bluuebunny/crossref_metadata_2025_split huggingface dataset:
First report on Bacterial Diversity of Potable Spring water of Indian Himalayan Region
Authors: Singh Ashish Kumar , Das Saurav , Singh Samer , Gajamer Varsha Rani , Pradhan Nilu , Lepcha Yangchen D. , Tiwari Hare Krishna 
Published: May 2018

AbstractWater quality of a region directly corroborates with the health index of people. People in the Himalayan hills mainly depend upon the spring water for potability. To determine the microbial ecology of the spring waters of Sikkim, the variable region of 16S rRNA has been sequenced using Illumina MiSeq. Phylum wise annotation showed the East and North district are mostly dominated byProteobacteria(41% and 35.80%), whereas West and South district is dominated byPlanctomycetes(38.46%) andVerrucomicrobia(33%). The consistent dominance phyla in the all the four districts wereBacteriodetes(34-24%) which was highest dominancy in North district and lowest in wets district. Genus wise distribution showed the abundance ofBrevifolis, Flavobacterium, Verrucomicrobia subdivision3, Emticica, Cytophaga, Prosthecobacter, Planctomycetes, Varivorax, Arcicella, Isosphera, Sedimunibacteriumetc. The East district showed highest dominancy of genusEmticiciawhereasPlanctomycetesin the West district. The North district was mainly dominated by genusArcicellaandBrevifollisin the South district. North on the antonymous showed totally different sets of microbial diversity. North district showed an abundance ofArcicella, Planctomycetes, SchlerensiaandAzohydromonas. The heat map produced by Bray Curtis distance method produced three clusters which showed the close relationship between West and East district microbiome that further related to South district. The sample of North district formed out group that showed different community structure from other three districts. The principle component analysis was showed that the east and South district samples are closely related and distantly correlated to the west Sikkim, but the North district showed completely different microbial community. The canonical correspondence analysis showed correlation between bacterial diversity and hydrochemistry and it was found that the bacterial diversity was influenced by the concentration of different metallic ions like sodium, calcium, barium and iron. This is a first report from the Eastern Himalayan region of India and it largely enhances our knowledge about the microbial structure of potable spring water of Eastern Himalayan. This study is useful for Government of India as well as the state government to adopt the different strategic treatment procedures to improve the quality of water that is supplied to the community resides in the Himalayan regions and solely dependent on this untreated spring water.
Bottlenecks in the transmission ofPorcine reproductive and respiratory syndrome virus(PRRSV1) to naïve pigs and quasi-species variation during infection in partially immune pigs
Authors: Cortey Martí , Arocena Gastón , Pileri Emanuela , Martín-Valls Gerard , Mateu Enric 
Published: May 2018

AbstractThe existence of bottlenecks during infection ofPorcine reproductive and respiratory syndrome virus(PRRSV) was studied in an experimental one-to-one model of transmission in pigs. Besides, the differences between viral quasi-species in vaccinated pigs that developed shorter or longer viremias after natural challenge were analysed. The results consistently reported the existence of bottlenecks during transmission. Several positions along the PRRSV genome were identified as being selected in partially immune animals that developed short viremias. Those positions accumulated in GP2, nsp9 and M proteins and resulted in changes in the protein structure and in the interactions of those proteins with their targets. The fact that the affected proteins are known targets of the immunity against PRRSV suggested that the immune response selected those changes. This pig model can be useful for the study of other pathogens of interest in animals and humans.Author summaryPorcine reproductive and respiratory syndrome (PRRS) is one of the most economically important disease of pigs. It is caused by PRRS virus (PRRSV), a positive-sense, single-stranded RNA virus in theArteriviridaefamily within the orderNidovirales. Here, we study the existence of bottlenecks during disease transmission and the differences between viral quasi-species in vaccinated pigs that developed shorter or longer viremias after natural challenge. Our results consistently report the existence of bottlenecks during PRRSV1 transmission and identify several mutations along the viral genome selected by the host immune response that can be clear targets for new vaccine development.
Detection of shared balancing selection in the absence of trans-species polymorphism
Authors: Cheng Xiaoheng , DeGiorgio Michael 
Published: May 2018

