bluuebunny/crossref_metadata_2025_split huggingface dataset:
Furin controls β cell function via mTORC1 signaling
Authors: Brouwers Bas , Coppola Ilaria , Vints Katlijn , Dislich Bastian , Jouvet Nathalie , Van Lommel Leentje , Gounko Natalia V. , Thorrez Lieven , Schuit Frans , Lichtenthaler Stefan F. , Estall Jennifer L. , Declercq Jeroen , Ramos-Molina Bruno , Creemers John W.M. 
Published: April 2020

AbstractFurin is a proprotein convertase (PC) responsible for proteolytic activation of a wide array of precursor proteins within the secretory pathway. It maps to the PRC1 locus, a type 2 diabetes susceptibility locus, yet its specific role in pancreatic β cells is largely unknown. The aim of this study was to determine the role of furin in glucose homeostasis. We show that furin is highly expressed in human islets, while PCs that potentially could provide redundancy are expressed at considerably lower levels. β cell-specific furin knockout (βfurKO) mice are glucose intolerant, due to smaller islets with lower insulin content and abnormal dense core secretory granule morphology. RNA expression analysis and differential proteomics on βfurKO islets revealed activation of Activating Transcription Factor 4 (ATF4), which was mediated by mammalian target of rapamycin C1 (mTORC1). βfurKO cells show impaired cleavage of the essential V-ATPase subunit Ac45, and by blocking this pump in β cells the mTORC1 pathway is activated. Furthermore, βfurKO cells show lack of insulin receptor cleavage and impaired response to insulin. Taken together, these results suggest a model of mTORC1-ATF4 hyperactivation in β cells lacking furin, which causes β cell dysfunction.
MYB5a/NEGANactivates petal anthocyanin pigmentation and shapes the MBW regulatory network inMimulus luteusvar.variegatus
Authors: Zheng Xingyu , Om Kuenzang , Stanton Kimmy A. , Thomas Daniel , Cheng Philip A. , Eggert Allison , Yuan Yao-Wu , Puzey Joshua R. , Cooley Arielle M. 
Published: April 2020

AbstractMuch of the visual diversity of angiosperms is due to the frequent evolution of novel pigmentation patterns in flowers. The gene network responsible for anthocyanin pigmentation, in particular, has become a model for investigating how genetic changes give rise to phenotypic innovation. In the monkeyflower genusMimulus, an evolutionarily recent gain of petal lobe anthocyanin pigmentation inM. luteusvar.variegatuswas previously mapped to genomic regionpla2. Here, we use DNA sequence analysis and spatiotemporal patterns of gene expression to identifyMYB5a- homologous to theNEGANtranscriptional activator fromM. lewisii- as a likely candidate gene within thepla2region. Transgenic manipulation of gene expression confirms thatMYB5ais both necessary and sufficient for petal lobe anthocyanin pigmentation. The deployment ofMYB5a/NEGANto the petal lobe stands in contrast to its more restricted role as a nectar guide anthocyanin activator in otherMimulusspecies. Transcriptome sequencing of aMYB5aRNAi line reveals the degree to which other regulators of the anthocyanin pathway - including R3 MYB repressors and bHLH and WD40 co-activators - are responsive to the level of expression ofMYB5a. Overall, this work reveals that a genetically simple change, which we hypothesize to be a regulatory mutation incistoMYB5a, has cascading effects on gene expression, not only on the genes downstream ofMYB5abut also on all of its known partners in the anthocyanin regulatory network.Graphical abstract.Solid black arrows indicate the direction (though not magnitude) of gene expression change, following RNAi knockdown ofMYB5a/NEGANinM. l. variegatus. The number of black arrows corresponds to the number of gene copies identified in the transcriptome. Grey symbols denote positive and negative regulatory interactions. RTO is an R3 MYB protein that inhibits anthocyanin biosynthesis by sequestering bHLH proteins away from the MBW complex.
Systems Biology under heat stress in Indian Cattle
Authors: Khan Raja Ishaq Nabi , Sahu Amit Ranjan , Malla Waseem Akram , Praharaj Manas Ranjan , Hosamani Neelima , Kumar Shakti , Gupta Smita , Sharma Shweta , Saxena Archana , Varshney Anshul , Singh Pragya , Verma Vinay , Kumar Puneet , Singh Gyanendra , Pandey Aruna , Saxena Shikha , Gandham Ravi Kumar , Tiwari Ashok Kumar 
Published: April 2020

