bluuebunny/crossref_metadata_2025_split huggingface dataset:
Psychosocial stress and central adiposity: A Brazilian study with users of the public health system
Authors: Freitas Flávia Vitorino , Barbosa Wagner Miranda , Silva Laíz Aparecida Azevedo , Garozi Marianna Junger de Oliveira , Pinheiro Júlia de Assis , Ribeiro Borçoi Aline , Conti Catarine Lima , Arpini Juliana Krüger , de Paula Heberth , de Oliveira Mayara Mota , Archanjo Anderson Barros , de Freitas Érika Aparecida Silva , de Oliveira Daniela Rodrigues , Borloti Elizeu Batista , Louro Iuri Drumond , Alvares-da-Silva Adriana Madeira 
Published: May 2018

AbstractObjectiveTo assess the association between indicators of psychosocial stress and central adiposity in adult users of the Unified Health System (SUS) from Southeast of Brazil.MethodsThis cross-sectional study was conducted with 384 adults (20 to 59 years old) from the city of Alegre, Southeastern Brazil. The simple random sample represented the population using the public health system of the municipality. The prevalence of obesity was based on the Body Mass Index, and central adiposity (dependent variable) was measured by waist circumference in centimeters. The independent variables were the following indicators of psychosocial stress: food and nutrition insecurity (yes/no), serum cortisol (μg/dL), symptoms suggestive of depression using the Beck Depression Inventory-II ≥ 17 (yes/no), and altered blood pressure ≥ 130/85 mmHg (yes/no). Univariate linear regression was performed between central adiposity and each stress indicator, and later the models were adjusted for socioeconomic, health, and lifestyle variables. All analyses were stratified by rural and urban location.ResultsThe prevalence of weight excess was 68.3%, and 71.5% of individuals presented an increased risk for metabolic complications related to central adiposity. Mean waist circumference scores for the rural and urban population were 89.3 ± 12.7 cm and 92.9 ± 14.7 cm, respectively (p = 0.012). Indicators of stress that were associated with central adiposity were: cortisol in the rural population and altered blood pressure in the urban population. This occurred both in the raw analysis and in the models adjusted for confounding factors.ConclusionThe associations between stress and adiposity were different between rural (cortisol - inverse association) and urban (altered blood pressure) lifestyles, confirming the influence of local and psychosocial subsistence on the modulation of stress and on how individuals react or restrain stressors. Stress reduction strategies can be useful in public health programs designed to prevent or treat obesity.
Binding specificities of human RNA binding proteins towards structured and linear RNA sequences
Authors: Jolma Arttu , Zhang Jilin , Mondragón Estefania , Morgunova Ekaterina , Kivioja Teemu , Laverty Kaitlin U. , Yin Yimeng , Zhu Fangjie , Bourenkov Gleb , Morris Quaid , Hughes Timothy R. , Maher Louis James , Taipale Jussi 
Published: May 2018

ABSTRACTSequence specific RNA-binding proteins (RBPs) control many important processes affecting gene expression. They regulate RNA metabolism at multiple levels, by affecting splicing of nascent transcripts, RNA folding, base modification, transport, localization, translation and stability. Despite their central role in most aspects of RNA metabolism and function, most RBP binding specificities remain unknown or incompletely defined. To address this, we have assembled a genome-scale collection of RBPs and their RNA binding domains (RBDs), and assessed their specificities using high throughput RNA-SELEX (HTR-SELEX). Approximately 70% of RBPs for which we obtained a motif bound to short linear sequences, whereas ~30% preferred structured motifs folding into stem-loops. We also found that many RBPs can bind to multiple distinctly different motifs. Analysis of the matches of the motifs in human genomic sequences suggested novel roles for many RBPs. We found that three cytoplasmic proteins, ZC3H12A, ZC3H12B and ZC3H12C bound to motifs resembling the splice donor sequence, suggesting that these proteins are involved in degradation of cytoplasmic viral and/or unspliced transcripts. Surprisingly, structural analysis revealed that the RNA motif was not bound by the conventional C3H1 RNA-binding domain of ZC3H12B. Instead, the RNA motif was bound by the ZC3H12B’s PilT N-terminus (PIN) RNase domain, revealing a potential mechanism by which unconventional RNA binding domains containing active sites or molecule-binding pockets could interact with short, structured RNA molecules. Our collection containing 145 high resolution binding specificity models for 86 RBPs is the largest systematic resource for the analysis of human RBPs, and will greatly facilitate future analysis of the various biological roles of this important class of proteins.
Changing Times: Fluorescence-lifetime Analysis of Amyloidogenic SF-IAPP Fusion Protein
Authors: Antimonova Olga I , Lebedev Dmitry V , Zabrodskaya Yana A , Grudinina Natalia A , Shavlovsky Michael M , Egorov Vladimir V 
Published: May 2018

