bluuebunny/crossref_metadata_2025_split huggingface dataset:
Surface Sensing Stimulates Cellular Differentiation inCaulobacter crescentus
Authors: Snyder Rhett A. , Ellison Courtney K. , Severin Geoffrey B. , Waters Christopher M. , Brun Yves V. 
Published: November 2019

AbstractCellular differentiation is a fundamental strategy used by cells to generate specialized functions at specific stages of development. The bacteriumC. crescentusemploys a specialized dimorphic life cycle consisting of two differentiated cell types. How environmental cues, including mechanical inputs such as contact with a surface, regulate this cell cycle remain unclear. Here, we find that surface sensing by the physical perturbation of retracting extracellular pilus filaments accelerates cell cycle progression and cellular differentiation. We show that physical obstruction of dynamic pilus activity by chemical perturbation or by a mutation in the outer membrane pilus pore protein, CpaC, stimulates early initiation of chromosome replication. In addition, we find that surface contact stimulates cell cycle progression by demonstrating that surface-stimulated cells initiate early chromosome replication to the same extent as planktonic cells with obstructed pilus activity. Finally, we show that obstruction of pilus retraction stimulates the synthesis of the cell cycle regulator, cyclic diguanylate monophosphate (c-di-GMP) through changes in the activity and localization of two key regulatory histidine kinases that control cell fate and differentiation. Together, these results demonstrate that surface contact and mechanosensing by alterations in pilus activity stimulateC. crescentusto bypass its developmentally programmed temporal delay in cell differentiation to more quickly adapt to a surface-associated lifestyle.SignificanceCells from all domains of life sense and respond to mechanical cues [1–3]. In eukaryotes, mechanical signals such as adhesion and surface stiffness are important for regulating fundamental processes including cell differentiation during embryonic development [4]. While mechanobiology is abundantly studied in eukaryotes, the role of mechanical influences on prokaryotic biology remains under-investigated. Here, we demonstrate that mechanosensing mediated through obstruction of the dynamic extension and retraction oftightadherence (tad) pili stimulates cell differentiation and cell cycle progression in the dimorphic α-proteobacteriumCaulobacter crescentus. Our results demonstrate an important intersection between mechanical stimuli and the regulation of a fundamental aspect of cell biology.
Retrieval of the Complete Coding Sequence of the UK-Endemic Tatenale Orthohantavirus Reveals Extensive Strain Variation and Supports its Classification as a Novel Species
Authors: Chappell Joseph G. , Tsoleridis Theocharis , Onianwa Okechukwu , Drake Gabby , Ashpole Ian , Dobbs Phillipa , Edema William , Kumi-Ansah Frederick , Bennett Malcolm , Tarlinton Rachael E , Ball Jonathan K , McClure C. Patrick 
Published: November 2019

AbstractHantaviruses are a diverse group of single-stranded, negative-sensed RNA viruses, known to cause sporadic outbreaks of potentially fatal human disease. To date, only two Orthohantavirus species have been detected in the UK - Seoul virus and Tatenale. Whilst Seoul is known to be pathogenic in humans, only partial fragments of Tatenale have been recovered, precluding any accurate analysis of its phylogeny or potential pathogenicity. To overcome this shortfall we used a degenerate primer PCR method to identify Tatenale-infection in rodents living in two separate locations in the UK. PCR positive samples were then subjected to either unbiased high-throughput sequencing or overlapping PCR product sequencing to recover the complete coding sequence of the Tatenale virus. This analysis provided in-depth insight into the evolutionary origins of this recently identified UK Orthohantavirus and unequivocally showed that Tatenale virus meets the established criteria for classification as a novel species. Crucially, our data will facilitate in vitro investigation into the zoonotic potential of Tatenale virus.
Comprehensive analysis of horizontal gene transfer among multidrug-resistant bacterial pathogens in a single hospital
Authors: Evans Daniel R. , Griffith Marissa P. , Mustapha Mustapha M. , Marsh Jane W. , Sundermann Alexander J. , Cooper Vaughn S. , Harrison Lee H. , Van Tyne Daria 
Published: November 2019

