bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gut Microbiome Signatures Linked to HIV-1 Reservoir Size and Viremia Control
Authors: Borgognone Alessandra , Noguera-Julian Marc , Oriol Bruna , Noël-Romas Laura , Ruiz-Riol Marta , Guillén Yolanda , Parera Mariona , Casadellà Maria , Duran Clara , Puertas Maria C. , Català-Moll Francesc , De Leon Marlon , Knodel Samantha , Birse Kenzie , Manzardo Christian , Miró Jose M. , Clotet Bonaventura , Martinez-Picado Javier , Moltó José , Mothe Beatriz , Burgener Adam , Brander Christian , Paredes Roger ,   the BCN02 Study Group
Published: October 2021

AbstractBackgroundThe potential role of the gut microbiome as a predictor of immune-mediated HIV-1 control in the absence of antiretroviral therapy (ART) is still unknown. In the BCN02 clinical trial, which combined the MVA.HIVconsv immunogen with the latency-reversing agent romidepsin in early-ART treated HIV-1 infected individuals, 23% (3/13) of participants showed sustained low-levels of plasma viremia during 32 weeks of a monitored ART pause (MAP). Here, we present a multi-omics analysis to identify compositional and functional gut microbiome patterns associated with HIV-1 control in the BCN02 trial.ResultsViremic controllers during the MAP (controllers) exhibited higher Bacteroidales/Clostridiales ratio and lower microbial gene richness before vaccination and throughout the study intervention when compared to non-controllers. Longitudinal assessment indicated that the gut microbiome of controllers was enriched in pro-inflammatory bacteria and depleted in butyrate-producing bacteria and methanogenic archaea. Functional profiling also showed that metabolic pathways, including methanogenesis and carbohydrate biosynthesis, were significantly decreased in controllers. Fecal metaproteome analyses confirmed that baseline functional differences were mainly driven by Clostridiales. Participants with high baseline Bacteroidales/Clostridiales ratio had increased pre-existing immune activation-related transcripts. The Bacteroidales/Clostridiales ratio as well as host immune-activation signatures inversely correlated with HIV-1 reservoir size.ConclusionsThis proof-of-concept study suggests the Bacteroidales/Clostridiales ratio as a novel gut microbiome signature associated with HIV-1 reservoir size and immune-mediated viral control after ART interruption.
Fine-mapping of nuclear compartments using ultra-deep Hi-C shows that active promoter and enhancer elements localize in the active A compartment even when adjacent sequences do not
Authors: Gu Huiya , Harris Hannah , Olshansky Moshe , Eliaz Yossi , Krishna Akshay , Kalluchi Achyuth , Jacobs Mozes , Cauer Gesine , Pham Melanie , Rao Suhas S.P. , Dudchenko Olga , Omer Arina , Mohajeri Kiana , Kim Sungjae , Nichols Michael H , Davis Eric S. , Udupa Devika , Aiden Aviva Presser , Corces Victor G. , Phanstiel Douglas H. , Noble William Stafford , Seo Jeong-Sun , Talkowski Michael E. , Aiden Erez Lieberman , Rowley M. Jordan 
Published: October 2021

AbstractMegabase-scale intervals of active, gene-rich and inactive, gene-poor chromatin are known to segregate, forming the A and B compartments. Fine mapping of the contents of these A and B compartments has been hitherto impossible, owing to the extraordinary sequencing depths required to distinguish between the long-range contact patterns of individual loci, and to the computational complexity of the associated calculations. Here, we generate the largest published in situ Hi-C map to date, spanning 33 billion contacts. We also develop a computational method, dubbed PCA of Sparse, SUper Massive Matrices (POSSUMM), that is capable of efficiently calculating eigenvectors for sparse matrices with millions of rows and columns. Applying POSSUMM to our Hi-C dataset makes it possible to assign loci to the A and B compartment at 500 bp resolution. We find that loci frequently alternate between compartments as one moves along the contour of the genome, such that the median compartment interval is only 12.5 kb long. Contrary to the findings in coarse-resolution compartment profiles, we find that individual genes are not uniformly positioned in either the A compartment or the B compartment. Instead, essentially all (95%) active gene promoters localize in the A compartment, but the likelihood of localizing in the A compartment declines along the body of active genes, such that the transcriptional termini of long genes (>60 kb) tend to localize in the B compartment. Similarly, nearly all active enhancers elements (95%) localize in the A compartment, even when the flanking sequences are comprised entirely of inactive chromatin and localize in the B compartment. These results are consistent with a model in which DNA-bound regulatory complexes give rise to phase separation at the scale of individual DNA elements.
Neuropeptidergic regulation of Compulsive Ethanol Seeking in C. elegans
Authors: Salim Chinnu , Kan Ann Ke , Patterson E. Clare , Jee Changhoon 
Published: October 2021

