bluuebunny/crossref_metadata_2025_split huggingface dataset:
AncestryPainter2.0: Visualizing ancestry composition and admixture history graph
Authors: Chen Shuanghui , Lei Chang , Zhao Xiaohan , Pan Yuwen , Lu Dongsheng , Xu Shuhua 
Published: April 2024

AbstractTo effectively depict the results of population genetics studies, it is essential to present ancestry composition and genetic distance. The growing amount of genomic data prompted us to designAncestryPainter1.0, a Perl program to display the ancestry composition of numerous individuals using a rounded graph. Motivated by the requests of users in practical applications, we updatedAncestryPainterto version 2.0 by coding in an R package and improving the layout, providing more options and compatible statistical functions for graphing. In particular,AncestryPainter2.0 implements a method admixture history graph (AHG) to infer the admixture sequence of multiple ancestry populations, and allows for multiple pie charts at the center of the graph to display the ancestry composition of more than one target population. We also introduced an additional graphing module to visualize genetic distance through radial bars of varying lengths surrounding a core. Visualization functionsper sehave been enhanced in this update as well. Furthermore,AncestryPainter2.0 includes two statistical modules to 1) merge ancestry proportion matrices and 2) infer admixture sequences through correlation analyses.AncestryPainter2.0 is publicly available athttps://github.com/Shuhua-Group/AncestryPainterV2andhttps://pog.fudan.edu.cn/#/Software.
Inhibitory Plasticity Enhances Sequence Storage Capacity and Retrieval Robustness
Authors: Gong Ziyi , Brunel Nicolas 
Published: April 2024

AbstractThe generation of motor behaviors and the performance of complex cognitive tasks rely on sequential activity in specific brain structures. The mechanisms of learning and retrieval of these temporal patterns of activity are still poorly understood. Emerging evidence has high-lighted the importance of inhibition to learning and memory. However, the specific functions of inhibitory plasticity in the learning and retrieval of sequential activity have been studied very little, apart from its role in maintaining excitation-inhibition (E-I) balance. Using simulations and dynamical mean-field theory of balanced E-I networks, we found that sequences can be stored and retrieved using plasticity in both E-to-I and I-to-E pathways, in the absence of recurrent excitatory plasticity. Networks with both E-to-I and I-to-E plasticity are shown to exhibit higher optimal capacity than models in which plasticity is restricted to recurrent excitation. We further show that inhibitory plasticity enhances robustness to external noise and initial cue perturbation. Thus, our work suggests new computational roles for inhibitory plasticity in improving capacity and robustness of sequence learning.
Selective modification of ascending spinal outputs in acute and neuropathic pain states
Authors: Yarmolinsky David A. , Zeng Xiangsunze , MacKinnon-Booth Natalie , Greene Caitlin , Kim Chloe , Woolf Clifford J. 
Published: April 2024

SummaryPain hypersensitivity arises from the plasticity of peripheral and spinal somatosensory neurons, which modifies nociceptive input to the brain and alters pain perception. We utilized chronic calcium imaging of spinal dorsal horn neurons to determine how the representation of somatosensory stimuli in the anterolateral tract, the principal pathway transmitting nociceptive signals to the brain, changes between distinct pain states. In healthy conditions, we identify stable, narrowly tuned outputs selective for cooling or warming, and a neuronal ensemble activated by intense/noxious thermal and mechanical stimuli. Induction of an acute peripheral sensitization with capsaicin selectively and transiently retunes nociceptive output neurons to encode low-intensity stimuli. In contrast, peripheral nerve injury-induced neuropathic pain results in a persistent suppression of innocuous spinal outputs coupled with activation of a normally silent population of high-threshold neurons. These results demonstrate the differential modulation of specific spinal outputs to the brain during nociceptive and neuropathic pain states.
A prion-like protein regulates the 2-dimensional to 3-dimensional growth transition in the mossPhyscomitrium patens
Authors: Weeks Zoe , Chaturvedi Gargi , Day Emily , Kelly Steven , Moody Laura A. 
Published: April 2024

