Thyroid cancer susceptibility polymorphisms: confirmation of loci on chromosomes 9q22 and 14q13, validation of a recessive 8q24 locus and failure to replicate a locus on 5q24

Five single nucleotide polymorphisms (SNPs) associated with thyroid cancer (TC) risk have been reported: rs2910164 (5q24); rs6983267 (8q24); rs965513 and rs1867277 (9q22); and rs944289 (14q13). Most of these associations have not been replicated in independent populations and the combined effects of the SNPs on risk have not been examined. This study genotyped the five TC SNPs in 781 patients recruited through the TCUKIN study. Genotype data from 6122 controls were obtained from the CORGI and Wellcome Trust Case-Control Consortium studies. Significant associations were detected between TC and rs965513A (p=6.35×10−34), rs1867277A (p=5.90×10−24), rs944289T (p=6.95×10−7), and rs6983267G (p=0.016). rs6983267 was most strongly associated under a recessive model (PGG vs GT + TT=0.004), in contrast to the association of this SNP with other cancer types. However, no evidence was found of an association between rs2910164 and disease under any risk model (p>0.7). The rs1867277 association remained significant (p=0.008) after accounting for genotypes at the nearby rs965513 (p=2.3×10−13) and these SNPs did not tag a single high risk haplotype. The four validated TC SNPs accounted for a relatively large proportion (∼11%) of the sibling relative risk of TC, principally owing to the large effect size of rs965513 (OR 1.74)

Cyr61/CCN1 Displays High-Affinity Binding to the Somatomedin B 1–44 Domain of Vitronectin

OV) family of extracellular-associated (matricellular) proteins that present four distinct functional modules, namely insulin-like growth factor binding protein (IGFBP), von Willebrand factor type C (vWF), thrombospondin type 1 (TSP), and C-terminal growth factor cysteine knot (CT) domain. While heparin sulphate proteoglycans reportedly mediate the interaction of Cyr61 with the matrix and cell surface, the role of other extracellular associated proteins has not been revealed. at high concentrations attenuate Cyr61 binding to immobilized VTNC, while monomeric VTNC was ineffective. Therefore, immobilization of VTNC exposes cryptic epitopes that recognize Cyr61 with high affinity, as reported for a number of antibodies, β-endorphin, and other molecules. domain suggests that VTNC represent a point of anchorage for CCN family members to the matrix. Results are discussed in the context of the role of CCN and VTNC in matrix biology and angiogenesis

Seasonal differences in leaf-level physiology give lianas a competitive advantage over trees in a tropical seasonal forest

Lianas are an important component of most tropical forests, where they vary in abundance from high in seasonal forests to low in aseasonal forests. We tested the hypothesis that the physiological ability of lianas to fix carbon (and thus grow) during seasonal drought may confer a distinct advantage in seasonal tropical forests, which may explain pan-tropical liana distributions. We compared a range of leaf-level physiological attributes of 18 co-occurring liana and 16 tree species during the wet and dry seasons in a tropical seasonal forest in Xishuangbanna, China. We found that, during the wet season, lianas had significantly higher CO2 assimilation per unit mass (Amass), nitrogen concentration (Nmass), and δ13C values, and lower leaf mass per unit area (LMA) than trees, indicating that lianas have higher assimilation rates per unit leaf mass and higher integrated water-use efficiency (WUE), but lower leaf structural investments. Seasonal variation in CO2 assimilation per unit area (Aarea), phosphorus concentration per unit mass (Pmass), and photosynthetic N-use efficiency (PNUE), however, was significantly lower in lianas than in trees. For instance, mean tree Aarea decreased by 30.1% from wet to dry season, compared with only 12.8% for lianas. In contrast, from the wet to dry season mean liana δ13C increased four times more than tree δ13C, with no reduction in PNUE, whereas trees had a significant reduction in PNUE. Lianas had higher Amass than trees throughout the year, regardless of season. Collectively, our findings indicate that lianas fix more carbon and use water and nitrogen more efficiently than trees, particularly during seasonal drought, which may confer a competitive advantage to lianas during the dry season, and thus may explain their high relative abundance in seasonal tropical forests

Protandim, a Fundamentally New Antioxidant Approach in Chemoprevention Using Mouse Two-Stage Skin Carcinogenesis as a Model

