bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring the Plant Aquaporin Solute Transport Network: Functional characterisation ofNicotiana tabacumPIP, TIP and NIP isoforms
Authors: De Rosa Annamaria , Zhang Rose , Byrt Caitlin , Evans John R , Groszmann Michael 
Published: March 2021

AbstractAquaporins (AQPs) are multifunctional membrane proteins which have greatly diversified in number and function in the plant Kingdom. In plants, AQPs have evolved to comprise a dynamic solute transport network occurring in all tissues and facilitating transport of water and vital solutes across various cellular membranes. Plant AQPs are involved in a multitude of plant physiological processes, however a better understanding is required of AQP structure-function relationships, multifunctionality and cell membrane localisation in order to begin to describe putative functional roles for the numerous plant AQP gene isoforms. Using an integrated approach, we characterised nine diverseNicotiana tabacum(tobacco) aquaporins, spanning the 3 largest AQP subfamilies (PIP, TIP, and NIP) and with varied gene expression profiles. High-throughput yeast-based functional screens identified novel candidates for water, hydrogen peroxide (H2O2), boric acid (BA) and urea transport across the 3 AQP subfamilies. Using GFP translational fusions, AQPs observedin plantawere localised to the plasma membrane, tonoplast and endoplasmic reticulum. AlphaFold protein models illustrated differences in pore shape and size across subfamilies. Our analysis supports the importance of functional data for deciphering unknown AQP structure-function relationships and uncovering novel candidates forin plantasolute transport.
Tribbles 2 confers enzalutamide resistance in prostate cancer by promoting lineage plasticity
Authors: Monga Jitender , Adrianto Indra , Rogers Craig , Gadgeel Shirish , Chitale Dhananjay , Alumkal Joshi J. , Beltran Himisha , Zoubeidi Amina , Ghosh Jagadananda 
Published: March 2021

AbstractSecond-generation anti-androgen, such as enzalutamide (Xtandi), is commonly prescribed for prostate cancer therapy, but enzalutamide-resistant, lethally incurable disease invariably develops. To understand the molecular basis of enzalutamide resistance, we comprehensively analyzed prostate tumors and clinically relevant models. These studies revealed that enzalutamide resistant prostate cancer cells overexpress Tribbles 2 (Trib2), a pseudokinase. Expression of Trib2 is negatively regulated by androgen receptor signaling. Overexpression of Trib2 makes prostate cancer cells completely resistant to clinically relevant doses of enzalutamide. Trib2 downregulates expression of luminal markers but upregulates the neuronal transcription factor, BRN2, and the stemness factor, SOX2, to induce neuroendocrine differentiation. Our findings indicate that Trib2 confers resistance to enzalutamide therapy via a mechanism involving increased cellular plasticity and lineage switching.
Chromatic bacteria v.2 - A Himar1 transposon based delivery vector to extend the host range of a toolbox to fluorescently tag bacteria
Authors: Stocks Christian , Schlechter Rudolf , Remus-Emsermann Mitja 
Published: March 2021

AbstractA recent publication described the construction and utility of a comprehensive “Chromatic Bacteria” toolbox containing a set of genetic tools that allows for fluorescently tagging a variety of Proteobacteria. In an effort to expand the range of bacteria taggable with the Chromatic Bacteria toolbox, a Himar1 transposon vector was constructed to mediate insertion of fluorescent protein and abiotic resistant genes. The Himar1 transposon was chosen as it is known to function in a wide range of bacteria. To test the use of the Himar1 derivative of the Chromatic Bacteria plasmid series for fluorescently tagging bacteria, recently isolated non-model organisms were conjugated with the Himar1 transposon plasmids. We were unsuccessful in delivering the plasmids into Gram positive bacterial isolates but were able to successfully integrate the transposon in isolates that we were previously unable to modify such asSphingomonassp. Leaf357 andAcidovoraxsp. Leaf84. This manuscript reports on the currently available plasmids and transposition success in different bacteria. The manuscript will be updated regularly until a full plasmid series is available and a large range of recipient strains was tested.
Gene structure, differential exon usage, and expression of the testis long intergenic non-protein coding RNA 1016 in humans reveals isoform-specific roles in controlling biological processes
Authors: Ramos Enrique I. , Yang Barbara , Vasquez Yasmin M. , Lin Ken Y. , Choudhari Ramesh , Gadad Shrikanth S. 
Published: March 2021

