bluuebunny/crossref_metadata_2025_split huggingface dataset:
Towards Internationally standardised humoral Immune Correlates of Protection from SARS-CoV-2 infection and COVID-19 disease
Authors: Castillo-Olivares Javier , Wells David A. , Ferrari Matteo , Chan Andrew , Smith Peter , Nadesalingam Angalee , Paloniemi Minna , Carnell George , Ohlendorf Luis , Cantoni Diego , Mayora-Neto Martin , Palmer Phil , Tonks Paul , Temperton Nigel , Wagner Ralf , Neckermann Patrick , Peterhoff David , Doffinger Rainer , Kempster Sarah , Otter Ashley , Semper Amanda , Brooks Tim , Page Mark , Albecka Anna , James Leo C. , Briggs John , Schwaeble Wilhelm , Baxendale Helen , Heeney Jonathan 
Published: May 2021

AbstractPrecision monitoring of antibody responses during the COVID-19 pandemic is increasingly important during large scale vaccine rollout and rise in prevalence of Severe Acute Respiratory Syndrome-related Coronavirus-2 (SARS-CoV-2) variants of concern (VOC). Equally important is defining Correlates of Protection (CoP) for SARS-CoV-2 infection and COVID-19 disease. Data from epidemiological studies and vaccine trials identified virus neutralising antibodies (Nab) and SARS-CoV-2 antigen-specific (notably RBD, and S) binding antibodies as candidate CoP. In this study, we used the World Health Organisation (WHO) international standard to benchmark neutralising antibody responses and a large panel of binding antibody assays to compare convalescent sera obtained from: a) COVID-19 patients; b) SARS-CoV-2 seropositive healthcare workers (HCW) and c) seronegative HCW. The ultimate aim of this study, was to identify biomarkers of humoral immunity that could be used as candidate CoP in internationally accepted unitage. Whenever suitable, the antibody levels of the samples studied were expressed in International Units (INU) for virus neutralisation assays or International Binding Antibody Units (BAU) for ELISA tests. In this work we used commercial and non-commercial antibody binding assays; a lateral flow test for detection of SARS-CoV-2-specific IgG / IgM; a high throughput multiplexed particle flow cytometry assay for SARS-CoV-2 Spike (S), Nucleocapsid (N) and Receptor Binding Domain (RBD) proteins); a multiplex antigen semi-automated immuno-blotting assay measuring IgM, IgA and IgG; a pseudotyped microneutralisation test (pMN) and electroporation-dependent neutralisation assay (EDNA). Our results indicate that overall, severe COVID-19 patients showed statistically significantly higher levels of SARS-CoV-2-specific neutralising antibodies (average 1029 IU/ml) than those observed in seropositive HCW with mild or asymptomatic infections (379 IU/ml) and that clinical severity scoring, based on WHO guidelines was tightly correlated with neutralisation and RBD / S binding assays. In addition, there was a positive correlation between severity, N-antibody assays and intracellular virus neutralisation.
Synergistic epistasis of the deleterious effects of transposable elements
Authors: Lee Yuh Chwen G. 
Published: May 2021

AbstractThe replicative nature and generally deleterious effects of transposable elements (TEs) give rise to an outstanding question about how TE copy number is stably contained in host populations. Classic theoretical analyses predict that, when the decline in fitness due to each additional TE insertion is greater than linear, or when there is synergistic epistasis, selection against TEs can result in a stable equilibrium of TE copy number. While several mechanisms are predicted to yield synergistic deleterious effects of TEs, we lack empirical investigations of the presence of such epistatic interactions. Purifying selection with synergistic epistasis generates repulsion linkage between deleterious alleles and, accordingly, an underdispersed distribution for the number of deleterious mutations among individuals. We investigated this population genetic signal in an African Drosophila melanogaster population and found evidence for synergistic epistasis among TE insertions, especially those expected to have large fitness impacts. Curiously, even though ectopic recombination has long been predicted to generate nonlinear fitness decline with increased TE copy number, TEs predicted to suffer higher rates of ectopic recombination are not more likely to be underdispersed. On the other hand, underdispersed TE families are more likely to show signatures of deleterious epigenetic effects and stronger ping-pong signals of piRNA amplification, a hypothesized source from which synergism of TE-mediated epigenetic effects arises. Our findings set the stage for investigating the importance of epistatic interactions in the evolutionary dynamics of TEs.
Bimanual digit training improves right-hand dexterity in older adults by reactivating declined ipsilateral motor-cortical inhibition
Authors: Naito Eiichi , Morita Tomoyo , Hirose Satoshi , Kimura Nodoka , Okamoto Hideya , Kamimukai Chikako , Asada Minoru 
Published: May 2021

