Renin, endothelial no synthase and endothelin gene expression in the 2Kidney-1clip goldblatt model of long-term renovascular hypertension

<p>Abstract</p> <p>Objective</p> <p>Numerous reports have shown the influence of renin, nitric oxide (NO) and the endothelin (ET) systems for regulation of blood pressure and renal function. Furthermore, interactions between these peptides have been reported. Aim of our study was to investigate the relative contribution of these compounds in long-term renovascular hypertension/renal ischemia.</p> <p>Methods</p> <p>Hypertension/left-sided renal ischemia was induced using the 2K1C-Goldblatt rat model. Renal renin, ET-1, ET-3 and endothelial NO synthase (eNOS) gene expression was measured by means of RNAse protection assay at different timepoints up to 10 weeks after induction of renal artery stenosis.</p> <p>Results</p> <p>Plasma renin activity and renal renin gene expression in the left kidney were increased in the clipped animals while eNOS expression was unchanged. Furthermore, an increase in ET-1 expression and a decrease of ET-3 expression was detected in early stenosis.</p> <p>Conclusions</p> <p>While renin is obviously involved in regulation of blood pressure and renal function in unilateral renal artery stenosis, ET-1, ET-3 and endothelium derived NO do not appear to play an important role in renal adaptation processes in long-term renal artery stenosis, although ET-1 and ET-3 might be involved in short-term adaptation processes.</p

Bad news from Fallujah

This study uses the thematic analysis developed by the Glasgow University Media Group to explore how the US, UK and German national press covered the US/Coalition assault on the Iraqi city of Fallujah in November 2004. The study relies on quantitative and qualitative full text content analyses to assess 428 news, editorial and commentary items. The article suggests that, while government and military officials of the US/Coalition had argued the military ‘operation’ was necessary to secure Iraq and defeat an ‘insurgency’, organisations and actors from Iraqi society refer to the ‘operation’ as ‘collective punishment’ and a ‘massacre’ that targeted the Iraqi population. The article investigates how the press represented each of these perspectives. The findings suggest that the press overemphasised the US/Coalition perspective despite striking counter evidence. Critical aspects of coverage largely focused on tactical elements of the military dimension of the event. The article concludes that such findings are in accord with hegemonic models of media performance

Students' Models of Newton's Second Law in Mechanics and Electromagnetism

We investigated students' use of Newton's second law in mechanics and electromagnetism contexts by interviewing students in a two-semester calculus-based physics course. We observed that students' responses are consistent with three mental models. These models appeard in mechanics contexts and were transferred to electromagnetism contexts. We developed an inventory to help instructors identify these models and direct students towards the correct one.Comment: 15 pages, 3 figues and 4 table

MVA-infected dendritic cells present CD4⁺ T-cell epitopes by endogenous MHC class II presentation pathways.

CD4+ T-lymphocytes play a central role in the immune system and mediate their function after recognition of their respective antigens presented on MHCII molecules on antigen presenting cells (APCs). Conventionally, phagocytosed antigens are loaded on MHCII for stimulation of CD4+ T-cells. Certain epitopes, however, can be directly processed from intracellular antigens and are presented on MHCII (endogenous MHCII presentation). Here we characterized the MHCII antigen presentation pathways being possibly involved in the immune response upon vaccination with MVA (modified vaccinia virus Ankara), a promising live viral vaccine vector. We established CD4+ T-cell lines specific for MVA-derived epitopes as tools for in vitro analysis of MHCII antigen processing and presentation in MVA-infected APCs. We provide evidence that infected APCs are able to directly transfer endogenous viral proteins into the MHCII pathway to efficiently activate CD4+ T-cells. By using knockout mice and chemical inhibitory compounds we further elucidate the molecular basis showing that among the various subcellular pathways investigated proteasomes and autophagy are key players in the endogenous MHCII presentation during MVA infection. Interestingly, although proteasomal processing plays an important role neither TAP nor LAMP-2 were found to be involved in the peptide transport. Defining the molecular mechanism of MHCII presentation during MVA infection provides a basis to improve MVA-based vaccination strategies aiming for enhanced CD4+ T-cell activation by targeting antigens into the responsible pathways. IMPORTANCE STATEMENT: This work contributes significantly to our understanding of the immunogenic properties of pathogens by deciphering antigen processing pathways contributing to efficient activation of antigen-specific CD4+ T-cells. We identified autophagosome formation, proteasomal activity and lysosomal integrity to be crucial for endogenous CD4+ T-cell activation. Since poxvirus vectors such as MVA are already used in clinical trials as recombinant vaccines, the data provide important information for the future design of optimized poxviral vaccines for the study of advanced immunotherapy options

Distinct Signal Transduction Pathways Downstream of the (P)RR Revealed by Microarray and ChIP-chip Analyses

The (pro)renin receptor ((P)RR) signaling is involved in different pathophysiologies ranging from cardiorenal end-organ damage via diabetic retinopathy to tumorigenesis. We have previously shown that the transcription factor promyelocytic leukemia zinc finger (PLZF) is an adaptor protein of the (P)RR. Furthermore, recent publications suggest that major functions of the (P)RR are mediated ligand-independently by its transmembrane and intracellular part, which acts as an accessory protein of V-ATPases. The transcriptome and recruitmentome downstream of the V-ATPase function and PLZF in the context of the (P)RR are currently unknown. Therefore, we performed a set of microarray and chromatin-immunoprecipitation (ChIP)-chip experiments using siRNA against the (P)RR, stable overexpression of PLZF, the PLZF translocation inhibitor genistein and the specific V-ATPase inhibitor bafilomycin to dissect transcriptional pathways downstream of the (P)RR. We were able to identify distinct and overlapping genetic signatures as well as novel real-time PCR-validated target genes of the different molecular functions of the (P)RR. Moreover, bioinformatic analyses of our data confirm the role of (P)R?s signal transduction pathways in cardiovascular disease and tumorigenesis