bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systematic Discovery of Conservation States for Single-Nucleotide Annotation of the Human Genome
Authors: Sperlea Adriana , Ernst Jason 
Published: February 2018

AbstractComparative genomics sequence data is an important source of information for interpreting genomes. Genome-wide annotations based on this data have largely focused on univariate scores or binary calls of evolutionary constraint. Here we present a complementary whole genome annotation approach, ConsHMM, which applies a multivariate hidden Markov model to learn de novo different ‘conservation states’ based on the combinatorial and spatial patterns of which species align to and match a reference genome in a multiple species DNA sequence alignment. We applied ConsHMM to a 100-way vertebrate sequence alignment to annotate the human genome at single nucleotide resolution into 100 different conservation states. These states have distinct enrichments for other genomic information including gene annotations, chromatin states, and repeat families, which were used to characterize their biological significance. Conservation states have greater or complementary predictive information than standard constraint based measures for a variety of genome annotations. Bases in constrained elements have distinct heritability enrichments depending on the conservation state assignment, demonstrating their relevance to analyzing phenotypic associated variation. The conservation states also highlight differences in the conservation patterns of bases prioritized by a number of scores used for variant prioritization. The ConsHMM method and conservation state annotations provide a valuable resource for interpreting genomes and genetic variation.
AnEscherichia colinitrogen starvation response is important for mutualistic coexistence withRhodopseudomonas palustris
Authors: McCully Alexandra L. , Behringer Megan G. , Gliessman Jennifer R. , Pilipenko Evgeny V. , Mazny Jeffrey L. , Lynch Michael , Drummond D. Allan , McKinlay James B. 
Published: February 2018

AbstractMicrobial mutualistic cross-feeding interactions are ubiquitous and can drive important community functions. Engaging in cross-feeding undoubtedly affects the physiology and metabolism of individual species involved. However, the nature in which an individual’s physiology is influenced by cross-feeding and the importance of those physiological changes for the mutualism have received little attention. We previously developed a genetically tractable coculture to study bacterial mutualisms. The coculture consists of fermentativeEscherichia coliand phototrophicRhodopseudomonas palustris. In this coculture, E. coli anaerobically ferments sugars into excreted organic acids as a carbon source for R. palustris. In return, a genetically-engineered R. palustris constitutively converts N2into NH4+, providingE. coliwith essential nitrogen. Using RNA-seq and proteomics, we identified transcript and protein levels that differ in each partner when grown in coculture versus monoculture. When in coculture withR. palustris, E. coligene-expression changes resembled a nitrogen starvation response under the control of the transcriptional regulator NtrC. By genetically disruptingE. coliNtrC, we determined that a nitrogen starvation response is important for a stable coexistence, especially at lowR. palustrisNH4+excretion levels. Destabilization of the nitrogen starvation regulatory network resulted in variable growth trends and in some cases, extinction. Our results highlight that alternative physiological states can be important for survival within cooperative cross-feeding relationships.ImportanceMutualistic cross-feeding between microbes within multispecies communities is widespread. Studying how mutualistic interactions influence the physiology of each species involved is important for understanding how mutualisms function and persist in both natural and applied settings. Using a bacterial mutualism consisting ofRhodopseudomonas palustrisandEscherichia coligrowing cooperatively through bidirectional nutrient exchange, we determined that anE. colinitrogen starvation response is important for maintaining a stable coexistence. The lack of anE. colinitrogen starvation response ultimately destabilized the mutualism and, in some cases, led to community collapse after serial transfers. Our findings thus inform on the potential necessity of an alternative physiological state for mutualistic coexistence with another species compared to the physiology of species grown in isolation.
Molecular Clock and Phylogeny ofAnophelesspecies of the subgenusNyssorhynchus(Diptera: Culicidae)
Authors: Hoyos-López Richard 
Published: February 2018

