Genome-wide association study identifies multiple risk loci for renal cell carcinoma

Previous genome-wide association studies (GWAS) have identified six risk loci for renal cell carcinoma (RCC). We conducted a meta-analysis of two new scans of 5,198 cases and 7,331 controls together with four existing scans, totalling 10,784 cases and 20,406 controls of European ancestry. Twenty-four loci were tested in an additional 3,182 cases and 6,301 controls. We confirm the six known RCC risk loci and identify seven new loci at 1p32.3 (rs4381241, P=3.1 × 10−10), 3p22.1 (rs67311347, P=2.5 × 10−8), 3q26.2 (rs10936602, P=8.8 × 10−9), 8p21.3 (rs2241261, P=5.8 × 10−9), 10q24.33-q25.1 (rs11813268, P=3.9 × 10−8), 11q22.3 (rs74911261, P=2.1 × 10−10) and 14q24.2 (rs4903064, P=2.2 × 10−24). Expression quantitative trait analyses suggest plausible candidate genes at these regions that may contribute to RCC susceptibility

Cell–cell and cell–matrix dynamics in intraperitoneal cancer metastasis

The peritoneal metastatic route of cancer dissemination is shared by cancers of the ovary and gastrointestinal tract. Once initiated, peritoneal metastasis typically proceeds rapidly in a feed-forward manner. Several factors contribute to this efficient progression. In peritoneal metastasis, cancer cells exfoliate into the peritoneal fluid and spread locally, transported by peritoneal fluid. Inflammatory cytokines released by tumor and immune cells compromise the protective, anti-adhesive mesothelial cell layer that lines the peritoneal cavity, exposing the underlying extracellular matrix to which cancer cells readily attach. The peritoneum is further rendered receptive to metastatic implantation and growth by myofibroblastic cell behaviors also stimulated by inflammatory cytokines. Individual cancer cells suspended in peritoneal fluid can aggregate to form multicellular spheroids. This cellular arrangement imparts resistance to anoikis, apoptosis, and chemotherapeutics. Emerging evidence indicates that compact spheroid formation is preferentially accomplished by cancer cells with high invasive capacity and contractile behaviors. This review focuses on the pathological alterations to the peritoneum and the properties of cancer cells that in combination drive peritoneal metastasis

The regulation of brain states by neuroactive substances distributed via the cerebrospinal fluid; a review.

Contains fulltext : 83842.pdf (publisher's version ) (Open Access)The cerebrospinal fluid (CSF) system provides nutrients to and removes waste products from the brain. Recent findings suggest, however, that in addition, the CSF contains message molecules in the form of actively released neuroactive substances. The concentrations of these vary between locations, suggesting they are important for the changes in brain activity that underlie different brain states, and induce different sensory input and behavioral output relationships.The cranial CSF displays a rapid caudally-directed ventricular flow followed by a slower rostrally-directed subarachnoid flow (mainly towards the cribriform plate and from there into the nasal lymphatics). Thus, many brain areas are exposed to and can be influenced by substances contained in the CSF. In this review we discuss the production and flow of the CSF, including the mechanisms involved in the regulation of its composition. In addition, the available evidence for the release of neuropeptides and other neuroactive substances into the CSF is reviewed, with particular attention to the selective effects of these on distant downstream receptive brain areas. As a conclusion we suggest that (1) the flowing CSF is involved in more than just nutrient and waste control, but is also used as a broadcasting system consisting of coordinated messages to a variety of nearby and distant brain areas; (2) this special form of volume transmission underlies changes in behavioral states

Dietary flavanol intervention lowers the levels of endothelial microparticles in coronary artery disease patients

Current evidence suggests that regenerative v. degenerative endothelial responses can be integrated in a clinical endothelial phenotype, reflecting the net result between damage from risk factors and endogenous repair capacity. We have previously shown that a cocoa flavanol (CF) intervention can improve endothelial function and increase the regenerative capacity of the endothelium by mobilising circulating angiogenic cells in patients with coronary artery disease (CAD). The aim of the present study was to investigate whether CF can lower the levels of circulating endothelial microparticles (EMP), markers of endothelial integrity, along with improvements in endothelial function. The levels of EMP in the frozen plasma samples of CAD patients were measured along with endothelial function (flow-mediated vasodilation, FMD); n 16, FMD data published previously), and these data were compared with those of young (n 12) and age-matched (n 12) healthy control subjects. The CAD patients exhibited significantly increased levels of EMP along with impaired FMD when compared with the healthy control subjects. The levels of CD144+ and CD31+/41- EMP were inversely correlated with FMD (r - 0·67, P= 0·01 and r - 0·59, P= 0·01, respectively). In these CAD patients, the levels of EMP were measured after they had consumed a drink containing 375 mg of CF (high-CF intervention, HiFI) or 9 mg of CF (macro- and micronutrient-matched low-CF control, LoFl) twice daily over a 30-d period in a randomised, double-blind, cross-over study. After 1 month of HiFI, the levels of CD31+/41- and CD144+ EMP decreased ( - 25 and - 23 %, respectively), but not after LoFl. Our data show that flavanols lower the levels of EMP along with higher endothelial function, lending evidence to the novel concept that flavanols may improve endothelial integrity. Copyright © The Authors 2013

Sialic acids are absent from the dermatophytes Trichophyton mentagrophytes and Trichophyton rubrum

Experiments were performed to determine whether sialic acids are expressed in two dermatophytes: Trichophyton rubrum and T. mentagrophytes, similarly to other fungal pathogens. Chemical extraction of mycelia and microconidia followed by high-performance thin-layer chromatography and colorimetric assays were all negative for sialic acid. Incubation of dermatophytes in the presence of Limax flavus agglutinin, specific for sialic acid, was negative in a fluorescence staining test. We have also used other lectins that bind to sialic acid and/or other sugar residues, and these ligands coupled to fluorescein strongly stained these fungi. Such fluorescence staining was not abolished or reduced when fungi were pretreated with sialidase. Different strains of influenza virus which recognize sialic acid residues were also used, but no agglutination of the dermatophytes was observed. Based on these methods, which successfully revealed the presence of sialic acids in other fungal pathogens, we show that these monosaccharides do not occur in both dermatophyte species. Thus, sialic acids do not seem to play a role in the pathogenicity of these fungi.Univ Fed Rio de Janeiro, Inst Biofis Carlos Chagas Filho, Lab Biol Celular Fungos, CCS, BR-21949970 Rio de Janeiro, BrazilUniv Fed Rio de Janeiro, Inst Microbiol Prof Paulo de Goes, Rio de Janeiro, BrazilUniversidade Federal de São Paulo, Disciplina Biol Celular, São Paulo, BrazilUniv Kiel, Inst Biochem, D-2300 Kiel, GermanyUniversidade Federal de São Paulo, Disciplina Biol Celular, São Paulo, BrazilWeb of Scienc