bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Burden of Antimicrobial Resistance among Urinary Tract Isolates of Escherichia coli in the United States in 2017
Authors: Critchley Ian A , Cotroneo Nicole , Pucci Michael J , Mendes Rodrigo 
Published: July 2019

AbstractUrinary tract infections (UTIs) caused by Escherichia coli have been historically managed with oral antibiotics including the cephalosporins, fluoroquinolones and trimethoprim-sulfamethoxazole. The use of these agents is being compromised by the increase in extended spectrum β-lactamase (ESBL)-producing organisms, mostly caused by the emergence and clonal expansion of E. coli multilocus sequence typing (ST) 131. In addition, ESBL isolates show co-resistance to many of oral agents. Management of UTIs caused by ESBL and fluoroquinolone-resistant organisms is becoming increasingly challenging to treat outside of the hospital setting with clinicians having to resort to intravenous agents. The aim of this study was to assess the prevalence of ESBL phenotypes and genotypes among UTI isolates of E. coli collected in the US during 2017 as well as the impact of co-resistance to oral agents such as the fluoroquinolones and trimethoprim-sulfamethoxazole. The national prevalence of ESBL phenotypes of E. coli was 15.7% and was geographically distributed across all nine Census regions. Levofloxacin and trimethoprim-sulfamethoxazole-resistance rates were ≥ 24% among all isolates and this co-resistance phenotype was considerably higher among isolates showing an ESBL phenotype (≥ 59.2%) and carrying blaCTX-M-15 (≥ 69.5%). The agents with the highest potency against UTI isolates of E. coli, including ESBL isolates showing cross-resistance across oral agents, were the intravenous carbapenems. The results of this study indicate that new oral options with the spectrum and potency similar to the intravenous carbapenems would address a significant unmet need for the treatment of UTIs in an era of emergence and clonal expansion of ESBL isolates resistant to several classes of antimicrobial agents, including oral options.
Independent transposon exaptation is a widespread mechanism of shadow enhancer evolution in the mammalian genome
Authors: Barth Nicolai K. H. , Li Lifei , Taher Leila 
Published: July 2019

ABSTRACTMany regulatory networks involve (possibly partially) redundantcis-regulatory elements. These elements are commonly referred to as shadow enhancers and have been assumed to mainly originate by sequence duplication. An alternative mechanism that has not been examined involves the independent exaptation of transposons. Here, we identified 2,117 and 2,787 pairs of shadow enhancers in the human and mouse genomes, respectively, and found that 34% and 18% of these pairs derive from transposons. Moreover, we show that virtually all the enhancer partners of these transposon-derived shadow enhancer pairs are independent exaptations from different transposon types and hypothesize that the increase in the expression and tissue-specificity of their targets as compared to those of non-shadow enhancers facilitates their fixation in the genome. Finally, we provide evidence that the regulatory redundancy observed in many mammalian regulatory networks is predominantly driven by convergent evolution, since shadow enhancers are hardly ever conserved across species.
The Evolutionary History of Common Genetic Variants Influencing Human Cortical Surface Area
Authors: Tilot Amanda K. , Khramtsova Ekaterina A. , Grasby Katrina , Jahanshad Neda , Painter Jodie , Colodro-Conde Lucía , Bralten Janita , Hibar Derrek P. , Lind Penelope A. , Liu Siyao , Brotman Sarah M. , Thompson Paul M. , Medland Sarah E. , Macciardi Fabio , Stranger Barbara E. , Davis Lea K. , Fisher Simon E. , Stein Jason L. 
Published: July 2019

AbstractStructural brain changes along the lineage that led to modern Homo sapiens have contributed to our unique cognitive and social abilities. However, the evolutionarily relevant molecular variants impacting key aspects of neuroanatomy are largely unknown. Here, we integrate evolutionary annotations of the genome at diverse timescales with common variant associations from large-scale neuroimaging genetic screens in living humans, to reveal how selective pressures have shaped neocortical surface area. We show that variation within human gained enhancers active in the developing brain is associated with global surface area as well as that of specific regions. Moreover, we find evidence of recent polygenic selection over the past 2,000 years influencing surface area of multiple cortical regions, including those involved in spoken language and visual processing.
Decontamination of ambient RNA in single-cell RNA-seq with DecontX
Authors: Yang Shiyi , Corbett Sean E. , Koga Yusuke , Wang Zhe , Johnson W. Evan , Yajima Masanao , Campbell Joshua D. 
Published: July 2019

