bluuebunny/crossref_metadata_2025_split huggingface dataset:
Arthropod IGF, Relaxin and Gonadulin, putative orthologs ofDrosophilainsulin-like peptides 6, 7 and 8, likely originated from an ancient gene triplication
Authors: Veenstra Jan A. 
Published: May 2020

AbstractBackgroundInsects have several genes coding for insulin-like peptides and they have been particularly well studied inDrosophila. Some of these hormones function as growth hormones and are produced by the fat body and the brain. These act through a typical insulin receptor tyrosine kinase. Two otherDrosophilainsulin-like hormones are either known or suspected to act through a G-protein coupled receptor. Although insulin-related peptides are known from other insect species,Drosophilainsulin-like peptide 8, one that uses a G-protein coupled receptor, has so far only been identified fromDrosophilaand other flies. However, its receptor is widespread within arthropods and hence it should have orthologs. Such putative orthologs were recently identified in decapods and have been called gonadulins.MethodologyIn an effort to identify gonadulins in other arthropods public genome assemblies and short-read archives from insects and other arthropods were explored for the presence of genes and transcripts coding insulin-like peptides and their putative receptors.ResultsGonadulins were detected in a number of arthropods. In those species for which transcriptome data from the gonads is available insect gonadulin genes are expressed in the ovaries and at least in some species also in the testes. In some insects differences in gonadulin expression in the ovary between actively reproducing and non-reproducing females differs more than 100-fold. Putative orthologs ofDrosophilailp 6 were also identified. In several non-Dipteran insects these peptides have C-terminally extensions that are alternatively spliced. The predicted peptides have been called arthropod insulin-like growth factors. In cockroaches, termites and stick insects genes coding for the arthropod insulin-like growth factors, gonadulin and relaxin, a third insulin-like peptide, are encoded by genes that are next to one another suggesting that they are the result of a local gene triplication. Such a close chromosomal association was also found for the arthropod insulin-like growth factor and gonadulin genes in spiders. Phylogenetic tree analysis of the typical insulin receptor tyrosine kinases from insects, decapods and chelicerates shows that the insulin signaling pathway evolved differently in these three groups. The G-protein coupled receptors that are related to theDrosophilailp 8 receptor similarly show significant differences between those groups.ConclusionA local gene triplication in an early ancestor likely yielded three genes coding gonadulin, arthropod insulin-like growth factor and relaxin. Orthologs of these genes are now commonly present in arthropods and almost certainly include theDrosophilainsulin-like peptides 6, 7 and 8.
Dietary intervention improves health metrics and life expectancy of the genetically obese DU6 (Titan) mouse
Authors: Müller-Eigner Annika , Sanz-Moreno Adrián , de-Diego Irene , Venkatasubramani Anuroop Venkateswaran , Langhammer Martina , Gerlini Raffaele , Rathkolb Birgit , Aguilar-Pimentel Antonio , Klein-Rodewald Tanja , Calzada-Wack Julia , Becker Lore , Palma-Vera Sergio , Gille Benedikt , Forne Ignasi , Imhof Axel , Meng Chen , Ludwig Christina , Koch Franziska , Kuhla Angela , Caton Vanessa , Brenmoehl Julia , Schoen Jennifer , Fuchs Helmut , Gailus-Durner Valerie , Hoeflich Andreas , de Angelis Martin Hrabe , Peleg Shahaf 
Published: May 2020

AbstractSuitable animal models are essential for translational research, especially in the case of complex, multifactorial conditions, such as obesity. The outbred mouse line Titan (DU6) results from the world’s longest selection experiment for high body mass and was previously described as a model for metabolic healthy (benign) obesity. The present study deeper characterized the geno- and phenotypes of this outbred mouse line and tested its suitability as an interventional obesity model. In contrast to previous findings, our data suggests that Titan mice are metabolically unhealthy obese and short-lived. Line-specific patterns of genetic invariability are in accordance with observed phenotypic traits. Titan mice show modifications in the liver transcriptome, proteome and epigenome that are linked to metabolic (dys)regulations. However, dietary intervention partially reversed the metabolic phenotype in Titan mice and significantly extended their life expectancy. Therefore, the Titan mouse line is a valuable resource for translational and interventional obesity research.
Gene expression and chromatin accessibility during progressive EMT and MET linked to dynamic CTCF engagement
Authors: Johnson Kelsey S. , Hussein Shaimaa , Song Shuxuan , Chakraborty Priyanka , Jolly Mohit Kumar , Toneff Michael J. , Lin Yin C. , Taube Joseph H. 
Published: May 2020