AbstractTrans-species polymorphism has been widely used as a key sign of long-term balancing selection across multiple species. However, such sites are often rare in the genome, and could result from mutational processes or technical artifacts. Few methods are yet available to specifically detect footprints of trans-species balancing selection without using trans-species polymorphic sites. In this study, we develop summary- and model-based approaches that are each specifically tailored to uncover regions of long-term balancing selection shared by a set of species by using genomic patterns of intra-specific polymorphism and inter-specific fixed differences. We demonstrate that our trans-species statistics have substantially higher power than single-species approaches to detect footprints of trans-species balancing selection, and are robust to those that do not affect all tested species. We further apply our model-based methods to human and chimpanzee whole genome sequencing data. In addition to the previously-established MHC and malaria resistance-associatedFREM3/GYPEregions, we also find outstanding genomic regions involved in barrier integrity and innate immunity, such as theGRIK1/CLDN17intergenic region, and theSLC35F1andABCA13genes. Our findings not only echo the significance of pathogen defense, but also reveal novel candidates in maintaining balanced polymorphisms across human and chimpanzee lineages. Finally, we show that these trans-species statistics can be applied to and work well for an arbitrary number of species, and integrate them into open-source software packages for ease of use by the scientific community.
A hypothetical new role for single-stranded DNA binding proteins in the immune system
Authors: Vijay Nagarjun , Chande Ajit 
Published: May 2018

AbstractThe breadth of the host range of single-stranded DNA (ssDNA) viruses is roughly comparable to the host range of double-stranded DNA viruses (dsDNA). Yet, general ssDNA sensing receptors that activate the immune system have not been unequivocally identified while numerous dsDNA sensing receptors are known. Here, we hypothesize that some of the Single-Stranded DNA Binding (SSB) proteins may act as receptors that detect single-stranded DNA from pathogens and activate the innate immune system. As the first test of our hypothesis, we checked whether human genes that are known to bind to ssDNA are potentially interferon-regulated. Out of the 102 human genes that are known to have ssDNA binding ability 23 genes show a more than two-fold increase in gene expression upon interferon treatment. Single-stranded DNA viruses are pathogens of not only animals but also of plants and protozoans. We used this information to further prioritize our candidate list to ssDNA binding genes that are common between the model plant Arabidopsis thaliana and humans. Based on these strategies, we shortlist several promising candidate genes including the HMGB1 gene which could act as a ssDNA sensor that activates the immune system. Agreeably though we cannot establish a definitive role for these genes as ssDNA sensors of the immune system as yet, our preliminary analysis suggests the potential existence of ssDNA binding protein-like receptors (SLR’s) that are worth investigating further.
Changes in lipid and proteome composition accompany growth ofBacillus subterraneusMITOT1 under supercritical CO2and may promote acclimation to associated stresses
Authors: Peet Kyle C. , Ravindra Kodihalli C. , Wishnok John S. , Summons Roger E. , Thompson Janelle R. 
Published: May 2018

