bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multiple Cross Displacement Amplification Coupled with Gold Nanoparticles-Based Lateral Flow Biosensor for Detection of the Mobilized Colistin Resistance Gene mcr-1
Authors: Gong Lin , Liu Ernan , Che Jie , Li Juan , Liu Xiaoli , Xu Huiqiong , Liang Jiansheng 
Published: March 2019

AbstractFast dissemination of the mobilized colistin resistance (mcr) gene mcr-1 in Enterobacteriaceae causes a huge threat to the treatment of severe infection. In the current report, a multiple cross displacement amplification (MCDA) coupled with the detection of amplified products by gold nanoparticles-based lateral flow biosensor (LFB) assay (MCDA-LFB) was established to identify the mcr-1 gene with simpleness, rapidity, specificity and sensitivity. The MCDA-LFB assay was performed at a isothermal temperature (63°C) for only 30 min during the amplification stage, and the reaction products were directly identified by using LFB which obtained the result with 2 min. The entire process of experiments, from templates extraction to result judging, was accomplished less than 60 min. For the analytical specificity of this method, all of the 16 mcr-1-producing strains were positive, and all of the non-mcr-1 isolates got the negative results. The sensitivity of mcr-1-MCDA-LFB assay was as little as 600 fg of plasmid DNA per reaction in pure culture, and approximately 4.5×103 CFU/mL (~4.5 CFU/reaction) in fecal samples spiked with 100 μl of strains. Therefore, this technique established in the present study is suitable for the surveillance of mcr-1 gene in clinic and livestock industry.
Pyridox(am)ine 5’-phosphate oxidase deficiency induces seizures inDrosophila melanogaster
Authors: Chi Wanhao , Iyengar Atulya , Albersen Monique , Bosma Marjolein , Verhoeven-Duif Nanda M. , Wu Chun-Fang , Zhuang Xiaoxi 
Published: March 2019

AbstractPyridox(am)ine 5’-phosphate oxidase (PNPO) is a rate-limiting enzyme in converting dietary vitamin B6 (VB6) to pyridoxal 5’-phosphate (PLP), the biologically active form of VB6, and involved in the synthesis of neuro-transmitters including GABA, dopamine, and serotonin. In humans, PNPO mutations have been increasingly identified in neonatal epileptic encephalopathy and more recently also in early-onset epilepsy. Till now, little is known about the neurobiological mechanisms underlying PNPO-deficiency-induced seizures due to the lack of animal models. Previously we identified a c.95 C > A missense mutation insgll- theDrosophilahomolog of humanPNPO(hPNPO) and found mutant (sgll95) flies exhibiting a lethal phenotype on a diet devoid of VB6. Here we report the establishment of bothsgll95and ubiquitoussgllknockdown (KD) flies as valid animal models of PNPO-deficiency-induced epilepsy. Bothsgll95andsgllKD flies exhibit spontaneous seizures before they die. Electrophysiological recordings reveal that seizures caused by PNPO deficiency have characteristics similar to that in flies treated with GABA antagonist picrotoxin. Both seizures and lethality are associated with low PLP levels and can be rescued by ubiquitous expression of wild-typesgllorhPNPO, suggesting the functional conservation of the PNPO enzyme between humans and flies. Results from cell type-specificsgllKD further demonstrate that PNPO in the brain is necessary for seizure prevention and survival. Our establishment of the first animal model of PNPO deficiency will lead to better understanding of VB6 biology, thePNPOgene and its mutations discovered in patients, and can be a cost-effective system to test therapeutic strategies.
Multiple genetic loci affect place learning and memory performance in Drosophila melanogaster
Authors: Williams-Simon P.A. , Posey C. , Mitchell S. , Ng’oma E. , Mrkvicka J.A. , Zars T. , King E.G. 
Published: March 2019

