bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prolonged Detection of SARS CoV2 RNA in Extracellular Vesicles in Nasal Swab RT-PCR Negative Patients
Authors: Subudhi P. Debishree , Rooge Sheetalnath , Thangariyal Swati , Goswami Sivang , Agarwal Reshu , Gupta Ekta , Baweja Sukriti 
Published: December 2021

ABSTRACTBackgroundThere is a prolonged RT-PCR positivity seen in COVID-19 infected patients up to 2-3 months. We aim to investigate the presence of viral particles inside Extracellular vesicles (EV) and its role in underlying liver disease patients.MethodsSARS CoV2 nasal RT-PCR positive n=78 {n=24(66.6%) chronic liver disease (CLD); n=52 (81.3%) non-liver disease} were studied. SARS CoV2 patients were also followed up for day (d) 7, 14 and 28. Extracellular vesicles were isolated using differential ultracentrifugation. SARS CoV2 RNA was measured using qRT-PCR by Altona Real Star kit.ResultsIn baseline RT-PCR positive patients, SARS-CoV2 RNA inside the EV was present in 64/74 (82%) patients with comparable viral load between VTM and EV (mean 1CT – 0.033±0.005 vs. 1CT – 0.029±0.014, p=ns). On follow-up at day 7, of the 24 patients negative for COVID19, 10 (41%) had persistence of virus in the EV (1CT – 0.028±0.004) and on day 14, 14 of 40 (35%) negative RT-PCR had EVs with SARS CoV2 RNA (1CT – 0.028±0.06). The mean viral load decreased at day7 and day14 in nasal swab from baseline (p=0.001) but not in EV. SARS-CoV2 RNA otherwise undetectable in plasma, was found to be positive in EV in 12.5% of COVID19 positive patients. Interestingly, significantly prolonged and high viral load was found in EV at day 14 in CLD-COVID19 patients compared to COVID19 alone (p=0.002). The high cellular injury was seen in CLD-COVID19 infected patients with significant high levels of EV associated with endothelial cells and hepatocytes than COVID19 alone (p=0.004; 0.001).ConclusionIdentification of SARS-CoV2 RNA in EV, in RT-PCR negative patients indicates persistence of infection for and likely recurrence of the infection. EV associated RNA may determine the clinical course of subjects with undetectable SARS-CoV2 virus and this may also have relevance in management of chronic liver disease patients.
A Single Dose of COVID-19 mRNA Vaccine Induces Airway Immunity in COVID-19 Convalescent Patients
Authors: Martinuzzi Emanuela , Benzaquen Jonathan , Guerin Olivier , Leroy Sylvie , Simon Thomas , Ilie Marius , Hofman Véronique , Allegra Maryline , Tanga Virginie , Michel Emeline , Boutros Jacques , Maniel Charlotte , Sicard Antoine , Glaichenhaus Nicolas , Czerkinsky Cecil , Blancou Philippe , Hofman Paul , Marquette Charles 
Published: December 2021

BackgroundMucosal antibodies can prevent virus entry and replication in mucosal epithelial cells and hence virus shedding. Preclinical and clinical studies have shown that a parenteral booster injection of a vaccine against a mucosal pathogen promotes stronger mucosal immune responses following prior infection compared to two injections of a parenteral vaccine. We investigated whether this was also the case for a COVID-19 mRNA vaccine.MethodsTwenty-three COVID-19 convalescent patients and 20 SARS-CoV-2-naive subjects were vaccinated with respectively one and two doses of the Pfizer-BioNTech COVID-19 RNA vaccine. Nasal Epithelial Lining Fluid (NELF) and plasma were collected before and after vaccination and assessed for Immunoglobulin (Ig)G and IgA to Spike and for their ability to inhibit the binding of Spike to its ACE-2 receptor. Blood was analyzed one week after vaccination for the number of Spike-specific Antibody Secreting Cells (ASCs) with a mucosal tropism.ResultsIn COVID-19 convalescent patients, a single dose of vaccine amplified pre-existing Spike-specific IgG and IgA antibody responses in both NELF and blood against both vaccine homologous and variant strains, including delta. These responses were associated with Spike-specific IgG and IgA ASCs with a mucosal tropism in blood. Nasal IgA and IgG antibody responses were lower in magnitude in SARS-CoV-2-naive subjects after two vaccine dosesConclusionThis study showed that a parenteral booster injection of a COVID-19 RNA vaccine promoted stronger mucosal immune responses in COVID-19 convalescent patients compared to SARS-CoV-2 naive subjects who had received a first vaccine dose.
Categorical working memory codes in human visual cortex
Authors: Yan Chang , Christophel Thomas B. , Allefeld Carsten , Haynes John-Dylan 
Published: December 2021

