bluuebunny/crossref_metadata_2025_split huggingface dataset:
Guideline-based Chinese herbal medicine treatment plus standard care for severe coronavirus disease 2019 (G-CHAMPS): evidence from China
Authors: Ye Yong-an 
Published: April 2020

AbstractObjectivesTo assess outcomes in patients who have severe coronavirus disease 2019 (COVID-19) and were treated with either China guideline based Chinese herbal medicines (CHMs) plus standard care or standard care alone.DesignA pilot randomized controlled trial.SettingHubei Provincial Hospital of Integrated Chinese and Western Medicine, Wuhan, ChinaPatientsA total of 42 adults with severe COVID-19.InterventionsParticipants in the CHM plus standard care group received CHM and standard care, and the control group received standard care alone.Measurements and Main ResultsThe primary outcome was the change in the disease severity category of COVID-19 after treatment at 7 days. Among 42 participants who were randomized (mean [SD] age 60.43 years [12.69 years]; 21 [50%] were aged ≥ 65 years; and 35 [83%] women, 42 (100%) had data available for the primary outcome. For the primary outcome, one patient from each group died during treatment; the odds of a shift towards death was lower in the CHM plus group than the standard care alone group (common OR 0.59, 95% CI 0.148 to 2.352 P=.454). Three (2 from the CHM plus group and 1 from the standard care alone group) patients progressed from severe to critical illness. After treatment, mild, moderate, and severe COVID-19 disease accounted for 18% (5) vs 14% (2), 71% (20) vs 64% (9), and 0% (0) vs 7% (1) of the patients treated with CHM plus standard care vs. standard care alone.ConclusionsFor the first time, the G-CHAMPS trial provided valuable information for the national guideline-based CHM treatment for hospitalized patients with severe COVID-19. CHM effects in COVID-19 may be clinically important and warrant further consideration and studies.
Lectin-like Intestinal Defensin Inhibits 2019-nCoV Spike binding to ACE2
Authors: Wang Cheng , Wang Shaobo , Li Daixi , Zhao Xia , Han Songling , Wang Tao , Zhao Gaomei , Chen Yin , Chen Fang , Zhao Jianqi , Wang Liting , Sun Wei , Huang Yi , Su Yongping , Wei Dongqing , Zhao Jinghong , Wang Junping 
Published: April 2020

AbstractThe burgeoning epidemic caused by novel coronavirus 2019 (2019-nCoV) is currently a global concern. Angiotensin-converting enzyme-2 (ACE2) is a receptor of 2019-nCoV spike 1 protein (S1) and mediates viral entry into host cells. Despite the abundance of ACE2 in small intestine, few digestive symptoms are observed in patients infected by 2019-nCoV. Herein, we investigated the interactions between ACE2 and human defensins (HDs) specifically secreted by intestinal Paneth cells. The lectin-like HD5, rather than HD6, bound ACE2 with a high affinity of 39.3 nM and weakened the subsequent recruitment of 2019-nCoV S1. The cloak of HD5 on the ligand-binding domain of ACE2 was confirmed by molecular dynamic simulation. A remarkable dose-dependent preventive effect of HD5 on 2019-nCoV S1 binding to intestinal epithelial cells was further evidenced byin vitroexperiments. Our findings unmasked the innate defense function of lectin-like intestinal defensin against 2019-nCoV, which may provide new insights into the prevention and treatment of 2019-nCoV infection.
A new mutant mouse model lacking mitochondrial-associated CB1receptor
Authors: Pagano Zottola Antonio C. , Soria-Gomez Edgar , Bonilla-del-Río Itziar , Muguruza Carolina , Terral Geoffrey , Robin Laurie M. , da Cruz José F. Oliveira , Redon Bastien , Lesté-Lasserre Thierry , Tolentino-Cortes Tarson , Puente Nagore , Barreda-Gómez Gabriel , Chaouloff Francis , Callado Luis F. , Grandes Pedro , Marsicano Giovanni , Bellocchio Luigi 
Published: April 2020