AbstractAn improved understanding of the molecular basis of alcohol seeking despite the catastrophic consequences of alcohol abuse is likely to enrich our treatments for Alcohol Use Disorders (AUD) and comorbidities. The compulsive seeking is characterized by an imbalance between the superior drive to substance and disruption in control of substance use. To model the development of compulsive engagement of alcohol seeking, we exploit two distinct behavioral programs of C. elegans in conflict, ethanol preference and avoidance of aversive stimulus, simultaneously. We demonstrate that C. elegans exhibited the recapitulation of the pivotal features of compulsive alcohol seeking in mammals, which are repeated attempts, endurance, and finally aversion-resistant ethanol seeking. We find that the neuropeptide signaling via SEB-3, CRF receptor-like GPCR, facilitates the development of ethanol preference and compels animals to seek ethanol compulsively. Furthermore, our functional genomic approach and behavioral elucidation suggest the interaction between neuropeptidergic signaling, SEB-3 and TKR-1, Neurokinin receptor orthologue, to progress compulsive ethanol seeking behavior.
Neutrophil reverse migration from liver fuels neutrophilic inflammation to tissue injury in Nonalcoholic Steatohepatitis
Authors: Feliz-Norberto Maria , Michael Cassia , de Oliveira Sofia 
Published: October 2021

AbstractInflammation is a hallmark in the progression of nonalcoholic-fatty liver disease (NAFLD) to non-alcoholic steatohepatitis (NASH). Patients with NAFLD are characterized by a chronic low-grade systemic metabolic inflammation (i.e., metainflammation), which contributes to exacerbated however dysfunctional immune response. Neutrophils play an important pathological role in NAFLD progression to NASH; however, how NASH and associated chronic systemic inflammation impact overall the neutrophil response to injury is completely unexplored. Here, we investigated how neutrophil response to tissue injury is altered by the presence of NASH. We used a diet-induced NASH zebrafish model combined with tailfin transection in transgenic zebrafish larvae to study neutrophilic inflammation. Live non-invasive confocal microscopy was used to investigate neutrophil recruitment to tailfin injury through time. Photoconvertion of neutrophils at the liver area followed by time-lapse microscopy was performed to evaluate migration of neutrophils from liver to tailfin injury. Metformin and Pentoxifylline were used to pharmacologically reduce NASH and liver inflammation. We found that larvae with NASH display systemic inflammation and increased myelopoiesis. NASH larvae display a dysfunctional and exacerbated neutrophil response to tailfin injury, characterized by increased neutrophil recruitment, and delayed resolution of inflammation. Interestingly, we showed that neutrophils undergo reverse migration from the NASH liver to the wounded tailfin area. Finally, pharmacological treatment of NASH with Pentoxifylline and Metformin significantly reduced systemic chronic inflammation and the exacerbated recruitment of neutrophils to tissue injury. Taken together, our findings suggest that NASH exacerbates neutrophilic inflammation probably via neutrophil priming at the liver, which can further undergo reverse migration and respond to secondary inflammatory triggers such as tissue injury. Reverse migration of primed neutrophils from the liver might be an important mechanism that fuels the exacerbated neutrophil response observed in NASH conditions and associated metainflammation contributing to poor prognosis and increasing death in patients with metabolic syndrome.
Identifying a novel role for the master regulator Tal1 in the Endothelial to Hematopoietic Transition
Authors: Serina Secanechia Yasmin Natalia , Bergiers Isabelle , Rogon Matt , Arnold Christian , Descostes Nicolas , Le Stephanie , Lopez Anguita Natalia , Ganter Kerstin , Kapsali Chrysi , Bouilleau Lea , Gut Aaron , Uzuotaite Auguste , Aliyeva Ayshan , Zaugg Judith , Lancrin Christophe 
Published: October 2021