AbstractBackgroundEpithelial-mesenchymal transition (EMT) facilitates cellular movements critical for proper development; however, in a carcinoma, EMT promotes metastatic dissemination. Stable intermediate states (partial-EMT) are increasingly implicated in metastatic dissemination while reversal of EMT, termed mesenchymal-epithelial transition (MET), is increasingly implicated in metastatic colonization. To understand the partial and reversible nature of EMT, we characterized chromatin accessibility dynamics, transcriptome changes, protein expression patterns, as well as E-cadherin expression, localization, and gene-level dynamics in mammary epithelial cells undergoing stepwise reversible EMT.ResultsWhile shorter EMT induction induced internalization of E-cadherin protein, surface expression was recovered upon MET without loss of transcript or bulk protein. Conversely, a longer EMT induced stable repression of E-cadherin indicated by loss of chromatin accessibility and induced global expansion of accessible sites across the genome, facilitated by increased engagement of multiple transcription factor families, including AP-1 and SMAD. We observe enrichment for binding sites for the insulator proteins CTCF and BORIS was significantly diminished in both stemness-enriched partial-EMT and partial-MET states and determined that CTCF repression imparts alterations in some histone covalent modifications concomitant with those observed during TGFβ-induced EMT.ConclusionsThese findings are indicative of a major role for chromatin looping and reorganization in plasticity, stemness, and partial EMT phenotypes.
MapA, a second large RTX adhesin, contributes to biofilm formation byPseudomonas fluorescens
Authors: Collins Alan J. , Pastora Alexander B. , Smith T. Jarrod , Dahlstrom Kurt , O’Toole George A. 
Published: May 2020

AbstractMechanisms by which cells attach to a surface and form a biofilm are diverse and differ greatly between organisms. The Gram-negative, GammaproteobacteriumPseudomonasfluorescens attaches to a surface through the localization of the large type 1-secreted RTX adhesin LapA to the outer surface of the cell. LapA localization to the cell surface is controlled by the activities of a periplasmic protease, LapG and an inner-membrane spanning cyclic di-GMP responsive effector protein, LapD. A previous study identified a second, LapA-like protein encoded in theP. fluorescensPf0-1 genome: Pfl01_1463. However, deletion of this gene had no discernible phenotype under our standard laboratory growth conditions. Here, we identified specific growth conditions wherein, Pfl01_1463, hereafter called MapA (MediumAdhesionProtein A) is a functional adhesin contributing to biofilm formation. This adhesin, like LapA, appears to be secreted through a Lap-related type 1 secretion machinery. We show MapA involvement in biofilm formation is also controlled by LapD and LapG, and that the differing roles of LapA and MapA in biofilm formation are achieved, at least in part, through the differences in the sequences of the two adhesins and their differential, cyclic di-GMP-dependent transcriptional regulation. This differential regulation appears to lead to different distributions of the expression oflapAandmapAwithin a biofilm. Our data indicate that the mechanisms by which a cell forms a biofilm and the components of a biofilm matrix can differ depending on growth conditions in the biofilm.ImportanceAdhesins are critical for the formation and maturation of bacterial biofilms. We identify a second adhesin inP. fluorescens, called MapA, which appears to play a role in biofilm maturation and whose regulation is distinct from the previously reported LapA adhesin, which is critical for biofilm initiation. Analysis of bacterial adhesins show that LapA-like and MapA-like adhesins are found broadly in Pseudomonads and related organisms, indicating that the utilization of different suites of adhesins may be broadly important in the Gammaproteobacteria.
Evaluation of the EUROIMMUN Anti-SARS-CoV-2 ELISA Assay for detection of IgA and IgG antibodies
Authors: Matushek Scott M. , Beavis Kathleen G. , Abeleda Ana , Bethel Cindy , Hunt Carlissa , Gillen Stephanie , Moran Angelica , Tesic Vera 
Published: May 2020

