Genome-Wide Mapping of DNA Methylation in Chicken

Cytosine DNA methylation is an important epigenetic modification termed as the fifth base that functions in diverse processes. Till now, the genome-wide DNA methylation maps of many organisms has been reported, such as human, Arabidopsis, rice and silkworm, but the methylation pattern of bird remains rarely studied. Here we show the genome-wide DNA methylation map of bird, using the chicken as a model organism and an immunocapturing approach followed by high-throughput sequencing. In both of the red jungle fowl and the avian broiler, DNA methylation was described separately for the liver and muscle tissue. Generally, chicken displays analogous methylation pattern with that of animals and plants. DNA methylation is enriched in the gene body regions and the repetitive sequences, and depleted in the transcription start site (TSS) and the transcription termination site (TTS). Most of the CpG islands in the chicken genome are kept in unmethylated state. Promoter methylation is negatively correlated with the gene expression level, indicating its suppressive role in regulating gene transcription. This work contributes to our understanding of epigenetics in birds

SNAP-tagged Chikungunya Virus Replicons Improve Visualisation of Non-Structural Protein 3 by Fluorescence Microscopy

Chikungunya virus (CHIKV), a mosquito-borne alphavirus, causes febrile disease, muscle and joint pain, which can become chronic in some individuals. The non-structural protein 3 (nsP3) plays essential roles during infection, but a complete understanding of its function is lacking. Here we used a microscopy-based approach to image CHIKV nsP3 inside human cells. The SNAP system consists of a self-labelling enzyme tag, which catalyses the covalent linking of exogenously supplemented synthetic ligands. Genetic insertion of this tag resulted in viable replicons and specific labelling while preserving the effect of nsP3 on stress granule responses and co-localisation with GTPase Activating Protein (SH3 domain) Binding Proteins (G3BPs). With sub-diffraction, three-dimensional, optical imaging, we visualised nsP3-positive structures with variable density and morphology, including high-density rod-like structures, large spherical granules, and small, low-density structures. Next, we confirmed the utility of the SNAP tag for studying protein turnover by pulse-chase labelling. We also revealed an association of nsP3 with cellular lipid droplets and examined the spatial relationships between nsP3 and the non-structural protein 1 (nsP1). Together, our study provides a sensitive, specific, and versatile system for fundamental research into the individual functions of a viral non-structural protein during infection with a medically important arthropod-borne virus (arbovirus)

Hypermethylation of Tumor Suppressor Genes Involved in Critical Regulatory Pathways for Developing a Blood-Based Test in Breast Cancer

Aberrant DNA methylation patterns might be used as a biomarker for diagnosis and management of cancer patients

Discovering Cooperative Relationships of Chromatin Modifications in Human T Cells Based on a Proposed Closeness Measure

BACKGROUND: Eukaryotic transcription is accompanied by combinatorial chromatin modifications that serve as functional epigenetic markers. Composition of chromatin modifications specifies histone codes that regulate the associated gene. Discovering novel chromatin regulatory relationships are of general interest. METHODOLOGY/PRINCIPAL FINDINGS: Based on the premise that the interaction of chromatin modifications is hypothesized to influence CpG methylation, we present a closeness measure to characterize the regulatory interactions of epigenomic features. The closeness measure is applied to genome-wide CpG methylation and histone modification datasets in human CD4+T cells to select a subset of potential features. To uncover epigenomic and genomic patterns, CpG loci are clustered into nine modules associated with distinct chromatin and genomic signatures based on terms of biological function. We then performed Bayesian network inference to uncover inherent regulatory relationships from the feature selected closeness measure profile and all nine module-specific profiles respectively. The global and module-specific network exhibits topological proximity and modularity. We found that the regulatory patterns of chromatin modifications differ significantly across modules and that distinct patterns are related to specific transcriptional levels and biological function. DNA methylation and genomic features are found to have little regulatory function. The regulatory relationships were partly validated by literature reviews. We also used partial correlation analysis in other cells to verify novel regulatory relationships. CONCLUSIONS/SIGNIFICANCE: The interactions among chromatin modifications and genomic elements characterized by a closeness measure help elucidate cooperative patterns of chromatin modification in transcriptional regulation and help decipher complex histone codes

Predicting climate change using response theory: global averages and spatial patterns

The provision of accurate methods for predicting the climate response to anthropogenic and natural forcings is a key contemporary scientific challenge. Using a simplified and efficient open-source general circulation model of the atmosphere featuring O(105105) degrees of freedom, we show how it is possible to approach such a problem using nonequilibrium statistical mechanics. Response theory allows one to practically compute the time-dependent measure supported on the pullback attractor of the climate system, whose dynamics is non-autonomous as a result of time-dependent forcings. We propose a simple yet efficient method for predicting—at any lead time and in an ensemble sense—the change in climate properties resulting from increase in the concentration of CO22 using test perturbation model runs. We assess strengths and limitations of the response theory in predicting the changes in the globally averaged values of surface temperature and of the yearly total precipitation, as well as in their spatial patterns. The quality of the predictions obtained for the surface temperature fields is rather good, while in the case of precipitation a good skill is observed only for the global average. We also show how it is possible to define accurately concepts like the inertia of the climate system or to predict when climate change is detectable given a scenario of forcing. Our analysis can be extended for dealing with more complex portfolios of forcings and can be adapted to treat, in principle, any climate observable. Our conclusion is that climate change is indeed a problem that can be effectively seen through a statistical mechanical lens, and that there is great potential for optimizing the current coordinated modelling exercises run for the preparation of the subsequent reports of the Intergovernmental Panel for Climate Change

