bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptomics, metabolomics and lipidomics of chronically injured alveolar epithelial cells reveals similar features of IPF lung epithelium
Authors: Roque Willy , Cuevas-Mora Karina , Sales Dominic , Li Wei Vivian , Rosas Ivan O. , Romero Freddy 
Published: May 2020

AbstractThe current hypothesis suggests that Idiopathic pulmonary fibrosis (IPF) arises as a result of chronic injury to alveolar epithelial cells and aberrant activation of multiple signaling pathways. Dysfunctional IPF lung epithelium manifests many hallmarks of aging tissues, including cellular senescence, mitochondrial dysfunction, metabolic dysregulation, and loss of proteostasis. Unfortunately, this disease is often fatal within 3-5 years from diagnosis, and there is no effective treatment. One of the major limitations to the development of novel treatments in IPF is that current models of the disease fail to resemble several features seen in elderly IPF patients. In this study, we sought to develop anin vitroepithelial injury model using repeated low levels of bleomycin to mimic the phenotypic and functional characteristics of the IPF lung epithelium. Consistent with the hallmarks of the aging lung epithelium, we found that chronic-injured epithelial cells exhibited features of senescence cells, including an increase in β-galactosidase staining, induction of p53 and p21, mitochondrial dysfunction, excessive ROS production, and proteostasis alteration. Next, combined RNA sequencing, untargeted metabolomics, and lipidomics were performed to investigate the dynamic transcriptional, metabolic, and lipidomic profiling of ourin vitromodel. We identified that a total of 8,484 genes with different expression variations between the exposed group and the control group. According to our GO enrichment analysis, the down-regulated genes are involved in multiple biosynthetic and metabolic processes. In contrast, the up-regulated genes in our treated cells are responsible for epithelial cell migration and regulation of epithelial proliferation. Furthermore, metabolomics and lipidomics data revealed that overrepresented pathways were amino acid, fatty acid, and glycosphingolipid metabolism. This result suggests that by using ourin vitromodel, we were able to mimic the transcriptomic and metabolic alterations of those seen in the lung epithelium of IPF patients. We believe this model will be ideally suited for use in uncovering novel insights into the gene expression and molecular pathways of the IPF lung epithelium and performing screening of pharmaceutical compounds.
Targeted sequence capture array for phylogenetics and population genomics in the Salicaceae
Authors: Sanderson Brian J. , DiFazio Stephen P. , Cronk Quentin C. , Ma Tao , Olson Matthew S. 
Published: May 2020

AbstractPremise of the studyThe family Salicaceae has proved taxonomically challenging, especially in the genusSalix, which is speciose and features frequent hybridization and polyploidy. Past efforts to reconstruct the phylogeny with molecular barcodes have failed to resolve the species relationships of many sections of the genus.MethodsWe used the wealth of sequence data in the family to design sequence capture probes to target regions of 300-1200 base pairs of exonic regions of 972 genes.ResultsWe recovered sequence data for nearly all of the targeted genes in three species ofPopulusand three species ofSalix. We present a species tree, discuss concordance among gene trees, as well as some population genomic summary statistics for these loci.ConclusionsOur sequence capture array has extremely high capture efficiency within the generaPopulusandSalix, resulting in abundant phylogenetic information. Additionally, these loci show promise for population genomic studies.
Deterministic Critical Community Size for the SIR System and Viral Strain Selection
Authors: Dos Santos Marcílio Ferreira , Castilho César 
Published: May 2020

AbstractIn this paper the concept of Critical Community Size (CCS) for the deterministic SIR model is introduced and its consequences for the disease dynamics are stressed. The disease can fade out after an outburst. Also the principle of competitive exclusion holds no longer true. This is exemplified for the dynamics of two competing virus strains. The virus with higherR0can be eradicated from the population.
Xela DS2 and Xela VS2: two novel skin epithelial-like cell lines from adult African clawed frog (Xenopus laevis) and their response to an extracellular viral dsRNA analogue
Authors: Bui-Marinos Maxwell P. , Varga Joseph F. A. , Vo Nguyen T.K. , Bols Niels C. , Katzenback Barbara A. 
Published: May 2020

