 385, Issue 6715, Page 1338-1347, September 2024.
+ Science Advances, Volume 10, Issue 38, September 2024.
- in Science on 2024-09-19 05:59:01 UTC.
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in Science Advances on 2024-09-20 07:00:00 UTC.
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- Science, Volume 385, Issue 6715, Page 1354-1359, September 2024.
+ Science Advances, Volume 10, Issue 38, September 2024.
- in Science on 2024-09-19 05:59:01 UTC.
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in Science Advances on 2024-09-20 07:00:00 UTC.
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- Science, Volume 385, Issue 6715, Page 1366-1375, September 2024.
+ Hao, Lee, et al. report ASAP5, a GEVI that enhances responsivity and accelerates kinetics. It enables single-trial recordings of sub- and suprathreshold activities in flies, mice, and human stem-cell-derived neurons, offering new possibilities to study the dynamics of membrane potentials from 1 to 100 mV.
- in Science on 2024-09-19 05:59:01 UTC.
+
in Neuron: In press on 2024-09-20 00:00:00 UTC.
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- Science, Volume 385, Issue 6715, Page 1360-1366, September 2024.
+ Abecunas et al. use multivariate modeling to explore recurrent metabolic states in cancer cells and uncover synthetically lethal interactions across diverse metabolic, oncogenic, and tissue contexts. They validate key findings via independent data analysis and new experiments. They find that PTEN loss predicts increased dependency on mitochondrial respiratory chain in OxphosHigh tumor cells.
- in Science on 2024-09-19 05:59:01 UTC.
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in Cell Reports: Current Issue on 2024-09-20 00:00:00 UTC.
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- Science, Volume 385, Issue 6715, Page 1347-1354, September 2024.
+ The conserved microtubule regulator EFA-6 forms punctate foci in the apical cortex of mature epithelia, dependent on its intrinsically disordered region. α-tubulin gain-of-function mutations induce ectopic EFA-6 foci, involving the EFA-6 microtubule interacting domain. Sandhu et al. show functionally important crosstalk between cellular tubulins and cortical MT regulators in vivo.
- in Science on 2024-09-19 05:59:01 UTC.
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in Cell Reports: Current Issue on 2024-09-20 00:00:00 UTC.
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- Science, Volume 385, Issue 6715, Page 1327-1331, September 2024.
+ Cancer patients often experience changes in mental health, prompting an exploration into whether nerves infiltrating tumors contribute to these alterations by impacting brain functions. Using a mouse model for head and neck cancer and neuronal tracing, we show that tumor-infiltrating nerves connect to distinct brain areas. The activation of this neuronal circuitry altered behaviors (decreased nest-building, increased latency to eat a cookie, and reduced wheel running). Tumor-infiltrating nociceptor neurons exhibited heightened calcium activity and brain regions receiving these neural projections showed elevated Fos as well as increased calcium responses compared to non-tumor-bearing counterparts. The genetic elimination of nociceptor neurons decreased brain Fos expression and mitigated the behavioral alterations induced by the presence of the tumor. While analgesic treatment restored nesting and cookie test behaviors, it did not fully restore voluntary wheel running indicating that pain is not the exclusive driver of such behavioral shifts. Unraveling the interaction between the tumor, infiltrating nerves, and the brain is pivotal to developing targeted interventions to alleviate the mental health burdens associated with cancer.
- in Science on 2024-09-19 05:59:01 UTC.
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in eLife on 2024-09-20 00:00:00 UTC.
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- Science, Volume 385, Issue 6715, Page 1318-1321, September 2024.
+ Glycans play an important role in modulating the interactions between natural killer cells and antibodies to fight pathogens and harmful cells.
- in Science on 2024-09-19 05:59:01 UTC.
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in eLife on 2024-09-20 00:00:00 UTC.
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- Science, Volume 385, Issue 6715, Page 1288-1289, September 2024.
+ -/-
- in Science on 2024-09-19 05:59:01 UTC.
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in eLife on 2024-09-20 00:00:00 UTC.
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- Science, Volume 385, Issue 6715, Page 1292-1297, September 2024.
+ In tumors with WT p53, alternate mechanisms of p53 inactivation are reported. Here, we have identified a long noncoding RNA, PITAR (p53 Inactivating TRIM28 Associated RNA), as an inhibitor of p53. PITAR is an oncogenic Cancer/testis lncRNA and is highly expressed in glioblastoma (GBM) and glioma stem-like cells (GSC). We establish that TRIM28 mRNA, which encodes a p53-specific E3 ubiquitin ligase, is a direct target of PITAR. PITAR interaction with TRIM28 RNA stabilized TRIM28 mRNA, which resulted in increased TRIM28 protein levels and reduced p53 steady-state levels due to enhanced p53 ubiquitination. DNA damage activated PITAR, in addition to p53, in a p53-independent manner, thus creating an incoherent feedforward loop to inhibit the DNA damage response by p53. While PITAR silencing inhibited the growth of WT p53 containing GSCs in vitro and reduced glioma tumor growth in vivo, its overexpression enhanced the tumor growth in a TRIM28-dependent manner and promoted resistance to Temozolomide. Thus, we establish an alternate way of p53 inactivation by PITAR, which maintains low p53 levels in normal cells and attenuates the DNA damage response by p53. Finally, we propose PITAR as a potential GBM therapeutic target.
- in Science on 2024-09-19 05:59:01 UTC.
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in eLife on 2024-09-20 00:00:00 UTC.
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- Science, Volume 385, Issue 6715, Page 1305-1310, September 2024.
+ Emotional responsiveness in neonates, particularly their ability to discern vocal emotions, plays an evolutionarily adaptive role in human communication and adaptive behaviors. The developmental trajectory of emotional sensitivity in neonates is crucial for understanding the foundations of early social-emotional functioning. However, the precise onset of this sensitivity and its relationship with gestational age (GA) remain subjects of investigation. In a study involving 120 healthy neonates categorized into six groups based on their GA (ranging from 35 and 40 weeks), we explored their emotional responses to vocal stimuli. These stimuli encompassed disyllables with happy and neutral prosodies, alongside acoustically matched nonvocal control sounds. The assessments occurred during natural sleep states using the odd-ball paradigm and event-related potentials. The results reveal a distinct developmental change at 37 weeks GA, marking the point at which neonates exhibit heightened perceptual acuity for emotional vocal expressions. This newfound ability is substantiated by the presence of the mismatch response, akin to an initial form of adult mismatch negativity, elicited in response to positive emotional vocal prosody. Notably, this perceptual shift’s specificity becomes evident when no such discrimination is observed in acoustically matched control sounds. Neonates born before 37 weeks GA do not display this level of discrimination ability. This developmental change has important implications for our understanding of early social-emotional development, highlighting the role of gestational age in shaping early perceptual abilities. Moreover, while these findings introduce the potential for a valuable screening tool for conditions like autism, characterized by atypical social-emotional functions, it is important to note that the current data are not yet robust enough to fully support this application. This study makes a substantial contribution to the broader field of developmental neuroscience and holds promise for future research on early intervention in neurodevelopmental disorders.
- in Science on 2024-09-19 05:59:01 UTC.
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in eLife on 2024-09-20 00:00:00 UTC.
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- Science, Volume 385, Issue 6715, Page 1298-1305, September 2024.
+ Genome-wide association studies (GWAS) have identified hundreds of genetic signals associated with autoimmune disease. The majority of these signals are located in non-coding regions and likely impact cis-regulatory elements (cRE). Because cRE function is dynamic across cell types and states, profiling the epigenetic status of cRE across physiological processes is necessary to characterize the molecular mechanisms by which autoimmune variants contribute to disease risk. We localized risk variants from 15 autoimmune GWAS to cRE active during TCR-CD28 co-stimulation of naïve human CD4+ T cells. To characterize how dynamic changes in gene expression correlate with cRE activity, we measured transcript levels, chromatin accessibility, and promoter–cRE contacts across three phases of naive CD4+ T cell activation using RNA-seq, ATAC-seq, and HiC. We identified ~1200 protein-coding genes physically connected to accessible disease-associated variants at 423 GWAS signals, at least one-third of which are dynamically regulated by activation. From these maps, we functionally validated a novel stretch of evolutionarily conserved intergenic enhancers whose activity is required for activation-induced IL2 gene expression in human and mouse, and is influenced by autoimmune-associated genetic variation. The set of genes implicated by this approach are enriched for genes controlling CD4+ T cell function and genes involved in human inborn errors of immunity, and we pharmacologically validated eight implicated genes as novel regulators of T cell activation. These studies directly show how autoimmune variants and the genes they regulate influence processes involved in CD4+ T cell proliferation and activation.
- in Science on 2024-09-19 05:59:01 UTC.
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in eLife on 2024-09-20 00:00:00 UTC.
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- Science, Volume 385, Issue 6715, Page 1280-1280, September 2024.
+ Memory is a crucial cognitive process involving several subsystems: sensory memory (SM), short-term memory (STM), working memory (WM), and long-term memory (LTM). While each has been extensively studied, the interaction between WM and LTM, particularly in relation to predicting temporal sequences, remains largely unexplored. This study investigates the relationship between WM and LTM, and how these relate to aging and musical training. Using three datasets with a total of 244 healthy volunteers across various age groups, we examined the impact of WM on LTM recognition of novel and previously memorized musical sequences. Our results show that WM abilities are significantly related to recognition of novel sequences, with a more pronounced effect in older compared to younger adults. In contrast, WM did not similarly impact the recognition of memorized sequences, which implies that different cognitive processes are involved in handling prediction errors compared to confirmatory predictions, and that WM contributes to these processes differently. Additionally, our findings confirm that musical training enhances memory performance. Future research should extend our investigation to populations with cognitive impairments and explore the underlying neural substrates.
- in Science on 2024-09-19 05:59:01 UTC.
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in bioRxiv: Neuroscience on 2024-09-20 00:00:00 UTC.
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- Science, Volume 385, Issue 6715, Page 1382-1382, September 2024.
+ It was suggested that during locomotion, the nervous system controls movement by activating groups of muscles, or muscle synergies. Analysis of muscle synergies can reveal the organization of spinal locomotor networks and how it depends on the state of the nervous system, such as before and after spinal cord injury, and on different locomotor conditions, including a change in speed. The goal of this study was to investigate the effects of spinal transection and locomotor speed on hindlimb muscle synergies and their time-dependent activity patterns in adult cats. EMG activities of 15 hindlimb muscles were recorded in 9 adult cats of either sex during tied-belt treadmill locomotion at speeds of 0.4, 0.7, and 1.0 m/s before and after recovery from a low thoracic spinal transection. We determined EMG burst groups using cluster analysis of EMG burst onset and offset times and muscle synergies using non-negative matrix factorization. We found five major EMG burst groups and five muscle synergies in each of six experimental conditions (2 states x 3 speeds). In each case, the synergies accounted for at least 90% of muscle EMG variance. Both spinal transection and locomotion speed modified subgroups of EMG burst groups and the composition and activation patterns of selected synergies. However, these changes did not modify the general organization of muscle synergies. Based on the obtained results, we propose an organization for a pattern formation network of a two-level central pattern generator that can be tested in neuromechanical simulations of spinal circuits controlling cat locomotion.
- in Science on 2024-09-19 05:59:01 UTC.
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in bioRxiv: Neuroscience on 2024-09-20 00:00:00 UTC.
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- Science, Volume 385, Issue 6715, Page 1312-1313, September 2024.
+ Cognitive deficits frequently arise after traumatic brain injury. The murine closed head injury (CHI) models these deficits since injured mice cannot acquire Barnes maze. Dosing of minocycline plus N-acetylcysteine beginning 12 hours post-CHI (MN12) restores Barnes maze acquisition by an unknown mechanism. Increased hippocampal synaptic efficacy is needed to acquire Barnes maze, synaptic long-term potentiation (LTP) models this increased synaptic efficacy in vitro. LTP has an early phase (E-LTP) lasting up to one hour that is mediated by second messengers that is followed by a late phase (L-LTP) that needs new synthesis of protein kinase M zeta (PKM{zeta}). PKM{zeta} has constitutive kinase activity because it lacks the autoinhibitory regulatory domain found in other PKCs. Due to its constitutive activity, the amount of PKM{zeta} kinase activity is determined by PKMz protein levels. We report that CHI bilaterally decreases PKM{zeta} levels in the CA3 and CA1 hippocampus. MN12 increases CA1 PKM{zeta} expression. CHI inhibits E-LTP in slices from the ipsilesional hippocampus and inhibits L-LTP in slices from both hippocamppi. MN12 treatment reestablishes both E-LTP and L-LTP in slices from the injured MN12-treated hippocampus. The restoration of L-LTP from injured MN12-treated hippocampus is mediated by PKM{zeta} because L-LTP is blocked by the specific PKM{zeta} inhibitor, {zeta}-stat. Hippocampal {zeta}-stat infusions also prevent Barnes maze acquisition in injured, MN12-treated mice. These data suggest that post-injury minocycline plus N-acetylcysteine targets PKM{zeta} to improve synaptic plasticity and cognition in mice with closed-head injury.
- in Science on 2024-09-19 05:59:01 UTC.
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in bioRxiv: Neuroscience on 2024-09-20 00:00:00 UTC.
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- Science, Volume 385, Issue 6715, Page 1275-1276, September 2024.
+ Leptin receptor (LepRb)-expressing neurons are known to link body growth and reproduction, but whether these functions are mediated via insulin-like growth factor 1 receptor (IGF1R) signaling is unknown. IGF-1 and insulin can bind to each other's receptors, permitting IGF-1 signaling in the absence of IGF1R. Therefore, we created mice lacking IGF1R exclusively in LepRb neurons (IGF1RLepRb mice) and simultaneously lacking IGF1R and insulin receptor (IR) in LepRb neurons (IGF1R/IRLepRb mice) and then characterized their body growth, bone morphology, reproductive and metabolic functions. We found that IGF1R and IR in LepRb neurons were required for normal timing of pubertal onset, while IGF1R in LepRb neurons played a predominant role in regulating adult fertility and exerted protective effects against reproductive aging. Accompanying these reproductive deficits, IGF1RLepRb mice and IGF1R/IRLepRb mice had transient growth retardation. Notably, IGF1R in LepRb neurons was indispensable for normal trabecular and cortical bone mass accrual in both sexes. These findings suggest that IGF1R in LepRb neurons is involved in the interaction among body growth, bone development, and reproduction. Though only mild changes in body weight were detected, simultaneous deletion of IGF1R and IR in LepRb neurons caused dramatically increased fat mass composition, decreased lean mass composition, lower energy expenditure, and locomotor activity in both sexes. Male IGF1R/IRLepRb mice exhibited impaired insulin sensitivity. These findings suggest that IGF1R and IR in LepRb neurons jointly regulated body composition, energy balance, and glucose homeostasis. Taken together, our studies identified the sex-dependent complex roles of IGF1R and IR in LepRb neurons in regulating body growth, reproduction, and metabolism.
- in Science on 2024-09-19 05:59:01 UTC.
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in bioRxiv: Neuroscience on 2024-09-20 00:00:00 UTC.
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- Science, Volume 385, Issue 6715, Page 1274-1275, September 2024.
+ Protein monoaminylation is a class of posttranslational modification (PTM) that contributes to transcription, physiology and behavior. While recent analyses have focused on histones as critical substrates of monoaminylation, the broader repertoire of monoaminylated proteins in brain remains unclear. Here, we report the development/implementation of a chemical probe for the biorthogonal labeling, enrichment and proteomics-based detection of dopaminylated proteins in brain. We identified 1,557 dopaminylated proteins - many synaptic - including {gamma}CaMKII, which mediates Ca2+-dependent cellular signaling and hippocampal-dependent memory. We found that {gamma}CaMKII dopaminylation is largely synaptic and mediates synaptic-to-nuclear signaling, neuronal gene expression and intrinsic excitability, and contextual memory. These results indicate a critical role for synaptic dopaminylation in adaptive brain plasticity, and may suggest roles for these phenomena in pathologies associated with altered monoaminergic signaling.
- in Science on 2024-09-19 05:59:01 UTC.
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in bioRxiv: Neuroscience on 2024-09-20 00:00:00 UTC.
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- Science, Volume 385, Issue 6715, Page 1276-1278, September 2024.
+ The dorsal vagal complex (DVC) is a region in the brainstem comprised of an intricate network of specialized cells responsible for sensing and propagating many appetite-related cues. Understanding the dynamics controlling appetite requires deeply exploring the cell types and transitory states harbored in this brain site. We generated a multi-species DVC cell atlas using single nuclei RNAseq (sn-RNAseq), thorough curation and harmonization of mouse and rat data which includes >180,000 cells and 123 cell identities at 5 granularities of cellular resolution. We report unique DVC features such as Kcnj3 expression in Ca-permeable astrocytes as well as new cell populations like neurons co-expressing Th and Cck, and a leptin receptor-expressing neuron population in the rat area postrema which is marked by expression of the progenitor marker, Pdgfra. In summary, our findings suggest there are distinct cellular populations specific to the DVC compared to other brain sites and our comprehensive atlas is a valuable tool for the study of this metabolic center.
- in Science on 2024-09-19 05:59:01 UTC.
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in bioRxiv: Neuroscience on 2024-09-20 00:00:00 UTC.
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- Science, Volume 385, Issue 6715, Page 1278-1279, September 2024.
+ Persistent DNA double-strand breaks (DSBs) are enigmatically implicated in neurodegenerative diseases including Huntingtons disease (HD), the inherited late-onset disorder caused by CAG repeat elongations in Huntingtin (HTT). Here we combine biochemistry, computation and molecular cell biology to unveil a mechanism whereby HTT coordinates a Transcription-Coupled Non-Homologous End-Joining (TC-NHEJ) complex. HTT joins TC-NHEJ proteins PNKP, Ku70/80, and XRCC4 with chromatin remodeler Brahma-related Gene 1 (BRG1) to resolve transcription-associated DSBs in brain. HTT recruitment to DSBs in transcriptionally active gene-rich regions is BRG1-dependent while efficient TC-NHEJ protein recruitment is HTT-dependent. Notably, mHTT compromises TC-NHEJ interactions and repair activity, promoting DSB accumulation in HD tissues. Importantly, HTT or PNKP overexpression restores TC-NHEJ in a Drosophila HD model dramatically improving genome integrity, motor defects, and lifespan. Collective results uncover HTT stimulation of DSB repair by organizing a TC-NHEJ complex that is impaired by mHTT thereby implicating dysregulation of transcription-coupled DSB repair in mHTT pathophysiology.
- in Science on 2024-09-19 05:59:01 UTC.
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in bioRxiv: Neuroscience on 2024-09-20 00:00:00 UTC.
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- Science, Volume 385, Issue 6715, Page 1285-1286, September 2024.
+ The fundus of the superior temporal sulcus (FST) in macaques is implicated in the processing of complex motion signals, yet a human homolog remains elusive. Here we considered potential localizers and evaluated their effectiveness in delineating putative FST (pFST), from hMT and MST, two nearby motion-sensitive areas in humans. Nine healthy participants underwent scanning sessions with 2D and 3D motion localizers, as well as population receptive field (pRF) mapping. We observed consistent anterior and inferior activation relative to hMT and MST in response to stimuli that contained coherent 3D, but not 2D, motion. Motion opponency and myelination measures further validated the functional and structural distinction between pFST and hMT/MST. At the same time, standard pRF mapping techniques that reveal the visual field organization of hMT/MST proved suboptimal for delineating pFST. Our findings provide a robust framework for localizing pFST in humans, and underscore its distinct functional role in motion processing.
- in Science on 2024-09-19 05:59:01 UTC.
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in bioRxiv: Neuroscience on 2024-09-20 00:00:00 UTC.
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- Science, Volume 385, Issue 6715, Page 1285-1285, September 2024.
+ Exercise has been extensively studied in Parkinson's Disease, with a particular focus on the potential for neuroprotection that has been demonstrated in animal models. While this preclinical work has provided insight into the underlying molecular mechanisms, it has not addressed the neurophysiological changes during exercise. Here, first, we tested for neuroprotective effects of adaptive wheel exercise in the 6-hydroxydopamine mouse model of Parkinson's disease. Finding none, we probed the neurophysiology of exercise as a state of high motor function amidst an unameliorated Parkinsonian lesion. Exercise was associated with characteristic, excitatory changes in the dopamine-depleted substantia nigra, which could be suppressed along with exercise itself by dopamine receptor blockade. Going forward, the functional state evoked by exercise merits further study, as it may represent an optimal target for neuromodulation, even if the underlying pathology cannot be averted.
- in Science on 2024-09-19 05:59:01 UTC.
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in bioRxiv: Neuroscience on 2024-09-20 00:00:00 UTC.
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- Science, Volume 385, Issue 6715, Page 1286-1286, September 2024.
+ Throughout the brain information is coded in the activity of multiple neurons at once, so called population codes. Population codes are a robust and accurate way of coding information. One can evaluate the quality of population coding by trying to read out the code with a decoder, and estimate the encoded stimulus. Coding quality has traditionally been evaluated in terms of the trial-to-trial variation in the estimate. However, codes can also display biases. While most decoders yield unbiased estimators in the limit of many active neurons, we find that when only few neurons are active, biases readily emerge for many decoders. We show that the biases turn out to have a non-trivial dependence on noise and tuning curve properties. We also introduce a technique to estimate the bias and variance of Bayesian decoders. Overall, the work expands our understanding of population coding.
- in Science on 2024-09-19 05:59:01 UTC.
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- Science, Volume 385, Issue 6715, Page 1256-1257, September 2024.
+ An exceptional human ability to adapt to the dynamics of novel environments relies on abstracting and generalizing past experiences. While previous research has examined how humans generalize isolated sequential processes, we know little concerning the neural mechanisms that enable adaptation to the more complex dynamics that govern everyday experience. Here, we deployed a novel sequence learning task based on graph factorization, coupled with simultaneous magnetoencephalography (MEG) recordings, to ask whether reuse of experiential 'building blocks' provides an abstract structural scaffolding that enables inference and generalization. We provide behavioral evidence that participants decomposed task experience into subprocesses, abstracted dynamical subprocess structures away from sensory specifics, and transferred these to a new task environment. Neurally we show this transfer is underpinned by a representational alignment of abstract subprocesses across task phases, where this included enhanced neural similarity among stimuli that adhered to the same subprocess, a temporally evolving mapping between predictive representations of subprocesses and a generalization of the precise dynamical roles that stimuli occupy within graph structures. Crucially, decoding strength for dynamical role representations predicted behavioral success in transfer of subprocess knowledge, consistent with a role in supporting behavioral adaptation in new environments. We propose a structural scaffolding mechanism enables compositional generalization of dynamical subprocesses that facilitate efficient adaptation within new contexts.
- in Science on 2024-09-19 05:59:01 UTC.
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- Science, Volume 385, Issue 6715, Page 1258-1259, September 2024.
+ Early dorsal telencephalon development is coordinated by an interplay of transcription factors that exhibit a graded expression pattern in neural progenitors. How they function together to orchestrate cortical development remains largely unknown. The Emx2 and Dmrta2 genes encode TFs that are expressed in a similar caudomedial-high/ rostrolateral-low gradient in the ventricular zone of the developing dorsal telencephalon with, in the medial pallium, Dmrta2 but not Emx2 expressed in the developing choroid plexus. Their constitutive loss has been shown to impart similar cortical abnormalities, and their combined deletion exacerbates the phenotypes, suggesting possible cooperation during cortex development. In this study, we utilized molecular and genetic approaches to dissect how Emx2 functions with Dmrta2 during cortical development. Our results show that while they regulate a similar set of genes, their common direct targets are limited but include key regulators of cortical development. Identification of the interaction partners of Emx2 suggests that it coordinates with the LIM-domain binding protein Ldb1 to execute the activation and repression of some of its downstream targets. Finally, while Emx2 is known to suppress choroid plexus development, we also provide evidence that Dmrta2 is in contrast required for choroid plexus since in its absence in medial telencephalic progenitors, mice develop hydrocephalous postnatally, a phenotype that appears to be due to a compromised cytoarchitecture. Together, these data indicate that Emx2 and Dmrta2 have similar but also distinct functions in telencephalon development and provide the first insights into Emx2 mechanism of action.
- in Science on 2024-09-19 05:59:01 UTC.
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- Science, Volume 385, Issue 6715, Page 1259-1260, September 2024.
+ Multiple pathological cell biological processes in midbrain dopaminergic (mDA) neurons contribute to Parkinson's disease (PD). Described disease mechanisms converge upon defects in protein degradation, disruption of vesicular trafficking, endolysosomal function, mitochondrial dysfunction and oxidative stress. Current cellular PD models for in vitro drug discovery are often of non-neuronal origin and do not take complex pathological interactions into account and focus on a single readout or phenotype. Here, we used patient-derived SNCA triplication (SNCA-4x) and isogenic control (SNCA-corr) mDA neurons and applied high-content imaging-based morphological profiling with the goal to determine and rescue multiple phenotypes simultaneously. We performed compound screening using a total of 1,020 compounds with biological activity annotations relevant to PD pathobiology including some FDA-approved drugs. We scored compounds based on their ability to revert the SNCA-4x mDA neuron morphological profile towards a healthy-like isogenic control neuronal profile. Top-scoring compounds led to a morphological rescue in SNCA-4x mDA neurons including increased Tyrosine hydroxylase (TH) level and decreased total -synuclein (Syn) protein levels. Multiple hit compounds were also linked to mitochondrial biology and we further evaluated them by determining their effect on neuronal mitochondrial membrane potential and cytoplasmic ROS levels. Additional biochemical analysis of the protonophore and mitochondrial uncoupler Tyrphostin A9 showed decreased total ROS levels and normalized mitochondrial membrane potential, and an increase in mitochondrial respiration. We confirmed this effect in mDA neurons by using five structurally related molecules and measuring mitochondrial activity and membrane potential. Additionally, Western blotting indicated that mitochondrial uncouplers, such as Tyrphostin A9, can decrease both low and high molecular weight forms of Syn. Based on target agnostic morphological profiling in human mDA neurons, we therefore identified a connection between the compound-induced rescue of multiple morphological features, mild mitochondrial uncoupling, and a Syn protein level decrease.
- in Science on 2024-09-19 05:59:01 UTC.
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- Science, Volume 385, Issue 6715, Page 1260-1261, September 2024.
+ Extracellular vesicles are easily accessible in various biofluids and allow the assessment of disease-related changes of the proteome. This has made them a promising target for biomarker studies, especially in the field of neurodegeneration where access to diseased tissue is very limited. Genetic variants in the LRRK2 gene have been linked to both familial and sporadic forms of Parkinson's disease. With LRRK2 inhibitors entering clinical trials, there is an unmet need for biomarkers that reflect LRRK2-specific pathology and target engagement. In this study, we used induced pluripotent stem cells derived from a patient with Parkinson's disease carrying the LRRK2 G2019S mutation and an isogenic gene corrected control to generate human dopaminergic neurons. We isolated extracellular vesicles and neuronal cell lysates and characterized their proteomic signature using data-independent acquisition proteomics. We performed differential expression analysis and identified 595 significantly differentially regulated proteins in extracellular vesicles and 3205 in cell lysates. Next, we performed gene ontology enrichment analyses on the dysregulated proteins and found close association to biological processes relevant in neurodegeneration and Parkinson's disease. Finally, we focused on proteins that were dysregulated in both the extracellular and cellular proteomes and provide a list of ten promising biomarker candidates that are functionally relevant in neurodegeneration and linked to LRRK2 associated pathology. Among those was the sonic hedgehog signaling molecule, a protein that has tightly been linked to LRRK2-related disruption of cilia function. In conclusion, we characterized the cellular and extracellular proteome of dopaminergic neurons carrying the LRRK2 G2019S mutation and propose an experimentally based list of promising biomarker candidates for future studies.
- in Science on 2024-09-19 05:59:01 UTC.
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- Science, Volume 385, Issue 6715, Page 1262-1263, September 2024.
+ Consolidation of encoded information is vital for learning and memory, often explored during sleep. However, the consolidation during post-encoding offline wakefulness remains largely uncharted, especially regarding its modulation and brain mechanisms. Here, we unraveled frequency-dependent modulatory effects of repetitive visual stimulation (RVS) on wakeful consolidation of visual learning and investigated the underlying neural substrates. After training on an orientation discrimination task, exposure to 10-Hz grating-form RVS enhanced, while 1-Hz RVS deteriorated, the discrimination performance in a subsequent retest. However, 10-Hz uniform-disk RVS failed to facilitate wakeful consolidation, suggesting that alpha entrainment alone was not the facilitative mechanism. Using neuroimaging of multiple modalities, we observed augmented event-related potential and heightened neural excitation in the early visual cortex after 10-Hz grating-form RVS, implying an involvement of long-term potentiation-like (LTP-like) plasticity. Collectively, we provide a new photic method for modulating the offline processing of encoded sensory information and suggest a role of sensory tetanization in the modulation.
- in Science on 2024-09-19 05:59:01 UTC.
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- Science, Volume 385, Issue 6715, Page 1263-1263, September 2024.
+ Lipids are essential for neuron development and physiology. Yet, the central hubs that coordinate lipid supply and demand in neurons remain unclear. Here, we combine invertebrate and vertebrate models to establish the presence and functional significance of neuronal lipid droplets (LD) in vivo. We find that LD are normally present in neurons in a non-uniform distribution across the brain, and demonstrate triglyceride metabolism enzymes and lipid droplet-associated proteins control neuronal LD formation through both canonical and recently-discovered pathways. Appropriate LD regulation in neurons has conserved and male-biased effects on whole-body energy homeostasis across flies and mice, specifically neurons that couple environmental cues with energy homeostasis. Mechanistically, LD-derived lipids support neuron function by providing phospholipids to sustain mitochondrial and endoplasmic reticulum homeostasis. Together, our work identifies a conserved role for LD as the organelle that coordinates lipid management in neurons, with implications for our understanding of mechanisms that preserve neuronal lipid homeostasis and function in health and disease.
- in Science on 2024-09-19 05:59:01 UTC.
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- Science, Volume 385, Issue 6715, Page 1264-1269, September 2024.
+ The Human Connectome Project Lifespan studies cover the Development (5-21) and Aging (36-100+) phases of life. Arterial spin labelling (ASL) was included in the imaging protocol, resulting in one of the largest datasets collected to-date of high spatial resolution multiple delay ASL covering 3,000 subjects. The HCP-ASL minimal processing pipeline was developed specifically for this dataset to pre-process the image data and produce perfusion estimates in both volumetric and surface template space. Applied to the whole dataset, the outputs of the pipeline revealed significant and expected differences in perfusion between the Development and Ageing cohorts. Visual inspection of the group average surface maps showed that cortical perfusion often followed cortical areal boundaries, suggesting differential regulation of cerebral perfusion within brain areas at rest. Group average maps of arterial transit time also showed differential transit times in core and watershed areas of the cerebral cortex, which are useful for interpreting haemodynamics of functional MRI images. The pre-processed dataset will provide a valuable resource for understanding haemodynamics across the human lifespan.
- in Science on 2024-09-19 05:59:01 UTC.
