bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acid-sensing ion channel 1a contributes to the prefrontal cortex ischemia-enhanced neuronal activities in the amygdala
Authors: Park Gyeongah , Ge Qian , Jin Zhen , Du Jianyang 
Published: September 2023

ABSTRACTFollowing a stroke, the emergence of amygdala-related disorders poses a significant challenge, with severe implications for post-stroke mental health, including conditions such as anxiety and depression. These disorders not only hinder post-stroke recovery but also elevate mortality rates. Despite their profound impact, the precise origins of aberrant amygdala function after stroke remain elusive. As a target of reduced brain pH in ischemia, acid-sensing ion channels (ASICs) have been implicated in synaptic transmission after ischemia, hinting at their potential role in reshaping neural circuits following a stroke. This study delves into the intriguing relationship between post-stroke alterations and ASICs, specifically focusing on postsynaptic ASIC1a enhancement in the amygdala following prefrontal cortex (PFC) ischemia induced by endothelin-1 (ET-1) injection. Our findings intriguingly illustrate that mPFC ischemia not only accentuates the PFC to amygdala circuit but also implicates ASIC1a in fostering augmented synaptic plasticity after ischemia. In contrast, the absence of ASIC1a impairs the heightened induction of long-term potentiation (LTP) in the amygdala induced by ischemia. This pivotal research introduces a novel concept with the potential to inaugurate an entirely new avenue of inquiry, thereby significantly enhancing our comprehension of the intricate mechanisms underlying post-stroke neural circuit reconfiguration. Importantly, these revelations hold the promise of paving the way for groundbreaking therapeutic interventions.
The small G-protein Rac1 in the dorsomedial striatum promotes alcohol-dependent structural plasticity and goal-directed learning in mice
Authors: Hoisington Zachary W. , Salvi Alexandra , Laguesse Sophie , Ehinger Yann , Shukla Chhavi , Phamluong Khanhky , Ron Dorit 
Published: September 2023

AbstractThe small G-protein Rac1 promotes the formation of filamentous actin (F-Actin). Actin is a major component of dendritic spines, and we previously found that alcohol alters actin composition and dendritic spine structure in the nucleus accumbens (NAc) and the dorsomedial striatum (DMS). To examine if Rac1 contributes to these alcohol-mediated adaptations, we measured the level of GTP-bound active Rac1 in the striatum of mice following 7 weeks of intermittent access to 20% alcohol. We found that chronic alcohol intake activates Rac1 in the DMS of male mice. In contrast, Rac1 is not activated by alcohol in the NAc and DLS of male mice, or in the DMS of female mice. Similarly, closely related small G-proteins are not activated by alcohol in the DMS, and Rac1 activity is not increased in the DMS by moderate alcohol or natural reward. To determine the consequences of alcohol-dependent Rac1 activation in the DMS of male mice, we inhibited endogenous Rac1 by infecting the DMS of mice with an AAV expressing a dominant negative form of the small G-protein (Rac1-DN). We found that overexpression of AAV-Rac1-DN in the DMS inhibits alcohol-mediated Rac1 signaling and attenuates alcohol-mediated F-actin polymerization, which corresponded with a decrease in dendritic arborization and spine maturation. Finally, we provide evidence to suggest that Rac1 in the DMS plays a role in alcohol-associated goal-directed learning. Together, our data suggest that Rac1 in the DMS plays an important role in alcohol-dependent structural plasticity and aberrant learning.Significance StatementAddiction, including alcohol use disorder, is characterized by molecular and cellular adaptations that promote maladaptive behaviors. We found that Rac1 was activated by alcohol in the dorsomedial striatum (DMS) of male mice. We show that alcohol-mediated Rac1 signaling is responsible for alterations in actin dynamics and neuronal morphology. We also present data to suggest that Rac1 is important for alcohol-associated learning processes. These results suggest that Rac1 in the DMS is an important contributor to adaptations that promote alcohol use disorder.
FindingCandida aurisin public metagenomic repositories
Authors: Mario-Vasquez Jorge E. , Bagal Ujwal R. , Lowe Elijah , Morgulis Aleksandr , Phan John , Sexton D. Joseph , Shiryev Sergey , Slatkevičius Rytis , Welsh Rory , Litvintseva Anastasia P. , Blumberg Matthew , Agarwala Richa , Chow Nancy A. 
Published: September 2023

