Project description:Vascular calcification contributes to high cardiovascular mortality in chronic kidney disease (CKD) patients. An association between the uremic toxins indoxyl sulfate (IS) and p-cresyl sulfate (PCS) and cardiovascular disease has been suggested. This study provides strong etiological evidence for indoxyl sulfate and p-cresyl sulfate as major contributors to vascular calcification in chronic kidney disease patients. Continuous exposure to indoxyl sulfate or p-cresyl sulfate in rats with chronic kidney disease promotes moderate to severe calcification in the aorta and peripheral vessels. Unbiased proteomic analyses of arterial samples coupled to functional bioinformatics annotation analysis revealed that calcification events were associated with acute phase response signaling, coagulation and glucometabolic signaling pathways, while escape from toxin-induced calcification was linked with liver X receptors and farnesoid X/liver X receptor signaling pathways. Activation of inflammation and coagulation pathways in the arterial wall plays a pivotal role in toxin-induced calcification and strongly associates with hyperglycemia and insulin resistance. These findings reveal new perspectives to establish novel therapeutic targets to prevent, halt progression or cure vascular calcification.
Project description:Exoproteomes generated from Synechococcus sp. WH7803 and Prochlorococcus sp. MIT9313 cultures grown under different nutrient, light and temperature conditions. The aim was to see how the production of the pili were affected. Exoproteomes of marine Synechococcus under different light regimes analysed by LC-MS/MS
Project description:Exoproteomes generated from Synechococcus sp. WH7803 and Prochlorococcus sp. MIT9313 cultures grown under different nutrient, light and temperature conditions. The aim was to see how the production of the pili were affected. Exoproteomes of marine Prochlorococcus under different growth regimes analysed by LC-MS/MS
Project description:Exoproteomes generated from Synechococcus sp. WH7803 and Prochlorococcus sp. MIT9313 cultures grown under different nutrient, light and temperature conditions. The aim was to see how the production of the pili were affected. Exoproteomes of marine Synechococcus under different nutrient regimes analysed by LC-MS/MS
Project description:Exoproteomes generated from Synechococcus sp. WH7803 and Prochlorococcus sp. MIT9313 cultures grown under different nutrient, light and temperature conditions. The aim was to see how the production of the pili were affected. Exoproteomes of marine Synechococcus under different nutrient limitations analysed by LC-MS/MS
Project description:Pre-mRNA splicing relies on the still poorly understood dynamic interplay between more than 150 protein components of the Spliceosome, and the steps at which splicing can be regulated remain largely unknown. Here we systematically analyze the effect of knocking down the components of the splicing machinery on alternative splicing events relevant for cell proliferation and apoptosis and use this information to reconstruct a network of functional interactions. The network accurately captures well-established physical and functional associations and identifies new, revealing remarkable regulatory potential of core spliceosomal components, related to the order and duration of their recruitment during Spliceosome assembly. In contrast with standard models of regulation at early events of splice site recognition, factors involved in catalytic activation of the Spliceosome display regulatory properties. The network also sheds light on the antagonism between hnRNP C and U2AF and on targets of anti-tumor drugs, and can be widely used to identify mechanisms of splicing regulation. RNA from 3 biological replicates of 72 hours knockdowns of human IK or SMU1 and a control set were used. Changes between the control and knockdowns were measured based on using a splice-junction array (Affymetrix HJAY).
Project description:We demonstrated that a visceral immunosuppressive tumor can influence a distant, normally-responsive tumor, located in the skin and rend it resistant to a particular immunotherapy. Examination of the transcriptome of sub-cutaneous tumors that were growing in a mouse model, in the presence or in the absence of a concomitant intra-kidney immunosuppressive tumor