AbstractLong noncoding RNAs (lncRNAs) have emerged as critical regulators of biological processes. The constant expansion of newly-identified lncRNA genes requires that each one be comprehensively annotated to understand its molecular functions. Here, we describe a detailed characterization of the gene which encodes long intergenic non-protein coding RNA 01016 (LINC01016, a.k.a., LncRNA1195) with a focus on its structure, exon usage, and expression in human and macaque tissues. In this study, we show that it is exclusively conserved among non-human primates, suggesting its recent evolution and is expressed and processed into 12 distinct RNAs in testis, cervix, and uterus tissues. Further, we integrate de novo annotation of expressed LINC01016 transcripts and isoform-dependent gene expression analyses to show that human LINC01016 is a multi-exon gene, processed through differential exon usage with isoform-specific functions. Furthermore, in gynecological cancers, such as cervical squamous cell carcinoma and uterine corpus endometrial carcinoma, LINC01016 is downregulated; however, its higher expression is predictive of relapse-free survival in these cancers. Collectively, these analyses reveal that, unlike coding RNAs, lncRNA isoforms are differentially regulated and precisely processed in specific tissues to perform distinct biological roles.One sentence summaryThe distinct molecular role of LINC01016 isoforms reveals intricate biology associated with lncRNA transcription and processing.
Rapid evolutionary turnover of mobile genetic elements drives microbial resistance to viruses
Authors: Hussain Fatima Aysha , Dubert Javier , Elsherbini Joseph , Murphy Mikayla , VanInsberghe David , Arevalo Philip , Kauffman Kathryn , Rodino-Janeiro Bruno Kotska , Polz Martin 
Published: March 2021

AbstractAlthough it is generally accepted that viruses (phages) drive bacterial evolution, how these dynamics play out in the wild remains poorly understood. Here we show that the arms race between phages and their hosts is mediated by large and highly diverse mobile genetic elements. These phage-defense elements display exceedingly fast evolutionary turnover, resulting in differential phage susceptibility among clonal bacterial strains while phage receptors remain invariant. Protection afforded by multiple elements is cumulative, and a single bacterial genome can harbor as many as 18 putative phage-defense elements. Overall, elements account for 90% of the flexible genome amongst closely related strains. The rapid turnover of these elements demonstrates that phage resistance is unlinked from other genomic features and that resistance to phage therapy might be as easily acquired as antibiotic resistance.
Genomic signatures of past and present chromosomal instability in the evolution of Barrett’s esophagus to esophageal adenocarcinoma
Authors: Stachler Matthew D. , Bao Chunyang , Tourdot Richard W. , Brunette Gregory J. , Stewart Chip , Sun Lili , Baba Hideo , Watanabe Masayuki , Agoston Agoston , Jajoo Kunal , Davison Jon M. , Nason Katie , Getz Gad , Wang Kenneth K. , Imamura Yu , Odze Robert , Bass Adam J. , Zhang Cheng-Zhong 
Published: March 2021

AbstractThe progression of precancerous lesions to malignancy is often accompanied by increasing complexity of chromosomal alterations but how these alterations arise is poorly understood. Here we performed haplotype-specific analysis of chromosomal copy-number evolution in the progression of Barrett’s esophagus (BE) to esophageal adenocarcinoma (EAC) on multiregional whole-genome sequencing data of BE with dysplasia and microscopic EAC foci. We identified distinct patterns of copy-number evolution indicating multigenerational chromosomal instability that is initiated by cell division errors but propagated only after p53 loss. While abnormal mitosis, including whole-genome duplication, underlies chromosomal copy-number changes, segmental alterations display signatures of successive breakage-fusion-bridge cycles and chromothripsis of unstable dicentric chromosomes. Our analysis elucidates how multigenerational chromosomal instability generates copy-number variation in BE cells, precipitates complex alterations including DNA amplifications, and promotes their independent clonal expansion and transformation. In particular, we suggest sloping copy-number variation as a signature of ongoing chromosomal instability that precedes copy-number complexity.These findings suggest copy-number heterogeneity in advanced cancers originates from chromosomal instability in precancerous cells and such instability may be identified from the presence of sloping copy-number variation in bulk sequencing data.
Parental-fetal interplay of immune genes leads to intrauterine growth restriction
Authors: Kaur Gurman , Porter Caroline B. M. , Ashenberg Orr , Lee Jack , Riesenfeld Samantha J. , Hofree Matan , Aggelakopoulou Maria , Subramanian Ayshwarya , Kuttikkatte Subita Balaram , Attfield Kathrine E. , Desel Christiane A. E. , Davies Jessica L. , Evans Hayley G. , Avraham-Davidi Inbal , Nguyen Lan T. , Dionne Danielle A. , Neumann Anna E. , Jensen Lise Torp , Barber Thomas R. , Soilleux Elizabeth , Carrington Mary , McVean Gil , Rozenblatt-Rosen Orit , Regev Aviv , Fugger Lars 
Published: March 2021

