bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adenosine metabolized from extracellular ATP promotes type 2 immunity through triggering A2BAR signaling on intestinal epithelial cells
Authors: El-Naccache Darine W. , Chen Fei , Palma Mark , Lemenze Alexander , Wu Wenhui , Mishra Pankaj K. , Eltzschig Holger K. , Robson Simon C. , Di Virgilio Francesco , Haskó György , Gause William C. 
Published: January 2021

AbstractMulticellular intestinal nematode parasites can cross the epithelial barrier potentially causing tissue damage and release of danger associated molecular patterns (DAMPs) that may promote type 2 responses and host protective immunity. We investigated whether adenosine specifically binding the A2Badenosine receptor (A2BAR) on epithelial cells played an important role in driving intestinal immunity. Specific blockade of epithelial cell A2BAR inhibited the host protective memory response to the enteric helminth,Heligmosomoides polygyrus bakeri, including disruption of granuloma development at the host:parasite interface during the transient tissue dwelling larval stage. Memory T cell development was blocked during the primary response and transcriptional analyses revealed profound impairment of A2BAR signaling in epithelial cells and reduced type 2 markers by 24 hours after inoculation. Extracellular ATP was visualized by 24 hours after inoculation and shown in CD39 deficient mice to be critical for the adenosine production mediating initiation of type 2 immunity.
Reproducibility of protein X-ray diffuse scattering and potential utility for modeling atomic displacement parameters
Authors: Su Zhen , Dasgupta Medhanjali , Poitevin Frédéric , Mathews Irimpan I. , van den Bedem Henry , Wall Michael E. , Yoon Chun Hong , Wilson Mark A. 
Published: January 2021

AbstractProtein structure and dynamics can be probed using X-ray crystallography. Whereas the Bragg peaks are only sensitive to the average unit-cell electron density, the signal between the Bragg peaks -- diffuse scattering -- is sensitive to spatial correlations in electron-density variations. Although diffuse scattering contains valuable information about protein dynamics, the diffuse signal is more difficult to isolate from the background compared to the Bragg signal, and the reproducibility of diffuse signal is not yet well understood. We present a systematic study of the reproducibility of diffuse scattering from isocyanide hydratase (ICH) in three different protein forms. Both replicate diffuse datasets and datasets obtained from different mutants were similar in pairwise comparisons (Pearson correlation coefficient (CC) ≥0.8). The data were processed in a manner inspired by previously published methods using custom software with modular design, enabling us to perform an analysis of various data processing choices to determine how to obtain the highest quality data as assessed using unbiased measures of symmetry and reproducibility. The diffuse data then were used to characterize atomic mobility using a liquid-like motions (LLM) model. This characterization was able to discriminate between distinct anisotropic atomic displacement parameter (ADP) models arising from different anisotropic scaling choices that agreed comparably with the Bragg data. Our results emphasize the importance of data reproducibility as a model-free measure of diffuse data quality, illustrate the ability of LLM analysis of diffuse scattering to select among alternative ADP models, and offer insights into the design of successful diffuse scattering experiments.
Mild impacts do not subsidize aquatic insect communities in an Atlantic Forest stream
Authors: Jonck Celio Roberto , de Oliveira Luiza Hoehne Mattos , Silva Rafael Jordão Pires , Nessimian Jorge Luiz 
Published: January 2021

