University of Mainz

About: University of Mainz is a education organization based out in Mainz, Rheinland-Pfalz, Germany. It is known for research contribution in the topics: Population & Immune system. The organization has 37673 authors who have published 71163 publications receiving 2497880 citations. The organization is also known as: Johannes Gutenberg-Universität Mainz & Universität Mainz.

An essential role for the IL-2 receptor in Treg cell function

Abstract: Regulatory T cells (Treg cells), which have abundant expression of the interleukin 2 receptor (IL-2R), are reliant on IL-2 produced by activated T cells. This feature indicates a key role for a simple network based on the consumption of IL-2 by Treg cells in their suppressor function. However, congenital deficiency in IL-2R results in reduced expression of the Treg cell lineage-specification factor Foxp3, which has confounded experimental efforts to understand the role of IL-2R expression and signaling in the suppressor function of Treg cells. Using genetic gain- and loss-of-function approaches, we found that capture of IL-2 was dispensable for the control of CD4+ T cells but was important for limiting the activation of CD8+ T cells, and that IL-2R-dependent activation of the transcription factor STAT5 had an essential role in the suppressor function of Treg cells separable from signaling via the T cell antigen receptor.

Interleukin-18 Is a Strong Predictor of Cardiovascular Death in Stable and Unstable Angina

Abstract: Background— Interleukin (IL)-18 plays a central role in orchestrating the cytokine cascade and accelerates atherosclerosis and plaque vulnerability in animal models. However, epidemiological data evaluating the role of IL-18 levels in atherosclerosis are lacking. Methods and Results— In a prospective study of 1229 patients with documented coronary artery disease, we measured baseline serum concentrations of IL-18 and other markers of inflammation. During the follow-up period (median, 3.9 years), 95 patients died of cardiovascular causes. Median serum concentrations of IL-18 were significantly higher among patients who had a fatal cardiovascular event than among those who did not (68.4 versus 58.7 pg/mL; P<0.0001). The hazard risk ratio of future cardiovascular death increased with increasing quartiles of IL-18 (hazard risk ratio, 1.46; 95% CI 1.21 to 1.76; P for trend <0.0001). After adjustment for most potential confounders, including the strong predictor ejection fraction as well as the inflammatory var...

Activity–composition relations for the calculation of partial melting equilibria in metabasic rocks

Abstract: A set of thermodynamic models is presented that, for the first time, allows partial melting equilibria to be calculated for metabasic rocks. The models consist of new activity–composition relations combined with end-member thermodynamic properties from the Holland & Powell dataset, version 6. They allow for forward modelling in the system Na (Formula presented.) O–CaO–K (Formula presented.) O–FeO–MgO–Al (Formula presented.) O (Formula presented.) –SiO (Formula presented.) –H (Formula presented.) O–TiO (Formula presented.) –Fe (Formula presented.) O (Formula presented.). In particular, new activity–composition relations are presented for silicate melt of broadly trondhjemitic–tonalitic composition, and for augitic clinopyroxene with Si–Al mixing on the tetrahedral sites, while existing activity–composition relations for hornblende are extended to include K (Formula presented.) O and TiO (Formula presented.). Calibration of the activity–composition relations was carried out with the aim of reproducing major experimental phase-in/phase-out boundaries that define the amphibolite–granulite transition, across a range of bulk compositions, at ≤13 kbar.

TP53 mutations and hepatocellular carcinoma: insights into the etiology and pathogenesis of liver cancer

Abstract: Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide and the major risk factors include chronic infections with the hepatitis B (HBV) or C (HCV) virus, and exposure to dietary aflatoxin B(1) (AFB(1)) or alcohol consumption. Multiple genetic and epigenetic changes are involved in the molecular pathogenesis of HCC, for example, somatic mutations in the p53 tumor suppressor gene (TP53) and the activation of the WNT signal transduction pathway. AFB(1) frequently induces G:C to T:A transversions at the third base in codon 249 of TP53 and cooperates with HBV in causing p53 mutations in HCC. The detection of TP53 mutant DNA in plasma is a biomarker of both AFB(1) exposure and HCC risk. Chronic infection with HBV and HCV viruses, and oxyradical disorders including hemochromatosis, also generate reactive oxygen/nitrogen species that can both damage DNA and mutate cancer-related genes such as TP53. Certain mutant p53 proteins may exhibit a 'gain of oncogenic function'. The p53 biological network is a key responder to this oxidative and nitrosative stress. Depending on the extent of the DNA damage, p53 regulates the transcription of protective antioxidant genes and with extensive DNA damage, transactivates pro-oxidant genes that contribute to apoptosis. The X gene of HBV (HBx) is the most common open reading frame integrated into the host genome in HCC and the integrated HBx is frequently mutated. Mutant HBx proteins still retain their ability to bind to p53, and attenuate DNA repair and p53-mediated apoptosis. In summary, both viruses and chemicals are implicated in the etiology of TP53 mutations during the molecular pathogenesis of HCC.