bluuebunny/crossref_metadata_2025_split huggingface dataset:
Partial observation can induce mechanistic mismatches in data-constrained models of neural dynamics
Authors: Qian William , Zavatone-Veth Jacob A. , Ruben Benjamin S. , Pehlevan Cengiz 
Published: May 2024

AbstractOne of the central goals of neuroscience is to gain a mechanistic understanding of how the dynamics of neural circuits give rise to their observed function. A popular approach towards this end is to train recurrent neural networks (RNNs) to reproduce experimental recordings of neural activity. These trained RNNs are then treated as surrogate models of biological neural circuits, whose properties can be dissected via dynamical systems analysis. How reliable are the mechanistic insights derived from this procedure? While recent advances in population-level recording technologies have allowed simultaneous recording of up to tens of thousands of neurons, this represents only a tiny fraction of most cortical circuits. Here we show that observing only a subset of neurons in a circuit can create mechanistic mismatches between a simulated teacher network and a data-constrained student, even when the two networks have matching single-unit dynamics. In particular, partial observation of models of low-dimensional cortical dynamics based on functionally feedforward or low-rank connectivity can lead to surrogate models with spurious attractor structure. Our results illustrate the challenges inherent in accurately uncovering neural mechanisms from single-trial data, and suggest the need for new methods of validating data-constrained models for neural dynamics.
The fruit fly,Drosophila melanogaster, as a micro-robotics platform
Authors: Iwasaki Kenichi , Neuhauser Charles , Stokes Chris , Rayshubskiy Aleksandr 
Published: May 2024

AbstractEngineering small autonomous agents capable of operating in the microscale environment remains a key challenge, with current systems still evolving. Our study explores the fruit fly,Drosophila melanogaster, a classic model system in biology and a species adept at microscale interaction, as a biological platform for micro-robotics. Initially, we focus on remotely directing the walking paths of fruit flies in an experimental arena. We accomplish this through two distinct approaches: harnessing the fruit flies’ opto-motor response and optogenetic modulation of its olfactory system. These techniques facilitate reliable and repeated guidance of flies between arbitrary spatial locations. We guide flies along predetermined trajectories, enabling them to scribe patterns resembling textual characters through their locomotion. We enhance olfactory-guided navigation through additional optogenetic activation of positive valence mushroom body output neurons. We extend this control to collective behaviors in shared spaces and navigation through constrained maze-like environments. We further use our guidance technique to enable flies to carry a load across designated points in space, establishing the upper bound on their weight carrying capabilities. Additionally, we demonstrate that visual guidance can facilitate novel interactions between flies and objects, showing that flies can consistently relocate a small spherical object over significant distances. Beyond expanding tools available for micro-robotics, these novel behavioral contexts can provide insights into the neurological basis of behavior in fruit flies.
Blast Traumatic Brain Injury Induces Long-Term Alterations in Inflammatory Gene Expression in Chinchilla Brains
Authors: Schmitt Rebecca , Kaliyappan Kathiravan , Mahajan Supriya D. , Krishnan Muthaiah Vijaya Prakash 
Published: May 2024

AbstractBlast traumatic brain injury (bTBI) due to high-intensity impulsive noise exposure from explosions and munitions exposure is highly prevalent among military personnel, which leads to diffuse brain injury resulting in a spectrum of brain dysfunction and cognitive deficits. The resultant prolonged neuroinflammation and consequent failure of inflammation resolution is a key contributor to long-term complications, including post-traumatic stress disorder and early-onset of neurodegenerative disease; however, there is little evidence for the duration and extent of long term neuroinflammation in distinct brain regions. To investigate this, due to human-like audiogram, we use chinchillas as anin-vivobTBI model to analyze the relative gene expression of inflammatory markers (TNFα, TGFβ2, Gal1, HSP90, S100B, NRGN, MAPK14, IL8, NFL, and BDNF) in the hippocampus, striatum, and higher centers of the auditory pathway 90 days following varying intensities of blast exposures (144 dB, 155 dB, and 172 dB sound pressure level). Our study revealed aberrant gene expression across all analyzed brain regions and all injury conditions; however, no specific pattern emerged. Many of the inflammatory markers were downregulated, suggesting a possible attempt by the brain to overcome prior inflammation. Conversely, the hippocampus, striatum, inferior colliculus, and medial geniculate body all exhibited upregulation of inflammatory markers, including the TBI prognostic marker, S100B. Thus, chinchilla brains exhibit evidence of prolonged neuroinflammation 90 days following injury, even during mild blast exposure. Ultimately, the observed alterations in the gene expression of inflammatory markers may contribute to the long-term neurological dysfunction and neurodegenerative disease experienced by veterans and other bTBI patients.
Chromatin remodeling protein BPTF regulates transcriptional stability in planarian stem cells
Authors: Verma Prince , Sánchez Alvarado Alejandro , Duncan Elizabeth M. 
Published: May 2024