SUMMARYThe idea that the effects of drugs largely depend on subcellular target location is emerging as a novel predictive factor of their beneficial or adverse outcomes. G protein-coupled type-1 cannabinoid receptors (CB1) are regulators of several brain functions as well as the main targets of cannabinoid-based medicines.Besides their classical location at plasma membranes, CB1receptors are present at different locations within cells, including in association to mitochondrial membranes (mtCB1). Here we report the generation and characterization of a mutant mouse line, which lack mtCB1receptors.
Epitope-based chimeric peptide vaccine design against S, M and E proteins of SARS-CoV-2 etiologic agent of global pandemic COVID-19: anin silicoapproach
Authors: Rahman M. Shaminur , Hoque M. Nazmul , Islam M. Rafiul , Akter Salma , Rubayet-Ul-Alam A. S. M. , Siddique Mohammad Anwar , Saha Otun , Rahaman Md. Mizanur , Sultana Munawar , Hossain M. Anwar 
Published: April 2020

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the ongoing pandemic of coronavirus disease 2019 (COVID-19), a public health emergency of international concern declared by the World Health Organization (WHO). An immuno-informatics approach along with comparative genomic was applied to design a multi-epitope-based peptide vaccine against SARS-CoV-2 combining the antigenic epitopes of the S, M and E proteins. The tertiary structure was predicted, refined and validated using advanced bioinformatics tools. The candidate vaccine showed an average of ≥ 90.0% world population coverage for different ethnic groups. Molecular docking of the chimeric vaccine peptide with the immune receptors (TLR3 and TLR4) predicted efficient binding. Immune simulation predicted significant primary immune response with increased IgM and secondary immune response with high levels of both IgG1 and IgG2. It also increased the proliferation of T-helper cells and cytotoxic T-cells along with the increased INF-γ and IL-2 cytokines. The codon optimization and mRNA secondary structure prediction revealed the chimera is suitable for high-level expression and cloning. Overall, the constructed recombinant chimeric vaccine candidate demonstrated significant potential and can be considered for clinical validation to fight against this global threat, COVID-19.
Burst-dependent synaptic plasticity can coordinate learning in hierarchical circuits
Authors: Payeur Alexandre , Guerguiev Jordan , Zenke Friedemann , Richards Blake A. , Naud Richard 
Published: April 2020

AbstractSynaptic plasticity is believed to be a key physiological mechanism for learning. It is well-established that it depends on pre and postsynaptic activity. However, models that rely solely on pre and postsynaptic activity for synaptic changes have, to date, not been able to account for learning complex tasks that demand credit assignment in hierarchical networks. Here, we show that if synaptic plasticity is regulated by high-frequency bursts of spikes, then neurons higher in a hierarchical circuit can coordinate the plasticity of lower-level connections. Using simulations and mathematical analyses, we demonstrate that, when paired with short-term synaptic dynamics, regenerative activity in the apical dendrites, and synaptic plasticity in feedback pathways, a burst-dependent learning rule can solve challenging tasks that require deep network architectures. Our results demonstrate that well-known properties of dendrites, synapses, and synaptic plasticity are sufficient to enable sophisticated learning in hierarchical circuits.
Divergent microbiota of echinoid eggs separated by the Isthmus of Panama
Authors: Carrier Tyler J. , Lessios Harilaos A. , Reitzel Adam M. 
Published: April 2020

AbstractRelationships between animals and their associated microbiota is dependent on the evolutionary history of the host and on the environment. The majority of studies tend to focus on one of these factors and rarely consider how both determine the community composition of the associated bacteria. One “natural experiment” to test how evolutionary history, shared environments, and the interaction between these factors drive community composition is to compare geminate species pairs. Echinoids separated by the Isthmus of Panama are suitable for this comparison due to the known evolutionary history and differences in oceanographic characteristics of the Caribbean Sea and Pacific Ocean. By comparing the egg-associated microbiota for theEchinometraandDiademageminate species pairs, we show that both pairs of geminate species associate with distinct bacterial communities in patterns consistent with phylosymbiosis, and that the interaction between the evolutionary history of the host and the environment best explain differences in these communities. Moreover, we find that particular microbial taxa differed considerably between, but not within, oceans and that the microbiota of the two CaribbeanEchinometraspecies were dominated by the phototrophic Oxyphotobacteria.
Nutritional inter-dependencies and a carbazole-dioxygenase are key elements of a bacterial consortium relying on aSphingomonasfor the degradation of the fungicide thiabendazole
Authors: Sotirios Vasileiadis , Chiara Perruchon , Benjamin Scheer , Lorenz Adrian , Nicole Steinbach , Marco Trevisan , Patricia Plaza-Bolaños , Ana Agüera , Antonis Chatzinotas , Dimitrios Karpouzas G 
Published: April 2020