ABSTRACTThe colonization of the land by plants coincided with the evolution of 3-dimensional (3D) growth; the acquisition of apical cells with the capacity to rotate the plane of cell division. The mossPhyscomitrium patenshas recently been developed as a model to dissect the genetic basis of 3D growth, an invariable and unifying feature of all land plants. The cytokinin-unresponsivePpnog1-Rmutant incorrectly orients division planes in developing buds and thus fails to make the transition to 3D growth. To reveal the genetic interactors of thePpNOG1gene, which encodes a protein with a C-terminal UBA domain, we performed a screen and identified thesuppressor of nog1a(snog1a) mutant. We have mapped the causative mutation to a gene that encodes a prion-like protein related to FLOE2/3 and demonstrated that the mutant phenotypes observed in both anog1disruptant mutant (nog1dis) andsnog1acan be attributed to changes in cytokinin perception. We present a revised model for 3D growth and suggest that the 2D-to-3D growth transition is regulated, at least in part, by liquid-liquid phase separation (LLPS).SUMMARY STATEMENTThe transition to 3D growth is negatively regulated by a prion-like protein that both alters cytokinin signaling and has been implicated in liquid-liquid phase separation (LLPS).
CONCERTED PLANT GROWTH AND DEFENSE THROUGH TARGETED PHYTOHORMONE CROSSTALK MODIFICATION
Authors: Johnston Grace A. , Berry Hannah M. , Kojima Mikiko , Sakakibara Hitoshi , Argueso Cristiana T. 
Published: April 2024

ABSTRACTPlant immunity activation often results in suppression of plant growth, particularly in the case of constitutive immune activation. We discovered that signaling of the phytohormone cytokinin (CK), known to regulate plant growth through the control of cell division and shoot apical meristem (SAM) activity, can be suppressed by negative crosstalk with the defense phytohormones jasmonic acid (JA), and most evidently, salicylic acid (SA). We show that changing the negative crosstalk of SA on CK signaling in autoimmunity mutants by targeted increase of endogenous CK levels results in plants resistant to pathogens from diverse lifestyles, and relieves suppression of reproductive growth. Moreover, such changes in crosstalk result in a novel reproductive growth phenotype, suggesting a role for defense phytohormones in the SAM, likely through regulation of nitrogen response and cellular redox status. Our data suggest that targeted phytohormone crosstalk engineering can be used to achieve increased reproductive growth and pathogen resistance.SIGNIFICANCE STATEMENTPlants constantly integrate environmental stimuli with developmental programs to optimize their growth and fitness. Excessive activation of the plant immune system often leads to decreased plant growth, a process known as the growth-defense tradeoff. Here, we adapted phytohormone levels in Arabidopsis reproductive tissues of autoimmunity mutants to change phytohormonal crosstalk and diminish the growth tradeoff, resulting in increased broad resistance to pathogens and decreased growth suppression. Similar approaches to phytohormone crosstalk engineering could be used in different contexts to achieve outcomes of higher plant stress resilience and yield.
Clemastine fumarate accelerates accumulation of disability in progressive multiple sclerosis by enhancing pyroptosis
Authors: Kocot Joanna , Kosa Peter , Ashida Shinji , Pirjanian Nicolette , Goldbach-Mansky Raphaela , Peterson Karin , Fossati Valentina , Holland Steven M. , Bielekova Bibiana 
Published: April 2024

AbstractMultiple sclerosis (MS) is an immune-mediated demyelinating disease of the central nervous system (CNS). Clemastine fumarate, the over-the-counter antihistamine and muscarinic receptor blocker, has remyelinating potential in MS. A clemastine arm was added to an ongoing platform clinical trial TRAP-MS (NCT03109288) to identify a cerebrospinal fluid (CSF) remyelination signature and to collect safety data on clemastine in patients progressing independently of relapse activity (PIRA). The clemastine arm was stopped per protocol-defined criteria when 3/9 patients triggered individual safety stopping criteria (χ2p=0.00015 compared to remaining TRAP-MS treatments). Clemastine treated patients had significantly higher treatment-induced disability progression slopes compared to remaining TRAP-MS participants (p=0.0075). Quantification of ∼7000 proteins in CSF samples collected before and after clemastine treatment showed significant increase in purinergic/ATP signaling and pyroptosis cell death. Mechanistic studies showed that clemastine with sub-lytic doses of extracellular ATP activates inflammasome and induces pyroptotic cell death in macrophages. Clemastine with ATP also caused pyroptosis of induced pluripotent stem cell-derived human oligodendrocytes. Antagonist of the purinergic channel P2RX7 that is strongly expressed in oligodendrocytes and myeloid cells, blocked these toxic effects of clemastine. Finally, re-analyses of published snRNAseq studies revealed increased P2RX7 expression and pyroptosis transcriptional signature in microglia and oligodendrocytes in MS brain, especially in chronic active lesions. CSF proteomic pyroptosis score was increased in untreated MS patients, was higher in patients with progressive than relapsing-remitting disease and correlated significantly with rates of MS progression. Thus, pyroptosis is likely first well-characterized mechanism of CNS injury underlying PIRA even outside of clemastine toxicity.One Sentence SummaryClemastine enhanced disability accumulation in patients progressing by non-lesional MS activity by potentiating intrathecal P2RX7 signaling and pyroptosis.
vcfgl: A flexible genotype likelihood simulator for VCF/BCF files
Authors: Altinkaya Isin , Nielsen Rasmus , Korneliussen Thorfinn Sand 
Published: April 2024

