bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of a weak mode of bacterial adhesion by applying an electric field
Authors: Araujo George , Zheng Joy , Oh Jae Jong , Tang Jay X. 
Published: April 2020

ABSTRACTMicrobial attachment to surfaces is ubiquitous in nature. Most species of bacteria attach and adhere to surfaces via special appendages such as pili and fimbriae, the roles of which have been extensively studied. Here we report an experiment on pilus-less mutants ofCaulobacter crescentusweakly attached to a plastic surface and subjected to an electric field parallel to the surface. We find that some individual cells transiently but repeatedly adhere to the surface in a stick-slip fashion in the presence of an electric field. Even while transiently detached, these bacteria move significantly slower than the unattached ones in the same field of view undergoing electrophoretic motion. We refer this behavior of repeated and transient attachment as “quasi-attachment”. The speed of the quasi-attached bacteria exhibits large variations, frequently dropping close to zero for short intervals of time. This study suggests applying electric field as a useful method to investigate bacteria-surface interaction, which is significant in broader contexts such as infection and environmental control.SignificanceInteraction between bacteria and surfaces occur widely in nature, including those in industrial, environmental, and medical settings. It is therefore important to understand various mechanisms and factors that affect numerous forms of bacterium-surface interaction, particularly those resulting in adhesion or attachment, be they strong or weak, permanent or transient. This work takes a unique approach to identify a transient and reversible mode of bacterial attachment to a solid surface, by applying an electric field to exert a force for detachment. The force thus exerted proves to reach the amplitude required to detach bacteria of a pilus-less strain that weakly attach to a plastic surface. The method may be applied broadly to investigate bacteria-surface interaction.
Multiple lineages, same molecular basis: task specialization is commonly regulated across all eusocial bee groups
Authors: de Souza Araujo Natalia , Arias Maria Cristina 
Published: April 2020

AbstractA striking feature of advanced insect societies is the existence of workers that forgo reproduction. Two broad types of workers exist in eusocial bees: nurses which care for their young siblings and the queen, and foragers who guard the nest and forage for food. Comparisons between this two worker subcastes have been performed in honeybees, but data from other bees are scarce. To understand whether similar molecular mechanisms are involved in nurse-forager differences across distinct species, we compared gene expression and DNA methylation profiles between nurses and foragers of the buff-tailed bumblebeeBombus terrestrisand of the stingless beeTetragonisca angustula. These datasets were then discussed comparatively to previous findings on honeybees. Our analyses revealed that although the expression pattern of genes is often species-specific, many of the biological processes and molecular pathways involved are common. Moreover, DNA methylation and gene expression correlation were dependent on the nucleotide context.
RDoC Mechanisms of Transdiagnostic Polygenic Risk for Trajectories of Depression: From Early Adolescence to Adulthood
Authors: Li James J. , Zhang Qi , Lu Qiongshi 
Published: April 2020

AbstractThere is substantial heterogeneity in the development of depression across early adolescence into adulthood. Yet, little is known about the risk factors underlying individual differences in the development of depression. For instance, despite the discovery of genetic variants for depression, there is also significant genetic overlap between depression and other mental disorders. Thus, depression may have etiologically complex (i.e., transdiagnostic) origins when accounting for its heterogeneous developmental presentations. This study examined the association between a transdiagnostic polygenic score for psychopathology (p-factor PGS) and depressive trajectories, spanning early adolescence into adulthood, in the National Longitudinal Study of Adolescent to Adult Health. We also examined whether the Research Domains Criteria (RDoC) negative valence (i.e., negative emotionality), positive valence (i.e., novelty seeking), and cognitive systems (i.e., picture vocabulary) could explain how thep-factor PGS eventuates into the various pathways of depressive development. Four trajectories of depression were identified:low depression(78.9%), low increasing(7.3%), high declining(8.2%), andearly adult peaked(5.7%). Thep-factor PGS was only associated with the trajectory that showed increasing depression over time –low increasing.There was also a specific indirect effect by which the association ofp-factor PGS onearly adult peakedandhigh decliningdepression was partially mediated by negative emotionality, but not by picture vocabulary or novelty seeking. Our findings reinforce the crucial role of development in genetically-informed RDoC models of depression, as there appear to be distinct correlates and risk factors that underlie the various developmental pathways of depression. Clinical implications were also discussed.General Scientific SummaryThere are individual differences in how depression symptoms progress over time, but little is known about the risk factors that underlie these various patterns of development. This study suggests that there are distinct correlates and risk factors that underlie the various developmental pathways of depression. We found that transdiagnostic polygenic risks for psychopathology are directly associated with worsening patterns of adolescent to adult depression and indirectly associated with the less severe patterns of depression via negative emotionality.
Structure of the Visual Signaling Complex between Transducin and Phosphodiesterase 6
Authors: Gao Yang , Eskici Gözde , Ramachandran Sekar , Poitevin Frédéric , Seven Alpay Burak , Panova Ouliana , Skiniotis Georgios , Cerione Richard A. 
Published: April 2020

