bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inferring metabolite interactomes via molecular structure informed Bayesian graphical model selection with an application to coronary artery disease
Authors: Trainor Patrick J. , Mitchell Joshua M. , Carlisle Samantha M. , Moseley Hunter N.B. , DeFilippis Andrew P. , Rai Shesh N. 
Published: August 2018

AbstractIntroductionWhile the generation of reference genomes facilitates the elucidation of gene-phenome associations, reference models of the metabolome that are specific to organism, sample type (e.g. plasma, serum, urine, cell-culture), and state (including disease), remain uncommon. In studying heart disease in humans, a reference model describing the relationships between metabolites in plasma has not been determined but would have great utility as a reference for comparing acute disease states such as myocardial infarction.Materials and MethodsWe present a methodology for deriving probabilistic models that describe the partial correlation structure of metabolite distributions (“interactomes”) from metabolomics data. As determining partial correlation structures requires estimating p*(p-1)/2 parameters for p metabolites, the dimension of the search space for parameter values is immense. Consequently, we have developed a Bayesian methodology for the penalized estimation of model parameters in which the magnitude of penalization is drawn from probability distributions with hyperparameters linked to molecular structure similarity. In our work, structural similarity was determined as the Tanimoto coefficient of algorithmically-generated “atom colors” that capture the local structure around each atom within each structure. A Gibbs sampler (a Markov chain Monte Carlo technique) was implemented for simulating the posterior distribution of model parameters. We have made software for implementing this methodology publicly available via the R package BayesianGLasso.Results / ConclusionsFirst, we demonstrate robust performance of our methodology (sensitivity, specificity, and measures of accuracy) for recovering the true underlying partial correlation structure over simulated datasets (with simulated metabolite abundances and simulated known structural similarity). We then present an interactome model for stable heart disease inferred from non-targeted mass spectrometry data via this methodology. Inspection of the local graph topology about cholate reveals probabilistic interactions with other primary bile acids, secondary bile acids, and many steroid hormones sharing the same precursors.
Infection of theBiomphalaria glabrata vector snailbySchistosoma mansoniparasites drives snail microbiota dysbiosis
Authors: Portet Anaïs , Toulza Eve , Lokmer Ana , Huot Camille , Duval David , Galinier Richard , Gourbal Benjamin 
Published: August 2018

SummaryHost-associated microbiota cari affect the fitness of its host i η a number of ways, including the modification of host-parasite interactions and thus the outcome of disease.Biomphalaria glabratais the vector snail of the trematodeSchistosoma mansoni,the agent of human schistosomiasis, causing hundreds of thousands of deaths every year. Here, we present the first study of the snail bacterial microbiota in response toSchistosomainfection. To examine the interplay betweenB. glabrata, S. mansoniand snail microbiota, snails were infected and the microbiota composition was analysed by massive 16S rDNA amplicon sequencing approach. We characterized theBiomphalariabacterial microbiota at the individual level in both naive and infected snails. Sympatric and allopatric strains of parasites were used for infections and re­infections to analyse the modification or dysbiosis of snail microbiota in different host-parasite co-evolutionary contexts. Concomitantly, using RNAseq data, we investigated the link between bacterial microbiota dysbiosis and snail anti-microbial peptide immune response. This work paves the way for a better understanding of snail/schistosome interaction, and would have critical consequences in terms of snail control strategies for fighting schistosomiasis disease in the field.
“ER-Ca2+ sensor STIM regulates neuropeptides required for development under nutrient restriction in Drosophila”
Authors: Megha  , Wegener Christian , Hasan Gaiti 
Published: August 2018

