bluuebunny/crossref_metadata_2025_split huggingface dataset:
SpinalTRAQ: A novel volumetric cervical spinal cord atlas identifies the corticospinal tract synaptic projectome in healthy and post-stroke mice
Authors: Poinsatte Katherine , Kenwood Matthew , Betz Dene , Nawaby Ariana , Ajay Apoorva D , Xu Wei , Plautz Erik J , Kong Xiangmei , Ramirez Denise M O , Goldberg Mark P 
Published: August 2024

Abstract/SummaryDescending corticospinal tract (CST) connections to the neurons of the cervical spinal cord are vital for performance of forelimb-specific fine motor skills. In rodents, CST axons are almost entirely crossed at the level of the medullary decussation. While specific contralateral axon projections have been well-characterized using anatomic and molecular approaches, the field currently lacks a cohesive imaging modality allowing rapid quantitative assessment of the entire, bilateral cervical cord projectome at the level of individual laminae and cervical levels. This is potentially important as the CST is known to undergo marked structural remodeling in development, injury, and disease. We developed SpinalTRAQ (Spinal cordTomographicRegistration andAutomatedQuantification), a novel volumetric cervical spinal cord atlas and machine learning-driven microscopy acquisition and analysis pipeline that uses serial two-photon tomography-images to generate unbiased, region-specific quantification of the fluorescent pixels of anterograde AAV-labeled CST pre-synaptic terminals. In adult mice, the CST synaptic projectome densely innervates the contralateral hemicord, particularly in laminae 5 and 7, with sparse, monosynaptic input to motoneurons in lamina 9. Motor pools supplying axial musculature in the upper cervical cord are bilaterally innervated. The remainder of the ipsilateral cord has sparse labeling in a distinct distribution compared to the contralateral side. Following a focal stroke of the motor cortex, there is a complete loss of descending corticospinal axons from the injured side. Consistent with prior reports of axon collateralization, the CST spinal projectome increases at four weeks post-stroke and continues to elevate by six weeks post stroke. At six weeks post-stroke, we observed striking synapse formation in the denervated hemicord from the uninjured CST in a homotopic distribution. Additionally, CST synaptic reinnervation increases in the denervated lamina 9 in nearly all motoneuron pools, exhibiting novel patterns of connectivity. Detailed level- and lamina-specific quantification of the bilateral cervical spinal cord synaptic projectome reveals previously undescribed patterns of CST connectivity in health and injury-related plasticity.
In vivo transition in chromatin accessibility during differentiation of deep-layer excitatory neurons in the neocortex
Authors: Sakai Seishin , Maeda Yurie , Kawaji Keita , Suzuki Yutaka , Gotoh Yukiko , Kishi Yusuke 
Published: August 2024

AbstractDuring the differentiation process of neurons, their gene transcription pattern changes according to both intrinsic and extrinsic stimuli-induced programs. Chromatin regulation at regulatory elements is involved in this precise control of gene expression. However, developmental changes in chromatin accessibility of the cortical neurons in vivo are less understood, partly because there is no convenient method to genetically label neurons of a specific lineage. Here, we establish a method for labeling the differentiating neurons of specific birthdates. Using this method, we traced the four-day differentiation process of in vivo deep-layer excitatory neurons in mouse embryonic cortex and examined the changes in the genome-wide transcription pattern and chromatin accessibility with RNA-seq and DNase-seq, respectively. The genomic regions of genes associated with mature neuron functions, such as deep layer–specific genes and genes responsive to external stimuli, became open even in the embryonic stage. Moreover, genes with bivalent marks in neural precursor/stem cells (NPCs) became open. Together, our data demonstrate the importance of chromatin regulation in vivo differentiating neurons during the embryonic stage to follow activation of neuronal genes in their maturation process.
SLC35A2modulates paramyxovirus fusion events during infection
Authors: Yang Yanling , Wang Yuchen , Campbell Danielle E. , Lee Heng-Wei , Wang Leran , Baldridge Megan , López Carolina B. 
Published: August 2024

