bluuebunny/crossref_metadata_2025_split huggingface dataset:
Legionella pneumophila’s Tsp is important for surviving thermal stress in water and inside amoeba
Authors: Saoud Joseph , Mani Thangadurai , Faucher Sébastien P. 
Published: December 2020

ABSTRACTLegionella pneumophila(Lp) is an inhabitant of natural and man-made water systems where it replicates within amoebae and ciliates and survives within biofilms. WhenLp-contaminated aerosols are breathed in,Lpwill enter the lungs and infect human alveolar macrophages, causing a severe pneumonia known as Legionnaires Disease.Lpis often found in hot water distribution systems (HWDS), which are linked to nosocomial outbreaks. Heat treatment is used to disinfect HWDS and reduce the concentration ofLp. However,Lpis often able to recolonize these water systems, indicating an efficient heat-shock response. Tail-specific proteases (Tsp) are typically periplasmic proteases implicated in degrading aberrant proteins in the periplasm and important for surviving thermal stress. In this paper, we show that Tsp, encoded by thelpg0499gene inLpPhiladelphia-1, is important for surviving thermal stress in water and for optimal infection of amoeba when a shift in temperature occurs during intracellular growth. Tsp is expressed in the post-exponential phase but repressed in the exponential phase. Thecis-encoded small regulatory RNA Lpr17 shows opposite expression, suggesting that it represses translation oftsp. In addition,tspis regulated by CpxR, a major regulator inLp, in a Lpr17-independent manner. Deletion of CpxR also reduced the ability ofLpto survive heat shock. In conclusion, this study shows that Tsp is an important factor for the survival and growth ofLpin water systems.IMPORTANCELegionella pneumophila(Lp) is a major cause of nosocomial and community-acquired pneumonia.Lpis found in water systems including hot water distribution systems. Heat treatment is a method of disinfection often used to limitLp’s presence in such systems; however, the benefit is usually short term asLpis able to quickly recolonize these systems. Presumably,Lprespond efficiently to thermal stress, but so far not much is known about the genes involved. In this paper, we show that the Tail-specific protease (Tsp) and the two-component system CpxRA are required for resistance to thermal stress, whenLpis free in water and when it is inside host cells. Our study identifies critical systems for the survival ofLpin its natural environment under thermal stress.
Age and axon-specific forms of cortical remyelination by divergent populations of NG2-glia
Authors: Chapman Timothy W. , Olveda Genaro E. , Pereira Elizabeth , Hill Robert A. 
Published: December 2020

ABSTRACTMyelin is critical for neural circuit function and its destruction is widespread in neurodegenerative disease and aging. In these conditions, homeostatic repair mechanisms initiate oligodendrocyte replacement by resident progenitor cells called NG2-glia. To investigate the cellular dynamics of this repair we developed a novel demyelination model by combining intravital myelin imaging with a targeted single-cell ablation technique called 2Phatal. Oligodendrocyte 2Phatal activated a stereotyped degeneration cascade which triggered remyelination by local NG2-glia. Remyelination efficiency was dependent on initial myelin patterning and dynamic imaging revealed rapid repair mechanisms resulting in near-seamless transitions between myelin loss and repair. A subset of morphologically complex NG2-glia executed this remyelination, pointing towards unrecognized functional diversity within this population. Age-related demyelination mirrored the degenerative cascade observed with 2Phatal, while remyelination in aging was defective due to failed oligodendrogenesis. Thus, oligodendrocyte 2Phatal revealed cellular diversity within the oligodendrocyte lineage and uncovered novel forms of rapid remyelination.
PopAmaranth: A population genetic genome browser for grain amaranths and their wild relatives
Authors: Gonçalves-Dias José , Stetter Markus G 
Published: December 2020