AbstractNeuroendocrine cells communicate via neuropeptides to regulate behaviour and physiology. This study examines how STIM (Stromal Interacting Molecule), an ER-Ca2+ sensor required for Store-operated Ca2+ entry, regulates neuropeptides required for Drosophila development under nutrient restriction (NR). We find two STIM-regulated peptides, Corazonin and short Neuropeptide F, to be required for NR larvae to complete development. Further, a set of secretory DLP (Dorso lateral peptidergic) neurons which co-express both peptides was identified. Partial loss of dSTIM caused peptide accumulation in the DLPs, and reduced systemic Corazonin signalling. Upon NR, larval development correlated with increased peptide levels in the DLPs, which failed to occur when dSTIM was reduced. Comparison of systemic and cellular phenotypes associated with reduced dSTIM, with other cellular perturbations, along with genetic rescue experiments, suggested that dSTIM primarily compromises neuroendocrine function by interfering with neuropeptide release. Under chronic stimulation, dSTIM also appears to regulate neuropeptide synthesis.
Genome Wide Meta-Analysis identifies new loci associated with cardiac phenotypes and uncovers a common genetic signature shared by heart function and Alzheimer’s disease
Authors: Sáez MªEugenia , González-Pérez Antonio , Hernández-Olasagarre Begoña , Beà Aida , Moreno-Grau Sonia , Rojas Itziar de , Monté Gemma , Orellana Adela , Valero Sergi , Comella Joan X. , Sanchis Daniel , Ruiz Agustín ,   For the Alzheimer’s Disease Neuroimaging Initiative
Published: August 2018

ABSTRACTAimsEchocardiography has become an indispensable tool for the study of heart performance, improving the monitoring of individuals with cardiac diseases. Diverse genetic factors associated with echocardiographic measures of heart structure and functions have been previously reported. The impact of several apoptotic genes in heart development identified in experimental models prompted us to assess their potential association with indicators of human cardiac function. This study started with the aim to investigate the possible association of variants of apoptotic genes with echocardiographic traits and to identify new genetic markers associated with cardiac function.Methods and resultsGenome wide data from different studies were obtained from public repositories. After quality control and imputation, association analyses confirm the role of caspases and other apoptosis related genes with cardiac phenotypes. Moreover, enrichment analysis showed an over-representation of genes, including some apoptotic regulators, associated with Alzheimer’s disease (AD). We further explored this unexpected observation which was confirmed by genetic correlation analyses.ConclusionsOur findings show the association of apoptotic gene variants with echocardiographic indicators of heart function and reveal a novel potential genetic link between echocardiographic measures in healthy populations and cognitive decline later on in life. These findings may have important implications for preventative strategies combating Alzheimer’s disease.
TP promotes malignant progression in hepatocellular carcinoma through pentose Warburg effect
Authors: Zhang Qiang , Qin Yuan , Zhao Jianmin , Tang Yuanhao , Hu Xuejiao , Zhong Weilong , Li Mimi , Zong Shumin , Li Meng , Tao Honglian , Zhang Zhen , Chen Shuang , Liu Huijuan , Yang Lan , Zhou Honggang , Liu Yanrong , Sun Tao , Yang Cheng 
Published: August 2018

AbstractTumor progression is dependent on metabolic reprogramming. Metastasis and vasculogenic mimicry (VM) are typical tumor progression. The relationship of metastasis, VM and metabolic reprogramming is not clear. In this study, we identified the novel role of Twist1, a VM regulator, in the transcriptional regulation of the expression of thymidine phosphorylase (TP). We demonstrated that TP promoted extracellular thymidine metabolization into ATP and amino acids through pentose Warburg effect by coupling the pentose phosphate pathway and glycolysis. Moreover, Twist1 relied on TP-induced metabolic reprogramming to promote hepatocellular carcinoma (HCC) metastasis and VM formation mediated by VE-Cad, VEGFR1, and VEGFR2 in vitro and in vivo. TP inhibitor tipiracil reduced promotion effect of TP enzyme activity on HCC VM formation and metastasis. Our findings demonstrate that TP, transcriptionally activated by Twist1, promotes HCC VM formation and metastasis through pentose Warburg effect, contributing to tumor progression.
Calcium negatively regulates secretion from dense granules inToxoplasma gondii
Authors: Katris Nicholas J , McFadden Geoffrey I , Dooren Giel G. van , Waller Ross F 
Published: August 2018