AbstractLearning and memory are critical functions for all animals, giving individuals the ability to respond to changes in their environment. Within populations, individuals vary, however the mechanisms underlying this variation in performance are largely unknown. Thus, it remains to be determined what genetic factors cause an individual to have high learning ability, and what factors determine how well an individual will remember what they have learned. To genetically dissect learning and memory performance, we used the DSPR, a multiparent mapping resource in the model system Drosophila melanogaster, consisting of a large set of recombinant inbred lines (RILs) that naturally vary in these and other traits. Fruit flies can be trained in a “heat box” to learn to remain on one side of a chamber (place learning), and can remember this (place memory) over short timescales. Using this paradigm, we measured place learning and memory for ∼49,000 individual flies from over 700 DSPR RILs. We identified 16 different loci across the genome that significantly affect place learning and/or memory performance, with 5 of these loci affecting both traits. To identify transcriptomic differences associated with performance, we performed RNA-Seq on pooled samples of 7 high performing and 7 low performing RILs for both learning and memory and identified hundreds of genes with differences in expression in the two sets. Integrating our transcriptomic results with the mapping results allowed us to identify nine promising candidate genes, advancing our understanding of the genetic basis underlying natural variation in learning and memory performance.
Prioritizing putatively etiological T cell epitopes across autoimmune diseases
Authors: Ogishi Masato 
Published: March 2019

AbstractAutoimmune diseases remain a leading cause of mortality among adolescents and young adults worldwide. Despite their clinical impact, there are still significant knowledge gaps in our understanding of immunological tolerance and its breach that characterizes the onset of autoimmune diseases. Genetic associations between the histocompatibility leukocyte antigen (HLA) loci and various autoimmune diseases have been well established. The HLA class I and class II molecules present epitopes to T cells, and T cells play indispensable roles both in the maintenance of tolerance and the pathogenesis of autoimmune diseases. Although a vast number of epitopes and reactive T cell clones have been identified from animal model studies and observational studies, however, only a few have been proven to be causally relevant to disease pathogenesis. Here, we propose a computational framework to prioritize etiologically relevant epitopes by integrating the putatively causal associations between HLA alleles and disease risk identified from population genetics; we define a metric, termed “differential presentation index (DPI),” which principally reflects the relative difference of epitope abundance presented onto HLA molecules whose alleles are genetically predisposing to or protective against the specific disease. We systematically examined publicly available epitope sequence data previously studied in the context of autoimmune diseases. Self-epitopes were generally more stably presented on disease-protective HLAs than non-self epitopes, and hence had a negative DPI. Conversely, proteome-wide sequence alignment revealed that epitopes with highly positive DPI were less similar to self. As a case study, we performed a focused analysis of multiple sclerosis (MS), and identified epitopes from myelin basic protein (MBP), a well-established MS autoantigen, based on DPI-guided prioritization. Moreover, we found several non-MBP-derived self-epitopes with high DPI that are potentially involved in the pathogenesis of MS. Our framework facilitates the identification of etiologically relevant epitopes across autoimmune diseases with known HLA allele association, which in turn expedites the development of epitope-specific disease monitoring and intervention strategies.
Active behaviour during early development shapes glucocorticoid reactivity
Authors: Castillo-Ramírez Luis A. , Ryu Soojin , De Marco Rodrigo J. 
Published: March 2019

AbstractGlucocorticoids are the final effectors of the stress axis, with numerous targets in the central nervous system and the periphery. They are essential for adaptation, yet currently it is unclear how early life events program the glucocorticoid response to stress. Here we provide evidence that involuntary swimming at early developmental stages can reconfigure the cortisol response to homotypic and heterotypic stress in larval zebrafish (Danio rerio), also reducing startle reactivity and increasing spontaneous activity as well as energy efficiency during active behaviour. Collectively, these data identify a role of the genetically malleable zebrafish for linking early life stress with glucocorticoid function in later life.
Cell morphology and nucleoid dynamics in dividing D. radiodurans
Authors: Floc’h Kevin , Lacroix Françoise , Servant Pascale , Wong Yung-Sing , Kleman Jean-Philippe , Bourgeois Dominique , Timmins Joanna 
Published: March 2019

