bluuebunny/crossref_metadata_2025_split huggingface dataset:
Qingshengfaniella alkalisoli gen. nov., sp. nov., a p-hydroxybenzoate-degrading strain isolated from saline soil
Authors: Wang Shuai , Yang Rui , Xu Lian , Xing Ya-Ting , Sun Ji-Quan 
Published: February 2021

p-Hydroxybenzoate is an allelopathic compound commonly found in soil from long-term monoculture cropping systems. During the bacterial diversity analysis of saline soil, a Gram-negative, non-spore forming, non-motile, aerobic p-hydroxybenzoate-degrading bacterial strain, designated LN3S51T, was isolated from saline soil which was sampled from Tumd Right Banner, Inner Mongolia, northern China. Strain LN3S51T grew at 4–40 °C (optimum, 30 °C), pH 5.0–10.0 (optimum, pH 7.0) and 0–15 % NaCl (optimum 3.0 %). Though strain LN3S51T has the highest 16S rRNA gene similarities to

Litoreibacter ponti

GJSW-31T (96.0 %), the phylogenetic tree based on the 16S rRNA gene sequences showed that it clustered with

Fluviibacterium aquatile

SM1902T (95.8 %),

Meridianimarinicoccus roseus

TG-679T (93.9 %), and

Phycocomes zhengii

LMIT002T (93.9 %). Strain LN3S51T contained Q-10 as the major ubiquinone. Phosphatidylethanolamine (PE), phosphatidylglycerol (PG), phosphatidylcholine (PC), diphosphatidylglycerol (DPG), an unidentified aminolipid (AL), and two unidentified lipids (L) were the major polar lipids. The major fatty acids were sum feature 8 (C18 : 1
ω7c and/or C18 : 1
ω6c), C16 : 0, C18 : 0, and C18 : 1
ω7c 11-methyl. The genome of strain LN3S51T consisted of a 2 257 066 bp chromosome and four plasmids with a 59.1 mol% of genomic DNA G+C content. The average nucleotide identity (ANI) and digital DNA–DNA hybridization score (dDDH) values of strain LN3S51T to

F. aquatile

SM1902T,

M. roseus

TG-679T,

P. zhengii

LMIT002T, and

L. ponti

GJSW-31T were 69.6, 70.9, 70.6, and 69.5 %, and 20.0, 19.5, 19.0, and 20.0 %, respectively. Based on the results of phylogenetic, chemtaxonomic and phenotypic characterization, strain LN3S51T is considered to represent a novel species in a new genus within the family

Rhodobacteraceae

, for which Qingshengfaniella alkalisoli gen. nov., sp. nov. is proposed. The type strain is LN3S51T (=CGMCC 1.17099T=KCTC 72457T).
SARS-CoV-2 detection and genomic sequencing from hospital surface samples collected at UC Davis
Authors: Coil David A. , Albertson Timothy , Banerjee Shefali , Brennan Greg , Campbell A.J. , Cohen Stuart H. , Dandekar Satya , Díaz-Muñoz Samuel L. , Eisen Jonathan A. , Goldstein Tracey , Jose Ivy R. , Juarez Maya , Robinson Brandt A , Rothenburg Stefan , Sandrock Christian , Stoian Ana M. M. , Tompkins Daniel G , Tremeau-Bravard Alexandre , Haczku Angela 
Published: February 2021

AbstractRationaleThere is little doubt that aerosols play a major role in the transmission of SARS-CoV-2. The significance of the presence and infectivity of this virus on environmental surfaces, especially in a hospital setting, remains less clear.ObjectivesWe aimed to analyze surface swabs for SARS-CoV-2 RNA and infectivity, and to determine their suitability for sequence analysis.MethodsSamples were collected during two waves of COVID-19 at the University of California, Davis Medical Center, in COVID-19 patient serving and staff congregation areas. qRT-PCR positive samples were investigated in Vero cell cultures for cytopathic effects and phylogenetically assessed by whole genome sequencing.Measurements and Main ResultsImproved cleaning and patient management practices between April and August 2020 were associated with a substantial reduction of SARS-CoV-2 qRT-PCR positivity (from 11% to 2%) in hospital surface samples. Even though we recovered near-complete genome sequences in some, none of the positive samples (11 of 224 total) caused cytopathic effects in cultured cells suggesting this nucleic acid was either not associated with intact virions, or they were present in insufficient numbers for infectivity. Phylogenetic analysis suggested that the SARS-CoV-2 genomes of the positive samples were derived from hospitalized patients. Genomic sequences isolated from qRT-PCR negative samples indicate a superior sensitivity of viral detection by sequencing.ConclusionsThis study confirms the low likelihood that SARS-CoV-2 contamination on hospital surfaces contains infectious virus, disputing the importance of fomites in COVID-19 transmission. Ours is the first report on recovering near-complete SARS-CoV-2 genome sequences directly from environmental surface swabs.
A scoping review exploring the impact of digital systems on processes and outcomes in the care management of acute kidney injury and progress towards establishing learning healthcare systems
Authors: Chew Clair , Hogan Helen , Jani Yogini 
Published: February 2021