SUMMARYHeterotrimeric G proteins communicate signals from activated G protein-coupled receptors to downstream effector proteins. In the phototransduction pathway responsible for vertebrate vision, the G protein-effector complex is comprised of the GTP-bound transducin α subunit (GαT·GTP) and the cyclic GMP (cGMP) phosphodiesterase 6 (PDE6), which stimulates cGMP hydrolysis to transmit signals to the optic nerve. Here we report a cryo-electron microscopy (cryoEM) structure of PDE6 complexed to GTP-bound GαT. The structure reveals two GαT·GTP subunits engaging the PDE6 hetero-tetramer at both the PDE6 catalytic core and the PDEγ subunits, driving extensive rearrangements to relieve all inhibitory constraints on enzyme catalysis. Analysis of the conformational ensemble in the cryoEM data highlights the dynamic nature of the contacts between the two GαT·GTP subunits and PDE6 that support an alternating-site catalytic mechanism.
VISTA: Virtual ImmunoSTAining for pancreatic disease quantification in murine cohorts
Authors: Ternes Luke , Huang Ge , Lanciault Christian , Thibault Guillaume , Riggers Rachelle , Gray Joe W. , Muschler John , Chang Young Hwan 
Published: April 2020

AbstractMechanistic studies of pancreatic disease progression using animal models require objective and quantifiable assessment of tissue changes among animal cohorts. Disease state quantification, however, relies heavily on tissue immunostaining, which can be expensive, labor- and time-intensive, and all too often produces uneven staining that is prone to variable interpretation between experts and inaccurate quantification. Here we develop a fully automated semantic segmentation tool using deep learning for the rapid and objective quantification of histologic features using hematoxylin and eosin (H&E) stained pancreatic tissue sections acquired from murine pancreatic cancer models. The tool was successfully trained to segment and quantify multiple histopathologic features of pancreatic pre-cancer evolution, including normal acinar structures, the ductal phenotype of acinar-to ductal metaplasia (ADM), dysplasia, and the expanding stromal compartment. Disease quantifications produced by our computational tool were highly correlated to the results obtained by immunostaining markers of normal and diseased tissue (DAPI, amylase, and cytokeratins; correlation score= 0.9, 0.95, and 0.91, respectively) and were able to accurately reproduce immunostain patterns. Moreover, our tool was able to distinguish ADM from dysplasia, which are not reliably distinguished by immunostaining, and avoid the pitfalls of uneven or poor-quality staining. Using this tool, we quantified the changes in histologic feature abundance for murine cohorts with oncogenic Kras-driven disease at 2 months and 5 months of age (n=12, n=13). The calculated changes in histologic feature abundance were consistent with biological expectations, showing an expansion of the stromal compartment, a reduction of normal acinar tissue, and an increase in both ADM and dysplasia as disease progresses (p= 2e-6, 6e-7, 4e-4, and 3e-5, respectively). These results demonstrate the tool’s efficacy for accurate and rapid quantification of multiple histologic features using an objective and automated platform. Our tool promises to rapidly accelerate and improve the quantification of altered pancreatic disease progression in animal studies.
LxxIxE-like Motif in Spike Protein of SARS-CoV-2 that is Known to Recruit the Host PP2A-B56 Phosphatase Mimics Artepillin C, an Immunomodulator, of Brazilian Green Propolis
Authors: Maaroufi Halim 
Published: April 2020