AbstractOdum’s perturbation theory hypothesizes that toxic pollutants cause damage to ecosystems early in the course of contamination. In contrast, organic pollutants enrich the ecosystem until it exceeds their carrying capacity, an effect known as the subsidy-stress gradient. Understanding this dynamic can improve the efficiency of river restoration programs and bring significant benefits to society by providing ecosystem services that were lost. However, the initial effects of the most common human-induced disturbances in Atlantic Forest streams are not well known, indicating the necessity to evaluate the subsidy-stress gradient in these vulnerable and diverse ecosystems.AimWe evaluated the composition and abundance of the community of aquatic insects from leaf litter of headwater streams in three conditions: a fully forested area (reference stream), a low-intensity urban settlement (urban stream), and a region with small farms dedicated to the cultivation of fruits and vegetables (agricultural stream).MethodsWe used alpha and beta diversity metrics and a specific biotic index to test the subsidy-stress gradient prediction.ResultsThe agricultural stream showed the most degraded ecological condition. The urban stream and the reference stream showed similarity in alpha diversity metrics. According to the biotic index, the streams showed a gradient of environmental quality, with the reference stream showing the best quality and the agricultural stream the worst quality.ConclusionsThe agricultural stream showed a decrease in the environmental quality consistent with the effect predicted by the subsidy-stress gradient due to toxic pollutants’ contribution. However, the low-intensity enrichment of organic matter from the urban settlement causes a disorder in the ecosystem that reduces its environmental quality, contrary to the predicted by the subsidy-stress gradient.
Deconstruction of the retrosplenial granular cortex for social behavior in the mouse model of fragile X syndrome
Authors: Shang Hui-Fang , Cai Ruonan , Sun Hao , Sheng Tao , Lian Yan-Na , Liu Li , Chen Wei , Gao Lixia , Xu Han , Zhang Chen , Luo Jian-Hong , Li Xinjian , Li Xiang-Yao 
Published: January 2021

ABSTRACTDeficits in fragile X mental retardation 1 protein lead to fragile X syndrome (FXS) with mental retardation and social activity disorder. Until now, the neuronal circuits that mediate the social impairments of FXS were mostly unclear. Accidently, we found fewer c-fos expression in RSG of KO than WT mice after social behavior test. Inactivation of RSG neurons decreased social novelty but not the sociability of naive mice. Interestingly, although the RSG neurons of KO mice had higher background activity, fewer social contact-related Ca2+neurons were observed during social interaction testviaone-photon Ca2+imaging in freely-behaving mice. Strikingly, enhancing the activity of RSG neurons rescued the abnormal social novelty in KO mice. Further studies proved that the innervations from the subiculum and ACC to RSG contributes to the social behavior. Take together, we found that abnormal activity in the retrosplenial granular cortex (RSG) led to social novelty deficits inFmr1-knockout (KO) mice. Moreover, selective manipulation of RSG neurons may be an effective strategy to treat the social deficits in FXS.One Sentence SummaryDeletion of FMRP leads to lower social-related neuronal activity in the RSG; this causes social novelty deficits inFmr1-KO mice.
Design of a novel DNA Gyrase B inhibitor with a rhodanine scaffold:in silicoandin vitroapproaches
Authors: Pudipeddi Akhila , Vasudevan Sahana , Shanmugam Karthi , Stanley Alex , Pothiappan Vairaprakash , Neelakantan Prasanna , Solomon Adline Princy 
Published: January 2021

AbstractMethicillin-resistantStaphylococcus aureus(MRSA) and vancomycin intermediate-resistantStaphylococcus aureus(VRSA) is one among the WHO high priority pathogens. Among these two, MRSA is the most globally documented pathogen that necessitates the pressing demand for new classes of anti-MRSA drugs. Bacterial gyrase targeted therapeutics are unique strategies to overcome cross-resistance as they are present only in bacteria and absent in higher eukaryotes. The GyrB subunit is essential for the catalytic functions of the bacterial enzyme DNA Gyrase, thereby constituting a promising druggable target. The current study performed a structure-based virtual screening to designing GyrB target-specific candidate molecules. Thede novoligand design of novel hit molecules was performed using a rhodanine scaffold. Through a systematicin silicoscreening process, the hit molecules were screened for their synthetic accessibility, drug likeliness and pharmacokinetics properties in addition to its target specific interactions. Of the total 374 hit molecules obtained throughde novoligand design, qsl-304 emerged as the most promising ligand. qsl-304 was synthesized through a one-step chemical synthesis procedure, and thein vitroactivity was proven, with an IC50of 31.23 μg/mL against the novobiocin resistant clinical isolate ofStaphylococcus aureus sa-P2003. Further studies on time-kill kinetics showed the bacteriostatic nature with the diminished recurrence of resistance.
Basis profile curve identification to understand electrical stimulation effects in human brain networks
Authors: Miller Kai J. , Müller Klaus-Robert , Hermes Dora 
Published: January 2021