AbstractImproving deteriorated sensorimotor functions in older individuals is a social necessity in a super-aging society. Previous studies suggested that the declined interhemispheric sensorimotor inhibition observed in older adults is associated with their deteriorated hand/finger dexterity. Here, we examined whether bimanual digit exercises, which can train the interhemispheric inhibitory system, improve deteriorated hand/finger dexterity in older adults. Forty-eight healthy, right-handed, older adults (65-78 years old) were divided into two groups, i.e., the bimanual (BM) digit training and right-hand (RH) training groups, and intensive daily training was performed for 2 months. Before and after the training, we evaluated individual right hand/finger dexterity using a peg task, and the individual state of interhemispheric sensorimotor inhibition by analyzing ipsilateral sensorimotor deactivation via functional magnetic resonance imaging when participants experienced a kinesthetic illusory movement of the right-hand without performing any motor tasks. Before training, the degree of reduction/loss of ipsilateral motor-cortical deactivation was associated with dexterity deterioration. After training, the dexterity improved only in the BM group, and the dexterity improvement was correlated with reduction in ipsilateral motor-cortical activity. The capability of the brain to inhibit ipsilateral motor-cortical activity during a simple right-hand sensory-motor task is tightly related to right-hand dexterity in older adults.
The Neural Correlates of Working Memory Training in Typically Developing Children – Working Paper
Authors: Jones J. S. , Adlam A-L. R. , Benatayallah A. , Milton F. 
Published: May 2021

AbstractWorking memory training improves children’s cognitive performance on untrained tasks; however, little is known about the underlying neural mechanisms. We investigated this in 32 typically developing children aged 10-14 years (19 girls and 13 boys; Devon, UK) using a randomized controlled design and multi-modal MRI. Training improved working memory performance and increased intrinsic functional connectivity between the bilateral intraparietal sulci. Furthermore, improvements in working memory were associated with greater recruitment of the left middle frontal gyrus on a complex span task. The repeated engagement of fronto-parietal regions during training may increase their activity and functional connectivity over time, affording greater working memory performance. We discuss the plausibility of generalizable cognitive benefits from a neurobiological perspective and implications for neurodevelopmental theory. This is not the version of record.
Schmidtea sp., from the S-W Romania (Platyhelminthes, Tricladida, Dugesiidae)
Authors: Felicia Babalean Anda 
Published: May 2021

AbstractThe morphology and the anatomy of the copulatory apparatus in a Dugesiidae population from the SW Romania are presented. The copulatory apparatus is characterized by intermingled bursal canal musculature and two distinct penis bulbs with two large seminal vesicles. Based on these morphological characters, the population is assigned to the “lugubris-polychroa” group of species, now belonging to the genusSchmidtea(de Vries & Sluys 1991). The copulatory apparatus is also characterised by the presence of an atrial fold, characteristic ofS. mediterranea. The assign of the morphotype here presented to the species level is delayed until integrative molecular analysis.
No one tool to rule them all: Prokaryotic gene prediction tool performance is highly dependent on the organism of study
Authors: Dimonaco Nicholas J. , Aubrey Wayne , Kenobi Kim , Clare Amanda , Creevey Christopher J. 
Published: May 2021