AbstractBackgroundThiabendazole (TBZ), is a benzimidazole fungicide and anthelminthic whose high persistence and toxicity pose a serious environmental threat. In our quest for environmental mitigation we previously isolated the first TBZ-degrading bacterial consortium and provided preliminary evidence for its composition and the degrading role of aSphingomonas. Here, we employed a multi-omic approach combined with DNA-stable isotope probing (SIP) to determine the genetic make-up of the key consortium members, to disentangle nutritional and metabolic interdependencies, to identify the transformation pathway of TBZ and to understand the genetic network driving its transformation.ResultsTime-series SIP in combination with amplicon sequencing analysis verified the key role ofSphingomonasin TBZ degradation by assimilating over 80% of the13C-labelled phenyl moiety of TBZ. Non-target mass spectroscopy (MS) analysis showed the accumulation of thiazole-4-carboxamidine as a single dead-end transformation product and no phenyl-containing derivative, in line with the phenyl moiety assimilation in the SIP analysis. Time series metagenomic analysis of the consortium supplemented with TBZ or succinate led to the assembly of 18 metagenome-assembled genomes (MAGs) with >80% completeness, six (Sphingomonas3X21F,γ-Proteobacterium34A,Bradyrhizobiaceae9B andHydrogenophaga19A, 13A, and 23F) being dominant. Meta-transcriptomic and -proteomic analysis suggested thatSphingomonasmobilize a carbazole dioxygenase (car) operon during the initial cleavage of TBZ to thiazole-4-carboxamidine and catechol, the latter is further transformed by enzymes encoded in a catecholortho-cleavage (cat) operon; both operons being up-regulated during TBZ degradation. Computational docking analysis of the terminal oxygenase component ofcar, CarAa, showed high affinity to TBZ, comparable to carbazole, reinforcing its high potency for TBZ transformation. These results suggest no interactions between consortium members in TBZ transformation, performed solely bySphingomonas. In contrast, gene expression network analysis revealed strong interactions betweenSphingomonasMAG 3X12F andHydrogenophagaMAG 23F, withHydrogenophagaactivating its cobalamin biosynthetic pathway andSphingomonasits cobalamin salvage pathway along TBZ degradation.ConclusionsOur findings suggest interactions between consortium members which align with the “black queen hypothesis”:Sphingomonasdetoxifies TBZ, releasing consortium members by a toxicant; in return for this,Hydrogenophaga23F provides cobalamin to the auxotrophicSphingomonas.
AutoRELACS: Automated Generation And Analysis Of Ultra-parallel ChIP-seq
Authors: Arrigoni L. , Ferrari F. , Weller J. , Bella C. , Bönisch U. , Manke T. 
Published: April 2020

ABSTRACTChromatin immunoprecipitation followed by sequencing (ChIP-seq) is a method used to profile protein-DNA interactions genome-wide. RELACS (Restriction Enzyme-based Labeling of Chromatinin Situ) is a recently developed ChIP-seq protocol that deploys a chromatin barcoding strategy to enable standardized and high-throughput generation of ChIP-seq data. The manual implementation of RELACS is constrained by human processivity in both data generation and data analysis. To overcome these limitations, we have developed AutoRELACS, an automated implementation of the RELACS protocol using the liquid handler Biomek i7 workstation. We match the unprecedented processivity in data generation allowed by AutoRELACS with the automated computation pipelines offered by snakePipes. In doing so, we build a continuous workflow that streamlines epigenetic profiling, from sample collection to biological interpretation. Here, we show that AutoRELACS successfully automates chromatin barcode integration, and is able to generate high-quality ChIP-seq data comparable with the standards of the manual protocol, also for limited amounts of biological samples.
Canonical and noncanonical features of the mouse visual cortical hierarchy
Authors: D’Souza Rinaldo D. , Wang Quanxin , Ji Weiqing , Meier Andrew M. , Kennedy Henry , Knoblauch Kenneth , Burkhalter Andreas 
Published: April 2020