ABSTRACTTrimethylation of histone H3 lysine 4 (H3K4me3) correlates strongly with gene expression in many different organisms, yet the question of whether it plays a causal role in transcriptional activity remains unresolved. Although H3K4me3 does not directly affect chromatin accessibility, it can indirectly affect genome accessibility by recruiting the ATP-dependent chromatin remodeling complex NuRF (Nucleosome Remodeling Factor). The largest subunit of NuRF, BPTF/NURF301, binds H3K4me3 specifically and recruits the NuRF complex to loci marked by this modification. Studies have shown that the strength and duration of BPTF binding likely also depends on additional chromatin features at these loci, such as lysine acetylation and variant histone proteins. However, the exact details of this recruitment mechanism vary between studies and have largely been tested in vitro. Here, we use stem cells isolated directly from live planarian animals to investigate the role of BPTF in regulating chromatin accessibility in vivo. We find that BPTF operates at gene promoters and is most effective at facilitating transcription at genes marked by Set1-dependent H3K4me3 peaks, which are significantly broader than those added by the lysine methyltransferase MLL1/2. Moreover, BPTF is essential for planarian stem cell biology and its loss of function phenotype mimics that of Set1 knockdown. Together, these data suggest that BPTF and H3K4me3 are important mediators of both transcription and in vivo stem cell function.
Sex Differences in the Association between Skeletal Muscle Energetics and Perceived Physical Fatigability: The Study of Muscle, Mobility and Aging (SOMMA)
Authors: Gay Emma L. , Coen Paul M. , Harrison Stephanie , Garcia Reagan E. , Qiao Yujia (Susanna) , Goodpaster Bret H. , Forman Daniel E. , Toledo Frederico G. S. , Distefano Giovanna , Kramer Philip A. , Ramos Sofhia V. , Molina Anthony J. A. , Nicklas Barbara J. , Cummings Steven R. , Cawthon Peggy M. , Hepple Russell T. , Newman Anne B. , Glynn Nancy W. 
Published: May 2024

AbstractGreater perceived physical fatigability and lower skeletal muscle energetics are predictors of mobility decline. Characterizing associations between muscle energetics and perceived fatigability may provide insight into potential targets to prevent mobility decline. We examined associations ofin vivo(maximal ATP production, ATPmax) andex vivo(maximal carbohydrate supported oxidative phosphorylation [max OXPHOS] and maximal fatty acid supported OXPHOS [max FAO OXPHOS]) measures of mitochondrial energetics with two measures of perceived physical fatigability, Pittsburgh Fatigability Scale (PFS, 0-50, higher=greater) and Rating of Perceived Exertion (RPE Fatigability, 6-20, higher=greater) after a slow treadmill walk. Participants from the Study of Muscle, Mobility and Aging (N=873) were 76.3±5.0 years old, 59.2% women, and 85.3% White. Higher muscle energetics (bothin vivoandex vivo) were associated with lower perceived physical fatigability, all p<0.03. When stratified by sex, higher ATPmax was associated with lower PFS Physical for men only; higher max OXPHOS and max FAO OXPHOS were associated with lower RPE fatigability for both sexes. Higher skeletal muscle energetics were associated with 40-55% lower odds of being in the most (PFS≥25, RPE Fatigability≥12) vs least (PFS 0-4, RPE Fatigability 6-7) severe fatigability strata, all p<0.03. Being a woman was associated with 2-3 times higher odds of being in the most severe fatigability strata when controlling for ATPmax but not thein vivomeasures (p<0.05). Better mitochondrial energetics were linked to lower fatigability and less severe fatigability in older adults. Findings imply that improving skeletal muscle energetics may mitigate perceived physical fatigability and prolong healthy aging.
Tonotopy is not preserved in a descending stage of auditory cortex
Authors: Gu Miaoqing , Liang Shanshan , Zhu Jiahui , Li Ruijie , Liu Ke , Wang Xuanyue , Ohl Frank , Zhang Yun , Liao Xiang , Zhang Chunqing , Jia Hongbo , Zhou Yi , Zhang Jianxiong , Chen Xiaowei 
Published: May 2024