Intestinal Epithelial Serum Amyloid A Modulates Bacterial Growth In Vitro and Pro-Inflammatory Responses in Mouse Experimental Colitis

<p>Abstract</p> <p>Background</p> <p>Serum Amyloid A (SAA) is a major acute phase protein of unknown function. SAA is mostly expressed in the liver, but also in other tissues including the intestinal epithelium. SAA reportedly has anti-bacterial effects, and because inflammatory bowel diseases (IBD) result from a breakdown in homeostatic interactions between intestinal epithelia and bacteria, we hypothesized that SAA is protective during experimental colitis.</p> <p>Methods</p> <p>Intestinal SAA expression was measured in mouse and human samples. Dextran sodium sulfate (DSS) colitis was induced in SAA 1/2 double knockout (DKO) mice and in wildtype controls. Anti-bacterial effects of SAA1/2 were tested in intestinal epithelial cell lines transduced with adenoviral vectors encoding the CE/J SAA isoform or control vectors prior to exposure to live <it>Escherichia coli</it>.</p> <p>Results</p> <p>Significant levels of SAA1/SAA2 RNA and SAA protein were detected by in situ hybridization and immunohistochemistry in mouse colonic epithelium. SAA3 expression was weaker, but similarly distributed. SAA1/2 RNA was present in the ileum and colon of conventional mice and in the colon of germfree mice. Expression of SAA3 was strongly regulated by bacterial lipopolysaccharides in cultured epithelial cell lines, whereas SAA1/2 expression was constitutive and not LPS inducible. Overexpression of SAA1/2 in cultured epithelial cell lines reduced the viability of co-cultured <it>E. coli</it>. This might partially explain the observed increase in susceptibility of DKO mice to DSS colitis. SAA1/2 expression was increased in colon samples obtained from Crohn's Disease patients compared to controls.</p> <p>Conclusions</p> <p>Intestinal epithelial SAA displays bactericidal properties in vitro and could play a protective role in experimental mouse colitis. Altered expression of SAA in intestinal biopsies from Crohn's Disease patients suggests that SAA is involved in the disease process..</p

Re-examining the Unified Theory of Acceptance and Use of Technology (UTAUT): Towards a Revised Theoretical Model

YesBased on a critical review of the Unified Theory of Acceptance and Use of Technology (UTAUT), this study first formalized an alternative theoretical model for explaining the acceptance and use of information system (IS) and information technology (IT) innovations. The revised theoretical model was then empirically examined using a combination of meta-analysis and structural equation modelling (MASEM) techniques. The meta-analysis was based on 1600 observations on 21 relationships coded from 162 prior studies on IS/IT acceptance and use. The SEM analysis showed that attitude: was central to behavioural intentions and usage behaviours, partially mediated the effects of exogenous constructs on behavioural intentions, and had a direct influence on usage behaviours. A number of implications for theory and practice are derived based on the findings

Development of a core set of outcome measures for OAB treatment

© 2017, The Author(s). Introduction and hypothesis: Standardized measures enable the comparison of outcomes across providers and treatments giving valuable information for improving care quality and efficacy. The aim of this project was to define a minimum standard set of outcome measures and case-mix factors for evaluating the care of patients with overactive bladder (OAB). Methods: The International Consortium for Health Outcomes Measurement (ICHOM) convened an international working group (WG) of leading clinicians and patients to engage in a structured method for developing a core outcome set. Consensus was determined by a modified Delphi process, and discussions were supported by both literature review and patient input. Results: The standard set measures outcomes of care for adults seeking treatment for OAB, excluding residents of long-term care facilities. The WG focused on treatment outcomes identified as most important key outcome domains to patients: symptom burden and bother, physical functioning, emotional health, impact of symptoms and treatment on quality of life, and success of treatment. Demographic information and case-mix factors that may affect these outcomes were also included. Conclusions: The standardized outcome set for evaluating clinical care is appropriate for use by all health providers caring for patients with OAB, regardless of specialty or geographic location, and provides key data for quality improvement activities and research

Large herbivores may alter vegetation structure of semi-arid savannas through soil nutrient mediation

In savannas, the tree–grass balance is governed by water, nutrients, fire and herbivory, and their interactions. We studied the hypothesis that herbivores indirectly affect vegetation structure by changing the availability of soil nutrients, which, in turn, alters the competition between trees and grasses. Nine abandoned livestock holding-pen areas (kraals), enriched by dung and urine, were contrasted with nearby control sites in a semi-arid savanna. About 40 years after abandonment, kraal sites still showed high soil concentrations of inorganic N, extractable P, K, Ca and Mg compared to controls. Kraals also had a high plant production potential and offered high quality forage. The intense grazing and high herbivore dung and urine deposition rates in kraals fit the accelerated nutrient cycling model described for fertile systems elsewhere. Data of a concurrent experiment also showed that bush-cleared patches resulted in an increase in impala dung deposition, probably because impala preferred open sites to avoid predation. Kraal sites had very low tree densities compared to control sites, thus the high impala dung deposition rates here may be in part driven by the open structure of kraal sites, which may explain the persistence of nutrients in kraals. Experiments indicated that tree seedlings were increasingly constrained when competing with grasses under fertile conditions, which might explain the low tree recruitment observed in kraals. In conclusion, large herbivores may indirectly keep existing nutrient hotspots such as abandoned kraals structurally open by maintaining a high local soil fertility, which, in turn, constrains woody recruitment in a negative feedback loop. The maintenance of nutrient hotspots such as abandoned kraals by herbivores contributes to the structural heterogeneity of nutrient-poor savanna vegetation