AbstractOur knowledge of bacterial nucleoids originates mostly from studies of rod- or crescent-shaped bacteria. Here, we reveal that Deinococcus radiodurans, a relatively large, spherical bacterium, possessing a multipartite genome, and well-known for its radioresistance, constitutes a valuable system for the study of nucleoids in cocci. Using advanced microscopy, we show that as D. radiodurans progresses through its cell cycle, it undergoes coordinated morphological changes at both the cellular and nucleoid level. D. radiodurans nucleoids were found to be highly condensed, but also surprisingly dynamic, adopting multiple distinct configurations and presenting a novel chromosomal arrangement in which oriC loci are radially distributed around clustered ter sites maintained at the centre of cells. Single-molecule and ensemble studies of the abundant histone-like HU protein suggest that its loose binding to DNA may contribute to this remarkable plasticity. These findings clearly demonstrate that nucleoid organization is complex and tightly coupled to cell cycle progression.
Analysis-ready datasets for insecticide resistance phenotype and genotype frequency in African malaria vectors
Authors: Moyes Catherine L. , Wiebe Antoinette , Gleave Katherine , Trett Anna , Hancock Penelope A. , Padonou Germain Gil , Chouaïbou Mouhamadou S. , Sovi Arthur , Abuelmaali Sara A. , Ochomo Eric , Antonio-Nkondjio Christophe , Dengela Dereje , Kawada Hitoshi , Dabire Roch K. , Donnelly Martin J. , Mbogo Charles , Fornadel Christen , Coleman Michael 
Published: March 2019

AbstractThe impact of insecticide resistance in malaria vectors is poorly understood and quantified. Here a series of geospatial datasets for insecticide resistance in malaria vectors are provided so that trends in resistance in time and space can be quantified and the impact of resistance found in wild populations on malaria transmission in Africa can be assessed. Data are also provided for common genetic markers of resistance to support analyses of whether these genetic data can improve the ability to monitor resistance in low resource settings. Specifically, data have been collated and geopositioned for the prevalence of insecticide resistance, as measured by standard bioassays, in representative samples of individual species or species complexes. Data are provided for theAnopheles gambiaespecies complex, theAnopheles funestussubgroup, and for nine individual vector species. In addition, allele frequencies for known resistance associated markers in the Voltage-gated sodium channel (Vgsc) are provided. In total, eight analysis-ready, standardised, geopositioned datasets encompassing over 20,000 African mosquito collections between 1957 and 2017 are provided.
Strain- or Stress-sensing in mechanochemical patterning by the phytohormone auxin
Authors: Julien Jean-Daniel , Pumir Alain , Boudaoud Arezki 
Published: March 2019

AbstractBoth chemical and mechanical fields are known to play a major role in morphogenesis. In plants, the phytohormone auxin and its directional transport are essential for the formation of robust patterns of organs, such as flowers or leaves, known as phyllotactic patterns. The transport of auxin was recently shown to be affected by mechanical signals, and conversely, auxin accumulation in incipient organs affects the mechanical properties of the cells. The precise interaction between mechanical fields and auxin transport, however, is poorly understood. In particular, it is unknown whether transport is sensitive to the strain or to the stress exerted on a given cell. Here, we investigate the nature of this coupling with the help of theoretical models. Namely, we introduce the effects of either mechanical stress or mechanical strain in a model of auxin transport, and compare the patterns predicted with available experimental results, in which the tissue is perturbed by ablations, chemical treatments, or genetic manipulations. We also study the robustness of the patterning mechanism to noise and investigate the effect of a shock that changes abruptly its parameters. Although the model predictions with the two different feedbacks are often indistinguishable, the strain-feedback seems to better agree with some of the experiments. The computational modeling approach used here, which enables us to distinguish between several possible mechanical feedbacks, offers promising perspectives to elucidate the role of mechanics in tissue development, and may help providing insight into the underlying molecular mechanisms.
Familial influences on Neuroticism and Education in the UK Biobank
Authors: Cheesman R. , Coleman J. , Rayner C. , Purves K.L. , Morneau-Vaillancourt G. , Glanville K. , Choi S.W. , Breen G. , Eley T.C. 
Published: March 2019

