Author Correction: The future of Blue Carbon science.

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Obesity related methylation changes in DNA of peripheral blood leukocytes

<p>Abstract</p> <p>Background</p> <p>Despite evidence linking obesity to impaired immune function, little is known about the specific mechanisms. Because of emerging evidence that immune responses are epigenetically regulated, we hypothesized that DNA methylation changes are involved in obesity induced immune dysfunction and aimed to identify these changes.</p> <p>Method</p> <p>We conducted a genome wide methylation analysis on seven obese cases and seven lean controls aged 14 to 18 years from extreme ends of the obesity distribution and performed further validation of six CpG sites from six genes in 46 obese cases and 46 lean controls aged 14 to 30 years.</p> <p>Results</p> <p>In comparison with the lean controls, we observed one CpG site in the UBASH3A gene showing higher methylation levels and one CpG site in the TRIM3 gene showing lower methylation levels in the obese cases in both the genome wide step (<it>P </it>= 5 × 10^-6and <it>P </it>= 2 × 10^-5for the UBASH3A and the TRIM3 gene respectively) and the validation step (<it>P </it>= 0.008 and <it>P </it>= 0.001 for the UBASH3A and the TRIM3 gene respectively).</p> <p>Conclusions</p> <p>Our results provide evidence that obesity is associated with methylation changes in blood leukocyte DNA. Further studies are warranted to determine the causal direction of this relationship as well as whether such methylation changes can lead to immune dysfunction.</p> <p>See commentary: <url>http://www.biomedcentral.com/1741-7015/8/88/abstract</url></p

Basal LAT-diacylglycerol-RasGRP1 Signals in T Cells Maintain TCRα Gene Expression

In contrast to the well-characterized T cell receptor (TCR) signaling pathways that induce genes that drive T cell development or polarization of naïve CD4 T cells into the diverse TH1, TH2, TH17 and Treg lineages, it is unclear what signals maintain specific gene expression in mature resting T cells. Resting T cells residing in peripheral lymphoid organs exhibit low-level constitutive signaling. Whereas tonic signals in B cells are known to be critical for survival, the roles of tonic signals in peripheral T cells are unknown. Here we demonstrate that constitutive signals in Jurkat T cell lines are transduced via the adapter molecule LAT and the Ras exchange factor RasGRP1 to maintain expression of TCRα mRNA and surface expression of the TCR/CD3 complex. Independent approaches of reducing basal activity through the LAT-diacylglycerol-RasGRP pathway led to reduced constitutive Ras-MEK-ERK signals and decreased TCRα mRNA and surface TCR expression in Jurkat cells. However, loss of TCR expression takes several days in these cell line experiments. In agreement with these in vitro approaches, inducible deletion of Lat in vivo results in reduced TCRα mRNA- and surface TCR- expression in a delayed temporal manner as well. Lastly, we demonstrate that loss of basal LAT-RasGRP signals appears to lead to silencing or repression of TCRα transcription. We postulate that basal LAT-diacylglycerol-RasGRP signals fulfill a regulatory function in peripheral T lymphocytes by maintaining proper gene expression programs

Monotone and near-monotone biochemical networks

Monotone subsystems have appealing properties as components of larger networks, since they exhibit robust dynamical stability and predictability of responses to perturbations. This suggests that natural biological systems may have evolved to be, if not monotone, at least close to monotone in the sense of being decomposable into a “small” number of monotone components, In addition, recent research has shown that much insight can be attained from decomposing networks into monotone subsystems and the analysis of the resulting interconnections using tools from control theory. This paper provides an expository introduction to monotone systems and their interconnections, describing the basic concepts and some of the main mathematical results in a largely informal fashion

Analysis of the human monocyte-derived macrophage transcriptome and response to lipopolysaccharide provides new insights into genetic aetiology of inflammatory bowel disease