AbstractThe fluorescence lifetime of the superfolder green fluorescent protein (SF) and the SF protein fused with islet amyloid polypeptide (SF-IAPP) were studied in polyacrylamide gel. It was shown that the SF average fluorescence lifetime under these conditions slightly differs from that of the SF-IAPP monomer. SF-IAPP does not lose the ability to form amyloid-like fibrils; meanwhile, the average fluorescence lifetime of the fusion protein in fibrils is reduced. We propose the application of Fluorescent-lifetime Imaging Microscopy (FLIM) to the measurement of average fluorescence lifetimes of fusion proteins (amyloidogenic protein–SF) in the context of studies using cellular models of conformational diseases.
Combined use of procalcitonin and C-reactive protein levels can help clinically diagnose bacterial co-infections in children infected with H1N1 influenza
Authors: Li Zhihao , He Liya , Li Shuhua , He Waner , Zha Caihui , Hou Qiaozhen , Wang Weiying , Sun Xin , Liang Huiying , Ou Wanxing 
Published: May 2018

AbstractObjectiveThis study evaluated the diagnostic value of measuring the levels of procalcitonin (PCT) and C-reactive protein (CRP) to differentiate children co-infected with H1N1 influenza and bacteria from children infected with H1N1 influenza alone and to provide a reliable clinical diagnostic support system with improved accuracy and precision control.MethodsConsecutive patients (children aged <5 years) with laboratory-confirmed H1N1 influenza who were hospitalized or received outpatient care from a tertiary-care hospital in Canton, China between 1 January 2012 and 1 September 2017 were included in the present study. Laboratory results, including serum PCT and CRP levels, white blood cell (WBC) counts, and blood and sputum cultures, were analyzed. The predictive value of the combination of biomarkers versus either biomarker alone for diagnosing bacterial co-infections was evaluated using logistic regression analyses.ResultsOf 3180 children infected with H1N1 influenza, 226 (7.1%) met the bacterial co-infection criteria, with Staphylococcus pneumoniae being the most commonly identified bacteria (36.28%). Significantly higher PCT (1.46 vs 0.21 ng/ml, p<0.001) and CRP (19.20 vs 5.10 mg/dl, p<0.001) levels were detected in the bacterial co-infection group than in the H1N1 infection only group. Multivariate logistic regression analysis showed independent associations between PCT (odds ratio [OR]: 1.73, 95% confidence interval [CI],1.34-2.42, p<0.001) and CRP levels (OR:1.09, 95% CI, 1.06-1.13, p<0.001) with bacterial co-infections. Using PCT or CRP levels alone, the areas under the curves (AUCs) for predicting bacterial co-infections were 0.801 (95%CI, 0.772-0.855) and 0.762 (95%CI, 0.722-0.803), respectively. Using a combination of PCT and CRP, the logistic regression-based model, Logit(P)=-1.912+0.546 PCT+0.087 CRP, showed significantly greater accuracy (AUC: 0.893, 95%CI: 0.842-0.934) than did the other three biomarkers.ConclusionsThe combination of PCT and CRP levels could provide a useful method of distinguishing bacterial co-infections from an H1N1 influenza infection alone in children during the early disease phase. After further validation, the flexible model derived here could assist clinicians in decision-making processes.
Stabilized Independent Component Analysis outperforms other methods in finding reproducible signals in tumoral transcriptomes
Authors: Cantini Laura , Kairov Ulykbek , de Reyniès Aurélien , Barillot Emmanuel , Radvanyi François , Zinovyev Andrei 
Published: May 2018