AbstractBrain networks can be explored by delivering brief pulses of electrical current in one area while measuring voltage responses in other areas. We propose a convergent paradigm to study brain dynamics, focusing on a single brain site to observe the average effect of stimulating each of many other brain sites. Viewed in this manner, visually-apparent motifs in the temporal response shape emerge from adjacent stimulation sites. This work constructs and illustrates a data-driven approach to determine characteristic spatiotemporal structure in these response shapes, summarized by a set of unique “basis profile curves” (BPCs). Each BPC may be mapped back to underlying anatomy in a natural way, quantifying projection strength from each stimulation site using simple metrics. Our technique is demonstrated for an array of implanted brain surface electrodes in a human patient. This framework enables straightforward interpretation of single-pulse brain stimulation data, and can be applied generically to explore the diverse milieu of interactions that comprise the connectome.Author summaryWe present a new machine learning framework to probe how brain regions interact using single-pulse electrical stimulation. Unlike previous studies, this approach does not assume a form for how one brain area will respond to stimulation in another area, but rather discovers the shape of the response in time from the data. We call the set of characteristic discovered response shapes “basis profile curves” (BPCs), and show how these can be mapped back onto the brain quantitatively. An illustrative example is included from one of our human patients to characterize inputs to the parahippocampal gyrus. A code package is downloadable fromhttps://purl.stanford.edu/rc201dv0636so the reader may explore the technique for own data, or study sample data provided to reproduce the illustrative case presented in the manuscript.
RegEnrich: An R package for gene regulator enrichment analysis reveals key role of ETS transcription factor family in interferon signaling
Authors: Tao Weiyang , Radstake Timothy R.D.J. , Pandit Aridaman 
Published: January 2021

AbstractChanges in a few key transcriptional regulators can lead to different biological states, including cell activation and differentiation, and diseases. Extracting the key gene regulators governing a biological state allows us to gain mechanistic insights and can further help in translational research. Most current tools perform pathway/GO enrichment analysis to identify key genes and regulators but tend to overlook the regulatory interactions between genes and proteins. Here we presentRegEnrich, an open-source Bioconductor R package, which combines differential expression analysis, data-driven gene regulatory network inference, enrichment analysis, and gene regulator ranking to identify key regulators using gene/protein expression profiling data. By benchmarking using multiple gene expression datasets of gene silencing studies, we found thatRegEnrichusing the GSEA method to rank the regulators performed the best to retrieve the key regulators. Further,RegEnrichwas applied to 21 publicly available datasets onin vitrointerferon-stimulation of different cell types. We found that not only IRF and STAT transcription factor families played an important role in cells responding to IFN, but also several ETS transcription factor family members, such as ELF1 and ETV7, are highly associated with IFN stimulations. Collectively,RegEnrichcan accurately identify key gene regulators from the cells under different biological states in a data-driven manner, which can be valuable in mechanistically studying cell differentiation, cell response to drug stimulation, disease development, and ultimately drug development.
Ultrasensitive measurement of both SARS-CoV2 RNA and serology from saliva
Authors: Ter-Ovanesyan Dmitry , Gilboa Tal , Lazarovits Roey , Rosenthal Alexandra , Yu Xu G. , Li Jonathan Z. , Church George M. , Walt David R. 
Published: January 2021

AbstractTests for COVID-19 generally measure SARS-CoV2 viral RNA from nasal swabs or antibodies against the virus from blood. It has been shown, however, that both viral particles and antibodies against those particles are present in saliva, which is more accessible than both swabs and blood. We present methods for highly sensitive measurements of both viral RNA and serology from the same saliva sample. We developed an efficient saliva RNA extraction method and combined it with an ultrasensitive serology test based on Single Molecule Array (Simoa) technology. We apply our test to the saliva of patients who presented to the hospital with COVID-19 symptoms, some of whom tested positive with a conventional RT-qPCR nasopharyngeal swab test. We demonstrate that combining viral RNA detection by RT-qPCR with serology identifies more patients as infected than either method alone. Our results suggest the utility of combining viral RNA and serology testing from saliva, a single easily accessible biofluid.
Disentangling sex differences in the shared genetic architecture of posttraumatic stress disorder, traumatic experiences, and social support with body size and composition
Authors: Carvalho Carolina Muniz , Wendt Frank R. , Pathak Gita A. , Maihofer Adam X. , Stein Dan J. , Sumner Jennifer A. , Hemmings Sian M. J. , Nievergelt Caroline M. , Koenen Karestan C. , Gelernter Joel , Belangero Sintia I. , Polimanti Renato 
Published: January 2021