AbstractTranscriptome profiling of Vrindavani and Tharparkar cattle revealed that more numbers of genes dysregulated in Vrindavani than in Tharparkar. A contrast in gene expression was observed with 18.5 % of upregulated genes in Vrindavani were downregulated in Tharparkar and 17.5% upregulated genes in Tharparkar were downregulated in Vrindavani. Functional annotation of genes differentially expressed in Tharparkar and Vrindavani revealed that the systems biology in Tharparkar is moving towards counteracting the effects due to heat stress. Unlike Vrindavani, Tharparkar is not only endowed with higher expression of the scavengers (UBE2G1, UBE2S, andUBE2H) of misfolded proteins but also with protectors (VCP, Serp1, andCALR) of naïve unfolded proteins. Further, higher expression of the antioxidants in Tharparkar enables it to cope up with higher levels of free radicals generated as a result of heat stress. In this study we found relevant genes dysregulated in Tharparkar in the direction that can counter heat stress.
Assessing the Performance of qpAdm: A Statistical Tool for Studying Population Admixture
Authors: Harney Éadaoin , Patterson Nick , Reich David , Wakeley John 
Published: April 2020

ABSTRACTqpAdm is a statistical tool for studying the ancestry of populations with histories that involve admixture between two or more source populations. Using qpAdm, it is possible to identify plausible models of admixture that fit the population history of a group of interest and to calculate the relative proportion of ancestry that can be ascribed to each source population in the model. Although qpAdm is widely used in studies of population history of human (and non-human) groups, relatively little has been done to assess its performance. We performed a simulation study to assess the behavior of qpAdm under various scenarios in order to identify areas of potential weakness and establish recommended best practices for use. We find that qpAdm is a robust tool that yields accurate results in many cases, including when data coverage is low, there are high rates of missing data or ancient DNA damage, or when diploid calls cannot be made. However, we caution against co-analyzing ancient and present-day data, the inclusion of an extremely large number of reference populations in a single model, and analyzing population histories involving extended periods of gene flow. We provide a user guide suggesting best practices for the use of qpAdm.
The eccDNA Replicon: A heritable, extra-nuclear vehicle that enables gene amplification and glyphosate resistance inAmaranthus palmeri
Authors: Molin William T. , Yaguchi Allison , Blenner Mark , Saski Christopher A. 
Published: April 2020

ABSTRACTGene copy number variation is a predominant mechanism by which organisms respond to selective pressures in nature, which often results in unbalanced structural variations that perpetuate as adaptations to sustain life. However, the underlying mechanisms that give rise to gene proliferation are poorly understood. Here, we show a unique result of genomic plasticity inAmaranthus palmeri, a massive, ∼400kb extrachromosomal circular DNA (eccDNA), that harbors the 5-enoylpyruvylshikimate-3-phosphate synthase (EPSPS) gene and 58 other encoded genes whose functions traverse detoxification, replication, recombination, transposition, tethering, and transport. Gene expression analysis under glyphosate stress showed transcription of 41 of the 59 genes, with high expression ofEPSPS, aminotransferase, zinc-finger, and several uncharacterized proteins. The genomic architecture of the eccDNA replicon is comprised of a complex arrangement of repeat sequences and mobile genetic elements interspersed among arrays of clustered palindromes that may be crucial for stability, DNA duplication and tethering, and/or a means of nuclear integration of the adjacent and intervening sequences. Comparative analysis of orthologous genes in grain amaranth (Amaranthus hypochondriacus) and water-hemp (Amaranthus tuberculatus) suggest higher order chromatin interactions contribute to the genomic origins of theAmaranthus palmerieccDNA replicon structure.One-sentence summaryThe eccDNA replicon is a large extra-nuclear circular DNA that is composed of a sophisticated repetitive structure, harbors theEPSPSand several other genes that are transcribed during glyphosate stress.
Whales and Men: genetic inferences uncover a detailed history of hunting in bowhead whale
Authors: Hoareau TB 
Published: April 2020