AbstractMotivationAccurate quantification of genotype uncertainty is pivotal in ensuring the reliability of genetic inferences drawn from NGS data. Genotype uncertainty is typically modeled using Genotype Likelihoods (GLs), which can help propagate measures of statistical uncertainty in base calls to downstream analyses. However, the effects of errors and biases in the estimation of GLs, introduced by biases in the original base call quality scores or the discretization of quality scores, as well as the choice of the GL model, remain under-explored.ResultsWe present vcfgl, a versatile tool for simulating genotype likelihoods associated with simulated read data. It offers a framework for researchers to simulate and investigate the uncertainties and biases associated with the quantification of uncertainty, thereby facilitating a deeper understanding of their impacts on downstream analytical methods. Through simulations, we demonstrate the utility of vcfgl in benchmarking GL-based methods. The program can calculate GLs using various widely used genotype likelihood models and can simulate the errors in quality scores using a Beta distribution. It is compatible with modern simulators such as msprime and SLiM, and can output data in pileup, VCF/BCF and gVCF file formats. The vcfgl program is freely available as an efficient and user-friendly software written in C/C++.Availabilityvcfgl is freely available athttps://github.com/isinaltinkaya/vcfgl.Contactisin.altinkaya@sund.ku.dkSupplementary informationSupplementary information is available online.
Quantitative RNA spatial profiling using single-molecule RNA FISH on plant tissue cryosections
Authors: Zhang Xue , Fonseca Alejandro , Kutashev Konstantin , Sicard Adrien , Duncan Susan , Rosa Stefanie 
Published: April 2024

ABSTRACTSingle-molecule fluorescencein situhybridization (smFISH) has emerged as a powerful tool to study gene expression dynamics with unparalleled precision and spatial resolution in a variety of biological systems. Recent advancements have expanded its application to encompass plant studies, yet a demand persists for a simple and robust smFISH method adapted to plant tissue sections. Here, we present an optimized smFISH protocol (cryo-smFISH) for visualizing and quantifying single mRNA molecules in plant tissue cryosections. This method exhibits remarkable sensitivity, capable of detecting low-expression transcripts, including long non-coding RNAs. Integrating a deep learning-based algorithm in our image analysis pipeline, our method enables us to assign RNA abundance precisely in nuclear and cytoplasmic compartments. Compatibility with Immunofluorescence also allows RNA and endogenous proteins to be visualized and quantified simultaneously. Finally, this study presents for the first time the use of smFISH for single-cell RNA sequencing (scRNA-seq) validation in plants. By extending the smFISH method to plant cryosections, an even broader community of plant scientists will be able to exploit the multiple potentials of quantitative transcript analysis at cellular and subcellular resolutions.
Interplay between the Xer recombination system and the dissemination of antibioresistance inAcinetobacter baumannii
Authors: Corentin Blanchais , Carine Pages , Campos Manuel , Boubekeur Kenza , Rachel Contarin , Orlando Mathias , Patricia Siguier , Maria-Halima Laaberki , François Cornet , Xavier Charpentier , Philippe Rousseau 
Published: April 2024