AbstractAs the Coronavirus 2019 (COVID-19) pandemic evolves, the development of immunoassays to help determine exposure and potentially predict immunity has become a pressing priority. In this report we present the performance of the EUROIMMUN enzyme-linked immunosorbent assay (ELISA) for semi-quantitative detection of IgA and IgG antibodies in serum and plasma samples using recombinant S1 domain of the SARS-CoV-2 spike protein as antigen. Specimens from patients, with and without COVID-19 infection, were tested at the University of Chicago Clinical Microbiology and Immunology Laboratory. Of 57 samples from COVID-19 PCR-negative patients, including 28 samples positive for common human coronavirus strains, 53 tested negative and 4 tested positive for IgA (93.0% agreement) while 56 tested negative and 1 tested positive for IgG (98.2% agreement). For COVID-19 PCR-positive patients, 29 of 30 (96.7%) samples collected ≥3 days after positive PCR were positive for IgA, and 28 of 28 samples collected ≥4 days after positive PCR were positive for IgG.The EUROIMMUN Anti-SARS-CoV-2 ELISA Assay demonstrates excellent sensitivity for detection of IgA and IgG antibodies from samples collected ≥3 days and ≥4 days, respectively, after COVID-19 diagnosis by PCR. This assay did not demonstrate cross reaction in any of the 28 samples from patients with common human coronaviruses, including types HKU1, NL63, CV229E, and OC43.
A Darwinian Selection Based Explanation of Peacock’s Tail
Authors: Wadhwa Dinkar 
Published: May 2020

AbstractThere is no satisfactory explanation for why peacock possesses a tail, presence and especially courtship display of which makes the organism vulnerable to predation. Here, I present a model according to which in a polygynous mating system a mechanism which increases vulnerability to predation, a Zahavian handicap, evolves when other two mechanisms to identify high-quality males are either absent or are not sufficiently strong. The two mechanisms are: 1) male resource acquisition ability, and 2) male-male competition for females. The three mechanisms are not necessarily mutually exclusive. Assuming the locus for the tail and choosiness to be sex-specific, it is shown through stochastic simulation that sexual selection, mediated by the tail (a Zahavian handicap), leads to higher rate of increase in the quality of the population of tailed peacocks and tailed-choosy peahens (which exclusively mate with tailed peacocks) as compared to the population of tailless peacocks and tailless-choosy peahens (which exclusively mate with tailless peacocks), through a positive feedback, as daughters of tailed-choosy peahens are of higher average quality and, by virtue of not carrying the tail’s handicap, also fitness than daughters of tailless-choosy peahens. Also, the fold-change in the population of tailed peacocks and tailless-choosy peahens are higher than the fold-change in the population of tailless peacocks and tailless-choosy peahens, for all combinations of the initial conditions. The same results were got, though in milder form, when tailless-choosy peahens were replaced by undiscriminating peahens (which mate with tailless and tailed peacocks in proportion to their frequencies in the population). Although sons of tailed-choosy peahens have lower average fitness than sons of undiscriminating peahens, this difference is inconsequential, because in a polygynous mating system a single male can potentially mate with every female. The work presented here reconciles Zahavi’s handicap principle with Darwin’s theories of natural and sexual selection. Further, it is hypothesized that a genotype responsible for producing in males a reliable indicator of high quality (a Zahavian handicap) or paternal care ability generates mating desirability in females towards males possessing the indicator. It is demonstrated through simulation that this cross-gender pleiotropy expedites the evolution of tailed peacocks and tailed-choosy peahens and leads to higher rate of increase in their quality.
Potent neutralizing antibodies from COVID-19 patients define multiple targets of vulnerability
Authors: Brouwer Philip J.M. , Caniels Tom G. , van der Straten Karlijn , Snitselaar Jonne L. , Aldon Yoann , Bangaru Sandhya , Torres Jonathan L. , Okba Nisreen M.A. , Claireaux Mathieu , Kerster Gius , Bentlage Arthur E.H. , van Haaren Marlies M. , Guerra Denise , Burger Judith A. , Schermer Edith E. , Verheul Kirsten D. , van der Velde Niels , van der Kooi Alex , van Schooten Jelle , van Breemen Mariëlle J. , Bijl Tom P. L. , Sliepen Kwinten , Aartse Aafke , Derking Ronald , Bontjer Ilja , Kootstra Neeltje A. , Wiersinga W. Joost , Vidarsson Gestur , Haagmans Bart L. , Ward Andrew B. , de Bree Godelieve J. , Sanders Rogier W. , van Gils Marit J. 
Published: May 2020

