bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of super-spreaders in COVID-19: mapping genome variation worldwide
Authors: Gómez-Carballa Alberto , Bello Xabier , Pardo-Seco Jacobo , Martinón-Torres Federico , Salas Antonio 
Published: May 2020

AbstractThe human pathogen severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the major pandemic of the 21stcentury. We analyzed >4,700 SARS-CoV-2 genomes and associated meta-data retrieved from public repositories. SARS-CoV-2 sequences have a high sequence identity (>99.9%), which drops to >96% when compared to bat coronavirus. We built a mutation-annotated reference SARS-CoV-2 phylogeny with two main macro-haplogroups, A and B, both of Asian origin, and >160 sub-branches representing virus strains of variable geographical origins worldwide, revealing a uniform mutation occurrence along branches that could complicate the design of future vaccines. The root of SARS-CoV-2 genomes locates at the Chinese haplogroup B1, with a TMRCA dating to 12 November 2019 - thus matching epidemiological records. Sub-haplogroup A2a originates in China and represents the major non-Asian outbreak. Multiple founder effect episodes, most likely associated with super-spreader hosts, explain COVID-19 pandemic to a large extent.
Metagenomic association analysis of gut symbiontLactobacillus reuteriwithout host-specific genome isolation
Authors: Park Sein , Steinegger Martin , Cho Ho-Seong , Chun Jongsik 
Published: May 2020

AbstractLactobacillus reuteriis a model symbiont colonizing the guts of vertebrates used for studies on host adaptation of the gut symbiont. Previous studies investigated host-specific phylogenetic and functional properties by isolating its genomic sequence. This dependency on genome isolation is a significant bottleneck. Here we propose a method to study the association betweenL. reuteriand its hosts directly from metagenomic reads without strain isolation by using pan-genomes.We characterized the host-specificity ofL. reuteriin metagenomic samples not only in the previously studied organisms (mice and pigs) but additionally in dogs. For each sample, two types of profiles were generated: (1) genome-based strain type abundance profiles and (2) gene composition profiles. Our profiles showed host-association ofL. reuteriin both phylogenetic and functional aspects without depending on the host-specific genome isolation. We could observe not only the presence of host-specific lineages but also the dominant lineages associated with the different hosts.Furthermore, we show that metagenome-assembled genomes provide detailed insights into the host-specificity ofL. reuteri. We could infer evolutionary trajectories of host-associativeL. reuteristrains in the metagenomic samples by placing the metagenome-assembled genomes into a phylogenetic tree and identify novel host-specific genes which were unannotated in existing pan-genome databases.Our pan-genomic approach drops the need for time-consuming and expensive host-specific genome isolation while producing consistent results with previous host-association findings in mice and pigs. Additionally, we could predict associations that have not yet been studied in dogs.
Metagenomic profiling of ammonia- and methane-oxidizing microorganisms in a Dutch drinking water treatment plant
Authors: Poghosyan Lianna , Koch Hanna , Frank Jeroen , van Kessel Maartje A.H.J. , Cremers Geert , van Alen Theo , Jetten Mike S.M. , Op den Camp Huub J.M. , Lücker Sebastian 
Published: May 2020

AbstractElevated concentrations of ammonium and methane in groundwater can cause severe problems during drinking water production. To avoid their accumulation, raw water in the Netherlands, and many other countries, is purified by sand filtration. These drinking water filtration systems select for microbial communities that mediate the biodegradation of organic and inorganic compounds. In this study, the active layers and wall biofilm of a Dutch drinking water treatment plant (DWTP) were sampled at different locations along the filtration units of the plant over three years. We used high-throughput sequencing in combination with differential coverage and sequence composition-based binning to recover 56 near-complete metagenome-assembled genomes (MAGs) with an estimated completion of ≥70% and with ≤10% redundancy. These MAGs were used to characterize the microbial communities involved in the conversion of ammonia and methane. The methanotrophic microbial communities colonizing the wall biofilm (WB) and the granular material of the primary rapid sand filter (P-RSF) were dominated by members of theMethylococcaceaeandMethylophilaceae.The abundance of these bacteria drastically decreased in the secondary rapid sand filter (S-RSF) samples. In all samples, complete ammonia-oxidizing (comammox)Nitrospirawere the most abundant nitrifying guild. Clade A comammoxNitrospiradominated the P-RSF, while clade B was most abundant in WB and S-RSF, where ammonium concentrations were much lower. In conclusion, the knowledge obtained in this study contributes to understanding the role of microorganisms in the removal of carbon and nitrogen compounds during drinking water production. We furthermore found that drinking water treatment plants represent valuable model systems to study microbial community function and interaction.HighlightsMicrobial distribution was mainly influenced by sampling location within the DWTPClade A comammoxNitrospirawere the dominant nitrifiers in the primary sand filterClade B was most abundant in samples from wall biofilm and the secondary filterA novelMethylophilaceae-affiliated methanotroph dominated the primary sand filter
Protective role of neuronal and lymphoid cannabinoid CB2 receptors in neuropathic pain
Authors: Cabañero David , Ramírez-López Angela , Drews Eva , Schmöle Anne , Otte David M. , Wawrzczak-Bargiela Agnieszka , Encabo Hector Huerga , Kummer Sami , Przewlocki Ryszard , Zimmer Andreas , Maldonado Rafael 
Published: May 2020