AbstractParamyxoviruses are significant human and animal pathogens that include mumps virus (MuV), Newcastle disease virus (NDV) and the murine parainfluenza virus Sendai (SeV). Despite their importance, few host factors implicated in paramyxovirus infection are known. Using a recombinant SeV expressing destabilized GFP (rSeVCdseGFP) in a loss-of-function CRISPR screen, we identified the CMP-sialic acid transporter (CST) geneSLC35A1and the UDP-galactose transporter (UGT) geneSLC35A2as essential for paramyxovirus infection.SLC35A1knockout (KO) cells showed significantly reduced binding and infection of SeV, NDV and MuV due to the lack of cell surface sialic acids, which act as their receptors. However,SLC35A2KO cells revealed unknown critical roles for this factor in virus-cell and cell-to-cell fusion events during infection with different paramyxoviruses. While the UGT was essential for virus-cell fusion during SeV entry to the cell, it was not required for NDV or MuV entry. Importantly, the UGT promoted the formation of larger syncytia during MuV infection, suggesting a role in cell-to-cell virus spread. Our findings demonstrate that paramyxoviruses can bind to or enter A549 cells in the absence of canonical galactose-bound sialic-acid decorations and show that the UGT facilitates paramyxovirus fusion processes involved in entry and spread.
Antihypertensive medications and dementia in older adults with hypertension
Authors: Orchard Suzanne G. , Zhou Zhen , Fravel Michelle , Ryan Joanne , Woods Robyn L. , Wolfe Rory , Shah Raj C. , Murray Anne , Sood Ajay , Reid Christopher M. , Nelson Mark R. , Bellin Lawrie , Polkinghorne Kevan R , Stocks Nigel , Ernst Michael E. 
Published: August 2024

ABSTRACTBackgroundStudies on middle-aged or individuals with cognitive or cardiovascular impairments, have established that intensive blood pressure (BP) control reduces cognitive decline risk. However, uncertainty exists on differential effects between antihypertensive medications (AHM) classes on this risk, independent of BP-lowering efficacy, particularly in community-dwelling hypertensive older adults.MethodsA post-hoc analysis of the ASPREE study, a randomized trial of low-dose aspirin in adults aged 70+ years (65+ if US minorities) without baseline dementia, and followed for two years post-trial. Cox proportional-hazards regression models were used to estimate associations between baseline and time-varying AHM exposure and incident dementia (an adjudicated primary trial endpoint), in participants with baseline hypertension. Subgroup analyses included prespecified factors, APO ε4 carrier status and monotherapy AHM use.ResultsMost hypertensive participants (9,843/13,916; 70.7%) used AHMs. Overall, ‘any’ AHM use was not associated with lower incident dementia risk, compared with untreated participants (HR 0.84, 95%CI 0.70-1.02, p=0.08), but risk was decreased when angiotensin receptor blockers (ARBs) were included (HR 0.73, 95%CI 0.59-0.92, p=0.007). ARBs and β-blockers decreased dementia risk, whereas angiotensin-converting enzyme inhibitors (ACEIs) and diuretics increased risk. There was no association with RAS modulating or blood-brain-barrier crossing AHMs on dementia risk.ConclusionsOverall, AHM exposure in hypertensive older adults was not associated with decreased dementia risk, however, specific AHM classes were with risk direction determined by class; ARBs and β-blockers were superior to ACEIs and other classes in decreasing risk. Our findings emphasize the importance of considering effects beyond BP-lowering efficacy when choosing AHM in older adults.
Quantifying immune cell telomere content at single-cell resolution in context of PD-1 checkpoint immunotherapy
Authors: Engel Niklas L. , Herzel Lea , Surmely Julie , Frieß Hanna , Simon Malte , Brors Benedikt , Imbusch Charles , Feuerbach Lars 
Published: August 2024