AbstractCandida aurisis a newly emerged multidrug-resistant fungus capable of causing invasive infections with high mortality. Despite intense efforts to understand how this pathogen rapidly emerged and spread worldwide, its environmental reservoirs are poorly understood. Here, we present a collaborative effort between the U.S. Centers for Disease Control and Prevention, the National Center for Biotechnology Information, and GridRepublic (a volunteer computing platform) to identifyC. aurissequences in publicly available metagenomic datasets. We developed the MetaNISH pipeline that uses SRPRISM to align sequences to a set of reference genomes and computes a score for each reference genome. We used MetaNISH to scan ∼300,000 SRA metagenomic runs from 2010 onwards and identified five datasets containingC. aurisreads. Finally, GridRepublic has implemented a prospectiveC. aurismolecular monitoring system using MetaNISH and volunteer computing.
Sperm competition intensity shapes divergence in both sperm morphology and reproductive genes across murine rodents
Authors: Kopania Emily E. K. , Thomas Gregg W. C. , Hutter Carl R. , Mortimer Sebastian M. E. , Callahan Colin M. , Roycroft Emily , Achmadi Anang S. , Breed William G. , Clark Nathan L. , Esselstyn Jacob A. , Rowe Kevin C. , Good Jeffrey M. 
Published: September 2023

AbstractIt remains unclear how variation in the intensity of sperm competition shapes phenotypic and molecular evolution across clades. Mice and rats in the subfamily Murinae are a rapid radiation exhibiting incredible diversity in sperm morphology and production. We combined phenotypic and genomic data to perform phylogenetic comparisons of male reproductive traits and genes across 78 murine species. We identified several shifts towards smaller relative testes mass, presumably reflecting reduced sperm competition. Several sperm traits were associated with relative testes mass, suggesting that mating system evolution selects for convergent suites of traits related to sperm competitive ability. We predicted that sperm competition would also drive more rapid molecular divergence in species with large testes. Contrary to this, we found that many spermatogenesis genes evolved more rapidly in species with smaller relative testes mass due to relaxed purifying selection. While some reproductive genes evolved rapidly under recurrent positive selection, relaxed selection played a greater role in underlying rapid evolution in small testes species. Our work demonstrates that postcopulatory sexual selection can impose strong purifying selection shaping the evolution of male reproduction, and that broad patterns of molecular evolution may help identify genes that contribute to male fertility.
Gigantic Animal Cells Suggest Organellar Scaling Mechanisms Across a 50-fold Range in Cell Volume
Authors: Adams Alexander Nichols , Smith Bradford Julian , Raad Thomas John , Mueller Rachel Lockridge 
Published: September 2023

AbstractAcross the tree of life, cell size varies by orders of magnitude, and organelles scale to maintain cell function. Depending on their shape, organelles can scale by increasing volume, length, or number. Scaling may also reflect demands placed on organelles by increased cell size. The 8,653 species of amphibians exhibit diverse cell sizes, providing a powerful system to investigate organellar scaling. Using transmission electron microscopy and stereology, we analyzed three frog and salamander species whose enterocyte cell volumes range from 228 to 10,593 μm3. We show that the nucleus increases in radius while the mitochondria increase in total network length; the endoplasmic reticulum and Golgi apparatus, with their complex shapes, are intermediate. Notably, all four organelles increase in volume proportionate to cell volume. This pattern suggests that protein concentrations are the same across amphibian species that differ 50-fold in cell size, and that organellar building blocks are incorporated into more or larger organelles following the same “rules” across cell sizes, despite variation in metabolic and transport demands. This conclusion contradicts results from experimental cell size increases, which produce severe proteome dilution. We hypothesize that salamanders have evolved the biosynthetic capacity to maintain a functional proteome despite a huge cell volume.
Mating system and environment predict the direction and extent of introgression between incipientClarkiaspecies
Authors: Sianta Shelley A. , Moeller David A. , Brandvain Yaniv 
Published: September 2023