AbstractThe skin epithelial layer acts as an important immunological barrier against pathogens and is capable of recognizing and responding to pathogen associated molecular patterns (PAMPs) in human and mouse models. Although presumed, it is unknown whether amphibian skin epithelial cells exhibit the ability to respond to PAMPs such as viral double-stranded RNA (dsRNA). To address this, two cell lines from the dorsal skin (Xela DS2) and ventral skin (Xela VS2) of the African clawed frog (Xenopus laevis) were established. Xela DS2 and Xela VS2 cells have an epithelial-like morphology, express genes associated with epithelial cells, and lack senescence-associated beta-galactosidase activity. Cells grow optimally in 70% Leibovitz’s L-15 medium supplemented with 15% fetal bovine serum at 26°C. Upon treatment with poly(I:C), a synthetic viral dsRNA analogue and known type I interferon inducer, Xela DS2 and Xela VS2 exhibit marked upregulation of key pro-inflammatory and antiviral transcripts suggesting frog epithelial cells participate in the recognition of extracellular viral dsRNA and production of local inflammatory signals; similar to human and mouse models. Currently, these are the only knownXenopus laevisskin epithelial-like cell lines and will be important for future research in amphibian epithelial cell biology, initial host-pathogen interactions, and rapid screening of the effects of environmental stressors, including contaminants, on frog skin epithelial cells.
Condensation of pericentrin proteins in human cells illuminates phase separation in centrosome assembly
Authors: Jiang Xueer , Ho Dac Bang Tam , Mahe Karan , Mia Jennielee , Sepulveda Guadalupe , Antkowiak Mark , Jiang Linhao , Yamada Soichiro , Jao Li-En 
Published: May 2020

AbstractAt the onset of mitosis, centrosomes expand the pericentriolar material (PCM) to maximize their microtubule-organizing activity. This step, termed centrosome maturation, ensures proper spindle organization and faithful chromosome segregation. However, as the centrosome expands, how PCM proteins are recruited and held together without membrane enclosure remains elusive. We found that endogenously expressed pericentrin (PCNT), a conserved PCM scaffold protein, condenses into dynamic granules during late G2/early mitosis before incorporating into mitotic centrosomes. Furthermore, the N-terminal portion of PCNT—enriched with conserved coiled-coils (CCs) and low-complexity regions (LCRs)—phase separates into dynamic condensates that selectively recruit PCM proteins and nucleate microtubules in cells. We propose that CCs and LCRs, two prevalent sequence features in the centrosomal proteome, are preserved under evolutionary pressure in part to mediate liquid-liquid phase separation, a process that bestows upon the centrosome distinct properties critical for its assembly and functions.
Host behavior alteration by its parasite: from brain gene expression to functional test
Authors: Grecias Lucie , Hebert Francois Olivier , Alves Verônica Angelica , Barber Iain , Aubin-Horth Nadia 
Published: May 2020

ABSTRACTMany parasites with complex life cycles modify their intermediate hosts’ behaviour, presumably to increase transmission to their final host. The threespine stickleback (Gasterosteus aculeatus) is an intermediate host in the cestodeSchistocephalus soliduslife cycle, which ends in an avian host, and shows increased risky behaviours when infected. We studied brain gene expression profiles of sticklebacks infected withS.solidusto determine the proximal causes of these behavioural alterations. We show that infected fish have altered expression levels in genes involved in the inositol pathway. We thus tested the functional implication of this pathway and successfully rescued normal behaviours in infected sticklebacks using lithium exposure. We also show that exposed but uninfected fish have a distinct gene expression profile from both infected fish and control individuals, allowing us to separate gene activity related to parasite exposure from consequences of a successful infection. Finally, we find that Selective Serotonin Reuptake Inhibitor (SSRI)-treated sticklebacks and infected fish do not have similarly altered gene expression, despite their comparable behaviours, suggesting that the serotonin pathway is probably not the main driver of phenotypic changes in infected sticklebacks. Taken together, our results allow us to predict that ifS.solidusdirectly manipulates its host, it could target the inositol pathway.
L-bodies are novel RNA-protein condensates driving RNA transport inXenopusoocytes
Authors: Neil Christopher R. , Jeschonek Samantha P. , Cabral Sarah E. , O’Connell Liam C. , Powrie Erin A. , Wood Timothy A. , Mowry Kimberly L. 
Published: May 2020