AbstractRecent demonstration that multipleBacillusstrains grow in batch bioreactors containing supercritical (sc) CO2(i.e. >73 atm, >31°C) is surprising given the recognized roles of scCO2as a sterilant and solvent. Growth under scCO2is of interest for biotechnological applications and for microbially-enhanced geologic carbon sequestration. We hypothesize thatBacillusspp. may alter cell wall and membrane composition in response to scCO2-associated stresses. In this study, protein expression and membrane lipids ofB. subterraneusMITOT1 were profiled in cultures grown under headspaces of 1 and 100 atm of CO2or N2. Growth under 100 atm CO2revealed significantly decreased fatty acid branching and increased fatty acyl chain lengths relative to 1 atm cultures. Proteomes of MITOT1 grown under 1 and 100 atm pressures of CO2and N2were similar (Spearman R>0.65), and principal component analysis revealed variation by treatment with the first two principal components corresponding to headspace gas (CO2or N2) and pressure (1 atm and 100 atm), respectively. Amino acid metabolic proteins were enriched under CO2, including the glycine cleavage system, previously shown to be upregulated in acid stress response. These results provide insights into the stationary phase physiology of strains grown under scCO2, suggesting modifications of cell membranes and amino acid metabolism may be involved in response to acidic, high CO2conditions under scCO2.
In Vitro Growth Effects of Morphine and Naloxone on Various Head and Neck Squamous Cell Cancer Cell Lines
Authors: Denton Stephen R , Padia Reema , Shea Jill E. , Buchmann Luke O , Stoddard Gregory J , Firpo Matthew A , Call Tyler R 
Published: May 2018

AbstractUnderstanding the potential effects of mu-agonism and antagonism on cancer cells is important for the perioperative physician. Previous studies suggest some tumor cells may have altered growth with mu-agonism or antagonism. This study investigates the effects of morphine (mu-agonist) and naloxone (mu-antagonist) in head and neck tumor cell lines (laryngeal squamous cell carcinoma (SCC), lateral tongue SCC and base of tongue SCC). Morphine showed no significant effect on tumor cell growth. Naloxone showed significant inhibition of growth in laryngeal SCC, but not in lateral or base of tongue SCC.
RNA polymerase organizes into distinct spatial clusters independent of ribosomal RNA transcription inE. coli
Authors: Weng Xiaoli , Bohrer Christopher H. , Bettridge Kelsey , Lagda Arvin Cesar , Cagliero Cedric , Jin Ding Jun , Xiao Jie 
Published: May 2018

AbstractRecent studies have shown that RNA polymerase (RNAP) is spatially organized into distinct clusters inE. coliandB. subtiliscells. Spatially organized molecular components in prokaryotic systems imply compartmentalization without the use of membranes, which may offer new insights into pertinent functions and regulations. However, the function of RNAP clusters and whether its formation is driven by active ribosomal RNA (rRNA) transcription remain elusive. In this work, we investigated the spatial organization of RNAP inE. colicells using quantitative superresolution imaging. We observed that RNAP formed large, distinct clusters under a rich medium growth condition and preferentially located in the center of the nucleoid. Two-color superresolution colocalization imaging showed that under the rich medium growth condition, nearly all RNAP clusters were active in synthesizing rRNA, suggesting that rRNA synthesis may be spatially separated from mRNA synthesis that most likely occurs at the nucleoid periphery. Surprisingly, a large fraction of RNAP clusters persisted under conditions in which rRNA synthesis was reduced or abolished, or when only one out of the seven rRNA operons (rrn)remained. Furthermore, when gyrase activity was inhibited, we observed a similar rRNA synthesis level, but multiple dispersed, smaller rRNA and RNAP clusters occupying not only the center but also the periphery of the nucleoid, comparable to an expanded nucleoid. These results suggested that RNAP was organized into active transcription centers for rRNA synthesis under the rich medium growth condition; their presence and spatial organization, however, were independent of rRNA synthesis activity under the conditions used but were instead influenced by the structure and characteristics of the underlying nucleoid. Our work opens the door for further investigations of the function and molecular nature of RNAP clusters and points to a potentially new mechanism of transcription regulation by the spatial organization of individual molecular components.
Localizing and classifying adaptive targets with trend filtered regression
Authors: Mughal Mehreen R. , DeGiorgio Michael 
Published: May 2018