ABSTRACTDroplet-based microfluidic devices have become widely used to perform single-cell RNA sequencing (scRNA-seq) and discover novel cellular heterogeneity in complex biological systems. However, ambient RNA present in the cell suspension can be incorporated into these droplets and aberrantly counted along with a cell’s native mRNA. This results in cross-contamination of transcripts between different cell populations and can potentially decrease the precision of downstream analyses. We developed a novel hierarchical Bayesian method called DecontX to estimate and remove contamination in individual cells from scRNA-seq data. DecontX accurately predicted the proportion of contaminated counts in a mixture of mouse and human cells. Decontamination of PBMC datasets removed aberrant expression of cell type specific marker genes from other cell types and improved overall separation of cell clusters. In general, DecontX can be incorporated into scRNA-seq workflows to assess quality of dissociation protocols and improve downstream analyses.
Diatoms structure the plankton community based on selective segregation in the world’s ocean
Authors: Vincent Flora , Bowler Chris 
Published: July 2019

ABSTRACTDiatoms are a major component of phytoplankton, believed to be responsible for around 20% of the annual primary production on Earth. As abundant and ubiquitous organisms, they are known to establish biotic interactions with many other members of the plankton. Through analysis of co-occurrence networks derived from theTaraOceans expedition that take into account the importance of both biotic and abiotic factors in shaping the spatial distributions of species, we show that only 13% of diatom pairwise associations are driven by environmental conditions, whereas the vast majority are independent of abiotic factors. In contrast to most other plankton groups, at a global scale diatoms display a much higher proportion of negative correlations with other organisms, particularly towards potential predators and parasites, suggesting that their biogeography is constrained by top down pressure. Genus level analyses indicate that abundant diatoms are not necessarily the most connected, and that species-specific abundance distribution patterns lead to negative associations with other organisms. In order to move forward in the biological interpretation of co-occurrence networks, an open access extensive literature survey of diatom biotic interactions was compiled, of which 18.5% were recovered in the computed network. This result reveals the extent of what likely remains to be discovered in the field of planktonic biotic interactions, even for one of the best known organismal groups.ImportanceDiatoms are key phytoplankton in the modern ocean involved in numerous biotic interactions, ranging from symbiosis to predation and viral infection, which have considerable effects on global biogeochemical cycles. However, despite recent large-scale studies of plankton, we are still lacking a comprehensive picture of the diversity of diatom biotic interactions in the marine microbial community. Through the ecological interpretation of both inferred microbial association networks and available knowledge on diatom interactions compiled in an open access database, we propose an eco-systems level understanding of diatom interactions in the ocean.
Assessing by modeling the consequences of increased recombination in genomic selection ofOryza sativaandBrassica rapa
Authors: Tourrette E. , Bernardo R. , Falque M. , Martin O. 
Published: July 2019

