bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rotavirus A Infections in Community Childhood Diarrhea in the Brazilian Semiarid Region During Postvaccination Era
Authors: Pankov Rafaela C. , Gondim Rafhaella N.D.G. , Prata Mara M.G. , Medeiros Pedro H.Q.S. , Veras Herlice N. , Santos Ana K.S. , Havt Alexandre , da Silva Marcelle F.M. , Fumian Tulio M. , Miagostovich Marize P. , Leite José P.G. , Lima Aldo A.M. 
Published: June 2019

ABSTRACTBackground:Rotavirus A (RVA) is one of the leading causes of acute gastroenteritis worldwide; however, few studies assessed RVA genetics with community surveillance.Objectives:This study aimed to investigate clinical data, genetic diversity, and coinfection patterns of RVA infections in children from 2 to 36 months old with or without community childhood diarrhea in the Brazilian semiarid region during postvaccination era.Methods:We enrolled and collected socioeconomic/clinical information using a standardized questionnaire and fecal samples from 291 children. Viral RNA samples were extracted and analyzed using quantitative reverse transcription polymerase chain reaction to establish the diagnosis of RVA. Sequencing of VP7 and VP4 (VP8*) regions and phylogenetic analysis were performed.Results:RVA‐negative diagnosis was associated with children 24 to 36 months old with complete vaccination schedule. Genotype G1P[8] was the most prevalent (57%), whereas unusual genotypes including G1P[4], G2P[8], and G3P[9] were also detected. G1‐ and P[8]‐positive samples showed high degrees of similarity with the vaccine strain. RVA coinfections were frequently observed, and enteroaggregative Escherichia coli was the most prevalent copathogen.Conclusions:These results demonstrate that genotype G1P[8] is the most prevalent strain. VP7 and/or VP8* gene segments arising from RV1 vaccine strain were documented in these children, suggesting shedding or herd vaccination. Moreover, our study indicates full vaccination is important for protection against RVA infections.
The Risk of Autoimmune Disorders in Treated Celiac Disease Patients in Olmsted County, Minnesota
Authors: Khan Muhammad R. , Nellikkal Shilpa S. , Barazi Ahmed , Larson Joseph J. , Murray Joseph A. , Absah Imad 
Published: June 2019

ABSTRACTBackground:Patients with autoimmune disorders (ADs) are at increased risk for celiac disease (CD), but data are conflicting on the risk of ADs in treated patients with CD. We aimed to assess the incidence of ADs in treated patients with CD.Methods:Using the Rochester Epidemiology Project, we retrospectively searched for the medical records at Mayo Clinic and Olmsted Medical Center from January 1997 to December 2015 for patients with CD who met accepted diagnostic criteria. For each patient with CD, we identified 2 age and sex‐matched controls during the same study period. The incidence rate of AD diagnosis 5 years after index date was calculated using Kaplan‐Meier analysis for the CD cases and controls and compared using the log‐rank test.Results:We identified 249 treated patients with CD during the study period and 498 matched controls, with mean (standard deviation) ages of 32 (22) years and 33 (22) years, respectively. One third of patients (n = 85) and controls (n = 170) were boys. Five years after the index date, 5.0% of patients with CD and 1.3% of controls had a de novo AD diagnosis (P = 0.006). In the presence of a prior AD, the cumulative risk of a de novo or additional AD was significantly higher in the CD group compared with controls (P < 0.001). Children had a significantly higher risk of AD development compared with adults (P = 0.010).Conclusions:Treated patients with CD are at higher risk for the development of ADs. The risk of a new AD is higher in children, especially when >1 AD diagnosis exists.
Regulation of Ascorbic acid by gonadotropins in rat Ovary
Authors: Hussain Shah Saddad , Arora Taruna , Chaturvedi Madan Mohan , Basu-Modak Sharmila , Chaudhary Rajesh , Muralidhar Kambadur 
Published: June 2019