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- Science, Volume 385, Issue 6715, Page 1290-1291, September 2024.
+ Brain networks oscillate between sleep and wakefulness, following circadian rhythms. Theoretical models suggest distinct phases within this cycle, separated by a critical point where long-range activity patterns emerge, an advantageous condition for information processing in cortical networks. However, the exact nature of this critical dynamics remains elusive. A key question is whether the brain operates at this critical point during cognitive tasks or only during resting wakefulness. Here, we analyzed neural signals from the premotor cortex (PMC) of two macaque monkeys engaged in a delayed-reaching task and under drug-induced unconsciousness. We found evidence of criticality during resting periods at the end of behavioral trials in the awake state. This scale-free activity appeared as coordinated traveling waves, like those observed during anesthesia. As predicted by spiking networks models, activity-dependent adaptation influences wave size, supporting the hypothesis that the PMC operates near a synchronization phase transition while avoiding it during active behaviors.
- in Science on 2024-09-19 05:59:01 UTC.
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- Science, Volume 385, Issue 6715, Page 1255-1255, September 2024.
+ Purpose: High-resolution fMRI at 7T is challenged by suboptimal alignment quality between functional data and structural scans. This study aims to develop a rapid acquisition method that provides distortion-matched, artifact-mitigated structural reference data. Methods: We introduce an efficient sequence protocol termed T1234, which offers adjustable distortions. This approach involves a T1-weighted 2-inversion 3D-EPI sequence with four spatial encoding directions optimized for high-resolution fMRI. A forward Bloch model was used for T1 quantification and protocol optimization. Twenty participants were scanned at 7T using both structural and functional protocols to evaluate the utility of T1234. Results: Results from two protocols are presented. A fast distortion-free protocol reliably produced whole-brain segmentations at 0.8mm isotropic resolution within 3:00-3:40 minutes. It demonstrates robustness across sessions, participants, and three different 7T SIEMENS scanners. For a protocol with geometric distortions that matched functional data, T1234 facilitates layer-specific fMRI signal analysis with enhanced laminar precision. Conclusion: This structural mapping approach enables precise registration with fMRI data. T1234 has been successfully implemented, validated, and tested, and is now available to users at our center and at over 50 centers worldwide.
- in Science on 2024-09-19 05:59:01 UTC.
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- Science, Volume 385, Issue 6715, Page 1270-1273, September 2024.
+ The gray matter of the higher brain undergoes spreading depolarization (SD) in response to the increased metabolic demand of ischemia, promoting acute neuronal injury and death. The mechanism linking ischemic failure of the Na+/K+ ATPase (NKA) to the subsequent onset of a large inward current driving SD in neurons has remained a mystery because blockade of conventional channels does not prevent SD nor ischemic death. The marine poison palytoxin (PLTX) specifically binds the NKA transporter at extremely low concentrations, converting it to an open cationic channel, causing sudden neuronal Na+ influx and K+ efflux. Pump failure and induction of a strong inward current should induce dramatic SD-like activity. Indeed,1-10 nM PLTX applied to live coronal brain slices induces a propagating depolarization remarkably like SD induced by oxygen/glucose deprivation (OGD) as revealed by imaging. This PLTX depolarization (PD) mimicked other effects of OGD. In neocortex, as the elevated LT front passed by an extracellular pipette, a distinct negative DC shift was recorded, indicating cell depolarization, whether induced by OGD or by bath PLTX. Either treatment induced strong SD-like responses in the same higher and lower brain regions. Further, we imaged identical real-time OGD-SD or PD effects upon live pyramidal neurons using 2-photon microscopy. Taken together, these findings support our proposal that, like most biological poisons, PLTX mimics (and takes advantage of) a biological process,i.e., brain ischemia. An endogenous PLTX-like molecule may open the NKA to evoke Na+ influx/K+ efflux that drive SD and the ensuing neuronal damage in its wake.
- in Science on 2024-09-19 05:59:01 UTC.
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- Science, Volume 385, Issue 6715, Page 1311-1313, September 2024.
+ The initial months of life constitute a crucial period for human development. A comprehensive understanding of this early phase is essential for unraveling the origins of neurodevelopmental disorders and promoting infant brain health. This study uniquely focuses on the spatial development of intrinsic brain connectivity networks during infancy, which has been less explored compared to functional connectivity. We utilized independent component analysis (ICA) on resting-state fMRI data from 74 infants to assess how the spatial organization of infant brain networks evolves between birth and six months. Our findings reveal significant changes in spatial characteristics, including an a notable rise in the network-averaged spatial similarity across age, reflecting how closely each participant-specific spatial map aligns with the group-level map for each network. We also observed a marked reduction in the network engagement range by age, representing the extent of voxel intensity range fluctuation within each network. This suggests a continuing process of consolidation, where voxel contributions to the network become more uniform, as indicated by the narrowing of intensity values. The network strength, calculated as the average of all the voxel intensities in the network, indicating the degree of involvement to the specific functional network, increased across age in several networks, such as frontal-mPFC, primary, and secondary visual networks. The network size, along with the network center of mass, illustrating spatial distribution alterations of brain networks by age, varied across different networks. For instance, both metrics increased across age in the secondary visual network but decreased in the temporal network. Additionally, we examined the networks in relation to their linear versus non-linear developmental trajectories across all spatial characteristics, providing a deeper understanding of how these patterns evolve during early infancy. These findings contribute to early brain development understanding and offer insights into potential markers of consolidation and spatial reorganization in large-scale brain networks during infancy.
- in Science on 2024-09-19 05:59:01 UTC.
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+ The macaque monkey's ventral intraparietal area (VIP) in the intraparietal sulcus (IPS) responds to visual, vestibular, tactile and auditory signals and is involved in higher cognitive functions including the processing of peripersonal space. In humans, VIP appears to have expanded into three functionally distinct regions. Macaque VIP has been divided cytoarchitonically into medial and lateral parts; however, no functional specialization has so far been associated with this anatomical division. Functional MRI suggests a functional gradient along the anterior-posterior axis of the macaque IPS: anterior VIP shows visio-tactile properties and face preference, whereas posterior VIP responds to large-field visual dynamic stimuli. This functional distinction matches with functional differences among the three human VIP regions, suggesting that a regional specialization may also exist within macaque VIP. Here, we characterized the ipsilateral, whole-brain functional connectivity, assessed during awake resting state, along VIP's anterior-posterior axis by dividing VIP into three regions of interest (ROIs). The functional connectivity profiles of the three VIP ROIs resembled anatomical connectivity profiles obtained by chemical tracing. Anterior VIP was functionally connected to regions associated with motor, tactile, and proprioceptive processing and with regions involved in reaching, grasping, and processing peripersonal space. Posterior VIP had the strongest functional connectivity to regions involved in motion processing and eye movements. These profiles are consistent with the connectivity profiles of the anterior and posterior VIP areas identified in humans. Viewed together, resting state functional connectivity, task-related fMRI and anatomical tracing consistently suggest specific functional specializations of macaque anterior and posterior VIP. This specialization corroborates the distinction of VIP into three anatomically and functionally separate VIP areas in humans.
- in Hippocampus on 2024-09-19 03:49:54 UTC.
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-The cover image is based on the article Scene construction processes in the anterior hippocampus during temporal episodic memory retrieval by Maria Jieun Hwang and Sang Ah Lee (https://doi.org/10.1002/hipo.23624).
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+ Synthesizing perceivable artificial neural inputs independent of typical sensory channels remains a fundamental challenge in the development of next-generation brain-machine interfaces. Establishing a minimally invasive, wirelessly effective, and miniaturized platform with long-term stability is crucial for creating a clinically meaningful interface capable of mediating artificial perceptual feedback. In this study, we demonstrate a miniaturized fully implantable wireless transcranial optogenetic encoder designed to generate artificial perceptions through digitized optogenetic manipulation of large cortical ensembles. This platform enables the spatiotemporal orchestration of large-scale cortical activity for remote perception genesis via real-time wireless communication and control, with optimized device performance achieved by simulation-guided methods addressing light and heat propagation during operation. Cue discrimination during operant learning demonstrates the wireless genesis of artificial percepts sensed by mice, where spatial distance across large cortical networks and sequential order-based analyses of discrimination performance reveal principles that adhere to general perceptual rules. These conceptual and technical advancements expand our understanding of artificial neural syntax and its perception by the brain, guiding the evolution of next-generation brain-machine communication.
- in Hippocampus on 2024-09-19 03:49:54 UTC.
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- Abstract
-The dorsal region of the hippocampus (dHC) mediates many of the mnemonic functions traditionally associated with the hippocampus proper, such as spatial and episodic memory, whereas ventral hippocampus (vHC) has been extensively implicated in emotional memory and motivational processes. By contrast, the functions of the intermediate hippocampus (iHC) are far less understood. In this study, we aimed to investigate the mnemonic functions of iHC by reversibly inactivating iHC prior to testing memory in behavioral tasks dependent on the integrity of dHC, iHC, or vHC, namely, rapid place water maze, inhibitory avoidance, spontaneous alternation, and temporal ordering of odors. Given our previous findings showing that dHC and vHC are involved in mnemonic control of ingestive behavior, we also assessed the effects of iHC inactivation on sucrose intake. The results showed that pharmacological inhibition of iHC impairs rapid place water maze memory, which has been previously shown to be dependent on iHC but not dHC or vHC. iHC inactivation does not impact memory dependent on dHC (spontaneous alternation), vHC (temporal odor memory), or either dHC or vHC (inhibitory avoidance), and only modestly affects sucrose intake. These findings provide support for the involvement of iHC in mnemonic functions that are distinct from dHC and vHC and highlight the need to further advance our understanding of the functions of this hippocampal region that has been relatively understudied.
+ Ultrasound localization microscopy is a super-resolution vascular imaging technique which has garnered substantial interest as a tool for small animal neuroimaging, neuroscience research, and the characterization of vascular pathologies. In the pursuit of increasingly high-fidelity reconstructions of microvasculature, there remains several outstanding questions concerning this sub-diffraction imaging technology, including the accurate reconstruction of microvessels approaching the capillary scale and the pragmatic challenges associated with long data acquisition times. In the context of small animal neurovascular imaging, we posit that increasing the ultrasound imaging frequency is a straightforward approach to enable higher concentrations of microbubble contrast agents, thus increasing the likelihood of microvascular/capillary mapping and decreasing the imaging duration. We demonstrate that higher frequency imaging results in improved ULM fidelity and more efficient microbubble localization due to a smaller microbubble point-spread function that is easier to localize, and which can achieve a higher localizable concentration within the same unit volume of tissue. A select example of in vivo capillary-level vascular reconstruction is demonstrated for the highest frequency imaging probe, which has substantial implications for neuroscientists investigating microvascular function in disease states, regulation, and brain development. High frequency ULM yielding a spatial resolution of 7.1m, as measured by Fourier ring correlation, throughout the entire depth of the brain, highlighting this technology as a highly relevant tool for neuroimaging research.
- in Hippocampus on 2024-09-19 03:49:54 UTC.
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- Abstract
-The hippocampus is considered essential for several forms of declarative memory, including spatial and social memory. Despite the extensive research of the classic subfields of the hippocampus, the fasciola cinerea (FC)—a medially located structure within the hippocampal formation—has remained largely unexplored. In the present study, we performed a morpho-functional characterization of principal neurons in the mouse FC. Using in vivo juxtacellular recording of single neurons, we found that FC neurons are distinct from neighboring CA1 pyramidal cells, both morphologically and electrophysiologically. Specifically, FC neurons displayed non-pyramidal morphology and granule cell-like apical dendrites. Compared to neighboring CA1 pyramidal neurons, FC neurons exhibited more regular in vivo firing patterns and a lower tendency to fire spikes at short interspike intervals. Furthermore, tracing experiments revealed that the FC receives inputs from the lateral but not the medial entorhinal cortex and CA3, and it provides a major intra-hippocampal projection to the septal CA2 and sparser inputs to the distal CA1. Overall, our results indicate that the FC is a morphologically and electrophysiologically distinct subfield of the hippocampal formation; given the established role of CA2 in social memory and seizure initiation, the unique efferent intra-hippocampal connectivity of the FC points to possible roles in social cognition and temporal lobe epilepsy.
+ Dmrta2 (also designated Dmrt5) is a transcriptional regulator expressed in cortical progenitors in a caudomedial-high/rostrolateral-low gradient with important roles at different steps of cortical development. Dmrta2 has been suggested to act in cortex development mainly by differential suppression of Pax6 and other homeobox transcription factors such as the ventral telencephalic regulator Gsx2, which remains to be fully demonstrated. Here we have addressed the epistatic relation between Pax6 and Dmrta2 by comparing phenotypes in mutant embryos or embryos overexpressing both genes in various allelic combinations. We showed that Dmrta2 cooperates with Pax6 in the maintenance of cortical identity in dorsal telencephalic progenitors and that it acts as a transcriptional repressor of Pax6 to control cortical patterning. Mechanistically, we show that in P19 cells, Dmrta2 can act as a DNA-binding dependent repressor on the Pax6 E60 enhancer and that a point mutation that affects its DNA binding properties leads to agenesis of the corpus callosum, pachygyria, and the absence of the cingulate gyrus. Finally, we provide evidence that Dmrta2 binds to the Zfp423 zinc finger protein and that it enhances its ability to recruit the NurD repressor complex. Together, our results highlight the importance and conserved function of Dmrta2 in cortical development and provide novel insights into its mechanism of action.
- in Hippocampus on 2024-09-19 03:49:54 UTC.
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- Abstract
-Although the hippocampus has been implicated in both the temporal organization of memories and association of scene elements, some theoretical accounts posit that the role of the hippocampus in episodic memory is largely atemporal. In this study, we set out to explore this discrepancy by identifying hippocampal activity patterns related to scene construction while participants performed a temporal order memory task. Participants in the fMRI scanner were shown a sequence of photographs, each consisting of a central object and a contextual background scene. On each retrieval trial, participants were shown a pair of the original photographs (FULL), objects from the scenes without the background (OBJ), or background contexts without the main foreground object (BACK). In the temporal order judgment (TOJ) task, participants judged the temporal order of the pair of scenes; in the Viewing trials, two identical scenes were shown without any task. First, we found that the anterior hippocampus—particularly the CA1 and subiculum—showed similar patterns of activation between the BACK and OBJ conditions, suggesting that scene construction occurred spontaneously during both TOJ and Viewing. Furthermore, neural markers of scene construction in the anterior hippocampus did not apply to incorrect trials, showing that successful temporal memory retrieval was functionally linked to scene construction. In the cortex, time-processing areas, such as the supplementary motor area and the precuneus, and scene-processing areas, such as the parahippocampal cortex, were activated and functionally connected with the hippocampus. Together, these results support the view that the hippocampus is concurrently involved in scene construction and temporal organization of memory and propose a model of hippocampal episodic memory that takes both processes into account.
+ Retinal bipolar cells (BCs) convey visual signals from photoreceptors to more than 50 types of rabbit retinal ganglion cells (Famiglietti, 2020). More than 40 years ago, 10-11 types of bipolar cell were recognized in rabbit and cat retinas (Famiglietti, 1981). Twenty years later 10 were identified in mouse, rat, and monkey (Gosh et al., 2004), while recent molecular genetic studies indicate that there are 15 types of bipolar cell in mouse retina (Shekhar et al., 2016). The present detailed study of more than 800 bipolar cells in ten Golgi-impregnated rabbit retinas indicates that there are 14-16 types of cone bipolar cell and one type of rod bipolar cell in rabbit retina. These have been carefully analyzed in terms of dendritic and axonal morphology, and axon terminal stratification with respect to fiducial starburst amacrine cells. In fortuitous proximity, several types of bipolar cell can be related to identified ganglion cells by stratification and by contacts suggestive of synaptic connection. These results are compared with other studies of rabbit bipolar cells. Homologies with bipolar cells of mouse and monkey are considered in functional terms.
- in Hippocampus on 2024-09-19 03:49:54 UTC.
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- Abstract
-The processing of rich synaptic information in the dentate gyrus (DG) relies on a diverse population of inhibitory GABAergic interneurons to regulate cellular and circuit activity, in a layer-specific manner. Metabotropic GABAB-receptors (GABABRs) provide powerful inhibition to the DG circuit, on timescales consistent with behavior and learning, but their role in controlling the activity of interneurons is poorly understood with respect to identified cell types. We hypothesize that GABABRs display cell type-specific heterogeneity in signaling strength, which will have direct ramifications for signal processing in DG networks. To test this, we perform in vitro whole-cell patch-clamp recordings from identified DG principal cells and interneurons, followed by GABABR pharmacology, photolysis of caged GABA, and extracellular stimulation of endogenous GABA release to classify the cell type-specific inhibitory potential. Based on our previous classification of DG interneurons, we show that postsynaptic GABABR-mediated currents are present on all interneuron types albeit at different amplitudes, dependent largely on soma location and synaptic targets. GABABRs were coupled to inwardly-rectifying K+ channels that strongly reduced the excitability of those interneurons where large currents were observed. These data provide a systematic characterization of GABABR signaling in the rat DG to provide greater insight into circuit dynamics.
+ Background: The continuous attractor network (CAN) model has been effective in explaining grid-patterned firing in the rodent medial entorhinal cortex, with strong lines of experimental evidence and widespread utilities in understanding spatial navigation and path integration. A surprising lacuna in CAN analyses is the paucity of quantitative studies on the impact of afferent sensory noise on path integration. Here, we evaluate the impact of afferent sensory noise on grid-patterned firing and on the accuracy of position estimates derived from network pattern flow velocity. Motivated by the ability of border cells to act as an error-correction mechanism, we also assess the impact of interaction between afferent noise and border cell inputs on CAN performance. Methodology: We used an established 2D CAN model that received velocity inputs from a virtual animal traversing a 2D arena to generate grid-patterned firing. We estimated network pattern flow velocity from network activity and used that to compute an activity-based position estimate at each time step. We tracked the difference between the real and the estimated positions as a function of time and called it the deviation in integrated path (DIP). We defined afferent sensory noise to be additive Gaussian, with different noise levels achieved by changing the variance. We introduced north and east border cells and connected them to grid cells based on co-activity patterns. For different levels of noise, we computed DIP and metrics for grid-patterned activity in the presence vs. absence of border cells. Importantly, to avoid potential bias owing to the use of a single trajectory in computing these measurements, we performed all simulations across 50 different trajectories. Results: The computed grid scores and position accuracy (as DIP) showed pronounced trajectory-to-trajectory variability, even in a noise-free network. With the introduction of sensory noise, the variability prevailed and unveiled a dichotomous impact of afferent sensory noise on position accuracy vs. grid-patterned activity. Specifically, low levels of sensory noise improved position estimation accuracy without altering the ability of the network to generate grid-patterned activity. In contrast, high levels of sensory noise impaired position estimates as well as grid-patterned activity, although position estimates were more sensitive to sensory noise compared to grid-patterned activity. The stochastic resonance observed in the relationship between position accuracy and sensory noise level was partially explained by the interaction of noisy inputs with the rectification nonlinearity in the neural transfer function. Finally, across noise levels, pronounced trajectory-to-trajectory variability in grid-score and position accuracy was observed with the addition of border inputs. Across the population of trajectories, addition of border inputs yielded modest changes in both measurements across noise levels. Implications: Our analyses demonstrate that the robustness of grid-patterned activity in CAN models to noise does not extend to other functions of the CAN model. Stochastic resonance with reference to position estimation and sensory noise implies that biological CANs could evolve to yield optimal performance (path integration) in the presence of noise in biological sensory systems. An important methodological implication that emerges from our observations is the critical need to account for trajectory-to-trajectory variability in position estimates and path integration. Given the pronounced nature of trajectory-to-trajectory variability, conclusions based on a single trajectory are bound to be erroneous thereby warranting analyses with multiple trajectories. Together, our analyses unveil important roles for sensory noise in improving position estimates obtained from activity in CAN models.
- in Hippocampus on 2024-09-19 03:49:54 UTC.
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in bioRxiv: Neuroscience on 2024-09-20 00:00:00 UTC.
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- Abstract
-Neural progenitor cells (NPCs) reside in the brain and participate in the mechanism of neurogenesis that permits the brain to generate the building blocks for enhancement of cognitive abilities and acquisition of new skills. The existence of NPCs in brain has opened a novel dimension of research to explore their potential for treatment of various neurodegenerative disorders. The present study provides novel insights into the intracellular mechanisms in neuronal cells proliferation, maturation and differentiation regulated by Quinic acid (QA). Furthermore, this study might help in discovery and development of lead molecule that can overcome the challenges in the treatment of neurodegenerative diseases. The growth supporting effect of QA was studied using MTT assay. For that purpose, hippocampal cell cultures of neonatal rats were treated with different concentrations of QA and incubated for 24, 48 and 72 h. Gene and protein expressions of the selected molecular markers nestin, neuron-specific class III beta-tubulin (Tuj-1), neuronal nuclear protein (NeuN), neuronal differentiation 1 (NeuroD1), glial fibrillary acidic protein (GFAP), neuroligin (NLGN) and vimentin were analyzed. QA-induced cell proliferation and differentiation of hippocampal progenitor cells was also accompanied by significantly increased expression of progenitor and immature neuronal marker, mature neuronal marker and differentiating factor, that is, nestin, Tuj-1, NeuN and NeuroD1, respectively. On the other hand, vimentin downregulation and constant GFAP expression were observed following QA treatment. Additionally, the effects of QA on the recovery of stressed cells was studied using in vitro model of oxygen glucose deprivation (OGD). It was observed that hippocampal cells were able to recover from OGD following the treatment with QA. These findings suggest that QA treatment promotes hippocampal neurogenesis by proliferating and differentiating of NPCs and recovers neurons from stress caused by OGD. Thus, the neurogenic potential of QA can be explored for the treatment of neurodegenerative disorders.
+ Dysfunction of the endolysosomal system within neurons is a prominent feature of Alzheimer's disease (AD) pathology. Multiple AD-risk factors are known to cause hyper-activity of the early-endosome small GTPase rab5, resulting in neuronal endosomal pathway disruption. APPL1, an important rab5 effector protein, is an interface between endosomal and neuronal function through a rab5-activating interaction with the BACE1-generated C-terminal fragment ({beta}CTF or C99) of the amyloid precursor protein (APP), a pathogenic APP fragment generated within endolysosomal compartments. To better understand the role of APPL1 in the AD endosomal phenotype, we generated a transgenic mouse model over-expressing human APPL1 within neurons (Thy1-APPL1 mice). Consistent with the important endosomal regulatory role of APPL1, Thy1-APPL1 mice have enlarged neuronal early endosomes and increased synaptic endocytosis due to increased rab5 activation. We additionally demonstrate pathological consequences of APPL1 overexpression, including functional changes in hippocampal long-term potentiation (LTP) and long-term depression (LTD), as well as degeneration of the large projection cholinergic neurons of the basal forebrain and impairment of hippocampal-dependent memory. Our findings show that increased neuronal APPL1 levels lead to a cascade of pathological effects within neurons, including early endosomal alterations, synaptic dysfunction, and neurodegeneration. Multiple risk factors and molecular regulators, including APPL1 activity, are known to contribute to the endosomal dysregulation seen in the early stages of AD, and these findings further highlighting the shared pathobiology and consequences to a neuron of early endosomal pathway disruption.
- in Hippocampus on 2024-09-19 03:49:54 UTC.
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in bioRxiv: Neuroscience on 2024-09-20 00:00:00 UTC.
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- Migraine is a highly prevalent and disabling pain disorder that affects >1 billion people worldwide. One central hypothesis points to the cranial meninges as a key site underlying migraine headache genesis through complex interplay between meningeal sensory nerves, blood vessels, and adjacent immune cells. How these interactions might generate migraine headaches remains incompletely understood and a subject of much debate. In this review we discuss clinical and preclinical evidence supporting the concept that meningeal sterile inflammation, involving neurovascular and neuroimmune interactions, underlies migraine headache genesis. We examine downstream signaling pathways implicated in the development of migraine pain in response to exogenous events such as infusing migraine-triggering chemical substances. We further discuss cortex-to-meninges signaling pathways that could underlie migraine pain in response to endogenous events, such as cortical spreading depolarization (CSD), and explore future directions for the field.
+ Development from a zygote to an adult organism involves complex interactions among thousands of genes. These genes exhibit highly dynamic expression across space and time. Here we report a striking simplicity amidst this complexity: Despite individual gene expression variability, the eigengene--the principal component of gene expression--exhibits an invariant global spatial pattern throughout the embryonic and post-natal stages of the mouse brain. Furthermore, the mouse pattern is observed also in the larval zebrafish, suggesting that eigengene expression is conserved over 400 million years of evolution. We show that the eigengene pattern can be explained by a simple mitotic lineage model in which daughter cells' gene expression is similar to that of their parent, but cannot be explained by one in which gene expression arises through local cellular signaling. The constrained mitotic lineage gives rise naturally to a global eigengene expression hierarchy that could provide a bias toward the formation of its dual: a spatial hierarchy of long-range signal gradients. We propose that mitosis thus induces an address-like organization, which could have been co-opted by evolution for developmental processes that require positional information over a wide range of spatial scales, such as tissue patterning and axon navigation.
- in Trends in Neurosciences: In press on 2024-09-19 00:00:00 UTC.
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in bioRxiv: Neuroscience on 2024-09-20 00:00:00 UTC.
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- Antidepressant drugs promote neuronal plasticity, and activation of brain-derived neurotrophic factor (BDNF) signaling through its receptor neuronal receptor tyrosine kinase 2 (NTRK2 or TRKB) is among the critical steps in this process. These mechanisms are shared by typical slow-acting antidepressants, fast-acting ketamine, and psychedelic compounds, although the cellular targets of each drug differ. In this opinion, we propose that some of these antidepressants may directly bind to TRKB and allosterically potentiate BDNF signaling, among other possible effects. TRKB activation in parvalbumin-containing interneurons disinhibits cortical networks and reactivates a juvenile-like plasticity window. Subsequent rewiring of aberrant networks, coupled with environmental stimuli, may underlie its clinical antidepressant effects. The end-to-end hypothesis proposed may stimulate the search for new treatment strategies.
+ Previous functional magnetic resonance imaging (fMRI) studies have shown that activity in premotor and parietal brain-regions covaries with the intensity of upcoming grip-force. However, it remains unclear how information about the intended grip-force intensity is initially represented and subsequently transformed into a motor code before motor-execution. In this fMRI study, we used multivoxel pattern analysis (MVPA) to decode where and when information about grip-force intensities is parametrically coded in the brain. Human participants performed a delayed grip-force task in which one of four cued levels of grip-force intensity had to be maintained in working memory (WM) during a 9-second delay-period preceding motor execution. Using time-resolved MVPA, with a searchlight approach and support vector regression (SVR), we tested which brain regions exhibit multivariate WM codes of anticipated grip-force intensities. During an early delay-period, we observed above-chance decoding in the ventromedial prefrontal cortex (vmPFC). During a late delay-period, we found a network of action-specific brain regions, including the bilateral intraparietal sulcus (IPS), left dorsal premotor cortex (l-PMd) and supplementary motor areas (SMA). Additionally, cross-regression decoding was employed to test for temporal generalization of activation patterns between early and late delay-periods with those during cue presentation and motor execution. Cross-regression decoding indicated temporal generalization to the cue-period in the vmPFC, and to motor-execution in the l-IPS and l-PMd. Together, these findings suggest that the WM representation of grip-force intensities undergoes a transformation where the vmPFC encodes information about the intended grip-force, which is subsequently converted into a motor code in the l-IPS and l-PMd before execution.
- in Trends in Neurosciences: In press on 2024-09-19 00:00:00 UTC.
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in bioRxiv: Neuroscience on 2024-09-20 00:00:00 UTC.
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- The identity and function of local brain oscillators remain poorly understood. Liu et al. use mWAKE as a genetic entrée to uncover a local clock mechanism in the lateral amygdala that coordinates sensory perception and internal state in a time-dependent manner.
+ Brain Sciences, Vol. 14, Pages 940: How Sports Involvement and Brand Fit Influence the Effectiveness of Sports Sponsorship from the Perspective of Predictive Coding Theory: An Event-Related Potential (ERP)-Based Study
+ Brain Sciences doi: 10.3390/brainsci14090940
+ Authors:
+ Haonan Shi
+ Li Zhang
+ Hongfei Zhang
+ Jianlan Ding
+ Zilong Wang
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+ Background/Objectives: With the rapid expansion of the global sports market, the significance of sports sponsorship has attracted growing attention. However, during the golden age of the sports industry&rsquo;s development in China, international sports brand giants such as Nike, Adidas, and Under Armour have rapidly captured a substantial share of the Chinese sports consumer market through their distinctive product designs and varied marketing strategies. This has resulted in a highly competitive environment for China&rsquo;s sports goods industry. Therefore, fostering the improved development of domestic sports brands has become a crucial issue deserving of thorough scholarly investigation. This study examines how consumers&rsquo; differing levels of sports involvement and the degree of fit between the sponsoring brand and the sponsored event affect their cognitive and emotional responses to sports sponsorships. Methods: By employing Predictive Coding Theory and ERP (event-related potential) brainwave technology, this study delves into the psychological and neurobiological levels to analyze the impact of consumer sports involvement on the processing of sponsorship information. Results: The results indicate significant differences in cognitive and emotional responses between high-involvement and low-involvement consumers. Additionally, the fit between the sponsoring brand and the sponsored event also significantly affects consumers&rsquo; cognitive and emotional responses. These differences stem from consumers&rsquo; complex and sophisticated predictive coding models. Conclusions: This study not only provides scientific evidence for sports brands in selecting and executing sponsorship activities, but also offers new perspectives for evaluating and optimizing sponsorship effectiveness.
- in Neuron: In press on 2024-09-19 00:00:00 UTC.
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in Brain Sciences on 2024-09-20 00:00:00 UTC.
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- Fat and Dachsous interact in neighboring cells via their cadherin repeats to regulate cell behaviors and tissue shape. Strutt et al. show that interactions between two distinct cadherin regions in each molecule regulate the stability of Fat-Dachsous binding and modulate Fat-Dachsous function in the developing fly wing.
+ Brain Sciences, Vol. 14, Pages 939: Utility of Quantitative EEG in Neurological Emergencies and ICU Clinical Practice
+ Brain Sciences doi: 10.3390/brainsci14090939
+ Authors:
+ Misericordia Veciana de las Heras
+ Jacint Sala-Padro
+ Jordi Pedro-Perez
+ Beliu García-Parra
+ Guillermo Hernández-Pérez
+ Merce Falip
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+ The electroencephalogram (EEG) is a cornerstone tool for the diagnosis, management, and prognosis of selected patient populations. EEGs offer significant advantages such as high temporal resolution, real-time cortical function assessment, and bedside usability. The quantitative EEG (qEEG) added the possibility of long recordings being processed in a compressive manner, making EEG revision more efficient for experienced users, and more friendly for new ones. Recent advancements in commercially available software, such as Persyst, have significantly expanded and facilitated the use of qEEGs, marking the beginning of a new era in its application. As a result, there has been a notable increase in the practical, real-world utilization of qEEGs in recent years. This paper aims to provide an overview of the current applications of qEEGs in daily neurological emergencies and ICU practice, and some elementary principles of qEEGs using Persyst software in clinical settings. This article illustrates basic qEEG patterns encountered in critical care and adopts the new terminology proposed for spectrogram reporting.