AbstractGenome-wide studies often exclude family members, even though they are a valuable source of information. We identified parent-offspring pairs, siblings and couples in the UK Biobank and implemented a family-based DNA-derived heritability method to capture additional genetic effects and multiple sources of environmental influence on neuroticism and years of education. Compared to estimates from unrelated individuals, heritability increased from 10% to 27% and from 19% to 57% for neuroticism and education respectively by including family-based genetic effects. We detected no family environmental influences on neuroticism, but years of education was substantially influenced by couple similarity (38%). Overall, our genetic and environmental estimates closely replicate previous findings from an independent sample, but more research is required to dissect contributions to the additional heritability, particularly rare and structural genetic effects and residual environmental confounding. The latter is especially relevant for years of education, a highly socially-contingent variable, for which our heritability estimate is at the upper end of twin estimates in the literature. Family-based genetic effects narrow the gap between twin and DNA-based heritability methods, and could be harnessed to improve polygenic prediction.
MM-MRE: a new technique to quantify individual muscle forces during isometric tasks of the wrist using MR elastography
Authors: Zonnino Andrea , Smith Daniel R. , Delgorio Peyton L. , Johnson Curtis L. , Sergi Fabrizio 
Published: March 2019

AbstractNon-invasive in-vivo measurement of individual muscle force is limited by the infeasibility of placing force sensing elements in series with the musculo-tendon structures. At the same time, estimating muscle forces using EMG measurements is prone to inaccuracies, as EMG is not always measurable for the complete set of muscles acting around the joints of interest. While new methods based on shear wave elastography have been recently proposed to directly characterize muscle mechanics, they can only be used to measure muscle forces in a limited set of superficial muscles. As such, they are not suitable to study the neuromuscular control of movements that require coordinated action of multiple muscles.In this work, we present multi-muscle magnetic resonance elastography (MM-MRE), a new technique capable of quantifying individual muscle force from the complete set of muscles in the forearm, thus enabling the study of the neuromuscular control of wrist movements. MM-MRE integrates measurements of joint torque provided by an MRI-compatible instrumented handle with muscle-specific measurements of shear wave speed obtained via MRE to quantify individual muscle force using model-based estimator.A single-subject pilot experiment demonstrates the possibility of obtaining measurements from individual muscles and establishes that MM-MRE has sufficient sensitivity to detect changes in muscle mechanics following the application of isometric joint torque with self-selected intensity.
Epistatic Transcription Factor Networks Differentially Modulate Arabidopsis Growth and Defense
Authors: Li Baohua , Tang Michelle , Caseys Céline , Nelson Ayla , Zhou Marium , Zhou Xue , Brady Siobhan M. , Kliebenstein Daniel J. 
Published: March 2019

AbstractPlants integrate internal and external signals to finely coordinate growth and defense allowing for maximal fitness within a complex environment. One common model for the relationship between growth and defense is a trade-off model in which there is a simple negative interaction between growth and defense theoretically driven by energy costs. However, there is a developing consensus that the coordination of growth and defense likely involves a more conditional and intricate connection. To explore how a transcription factor network may coordinate growth and defense, we used high-throughput phenotyping to measure growth and flowering in a set of single and pairwise mutants previously linked to the aliphatic glucosinolate defense pathway. Showing the link between growth and aliphatic glucosinolate defense, 17 of the 20 tested TFs significantly influence plant growth and/or flowering time. These effects were conditional upon the environment, age of the plant and more critically varied amongst the phenotypes when using the same genotype. The phenotypic effects of the TF mutants on SC GLS accumulation and on growth did not display a simple correlation, supporting the coordination model. We propose that large transcription factor networks create a system to integrate internal and external signals and separately modulate growth and the accumulation of the defensive aliphatic GLS.
MitoToxy Assay: a novel cell-based method for the assessment of metabolic toxicity in a multiwell plate format using a lactate FRET nanosensor, Laconic
Authors: Contreras-Baeza Y , Ceballo S , Arce-Molina R , Sandoval PY , Alegría K , Barros L.F. , San Martín A. 
Published: March 2019