AbstractThe dose dependent depletion of ovarian Ascorbic acid (AA) in rat ovaries, has been used as a bioassay for measurement of Luteinizing Hormone (LH). However, the mechanism of action of gonadotropin (LH, FSH) on ascorbic acid depletion is not completely clear in biochemical terms. To elucidate the mechanism, we looked for the pathways; one, where L-GulonateDehydrogenase (L-GuDH) catalyzes the conversion of L-Gulonic acid (L-GuA) to L-Xylulose, and, in the second the pathway conversion of L-GuA to AA, in a cats, dogs and Rats. Kinetic analysis of the enzyme L-GuDHin vitroshowed the inhibitory effect of AA on L-GuDH. Therefore, we hypothesized that gonadotropins (FSH and LH) may regulate the L-GuDH maintain level of AA in ovary. LH administration to super-ovulated immature female rats caused depletion of ovarian AA but did not result in any change in the specific activity of the ovarian L-GuDH. Further, we administrated a surrogate FSH like hormone (PMSG) to immature female rats which, resulted in increased specific activity of ovarian L-GuDH. However, microarray data on RNA from ovaries exposed to FSH like hormone such as Pregnant Mare serum Gonadotropin (PMSG) did not reveal any increased expression of L-GuDH transcript. It is therefore concluded from the results obtained that; that neither LH, in decreasing the ovarian AA, nor FSH, in increasing the ovarian AA do so by regulating the activity of enzyme L-GuDH at transcriptional level. The results obtained have also been discussed by giving emphasis on the mechanism of ovarian ascorbic acid regulation of LH and FSH.
Single-cell analysis of the muscle stem cell hierarchy identifies heterotypic communication signals involved in skeletal muscle regeneration
Authors: De Micheli Andrea J. , Fraczek Paula , Soueid-Baumgarten Sharon , Ravichandran Hiranmayi , De Vlaminck Iwijn , Elemento Olivier , Cosgrove Benjamin D. 
Published: June 2019

AbstractMuscle stem cells (MuSCs) are an essential adult stem cell population with the capacity to self-renew and regenerate muscle tissue. Functionally heterogeneous subpopulations of MuSCs have been identified based on their expression of myogenic regulatory factors and surface markers. However, a unified organization of muscle stem and progenitor cells and their subpopulations remains unresolved. Here, we performed temporal analysis of skeletal muscle regeneration using single-cell RNA-sequencing (scRNA-seq) of myotoxin-injured adult mouse hindlimb muscles. We generated over 34,000 single-cell transcriptomes spanning four muscle regeneration time-points and identified 15 distinct cell types, including a heterogeneous population of MuSCs and progenitor cells. Our analysis provides a hierarchical map of myogenic cell populations and identifies stage-specific regulatory programs that govern their contributions to muscle regeneration. In this transcriptomic atlas, we observed cell type-specific regenerative dynamics, exemplified by waves of transient amplification and diversification of multiple immune cell types and, subsequently, myogenic cells. Unbiased trajectory inference organized the myogenic cell populations within the atlas into a continuum, consisting of a hierarchy of quiescent MuSCs, cycling progenitors, committed myoblasts, and terminally differentiated myocytes. This myogenic trajectory matched prior understanding and also revealed that MuSC stages are defined by synchronous changes in regulatory factors, cell cycle-associated, and surface receptor gene expression. Lastly, we analyzed the transcriptomic atlas to identify over 100 candidate heterotypic communication signals between myogenic and non-myogenic cell populations, including many involving the fibroblast growth factor (FGF), Notch, and Syndecan receptor families and their associated ligands. Syndecan receptors were implicated in a large fraction of these cell communication interactions and were observed to exhibit transcriptional heterogeneity within the myogenic continuum. Using multiparameter mass cytometry (CyTOF), we confirmed that cycling MuSCs exhibit diversified Syndecan-1/2 expression, which suggests that dynamic alterations in Syndecan signaling interactions may coordinate stage-specific myogenic cell fate regulation. This scRNA-seq reference atlas provides a resolved hierarchical organization of myogenic subpopulations as a resource to investigate cell-cell interactions that regulate myogenic stem and progenitor cell fates in muscle regeneration.
Mass Spectrometry based Metabolomics Deciphered Metabolic Reprogramming That Was Required for Biofilm formation in UropathogenicEscherichia coli
Authors: Lu Haitao , Que Yumei , Wu Xia , Guan Tianbing , Guo Hao 
Published: June 2019