- in Cell Reports: Current Issue on 2024-09-19 00:00:00 UTC.
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in Brain Sciences on 2024-09-20 00:00:00 UTC.
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- During zebrafish maternal-to-zygotic transition, massive mRNA changes are not observed at the protein level. mRNAs expressed only after genome activation are deposited as proteins since fertilization in both zebrafish and mouse. Further, da Silva Pescador et al. highlight the need to combine multiple omics to fully understand gene regulation.
+ Background The use of chemical pesticides without proper health literacy (HL) and necessary pesticide protective behaviors (PPB) can result in adverse effects on human health. Methods This study aims to determine if there is a correlation between HL and PPB among farmers in the Nakhon Ratchasima province, using a random sample of 464 farmers. Structured interviews consisted of three parts: 1. General information, 2. Health literacy (including knowledge, understanding, and other sub-aspects), and 3. Protective behaviors against chemical exposure. Each part of the questionnaire had a reliability index of 0.60 or higher. The reliability of the 2nd and 3rd parts of the questionnaire were as follows: sub-sections of part 2 had a Kuder-Richardson (KR-20) coefficient of 0.79 and Cronbach’s alpha (α) coefficient of 0.85-0.86, while part 3 had an α of 0.88. Risk of chemical exposure was assessed using a Cholinesterase Reactive Paper test administered by a finger-prick blood test. Data was analyzed using the Spearman correlation and binary logistic regression. The study was reviewed by the Human Research Ethics Committee with the approval date: August 9, 2021, and expiry date: August 9, 2022. Results Most participants had moderate levels of overall HL (48.8%) and PPB (44.6%). There was a statistically significant positive correlation between HL and PPB (rs(478) = 0.70, p<.005). Logistic regression analysis demonstrated that HL had a statistically significant positive association with PPB (p<.001, OR = 6.57, 95% CI 3.95, 10.94) and was associated with blood cholinesterase levels. Conclusions These findings highlight the need for increased health literacy among farmers in Thailand to ensure correct protective behaviors against chemical exposure and reduce the adverse effects of pesticide exposure on human health.
- in Cell Reports: Current Issue on 2024-09-19 00:00:00 UTC.
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in F1000Research on 2024-09-19 16:42:51 UTC.
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- Here, Xu et al. show that inhibition of de novo ceramide synthesis by either myriocin treatment or DES1 knockdown protects against lipid-induced hepatic insulin resistance independently of C16 ceramide concentration. Instead, these ceramide synthesis inhibitors mediate their effects to protect from lipid-induced hepatic insulin resistance via the PM-sn-1,2-diacylglycerol-PKCε-INSRT1150 phosphorylation pathway.
+ Background Organizations recognized the importance of workplace inclusion. However, up to date, few organizations had developed strategic initiatives to improve workplace diversity. This research examines the impact of awareness of inclusion, inclusive leadership, psychosocial capital, and meaningful engagement on employee’s inclusion in the context of Malaysia. Methods The study employed a quantitative survey approach and collected data through a questionnaire survey administered to 204 participants. Descriptive analysis, reliability analysis and multiple linear regression analysis were utilized to explore the relationships between the independent and dependent variables. Results The findings indicate a significant correlation between awareness of inclusion and psychosocial capital with employee’s inclusion. However, no significant correlations were found between inclusive leadership and meaningful engagement with employee’s inclusion. These results underscore the importance of fostering an inclusive culture and nurturing psychosocial support to enhance employee’s inclusion experiences in the workplace. Conclusion This study contributes to the knowledge by being one of the pioneer research in Malaysia that provides insights into the factors influencing employee’s inclusion in Malaysia. The findings is important for organizations, particularly small and medium enterprise in Malaysia to promote employee inclusion in a multi-racial diversity society.
- in Cell Reports: Current Issue on 2024-09-19 00:00:00 UTC.
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in F1000Research on 2024-09-19 16:25:26 UTC.
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- Konstantinidou et al. build and compare piRNA-generating genomic intervals (piRNA clusters) across seven species. Their comprehensive analysis uncovers a mechanism for the formation of piRNA clusters downstream of genes (piC-DoGs) in mammals and identifies three distinct classes of piRNA clusters in adult human testes.
+ Shade selection is one of the most important factors that determines the satisfaction of the patient with the dental prosthesis and thus the overall success of the treatment. Conventional methods of shade selection require the presence of existing teeth or past dental/photographic records. In the absence of these, shade selection becomes challenging and must be done subjectively and arbitrarily based on the patient’s age and sex. This study aims to assess the prevalence, satisfaction, and preference of tooth shades, investigating their correlation with age, sex, and skin shade in a diverse sample of 120 participants. Methods A total of 120 participants, evenly distributed among 60 males and 60 females, were surveyed. Participants were categorized into age groups (n=15) and asked about their satisfaction with existing tooth shades and their preferences. Results The most common existing tooth shade was Value 2 (52.5%). Statistical analysis using Chi-square tests revealed that Value 2 was the most desired shade among males and females alike, particularly in the age group of 41 to 50 years (p < 0.001). Shade 2L1.5 was the most prevalent (n=26), with Value 2 (59.16%) being the most sought-after shade, followed by Shade 2L1.5 (n=21), Shade 2M1 (n=18), Shade 1M1 (n=15), and Shade 2R1.5 (n=14). Existing tooth shades of Value 0 were the least common. The highest satisfaction with existing shades was observed in males aged 41 to 50 (n=15), followed by males aged 51 to 60 (n=14) and females aged 31 to 40 (n=12) and 41 to 50 (n=12). Significant differences in satisfaction were noted among males (p < 0.001). Conclusions This study reveals a consistent and strong preference among both males and females for tooth shades classified as Value 2, following the VITA Tooth-Guide 3D Master shade guide. This universal preference suggests the relevance and acceptance of this shade category across diverse patient groups.
- in Cell Reports: Current Issue on 2024-09-19 00:00:00 UTC.
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in F1000Research on 2024-09-19 16:22:41 UTC.
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- Lu et al. show that CSN5A is involved in chloroplast protein turnover, revealing a ubiquitin-dependent degradation pathway of intra-chloroplast proteins and CCVs jointly participated by CV and CSN5A.
+ Background Glioblastoma (GBM) is a clinically challenging primary brain tumor with poor survival outcome despite surgical resection and intensive chemoradiation. The metabolic heterogeneity of GBM can become biomarkers for treatment response, resistance, and outcome prediction. The aim of the study is to investigate metabolic distinctions between primary and recurrent GBM tissue and patient plasma to establish feasibility for metabolic profiling. Methods A single-center cohort study analyzed tissue and blood samples from 15 patients with GBM using untargeted metabolomic/lipidomic assays. Metabolomic, lipidomic, and biogenic amine analyses were conducted on GBM tissue and patient plasma at diagnosis and recurrence using untargeted mass spectrometry. The study utilized a small but longitudinally collected cohort to evaluate alteration in metabolites, lipids, and biogenic amines between specimens at diagnosis and recurrence. Results Exploratory analysis revealed significant alteration in metabolites, lipids, and biogenic amines between diagnostic and recurrent states in both tumor and plasma specimens. Notable metabolites differed at recurrence, including N-alpha-methylhistamine, glycerol-3-phosphate, phosphocholine, and succinic acid in tissue, and indole-3-acetate, and urea in plasma. Principal component analysis revealed distinct metabolomic profiles between tumor tissue and patient plasma. Distinct metabolic profiles were observed in GBM tissue and patient plasma at recurrence, demonstrating the feasibility of using metabolomic methodologies for longitudinal studies. One patient exhibited a unique tumor resistance signature at diagnosis, possibly indicating a high-risk metabolomic phenotype. Conclusions In this small cohort, the findings suggest the potential of metabolomic signatures of GBM tissue and patient plasma for risk stratification, outcome prediction, and the development of novel adjuvant metabolic-targeting therapies. The findings suggest metabolic discrepancies at diagnosis and recurrence in tissue and plasma, highlighting potential implications for evaluation of clinical response. The identification of significant changes in metabolite abundance emphasizes the need for larger studies using targeted metabolomics to validate and further explore these profiles.
- in Cell Reports: Current Issue on 2024-09-19 00:00:00 UTC.
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in F1000Research on 2024-09-19 16:19:17 UTC.
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- The Trp53 gene encodes several isoforms of elusive biological significance. Here, we show that mice lacking the Trp53 alternatively spliced (AS) exon, thereby expressing the canonical p53 protein but not isoforms with the AS C-terminus, have unexpectedly lost a male-specific protection against Myc-induced B-cell lymphomas. Lymphomagenesis was delayed in Trp53+/+Eμ-Myc males compared to Trp53ΔAS/ΔAS Eμ-Myc males, but also compared to Trp53+/+Eμ-Myc and Trp53ΔAS/ΔAS Eμ-Myc females. Pre-tumoral splenic cells from Trp53+/+Eμ-Myc males exhibited a higher expression of Ackr4, encoding an atypical chemokine receptor with tumor suppressive effects. We identified Ackr4 as a p53 target gene whose p53-mediated transactivation is inhibited by estrogens, and as a male-specific factor of good prognosis relevant for murine Eμ-Myc-induced and human Burkitt lymphomas. Furthermore, the knockout of ACKR4 increased the chemokine-guided migration of Burkitt lymphoma cells. These data demonstrate the functional relevance of alternatively spliced p53 isoforms and reveal sex disparities in Myc-driven lymphomagenesis.
+ Background Primary cam morphology, an acquired bony prominence at the head-neck junction of the femur, is highly prevalent in athlete populations, and causally associated with femoroacetabular impingement syndrome and early hip osteoarthritis. Experts agreed on key elements for primary cam morphology and a prioritised research agenda for the field. This research agenda will require higher-quality research to achieve meaningful progress on the aetiology, prognosis and treatment of primary cam morphology in athletes. Aim To explore stakeholders’ perspectives of high-quality research in the research field of primary cam morphology and its natural history. Methods Grounded in interpretive description, we used semi-structured interviews to explore stakeholders’ perspectives of high-quality research in the primary cam morphology research field. The framework for INcreasing QUality In patient-orientated academic clinical REsearch (INQUIRE) informed the interview guide. Audio-recorded interviews were transcribed and analysed using thematic analysis. We recruited a heterogenous and purposive maximum variation sample, drawing from a network of research contacts. Results Fifteen individuals, several with multiple perspectives on research quality in the field, participated. Exploring stakeholders’ perspectives on research quality through an established research quality framework (INQUIRE) illuminated areas for immediate action for research communities in the field of primary cam morphology and its natural history. We crafted five action inviting themes: research communities should: partner with athletes/patients; champion equity, diversity and inclusion; collaborate with one another; pursue open science; and nurture young scholars. Conclusion The findings of this study could inform concrete actions by research communities to pursue higher quality research—more research value and less waste—in the field of primary cam morphology and its natural history. Although the five action-inviting themes reflect contemporary trends in research, and could therefore be transferable to other areas of research, their practical application remains context- and field-specific.
- in eLife on 2024-09-19 00:00:00 UTC.
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in F1000Research on 2024-09-19 15:05:56 UTC.
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- The excessive cosolute densities in the intracellular fluid create a physicochemical condition called macromolecular crowding (MMC). Intracellular MMC entropically maintains the biochemical thermodynamic equilibria by favouring associative reactions while hindering transport processes. Rapid cell volume shrinkage during extracellular hypertonicity elevates the MMC and disrupts the equilibria, potentially ushering cell death. Consequently, cells actively counter the hypertonic stress through regulatory volume increase (RVI) and restore the MMC homeostasis. Here, we establish fluorescence anisotropy of EGFP as a reliable tool for studying cellular MMC and explore the spatiotemporal dynamics of MMC during cell volume instabilities under multiple conditions. Our studies reveal that the actin cytoskeleton enforces spatially varying MMC levels inside adhered cells. Within cell populations, MMC is uncorrelated with nuclear DNA content but anti-correlated with the cell spread area. Although different cell lines have statistically similar MMC distributions, their responses to extracellular hypertonicity vary. The intensity of the extracellular hypertonicity determines a cell's ability for RVI, which correlates with Nuclear Factor Kappa Beta (NFkB) activation. Pharmacological inhibition and knockdown experiments reveal that Tumour Necrosis Factor Receptor 1 (TNFR1) initiates the hypertonicity induced NFkB signalling and RVI. At severe hypertonicities, the elevated MMC amplifies cytoplasmic microviscosity and hinders Receptor Interacting Protein Kinase 1 (RIPK1) recruitment at the TNFR1 complex, incapacitating the TNFR1-NFkB signalling and consequently, RVI. Together, our studies unveil the involvement of TNFR1-NFkB signalling in modulating RVI and demonstrate the pivotal role of MMC in determining cellular osmoadaptability.
+ Background Ruptured abdominal aortic aneurysm (rAAA) is commonly fatal, with an overall mortality rate of nearly 90%, and the risk of subsequent rupture remains high, especially in large aneurysm diameters or progressive disease. Unfavorable neck anatomy in EVAR is linked to early graft failure and long-term complications. Recently, a novel multiple stiff wire (MSW) technique has been developed to overcome the challenges of hostile neck anatomy without introducing additional devices and procedural complexity. It has also been feasible in a series of elective cases. In this case, we report the first-ever utilization of the MSW technique in an emergency case of an acute contained rAAA with a conical-shaped, severely angulated neck who underwent Endovascular Aortic Repair (EVAR). Case presentation A 61-year-old man came with intermittent sharp stomach pain radiating to his back since three weeks ago. Physical examination showed elevated blood pressure and anemic conjunctiva. Laboratory examinations showed anemia, leukocytosis, elevated D-dimer level, high creatinine level, and low eGFR. CT-Scan Angiography (CTA) revealed severely hostile anatomy, a conical-shaped abdominal aorta aneurysm with a length of 13.2 cm and a maximum diameter of 9.3 cm with angulation of 90.1°. The patient was diagnosed with Ruptured AAA with a conical-shaped, severely angulated neck. Endovascular Aortic Repair (EVAR) management with MSW technique was planned for him. After four days, The patient was discharged in a clinically stable condition with optimal medical treatment and education. Conclusion The endovascular approach could be performed in emergency settings and has been proven to reduce length of stay, mortality, and morbidity rates. In this case, the endovascular approach with the MSW technique showed promising results for the patient.
- in eLife on 2024-09-19 00:00:00 UTC.
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in F1000Research on 2024-09-19 14:49:08 UTC.
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- Arpin was discovered as an inhibitor of the Arp2/3 complex localized at the lamellipodial tip of fibroblasts, where it regulated migration steering. Recently, we showed that arpin stabilizes the epithelial barrier in an Arp2/3-dependent manner. However, the expression and functions of arpin in endothelial cells (EC) have not yet been described. Arpin mRNA and protein are expressed in EC and downregulated by pro-inflammatory cytokines. Arpin depletion in Human Umbilical Vein Endothelial Cells causes the formation of actomyosin stress fibers leading to increased permeability in an Arp2/3-independent manner. Instead, inhibitors of ROCK1 and ZIPK, kinases involved in the generation of stress fibers, normalize the loss-of-arpin effects on actin filaments and permeability. Arpin-deficient mice are viable but show a characteristic vascular phenotype in the lung including edema, microhemorrhage, and vascular congestion, increased F-actin levels, and vascular permeability. Our data show that, apart from being an Arp2/3 inhibitor, arpin is also a regulator of actomyosin contractility and endothelial barrier integrity.
+ Background Traditional optimization methods often struggle to balance global exploration and local refinement, particularly in complex real-world problems. To address this challenge, we introduce a novel hybrid optimization strategy that integrates the Nelder-Mead (NM) technique and the Genetic Algorithm (GA), named the Genetic and Nelder-Mead Algorithm (GANMA). This hybrid approach aims to enhance performance across various benchmark functions and parameter estimation tasks. Methods GANMA combines the global search capabilities of GA with the local refinement strength of NM. It is first tested on 15 benchmark functions commonly used to evaluate optimization strategies. The effectiveness of GANMA is also demonstrated through its application to parameter estimation problems, showcasing its practical utility in real-world scenarios. Results GANMA outperforms traditional optimization methods in terms of robustness, convergence speed, and solution quality. The hybrid algorithm excels across different function landscapes, including those with high dimensionality and multimodality, which are often encountered in real-world optimization issues. Additionally, GANMA improves model accuracy and interpretability in parameter estimation tasks, enhancing both model fitting and prediction. Conclusions GANMA proves to be a flexible and powerful optimization method suitable for both benchmark optimization and real-world parameter estimation challenges. Its capability to efficiently explore parameter spaces and refine solutions makes it a promising tool for scientific, engineering, and economic applications. GANMA offers a valuable solution for improving model performance and effectively handling complex optimization problems.
- in eLife on 2024-09-19 00:00:00 UTC.
+
in F1000Research on 2024-09-19 14:47:04 UTC.
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- The Sonic hedgehog (Shh) signaling pathway controls embryonic development and tissue homeostasis after birth. This requires regulated solubilization of dual-lipidated, firmly plasma membrane-associated Shh precursors from producing cells. Although it is firmly established that the resistance-nodulation-division transporter Dispatched (Disp) drives this process, it is less clear how lipidated Shh solubilization from the plasma membrane is achieved. We have previously shown that Disp promotes proteolytic solubilization of Shh from its lipidated terminal peptide anchors. This process, termed shedding, converts tightly membrane-associated hydrophobic Shh precursors into delipidated soluble proteins. We show here that Disp-mediated Shh shedding is modulated by a serum factor that we identify as high-density lipoprotein (HDL). In addition to serving as a soluble sink for free membrane cholesterol, HDLs also accept the cholesterol-modified Shh peptide from Disp. The cholesteroylated Shh peptide is necessary and sufficient for Disp-mediated transfer because artificially cholesteroylated mCherry associates with HDL in a Disp-dependent manner, whereas an N-palmitoylated Shh variant lacking C-cholesterol does not. Disp-mediated Shh transfer to HDL is completed by proteolytic processing of the palmitoylated N-terminal membrane anchor. In contrast to dual-processed soluble Shh with moderate bioactivity, HDL-associated N-processed Shh is highly bioactive. We propose that the purpose of generating different soluble forms of Shh from the dual-lipidated precursor is to tune cellular responses in a tissue-type and time-specific manner.
+ by Diego A. Forero, Walter H. Curioso, Wei Wang
- in eLife on 2024-09-19 00:00:00 UTC.
+
in PLoS Computational Biology on 2024-09-19 14:00:00 UTC.
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- Hydrostatic pressure is a dominant environmental cue for vertically migrating marine organisms but the physiological mechanisms of responding to pressure changes remain unclear. Here, we uncovered the cellular and circuit bases of a barokinetic response in the planktonic larva of the marine annelid Platynereis dumerilii. Increased pressure induced a rapid, graded, and adapting upward swimming response due to the faster beating of cilia in the head multiciliary band. By calcium imaging, we found that brain ciliary photoreceptors showed a graded response to pressure changes. The photoreceptors in animals mutant for ciliary opsin-1 had a smaller sensory compartment and mutant larvae showed diminished pressure responses. The ciliary photoreceptors synaptically connect to the head multiciliary band via serotonergic motoneurons. Genetic inhibition of the serotonergic cells blocked pressure-dependent increases in ciliary beating. We conclude that ciliary photoreceptors function as pressure sensors and activate ciliary beating through serotonergic signalling during barokinesis.
+ by Wilson Wen Bin Goh, Mohammad Neamul Kabir, Sehwan Yoo, Limsoon Wong
+Author summary: Artificial Intelligence (AI) and Machine Learning (ML) models are increasingly deployed on biomedical and health data to shed insights on biological mechanism, predict disease outcomes, and support clinical decision-making. However, ensuring model validity is challenging. The 10 quick tips described here discuss useful practices on how to check AI/ML models from 2 perspectives—the user and the developer.
- in eLife on 2024-09-19 00:00:00 UTC.
+
in PLoS Computational Biology on 2024-09-19 14:00:00 UTC.
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- In the mammalian neocortex, inhibition is important for dynamically balancing excitation and shaping the response properties of cells and circuits. The various computational functions of inhibition are thought to be mediated by different inhibitory neuron types, of which a large diversity exists in several species. Current understanding of the function and connectivity of distinct inhibitory neuron types has mainly derived from studies in transgenic mice. However, it is unknown whether knowledge gained from mouse studies applies to the non-human primate, the model system closest to humans. The lack of viral tools to selectively access inhibitory neuron types has been a major impediment to studying their function in the primate. Here, we have thoroughly validated and characterized several recently developed viral vectors designed to restrict transgene expression to GABAergic cells or their parvalbumin (PV) subtype, and identified two types that show high specificity and efficiency in marmoset V1. We show that in marmoset V1, AAV-h56D induces transgene expression in GABAergic cells with up to 91–94% specificity and 79% efficiency, but this depends on viral serotype and cortical layer. AAV-PHP.eB-S5E2 induces transgene expression in PV cells across all cortical layers with up to 98% specificity and 86–90% efficiency, depending on layer. Thus, these viral vectors are promising tools for studying GABA and PV cell function and connectivity in the primate cortex.
+ by Sofia Batista Leite, Matthew A. Brooke, Annamaria Carusi, Andy Collings, Pierre Deceuninck, Jean-François Dechamp, Bronwen Dekker, Elisa De Ranieri, Emma Ganley, Annalisa Gastaldello, Fanglian He, Marcel LaFlamme, Ingrid Langezaal, James Morris, David Pamies, Monica Piergiovanni, Bernd Pulverer, David Sadler, Caroline Shamu, Vivian Siegel, Marco Straccia, Tracey L. Weissgerber
+
+Detailed method descriptions are essential for reproducibility, research evaluation, and effective data reuse. We summarize the key recommendations for life sciences researchers and research institutions described in the European Commission PRO-MaP report.
+
+Essential details about study methods are often missing from academic research papers in the life sciences, which can adversely affect reproducibility, undermine trust and impair researchers’ ability to reuse methods and data. This Perspective article describes PRO-MaP (Promoting Reusable and Open Methods And Protocols), which aims to increase and improve the reporting of detailed, structured and open methods and reusable step-by-step protocols in the life sciences.
- in eLife on 2024-09-19 00:00:00 UTC.
+
in PLoS Biology on 2024-09-19 14:00:00 UTC.
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- -Synuclein (Syn) is a major component of Lewy bodies (LBs) and Lewy neurites (LNs) which are pathological features of Parkinson's disease (PD) and Dementia with Lewy bodies. In the PD brain, with disease progression, LB/LN formation is propagated from the lower brainstem to the cerebral cortex. Prion-like cell-to-cell seed-transmission has been implicated as an underlying mechanism for Lewy-pathology propagation. However, the biochemical properties and production mechanism of those pathogenic seeds are unelucidated. In this study, we ascertained that the seeds released from pathological neurons that harbour LB/LN-like aggregates have the N-terminally truncated form of Syn. This N-terminal truncation is directly catalysed by SENP2, which is a well-known deSUMOylation enzyme. After SENP2 processing of recombinant Syn, the SDS-resistant high-molecular oligomer formation was promoted in vitro. Inhibition of SENP2 activity suppressed aggregate formation and propagation in cultured neurons and mouse brains. Thus, SENP2 might be a novel therapeutic target in LB diseases.
+ by Chonprakun Thagun, Masaki Odahara, Yutaka Kodama, Keiji Numata
+
+Plastids are pivotal target organelles for comprehensively enhancing photosynthetic and metabolic traits in plants via plastid engineering. Plastidial proteins predominantly originate in the nucleus and must traverse membrane-bound multiprotein translocons to access these organelles. This import process is meticulously regulated by chloroplast-targeting peptides (cTPs). Whereas many cTPs have been employed to guide recombinantly expressed functional proteins to chloroplasts, there is a critical need for more efficient cTPs. Here, we performed a comprehensive exploration and comparative assessment of an advanced suite of cTPs exhibiting superior targeting capabilities. We employed a multifaceted approach encompassing computational prediction, in planta expression, fluorescence tracking, and in vitro chloroplast import studies to identify and analyze 88 cTPs associated with Arabidopsis thaliana mutants with phenotypes linked to chloroplast function. These polypeptides exhibited distinct abilities to transport green fluorescent protein (GFP) to various compartments within leaf cells, particularly chloroplasts. A highly efficient cTP derived from Arabidopsis plastid ribosomal protein L35 (At2g24090) displayed remarkable effectiveness in chloroplast localization. This cTP facilitated the activities of chloroplast-targeted RNA-processing proteins and metabolic enzymes within plastids. This cTP could serve as an ideal transit peptide for precisely targeting biomolecules to plastids, leading to advancements in plastid engineering.
- in bioRxiv: Neuroscience on 2024-09-19 00:00:00 UTC.
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in PLoS Biology on 2024-09-19 14:00:00 UTC.
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- 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 target distance in single or multiple reference frames and encoded 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.
+
+High nicotine dose induces anxiety-like behavior in mice in the Open Field Test, alongside oxidative stress, proinflammatory cytokine secretion, and brain-derived neurotrophic factor (BDNF) reduction in brain regions. Cannabidiol acts as an anxiolytic, exhibiting antioxidant activities, reducing cytokines, and normalizing BDNF levels.
+
+ABSTRACT
+High doses of nicotine administered to rodents serve as a model for studying anxiety and test compounds' potential anxiolytic effects. At these doses, anxiety in rodents is accompanied by disruption of brain-derived neurotrophic factor (BDNF). The endocannabinoids and nicotine modulate several central nervous system processes via their specific receptors, impacting locomotion, anxiety, memory, nociception, and reward. Cannabidiol (CBD), an active ingredient of Cannabis sativa L., is devoid of psychoactive actions and has gained attention for its anxiolytic, antioxidant, and anti-inflammatory properties, among others. This work aims to examine the potential anxiety-reducing properties of CBD in a well-established experimental mouse model of anxiety-like behavior induced by high doses of nicotine on male C57BL/6 mice. In this context, the open-field behavioral test was specially conducted to assess CBD's effects on anxiety-like behavior and locomotion. Brain neuronal plasticity, modulated by BDNF, along with a diverse array of blood's metabolic markers, was examined as a means of evaluating systemic toxicity under various treatments. Finally, oxidative stress was evaluated through the measurement of glutathione (GSH), superoxide dismutase (SOD), and malondialdehyde (MDA), while pro-inflammatory cytokine assessments were conducted to evaluate redox status and immune system function. Our research suggests that CBD shows potential in reducing anxiety-like behaviors induced by high doses of nicotine, by mitigating changes in BDNF protein levels in cerebral hemispheres and cerebellum. At the same time, CBD targets specific liver enzymes, maintains tissue's systemic toxicity (i.e., renal, kidney, and pancreatic), balances redox status (SOD, GSH, and MDA), and regulates the secretion of pro-inflammatory cytokines (TNF-alpha and IL-6).
- in bioRxiv: Neuroscience on 2024-09-19 00:00:00 UTC.
+
in Journal of Neuroscience Research on 2024-09-19 11:54:37 UTC.
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- Turmeric is a centuries-old ethnomedicine in Asia. Previously our laboratory demonstrated in the adult life stage-specific (ALSS) Drosophila model of Parkinson disease (PD) that Curcumin (K)-mediated dopaminergic (DAergic) neuroprotection is absent in the transition stage of adult life during which late-onset neurodegenerative disorders like PD sets-in, suggesting its limitation as a therapeutic agent. The present study demonstrates that K can sequester the enhanced levels of brain oxidative stress (OS) during both adult life phases i.e. health and transition stages but confers neuroprotection only during the health phase. However, literature reviews illustrate that efficacy of supposed therapeutic agents was asserted by their ability to sequester OS in only young PD animal models. In this context, it is important to point out that despite encouraging results in animal models, therapeutic efforts to target the general state of OS failed to retard PD progression. To understand this paradigm, we further investigated ALSS regulation of molecular players in the brain of the ALSS fly PD model and discovered that K-mediated differential modulation of adaptive stress response through dFOXO contributes to health phase-specific neuroprotection. These observations suggest that apart from the study of OS markers; it is essential to understand the ALSS regulation of molecular players. The synergistic influence of OS and the ALSS dysfunctional molecular networks could be responsible for the DAergic neurodegeneration in PD. The insights suggest that sequestration of OS by a therapeutic agent is necessary, but inadequate to conclude its neuroprotective efficacy and push it to the next phase of preclinical/clinical evaluation.
+ Objective
+Periventricular nodular heterotopia (PVNH) is the most common neuronal heterotopia, frequently resulting in pharmaco-resistant epilepsy. Here, we characterize variables that predict good epilepsy outcomes following surgical intervention using stereo-electroencephalography (SEEG) -informed magnetic resonance-guided laser interstitial thermal therapy (MRgLITT).
+Methods
+A retrospective review of consecutive cases from a single high-volume epilepsy referral center identified patients who underwent SEEG evaluation for PVNH to characterize the intervention and outcomes.
+Results
+Thirty-nine patients underwent SEEG-guided MRgLITT of the seizure onset zone (SoZ) in PVNH and associated epileptic tissue. PVNH and polymicrogyria (PMG) were densely sampled with a mean of 16.5 (SD = 2)/209.4 (SD = 36.9) SEEG probes/recording contacts per patient. Ablation principally targeted just the PVNH and cortex that was abnormal on imaging was ablated (5 patients) only if implicated in the SoZ. Volumetric analyses revealed a high percentage of PVNH SoZ ablation (96.6%, SD = 5.3%) in unilateral and bilateral (92.9%, SD = 7.2%) cases. Mean follow-up duration was 31.4 months (SD = 20.9). Seizure freedom (ILAE 1) was excellent: unilateral PVNH without other imaging abnormalities, 80%; PVNH with mesial temporal sclerosis (MTS) or PMG, 63%; bilateral PVNH, 50%. SoZ ablation percentage significantly impacted surgical outcomes (p < 0.001).
+Interpretation
+PVNH plays a central role in seizure genesis as revealed by dense recordings and selective targeting by LITT. MRgLITT represents a transformative technological advance in PVNH-associated epilepsy with seizure control outcomes consistent with those seen in focal lesional epilepsies. In localized unilateral cases and otherwise normal imaging, PVNH ablation without invasive recordings may be considered, and this approach deserves to be explored further. ANN NEUROL 2024
- in bioRxiv: Neuroscience on 2024-09-19 00:00:00 UTC.
+
in Annals of Neurology on 2024-09-19 10:32:58 UTC.