The last decades of genomic, physiological, and population genetic research have accelerated the understanding and improvement of a numerous crops. The transfer of methods to minor crops could accelerate their improvement if knowledge is effectively shared between disciplines. Grain amaranth is an ancient nutritious pseudocereal from the Americas that is regaining importance due to its high protein content and favorable amino acid and micronutrient composition. To effectively combine genomic and population genetic information with molecular genetics, plant physiology, and use it for interdisciplinary research and crop improvement, an intuitive interaction for scientists across disciplines is essential. Here, we present PopAmaranth, a population genetic genome browser, which provides an accessible representation of the genetic variation of the three grain amaranth species (A. hypochondriacus, A. cruentus, andA. caudatus) and two wild relatives (A. hybridusandA. quitensis) along theA. hypochondriacusreference sequence. We performed population-scale diversity and selection analysis from whole-genome sequencing data of 88 curated genetically and taxonomically unambiguously classified accessions. We incorporate the domestication history of the three grain amaranths to make an evolutionary perspective for candidate genes and regions available. We employ the platform to show that genetic diversity in the water stress-related MIF1 gene declined during amaranth domestication and provide evidence for convergent saponin reduction between amaranth and quinoa. These examples show that our tool enables the detailed study of individual genes, provides target regions for breeding efforts and can enhance the interdisciplinary integration of population genomic findings across species. PopAmaranth is available through amaranthGDB at amaranthgdb.org/popamaranth.htmlSignificanceSharing population genetic results between disciplines can facilitate interdisciplinary research and accelerate the improvement of crops. Since the onset of genome sequencing online genome browser platforms have provide access to features of an organisms genetic information. Rarely this has been extended to population-wide summary statistics for evolutionary hypothesis testing. We implemented a population genetic genome browser PopAmaranth for three grain amaranth species and their two wild relatives. The intuitive and user-friendly interface of PopA-maranth makes the genetic diversity of the species complex available to broad audience of biologists across disciplines. We show how our tool can be used to study convergence across distant genera and find signals of past selection in domestication and stress related genes. Community platforms and genome browsers are an integrative element of numerous study systems. PopAmaranth can serve as template for other research communities to integrate and share their results.
Identification of a Novel Susceptibility Marker for SARS-CoV-2 Infection in Human Subjects and Risk Mitigation with a Clinically Approved JAK Inhibitor in Human/Mouse Cells
Authors: Spalinger Marianne R. , Hai Rong , Li Jiang , Santos Alina N. , Nordgren Tara M. , Tremblay Michel L. , Eckmann Lars , Hanson Elaine , Scharl Michael , Wu Xiwei , Boland Brigid S. , McCole Declan F. 
Published: December 2020

ABSTRACTCoronavirus disease (COVID-19), caused by SARS-CoV-2, has affected over 65 million individuals and killed over 1.5 million persons (December 8, 2020;www.who.int)1. While fatality rates are higher among the elderly and those with underlying comorbidities2, host factors that promote susceptibility to SARS-CoV-2 infection and severe disease are poorly understood. Although individuals with certain autoimmune/inflammatory disorders show increased susceptibility to viral infections, there is incomplete knowledge of SARS-CoV-2 susceptibility in these diseases.3–7We report that the autoimmunePTPN2risk variant rs1893217 promotes expression of the SARS-CoV-2 receptor, ACE2, and increases cellular entry mediated by SARS-CoV-2 spike protein. Elevated ACE2 expression and viral entry were mediated by increased JAK-STAT signalling, and were reversed by the JAK inhibitor, tofacitinib. Collectively, our findings uncover a novel risk biomarker for increased expression of the SARS-CoV-2 receptor and viral entry, and identify a clinically approved therapeutic agent to mitigate this risk.
An interactive viral genome evolution network analysis system enabling rapid large-scale molecular tracing of SARS-CoV-2
Authors: Ling Yunchao , Cao Ruifang , Qian Jiaqiang , Li Jiefu , Zhou Haokui , Yuan Liyun , Wang Zhen , Zheng Guangyong , Zhao Guoping , Li Yixue , Wang Zefeng , Zhang Guoqing 
Published: December 2020

AbstractComprehensive analyses of viral genomes can provide a global picture on SARS-CoV-2 transmission and help to predict the oncoming trends of pandemic. This molecular tracing is mainly conducted through extensive phylogenetic network analyses. However, the rapid accumulation of SARS-CoV-2 genomes presents an unprecedented data size and complexity that has exceeded the capacity of existing methods in constructing evolution network through virus genotyping. Here we report a Viral genome Evolution Network Analysis System (VENAS), which uses Hamming distances adjusted by the minor allele frequency to construct viral genome evolution network. The resulting network was topologically clustered and divided using community detection algorithm, and potential evolution paths were further inferred with a network disassortativity trimming algorithm. We also employed parallel computing technology to achieve rapid processing and interactive visualization of >10,000 viral genomes, enabling accurate detection and subtyping of the viral mutations through different stages of Covid-19 pandemic. In particular, several core viral mutations can be independently identified and linked to early transmission events in Covid-19 pandemic. As a general platform for comprehensive viral genome analysis, VENAS serves as a useful computational tool in the current and future pandemics.
A vacuolar hexose transport is required for xylem development in the inflorescence stem of Arabidopsis
Authors: Aubry Emilie , Hoffmann Beate , Vilaine Françoise , Gilard Françoise , Klemens Patrick A.W. , Guérard Florence , Gakière Bertrand , Neuhaus H. Ekkehard , Bellini Catherine , Dinant Sylvie , Hir Rozenn Le 
Published: December 2020