AbstractWorking memory contents are represented in neural activity patterns across multiple regions of the cortical hierarchy. It has remained unclear to which degree this reflects a specialization for different levels of abstraction. Here, we demonstrate that for color stimuli categorical codes are already present at the level of extrastriate visual cortex (V4 and VO1). Interestingly, this categorical coding was observed during working memory, but not during perception.
seGMM: a new tool to infer sex from massively parallel sequencing data
Authors: Liu Sihan , Zeng Yuanyuan , Chen Meilin , Zhang Qian , Wang Lanchen , Wang Chao , Lu Yu , Guo Hui , Bu Fengxiao 
Published: December 2021

AbstractInspecting concordance between self-reported sex and genotype-inferred sex from genomic data is a significant quality control measure in clinical genetic testing. Numerous tools have been developed to infer sex for genotyping array, whole-exome sequencing, and whole-genome sequencing data. However, improvements in sex inference from targeted gene sequencing panels are warranted. Here, we propose a new tool, seGMM, which applies unsupervised clustering (Gaussian Mixture Model) to determine the gender of a sample from the called genotype data integrated aligned reads. seGMM consistently demonstrated > 99% sex inference accuracy in publicly available (1000 Genomes) and our in-house panel dataset, which achieved obviously better sex classification than existing popular tools. Compared to including features only in the X chromosome, our results show that adding additional features from Y chromosomes (e.g. reads mapped to the Y chromosome) can increase sex classification accuracy. Notably, for WES and WGS data, seGMM also has an extremely high degree of accuracy. Finally, we proved the ability of seGMM to infer sex in single patient or trio samples by combining with reference data and pinpointing potential sex chromosome abnormality samples. In general, seGMM provides a reproducible framework to infer sex from massively parallel sequencing data and has great promise in clinical genetics.
AliSim: A Fast and Versatile Phylogenetic Sequence Simulator For the Genomic Era
Authors: Ly-Trong Nhan , Naser-Khdour Suha , Lanfear Robert , Minh Bui Quang 
Published: December 2021

AbstractSequence simulators play an important role in phylogenetics. Simulated data has many applications, such as evaluating the performance of different methods, hypothesis testing with parametric bootstraps, and, more recently, generating data for training machine-learning applications. Many sequence simulation programs exist, but the most feature-rich programs tend to be rather slow, and the fastest programs tend to be feature-poor. Here, we introduce AliSim, a new tool that can efficiently simulate biologically realistic alignments under a large range of complex evolutionary models. To achieve high performance across a wide range of simulation conditions, AliSim implements an adaptive approach that combines the commonly-used rate matrix and probability matrix approach. AliSim takes 1.3 hours and 1.3 GB RAM to simulate alignments with one million sequences or sites, while popular software Seq-Gen, Dawg, and INDELible require two to five hours and 50 to 500 GB of RAM. We provide AliSim as an extension of the IQ-TREE software version 2.2, freely available at www.iqtree.org, and a comprehensive user tutorial at http://www.iqtree.org/doc/AliSim.
Declining population sizes and loss of genetic diversity in commercial fishes: a simple method for a first diagnostic
Authors: Petit-Marty Natalia , Min Liu , Tan Iris Ziying , Chung Arthur , Terrasa Bàrbara , Guijarro Beatriz , Ordines Francesc , Ramírez-Amaro Sergio , Massutí Enric , Schunter Celia 
Published: December 2021