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- The function of microglia during progression of Alzheimer's disease (AD) can be investigated using mouse models that enable genetic manipulation of microglial subpopulations in a temporal manner. We developed a mouse strain that expresses destabilized-domain Cre recombinase (DD-Cre) from the Cst7 locus (Cst7DD-Cre) and tested this in 5xFAD amyloidogenic, Ai14 tdTomato cre-reporter line mice. Dietary administration of trimethoprim to induce DD-Cre activity produces long-term labeling in disease associated microglia (DAM) without evidence of leakiness, with tdTomato-expression restricted to cells surrounding plaques. Using this model, we found that DAMs are a subset of plaque-associated microglia (PAMs) and their transition to DAM increases with age and disease stage. Spatial transcriptomic analysis revealed that tdTomato+ cells show higher expression of disease and inflammatory genes compared to other microglial populations, including non-labeled PAMs. This model should allow inducible cre-loxP targeting of DAMs, without leakiness.
+ Author(s): Ian Braga, Emmanuel Pereira, and Lucas Wardil
Here, we derive stochastic adaptive dynamics from the microscopic death-birth process by explicitly modeling the trait variation from offspring to parent in each reproductive event, thereby accounting for a highly polymorphic population. This generalization enables the construction of a quantitative…
[Phys. Rev. E 110, L032401] Published Thu Sep 19, 2024
- in bioRxiv: Neuroscience on 2024-09-19 00:00:00 UTC.
+
in Physical Review E: Biological physics on 2024-09-19 10:00:00 UTC.
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- Daily rhythms in mosquito attraction to humans are thought to drive biting patterns and contribute to disease transmission dynamics. Behavioral rhythms in many insects are controlled by specialized clock cells in the brain that are coordinated by the neuropeptide Pigment-Dispersing Factor (PDF). We show that female Aedes aegypti mosquitoes with genetically disrupted PDF display altered daily behavioral timing with reduced locomotor activity and biting in the morning. Using an automated behavioral tracking system, we also report that mosquitoes exhibit daily modulation of response persistence to the host cue carbon dioxide and loss of PDF alters this pattern. These findings indicate that PDF regulates temporal features of host-seeking behavior that promote biting success at specific times of day and may underlie blood feeding patterns observed in the field.
+ Background Major depressive disorder (MDD) and schizophrenia are linked to accelerated aging leading to reduced lifespan, health span and cognitive decline. Cellular senescence, in which cells lose proliferative capacity and develop a senescence-associated secretory phenotype (SASP), plays a role in this process. Emerging research suggests that the senolytic regimen of dasatinib+quercetin (D+Q) reduces senescent cells, potentially mitigating age-related health and cognitive decline. This pilot study aims to assess the feasibility and safety of D+Q in older adults with schizophrenia, schizoaffective disorder, and treatment-resistant depression (TRD). Methods This single-center study will recruit 30 participants total aged 50 years or older with schizophrenia/schizoaffective disorder or 60 years or older with TRD; the difference in age limits is because individuals with schizophrenia are biologically about 10 years older than general population owing to metabolic burden. Each participant will receive two consecutive days of 100 mg oral dasatinib plus 1250 mg oral quercetin at baseline and weeks one through three, (i.e., two days on, five days off) along with lifestyle risk management education. Questionnaires and assessments will measure health and cognitive function as well as psychiatric function at baseline, week 10, and one year. Magnetic Resonance Imaging (MRI) will measure structural and functional brain health at baseline and 10 weeks. Blood sampling for SASP testing will occur at seven time points: baseline, weeks one through four, week 10, and one year. Conclusion This pilot aims to evaluate the safety and feasibility of the senolytic regimen and D+Q’s potential to counteract accelerated aging in adults with schizophrenia/schizoaffective disorder and TRD. Trial registration Dasatinib Plus Quercetin for Accelerated Aging in Mental Disorders is registered on ClinicalTrials.gov: NCT05838560; posted May 1, 2023.
- in bioRxiv: Neuroscience on 2024-09-19 00:00:00 UTC.
+
in F1000Research on 2024-09-19 09:43:15 UTC.
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- Rhythms are intrinsic to biological processes across temporal and spatial scales. In the brain, the synchronized oscillatory activity of neurons creates collective rhythms that are essential for complex functions. While this is a recognized phenomenon in the mammalian brain, information about insect neuronal synchrony and its underlying mechanisms is scarce. In the fly brain, neuronal oscillations were reported in individual lateral ventral neurons (LNvs), which play a key role in circadian and sleep behaviors. However, it is still unclear whether and how these participate in a collective rhythm. In this work, we perform thorough whole-cell patch clamp recordings of LNvs, and demonstrate consistent membrane potential oscillations. We show that oscillations degrade over time, and disappear upon exposure to an acetylcholine receptor blocker. Together with a flat phase response curve, these results suggest that oscillations are exogenously produced. Prompted by these results, we propose a generic forced oscillator theory that can account for the experimental phase response. The theory further predicts that neurons with similar properties should oscillate in synchrony with zero lags, while neurons with different properties may show coherent oscillations with non-zero lags. We confirm this prediction through simultaneous patch clamp recordings of neuronal pairs, revealing that large LNvs are consistently advanced relative to small LNvs. Additionally, we find that other neurons in the accessory medulla also exhibit coherent membrane potential oscillations, with diverse lags. Our findings suggest the intriguing possibility that brain waves may arise from collective neuronal activity within this region of the fly brain.
+ Biopesticides are pest control products derived from natural sources such as microbes, macro-organisms (insects and pathogens), plant extracts, and certain minerals. Many biopesticides are considered environmentally safe and can complement or substitute conventional chemical pesticides. They can also be highly specific or broad spectrum with a unique mode of action controlling a wide range of pest species. Due to their target-specificity and low to no environmental residuality, biopesticides conform to the 3 pillars of Climate-Smart Agriculture, the Sustainable Development Goals, and ultimately, the Paris Agreement. This review focuses largely on microbial biopesticides derived from fungi, bacteria, viruses, and nematodes. It discusses (i) the various microbial biopesticide formulations, (ii) the mode of microbial biopesticide action, (iii) the factors that affect the potential efficacy of biopesticides, (iv) challenges to the adoption of microbial biopesticides, and (v) the role of microbial biopesticides in Integrated Pest Management programs. Finally, advancements in application techniques, as well as future research directions and gaps are highlighted.
- in bioRxiv: Neuroscience on 2024-09-19 00:00:00 UTC.
+
in F1000Research on 2024-09-19 09:40:49 UTC.
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- Functional MRI (fMRI) is an important tool for investigating functional networks. However, the widely used fMRI with T2*-weighted imaging in rodents has the problem of signal lack in the lateral ventral area of forebrain including the amygdala, which is essential for not only emotion but also noxious pain. Here, we scouted the zero-echo time (ZTE) sequence, which is robust to magnetic susceptibility and motion-derived artifacts, to image activation in the whole brain including the amygdala following the noxious stimulation to the hind paw. ZTE exhibited higher spatial and temporal signal-to-noise ratios than conventional fMRI sequences. Electrical sensory stimulation of the hind paw evoked ZTE signal increase in the primary somatosensory cortex. Formalin injection into the hind paw evoked early and latent change of ZTE signals throughout the whole brain including the subregions of amygdala. Furthermore, resting-state fMRI using ZTE demonstrated the functional connectivity, including that of the amygdala. These results indicate the feasibility of ZTE for whole brain fMRI, including the amygdala and we first show acute and latent activity in different subnuclei of the amygdala complex after nociceptive stimulation.
+ Science, Volume 385, Issue 6715, September 2024.
- in bioRxiv: Neuroscience on 2024-09-19 00:00:00 UTC.
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in Science on 2024-09-19 07:00:00 UTC.
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- Transcardiac perfusion of fixative agent is generally recommended for quality preparations for cerebral histology, ensuring rapid and deep penetration in the tissue to preserve the most fragile brain structures. Despite being performed under anesthesia and with proper analgesia, this procedure is cumbersome for the experimenter and raises ethical questions. Recently, alternative protocols have been proposed, based on prior sacrifice of the animal followed by an injection of a fixative agent into the circulation. These so-called post-mortem perfusion protocols should in theory ensure an equivalent quality of tissue fixation, without exposing live animals to a procedure. Before adopting this new method, it is necessary to validate that sample quality is equivalent, ensuring the validity of scientific results. We performed a parallel comparison of several protocols of tissue fixation, by transcardiac or post-mortem perfusion, and measured the impact on the maintenance of axonal structures, dendritic spines, and mitochondrial morphology. Our results showed that histological parameters show variable sensitivity to perfusion condition and fixative used. For instance, axon fragmentation and altered mitochondrial morphology were observed in post-mortem perfusion groups. We furthermore determined that fixation condition had a variable effect on immunostaining, impacting detected expression level or pattern. Our results serve as a guide to orient the experimenter in selecting the best condition for optimal tissue fixation, which minimizes animal suffering while guaranteeing the integrity of the biological results obtained.
+ Science, Volume 385, Issue 6715, Page 1282-1282, September 2024.
- in bioRxiv: Neuroscience on 2024-09-19 00:00:00 UTC.
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in Science on 2024-09-19 05:59:01 UTC.
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- Mendoza-Halliday, Major et al. 2024 ("The Paper") advocates a local field potential (LFP)-based approach to functional identification of cortical layers during "laminar" (simultaneous recordings from all cortical layers) multielectrode recordings in nonhuman primates (NHPs). The Paper describes a "ubiquitous spectrolaminar motif" in the primate neocortex: 1) 75-150 Hz power peaks in the supragranular layers, 2) 10-19 Hz power peaks in the infragranular layers and 3) the crossing point of their laminar power gradients identifies layer 4 (L4). Identification of L4 is critical in general, but especially for The Paper as the "motif" discovery is couched within a framework whose central hypothesis is that gamma activity originates in the supragranular layers and reflects feedforward activity, while alpha-beta activity originates in the infragranular layers and reflects feedback activity. In an impressive scientific effort, The Paper analyzed laminar data from 14 cortical areas in 2 prior macaque studies and compared them to marmoset, mouse and human data to further bolster the canonical nature of the motif. Identification of such canonical principles of brain operation is clearly a topic of broad scientific interest. Similarly, a reliable online method for L4 identification would be of broad scientific value for the rapidly increasing use of laminar recordings using numerous evolving technologies. Despite The Paper's strengths, and its potential for scientific impact, a series of concerns that are fundamental to the analysis and interpretation of laminar activity profile data in general, and local field potential (LFP) signals in particular, led us to question its conclusions. We thus evaluated the generality of The Paper's methods and findings using new sets of data comprised of stimulus-evoked laminar response profiles from primary and higher-order auditory cortices (A1 and belt cortex), and primary visual cortex (V1). The rationale for using these areas as a test bed for new methods is that their laminar anatomy and physiology have already been extensively characterized by prior studies, and there is general agreement across laboratories on key matters like L4 identification. Our analyses indicate that The Paper's findings do to generalize well to any of these cortical areas. In particular, we find The Paper's methods for L4 identification to be unreliable. Moreover, both methodological and statistical concerns, outlined below and in the supplement, question the stated prevalence of the motif in The Paper's published dataset. After summarizing our findings and related broader concerns, we briefly critique the evidence from biophysical modeling studies cited to support The Paper's conclusions. While our findings are at odds with the proposition of a ubiquitous spectrolaminar motif in the primate neocortex, The Paper already has, and will continue to spark debate and further experimentation. Hopefully this countervailing presentation will lead to robust collegial efforts to define optimal strategies for applying laminar recording methods in future studies.
+ Science, Volume 385, Issue 6715, Page 1281-1281, September 2024.
- in bioRxiv: Neuroscience on 2024-09-19 00:00:00 UTC.
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in Science on 2024-09-19 05:59:01 UTC.
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- This study aims to investigate the impact of vocabulary acquisition through short-term classroom learning and its relation to broader forms of vocabulary learning through long-term exposure in daily life. Through a two week of "learning sprint" in collaboration with a local elementary school and EEG-Steady State Visual Evoked Potentials (EEG SSVEP) paradigm, we assessed new vocabulary learning in first and second graders within their pedagogical environment. We then compared the results with the word frequency effect, a well-established phenonmenon that reflects long-term vocabulary learning. After two weeks of classroom instruction, newly acquired words elicited neural responses similar to those of high-frequency words, with the effect significantly correlated with children's phonological decoding skills. Additionally, we successfully replicated the word frequency effect using the SSVEP paradigm for the first time. These findings highlight the potential of the "learning sprint" model for conducting neuroscience research in authentic educational settings, thereby fostering a stronger connection between education and neuroscience.
+ Science, Volume 385, Issue 6715, Page 1331-1337, September 2024.
- in bioRxiv: Neuroscience on 2024-09-19 00:00:00 UTC.
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in Science on 2024-09-19 05:59:01 UTC.
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- Motor rehabilitation is a therapeutic process to facilitate functional recovery in people with spinal cord injury (SCI). However, its efficacy is limited to areas with remaining sensorimotor function. Spinal cord stimulation (SCS) creates a temporary prosthetic effect that may allow further rehabilitation-induced recovery in individuals without remaining sensorimotor function, thereby extending the therapeutic reach of motor rehabilitation to individuals with more severe injuries. In this work, we report our first steps in developing a non-invasive brain-spine interface (BSI) based on electroencephalography (EEG) and transcutaneous spinal cord stimulation (tSCS). The objective of this study was to identify EEG-based neural correlates of lower limb movement in the sensorimotor cortex of unimpaired individuals and to quantify the performance of a linear discriminant analysis (LDA) decoder in detecting movement onset from these neural correlates. Our results show that initiation of knee extension was associated with event-related desynchronization in the central-medial cortical regions at frequency bands between 4-44 Hz. Our neural decoder using (8-12 Hz), low {beta} (16-20 Hz), and high {beta} (24-28 Hz) frequency bands achieved an average area under the curve (AUC) of 0.83 {+/-} 0.06 s.d. (n = 7) during a cued movement task offline. Generalization to imagery and uncued movement tasks served as positive controls to verify robustness against movement artifacts and cue-related confounds, respectively. With the addition of real-time decoder-modulated tSCS, the neural decoder performed with an average AUC of 0.81 {+/-} 0.05 s.d. (n = 9) on cued movement and 0.68 {+/-} 0.12 s.d. (n = 9) on uncued movement. Our results suggest that the decrease in decoder performance in uncued movement may be due to differences in underlying cortical strategies between conditions. Furthermore, we explore alternative applications of the BSI system by testing neural decoders trained on uncued movement and imagery tasks. By developing a non-invasive BSI, tSCS can be timed to be delivered only during voluntary effort, which may have implications for improving rehabilitation.
+ Science, Volume 385, Issue 6715, Page 1338-1347, September 2024.
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- The striatum consists of two anatomically and neurochemically distinct compartments, striosomes and the matrix, which receive dopaminergic inputs from the midbrain and exhibit distinct dopamine release dynamics in acute brain slices. Striosomes comprise approximately 15% of the striatum by volume and are distributed mosaically. Therefore, it is difficult to selectively record dopamine dynamics in striosomes using traditional neurochemical measurements in behaving animals, and it is unclear whether distinct dynamics play a role in associative learning. In this study, we used transgenic mice selectively expressing Cre in striosomal neurons, combined with a fiber photometry technique, to selectively record dopamine release in striosomes during classical conditioning. Water-restricted mice could distinguish the conditioned stimulus (CS) associated with saccharin water from the air-puff-associated CS. The air-puff-associated CS evoked phasic dopamine release only in striosomes. Furthermore, air puff presentation induced dopamine release to striosomal neurons but suppressed release to putative matrix neurons. These findings suggest that dopamine is released in a differential manner in striosomes and the matrix in behaving animals and that dopamine release in striosomes is preferentially induced by the air-puff-associated CS and air puff presentation. These findings support the hypothesis that striosomal neurons play a dominant role in aversive stimuli prediction.
+ Science, Volume 385, Issue 6715, Page 1354-1359, September 2024.
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- Microglia, the brains resident macrophages, can be reconstituted by surrogate cells - a process termed "microglia replacement." To expand the microglia replacement toolkit, we here introduce estrogen-regulated (ER) homeobox B8 (Hoxb8) conditionally immortalized macrophages, a cell model for generation of immune cells from murine bone marrow, as a versatile model for microglia replacement. We find that ER-Hoxb8 macrophages are highly comparable to primary bone marrow-derived (BMD) macrophages in vitro, and, when transplanted into a microglia-free brain, engraft the parenchyma and differentiate into microglia-like cells. Furthermore, ER-Hoxb8 progenitors are readily transducible by virus and easily stored as stable, genetically manipulated cell lines. As a demonstration of this systems power for studying the effects of disease mutations on microglia in vivo, we created stable, Adar1-mutated ER-Hoxb8 lines using CRISPR-Cas9 to study the intrinsic contribution of macrophages to Aicardi-Goutieres Syndrome (AGS), an inherited interferonopathy that primarily affects the brain and immune system. We find that Adar1 knockout elicited interferon secretion and impaired macrophage production in vitro, while preventing brain macrophage engraftment in vivo - phenotypes that can be rescued with concurrent mutation of Ifih1 (MDA5) in vitro, but not in vivo. Lastly, we extended these findings by generating ER-Hoxb8 progenitors from mice harboring a patient-specific Adar1 mutation (D1113H). We demonstrated the ability of microglia-specific D1113H mutation to drive interferon production in vivo, suggesting microglia drive AGS neuropathology. In sum, we introduce the ER-Hoxb8 approach to model microglia replacement and use it to clarify macrophage contributions to AGS.
+ Science, Volume 385, Issue 6715, Page 1366-1375, September 2024.
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- Neuroscience research has extensively explored the commonality of neural representations of sensory stimuli across individuals to uncover universal neural mechanisms in the encoding of sensory information. To compare neural representations across different brains, Representational Similarity Analysis (RSA) has been used, which focuses on the similarity structures of neural representations for different stimuli. Despite the broad applicability and utility of RSA, one limitation is that its conventional framework assumes that neural representations of particular stimuli correspond directly to those of the same stimuli in different brains. This assumption excludes the possibility that neural representations correspond differently and limits the exploration of finer structural similarities. To overcome this limitation, we propose to use an unsupervised alignment framework based on Gromov-Wasserstein Optimal Transport (GWOT) to compare similarity structures without presupposing stimulus correspondences. This method allows for the identification of optimal correspondence between neural representations of stimuli based solely on internal neural representation relationships, and thereby provides a more detailed comparison of neural similarity structures across individuals. We applied this unsupervised alignment to investigate the commonality of representational similarity structures of natural scenes, using large datasets of Neuropixels recordings in mice and fMRI recordings in humans. We found that the similarity structure of neural representations in the same visual cortical areas can be well aligned across individuals in an unsupervised manner in both mice and humans. In contrast, we found that the degree of alignment across different brain areas cannot be fully explained by proximity in the visual processing hierarchy alone, but also found some reasonable alignment results, such that the similarity structures of higher-order visual areas can be well aligned with each other but not with lower-order visual areas. We expect that our unsupervised approach will be useful for revealing more detailed structural commonalities or differences that may not be captured by the conventional supervised approach.
+ Science, Volume 385, Issue 6715, Page 1360-1366, September 2024.
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- Background: Degeneration of optic nerve (ON) axons and loss of retinal ganglion cells (RGCs) are the pathological hallmarks of Primary Open Angle Glaucoma (POAG). Elevation of intraocular pressure (IOP) due to dysfunction of trabecular meshwork (TM) is known to induce neurodegeneration. However, the early pathological events of glaucomatous neurodegeneration are poorly understood due to lack of robust and faithful mouse model that replicates all features of human POAG. Here, we report the generation and characterization of a novel Cre-inducible transgenic mouse model of myocilin (MYOC), the leading known genetic cause of POAG. Using this model, we further explore early pathological events of glaucomatous neurodegeneration due to chronic IOP elevation. Methods: We generated a Cre-inducible transgenic mouse model expressing DsRed-tagged Y437H mutant of human myocilin (Tg.CreMYOCY437H). A single intravitreal injection of helper adenovirus (HAd) 5 expressing empty cassette or Cre was performed in adult Tg.CreMYOCY437H mice, and glaucoma phenotypes including IOP, outflow facility, structural and functional loss of RGCs, ON degeneration, gliosis, and axonal transport deficits were examined at various stages of IOP elevation. Results: An intravitreal injection of HAd5-Cre led to selective MYOC expression in the TM at the level similar to endogenous Myoc. Expression of mutant MYOC induced biochemical and ultrastructural changes in TM leading to reduced outflow facility and significant IOP elevation. Notably, sustained IOP elevation led to significant functional and structural loss of RGCs and progressive ON degeneration. Glaucomatous neurodegeneration was associated with activation of astrocytes and neurodegenerative changes in the optic nerve head (ONH) region. Remarkably, chronic IOP elevation blocked anterograde axonal transport at the ONH prior to axonal degeneration and RGC loss. Interestingly, impaired axonal transport was associated with loss of cytoskeleton proteins including microtubules and neurofilaments resulting into accumulation of mitochondria in the ONH and neuronal dysfunction. Conclusions: Our studies indicate that Cre-inducible Tg.CreMYOCY437H mice recapitulates all glaucoma phenotypes observed in POAG patients. Importantly, sustained IOP elevation impairs axonal transport at ONH leading to glaucomatous neurodegeneration.
+ Science, Volume 385, Issue 6715, Page 1347-1354, September 2024.
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- Substantia nigra pars compacta (SNc) dopaminergic (DA) neurons are characterized by specific morphological and electrophysiological properties. First, in ~90% of the cases, their axon arises from an axon-bearing dendrite (ABD) at highly variable distances from the soma. Second, they display a highly regular pattern of spontaneous activity (aka pacemaking) and a broad action potential (AP) that faithfully back-propagate through the entire dendritic arbor. In previous studies (Moubarak et al., 2019; Moubarak et al., 2022), we demonstrated that the presence of a high density of sodium current in the ABD and the complexity of this dendrite played a critical role in the robustness of pacemaking and setting the half-width of the AP. In the current study, we investigated the postnatal development of both morphology and AP shape in SNc DA neurons in order to determine when and how the mature electrophysiological phenotype of these neurons was achieved. To do so, we performed electrophysiological recordings of SNc DA neurons at 4 postnatal ages (P3, P7, P14, P21) and fully reconstructed their dendritic and proximal axon morphology. Our results show that several morphological parameters, including the length of the ABD, display abrupt changes between P7 and P14, such that a mature morphology is reached by P14. We then showed that AP shape followed a similar timecourse. Using realistic multicompartment Hodgkin-Huxley modeling, we then demonstrated that the rapid morpho-electrical maturation of SNc DA neurons likely arises from synergistic increases in dendritic length and in somatodendritic sodium channel density.
+ Science, Volume 385, Issue 6715, Page 1327-1331, September 2024.
- in bioRxiv: Neuroscience on 2024-09-19 00:00:00 UTC.
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- Copper plays crucial roles in various physiological functions of the nervous and immune systems. Dysregulation of copper homeostasis is linked to several diseases, including neurodegenerative diseases. Since dysfunctional microglial immunity can contribute to such diseases, we investigated the role of copper in microglial immunity. We found that both increased and decreased copper levels induced by chemical treatments suppresses lipopolysaccharide (LPS)-mediated inflammation in microglial cells, as determined by RT-qPCR analysis. RNA sequencing (RNA-seq) analysis confirmed that increased copper level reduces the inflammatory response to LPS; however, it also showed that decreased copper level affects genes involved in cell proliferation, transcription, and autophagosome regulation. These findings suggest that copper is vital for maintaining normal immune function in microglia, and both copper excess and deficiency can disrupt microglial immunity.
+ Science, Volume 385, Issue 6715, Page 1318-1321, September 2024.
- in bioRxiv: Neuroscience on 2024-09-19 00:00:00 UTC.
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- Survey-based evidence suggests that men experience a distinct post-ejaculation affective state1,2, marked by intense pleasure sometimes compared to the euphoric rush from intravenous injection of opioid drugs such as heroin3. However, the intrinsic neural circuit mechanisms underlying the ejaculation-triggered affective state remain unclear. Here, we discovered that Calbindin1-expressing (Calb1+) neurons in the preoptic area (POA) of the hypothalamus, an evolutionarily conserved regulatory region for male mating behavior4, are specifically activated during ejaculation in male mice. Inhibiting POA Calb1+ neurons prolongs mating and delays ejaculation. Importantly, POA Calb1+ neurons transmit the ejaculation signal and activate proopiomelanocortin-expressing (Pomc+) neurons in the arcuate nucleus of the hypothalamus, which show robust and sustained activity lasting for tens of seconds, specifically upon ejaculation. This activity is accompanied by elevated levels of {beta}-endorphins5, opioid peptides secreted by Pomc+ neurons, post-ejaculation in male mice. Optogenetic activation of Pomc+ neurons increases {beta}-endorphins levels and conditioned placed preference, similar to ejaculation. Conversely, intracerebroventricular (i.c.v.) infusion of drugs blocking Pomc neuropeptides signaling eliminates ejaculation-conditioned place preference. Collectively, these results elucidate an intra-hypothalamic circuit from POA Calb1+ neurons to arcuate Pomc+ neurons that coordinate {beta}-endorphin release with ejaculation, shedding light on the neurobiological basis of the post-ejaculation affective state.
+ Science, Volume 385, Issue 6715, Page 1288-1289, September 2024.
- in bioRxiv: Neuroscience on 2024-09-19 00:00:00 UTC.
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- Primary sensory axons fail to regenerate into the spinal cord following dorsal root injury leading to permanent sensory deficits. Re-entry is prevented at the dorsal root entry zone (DREZ), the CNS-PNS interface. Current approaches for promoting DR regeneration across the DREZ have had some success, but sustained, long-distance regeneration, particularly of large-diameter myelinated axons, still remains a formidable challenge. We have previously shown that induced expression of constitutively active B-RAF (kaBRAF) enhanced the regenerative competence of injured DRG neurons in adult mice. In this study, we investigated whether robust intraspinal regeneration can be achieved after a cervical DR injury by selective expression of kaBRAF alone or in combination with deletion of the myelin-associated inhibitors or neuron-intrinsic growth suppressors (PTEN or SOCS3). We found that kaBRAF promoted some axon regeneration across the DREZ but did not produce significant functional recovery by two months. Supplementary deletion of Nogo, MAG, and OMgp only modestly improved kaBRAF-induced regeneration. Deletion of PTEN or SOCS3 individually or in combination failed to promote any growth across the DREZ. In marked contrast, simultaneous deletion of PTEN, but not SOCS3, dramatically enhanced kaBRAF-mediated regeneration enabling many more axons to penetrate the DREZ and grow deep into the spinal cord. This study shows that dual activation of BRAF-MEK-ERK and PI3K-Akt-mTOR signaling is an effective strategy to stimulate robust intraspinal DR regeneration.
+ Science, Volume 385, Issue 6715, Page 1292-1297, September 2024.
- in bioRxiv: Neuroscience on 2024-09-19 00:00:00 UTC.
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- Grid cells, known for their hexagonal spatial firing patterns, are widely regarded as essential to the brain's internal representation of the external space. Maintaining an accurate internal spatial representation is challenging when an animal is running at high speeds, as its self-location constantly changes. Previous studies of speed modulation of grid cells focused on individual or pairs of grid cells, yet neurons represent information via collective population activity. Population noise covariance can have significant impact on information coding that is impossible to infer from individual neuron analysis. To address this issue, we developed a novel Gaussian Process with Kernel Regression (GKR) method that allows study the simultaneously recorded neural population representation from an information geometry framework. We applied GKR to grid cell population activity, and found that running speed increases both grid cell activity toroidal-like manifold size and noise strength. Importantly, the effect of manifold dilation outpaces the effect of noise increasement, as indicated by the overall higher Fisher information at increasing speeds. This result is further supported by improved spatial information decoding accuracy at high speeds. Finally, we showed that the existence of noise covariance is information detrimental because it causes more noise projected onto the manifold surface. In total, our results indicate that grid cell spatial coding improves with increasing running speed. GKR provides a useful tool to understand neural population coding from an intuitive information geometric perspective.
+ Science, Volume 385, Issue 6715, Page 1305-1310, September 2024.
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- Oxytocin (OT) neurons in the hypothalamic paraventricular nucleus (PVH) play an important role in a range of physiological and behavioral processes, including the initiation of milk ejection and the regulation of parental behaviors in mothers. However, their activity patterns at the single-cell level remain poorly understood. Using microendoscopic Ca2+ imaging in freely moving mother mice, we demonstrate highly correlated pulsatile activity among individual OT neurons during lactation. The number of OT neurons engaged in the pulsatile activity, along with the characteristics of individual waveforms, was dynamically modulated by lactation and weaning experiences. Notably, only approximately 10% of the imaged OT neurons exhibited a significantly elevated response during pup retrieval, a hallmark of maternal behaviors, with a magnitude 18 times smaller than that observed during lactation. Collectively, these findings demonstrate the utility of microendoscopic imaging for PVH OT neurons and highlight the flexible adjustments of their individual activity patterns in freely behaving mother mice.
+ Science, Volume 385, Issue 6715, Page 1298-1305, September 2024.
- in bioRxiv: Neuroscience on 2024-09-19 00:00:00 UTC.
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- Advancements in calcium indicators and optical techniques have made optical neural recording a common tool in neuroscience. As the volume of optical neural recording data grows, streamlining the data analysis pipelines for image preprocessing, signal extraction, and subsequent neural activity analyses becomes essential. There are a number of challenges in optical neural data analysis. 1) The quality of original and processed data needs to be carefully examined at each step. 2) As there are numerous image preprocessing, cell extraction, and activity analysis algorithms, each with pros and cons, experimenters need to implement or install them to compare and select optimal methods and parameters for each step of processing. 3) To ensure the reproducibility of the research, each analysis step needs to be recorded in a systematic way. 4) For data sharing and meta-analyses, adoption of standard data formats and processing protocols is required. To address these challenges, we developed Optical Neuroimage Studio (OptiNiSt) (https://github.com/oist/optinist), a framework for intuitively creating calcium data analysis pipelines that are scalable, extendable, and reproducible. OptiNiSt includes the following features. 1) Researchers can easily create analysis pipelines by selecting multiple processing modules, tuning their parameters, and visualizing the results at each step through a graphic user interface in a web browser. 2) In addition to common analytical tools that are pre-installed, new analysis algorithms in Python can be easily added. 3) Once a processing pipeline is designed, the entire workflow with its modules and parameters are stored in a YAML file, which makes the pipeline reproducible and deployable on high-performance computing clusters. 4) OptiNiSt can read image data in a variety of file formats and store the analysis results in NWB (Neurodata Without Borders), a standard data format for data sharing. We expect that this framework will be helpful in standardizing optical neural data analysis protocols.
+ Science, Volume 385, Issue 6715, Page 1280-1280, September 2024.