AbstractMotivationThe biases in Open Reading Frame (ORF) prediction tools, which have been based on historic genomic annotations from model organisms, impact our understanding of novel genomes and metagenomes. This hinders the discovery of new genomic information as it results in predictions being biased towards existing knowledge. To date users have lacked a systematic and replicable approach to identify the strengths and weaknesses of any ORF prediction tool and allow them to choose the right tool for their analysis.ResultsWe present an evaluation framework (ORForise) based on a comprehensive set of 12 primary and 60 secondary metrics that facilitate the assessment of the performance of ORF prediction tools. This makes it possible to identify which performs better for specific use-cases. We use this to assess 15 ab initio and model-based tools representing those most widely used (historically and currently) to generate the knowledge in genomic databases. We find that the performance of any tool is dependent on the genome being analysed, and no individual tool ranked as the most accurate across all genomes or metrics analysed. Even the top-ranked tools produced conflicting gene collections which could not be resolved by aggregation. The ORForise evaluation framework provides users with a replicable, data-led approach to make informed tool choices for novel genome annotations and for refining historical annotations.Availabilityhttps://github.com/NickJD/ORForiseContactnicholas@dimonaco.co.ukSupplementary informationSupplementary data are available at bioRxiv online.
Comparison of Resources and Methods to infer Cell-Cell Communication from Single-cell RNA Data
Authors: Dimitrov Daniel , Türei Dénes , Boys Charlotte , Nagai James S. , Ramirez Flores Ricardo O. , Kim Hyojin , Szalai Bence , Costa Ivan G. , Dugourd Aurélien , Valdeolivas Alberto , Saez-Rodriguez Julio 
Published: May 2021

AbstractThe growing availability of single-cell data has sparked an increased interest in the inference of cell-cell communication from this data. Many tools have been developed for this purpose. Each of them consists of a resource of intercellular interactions prior knowledge and a method to predict potential cell-cell communication events. Yet the impact of the choice of resource and method on the resulting predictions is largely unknown. To shed light on this, we created a framework, available athttps://github.com/saezlab/ligrec_decoupler, to facilitate a comparative assessment of methods for inferring cell-cell communication from single cell transcriptomics data and then compared 15 resources and 6 methods. We found few unique interactions and a varying degree of overlap among the resources, and observed uneven coverage in terms of pathways and biological categories. We analysed a colorectal cancer single cell RNA-Seq dataset using all possible combinations of methods and resources. We found major differences among the highest ranked intercellular interactions inferred by each method even when using the same resources. The varying predictions lead to fundamentally different biological interpretations, highlighting the need to benchmark resources and methods.FindingsBuilt a framework to systematically combine 15 resources and 6 methods to estimate cell-cell communication from single-cell RNA dataCell-cell communication resources are often built from the same original databases and very few interactions are unique to a single resource. Yet overlap varies among resources and certain biological terms are unevenly representedDifferent methods and resources provided notably different resultsThe observed disagreement among the methods could have a considerable impact on the interpretation of results
Mast cell-specific receptor/corticotropin-releasing factor axis regulates alcohol withdrawal-associated headache
Authors: Son Hyeonwi , Zhang Yan , Shannonhouse John , Ishida Hirotake , Gomez Ruben , Akopian Armen , Kim Yu Shin 
Published: May 2021

AbstractRehabilitation from alcohol addiction or abuse is challenging due to alcohol withdrawal symptoms. Headache is a severe alcohol withdrawal symptom that frequently contributes to rehabilitation failure. Despite the need for treating alcohol withdrawal-induced headache, there is no appropriate therapeutic option available. Development of improved therapeutics will depend on obtaining a clearer understanding of alcohol withdrawal-induced headache pain mechanisms. Here, we show that the mast cell-specific receptor MrgprB2 controls development of alcohol withdrawal-induced headache. Withdrawing alcohol from alcohol-acclimated mice induces strong headache behaviors, including facial allodynia, facial pain expressions, and reduced walking movement, symptoms often observed in humans suffering from headache. Observed pain behaviors were abolished in MrgprB2-deficient mice. We observed in vivo spontaneous activation and hypersensitization of trigeminal ganglia neurons in alcohol withdrawal mice, but not in MrgprB2-deficient mice. Corticotropin-releasing factor (CRF) was increased in dura mater after alcohol withdrawal. Injection of CRF into dura mater resulted in activation of trigeminal ganglia neurons and vasodilation, which was accompanied by headache behavior. In cells, CRF evoked Ca2+ transients via MrgprB2 or human MrgprX2. The results indicate that alcohol withdrawal causes headache via mast cell degranulation in dura mater. The process is under control of MrgprB2/MrgprX2, which would appear to represent a potential target for treating alcohol withdrawal-related headache.
Met is required for oligodendrocyte progenitor cell migration in Danio rerio
Authors: Ali Maria F. , Latimer Andrew J. , Wang Yinxue , Hogenmiller Leah , Fontenas Laura , Isabella Adam J. , Moens Cecilia B. , Yu Guoqiang , Kucenas Sarah 
Published: May 2021