AbstractRNP granules are membrane-less compartments within cells, formed by phase separation, that function as regulatory hubs for diverse biological processes. However, the mechanisms by which RNAs and proteins interact to promote RNP granule structure and functionin vivoremain unclear. InXenopus laevisoocytes, maternal mRNAs are transported as large RNPs to the vegetal hemisphere of the developing oocyte, where local translation is critical for proper embryonic patterning. Here, we demonstrate that vegetal transport RNPs represent a new class of cytoplasmic RNP granule, termed Localization-bodies (L-bodies). We show that L-bodies are multiphase RNP granules, containing a dynamic protein-containing phase surrounding a non-dynamic RNA-containing substructure. Our results support a role for RNA as a critical scaffold component within these RNP granules and suggest thatcis-elements within localized mRNAs may drive subcellular RNA localization through control over phase behavior.
The microbiome mediates subchondral bone loss and metabolomic changes after acute joint trauma
Authors: Hahn Alyssa K. , Wallace Cameron W. , Welhaven Hope D. , Brooks Ellen , McAlpine Mark , Christiansen Blaine A. , Walk Seth T. , June Ronald K. 
Published: May 2020

AbstractObjectiveTo compare the early responses to joint injury in conventional and germ-free mice.DesignPost traumatic osteoarthritis PTOA was induced using a non-invasive anterior cruciate ligament rupture model in 20-week old germ-free (GF) and conventional C57BL/6 mice. Injury was induced in the left knees of n=8 GF and n=10 conventional mice. To examine the effects of injury, n=5 GF and n=9 conventional control mice were used. Mice were euthanized seven days post-injury, followed by synovial fluid recovery for global metabolomic profiling and analysis of epiphyseal trabecular bone by micro-computed tomography (μCT). Global metabolomic profiling assessed metabolic differences in the joint response to injury between GF and conventional mice. Magnitude of trabecular bone volume loss measured using μCT assessed early OA progression in GF and conventional mice.ResultsμCT found that GF mice had significantly less trabecular bone loss compared to conventional mice, indicating that the GF status was protective against early OA changes in bone structure. Global metabolomic profiling showed that conventional mice had greater variability in their metabolic response to injury, and a more distinct joint metabolome compared to their corresponding controls. Furthermore, differences in the response to injury in GF compared to conventional mice were linked to mouse metabolic pathways that regulate inflammation associated with the innate immune system.ConclusionsThese results suggest that the gut microbiota promote the development of PTOA during the acute phase following joint trauma possibly through the regulation of the innate immune system.
Mapping transmembrane binding partners for E-cadherin ectodomains
Authors: Shafraz Omer , Xie Bin , Yamada Soichiro , Sivasankar Sanjeevi 
Published: May 2020

ABSTRACTWe combine proximity labeling and single molecule binding assays, to discover novel transmembrane protein interactions in cells. We first screen for candidate binding partners by tagging the extracellular and cytoplasmic regions of a bait protein with TurboID biotin ligase, and identify proximal proteins that are biotin-tagged on both their extracellular and intracellular regions. We then test direct binding interactions between the proximal proteins and the bait, using single molecule Atomic Force Microscope binding assays. Using this approach, we identify novel binding partners for the extracellular region of E-cadherin, an essential cell-cell adhesion protein. We show that the desmosomal proteins desmoglein-2 and desmocollin-3, the focal adhesion protein integrin-α2β1, and the receptor tyrosine kinase ligand ephrin-B1, all directly interact with E-cadherin ectodomains. Our discovery of previously unknown heterophilic E-cadherin binding interactions, suggest the existence of novel cadherin cross-talk in epithelial cells.
Elevated ACE2 expression in the olfactory neuroepithelium: implications for anosmia and upper respiratory SARS-CoV-2 entry and replication
Authors: Chen Mengfei , Shen Wenjuan , Rowan Nicholas R. , Kulaga Heather , Hillel Alexander , Ramanathan Murugappan , Lane Andrew P. 
Published: May 2020