ABSTRACTBackgroundDigital systems have long been used to improve the quality and safety of care when managing Acute Kidney Injury (AKI). The availability of digitised clinical data can also turn organisations and their networks into Learning Healthcare Systems (LHSs) if used across all levels of health and care. This review explores the impact of digital systems on AKI patient care to gauge progress towards establishing LHSs and to identify existing gaps in the research.MethodEmbase, PubMed, Medline, Cochrane, Scopus and Web of Science databases were searched. Studies of real-time or near real-time digital AKI management systems which reported process and outcome measures were included.ResultsThematic analysis of 43 studies showed that most interventions used real-time serum creatinine (SCr) levels to trigger responses to enable risk prediction, early recognition of AKI or harm prevention by individual clinicians (micro level) or specialist teams (meso level). Interventions at system (macro level) were rare. There was limited evidence of change in outcomes.ConclusionWhilst the benefits of real time digital clinical data at micro level for AKI management have been evident for some time, their application at meso and macro levels is emergent therefore limiting progress towards establishing LHSs. Lack of progress is due to digital maturity, system design, human factors and policy levers. Future approaches need to harness the potential of interoperability and data analytic advances and include multiple stakeholder perspectives to overcome these factors.
Cortical Tension Initiates the Positive Feedback Loop Between E-cadherin and F-actin
Authors: Yu Qilin , Holmes William R. , Thiery Jean P. , Luwor Rodney B. , Rajagopal Vijay 
Published: February 2021

AbstractAdherens junctions (AJs) physically link two cells at their contact interface via extracellular homophilic interactions between cadherin molecules and intracellular connections between cadherins and the actomyosin cortex. Both cadherin and actomyosin cytoskeletal dynamics are reciprocally regulated by mechanical and chemical signals, which subsequently determine the strength of cell-cell adhesions and the emergent organization and stiffness of the tissues they form. However, an understanding of the integrated system is lacking. We present a new mechanistic computational model of intercellular junction maturation in a cell doublet to investigate the mechano-chemical crosstalk that regulates AJ formation and homeostasis. The model couples a 2D lattice-based model of cadherin dynamics with a continuum, reaction-diffusion model of the reorganizing actomyosin network through its regulation by Rho signaling at the intercellular junction. We demonstrate that local immobilization of cadherin induces cluster formation in a cis less dependent manner. We further investigate how cadherin and actin regulate and cooperate. By considering the force balance during AJ maturation and the force-sensitive property of the cadherin/F-actin linking molecules, we show that cortical tension applied on the contact rim can explain the ring distribution of cadherin and F-actin on the cell-cell contact of the cell-doublet. Meanwhile, the positive feedback loop between cadherin and F-actin is necessary for maintenance of the ring. Different patterns of cadherin distribution can be observed as an emergent property of disturbances of this feedback loop. We discuss these findings in light of available experimental observations on underlying mechanisms related to cadherin/F-actin binding and the mechanical environment.Significance StatementThe formation, maintenance and disassembly of adherens junctions (AJs) is fundamental to organ development, tissue integrity as well as tissue function. E-cadherins and F-actin are two major players of the adherens junctions (AJs). Although it is well known that cadherins and F-actin affect each other, how these two players work together to maintain the intercellular contact is unclear. Using a novel mechano-chemical model of E-cadherin and F-actin remodeling, we demonstrate that a positive feedback loop between cadherins and F-actin allows them to stabilize each other locally. Mechanical and chemical stimuli applied to the cell adhesion change E-cadherin and F-actin distribution by consolidating or interrupting the feedback loop locally. Our study mechanistically links mechanical force to E-cadherin patterning at cell-cell junctions.
BMSS2: a unified database-driven modelling tool for systematic model selection and identifiability analysis
Authors: Jie Ngo Russell Kai , Wui Yeoh Jing , Wei Fan Gerald Horng , Siang Loh Wilbert Keat , Loo Poh Chueh 
Published: February 2021