ABSTRACTRecombination generates genetic diversity but the number of crossovers per meiosis is limited in most species. Previous studies showed that increasing recombination can enhance response to selection. However, such studies did not assume a specific method of modifying recombination. Our objective was to test whether two methods used to increase recombination in plants could increase the genetic gain in a population undergoing genomic selection. The first method, inOryza sativa,used a mutant of anti-crossover genes to increase global recombination without affecting the recombination landscape. The second one uses the ploidy level of a cross betweenBrassica rapaandBrassica napusto increase the recombination particularly in pericentromeric regions. These recombination landscapes were used to model recombination while quantitative trait loci positions were based on the actual gene distribution. We simulated selection programs with initially a cross between two inbred lines, for two species. Increased recombination enhanced the response to selection. The amount of enhancement in the cumulative gain largely depended on the species and the number of quantitative trait loci (2, 10, 20, 50, 200 or 1000 per chromosome). Genetic gains were increased up to 30% after 20 generations. Furthermore, modifying the recombination landscape was the most effective: the gain was larger by 25% with the first method and 33% with the second one inB. rapa, and 15% compared to 11% inO. sativa. Thus, increased recombination enhances the genetic gain in genomic selection for long-term selection programs, with visible effects after four to five generations.
Diet diversification shapes broad-scale distribution patterns in European bats
Authors: Alberdi Antton , Razgour Orly , Aizpurua Ostaizka , Novella-Fernandez Roberto , Aihartza Joxerra , Budinski Ivana , Garin Inazio , Ibáñez Carlos , Izagirre Eñaut , Rebelo Hugo , Russo Danilo , Vlaschenko Anton , Zhelyazkova Violeta , Zrncic Vida , Gilbert M Thomas P 
Published: July 2019

AbstractLarge-scale species’ distributions have been traditionally attributed to physiological traits related to abiotic factors, while behavioural features linked to biotic interactions have received little attention. We tested the relationship between trophic and spatial niche breadths through combining species distribution modelling with dietary DNA metabarcoding of over 400 bats sampled across Europe belonging to seven species. Our results point to a causality cascade between hunting plasticity, trophic niche breadth and spatial niche breadth, and thus indicate that behavioral plasticity and dietary diversification can contribute to shaping broad-scale species distributions.
Computational Finite Element Method (FEM) forward modeling workflow for transcranial Direct Current Stimulation (tDCS) current flow on MRI-derived head: Simpleware and COMSOL Multiphysics tutorial
Authors: Seibt Ole , Truong Dennis , Khadka Niranjan , Huang Yu , Bikson Marom 
Published: July 2019

AbstractTranscranial Direct Current Stimulation (tDCS) dose designs are often based on computational Finite Element Method (FEM) forward modeling studies. These FEM models educate researchers about the resulting current flow (intensity and pattern) and so the resulting neurophysiological and behavioral changes based on tDCS dose (mA), resistivity of head tissues (e.g. skin, skull, CSF, brain), and head anatomy. Moreover, model support optimization of montage to target specific brain regions. Computational models are thus an ancillary tool used to inform the design, set-up and programming of tDCS devices, and investigate the role of parameters such as electrode assembly, current directionality, and polarity of tDCS in optimizing therapeutic interventions. Computational FEM modeling pipeline of tDCS initiates with segmentation of an exemplary magnetic resonance imaging (MRI) scan of a template head into multiple tissue compartments to develop a higher resolution (< 1 mm) MRI derived FEM model using Simpleware ScanIP. Next, electrode assembly (anode and cathode of variant dimension) is positioned over the brain target and meshed at different mesh densities. Finally, a volumetric mesh of the head with electrodes is imported in COMSOL and a quasistatic approximation (stead-state solution method) is implemented with boundary conditions such as inward normal current density (anode), ground (cathode), and electrically insulating remaining boundaries. A successfully solved FEM model is used to visualize the model prediction via different plots (streamlines, volume plot, arrow plot).
Chemogenetic evidence that rapid neuronal de novo protein synthesis is required for consolidation of long-term memory
Authors: Shrestha Prerana , Ayata Pinar , Herrero-Vidal Pedro , Longo Francesco , Gastone Alexandra , Ledoux Joseph E. , Heintz Nathaniel , Klann Eric 
Published: July 2019