AbstractCannabinoid CB2 receptor (CB2r) agonists are potential painkillers void of psychotropic effects. Peripheral immune cells, neurons and glia express CB2r, however the involvement of CB2r from these cells in neuropathic pain remains unresolved. We explored spontaneous neuropathic pain through on-demand self-administration of the selective CB2r agonist JWH133 in wild-type and knockout mice lacking CB2r in neurons, monocytes or constitutively. Operant self-administration reflected drug-taking to alleviate spontaneous pain, nociceptive and affective manifestations. While constitutive deletion of CB2r disrupted JWH133-taking behavior, this behavior was not modified in monocyte-specific CB2r knockouts and was increased in mice defective in neuronal CB2r knockouts suggestive of increased spontaneous pain. Interestingly, CB2r-positive lymphocytes infiltrated the injured nerve and possible CB2r transfer from immune cells to neurons was found. Lymphocyte CB2r depletion also exacerbated JWH133 self-administration and inhibited antinociception. This work identifies a simultaneous activity of neuronal and lymphoid CB2r that protects against spontaneous and evoked neuropathic pain.
Deciphering the genetic diversity of landraces with high-throughput SNP genotyping of DNA bulks: methodology and application to the maize 50k array
Authors: Arca Mariangela , Mary-Huard Tristan , Gouesnard Brigitte , Bérard Aurélie , Bauland Cyril , Combes Valérie , Madur Delphine , Charcosset Alain , Nicolas Stéphane D. 
Published: May 2020

ABSTRACTGenebanks harbor original landraces carrying many original favorable alleles for mitigating biotic and abiotic stresses. Their genetic diversity remains however poorly characterized due to their large within genetic diversity. We developed a high-throughput, cheap and labor saving DNA bulk approach based on SNP Illumina Infinium HD array to genotype landraces. Samples were gathered for each landrace by mixing equal weights from young leaves, from which DNA was extracted. We then estimated allelic frequencies in each DNA bulk based on fluorescent intensity ratio (FIR) between two alleles at each SNP using a two step-approach. We first tested either whether the DNA bulk was monomorphic or polymorphic according to the two FIR distributions of individuals homozygous for allele A or B, respectively. If the DNA bulk was polymorphic, we estimated its allelic frequency by using a predictive equation calibrated on FIR from DNA bulks with known allelic frequencies. Our approach: (i) gives accurate allelic frequency estimations that are highly reproducible across laboratories, (ii) protects against false detection of allele fixation within landraces. We estimated allelic frequencies of 23,412 SNPs in 156 landraces representing American and European maize diversity. Modified Roger’s genetic Distance between 156 landraces estimated from 23,412 SNPs and 17 SSRs using the same DNA bulks were highly correlated, suggesting that the ascertainment bias is low. Our approach is affordable, easy to implement and does not require specific bioinformatics support and laboratory equipment, and therefore should be highly relevant for large-scale characterization of genebanks for a wide range of species.
Gamma secretase inhibitors inhibit ovarian cancer development and enhance olaparib’s anti-ovarian cancer activity and its mechanism
Authors: Xiaoxiao Yao , Nan Zheng 
Published: May 2020