ABSTRACTIn higher plants, the development of the vascular system is controlled by a complex network of transcription factors. However, how nutrient availability in the vascular cells affects their development remains to be addressed. At the cellular level, cytosolic sugar availability is regulated mainly by sugar exchanges at the tonoplast through active and/or facilitated transport. InArabidopsis thaliana, among the tonoplastic transporters,SWEET16andSWEET17genes have been previously localized in the vascular system. Here, using a reverse genetic approach, we propose that sugar exchanges at the tonoplast, regulated by SWEET16, are important for xylem cell division as revealed in particular by the decreased number of xylem cells in theswt16mutant and the expression of SWEET16 at the procambium-xylem boundary. In addition, we demonstrate that transport of hexoses mediated by SWEET16 and/or SWEET17 is required to sustain the formation of the xylem secondary cell wall. This result is in line with a defect in the xylem cell wall composition as measured by FTIR in theswt16swt17double mutant and by upregulation of several genes involved in secondary cell wall synthesis. Our work therefore supports a model in which xylem development is partially dependent on the exchange of hexoses at the tonoplast of xylem-forming cells.
DDK regulates replication initiation by controlling the multiplicity of Cdc45-GINS binding to Mcm2-7
Authors: De Jesús-Kim Lorraine , Friedman Larry J. , Ramsoomair Christian , Gelles Jeff , Bell Stephen P. 
Published: December 2020

AbstractThe committed step of eukaryotic DNA replication occurs when the replicative Mcm2-7 helicase pairs that license each replication origin are activated. Helicase activation requires the recruitment of Cdc45 and GINS to Mcm2-7, forming Cdc45-Mcm2-7-GINS complexes (CMGs). Using single-molecule biochemical assays to monitor CMG formation, we found that Cdc45 and GINS are recruited to loaded Mcm2-7 in two stages. Initially, Cdc45 and GINS are individually recruited to unstructured Mcm2-7 N-terminal tails in a Dbf4-dependent kinase (DDK)-dependent manner, forming Cdc45-tail-GINS intermediates (CtGs). The multiple phosphorylation sites on the Mcm2-7 tails promote DDK-dependent modulation of the number of CtGs formed per Mcm2-7. In a second, inefficient event, a subset of CtGs transfer their Cdc45 and GINS components to form CMGs. Importantly, higher CtG multiplicity results in increased frequency of CMG formation. Our findings reveal molecular mechanisms sensitizing helicase activation to DDK levels with implications for the control of replication origin efficiency and timing.
Spatio-temporal dynamics of intra-host variability in SARS-CoV-2 genomes
Authors: Pathak Ankit K. , Mishra Gyan Prakash , Uppili Bharathram , Walia Safal , Fatihi Saman , Abbas Tahseen , Banu Sofia , Ghosh Arup , Kanampalliwar Amol , Jha Atimukta , Fatima Sana , Aggarwal Shifu , Dhar Mahesh Shanker , Marwal Robin , Radhakrishnan V. S. , Ponnusamy Kalaiarasan , Kabra Sandhya , Rakshit Partha , Bhoyar Rahul C. , Jain Abhinav , Divakar Mohit Kumar , Imran Mohamed , Faruq Mohammed , Sowpati Divya Tej , Thukral Lipi , Raghav Sunil K. , Mukerji Mitali 
Published: December 2020