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- alpha-synuclein accumulation is recognized as a prominent feature in the majority of Parkinson disease cases and also occurs in a broad range of neurodegenerative disorders including Alzheimer disease. It has been shown that alpha-synuclein can spread from a donor cell to neighboring cells and thus propagate cellular damage, antagonizing the effectiveness of therapies such as transplantation of fetal or iPSC derived dopaminergic cells. As we and others previously have shown, insufficient lysosomal function due to genetic mutations or targeted disruption of cathepsin D can cause alpha-synuclein accumulation. We here investigated whether overexpression of cathepsin D or knockout (KO) of the transcriptional suppressor of lysosomal biogenesis ZKSCAN3 can attenuate propagation of alpha-synuclein aggregation and cell death. We examined dopaminergic neurodegeneration in the substantia nigra using stereology of tyrosine hydroxylase-immunoreactive cells 4 months and 6 months after intrastriatal injection of alpha-synuclein preformed fibrils or monomeric alpha-synuclein control in control, central nervous system (CNS)-cathepsin D overexpressing and CNS-specific ZKSCAN3 KO mice. We also examined pS129-alpha-synuclein aggregates in the substantia nigra, cortex, amygdala and striatum. The extent of dopaminergic neurodegeneration and pS129-alpha-synuclein aggregation in the brains of CNS-specific ZKSCAN3 knockout mice and CNS-cathepsin D overexpressing mice was similar to that observed in wild-type mice. Our results indicate that neither enhancing cathepsin D expression nor disrupting ZKSCAN3 in the CNS is sufficient to attenuate pS129-alpha-synuclein aggregate accumulation or dopaminergic neurodegeneration.
+ Science, Volume 385, Issue 6715, Page 1382-1382, September 2024.
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- Brain Microphysiological Systems including neural organoids derived from human induced pluripotent stem cells offer a unique lens to study the intricate workings of the human brain. This paper investigates the foundational elements of learning and memory in neural organoids, also known as Organoid Intelligence by quantifying immediate early gene expression, synaptic plasticity, neuronal network dynamics, and criticality to demonstrate the utility of these organoids in basic science research. Neural organoids showed synapse formation, glutamatergic and GABAergic receptor expression, immediate early gene expression basally and evoked, functional connectivity, criticality, and synaptic plasticity in response to theta-burst stimulation. In addition, pharmacological interventions on GABAergic and glutamatergic receptors, and input specific theta-burst stimulation further shed light on the capacity of neural organoids to mirror synaptic modulation and short-term potentiation, demonstrating their potential as tools for studying neurophysiological and neurological processes and informing therapeutic strategies for diseases.
+ Science, Volume 385, Issue 6715, Page 1312-1313, September 2024.
- in bioRxiv: Neuroscience on 2024-09-19 00:00:00 UTC.
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- Background Virtual reality (VR) and immersive technologies offer benefits in anxiety reduction and mood enhancement. This study examines the effectiveness of rain stimuli and guided breathwork delivered through MindGym, a novel reflective chamber, and a traditional VR headset. Methods Physiological measures, cognitive, and trait and state assessments were collected for 126 participants, randomly assigned to VR (Breathwork), VR (Rain), MindGym (Breathwork), or MindGym (Rain) conditions. Results Significant improvements in cognitive performance, anxiety, and mood were observed across all groups, with an 11.67% reduction in anxiety (STAI). Breathwork conditions showed a greater decrease in breath rate compared to Rain. MODTAS, DPES, and Immersion positively moderated experiences of Awe and Ego Dissolution. Openness interacted with stimuli type, with higher openness associated with greater anxiety reduction in Breathwork conditions. No significant differences were found between MindGym and VR in effectiveness or immersion. Conclusions MindGym and VR demonstrated promise as acute anxiolytics, with MindGym-generated content maintaining effectiveness when translated to VR. This highlights MindGym's potential as a versatile content creation platform for immersive, anxiety-reducing experiences. Individual differences moderated treatment responses, suggesting opportunities for personalized interventions. Future research should explore complex MindGym experiences and adaptation to various delivery systems for accessible, effective anxiety management tools.
+ Science, Volume 385, Issue 6715, Page 1275-1276, September 2024.
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- Humans and animals have a remarkable capacity to collectively coordinate their behavior to respond to environmental challenges. However, the underlying neurobiology remains poorly understood. Here, we found that groups of mice self-organize into huddles at cold ambient temperature during the thermal challenge assay. We found that mice make active (self-initiated) and passive (partner-initiated) decisions to enter or exit a huddle. Using microendoscopic calcium imaging, we found that active and passive decisions are encoded distinctly within the dorsomedial prefrontal cortex (dmPFC). Silencing dmPFC activity in some mice reduced their active decision-making, but also induced a compensatory increase in active decisions by non-manipulated partners, conserving the group's overall huddle time. These findings reveal how collective behavior is implemented in neurobiological mechanisms to meet homeostatic needs during environmental challenges.
+ Science, Volume 385, Issue 6715, Page 1274-1275, September 2024.
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- FUS is an RNA binding protein mutated in amyotrophic lateral sclerosis (ALS), a neurodegenerative disease characterized by progressive muscle weakness. We show that ALS-associated FUS mutations lead to ultrastructural defects in muscle of FUS-ALS patients, with disruption of sarcomeres and mitochondria. Studies in mouse and Drosophila models demonstrate an evolutionary-conserved cell autonomous function of FUS in muscle development. Mechanistically, FUS is required for transcription of MEF2 dependent genes, binds to the promoter of genes bound by ETS transcription factors in particular ETV5 and co-activates transcription of MEF2 dependent genes with ETV5. FUS phase separates with ETV5 and MEF2A, and MEF2A binding to FUS is potentiated by ETV5. Last, Etv5 haploinsufficiency exacerbates muscle weakness in a mouse model of FUS-ALS. These findings establish FUS as an essential protein for skeletal muscle structure through its phase separation-dependent recruitment of ETV5 and MEF2, defining a novel pathway compromised in FUS-ALS.
+ Science, Volume 385, Issue 6715, Page 1276-1278, September 2024.
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- Neural circuits in the spinal cord are composed of diverse sets of interneurons that play crucial roles in shaping motor output. Despite progress in revealing the cellular architecture of the spinal cord, the extent of cell type heterogeneity within interneuron populations remains unclear. Here, we present a single-nucleus transcriptomic atlas of spinal V1 interneurons across postnatal development. We find that the core molecular taxonomy distinguishing neonatal V1 interneurons perdures into adulthood, suggesting conservation of function across development. Moreover, we identify a key role for En1, a transcription factor that marks the V1 population, in specifying one unique subset of V1-Pou6f2 interneurons. Loss of En1 selectively disrupts the frequency of rhythmic locomotor output but does not disrupt flexion/extension limb movement. Beyond serving as a molecular resource for this neuronal population, our study highlights how deep neuronal profiling provides an entry point for functional studies of specialized cell types in motor output.
+ Science, Volume 385, Issue 6715, Page 1278-1279, September 2024.
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- We report the first application of diffusion tractography to a mysticete, which was analyzed alongside three odontocete brains, allowing the first direct comparison of strength and laterality of auditory pathways in echolocating and non-echolocating whales. Brains were imaged post-mortem at high resolution with a specialized steady state free precession diffusion sequence optimized for dead tissue. We conducted probabilistic tractography to compare the qualitative features, tract strength, and lateralization of potential ascending and descending auditory paths in the mysticete versus odontocetes. Tracts were seeded in the inferior colliculi (IC), a nexus for ascending auditory information, and the cerebellum, a center for sensorimotor integration. Direct IC to temporal lobe pathways were found in all animals, replicating previous cetacean tractography and suggesting conservation of the primary auditory projection path in the cetacean clade. Additionally, odontocete IC-cerebellum pathways exhibited higher overall tract strength than in the mysticete, suggesting a role as descending acousticomotor tracts supporting the rapid sensorimotor integration demands of echolocation. Further, in the mysticete, contralateral right IC to left cerebellum pathways were 17x stronger than those between left IC and right cerebellum, while in odontocetes, the laterality was reversed, and left IC to right cerebellum pathways were 2-4x stronger than those between right IC and left cerebellum. The stronger left IC-right cerebellum connectivity observed in odontocetes corroborates the theory that odontocetes preferentially echolocate with their right phonic lips, as the right phonic lips are likely innervated by left-cortical motor efferents that integrate with left-cortical auditory afferents in right cerebellum. This interpretation is further supported by the reversed lateralization of IC-cerebellar tracts observed in the non-echolocating mysticete. We also found differences in the specific subregions of cerebellum targeted by the IC, both between the mysticete and odontocetes, and between left and right sides. This study establishes foundational knowledge on mysticete auditory connectivity and extends knowledge on the neural basis of echolocation in odontocetes.
+ Science, Volume 385, Issue 6715, Page 1285-1286, September 2024.
- in bioRxiv: Neuroscience on 2024-09-19 00:00:00 UTC.
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- Ample studies attribute cognitive decline in Alzheimer's disease to amyloid-{beta} deposition 1-6. However, brain amyloid-{beta} accumulation that saturates years before the manifestation of clinical symptoms is dissociated with cognitive decline of the disease 7. It is unknown how these two processes are mechanistically linked. In this and our accompanied study, we report that thiamine pyrophosphokinase-1 (TPK) deficiency plays essential roles in both processes via distinct mechanisms. Here we describe that diminished microglia Tpk controls the propagation of amyloid-{beta} plaques. In APP/PS1 transgenic mice, microglia showed elevated Tpk expression at 2-month-old, but reduction in a plaque-centric manner at 8-month-old. Interestingly, lipopolysaccharide, but not amyloid-{beta}, induceed Tpk reduction in cultured microglia. Tpk reduction led to microglia dysfunction, showing volatile motility but reduced phagocytosis and weak response to focal tissue injury, with accumulation of intracellular lipid droplets and abnormal mitochrondria. In Alzheimer's disease mice, microglia-specific knockout of Tpk caused diminished plaque coverage, exacerbated plaque burden and synaptic loss. However, increased plaques were not accompanied by the development of neurofibrillary tangles or brain atrophy, in contrast to the phenotype described in our accompanied paper with neuronal Tpk deletion. In conclusion, plaque-induced inflammation reduces Tpk in microglia, selectively exacerbating the spread of amyloid pathology.
+ Science, Volume 385, Issue 6715, Page 1285-1285, September 2024.
- in bioRxiv: Neuroscience on 2024-09-19 00:00:00 UTC.
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- Brain Sciences, Vol. 14, Pages 938: Prevalence and Awareness of Medication Overuse Headache among Undergraduate Students at the University of Belgrade
- Brain Sciences doi: 10.3390/brainsci14090938
- Authors:
- Aleksandra Radojičić
- Ana Milićević
- Mirjana Ždraljević
- Marta Jeremić
- Dajana Orlović
- Milija Mijajlović
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- Background: Medication overuse headache (MOH) is a prevalent and potentially preventable secondary headache disorder linked to the excessive use of medications intended for primary headache management, particularly migraine. Aim: The aim of our study was to assess the prevalence of MOH among undergraduate students and explore their awareness. Methodology: This observational cross-sectional study included 401 active undergraduate students from the University of Belgrade. Data were collected through an anonymous online questionnaire which was distributed among student groups and via social media. The questionnaire specially designed for this study was developed in accordance with established guidelines for headache epidemiological research. Results: Among the surveyed students, 10 of them (2.5%) met the criteria for the diagnosis of MOH. Awareness of MOH was noted in 149 (37.2%) students, with higher awareness among medical students and those aged 22&ndash;25 years. Despite this awareness, there was no significant difference in MOH occurrence between those aware and unaware of the condition (aware 2.7% vs. unaware 2.4%, p = 1.000). Additionally, significant gaps in education and communication about MOH were evident. Limitations: Participants were recruited through convenience sampling from a single university at one time point. The questionnaire was not specifically validated in the student population, and the data relied on self-reporting. Conclusions: Our study highlighted a notable prevalence of MOH among undergraduate students, with a substantial portion exhibiting awareness of its risks. Despite this awareness, our findings suggest ongoing gaps in education and communication regarding MOH, emphasizing the need for targeted interventions.
+ Science, Volume 385, Issue 6715, Page 1286-1286, September 2024.
- in Brain Sciences on 2024-09-19 00:00:00 UTC.
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- Brain Sciences, Vol. 14, Pages 937: The Effectiveness of Lee Silverman Voice Treatment (LSVT LOUD) on Children’s Speech and Voice: A Scoping Review
- Brain Sciences doi: 10.3390/brainsci14090937
- Authors:
- Angelos Papadopoulos
- Louiza Voniati
- Nafsika Ziavra
- Dionysios Tafiadis
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- Background: This scoping review had as a primary goal a review of the literature and the an analysis of the possible effectiveness of the LSVT LOUD approach in children with voice and speech deficits. Methods: A search was conducted in the Scopus and PubMed databases in May of 2024. Eleven articles were obtained from the search. The standards of PRISMA recommendations were used for scoping reviews and the PCC framework was used for the eligibility criteria. Furthermore, the study used the instructions in the Cochrane Handbook for a quality assessment. The Mendeley Reference Manager software collected the studies and removed duplicates. Results: The reviewed studies employed formal and informal measures to assess voice and speech abilities in the children. Regarding the sample&rsquo;s characteristics, the studies mostly included children with Cerebral Palsy (CP) and also those with Down Syndrome (DS). All the studies reported that children with CP and DS undertook a total dose of the LSVT LOUD treatment. Significant post-treatment findings indicated increased speech function and sound pressure level, regarding the auditory&ndash;perceptual ratings of voice and speech improvement. In many studies, parents&rsquo; and expert listeners&rsquo; ratings of voice, perception of vocal loudness, speech, and communication indicated improvement. Conclusions: The majority of the included studies provide positive evidence for the LSVT as an approach. However, the small sample size that featured in the studies, as well as their limitations, made these conclusions uncertain. Moreover, the study&rsquo;s findings provided recommendations that speech language therapists and other clinicians need to follow when setting a treatment plan with children with CP and DS.
+ Science, Volume 385, Issue 6715, Page 1256-1257, September 2024.
- in Brain Sciences on 2024-09-19 00:00:00 UTC.
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- Brain Sciences, Vol. 14, Pages 936: Effects of Stress Exposure to Pain Perception in Pre-Clinical Studies: Focus on the Nociceptin/Orphanin FQ–NOP Receptor System
- Brain Sciences doi: 10.3390/brainsci14090936
- Authors:
- Pietro Pola
- Alessia Frezza
- Elaine C. Gavioli
- Girolamo Calò
- Chiara Ruzza
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- Exposure to physical and psychological stress modulates pain transmission in a dual manner. Stress-induced analgesia (SIA) refers to the reduction in pain sensitivity that can occur in response to acute stress. On the contrary, chronic stress exposure may lead to a phenomenon named stress-induced hyperalgesia (SIH). SIH is a clinically relevant phenomenon since it has been well documented that physical and psychological stress exacerbates pain in patients with several chronic pain syndromes, including migraine. The availability of animal models of SIA and SIH is of high importance for understanding the biological mechanisms leading to these phenomena and for the identification of pharmacological targets useful to alleviate the burden of stress-exacerbated chronic pain. Among these targets, the nociceptin/orphanin FQ (N/OFQ)&ndash;N/OFQ peptide (NOP) receptor system has been identified as a key modulator of both pain transmission and stress susceptibility. This review describes first the experimental approaches to induce SIA and SIH in rodents. The second part of the manuscript summarizes the scientific evidence that suggests the N/OFQ&ndash;NOP receptor system as a player in the stress&ndash;pain interaction and candidates NOP antagonists as useful drugs to mitigate the detrimental effects of stress exposure on pain perception.
+ Science, Volume 385, Issue 6715, Page 1258-1259, September 2024.
- in Brain Sciences on 2024-09-19 00:00:00 UTC.
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- Brain Sciences, Vol. 14, Pages 935: Abnormal Dynamic Reconfiguration of Multilayer Temporal Networks in Patients with Bipolar Disorder
- Brain Sciences doi: 10.3390/brainsci14090935
- Authors:
- Luyao Lai
- Dandan Li
- Yating Zhang
- Jianchao Hao
- Xuedong Wang
- Xiaohong Cui
- Jie Xiang
- Bin Wang
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- Background: Multilayer networks have been used to identify abnormal dynamic reconfiguration in bipolar disorder (BD). However, these studies ignore the differences in information interactions between adjacent layers when constructing multilayer networks, and the analysis of dynamic reconfiguration is not comprehensive enough; Methods: Resting-state functional magnetic resonance imaging data were collected from 46 BD patients and 54 normal controls. A multilayer temporal network was constructed for each subject, and inter-layer coupling of different nodes was considered using network similarity. The promiscuity, recruitment, and integration coefficients were calculated to quantify the different dynamic reconfigurations between the two groups; Results: The global inter-layer coupling, recruitment, and integration coefficients were significantly lower in BD patients. These results were further observed in the attention network and the limbic/paralimbic and subcortical network, reflecting reduced temporal stability, intra- and inter-subnetwork communication abilities in BD patients. The whole-brain promiscuity was increased in BD patients. The same results were observed in the somatosensory/motor and auditory network, reflecting more functional interactions; Conclusions: This study discovered abnormal dynamic interactions of BD from the perspective of dynamic reconfiguration, which can help to understand the pathological mechanisms of BD.
+ Science, Volume 385, Issue 6715, Page 1259-1260, September 2024.
- in Brain Sciences on 2024-09-19 00:00:00 UTC.
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- Brain Sciences, Vol. 14, Pages 934: Clinical and Anatomical Characteristics of Perforator Aneurysms of the Posterior Cerebral Artery: A Single-Center Experience
- Brain Sciences doi: 10.3390/brainsci14090934
- Authors:
- Anahita Malvea
- Shigeta Miyake
- Ronit Agid
- Hugo Andrade Barazarte
- Richard Farb
- Timo Krings
- Pascal John Roger Mosimann
- Patrick Joseph Nicholson
- Ivan Radovanovic
- Karel Terbrugge
- Robert Willinsky
- Joanna Danielle Schaafsma
- Eef J. Hendriks
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- Introduction: Posterior cerebral artery (PCA) aneurysms represent up to 1% of all cerebral aneurysms. P1-P2 perforator aneurysms are thought to be even less prevalent and often require complex treatment strategies due to their anatomical and morphological characteristics, with risk of a perforator infarct. We studied the treatment of P1-P2 perforator aneurysms in a single-center cohort from a high-volume tertiary center, reporting clinical and anatomical characteristics, treatment strategies, and outcomes. Methods: A retrospective analysis of adult patients with a P1-P2 perforator aneurysm who presented at our institution between January 2000 and January 2023 was performed. The patients were analyzed for demographics, clinical presentation, imaging findings, treatment techniques, outcomes, and complications. Subgroup analyses between ruptured versus non-ruptured cases were included. Results: Out of 2733 patients with a cerebral aneurysm, 14 patients (0.5%) presented with a P1-P2 perforator aneurysm. All six patients with a ruptured aneurysm were treated by endovascular coiling, of whom one patient (16.7%) required surgical clipping of a recurrence. One out of eight (12.5%) patients with unruptured aneurysms was treated by surgical clipping. P1-P2 perforator aneurysms predominantly affected middle-aged individuals (median 59.5 years), with 10/14 (71.4%) being female. Endovascular coiling was the primary treatment modality overall, yielding favorable technical outcomes, however, it was complicated by a perforator infarct in two patients (33.3%) without new permanent morbidity or mortality secondary to treatment. Conclusions: P1-P2 perforator aneurysms are a rare subtype of intracranial aneurysm. Endovascular coiling could present an effective treatment modality; however, care should be taken for ischemic complications in the dependent perforator territory. Larger studies are required to provide more insights.
+ Science, Volume 385, Issue 6715, Page 1260-1261, September 2024.
- in Brain Sciences on 2024-09-19 00:00:00 UTC.
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- Millisecond-scale temporal spiking patterns encode sensory information in the periphery, but their role in the neocortex remains controversial. The sense of touch provides a window into temporal coding because tactile neurons often exhibit precise, repeatable, and informative temporal spiking patterns. In the somatosensory cortex (S1), responses to skin vibrations exhibit phase locking that faithfully carries information about vibratory frequency. However, the respective roles of spike timing and rate in frequency coding are confounded because vibratory frequency shapes both the timing and rates of responses. To disentangle the contributions of these two neural features, we measured S1 responses as rhesus macaques performed frequency discrimination tasks in which differences in frequency were accompanied by orthogonal variations in amplitude. We assessed the degree to which the strength and timing of responses could account for animal performance. First, we showed that animals can discriminate frequency, but their performance is biased by amplitude variations. Second, rate-based representations of frequency are susceptible to changes in amplitude but in ways that are inconsistent with the animals’ behavioral biases, calling into question a rate-based neural code for frequency. In contrast, timing-based representations are highly informative about frequency but impervious to changes in amplitude, which is also inconsistent with the animals’ behavior. We account for the animals’ behavior with a model wherein frequency coding relies on a temporal code, but frequency judgments are biased by perceived magnitude. We conclude that information about vibratory frequency is not encoded in S1 firing rates but primarily in temporal patterning on millisecond timescales.
+ Science, Volume 385, Issue 6715, Page 1262-1263, September 2024.
- in Journal of Neuroscience on 2024-09-18 16:30:21 UTC.
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- Navigation requires integrating sensory information with a stable schema to create a dynamic map of an animal’s position using egocentric and allocentric coordinate systems. In the hippocampus, place cells encode allocentric space, but their firing rates may also exhibit directional tuning within egocentric or allocentric reference frames. We compared experimental and simulated data to assess the prevalence of tuning to egocentric bearing (EB) among hippocampal cells in rats foraging in an open field. Using established procedures, we confirmed egocentric modulation of place cell activity in recorded data; however, simulated data revealed a high false-positive rate (FPR). When we accounted for false positives by comparing with shuffled data that retain correlations between the animal’s direction and position, only a very low number of hippocampal neurons appeared modulated by EB. Our study highlights biases affecting FPRs and provides insights into the challenges of identifying egocentric modulation in hippocampal neurons.
+ Science, Volume 385, Issue 6715, Page 1263-1263, September 2024.
- in Journal of Neuroscience on 2024-09-18 16:30:21 UTC.
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+ Science, Volume 385, Issue 6715, Page 1264-1269, September 2024.
- in Journal of Neuroscience on 2024-09-18 16:30:21 UTC.
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- Attention and decision-making processes are fundamental to cognition. However, they are usually experimentally confounded, making it difficult to link neural observations to specific processes. Here we separated the effects of selective attention from the effects of decision-making on brain activity obtained from human participants (both sexes), using a two-stage task where the attended stimulus and decision were orthogonal and separated in time. Multivariate pattern analyses of multimodal neuroimaging data revealed the dynamics of perceptual and decision-related information coding through time with magnetoencephalography (MEG), through space with functional magnetic resonance imaging (fMRI), and their combination (MEG-fMRI fusion). Our MEG results showed an effect of attention before decision-making could begin, and fMRI results showed an attention effect in early visual and frontoparietal regions. Model-based MEG-fMRI fusion suggested that attention boosted stimulus information in the frontoparietal and early visual regions before decision-making was possible. Together, our results suggest that attention affects neural stimulus representations in the frontoparietal regions independent of decision-making.
+ Science, Volume 385, Issue 6715, Page 1290-1291, September 2024.
- in Journal of Neuroscience on 2024-09-18 16:30:21 UTC.
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- Making choices about whether and when to engage cognitive effort are a common feature of everyday experience, with important consequences for academic, career, and health outcomes. Yet, despite their hypothesized importance, very little is understood about the underlying mechanisms that support this form of human cost–benefit decision-making. To investigate these mechanisms, we used the Cognitive Effort Discounting Paradigm (Cog-ED) during fMRI scanning to precisely quantify the neural encoding of varying cognitive effort demands relative to reward outcomes, within two distinct cognitive domains (working memory, speech comprehension). The findings provide strong evidence that the dorsal anterior cingulate cortex (dACC) plays a central and selective role in this decision-making process. Trial-by-trial modulations in dACC activation tracked the relative subjective value of the low-effort, low-reward option, with the strongest activity occurring when this was of greater value than the high-effort, high-reward option. In contrast, dACC activity was not modulated by decision difficulty, though such effects were found in other frontoparietal regions. Critically, dACC activity was also strongly correlated across the two decision-making task domains and further predicted subsequent choice behavior in both. Together, the results suggest that dACC activity modulation reflects a domain-general valuation comparison mechanism, which acts to bias participants away from decisions to engage in cognitive effort, when the perceived subjective costs of such engagement outweigh the reward-related benefits. These findings complement work in other cost domains and species by pointing to a clear role of the dACC in representing subjective value differences between choice options during cost–benefit decision-making.
+ Science, Volume 385, Issue 6715, Page 1255-1255, September 2024.
- in Journal of Neuroscience on 2024-09-18 16:30:21 UTC.
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- Neuroscience research has evolved to generate increasingly large and complex experimental data sets, and advanced data science tools are taking on central roles in neuroscience research. Neurodata Without Borders (NWB), a standard language for neurophysiology data, has recently emerged as a powerful solution for data management, analysis, and sharing. We here discuss our labs’ efforts to implement NWB data science pipelines. We describe general principles and specific use cases that illustrate successes, challenges, and non-trivial decisions in software engineering. We hope that our experience can provide guidance for the neuroscience community and help bridge the gap between experimental neuroscience and data science. Key takeaways from this article are that (1) standardization with NWB requires non-trivial design choices; (2) the general practice of standardization in the lab promotes data awareness and literacy, and improves transparency, rigor, and reproducibility in our science; (3) we offer several feature suggestions to ease the extensibility, publishing/sharing, and usability for NWB standard and users of NWB data.
+ Science, Volume 385, Issue 6715, Page 1270-1273, September 2024.
- in Journal of Neuroscience on 2024-09-18 16:30:21 UTC.
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- The frontal eye field (FEF) plays a well-established role in the control of visual attention. The strength of an FEF neuron's response to a visual stimulus presented in its receptive field is enhanced if the stimulus captures spatial attention by virtue of its salience. A stimulus can be rendered salient by cognitive factors as well as by physical attributes. These include surprise. The aim of the present experiment was to determine whether surprise-induced salience would result in enhanced visual-response strength in the FEF. Toward this end, we monitored neuronal activity in two male monkeys while presenting first a visual cue predicting with high probability that the reward delivered at the end of the trial would be good or bad (large or small) and then a visual cue announcing the size of the impending reward with certainty. The second cue usually confirmed but occasionally violated the expectation set up by the first cue. Neurons responded more strongly to the second cue when it violated than when it confirmed expectation. The increase in the firing rate was accompanied by a decrease in spike-count correlation as expected from capture of attention. Although both good surprise and bad surprise induced enhanced firing, the effects appeared to arise from distinct mechanisms as indicated by the fact that the bad-surprise signal appeared at a longer latency than the good-surprise signal and by the fact that the strength of the two signals varied independently across neurons.
+ Science, Volume 385, Issue 6715, Page 1311-1313, September 2024.
- in Journal of Neuroscience on 2024-09-18 16:30:21 UTC.
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- Circadian, infradian, and seasonal changes in steroid hormone secretion have been tied to changes in brain volume in several mammalian species. However, the relationship between circadian changes in steroid hormone production and rhythmic changes in brain morphology in humans is largely unknown. Here, we examined the relationship between diurnal fluctuations in steroid hormones and multiscale brain morphology in a precision imaging study of a male who completed 40 MRI and serological assessments at 7 A.M. and 8 P.M. over the course of a month, targeting hormone concentrations at their peak and nadir. Diurnal fluctuations in steroid hormones were tied to pronounced changes in global and regional brain morphology. From morning to evening, total brain volume, gray matter volume, and cortical thickness decreased, coincident with decreases in steroid hormone concentrations (testosterone, estradiol, and cortisol). In parallel, cerebrospinal fluid and ventricle size increased from A.M. to P.M. Global changes were driven by decreases within the occipital and parietal cortices. These findings highlight natural rhythms in brain morphology that keep time with the diurnal ebb and flow of steroid hormones.
+
- in Journal of Neuroscience on 2024-09-18 16:30:21 UTC.
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- The presence of valence coding neurons in the basolateral amygdala (BLA) that form distinct projections to other brain regions implies functional opposition between aversion and reward during learning. However, evidence for opponent interactions in fear learning is sparse and may only be apparent under certain conditions. Here we test this possibility by studying the roles of the BLA->central amygdala (CeA) and BLA->nucleus accumbens (Acb) pathways in fear learning in male rats. First, we assessed the organization of these pathways in the rat brain. BLA->CeA and BLA->Acb pathways were largely segregated in the BLA but shared overlapping molecular profiles. Then we assessed activity of the BLA->CeA and BLA->Acb pathways during two different forms of fear learning—fear learning in a neutral context and fear learning in a reward context. BLA->CeA neurons were robustly recruited by footshock regardless of where fear learning occurred, whereas recruitment of BLA->Acb neurons was state-dependent because footshock only recruited this pathway in a reward context. Finally, we assessed the causal roles of activity in these pathways in fear learning. Photoinhibition of the BLA->CeA pathway during the footshock US impaired fear learning, regardless of where fear learning occurred. In contrast, photoinhibition of the BLA->Acb pathway augmented fear learning, but only in the reward context. Taken together, our findings show circuit- and state-dependent opponent processing of fear. Footshock activity in the BLA->Acb pathway limits how much fear is learned.
+
+The cover image is based on the article Scene construction processes in the anterior hippocampus during temporal episodic memory retrieval by Maria Jieun Hwang and Sang Ah Lee (https://doi.org/10.1002/hipo.23624).
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- in Journal of Neuroscience on 2024-09-18 16:30:21 UTC.
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+ Abstract
+The dorsal region of the hippocampus (dHC) mediates many of the mnemonic functions traditionally associated with the hippocampus proper, such as spatial and episodic memory, whereas ventral hippocampus (vHC) has been extensively implicated in emotional memory and motivational processes. By contrast, the functions of the intermediate hippocampus (iHC) are far less understood. In this study, we aimed to investigate the mnemonic functions of iHC by reversibly inactivating iHC prior to testing memory in behavioral tasks dependent on the integrity of dHC, iHC, or vHC, namely, rapid place water maze, inhibitory avoidance, spontaneous alternation, and temporal ordering of odors. Given our previous findings showing that dHC and vHC are involved in mnemonic control of ingestive behavior, we also assessed the effects of iHC inactivation on sucrose intake. The results showed that pharmacological inhibition of iHC impairs rapid place water maze memory, which has been previously shown to be dependent on iHC but not dHC or vHC. iHC inactivation does not impact memory dependent on dHC (spontaneous alternation), vHC (temporal odor memory), or either dHC or vHC (inhibitory avoidance), and only modestly affects sucrose intake. These findings provide support for the involvement of iHC in mnemonic functions that are distinct from dHC and vHC and highlight the need to further advance our understanding of the functions of this hippocampal region that has been relatively understudied.
- in Journal of Neuroscience on 2024-09-18 16:30:21 UTC.
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in Hippocampus on 2024-09-19 03:49:54 UTC.