AbstractBackgroundOvarian cancer is the fifth leading cause of cancer-related deaths in women. Although cytoreductive surgery combined with chemotherapy and / or targeted therapy has achieved a certain effect, but advanced patients have limited clinical benefits and are prone to relapse. Among them, Notch / jagged1 and Wnt / β-catenin signal transduction plays an important role in the development of ovarian cancer and chemotherapy resistance, and it is very important to find new effective therapeutic drugs to inhibit tumor development and increase tumor chemotherapy sensitivity.MethodsTo establish ovarian cancer xenotransplantation model, to detect the effects of γ-secretase inhibitor, olaparib and combination drugs on the development of ovarian cancer, and to detect the proliferation and apoptosis of ovarian cancer cells with γ-secretase inhibitor, olaparib and combination drugs .After knocking down Jagged1 or β-catenin, the protein expression levels of related signaling pathways under different drug treatments were analyzed by immunoblotting, and related gene expression changes were analyzed.ResultsDAPT reduced β-catenin expression in a proteasome-synthetic pathway-dependent manner, thereby inhibiting the synthesis and transcription of Jagged1 protein, thereby inhibiting the expression of Notch signal transduction pathway-related proteins and gene transcription, inhibiting the activity of ovarian cancer cells and inducing cell apoptosis death, enhance the anti-ovarian cancer activity of olaparib.ConclusionDAPT inhibits cell proliferation, induces cell apoptosis, inhibits tumor development in vivo through β-catenin / Jagged1 inhibition, and exerts anti-ovarian cancer activity sensitizing effect of olaparib.
Isolation of and Characterization of Neutralizing Antibodies to Covid-19 from a Large Human Naïve scFv Phage Display Library
Authors: Yuan Andy Q. , Zhao Likun , Bai Lili , Meng Qingwu , Wen Zhenguo , Li Yanhu , Guo Daqing , Zhen Shanshan , Chen Xiaojun , Yang Ji , Xue Xiaoying 
Published: May 2020

AbstractSARS-CoV-2 (Covid-19) has caused currently ongoing global plague and imposed great challenges to health managing systems all over the world, with millions of infections and hundreds of thousands of deaths. In addition to racing to develop vaccines, neutralizing antibodies (nAbs) to this virus have been extensively sought and are expected to provide another prevention and therapy tool against this frantic pandemic. To offer fast isolation and shortened early development, a large human naïve phage display antibody library, was built and used to screen specific nAbs to the receptor-binding domain, RBD, the key for Covid-19 virus entry through a human receptor, ACE2. The obtained RBD-specific antibodies were characterized by epitope mapping, FACS and neutralization assay. Some of the antibodies demonstrated spike-neutralizing property and ACE2-competitiveness. Our work proved that RBD-specific neutralizing binders from human naïve antibody phage display library are promising candidates to for further Covid-19 therapeutics development.
EHBP1 and EHD2 regulate Dll4 caveolin-mediated endocytosis during blood vessel development
Authors: Webb Amelia M , Francis Caitlin R , Webb Jayson M , Kincross Hayle , Lundy Keanna M , Judson Rachael , Westhoff Dawn , Meadows Stryder M , Kushner Erich J 
Published: May 2020

ABSTRACTDespite the absolute requirement of Delta/Notch signaling to activate lateral inhibition during early blood vessel development, many mechanisms remain unclear. Here, we identify EHD2 and EHBP1 as novel regulators of Notch activation in endothelial cells through controlling endocytosis of Delta-like ligand 4 (Dll4). Knockout of EHBP1 and EHD2 in zebrafish produced a significant increase in ectopic sprouts in zebrafish intersomitic vessels during development and a reduction in downstream Notch signaling.In vitro, EHBP1 and EHD2 localized to plasma membrane-bound Dll4 and actin independently of clathrin. Disruption of caveolin endocytosis resulted in EHBP1 and EHD2 failing to organize around Dll4 as well as loss of Dll4 internalization in endothelial cells. Overall, we demonstrate that EHBP1 and EHD2 regulate Dll4 endocytosis by anchoring caveolar endocytic pits to the actin cytoskeleton.
Spontaneous restoration of functional β-cell mass in obese SM/J mice
Authors: Miranda Mario A , Carson Caryn , St Pierre Celine L , Macias-Velasco Juan F , Hughes Jing W , Kunzmann Marcus , Schmidt Heather , Wayhart Jessica P , Lawson Heather A 
Published: May 2020

