bluuebunny/crossref_metadata_2025_split huggingface dataset:
Emergence ofoptrA-mediated linezolid resistance in multiple lineages and plasmids ofEnterococcus faecalisrevealed by long read sequencing
Authors: McHugh Martin P , Parcell Benjamin J , Pettigrew Kerry A , Toner Geoff , Khatamzas Elham , Karcher Anne Marie , Walker Joanna , Weir Robert , Meunier Danièle , Hopkins Katie L , Woodford Neil , Templeton Kate E , Gillespie Stephen H , Holden Matthew TG 
Published: March 2020

ABSTRACTObjectivesTo characterise the genetic environment ofoptrAin linezolid-resistantEnterococcus faecalisisolates from Scotland.MethodsLinezolid-resistantE. faecaliswere identified in three Scottish Health Boards and confirmed to carry theoptrAgene at the national reference laboratory. WGS was performed with short read (Illumina MiSeq) and long read (Oxford Nanopore MinION) technologies to generate complete genome assemblies. Illumina reads for 94E. faecalisbloodstream isolates were used to place theoptrA-positive isolates in a larger UK phylogeny.ResultsSixoptrA-positive linezolid-resistantE. faecaliswere isolated from urogenital samples in three Scottish Health Boards (2014-2017). No epidemiological links were identified between the patients, four were community-based, and only one had recent linezolid exposure. Reference-based mapping confirmed the isolates were genetically distinct (>13,900 core SNPs).optrAwas located on a plasmid in each isolate and these plasmids showed limited nucleotide similarity. There was variable presence of transposable elements surroundingoptrA, (including IS1216, IS3, and Tn3) and not always as a recognisable gene cassette. OptrA amino acid sequences were also divergent, resulting in four protein variants differing in 1-20 residues. One isolate belonged to ST16 and clustered with three other isolates in the UK collection (76-182 SNPs), otherwise theoptrA-positive isolates were genetically distinct from the bloodstream isolates (>6,000 SNPs).ConclusionsWe report multiple variants of the linezolid resistance geneoptrAin diverseE. faecalisstrain and plasmid backgrounds, suggesting multiple introductions of the gene into theE. faecalispopulation and selection driving recent emergence.
Adding carbon fiber to shoe soles does not improve running economy: a muscle-level explanation
Authors: Beck Owen N. , Golyski Pawel R. , Sawicki Gregory S. 
Published: March 2020

AbstractIn an attempt to improve their distance-running performance, many athletes race with carbon fiber plates embedded in their shoe soles. Accordingly, we sought to establish whether, and if so how, adding carbon fiber plates to shoes soles reduces athlete aerobic energy expenditure during running (improves running economy). We tested 15 athletes during running at 3.5 m/s in four footwear conditions that varied in shoe sole carbon fiber plate bending stiffness. For each condition, we quantified athlete aerobic energy expenditure and performed biomechanics analyses, which included the use of ultrasound imaging to examine soleus muscle dynamicsin vivo. Overall, increased footwear bending stiffness lengthened ground contact time (p=0.048), but did not affect ankle (p≥0.060), knee (p≥0.128), or hip (p≥0.076) joint angles or moments. Additionally, increased footwear bending stiffness did not affect muscle activity (all seven measured leg muscles (p≥0.146)), stride averaged active soleus volume, (p=0.068) or aerobic power (p=0.458) during running. Hence, footwear bending stiffness does not appear to alter the volume of aerobic energy consuming muscle in the soleus, or any other leg muscle, during running. Therefore, adding carbon fiber plates to shoe soles slightly alters whole-body and calf muscle biomechanics but does not improve running economy.
Mitochondrial DNA Sequence Diversity in Mammals: a Correlation Between the Effective and Census Population Sizes
Authors: James Jennifer , Eyre-Walker Adam 
Published: March 2020

AbstractWhat determines the level of genetic diversity of a species remains one of the enduring problems of population genetics. Since, neutral diversity depends upon the product of the effective population size and mutation rate there is an expectation that diversity should be correlated to measures of census population size. This correlation is often observed for nuclear but not for mitochondrial DNA. Here we revisit the question of whether mitochondrial DNA sequence diversity is correlated to census population size by compiling the largest dataset to date from 639 mammalian species. In a multiple regression we find that nucleotide diversity is significantly correlated to both range size and mass-specific metabolic rate, but not a variety of other factors. We also find that a measure of the effective population size, the ratio of non-synonymous to synonymous diversity, is also significantly negatively correlated to both range and mass-specific metabolic rate. These results together suggest that species with larger ranges have larger effective population sizes. The slope of the relationship between diversity and range is such that doubling the range increases diversity by 12 to 20%, providing one of the first quantifications of the relationship between effective and census population sizes.
Large-Scale Analysis of Cell Death Phenotypic Heterogeneity
Authors: Inde Zintis , Forcina Giovanni C. , Denton Kyle , Dixon Scott J. 
Published: March 2020