AbstractIntrauterine growth restriction (IUGR) of fetuses affects 5-10% of pregnancies and is associated with perinatal morbidity, mortality and long-term health issues. Understanding genetic predisposition to IUGR is challenging, owing to extensive gene polymorphisms, linkage disequilibrium, and maternal and paternal influence. Here, we demonstrate that the inhibitory receptor, KIR2DL1, expressed on maternal uterine natural killer (uNK) cells, in interaction with the paternally-inherited HLA-C*05, an HLA-C group 2 allotype, expressed on fetal trophoblast cells, causes IUGR in a humanised mouse model. Micro-CT imaging of the uteroplacental vasculature revealed reduced uterine spiral artery diameter and increased segment length, increasing fetal blood flow resistance. Single cell RNA-Seq from the maternal-fetal interface highlighted expression programs activated by KIR2DL1-induced IUGR in several placental cell types, including degradation of extracellular matrix components, angiogenesis, and uNK cell communication, suggesting a complex response underlying IUGR. As current IUGR treatments are insufficient, our findings provide important insight for drug development.
Paenibacillussp. strain UY79, isolated from a root nodule ofArachis villosa, displays a broad spectrum of antifungal activity
Authors: Costa Andrés , Corallo Belén , Amarelle Vanesa , Stewart Silvina , Pan Dinorah , Tiscornia Susana , Fabiano Elena 
Published: March 2021

ABSTRACTA nodule-inhabitingPaenibacillussp. strain (UY79) isolated from wild peanut (Arachis villosa) was screened for its antagonistic activity against diverse fungi and oomycetes (Botrytis cinerea, Fusarium verticillioides, Fusarium oxysporum, Fusarium graminearum, Fusarium semitectum, Macrophomina phaseolina, Phomopsis longicolla, Pythium ultimum, Phytophthora sojae, Rhizoctonia solani, Sclerotium rolfsiiandTrichoderma atroviride). Results obtained show thatPaenibacillussp. UY79 was able to antagonize these fungi/oomycetes and that agar-diffusible metabolites and enzymes, as well as volatile compounds (different from HCN), participate in the antagonism exerted. We found thatPaenibacillussp. strain UY79 did not affect symbiotic association or growth promotion of alfalfa plants when co-inoculated with rhizobia. By whole genome sequence analysis, we determined that strain UY79 is a new species ofPaenibacilluswithin thePaenibacillus polymyxacomplex. Diverse genes putatively involved in biocontrol activity were identified in the UY79 genome. Moreover, according to genome mining and antibiosis assays, strain UY79 would have the capability to modulate the growth of bacteria commonly found in soil/plant communities.IMPORTANCEPhytopathogenic fungi and oomycetes are responsible for causing devastating losses in agricultural crops. Therefore, there is an enormous interest in the development of effective and complementary strategies that allow the control of the phytopathogens, reducing the input of agrochemicals in croplands. Discovery of new strains with expanded antifungal activities and with a broad spectrum of action is challenging and of great future impact. Diverse strains belonging to theP. polymyxacomplex have been reported to be effective biocontrol agents. Results presented here show that the novel discovered strain ofPaenibacillussp. presents diverse traits involved in antagonistic activity against a broad spectrum of pathogens and would be a potential and valuable strain to be further assessed for the development of biofungicides.
The Detection ofBergeyella zoohelcumin Young Children after Cat Bite
Authors: Hu Min , Li Hao , Hu Tao , Zhou Shuang-Yan , Yang Ze-Hua , Fan Cai-Lan , Bao Rong , Shi Jian-Guo , Zhao Ke-Bin 
Published: March 2021