ABSTRACTDuring the course of the COVID-19 pandemic, large-scale genome sequencing of SARS-CoV-2 has been useful in tracking its spread and in identifying Variants Of Concern (VOC). Besides, viral and host factors could contribute to variability within a host that can be captured in next-generation sequencing reads as intra-host Single Nucleotide Variations (iSNVs). Analysing 1, 347 samples collected till June 2020, we recorded 18, 146 iSNV sites throughout the SARS-CoV-2 genome. Both, mutations in RdRp as well as APOBEC and ADAR mediated RNA editing seem to contribute to the differential prevalence of iSNVs in hosts. Noteworthy, 41% of all unique iSNVs were reported as SNVs by 30th September 2020 in samples submitted to GISAID, which increased to ∼80% by 30th June 2021. Following this, analysis of another set of 1, 798 samples sequenced in India between November 2020 and May 2021 revealed that majority of the Delta (B.1.617.2) and Kappa (B.1.617.1) variations appeared as iSNVs before getting fixed in the population. We also observe hyper-editing events at functionally critical residues in Spike protein that could alter the antigenicity and may contribute to immune escape. Thus, tracking and functional annotation of iSNVs in ongoing genome surveillance programs could be important for early identification of potential variants of concern and actionable interventions.GRAPHICAL ABSTRACT
Effect of host genetics on the gut microbiome in 7,738 participants of the Dutch Microbiome Project
Authors: Lopera-Maya E.A. , Kurilshikov A. , van der Graaf A. , Hu S. , Andreu-Sánchez S. , Chen L. , Vich Vila A. , Gacesa R. , Sinha T. , Collij V. , Klaassen M.A.Y. , Bolte L.A. , Brandao Gois M.F. , Neerincx P.B.T. , Swertz M.A. ,   LifeLines Cohort Study, Harmsen H.J.M. , Wijmenga C. , Fu J. , Weersma R.K. , Zhernakova A. , Sanna S. 
Published: December 2020

AbstractHost genetics are known to influence the gut microbiome, yet their role remains poorly understood. To robustly characterize these effects, we performed a genome-wide association study of 207 taxa and 205 pathways representing microbial composition and function within the Dutch Microbiome Project, a population cohort of 7,738 individuals from the northern Netherlands. Two robust, study-wide significant (p<1.89×10-10) signals near theLCTandABOgenes were found to affect multiple microbial taxa and pathways, and were replicated in two independent cohorts. TheLCTlocus associations were modulated by lactose intake, while those atABOreflected participant secretor status determined byFUT2genotype. Eighteen other loci showed suggestive evidence (p<5×10-8) of association with microbial taxa and pathways. At a more lenient threshold, the number of loci identified strongly correlated with trait heritability, suggesting that much larger sample sizes are needed to elucidate the remaining effects of host genetics on the gut microbiome.
Loss of p32 triggers energy deficiency and impairs goblet cell differentiation in ulcerative colitis
Authors: Sünderhauf Annika , Hicken Maren , Schlichting Heidi , Skibbe Kerstin , Ragab Mohab , Raschdorf Annika , Hirose Misa , Schäffler Holger , Bokemeyer Arne , Bettenworth Dominik , Savitt Anne G. , Perner Sven , Ibrahim Saleh , Peerschke Ellinor I. , Ghebrehiwet Berhane , Derer Stefanie , Sina Christian 
Published: December 2020

AbstractCell differentiation in the colonic crypt is driven by a metabolic switch from glycolysis to mitochondrial oxidation. Mitochondrial and goblet cell (GC) dysfunction have been attributed to the pathology of ulcerative colitis (UC). We hypothesized that p32/gC1qR/HABP1, which critically maintains oxidative phosphorylation, is involved in GC differentiation and hence in the pathogenesis of UC. In UC patients in remission, colonic GC differentiation was significantly decreased compared to controls in a p32-dependent manner. Plasma/serum lactate and colonic pAMPK level were increased, pointing at high glycolytic activity and energy deficiency. Consistently,p32silencing in mucus-secreting HT29-MTX cells abolished butyrate-induced differentiation and induced a shift towards glycolysis. In mitochondrial respiratory chain complex V-deficient mice, colonic p32 expression correlated with loss of differentiated GCs, resulting in a thinner mucus layer. Conversely, feeding mice an isocaloric glucose-free, high-protein diet increased mucosal energy supply that promoted colonic p32 level, GC differentiation and mucus production. We here describe a new molecular mechanism linking mucosal energy deficiency in UC to impaired p32-dependent GC differentiation that may be therapeutically prevented by nutritional intervention.
Allele Mining in Diverse Accessions ofUrochloaandMegathyrsusspp. Tropical Grasses to Improve Forage Quality and Reduce Environmental Impact
Authors: Hanley SJ , Pellny TK , de Vega JJ , Castiblanco V , Arango J , Eastmond PJ , Heslop-Harrison JS , Mitchell RAC 
Published: December 2020