AbstractPrevious studies based on layer specificity suggest that ascending signals from the thalamus to sensory neocortex preserve spatially organized information, but it remains unknown whether sensory information descending from sensory neocortex to thalamus also maintains such spatial organization pattern. By focusing on projection specificity, we mapped tone response properties of two groups of cortical neurons in the primary auditory cortex (A1), based on the relationship between their specific connections to other regions and their function in ascending (thalamocortical recipient, TR neurons) or descending (corticothalamic, CT neurons) auditory information. A clear tonotopic gradient was observed among TR, but not CT neurons. Additionally, CT neurons exhibited markedly higher heterogeneity in their frequency tuning and had broader bandwidth than TR neurons. These results reveal that the information flow descending from A1 to thalamus via CT neurons does not arrange tonotopically, suggesting that the descending information flow possibly contributes to higher-order feedback processing of diverse auditory inputs.
Dynamic and topological properties of large-scale brain networks in rapid eye movement behavior disorder
Authors: Li Yidi , Yoshinaga Kenji , Hanakawa Takashi ,   Japan Parkinson’s Progression Markers Initiative (J-PPMI) study group
Published: May 2024

AbstractIntroductionThere is a lack of research in the existing literature when it comes to analyzing the dynamics of resting-state functional magnetic resonance imaging to understand the underlying mechanisms of isolated rapid eye movement sleep behavior disorder (iRBD). This study aims to contribute to our understanding of abnormalities in brain network dynamics in iRBD and their association with alpha-synucleinopathy. Additionally, I employed graph theoretical metrics to obtain a topological insight into the brain network of iRBD.MethodsResting-state fMRI data from 55 iRBD patients and 97 healthy controls (HCs) were utilized. A sliding window approach, functional connectivity analysis, and graph theory analysis were applied to the data. I calculated the mean, standard deviation, skewness, and kurtosis of the time series for both dynamic functional connectivity (dFC) and four graph metrics (clustering coefficient, global efficiency, assortativity coefficients, and eigenvector centrality). Subsequently, I compared the those metrices between iRBDs and HCs. Relationships between clinical scales and abnormal dFC were assessed using a general linear model.ResultsiRBD patients exhibited abnormal mean dFC, particularly in the default mode network, sensorimotor network, basal ganglia network, and cerebellum. Kurtosis of dFC revealed abnormalities between the middle temporal gyrus and cerebellum. Group differences were also observed in the mean eigenvector centrality of the precentral gyrus and thalamus.ConclusionThe mean of dFC identified impairments putatively in movement functions and various compensatory mechanisms. Moreover, mean eigenvector centrality revealed topological changes in motor-related network in iRBDs. The use of kurtosis as a potential index for extracting dynamic information may provide additional insights into pathophysiology in iRBDs.
Salience Network Segregation Mediates the Effect of Tau Pathology on Mild Behavioral Impairment
Authors: Iordan Alexandru D. , Ploutz-Snyder Robert , Ghosh Bidisha , Rahman-Filipiak Annalise , Koeppe Robert , Peltier Scott , Giordani Bruno , Albin Roger L. , Hampstead Benjamin M. 
Published: May 2024

