bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anin silicosurvey ofClostridioides difficileextrachromosomal elements
Authors: Hornung Bastian , Kuijper Ed J. , Smits Wiep Klaas 
Published: May 2019

AbstractThe gram-positive enteropathogenClostridioides difficileis the major cause of healthcare associated diarrhoea and is also an important cause of community-acquired infectious diarrhoea. Considering the burden of the disease, many studies have employed whole genome sequencing to identify factors that contribute to virulence and pathogenesis. Though extrachromosomal elements such as plasmids are important for these processes in other bacteria, the few characterized plasmids ofC. difficilehave no relevant functions assigned and no systematic identification of plasmids has been carried out to date. Here, we perform anin silicoanalysis of publicly available sequence data, to show that ∼13% of allC. difficilestrains contain extrachromosomal elements, with 1-6 elements per strain. Our approach identifies known plasmids (e.g. pCD6, pCD630 and cloning plasmids) and 6 novel putative plasmid families. Our study shows that plasmids are abundant and may encode functions that are relevant forC. difficilephysiology. The newly identified plasmids may also form the basis for the construction of novel cloning plasmids forC. difficilethat are compatible with existing tools.RepositoriesThe assembled circular type plasmids have been deposited at the European Nucleotide Archive (ENA) under accession numbers ERZ940801 and ERZ940803-ERZ940808.
Designing Distributed Cell Classifier Circuits using a Genetic Algorithm
Authors: Nowicka Melania , Siebert Heike 
Published: May 2019

AbstractCell classifiers are decision-making synthetic circuits that allow in vivo cell-type classification. Their design is based on finding a relationship between differential expression of miRNAs and the cell condition. Such biological devices have shown potential to become a valuable tool in cancer treatment as a new type-specific cell targeting approach. So far, only single-circuit classifiers were designed in this context. However, reliable designs come with high complexity, making them difficult to assemble in the lab. Here, we apply so-called Distributed Classifiers (DC) consisting of simple single circuits, that decide collectively according to a threshold function. Such architecture potentially simplifies the assembly process and provides design flexibility. Here, we present a genetic algorithm that allows the design and optimization of DCs. Breast cancer case studies show that DCs perform with high accuracy on real-world data. Optimized classifiers capture biologically relevant miRNAs that are cancer-type specific. The comparison to a single-circuit classifier design approach shows that DCs perform with significantly higher accuracy than individual circuits. The algorithm is implemented as an open source tool.
Low handgrip strength is closely associated with anemia among adults: A cross-sectional study using Korea National Health and Nutrition Examination Survey (KNHANES)
Authors: Gi Yu-mi , Jung Boyoung , Kim Koh-Woon , Cho Jae-Heung , Ha In-Hyuk 
Published: May 2019

ABSTRACTBackgroundAnemia occurs because of insufficient hemoglobin, which provides oxygen to the body. Because of its close relationship with various illnesses, it must always be investigated clinically. Previous studies have demonstrated an association between hemoglobin concentration and handgrip strength. Thus, we aimed to analyze the association between handgrip strength and anemia in Korean adults to determine whether the handgrip strength test can be used as a tool to identify anemia.MethodsThe research subjects’ data were extracted from the 6thand 7thKorean National Health and Nutrition Examination Survey, between January 2013 and December 2017. Overall, data of 16,637 adults (weighted n= 9,734,598) were analyzed. Differences in sociodemographic factors (sex, age, education, income, and employment), lifestyle factors (alcohol consumption, smoking, and physical activity), and illness and health factors (body mass index, vitamin intake, iron intake, comorbid illnesses, and handgrip strength) by existence of anemia were analyzed using a chi square test. Binary logistic regression was performed to identify factors of anemia. Subgroup analysis, stratified by sex and age, was performed.ResultsAmong Korean adults aged ≥ 19 years, 745,296 (7.7%) had anemia. Higher odds ratio (OR) of anemia occurred in the weak handgrip strength group compared to the strong handgrip strength group (OR=1.92, 95% CI: 1.58-2.33). The subgroup analysis showed a higher OR for anemia in the weak handgrip strength group than in the strong handgrip strength group, regardless of sex or age. However, the results showed that this association was greater for males (OR=2.13, 95% CI: 1.35-3.34) and for those aged ≥65 years (OR=1.92, 95% CI: 1.42-2.58).ConclusionThis study showed a strong association between handgrip strength and anemia, which was particularly strong for males and those aged ≥65 years. Therefore, it is anticipated that handgrip strength can be used in anemia screening tests as a useful tool.
A systems biology-based molecular model of the protein kinase C life cycle
Authors: Aslam Naveed , Alvi Farah 
Published: May 2019