SUMMARYIndividual cancer cells within a population can exhibit substantial phenotypic heterogeneity such that exposure to a lethal agent will kill only a fraction of cells at a given time. Whether common molecular mechanisms govern this fractional killing in response to different lethal stimuli is poorly understood. In part, this is because it is difficult to compare fractional killing between conditions using existing approaches. Here, we show that fractional killing can be quantified and compared for hundreds of populations in parallel using high-throughput time-lapse imaging. We find that fractional killing is highly variable between lethal agents and between cell lines. At the molecular level, we find that the antiapoptotic protein MCL1 is an important determinant of fractional killing in response to mitogen activated protein kinase (MAPK) pathway inhibitors but not other lethal stimuli. These studies lay the foundation for the large-scale, quantitative analysis of cell death phenotypic heterogeneity.
Moving Beyond the Mean: Subgroups and dimensions of brain activity and cognitive performance across domains
Authors: Hawco Colin , Dickie Erin W. , Jacobs Grace , Daskalakis Zafiris J. , Voineskos Aristotle N. 
Published: March 2020

AbstractHuman neuroimaging during cognitive tasks has provided unique and important insights into the neurobiology of cognition. However, the vast majority of research relies upon group aggregate or average statistical maps of activity, which do not fully capture the rich variability which exists across individuals. To better characterize individual variability, hierarchical clustering was performed separately on six fMRI tasks in 822 participants from the Human Connectome Project. Across all tasks, clusters ranged from a predominantly ‘deactivating’ pattern towards a more ‘activating’ pattern of brain activity, with differences in out-of-scanner cognitive test scores between clusters. Cluster stability was assessed via bootstrapping approach. Cluster probability did not indicate distinct/clear clustering. However, when participants were plotted in a dimensionally reduced ‘similarity space’ derived from bootstrapping, variability in brain activity among participants was best represented multidimensionally. A ‘positive to negative’ axis of activity was the strongest driver of individual differences.
ARHGEF3 regulates skeletal muscle regeneration and strength through autophagy
Authors: You Jae-Sung , Singh Nilmani , Reyes-Ordonez Adriana , Khanna Nidhi , Bao Zehua , Zhao Huimin , Chen Jie 
Published: March 2020

SummarySkeletal muscle regeneration is essential for restoring muscle function upon injury and for the maintenance of muscle health with aging. ARHGEF3, a Rho-specific GEF, negatively regulates myoblast differentiation via mammalian target of rapamycin complex 2 (mTORC2)-Akt signaling in a GEF-independent mannerin vitro. Here, we investigated ARHGEF3’s role in skeletal muscle regeneration by creating ARHGEF3 KO mice. These mice exhibited no discernible phenotype under normal conditions. Upon injury, however, ARHGEF3 deficiency enhanced the mass, fiber size and function of regenerating muscles in both young and aged mice. Surprisingly, these effects were not mediated by mTORC2-Akt signaling, but by the GEF activity of ARHGEF3. Furthermore, ARHGEF3 KO promoted muscle regeneration through activation of autophagy, a process that is also critical for maintaining muscle strength. Accordingly, in old mice, ARHGEF3 depletion prevented muscle weakness by restoring autophagy flux. Collectively, our findings identify an unexpected link between ARHGEF3 and autophagy-related muscle pathophysiology.
Notch1 regulates breast cancer stem cell function via a non-canonical cleavage-independent pathway
Authors: Sui Lufei , Wang Suming , Rodriguez Roberto K. , Sim Danielle , Bhattacharya Nandita , Blois Anna L. , Chen Siqi , Aziz Sura , Schlaeger Thorsten , Rogers Michael S. , Bielenberg Diane , Akslen Lars A. , Watnick Randolph S. 
Published: March 2020