ABSTRACTBiofilm formation plays a key role in many bacteria causing infections, which mostly accounts for high-frequency infectious recurrence and antibiotics resistance. In this study, we sought to compare modified metabolism of biofilm and planktonic populations with UIT89, a predominant agent of urinary tract infection, by combining mass spectrometry based untargeted and targeted metabolomics methods, as well as cytological visualization, which enable us to identify the driven metabolites and associated metabolic pathways underlying biofilm formation. Surprisingly, our finding revealed distinct differences in both phenotypic morphology and metabolism between two patterns. Furthermore, we identified and characterized 38 differential metabolites and associated three metabolic pathways involving glycerolipid metabolism, amino acid metabolism and carbohydrate metabolism that were altered mostly during biofilm formation. This discovery in metabolic phenotyping permitted biofilm formation shall provide us a novel insight into the desperation of biofilm, which enable to develop novel biofilm based treatments against pathogen causing infections, with lower antibiotic resistance.
The repertoire of serous ovarian cancer non-genetic heterogeneity revealed by single-cell sequencing of normal fallopian tube epithelial cells
Authors: Hu Zhiyuan , Artibani Mara , Alsaadi Abdulkhaliq , Wietek Nina , Morotti Matteo , Gonzalez Laura Santana , El-Sahhar Salma , KaramiNejadRanjbar Mohammad , Mallett Garry , Shi Tingyan , Masuda Kenta , Zheng Yiyan , Chong Kay , Damato Stephen , Dhar Sunanda , Campanile Riccardo Garruto , majd Hooman Soleymani , Cerundolo Vincenzo , Sauka-Spengler Tatjana , Yau Christopher , Ahmed Ahmed A. 
Published: June 2019

SummaryThe inter-differentiation between cell states promotes cancer cell survival under stress and fosters non-genetic heterogeneity (NGH). NGH is, therefore, a surrogate of tumor resilience but its quantification is confounded by genetic heterogeneity. Here we show that NGH can be accurately measured when informed by the molecular signatures of the normal cells of origin. We surveyed the transcriptomes of ∼ 4000 normal fallopian tube epithelial (FTE) cells, the cells of origin of serous ovarian cancer (SOC), and identified six FTE subtypes. We used subtype signatures to deconvolute SOC expression data and found substantial intra-tumor NGH that was previously unrecognized. Importantly, NGH-based stratification of ∼1700 tumors robustly predicted survival. Our findings lay the foundation for accurate prognostic and therapeutic stratification of SOC.HighlightsThe projection of FTE subtypes refines the molecular classification of serous OCComprehensive single-cell profiling of FTE cells identifies 6 molecular subtypesSubstantial non-genetic heterogeneity of HGSOC identified in 1700 tumorsA mesenchymal-high HGSOC subtype is robustly correlated with poor prognosis
CRISPR-assisted targeted enrichment-sequencing (CATE-seq)
Authors: Xu Xinhui , Xia Qiang , Zhang Shuyan , Gao Jinliang , Dai Wei , Wu Jian , Wang Jinke 
Published: June 2019

AbstractThe current targeted sequencing of genome is mainly dependent on various hybridization-based methods. However, the hybridization-based methods are still limited by the intrinsic shortcomings of nucleic acid hybridization. This study developed a new CRISPR-based targeted sequencing technique, CRISPR-assisted targeted enrichment-sequencing (CATE-seq). In this technique, the input genomic DNA (gDNA) was firstly bound by a complex of dCas9 and capture sgRNA (csgRNA). The DNA-dCas9-csgRNA complex was then captured on magnetic beads through an easy room-temperature annealing between a short universal capture sequence (24 bp) at the 3′ end of csgRNA and capture oligonucleotide coupled on magnetic beads. The enriched DNAs were finally analyzed by next generation sequencing. Using this technique, three different scales of targeted enrichments were successfully performed, including enriching 35 target exons of 6 genes from 6 gDNA samples with 54 csgRNAs, 339 target exons of 186 genes from 9 gDNA samples with 367 csgRNAs, and 2031 target exons of 451 genes from 2 gDNA samples with 2302 csgRNAs. This technique has several significant advantages over the current hybridization-based methods, including high simplicity, specificity, sensitivity, throughput, and scalability.
Controlled dehydration, structural flexibility, and Gadolinium MRI contrast compound binding in human plasma glycoprotein afamin
Authors: Naschberger Andreas , Juyoux Pauline , von Velsen Jill , Rupp Bernhard , Bowler Matthew W. 
Published: June 2019