ABSTRACTNeocortical circuit computations underlying active vision are performed by a distributed network of reciprocally connected, functionally specialized areas. Mouse visual cortex is a dense, hierarchically organized network, comprising subnetworks that form preferentially interconnected processing streams. To determine the detailed layout of the mouse visual hierarchy, laminar patterns formed by interareal axonal projections, originating in each of ten visual areas were analyzed. Reciprocally connected pairs of areas, and shared targets of pairs of source areas, exhibited structural features consistent with a hierarchical organization. Beta regression analyses, which estimated a continuous measure of hierarchical distance, indicated that the network comprises multiple hierarchies embedded within overlapping processing levels. Single unit recordings showed that within each processing stream, receptive field sizes typically increased with increasing hierarchical level; however, ventral stream areas showed overall larger receptive field diameters. Together, the results reveal canonical and noncanonical hierarchical network motifs in mouse visual cortex.
Minimal structural elements required for midline repulsive signaling and regulation ofDrosophilaRobo1
Authors: Brown Haley E. , Evans Timothy A. 
Published: April 2020

AbstractThe Roundabout (Robo) family of axon guidance receptors has a conserved ectodomain arrangement of five immunoglobulin-like (Ig) domains plus three fibronectin (Fn) repeats. Based on the strong evolutionary conservation of this domain structure among Robo receptors, as well asin vitrostructural and domain-domain interaction studies of Robo family members, this ectodomain arrangement is predicted to be important for Robo receptor signaling in response to Slit ligands. Here, we define the minimal ectodomain structure required for Slit binding and midline repulsive signalingin vivobyDrosophilaRobo1. We find that the majority of the Robo1 ectodomain is dispensable for both Slit binding and repulsive signaling. We show that a significant level of midline repulsive signaling activity is retained when all Robo1 ectodomain elements apart from Ig1 are deleted, and that the combination of Ig1 plus one additional ectodomain element (Ig2, Ig5, or Fn3) is sufficient to restore midline repulsion to wild type levels. Further, we find that deleting four out of five Robo1 Ig domains (ΔIg2-5) does not affect negative regulation of Robo1 by Commissureless (Comm) or Robo2, while variants lacking all three fibronectin repeats (ΔFn1-3 and ΔIg2-Fn3) are insensitive to regulation by both Comm and Robo2, signifying a novel regulatory role for Robo1’s Fn repeats. Our results provide anin vivoperspective on the importance of the conserved 5+3 ectodomain structure of Robo receptors, and suggest that specific biochemical properties and/or ectodomain structural conformations observedin vitrofor domains other than Ig1 may have limited significance forin vivosignaling in the context of midline repulsion.
Sequence analysis of SARS-CoV-2 genome reveals features important for vaccine design
Authors: Kames Jacob , Holcomb David D. , Kimchi Ofer , DiCuccio Michael , Hamasaki-Katagiri Nobuko , Wang Tony , Komar Anton A. , Alexaki Aikaterini , Kimchi-Sarfaty Chava 
Published: April 2020

AbstractAs the SARS-CoV-2 pandemic is rapidly progressing, the need for the development of an effective vaccine is critical. A promising approach for vaccine development is to generate, through codon pair deoptimization, an attenuated virus. This approach carries the advantage that it only requires limited knowledge specific to the virus in question, other than its genome sequence. Therefore, it is well suited for emerging viruses for which we may not have extensive data. We performed comprehensivein silicoanalyses of several features of SARS-CoV-2 genomic sequence (e.g., codon usage, codon pair usage, dinucleotide/junction dinucleotide usage, RNA structure around the frameshift region) in comparison with other members of the coronaviridae family of viruses, the overall human genome, and the transcriptome of specific human tissues such as lung, which are primarily targeted by the virus. Our analysis identified the spike (S) and nucleocapsid (N) proteins as promising targets for deoptimization and suggests a roadmap for SARS-CoV-2 vaccine development, which can be generalizable to other viruses.
rapidPop: Rapid population assessments of wildlife using camera trap data in R Shiny Applications
Authors: Tabak Michael A. , Lewis Jesse S. , Schlichting Peter E , Snow Nathan P. , VerCauteren Kurt C. , Miller Ryan S. 
Published: April 2020