AbstractIntrogression is pervasive across the tree of life, varying across taxa, geography, and genomes. However, we are only beginning to understand the factors that modulate this variation and how they may be affected by global change. Here, we used 200 genomes and a 15-year site-specific environmental dataset to investigate the effect of mating system divergence and environmental variation on the magnitude of introgression between two recently diverged annual plants. Two subspecies ofClarkia xantianadiverged ca. 65k years ago and subsequently came into secondary sympatry where they form replicated contact zones. We found that introgression is asymmetric between taxa, with substantially more introgression from the self-fertilizing taxon to the outcrossing taxon. This asymmetry is caused by a bias in the direction of initial F1 hybrid formation and subsequent backcrossing. We also found extensive variation in the outcrosser’s admixture proportion among contact zones, which is predicted nearly entirely by interannual variance in spring precipitation. Greater fluctuations in spring precipitation result in higher admixture proportions, likely mediated by the effects of spring precipitation on the expression of traits that determine premating reproductive isolation. Climate-driven hybridization dynamics may be particularly affected by global change, potentially reshaping species boundaries and adaptation to novel environments.
Chromatin Profiling of CBFA2T3-GLIS2 AMLs Identifies Key Transcription Factor Dependencies and BRG1 Inhibition as a Novel Therapeutic Strategy
Authors: Kaonis Samantha , Smith Jenny L. , Katiyar Neerja , Merrill Morgan , Hyelkma Tiffany , Namciu Stephanie , Le Quy , Babaeva Ekaterina , Ishida Takashi , Morris Shelli M. , Girard Emily , Furuyama Suzanne , Ries Rhonda , Bernstein Irwin , Meshinchi Soheil , Henikoff Steven , Meers Michael , Hadland Brandon , Sarthy Jay F. 
Published: September 2023

AbstractOncogenic fusions involving transcription factors are present in the majority of pediatric leukemias; however, the context-specific mechanisms they employ to drive cancer remain poorly understood. CBFA2T3-GLIS2 (C/G) fusions occur in treatment-refractory acute myeloid leukemias and are restricted to young children. To understand how the C/G fusion drives oncogenesis we applied CUT&RUN chromatin profiling to an umbilical cord blood/endothelial cell (EC) co-culture model of C/G AML that recapitulates the biology of this malignancy. We find C/G fusion binding is mediated by its zinc finger domains. Integration of fusion binding sites in C/G- transduced cells with Polycomb Repressive Complex 2 (PRC2) sites in control cord blood cells identifiesMYCN, ZFPM1, ZBTB16 and LMO2as direct C/G targets. Transcriptomic analysis of a large pediatric AML cohort shows that these genes are upregulated in C/G patient samples. Single cell RNA-sequencing of umbilical cord blood identifies a population of megakaryocyte precursors that already express many of these genes despite lacking the fusion. By integrating CUT&RUN data with CRISPR dependency screens we identifyBRG1/SMARCA4as a vulnerability in C/G AML. BRG1 profiling in C/G patient-derived cell lines shows that theCBFA2T3locus is a binding site, and treatment with clinically-available BRG1 inhibitors reduces fusion levels and downstream C/G targets including N-MYC, resulting in C/G leukemia cell death and extending survival in a murine xenograft model.
Learning induced neuronal identity switch in the superficial layers of the primary somatosensory cortex
Authors: Dai Jiaman , Sun Qian-Quan 
Published: September 2023

AbstractDuring learning, multi-dimensional inputs are integrated within the sensory cortices. However, the strategies by which the sensory cortex employs to achieve learning remains poorly understood. We studied the sensory cortical neuronal coding of trace eyeblink conditioning (TEC) in head-fixed, freely running mice, where whisker deflection was used as a conditioned stimulus (CS) and an air puff to the cornea delivered after an interval was used as unconditioned stimulus (US). After training, mice learned the task with a set of stereotypical behavioral changes, most prominent ones include prolonged closure of eyelids, and increased reverse running between CS and US onset. The local blockade of the primary somatosensory cortex (S1) activities with muscimol abolished the behavior learning suggesting that S1 is required for the TEC. In naive animals, based on the response properties to the CS and US, identities of the small proportion (∼20%) of responsive primary neurons (PNs) were divided into two subtypes: CR (i.e. CS-responsive) and UR neurons (i.e. US-responsive). After animals learned the task, identity of CR and UR neurons changed: while the CR neurons are less responsive to CS, UR neurons gain responsiveness to CS, a new phenomenon we defined as ‘learning induced neuronal identity switch (LINIS)’. To explore the potential mechanisms underlying LINIS, we found that systemic and local (i.e. in S1) administration of the nicotinic receptor antagonist during TEC training blocked the LINIS, and concomitantly disrupted the behavior learning. Additionally, we monitored responses of two types of cortical interneurons (INs) and observed that the responses of the somatostatin-expressing (SST), but not parvalbumin-expressing (PV) INs are negatively correlated with the learning performance, suggesting that SST-INs contribute to the LINIS. Thus, we conclude that L2/3 PNs in S1 encode perceptual learning by LINIS like mechanisms, and cholinergic pathways and cortical SST interneurons are involved in the formation of LINIS.
Chemical Tools for Profiling the Intracellular ADP-ribosylated Proteome
Authors: Draganov Simeon D. , Gruet Michael J. , Conole Daniel , Balcells Cristina , Siskos Alexandros P. , Keun Hector C. , Haskard Dorian O. , Tate Edward W. 
Published: September 2023