ABSTRACTSARS-CoV-2 is highly contagious and can cause acute respiratory distress syndrome (ARDS) and multiple organ failure that are largely attributed to the cytokine storm. The surface coronavirus spike (S) glycoprotein is considered as a key factor in host specificity because it mediates infection by receptor-recognition and membrane fusion. Here, the analysis of SARS-CoV-2 S protein revealed two B56-binding LxxIxE-like motifs in S1 and S2 subunits that could recruit the host protein phosphatase 2A (PP2A). The motif in S1 subunit is absent in SARS-CoV and MERS-CoV. Phosphatases and kinases are major players in the regulation of pro-inflammatory responses during pathogenic infections. Moreover, studies have shown that viruses target PP2A in order to manipulate host’s antiviral responses. Recent researches have indicated that SARS-CoV-2 is involved in sustained host inflammation. Therefore, by controlling acute inflammation, it is possible to eliminate its dangerous effects on the host. Among efforts to fight COVID-19, the interaction between LxxIxE-like motif and the PP2A-B56-binding pocket could be a target for the discovery and/or development of a bioactive ligand inhibitor for therapeutic purposes. Indeed, a small molecule called Artepillin C (ArtC), a main compound in Brazilian honeybee green propolis, mimics the side chains of LxxLxE motif. Importantly, ArtC is known, among other effects, to have anti-inflammatory activity that makes it an excellent candidate for future clinical trials in COVID-19 patients.
Deducing the N- and O- glycosylation profile of the spike protein of novel coronavirus SARS-CoV-2
Authors: Shajahan Asif , Supekar Nitin T. , Gleinich Anne S. , Azadi Parastoo 
Published: April 2020

AbstractThe current emergence of the novel coronavirus pandemic caused by SARS-CoV-2 demands the development of new therapeutic strategies to prevent rapid progress of mortalities. The coronavirus spike (S) protein, which facilitates viral attachment, entry and membrane fusion is heavily glycosylated and plays a critical role in the elicitation of the host immune response. The spike protein is comprised of two protein subunits (S1 and S2), which together possess 22 potential N-glycosylation sites. Herein, we report the glycosylation mapping on spike protein subunits S1 and S2 expressed on human cells through high resolution mass spectrometry. We have characterized the quantitative N-glycosylation profile on spike protein and interestingly, observed unexpected O-glycosylation modifications on the receptor binding domain (RBD) of spike protein subunit S1. Even though O-glycosylation has been predicted on the spike protein of SARS-CoV-2, this is the first report of experimental data for both the site of O-glycosylation and identity of the O-glycans attached on the subunit S1. Our data on the N- and O-glycosylation is strengthened by extensive manual interpretation of each glycopeptide spectra in addition to using bioinformatics tools to confirm the complexity of glycosylation in the spike protein. The elucidation of the glycan repertoire on the spike protein provides insights into the viral binding studies and more importantly, propels research towards the development of a suitable vaccine candidate.
modleR: a modular workflow to perform ecological niche modeling in R
Authors: Sánchez-Tapia Andrea , Mortara Sara Ribeiro , Bezerra Rocha Diogo Souza , Mendes Barros Felipe Sodré , Gall Guilherme , de Siqueira Marinez Ferreira 
Published: April 2020