AbstractSummaryModelling in Synthetic Biology constitutes a powerful tool in our continuous search for improved performance with rational Design-Build-Test-Learn approach. In particular, kinetic models unravel system dynamics, enabling system analysis for guiding experimental designs. However, a systematic yet modular pipeline that allows one to identify the “right” model and guide the experimental designs while tracing the entire model development and analysis is still lacking. Here, we introduce a unified python package, BMSS2, which offers the principal tools in model development and analysis—simulation, Bayesian parameter inference, global sensitivity analysis, with an emphasis on model selection, and a priori and a posteriori identifiability analysis. The whole package is database-driven to support interactive retrieving and storing of models for reusability. This allows ease of manipulation and deposition of models for the model selection and analysis process, thus enabling better utilization of models in guiding experimental designs.Availability and ImplementationThe python package and examples are available onhttps://github.com/EngBioNUS/BMSS2. A web page which allows users to browse and download the models (SBML format) in MBase is also available with the link provided on GitHub.Supplementary InformationSupplementary data is available.
What is the evidence available to support our knowledge about threats to the conservation of Galliformes in the Greater Himalaya?
Authors: Gupta Garima , Grainger Matthew , Dunn Jonathon C. , Sanderson Roy , McGowan Philip J.K. 
Published: February 2021

1.AbstractBiodiversity is at a heightened risk of extinction and we are losing species faster than any other time. It is important to understand the threats that drive a species towards extinction in order to address those drivers. In this paper, we assess our knowledge of the threats faced by 24 Himalayan Galliformes species by undertaking a review to identify threats reported in the published literature and the supporting evidence that the threat is having an impact on the species population. Only 24 papers were deemed suitable to be included in the study. We found that biological resource use, agriculture and aquaculture are the predominant threats to the Galliformes in the Greater Himalaya but the evidence available in the studies is quite poor as only one paper quantified the impact on species. This study shows that major gaps exist in our understanding of threats to species and it is imperative to fill those gaps if we want to prevent species from going extinct.
Identification of host antiviral genes differentially induced by clinically diverse strains of Tick-Borne Encephalitis Virus
Authors: Goonawardane Niluka , Upstone Laura , Harris Mark , Jones Ian M 
Published: February 2021

AbstractTick Borne Encephalitis Virus (TBEV) is an important human arthropod-borne virus, which causes tick-borne encephalitis (TBE), an acute viral infection of the central nervous system (CNS) that causes neurological symptoms of varying severity. TBEV is prevalent in large parts of central- and northern-Europe as well as Northern Asia, and strains of varying pathogenicity have been described. Both host and viral specific characteristics have been postulated to determine the outcome of TBEV infection, but the exact basis of their clinical variability remains undefined.Here, we report the generation of Spinach RNA aptamer labelled TBEV replicons of high (Hypr) and low (Vs) pathogenicity isolates and perform the first direct comparison of both strains in cell culture. We show that pathogenic Hypr replicates to higher levels than Vs in mammalian cells, but not in arthropod cells, and that the basis of this difference maps to the NS5 region, encoding the methyltransferase and RNA polymerase. For both Hypr and Vs strains, NS5 and the viral genome localized to defined intracellular structures typical of positive strand RNA viruses, but Hypr was associated with significant activation of IRF-3, caspase-3 and caspase-8, whilst Vs activated Akt, affording protection against caspase-mediated apoptosis. Activation of TIAR and the formation of cytoplasmic stress granules were an additional early feature of Vs but not Hypr replication. Taken together, these findings highlight NS5 and novel host cell responses as key underling factors for the differential clinical characteristics of TBEV strains.ImportanceTick-borne encephalitis virus (TBEV) is an emerging virus of the flavivirus family spread by ticks. Tick bite can transfer the virus and lead to a febrile infection, Tick-borne encephalitis, of varying severity. There is no specific therapeutic treatment and control in endemic areas is by vaccination. The basis of the different pathologies shown following TBEV infection, from mild to fatal, is not clear although the virus genotype clearly has a role. Mapping the basis of their differential effects would allow focus on the stages of the replication cycle responsible, which might guide the development of therapeutic interventions or the creation of purposefully attenuated strains as candidate vaccines.
The immunophilin protein FKBPL and its peptide derivatives are novel regulators of vascular integrity and inflammation via NF-κB signaling
Authors: Annett Stephanie , Spence Shaun , Garciarena Carolina , Campbell Ciaran , Dennehy Margaret , Drakeford Clive , Lai Jacqueline , Dowling Jennifer , Moore Gillian , Yakkundi Anita , Short Amy , Sharpe Danny , Furlong Fiona , O’Donnell James S. , Cavalleri Gianpiero , Kerrigan Steve , Tikhonova Irina G. , Johnson Pauline , Kissenpfennig Adrien , Robson Tracy 
Published: February 2021