AbstractTranslational control of memory processes is a tightly regulated process where the coordinated interaction and modulation of translation factors provides a permissive environment for protein synthesis during memory formation. Existing methods used to block translation lack the spatiotemporal precision to investigate cell-specific contributions to consolidation of long-term memories. Here, we have developed a novel chemogenetic mouse resource for cell type-specific and drug-inducible protein synthesis inhibition (ciPSI) that utilizes an engineered version of the catalytic kinase domain of dsRNA-activated protein (PKR). ciPSI allows rapid and reversible phosphorylation of eIF2α causing a block on general translation by 50% in vivo. Using this resource, we discovered that temporally structured pan-neuronal protein synthesis is required for consolidation of long-term auditory threat memory. Targeted protein synthesis inhibition in CamK2α expressing glutamatergic neurons in lateral amygdala (LA) impaired long-term memory, which was recovered with artificial chemogenetic reactivation at the cost of stimulus generalization. Conversely, genetically reducing phosphorylation of eIF2α in CamK2α positive neurons in LA enhanced memory strength, but was accompanied with reduced memory fidelity and behavior inflexibility. Our findings provide evidence for a finely tuned translation program during consolidation of long-term threat memories.
Structures of the ATP-fueled ClpXP proteolytic machine bound to protein substrate
Authors: Fei Xue , Bell Tristan A. , Jenni Simon , Stinson Benjamin M. , Baker Tania A. , Harrison Stephen C. , Sauer Robert T. 
Published: July 2019

SUMMARYClpXP is an ATP-dependent protease in which the ClpX AAA+ motor binds, unfolds, and translocates specific protein substrates into the degradation chamber of ClpP. We present cryo-EM studies of the E. coli enzyme that show how asymmetric hexameric rings of ClpX bind symmetric heptameric rings of ClpP and interact with protein substrates. Subunits in the ClpX hexamer assume a spiral conformation and interact with two-residue segments of substrate in the axial channel, as observed for other AAA+ proteases and protein-remodeling machines. Strictly sequential models of ATP hydrolysis and a power stroke that moves two residues of the substrate per translocation step have been inferred from these structural features for other AAA+ unfoldases, but biochemical and single-molecule biophysical studies indicate that ClpXP operates by a probabilistic mechanism in which five to eight residues are translocated for each ATP hydrolyzed. We propose structure-based models that could account for the functional results.
In silico identification of a molecular circadian system with novel features in the crustacean model organism Parhyale hawaiensis
Authors: Hunt Benjamin James , Mallon Eamonn , Rosato Ezio 
Published: July 2019

AbstractThe amphipod Parhyale hawaiensis is a model organism of growing importance in the fields of evolutionary development and regeneration. A small, hardy marine crustacean that breeds year-round with a short generation time, it has simple lab culture requirements and an extensive molecular toolkit including the ability to generate targeted genetic mutant lines. Here we identify canonical core and regulatory clock genes using genomic and transcriptomic resources as a first step in establishing this species as a model in the field of chronobiology. The molecular clock of P. hawaiensis lacks orthologs of the canonical circadian genes cryptochrome 1 and timeless, in common with the mammalian system but in contrast to many arthropods including Drosophila melanogaster. Furthermore the predicted CLOCK peptide is atypical and CRY2 shows an extended 5’ region of unknown function. These results appear to be shared by two other amphipod species.
Ethylene-mediated nitric oxide depletion pre-adapts plants to hypoxia stress
Authors: Hartman Sjon , Liu Zeguang , van Veen Hans , Vicente Jorge , Reinen Emilie , Martopawiro Shanice , Zhang Hongtao , van Dongen Nienke , Bosman Femke , Bassel George W. , Visser Eric J.W. , Bailey-Serres Julia , Theodoulou Frederica L. , Hebelstrup Kim H. , Gibbs Daniel J. , Holdsworth Michael J. , Sasidharan Rashmi , Voesenek Laurentius A.C.J. 
Published: July 2019