ABSTRACTMultidrug-resistant bacterial pathogens pose a serious public health threat, especially in hospital settings. Horizontal gene transfer (HGT) of mobile genetic elements (MGEs) contributes to this threat by facilitating the rapid spread of genes conferring antibiotic resistance, enhanced virulence, and environmental persistence between nosocomial pathogens. Despite recent advances in microbial genomics, studies of HGT in hospital settings remain limited in scope. The objective of this study was to identify and track the movement of MGEs within a single hospital system using unbiased methods. We screened the genomes of 2,173 bacterial isolates from healthcare-associated infections collected over an 18-month time period to identify nucleotide regions that were identical in the genomes of bacteria belonging to distinct genera. These putative MGEs were found in 196 isolates belonging to 11 different genera; they grouped into 51 clusters of related elements, and they were most often shared between related genera. To resolve the genomic locations of the most prevalent MGEs, we performed long-read sequencing on a subset of representative isolates and generated highly contiguous, hybrid-assembled genomes. Many of these genomes contained plasmids and chromosomal elements encoding one or more of the MGEs we identified, which were often arranged in a mosaic fashion. We then tracked the appearance of ten MGE-bearing plasmids in all 2,173 genomes, and found evidence supporting the transfer of plasmids between patients independent from bacterial transmission. Finally, we identified two instances of likely plasmid transfer across genera within individual patients. In one instance, the plasmid appeared to have subsequently transferred to a second patient. By surveying a large number of bacterial genomes sampled from infections at a single hospital in a systematic and unbiased manner, we were able to track the independent transfer of MGEs over time. This work expands our understanding of HGT in healthcare settings, and can inform efforts to limit the spread of drug-resistant pathogens in hospitals.
Bi-allelic MCM10 mutations cause telomere shortening with immune dysfunction and cardiomyopathy
Authors: Baxley Ryan M. , Leung Wendy , Schmit Megan M. , Matson Jacob Peter , Oram Marissa K. , Wang Liangjun , Taylor John , Yin Lulu , Hedberg Jack , Rogers Colette B. , Harvey Adam J. , Basu Debashree , Taylor Jenny C. , Pagnamenta Alistair T. , Dreau Helene , Craft Jude , Ormondroyd Elizabeth , Watkins Hugh , Hendrickson Eric A. , Mace Emily M. , Orange Jordan S. , Aihara Hideki , Stewart Grant S. , Blair Edward , Cook Jeanette Gowen , Bielinsky Anja-Katrin 
Published: November 2019

ABSTRACTMinichromosome maintenance protein 10 (Mcm10) is essential for eukaryotic DNA replication. Here, we describe compound heterozygous MCM10 mutations in patients with distinctive but overlapping clinical phenotypes – natural killer (NK) cell deficiency (NKD) and restrictive cardiomyopathy (RCM) with hypoplasia of the spleen and thymus. To understand the mechanism of Mcm10-associated disease, we modeled these mutations in human cell lines. Mcm10 deficiency causes chronic replication stress that reduces cell viability due to increased genomic instability and telomere erosion. Our data suggest that loss of Mcm10 function constrains telomerase activity by accumulating abnormal replication fork structures enriched with single-stranded DNA. Terminally-arrested replication forks in Mcm10-deficient cells require endonucleolytic processing by Mus81, as MCM10:MUS81 double mutants display decreased viability and accelerated telomere shortening. We propose that these bi-allelic mutations in MCM10 predispose specific cardiac and immune cell lineages to prematurely arrest during differentiation, causing the clinical phenotypes in both NKD and CM patients.
Correlated structure of neuronal firing in macaque visual cortex limits information for binocular depth discrimination
Authors: Smith Jackson E. T. , Parker Andrew J. 
Published: November 2019

