A model-based study delineating the roles of the two signaling branches of Saccharomyces cerevisiae, Sho1 and Sln1, during adaptation to osmotic stress.

Adaptation to osmotic shock in Saccharomyces cerevisiae is brought about by the activation of two independent signaling pathways, Sho1 and Sln1, which in turn trigger the high osmolarity glycerol (HOG) pathway. The HOG pathway thereby activates the transcription of Gpd1p, an enzyme necessary to synthesize glycerol. The production of glycerol brings about a change in the intracellular osmolarity leading to adaptation. We present a detailed mechanistic model for the response of the yeast to hyperosmotic shock. The model integrates the two branches, Sho1 and Sln1, of the HOG pathway and also includes the mitogen-activated protein kinase cascade, gene regulation and metabolism. Model simulations are consistent with known experimental results for wild-type strain, and Ste11Delta and Ssk1Delta mutant strains subjected to osmotic stress. Simulation results predict that both the branches contribute to the overall wild-type response for moderate osmotic shock, while under severe osmotic shock, the cell responds mainly through the Sln1 branch. The analysis shows that the Sln1 branch helps the cell in preventing cross-talk to other signaling pathways by inhibiting ste11ste50 activation and also by increasing the phosphorylation of Ste50. We show that the negative feedbacks to the Sho1 branch must be faster than those to the Sln1 branch to simultaneously achieve pathway specificity and adaptation during hyperosmotic shock. Sensitivity analysis revealed that the presence of both branches imparts robust behavior to the cell under osmoadaptation to perturbations.

Peripheral arterial revascularization causing parallel increased activity of pro- and anti-inflammatory mediators.

AIM: The aim of this study was to investigate the interaction between the proinflammatory mediator interleukin (IL)-6 and anti-inflammatory mediator IL-10 in ischemia reperfusion injury following peripheral arterial revascularization. METHODS: Three groups of patients were recruited (group 1: femoral angiography alone [n=14]; group 2: radiologically successful ilio/femoral angioplasty [n=10]; and group 3: peripheral surgical bypass [n=11]). Peripheral venous blood obtained for all patients at pre-procedure and at 1 h and 24 h post-procedure. After centrifugation supernatant plasma was separated and analysed for proinflammatory cytokine IL-6 and anti-inflammatory cytokine IL-10 using enzyme linked immunosorbent assay (ELISA) technique. RESULTS: Levels of IL-6 at 1 and 24 h were significantly higher in group 3 (P<0.05 and P<0.01, respectively) and at 24 h in group 2 as compared to group 1 (P<0.05). Levels of IL-10 were significantly higher in group 3 at 24 h (P<0.05). In group 2 levels of IL-10 higher than group 1, but this did not reach statistical significance (P=0.07). CONCLUSIONS: Raised levels of IL-6 at 1 and 24 h in patients undergoing operative peripheral bypass suggest early and persistent proinflammatory activity, similarly patients with successful angioplasty also demonstrated similar persistent proinflammatory activity of IL-6 at 24 h. Raised levels of IL-10 at 24 h represents anti-inflammatory properties of IL-10 counter acting inflammatory response.

Submucous lipoma of the ileocaecal valve presenting as caecal volvulus.

Caecal volvulus is a well described but unusual condition. We report here, a case of caecal volvulus in a 53-year-old Caucasian woman associated with intussuscepted submucous lipoma of the ileocaecal region. The imaging and pathology are presented. Submucous lipoma of the ileocaecal region is uncommon but well described. It can be mistaken as carcinoma of the ascending colon on barium enema and on computed tomography scan. The combination with caecal volvulus is a rare occurrence.