AbstractApicomplexan parasites includingToxoplasma gondiiandPlasmodiumspp. manufacture a complex arsenal of secreted proteins used to interact with and manipulate their host environment. These proteins are organised into three principle exocytotic compartment types according to their functions: micronemes for extracellular attachment and motility, rhoptries for host cell penetration, and dense granules for subsequent manipulation of the host intracellular environment. The order and timing of these events during the parasite’s invasion cycle dictates when exocytosis from each compartment occurs. Tight control of compartment secretion is, therefore, an integral part of apicomplexan biology. Control of microneme exocytosis is best understood, where cytosolic intermediate molecular messengers cGMP and Ca2+act as positive signals. The mechanisms for controlling secretion from rhoptries and dense granules, however, are virtually unknown. Here, we present evidence that dense granule exocytosis is negatively regulated by cytosolic Ca2+, and we show that this Ca2+-mediated response is contingent on the function of calcium-dependent protein kinasesTgCDPK1 andTgCDPK3. Reciprocal control of micronemes and dense granules provides an elegant solution to the mutually exclusive functions of these exocytotic compartments in parasite invasion cycles and further demonstrates the central role that Ca2+signalling plays in the invasion biology of apicomplexan parasites.
Structure of the Macrobrachium rosenbergii Nodavirus: A new genus within the Nodaviridae?
Authors: Ho Kok Lian , Gabrielsen Mads , Beh Poay Ling , Kueh Chare Li , Thong Qiu Xian , Streetley James , Tan Wen Siang , Bhella David 
Published: August 2018

AbstractMacrobrachium rosenbergii nodavirus (MrNV) is a pathogen of freshwater prawns that poses a threat to food-security and causes significant economic losses in the aquaculture industries of many developing nations. A detailed understanding of the MrNV virion structure will inform the development of strategies to control outbreaks. The MrNV capsid has also been engineered to display heterologous antigens, thus knowledge of its atomic resolution structure will benefit efforts to develop tools based on this platform. Here we present an atomic-resolution model of the MrNV capsid protein, calculated by cryogenic electron microscopy (cryoEM) of MrNV virus-like particles (VLPs) produced in insect cells, and three-dimensional image reconstruction at 3.3 Å resolution. CryoEM of MrNV virions purified from infected freshwater prawn post-larvae yielded a 6.6 Å resolution structure confirming the biological relevance of the VLP structure.Our data revealed that unlike other known nodaviruses structures, which have been shown to assemble capsids having trimeric spikes, MrNV assembles a T=3 capsid with dimeric spikes. We also found a number of surprising similarities between the MrNV capsid structure and that of the Tombusviridae. 1. An extensive network of N-terminal arms lines the capsid interior forming long-range interactions to lace together asymmetric units. 2. The capsid shell is stabilised by three pairs of Ca2+ ions in each asymmetric unit. 3. The protruding spike domain exhibits a very similar fold to that seen in the spikes of the tombusviruses. These structural similarities raise questions concerning the correct taxonomic classification of MrNV.
Molecular analysis ofDrosophila melanogasterB chromosomes reveals their origin, composition, and structure
Authors: Hanlon Stacey L. , Miller Danny E. , Eche Salam , Hawley R. Scott 
Published: August 2018

ABSTRACTThe number of chromosomes carried by an individual species is one of its defining characteristics. Some species, however, can also carry supernumerary chromosomes referred to as B chromosomes. B chromosomes were recently identified in a laboratory stock ofDrosophila melanogaster—an established model organism with a wealth of genetic and genomic resources—enabling us to subject them to extensive molecular analysis. We isolated the B chromosomes by pulsed-field gel electrophoresis and determined their composition through next-generation sequencing. Although these B chromosomes carry no known euchromatic sequence, they are rich in transposable elements and long arrays of short nucleotide repeats, the most abundant being the uncharacterizedAAGATsatellite repeat. Fluorescentin-situhybridization on metaphase chromosome spreads revealed this repeat is located on Chromosome4, strongly suggesting the origin of the B chromosomes is Chromosome4. Cytological and quantitative comparisons of signal intensity between Chromosome4and the B chromosomes supports the hypothesis that the structure of the B chromosome is an isochromosome. We also report the identification of a new B chromosome variant in a related laboratory stock. This B chromosome has a similar repeat signature as the original but is smaller and much less prevalent. We examined additional stocks with similar genotypes and did not find B chromosomes, but did find these stocks lacked theAAGATsatellite repeat. Our molecular characterization ofD. melanogasterB chromosomes is the first step towards understanding how supernumerary chromosomes arise from essential chromosomes and what may be necessary for their stable inheritance.
Genome-wide association study of multiple yield components in a diversity panel of polyploid sugarcane (Saccharum spp.)
Authors: Yang Xiping , Luo Ziliang , Todd James , Sood Sushma , Wang Jianping 
Published: August 2018