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- Ribbon synapses of inner hair cells (IHCs) are uniquely designed for ultrafast and indefatigable neurotransmission of the sound. The molecular machinery ensuring the efficient, compensatory recycling of the synaptic vesicles (SVs), however, remains elusive. This study showed that hair cell knock-out of murine Dmxl2, whose human homolog is responsible for nonsyndromic sensorineural hearing loss DFNA71, resulted in auditory synaptopathy by impairing synaptic endocytosis and recycling. The mutant mice in the C57BL/6J background of either sex had mild hearing loss with severely diminished wave I amplitude of the auditory brainstem response. Membrane capacitance measurements of the IHCs revealed deficiency in sustained synaptic exocytosis and endocytic membrane retrieval. Consistent with the electrophysiological findings, 3D electron microscopy reconstruction showed reduced reserve pool of SVs and endocytic compartments, while the membrane-proximal and ribbon-associated vesicles remain intact. Our results propose an important role of DMXL2 in hair cell endocytosis and recycling of the SVs.
+ Abstract
+The hippocampus is considered essential for several forms of declarative memory, including spatial and social memory. Despite the extensive research of the classic subfields of the hippocampus, the fasciola cinerea (FC)—a medially located structure within the hippocampal formation—has remained largely unexplored. In the present study, we performed a morpho-functional characterization of principal neurons in the mouse FC. Using in vivo juxtacellular recording of single neurons, we found that FC neurons are distinct from neighboring CA1 pyramidal cells, both morphologically and electrophysiologically. Specifically, FC neurons displayed non-pyramidal morphology and granule cell-like apical dendrites. Compared to neighboring CA1 pyramidal neurons, FC neurons exhibited more regular in vivo firing patterns and a lower tendency to fire spikes at short interspike intervals. Furthermore, tracing experiments revealed that the FC receives inputs from the lateral but not the medial entorhinal cortex and CA3, and it provides a major intra-hippocampal projection to the septal CA2 and sparser inputs to the distal CA1. Overall, our results indicate that the FC is a morphologically and electrophysiologically distinct subfield of the hippocampal formation; given the established role of CA2 in social memory and seizure initiation, the unique efferent intra-hippocampal connectivity of the FC points to possible roles in social cognition and temporal lobe epilepsy.
- in Journal of Neuroscience on 2024-09-18 16:30:21 UTC.
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in Hippocampus on 2024-09-19 03:49:54 UTC.
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+ Abstract
+Although the hippocampus has been implicated in both the temporal organization of memories and association of scene elements, some theoretical accounts posit that the role of the hippocampus in episodic memory is largely atemporal. In this study, we set out to explore this discrepancy by identifying hippocampal activity patterns related to scene construction while participants performed a temporal order memory task. Participants in the fMRI scanner were shown a sequence of photographs, each consisting of a central object and a contextual background scene. On each retrieval trial, participants were shown a pair of the original photographs (FULL), objects from the scenes without the background (OBJ), or background contexts without the main foreground object (BACK). In the temporal order judgment (TOJ) task, participants judged the temporal order of the pair of scenes; in the Viewing trials, two identical scenes were shown without any task. First, we found that the anterior hippocampus—particularly the CA1 and subiculum—showed similar patterns of activation between the BACK and OBJ conditions, suggesting that scene construction occurred spontaneously during both TOJ and Viewing. Furthermore, neural markers of scene construction in the anterior hippocampus did not apply to incorrect trials, showing that successful temporal memory retrieval was functionally linked to scene construction. In the cortex, time-processing areas, such as the supplementary motor area and the precuneus, and scene-processing areas, such as the parahippocampal cortex, were activated and functionally connected with the hippocampus. Together, these results support the view that the hippocampus is concurrently involved in scene construction and temporal organization of memory and propose a model of hippocampal episodic memory that takes both processes into account.
- in Journal of Neuroscience on 2024-09-18 16:30:21 UTC.
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in Hippocampus on 2024-09-19 03:49:54 UTC.
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+ Abstract
+The processing of rich synaptic information in the dentate gyrus (DG) relies on a diverse population of inhibitory GABAergic interneurons to regulate cellular and circuit activity, in a layer-specific manner. Metabotropic GABAB-receptors (GABABRs) provide powerful inhibition to the DG circuit, on timescales consistent with behavior and learning, but their role in controlling the activity of interneurons is poorly understood with respect to identified cell types. We hypothesize that GABABRs display cell type-specific heterogeneity in signaling strength, which will have direct ramifications for signal processing in DG networks. To test this, we perform in vitro whole-cell patch-clamp recordings from identified DG principal cells and interneurons, followed by GABABR pharmacology, photolysis of caged GABA, and extracellular stimulation of endogenous GABA release to classify the cell type-specific inhibitory potential. Based on our previous classification of DG interneurons, we show that postsynaptic GABABR-mediated currents are present on all interneuron types albeit at different amplitudes, dependent largely on soma location and synaptic targets. GABABRs were coupled to inwardly-rectifying K+ channels that strongly reduced the excitability of those interneurons where large currents were observed. These data provide a systematic characterization of GABABR signaling in the rat DG to provide greater insight into circuit dynamics.
- in Journal of Neuroscience on 2024-09-18 16:30:21 UTC.
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in Hippocampus on 2024-09-19 03:49:54 UTC.
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- The role of experience in the development and maintenance of emergent network properties such as cortical oscillations and states is poorly understood. To define how early-life experience affects cortical dynamics in the visual cortex of adult, head-fixed mice, we examined the effects of two forms of blindness initiated before eye opening and continuing through recording: (1) bilateral loss of retinal input (enucleation) and (2) degradation of visual input (eyelid suture). Neither form of deprivation fundamentally altered the state-dependent regulation of firing rates or local field potentials. However, each deprivation caused unique changes in network behavior. Laminar analysis revealed two different generative mechanisms for low-frequency synchronization: one prevalent during movement and the other during quiet wakefulness. The former was absent in enucleated mice, suggesting a mouse homolog of human alpha oscillations. In addition, neurons in enucleated animals were less correlated and fired more regularly, but no change in mean firing rate. Eyelid suture decreased firing rates during quiet wakefulness, but not during movement, with no effect on neural correlations or regularity. Sutured animals showed a broadband increase in depth EEG power and an increased occurrence, but reduced central frequency, of narrowband gamma oscillations. The complementary—rather than additive—effects of lid suture and enucleation suggest that the development of emergent network properties does not require vision but is plastic to modified input. Our results suggest a complex interaction of internal set points and experience determines mature cortical activity, with low-frequency synchronization being particularly susceptible to early deprivation.
+ Abstract
+Neural progenitor cells (NPCs) reside in the brain and participate in the mechanism of neurogenesis that permits the brain to generate the building blocks for enhancement of cognitive abilities and acquisition of new skills. The existence of NPCs in brain has opened a novel dimension of research to explore their potential for treatment of various neurodegenerative disorders. The present study provides novel insights into the intracellular mechanisms in neuronal cells proliferation, maturation and differentiation regulated by Quinic acid (QA). Furthermore, this study might help in discovery and development of lead molecule that can overcome the challenges in the treatment of neurodegenerative diseases. The growth supporting effect of QA was studied using MTT assay. For that purpose, hippocampal cell cultures of neonatal rats were treated with different concentrations of QA and incubated for 24, 48 and 72 h. Gene and protein expressions of the selected molecular markers nestin, neuron-specific class III beta-tubulin (Tuj-1), neuronal nuclear protein (NeuN), neuronal differentiation 1 (NeuroD1), glial fibrillary acidic protein (GFAP), neuroligin (NLGN) and vimentin were analyzed. QA-induced cell proliferation and differentiation of hippocampal progenitor cells was also accompanied by significantly increased expression of progenitor and immature neuronal marker, mature neuronal marker and differentiating factor, that is, nestin, Tuj-1, NeuN and NeuroD1, respectively. On the other hand, vimentin downregulation and constant GFAP expression were observed following QA treatment. Additionally, the effects of QA on the recovery of stressed cells was studied using in vitro model of oxygen glucose deprivation (OGD). It was observed that hippocampal cells were able to recover from OGD following the treatment with QA. These findings suggest that QA treatment promotes hippocampal neurogenesis by proliferating and differentiating of NPCs and recovers neurons from stress caused by OGD. Thus, the neurogenic potential of QA can be explored for the treatment of neurodegenerative disorders.
- in Journal of Neuroscience on 2024-09-18 16:30:21 UTC.
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in Hippocampus on 2024-09-19 03:49:54 UTC.
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- People parse continuous experiences at natural breakpoints called event boundaries, which is important for understanding an environment's causal structure and for responding to uncertainty within it. However, it remains unclear how different forms of uncertainty affect the parsing of continuous experiences and how such uncertainty influences the brain's processing of ongoing events. We exposed human participants of both sexes (N = 34) to a continuous sequence of semantically meaningless images. We generated sequences from random walks through a graph that grouped images into temporal communities. After learning, we asked participants to segment another sequence at natural breakpoints (event boundaries). Participants segmented the sequence at learned transitions between communities, as well as at novel transitions, suggesting that people can segment temporally extended experiences into events based on learned structure as well as prediction error. Greater segmentation at novel boundaries was associated with enhanced parietal scalp electroencephalography (EEG) activity between 250 and 450 ms after the stimulus onset. Multivariate classification of EEG activity showed that novel and learned boundaries evoked distinct patterns of neural activity, particularly theta band power in posterior electrodes. Learning also led to distinct neural representations for stimuli within the temporal communities, while neural activity at learned boundary nodes showed predictive evidence for the adjacent community. The data show that people segment experiences at both learned and novel boundaries and suggest that learned event boundaries trigger retrieval of information about the upcoming community that could underlie anticipation of the next event in a sequence.
+ Migraine is a highly prevalent and disabling pain disorder that affects >1 billion people worldwide. One central hypothesis points to the cranial meninges as a key site underlying migraine headache genesis through complex interplay between meningeal sensory nerves, blood vessels, and adjacent immune cells. How these interactions might generate migraine headaches remains incompletely understood and a subject of much debate. In this review we discuss clinical and preclinical evidence supporting the concept that meningeal sterile inflammation, involving neurovascular and neuroimmune interactions, underlies migraine headache genesis. We examine downstream signaling pathways implicated in the development of migraine pain in response to exogenous events such as infusing migraine-triggering chemical substances. We further discuss cortex-to-meninges signaling pathways that could underlie migraine pain in response to endogenous events, such as cortical spreading depolarization (CSD), and explore future directions for the field.
- in Journal of Neuroscience on 2024-09-18 16:30:21 UTC.
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in Trends in Neurosciences: In press on 2024-09-19 00:00:00 UTC.
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- Spike-and-wave discharges (SWDs) and sleep spindles are characteristic electroencephalographic (EEG) hallmarks of absence seizures and nonrapid eye movement sleep, respectively. They are commonly generated by the cortico–thalamo–cortical network including the thalamic reticular nucleus (TRN). It has been reported that SWD development is accompanied by a decrease in sleep spindle density in absence seizure patients and animal models. However, whether the decrease in sleep spindle density precedes, coincides with, or follows, the SWD development remains unknown. To clarify this, we exploited Pvalb-tetracycline transactivator (tTA)::tetO-ArchT (PV-ArchT) double-transgenic mouse, which can induce an absence seizure phenotype in a time-controllable manner by expressing ArchT in PV neurons of the TRN. In these mice, EEG recordings demonstrated that a decrease in sleep spindle density occurred 1 week before the onset of typical SWDs, with the expression of ArchT. To confirm such temporal relationship observed in these genetic model mice, we used a gamma-butyrolactone (GBL) pharmacological model of SWDs. Prior to GBL administration, we administered caffeine to wild-type mice for 3 consecutive days to induce a decrease in sleep spindle density. We then administered low-dose GBL, which cannot induce SWDs in normally conditioned mice but led to the occurrence of SWDs in caffeine-conditioned mice. These findings indicate a temporal relationship in which the decrease in sleep spindle density consistently precedes SWD development. Furthermore, the decrease in sleep spindle activity may have a role in facilitating the development of SWDs. Our findings suggest that sleep spindle reductions could serve as early indicators of seizure susceptibility.
+ Antidepressant drugs promote neuronal plasticity, and activation of brain-derived neurotrophic factor (BDNF) signaling through its receptor neuronal receptor tyrosine kinase 2 (NTRK2 or TRKB) is among the critical steps in this process. These mechanisms are shared by typical slow-acting antidepressants, fast-acting ketamine, and psychedelic compounds, although the cellular targets of each drug differ. In this opinion, we propose that some of these antidepressants may directly bind to TRKB and allosterically potentiate BDNF signaling, among other possible effects. TRKB activation in parvalbumin-containing interneurons disinhibits cortical networks and reactivates a juvenile-like plasticity window. Subsequent rewiring of aberrant networks, coupled with environmental stimuli, may underlie its clinical antidepressant effects. The end-to-end hypothesis proposed may stimulate the search for new treatment strategies.
- in eNeuro on 2024-09-18 16:30:21 UTC.
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in Trends in Neurosciences: In press on 2024-09-19 00:00:00 UTC.
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- Retinitis pigmentosa (RP) is a family of genetically heterogeneous diseases still without a cure. Despite the causative genetic mutation typically not expressed in cone photoreceptors, these cells inevitably degenerate following the primary death of rods, causing blindness. The reasons for the "bystander" degeneration of cones are presently unknown but decrement of survival factors, oxidative stress, and inflammation all play a role. Targeting these generalized biological processes represents a strategy to develop mutation-agnostic therapies for saving vision in large populations of RP individuals. A classical method to support neuronal survival is by employing neurotrophic factors, such as NGF. This study uses painless human NGF (hNGFp), a TrkA receptor-biased variant of the native molecule with lower affinity for nociceptors and limited activity as a pain inducer; the molecule has identical neurotrophic power of the native form but a reduced affinity for the p75NTR receptors, known to trigger apoptosis. hNGFp has a recognized activity on brain microglial cells, which are induced to a phenotype switch from a highly activated to a more homeostatic configuration. hNGFp was administered to RP-like mice in vivo with the aim of decreasing retinal inflammation and also providing retinal neuroprotection. However, the ability of this treatment to counteract the bystander degeneration of cones remained limited.
+ The identity and function of local brain oscillators remain poorly understood. Liu et al. use mWAKE as a genetic entrée to uncover a local clock mechanism in the lateral amygdala that coordinates sensory perception and internal state in a time-dependent manner.
- in eNeuro on 2024-09-18 16:30:21 UTC.
+
in Neuron: In press on 2024-09-19 00:00:00 UTC.
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- by Kiesha Prem, Kevin van Zandvoort, Petra Klepac, Rosalind M. Eggo, Nicholas G. Davies, Centre for the Mathematical Modelling of Infectious Diseases COVID-19 Working Group, Alex R. Cook, Mark Jit
+ Fat and Dachsous interact in neighboring cells via their cadherin repeats to regulate cell behaviors and tissue shape. Strutt et al. show that interactions between two distinct cadherin regions in each molecule regulate the stability of Fat-Dachsous binding and modulate Fat-Dachsous function in the developing fly wing.
- in PLoS Computational Biology on 2024-09-18 14:00:00 UTC.
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in Cell Reports: Current Issue on 2024-09-19 00:00:00 UTC.
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- by G. Eric Bastien, Rachel N. Cable, Cecelia Batterbee, A. J. Wing, Luis Zaman, Melissa B. Duhaime
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-Viruses of microbes are ubiquitous biological entities that reprogram their hosts’ metabolisms during infection in order to produce viral progeny, impacting the ecology and evolution of microbiomes with broad implications for human and environmental health. Advances in genome sequencing have led to the discovery of millions of novel viruses and an appreciation for the great diversity of viruses on Earth. Yet, with knowledge of only “who is there?” we fall short in our ability to infer the impacts of viruses on microbes at population, community, and ecosystem-scales. To do this, we need a more explicit understanding “who do they infect?” Here, we developed a novel machine learning model (ML), Virus-Host Interaction Predictor (VHIP), to predict virus-host interactions (infection/non-infection) from input virus and host genomes. This ML model was trained and tested on a high-value manually curated set of 8849 virus-host pairs and their corresponding sequence data. The resulting dataset, ‘Virus Host Range network’ (VHRnet), is core to VHIP functionality. Each data point that underlies the VHIP training and testing represents a lab-tested virus-host pair in VHRnet, from which meaningful signals of viral adaptation to host were computed from genomic sequences. VHIP departs from existing virus-host prediction models in its ability to predict multiple interactions rather than predicting a single most likely host or host clade. As a result, VHIP is able to infer the complexity of virus-host networks in natural systems. VHIP has an 87.8% accuracy rate at predicting interactions between virus-host pairs at the species level and can be applied to novel viral and host population genomes reconstructed from metagenomic datasets.
+ During zebrafish maternal-to-zygotic transition, massive mRNA changes are not observed at the protein level. mRNAs expressed only after genome activation are deposited as proteins since fertilization in both zebrafish and mouse. Further, da Silva Pescador et al. highlight the need to combine multiple omics to fully understand gene regulation.
- in PLoS Computational Biology on 2024-09-18 14:00:00 UTC.
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in Cell Reports: Current Issue on 2024-09-19 00:00:00 UTC.
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- by David Anaguano, Opeoluwa Adewale-Fasoro, Grace W. Vick, Sean Yanik, James Blauwkamp, Manuel A. Fierro, Sabrina Absalon, Prakash Srinivasan, Vasant Muralidharan
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-Malaria is a global and deadly human disease caused by the apicomplexan parasites of the genus Plasmodium. Parasite proliferation within human red blood cells (RBCs) is associated with the clinical manifestations of the disease. This asexual expansion within human RBCs begins with the invasion of RBCs by P. falciparum, which is mediated by the secretion of effectors from 2 specialized club-shaped secretory organelles in merozoite-stage parasites known as rhoptries. We investigated the function of the Rhoptry Neck Protein 11 (RON11), which contains 7 transmembrane domains and calcium-binding EF-hand domains. We generated conditional mutants of the P. falciparum RON11. Knockdown of RON11 inhibits parasite growth by preventing merozoite invasion. The loss of RON11 did not lead to any defects in processing of rhoptry proteins but instead led to a decrease in the amount of rhoptry proteins. We utilized ultrastructure expansion microscopy (U-ExM) to determine the effect of RON11 knockdown on rhoptry biogenesis. Surprisingly, in the absence of RON11, fully developed merozoites had only 1 rhoptry each. The single rhoptry in RON11-deficient merozoites were morphologically typical with a bulb and a neck oriented into the apical polar ring. Moreover, rhoptry proteins are trafficked accurately to the single rhoptry in RON11-deficient parasites. These data show that in the absence of RON11, the first rhoptry is generated during schizogony but upon the start of cytokinesis, the second rhoptry never forms. Interestingly, these single-rhoptry merozoites were able to attach to host RBCs but are unable to invade RBCs. Instead, RON11-deficient merozoites continue to engage with RBC for prolonged periods eventually resulting in echinocytosis, a result of secreting the contents from the single rhoptry into the RBC. Together, our data show that RON11 triggers the de novo biogenesis of the second rhoptry and functions in RBC invasion.
+ Here, Xu et al. show that inhibition of de novo ceramide synthesis by either myriocin treatment or DES1 knockdown protects against lipid-induced hepatic insulin resistance independently of C16 ceramide concentration. Instead, these ceramide synthesis inhibitors mediate their effects to protect from lipid-induced hepatic insulin resistance via the PM-sn-1,2-diacylglycerol-PKCε-INSRT1150 phosphorylation pathway.
- in PLoS Biology on 2024-09-18 14:00:00 UTC.
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in Cell Reports: Current Issue on 2024-09-19 00:00:00 UTC.
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- by Tianyuan Lei, Xuhong Liao, Xinyuan Liang, Lianglong Sun, Mingrui Xia, Yunman Xia, Tengda Zhao, Xiaodan Chen, Weiwei Men, Yanpei Wang, Leilei Ma, Ningyu Liu, Jing Lu, Gai Zhao, Yuyin Ding, Yao Deng, Jiali Wang, Rui Chen, Haibo Zhang, Shuping Tan, Jia-Hong Gao, Shaozheng Qin, Sha Tao, Qi Dong, Yong He
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-The modular structure of functional connectomes in the human brain undergoes substantial reorganization during development. However, previous studies have implicitly assumed that each region participates in one single module, ignoring the potential spatial overlap between modules. How the overlapping functional modules develop and whether this development is related to gray and white matter features remain unknown. Using longitudinal multimodal structural, functional, and diffusion MRI data from 305 children (aged 6 to 14 years), we investigated the maturation of overlapping modules of functional networks and further revealed their structural associations. An edge-centric network model was used to identify the overlapping modules, and the nodal overlap in module affiliations was quantified using the entropy measure. We showed a regionally heterogeneous spatial topography of the overlapping extent of brain nodes in module affiliations in children, with higher entropy (i.e., more module involvement) in the ventral attention, somatomotor, and subcortical regions and lower entropy (i.e., less module involvement) in the visual and default-mode regions. The overlapping modules developed in a linear, spatially dissociable manner, with decreased entropy (i.e., decreased module involvement) in the dorsomedial prefrontal cortex, ventral prefrontal cortex, and putamen and increased entropy (i.e., increased module involvement) in the parietal lobules and lateral prefrontal cortex. The overlapping modular patterns captured individual brain maturity as characterized by chronological age and were predicted by integrating gray matter morphology and white matter microstructural properties. Our findings highlight the maturation of overlapping functional modules and their structural substrates, thereby advancing our understanding of the principles of connectome development.
+ Konstantinidou et al. build and compare piRNA-generating genomic intervals (piRNA clusters) across seven species. Their comprehensive analysis uncovers a mechanism for the formation of piRNA clusters downstream of genes (piC-DoGs) in mammals and identifies three distinct classes of piRNA clusters in adult human testes.
- in PLoS Biology on 2024-09-18 14:00:00 UTC.
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in Cell Reports: Current Issue on 2024-09-19 00:00:00 UTC.
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- Background: Physical therapy (PT) services can be essential for recovery from coronavirus disease 2019 (COVID-19) infection. Maintaining an efficient healthcare service is achieved by ensuring the safety of a well-informed healthcare practitioner. This study aimed to assess the sources of knowledge, attitude, experience, and accessibility to the personal protective equipment (PPE) of the physical therapists working in Saudi Arabia. Methods: A cross-sectional study was conducted to survey on-duty PT practitioners using a web-based questionnaire. Licensed PT practitioners were invited to participate, and a sample of 424 therapists responded. The questionnaire comprised of 22 questions covering the demographic data and the following domains: sources of knowledge regarding the pandemic, experience, and attitude of the therapists during the pandemic, and accessibility to the PPE. Results: Around 83% of the participants (352) completed all the survey questions. Governmental websites were the most used source of knowledge (39%). Hand sanitization was implemented by the majority of participants (81%). Participants, mainly males and experienced therapist, were willing to treat COVID-19 patients. The COVID-19 complications of prolonged ventilation and immobilization were successfully treated by 91.2% of participants who treated positive cases. About a third of the participants were part of COVID-19 management planning teams or received training to deal with the pandemic. Most of the necessary PPE was adequately accessible during the pandemic. Conclusions: Therapists implemented the recommended hygienic practices and had no problems accessing the necessary PPE. More efforts should target therapists’ education about the social media misleading information and involving the therapists in the pandemic management planning teams.
+ Lu et al. show that CSN5A is involved in chloroplast protein turnover, revealing a ubiquitin-dependent degradation pathway of intra-chloroplast proteins and CCVs jointly participated by CV and CSN5A.
- in F1000Research on 2024-09-18 12:30:46 UTC.
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in Cell Reports: Current Issue on 2024-09-19 00:00:00 UTC.
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- Background The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had led to a global pandemic since December 2019. SARS-CoV-2 is a single-stranded RNA virus, which mutates at a higher rate. Multiple works had been done to study nonsynonymous mutations, which change protein sequences. However, there is little study on the effects of SARS-CoV-2 synonymous mutations, which may affect viral fitness. This study aims to predict the effect of synonymous mutations on the SARS-CoV-2 genome. Methods A total of 26645 SARS-CoV-2 genomic sequences retrieved from Global Initiative on Sharing all Influenza Data (GISAID) database were aligned using MAFFT. Then, the mutations and their respective frequency were identified. Multiple RNA secondary structures prediction tools, namely RNAfold, IPknot++ and MXfold2 were applied to predict the effect of the mutations on RNA secondary structure and their base pair probabilities was estimated using MutaRNA. Relative synonymous codon usage (RSCU) analysis was also performed to measure the codon usage bias (CUB) of SARS-CoV-2. Results A total of 150 synonymous mutations were identified. The synonymous mutation identified with the highest frequency is C3037U mutation in the nsp3 of ORF1a. Of these top 10 highest frequency synonymous mutations, C913U, C3037U, U16176C and C18877U mutants show pronounced changes between wild type and mutant in all 3 RNA secondary structure prediction tools, suggesting these mutations may have some biological impact on viral fitness. These four mutations show changes in base pair probabilities. All mutations except U16176C change the codon to a more preferred codon, which may result in higher translation efficiency. Conclusion Synonymous mutations in SARS-CoV-2 genome may affect RNA secondary structure, changing base pair probabilities and possibly resulting in a higher translation rate. However, lab experiments are required to validate the results obtained from prediction analysis.
+ Arpin was discovered as an inhibitor of the Arp2/3 complex localized at the lamellipodial tip of fibroblasts, where it regulated migration steering. Recently, we showed that arpin stabilizes the epithelial barrier in an Arp2/3-dependent manner. However, the expression and functions of arpin in endothelial cells (EC) have not yet been described. Arpin mRNA and protein are expressed in EC and downregulated by pro-inflammatory cytokines. Arpin depletion in Human Umbilical Vein Endothelial Cells causes the formation of actomyosin stress fibers leading to increased permeability in an Arp2/3-independent manner. Instead, inhibitors of ROCK1 and ZIPK, kinases involved in the generation of stress fibers, normalize the loss-of-arpin effects on actin filaments and permeability. Arpin-deficient mice are viable but show a characteristic vascular phenotype in the lung including edema, microhemorrhage, and vascular congestion, increased F-actin levels, and vascular permeability. Our data show that, apart from being an Arp2/3 inhibitor, arpin is also a regulator of actomyosin contractility and endothelial barrier integrity.
- in F1000Research on 2024-09-18 10:17:24 UTC.
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in eLife on 2024-09-19 00:00:00 UTC.
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-We investigated ultrastructural characteristics of the primary visual cortex in 18 phylogenetically diverse mammals, spanning a broad range of brain sizes from mouse to elephant. Our findings reveal remarkable uniformity in synapse density, postsynaptic density (PSD) length, and mitochondria density, indicating functional and metabolic constraints that maintain these fundamental features.
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-ABSTRACT
-The cerebral cortex accounts for substantial energy expenditure, primarily driven by the metabolic demands of synaptic signaling. Mitochondria, the organelles responsible for generating cellular energy, play a crucial role in this process. We investigated ultrastructural characteristics of the primary visual cortex in 18 phylogenetically diverse mammals, spanning a broad range of brain sizes from mouse to elephant. Our findings reveal remarkable uniformity in synapse density, postsynaptic density (PSD) length, and mitochondria density, indicating functional and metabolic constraints that maintain these fundamental features. Notably, we observed an average of 1.9 mitochondria per synapse across mammalian species. When considered together with the trend of decreasing neuron density with larger brain size, we find that brain enlargement in mammals is characterized by increasing proportions of synapses and mitochondria per cortical neuron. These results shed light on the adaptive mechanisms and metabolic dynamics that govern cortical ultrastructure across mammals.
+ Hydrostatic pressure is a dominant environmental cue for vertically migrating marine organisms but the physiological mechanisms of responding to pressure changes remain unclear. Here, we uncovered the cellular and circuit bases of a barokinetic response in the planktonic larva of the marine annelid Platynereis dumerilii. Increased pressure induced a rapid, graded, and adapting upward swimming response due to the faster beating of cilia in the head multiciliary band. By calcium imaging, we found that brain ciliary photoreceptors showed a graded response to pressure changes. The photoreceptors in animals mutant for ciliary opsin-1 had a smaller sensory compartment and mutant larvae showed diminished pressure responses. The ciliary photoreceptors synaptically connect to the head multiciliary band via serotonergic motoneurons. Genetic inhibition of the serotonergic cells blocked pressure-dependent increases in ciliary beating. We conclude that ciliary photoreceptors function as pressure sensors and activate ciliary beating through serotonergic signalling during barokinesis.
- in Journal of Comparative Neurology on 2024-09-18 10:04:23 UTC.
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in eLife on 2024-09-19 00:00:00 UTC.
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- Author(s): Viviane M. Oliveira and Paulo R. A. Campos
In this paper, we present an in-depth investigation into the dynamics of evolutionary rescue using a resource-based modelling approach. Utilizing classical consumer-resource models, we aim to understand how species can adapt to abrupt environmental changes that alter the availability of substitutabl…
[Phys. Rev. E 110, 034406] Published Wed Sep 18, 2024
+ The Trp53 gene encodes several isoforms of elusive biological significance. Here, we show that mice lacking the Trp53 alternatively spliced (AS) exon, thereby expressing the canonical p53 protein but not isoforms with the AS C-terminus, have unexpectedly lost a male-specific protection against Myc-induced B-cell lymphomas. Lymphomagenesis was delayed in Trp53+/+Eμ-Myc males compared to Trp53ΔAS/ΔAS Eμ-Myc males, but also compared to Trp53+/+Eμ-Myc and Trp53ΔAS/ΔAS Eμ-Myc females. Pre-tumoral splenic cells from Trp53+/+Eμ-Myc males exhibited a higher expression of Ackr4, encoding an atypical chemokine receptor with tumor suppressive effects. We identified Ackr4 as a p53 target gene whose p53-mediated transactivation is inhibited by estrogens, and as a male-specific factor of good prognosis relevant for murine Eμ-Myc-induced and human Burkitt lymphomas. Furthermore, the knockout of ACKR4 increased the chemokine-guided migration of Burkitt lymphoma cells. These data demonstrate the functional relevance of alternatively spliced p53 isoforms and reveal sex disparities in Myc-driven lymphomagenesis.
- in Physical Review E: Biological physics on 2024-09-18 10:00:00 UTC.
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in eLife on 2024-09-19 00:00:00 UTC.
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- Background The Indonesian government built the Mass Rapid Transit (MRT) in Jakarta to reduce traffic congestion and carbon dioxide (CO2) emissions. The objective of this study is to estimate the CO2 emissions reductions from switching from private transport to MRT by using a methodology proposed by the United Nations Convention on Climate Change (UNFCCC) for developing countries, namely the Clean Development Mechanism (CDM) methodology, which generates Certified Emission Reductions (CERs). This methodology is more comprehensive than other available methodologies. However, this method has not been widely used to calculate greenhouse gas (GHG) emission reductions in mass transit projects because it is complex enough to require a lot of data based on primary surveys. Therefore, this research simplifies the CDM formula to make it easier and applicable in Indonesia. Methods The primary data were collected using a questionnaire distributed to 480 MRT Jakarta Phase 1 user respondents in September 2019 (baseline); the secondary data were obtained from The MRT Jakarta. The data were processed using IBM SPSS Statistics 27. The simplified Clean Development Mechanism Approved Consolidated Methodology 0016 (CDM ACM 0016) was the analysis method used. Result The results of this study indicate that 53.75% of MRT Jakarta Phase 1 users are shifting from private transportation, which has reduced CO2 emissions by 2,732.7 tons in 2019 and 6,043.9 tons in 2023. Increasing the number of MRT passengers who switch from private transportation will further reduce CO2 emissions. Conclusion and implications The simplified CDM ACM 0016 formula may be suitable for use in Indonesia. This would enable the measurement of CO2 emission reductions through mitigation actions through MRT development to be certified by the UNFCCC. Applying this method in calculating CO2 emission reductions, implementing strategies to increase MRT passengers, and using renewable energy electricity sources would increase CO2 emission reductions.
