Docking suggested possible interactions at the 2′ and 6′ pore-lining residues, and mutagenesis of these residues supports this hypothesis for alpha-endosulfan. A selection of compounds that act at Cys-loop and other receptors also showed some efficacy PKC412 at blocking ELIC responses, but most were of low potency (IC50 > 100 mu M). Overall our data show that a number of compounds can inhibit ELIC, but it has limited pharmacological similarity to GLIC and to Cys-loop receptors. (C) 2012 Elsevier Ltd. All rights reserved.”
“Natural killer (NK) cells are central players

in the vertebrate immune system that rapidly eliminate malignantly transformed or infected cells. The natural cytotoxicity receptors (NCRs) NKp30, NKp44, and NKp46 are important mediators of NK cell cytotoxicity, which trigger an immune response on recognition of cognate cellular and viral ligands. Tumour and

viral immune escape strategies targeting these receptor-ligand systems impair NK cell cytotoxicity and promote disease. Therefore, a molecular understanding of the function of the NCRs in immunosurveillance is instrumental to discovering novel access points to combat infections and cancer.”
“Bladder cancer (BLCa) is a severe urological cancer of both men and women that commonly recurs and once invasive, is difficult to treat. MINA-05 (CK Life Sciences Int’l, Hong Kong) is a derivative of complex botanical extracts, shown to reduce cellular proliferation of bladder and prostate carcinomas. We tested the effects of MINA-05 against human AZD8931 research buy BLCa cell sublines, Bay 11-7085 B8, B8-RSP-GCK, B8-RSP-LN and C3, from a transitional cell carcinoma, grade IV, to determine the molecular targets of treatment by observing the cellular protein profile. Cells were acclimatised for 48

h then treated for 72 h with concentrations of MINA-05 reflecting 1/2 IC(50), IC(50) and 2 x IC(50) (n = 3) or with vehicle, (0.5% DMSO). Dose-dependant changes in protein abundance were detected and characterised using 2-dimensional electrophoresis and MS. We identified 10 proteins that underwent changes in abundance, pI and/or molecular mass in response to treatment. MINA-05 was shown to influence proteins across numerous functional classes including cytoskeletal proteins, energy metabolism proteins, protein degradation proteins and tumour suppressors, suggesting a global impact on these cell lines. This study implies that the ability of MINA-05 to retard cellular proliferation is attributed to its ability to alter cell cycling, metabolism, protein degradation and the cancer cell environment.”
“Both laboratory and epidemiological studies published over the past two decades have identified the risk of excess hearing loss when specific chemical contaminants are present along with noise.