AbstractMotivationMatrix factorization methods are widely exploited in order to reduce dimensionality of transcriptomic datasets to the action of few hidden factors (metagenes). Applying such methods to similar independent datasets should yield reproducible inter-series outputs, though it was never demonstrated yet.ResultsWe systematically test state-of-art methods of matrix factorization on several transcriptomic datasets of the same cancer type. Inspired by concepts of evolutionary bioinformatics, we design a new framework based on Reciprocally Best Hit (RBH) graphs in order to benchmark the method’s reproducibility. We show that a particular protocol of application of Independent Component Analysis (ICA), accompanied by a stabilisation procedure, leads to a significant increase in the inter-series output reproducibility. Moreover, we show that the signals detected through this method are systematically more interpretable than those of other state-of-art methods. We developed a user-friendly tool BIODICA for performing the Stabilized ICA-based RBH meta-analysis. We apply this methodology to the study of colorectal cancer (CRC) for which 14 independent publicly available transcriptomic datasets can be collected. The resulting RBH graph maps the landscape of interconnected factors that can be associated to biological processes or to technological artefacts. These factors can be used as clinical biomarkers or robust and tumor-type specific transcriptomic signatures of tumoral cells or tumoral microenvironment. Their intensities in different samples shed light on the mechanistic basis of CRC molecular subtyping.AvailabilityThe BIODICA tool is available from https://github.com/LabBandSB/BIODICA.Contactlaura.cantini@curie.fr and andrei.zinovyev@curie.frSupplementary informationSupplementary data are available at Bioinformatics online.
Variants ofDNMT3Acause transcript-specific DNA methylation patterns and affect hematopoietic differentiation
Authors: Božić Tanja , Frobel Joana , Raic Annamarija , Ticconi Fabio , Kuo Chao-Chung , Heilmann-Heimbach Stefanie , Goecke Tamme W. , Zenke Martin , Jost Edgar , Costa Ivan G. , Wagner Wolfgang 
Published: May 2018

AbstractThede novoDNA methyltransferase 3A (DNMT3A) plays pivotal roles in hematopoietic differentiation. In this study, we followed the hypothesis that alternative splicing ofDNMT3Ahas characteristic epigenetic and functional sequels. SpecificDNMT3Atranscripts were either downregulated or overexpressed in human hematopoietic stem and progenitor cells and this resulted in complementary and transcript-specific DNA methylation and gene expression changes. Functional analysis indicated that particularly transcript 2 (coding for DNMT3A2) activates proliferation and induces loss of a primitive immunophenotype, whereas transcript 4 interferes with colony formation of the erythroid lineage. Notably, in acute myeloid leukemia (AML) expression of transcript 2 correlates with itsin vitroDNA methylation and gene expression signatures and is associated with overall survival, indicating thatDNMT3Avariants impact also on malignancies. Our results demonstrate that specificDNMT3Avariants have distinct epigenetic and functional impact. Particularly DNMT3A2 triggers hematopoietic differentiation and the corresponding signatures are reflected in AML.
S phase R-loop formation is restricted by PrimPol-mediated repriming
Authors: Šviković Saša , Crisp Alastair , Tan-Wong Sue Mei , Guilliam Thomas A. , Doherty Aidan J. , Proudfoot Nicholas J. , Guilbaud Guillaume , Sale Julian E. 
Published: May 2018

SummaryDuring DNA replication, conflicts with ongoing transcription are frequent and require careful management to avoid genetic instability. R-loops, three stranded nucleic acid structures comprising a DNA:RNA hybrid and displaced single stranded DNA, are important drivers of damage arising from such conflicts. How R-loops stall replication and the mechanisms that restrain their formation during S phase are incompletely understood. Here we showin vivohow R-loop formation drives a short purine-rich repeat, (GAA)10, to become a replication impediment that requires the repriming activity of the primase-polymerase PrimPol for its processive replication. Further, we show that loss of PrimPol results in a significant increase in R-loop formation around the repeat during S phase. We extend this observation by showing that PrimPol suppresses R-loop formation in genes harbouring secondary structure-forming sequences, exemplified by G quadruplex and H-DNA motifs, across the genome in both avian and human cells. Thus, R-loops promote the creation of replication blocks at susceptible sequences, while PrimPol-dependent repriming limits the extent of unscheduled R-loop formation at these sequences, mitigating their impact on replication.
Type IV collagen is essential for proper function of integrin-mediated adhesion in Drosophila muscle fibers
Authors: Kiss András A. , Popovics Nikoletta , Márton Kiss , Boldogkői Zsolt , Csiszár Katalin , Mink Mátyás 
Published: May 2018