AbstractThe C4Urochloaspp (syn.Brachiaria) andMegathyrsus maximus(syn.Panicum maximum) are used as pasture for cattle across vast areas in tropical agriculture systems in Africa and South America. A key target for variety improvement is forage quality: enhanced digestibility could decrease amount of land required per unit production and enhanced lipid content could decrease methane emissions from cattle. For these traits, loss-of-function (LOF) alleles in known gene targets are predicted to improve them, making a reverse genetics approach of allele mining feasible. We studied allelic diversity of 20 target genes (11 for digestibility, 9 for lipid content) in 104 accessions selected to represent genetic diversity and ploidy levels ofU. brizantha,U. decumbens, U. humidicola, U. ruziziensisandM. maximum. We used RNAseq and then bait-capture DNA-seq to improve gene models in aU. ruziziensisreference genome to assign polymorphisms with high confidence. We found 953 non-synonymous polymorphisms across all genes and accessions; within these, we identified 7 putative LOF alleles with high confidence, including ones in the non-redundant SDP1 and BAHD01 genes present in diploid and tetraploid accessions. These LOF alleles could respectively confer increased lipid content and digestibility if incorporated into a breeding programme.HighlightWe found gene variants in a collection of tropical grasses that could help reduce environmental impact of cattle production.
UbiB proteins regulate cellular CoQ distribution
Authors: Kemmerer Zachary A. , Robinson Kyle P. , Schmitz Jonathan M. , Paulson Brett R. , Jochem Adam , Hutchins Paul D. , Coon Joshua J. , Pagliarini David J. 
Published: December 2020

AbstractCoenzyme Q (CoQ, ubiquinone) is a redox-active lipid essential for many core metabolic processes in mitochondria, including oxidative phosphorylation1-3. While lesser appreciated, CoQ also serves as a key membrane-embedded antioxidant throughout the cell4. However, how CoQ is mobilized from its site of synthesis on the inner mitochondrial membrane to other sites of action remains a longstanding mystery. Here, using a combination of yeast genetics, biochemical fractionation, and lipid profiling, we identify two highly conserved but poorly characterized mitochondrial proteins, Ypl109c (Cqd1) and Ylr253w (Cqd2), that reciprocally regulate this process. Loss of Cqd1 skews cellular CoQ distribution away from mitochondria, resulting in markedly enhanced resistance to oxidative stress caused by exogenous polyunsaturated fatty acids (PUFAs), whereas loss of Cqd2 promotes the opposite effects. The activities of both proteins rely on their atypical kinase/ATPase domains, which they share with Coq8—an essential auxiliary protein for CoQ biosynthesis. Overall, our results reveal new protein machinery central to CoQ trafficking in yeast and lend new insights into the broader interplay between mitochondrial and cellular processes.
Transcription factors drive opposite relationships between gene age and tissue specificity in male and femaleDrosophilagonads
Authors: Witt Evan , Svetec Nicolas , Benjamin Sigi , Zhao Li 
Published: December 2020

AbstractEvolutionarily young genes are usually preferentially expressed in the testis across species. While it is known that older genes are generally more broadly expressed than younger genes, the properties that shaped this pattern are unknown. Older genes may gain expression across other tissues uniformly, or faster in certain tissues than others. UsingDrosophilagene expression data, we confirmed previous findings that younger genes are disproportionately testis-biased and older genes are disproportionately ovary-biased. We found that the relationship between gene age and expression is stronger in the ovary than any other tissue, and weakest in testis. We performed ATAC-seq onDrosophilatestis and found that while genes of all ages are more likely to have open promoter chromatin in testis than in ovary, promoter chromatin alone does not explain the ovary-bias of older genes. Instead, we found that upstream transcription factor (TF) expression is highly predictive of gene expression in ovary, but not in testis. In ovary, TF expression is more predictive of gene expression than open promoter chromatin, whereas testis gene expression is similarly influenced by both TF expression and open promoter chromatin. We propose that the testis is uniquely able to expresses younger genes controlled by relatively few TFs, while older genes with more TF partners are broadly expressed with peak expression most likely in ovary. The testis allows widespread baseline expression that is relatively unresponsive to regulatory changes, whereas the ovary transcriptome is more responsive to trans-regulation and has a higher ceiling for gene expression.