AbstractDuring vertebrate central nervous system development, most oligodendrocyte progenitor cells (OPCs) are specified in the ventral spinal cord and must migrate throughout the neural tube until they become evenly distributed, occupying non-overlapping domains. While this process of developmental OPC migration is well characterized, the nature of the molecular mediators that govern it remain largely unknown. Here, using zebrafish as a model, we demonstrate that Met signaling is required for initial developmental migration of OPCs, and, using cell-specific knock-down of Met signaling, show that Met acts cell-autonomously in OPCs. Taken together, these findings demonstrate in vivo, the role of Met signaling in OPC migration and provide new insight into how OPC migration is regulated during development.
Cell type-specific signal analysis in EWAS
Authors: Breeze Charles E. 
Published: May 2021

AbstractHundreds of epigenome-wide association studies (EWAS) have been performed, successfully identifying replicated epigenomic signals in processes such as ageing and smoking. Despite this progress, it remains a major challenge in EWAS to detect both cell type-specific and cell type confounding effects impacting study results. One way to identify these effects is through eFORGE (experimentally derived Functional element Overlap analysis of ReGions from EWAS), a published tool that uses 815 datasets from large-scale mapping studies to detect enriched tissues, cell types and genomic regions. Here, I show that eFORGE analysis can be extended to EWAS differentially variable positions (DVPs), identifying target cell types and tissues. In addition, I also show that eFORGE tissue-specific enrichment can be detected for sites below EWAS significance threshold. I develop on these and other analysis examples, extending our knowledge of eFORGE cell type- and tissue-specific enrichment results for different EWAS.
Istradefylline, an adenosine A2a receptor antagonist, ameliorates neutrophilic airway inflammation and psoriasis in mice
Authors: Tokano Mieko , Kawano Masaaki , Takagi Rie , Matsushita Sho 
Published: May 2021

AbstractObjectiveExtracellular adenosine is produced from secreted ATP by cluster of differentiation (CD)39 and CD73. Both are critical nucleotide metabolizing enzymes of the adenosine generating pathway and are secreted by neuronal or immune cells. Adenosine plays a role in energy processes, neurotransmission, and endogenous regulation of inflammatory responses. Istradefylline is a selective adenosine A2a receptor (A2aR) antagonist used for the treatment of Parkinson’s disease. We have reported that adenosine primes hypersecretion of interleukin (IL)-17A via A2aR. Istradefylline, as well as an inhibitor of CD39 (ARL67156) and an inhibitor of CD73 (AMP-CP), suppressed IL-17A production, and the administration of istradefylline to mice with experimental autoimmune encephalomyelitis (EAE) led to the marked amelioration of the disease. These previous results suggest that adenosine is an endogenous modulator of neutrophilic inflammation. We investigated the effect of istradefylline, ARL67156 and AMP-CP on other mouse models of neutrophilic inflammation.MethodsWe tested the effect of istradefylline, ARL67156 and AMP-CP on OVA-induced neutrophilic airway inflammation or imiquimod (IMQ)-induced psoriasis in mice. These two model mice received these drugs orally or percutaneously, respectively. The production of IL-17A in the lung and ear thickness were used as an index of the effects.ResultsWe show that istradefylline, ARL67156 and AMP-CP suppressed the OVA-induced IL-17A production in the lung and IMQ-induced psoriasis.ConclusionThese results indicate that adenosine-mediated IL-17A production plays a role in neutrophilic inflammation models, and moreover, istradefylline, ARL67156, and AMP-CP are effective in animal models of neutrophilic inflammation. Some clinical relevancies in COVID-19 are discussed.
Evidence for Normalization as a Fundamental Operation Across the Human Visual Cortex
Authors: Doostani Narges , Hossein-Zadeh Gholam-Ali , Vaziri-Pashkam Maryam 
Published: May 2021