AbstractEcological niche models (ENM) use the environmental variables associated with the currently known distribution of a species to model its ecological niche and project it into the geographic space. Widely used and misused, ENM has become a common tool for ecologists and decision-makers.Many ENM platforms have been developed over the years, first as standalone programs, later as packages within script-based programming languages and environments. The democratization of these programming tools and the advent of Open Science brought a growing concern regarding the reproducibility, transparency, robustness, portability, and interoperability in ENM workflows.ENM workflows have some core components that are replicated between projects. However, they have a large internal variation due to the variety of research questions and applications. Any ecological niche modeling platform should take into account this trade-off between stability and reproducibility on one hand, and flexibility and decision-making on the other.Here, we presentmodleR, a four-step workflow that wraps some of the common phases executed during an ecological niche model procedure. We have divided the process into (1) data setup, (2) model fitting and projection, (3) partition joining and (4) ensemble modeling (consensus between algorithms).modleRis highly adaptable and replicable depending on the user’s needs and is open to deeper internal parametrization. It can be used as a testing platform due to its consistent folder structure and its capacity to control some sources of variation while changing others. It can be run in interactive local sessions and in high-performance or high-throughput computational (HPC/HTC) platforms and parallelized by species or algorithms. It can also communicate with other tools in the field, allowing the user to enter and exit the workflow at any phase, and execute complementary routines outside the package. Finally, it records metadata and session information at each step, ensuring reproducibility beyond the use of script-based applications.
Lessons from the analysis of TAD boundary deletions in normal population
Authors: Smol Thomas , Sigé Jérôme , Thuillier Caroline , Frénois Frédéric , Brunelle Perrine , Rama Mélanie , Roche-Lestienne Catherine , Manouvrier-Hanu Sylvie , Petit Florence , Ghoumid Jamal 
Published: April 2020

AbstractTopologically Associating Domains (TAD)-boundaries induce spatial constraints, allowing interaction between regulatory elements and promoters only within their TAD. Their disruption could lead to disease, through gene-expression deregulation. This mechanism has been shown in only a relatively low number of diseases and a relatively low proportion of patients, raising the possibility of TAD boundary disruption without phenotypical consequence. We investigated, therefore, the occurrence of TAD boundaries disruption in the general population. Coordinates of 307,430 benign deletions from public databases were crossed with 36 Hi-C datasets. Differences in gene content and gene localization were compared in the TADs, according to the possible disruption of their boundaries by a deletion found in the general population. TADs with no deletion encompassing their boundaries (R-TAD) represented 38% of TADs. Enrichment in OMIM genes as well as in morbid genes was observed in R-TADs and genes in R-TADs were found to localize closer to the boundaries. Our results support recent publications tempering the impact of breaking TADs on gene expression with a majority of broken TADs in the general population. A subgroup of R-TAD emerges from this analysis with enrichment in disease genes and their coordinates could be used to annotate CNV from pangenomic approaches to enhance data interpretation.
IL-6 signalling pathway inactivation with siltuximab in patients with COVID-19 respiratory failure: an observational cohort study
Authors: Gritti Giuseppe , Raimondi Federico , Ripamonti Diego , Riva Ivano , Landi Francesco , Alborghetti Leonardo , Frigeni Marco , Damiani Marianna , Micò Caterina , Fagiuoli Stefano , Cosentini Roberto , Lorini Ferdinando Luca , Gandini Lucia , Novelli Luca , Morgan Jonathan P , Owens Benjamin M J , Kanhai Karan J K , Reljanovic Gordana Tonkovic , Rizzi Marco , Di Marco Fabiano , Rambaldi Alessandro 
Published: April 2020