AbstractA breakdown in vascular integrity and excessive inflammation are hallmarks of serious pathological conditions including sepsis, acute respiratory distress syndrome (ARDs) and most recently, severe COVID-19. FK506 – binding protein like (FKBPL) is a member of the immunophilin protein superfamily with potent anti-tumor activity through inhibition of angiogenesis and cancer stemness. An FKBPL-based 23mer peptide, ALM201, displayed a good safety and pharmacokinetic profile in a Phase 1a oncology clinical trial and was subsequently designated orphan drug status by the FDA in ovarian cancer. Here we describe a novel role for FKBPL and its peptides in regulating vascular integrity and cytokine production though modulating NF-κB signaling. FKBPL knockdown promoted endothelial cell barrier permeability, which was further exacerbated upon stimulation with lipopolysaccharide (LPS) and accompanied by increased expression of TNF mRNA and phosphorylation of p65(RelA). Whilst treatment with the FKBPL based pre-clinical peptide, AD-01, increased VE-cadherin endothelial tight junctions following LPS stimulation. Bone marrow derived macrophages (BMDM) from FKBPL haploinsufficient mice (Fkbpl+/−) also demonstrated increased phosphorylation of p65(RelA) in response to LPS stimulation compared to wild-type mice. Furthermore, treatment with AD-01 inhibited p65(RelA) phosphorylation following LPS stimulation resulting in reduced NF-κB target gene expression and proinflammatory cytokine production. In anin vivoLPS survival model,Fkbpl+/−mice have reduced survival compared to wild-type mice. Moreover, treatment of wild-type mice with the clinical FKBPL-based peptide, ALM201, following LPS injection resulted in a 100% survival rate in mice at experimental endpoint, as well as an abrogation of production of pro-inflammatory cytokines, TNF and IL-6, in peritoneal lavage washings. Analysis of human genetic biobanks found an association between common genetic variants associated with FKBPL and traits associated with inflammatory disorders such as psoriasis, rheumatoid arthritis and high lymphocyte count. In summary, for the first time, we describe a novel role for FKBPL as a regulator of inflammation and vascular integrity through modulating NF-κB signaling and FKBPL based therapies demonstrate potent anti-inflammatory activity.
Truly Privacy-Preserving Federated Analytics for Precision Medicine with Multiparty Homomorphic Encryption
Authors: Froelicher David , Troncoso-Pastoriza Juan R. , Raisaro Jean Louis , Cuendet Michel A. , Sousa Joao Sa , Cho Hyunghoon , Berger Bonnie , Fellay Jacques , Hubaux Jean-Pierre 
Published: February 2021

