Dnmt2-dependent methylomes lack defined DNA methylation patterns

Several organisms have retained methyltransferase 2 (Dnmt2) as their only candidate DNA methyltransferase gene. However, information about Dnmt2-dependent methylation patterns has been limited to a few isolated loci and the results have been discussed controversially. In addition, recent studies have shown that Dnmt2 functions as a tRNA methyltransferase, which raised the possibility that Dnmt2-only genomes might be unmethylated. We have now used whole-genome bisulfite sequencing to analyze the methylomes of Dnmt2-only organisms at single-base resolution. Our results show that the genomes of Schistosoma mansoni and Drosophila melanogaster lack detectable DNA methylation patterns. Residual unconverted cytosine residues shared many attributes with bisulfite deamination artifacts and were observed at comparable levels in Dnmt2-deficient flies. Furthermore, genetically modified Dnmt2-only mouse embryonic stem cells lost the DNA methylation patterns found in wild-type cells. Our results thus uncover fundamental differences among animal methylomes and suggest that DNA methylation is dispensable for a considerable number of eukaryotic organisms

Divergencia en la Organización de la Industria Cárnica: un Análisis Comparativo de Estados Unidos y Chile.

This study compares the beef, pork and poultry sectors of the United States and Chile to identify similarities and differences in patterns of industrial organization (concentration and mechanisms of vertical integration). The principal determinants of organizational structures are discussed. The similarities found in the sectors of both countries can be explained in terms of market imperfections, production technology, transaction costs and principal-agent theory. Nevertheless, important differences exist between the two countries, especially with respect to mechanisms of vertical control. To explain these differences it is necessary to consider the peculiarities of each country’s economic and institutional environments, factors that to date have been infrequently examined in the literature relevant to the sectors.Este estudio compara la organización industrial de los sectores productores de vacunos, cerdos y aves de los Estados Unidos y Chile, con objeto de identificar similitudes y diferencias en los patrones de organización industrial (concentración y mecanismos de coordinación vertical). Luego, se discuten los principales determinantes de dicha organización. Las similitudes encontradas entre los países y sectores considerados pueden ser explicadas a través de conceptos y modelos tales como imperfecciones de mercado, tecnologías de producción, costos de transacción y teoría de agencia. Sin embargo, existen importantes diferencias en la organización de las industrias de Chile y Estados Unidos, especialmente respecto a los mecanismos de coordinación vertical. Para explicar estas diferencias es necesario considerar las particularidades en el ambiente económico e institucional, variables que hasta la fecha han sido escasamente consideradas por la literatura especializada

Sovereign Default, International Lending and Trade

This paper sheds new light on the “trade costs” of sovereign default. It argues that the decline in trade in the wake of sovereign debt crises documented in earlier studies is the result of a reduction in exporters’ access to foreign credit. Using an annual panel of 28 industries in 100 countries between 1980 and 2007, it shows that default leads to a stronger contraction in the exports of sectors which are more dependent on external financing, consistent with this hypothesis. This finding is robust across different econometric specifications, and of economically significant magnitude. It suggests that any impact of sovereign default on trade, rather than a cost of default in its own right, may be a symptom of reduced access to international capital markets

Climate Vulnerability and the Cost of Debt

We use indices from the Notre Dame Global Adaptation Initiative to investigate the impact of climate vulnerability on bond yields. Our methodology invokes panel ordinary least squares with robust standard errors and principal component analysis. The latter serves to address the multicollinearity between a set of vulnerability measures. We find that countries with higher exposure to climate vulnerability, such as the member countries of the V20 climate vulnerable forum, exhibit 1.174 percent higher cost of debt on average. This effect is significant after accounting for a set of macroeconomic controls. Specifically, we estimate the incremental debt cost due to higher climate vulnerability, for the V20 countries, to have exceeded USD 62 billion over the last ten years. In other words, for every ten dollars they pay in interest cost, they pay another dollar for being climate vulnerable. We also find that a measure of social readiness, which includes education and infrastructure, has a negative and significant effect on bond yields, implying that social and physical investments can mitigate climate risk related debt costs and help to stabilize the cost of debt for vulnerable countries

The effect of cigarette smoke exposure on the development of inflammation in lungs, gut and joints of TNFΔARE mice