AbstractDivisive normalization of the neural responses by the activity of the neighboring neurons has been proposed as a fundamental operation in the nervous system based on its success in predicting neural responses recorded in primate electrophysiology studies. Nevertheless, experimental evidence for the existence of this operation in the human brain is still scant. Here, using functional MRI, we explored the role of normalization across the visual hierarchy in the human visual cortex. Using stimuli form the two categories of human bodies and houses, we presented objects in isolation or in clutter and asked participants to attend or ignore the stimuli.Focusing on the primary visual area V1, the object-selective regions LO and pFs, and the category-selective regions EBA and PPA, we first modeled single-voxel responses using a weighted sum, a weighted average, and a normalization model and demonstrated that the response to multiple stimuli could best be described by a model that takes normalization into account. We then explored the observed effects of attention on cortical responses and demonstrated that these effects were predicted by the normalization model, but not by the weighted sum or the weighted average models. Our results thus provide compelling evidence for normalization as a canonical computation operating in the human brain.
Mitigating antimicrobial resistance with aspirin (acetylsalicylic acid) and paracetamol (acetaminophen): Conversion of doxycycline and minocycline resistant bacteria into sensitive in presence of aspirin and paracetamol
Authors: Singh Bhoj Raj 
Published: May 2021

AbstractThe emergence of antimicrobial resistance (AMR) stimulated research for alternatives antimicrobials, repurposing of other drugs, antibiotic adjuvants and alternative therapies for infections. Antimicrobial activity of NSAIDs is often reported and this study evaluated the antimicrobial potential of the two most common NSAIDs, aspirin (acetylsalicylic acid) and paracetamol (acetaminophen), against 293 clinical strains of bacteria. The ability of aspirin and paracetamol to convert minocycline and doxycyclin-resistant bacteria into sensitivity was also tested using micro-broth dilution assays used for determining minimum inhibitory concentration (MIC). Aspirin inhibited all 293 bacterial strains at ≤10.24 mg/ mL concentration. Except for one strain each of Serratia grimaceae and S, aureus paracetamol inhibited none of the 293 strains at 10.24 mg/ mL. Of the 293 strains 116 (39.59%) were sensitive (MIC ≤4 μg/mL) to doxycycline and 127 (43.34%) to minocycline. Of the selected 57 minocycline-resistant (MIC >4 μg/mL) strains aspirin converted 32 (56.14%) to minocycline-sensitive. Of the 49 doxycycline-resistant (MIC >4 μg/mL) strains tested in presence of aspirin 30 (61.22%) turned sensitive. Of the 34 doxycycline-resistant strains tested in presence of paracetamol 11 (32.35%) become sensitive. The study concluded that most of the bacterial strains were not susceptible to aspirin and paracetamol at their concentrations often available in plasma at maximum therapeutic dose levels and had no significant change in their susceptibility to doxycycline and minocycline. The study indicated the potential of aspirin and its combination with antibiotics in the development of therapeutically useful topical antimicrobial formulations.
Diversification through sexual selection on gustatorial courtship traits in dwarf spiders
Authors: Lin Shou-Wang , Lopardo Lara , Uhl Gabriele 
Published: May 2021

AbstractSexual dimorphism can evolve under sexual selection or ecological factors. Sexually dimorphic male prosomal modifications are associated with gustatorial courtship in erigonines. The modifications vary from moderate elevations to bizarre shapes. Males transfer substances from these structures to females, which affect mate acceptance and fecundity. Here, we explore lability of these traits by investigating if modified prosomata are inherently linked to secretory glands, if glands evolved prior to prosomal modifications, and the possibility of convergent evolution and cryptic differentiation, aiming at assessing the possible role of this trait complex in speciation. We reconstructed the positions of glands and the musculature in the anterior part of prosomata of 76 erigonines and three outgroups using micro-CT. We incorporated these characters into an existing morphological character matrix and reanalyzed the phylogeny. Our results support the possession of glands as the ancestral state. The manifold modifications of the prosomal shape have evolved convergently. Differences in glandular positions between species with modified/unmodified prosomata suggest high lability of these traits. Cases of gland loss suggest considerable costs of gustatorial courtship. Our findings demonstrate divergent evolutionary patterns of these traits, and a likely facilitating effect of this type of sexual selection on speciation.