AbstractExploited fish species may have or are experiencing declines in population sizes coupled with a decrease in genetic diversity. This can lead to the loss of adaptive potential to face current and future environmental changes. However, little is known about this subject while research on it is urgently needed. Thus, this study aims to answer a simple, even naive question, given the complexity of the subject: Could we use a simple method to obtain information on the loss of genetic diversity in exploited fish species? We investigated the use of the levels of genetic diversity in the widely used genetic marker Cytochrome C Oxidase subunit I (COI) mitochondrial gene. Estimates of genetic diversity in COI were obtained for populations of seven fish species with different commercial importance from the East China Sea. These estimates were contrasted against a large dataset of fish species distributed worldwide (N=1426), a dataset of East-Asian fish species (N=118), two farmed species with expected low genetic diversity, and four long-term managed species from the Mediterranean Sea. We found that estimates of genetic diversity in COI match the expectations from theoretical predictions, known population declines, and fishing pressures. Thus, the answer to our question is affirmative and we conclude that estimates of genetic diversity in COI provide an effective first diagnostic of the conservation status of exploited fish species. This simple and cost-effective tool can help prioritize research, management, and conservation on species with suspected loss of genetic diversity potentially eroding their adaptive potential to global change.
Anti-inflammatory and neuroprotective activity of Viphyllin a standardized extract of β-caryophyllene from black pepper (Piper Nigrum L) and its associated mechanisms in mouse macrophage cells and Human Neuroblastoma SH-SY5Y cells
Authors: Gouthamchandra Kuluvar , Venkataramana Sudeep Heggar , Sathish Anusha , Amritharaj  , Basavegowda Lingaraju Harakanahalli , Puttaswamy Naveen , Kodimule Shyam Prasad 
Published: December 2021

AbstractOxidative stress breeds various chronic lifestyle ailments including inflammatory conditions and neurodegenerative diseases. β-caryophyllene natural bicyclic sesquiterpene, obtained from various plants sources found to be effective against inflammation and neuroprotection. In this study, we have evaluated the protective effect of Viphyllin, a standardized extract of β-caryophyllene from black pepper against inflammation induced by lipopolysaccharide in RAW264.7 macrophage cells and mechanisms involved in hydrogen peroxide (H2O2)-challenged oxidative stress in human neuroblastoma SH-SY5Y cells. Viphyllin demonstrated the anti-inflammatory activity by subsiding the release of the pro-inflammatory intermediaries like NO, cytokines, interleukins, and protein expression levels of cyclooxygenase (COX-2) and inducible nitric oxide synthase (iNOS). In addition, Viphyllin suppressed the extracellular signal-regulated kinase (ERK). c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) phosphorylation. On the other hand, Viphyllin showed neuroprotective effect against neuronal oxidative damage caused by H2O2. Viphyllin lessened the expression B-cell lymphoma-2 (Bcl-2), B-cell lymphoma-2-associated X protein (BAX), cleaved caspase-9, and PARP-1 proteins associated with apoptosis. Our results indicate that Viphyllin ameliorated LPS-mediated inflammation in macrophages by regulating inflammation and Viphyllin exerted remarkable anti apoptotic effect against neuronal damage challenged by H2O2. Altogether, Viphyllin could be potential functional food ingredient for inflammation and neurodegenerative diseases.
Interferon-gamma mediates skeletal muscle lesions through JAK/STAT pathway activation in inclusion body myositis
Authors: Hou Cyrielle , Periou Baptiste , Gervais Marianne , Berthier Juliette , Baba-Amer Yasmine , Souvannanorath Sarah , Malfatti Edoardo , Relaix Fréderic , Bencze Maximilien , Authier François Jérôme 
Published: December 2021

AbstractDysimmune and Inflammatory Myopathies (DIMs) are acquired idiopathic myopathy associated with immune response dysregulation. Inclusion Body Myositis (IBM), the most common DIMs, is characterized by endomysial infiltrates of cytotoxic T lymphocytes CD8, muscle type II-interferon (IFNγ) signature, and by the lack of response to immunomodulatory therapies. We showed that IBM was pathologically characterized by the presence of chronic degenerative myopathic features including myofiber atrophy, fibrosis, adipose involution, and the altered functions of skeletal muscle stem cells. Here, we demonstrated that protracted systemic exposure to IFNγ delayed muscle regeneration and led to IBM-like muscular degenerative changes in mice. In vitro, IFNγ treatment inhibited the activation, proliferation, migration, differentiation, and fusion of myogenic progenitor cells and promoted their senescence through JAK-STAT-dependent activation. Finally, JAK-STAT inhibitor, ruxolitinib abrogated the deleterious effects of IFNγ on muscle regeneration, suggesting that the JAK-STAT pathway could represent a new therapeutic target for IBM.
Alterations in human gut microbiome composition and metabolism after exposure to glyphosate and Roundup and/or a spore-based formulation using the SHIME® technology
Authors: Mesnage Robin , Calatayud Marta , Duysburgh Cindy , Marzorati Massimo , Antoniou Michael N 
Published: December 2021