The inflammatory cytokine TNF-alpha is a central mediator in many immune-mediated diseases, such as Crohn's disease (CD), spondyloarthritis (SpA) and chronic obstructive pulmonary disease (COPD). Epidemiologic studies have shown that cigarette smoking (CS) is a prominent common risk factor in these TNF-dependent diseases. We exposed TNF Delta ARE mice; in which a systemic TNF-alpha overexpression leads to the development of inflammation; to 2 or 4 weeks of air or CS. We investigated the effect of deregulated TNF expression on CS-induced pulmonary inflammation and the effect of CS exposure on the initiation and progression of gut and joint inflammation. Upon 2 weeks of CS exposure, inflammation in lungs of TNF Delta ARE mice was significantly aggravated. However, upon 4 weeks of CS-exposure, this aggravation was no longer observed. TNF Delta ARE mice have no increases in CD4+ and CD8+ T cells and a diminished neutrophil response in the lungs after 4 weeks of CS exposure. In the gut and joints of TNF Delta ARE mice, 2 or 4 weeks of CS exposure did not modulate the development of inflammation. In conclusion, CS exposure does not modulate gut and joint inflammation in TNF Delta ARE mice. The lung responses towards CS in TNF Delta ARE mice however depend on the duration of CS exposure

Interleukin-10 enhances the intestinal epithelial barrier in the presence of corticosteroids through p38 MAPK activity in Caco-2 monolayers : a possible mechanism for steroid responsiveness in ulcerative colitis

Altres ajuts: 2012 Spanish Gastroenterological Association i CIBER G0034Glucocorticosteroids are the first line therapy for moderate-severe flare-ups of ulcerative colitis. Despite that, up to 60% of patients do not respond adequately to steroid treatment. Previously, we reported that low IL-10 mRNA levels in intestine are associated with a poor response to glucocorticoids in active Crohn's disease. Here, we test whether IL-10 can favour the response to glucocorticoids by improving the TNFα-induced intestinal barrier damage (assessed by transepithelial electrical resistance) in Caco-2 monolayers, and their possible implications on glucocorticoid responsiveness in active ulcerative colitis. We show that the association of IL-10 and glucocorticoids improves the integrity of TNFα-treated Caco-2 cells and that p38 MAPK plays a key role. In vitro, IL-10 facilitates the nuclear translocation of p38 MAPK-phosphorylated thereby modulating glucocorticoids-receptor-α, IL-10-receptor-α and desmoglein-2 expression. In glucocorticoids-refractory patients, p38 MAPK phosphorylation and membrane desmoglein-2 expression are reduced in colonic epithelial cells. These results suggest that p38 MAPK-mediated synergism between IL-10 and glucocorticoids improves desmosome straightness contributing to the recovery of intestinal epithelium and reducing luminal antigens contact with lamina propria in ulcerative colitis. This study highlights the link between the intestinal epithelium in glucocorticoids-response in ulcerative colitis

Influence of grape rot on the contents of sulfur binding compounds in wine after automated optical grape sorting

In the last years, climate change has played an important role in some wine growing regions because of the increasing hazard of different kinds of bunch rot. Botrytis cinerea is the most important kind of rot on grapes. Beside sensory effects, this rot can influence the content of yeast nutrients, e.g. thiamine, in the must and thus affect the alcoholic fermentation. To get insight into the influence of Botrytis cinerea on the content of sulfur binding compounds formed during the fermentation process in wine, tons of grapes from the Mosel valley were sorted by an automated optical grape sorter, an innovative possibility of grape sorting, in 2011. Wine samples before sulfurisation of the four sorting fractions, namely control (unsorted berries), free-run (juice from opened berries), positive (healthy, intact berries) and negative (rotten berries) were analysed for the sulfur-binding compounds acetaldehyde, pyruvic acid, 2-oxoglutaric acid and for bound sulfur dioxide. The results show that acetaldehyde concentrations were not affected by rot, while pyruvic acid and 2-oxoglutaric acid levels were significantly higher in the negative fractions and lower in the positive fractions. Accordingly, bound sulfur levels were significantly higher in wines from the negative fraction. In conclusion, it could be shown that fractionation of the berries can efficiently help to reduce sulfur binding compounds in wine and thus reduce the addition of sulfur dioxide

The HadGEM2-ES implementation of CMIP5 centennial simulations

The scientific understanding of the Earth's climate system, including the central question of how the climate system is likely to respond to human-induced perturbations, is comprehensively captured in GCMs and Earth System Models (ESM). Diagnosing the simulated climate response, and comparing responses across different models, is crucially dependent on transparent assumptions of how the GCM/ESM has been driven - especially because the implementation can involve subjective decisions and may differ between modelling groups performing the same experiment. This paper outlines the climate forcings and setup of the Met Office Hadley Centre ESM, HadGEM2-ES for the CMIP5 set of centennial experiments. We document the prescribed greenhouse gas concentrations, aerosol precursors, stratospheric and tropospheric ozone assumptions, as well as implementation of land-use change and natural forcings for the HadGEM2-ES historical and future experiments following the Representative Concentration Pathways. In addition, we provide details of how HadGEM2-ES ensemble members were initialised from the control run and how the palaeoclimate and AMIP experiments, as well as the "emission-driven" RCP experiments were performed.</p