AbstractThe rapid spread of SARS-CoV-2 has a significant impact on global health, travel and economy. Therefore, preventative and therapeutic measures are urgently needed. Here, we isolated neutralizing antibodies from convalescent COVID-19 patients using a SARS-CoV-2 stabilized prefusion spike protein. Several of these antibodies were able to potently inhibit live SARS-CoV-2 infection at concentrations as low as 0.007 µg/mL, making them the most potent human SARS-CoV-2 antibodies described to date. Mapping studies revealed that the SARS-CoV-2 spike protein contained multiple distinct antigenic sites, including several receptor-binding domain (RBD) epitopes as well as previously undefined non-RBD epitopes. In addition to providing guidance for vaccine design, these mAbs are promising candidates for treatment and prevention of COVID-19.
Visualizing the dynamics of exported bacterial proteins with the chemogenetic fluorescent reporter FAST
Authors: Chekli Yankel , Peron-Cane Caroline , Dell’Arciprete Dario , Allemand Jean-François , Li Chenge , Ghigo Jean-Marc , Gautier Arnaud , Lebreton Alice , Desprat Nicolas , Beloin Christophe 
Published: May 2020

AbstractBacterial proteins exported to the cell surface play key cellular functions. However, despite the interest to study the localization of surface proteins such as adhesins, transporters or hydrolases, monitoring their dynamics in live imaging remains challenging, due to the limited availability of fluorescent probes remaining functional after secretion. In this work, we used theEscherichia coliintimin and theListeria monocytogenesInlB invasin as surface exposed scaffolds fused with the recently developed chemogenetic fluorescent reporter protein FAST. Using both membrane permeant (HBR-3,5DM) and non-permeant (HBRAA-3E) fluorogens that fluoresce upon binding to FAST, we demonstrated that fully functional FAST can be exposed at the cell surface and specifically tagged on the external side of the bacterial envelop in both diderm and monoderm bacteria. Our work opens new avenues to study of the organization and dynamics of the bacterial cell surface proteins.
Population genomic molecular epidemiological study of macrolide resistantStreptococcus pyogenesin Iceland, 1995-2016: Identification of a large clonal population with apbp2xmutation conferring reducedin vitroβ-lactam susceptibility
Authors: Southon Sara B. , Beres Stephen B. , Kachroo Priyanka , Saavedra Matthew Ojeda , Erlendsdóttir Helga , Haraldsson Gunnsteinn , Yerramilli Prasanti , Pruitt Layne , Zhu Luchang , Musser James M. , Kristinsson Karl G. 
Published: May 2020

ABSTRACTResistance to macrolide antibiotics is a global concern in the treatment ofStreptococcus pyogenes(Group A Streptococcus, GAS) infections. In Iceland, since the detection of the first macrolide-resistant isolate in 1998, three epidemic waves of macrolide-resistant GAS infections have occurred with peaks in 1999, 2004, and 2008. We conducted whole genome sequencing of all 1,575 available GAS macrolide-resistant clinical isolates of all infection types collected at the national reference laboratory in Reykjavik from 1998 to 2016. Among 1,515 erythromycin-resistant isolates, 90.3% were of only threeemmtypes:emm4(n= 713),emm6(n= 324), andemm12(n= 332), with each being predominant in a distinct epidemic peak. The antibiotic efflux pump genes,mef(A) andmsr(D), were present on chimeric mobile genetic elements in 99.3% of the macrolide-resistant isolates of theseemmtypes. Of note, in addition to macrolide resistance, virtually allemm12isolates had a single amino acid substitution in penicillin-binding protein PBP2X that conferred a two-fold increased penicillin G and ampicillin MIC among isolates tested. We conclude that each of the three large epidemic peaks of macrolide-resistant GAS infections occurring in Iceland since 1998 was caused by the emergence and clonal expansion of progenitor strains, with macrolide resistance being conferred predominantly by inducible Mef(A)-Msr(D) drug efflux pumps. The occurrence ofemm12strains with macrolide resistance and decreased beta-lactam susceptibility was unexpected and is of public health concern.RepositoriesGenomic sequencing data for all 1,515 macrolide/erythromycin-resistant isolates were deposited into the National Center for Biotechnology Information Sequence Read Archive under bioproject accession PRJNA614628 and assembled sequences for composite elements Φ29854, Φ29862 and Φ29661 were deposited in Genbank under accessions ###, ### and ### respectively.
Inhibition of TRPV1 and TRPA1 by mosquito and mouse saliva
Authors: Li Tianbang , Derouiche Sandra , Sakai Yuya , Uta Daisuke , Aoyagi Seiji , Tominaga Makoto 
Published: May 2020