AbstractCurrent treatment of triple negative breast cancer patients is hindered by a high incidence of chemoresistance (30-50%). The prevailing theory is that resistance and subsequent recurrence is driven by cancer stem cells. Unfortunately, the functional characterization of cancer stem cells at the molecular level is still incomplete. We show here, that within the canonical breast cancer stem cell population, a subset of cells characterized by high Notch1 expression possesses the tumor-initiating property associated with cancer stem cells. Moreover, the tumor initiating property of these high Notch1-expressing breast cancer stem cells is mediated by a cleavage independent Notch signaling pathway culminating in the repression of SIRT1. Of note, the Notch1-mediated repression of SIRT1 is required not only for tumor initiation, but also for chemoresistance in breast cancer stem cells. Strikingly, inhibition of SIRT1 obviates the requirement for Notch1, marking the first example of conferring cancer stem cell function by inhibiting the activity of a single protein. We also demonstrate that progenitor-like mammary epithelial cells, which possess both luminal and basal properties, are also characterized by high Notch1 expression and repression of SIRT1 via the non-canonical pathway. These findings provide the first functional mechanistic requirements for tumor initiation by breast cancer stem cells and suggest that activation of the non-canonical Notch1 pathway is hardwired into tumor-initiating progenitor cells and thus a prerequisite for tumor initiation.Statement of SignificanceWe demonstrate that chemoresistant and tumor-initiating properties of breast cancer stem cells are driven by repression of SIRT1 via non-canonical Notch signaling, suggesting a novel therapeutic strategy for triple negative breast cancer.
Association of Cardiovascular Manifestations with In-hospital Outcomes in Patients with COVID-19: A Hospital Staff Data
Authors: Liu Ru , Ming Xiaoyan , Xu Ou , Zhou Jianli , Peng Hui , Xiang Ning , Zhang Jiaming , Zhu Hong 
Published: March 2020

AbstractBackgroundThe outbreaks of coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remain a huge threat to the public health worldwide. Clinical data is limited up to now regarding the risk factors in favor of severe conversion of non-severe case with COVID-19.AimsThis study analyzed a hospital staff data to figure out general clinical features of COVID-19 in terms of the association of cardiovascular manifestations (CVMs) with in-hospital outcomes of COVID-19 cases.MethodsRetrospective, single-center case series of 41 consecutive hospitalized health staff with confirmed COVID-19 were collected at the Central Hospital of Wuhan in Wuhan, China, from January 15 to January 24, 2020. Epidemiological, demographic, clinical, laboratory, radiological, treatment data and in-hospital adverse events were collected and analyzed. Final date of follow-up was March 3, 2020. A comparative study was applied between cases with CVMs and those without CVMs.ResultsOf all, clinicians and clinical nurses accounted for 80.5%, while 87.8% of all had history of patient contact. The population was presented with a mean age of 39.1 ± 9.2 and less comorbidities than community population. The three most frequent symptoms of COVID-19 cases analyzed were fever (82.9%), myalgia or fatigue (80.5%) and cough (63.4%). While, the three most frequent initial symptoms were myalgia or fatigue (80.5%), fever (73.2%) and cough (41.5%). There were 95.1% cases featured as non-severe course of disease according to the official standard in China. Patients with CVMs and those without CVMs accounted for 58.5% and 41.5%, respectively. Compared with cases without CVMs, patients with CVMs were presented with lower baseline lymphocyte count (0.99 ± 0.43 and 1.55 ± 0.61, P<0.001), more who had at least once positive nucleic acid detection of throat swab during admission (50.0% and 11.8%, P=0.011), and more received oxygen support (79.2% and 23.5%, P<0.001). The rate of in-hospital adverse events was significantly higher in patients with CVMs group (75.0% and 23.5%, P=0.001). Multivariable logistic regression model indicated that, coexisting with CVMs in COVID-19 patients was not independently associated with in-hospital adverse events.ConclusionsMost of hospital staff with COVID-19 had history of patient contact, featured non-severe course of disease. Cases with CVMs suffered from more in-hospital adverse events than those without CVMs. But concomitant CVMs were not independently associated with in-hospital adverse events in COVID-19 patients.
Light environment drives evolution of color vision genes in butterflies and moths
Authors: Sondhi Yash , Ellis Emily A. , Theobald Jamie C. , Kawahara Akito Y. 
Published: March 2020