STRUCTURED ABSTRACTINTRODUCTIONA recently developed mild behavioral impairment (MBI) diagnostic framework standardizes the early characterization of neuropsychiatric symptoms in older adults. However, the links between MBI, brain function, and Alzheimer’s disease (AD) biomarkers are unclear.METHODSUsing data from 128 participants with diagnosis of amnestic mild cognitive impairment and mild dementia – Alzheimer’s type, we test a novel model assessing direct relationships between AD biomarker status and MBI symptoms, as well as mediated effects through segregation of the salience and default-mode networks.RESULTSWe identified a mediated effect of tau positivity on MBI through functional segregation of the salience network from the other high-level, association networks. There were no direct effects of AD biomarkers status on MBI.DISCUSSIONOur findings suggest an indirect role of tau pathology in MBI through brain network dysfunction and emphasize the role of the salience network in mediating relationships between neuropathological changes and behavioral manifestations.
Services in Minoritized Autistic Adolescents and Adults Varying in Language Skills
Authors: Girolamo Teresa , Escobedo Alicia , Ghali Samantha , Greene-Pendelton Kyle , Campos Iván , Ram-Kiran Poornima 
Published: May 2024

AbstractBackgroundRacially and ethnically minoritized (minoritized) autistic individuals face intersectional disparities in services access in the transition to adulthood. Our understanding of disparities is limited by systematic exclusion from research and inadequate approaches to characterizing services. To address these gaps and effect advocacy, this study: 1) examined services received, unmet service needs, and barriers in minoritized autistic adolescents and adults, and 2) determined if language, NVIQ, and autism traits predict services when deployed as binary or continuous variables.MethodAcademic and community partners tailored CBPR to a local context. Participants (N= 73, ages 13-30) completed a behavioral assessment protocol. Participants and caregivers provided information on services received, unmet service needs, and barriers to services. Data were analyzed using descriptives and regression.ResultsParticipants received multiple services yet had multiple unmet service needs and barriers. Effects of services differed by approach. Language impairment, but not language scores, predicted receiving more services. High levels of autism traits and autism trait scores predicted more unmet service needs.ImplicationsWhile the number of services and unmet service needs were similar to prior work, differences in individual service variables and effects support attention to heterogeneity. Findings support intersectional approaches to CBPR and autism research.Learning outcomesAfter reading the article, the learner will be able to: 1) summarize knowledge gaps about access to services; 2) explain the relevance of tailoring CBPR to a local context; and 3) describe implications of findings for clinicians and autistic individuals.
Obtaining high-resolution cryo-EM structures using a common LaB6, 120-keV electron microscope equipped with a sub 200-keV optimised direct electron detector
Authors: Venugopal Hariprasad , Mobbs Jesse , Taveneau Cyntia , Fox Daniel R. , Vuckovic Ziva , Knott Gavin , Grinter Rhys , Thal David , Mick Stephen , Czarnik Cory , Ramm Georg 
Published: May 2024

AbstractCryo-electron microscopy (Cryo-EM) single particle analysis (SPA) has become a major structural biology technique in recent years. High-resolution cryo-EM typically requires higher voltage cryo-TEMs with coherent FEG sources, stable columns, autoloader systems and direct electron detectors. These setups are specialised for Cryo-EM work and are expensive to establish and maintain. More recently the concept of using 100-keV cryo-TEMs has been introduced as a way to make cryo-EM more affordable and hence accessible to a larger group of researchers. So far, the implementation of these 100-keV cryo-TEMs have relied on specialised microscopes with FEG sources as well as more stable optics than usually present on the common 120-keV TEMs. We here explored whether a standard 120-keV TEM, commonly available at many laboratories worldwide, can be upgraded with a direct electron detector and its suitability for high-resolution cryo-EM using a standard side entry cryo-holder. Using this imaging configuration, we were successful in achieving a 2.65Å reconstruction for standard apoferritin. We were also able to resolve a more challenging small 64kDa protein haemoglobin to 4.33Å. Furthermore, we were able to solve an asymmetric 153 kDa membrane protein GPCR (M4 muscarinic acid receptor) to a resolution of 4.4Å. Importantly, all these results were achieved using a standard automated data collection routine implemented through SerialEM, making it feasible to collect large cryo-EM data sets with a side entry cryo-holder. These results showcase a potentially widely accessible solution to obtaining interpretable cryo-EM structures. Furthermore, we envisage that this imaging configuration gives an option for many EM facilities and laboratories to set up a high-quality cryo-EM SPA sample screening capability without the need to procure costly specialised Cryo-TEMs. This could help to considerably lower the economic entry barrier for cryo-EM SPA and contribute to the “democratisation” of cryo-EM.
Diffusion model-based image generation from rat brain activity
Authors: Yamashiro Kotaro , Matsumoto Nobuyoshi , Ikegaya Yuji 
Published: May 2024