AbstractIntroductionBiological processes such as aging, carcinogenesis, and immune response rely on the ability to maintain or rapidly expand cell populations. The fitness of the involved cells is constrained by their replicative potential, which is reflected in the cellular telomere content.MethodWe apply TelomereHunter to scATAC-seq data to determine telomere content on single-cell level, in a hematopoietic dataset consisting of 35,139 cells from samples of basal cell carcinoma patients receiving programmed cell death protein 1 (PD1) blockade treatment. Integrating information from open-chromatin-based signatures to assess cell identity, we characterize the heterogeneity of telomere length for individual cell populations pre- and post-immunotherapy.ResultsThe extracted telomeric reads reflect the expected telomereome-to-genome fraction. Telomere content distributions differ significantly between cell populations, and the median telomere content in intermediate and terminal exhausted CD8+ T-cells pre-treatment is significantly correlated to response to PD-1 checkpoint blockade. Likewise, telomere content correlates with post-treatment cell proliferation in terminally exhausted and T follicular helper cells from responding patients.ConclusionTelomere content measurement from scATAC-seq data has a sufficiently high signal-to-noise ratio to detect significant differences between cell types. Furthermore, the telomere content of CD8+ exhausted T-cells pre-treatment is a putative biomarker for successful PD-1-based immunotherapy.
ThevprAB-ompV-virKoperon ofVibrio choleraesenses antimicrobial peptides and activates the expression of multiple resistance systems
Authors: Mathieu-Denoncourt Annabelle , Whitfield Gregory B. , Vincent Antony T. , Pauzé-Foixet Julien , Mahieddine Feriel , Brun Yves V. , Duperthuy Marylise 
Published: August 2024

AbstractAntimicrobial peptides are small cationic molecules produced by eukaryotic cells to combat infection, as well as by bacteria for niche competition. Polymyxin B (PmB), a cationic cyclic antimicrobial peptide, is used prophylactically in livestock for infection prevention and as a last-resort treatment for multidrug-resistant bacterial infections in humans. In this study, a transcriptomic analysis inVibrio choleraeshowed that expression of the uncharacterized geneompVis stimulated in response to PmB. We found thatompVis organized in a conserved four-gene operon with the two-component systemvprAB(carRS) andvirKinV. cholerae, and that these genes are also upregulated in response to PmB treatment. AvirKdeletion mutant was more sensitive to the human cathelicidin LL-37 than the wild-type strain, while anompVmutant was more sensitive to PmB and LL-37, suggesting that both OmpV and VirK contribute to antimicrobial resistance inV. cholerae. This increased sensitivity to antimicrobial peptides was not due to membrane destabilization or reduced sequestration by membrane vesicles as a result ofompVdeletion. Instead, our transcriptomic analysis showed that the efflux pumpvexAB, a known effector of PmB resistance, was also upregulated in the presence of PmB in anompV-dependent manner. Examination of the predicted structure of OmpV revealed a lateral opening in the β-barrel wall with access to an electronegative pocket in the barrel lumen that can accommodate PmB. Such an interaction could facilitate intracellular signaling through a conformational change in OmpV. This is the first evidence of a specialized operon governing multiple systems for antimicrobial resistance inV. cholerae.Author SummaryIn this study, we identified the first specialized operon controlling multiple systems of antimicrobial resistance inV. cholerae. The operon encodes the two-component systemvprAB, which activates the main mechanism of polymyxin B resistance inV. cholerae, and the uncharacterized genesompVandvirK. We provide evidence that OmpV and VirK are implicated in antimicrobial resistance and show that OmpV has a membrane-accessible lateral opening into a pocket that could accommodate the antimicrobial peptide polymyxin B. We propose that OmpV acts as an outer membrane sensor that signals the presence of antimicrobial peptides to activate the expression of the operon, leading to the activation of multiple mechanisms of resistance, including modifications of the outer membrane and the multi-drug efflux systemvexAB.
Fast Low-Input Efficient Hi-C
Authors: Guetta Mor , Avidan Nili , Kariti Hagai , Davis Liron , Shemer Revital , Elliot Evan , Kaplan Noam 
Published: August 2024

AbstractWe developed FLIE (Fast Low-Input Efficient) Hi-C, a highly optimized and simplified version of Hi-C. Our method shortens the duration of Hi-C from five days to two days and decreases key reagent amounts 5-20 fold, while maintaining experimental controls and data quality. Importantly, the method also reduces the required input material by 100-1000 fold, as we demonstrate by generating detailed high complexity interaction maps from low-input sorted mouse frozen neuron nuclei and from 5,000-10,000 human Hap1 cells.
Single-nucleosome imaging reveals principles of transient multiscale chromatin unfolding triggered by histone ADP-ribosylation at DNA lesions
Authors: García Fernández Fabiola , Chapuis Catherine , Park Junwoo , Pinto Eva , Imburchia Victor , Longarini Edoardo José , Taddei Angela , Sokolovska Nataliya , Matić Ivan , Huet Sébastien , Miné-Hattab Judith 
Published: August 2024