AbstractOpsins are the primary light-sensing molecules in animals. Opsins have peak sensitivities to specific wavelengths which allows for color discrimination. The opsin protein family has undergone duplications and losses, dynamically expanding and contracting the number of opsins, throughout invertebrate evolution, but it is unclear what drives this diversity. Light availability, however, appears to play a significant role. Dim environments are associated with low opsin diversity in deep-sea fishes and cave-dwelling animals. Correlations between high opsin diversity and bright environments, however, are tenuous. Insects are a good system to test whether opsin expansion is associated with greater light availability because they are enormously diverse and consequently display large variation in diel activity. To test this, we used 200 insect transcriptomes and examined the patterns of opsin diversity associated with diel-niche. We focused on the butterflies and moths (Lepidoptera) because this group has significant variation in diel-niche, substantial opsin recovery (n=100), and particularly well-curated transcriptomes. We identified opsin duplications using ancestral state reconstruction and examined rates of opsin evolution, and compared them across diel-niches. We find Lepidoptera species active in high light environments have independently expanded their opsins at least 10 times. Opsins from diurnal taxa also evolve faster; 13 amino acids were identified across different opsins that were under diversifying selection. Structural models reveal that four of these amino acids overlap with opsin color-tuning regions. By parsing nocturnal and diurnal switches, we show that light environment can influence gene diversity, selection, and protein structure of opsins in Lepidoptera.
Correlating predicted epigenetic marks with expression data to find interactions between SNPs and genes
Authors: Despinasse Antoine , Park Yongjin , Lapi Michael , Kellis Manolis 
Published: March 2020

ABSTRACTDespite all the work done, mapping GWAS SNPs in non-coding regions to their target genes remains a challenge. The SNP can be associated with target genes by eQTL analysis. Here we introduce a method to make these eQTLs more robust. Instead of correlating the gene expression with the SNP value like in eQTLs, we correlate it with epigenomic data. This epigenomic data is very expensive and noisy. We therefore predict the epigenomic data from the DNA sequence using the deep learning framework DeepSEA (Zhou and Troyanskaya, 2015).
Systematic tools for reprogramming plant gene expression in a simple model,Marchantia polymorpha
Authors: Sauret-Güeto Susanna , Frangedakis Eftychios , Silvestri Linda , Rebmann Marius , Tomaselli Marta , Markel Kasey , Delmans Mihails , West Anthony , Patron Nicola J. , Haseloff Jim 
Published: March 2020

ABSTRACTWe present the OpenPlant toolkit, a set of interlinked resources and techniques to develop Marchantia as testbed for bioengineering in plants. Marchantia is a liverwort, a simple plant with an open form of development that allows direct visualization of gene expression and dynamics of cellular growth in living tissues. We describe new techniques for simple and efficient axenic propagation and maintenance of Marchantia lines with no requirement for glasshouse facilities. Marchantia plants spontaneously produce clonal propagules within a few weeks of regeneration, and lines can be amplified million-fold in a single generation by induction of the sexual phase of growth, crossing and harvesting of progeny spores. The plant has a simple morphology and genome with reduced gene redundancy, and the dominant phase of its life cycle is haploid, making genetic analysis easier. We have built robust Loop assembly vector systems for nuclear and chloroplast transformation and genome editing. These have provided the basis for building and testing a modular library of standardized DNA elements with highly desirable properties. We have screened transcriptomic data to identify a range of candidate genes, extracted putative promoter sequences, and tested themin vivoto identify new constitutive promoter elements. The resources have been combined into a toolkit for plant bioengineering that is accessible for laboratories without access to traditional facilities for plant biology research. The toolkit is being made available under the terms of the OpenMTA and will facilitate the establishment of common standards and the use of this simple plant as testbed for synthetic biology.
Transient opening of tricellular vertices controls paracellular transport through the follicle epithelium duringDrosophilaoogenesis
Authors: Isasti-Sanchez Jone , Münz-Zeise Fenja , Luschnig Stefan 
Published: March 2020