AbstractSugarcane (Saccharum spp.) is an important economic crop, contributes up to 80% of sugar and approximately 60% bio-fuel globally. To meet the increased demand for sugar and bio-fuel supplies, it is critical to breed sugarcane cultivars with robust performance in yield components. Therefore, dissection of causal DNA sequence variants is of great importance by providing genetic resources and fundamental information for crop improvement. In this study, we evaluated and analyzed nine yield components in a sugarcane diversity panel consisting of 308 accessions primarily selected from the “world collection of sugarcane and related grasses”. By genotyping the diversity panel using target enrichment sequencing, we identified a large number of sequence variants. Genome-wide association study between the markers and traits were conducted with dosages and gene actions taken into consideration. In total, 217 non-redundant markers and 225 candidate genes were identified to be significantly associated with the yield components, which can serve as a comprehensive genetic resource database for future gene identification, characterization, and selection for sugarcane improvement. We further investigated runs of homozygosity (ROH) in the sugarcane diversity panel. We characterized 282 ROHs, and found that the occurrence of ROH in the genome were non-random and probably under selection. ROHs were associated with total weight and dry weight, and high ROHs resulted in decrease of the two traits. This study approved that genomic inbreeding has led to negative impacts on sugarcane yield.
Inducible formation of leading cells driven by CD44 switching gives rise to collective invasion
Authors: Yang Cuixia , Cao Manlin , Liu Yiwen , He Yiqing , Du Yan , Zhang Guoliang , Gao Feng 
Published: August 2018

AbstractCollective invasion into adjacent tissue is a hallmark of luminal breast cancer, with about 20% of cases that eventually undergo metastasis. It remained unclear how less aggressive luminal-like breast cancer transit to invasive cancer. Our study revealed that CD44hicancer cells are the leading subpopulation in collective invading cancer cells, which could efficiently lead the collective invasion of CD44lo/follower cells. CD44hi/leading subpopulation showed specific gene signature of a cohort of hybrid epithelial/mesenchymal state genes and key functional co-regulators of collective invasion, which was distinct from CD44lo/follower cells. However, the CD44hi/leading cells, in partial-EMT state, were readily switching to CD44lophenotype along with collective movements and vice versa, which is spontaneous and sensitive to tumor microenvironment. The CD44lo-to-CD44hiconversion is accompanied with a shift of CD44s-to-CD44v, but not corresponding to the conversion of non-CSC-to-CSC. Therefore, the CD44hileader cells are not a stable subpopulation in breast tumors. This plasticity and ability to generate CD44hicarcinoma cells with enhanced invasion-initiating powers might be responsible for the transition from in situ to invasive behavior of luminal-type breast cancer.SignificanceNow, the mechanisms involved in local invasion and distant metastasis are still unclear. We identified a switch of CD44 that drives leader cell formation during collective invasion in luminal breast cancer. We provided evidence that interconversions between low and high CD44 states occur frequently during collective invasion. Furthermore, these findings demonstrated that the CD44hi/leader cells featuring partial EMT are inducible and attainable in response to tumor microenvironment. The CD44locancer cells are plastic that readily shift to CD44histate, accompanied with shifts of CD44s-to-CD44v, thereby increasing tumorigenic and malignant potential. There are many “non-invasiveness” epithelial/follower cells with reversible invasive potential within an individual tumor, that casting some challenges on molecular targeting therapy.
Human pluripotent stem cell-derived brain pericyte-like cells induce blood-brain barrier properties
Authors: Stebbins Matthew J. , Gastfriend Benjamin D. , Canfield Scott G. , Lee Ming-Song , Richards Drew , Faubion Madeline G. , Li Wan-Ju , Daneman Richard , Palecek Sean P. , Shusta Eric V. 
Published: August 2018