ABSTRACTTimely access to DNA lesions is crucial for genome integrity. This process requires profound remodeling of densely packed chromatin to establish a repair-competent architecture. However, limited resolution has made it impossible to fully understand these remodeling events. Here, combining microirradiation with live-cell multiscale imaging, we report that DNA damage-induced changes in genome packing rely on the conformational behaviour of the chromatin fiber. Immediately after damage, a transient increase in nucleosome mobility switches chromatin from a densely-packed state to a looser conformation, making it accessible to repair. While histone poly-ADP-ribosylation is required to trigger this switch, mono-ADP-ribosylation is sufficient to maintain the open-chromatin state. The removal of these histone marks by the ARH3 hydrolase then leads to chromatin recondensation. Together, our multiscale study of chromatin dynamics establishes a global model: distinct waves of histone ADP-ribosylation control nucleosome mobility, triggering a transient breathing of chromatin, crucial for initiating the DNA damage response.
Charting the Silent Signals of Social Gaze: Automating Eye Contact Assessment in Face-to-Face Conversations
Authors: Schmälzle Ralf , Jahn Nolan T. , Bente Gary 
Published: August 2024

AbstractSocial gaze is a crucial yet often overlooked aspect of nonverbal communication. During conversations, it typically operates subconsciously, following automatic co-regulation patterns. However, deviations from typical patterns, such as avoiding eye contact or excessive gazing, can significantly affect social interactions and perceived relationship quality. The principles and effects of social gaze have intrigued researchers across various fields, including communication science, social psychology, animal biology, and psychiatry. Despite its significance, research in social gaze has been limited by methodological challenges in assessing eye movements and gaze direction during natural social interactions. To address these obstacles, we have developed a new approach combining mobile eye tracking technology with automated analysis tools. In this paper, we introduce, validate, and apply a pipeline for recording and analyzing gaze behavior in dyadic conversations. We present a sample study where dyads engaged in two types of interactions: a get-to-know conversation and a conflictual conversation. Our new analysis pipeline corroborated previous findings, such as people directing more eye gaze while listening than talking, and gaze typically lasting about three seconds before averting. These results demonstrate the potential of our methodology to advance the study of social gaze in natural interactions.
AMOEBA Polarizable Molecular Dynamics Simulations of Guanine Quadruplexes: from the c-Kit Proto-oncogene to HIV-1
Authors: El Ahdab Dina S. , Lagardère Louis , Hobaika Zeina , Inizan Théo Jaffrelot , Célerse Frédéric , Gresh Nohad , Maroun Richard G. , Piquemal Jean-Philip 
Published: August 2024

AbstractLong oligomer sequences, rich in guanine and cytosine, such asc-kit1and the HIV-1 LTR-III sequence, are prevalent in oncogenes and retroviruses and play crucial roles in cancer. Understanding the conformational dynamics of such guanine quadruplexes and identifying druggable regions are therefore essential for developing new inhibition strategies. In this study, we used extensive AMOEBA polarizable force field molecular dynamics simulations combined with data-driven adaptive sampling and clustering algorithms, reaching a cumulative simulation time of 7.5µs forc-kit1. Our results reveal novel structural stabilizations and flexible loop dynamics, as well as the critical role of polarizable water in stabilizing the G-quadruplex, leading to the identification of two new druggable pockets inc-kit1. Additionally, 400 ns simulation of the HIV-1 LTR-III sequence confirmed its quadruplex stability and uncovered a potentially druggable cryptic pocket.Abstract Figure
Inflammatory pain in mice induces light cycle-dependent effects on sleep architecture
Authors: Burek Dominika J. , Ibrahim Khairunisa Mohamad , Hall Andrew G. , Sharma Ashish , Musiek Erik S. , Morón Jose A. , Carlezon William A. 
Published: August 2024