AbstractProtein kinase C (PKC) enzymes are a family of kinases that mediate signal transduction originating at the cell surface. Most cell membranes can contain functional PKC enzymes. Aberrations in the PKC life cycle may result cellular damage and dysfunction. For example, some cancerous cells exhibit alterations in PKC activity. Here, we use a systems biology approach to describe a molecular model of the PKC life cycle. Understanding the PKC life cycle is necessary to identify new anticancer drug targets. The PKC life cycle is composed of three key regulatory processes: maturation, activation and termination. These processes precisely control PKC enzyme levels. This model describes the fate of PKC duringde novosynthesis and PKC’s lipid-mediated activation cycle. We utilize a systems biology approach to show the PKC life cycle is controlled by multiple phosphorylation and dephosphorylation events. PKC processing events can be divided into two types: maturation via processing of newly synthesized enzyme and secondary messenger-dependent activation of dormant, but catalytically-competent enzyme. Newly synthesized PKC enzyme is constitutively processed through three ordered phosphorylations and stored in the cytosol as a stable, signaling-competent inactive and autoinhibited molecule. Upon extracellular stimulation, diacylglycerol (DAG) and calcium ion (Ca+2) generated at the membrane bind PKC. PKC then undergoes cytosol-to-membrane translocation and subsequent activation. Our model shows that, once activated, PKC is prone to dephosphorylation and subsequent degradation. This model also describes the role of HSP70 in stabilization and re-phosphorylation of dephosphorylated PKC, replenishing the PKC pool. Our model shows how the PKC pool responds to different intensities of extracellular stimuli? We show that blocking PHLPP dephosphorylation replenishes the PKC pool in a dose-dependent manner. This model provides a comprehensive understanding of PKC life cycle regulation.
Protein lysine methylation is involved in modulating the response of sensitive and tolerant Arabidopsis species to cadmium stress
Authors: Serre Nelson B.C. , Sarthou Manon , Gigarel Océane , Figuet Sylvie , Corso Massimiliano , Choulet Justine , Rofidal Valérie , Alban Claude , Santoni Véronique , Bourguignon Jacques , Verbruggen Nathalie , Ravanel Stéphane 
Published: May 2019

ABSTRACTThe mechanisms underlying the response and adaptation of plants to excess of trace elements are not fully described. Here, we analyzed the importance of protein lysine methylation for plants to cope with cadmium. We analyzed the effect of cadmium on lysine-methylated proteins and protein lysine methyltransferases (KMTs) in two cadmium-sensitive species,Arabidopsis thalianaandA. lyrata, and in three populations ofA. halleriwith contrasting cadmium accumulation and tolerance traits. We showed that some proteins are differentially methylated at lysine residues in response to Cd and that a few genes coding KMTs is regulated by cadmium. Also, we showed that nine out of 23A. thalianamutants interrupted inKMTgenes have a tolerance to cadmium that is significantly different from that of wild-type seedlings. We further characterized two of these mutants, one was knocked-out in the calmodulin lysine methyltransferase gene and displayed increased tolerance to cadmium, the other was interrupted in aKMTgene of unknown function and showed a decreased capacity to cope with cadmium. Together, our results showed that lysine methylation of non-histone proteins is impacted by cadmium and that several methylation events are important for modulating the response of Arabidopsis plants to cadmium stress.
The dynamics of motor learning through the formation of internal models
Authors: Pierella Camilla , Casadio Maura , Solla Sara A. , Mussa-Ivaldi Ferinando A. 
Published: May 2019