ABSTRACTDespite extensive research into the toxicology of the herbicide glyphosate, there are still major unknowns regarding its effects on the human gut microbiome. As a step in addressing this knowledge gap, we describe for the first time the effects of glyphosate and a Roundup glyphosate-based herbicide on infant gut microbiota using SHIME technology, which mimics the entire gastrointestinal tract. SHIME® microbiota culture was undertaken in the presence of a concentration of 100 mg/L (corresponding to a dose of 1.6 mg/kg/day) glyphosate and the same glyphosate equivalent concentration of Roundup, which is in the range of the US chronic reference dose, and subjected to molecular profiling techniques to assess outcomes. Roundup and to a lesser extent glyphosate caused an increase in fermentation activity, resulting in acidification of the microbial environment. This was also reflected by an increase in lactate and acetate production concomitant to a decrease in the levels of propionate, valerate, caproate and butyrate. Ammonium production reflecting proteolytic activities was increased by Roundup exposure. Global metabolomics revealed large scale disturbances in metabolite profiles, including an increased abundance of long chain polyunsaturated fatty acids (n3 and n6). Although changes in bacterial composition measured by qPCR and 16S rRNA sequencing were less clear, our results suggested that lactobacilli had their growth stimulated as a result of microenvironment acidification. Co-treatment with the spore-based probiotic formulation MegaSporeBiotic reverted some of the changes in short-chain fatty acid levels. Altogether, our results suggest that glyphosate can exert effects on human gut microbiota at permitted regulatory levels of exposure, highlighting the need for epidemiological studies aimed at evaluating the effects of glyphosate herbicides on human gut microbiome function.
Systemic and intra-amygdala administrations of midazolam reverse anxiety-like behavior induced by cohabiting with a cagemate in chronic pain condition
Authors: Carmona Isabela Miranda , de Oliveira Paulo Eduardo Carneiro , Baptista-de-Souza Daniela , Canto-de-Souza Azair 
Published: December 2021

AbstractThe affective component of pain may be shared among conspecifics through emotional contagion, a form of empathic expression. In this sense, reverberation of negative emotions could generate distress behavioral responses, such as pathological anxiety. Evidences reported that amygdala and its benzodiazepine receptors are involved in perception of pain in others. However, relatively little is known about the neural processes underlying emotional contagion induced by pain observation. In the present study, we investigated the effects of midazolam, an allosteric GABAergic receptor agonist, in anxiety-like behaviors induced by cohabitation with cagemate submitted to sciatic nerve constriction. For this purpose, we administrated systemic (0.5, 1.0 and 2.0 mg/kg) and intra-amygdala midazolam injections (3.0 and 30.0 nmol) in observer cagemates before elevated plus-maze (EPM) evaluation. We found that mice subjected to nerve constriction and their observer cagemates increased anxiety-like behavior in the EPM. Further, systemically (1.0 and 2.0 mg/kg) and intra-amygdala administration of midazolam (3.0 and 30 nmol) reverse this anxiogenic effect. Collectively, these results suggest that social interaction with a cagemate under chronic pain produces anxiety-like responses that could be blocked through midazolam application.
Understanding p300-transcription factor interactions using sequence variation and hybridization
Authors: Hobor Fruzsina , Hegedus Zsofia , Ibarra Amaurys Avila , Petrovicz Vencel L. , Bartlett Gail J. , Sessions Richard B. , Wilson Andrew J. , Edwards Thomas A. 
Published: December 2021

AbstractThe hypoxic response is central to cell function and plays a significant role in the growth and survival of solid tumours. HIF-1 regulates the hypoxic response by activating over 100 genes responsible for adaptation to hypoxia, making it a potential target for anticancer drug discovery. Although there is significant structural and mechanistic understanding of the interaction between HIF-1α and p300 alongside negative regulators of HIF-1α such as CITED2, there remains a need to further understand the sequence determinants of binding. In this work we use a combination of protein expression, chemical synthesis, fluorescence anisotropy and isothermal titration calorimetry for HIF-1α sequence variants and a HIF-1α- CITED hybrid sequence which we term CITIF. We show the HIF-1α sequence is highly tolerant to sequence variation through reduced enthalpic and less unfavourable entropic contributions, These data imply backbone as opposed to side chain interactions and ligand folding control the binding interaction and that sequence variations are tolerated as a result of adopting a more disordered bound interaction or “fuzzy” complex.
ortho2align: a sensitive approach for searching for orthologues of novel lncRNAs
Authors: Mylarshchikov Dmitry Evgenevich , Mironov Andrey Alexandrovich 
Published: December 2021