AbstractMaintenance of functional β-cell mass is critical to preventing diabetes, but the physiological mechanisms that cause β-cell populations to thrive or fail in the context of obesity are unknown. High fat-fed SM/J mice spontaneously transition from hyperglycemic-obese to normoglycemic-obese with age, providing a unique opportunity to study β-cell adaptation. Here, we characterize insulin homeostasis, islet morphology, and β-cell function during SM/J’s diabetic remission. As they resolve hyperglycemia, obese SM/J mice dramatically increase circulating and pancreatic insulin levels while improving insulin sensitivity. Immunostaining of pancreatic sections reveals that obese SM/J mice selectively increase β-cell mass but not α-cell mass. Obese SM/J mice do not show elevated β-cell mitotic index, but rather elevated α-cell mitotic index. Functional assessment of isolated islets reveals that obese SM/J mice increase glucose stimulated insulin secretion, decrease basal insulin secretion, and increase islet insulin content. These results establish that β-cell mass expansion and improved β-cell function underlie the resolution of hyperglycemia, indicating that obese SM/J mice are a valuable tool for exploring how functional β-cell mass can be recovered in the context of obesity.
Neighbor QTL: an interval mapping method for quantitative trait loci underlying plant neighborhood effects
Authors: Sato Yasuhiro , Takeda Kazuya , Nagano Atsushi J. 
Published: May 2020

AbstractPhenotypes of sessile organisms, such as plants, rely not only on their own genotype but also on the genotypes of neighboring individuals. Previously, we incorporated such neighbor effects into a single-marker regression using the Ising model of ferromagnetism. However, little is known about how to incorporate neighbor effects in quantitative trait locus (QTL) mapping. In this study, we propose a new method for interval QTL mapping of neighbor effects, named “Neighbor QTL”. The algorithm of neighbor QTL involves the following: (i) obtaining conditional self-genotype probabilities with recombination fraction between flanking markers, (ii) calculating neighbor genotypic identity using the self-genotype probabilities, and (iii) estimating additive and dominance deviation for neighbor effects. Our simulation using F2 and backcross lines showed that the power to detect neighbor effects increased as the effective range became smaller. The neighbor QTL was applied to insect herbivory on Col × Kas recombinant inbred lines ofArabidopsis thaliana. Consistent with previous evidence, the pilot experiment detected a self QTL effect on the herbivory atGLABRA1locus. We also observed a weak QTL on chromosome 4 regarding neighbor effects on the herbivory. The neighbor QTL method is available as an R package (https://cran.r-project.org/package=rNeighborQTL), providing a novel tool to investigate neighbor effects in QTL studies.
Pulsed Third-Spin-Assisted Recoupling NMR for Obtaining Long-Range13C-13C and15N-13C Distance Restraints
Authors: Gelenter Martin D. , Dregni Aurelio J. , Hong Mei 
Published: May 2020

AbstractWe introduce a class of pulsed third-spin-assisted recoupling (P-TSAR) magic-angle-spinning (MAS) solid-state NMR techniques that achieve efficient polarization transfer over long distances to provide important restraints for structure determination. These experiments operate with the same principle as continuous-wave (CW) TSAR experiments, by utilizing second-order cross terms between strong1H-13C and1H-15N dipolar couplings to achieve13C-13C and13C-15N polarization transfer. However, in contrast to the CW-TSAR experiments, these pulsed P-TSAR experiments require much less radiofrequency (rf) energy and allow a much simpler routine for optimizing the rf field strength. We call the techniques PULSAR (PULSed proton Asissted Recoupling) for homonuclear spin pairs andPERSPIRATIONCP (Proton-Enhanced Rotor-echo Short Pulse IRradiATION Cross-Polarization) for heteronuclear spin pairs. We demonstrate these techniques on the model protein GB1, and found cross peaks for distances as long as 10 and 8 Å for13C-13C and15N-13C spin pairs, respectively. We also apply these methods to the amyloid fibrils formed by the peptide hormone glucagon, and show that long-range correlation peaks are readily observed to constrain intermolecular packing in this cross-β fibril. We provide an analytical model for the PULSAR andPERSPIRATIONCP experiments to explain the measured and simulated chemical shift dependence and pulse flip angle dependence of polarization transfer. These two techniques are useful for measuring long-range distance restraints to determine the three-dimensional structures of proteins and other biological macromolecules.
Genome-wide CRISPR-Cas9 screen reveals the importance of the heparan sulfate pathway and the conserved oligomeric golgi complex for synthetic dsRNA uptake and Sindbis virus infection
Authors: Petitjean Olivier , Girardi Erika , Ngondo Richard Patryk , Lupashin Vladimir , Pfeffer Sébastien 
Published: May 2020