AbstractThe site of SARS-CoV-2 entry and replication critically impacts strategies for COVID-19 diagnosis, transmission mitigation, and treatment. We determined the cellular location of the SARS-CoV-2 target receptor protein, ACE2, in the human upper airway, finding striking enrichment (200-700 folds) in the olfactory neuroepithelium relative to nasal respiratory or tracheal epithelial cells. This cellular tropism of SARS-CoV-2 may underlie its high transmissibility and association with olfactory dysfunction, while suggesting a viral reservoir potentially amenable to intranasal therapy.
The evolution of skin pigmentation associated variation in West Eurasia
Authors: Ju Dan , Mathieson Iain 
Published: May 2020

AbstractSkin pigmentation is a classic example of a polygenic trait that has experienced directional selection in humans. Genome-wide association studies have identified well over a hundred pigmentation-associated loci, and genomic scans in present-day and ancient populations have identified selective sweeps for a small number of light pigmentation-associated alleles in Europeans. It is unclear whether selection has operated on all the genetic variation associated with skin pigmentation as opposed to just a small number of large-effect variants. Here, we address this question using ancient DNA from 1158 individuals from West Eurasia covering a period of 40,000 years combined with genome-wide association summary statistics from the UK Biobank. We find a robust signal of directional selection in ancient West Eurasians on skin pigmentation variants ascertained in the UK Biobank, but find this signal is driven mostly by a limited number of large-effect variants. Consistent with this observation, we find that a polygenic selection test in present-day populations fails to detect selection with the full set of variants; rather, only the top five show strong evidence of selection. Our data allow us to disentangle the effects of admixture and selection. Most notably, a large-effect variant at SLC24A5 was introduced to Europe by migrations of Neolithic farming populations but continued to be under selection post-admixture. This study shows that the response to selection for light skin pigmentation in West Eurasia was driven by a relatively small proportion of the variants that are associated with present-day phenotypic variation.SignificanceSome of the genes responsible for the evolution of light skin pigmentation in Europeans show signals of positive selection in present-day populations. Recently, genome-wide association studies have highlighted the highly polygenic nature of skin pigmentation. It is unclear whether selection has operated on all of these genetic variants or just a subset. By studying variation in over a thousand ancient genomes from West Eurasia covering 40,000 years we are able to study both the aggregate behavior of pigmentation-associated variants and the evolutionary history of individual variants. We find that the evolution of light skin pigmentation in Europeans was driven by frequency changes in a relatively small fraction of the genetic variants that are associated with variation in the trait today.
VIRTUS: a pipeline for comprehensive virus analysis from conventional RNA-seq data
Authors: Yasumizu Yoshiaki , Hara Atsushi , Sakaguchi Shimon , Ohkura Naganari 
Published: May 2020

AbstractThe possibility that RNA transcripts from clinical samples contain plenty of virus RNAs has not been pursued actively so far. We here developed a new tool for analyzing virus-transcribed mRNAs, not virus copy numbers, in the data of conventional and single-cell RNA-sequencing of human cells. Our pipeline, named VIRTUS (VIRal Transcript Usage Sensor), was able to detect 763 viruses including herpesviruses, retroviruses, and even SARS-CoV-2 (COVID-19), and quantify their transcripts in the sequence data. This tool thus enabled simultaneously detecting infected cells, the composition of multiple viruses within the cell, and the endogenous host gene expression profile of the cell. This bioinformatics method would be instrumental in addressing the possible effects of covertly infecting viruses on certain diseases and developing new treatments to target such viruses.Availability and implementationVIRTUS is implemented using Common Workflow Language and Docker under a CC-NC license. VIRTUS is freely available athttps://github.com/yyoshiaki/VIRTUS.Supplementary informationSupplementary data are available at Bioinformatics online.
SURF: integrative analysis of a compendium of RNA-seq and CLIP-seq datasets highlights complex governing of alternative transcriptional regulation by RNA-binding proteins
Authors: Chen Fan , Keleş Sündüz 
Published: May 2020