AbstractBackgroundSevere COVID-19 is characterised by interstitial pneumonia and hyperinflammation, with elevated levels of pro-inflammatory cytokines, such as IL-6. Effective treatments are urgently needed, and IL-6 is a rational target to reduce hyperinflammation.MethodsAn observational, control cohort, single-centre study initiated at the Papa Giovanni XXIII Hospital in Bergamo, Italy included patients with COVID-19 confirmed by a nasopharyngeal swab positive for severe acute respiratory syndrome coronavirus 2 RNA and interstitial pneumonia requiring ventilatory support. Patients were treated with either best supportive care and siltuximab or best supportive care alone. Propensity score matching was applied to minimise differences in baseline covariates between patient cohorts. The main outcome was mortality in siltuximab-treated patients compared with patients in the matched-control cohort. This study (Siltuximab in Severe COVID-19, SISCO) is registered with ClinicalTrials.gov, identifier NCT04322188.FindingsThirty patients received siltuximab, while 188 control patients received only best supportive care. Siltuximab-treated patients were matched to 30 control patients using the propensity score analysis of baseline covariates. The 30-day mortality rate was significantly lower in the siltuximab-treated than the matched-control cohort patients (HR 0·462, 95% CI 0·221– 0·965); p=0·0399). The mean follow-up was 33·3 days (range 7–58 days) for the siltuximab-treated patients and 22·8 days (range 2–45 days) for the control cohort. Sixteen siltuximab-treated patients were discharged from hospital, four remained on mechanical ventilation, and 10 patients died.InterpretationPatients with rapidly progressing COVID-19 respiratory failure requiring ventilatory support may benefit from treatment with siltuximab to reduce mortality and cytokine-driven hyperinflammation associated with severe disease. These findings require validation in a randomised controlled clinical trial.FundingPapa Giovanni XXIII Hospital and the Italian Association for Cancer Research funded the study. EUSA Pharma supplied siltuximab, and provided funding for data collection, analysis, and development of the publication.
SEIR and Regression Model based COVID-19 outbreak predictions in India
Authors: Gupta Rajan , Pandey Gaurav , Chaudhary Poonam , Pal Saibal 
Published: April 2020

AbstractCOVID-19 pandemic has become a major threat to the country. Till date, well tested medication or antidote is not available to cure this disease. According to WHO reports, COVID-19 is a severe acute respiratory syndrome which is transmitted through respiratory droplets and contact routes. Analysis of this disease requires major attention by the Government to take necessary steps in reducing the effect of this global pandemic. In this study, outbreak of this disease has been analyzed for India till 30th March 2020 and predictions have been made for the number of cases for the next 2 weeks. SEIR model and Regression model have been used for predictions based on the data collected from John Hopkins University repository in the time period of 30th January 2020 to 30th March 2020. The performance of the models was evaluated using RMSLE and achieved 1.52 for SEIR model and 1.75 for the regression model. The RMSLE error rate between SEIR model and Regression model was found to be 2.01. Also, the value of R0 which is the spread of the disease was calculated to be 2.02. Expected cases may rise between 5000-6000 in the next two weeks of time. This study will help the Government and doctors in preparing their plans for the next two weeks. Based on the predictions for short-term interval, these models can be tuned for forecasting in long-term intervals.
Clinical Manifestations of Children with COVID-19: a Systematic Review
Authors: de Souza Tiago H. , Nadal José A. , Nogueira Roberto J. N. , Pereira Ricardo M. , Brandão Marcelo B. 
Published: April 2020

ABSTRACTBackgroundThe coronavirus disease 2019 (COVID-19) outbreak is an unprecedented global public health challenge, leading to thousands of deaths every day worldwide. Despite the epidemiological importance, clinical patterns of children with COVID-19 remain unclear. The aim of this study was to describe the clinical, laboratorial and radiological characteristics of children with COVID-19.MethodsThe Medline database was searched between December 1st 2019 and April 6th 2020. No language restrictions were applied. Inclusion criteria were: (1) studied patients younger than 18 years old; (2) presented original data from cases of COVID-19 confirmed by reverse-transcription polymerase chain reaction; and (3) contained descriptions of clinical manifestations, laboratory tests or radiological examinations.ResultsA total of 38 studies (1,124 cases) were included. From all the cases, 1,117 had their severity classified: 14.2% were asymptomatic, 36.3% were mild, 46.0% were moderate, 2.1% were severe and 1.2% were critical. The most prevalent symptom was fever (47.5%), followed by cough (41.5%), nasal symptoms (11.2%), diarrhea (8.1%) and nausea/vomiting (7.1%). One hundred forty-five (36.9%) children were diagnosed with pneumonia and 43 (10.9%) upper airway infections were reported. Reduced lymphocyte count were reported in 12.9% of cases. Abnormalities on computed tomography was reported in 63.0% of cases. The most prevalent abnormalities reported were ground glass opacities, patchy shadows and consolidations. Only one death was reported.ConclusionsClinical manifestations of children with COVID-19 differ widely from adults cases. Fever and respiratory symptoms should not be considered a hallmark of COVID-19 in children.