ABSTRACTVariability in cortical neural activity potentially limits sensory discriminations. Theoretical work shows that information required to discriminate two similar stimuli is limited by the correlation structure of cortical variability. We investigated these information-limiting correlations by recording simultaneously from visual cortical areas V1 and V4 in macaque monkeys, performing a binocular, stereo-depth discrimination task. Within both areas, noise correlations on a rapid temporal scale (20-30ms) were stronger for neuron-pairs with similar selectivity for binocular depth, meaning that these correlations potentially limit information for making the discrimination. Between-area correlations (V1 to V4) were different, being weaker for neuron pairs with similar tuning, and having a slower temporal scale (100+ms). Fluctuations in these information-limiting correlations just prior to the detection event were associated with changes in behavioural accuracy. Although these correlations limit the recovery of information about sensory targets, their impact may be curtailed by integrative processing of signals across multiple brain areas.
Brief communication: Long-term absence of Langerhans cells alters the gene expression profile of keratinocytes and dendritic epidermal T cells
Authors: Su Qingtai , Bouteau Aurélie , Cardenas Jacob , Uthra Balaji , Wang Yuanyaun , Smitherman Cynthia , Gu Jinghua , Igyártó Botond Z. 
Published: November 2019

ABSTRACTTissue-resident and infiltrating immune cells are continuously exposed to molecules derived from the niche cells that often come in form of secreted factors, such as cytokines. These factors are known to impact the immune cells’ biology. However, very little is known about whether the tissue resident immune cells in return also affect the local environment. In this study, with the help of RNA-sequencing, we show for the first time that long-term absence of epidermal resident Langerhans cells (LCs) led to significant gene expression changes in the local keratinocytes and resident dendritic epidermal T cells. Thus, immune cells might play an active role in maintaining tissue homeostasis, which should be taken in consideration at data interpretation.
De novo assembly and characterization of transcriptome towards understanding molecular mechanism associated with MYMIV-resistance in Vigna mungo - A computational study
Authors: Gupta Manoj Kumar , Donde Ravindra , Gouda Gayatri , Vadde Ramakrishna , Behera Lambodar 
Published: November 2019

AbstractThe fast climate change affects yield in Vigna mungo via enhancing both biotic and abiotic stresses. Out of all factors, the yellow mosaic disease has the most damaging effect. However, due to lack of reference genome of Vigna mungo, the complete mechanism associated with MYMIV (Mungbean Yellow Mosaic Indian Virus) resistance in Vigna mungo remain elusive to date. Considering this, the authors made an attempt to release new transcriptome and its annotation by employing computational approaches. Quality assessment of the generated transcriptomes reveals that it successfully aligned with 99.03% of the raw reads and hence can be employed for future research. Functional annotation of the transcriptome reveals that 31% and ∼14% of the total transcripts encode lncRNAs and protein-coding sequences, respectively. Further, analysis reveals that, out of total transcripts, only 4536 and 78808 are significantly down and up-regulated during MYMIV infection in Vigna mungo, respectively. These significant transcripts are mainly associated with ribosome, spliceosome, glycolysis /gluconeogenesis, RNA transport, oxidative phosphorylation, protein processing in the endoplasmic reticulum, MAPK signaling pathway - plant, methionine and cysteine metabolism, purine metabolism and RNA degradation. Unlike the previous study, this is for the first time, the present study identified these pathways may play key role in MYMIV resistance in Vigna mungo. Thus, information and transcriptomes data available in the present study make a significant contribution to understanding the genomic structure of Vigna mungo, enabling future analyses as well as downstream applications of gene expression, sequence evolution, and genome annotation.
Defined microbiota transplant restores Th17/RORγt+ regulatory T cell balance in mice colonized with inflammatory bowel disease microbiotas
Authors: Britton Graham J. , Contijoch Eduardo J. , Spindler Matthew P. , Aggarwala Varun , Bongers Gerold , Mateo Lani San , Baltus Andrew , Das Anuk , Gevers Dirk , Borody Thomas J. , Kaakoush Nadeem O. , Kamm Michael A. , Mitchell Hazel , Paramsothy Sudarshan , Clemente Jose C. , Colombel Jean-Frederic , Dubinsky Marla C. , Grinspan Ari , Faith Jeremiah J. 
Published: November 2019