AbstractrapidPopis a new R package for implementing occupancy models for Rapid Population Assessments (RPAs) with data from camera traps. RPAs are designed to provide quick assessments of a density index so that users can identify relative changes in density associated with changes in conditions (Schlichtinget al., 2020). For example, users may want to assess if there was a change in density after an effort to cull an invasive species.rapidPopprovides a Shiny Application for running occupancy models with the option to include the effect of parameters on occupancy (e.g., before or after a culling operation).
Root xylem in three woody angiosperm species is not more vulnerable to embolism than stem xylem
Authors: Wu Min , Zhang Ya , Oya Thais , Marcati Carmen Regina , Pereira Luciano , Jansen Steven 
Published: April 2020

AbstractAimsSince plants are compartmentalised organisms, failure of their hydraulic transport system could differ between organs. We test here whether xylem tissue of stems and roots differ in their drought-induced embolism resistance, and whether intact roots are equally resistant to embolism than root segments.MethodsEmbolism resistance of stem and root xylem was measured based on the pneumatic technique forAcer campestre,A. pseudoplatanusandCorylus avellana, comparing also intact roots and root segments ofC. avellana. Moreover, we compared anatomical features such as interconduit pit membrane between roots and stems.ResultsWe found a higher embolism resistance for roots than stems, although a significant difference was only found forA. pseudoplatanus.Interconduit pit membrane thickness was similar for both organs of the twoAcerspecies, but pit membranes were thicker in roots than stems ofC. avellana. Also, embolism resistance of an intact root network was similar to thick root segments forC. avellana.ConclusionOur observations show that root xylem is not more vulnerable to embolism than stem xylem, although more species need to be studied to test if this finding can be generalised. We also demonstrated that the pneumatic method can be applied to non-terminal plant samples.
Characterization of Met25 as a Color Associated Genetic Marker inYarrowia lipolytica
Authors: Edwards Harley , Yang Zhiliang , Xu Peng 
Published: April 2020

AbstractYarrowia lipolyticaoffers an ideal host for biosynthesis of high value natural products and oleochemicals through metabolic engineering despite being restricted to a limited number of selective markers, and counter-selection achieved primarily withURA3. In this work, we investigateMET25, a locus of sulfide housekeeping within the cell, to be exploited as a standard genetic marker. Divalent lead supplemented in media induces lead sulfide (PbS) aggregation inMET25-deficient cells such that deficient cells grow brown/black, and cells with functional copies ofMET25grow white. Loss ofMET25did not induce strict auxotrophic requirements for methionine inY.lipolytica, indicatingMET25deficiency could be rescued by alternative pathways. Plasmid and chromosomal-based complementation ofMET25deficient cells on a double layer agar plate with nutrient gradients demonstrates delayed phenotype (white morphology) restoration, indicating post-transcriptional feedback regulation of methionine biosynthesis in this yeast.MET25deficientY. lipolyticacould be used as an efficient whole-cell lead sensor with detection limit as low as 10 ppm of lead in drinking water. We further tested whetherMET25deficiency can be exploited to confer resistance to methyl-mercury through chemical neutralization and detoxification. Kinetic growth curves of wild type andMET25-deficient cells were obtained under varying concentrations of methylmercury and cellular toxicity to methyl mercury was calculated from the Hill equation. Our results indicate that methylmecury may not be used as the counter-selectable marker due to insignificant changes of growth fitness. This work demonstrates the utility of usingMET25as a sensitive lead sensor and the challenges of usingMET25as a counter-selectable genetic marker, as well as the complex regulation of methionine biosynthesis inY. lipolyitca, which may shed lights for us to develop valuable biotechnological applications centering around the sulfur house-keeping metabolism of the nonconventional yeast.