AbstractThere is a well-known association of posttraumatic stress disorder (PTSD) and traumatic experiences with body size and composition, including consistent differences between sexes. However, the biology underlying these associations is unclear. To understand this complex relationship, we investigated large-scale datasets from the Psychiatric Genomic Consortium (12 823 cases and 35 648 controls), the UK Biobank (up to 360 000 individuals), and the GIANT (Genetic Investigation of Anthropometric Traits) Consortium (up to 339 224 individuals). We used genome-wide association statistics to estimate sex-specific genetic correlations (rg) among PTSD, traumatic experiences, social support, and multiple anthropometric traits. After multiple testing corrections (false discovery rate, FDR q<0.05), we observed 58 significant rg relationships in females (e.g., childhood physical abuse and body mass index, BMI rg=0.245, p=3.88×10−10) and 21 significant rg relationships in males (e.g., been involved in combat or exposed to warzone and leg fat percentage; rg=0.405, p=4.42×10−10). We performed causal inference analyses of these genetic overlaps using Mendelian randomization and latent causal variable approaches. Multiple female-specific putative causal relationships were observed linking body composition/size with PTSD (e.g., leg fat percentage➔PTSD; beta=0.319, p=3.13×10−9), traumatic experiences (e.g., childhood physical abuse➔waist circumference; beta=0.055, p=5.07×10−4), and childhood neglect (e.g., “someone to take you to doctor when needed as a child”➔BMI; beta=-0.594, p=1.09×10−5). In males, we observed putative causal effects linking anthropometric-trait genetic liabilities to traumatic experiences (e.g., BMI➔childhood physical abuse; beta=0.028, p=8.19×10−3). In conclusion, our findings provide insights regarding sex-specific causal networks linking anthropometric traits to PTSD, traumatic experiences, and social support.
SARS-CoV-2 RNA screening in routine pathology specimens
Authors: Stillfried Saskia von , Villwock Sophia , Bülow Roman D. , Djudjaj Sonja , Buhl Eva M. , Maurer Angela , Ortiz-Brüchle Nadina , Celec Peter , Klinkhammer Barbara M. , Wong Dickson W.L. , Cacchi Claudio , Braunschweig Till , Knüchel-Clarke Ruth , Dahl Edgar , Boor Peter 
Published: January 2021

SummaryVirus detection methods are important to cope with the SARS-CoV-2 pandemics. Apart from the lung, SARS-CoV-2 was detected in multiple organs in severe cases. Less is known on organ tropism in patients developing mild or no symptoms, and some of such patients might be missed in symptom-indicated swab testing.Here we tested and validated several approaches and selected the most reliable RT-PCR protocol for the detection of SARS-CoV-2 RNA in patients’ routine diagnostic formalin-fixed and paraffin-embedded (FFPE) specimens available in pathology, to assess a) organ tropism in samples from COVID-19-positive patients, b) unrecognized cases in selected tissues from negative or not-tested patients during a pandemic peak, and c) retrospectively, pre-pandemic lung samples.We identified SARS-CoV-2 RNA in four samples from confirmed COVID-19 patients, in two gastric biopsies, one colon resection, and one pleural effusion specimen, while all other specimens, particularly from patients with mild COVID-19 disease course, were negative. In the pandemic peak cohort, we identified one previously unrecognized COVID-19 case in tonsillectomy samples. All pre-pandemic lung samples were negative.In conclusion, SARS-CoV-2 RNA detection in FFPE pathology specimens can potentially improve surveillance of COVID-19, allow retrospective studies, and advance our understanding of SARS-CoV-2 organ tropism and effects.
Hepatitis E virus seroprevalence and associated risk factors in high-risk groups: A cross-sectional study from Turkey
Authors: Balaban H. Yasemin , Aslan Abdullah Tarık , Akdoğan Kittana Fatma Nur , Alp Alpaslan , Dağ Osman , Ayar Şefika Nur , Vahabov Cavanşir , Şimşek Cem , Yıldırım Tolga , Göker Hakan , Ergünay Koray , Erdem Yunus , Büyükaşık Yahya , Şimşek Halis 
Published: January 2021