AbstractBackgroundMany novel long noncoding RNAs have been discovered in recent years due to advances in high-throughput sequencing experiments. Finding orthologues of these novel lncRNAs might facilitate clarification of their functional role in living organisms. However, lncRNAs exhibit low sequence conservation, so specific methods for enhancing the signal-to-noise ratio were developed. Nevertheless, current methods such as transcriptomes comparison approaches or searches for conserved secondary structures are not applicable to novel lncRNAs dy design.ResultsWe present ortho2align — a versatile sensitive synteny-based lncRNA orthologue search tool with statistical assessment of sequence conservation. This tool allows control of the specificity of the search process and optional annotation of found orthologues. ortho2align shows similar performance in terms of sensitivity and resource usage as the state-of-the-art method for aligning orthologous lncRNAs but also enables scientists to predict unannotated orthologous sequences for lncRNAs in question. Using ortho2align, we predicted orthologues of three distinct classes of novel human lncRNAs in six Vertebrata species to estimate their degree of conservation.ConclusionsBeing designed for the discovery of unannotated orthologues of novel lncRNAs in distant species, ortho2align is a versatile tool applicable to any genomic regions, especially weakly conserved ones. A small amount of input files makes ortho2align easy to use in orthology studies as a single tool or in bundle with other steps that researchers will consider sensible.
Structure of human CST-pol-α/primase bound to a telomeric overhang poised for initiation of telomere C-strand synthesis
Authors: He Qixiang , Lin Xiuhua , Chavez Bianca L. , Lusk Benjamin L. , Lim Ci Ji 
Published: December 2021

AbstractTelomere replication and regulation protect mammalian chromosome ends and promote genome stability. An essential step in telomere maintenance is the C-strand fill-in process, which is the de novo synthesis of the complementary strand of the telomere overhang. This step is catalyzed by polymerase-alpha/primase complex (pol-α/primase) and coordinated by an accessory factor, CTC1-STN1-TEN1 (CST). Using cryogenic-electron microscopy single-particle analysis, we report the structure of the human telomere C-strand fill-in preinitiation complex (PIC) at 3.9 Å resolution. The structure reveals a CST and a pol-α/primase co-bound to a single telomere overhang, poised for de novo RNA primer synthesis. Upon PIC assembly, the pol-α/primase undergoes large conformation change from its apo-state; CST partitions the DNA and RNA catalytic centers of pol-α/primase into two separate domains and positions the 3′ end of an extended telomere single-stranded DNA template towards the RNA catalytic center (PRIM1 or p49). The telomeric single-stranded DNA template is further positioned by the POLA1 (or p180) catalytically dead exonuclease domain. Together with CST, the exonuclease domain forms a tight-fit molecular tunnel for template direction. Given the structural homology of CST to Replication Protein A (RPA), our structure provides the structural basis for a new model of how pol-α/primase lagging-strand DNA synthesis is coordinated by single-stranded DNA-binding accessory factors.
Cancer metabolic subtypes and their association with molecular and clinical features
Authors: Moiso Enrico , Provero Paolo 
Published: December 2021

AbstractAlterations of metabolic pathways in cancer have been investigated for many years, beginning way before the discovery of the role of oncogenes and tumor suppressors, and the last few years have witnessed a renewed interest in this topic. Large-scale molecular and clinical data on tens of thousands of samples allow us today to tackle the problem from a general point of view.Here we show that transcriptomic profiles of tumors can be exploited to define metabolic cancer subtypes, which can be systematically investigated for association with other molecular and clinical data. We find thousands of significant associations between metabolic subtypes and molecular features such as somatic mutations, structural variants, epigenetic modifications, protein abundance and activation; and with clinical/phenotypic data including survival probability, tumor grade, and histological types.Our work provides a methodological framework and a rich database of statistical associations, accessible from metaminer.unito.it, that will contribute to the understanding of the role of metabolic alterations in cancer and to the development of precision therapeutic strategies.