+ The excessive cosolute densities in the intracellular fluid create a physicochemical condition called macromolecular crowding (MMC). Intracellular MMC entropically maintains the biochemical thermodynamic equilibria by favouring associative reactions while hindering transport processes. Rapid cell volume shrinkage during extracellular hypertonicity elevates the MMC and disrupts the equilibria, potentially ushering cell death. Consequently, cells actively counter the hypertonic stress through regulatory volume increase (RVI) and restore the MMC homeostasis. Here, we establish fluorescence anisotropy of EGFP as a reliable tool for studying cellular MMC and explore the spatiotemporal dynamics of MMC during cell volume instabilities under multiple conditions. Our studies reveal that the actin cytoskeleton enforces spatially varying MMC levels inside adhered cells. Within cell populations, MMC is uncorrelated with nuclear DNA content but anti-correlated with the cell spread area. Although different cell lines have statistically similar MMC distributions, their responses to extracellular hypertonicity vary. The intensity of the extracellular hypertonicity determines a cell's ability for RVI, which correlates with Nuclear Factor Kappa Beta (NFkB) activation. Pharmacological inhibition and knockdown experiments reveal that Tumour Necrosis Factor Receptor 1 (TNFR1) initiates the hypertonicity induced NFkB signalling and RVI. At severe hypertonicities, the elevated MMC amplifies cytoplasmic microviscosity and hinders Receptor Interacting Protein Kinase 1 (RIPK1) recruitment at the TNFR1 complex, incapacitating the TNFR1-NFkB signalling and consequently, RVI. Together, our studies unveil the involvement of TNFR1-NFkB signalling in modulating RVI and demonstrate the pivotal role of MMC in determining cellular osmoadaptability.
- in F1000Research on 2024-09-18 09:58:52 UTC.
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in eLife on 2024-09-19 00:00:00 UTC.
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- Introduction The emotional impact of patient loss in oncology and palliative care profoundly affects healthcare professionals. This study explores clinicians’ experiences, emotional reactions, and coping mechanisms in these fields, focusing on their professional and personal growth. It aims to provide a comprehensive understanding of how healthcare professionals from different regions and with varying years of experience deal with patient loss, emphasizing cultural, social, and institutional influences on their coping strategies. Methods A mixed-methods approach combined qualitative and quantitative elements. Data were collected using a Microsoft® Forms© survey targeting oncology and palliative care healthcare professionals. The survey included questions on experiences with patient loss, coping strategies, personal and professional growth, and beliefs. Statistical methods and thematic analysis were used to analyse quantitative and qualitative data. Ethical approval was obtained, and the survey ensured participant anonymity and confidentiality. Results The survey received 125 responses from nineteen countries. Emotional reactions to patient loss were significant, with various coping strategies reported, including spiritual practices, self-care, and professional support groups. Personal and professional growth were key outcomes of dealing with patient loss. Themes like Emotional Impact, Coping Mechanisms, and Reflections on Death and Dying were prevalent. Analysis revealed no significant correlation between the time taken by the participants to complete the survey and years of healthcare experience. Conclusion Healthcare professionals in oncology and palliative care face significant emotional challenges due to patient loss. The study emphasizes the importance of diverse and effective coping mechanisms, the supportive role of personal beliefs and workplace environments, and the journey of personal and professional growth amidst these challenges. It highlights the resilience of healthcare workers and underscores the need for supportive systems in managing the emotional aspects of patient care.
+ The Sonic hedgehog (Shh) signaling pathway controls embryonic development and tissue homeostasis after birth. This requires regulated solubilization of dual-lipidated, firmly plasma membrane-associated Shh precursors from producing cells. Although it is firmly established that the resistance-nodulation-division transporter Dispatched (Disp) drives this process, it is less clear how lipidated Shh solubilization from the plasma membrane is achieved. We have previously shown that Disp promotes proteolytic solubilization of Shh from its lipidated terminal peptide anchors. This process, termed shedding, converts tightly membrane-associated hydrophobic Shh precursors into delipidated soluble proteins. We show here that Disp-mediated Shh shedding is modulated by a serum factor that we identify as high-density lipoprotein (HDL). In addition to serving as a soluble sink for free membrane cholesterol, HDLs also accept the cholesterol-modified Shh peptide from Disp. The cholesteroylated Shh peptide is necessary and sufficient for Disp-mediated transfer because artificially cholesteroylated mCherry associates with HDL in a Disp-dependent manner, whereas an N-palmitoylated Shh variant lacking C-cholesterol does not. Disp-mediated Shh transfer to HDL is completed by proteolytic processing of the palmitoylated N-terminal membrane anchor. In contrast to dual-processed soluble Shh with moderate bioactivity, HDL-associated N-processed Shh is highly bioactive. We propose that the purpose of generating different soluble forms of Shh from the dual-lipidated precursor is to tune cellular responses in a tissue-type and time-specific manner.
- in F1000Research on 2024-09-18 09:26:32 UTC.
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in eLife on 2024-09-19 00:00:00 UTC.
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- The Neuroscientist, Volume 30, Issue 5, Page 518-518, October 2024.
+ In the mammalian neocortex, inhibition is important for dynamically balancing excitation and shaping the response properties of cells and circuits. The various computational functions of inhibition are thought to be mediated by different inhibitory neuron types, of which a large diversity exists in several species. Current understanding of the function and connectivity of distinct inhibitory neuron types has mainly derived from studies in transgenic mice. However, it is unknown whether knowledge gained from mouse studies applies to the non-human primate, the model system closest to humans. The lack of viral tools to selectively access inhibitory neuron types has been a major impediment to studying their function in the primate. Here, we have thoroughly validated and characterized several recently developed viral vectors designed to restrict transgene expression to GABAergic cells or their parvalbumin (PV) subtype, and identified two types that show high specificity and efficiency in marmoset V1. We show that in marmoset V1, AAV-h56D induces transgene expression in GABAergic cells with up to 91–94% specificity and 79% efficiency, but this depends on viral serotype and cortical layer. AAV-PHP.eB-S5E2 induces transgene expression in PV cells across all cortical layers with up to 98% specificity and 86–90% efficiency, depending on layer. Thus, these viral vectors are promising tools for studying GABA and PV cell function and connectivity in the primate cortex.
- in The Neuroscientist on 2024-09-18 07:55:44 UTC.
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in eLife on 2024-09-19 00:00:00 UTC.
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- The Neuroscientist, Volume 30, Issue 5, Page 519-519, October 2024.
+ Brain Sciences, Vol. 14, Pages 938: Prevalence and Awareness of Medication Overuse Headache among Undergraduate Students at the University of Belgrade
+ Brain Sciences doi: 10.3390/brainsci14090938
+ Authors:
+ Aleksandra Radojičić
+ Ana Milićević
+ Mirjana Ždraljević
+ Marta Jeremić
+ Dajana Orlović
+ Milija Mijajlović
+
+ Background: Medication overuse headache (MOH) is a prevalent and potentially preventable secondary headache disorder linked to the excessive use of medications intended for primary headache management, particularly migraine. Aim: The aim of our study was to assess the prevalence of MOH among undergraduate students and explore their awareness. Methodology: This observational cross-sectional study included 401 active undergraduate students from the University of Belgrade. Data were collected through an anonymous online questionnaire which was distributed among student groups and via social media. The questionnaire specially designed for this study was developed in accordance with established guidelines for headache epidemiological research. Results: Among the surveyed students, 10 of them (2.5%) met the criteria for the diagnosis of MOH. Awareness of MOH was noted in 149 (37.2%) students, with higher awareness among medical students and those aged 22&ndash;25 years. Despite this awareness, there was no significant difference in MOH occurrence between those aware and unaware of the condition (aware 2.7% vs. unaware 2.4%, p = 1.000). Additionally, significant gaps in education and communication about MOH were evident. Limitations: Participants were recruited through convenience sampling from a single university at one time point. The questionnaire was not specifically validated in the student population, and the data relied on self-reporting. Conclusions: Our study highlighted a notable prevalence of MOH among undergraduate students, with a substantial portion exhibiting awareness of its risks. Despite this awareness, our findings suggest ongoing gaps in education and communication regarding MOH, emphasizing the need for targeted interventions.
- in The Neuroscientist on 2024-09-18 07:55:43 UTC.
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in Brain Sciences on 2024-09-19 00:00:00 UTC.
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- The Neuroscientist, Volume 30, Issue 5, Page 519-519, October 2024.
+ Brain Sciences, Vol. 14, Pages 937: The Effectiveness of Lee Silverman Voice Treatment (LSVT LOUD) on Children’s Speech and Voice: A Scoping Review
+ Brain Sciences doi: 10.3390/brainsci14090937
+ Authors:
+ Angelos Papadopoulos
+ Louiza Voniati
+ Nafsika Ziavra
+ Dionysios Tafiadis
+
+ Background: This scoping review had as a primary goal a review of the literature and the an analysis of the possible effectiveness of the LSVT LOUD approach in children with voice and speech deficits. Methods: A search was conducted in the Scopus and PubMed databases in May of 2024. Eleven articles were obtained from the search. The standards of PRISMA recommendations were used for scoping reviews and the PCC framework was used for the eligibility criteria. Furthermore, the study used the instructions in the Cochrane Handbook for a quality assessment. The Mendeley Reference Manager software collected the studies and removed duplicates. Results: The reviewed studies employed formal and informal measures to assess voice and speech abilities in the children. Regarding the sample&rsquo;s characteristics, the studies mostly included children with Cerebral Palsy (CP) and also those with Down Syndrome (DS). All the studies reported that children with CP and DS undertook a total dose of the LSVT LOUD treatment. Significant post-treatment findings indicated increased speech function and sound pressure level, regarding the auditory&ndash;perceptual ratings of voice and speech improvement. In many studies, parents&rsquo; and expert listeners&rsquo; ratings of voice, perception of vocal loudness, speech, and communication indicated improvement. Conclusions: The majority of the included studies provide positive evidence for the LSVT as an approach. However, the small sample size that featured in the studies, as well as their limitations, made these conclusions uncertain. Moreover, the study&rsquo;s findings provided recommendations that speech language therapists and other clinicians need to follow when setting a treatment plan with children with CP and DS.
- in The Neuroscientist on 2024-09-18 07:55:42 UTC.
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in Brain Sciences on 2024-09-19 00:00:00 UTC.
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- The Neuroscientist, Volume 30, Issue 5, Page 516-516, October 2024.
+ Brain Sciences, Vol. 14, Pages 936: Effects of Stress Exposure to Pain Perception in Pre-Clinical Studies: Focus on the Nociceptin/Orphanin FQ–NOP Receptor System
+ Brain Sciences doi: 10.3390/brainsci14090936
+ Authors:
+ Pietro Pola
+ Alessia Frezza
+ Elaine C. Gavioli
+ Girolamo Calò
+ Chiara Ruzza
+
+ Exposure to physical and psychological stress modulates pain transmission in a dual manner. Stress-induced analgesia (SIA) refers to the reduction in pain sensitivity that can occur in response to acute stress. On the contrary, chronic stress exposure may lead to a phenomenon named stress-induced hyperalgesia (SIH). SIH is a clinically relevant phenomenon since it has been well documented that physical and psychological stress exacerbates pain in patients with several chronic pain syndromes, including migraine. The availability of animal models of SIA and SIH is of high importance for understanding the biological mechanisms leading to these phenomena and for the identification of pharmacological targets useful to alleviate the burden of stress-exacerbated chronic pain. Among these targets, the nociceptin/orphanin FQ (N/OFQ)&ndash;N/OFQ peptide (NOP) receptor system has been identified as a key modulator of both pain transmission and stress susceptibility. This review describes first the experimental approaches to induce SIA and SIH in rodents. The second part of the manuscript summarizes the scientific evidence that suggests the N/OFQ&ndash;NOP receptor system as a player in the stress&ndash;pain interaction and candidates NOP antagonists as useful drugs to mitigate the detrimental effects of stress exposure on pain perception.
- in The Neuroscientist on 2024-09-18 07:55:41 UTC.
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in Brain Sciences on 2024-09-19 00:00:00 UTC.
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- The Neuroscientist, Volume 30, Issue 5, Page 517-517, October 2024.
+ Brain Sciences, Vol. 14, Pages 935: Abnormal Dynamic Reconfiguration of Multilayer Temporal Networks in Patients with Bipolar Disorder
+ Brain Sciences doi: 10.3390/brainsci14090935
+ Authors:
+ Luyao Lai
+ Dandan Li
+ Yating Zhang
+ Jianchao Hao
+ Xuedong Wang
+ Xiaohong Cui
+ Jie Xiang
+ Bin Wang
+
+ Background: Multilayer networks have been used to identify abnormal dynamic reconfiguration in bipolar disorder (BD). However, these studies ignore the differences in information interactions between adjacent layers when constructing multilayer networks, and the analysis of dynamic reconfiguration is not comprehensive enough; Methods: Resting-state functional magnetic resonance imaging data were collected from 46 BD patients and 54 normal controls. A multilayer temporal network was constructed for each subject, and inter-layer coupling of different nodes was considered using network similarity. The promiscuity, recruitment, and integration coefficients were calculated to quantify the different dynamic reconfigurations between the two groups; Results: The global inter-layer coupling, recruitment, and integration coefficients were significantly lower in BD patients. These results were further observed in the attention network and the limbic/paralimbic and subcortical network, reflecting reduced temporal stability, intra- and inter-subnetwork communication abilities in BD patients. The whole-brain promiscuity was increased in BD patients. The same results were observed in the somatosensory/motor and auditory network, reflecting more functional interactions; Conclusions: This study discovered abnormal dynamic interactions of BD from the perspective of dynamic reconfiguration, which can help to understand the pathological mechanisms of BD.
- in The Neuroscientist on 2024-09-18 07:55:41 UTC.
+
in Brain Sciences on 2024-09-19 00:00:00 UTC.
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- Journal of Neurophysiology, Ahead of Print.
+ Brain Sciences, Vol. 14, Pages 934: Clinical and Anatomical Characteristics of Perforator Aneurysms of the Posterior Cerebral Artery: A Single-Center Experience
+ Brain Sciences doi: 10.3390/brainsci14090934
+ Authors:
+ Anahita Malvea
+ Shigeta Miyake
+ Ronit Agid
+ Hugo Andrade Barazarte
+ Richard Farb
+ Timo Krings
+ Pascal John Roger Mosimann
+ Patrick Joseph Nicholson
+ Ivan Radovanovic
+ Karel Terbrugge
+ Robert Willinsky
+ Joanna Danielle Schaafsma
+ Eef J. Hendriks
+
+ Introduction: Posterior cerebral artery (PCA) aneurysms represent up to 1% of all cerebral aneurysms. P1-P2 perforator aneurysms are thought to be even less prevalent and often require complex treatment strategies due to their anatomical and morphological characteristics, with risk of a perforator infarct. We studied the treatment of P1-P2 perforator aneurysms in a single-center cohort from a high-volume tertiary center, reporting clinical and anatomical characteristics, treatment strategies, and outcomes. Methods: A retrospective analysis of adult patients with a P1-P2 perforator aneurysm who presented at our institution between January 2000 and January 2023 was performed. The patients were analyzed for demographics, clinical presentation, imaging findings, treatment techniques, outcomes, and complications. Subgroup analyses between ruptured versus non-ruptured cases were included. Results: Out of 2733 patients with a cerebral aneurysm, 14 patients (0.5%) presented with a P1-P2 perforator aneurysm. All six patients with a ruptured aneurysm were treated by endovascular coiling, of whom one patient (16.7%) required surgical clipping of a recurrence. One out of eight (12.5%) patients with unruptured aneurysms was treated by surgical clipping. P1-P2 perforator aneurysms predominantly affected middle-aged individuals (median 59.5 years), with 10/14 (71.4%) being female. Endovascular coiling was the primary treatment modality overall, yielding favorable technical outcomes, however, it was complicated by a perforator infarct in two patients (33.3%) without new permanent morbidity or mortality secondary to treatment. Conclusions: P1-P2 perforator aneurysms are a rare subtype of intracranial aneurysm. Endovascular coiling could present an effective treatment modality; however, care should be taken for ischemic complications in the dependent perforator territory. Larger studies are required to provide more insights.
- in Journal of Neurophysiology on 2024-09-18 07:01:25 UTC.
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in Brain Sciences on 2024-09-19 00:00:00 UTC.
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- Journal of Neurophysiology, Ahead of Print.
+ Millisecond-scale temporal spiking patterns encode sensory information in the periphery, but their role in the neocortex remains controversial. The sense of touch provides a window into temporal coding because tactile neurons often exhibit precise, repeatable, and informative temporal spiking patterns. In the somatosensory cortex (S1), responses to skin vibrations exhibit phase locking that faithfully carries information about vibratory frequency. However, the respective roles of spike timing and rate in frequency coding are confounded because vibratory frequency shapes both the timing and rates of responses. To disentangle the contributions of these two neural features, we measured S1 responses as rhesus macaques performed frequency discrimination tasks in which differences in frequency were accompanied by orthogonal variations in amplitude. We assessed the degree to which the strength and timing of responses could account for animal performance. First, we showed that animals can discriminate frequency, but their performance is biased by amplitude variations. Second, rate-based representations of frequency are susceptible to changes in amplitude but in ways that are inconsistent with the animals’ behavioral biases, calling into question a rate-based neural code for frequency. In contrast, timing-based representations are highly informative about frequency but impervious to changes in amplitude, which is also inconsistent with the animals’ behavior. We account for the animals’ behavior with a model wherein frequency coding relies on a temporal code, but frequency judgments are biased by perceived magnitude. We conclude that information about vibratory frequency is not encoded in S1 firing rates but primarily in temporal patterning on millisecond timescales.
- in Journal of Neurophysiology on 2024-09-18 07:01:25 UTC.
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in Journal of Neuroscience on 2024-09-18 16:30:21 UTC.
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- Journal of Neurophysiology, Ahead of Print.
+ Navigation requires integrating sensory information with a stable schema to create a dynamic map of an animal’s position using egocentric and allocentric coordinate systems. In the hippocampus, place cells encode allocentric space, but their firing rates may also exhibit directional tuning within egocentric or allocentric reference frames. We compared experimental and simulated data to assess the prevalence of tuning to egocentric bearing (EB) among hippocampal cells in rats foraging in an open field. Using established procedures, we confirmed egocentric modulation of place cell activity in recorded data; however, simulated data revealed a high false-positive rate (FPR). When we accounted for false positives by comparing with shuffled data that retain correlations between the animal’s direction and position, only a very low number of hippocampal neurons appeared modulated by EB. Our study highlights biases affecting FPRs and provides insights into the challenges of identifying egocentric modulation in hippocampal neurons.
- in Journal of Neurophysiology on 2024-09-18 07:01:25 UTC.
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in Journal of Neuroscience on 2024-09-18 16:30:21 UTC.
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- Science Advances, Volume 10, Issue 38, September 2024.
+
- in Science Advances on 2024-09-18 07:00:00 UTC.
+
in Journal of Neuroscience on 2024-09-18 16:30:21 UTC.
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- Science Advances, Volume 10, Issue 38, September 2024.
+ Attention and decision-making processes are fundamental to cognition. However, they are usually experimentally confounded, making it difficult to link neural observations to specific processes. Here we separated the effects of selective attention from the effects of decision-making on brain activity obtained from human participants (both sexes), using a two-stage task where the attended stimulus and decision were orthogonal and separated in time. Multivariate pattern analyses of multimodal neuroimaging data revealed the dynamics of perceptual and decision-related information coding through time with magnetoencephalography (MEG), through space with functional magnetic resonance imaging (fMRI), and their combination (MEG-fMRI fusion). Our MEG results showed an effect of attention before decision-making could begin, and fMRI results showed an attention effect in early visual and frontoparietal regions. Model-based MEG-fMRI fusion suggested that attention boosted stimulus information in the frontoparietal and early visual regions before decision-making was possible. Together, our results suggest that attention affects neural stimulus representations in the frontoparietal regions independent of decision-making.
- in Science Advances on 2024-09-18 07:00:00 UTC.
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in Journal of Neuroscience on 2024-09-18 16:30:21 UTC.
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- Science Advances, Volume 10, Issue 38, September 2024.
+ Making choices about whether and when to engage cognitive effort are a common feature of everyday experience, with important consequences for academic, career, and health outcomes. Yet, despite their hypothesized importance, very little is understood about the underlying mechanisms that support this form of human cost–benefit decision-making. To investigate these mechanisms, we used the Cognitive Effort Discounting Paradigm (Cog-ED) during fMRI scanning to precisely quantify the neural encoding of varying cognitive effort demands relative to reward outcomes, within two distinct cognitive domains (working memory, speech comprehension). The findings provide strong evidence that the dorsal anterior cingulate cortex (dACC) plays a central and selective role in this decision-making process. Trial-by-trial modulations in dACC activation tracked the relative subjective value of the low-effort, low-reward option, with the strongest activity occurring when this was of greater value than the high-effort, high-reward option. In contrast, dACC activity was not modulated by decision difficulty, though such effects were found in other frontoparietal regions. Critically, dACC activity was also strongly correlated across the two decision-making task domains and further predicted subsequent choice behavior in both. Together, the results suggest that dACC activity modulation reflects a domain-general valuation comparison mechanism, which acts to bias participants away from decisions to engage in cognitive effort, when the perceived subjective costs of such engagement outweigh the reward-related benefits. These findings complement work in other cost domains and species by pointing to a clear role of the dACC in representing subjective value differences between choice options during cost–benefit decision-making.
- in Science Advances on 2024-09-18 07:00:00 UTC.
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in Journal of Neuroscience on 2024-09-18 16:30:21 UTC.
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- Science Advances, Volume 10, Issue 38, September 2024.
+ Neuroscience research has evolved to generate increasingly large and complex experimental data sets, and advanced data science tools are taking on central roles in neuroscience research. Neurodata Without Borders (NWB), a standard language for neurophysiology data, has recently emerged as a powerful solution for data management, analysis, and sharing. We here discuss our labs’ efforts to implement NWB data science pipelines. We describe general principles and specific use cases that illustrate successes, challenges, and non-trivial decisions in software engineering. We hope that our experience can provide guidance for the neuroscience community and help bridge the gap between experimental neuroscience and data science. Key takeaways from this article are that (1) standardization with NWB requires non-trivial design choices; (2) the general practice of standardization in the lab promotes data awareness and literacy, and improves transparency, rigor, and reproducibility in our science; (3) we offer several feature suggestions to ease the extensibility, publishing/sharing, and usability for NWB standard and users of NWB data.
- in Science Advances on 2024-09-18 07:00:00 UTC.
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in Journal of Neuroscience on 2024-09-18 16:30:21 UTC.
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- Science Advances, Volume 10, Issue 38, September 2024.
+ The frontal eye field (FEF) plays a well-established role in the control of visual attention. The strength of an FEF neuron's response to a visual stimulus presented in its receptive field is enhanced if the stimulus captures spatial attention by virtue of its salience. A stimulus can be rendered salient by cognitive factors as well as by physical attributes. These include surprise. The aim of the present experiment was to determine whether surprise-induced salience would result in enhanced visual-response strength in the FEF. Toward this end, we monitored neuronal activity in two male monkeys while presenting first a visual cue predicting with high probability that the reward delivered at the end of the trial would be good or bad (large or small) and then a visual cue announcing the size of the impending reward with certainty. The second cue usually confirmed but occasionally violated the expectation set up by the first cue. Neurons responded more strongly to the second cue when it violated than when it confirmed expectation. The increase in the firing rate was accompanied by a decrease in spike-count correlation as expected from capture of attention. Although both good surprise and bad surprise induced enhanced firing, the effects appeared to arise from distinct mechanisms as indicated by the fact that the bad-surprise signal appeared at a longer latency than the good-surprise signal and by the fact that the strength of the two signals varied independently across neurons.
- in Science Advances on 2024-09-18 07:00:00 UTC.
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in Journal of Neuroscience on 2024-09-18 16:30:21 UTC.
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- Science Advances, Volume 10, Issue 38, September 2024.
+ Circadian, infradian, and seasonal changes in steroid hormone secretion have been tied to changes in brain volume in several mammalian species. However, the relationship between circadian changes in steroid hormone production and rhythmic changes in brain morphology in humans is largely unknown. Here, we examined the relationship between diurnal fluctuations in steroid hormones and multiscale brain morphology in a precision imaging study of a male who completed 40 MRI and serological assessments at 7 A.M. and 8 P.M. over the course of a month, targeting hormone concentrations at their peak and nadir. Diurnal fluctuations in steroid hormones were tied to pronounced changes in global and regional brain morphology. From morning to evening, total brain volume, gray matter volume, and cortical thickness decreased, coincident with decreases in steroid hormone concentrations (testosterone, estradiol, and cortisol). In parallel, cerebrospinal fluid and ventricle size increased from A.M. to P.M. Global changes were driven by decreases within the occipital and parietal cortices. These findings highlight natural rhythms in brain morphology that keep time with the diurnal ebb and flow of steroid hormones.
- in Science Advances on 2024-09-18 07:00:00 UTC.
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in Journal of Neuroscience on 2024-09-18 16:30:21 UTC.
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- Science Advances, Volume 10, Issue 38, September 2024.
+ The presence of valence coding neurons in the basolateral amygdala (BLA) that form distinct projections to other brain regions implies functional opposition between aversion and reward during learning. However, evidence for opponent interactions in fear learning is sparse and may only be apparent under certain conditions. Here we test this possibility by studying the roles of the BLA->central amygdala (CeA) and BLA->nucleus accumbens (Acb) pathways in fear learning in male rats. First, we assessed the organization of these pathways in the rat brain. BLA->CeA and BLA->Acb pathways were largely segregated in the BLA but shared overlapping molecular profiles. Then we assessed activity of the BLA->CeA and BLA->Acb pathways during two different forms of fear learning—fear learning in a neutral context and fear learning in a reward context. BLA->CeA neurons were robustly recruited by footshock regardless of where fear learning occurred, whereas recruitment of BLA->Acb neurons was state-dependent because footshock only recruited this pathway in a reward context. Finally, we assessed the causal roles of activity in these pathways in fear learning. Photoinhibition of the BLA->CeA pathway during the footshock US impaired fear learning, regardless of where fear learning occurred. In contrast, photoinhibition of the BLA->Acb pathway augmented fear learning, but only in the reward context. Taken together, our findings show circuit- and state-dependent opponent processing of fear. Footshock activity in the BLA->Acb pathway limits how much fear is learned.
- in Science Advances on 2024-09-18 07:00:00 UTC.
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in Journal of Neuroscience on 2024-09-18 16:30:21 UTC.
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- Science Advances, Volume 10, Issue 38, September 2024.
+
- in Science Advances on 2024-09-18 07:00:00 UTC.
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in Journal of Neuroscience on 2024-09-18 16:30:21 UTC.
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+
- Science Advances, Volume 10, Issue 38, September 2024.
+ Ribbon synapses of inner hair cells (IHCs) are uniquely designed for ultrafast and indefatigable neurotransmission of the sound. The molecular machinery ensuring the efficient, compensatory recycling of the synaptic vesicles (SVs), however, remains elusive. This study showed that hair cell knock-out of murine Dmxl2, whose human homolog is responsible for nonsyndromic sensorineural hearing loss DFNA71, resulted in auditory synaptopathy by impairing synaptic endocytosis and recycling. The mutant mice in the C57BL/6J background of either sex had mild hearing loss with severely diminished wave I amplitude of the auditory brainstem response. Membrane capacitance measurements of the IHCs revealed deficiency in sustained synaptic exocytosis and endocytic membrane retrieval. Consistent with the electrophysiological findings, 3D electron microscopy reconstruction showed reduced reserve pool of SVs and endocytic compartments, while the membrane-proximal and ribbon-associated vesicles remain intact. Our results propose an important role of DMXL2 in hair cell endocytosis and recycling of the SVs.
- in Science Advances on 2024-09-18 07:00:00 UTC.
+
in Journal of Neuroscience on 2024-09-18 16:30:21 UTC.
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- Science Advances, Volume 10, Issue 38, September 2024.
+
- in Science Advances on 2024-09-18 07:00:00 UTC.
+
in Journal of Neuroscience on 2024-09-18 16:30:21 UTC.
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- Science Advances, Volume 10, Issue 38, September 2024.
+
- in Science Advances on 2024-09-18 07:00:00 UTC.
+
in Journal of Neuroscience on 2024-09-18 16:30:21 UTC.
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- Science Advances, Volume 10, Issue 38, September 2024.
+ The role of experience in the development and maintenance of emergent network properties such as cortical oscillations and states is poorly understood. To define how early-life experience affects cortical dynamics in the visual cortex of adult, head-fixed mice, we examined the effects of two forms of blindness initiated before eye opening and continuing through recording: (1) bilateral loss of retinal input (enucleation) and (2) degradation of visual input (eyelid suture). Neither form of deprivation fundamentally altered the state-dependent regulation of firing rates or local field potentials. However, each deprivation caused unique changes in network behavior. Laminar analysis revealed two different generative mechanisms for low-frequency synchronization: one prevalent during movement and the other during quiet wakefulness. The former was absent in enucleated mice, suggesting a mouse homolog of human alpha oscillations. In addition, neurons in enucleated animals were less correlated and fired more regularly, but no change in mean firing rate. Eyelid suture decreased firing rates during quiet wakefulness, but not during movement, with no effect on neural correlations or regularity. Sutured animals showed a broadband increase in depth EEG power and an increased occurrence, but reduced central frequency, of narrowband gamma oscillations. The complementary—rather than additive—effects of lid suture and enucleation suggest that the development of emergent network properties does not require vision but is plastic to modified input. Our results suggest a complex interaction of internal set points and experience determines mature cortical activity, with low-frequency synchronization being particularly susceptible to early deprivation.
- in Science Advances on 2024-09-18 07:00:00 UTC.
+
in Journal of Neuroscience on 2024-09-18 16:30:21 UTC.
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- Science Advances, Volume 10, Issue 38, September 2024.