AbstractBackgroundThe renal transplant recipients (RT), allogeneic hematopoietic stem cell transplant recipients (allo-HSCT), patients with acute hepatitis (AH), and chronic hepatitis C patients (CHC) are at risk of hepatitis E virus (HEV) infection. However, seroepidemiology, risk factors to HEV exposure, and the prevalence of HEV viremia has not yet been investigated among these patients in Turkey.Materials&MethodsIn this cross-sectional study, 292 consecutive serum samples were tested for HEV immunoglobulin IgG/IgM and HEV RNA using commercial ELISA and in-house nested PCR with Sanger sequencing, respectively. Sociodemographic, clinical, laboratory data, and risk factors were collected using a questionnaire and hospital database. Multiple logistic regression analysis was employed to identify independent predictors for anti-HEV seropositivity.ResultsAmong all patients (n=292) tested for HEV RNA reactivity, only 2 patients (one RT recipient and one patient with AH) were identified as having HEV3 viremia. HEV viremia rate was 0.6% in whole group. These patients had shown no signs of chronic HEV infection for 6 months and was found to spontaneously seroconverted 6 months after enrollment. Anti-HEV IgG was positive in 29 patients yielding an HEV seroprevalence of 9.9%. Older age (aOR:1.03, 95% CI, 1.00-1.06; p:0.022) and eating undercooked meat (aOR:3.11, 95% CI, 1.08-8.92; p:0.034) were independent risk factors to anti-HEV seropositivity in all patients. Similarly, multiple logistic regression analysis demonstrated that age (aOR:1.03, 95% CI, 0.99-1.07, p:0.058) and eating undercooked meat (aOR:5.77, 95% CI, 1.49-22.25, p:0.011) were independent risk factors for anti-HEV IgG positivity in the non-immunosuppressive subgroup consisting of AH and CHC patients.ConclusionThe HEV seroprevalence rate was high (9.9%), despite low viremia rate (0.6%) in high-risk patients. The emergence of HEV3 might indicate a serious problem for these patients. Future investigations are needed to elucidate foodborne transmission routes of HEV in Turkey.
Effects of stricter management guidelines on return-to-play timeframes following concussion in professional Australian Rules football
Authors: Pearce Alan J , King Doug A , White Adam J , Suter Catherine M 
Published: January 2021

AbstractBackgroundManagement of concussion remains a serious issue for professional sports, particularly with the growing knowledge on the consequences of repetitive concussion. One primary concern is the subjective assessment of recovery that dictates the time until a concussed athlete is returned to competition. In response to this concern, the Australian Football League (AFL) changed its policy in 2020 such that clearance for return-to-play was extended from one day, to a minimum of five days, prior to the next scheduled match.ObjectiveWe sought to examine the impact of the AFL policy change by asking whether the time to return-to-play after concussion was increased in the 2020 season relative to previous years.MethodsRetrospective data on injury and return-to-play were sourced from publicly available tables published on the AFL website. We compared the number of matches missed and the number of days missed in concussed players across 2017 to 2020 inclusive.ResultsAnalysis of data from 166 concussed players revealed no increase in the number of matches missed in 2020 relative to previous years as would have been expected from an extend recovery protocol. Considering the number of days missed in 2020 relative to 2017-19 we found, paradoxically, that there was an overall reduction in the average time to return-to-play in 2020 (11.2 vs 16.2 days).ConclusionThis study demonstrates that any policy change around concussion management requires ongoing auditing to ensure clearance meets policy objectives and highlights the need for objective measures for return-to-play after concussion.