AbstractAntibiotic-resistant infections pose a pressing challenge in clinical settings. Plasmids are widely recognized for hastening the emergence of resistance by facilitating horizontal gene transfer of antibiotic resistance genes among bacteria. We explore this inquiry inAcinetobacter baumannii, a globally emerging nosocomial pathogen responsible for a wide array of infections with worrying accumulation of resistances, notably involving plasmids. In this specie, plasmids of the Rep_3 family harbor adaptive genes within variable regions edged by potential site-specific recombination sites recognized by the XerCD recombinase. We first show that the Xer system ofAcinetobacter baumanniifunctions as described inEscherichia coli, resolving chromosome dimers at thedifsite as well as recombining plasmid-borne sites. The multiple Xer recombination sites found in Rep_3 plasmids do not, however, allow excising plasmid fragments. They rather recombine to co-integrate plasmids, which may then further evolve to exchange genes. Co-integrates represent a significative part of the plasmid population and their formation is controlled by the sequence of the recombination sites determining their compatibility between the recombining sites. We conclude that plasmids frequently exchange genes inAcinetobacter baumanniiusing Xer recombination, allowing a high level yet controlled plasticity involved in the acquisition and combination of resistance genes.
Serotype and distribution of adhesion genes inStreptococcus mutansclinical isolates
Authors: Donnet Laura , Claisse Olivier , Samot Johan 
Published: April 2024

AbstractThe delicate balance of the oral cavity is disrupted by hygiene and diet changes, leading to caries. The virulence ofStreptococcus mutans, a key caries pathogen, is partly explained by its rhamnose-glucose polysaccharide (RGP) and its sucrose-dependent and -independent adhesion mechanisms. This study investigates the diversity ofS. mutansthrough analysis of its RGP and the distribution of sucrose-independent adhesion proteins (SpaP, WapA, Cnm, Cbm) in Parkinson’s disease patients.In the PARKIDENT clinical trial, strains were isolated from saliva samples of Parkinson’s patients before and after oral hygiene procedures. Strains were preanalyzed by multiplex PCR for serotype and collagen-binding proteins, followed by high-throughput sequencing and bioinformatics analysis using RAST® and BLAST®. Phylogenetic analyses and protein modeling were also conducted.Of 40 patients in the Parkident clinical trial, only 24 hadStreptococcus mutansstrains isolable from salivary swabs. Serotyping revealed that over 80% of the 44 strains isolated were serotype c, in line with prevalence data in the literature. Furthermore, only SpaP types A and B were identified in the strains. The low variability observed for the WapA protein underlines its functional importance. Finally, thecbmgene was not found in any strain, and only 5 strains possessed thecnmgene, all of them serotype c.The study of these 44Streptococcus mutansstrains showed characteristics similar to other populations. Serotype c predominates, with minimal peptide variability in adhesion proteins (SpaP, WapA). Collagen-binding proteins Cnm and Cbm are rare or absent. Further research is essential for detailed strain distribution in Parkinson’s-affected and general French populations due toS. mutans’growing role in extra-oral pathologies.
African Swine Fever Virus Protein B263R Inhibits Autophagy by Promoting Proteasomal Degradation of Beclin1
Authors: Ding Shuxiang , Wang Xingbo , Deng Tingjuan , Xu Kang , Dong Weiren , Yan Yan , Zhou Jiyong , Hu Boli 
Published: April 2024

ABSTRACTAfrican swine fever (ASF) is a highly contagious viral disease that affects both domestic and wild pigs, leading to substantial economic losses in the swine industry. However,the precise role of ASFV-encoded viral protein in viral replication and disease has remained elusive. In our study, we elucidated that B263R inhibited autophagy by interacting with Beclin1. Mechanistically, the binding of B263R to Beclin1 promotes its degradation through the mediation of K48-linked ubiquitination at site K31. Notably, the knockdown of Beclin1 mitigated the effect of B263R on reducing the levels of LC3-II, thus further affirming the pivotal role of Beclin1 in B263R-mediated autophagy inhibition. The proliferation of recombinant adenovirus inherently expressing B263R significantly decreased, underscoring the inherent role of B263R-mediated autophagy in virus replication. These findings shed light on the molecular mechanisms employed by ASFV to evade host cell autophagic defenses and offered potential targets for therapeutic interventions against ASFV infection.IMPORTANCEUnderstanding the mechanisms underlying the evasion of host cellular defenses by the African swine fever virus (ASFV) is of pivotal significance owing to its profound impact on the global swine industry. The precise functional roles of ASFV proteins in virus replication and disease remain incompletely characterized. In this study, it is demonstrated that a specific ASFV protein, B263R, acts to inhibit autophagy by interacting with Beclin1, thereby facilitating its degradation. The elucidation of this molecular pathway not only advances our comprehension of ASFV pathogenesis but also furnishes potential targets for therapeutic interventions against ASFV infection. By unraveling the intricate interplay between ASFV and host cell autophagy, this scholarly endeavor contributes invaluable insights to the development of strategies aimed at mitigating the spread of ASFV and minimizing its adverse repercussions on the swine industry.
Unique cortical and subcortical activation patterns for different conspecific calls in marmosets
Authors: Jafari Azadeh , Dureux Audrey , Zanini Alessandro , Menon Ravi S. , Gilbert Kyle M. , Everling Stefan 
Published: April 2024