ABSTRACTCongenital muscular dystrophy (CMD), a subgroup of myopathies and a genetically and clinically heterogeneous group of inherited muscle disorders is characterized by progressive muscle weakness, fiber size variability, fibrosis, clustered necrotic fibers, and central myonuclei present in regenerating muscle. Type IV collagen (COL4A1) mutations have recently been identified in patients with intracerebral, vascular, renal, ophthalmologic pathologies and congenital muscular dystrophy, consistent with diagnoses of Walker–Warburg Syndrome or Muscle–Eye–Brain disease. Morphological characteristics of muscular dystrophy have also been demonstrated Col4a1 mutant mice. Yet, several aspects of the pathomechanism of COL4A1-associated muscle defects remained largely uncharacterized. Based on the results of genetic, histological, molecular, and biochemical analyses in an allelic series of Drosophila col4a1 mutants, we provide evidence that col4a1 mutations associate with severely compromised muscle fibers within the single-layer striated muscle of the common oviduct, characterized by loss of sarcomere structure, disintegration and streaming of Z-discs, and aberrant integrin expression within the M-discs, indicating an essential role for the COL4A1 protein. Features of altered cytoskeletal phenotype include actin bundles traversing over sarcomere units, amorphous actin aggregates, atrophy and aberrant fiber size. The mutant COL4A1-associated defects appear to recapitulate integrin-mediated adhesion phenotypes observed in Drosophila by RNA-inhibition. Our results provide insight into the mechanistic details of COL4A1-associated muscle disorders and suggest a role for integrin-collagen interaction in the maintenance of sarcomeres.
An EST-SSR based genetic linkage map and identification of QTLs for anthracnose disease resistance in water yam (Dioscorea alata L.)
Authors: Bhattacharjee Ranjana , Nwadili Christian O , Saski Christopher A , Paterne Agre , Scheffler Brian E. , Augusto Joao , Lopez-Montes Antonio , Onyeka T. J. , Kumar P. Lava , Bandyopadhyay Ranajit 
Published: May 2018

AbstractWater yam (Dioscorea alata L.) is one of the most important food yams with wide geographical distribution in tropics. One of the major constraints to water yam production is anthracnose disease caused by a fungus, Colletotrichum gloesporioides (Penz.). There are no economically feasible solutions as chemical sprays or cultural practices, such as crop rotation are seldom convenient for smallholder farmers for sustainable control of the disease. Breeding for development of durable genetic resistant varieties is known to offer lasting solution to control endemic disease threats to crop production. However, breeding for resistance to anthracnose has been slow considering the biological constraints related to the heterozygous and vegetative propagation of the crop. The development of saturated linkage maps with high marker density, such as SSRs, followed by identification of QTLs can accelerate the speed and precision of resistance breeding in water yam. A total of 380 EST-SSRs were used to generate a saturated linkage map. About 60.19% of SSRs showed Mendelian segregation pattern, however, it had no effect on the construction of linkage map. All 380 EST-SSRs were mapped into 20 linkage groups covering a total length of 2559.66 cM, which agrees with the diploid nature (2n = 2x = 20) of the parents used in the cross. Majority of the markers were mapped on linkage group 1 comprising of 97 EST-SSRs. This is the first genetic linkage map of water yam constructed using EST-SSRs. QTL localization was based on phenotypic data collected over a 3-year period of inoculating the mapping population with the most virulent strain of C. gloeosporoides from West Africa. Using the mean permutation value of LOD scores as threshold value for declaring a putative QTL on all linkage groups, one QTL was consistently observed on linkage group (LG) 14 in all the three years and average score data. This QTL was found at position interval of 71.12 – 84.76 cM explaining 68.94% of the total phenotypic variation in the average score data. The high marker density allowed identification of QTLs and association for anthracnose disease, which could be validated in other mapping populations and used in marker-assisted breeding in D. alata improvement programmes.
Evolution of shell flattening and the loss of coiling in top shells (Gastropoda: Trochidae: Fossarininae) on wave-swept rock reefs
Authors: Yamamori Luna , Kato Makoto 
Published: May 2018