AbstractAfter millennia of hunting and a population collapse, it is still challenging to understand the genetic consequences of whaling on the circumarctic bowhead whale. Here I use published modern mtDNA sequences from the Bering-Chukchi-Beaufort population and a new time calibration to show that late–glacial climate changes and whaling have been the major drivers of population change. Cultures that hunted in the Arctic Seas from as early as 5000 years ago appear to be responsible for successive declines of the population growth, bringing the effective size down to 38% of its pristine population size. The Thules and the Basques (year 1000–1730) who only hunted in the North Atlantic had a major impact on this North Pacific population, indicating that bowhead whale stocks respond to harvesting as a single population unit. Recent positive growth is inferred only after the end of commercial whaling in 1915, and for levels of harvesting that are close to the current annual quota of 67 whales. By unfolding the population history of the bowhead whale, I provide compelling evidence that mtDNA yields critical yet undervalued information for management and conservation of natural populations.
A framework for detecting and quantifying relationship alterations in microbial community: Quantifying microbial relationship alteration
Authors: Liu Zhi , Mi Kai , Xu Zhenjiang Zech , Zhang Qiangkun , Liu Xingyin 
Published: April 2020

AbstractDysbiosis of gut microbiota is associated with the pathogenesis of human disease. Observing shifts in the microbe abundance cannot fully reveal underlying perturbations. Examining the relationship alteration (RA) in microbiome between different healthy status provides additional hints about the pathogenesis of human disease. However, no methods were designed to directly detect and quantify the RA between different conditions. Here, we present PM2RA (Profile Monitoring for Microbial Relationship Alteration), an analysis framework to identify and quantify the microbial RAs. The performance of PM2RA were evaluated in synthetic data, and found to show higher specificity and sensitivity than the co-occurrence-based methods. Analyses of real microbial dataset show that PM2RA is robust for quantifying microbial RA across different datasets in several diseases. By applying PM2RA, we identified both previously reported and novel microbes implicated in multiple diseases. The PM2RA is implemented as a web-based application available athttp://www.pm2ra-xingyinliulab.cn/.
FORK-seq: replication landscape of theSaccharomyces cerevisiaegenome by nanopore sequencing
Authors: Hennion Magali , Arbona Jean-Michel , Lacroix Laurent , Cruaud Corinne , Theulot Bertrand , Tallec Benoît Le , Proux Florence , Wu Xia , Novikova Elizaveta , Engelen Stefan , Lemainque Arnaud , Audit Benjamin , Hyrien Olivier 
Published: April 2020

ABSTRACTGenome replication mapping methods profile cell populations, masking cell-to-cell heterogeneity. Here, we describe FORK-seq, a nanopore sequencing method to map replication of single DNA molecules at 200 nucleotide resolution. By quantifying BrdU incorporation along pulse-chased replication intermediates fromSaccharomyces cerevisiae, we orient 58,651 replication tracks reproducing population-based replication directionality profiles and map 4,964 and 4,485 individual initiation and termination events, respectively. Although most events cluster at known origins and fork merging zones, 9% and 18% of initiation and termination events, respectively, occur at many locations previously missed. Thus, FORK-seq reveals the full extent of cell-to-cell heterogeneity in DNA replication.
Strand-specific cDNA library-based RNA sequencing dataset of un-infected andAscosphaera apis-infected larval guts ofApis cerana cerana
Authors: Chen Huazhi , Zhu Zhiwei , Wang Jie , Fan Yuanchan , Jiang Haibin , Zheng Yanzhen , Xiong Cuiling , Chen Dafu , Guo Rui 
Published: April 2020

ABSTRACTApis cerana ceranais a subspecies of eastern honeybee,Apis cerana.Ascosphaera apisis a widespread fungal pathogen of honeybee, leading to chalkbrood, which results in heavy losses for beekeeping industry. In this article, 4-, 5-, and 6-day-old larval guts of un-infected (AcCK1, AcCK2, and AcCK3) andA. apis-infectedA. c. cerana(AcT1, AcT2, and AcT3) were sequenced by next generation sequencing. Totally, 73830148, 96586212, 94552744, 76672564, 90954858, and 83418832 raw reads were respectively produced from AcCK1, AcCK2, AcCK3, AcT1, AcT2, and AcT3. The sequencing depth was enough to detect all expressed genes. After strict quality control, 73775592, 96513798, 94495000, 76593924, 90870608 and 83339288 clean reads were obtained, with a mean GC content of 48.54%. Additionally, average Q20 and Q30 for aforementioned six groups were 98.10% and 94.36%, respectively. Moreover, 45302685, 65872823, 52709987, 49947838, 56476339, and 42657156 clean reads from above-mentioned six groups were mapped to the reference genome ofApis cerana, respectively. In addition, exons were the most abundant regions in reference genome mapped by clean reads, followed by intergenic regions and introns. Our data presented here can be used to identify long non-coding RNAs (lncRNAs), circlular RNAs (circRNAs), mRNAs and their regulatory networks engaged in response of eastern honeybee larvae toA. apisinfection, and decipher molecular mechanisms underlying host-pathogen interaction.Value of the DataThe current data can be used for exploration of mRNAs, lncRNAs, circRNAs and their competing endogenous RNA (ceRNA) networks engaged in response ofA. c. ceranalarvae toA. apisinfection.This data provides a valuable genetic resource for better understanding non-coding RNA-mediated cross-kingdom regulation of eastern honey larvae toA. apis.The accessible data offers novel insights into understanding the molecular mechanism underlying interaction between eastern honeybee larvae andA. apis.
Spontaneous alpha and theta oscillations are related to complementary aspects of cognitive control in younger and older adults
Authors: Clements Grace M. , Bowie Daniel C. , Gyurkovics Mate , Low Kathy A. , Fabiani Monica , Gratton Gabriele 
Published: April 2020