AbstractThe common marmoset (Callithrix jacchus) is known for its highly vocal nature, displaying a diverse range of different calls. Functional imaging in marmosets has shown that the processing of conspecific calls activates a brain network that includes fronto-temporal cortical and subcortical areas. It is currently unknown whether different call types activate the same or different networks. Here we show unique activation patterns for different calls. Nine adult marmosets were exposed to four common vocalizations (phee, chatter, trill, and twitter), and their brain responses were recorded using event-related fMRI at 9.4T. We found robust activations in the auditory cortices, encompassing core, belt, and parabelt regions, and in subcortical areas like the inferior colliculus, medial geniculate nucleus, and amygdala in response to these conspecific calls. Different neural activation patterns were observed among the vocalizations, suggesting vocalization-specific neural processing. Phee and twitter calls, often used over long distances, activated similar neural circuits, whereas trill and chatter, associated with closer social interactions, demonstrated a closer resemblance in their activation patterns. Our findings also indicate the involvement of the cerebellum and medial prefrontal cortex (mPFC) in distinguishing particular vocalizations from others.Significance StatementThis study investigates the neural processing of vocal communications in the common marmoset (Callithrix jacchus), a species with a diverse vocal repertoire. Utilizing event-related fMRI at 9.4T, we demonstrate that different marmoset calls (phee, chatter, trill, and twitter) elicit distinct activation patterns in the brain, challenging the notion of a uniform neural network for all vocalizations. Each call type distinctly engages various regions within the auditory cortices and subcortical areas, reflecting the complexity and context-specific nature of primate communication. These findings offer insights into the evolutionary mechanisms of primate vocal perception and provide a foundation for understanding the origins of human speech and language processing.
Histone H3 Orchestrates the Ubiquitination of Nucleosomal H2A by BRCA1/BARD1-UbcH5c Complex
Authors: Goldman Alexandra R. , Shah Tejas , Torabifard Hedieh 
Published: April 2024

AbstractThe Breast Cancer Associated Protein 1 (BRCA1) is a human tumor suppressor protein that commonly functions as ubiquitin ligase enzyme (E3) in the ubiquitination of the C-terminal H2A. BRCA1 enhances ubiquitin ligase activity by forming a heterodimeric complex with the BRCA1 Associated Ring Domain Protein (BARD1). The BRCA1/BARD1 complex works in concert with the ubiquitin-conjugating enzyme (UbcH5c or E2) to ubiquitinate one of the five lysines of the H2A C-terminal, ultimately promoting the repair of double-stranded DNA breaks. The mutations in the BRCA1-UbcH5c portion of the E3-E2 complex have been linked to breast and ovarian cancer. However, the mechanism of BRCA1/BARD1-UbcH5c complex ubiquitination at H2A is poorly understood, and the ubiquitination of exact lysine is debated. In this study, we sought to expand on the current research on H2A ubiquitination by using all-atom molecular dynamics simulations to model the BRCA1/BARD1-UbcH5c complex with the human ubiquitin protein (Ub). The Ub protein covalently bonds to the active site of E2, resulting in diminished flexibility of the E3-E2 complex with respect to the nucleosome core particle. The results of this study suggest a possible contribution of H3 in determining the preferred orientation of E2-Ub with respect to the H2A C-terminal lysines.