AbstractThe main Phylogenetic hypothesis supporting the Myzorhynchella section as a natural group, but the sections Albimanus and Argyritarsis, do not present clearly resolved relationships, nor is it possible to recover the monophyly of both sections, even within these sections ofNyssorhynchus; it has not been possible identify the relationships between the species that make up these taxonomic subdivisions (Sallum, 2000, Sallum, 2002, Bourke, 2011, Foster, 2013). This lack of resolution has been attributed to the effect of few species for phylogenetic studies, making difficult the determination of monophyly of many groups, subgroups and complexes within sections Albimanus and ArgyritarsisWe infer the phylogeny of the subgenusNyssorhynchusthrough the sequences characterized for the molecular markers ND6, COI-Barcode, White and CAD, in addition we calculate the times of divergence for the main lineages corresponding to the sections Albimanus, Argyritarsis and Myzorhynchella using Bayesian approaches.
Absence of the Spindle Assembly Checkpoint restores mitotic fidelity upon loss of sister chromatid cohesion
Authors: Silva Rui D. , Mirkovic Mihailo , Guilgur Leonardo G. , Rathore Om S. , Martinho Rui Gonçalo , Oliveira Raquel A. 
Published: February 2018

AbstractSister chromatid cohesion is essential for faithful mitosis, as premature cohesion loss leads to random chromosome segregation and aneuploidy, resulting in abnormal development. To identify specific conditions capable of restoring defects associated with cohesion loss, we screened for genes whose depletion modulatesDrosophilawing development when sister chromatid cohesion is impaired. Cohesion deficiency was induced by knock-down of the acetyltransferase Separation anxiety (San)/Naa50, a cohesin complex stabilizer. Several genes whose function impacts wing development upon cohesion loss were identified. Surprisingly, knockdown of key Spindle Assembly Checkpoint (SAC) proteins, Mad2 and Mps1, suppressed developmental defects associated with San depletion. SAC impairment upon cohesin removal, triggered by San depletion or artificial removal of the cohesin complex, prevented extensive genome shuffling, reduced segregation defects and restored cell survival. This counterintuitive phenotypic suppression was caused by an intrinsic bias for efficient chromosome bi-orientation at mitotic entry, coupled with slow engagement of error-correction reactions. We conclude that mitotic timing determines the severity of defects associated with cohesion deficiency. Therefore, although divisions are still error-prone, SAC inactivation enhances cell survival and tissue homeostasis upon cohesion loss.
DNA methylation oscillation defines classes of enhancers
Authors: Libertini Emanuele , Hamoudi Rifat A. , Heath Simon , Lancashire Lee , Garcia Arcadio Rubio , Grassi Luigi , Downes Kate , Ouwehand Willem H. , Javierre Biola-Maria , Cairns Jonathan , Wingett Steven , Paul Dirk S. , Gut Marta , Gut Ivo G. , Martens Joost H. A. , Ivliev Alexandr , Stunnenberg Hendrik G. , Frontini Mattia , Spivakov Mikhail , Fraser Peter , Cutler Antony , Wallace Chris , Beck Stephan 
Published: February 2018

AbstractUnderstanding the regulatory landscape of human cells requires the integration of genomic and epigenomic maps, capturing combinatorial levels of cell type-specific and invariant activity states.Here, we segmented whole-genome bisulfite sequencing-derived methylomes into consecutive blocks of co-methylation (COMETs) to obtain spatial variation patterns of DNA methylation (DNAm oscillations) integrated with histone modifications and promoter-enhancer interactions derived from promoter capture Hi-C (PCHi-C) sequencing of the same purified blood cells.Mapping DNAm oscillations onto regulatory genome annotation revealed that enhancers are enriched for DNAm hyper-oscillations (>30-fold), where multiple machine learning models support DNAm as predictive of enhancer location. Based on this analysis, we report overall predictive power of 99% for DNAm oscillations, 77.3% for DNaseI, 41% for CGIs, 20% for UMRs and 0% for LMRs, demonstrating the power of DNAm oscillations over other methods for enhancer prediction. Methylomes of activated and non-activated CD4+ T cells indicate that DNAm oscillations exist in both states irrespective of activation; hence they can be used to determine the location of latent enhancers.Our approach advances the identification of tissue-specific regulatory elements and outperforms previous approaches defining enhancer classes based on DNA methylation.
Effects of different load on physiological, hematological, biochemical, cytokines indices of Zanskar ponies at high altitude
Authors: Vivek Prince , Bharti Vijay Kumar , Kumar Deepak , Kumar Rohit , Nehra Kapil , Singh Dhananjay , Chaurasia Om Prakash , Kumar Bhuvnesh 
Published: February 2018