AbstractDouble stranded RNA (dsRNA) is the hallmark of many viral infections. dsRNA is produced either by RNA viruses during replication or by DNA viruses upon convergent transcription. Synthetic dsRNA is also able to mimic viral-induced activation of innate immune response and cell death. In this study, we employed a genome-wide CRISPR-Cas9 loss of function screen based on cell survival in order to identify genes implicated in the host response to dsRNA. By challenging HCT116 human cells with either synthetic dsRNA or Sindbis virus (SINV), we identified the heparan sulfate (HS) pathway as a crucial factor for dsRNA entry and we validated SINV dependency on HS. Interestingly, we uncovered a novel role for COG4, a component of the Conserved Oligomeric Golgi (COG) complex, as a factor involved in cell survival to both dsRNA and SINV in human cells. We showed that COG4 knock-out led to a decrease of extracellular HS, specifically affected dsRNA transfection efficiency and reduced viral production, explaining the increased cell survival of these mutants.ImportanceWhen facing a viral infection, the organism has to put in place a number of defense mechanisms in order to clear the pathogen from the cell. At the early phase of this preparation for fighting against the invader, the innate immune response is triggered by the sensing of danger signals. Among those molecular cues, double-stranded (dsRNA) is a very potent inducer of different reactions at the cellular level that can ultimately lead to cell death. Using a genome-wide screening approach, we set to identify genes involved in dsRNA entry, sensing and apoptosis induction in human cells. This allowed us to determine that the heparan sulfate pathway and the Conserved Oligomeric Golgi complex are key determinants allowing entry of both dsRNA and viral nucleic acid leading to cell death.
The impact of formulation change and R&D cooperation types on the eWOM of extension products
Authors: Kim Nayeong , Hwang Jihee , Lee Dongmin , Jeong Jaeseok , Moon Junghoon 
Published: May 2020

PurposeThe purpose of this paper is to investigate the effect of formulation categories (parent brand and extension product) and research and development (R&D) cooperation types on electronic word-of-mouth (eWOM) volume for extension products.Design/methodology/approachThis study uses data from 109 extension products in the Korean dessert market whose formulations were changed between 1 February 2014 and 19 February 2019. The formulation categories and R&D cooperation types are transformed into dummy variables to conduct a linear regression.FindingsThe formulation categories and R&D cooperation types play key roles in proliferating eWOM for formulation change products. The most effective way to proliferate eWOM is through product extension by changing the formulation of ice cream, beverage and snack category products. Furthermore, vertical R&D cooperation positively affects the proliferation of products' eWOM.Originality/valueThese findings contribute to increasing the chance of successful food product development by providing information on the formulation changes that are effective at inducing consumers' interest.
The effect of organisational context on group work: evidence in the Rioja wine industry in Spain
Authors: Gil Alfonso J. , Lázaro Ruiz Vicente , Ruiz Vega Agustín V. 
Published: May 2020

PurposeThis paper aims to focus on two basic dimensions of group work: cooperation and transfer of information. This paper has two objectives. The first objective is to analyse the effect of cooperation and transfer of information in group work according to employees’ perceptions of the Rioja wine industry. The second objective is to analyse the existence of significant differences in the perception of the basic dimensions of group work under different organisational contexts in the Rioja wine industry.Design/methodology/approachThe participants in the study are 230 workers from the Rioja wine industry. The data is collected through a personal interview using a questionnaire. Hypotheses are tested by multiple regression analysis.FindingsThe results indicate firstly that cooperation and transfer of information is related to “group work” variable positively, and secondly, significant differences were found in each of the contexts analysed. Besides, it has been found that the variable “transfer of information” is more explanatory of group work differences in organisational contexts than the variable “cooperation”.Originality/valueThis study verified that there is no homogeneity in group work in the Rioja wine industry. This study contributes to the knowledge about a significant industry of the economy and culture of the Rioja region, and the wine sector in general.