AbstractMitochondrial toxicity is a primary source of pre-clinical drug attrition. Methods that detect mitochondrial toxicity as early as possible during the drug development process are required. Here we introduce a new method for detecting mitochondrial toxicity based on MDA-MB-231 cells stably expressing the genetically-encoded FRET lactate indicator, Laconic. The method takes advantage of the high cytosolic lactate accumulation observed during mitochondrial stress, regardless of the specific toxicity mechanism, explained by compensatory glycolytic activation. IC50 determination using a standard multi-well plate reader, shown that the methodology allowed to detect metabolic toxicity induced by azide, antimycin, oligomycin, rotenone and myxothiazol with high sensitivity. Suitability for high-throughput screening applications was evaluated resulting in a Z’-factor > 0.5 and CV% < 20. A pilot screening allowed sensitive detection of commercial drugs that were previously withdrawn from the market due to liver/cardiac toxicity issues, such as camptothecin, ciglitazone, troglitazone, rosiglitazone, and terfenadine, in ten minutes. We envisage that the availability of this technology, based on a fluorescent genetically-encoded indicator will allow direct assessment of mitochondrial metabolism, and will make the early detection of mitochondrial toxicity in the drug development process possible, saving time and resources.
Using cell yields and qPCR to estimate biotic contribution to 1,1,1-trichloroethane dechlorination at a field site treated with granular zero valent iron and guar gum
Authors: Yang M. Ivy , Previdsa Michael , Edwards Elizabeth A. , Sleep Brent E. 
Published: March 2019

AbstractChlorinated ethanes are environmental pollutants found frequently at many contaminated industrial sites. 1,1,1-Trichloroethane (1,1,1-TCA) can be dechlorinated and detoxified via abiotic transformation or biologically by the action of dechlorinating microorganisms such asDehalobacter(Dhb). At a field site, it is challenging to distinguish abiotic vs biotic mechanisms as both processes share common transformation products. In this study, we evaluated using theDhb16S rRNA gene and specific reductive dehalogenase genes as biomarkers for 1,1,1-TCA and 1,1-dichloroethane (1,1-DCA) dechlorination. We analyzed samples from laboratory groundwater microcosms and from an industrial site where a mixture of granular zero valent iron (ZVI) and guar gum was injected for 1,1,1-TCA remediation. Abiotic and biotic transformation products were monitored and the changes in dechlorinating organisms were tracked using quantitative PCR (qPCR) with primers targeting theDhb16S rRNA gene and two functional genescfrAanddcrAencoding enzymes that dechlorinate 1,1,1-TCA to 1,1-DCA and 1,1-DCA to chloroethane (CA), respectively. The abundance of thecfrA- anddcrA-like genes confirmed that the two dechlorination steps were carried out by two distinctDhbpopulations at the site. Using cell yields established in laboratory microcosms along with measured abundances of theDhb16S rRNA gene in site samples, biotic and abiotic transformation of 1,1,1-TCA at the site was estimated. The biomarkers used in this study proved useful for tracking biodechlorination of 1,1,1-TCA and 1,1-DCA where both abiotic (e.g. with ZVI) and biotic processes co-occur.
A transcription factor Abf1 facilitates ORC binding onto theSaccharomyces cerevisiaereplication origin via histone acetylase Gcn5
Authors: Kohzaki Hidetsugu , Murakami Yota 
Published: March 2019

AbstractChromatin structure has been implicated in the regulation of DNA replication but the molecular mechanism involved is unclear. In this study, we observed that binding of the transcription factor Abf1 to the replication originARS1facilitated the association of the origin recognition complex (ORC) withARS1using genetic interaction analysis and ChIP assay. The histone acetyltransferases (HATs), Gcn5 and Esa1, were also loaded ontoARS1in an Abf1 site-dependent manner, where they were then responsible for acetylating histone H3 lysine 18 (H3K18) and histone H4 lysine 12 (H4K12), respectively. Interestingly, Abf1 interacted with Gcn5, while ORC interacted with Esa1. Indeed the B3 element showed genetic interaction with Gcn5 and Rpd3 not with Esa1, Act3 and Tra1.These data suggest that Gcn5, which is recruited by Abf1, alters chromatin structure via histone acetylation and facilitates the loading of ORC. We therefore propose that transcription factors regulate chromatin structure at replication origins by recruiting chromatin-modifying proteins, such as HATs, to load the initiator.