AbstractThe building evidence for the contribution of microbiota to human disease has spurred an effort to develop therapies that target the gut microbiota. This is particularly evident in inflammatory bowel diseases, where clinical trials of fecal microbiota transplant have shown some efficacy. To aid the development of novel microbiota-targeted therapies and to better understand the biology underpinning such treatments, we have used gnotobiotic mice to model microbiota manipulations in the context of microbiotas from humans with inflammatory bowel disease. Mice colonized with IBD donor-derived microbiotas exhibit a stereotypical set of phenotypes, characterized by abundant mucosal Th17 cells and a deficit in the tolerogenic RORγt+ Treg cell subset. Transplanting healthy donor-derived microbiota into mice colonized with human IBD microbiotas lead to induction of RORγt+ Treg cells, which was associated with an increase in the density of the microbiotas following transplant. Microbiota transplant reduced gut Th17 cells in mice colonized with a microbiota from a donor with Crohn’s disease. By culturing strains from this microbiota and screening them in vivo, we identified a specific strain that potently induces Th17 cells. Microbiota transplants reduced the relative abundance of this strain in the gut microbiota, correlated with a reduction in Th17 cells.
The Rab5-Rab11 endosomal pathway is required for BDNF-induced CREB transcriptional regulation in neurons
Authors: González Andrés G. , Lazo Oscar M. , Bronfman Francisca C. 
Published: November 2019

AbstractBrain-derived neurotrophic factor (BDNF) is a key regulator of the morphology and connectivity of central neurons. We have previously shown that BDNF/TrkB signaling regulates the activity and mobility of the GTPases Rab5 and Rab11, which in turn determine the post-endocytic sorting of signaling TrkB receptors. Moreover, altered Rab5 or Rab11 activity inhibits BDNF-induced dendritic branching. Whether Rab5 or Rab11 activity is important for local events only, or also for regulating nuclear signaling and gene expression, is unknown. Here, we investigated whether BDNF-induced signaling cascades were altered when early and recycling endosomes were disrupted by the expression of dominant negative mutants of Rab5 and Rab11. The activities of both Rab5 and Rab11 were required for sustained activity of Erk1/2 and nuclear CREB phosphorylation and for increased transcription of BDNF-dependent genes containing CRE-binding sites that include activity-regulated genes such as Arc, Dusp1, c-fos and Egr1 and growth and survival genes such as Atf3 and Nf1. Based on our results, we propose that the early and recycling endosomes provide a platform for the integration of neurotrophic signaling from the plasma membrane to the nucleus in neurons and that this mechanism likely regulates neuronal plasticity and neuronal survival.Significance StatementBDNF is a soluble neurotrophic factor that regulates plastic changes in the brain, including dendritic growth, by binding to its plasma membrane receptor TrkB. BDNF/TrkB activates signaling cascades leading to activation of CREB, a key transcription factor regulating circuit development and learning and memory. Our results uncover the cellular mechanisms that central neurons use to integrate the signaling of plasma membrane receptors with nuclear transcriptional responses. We found that the endosomal pathway is required for the signaling cascade initiated by BDNF and its receptors in the plasma membranes to modulate BDNF-dependent gene expression and neuronal dendritic growth mediated by the CREB transcription factor in the nucleus.
TheDrosophila melanogasterortholog of RFWD3 functions independently of RAD51 during DNA repair
Authors: Carvajal-Garcia Juan , Gales Evan R. , Ramsden Dale A. , Sekelsky Jeff 
Published: November 2019