ABSTRACTHigh altitude people required high endurance pack animals for load carrying and riding at prevalent mountainous terrains and rugged region. So far no studies have been taken to evaluate effect of loads on physiology of ponies in high altitude region. So, in this view we evaluated variation in physiological, hematological, biochemical, and cytokines indices of Zanskar ponies during load carrying at high altitude. Total twelve (12) numbers of Zanskar ponies, mare, age 4–6 years, were divided into three groups; group-A (without load), group-B (60 kg), and group-C (80 kg) of back pack loads. Track was very narrow and slippery with gravel, uneven with rocky surface and has a steep gradient of 4 km uphill at altitude 3291 to 3500 m. When we evaluate these parameters, it is understood that the heart rate, pulse rate and respiration rate was significantly(p<0.05)increased in 80 kg group among the three groups. The hematology parameters viz. hemoglobin, PCV, lymphocytes, monocytes%, ESR and eosinophil% significantly(p<0.05)changed in 80 kg group after load carrying among the three groups which was followed by control and 60 kg group. In biochemical parameters viz. LA, LDH, TP, HK, CORT, T3, CRT, AST, CK-MB, GPx, FRAP and IL-6 significantly(p<0.05)changed in 80 kg group after load carrying among the three groups which was followed by control and 60 kg group. The ALT, ALB, GLB, UR and UA significantly(p<0.05)changed in 80 kg group before and after load carrying among the three groups which was followed by control and 60 kg group. It has been concluded that, this result has revealed strong correlation of change in biomarkers level with performance in ponies during load carry. Hence, these parameters might be use for performance of endurance of Zanskar ponies in high mountain region.
Effects of coil orientation on Motor Evoked Potentials from Orbicularis Oris and First Dorsal Interosseous
Authors: Adank Patti , Kennedy-Higgins Dan , Maegherman Gwijde , Hannah Ricci , Nuttall Helen 
Published: February 2018

AbstractObjectiveThis study aimed to characterise effects of coil orientation on the size of Motor Evoked Potentials (MEPs) from both sides of Orbicularis Oris (OO) and compare these effects with those reported for First Dorsal Interosseous (FDI), following stimulation to left lip and left hand Primary Motor Cortex.MethodsUsing a 70 mm figure-of-eight coil, we collected MEPs from eight different orientations while recording from contralateral and ipsilateral OO and FDI using a monophasic pulse.ResultsMEPs from OO were evoked consistently for six out of eight orientations for contralateral and ipsilateral sites. When latency and silent periods were taken into account, contralateral orientations 0°, 45°, 90°, and 315° were found to best elicit OO MEPs with a likely cortical origin. As expected, the largest FDI MEPs were recorded with an orientation of 45°, invoking a posterior-anterior (PA) current flow, from the contralateral location.ConclusionOrientations traditionally used for FDI were also found suitable for eliciting OO MEPs. Individuals vary more in their optimal coil orientation for eliciting MEPs from OO than for FDI. It is recommended that researchers iteratively probe several orientations when eliciting MEPs from OO. Care must be taken however because several orientations likely induced direct activation of facial muscles.
Evidence for rapid evolution in a grassland biodiversity experiment
Authors: van Moorsel Sofia J. , Schmid Marc W. , Wagemaker Niels C.A.M. , van Gurp Thomas , Schmid Bernhard , Vergeer Philippine 
Published: February 2018