AbstractFlattening of coiled shells has occurred in numerous gastropod lineages, probably as an adaptation to life in narrow protected spaces, such as crevices or the undersides of rocks. While several genera in the top snail family (Trochidae) have flattened shells, two Fossarininae genera,BroderipiaandRoya, are unique in having shells that are limpet-like and zygomorphic, lacking any trace of coiling. The sister genera of these two genera areFossarinaandSynaptocochlea, both of which have coiled shells and live in rock crevices or the vacant shells of sessile organisms. AlthoughBroderipiahas recently been identified as living symbiotically in the pits of sea urchins, the habitat and biology ofRoyaare poorly known. After an extensive search for rareRoyasnails on rocky shores of the Japanese Archipelago, we found liveRoya eximiasnails on intertidal/subtidal rock surfaces exposed to strong waves. TheRoyasnails crawled swiftly over wave-swept rock surfaces at low tide, while they retreated into the vacant shells of barnacles at high tide, where they adhered firmly to the inner wall. A survey of the macrobenthic communities around the snail habitat showed thatRoyasnails inhabited only wave-swept rocks of exposed reefs, where the substrata was covered by encrusting red algae and barnacles. Despite the abnormal shell morphology, the radula was similar to other species in the subfamily, and the diet ofRoyasnails was mainly pennate diatoms. The limpet-like shell ofRoyacaused loss of coiling and contraction of the soft body, acquisition of a zygomorphic flat body, expansion of the foot sole and loss of the operculum. All of these changes improved tolerance of strong waves and the ability to cling to rock surfaces, and thus enabled a lifestyle split between wave-swept rock surfaces and refugia of vacant barnacle shells.
Selective sweeps under dominance and inbreeding
Authors: Hartfield Matthew , Bataillon Thomas 
Published: May 2018

AbstractA major research goal in evolutionary genetics is to uncover loci experiencing positive selection. One approach involves finding ‘selective sweeps’ patterns, which can either be ‘hard sweeps’ formed byde novomutation, or ‘soft sweeps’ arising from recurrent mutation or existing standing variation. Existing theory generally assumes outcrossing populations, and it is unclear how dominance affects soft sweeps. We consider how arbitrary dominance and inbreeding via self-fertilisation affect hard and soft sweep signatures. With increased self-fertilisation, they are maintained over longer map distances due to reduced effective recombination and faster beneficial allele fixation times. Dominance can affect sweep patterns in outcrossers if the derived variant originates from either a single novel allele, or from recurrent mutation. These models highlight the challenges in distinguishing hard and soft sweeps, and propose methods to differentiate between scenarios.
Establishment and equilibrium levels of deleterious mutations in large populations
Authors: Viljoen Johan W. , de Villiers J. Pieter , Van Zyl Augustus J. , Mezzavilla Massimo , Pepper Michael S. 
Published: May 2018

AbstractAnalytical and statistical stochastic approaches are used to model and predict the dispersion of mutations through a large population. These approaches are used to quantify the magnitude of a heterozygous selective advantage of a mutation in the presence of a homozygous disadvantage. Random effects such as genetic drift are accounted for, which are likely to extinguish even highly advantageous mutations while the prevalence is still low. Dunbar’s results regarding the cognitive upper limit of the number of stable social relationships that humans can maintain are used to determine a realistic community size - a reduced local subset of the total population - from which an individual can select mates. This reduction in effective population size has a dramatic effect on the probability of establishing mutations, as well as the eventual equilibrium values that are reached in the case of mutations conferring a heterozygous selective advantage, but a homozygous disadvantage, as in the case of cystic fibrosis and sickle cell disease. The magnitude of this selective advantage can then be estimated based on observed occurrence levels of a specific mutation in a population, without requiring prior information regarding its phenotypic manifestation.Author summaryDeleterious mutations such as cystic fibrosis and sickle cell anemia can disperse through human populations due to the selective advantage that it bestows on heterozygous carriers, depending on environmental conditions. As its prevalence increases, the probability of generating homozygous offspring, with its concomitant selective disadvantage, also grows until an eventual equilibrium is reached between the number of carriers and wild-type individuals. In this work computer modelling is used to combine Dunbar’s anthropological observations predicting upper bounds to the number of stable human social relationships with observed prevalence levels, to estimate the absolute magnitude of the heterozygous selective advantage bestowed by such a deleterious genetic variation, without requiring knowledge regarding the specific mechanism whereby such an advantage is manifested.