AbstractRepair of damaged DNA is required for the viability of all organisms. Studies inDrosophila melanogaster, driven by the power of genetic screens, pioneered the discovery and characterization of many genes and pathways involved in DNA repair in animals. However, fewer than half of the alleles identified in these screens have been mapped to a specific gene, leaving a potential for new discoveries in this field. Here we show that the previously uncharacterized mutagen sensitive genemus302codes for theDrosophila melanogasterortholog of the E3 ubiquitin ligase RING finger and WD domain protein 3 (RFWD3). In human cells, RFWD3 promotes ubiquitylation of RPA and RAD51 to facilitate repair of collapsed replication forks and double strand breaks through homologous recombination. Despite the high similarity in sequence to the human ortholog, our evidence fails to support a role for Mus302 in the repair of these types of damage. Last, we observe that the N-terminal third of RFWD3 is only present in mammals and absent in the rest of vertebrates and invertebrates. We propose that the additional N-terminal portion accounts for the acquisition of a new biological function in mammals that explains the functional differences between the human and the fly orthologs, and thatDrosophilaMus302 may retain the ancestral function of the protein.
Nuclear GAPDH cascade mediates pathological cardiac hypertrophy
Authors: Zhang Manling , Kariya Taro , Numata Genri , Sasaki Hideyuki , Sasaki Masayuki , Ramos Adriana , Nakamura Shun , Iwakiri Masaki , Koitabashi Norimichi , Zhu Guangshuo , Tsujimura Tsuyoshi , Lee Dong-ik , Tristan Carlos , Shahani Neelam , Tsuchiya Yukihiro , Jaaro-Peled Hanna , Sasano Tetsuo , Slusher Barbara , Kass David A. , Saitoh Toshiaki , Ishizuka Koko , Sawa Akira , Takimoto Eiki 
Published: November 2019

AbstractPathological stressors disrupt cellular homeostasis, causing various diseases. We report a non-glycolytic role for glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in the pathological growth response of the heart. In cellular and animal models for cardiac hypertrophy, nuclear translocation of GAPDH was elicited in cardiac myocytes, followed by activation of p300 histone acetyl-transferase (HAT), an inducer of heart hypertrophy gene programs. The hypertrophy was inhibited by a compound antagonizing the nuclear GAPDH cascade. In mice with selective deletion of GAPDH’s nuclear function in cardiac myocytes, the stress-induced cardiac hypertrophy and functional deficits were normalized. Nuclear GAPDH cascade plays a pivotal role in stress response/homeostatic control in the heart. GAPDH may act as a key homeostatic mediator in living organisms through its stress-responsive nuclear translation.One-sentence summaryNon-glycolytic function of GAPDH critically regulates heart homeostasis and mediates cardiac pathological hypertrophy
A comparison of humans and baboons suggests germline mutation rates do not track cell divisions
Authors: Wu Felix L. , Strand Alva , Ober Carole , Wall Jeffrey D. , Moorjani Priya , Przeworski Molly 
Published: November 2019

AbstractIn humans, most germline mutations are inherited from the father. This observation is widely interpreted as resulting from the replication errors that accrue during spermatogenesis. If so, the male bias in mutation should be substantially lower in a closely related species with similar rates of spermatogonial stem cell divisions but a shorter mean age of reproduction. To test this hypothesis, we resequenced two 3–4 generation nuclear families (totaling 29 individuals) of olive baboons (Papio anubis), who reproduce at ~10 years of age on average. We inferred sex-specific mutation rates by analyzing the data in parallel with three three-generation human pedigrees (26 individuals). The mutation rate per generation in baboons is 0.55×10−8 per base pair, approximately half that of humans. Strikingly, however, the degree of male mutation bias is approximately 3:1, similar to that of humans; in fact, a similar male bias is seen across mammals that reproduce months, years or decades after birth. These results echo findings in humans that the male bias is stable with parental ages and cast further doubt on the assumption that germline mutations track cell divisions. Our mutation rate estimates for baboons raise a further puzzle in suggesting a divergence time between apes and Old World Monkeys of 67 My, too old to be consistent with the fossil record; reconciling them now requires not only a slowdown of the mutation rate per generation in humans but also in baboons.
Transversal otolithic membrane deflections evoked by the linear accelerations
Authors: Goussev V. 
Published: November 2019

AbstractConsidered is the model of the transversal utricle membrane deflections evoked by the linear accelerations. The real 3D utricle membrane structure was simplified by considering its middle section and evaluating its elastic properties in 2D space. The steady state transversal deflections along the membrane are analytically evaluated and numerically simulated using the 2D elasticity theory. The transversal deflections are found to be more expressive and stronger as compared to the conventional longitudinal deformations. The revealed properties could be used for explanation of the transduction processes in the otholith organ. Based on the implemented modeling approach the new otolithic membrane mechanical properties are discussed and new explanations for the available experimental data are given.