ABSTRACTThe post-translational modification (PTM) ADP-ribosylation plays an important role in cell signaling and regulating protein function and has been implicated in the development of multiple diseases, including breast and ovarian cancers. Studying the underlying mechanisms through which this PTM contributes towards disease development, however, has been hampered by the lack of appropriate tools for reliable identification of physiologically relevant ADP-ribosylated proteins in a live-cell environment. Herein, we explore the applications of an alkyne-tagged proprobe, 6Yn-ProTide-Ad (6Yn-Pro) as a chemical tool for the identification of intracellular ADP-ribosylated proteins through metabolic labelling. We applied targeted metabolomics and chemical proteomics in HEK293T cells treated with 6Yn-Pro to demonstrate intracellular metabolic conversion of the probe into ADP-ribosylation cofactor 6Yn-NAD+, and subsequent labelling and enrichment of PARP1 and multiple known ADP-ribosylated proteins in cells under hydrogen peroxide-induced stress. We anticipate that the approach and methodology described here will be useful for future identification of novel intracellular ADP-ribosylated proteins.Abstract Figure
Pathological brain states in Alzheimer’s disease
Authors: Adams Jenna N. , Kark Sarah M. , Chappel-Farley Miranda G. , Escalante Yuritza , Stith Lea A. , Rapp Paul E. , Yassa Michael A. ,   the Alzheimer’s Disease Neuroimaging Initiative
Published: September 2023

ABSTRACTDynamic and rapid reconfigurations of neural activation patterns, known as brain states, support cognition. Recent analytic advances applied to functional magnetic resonance imaging now enable the quantification of brain states, which offers a substantial methodological improvement in characterizing spatiotemporal dynamics of activation over previous functional connectivity methods. Dysfunction to the persistence and temporal transitions between discrete brain states may be proximal factors reflecting neurophysiological disruptions in Alzheimer’s disease, although this has not yet been established. Here, we identified six distinct brain states, representing spatiotemporal trajectories of coactivation at single time points, in older adults across the Alzheimer’s disease continuum. Critically, we identified a pathological brain state that reflects coactivation within limbic regions. Higher persistence within and transitions to this limbic state, at the expense of other brain states, is associated with an increased likelihood of a clinically impaired diagnosis, worse cognitive performance, greater Alzheimer’s pathology, and neurodegeneration. Together, our results provide compelling evidence that neural activity settling into a pathological limbic state reflects the progression to Alzheimer’s disease. As brain states have recently been shown to be modifiable targets, this work may inform the development of novel neuromodulation techniques to reduce limbic state persistence. This application would be an innovative clinical approach to rescue cognitive decline in the early stages of Alzheimer’s disease.
Propagating population activity patterns during spontaneous slow waves in the thalamus of rodents
Authors: Horváth Csaba , Ulbert István , Fiáth Richárd 
Published: September 2023