The FANTOM5 consortium utilised cap analysis of gene expression (CAGE) to provide an unprecedented insight into transcriptional regulation in human cells and tissues. In the current study, we have used CAGE-based transcriptional profiling on an extended dense time course of the response of human monocyte-derived macrophages grown in macrophage colony-stimulating factor (CSF1) to bacterial lipopolysaccharide (LPS). We propose that this system provides a model for the differentiation and adaptation of monocytes entering the intestinal lamina propria. The response to LPS is shown to be a cascade of successive waves of transient gene expression extending over at least 48 hours, with hundreds of positive and negative regulatory loops. Promoter analysis using motif activity response analysis (MARA) identified some of the transcription factors likely to be responsible for the temporal profile of transcriptional activation. Each LPS-inducible locus was associated with multiple inducible enhancers, and in each case, transient eRNA transcription at multiple sites detected by CAGE preceded the appearance of promoter-associated transcripts. LPS-inducible long non-coding RNAs were commonly associated with clusters of inducible enhancers. We used these data to re-examine the hundreds of loci associated with susceptibility to inflammatory bowel disease (IBD) in genome-wide association studies. Loci associated with IBD were strongly and specifically (relative to rheumatoid arthritis and unrelated traits) enriched for promoters that were regulated in monocyte differentiation or activation. Amongst previously-identified IBD susceptibility loci, the vast majority contained at least one promoter that was regulated in CSF1-dependent monocyte-macrophage transitions and/or in response to LPS. On this basis, we concluded that IBD loci are strongly-enriched for monocyte-specific genes, and identified at least 134 additional candidate genes associated with IBD susceptibility from reanalysis of published GWA studies. We propose that dysregulation of monocyte adaptation to the environment of the gastrointestinal mucosa is the key process leading to inflammatory bowel disease

Molecular marks for epigenetic identification of developmental and cancer stem cells

Epigenetic regulations of genes by reversible methylation of DNA (at the carbon-5 of cytosine) and numerous reversible modifications of histones play important roles in normal physiology and development, and epigenetic deregulations are associated with developmental disorders and various disease states, including cancer. Stem cells have the capacity to self-renew indefinitely. Similar to stem cells, some malignant cells have the capacity to divide indefinitely and are referred to as cancer stem cells. In recent times, direct correlation between epigenetic modifications and reprogramming of stem cell and cancer stem cell is emerging. Major discoveries were made with investigations on reprogramming gene products, also known as master regulators of totipotency and inducer of pluoripotency, namely, OCT4, NANOG, cMYC, SOX2, Klf4, and LIN28. The challenge to induce pluripotency is the insertion of four reprogramming genes (Oct4, Sox2, Klf4, and c-Myc) into the genome. There are always risks of silencing of these genes by epigenetic modifications in the host cells, particularly, when introduced through retroviral techniques. In this contribution, we will discuss some of the major discoveries on epigenetic modifications within the chromatin of various genes associated with cancer progression and cancer stem cells in comparison to normal development of stem cell. These modifications may be considered as molecular signatures for predicting disorders of development and for identifying disease states

IBD: IBD and spondyloarthritis: Joint management

Spondyloarthritis (SpA) is the most common extraintestinal manifestation of IBD. SpA symptoms are not always recognized in patients with IBD. Subsequently, patients with symptoms of SpA can be underdiagnosed with effective treatment delayed. Cooperation between gastroenterologists and rheumathologists is necessary and, ideally, an integrated management of these patients should be adopted

The role of agricultural cooperatives in sustaining the wheat diversity and productivity: the case of southern Italy

We hypothesize that institutions such as agricultural cooperatives influence regional levels of variety diversity through input supply, processing or marketing functions. This diversity can also affect yield, a partial measure of crop productivity. We test these hypotheses with data from southern Italy, a mega-diversity spot and centre of diversity for durum wheat. Cooperatives in the southern regions of Italy process farmers’ harvests of durum wheat into bread, label it, and sell it locally. In this relatively marginalized region of the country, cooperatives enable farmers to capture more of the value of the final product and reduce marketing costs. To test the hypothesis, we apply a two-stage estimation approach with a Cobb-Douglas production function and panel data analysis. Findings suggest that the density of cooperatives in a region is associated with greater spatial diversity in wheat varieties grown, and that, over a 14-year period, this diversity positively affected crop yields