AbstractBiodiversity often increases plant productivity. In long-term grassland experiments, positive biodiversity effects on plant productivity commonly increase with time. Also, it has been shown that such positive biodiversity effects persist not only in the local environment but also when plants are transferred into a common environment. Thus, we hypothesized that community diversity had acted as a selective agent, resulting in the emergence of plant monoculture and mixture types with differing genetic composition. To test our hypothesis, we grew offspring from plants that were grown for eleven years in monoculture or mixture environments in a biodiversity experiment (Jena Experiment) under controlled glasshouse conditions in monocultures or two-species mixtures. We used epiGBS, a genotyping-by-sequencing approach combined with bisulfite conversion to provide integrative genetic and epigenetic data. We observed significant genetic and epigenetic divergence according to selection history in three out of five perennial grassland species, namelyGalium mollugo,Prunella vulgarisandVeronica chamaedrys, with epigenetic differences mostly reflecting the genetic differences. In addition, current diversity levels in the glasshouse had weak effects on epigenetic variation. However, given the limited genome coverage of the reference-free bisulfite method epiGBS, it remains unclear how much of this epigenetic divergence was independent of underlying genetic differences. Our results thus suggest that selection of genetic variants, and possibly epigenetic variants, caused the rapid emergence of monoculture and mixture types within plant species in the Jena Experiment.
Active Function Learning
Authors: Jones Angela , Schulz Eric , Meder Björn , Ruggeri Azzurra 
Published: February 2018

AbstractHow do people actively explore to learn about functional relationships, that is, how continuous inputs map onto continuous outputs? We introduce a novel paradigm to investigate information search in continuous, multi-feature function learning scenarios. Participants either actively selected or passively observed information to learn about an underlying linear function. We develop and compare different variants of rule-based (linear regression) and non-parametric (Gaussian process regression) active learning approaches to model participants’ active learning behavior. Our results show that participants’ performance is best described by a rule-based model that attempts to efficiently learn linear functions with a focus on high and uncertain outcomes. These results advance our understanding of how people actively search for information to learn about functional relations in the environment.
Environmentally enriched pigs have transcriptional profiles consistent with neuroprotective effects and reduced microglial activity
Authors: Brown SM , Bush SJ , Summers KM , Hume DA , Lawrence AB 
Published: February 2018

AbstractEnvironmental enrichment (EE) is widely used to study the effects of external factors on brain development, function and health in rodent models, but very little is known of the effects of EE on the brain in a large animal model such as the pig. Twenty-four young pigs (aged 5 weeks at start of study, 1:1 male: female ratio) were housed in environmentally enriched (EE) pens and provided with additional enrichment stimulation (a bag filled with straw) once daily. Litter, weight and sex matched controls n= (24) were housed in barren (B) conditions. Behaviour was recorded on alternate days from study day 10. After 21 days, RNA-sequencing of the frontal cortex of male piglets culled one hour after the enrichment stimulation, but not those at 4 hours after stimulation, showed upregulation of genes involved in neuronal activity and synaptic plasticity in the EE compared to the B condition. This result is mirrored in the behavioural response to the stimulation which showed a peak in activity around the 1 hour time-point. By contrast, EE piglets displayed a signature consistent with a relative decrease in microglial activity compared to those in the B condition. These results confirm those from rodents, suggesting that EE may also confer neuronal health benefits in large mammal models, through a potential relative reduction in neuroinflammatory process and increase in neuroprotection driven by an enrichment-induced increase in behavioural activity.
Longitudinal immunosequencing in healthy people reveals persistent T cell receptors rich in public receptors
Authors: Chu Nathaniel D. , Bi Haixin Sarah , Emerson Ryan O. , Sherwood Anna M. , Birnbaum Michael E. , Robins Harlan S. , Alm Eric J. 
Published: February 2018