AbstractIdentifying genomic locations of natural selection from sequence data is an ongoing challenge in population genetics. Current methods utilizing information combined from several summary statistics typically assume no correlation of summary statistics regardless of the genomic location from which they are calculated. However, due to linkage disequilibrium, summary statistics calculated at nearby genomic positions are highly correlated. We introduce an approach termedTrendsetterthat accounts for the similarity of statistics calculated from adjacent genomic regions through trend filtering, while reducing the effects of multicollinearity through regularization. Our penalized regression framework has high power to detect sweeps, is capable of classifying sweep regions as either hard or soft, and can be applied to other selection scenarios as well. We find thatTrendsetteris robust to both extensive missing data and strong background selection, and has comparable power to similar current approaches. Moreover, the model learned byTrendsettercan be viewed as a set of curves modeling the spatial distribution of summary statistics in the genome. Application to human genomic data revealed positively-selected regions previously discovered such as LCT in Europeans and EDAR in East Asians. We also identified a number of novel candidates and show that populations with greater relatedness share more sweep signals.
High throughput single cell sequencing of bothT-cell-receptor-betaalleles
Authors: Hosoya Tomonori , Li Hongyang , Ku Chia-Jui , Wu Qingqing , Guan Yuanfang , Engel James Douglas 
Published: May 2018

ABSTRACTAllelic exclusion is a vital mechanism for the generation of monospecificity to foreign antigens in B- and T-lymphocytes. Here we developed a high-throughput barcoded method to simultaneously analyze the VDJ recombination status of both mouseT cell receptor betaalleles in hundreds of single cells using Next Generation Sequencing.
Peripheral blood DNA methylation and autism spectrum disorder
Authors: Andrews Shan V. , Sheppard Brooke , Windham Gayle C. , Schieve Laura A. , Schendel Diana E. , Croen Lisa A. , Chopra Pankaj , Alisch Reid S. , Newschaffer Craig J. , Warren Stephen T. , Feinberg Andrew P. , Fallin M. Daniele , Ladd-Acosta Christine 
Published: May 2018

AbstractBackgroundSeveral reports have suggested a role for epigenetic mechanisms in ASD etiology. Epigenome-wide association studies (EWAS) in autism spectrum disorder (ASD) may shed light on particular biological mechanisms. However, studies of ASD cases versus controls have been limited by post-mortem timing and severely small sample sizes. Reports from in-life sampling of blood or saliva have also been very limited in sample size, and/or genomic coverage. We present the largest case-control EWAS for ASD to date, combining data from population-based case-control and case-sibling pair studies.MethodsDNA from 968 blood samples from children in the Study to Explore Early Development (SEED 1) was used to generate epigenome-wide array DNA methylation (DNAm) data at 485,512 CpG sites for 453 cases and 515 controls, using the Illumina 450K Beadchip. The Simons Simplex Collection (SSC) provided 450K array DNAm data on an additional 343 cases and their unaffected siblings. We performed EWAS meta-analysis across results from the two data sets, with adjustment for sex and surrogate variables that reflect major sources of biological variation and technical confounding such as cell type, batch, and ancestry. We compared top EWAS results to those from a previous brain-based analysis. We also tested for enrichment of ASD EWAS CpGs for being targets of meQTL associations using available SNP genotype data in the SEED sample.FindingsIn this meta-analysis of blood-based DNA from 796 cases and 858 controls, no single CpG met a Bonferroni discovery threshold of p < 1.12×10−7. Seven CpGs showed differences at p < 1×10−5and 48 at 1×10−4. Of the top 7, 5 showed brain-based ASD associations as well, often with larger effect sizes, and the top 48 overall showed modest concordance (r = 0.31) in direction of effect with cerebellum samples. Finally, we observed suggestive evidence for enrichment of CpG sites controlled by SNPs (meQTL targets) among the EWAS CpGs hits, which was consistent across EWAS and meQTL discovery p-value thresholds.ConclusionsWe report the largest case-control EWAS study of ASD to date. No single CpG site showed a large enough DNAm difference between cases and controls to achieve epigenome-wide significance in this sample size. However, our results suggest the potential to observe disease associations from blood-based samples. Among the 7 sites achieving suggestive statistical significance, we observed consistent, and stronger, effects at the same sites among brain samples. Discovery-oriented EWAS for ASD using blood samples will likely need even larger samples and unified genetic data to further understand DNAm differences in ASD.
Stiffness Sensing and Cell Motility: Durotaxis and Contact Guidance
Authors: Feng Jingchen , Levine Herbert , Mao Xiaoming , Sander Leonard M. 
Published: May 2018