AbstractA medical student learning to perform a laparoscopic procedure as well as a recently paralyzed user of a powered wheelchair must learn to operate machinery via interfaces that translate their actions into commands for the external device. Mathematically, we describe this type of learning as a deterministic dynamical process, whose state is the evolving forward and inverse internal models of the interface. The forward model predicts the outcomes of actions while the inverse model generates actions designed to attain desired outcomes. Both the mathematical analysis of learning dynamics and the performance observed in a group of subjects demonstrate first-order exponential convergence of the learning process toward a particular state that depends only on the initial inverse and forward models and on the supplied sequence of targets. Noise is not only present but necessary for the convergence of learning through the minimization of the difference between actual and predicted outcomes.Author summarySeveral studies have suggested that as we learn a new skill our brain forms representations, or “internal models”, of the skill and of the environment in which we operate. Theories of motor learning postulate that the brain builds forward models that predict the sensory consequences of motor commands, and inverse models that generate successful commands from planned movements. We test this hypothesis taking advantage of a special interface that generates a novel relation between the subject’s actions and the position of a cursor on a computer monitor, thus allowing subjects to control an external device by movements of their body. We recorded the motions of the body and of the cursor, and obtained estimates of both forward and inverse models. We followed how these estimates evolved in time as subjects practiced and acquired a new skill. We found that the description of learning as a simple deterministic process driven by the sequence of targets is sufficient to capture the observed convergence to a single solution of the inverse model among an infinite variety of alternative possibilities. This work is relevant to the study of fundamental learning mechanisms as well as to the design of intelligent interfaces for people with paralysis.
Strain-level diversity impacts cheese rind microbiome assembly and function
Authors: Niccum Brittany A. , Kastman Erik K. , Kfoury Nicole , Robbat Albert , Wolfe Benjamin E. 
Published: May 2019

ABSTRACTTaxa that are consistently found across microbial communities are often considered members of a core microbiome. One common assumption is that taxonomically identical core microbiomes will have similar dynamics and functions across communities. However, strain-level genomic and phenotypic variation of core taxa could lead to differences in how core microbiomes assemble and function. Using cheese rinds, we tested whether taxonomically identical core microbiomes isolated from distinct locations have similar assembly dynamics and functional outputs. We first isolated the same three bacterial species (Staphylococcus equorum, Brevibacterium auranticum, andBrachybacterium alimentarium) from nine cheeses produced in different regions of the United States and Europe. Comparative genomics identified distinct phylogenetic clusters and significant variation in genome content across the nine core microbiomes. When we assembled each core microbiome with initially identical compositions, community structure diverged over time resulting in communities with different dominant taxa. The core microbiomes had variable responses to abiotic (high salt) and biotic (the fungusPenicillium) perturbations, with some communities showing no response and others substantially shifting in composition. Functional differences were also observed across the nine core communities, with considerable variation in pigment production (light yellow to orange) and composition of volatile organic compound profiles emitted from the rinds (nutty to sulfury). Our work demonstrates that core microbiomes isolated from independent communities may not function in the same manner due to strain-level variation of core taxa. Strain-level diversity across core cheese rind microbiomes may contribute to variability in the aesthetics and quality of surface-ripened cheeses.
Estimation of the Hemoglobin Glycation Rate Constant
Authors: Kameyama Masashi , Okumiya Toshika , Tokuhiro Shinji , Matsumura Yoshihisa , Matsui Hirotaka , Ono Yasuhiro , Iwasaka Tsuyoshi , Hiratani Kazuyuki , Koga Masafumi 
Published: May 2019

AbstractAimIn a previous study, a method of obtaining mean erythrocyte age (MRBC) from HbA1c and average plasma glucose (AG) was proposed. However, the true value of the hemoglobin glycation constant (kgdL/mg/day), required for this model has yet to be well characterized. Another study also proposed a method of derivingMRBCfrom erythrocyte creatine (EC). Utilizing these formulae, this study aimed to determine a more accurate estimate ofkg.Methods107 subjects including 31 patients with hemolytic anemia and 76 subjects without anemia were included in this study. EC and HbA1c data were analyzed, andMRBCusing HbA1c, AG and the newly-derived constant,kgwere compared toMRBCusing traditional51Cr in three patients whose data were taken from previous case studies.ResultA value of 7.0 × 10−6dL/mg/day was determined forkg.MRBCusing HbA1c, AG andkgwere found to no be significantly different (pairedt-test,p= 0.45) toMRBCusing traditional51Cr.Conclusionskgenables the estimation ofMRBCfrom HbA1c and AG.
The Deubiquitinating Enzyme USP37 Stabilizes CHK1 to Promote the Cellular Response to Replication Stress
Authors: Singh Mayank , Burrows Amy C. , Torres Adrian E. , Pal Debjani , Stromberg Benjamin , Insinna Christine , Dickson Andrew , Westlake Christopher J. , Summers Matthew K. 
Published: May 2019