ABSTRACTBergeyella zoohelcumis an uncommon zoonotic pathogen typically associated with cat or dog bites. Previously, only 14 cases ofB. zoohelcuminfection have been reported. We isolated the bacteria from the face of a 2-year-old girl who was bitten by a cat. The organism was identified by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) and 16S rRNA gene sequence, and phylogenetic analysise supported that this isolate was belong toB. zoohelcum. Due to the contradicts of culture characteristics ofB. zoohelcumwhich described in reported literatures, we used different media to culture the bacteria. After 24 h incubation, Colombia blood agar (CBA), Mueller-Hinton agar plate with 5% sheep blood and chocolate agar (CA) grew well, but blood agar (BA) grew well until 72 h. The strain did not grow on McConkey agar (MAC), Mueller-Hinton agar (MHA) and chocolate agar (containing vancomycin). The low detection rate of this strain was related to its harsh growth conditions and the limitations of traditional identification techniques. With the popularization of MALDI-TOF MS and 16S rRNA gene sequence and our further understanding of the fastidious bacteria, we will quickly and accurately identify theB. zoohelcum, meanwhile the detection rate of this bacterium will also be significantly improved. So that clinicians can achieve precise anti-infective treatment according to antimicrobial susceptibility testing.
How unequal vaccine distribution promotes the evolution of vaccine escape
Authors: Gerrish Philip J , Saldaña Fernando , Galeota-Sprung Benjamin , Colato Alexandre , Rodriguez Erika E , Hernández Jorge X Velasco 
Published: March 2021

AbstractHealth officials warn that SARS-CoV-2 vaccines must be uniformly distributed within and among countries if we are to quell the ongoing pandemic. Yet there has been little critical assessment of the underlying reasons for this warning. Here, we explicitly show why vaccine equity is necessary. Perhaps counter-intuitively, we find that vaccine escape mutants are less likely to come from highly vaccinated regions where there is strong selection pressure favoring vaccine escape and more likely to come from neighboring unvaccinated regions where there is no selection favoring escape. Unvaccinated geographic regions thus provide evolutionary reservoirs from which new strains can arise and cause new epidemics within neighboring vaccinated regions and beyond. Our findings have timely implications for vaccine rollout strategies and public health policy.
Estimation of SARS-CoV-2 antibody prevalence through integration of serology and incidence data
Authors: Wang Liangliang , Min Joosung , Doig Renny , Elliott Lloyd T , Colijn Caroline 
Published: March 2021

AbstractSerology tests for SARS-CoV-2 provide a paradigm for estimating the number of individuals who have had infection in the past (including cases that are not detected by routine testing, which has varied over the course of the pandemic and between jurisdictions). Classical statistical approaches to such estimation do not incorporate case counts over time, and may be inaccurate due to uncertainty about the sensitivity and specificity of the serology test. In this work, we provide a joint Bayesian model for case counts and serological data, integrating uncertainty through priors on the sensitivity and specificity. We also model the Phases of the pandemic with exponential growth and decay. This model improves upon maximum likelihood estimates by conditioning on more data, and by taking into account the epidemiological trajectory. We apply our model to the greater Vancouver area, British Columbia, Canada with data acquired during Phase 1 of the pandemic.
Th17 cell master transcription factor RORC2 regulates HIV-1 gene expression and viral outgrowth
Authors: Wiche Salinas Tomas Raul , Zhang Yuwei , Sarnello Daniele , Zhyvoloup Alexander , Raymond Marchand Laurence , Planas Delphine , Lodha Manivel , Chatterjee Debashree , Karwacz Kasia , Oxenford Sally , Routy Jean-Pierre , Amrine-Madsen Heather , Ancuta Petronela , Fassati Ariberto 
Published: March 2021