AbstractParacellular permeability is regulated to allow solute transport or migration of cells across epithelial or endothelial barriers. However, how occluding junction dynamics controls paracellular permeability is poorly understood. Here we describe patency, a developmentally regulated process inDrosophilaoogenesis, during which cell vertices in the follicle epithelium open transiently to allow paracellular transport of yolk proteins for uptake by the oocyte. We show that the sequential removal of E-Cadherin, N-Cadherin, NCAM/Fasciclin-2 and Sidekick from vertices precedes their basal-to-apical opening, while the subsequent assembly of tricellular occluding junctions terminates patency and seals the paracellular barrier. E-Cadherin-based adhesion is required to limit paracellular channel size, whereas stabilized adherens junctions, prolonged NCAM/Fasciclin-2 expression, impeded endocytosis, or increased actomyosin contractility prevent patency. Our findings reveal a key role of cell vertices as gateways controlling paracellular transport, and demonstrate that the dynamic regulation of adhesion and actomyosin contractility at vertices governs epithelial barrier properties.
An Improved 4’-Aminomethyltroxsalen-Based DNA Crosslinker for Biotinylation of DNA
Authors: Wielenberg Kevin , Wang Miao , Yang Min , Ozer Abdullah , Lis John T. , Lin Hening 
Published: March 2020

AbstractNucleic acid crosslinkers that covalently join commentary strands have applications as both pharmaceuticals and biochemical probes. Psoralen is a popular crosslinker moiety that reacts with double stranded DNA and RNA upon irradiation with long wave UV light. A commercially available compound EZ-Link Psoralen-PEG3-Biotin has been used in many studies to crosslink DNA and double strand RNA for genome-wide investigations. Here we present a novel probe, AP3B, which uses a psoralen derivative, 4’-aminomethyltrioxsalen, to biotinylate nucleic acids. We show that this compound is 8-fold more effective at labeling DNA in cells and several hundred-fold more effective at crosslinking two strands of DNAin vitrothan the commercially available compound EZ-Link Psoralen-PEG3-Biotin.
Trypanosoma bruceiultra-structure cell modifications caused by knockdown of the ribonuclease Rrp44/Dis3
Authors: Cesaro Giovanna , Hiraiwa Priscila M. , Carneiro Flavia R. G. , Rouam Valérie , Legrand Pierre , Conesa José Javier , Réfrégiers Matthieu , Pereiro Eva , Guimarães Beatriz G. , Jamme Frédéric , Zanchin Nilson I. T. 
Published: March 2020

AbstractRrp44/Dis3 is an essential protein conserved in all eukaryotes that functions in the maturation of many different RNA precursors and RNA surveillance. TheTrypanosoma bruceiRrp44/Dis3 homologue (TbRRP44) is required for maturation of pre-rRNA, spliced leader, and U3 snoRNA precursors. Its depletion leads to inhibition of cell proliferation and eventually to cell death. In this work, we showed that TbRRP44 depletion causes a massive expansion of acidic and lysosome-derived vacuoles, enlargement of cell and nuclei sizes without changes in DNA content, mitochondrial inactivation, and autophagy induction. Consistently, 3D reconstructions using cryo-soft X-ray tomography revealed extreme vacuolation of the cytoplasm and numerous cellular alterations, including an increase in size and number of calcium-containing vesicles and lipid droplets. These multiple defects indicate that a combination of alterations converge to induce lysosome expansion. With time, the cytoplasm is taken up by lysosome-derived vacuoles, which may be a final stage leading to the cell death triggered by TbRRP44 depletion. These studies provide the first evidence on the ultra-structure cell modifications caused by deficiency of this essential ribonuclease inT. brucei.
Environmental variability and the evolution of bet-hedging strategies
Authors: Slimon Kelley , Germain Rachel M. 
Published: March 2020

AbstractBet-hedging strategies, such as dispersal and dormancy, are predicted to evolve in varying and uncertain environments and are critical to ecological models of biodiversity maintenance. Theories of the specific ecological scenarios that favor the evolution of dispersal, dormancy, or their covariance are rarely tested, particularly for naturally-evolved populations that experience complex patterns of spatiotemporal environmental variation. We grew 23 populations ofVulpia microstachys, an annual grass native to California, in a greenhouse, and on the offspring generation measured seed dispersal ability and dormancy rates. We hypothesized that seed dormancy rates and dispersal abilities would be highest in populations from more productive, temporally variable sites, causing them to covary positively. Contrary to our hypothesis, our data suggest that both dispersal and dormancy evolve to combat different axes and scales of spatial heterogeneity, and are underlain by different seed traits, allowing them to evolve independently. Dormancy appears to have evolved as a strategy for overcoming microgeographic heterogeneity rather than temporal climate fluctuations, an outcome that to our knowledge has not been considered by theory. In sum, we provide much needed empirical data on the evolution of bet hedging, as well as a new perspective on the ecological function dormancy provides in heterogeneous landscapes.