AbstractArthropods are the largest group of living organisms and among them, mosquitoes spread parasites and viruses causing deathly diseases. Mosquito’s painless piercing is due to the thinness of their fascicle, but mosquito saliva might also contribute to it. We found that mosquito and mouse saliva inhibit TRPV1 and TRPA1 channels, either heterologously expressed in HEK293T cells or endogenously expressed in native mouse sensory neurons. We have also identified sialorphin as a candidate antinociceptive peptide as it showed similar effects on TRPV1 and TRPA1. Finally, we confirmed the antinociceptive effects of saliva and sialorphinin vivoby observing decreased pain-related behaviors in mice coinjected with these substances. Similar inhibitory effects of mosquito and mouse saliva suggest that the antinociceptive effects of saliva are universal, which could explain why many animals including humans often lick their wounds. These findings would lead to the development of novel anti-nociceptive agents.
Phenoxyalkylimidazoles with an oxadiazole moiety are subject to efflux inMycobacterium tuberculosis
Authors: Thayer Mai B. , Parish Tanya 
Published: May 2020

AbstractThe phenoxyalkylimidazoles (PAI) are an attractive chemical series with potent anti-tubercular activity targetingMycobacterium tuberculosisrespiration. We determined if PAI compounds are subject to efflux. Two analogs containing an oxadiazole had improved potency in the presence of the efflux inhibitors reserpine and carbonyl cyanide m-chlorophenylhydrazine, whereas the potency of an analog with a diazole was not affected. Verapamil was unable to boost compound potency.
Characterization of neutralizing antibodies from a SARS-CoV-2 infected individual
Authors: Seydoux Emilie , Homad Leah J. , MacCamy Anna J. , Parks K. Rachael , Hurlburt Nicholas K. , Jennewein Madeleine F. , Akins Nicholas R. , Stuart Andrew B. , Wan Yu-Hsin , Feng Junli , Nelson Rachael E. , Singh Suruchi , Cohen Kristen W. , McElrath M. Juliana , Englund Janet A. , Chu Helen Y. , Pancera Marie , McGuire Andrew T. , Stamatatos Leonidas 
Published: May 2020

ABSTRACTB cells specific for the SARS-CoV-2 S envelope glycoprotein spike were isolated from a COVID-19-infected subject using a stabilized spike-derived ectodomain (S2P) twenty-one days post-infection. Forty-four S2P-specific monoclonal antibodies were generated, three of which bound to the receptor binding domain (RBD). The antibodies were minimally mutated from germline and were derived from different B cell lineages. Only two antibodies displayed neutralizing activity against SARS-CoV-2 pseudo-virus. The most potent antibody bound the RBD in a manner that prevented binding to the ACE2 receptor, while the other bound outside the RBD. Our study indicates that the majority of antibodies against the viral envelope spike that were generated during the first weeks of COVID-19 infection are non-neutralizing and target epitopes outside the RBD. Antibodies that disrupt the SARS-CoV-2 spike-ACE2 interaction can potently neutralize the virus without undergoing extensive maturation. Such antibodies have potential preventive/therapeutic potential and can serve as templates for vaccine-design.IN BRIEFSARS-CoV-2 infection leads to expansion of diverse B cells clones against the viral spike glycoprotein (S). The antibodies bind S with high affinity despite being minimally mutated. Thus, the development of neutralizing antibody responses by vaccination will require the activation of certain naïve B cells without requiring extensive somatic mutation.HighlightsAnalysis of early B cell response to SARS-CoV-2 spike proteinMost antibodies target non-neutralizing epitopesPotent neutralizing mAb blocks the interaction of the S protein with ACE2Neutralizing antibodies are minimally mutated
Single-molecule 3D orientation imaging reveals nanoscale compositional heterogeneity in lipid membranes
Authors: Lu Jin , Mazidi Hesam , Ding Tianben , Zhang Oumeng , Lew Matthew D. 
Published: May 2020

AbstractIn soft matter, thermal energy causes molecules to continuously translate and rotate, even in crowded environments, impacting the spatial organization and function of most molecular assemblies, such as lipid membranes. Directly measuring the orientation and spatial organization of large collections (>3000 molecules/μm2) of single molecules with nanoscale resolution remains elusive. We present SMOLM, single-molecule orientation localization microscopy, to directly measure the orientation spectra (3D orientation plus “wobble”) of lipophilic probes transiently bound to lipid membranes, revealing that Nile red’s (NR) orientation spectra are extremely sensitive to membrane chemical composition. SMOLM images resolve nanodomains and enzyme-induced compositional heterogeneity within membranes, where NR within liquid-ordered vs. liquid-disordered domains shows a ~4° difference in polar angle and a ~0.3π sr difference in wobble angle. As a new type of imaging spectroscopy, SMOLM exposes the organizational and functional dynamics of lipid-lipid, lipid-protein, and lipid-dye interactions with single-molecule, nanoscale resolution.