ABSTRACTBrain pericytes play an important role in the formation and maintenance of the neurovascular unit (NVU), and their dysfunction has been implicated in central nervous system (CNS) disorders. While human pluripotent stem cells (hPSCs) have been used to model other components of the NVU including brain microvascular endothelial cells (BMECs), astrocytes, and neurons, cells having brain pericyte-like phenotypes have not been described. In this study, we generated neural crest stem cells (NCSCs), the embryonic precursor to forebrain pericytes, from human pluripotent stem cells (hPSCs) and subsequently differentiated NCSCs to brain pericyte-like cells. The brain pericyte-like cells expressed marker profiles that closely resembled primary human brain pericytes, and they self-assembled with endothelial cells to support vascular tube formation. Importantly, the brain pericyte-like cells induced blood-brain barrier (BBB) properties in BMECs, including barrier enhancement and reduction of transcytosis. Finally, brain pericyte-like cells were incorporated with iPSC-derived BMECs, astrocytes, and neurons to form an isogenic human NVU model that should prove useful for the study of the BBB in CNS health, disease, and therapy.
Traditional and regional food as seen by consumers – research results: the case of Poland
Authors: Barska Anetta , Wojciechowska-Solis Julia 
Published: August 2018

Purpose
This paper seeks to describe the perceptions and motives for acquiring traditional and regional products by Polish consumers. The purpose of this paper is to evaluate the state of regional and traditional food production in Poland and identify the prospects of its development.

Design/methodology/approach
Both secondary and primary data were used. The sample size included 1,067 respondents selected based on their place of residence and sex. The five-point Likert scale was used to measure the participant attitudes following the construction and validation procedure. Cronbach’s α test was used to evaluate the reliability of the measuring scale, estimated at 0.85, indicating the accuracy of the scales used. Statistica 13 – including t-test, ANOVA and regression analysis – was a software program used to carry out statistical analysis. Prior to the analysis, multivariate normality was examined by testing each variable for normal distribution.

Findings
The research showed the existence of a statistical relationship between the sex of respondents and the suggested traditional food consumption patterns such as organoleptic qualities, high quality, and finally, curiosity and trying new foods. Sex did not statistically influence the responses for the remaining factors.

Originality/value
The increased interest in traditional and regional food products is a manifestation of new food-related tendencies and is implied by the desire to exhibit behaviors and values resulting from cultural heritage. Polish consumers are becoming wealthier, better educated, more aware of both tangible and intangible product attributes, and they are having more opportunities to expose their social preferences when shopping. The importance of food attributes such as traditional and regional food certificates, source of origin or the image of the producer (e.g. respecting ethical behavior) is growing. This research is significant not only because of its theoretical input, but its applied value as well.
Characterization of extended-spectrum and CMY-2 ß-lactamases, and associated virulence genes in Escherichia coli from food of animal origin in México
Authors: Barrios-Villa Edwin , Cortés-Cortés Gerardo , Lozano Zarain Patricia , Romero-Romero Sergio , Lara Flores Norarizbeth , Estepa Vanesa , Somalo Sergio , Torres Carmen , Rocha-Gracia Rosa del Carmen 
Published: August 2018

Purpose
Broad-spectrum cephalosporin resistance is rapidly increasing in Escherichia coli, representing a food safety problem. The purpose of this paper is to characterize eight extended-spectrum-ß-lactamase (ESBL) and acquired AmpC ß-lactamase-producing E. coli isolates and virotypes associated, obtained from chicken and pork food samples in Puebla, Mexico.

Design/methodology/approach
Samples (36 from chicken and 10 from pork) were cultured on Levine agar plates supplemented with cefotaxime (2 mg/L) for isolation of cefotaxime-resistant (CTXR) E. coli. CTXR-E. coli isolates were detected in 33 of 46 samples (72 percent), and one isolate/sample was characterized (28 from chicken and 5 from pork), for ESBL production, phylogenetic group, sequence typing, resistance and virulence genes by PCR and sequencing.

Findings
Results showed 16 ESBL-E. coli (35 percent) (12/16 belonging to phylogroup B1) and 8 CMY-2-E. coli (17 percent). ESBL detected were as follows (number of isolates): CTX-M-2 (8); CTX-M-1 (2); CTX-M-15 (1); SHV-2a (4) and TEM-52c (1). In total, 20 different sequence types (STs) were identified among the ESBL- or CMY-2-producing E. coli strains, which included four new ones. The CTX-M-15 β-lactamase was detected in one E. coli ST617-ST10 Cplx-B1 strain that also carried ibeA gene. One CMY-2-positive strain of lineage ST224-B2 was detected and it carried the qnrA1 gene.

Originality/value
In this study, a ST131-based virotyping scheme for strains from food of animal origin was established since this kind of strains constitutes an important vehicle of virulent ESBL- and CMY-2-producing E. coli isolates, which could be transmitted to humans by direct contact or through the food chain.