AbstractThe resting-state human EEG power spectrum is dominated by alpha (8-12 Hz) and theta (4-8Hz) oscillations, and also includes non-oscillatory broadband activity inversely related to frequency (1/factivity). Gratton (2018) proposed that alpha and theta oscillations are both related to cognitive control function, though in a complementary manner. Alpha activity is hypothesized to facilitate themaintenanceof representations, such as task sets in preparation forexpectedtask conditions. In contrast, theta activity would facilitatechangesin representations, such as theupdatingof task sets in response tounpredictedtask demands. Therefore, theta should be related to reactive control (which may prompt changes in task representations), while alpha may be more relevant to proactive control (which implies the maintenance of current task representations). Less is known about the possible relationship between 1/factivity and cognitive control, which was analyzed here in an exploratory fashion. To investigate these hypothesized relationships, we recorded eyes-open and eyes-closed resting-state EEG from younger and older adults and subsequently tested their performance on a cued flanker task, expected to elicit both proactive and reactive control processes. Results showed that alpha power and 1/fslope were smaller in older than younger adults, whereas theta power did not show age-related reductions. Resting alpha power and 1/fslope were predictive of proactive control processes, whereas theta power was related to reactive control as measured by the cued flanker task. All predictive associations were present over and above the effect of age, suggesting that these resting-state EEG correlates could be indicative of trait-like individual differences in cognitive control performance, which may be already evident in younger adults, and are still similarly present in healthy older adults.
LipidLynxX: a data transfer hub to support integration of large scale lipidomics datasets
Authors: Ni Zhixu , Fedorova Maria 
Published: April 2020

AbstractModern high throughput lipidomics provides large-scale datasets reporting hundreds of lipid molecular species. However, cross-laboratory comparison, meta-analysis, and systems biology integration of in-house generated and published datasets remain challenging due to a high diversity of used lipid annotation systems, different levels of reported structural information, and shortage in links to data integration resources. To support lipidomics data integration and interoperability of experimental lipidomics with data integration tools, we developed LipidLynxX serving as a hub facilitating data flow from high-throughput lipidomics analysis to systems biology data integration. LipidLynxX provides the possibility to convert, cross-match, and link various lipid annotations to the tools supporting lipid ontology, pathway, and network analysis aiming systems-wide integration and functional annotation of lipidome dynamics in health and disease. LipidLynxX is a flexible, customizable open-access tool freely available for download athttps://github.com/SysMedOs/LipidLynxX.
High-throughput AFM analysis reveals unwrapping pathways of H3 and CENP-A nucleosomes
Authors: Konrad Sebastian F. , Vanderlinden Willem , Frederickx Wout , Brouns Tine , Menze Björn , De Feyter Steven , Lipfert Jan 
Published: April 2020

AbstractNucleosomes, the fundamental units of chromatin, regulate readout and expression of eukaryotic genomes. Single-molecule experiments have revealed force-induced transient nucleosome accessibility, but a high-resolution unwrapping landscape in the absence of external forces is currently lacking. Here, we introduce a high-throughput pipeline for the analysis of nucleosome conformations based on atomic force microscopy and automated, multi-parameter image analysis. Our data set of ~10,000 nucleosomes reveals multiple unwrapping states corresponding to steps of 5 bp DNA. For canonical H3 nucleosomes, we observe that dissociation from one side impedes unwrapping from the other side, but unlike to force-induced unwrapping, we find only a weak sequence-dependent asymmetry. Centromeric CENP-A nucleosomes do not unwrap anti-cooperatively, in stark contrast to H3 nucleosomes, likely due to their shorter N-terminal α-helix. Finally, our results reconcile previously conflicting findings about the differences in height between H3 and CENP-A nucleosomes. We expect our approach to enable critical insights into epigenetic regulation of nucleosome structure and stability.
A Systematic Analysis of Mosquito-Microbiome Biosynthetic Gene Clusters Reveals Antimalarial Siderophores that Reduce Mosquito Reproduction Capacity
Authors: Ganley Jack G. , Pandey Ashmita , Sylvester Kayla , Lu Kuan-Yi , Toro-Moreno Maria , Rütschlin Sina , Bradford James M. , Champion Cody J. , Böttcher Thomas , Xu Jiannong , Derbyshire Emily R. 
Published: April 2020