ABSTRACTRecent progress in the generation of bona-fide Hematopoietic Stem and Progenitor Cells (HSPCs) in vitro and ex vivo has been built on the knowledge of developmental hematopoiesis, underscoring the importance of understanding in detail this developmental process. Here, we sought to elucidate the function of the hematopoietic regulators Tal1, Lmo2 and Lyl1 in the Endothelial to Hematopoietic Transition (EHT), the process through which HSPCs are generated from endothelial precursors during embryogenesis. We used a mouse embryonic-stem cell (mESC)-based differentiation system to model hematopoietic development, and combined gain-of-function experiments in sorted vascular smooth muscle cells (VSM) with multi-omics to obtain mechanistic insights into the mode of action of Tal1, Lmo2 and Lyl1. We found that these factors promote the silencing of the VSM transcriptional program and the activation of the hematopoietic one. Through this approach and the use of a Tet-on system to control the expression of Tal1 during hematopoietic specification from mESCs, we discovered that its expression in endothelial cells is crucial for the EHT to occur.
Alterations in Connectome Dynamics in Autism Spectrum Disorder: A Harmonized Mega- and Meta-Analysis Study Using the ABIDE Dataset
Authors: Xie Yapei , Xu Zhilei , Xia Mingrui , Liu Jin , Shou Xiaojing , Cui Zaixu , Liao Xuhong , He Yong 
Published: October 2021

ABSTRACTBACKGROUNDNeuroimaging studies have reported functional connectome aberrancies in autism spectrum disorder (ASD). However, the time-varying patterns of connectome topology in ASD individuals and the connection between these patterns and gene expression profiles remain unknown.METHODSTo investigate case-control differences in dynamic connectome topology, we conducted mega- and meta-analyses of resting-state functional magnetic resonance imaging data of 939 participants (440 ASD patients and 499 healthy controls, all males) from 18 independent sites, selected from the ABIDE (Autism Brain Imaging Data Exchange) dataset. Functional data was preprocessed and analyzed using harmonized protocols, and brain module dynamics was assessed using a multilayer network model. We further leveraged postmortem brain-wide gene expression data to identify transcriptomic signatures associated with ASD-related alterations in brain dynamics.RESULTSCompared to healthy controls, ASD individuals exhibited a higher global mean and lower standard deviation of whole-brain module dynamics, indicating an unstable and less regionally differentiated pattern. More specifically, ASD individuals showed higher module switching, primarily in the medial prefrontal cortex, posterior cingulate gyrus, and angular gyrus, and lower switching in the visual regions. These alterations in brain dynamics were predictive of social impairments in ASD individuals and were linked with expression profiles of genes primarily involved in the regulation of neurotransmitter transport and secretion, as well as with previously identified autism-related genes.CONCLUSIONSThis study is the first to identify consistent alterations in brain network dynamics in ASD and the transcriptomic signatures related to those alterations, furthering insights into the biological basis behind this disorder.
Color is necessary for specialized face learning in the Northern paper wasp, Polistes fuscatus
Authors: Jernigan Christopher M. , Stafstrom Jay A. , Zaba Natalie C. , Vogt Caleb C. , Sheehan Michael J. 
Published: October 2021

ABSTRACTVisual individual recognition requires animals to distinguish among conspecifics based on appearance. Though visual individual recognition has been reported in a range of taxa, the features that animals rely on to discriminate between individuals are often not well understood. Northern paper wasp females, Polistes fuscatus, possess individually distinctive color patterns on their faces, which mediate individual recognition. It is currently unclear what facial features P. fuscatus use to distinguish individuals. The anterior optic tubercle, a chromatic processing brain region, is especially sensitive to social experience during development, suggesting that color may be important for recognition in this species. We sought to test the roles of color in wasp facial recognition. Color may be important simply because it creates a pattern. If this is the case, then wasps should perform similarly when discriminating color or grayscale images of the same faces. Alternatively, color itself may be important for recognition, which would predict poorer performance on grayscale image discrimination relative to color images. We found wasps trained on grayscale faces, unlike those trained on color images, did not perform better than chance. Suggesting that color is necessary for the recognition of an image as a face by the wasp visual system.
Sex chromosomes, sex ratios and sex gaps in longevity in plants
Authors: Marais Gabriel AB , Lemaitre J-F. 
Published: October 2021