SUMMARYThe deubiquitinating enzyme USP37 is known to contribute to timely S-phase onset. However, it is not clear if USP37 is essential beyond S-phase entry despite expression and activity of USP37 peaking within S-phase. Here, we determine that USP37-depleted cells exhibited altered S-phase kinetics and harbored increased levels of the replication stress and DNA damage markers γH2AX and 53BP1 in response to perturbed replication. Depletion of USP37 also reduced cellular proliferation and led to increased sensitivity to agents that induce replication stress. Underlying the increased sensitivity, we found that the checkpoint kinase CHK1 is destabilized in the absence of USP37, attenuating its function. We further demonstrated that USP37 deubquitinates and stabilizes CHK1. Our data contribute to an evolving understanding of UPS37 as a multifaceted regulator of genome regulation.
MemSTATS: A Benchmark Set of Membrane Protein Symmetries and Pseudo-Symmetries
Authors: Aleksandrova Antoniya A. , Sarti Edoardo , Forrest Lucy R. 
Published: May 2019

AbstractIn membrane proteins, symmetry and pseudo-symmetry often have functional or evolutionary implications. However, available symmetry detection methods have not been tested systematically on this class of proteins due to the lack of an appropriate benchmark set. Here we present MemSTATS, a publicly-available benchmark set of both quaternary and internal symmetries in membrane protein structures described in terms of order, repeated elements, and orientation of the axis with respect to the membrane plane. Moreover, using MemSTATS, we compare the performance of four widely-used symmetry detection algorithms and highlight specific challenges and areas for improvement in the future.
The methyl cycle is a conserved regulator of biological clocks
Authors: Fustin Jean-Michel , Ye Shiqi , Rakers Christin , Versteven Marijke , Cargill Samantha J. , Tamai T. Katherine , Xu Yao , Jabbur Maria Luísa , Kojima Rika , Lamberti Melisa L. , Yoshioka-Kobayashi Kumiko , Whitmore David , Kageyama Ryoichiro , Matsuo Takuya , Stanewsky Ralf , Golombek Diego A. , Johnson Carl Hirschie , van Ooijen Gerben , Okamura Hitoshi 
Published: May 2019

AbstractThe methyl cycle is a universally conserved metabolic pathway operating in prokaryotes and eukaryotes. In this pathway, the amino acid methionine is used to synthesize S-adenosylmethionine, the methyl donor co-substrate in the methylation of nucleic acids, histone and non-histone proteins and many other molecules within the cell. The methylation of nucleic acids and proteins is the foundation of epigenetic and epitranscriptomic regulations of gene expression, but whether the methyl cycle centrally regulates gene expression and function by controlling the availability of methyl moieties is poorly understood.From cyanobacteria to humans, a circadian clock that involves an exquisitely regulated transcription-translation-feedback loop driving oscillations in gene expression and orchestrating physiology and behavior has been described. We reported previously that inhibition of the methyl cycle in mammalian cells caused the lengthening of the period of these oscillations, suggesting the methyl cycle may indeed act as a central regulator of gene expression, at least in mammals. Here, we investigated whether the methyl cycle, given its universal presence among living beings, regulates the circadian clock in species across the phylogenetic tree of life.We reveal a remarkable evolutionary conservation of the link between the methyl cycle and the circadian clock. Moreover, we show that the methyl cycle also regulates the somite segmentation clock, another transcription-translation negative feedback loop-based timing mechanism that orchestrate embryonic development in vertebrates, highlighting the methyl cycle as a master regulator of biological clocks.SIGNIFICANCE STATEMENTHere we reveal that the methyl cycle, a universal metabolic pathway leading to the synthesis of S-adenosylmethionine, the methyl donor co-substrate in virtually all transmethylation reactions within the cell, is a conserved regulator of biological clocks. These discoveries highlight the methyl cycle as a metabolic hub that regulates gene expression via the availability of methyl moieties for the methylation of nucleic acids, proteins and many other molecules with the cell.
ASA3P: An automatic and scalable pipeline for the assembly, annotation and higher level analysis of closely related bacterial isolates
Authors: Schwengers Oliver , Hoek Andreas , Fritzenwanker Moritz , Falgenhauer Linda , Hain Torsten , Chakraborty Trinad , Goesmann Alexander 
Published: May 2019