ABSTRACTBackgroundThe adaptive immune system maintains a diversity of T cells capable of recognizing a broad array of antigens. Each T cell’s specificity and affinity for antigens is determined by its T cell receptors (TCRs), which together across all T cells form a repertoire of tens of millions of unique receptors in each individual. Although many studies have examined how TCR repertoires change in response to disease or drugs, few have explored the temporal dynamics of the TCR repertoire in healthy individuals.ResultsHere we report immunosequencing of TCR β chains (TCRβ) from the blood of three healthy individuals at eight time points over one year. TCRβ repertoires from samples of all T cells and memory T cells clearly clustered by individual, confirming that TCRβ repertoires are specific to individuals across time. This individuality was absent from TCRβs from naive T cells, suggesting that these differences result from an individual’s antigen exposure history. Many characteristics of the TCRβ repertoire (e.g., alpha diversity, clonality) were stable across time, although we found evidence of T cell expansion dynamics even within healthy individuals. We further identified a subset of “persistent” TCRβs present across all time points, and these receptors were rich in clonal and public receptors.ConclusionsOur results revealed persistent receptors that may play a key role in immune system maintenance. They further highlight the importance of longitudinal sampling of the immune system and provide a much-needed baseline for TCRβ dynamics in healthy individuals. Such a baseline should help improve interpretation of changes in the TCRβ repertoire during disease or treatment.
Conserved accessory proteins encoded with archaeal and bacterial Type III CRISPR-Cas gene cassettes that may specifically modulate, complement or extend interference activity
Authors: Shah Shiraz A. , Alkhnbashi Omer S. , Behler Juliane , Han Wenyuan , She Qunxin , Hess Wolfgang R. , Garrett Roger A. , Backofen Rolf 
Published: February 2018

AbstractA study was undertaken to identify conserved proteins that are encoded either within, or directly adjacent to, cas gene cassettes of Type III CRISPR-Cas interference modules. These Type III modules are especially versatile functionally and have been shown to target and degrade dsDNA, ssDNA and ssRNA. In addition, the interference gene cassettes are frequently intertwined with other accessory genes, including genes encoding CARF domains, some of which are likely to be cofunctional. Using a comparative genomics approach, and defining a Type III association score accounting for coevolution and specificity of flanking genes, we identified and classified 39 new Type III associated gene families. Most archaeal and bacterial Type III modules were seen to be flanked by several accessory genes, around half of which did not encode CARF domains and remain of unknown function. Non-CARF accessory genes were found to be more diverse than their CARF counterparts, encoding nuclease, helicase, protease, ATPase, transporter and transmembrane domains and including a considerable fraction that encoded no known domains. The diversity of non-CARF Type III accessory genes found in this study suggests that additional families exist which remain undetected because of the limited number of annotated genomes currently available. The method employed is scalable for potential application on metagenomic data once automated pipelines for annotation of CRISPR-Cas systems have been developed. All accessory genes found in this study are presented online in a readily accessible and searchable format for researchers to audit their model organism of choice: http://accessory.crispr.dk.
Sustained release and pharmacologic effects of human glucagon-like peptide-1 and liraglutide from polymeric microparticles
Authors: Icart Luis Peña , Gomes de Souza Fernando , Lima Luís Maurício T. R. 
Published: February 2018

AbstractThe GLP-1 class of peptide agonists has been shown to exert regulatory key roles in both diabetes, obesity and related complications. Given the short half-life of GLP-1 its use has been historically discouraged. We developed polymeric microparticles loaded with either human GLP-1 (7-37) or liraglutide peptides by double emulsion and solvent evaporation approach. The size distribution of all formulations was of about 30-50 μm. The in vitro kinetic release assays showed a sustained release of the peptides extending up to 30 to 40 days with varying profiles. Morphologic analysis demonstrated a more regular particle surface for those comprising polymers PLA, PLA-PEG and PLGA. In vivo evaluation in Swiss male mice demonstrated a similar extension of effect of decreasing in body weight gain for up to 25 days after a single subcutaneous administration of either hGLP-1 or liraglutide peptide-loaded microparticles (200 μg peptide / kg body weight) compared to controls. These demonstrate the effectiveness of hGLP-1 as a therapeutic agent in long-term, continuous release from peptide-load microparticles, and thus its plausibility as an unmodified therapeutic agent.