AbstractIn animals, males and females can display markedly different longevity (also called sex gap in longevity, SGLs). Recent work has revealed that sex chromosomes contribute to establishing these SGLs. X-hemizygosity and toxicity of the Y chromosomes are two mechanisms that have been suggested to reduce male longevity (Z-hemizygosity and W toxicity in females in ZW systems). In plants, SGLs are known to exist but the role of sex chromosomes remains to be established. Here, by using adult sex ratio as a proxy for measuring SGLs, we explored the relationship between sex chromosome and SGLs across 43 plant species. Based on the knowledge recently accumulated in animals, we specifically asked whether: (i) species with XY systems tend to have female-biased sex ratios (reduced male longevity) and species with ZW ones tend to have male-biased sex ratios (reduced female longevity), and (ii) this patterns was stronger in heteromorphic systems compared to homomorphic ones. Our results tend to support these predictions although we lack statistical power because of a small number of ZW systems and the absence of any heteromorphic ZW system in the dataset. We discuss the implications of these findings, which we hope will stimulate further research on sex-differences in lifespan and ageing across plants.
Increased remodeling and impaired adaption to endurance exercise in desminopathy
Authors: Mossakowski Agata A. , Langer Henning T. , Bizieff Alec , Avey Alec M. , Zbinden-Foncea Hermann , Hellerstein Marc , Baar Keith 
Published: October 2021

ABSTRACTDesminopathy the most common intermediate filament disease in humans. Desmin is an essential part of the filamentous network that aligns myofibrils, anchors nuclei and mitochondria, and connects the z-discs and the sarcolemma. We created a rat model with a mutation in R349P DES, analog to the most frequent R350P DES missense mutation in humans. To examine the effects of a chronic, physiological exercise stimulus on desminopathic muscle, we subjected R349P DES rats and their wildtype (WT) and heterozygous littermates to a treadmill running regime. We saw significantly lower running capacity in DES rats that worsened over the course of the study. We found indicators of increased autophagic and proteasome activity with running in DES compared to WT. Stable isotope labeling and LC-MS analysis displayed distinct adaptations of the proteomes of WT and DES animals at baseline as well as with exercise: While key proteins of glycolysis, mitochondria and thick filaments increased their synthetic activity with running in WT, these proteins were higher at baseline in DES and did not change with running. The results suggest an impairment in adaption to chronic exercise in DES muscle and a subsequent exacerbation in the functional and histopathological phenotype.
A Bidirectional Switch in the Shank3 Phosphorylation State Biases Synapses toward Up or Down Scaling
Authors: Wu Chi-Hong , Tatavarty Vedakumar , Beltran Pierre MJ , Guerrero Andrea , Keshishian Hasmik , Krug Karsten , MacMullan Melanie A , Li Li , Carr Steven A , Cottrell Jeffrey R , Turrigiano Gina G 
Published: October 2021

ABSTRACTHomeostatic synaptic plasticity requires widespread remodeling of synaptic signaling and scaffolding networks, but the role of posttranslational modifications in this process has not been systematically studied. Using deepscale, quantitative analysis of the phosphoproteome in mouse neocortical neurons, we found wide-spread and temporally complex changes during synaptic scaling up and down. We observed 424 bidirectionally modulated phosphosites that were strongly enriched for synapse-associated proteins, including S1539 in the ASD-associated synaptic scaffold protein Shank3. Using a parallel proteomic analysis performed on Shank3 isolated from rat neocortical neurons by immunoaffinity, we identified two sites that were hypo-phosphorylated during scaling up and hyper-phosphorylated during scaling down: one (rat S1615) that corresponded to S1539 in mouse, and a second highly conserved site, rat S1586. The phosphorylation status of these sites modified the synaptic localization of Shank3 during scaling protocols, and dephosphorylation of these sites via PP2A activity was essential for the maintenance of synaptic scaling up. Finally, phosphomimetic mutations at these sites prevented scaling up but not down, while phosphodeficient mutations prevented scaling down but not up. Thus, an activity-dependent switch between hypo- and hyperphosphorylation at S1586/ S1615 of Shank3 enables scaling up or down, respectively. Collectively our data show that activity-dependent phosphoproteome dynamics are important for the functional reconfiguration of synaptic scaffolds, and can bias synapses toward upward or downward homeostatic plasticity.
Fourteen-days Evolution of COVID-19 Symptoms During the Third Wave in Non-vaccinated Subjects and Effects of Hesperidin Therapy: A randomized, double-blinded, placebo-controlled study
Authors: Dupuis Jocelyn , Laurin Pierre , Tardif Jean-Claude , Hausermann Leslie , Rosa Camille , Guertin Marie-Claude , Thibaudeau Karen , Gagnon Lyne , Cesari Frank , Robitaille Martin , Moran John E. 
Published: October 2021