AbstractAdvances in high-throughput profiling of RNA binding proteins (RBPs) have resulted in CLIP-seq datasets coupled with transcriptome profiling by RNA-seq. However, analysis methods that integrate both types of data are lacking. We describe SURF, Statistical Utility for RBP Functions, for integrative analysis of large collections of CLIP-seq and RNA-seq data. We demonstrate SURF’s ability to accurately detect differential alternative transcriptional regulation events and associate them to local protein-RNA interactions. We apply SURF to ENCODE RBP compendium and carry out downstream analysis with additional reference datasets. The results of this application are browsable athttp://www.statlab.wisc.edu/shiny/surf/.
Genetic redundancy in iron and manganese transport in the metabolically versatile bacteriumRhodopseudomonas palustrisTIE-1
Authors: Singh Rajesh , Ranaivoarisoa Tahina Onina , Gupta Dinesh , Bai Wei , Bose Arpita 
Published: May 2020

ABSTRACTThe purple non-sulfur bacteriumRhodopseudomonas palustrisTIE-1 can produce useful biochemicals such as bioplastics and biobutanol. Production of such biochemicals requires intracellular electron availability, which is governed by the availability and the transport of essential metals such as iron (Fe). Because of the distinct chemical properties of ferrous [Fe(II)] and ferric iron [Fe(III)], different transport systems are required for their transport and storage in bacteria. Although Fe(III) transport systems are well characterized, we know much less about Fe(II) transport systems except for the FeoAB system. Iron transporters can also import manganese (Mn). Here, we study Fe and Mn transport by five putative Fe transporters in TIE-1 under metal-replete, -deplete, oxic and anoxic conditions. We observe that by overexpressingfeoAB, efeU, andnramp1AB, the intracellular concentration of Fe and Mn can be enhanced in TIE-1, under oxic and anoxic conditions, respectively. The deletion of a single gene/operon does not attenuate Fe or Mn uptake in TIE-1 regardless of the growth conditions used. This indicates that genetically dissimilar yet functionally redundant Fe transporters in TIE-1 can complement each other. Relative gene expression analysis shows thatfeoABandefeUare expressed during Fe and Mn depletion under both oxic and anoxic conditions. The promoters of these transporter genes contain a combination of Fur and Fnr boxes suggesting that their expression is regulated by both Fe and oxygen availability. The findings from this study will help us modulate intracellular Fe and Mn concentration, ultimately improving TIE-1’s ability to produce desirable biomolecules.IMPORTANCERhodopseudomonas palustrisTIE-1 is a metabolically versatile bacterium that can use various electron donors including Fe(II) and poised electrodes for photoautotrophic growth. TIE-1 can produce useful biomolecules such as biofuels and bioplastics during various growth conditions. Production of such reduced biomolecules is controlled by intracellular electron availability, which in turn is mediated by various iron-containing proteins in the cell. Several putative Fe transporters exist in TIE-1’s genome. Some of these transporters can also transport Mn, part of several important cellular enzymes. Therefore, understanding the ability to transport and respond to varying levels of Fe and Mn under different conditions is important to improve TIE-1’s ability to produce useful biomolecules. Our data suggest that by overexpressing Fe transporter genes via plasmid-based expression, we can increase the import of Fe and Mn in TIE-1. Future work will leverage these data to improve TIE-1 as an attractive microbial chassis and future biotechnological workhorse.