AbstractSlow waves (SWs) represent the most prominent electrophysiological events in the thalamocortical system under anesthesia and during deep sleep. Recent studies have revealed that SWs have complex spatiotemporal dynamics and propagate across neocortical regions. However, it is still unclear whether neuronal activity in the thalamus exhibits similar propagation properties during SWs. Here, we report propagating population activity in the thalamus of ketamine/xylazine-anesthetized rats and mice visualized by high-density silicon probe recordings. In both rodent species, propagation of spontaneous thalamic activity during up-states was most frequently observed in dorsal thalamic nuclei such as the higher order posterior (Po), lateral posterior (LP) or laterodorsal (LD) nuclei. The preferred direction of thalamic activity spreading was along the dorsoventral axis, with over half of the up-states exhibiting a gradual propagation in the ventral-to-dorsal direction. Furthermore, simultaneous neocortical and thalamic recordings demonstrated that there is a weak but noticeable interrelation between propagation patterns observed during cortical up-states and those displayed by thalamic population activity. In addition, using chronically implanted silicon probes, we detected propagating activity patterns in the thalamus of naturally sleeping rats during slow-wave sleep. However, in comparison to propagating up-states observed under anesthesia, these propagating patterns were characterized by a reduced rate of occurrence and a faster propagation speed. Our findings suggest that the propagation of spontaneous population activity is an intrinsic property of the thalamocortical network during synchronized brain states such as deep sleep or anesthesia. Additionally, our data implies that the neocortex may have partial control over the formation of propagation patterns within the dorsal thalamus.
ZBTB24 is a conserved multifaceted transcription factor at genes and centromeres that governs the DNA methylation state and expression of satellite repeats
Authors: Grillo Giacomo , Boyarchuk Ekaterina , Mihic Seed , Ivkovic Ivana , Bertrand Mathilde , Jouneau Alice , Dahlet Thomas , Dumas Michael , Weber Michael , Velasco Guillaume , Francastel Claire 
Published: September 2023

ABSTRACTSince its discovery as an Immunodeficiency with Centromeric instability and Facial anomalies syndrome-causative gene, ZBTB24 has emerged as a key player in DNA methylation, immunity and development. By extensively analyzing ZBTB24 genomic functions in ICF-relevant mouse and human cellular models, we revealed here its multiple facets as a transcription factor, with key roles in immune response-related genes expression and also in early embryonic development. Using a constitutiveZbtb24ICF-like mutant and an auxin-inducible degron system in mouse embryonic stem cells, we showed that ZBTB24 is recruited to centromeric satellite DNA where it is required to establish the correct DNA methylation patterns through the recruitment of DNMT3B. Thus, our results further revealed an essential role for ZBTB24 at human and mouse centromeric satellite arrays, as a transcriptional repressor. Together, we unveiled unprecedented functions of ZBTB24 at human and mouse centromeres by directly controlling DNA methylation and transcription of the underlying tandem satellite repeats.
Transcriptomic Response to Nitrogen Availability Highlights Signatures of Adaptive Plasticity During Tetraploid Wheat Domestication
Authors: Pieri Alice , Beleggia Romina , Gioia Tania , Tong Hao , Vittori Valerio di , Frascarelli Giulia , Bitocchi Elena , Nanni Laura , Bellucci Elisa , Fiorani Fabio , Pecchioni Nicola , Quattro Concetta De , Limongi Antonina Rita , Vita Pasquale De , Rossato Marzia , Schurr Ulrich , David Jacques L. , Nikoloski Zoran , Papa Roberto 
Published: September 2023

AbstractThe domestication of crops, with the development of the agroecosystems, is associated with major environmental changes and represent a model to test the role of phenotypic plasticity. Here we investigated 32 genotypes representing key stages of tetraploid wheat domestication. We developed a dedicated pipeline combining RNA-Seq data, estimates of evolvability andQSTto characterize the plasticity of gene expression and identify signatures of selection under different nitrogen conditions. The analysis of gene expression diversity showed contrasting results between primary and secondary domestication in relation to nitrogen availability. Indeed, nitrogen triggered the expression of twice the number of genes in durum wheat compared to emmer and wild emmer.QSTdistributions andQST–FSTcomparisons revealed distinct selection signatures at each domestication stage. While primary domestication affected the expression of genes involved in biotic interactions, secondary domestication was associated with changes in expression of genes involved in metabolism of amino acids, particularly lysine. Selection signatures were found also in differentially expressed genes, specifically involved in nitrogen metabolism, such asglutamate dehydrogenase. Overall, our findings show that nitrogen availability had a pivotal role during the domestication and adaptive responses of a major food crop, with varying effects across different traits and growth conditions.