AbstractAfamin, a human blood plasma glycoprotein, a putative multi-functional transporter of hydrophobic molecules and a marker for metabolic syndrome, poses multiple challenges for crystallographic structure determination, both practically and in analysis of the models. Several hundred crystals were analysed, and unusual variability in cell volume and difficulty solving the structure despite a ~34% sequence identity with non-glycosylated human serum albumin indicated that the molecule exhibits variable and context-sensitive packing, despite greatly simplified glycosylation in insect cell expressed recombinant afamin. Controlled dehydration of the crystals was able to stabilise the orthorhombic crystal form reducing the number of molecules in the asymmetric unit from the monoclinic form and changing the conformational states of the protein. An iterative strategy, using fully automatic experiments available on MASSIF-1, was used to quickly determine the optimal protocol to achieve the phase transition that should be readily applicable to many types of sample. The study also highlights the drawback of using a single crystallographic structure model for computation modelling purposes given that conformational state of the binding sites and electron density in the binding site, likely resulting from PEGs, greatly varies between models. This also holds for the analysis of unspecific low-affinity ligands, where often a variety fragments with similar uncertainty can be modelled, inviting interpretative bias. As a promiscuous transporter, afamin also seems to bind Gadoteridol, a magnetic resonance imaging contrast compound, in at least two sites. One pair of Gadoteridol molecules is located near the human albumin Sudlow-site, and a second Gadoteridol at an intermolecular site in proximity of domain IA. The data from the co-crystals provide an opportunity to evaluate modern metrics of data quality in the context of the information that can be gleaned from data sets that would be abandoned on classical measures.SynopsisControlled dehydration experiments have revealed a new crystal form of afamin, a human blood plasma glycoprotein and transporter of hydrophobic molecules. The comparison shows substantial molecular plasticity and amplifies the necessity to examine multiple crystal forms and to refine multiple models, while at the same time the new structure cautions against interpretation of fatty acid ligand density in crystals derived from PEG as major precipitants. An isomorphic low-resolution structure model suggests that afamin is capable of transporting Gadolinium-DO3A, a magnetic resonance imaging compound.
The multiple population genetic and demographic routes to islands of genomic divergence
Authors: Quilodrán Claudio S. , Ruegg Kristen , Sendell-Price Ashley T. , Anderson Eric , Coulson Tim , Clegg Sonya 
Published: June 2019

Abstract1. The way that organisms diverge into reproductively isolated species is a major question in biology. The recent accumulation of genomic data provides promising opportunities to understand the genomic landscape of divergence, which describes the distribution of differences across genomes. Genomic areas of unusually high differentiation have been called genomic islands of divergence. Their formation has been attributed to a variety of mechanisms, but a prominent hypothesis is that they result from divergent selection over a small portion of the genome, with surrounding areas homogenised by gene flow. Such islands have often been interpreted as being associated with divergence with gene flow. However other mechanisms related to genetic architecture and population history can also contribute to the formation of genomic islands of divergence.2. We currently lack a quantitative framework to examine the dynamics of genomic landscapes under the complex and nuanced conditions that are found in natural systems. Here, we develop an individual-based simulation to explore the dynamics of diverging genomes under various scenarios of gene flow, selection and genotype-phenotype maps.3. Our modelling results are consistent with empirical observations demonstrating the formation of genomic islands under genetic isolation. Importantly, we have quantified the range of conditions that produce genomic islands. We demonstrate that the initial level of genetic diversity, drift, time since divergence, linkage disequilibrium, strength of selection and gene flow are all important factors that can influence the formation of genomic islands. Because the accumulation of genomic differentiation over time tends to erode the signal of genomic islands, genomic islands are more likely to be observed in recently divergent taxa, although not all recently diverged taxa will necessarily exhibit islands of genomic divergence. Gene flow primarily slows the swamping of islands of divergence with time.4. By using this framework, further studies may explore the relative influence of particular suites of events that contribute to the emergence of genomic islands under sympatric, parapatric and allopatric conditions. This approach represents a novel tool to explore quantitative expectations of the speciation process, and should prove useful in elucidating past and projecting future genomic evolution of any taxa.
Photodamage repair pathways contribute to the accurate maintenance of the DNA methylome landscape upon UV exposure
Authors: Graindorge Stéfanie , Cognat Valérie , Johann to Berens Philippe , Mutterer Jérôme , Molinier Jean 
Published: June 2019