AbstractBrain-computer interface (BCI) technology has gained recognition in various fields, including clinical applications, assistive technology, and human-computer interaction research. BCI enables communication, control, and monitoring of the affective/cognitive states of users. Recently, BCI has also found applications in the artistic field, enabling real-time art composition using brain activity signals, and engaging performers, spectators, or an entire audience with brain activity-based artistic environments. Existing techniques use specific features of brain activity, such as the P300 wave and SSVEPs, to control drawing tools, rather than directly reflecting brain activity in the output image. In this study, we present a novel approach that uses a latent diffusion model, a type of deep neural network, to generate images directly from continuous brain activity. We demonstrate this technology using local field potentials from the neocortex of freely moving rats. This system continuously converted the recorded brain activity into images. Our end-to-end method for generating images from brain activity opens up new possibilities for creative expression and experimentation.
A single-nucleus transcriptomic atlas of medium spiny neurons in the rat nucleus accumbens
Authors: Reiner Benjamin C. , Chehimi Samar N. , Merkel Riley , Toikumo Sylvanus , Berrettini Wade H. , Kranzler Henry R. , Sanchez-Roige Sandra , Kember Rachel L. , Schmidt Heath D. , Crist Richard C. 
Published: May 2024

SummaryNeural processing of rewarding stimuli involves several distinct regions, including the nucleus accumbens (NAc). The majority of NAc neurons are GABAergic projection neurons known as medium spiny neurons (MSNs). MSNs are broadly defined by dopamine receptor expression, but evidence suggests that a wider array of subtypes exist. To study MSN heterogeneity, we analyzed single-nucleus RNA sequencing data from the largest available rat NAc dataset. Analysis of 48,040 NAc MSN nuclei identified major populations belonging to the striosome and matrix compartments. Integration with mouse and human data indicated consistency across species and disease-relevance scoring using genome-wide association study results revealed potentially differential roles for MSN populations in substance use disorders. Additional high-resolution clustering identified 34 transcriptomically distinct subtypes of MSNs definable by a limited number of marker genes. Together, these data demonstrate the diversity of MSNs in the NAc and provide a basis for more targeted genetic manipulation of specific populations.
A PI(3,5)P2/ESCRT-III axis terminates STING signalling by facilitating TSG101-mediated lysosomal microautophagy
Authors: Shoji Tsumugi , Shinojima Ayumi , Kusumi Satoshi , Koga Daisuke , Mukai Kojiro , Nakayama Jun , Higashiyama Shigeki , Kuchitsu Yoshihiko , Taguchi Tomohiko 
Published: May 2024

AbstractStimulator of interferon genes (STING) is critical for the type I interferon response to pathogen- or self-derived cytosolic DNA. STING is degraded by the endosomal sorting complexes required for transport (ESCRT)-driven lysosomal microautophagy (LMA), the impairment of which leads to sustained inflammatory responses. It has been unknown how ESCRT targets STING directly to lysosomes. Here, through kinase inhibitor screening and knockdown experiments of all the individual components of ESCRT, we show that STING degradation requires PIKfyve (a lipid kinase that generates PI(3,5)P2) and CHMP4B/C (components of ESCRT-III subcomplex). Knockdown of Pikfyve or Chmp4b/c results in the accumulation of STING vesicles of a recycling endosomal origin in the cytosol, leading to sustained type I interferon response. CHMP4B/C localize at lysosomes and their lysosomal localization is abolished by interference with PIKfyve activity. Our results identify lysosomal ESCRT-III as a PI(3,5)P2effector, reveal a role of the less characterized phosphoinositide PI(3,5)P2in lysosomal biology, and provide insights into the molecular framework that distinguishes LMA from other cellular processes engaged with ESCRT.