ABSTRACTCOVID-19 symptoms can cause substantial disability, yet no therapy can currently reduce their frequency or duration. We conducted a double-blind placebo-controlled trial of hesperidin 1000 mg once-daily for 14 days in 216 symptomatic non-vaccinated COVID-19 subjects. Thirteen symptoms were recorded after 3, 7, 10 and 14 days. The primary endpoint was the proportion of subjects with any of four cardinal (group A) symptoms: fever, cough, shortness of breath or anosmia. At baseline, symptoms in decreasing frequency were: cough (53.2%), weakness (44.9%), headache (42.6%), pain (35.2%), sore throat (28.7%), runny nose (26.9%), chills (22.7%), shortness of breath (22.2%), anosmia (18.5%), fever (16.2%), diarrhea (6.9%), nausea/vomiting (6.5%) and irritability/confusion (3.2%). Group A symptoms in the placebo vs hesperidin group was 88.8% vs 88.5% (day 1) and reduced to 58.5 vs 49.4 % at day 14 (OR 0.69, 95% CI 0.38–1.27, p = 0.23). At day 14, 15 subjects in the placebo group and 28 in the hesperidin group failed to report their symptoms. In an attrition bias analysis imputing “no symptoms” to missing values, the hesperidin group shows reduction of 14.5 % of group A symptoms from 50.9% to 36.4% (OR: 0.55, 0.32–0.96, p = 0.03). Anosmia, the most frequent persisting symptom (29.3%), was lowered by 7.3% at 25.3 % in the hesperidin group vs 32.6% in the placebo group (p = 0.29). Mean number of symptoms in placebo and hesperidin was 5.10 ± 2.26 vs 5.48 ± 2.35 (day 1) and 1.40 ± 1.65 vs 1.38 ± 1.76 (day 14) (p = 0.92). In conclusion, most non-vaccinated COVID-19 infected subjects remain symptomatic after 14 days with anosmia being the most frequently persisting symptom. Hesperidin 1g daily may help reduce group A symptoms. Earlier treatment of longer duration and/or higher dosage should be tested.
Use of an EHR to inform an administrative data algorithm to categorize inpatient COVID-19 severity
Authors: Garry Elizabeth M. , Weckstein Andrew R. , Quinto Kenneth , Lasky Tamar , Chakravarty Aloka , Leonard Sandy , Vititoe Sarah E. , Easthausen Imaani J. , Rassen Jeremy A. , Gatto Nicolle M. 
Published: October 2021

STRUCTURED ABSTRACTImportanceAlgorithms for classification of inpatient COVID-19 severity are necessary for confounding control in studies using real-world data (RWD).ObjectiveTo explore use of electronic health record (EHR) data to inform an administrative data algorithm for classification of supplemental oxygen or noninvasive ventilation (O2/NIV) and invasive mechanical ventilation (IMV) to assess disease severity in hospitalized COVID-19 patients.DesignIn this retrospective cohort study, we developed an initial procedure-based algorithm to identify O2/NIV, IMV, and NEITHER O2/NIV nor IMV in two inpatient RWD sources. We then expanded the algorithm to explore the impact of adding diagnoses indicative of clinical need for O2/NIV (hypoxia, hypoxemia) or IMV (acute respiratory distress syndrome) and O2-related patient vitals available in the EHR. Observed changes in severity categorization were used to augment the administrative algorithm.SettingOptum de-identified COVID-19 EHR data and HealthVerity claims and chargemaster data (March – August 2020).ParticipantsAmong patients hospitalized with COVID-19 in each RWD source, our motivating example selected dexamethasone (DEX+) initiators and a random selection of patients who were non-initiators of a corticosteroid of interest (CSI-) matched on date of DEX initiation, age, sex, baseline comorbidity score, days since admission, and COVID-19 severity level (NEITHER, O2/NIV, IMV) on treatment index.Main Outcome and MeasuresInpatient COVID-19 severity was defined using the algorithms developed to classify respiratory support requirements among hospitalized COVID-19 patients (NEITHER, O2/NIV, IMV). Measures were reported as the treatment-specific distributions of patients in each severity level, and as observed changes in severity categorization between the initial procedure-based and expanded algorithms.ResultsIn the administrative data cohort with 5,524 DEX+ and CSI- patient pairs matched using the initial procedure-based algorithm, 30% were categorized as O2/NIV, 5% as IMV, and 65% as NEITHER. Among patients assigned NEITHER via the initial algorithm, use of an expanded algorithm informed by the EHR-based algorithm shifted 54% DEX+ and 28% CSI- to O2/NIV, and 2% DEX+ and 1% CSI- to IMV. Among patients initially assigned O2/NIV, 7% DEX+ and 3% CSI- shifted to IMV.Conclusions and RelevanceApplication of learnings from an EHR-based exploration to our administrative algorithm minimized treatment-differential misclassification of COVID-19 severity.