AbstractPlants are exposed to the damaging effect of sunlight that induces DNA photolesions. In order to maintain genome integrity, specific DNA repair pathways are mobilized. Upon removal of UV-induced DNA lesions, the accurate re-establishment of epigenome landscape is expected to be a prominent step of these DNA repair pathways. However, it remains poorly documented whether DNA methylation is accurately maintained at photodamaged sites and how photodamage repair pathways contribute to the maintenance of genome/methylome integrities. Using genome wide approaches, we report that UV-C irradiation leads to asymmetric DNA methylation changes. We identified that the specific DNA repair pathways involved in the repair of UV-induced DNA lesions, Direct Repair (DR) and Global Genome Repair (GGR), prevent the excessive alterations of DNA methylation landscape. Moreover, we identified that UV-C irradiation induced chromocenter reorganization and that photodamage repair factors control this dynamics. The methylome changes rely on misregulation of maintenance, de novo and active DNA demethylation pathways highlighting that molecular processes related to genome and methylome integrities are closely interconnected. Importantly, we identified that photolesions are sources of DNA methylation changes in both, constitutive and facultative heterochromatin. This study unveils that DNA repair factors, together with small RNA, act to accurately maintain both genome and methylome integrities at photodamaged silent genomic regions, strengthening the idea that plants have evolved sophisticated interplays between DNA methylation dynamics and DNA repair.
Chronic Stability of Single-Channel Neurophysiological Correlates of Gross and Fine Reaching Movements in the Rat
Authors: Bundy David T. , Guggenmos David J , Murphy Maxwell D , Nudo Randolph J. 
Published: June 2019

AbstractFollowing injury to motor cortex, reorganization occurs throughout spared brain regions and is thought to underlie motor recovery. Unfortunately, the standard neurophysiological and neuroanatomical measures of post-lesion plasticity are only indirectly related to observed changes in motor execution. While substantial task-related neural activity has been observed during motor tasks in rodent primary motor cortex and premotor cortex, the long-term stability of these responses in healthy rats is uncertain, limiting the interpretability of longitudinal changes in the specific patterns of neural activity during motor recovery following injury. This study examined the stability of task-related neural activity associated with execution of reaching movements in healthy rodents. Rats were trained to perform a novel reaching task combining a ‘gross’ lever press and a ‘fine’ pellet retrieval. In each animal, two chronic microelectrode arrays were implanted in motor cortex spanning the caudal forelimb area (rodent primary motor cortex) and the rostral forelimb area (rodent premotor cortex). We recorded multiunit spiking and local field potential activity from 10 days to 7-10 weeks post-implantation to characterize the patterns of neural activity observed during each task component and analyzed the consistency of channel-specific task-related neural activity. Task-related changes in neural activity were observed on the majority of channels. While the task-related changes in multi-unit spiking and local field potential spectral power were consistent over several weeks, spectral power changes were more stable, despite the trade-off of decreased spatial and temporal resolution. These results show that rodent primary and premotor cortex are both involved in reaching movements with stable patterns of task-related activity across time, establishing the relevance of the rodent for future studies designed to examine changes in task-related neural activity during recovery from focal cortical lesions.
Nav1.5 single-molecule localization reveals different reorganization modes at cardiomyocyte domains
Authors: Vermij Sarah H. , Rougier Jean-Sébastien , Agulló-Pascual Esperanza , Rothenberg Eli , Delmar Mario , Abriel Hugues 
Published: June 2019

ABSTRACTMutations in the gene encoding the sodium channel Nav1.5 cause various cardiac arrhythmias. This variety may arise from different determinants of Nav1.5 expression between cardiomyocyte domains. At the lateral membrane and T-tubules, Nav1.5 localization and function remain insufficiently characterized. We used novel single-molecule localization microscopy (SMLM) and modeling to define nanoscale features of Nav1.5 localization and distribution at the lateral membrane, groove, and T-tubules in wild-type, dystrophin-deficient (mdx) mice, and mice expressing C-terminally truncated Nav1.5 (ΔSIV). We show that Nav1.5 organizes as distinct clusters in the groove and T-tubules which density and distribution partially depend on SIV and dystrophin. We found that overall reduction in Nav1.5 expression in mdx and ΔSIV cells results in a non-uniform redistribution with Nav1.5 being specifically reduced at the groove of ΔSIV and increased in T-tubules of mdx cardiomyocytes. Nav1.5 mutations may therefore site-specifically affect Nav1.5 localization and distribution depending on site-specific interacting proteins.