AbstractMechanical properties of the substrate plays a vital role in cell motility. Cells are shown to migrate up stiffness gradient (durotaxis) and along aligned fibers in the substrate (contact guidance). Here we present a simple mechanical model for cell migration, by placing a cell on lattice models for biopolymer gels and hydrogels. In our model cells attach to the substrate via focal adhesions (FAs). As the cells contract, forces are generated at the FAs, determining their maturation and detachment. At the same time, the cell also allowed to move and rotate to maintain force and torque balance. Our model, in which the cells only take the information of forces at the FAs, without a prior knowledge of the substrate stiffness or geometry, is able to reproduce both durotaxis and contact guidance.
Label propagation defines signaling networks associated with recurrently mutated cancer genes
Authors: Cakir Merve , Mukherjee Sayan , Wood Kris C. 
Published: May 2018

AbstractEach different tumor type has a distinct profile of genomic perturbations and each of these alterations causes unique changes to cellular homeostasis. Detailed analyses of these changes would reveal downstream effects of genomic alterations, contributing to our understanding of their roles in tumor development and progression. Across a range of tumor types, including bladder, lung, and endometrial carcinoma, we determined genes that are frequently altered in The Cancer Genome Atlas patient populations to study the effects of these alterations on signaling and regulatory pathways. To achieve this, we used a label propagation-based methodology to generate networks from gene expression signatures of mutations. Individual networks offered a comprehensive view of signaling changes represented by gene signatures, which in turn reflect the scope of molecular events that are perturbed in the presence of a given genomic alteration. Comparing different networks to each other revealed commonalities between them and biological pathways distinct genomic alterations converge on, highlighting the critical signaling events tumor dysregulate through multiple mechanisms. Finally, mutations inducing common changes to the signaling network were used to search for genomic markers of drug response, connecting shared perturbations to differential drug response.
Developmental system drift in motor ganglion patterning between distantly related tunicates
Authors: Lowe Elijah K. , Stolfi Alberto 
Published: May 2018

AbstractThe larval nervous system of the solitary tunicateCionais a simple model for the study of chordate neurodevelopment. The development and connectivity of theCionaMotor Ganglion (MG) has been studied in fine detail, but how this important structure develops in other tunicates is not well known. By comparing gene expression patterns in the developing MG of the distantly related tunicateMolgula occidentalis, we found that its patterning is highly conserved compared to theCionaMG. MG neuronal subtypes inMolgulawere specified in the exact same positions as inCiona, though the timing of subtype-specific gene expression onset was slightly shifted to begin earlier, relative to mitotic exit and differentiation. In transgenicMolgulaembryos electroporated withDmbxreporter plasmids, we were also able to characterize the morphology of the lone pair of descending decussating neurons (ddNs) inMolgula, revealing the same unique contralateral projection seen inCionaddNs and their putative vertebrate homologs the Mauthner cells. AlthoughDmbxexpression labels the ddNs in both species, cross-species transgenic assays revealed significant changes to thecis-regulatory logic underlyingDmbxtranscription. We found thatDmbx cis-regulatory DNAs fromCionacan drive highly specific reporter gene expression inMolguladdNs, butMolgulasequences are not active inCionaddNs. This acute divergence in the molecular mechanisms that underlie otherwise functionally conservedcis-regulatory DNAs supports the recently proposed idea that the extreme genetic plasticity observed in tunicates may be attributed to the extremerigidityof the spatial organization of their embryonic cell lineages.