AbstractWhole genome sequencing of bacteria has become daily routine in many fields. Advances in DNA sequencing technologies and continuously dropping costs have resulted in a tremendous increase in the amounts of available sequence data. However, comprehensive in-depth analysis of the resulting data remains an arduous and time consuming task. In order to keep pace with these promising but challenging developments and to transform raw data into valuable information, standardized analyses and scalable software tools are needed. Here, we introduce ASA3P, a fully automatic, locally executable and scalable assembly, annotation and analysis pipeline for bacterial genomes. The pipeline automatically executes necessary data processing steps, i.e. quality clipping and assembly of raw sequencing reads, scaffolding of contigs and annotation of the resulting genome sequences. Furthermore, ASA3P conducts comprehensive genome characterizations and analyses, e.g. taxonomic classification, detection of antibiotic resistance genes and identification of virulence factors. All results are presented via an HTML5 user interface providing aggregated information, interactive visualizations and access to intermediate results in standard bioinformatics file formats. We distribute ASA3P in two versions: a locally executable Docker container for small-to-medium-scale projects and an OpenStack based cloud computing version able to automatically create and manage self-scaling compute clusters. Thus, automatic and standardized analysis of hundreds of bacterial genomes becomes feasible within hours. The software and further information is available at: http://asap.computational.bio.
Evidence of the Cost-Efficiency of Scale as seen in Polio Vaccination and Surveillance Costs
Authors: Hagedorn Brittany L. , Mercer Laina D. , Chabot-Couture Guillaume 
Published: May 2019

AbstractThis analysis examined how polio program costs vary with scale for vaccination and disease surveillance, based on historical budget data published by the Global Polio Eradication Initiative (GPEI) from 2005 to 2018. We applied a linear mixed effects regression model in order to understand the cost structure of the historical GPEI budgets, with the goal that lessons learned from polio may be extended to other global disease elimination programs. Our findings demonstrate that there are economies of scale for vaccine delivery operations and for disease surveillance, which means that larger programs can leverage fixed costs and achieve better cost-efficiency as they scale. This finding should enable decision makers to create more reliable budgets, which support fundraising and optimal resource allocation. They also provide insight into how cost effectiveness changes as programs scale up during progressive disease control and elimination, as well as what level of resources are needed to sustain a program that is scaling back post-eradication and through to certification.
The acquisition of the Arabic construct state (CS) constructions by Arabic-speaking children with ASD
Authors: Altakhaineh Abdel Rahman Mitib , Alkhatib Razan N. 
Published: May 2019

PurposeThe purpose of this paper is to investigate whether age plays a role in the acquisition of construct state (CS) constructions in Arabic by 14 children with autism spectrum disorder (ASD). It also examined the challenges faced by children with ASD in producing different types of CS constructions. Finally, the study analysed the sources of difficulties children with ASD encounter during the learning process of the CS.Design/methodology/approachFor the purposes of this study, the participants were asked to orally complete short sentences with the help of illustrative pictures.FindingsResults revealed that the age of the 14 children with ASD plays a role in the acquisition of CS constructions. Children of age 12–15 performed better than those of age 8 and 10. Results also showed that children with ASD performed better in producing phrases rather than compounds. Moreover, the participants performed better on endocentric compounds as opposed to exocentric ones. Finally, analysing the errors produced on the text revealed that the acquisition of head direction precedes definiteness.Originality/valueThe topic of the study has not been investigated yet and the study concluded with some important findings concerning teaching Arabic CS to children with ADS.