ABSTRACTAdvances in infectious disease control strategies through genetic manipulation of insect microbiomes have heightened interest in microbially produced small molecules within mosquitoes. Herein, 33 mosquito-associated bacterial genomes were mined and over 700 putative biosynthetic gene clusters (BGCs) were identified, 135 of which belong to known classes of BGCs. After an in-depth analysis of the 135 BGCs, iron-binding siderophores were chosen for further investigation due to their high abundance and well-characterized bioactivities. Through various metabolomic strategies, eight siderophore scaffolds were identified in six strains of mosquito-associated bacteria. Among these, serratiochelin A and pyochelin were found to reduce femaleAnopheles gambiaeoverall fecundity likely by lowering their blood feeding rate. Serratiochelin A and pyochelin were further found to inhibit thePlasmodiumparasite asexual blood and liver stagesin vitro. Our work supplies a bioinformatic resource for future mosquito microbiome studies and highlights an understudied source of bioactive small molecules.
Type 2 and interferon inflammation strongly regulate SARS-CoV-2 related gene expression in the airway epithelium
Authors: Sajuthi Satria P. , DeFord Peter , Jackson Nathan D. , Montgomery Michael T. , Everman Jamie L. , Rios Cydney L. , Pruesse Elmar , Nolin James D. , Plender Elizabeth G. , Wechsler Michael E. , Mak Angel CY , Eng Celeste , Salazar Sandra , Medina Vivian , Wohlford Eric M. , Huntsman Scott , Nickerson Deborah A. , Germer Soren , Zody Michael C. , Abecasis Gonçalo , Kang Hyun Min , Rice Kenneth M. , Kumar Rajesh , Oh Sam , Rodriguez-Santana Jose , Burchard Esteban G. , Seibold Max A. 
Published: April 2020

AbstractCoronavirus disease 2019 (COVID-19) outcomes vary from asymptomatic infection to death. This disparity may reflect different airway levels of the SARS-CoV-2 receptor, ACE2, and the spike protein activator, TMPRSS2. Here we explore the role of genetics and co-expression networks in regulating these genes in the airway, through the analysis of nasal airway transcriptome data from 695 children. We identify expression quantitative trait loci (eQTL) for bothACE2andTMPRSS2, that vary in frequency across world populations. Importantly, we findTMPRSS2is part of a mucus secretory network, highly upregulated by T2 inflammation through the action of interleukin-13, and that interferon response to respiratory viruses highly upregulatesACE2expression. Finally, we define airway responses to coronavirus infections in children, finding that these infections upregulateIL6while also stimulating a more pronounced cytotoxic immune response relative to other respiratory viruses. Our results reveal mechanisms likely influencing SARS-CoV-2 infectivity and COVID-19 clinical outcomes.
Polymorphic centromere locations in the pathogenic yeastCandida parapsilosis
Authors: Ola Mihaela , O’Brien Caoimhe E. , Coughlan Aisling Y. , Ma Qinxi , Donovan Paul D. , Wolfe Kenneth H. , Butler Geraldine 
Published: April 2020

ABSTRACTCentromeres pose an evolutionary paradox: strongly conserved in function, but rapidly changing in sequence and structure. However, in the absence of damage, centromere locations are usually conserved within a species. We report here that isolates of the pathogenic yeast speciesCandida parapsilosisexhibit within-species polymorphism for the location of centromeres on two of its eight chromosomes. Its old centromeres have an inverted-repeat (IR) structure, whereas its new centromeres have no obvious structural features, but are located within 30 kb of the old site. Centromeres can therefore move naturally from one chromosomal site to another, apparently spontaneously and in the absence of any significant changes in DNA sequence. Our observations are consistent with a model where all centromeres are genetically determined, such as by the presence of short or long IRs, or the ability to form cruciforms. We also find that centromeres have been hotspots for genomic rearrangements in theC. parapsilosisclade.