+ People parse continuous experiences at natural breakpoints called event boundaries, which is important for understanding an environment's causal structure and for responding to uncertainty within it. However, it remains unclear how different forms of uncertainty affect the parsing of continuous experiences and how such uncertainty influences the brain's processing of ongoing events. We exposed human participants of both sexes (N = 34) to a continuous sequence of semantically meaningless images. We generated sequences from random walks through a graph that grouped images into temporal communities. After learning, we asked participants to segment another sequence at natural breakpoints (event boundaries). Participants segmented the sequence at learned transitions between communities, as well as at novel transitions, suggesting that people can segment temporally extended experiences into events based on learned structure as well as prediction error. Greater segmentation at novel boundaries was associated with enhanced parietal scalp electroencephalography (EEG) activity between 250 and 450 ms after the stimulus onset. Multivariate classification of EEG activity showed that novel and learned boundaries evoked distinct patterns of neural activity, particularly theta band power in posterior electrodes. Learning also led to distinct neural representations for stimuli within the temporal communities, while neural activity at learned boundary nodes showed predictive evidence for the adjacent community. The data show that people segment experiences at both learned and novel boundaries and suggest that learned event boundaries trigger retrieval of information about the upcoming community that could underlie anticipation of the next event in a sequence.
- in Science Advances on 2024-09-18 07:00:00 UTC.
+
in Journal of Neuroscience on 2024-09-18 16:30:21 UTC.
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- Science Advances, Volume 10, Issue 38, September 2024.
+ Spike-and-wave discharges (SWDs) and sleep spindles are characteristic electroencephalographic (EEG) hallmarks of absence seizures and nonrapid eye movement sleep, respectively. They are commonly generated by the cortico–thalamo–cortical network including the thalamic reticular nucleus (TRN). It has been reported that SWD development is accompanied by a decrease in sleep spindle density in absence seizure patients and animal models. However, whether the decrease in sleep spindle density precedes, coincides with, or follows, the SWD development remains unknown. To clarify this, we exploited Pvalb-tetracycline transactivator (tTA)::tetO-ArchT (PV-ArchT) double-transgenic mouse, which can induce an absence seizure phenotype in a time-controllable manner by expressing ArchT in PV neurons of the TRN. In these mice, EEG recordings demonstrated that a decrease in sleep spindle density occurred 1 week before the onset of typical SWDs, with the expression of ArchT. To confirm such temporal relationship observed in these genetic model mice, we used a gamma-butyrolactone (GBL) pharmacological model of SWDs. Prior to GBL administration, we administered caffeine to wild-type mice for 3 consecutive days to induce a decrease in sleep spindle density. We then administered low-dose GBL, which cannot induce SWDs in normally conditioned mice but led to the occurrence of SWDs in caffeine-conditioned mice. These findings indicate a temporal relationship in which the decrease in sleep spindle density consistently precedes SWD development. Furthermore, the decrease in sleep spindle activity may have a role in facilitating the development of SWDs. Our findings suggest that sleep spindle reductions could serve as early indicators of seizure susceptibility.
- in Science Advances on 2024-09-18 07:00:00 UTC.
+
in eNeuro on 2024-09-18 16:30:21 UTC.
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- Science Advances, Volume 10, Issue 38, September 2024.
+ Retinitis pigmentosa (RP) is a family of genetically heterogeneous diseases still without a cure. Despite the causative genetic mutation typically not expressed in cone photoreceptors, these cells inevitably degenerate following the primary death of rods, causing blindness. The reasons for the "bystander" degeneration of cones are presently unknown but decrement of survival factors, oxidative stress, and inflammation all play a role. Targeting these generalized biological processes represents a strategy to develop mutation-agnostic therapies for saving vision in large populations of RP individuals. A classical method to support neuronal survival is by employing neurotrophic factors, such as NGF. This study uses painless human NGF (hNGFp), a TrkA receptor-biased variant of the native molecule with lower affinity for nociceptors and limited activity as a pain inducer; the molecule has identical neurotrophic power of the native form but a reduced affinity for the p75NTR receptors, known to trigger apoptosis. hNGFp has a recognized activity on brain microglial cells, which are induced to a phenotype switch from a highly activated to a more homeostatic configuration. hNGFp was administered to RP-like mice in vivo with the aim of decreasing retinal inflammation and also providing retinal neuroprotection. However, the ability of this treatment to counteract the bystander degeneration of cones remained limited.
- in Science Advances on 2024-09-18 07:00:00 UTC.
+
in eNeuro on 2024-09-18 16:30:21 UTC.
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- Science Advances, Volume 10, Issue 38, September 2024.
+ by Kiesha Prem, Kevin van Zandvoort, Petra Klepac, Rosalind M. Eggo, Nicholas G. Davies, Centre for the Mathematical Modelling of Infectious Diseases COVID-19 Working Group, Alex R. Cook, Mark Jit
- in Science Advances on 2024-09-18 07:00:00 UTC.
+
in PLoS Computational Biology on 2024-09-18 14:00:00 UTC.
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- Science Advances, Volume 10, Issue 38, September 2024.
+ by G. Eric Bastien, Rachel N. Cable, Cecelia Batterbee, A. J. Wing, Luis Zaman, Melissa B. Duhaime
+
+Viruses of microbes are ubiquitous biological entities that reprogram their hosts’ metabolisms during infection in order to produce viral progeny, impacting the ecology and evolution of microbiomes with broad implications for human and environmental health. Advances in genome sequencing have led to the discovery of millions of novel viruses and an appreciation for the great diversity of viruses on Earth. Yet, with knowledge of only “who is there?” we fall short in our ability to infer the impacts of viruses on microbes at population, community, and ecosystem-scales. To do this, we need a more explicit understanding “who do they infect?” Here, we developed a novel machine learning model (ML), Virus-Host Interaction Predictor (VHIP), to predict virus-host interactions (infection/non-infection) from input virus and host genomes. This ML model was trained and tested on a high-value manually curated set of 8849 virus-host pairs and their corresponding sequence data. The resulting dataset, ‘Virus Host Range network’ (VHRnet), is core to VHIP functionality. Each data point that underlies the VHIP training and testing represents a lab-tested virus-host pair in VHRnet, from which meaningful signals of viral adaptation to host were computed from genomic sequences. VHIP departs from existing virus-host prediction models in its ability to predict multiple interactions rather than predicting a single most likely host or host clade. As a result, VHIP is able to infer the complexity of virus-host networks in natural systems. VHIP has an 87.8% accuracy rate at predicting interactions between virus-host pairs at the species level and can be applied to novel viral and host population genomes reconstructed from metagenomic datasets.
- in Science Advances on 2024-09-18 07:00:00 UTC.
+
in PLoS Computational Biology on 2024-09-18 14:00:00 UTC.
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- Science Advances, Volume 10, Issue 38, September 2024.
+ by David Anaguano, Opeoluwa Adewale-Fasoro, Grace W. Vick, Sean Yanik, James Blauwkamp, Manuel A. Fierro, Sabrina Absalon, Prakash Srinivasan, Vasant Muralidharan
+
+Malaria is a global and deadly human disease caused by the apicomplexan parasites of the genus Plasmodium. Parasite proliferation within human red blood cells (RBCs) is associated with the clinical manifestations of the disease. This asexual expansion within human RBCs begins with the invasion of RBCs by P. falciparum, which is mediated by the secretion of effectors from 2 specialized club-shaped secretory organelles in merozoite-stage parasites known as rhoptries. We investigated the function of the Rhoptry Neck Protein 11 (RON11), which contains 7 transmembrane domains and calcium-binding EF-hand domains. We generated conditional mutants of the P. falciparum RON11. Knockdown of RON11 inhibits parasite growth by preventing merozoite invasion. The loss of RON11 did not lead to any defects in processing of rhoptry proteins but instead led to a decrease in the amount of rhoptry proteins. We utilized ultrastructure expansion microscopy (U-ExM) to determine the effect of RON11 knockdown on rhoptry biogenesis. Surprisingly, in the absence of RON11, fully developed merozoites had only 1 rhoptry each. The single rhoptry in RON11-deficient merozoites were morphologically typical with a bulb and a neck oriented into the apical polar ring. Moreover, rhoptry proteins are trafficked accurately to the single rhoptry in RON11-deficient parasites. These data show that in the absence of RON11, the first rhoptry is generated during schizogony but upon the start of cytokinesis, the second rhoptry never forms. Interestingly, these single-rhoptry merozoites were able to attach to host RBCs but are unable to invade RBCs. Instead, RON11-deficient merozoites continue to engage with RBC for prolonged periods eventually resulting in echinocytosis, a result of secreting the contents from the single rhoptry into the RBC. Together, our data show that RON11 triggers the de novo biogenesis of the second rhoptry and functions in RBC invasion.
- in Science Advances on 2024-09-18 07:00:00 UTC.
+
in PLoS Biology on 2024-09-18 14:00:00 UTC.
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- Science Advances, Volume 10, Issue 38, September 2024.
+ by Tianyuan Lei, Xuhong Liao, Xinyuan Liang, Lianglong Sun, Mingrui Xia, Yunman Xia, Tengda Zhao, Xiaodan Chen, Weiwei Men, Yanpei Wang, Leilei Ma, Ningyu Liu, Jing Lu, Gai Zhao, Yuyin Ding, Yao Deng, Jiali Wang, Rui Chen, Haibo Zhang, Shuping Tan, Jia-Hong Gao, Shaozheng Qin, Sha Tao, Qi Dong, Yong He
+
+The modular structure of functional connectomes in the human brain undergoes substantial reorganization during development. However, previous studies have implicitly assumed that each region participates in one single module, ignoring the potential spatial overlap between modules. How the overlapping functional modules develop and whether this development is related to gray and white matter features remain unknown. Using longitudinal multimodal structural, functional, and diffusion MRI data from 305 children (aged 6 to 14 years), we investigated the maturation of overlapping modules of functional networks and further revealed their structural associations. An edge-centric network model was used to identify the overlapping modules, and the nodal overlap in module affiliations was quantified using the entropy measure. We showed a regionally heterogeneous spatial topography of the overlapping extent of brain nodes in module affiliations in children, with higher entropy (i.e., more module involvement) in the ventral attention, somatomotor, and subcortical regions and lower entropy (i.e., less module involvement) in the visual and default-mode regions. The overlapping modules developed in a linear, spatially dissociable manner, with decreased entropy (i.e., decreased module involvement) in the dorsomedial prefrontal cortex, ventral prefrontal cortex, and putamen and increased entropy (i.e., increased module involvement) in the parietal lobules and lateral prefrontal cortex. The overlapping modular patterns captured individual brain maturity as characterized by chronological age and were predicted by integrating gray matter morphology and white matter microstructural properties. Our findings highlight the maturation of overlapping functional modules and their structural substrates, thereby advancing our understanding of the principles of connectome development.
- in Science Advances on 2024-09-18 07:00:00 UTC.
+
in PLoS Biology on 2024-09-18 14:00:00 UTC.
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- Science Advances, Volume 10, Issue 38, September 2024.
+ Background: Physical therapy (PT) services can be essential for recovery from coronavirus disease 2019 (COVID-19) infection. Maintaining an efficient healthcare service is achieved by ensuring the safety of a well-informed healthcare practitioner. This study aimed to assess the sources of knowledge, attitude, experience, and accessibility to the personal protective equipment (PPE) of the physical therapists working in Saudi Arabia. Methods: A cross-sectional study was conducted to survey on-duty PT practitioners using a web-based questionnaire. Licensed PT practitioners were invited to participate, and a sample of 424 therapists responded. The questionnaire comprised of 22 questions covering the demographic data and the following domains: sources of knowledge regarding the pandemic, experience, and attitude of the therapists during the pandemic, and accessibility to the PPE. Results: Around 83% of the participants (352) completed all the survey questions. Governmental websites were the most used source of knowledge (39%). Hand sanitization was implemented by the majority of participants (81%). Participants, mainly males and experienced therapist, were willing to treat COVID-19 patients. The COVID-19 complications of prolonged ventilation and immobilization were successfully treated by 91.2% of participants who treated positive cases. About a third of the participants were part of COVID-19 management planning teams or received training to deal with the pandemic. Most of the necessary PPE was adequately accessible during the pandemic. Conclusions: Therapists implemented the recommended hygienic practices and had no problems accessing the necessary PPE. More efforts should target therapists’ education about the social media misleading information and involving the therapists in the pandemic management planning teams.
- in Science Advances on 2024-09-18 07:00:00 UTC.
+
in F1000Research on 2024-09-18 12:30:46 UTC.
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- Science Advances, Volume 10, Issue 38, September 2024.
+ Background The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had led to a global pandemic since December 2019. SARS-CoV-2 is a single-stranded RNA virus, which mutates at a higher rate. Multiple works had been done to study nonsynonymous mutations, which change protein sequences. However, there is little study on the effects of SARS-CoV-2 synonymous mutations, which may affect viral fitness. This study aims to predict the effect of synonymous mutations on the SARS-CoV-2 genome. Methods A total of 26645 SARS-CoV-2 genomic sequences retrieved from Global Initiative on Sharing all Influenza Data (GISAID) database were aligned using MAFFT. Then, the mutations and their respective frequency were identified. Multiple RNA secondary structures prediction tools, namely RNAfold, IPknot++ and MXfold2 were applied to predict the effect of the mutations on RNA secondary structure and their base pair probabilities was estimated using MutaRNA. Relative synonymous codon usage (RSCU) analysis was also performed to measure the codon usage bias (CUB) of SARS-CoV-2. Results A total of 150 synonymous mutations were identified. The synonymous mutation identified with the highest frequency is C3037U mutation in the nsp3 of ORF1a. Of these top 10 highest frequency synonymous mutations, C913U, C3037U, U16176C and C18877U mutants show pronounced changes between wild type and mutant in all 3 RNA secondary structure prediction tools, suggesting these mutations may have some biological impact on viral fitness. These four mutations show changes in base pair probabilities. All mutations except U16176C change the codon to a more preferred codon, which may result in higher translation efficiency. Conclusion Synonymous mutations in SARS-CoV-2 genome may affect RNA secondary structure, changing base pair probabilities and possibly resulting in a higher translation rate. However, lab experiments are required to validate the results obtained from prediction analysis.
- in Science Advances on 2024-09-18 07:00:00 UTC.
+
in F1000Research on 2024-09-18 10:17:24 UTC.
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- Science Advances, Volume 10, Issue 38, September 2024.
+
+We investigated ultrastructural characteristics of the primary visual cortex in 18 phylogenetically diverse mammals, spanning a broad range of brain sizes from mouse to elephant. Our findings reveal remarkable uniformity in synapse density, postsynaptic density (PSD) length, and mitochondria density, indicating functional and metabolic constraints that maintain these fundamental features.
+
+
+
+ABSTRACT
+The cerebral cortex accounts for substantial energy expenditure, primarily driven by the metabolic demands of synaptic signaling. Mitochondria, the organelles responsible for generating cellular energy, play a crucial role in this process. We investigated ultrastructural characteristics of the primary visual cortex in 18 phylogenetically diverse mammals, spanning a broad range of brain sizes from mouse to elephant. Our findings reveal remarkable uniformity in synapse density, postsynaptic density (PSD) length, and mitochondria density, indicating functional and metabolic constraints that maintain these fundamental features. Notably, we observed an average of 1.9 mitochondria per synapse across mammalian species. When considered together with the trend of decreasing neuron density with larger brain size, we find that brain enlargement in mammals is characterized by increasing proportions of synapses and mitochondria per cortical neuron. These results shed light on the adaptive mechanisms and metabolic dynamics that govern cortical ultrastructure across mammals.
- in Science Advances on 2024-09-18 07:00:00 UTC.
+
in Journal of Comparative Neurology on 2024-09-18 10:04:23 UTC.
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- Science Advances, Volume 10, Issue 38, September 2024.
+ Author(s): Viviane M. Oliveira and Paulo R. A. Campos
In this paper, we present an in-depth investigation into the dynamics of evolutionary rescue using a resource-based modelling approach. Utilizing classical consumer-resource models, we aim to understand how species can adapt to abrupt environmental changes that alter the availability of substitutabl…
[Phys. Rev. E 110, 034406] Published Wed Sep 18, 2024
- in Science Advances on 2024-09-18 07:00:00 UTC.
+
in Physical Review E: Biological physics on 2024-09-18 10:00:00 UTC.
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- Science Advances, Volume 10, Issue 38, September 2024.
+ Background The Indonesian government built the Mass Rapid Transit (MRT) in Jakarta to reduce traffic congestion and carbon dioxide (CO2) emissions. The objective of this study is to estimate the CO2 emissions reductions from switching from private transport to MRT by using a methodology proposed by the United Nations Convention on Climate Change (UNFCCC) for developing countries, namely the Clean Development Mechanism (CDM) methodology, which generates Certified Emission Reductions (CERs). This methodology is more comprehensive than other available methodologies. However, this method has not been widely used to calculate greenhouse gas (GHG) emission reductions in mass transit projects because it is complex enough to require a lot of data based on primary surveys. Therefore, this research simplifies the CDM formula to make it easier and applicable in Indonesia. Methods The primary data were collected using a questionnaire distributed to 480 MRT Jakarta Phase 1 user respondents in September 2019 (baseline); the secondary data were obtained from The MRT Jakarta. The data were processed using IBM SPSS Statistics 27. The simplified Clean Development Mechanism Approved Consolidated Methodology 0016 (CDM ACM 0016) was the analysis method used. Result The results of this study indicate that 53.75% of MRT Jakarta Phase 1 users are shifting from private transportation, which has reduced CO2 emissions by 2,732.7 tons in 2019 and 6,043.9 tons in 2023. Increasing the number of MRT passengers who switch from private transportation will further reduce CO2 emissions. Conclusion and implications The simplified CDM ACM 0016 formula may be suitable for use in Indonesia. This would enable the measurement of CO2 emission reductions through mitigation actions through MRT development to be certified by the UNFCCC. Applying this method in calculating CO2 emission reductions, implementing strategies to increase MRT passengers, and using renewable energy electricity sources would increase CO2 emission reductions.
- in Science Advances on 2024-09-18 07:00:00 UTC.
+
in F1000Research on 2024-09-18 09:58:52 UTC.
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- Science Advances, Volume 10, Issue 38, September 2024.
+ Introduction The emotional impact of patient loss in oncology and palliative care profoundly affects healthcare professionals. This study explores clinicians’ experiences, emotional reactions, and coping mechanisms in these fields, focusing on their professional and personal growth. It aims to provide a comprehensive understanding of how healthcare professionals from different regions and with varying years of experience deal with patient loss, emphasizing cultural, social, and institutional influences on their coping strategies. Methods A mixed-methods approach combined qualitative and quantitative elements. Data were collected using a Microsoft® Forms© survey targeting oncology and palliative care healthcare professionals. The survey included questions on experiences with patient loss, coping strategies, personal and professional growth, and beliefs. Statistical methods and thematic analysis were used to analyse quantitative and qualitative data. Ethical approval was obtained, and the survey ensured participant anonymity and confidentiality. Results The survey received 125 responses from nineteen countries. Emotional reactions to patient loss were significant, with various coping strategies reported, including spiritual practices, self-care, and professional support groups. Personal and professional growth were key outcomes of dealing with patient loss. Themes like Emotional Impact, Coping Mechanisms, and Reflections on Death and Dying were prevalent. Analysis revealed no significant correlation between the time taken by the participants to complete the survey and years of healthcare experience. Conclusion Healthcare professionals in oncology and palliative care face significant emotional challenges due to patient loss. The study emphasizes the importance of diverse and effective coping mechanisms, the supportive role of personal beliefs and workplace environments, and the journey of personal and professional growth amidst these challenges. It highlights the resilience of healthcare workers and underscores the need for supportive systems in managing the emotional aspects of patient care.
- in Science Advances on 2024-09-18 07:00:00 UTC.
+
in F1000Research on 2024-09-18 09:26:32 UTC.
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- Sato et al. show that obesity-related phenotypes in sPLA2-X-deficient C57BL/6 mice result from gut microbiota alteration. Colonic sPLA2-X releases ω3 PUFAs, ameliorates colonic inflammation, increases specific Clostridium species that produce SCFAs, and protects against diet-induced obesity and insulin resistance. Supplementation with ω3 PUFAs or SCFAs rescues the phenotypes caused by sPLA2-X deficiency.
+ The Neuroscientist, Volume 30, Issue 5, Page 518-518, October 2024.
- in Cell Reports: Current Issue on 2024-09-18 00:00:00 UTC.
+
in The Neuroscientist on 2024-09-18 07:55:44 UTC.
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- Casco et al. develop a dual-fluorescent lytic reporter Epstein-Barr virus (EBV) for isolating lymphoblastoid cell lines during early or late lytic replication. Their RNA-sequencing analysis shows extensive transcriptome remodeling during EBV reactivation from latency. Knockout of the host shutoff factor, BGLF5, subtly affects global gene downregulation, suggesting that other mechanisms significantly contribute to host shutoff.
+ The Neuroscientist, Volume 30, Issue 5, Page 519-519, October 2024.
- in Cell Reports: Current Issue on 2024-09-18 00:00:00 UTC.
+
in The Neuroscientist on 2024-09-18 07:55:43 UTC.
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- Severin et al. describe time-of-day changes in membrane capacitance in excitatory neurons from the visual cortex and hippocampus. Membrane capacitance is usually stable. These daily variations could profoundly impact neuronal physiology because of capacitance’s influence on the membrane time constant. Consistent with this, the authors show strong changes in synaptic integration.
+ The Neuroscientist, Volume 30, Issue 5, Page 519-519, October 2024.
- in Cell Reports: Current Issue on 2024-09-18 00:00:00 UTC.
+
in The Neuroscientist on 2024-09-18 07:55:42 UTC.
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- Forero et al. highlight heterogeneity in the protein content of EVs secreted by neural cells and cerebral organoids. Their findings show that neural cells present different EV uptake mechanisms and that EV treatment exerts transcriptional changes and an increase in proliferation in NPCs.
+ The Neuroscientist, Volume 30, Issue 5, Page 516-516, October 2024.
- in Cell Reports: Current Issue on 2024-09-18 00:00:00 UTC.
+
in The Neuroscientist on 2024-09-18 07:55:41 UTC.
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- Pumilio RNA-binding proteins are developmentally downregulated in the brain. Randolph et al. report that the simultaneous downregulation of Pumilio 1 and 2 promotes synapse maturation and increases the density of excitatory and inhibitory synapses. Thus, the regulation of Pumilio protein levels represents a cell-intrinsic mechanism for the modulation of synapse maturation.
+ The Neuroscientist, Volume 30, Issue 5, Page 517-517, October 2024.
- in Cell Reports: Current Issue on 2024-09-18 00:00:00 UTC.
+
in The Neuroscientist on 2024-09-18 07:55:41 UTC.
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- Xia et al. conduct genome sequencing and assembly for nine Rhododendron species, representing all five subgenera and various flower color types within this genus. By integrating genomic, metabolic, and phenotypic analyses, this study provides insights into the evolutionary adaptations of large cosmopolitan plant genera to diverse habitats.
+ Journal of Neurophysiology, Ahead of Print.
- in Cell Reports: Current Issue on 2024-09-18 00:00:00 UTC.
+
in Journal of Neurophysiology on 2024-09-18 07:01:25 UTC.
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- (Cell Reports 43, 114703; September 24, 2024)
+ Journal of Neurophysiology, Ahead of Print.
- in Cell Reports: Current Issue on 2024-09-18 00:00:00 UTC.
+
in Journal of Neurophysiology on 2024-09-18 07:01:25 UTC.
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- Yin et al. map the single-cell and spatial transcriptomes of the human and rat corpus cavernosum. They show that the spatial distribution of fibroblast subpopulations is related to the extracellular matrix stiffness in different regions. In addition, they demonstrate that mechanical force signaling can regulate the transition between fibroblast subpopulations.
+ Journal of Neurophysiology, Ahead of Print.
- in Cell Reports: In press on 2024-09-18 00:00:00 UTC.
+
in Journal of Neurophysiology on 2024-09-18 07:01:25 UTC.
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- Innate immunity across the tree of life requires enzymatic TIR-domain proteins, whose activity is engaged by aggregation. However, it is not known how this protein multimerization is regulated. Tse-Kang et al. discovered that the integrity of lysosome-related organelles, which express TIR-1, is actively maintained in C. elegans to limit inappropriate TIR-1 aggregation and toxic propagation of innate immunity.
+ Science Advances, Volume 10, Issue 38, September 2024.
- in Cell Reports: In press on 2024-09-18 00:00:00 UTC.
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in Science Advances on 2024-09-18 07:00:00 UTC.
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- Differentiation of female germline stem cells into a mature oocyte includes the expression of RNAs and proteins that drive early embryonic development in Drosophila. We have little insight into what activates the expression of these maternal factors. One candidate is the zinc-finger protein OVO. OVO is required for female germline viability and has been shown to positively regulate its own expression, as well as a downstream target, ovarian tumor, by binding to the transcriptional start site (TSS). To find additional OVO targets in the female germline and further elucidate OVO’s role in oocyte development, we performed ChIP-seq to determine genome-wide OVO occupancy, as well as RNA-seq comparing hypomorphic and wild type rescue ovo alleles. OVO preferentially binds in close proximity to target TSSs genome-wide, is associated with open chromatin, transcriptionally active histone marks, and OVO-dependent expression. Motif enrichment analysis on OVO ChIP peaks identified a 5’-TAACNGT-3’ OVO DNA binding motif spatially enriched near TSSs. However, the OVO DNA binding motif does not exhibit precise motif spacing relative to the TSS characteristic of RNA polymerase II complex binding core promoter elements. Integrated genomics analysis showed that 525 genes that are bound and increase in expression downstream of OVO are known to be essential maternally expressed genes. These include genes involved in anterior/posterior/germ plasm specification (bcd, exu, swa, osk, nos, aub, pgc, gcl), egg activation (png, plu, gnu, wisp, C(3)g, mtrm), translational regulation (cup, orb, bru1, me31B), and vitelline membrane formation (fs(1)N, fs(1)M3, clos). This suggests that OVO is a master transcriptional regulator of oocyte development and is responsible for the expression of structural components of the egg as well as maternally provided RNAs that are required for early embryonic development.
+ Science Advances, Volume 10, Issue 38, September 2024.
- in eLife on 2024-09-18 00:00:00 UTC.
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in Science Advances on 2024-09-18 07:00:00 UTC.
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- Synaptic heterogeneity is a hallmark of nervous systems that enables complex and adaptable communication in neural circuits. To understand circuit function, it is thus critical to determine the factors that contribute to the functional diversity of synapses. We investigated the contributions of voltage-gated calcium channel (VGCC) abundance, spatial organization, and subunit composition to synapse diversity among and between synapses formed by two closely related Drosophila glutamatergic motor neurons with distinct neurotransmitter release probabilities (Pr). Surprisingly, VGCC levels are highly predictive of heterogeneous Pr among individual synapses of either low- or high-Pr inputs, but not between inputs. We find that the same number of VGCCs are more densely organized at high-Pr synapses, consistent with tighter VGCC-synaptic vesicle coupling. We generated endogenously tagged lines to investigate VGCC subunits in vivo and found that the α2δ–3 subunit Straightjacket along with the CAST/ELKS active zone (AZ) protein Bruchpilot, both key regulators of VGCCs, are less abundant at high-Pr inputs, yet positively correlate with Pr among synapses formed by either input. Consistently, both Straightjacket and Bruchpilot levels are dynamically increased across AZs of both inputs when neurotransmitter release is potentiated to maintain stable communication following glutamate receptor inhibition. Together, these findings suggest a model in which VGCC and AZ protein abundance intersects with input-specific spatial and molecular organization to shape the functional diversity of synapses.
+ Science Advances, Volume 10, Issue 38, September 2024.
- in eLife on 2024-09-18 00:00:00 UTC.
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in Science Advances on 2024-09-18 07:00:00 UTC.
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- The significance of STING1 gene in tissue inflammation and cancer immunotherapy has been increasingly recognized. Intriguingly, common human STING1 alleles R71H-G230A-R293Q (HAQ) and G230A-R293Q (AQ) are carried by ~60% of East Asians and ~40% of Africans, respectively. Here, we examine the modulatory effects of HAQ, AQ alleles on STING-associated vasculopathy with onset in infancy (SAVI), an autosomal dominant, fatal inflammatory disease caused by gain-of-function human STING1 mutations. CD4 T cellpenia is evident in SAVI patients and mouse models. Using Sting1 knock-in mice expressing common human STING1 alleles HAQ, AQ, and Q293, we found that HAQ, AQ, and Q293 splenocytes resist STING1-mediated cell death ex vivo, establishing a critical role of STING1 residue 293 in cell death. The HAQ/SAVI(N153S) and AQ/SAVI(N153S) mice did not have CD4 T cellpenia. The HAQ/SAVI(N153S), AQ/SAVI(N153S) mice have more (~10-fold, ~20-fold, respectively) T-regs than WT/SAVI(N153S) mice. Remarkably, while they have comparable TBK1, IRF3, and NFκB activation as the WT/SAVI, the AQ/SAVI mice have no tissue inflammation, regular body weight, and normal lifespan. We propose that STING1 activation promotes tissue inflammation by depleting T-regs cells in vivo. Billions of modern humans have the dominant HAQ, AQ alleles. STING1 research and STING1-targeting immunotherapy should consider STING1 heterogeneity in humans.
+ Science Advances, Volume 10, Issue 38, September 2024.
- in eLife on 2024-09-18 00:00:00 UTC.
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in Science Advances on 2024-09-18 07:00:00 UTC.
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- Bumblebees (Bombus terrestris) have been shown to engage in string-pulling behavior to access rewards. The objective of this study was to elucidate whether bumblebees display means-end comprehension in a string-pulling task. We presented bumblebees with two options: one where a string was connected to an artificial flower containing a reward and the other presenting an interrupted string. Bumblebees displayed a consistent preference for pulling connected strings over interrupted ones after training with a stepwise pulling technique. When exposed to novel string colors, bees continued to exhibit a bias towards pulling the connected string. This suggests that bumblebees engage in featural generalization of the visual display of the string connected to the flower in this task. If the view of the string connected to the flower was restricted during the training phase, the proportion of bumblebees choosing the connected strings significantly decreased. Similarly, when the bumblebees were confronted with coiled connected strings during the testing phase, they failed to identify and reject the interrupted strings. This finding underscores the significance of visual consistency in enabling the bumblebees to perform the task successfully. Our results suggest that bumblebees’ ability to distinguish between continuous strings and interrupted strings relies on a combination of image matching and associative learning, rather than means-end understanding. These insights contribute to a deeper understanding of the cognitive processes employed by bumblebees when tackling complex spatial tasks.
+ Science Advances, Volume 10, Issue 38, September 2024.
- in eLife on 2024-09-18 00:00:00 UTC.
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in Science Advances on 2024-09-18 07:00:00 UTC.
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- Brain Sciences, Vol. 14, Pages 933: Correction: Amin et al. Hippocampal and Cerebellar Changes in Acute Restraint Stress and the Impact of Pretreatment with Ceftriaxone. Brain Sci. 2020, 10, 193
- Brain Sciences doi: 10.3390/brainsci14090933
- Authors:
- Shaimaa N. Amin
- Sherif S. Hassan
- Ahmed S. Khashaba
- Magdy F. Youakim
- Noha S. Abdel Latif
- Laila A. Rashed
- Hanan D. Yassa
-
- In the original publication [...]
+ Science Advances, Volume 10, Issue 38, September 2024.
- in Brain Sciences on 2024-09-18 00:00:00 UTC.
+
in Science Advances on 2024-09-18 07:00:00 UTC.