AbstractTimely perception of adverse environmental changes is critical for survival. Dynamic changes in gases are important cues for plants to sense environmental perturbations, such as submergence. In Arabidopsis thaliana, changes in oxygen and nitric oxide (NO) control the stability of ERFVII transcription factors. ERFVII proteolysis is regulated by the N-degron pathway and mediates adaptation to flooding-induced hypoxia. However, how plants detect and transduce early submergence signals remains elusive. Here we show that plants can rapidly detect submergence through passive ethylene entrapment and use this signal to pre-adapt to impending hypoxia. Ethylene can enhance ERFVII stability prior to hypoxia by increasing the NO-scavenger PHYTOGLOBIN1. This ethylene-mediated NO depletion and consequent ERFVII accumulation pre-adapts plants to survive subsequent hypoxia. Our results reveal the biological link between three gaseous signals for the regulation of flooding survival and identifies novel regulatory targets for early stress perception that could be pivotal for developing flood-tolerant crops.
Continuum descriptions of spatial spreading for heterogeneous cell populations: theory and experiment
Authors: Matsiaka Oleksii M , Baker Ruth E , Simpson Matthew J 
Published: July 2019

AbstractVariability in cell populations is frequently observed in bothin vitroandin vivosettings. Intrinsic differences within populations of cells, such as differences in cell sizes or differences in rates of cell motility, can be present even within a population of cells from the same cell line. We refer to this variability as cellheterogeneity. Mathematical models of cell migration, for example, in the context of tumour growth and metastatic invasion, often account for both undirected (random) migration and directed migration that is mediated by cell-to-cell contacts and cell-to-cell adhesion. A key feature of standard models is that they often assume that the population is composed of identical cells with constant properties. This leads to relatively simple single-specieshomogeneousmodels that neglect the role of heterogeneity. In this work, we use a continuum modelling approach to explore the role of heterogeneity in spatial spreading of cell populations. We employ a three-species heterogeneous model of cell motility that explicitly incorporates different types of experimentally-motivated heterogeneity in cell sizes: (i) monotonically decreasing; (ii) uniform; (iii) non-monotonic; and (iv) monotonically increasing distributions of cell size. Comparing the density profiles generated by the three-species heterogeneous model with density profiles predicted by a more standard single-species homogeneous model reveals that when we are dealing with monotonically decreasing and uniform distributions a simple and computationally efficient single-species homogeneous model can be remarkably accurate in describing the evolution of a heterogeneous cell population. In contrast, we find that the simpler single-species homogeneous model performs relatively poorly when applied to non-monotonic and monotonically in-creasing distributions of cell sizes. Additional results for heterogeneity in parameters describing both undirected and directed cell migration are also considered, and we find that similar results apply.
Comparison of Illumina MiSeq and the Ion Torrent PGM and S5 platforms for whole-genome sequencing of picornaviruses and caliciviruses
Authors: Marine Rachel L. , Magaña Laura C. , Castro Christina J. , Zhao Kun , Montmayeur Anna M. , Schmidt Alexander , Diez-Valcarce Marta , Ng Terry Fei Fan , Vinjé Jan , Burns Cara C. , Nix W. Allan , Rota Paul A. , Oberste M. Steven 
Published: July 2019

ABSTRACTNext-generation sequencing is a powerful tool for virological surveillance. While Illumina® and Ion Torrent® sequencing platforms are used extensively for generating viral RNA genome sequences, there is limited data comparing different platforms. We evaluated the Illumina MiSeq, Ion Torrent PGM and Ion Torrent S5 platforms using a panel of sixteen specimens containing picornaviruses and human caliciviruses (noroviruses and sapoviruses). The specimens were processed, using combinations of three library preparation and five sequencing kits, to assess the quality and completeness of assembled viral genomes, and an estimation of cost per sample to generate the data was calculated. The choice of library preparation kit and sequencing platform was found to impact the breadth of genome coverage and accuracy of consensus viral genomes. The Ion Torrent S5 outperformed the older Ion Torrent PGM platform in data quality and cost, and generated the highest proportion of reads for enterovirus D68 samples. However, indels at homopolymer regions impacted the accuracy of consensus genome sequences. For lower throughput sequencing runs (i.e., Ion Torrent 510 or Illumina MiSeq Nano V2), the cost per sample was lower on the MiSeq platform, whereas with higher throughput runs (Ion Torrent 530 or Illumina MiSeq V2) the cost per sample was comparable. These findings suggest that the Ion Torrent S5 and Illumina MiSeq platforms are both viable options for genomic sequencing of RNA viruses, each with specific advantages and tradeoffs.