ABSTRACTAs a syndrome, chronic pain comprises physical, emotional, and cognitive symptoms such as disability, negative affect, feelings of stress, and fatigue. A rodent model of long-term inflammatory pain, induced by complete Freund’s adjuvant (CFA) injection, has previously been shown to cause anhedonia and dysregulated naturalistic behaviors, in a manner similar to animal models of stress. We examined whether this extended to alterations in circadian rhythms and sleep, such as those induced by chronic social defeat stress, using actigraphy and wireless EEG. CFA-induced inflammatory pain profoundly altered sleep architecture in male and female mice. Injection of the hind paw, whether with CFA or saline, reduced some measures of circadian rhythmicity such as variance, period, and amplitude. CFA increased sleep duration primarily in the dark phase, while sleep bout length was decreased in the light and increased in the dark phase. Additionally, CFA reduced wake bout length, especially during the dark phase. Increases in REM and SWS duration and bouts were most significant in the dark phase, regardless of whether CFA had been injected at its onset or 12 hours prior. Taken together, these results indicate that inflammatory pain acutely promotes but also fragments sleep.
Glutamate uptake is transiently compromised in the perilesional cortex following controlled cortical impact
Authors: Garcia Jacqueline P , Armbruster Moritz , Sommer Mary , Nunez-Beringer Aliana , Dulla Chris G 
Published: August 2024

ABSTRACTGlutamate, the primary excitatory neurotransmitter in the CNS, is regulated by the excitatory amino acid transporters (EAATs) GLT-1 and GLAST. Following traumatic brain injury (TBI), extracellular glutamate levels increase, contributing to excitotoxicity, circuit dysfunction, and morbidity. Increased neuronal glutamate release and compromised astrocyte-mediated uptake contribute to elevated glutamate, but the mechanistic and spatiotemporal underpinnings of these changes are not well established. Using the controlled cortical impact (CCI) model of TBI and iGluSnFR glutamate imaging, we quantified extracellular glutamate dynamics after injury. Three days post-injury, glutamate release was increased, and glutamate uptake and GLT-1 expression were reduced. 7- and 14-days post-injury, glutamate dynamics were comparable between sham and CCI animals. Changes in peak glutamate response were unique to specific cortical layers and proximity to injury. This was likely driven by increases in glutamate release, which was spatially heterogenous, rather than reduced uptake, which was spatially uniform. The astrocyte K+channel, Kir4.1, regulates activity-dependent slowing of glutamate uptake. Surprisingly, Kir4.1 was unchanged after CCI and accordingly, activity-dependent slowing of glutamate uptake was unaltered. This dynamic glutamate dysregulation after TBI underscores a brief period in which disrupted glutamate uptake may contribute to dysfunction and highlights a potential therapeutic window to restore glutamate homeostasis.
Temperature and host plant ecotype drive nitrogen fixation, but not nodule community composition, in hairy vetch
Authors: Fudge Rebecca , Gardner Paula , Denison R Ford , Burghardt Liana , Grossman Julie 
Published: August 2024

AbstractHairy vetch (Vicia villosaRoth) is a commonly grown cover crop throughout the U.S., which can contribute nitrogen for subsequent cash crops through biological nitrogen fixation (BNF) in association withRhizobium leguminosarumbiovarviciae(Rlv) bacteria. Hairy vetch is one of the few cover crops sufficiently cold-tolerant to over-winter in the Upper Midwestern U.S. However, nitrogen contributions by hairy vetch vary across locations, potentially due to cold impacts on the legume/rhizobia symbiosis. The traditional route to improve BNF in legumes involves selecting superior rhizobia strains to create more effective inoculants to apply at planting, but inoculants often fail to compete and survive in agricultural soils. Instead, this study tested the effects of temperature and host plant ecotype on hairy vetch BNF and Rlv community composition in nodules, with the goal of potentially identifying vetch ecotypes able to select beneficial Rlv strains from the soil community. Four hairy vetch ecotypes trapped Rlv from three Minnesota soils, at warm or cold temperatures. Vetch ecotype was a key driver of BNF and nodule formation under warm and cold conditions. However, temperature and plant ecotype did not drive Rlv community composition in nodules, and Rlv community composition did not affect plant productivity. Taken together, these results suggest that the best strategy to improve BNF at low temperatures in hairy vetch likely depends on breeding for improved biomass accumulation and nitrogen fixation in host plants, rather than focusing on host plant selection of beneficial rhizobia.