AbstractAmong CD4+ T-cells, T helper 17 (Th17) cells are particularly susceptible to HIV-1 infection and are depleted from mucosal sites, which causes damage to the gut barrier resulting in microbial translocation-induced systemic inflammation, a hallmark of disease progression. Furthermore, a proportion of latently infected Th17 cells persist long-term in the gastro-intestinal lymphatic tract, where low-level HIV-1 transcription is observed. This residual viremia contributes to chronic immune activation. Thus, Th17 cells are key players in HIV pathogenesis and viral persistence, however it is unclear why these cells are highly susceptible to HIV-1 infection. Th17 cell differentiation depends on expression of the master transcriptional regulatorRORC2, aretinoic acid-related nuclear hormone receptor that regulates specific transcriptional programs by binding to promoter/enhancer DNA. Here, we report that RORC2 is a key host-cofactor for HIV replication in Th17 cells. We found that specific inhibitors that bind to the RORC2 ligand-binding domain reduced HIV replication in CD4+ T-cells. Depletion of RORC2 inhibited HIV-1 infection, whereas RORC2 overexpression enhanced it. RORC2 was found to promote HIV-1 gene expression. Chromatin immune precipitation revealed that RORC2 binds to the nuclear receptor responsive element (NRRE) in the HIV-1 LTR. In treated HIV-1 patients, RORC2+ CD4 T cells contained more proviral DNA than RORC2− cells. Pharmacological inhibition of RORC2 potently reduced HIV-1 outgrowth in CD4+ T-cells from antiretroviral-treated patients. Altogether, these results provide a new explanation as to why Th17 cells are highly susceptible to HIV-1 infection and point to RORC2 as a cell-specific target for HIV-1 therapy.Significance statementHIV-1 infects CD4 T cells and among these, Th17 cells are known to be particularly permissive for virus replication. Infection of Th17 cells is critical for AIDS pathogenesis and viral persistence, however it is not clear why these cells are highly permissive to HIV-1. We found that Th17 cell permissiveness depends on expression of the hormone receptor RORC2, which is the master transcriptional regulator of Th17 cell differentiation. We identify RORC2 as a new, cell-specific host-dependency factor that can be targeted by small molecules. Our results point to RORC2 as a cell-specific target for HIV-1 therapy, an entirely new concept in the field, and suggest HIV-1 might have evolved to exploit RORC2 to promote its own persistence.
Canagliflozin increases adenoma burden in female APCMin/+mice
Authors: Korfhage Justin , Skinner Mary E. , Basu Jookta , Greenson Joel K. , Miller Richard A. , Lombard David B. 
Published: March 2021

SummaryThe diabetes drug canagliflozin acts primarily by inhibiting glucose reuptake by the sodium glucose transporter 2 (SGLT2) in the kidney proximal tubule, thereby lowering serum glucose levels. Canagliflozin also acts on SGLT1, a related transporter responsible for glucose uptake in the small intestine and more distal kidney tubules. Several cancers overexpress SGLT1 and SGLT2, where these transporters fuel tumor metabolism. A recent study by NIA’s Interventions Testing Program (ITP) showed that canagliflozin treatment extends lifespan in male mice. Since cancer is the major cause of death in most mouse strains, including the UM-HET3 strain used by the ITP, this observation suggests that canagliflozin might exert anti-cancer effects in this context. Here, we treated a commonly-used mouse neoplasia model -- the intestinal adenoma-prone APCMin/+strain -- with canagliflozin, to test the effects of drug treatment on tumor burden. Surprisingly, canagliflozin increased the total area of intestine involved by adenomas, an effect that was most marked in the distal intestine and in female mice. Immunohistochemical analysis suggested that canagliflozin may not influence adenoma growth via direct SGLT1/2 inhibition in neoplastic cells themselves. Instead, our results are most consistent with a model whereby canagliflozin aggravates adenoma development by altering the anatomic distribution of intestinal glucose absorption, as evidenced by increases in postprandial GLP-1 levels consistent with delayed glucose absorption. Our results suggest that canagliflozin exacerbates adenomatosis in the APCMin/+model via complex, cell-non-autonomous mechanisms, and hint that sex differences in incretin responses may underlie differential effects of this drug on lifespan.
In vivodissection of Rhoa function in vascular development using zebrafish
Authors: Pillay Laura M. , Yano Joseph J. , Davis Andrew E. , Butler Matthew G. , Barnes Keith A. , Reyes Vanessa L. , Castranova Daniel , Gore Aniket V. , Swift Matthew R. , Iben James R. , Stratman Amber N. , Weinstein Brant M. 
Published: March 2021

ABSTRACTRationaleThe small monomeric GTPase RHOA acts as a master regulator of signal transduction cascades by activating effectors of cellular signaling, including the Rho-associated protein kinases ROCK1/2. Previousin vitrocell culture studies suggest that RHOA can regulate many critical aspects of vascular endothelial cell (EC) biology, including focal adhesion, stress fiber formation, and angiogenesis. However, the specificin vivoroles of RHOA during vascular development and homeostasis are still not well understood.ObjectiveIn this study we examine thein vivofunctions of RHOA in regulating vascular development and integrity in zebrafish.Methods and ResultsWe use zebrafish RHOA-ortholog (rhoaa) mutants, transgenic embryos expressing wild type, dominant-negative, or constitutively active forms ofrhoaain ECs, and a pharmacologic inhibitor of ROCK1/2 to study thein vivoconsequences of RHOA gain- and loss-of-function in the vascular endothelium. Our findings document roles for RHOA in vascular integrity, developmental angiogenesis, and vascular morphogenesis.ConclusionsOur results indicate that either too much or too little RHOA activity leads to vascular dysfunctionin vivo.