ABSTRACTUsing real-world evidence in biomedical research, an indispensable complement to clinical trials, requires access to large quantities of patient data that are typically held separately by multiple healthcare institutions. Centralizing those data for a study is often infeasible due to privacy and security concerns. Federated analytics is rapidly emerging as a solution for enabling joint analyses of distributed medical data across a group of institutions, without sharing patient-level data. However, existing approaches either provide only limited protection of patients’ privacy by requiring the institutions to share intermediate results, which can in turn leak sensitive patient-level information, or they sacrifice the accuracy of results by adding noise to the data to mitigate potential leakage. We propose FAMHE, a novel federated analytics system that, based on multiparty homomorphic encryption (MHE), enables privacy-preserving analyses of distributed datasets by yielding highly accurate results without revealing any intermediate data. We demonstrate the applicability of FAMHE to essential biomedical analysis tasks, including Kaplan-Meier survival analysis in oncology and genome-wide association studies in medical genetics. Using our system, we accurately and efficiently reproduce two published centralized studies in a federated setting, enabling biomedical insights that are not possible from individual institutions alone. Our work represents a necessary key step towards overcoming the privacy hurdle in enabling multi-centric scientific collaborations.
Targeted Drug Repurposing Against the SARS-CoV-2 E channel Identifies Blockers Within vitroAntiviral Activity
Authors: Tomar Prabhat Pratap Singh , Krugliak Miriam , Arkin Isaiah Tuvia 
Published: February 2021

It is difficult to overstate the impact that COVID-19 had on humankind. The pandemic’s etiological agent, SARS-CoV-2, is a member of the Coronaviridae, and as such, is an enveloped virus with ion channels in its membrane. Therefore, in an attempt to provide an option to curb the viral spread, we searched for blockers of its E protein viro-porin. Using three bacteria-based assays, we identified eight compounds that exhibited activity after screening a library of ca. 3000 approved-for-human-use drugs. Reassuringly, analysis of viral replication in tissue culture indicated that most of the compounds could reduce infectivity to varying extents. In conclusion, targeting a particular channel in the virus for drug repurposing may increase our arsenal of treatment options to combat COVID-19 virulence.Significance StatementThe goal of our study was to expand the treatment arsenal against COVID-19. To that end, we have decided to focus on drug therapy, and as a target - the E protein, an ion channel in the virus. Ion channels as a family are excellent drug targets, but viral channels have been underexploited for pharmaceutical point intervention. To hasten future regulatory requirements and focus the chemical search space, we screened a library of ca. 3000 approved-for-human-use drugs using three independent bacteria-based assays. Our results yielded eight compounds, which were subsequently tested for antiviral activity in tissue culture. Gratifyingly, most compounds were able to reduce viral replication, and as such, both validate our approach and potentially augment our anti-COVID tool kit.
Structural and Functional Diversity among Agonist-Bound States of the GLP-1 Receptor
Authors: Cary Brian P. , Zhao Peishen , Truong Tin T. , Piper Sarah J. , Belousoff Matthew J. , Danev Radostin , Sexton Patrick M. , Wootten Denise , Gellman Samuel H. 
Published: February 2021

ABSTRACTRecent advances in G protein-coupled receptor (GPCR) structural elucidation have strengthened previous hypotheses that multi-dimensional signal propagation mediated by these receptors is, in part, dependent on their conformational mobility. However, the relationship between receptor function and static structures determined via crystallography or cryo-electron microscopy is not always clear. This study examines the contribution of peptide agonist conformational plasticity to activation of the glucagon-like peptide-1 receptor (GLP-1R), an important clinical target. We employ variants of the peptides GLP-1 and exendin-4 to explore the interplay between helical propensity near the agonist N-terminus and the ability to bind to and activate the receptor. Cryo-EM analysis of a complex involving an exendin-4 analogue, the GLP-1R and Gsprotein revealed two receptor conformers with distinct modes of peptide-receptor engagement. Our functional and structural data suggest that receptor conformational dynamics associated with flexibility of the peptide N-terminal activation domain may be a key determinant of agonist efficacy.
REVA as a Well-curated Database for Human Expression-modulating Variants
Authors: Wang Yu , Shi Fang-Yuan , Liang Yu , Gao Ge 
Published: February 2021

AbstractMore than 80% of disease- and trait-associated human variants are noncoding. By systematically screening multiple large-scale studies, we compiled REVA, a manually curated database for over 11.8 million experimentally tested noncoding variants with expression-modulating potentials. We provided 2424 functional annotations that could be used to pinpoint plausible regulatory mechanism of these variants. We further benchmarked multiple state-of-the-art computational tools and found their limited sensitivity remains a serious challenge for effective large-scale analysis. REVA provides high-qualify experimentally tested expression-modulating variants with extensive functional annotations, which will be useful for users in the noncoding variants community. REVA is available at http://reva.gao-lab.org.