Oxidative stress is an important contributor to cancer development. Consistent with that, antioxidant enzymes have been demonstrated to suppress tumorigenesis when being elevated both in vitro and in vivo, making induction of these enzymes a more potent approach for cancer prevention. Protandim, a well-defined combination of widely studied medicinal plants, has been shown to induce superoxide dismutase (SOD) and catalase activities and reduce superoxide generation and lipid peroxidation in healthy human subjects. To investigate whether Protandim can suppress tumor formation by a dietary approach, a two-stage mouse skin carcinogenesis study was performed. At the end of the study, the mice on a Protandim-containing basal diet had similar body weight compared with those on the basal diet, which indicated no overt toxicity by Protandim. After three weeks on the diets, there was a significant increase in the expression levels of SOD and catalase, in addition to the increases in SOD activities. Importantly, at the end of the carcinogenesis study, both skin tumor incidence and multiplicity were reduced in the mice on the Protandim diet by 33% and 57% respectively, compared with those on basal diet. Biochemical and histological studies revealed that the Protandim diet suppressed tumor promoter-induced oxidative stress (evidenced by reduction of protein carbonyl levels), cell proliferation (evidenced by reduction of skin hyperplasia and suppression of PKC/JNK/Jun pathway), and inflammation (evidenced by reduction of ICAM-1/VCAM-1 expression, NF-κB binding activity, and nuclear p65/p50 levels). Overall, induction of antioxidant enzymes by Protandim may serve as a practical and potent approach for cancer prevention

Correlates of opium use: retrospective analysis of a survey of tribal communities in Arunachal Pradesh, India

BACKGROUND: Household survey data of Changlang district, Arunachal Pradesh, were used in the present study to assess the prevalence of opium use among different tribes, and to examine the association between sociodemographic factors and opium use. METHODS: A sample of 3421 individuals (1795 men and 1626 women) aged 15 years and older was analyzed using a multivariate logistic regression model to determine factors associated with opium use. Sociodemographic information such as age, education, occupation, religion, ethnicity and marital status were included in the analysis. RESULTS: The prevalence of opium use was significantly higher (10.6%) among men than among women (2.1%). It varied according to age, educational level, occupation, marital status and religion of the respondents. In both sexes, opium use was significantly higher among Singpho and Khamti tribes compared with other tribes. Multivariate logistic regression indicated that opium use was significantly associated with age, occupation, ethnicity, religion and marital status of the respondents of both sexes. Multivariate rate ratios (MRR) for opium use were significantly higher (4–6 times) among older age groups (≥35 years) and male respondents. In males, the MRR was also significantly higher in respondents of Buddhist and Indigenous religion, while in females, the MRR was significantly higher in Buddhists. Most of the female opium users had taken opium for more than 5 years and were introduced to it by their husbands after marriage. Use of other substances among opium users comprised mainly tobacco (76%) and alcohol (44%). CONCLUSIONS: The study reveals the sociodemographic factors, such as age, sex, ethnicity, religion and occupation, which are associated with opium use. Such information is useful for institution of intervention measures to reduce opium use

Identifying Alternative Hyper-Splicing Signatures in MG-Thymoma by Exon Arrays

BACKGROUND: The vast majority of human genes (>70%) are alternatively spliced. Although alternative pre-mRNA processing is modified in multiple tumors, alternative hyper-splicing signatures specific to particular tumor types are still lacking. Here, we report the use of Affymetrix Human Exon Arrays to spot hyper-splicing events characteristic of myasthenia gravis (MG)-thymoma, thymic tumors which develop in patients with MG and discriminate them from colon cancer changes. METHODOLOGY/PRINCIPAL FINDINGS: We combined GO term to parent threshold-based and threshold-independent ad-hoc functional statistics with in-depth analysis of key modified transcripts to highlight various exon-specific changes. These denote alternative splicing in MG-thymoma tumors compared to healthy human thymus and to in-house and Affymetrix datasets from colon cancer and healthy tissues. By using both global and specific, term-to-parent Gene Ontology (GO) statistical comparisons, our functional integrative ad-hoc method allowed the detection of disease-relevant splicing events. CONCLUSIONS/SIGNIFICANCE: Hyper-spliced transcripts spanned several categories, including the tumorogenic ERBB4 tyrosine kinase receptor and the connective tissue growth factor CTGF, as well as the immune function-related histocompatibility gene HLA-DRB1 and interleukin (IL)19, two muscle-specific collagens and one myosin heavy chain gene; intriguingly, a putative new exon was discovered in the MG-involved acetylcholinesterase ACHE gene. Corresponding changes in spliceosome composition were indicated by co-decreases in the splicing factors ASF/SF(2) and SC35. Parallel tumor-associated changes occurred in colon cancer as well, but the majority of the apparent hyper-splicing events were particular to MG-thymoma and could be validated by Fluorescent In-Situ Hybridization (FISH), Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and mass spectrometry (MS) followed by peptide sequencing. Our findings demonstrate a particular alternative hyper-splicing signature for transcripts over-expressed in MG-thymoma, supporting the hypothesis that alternative hyper-splicing contributes to shaping the biological functions of these and other specialized tumors and opening new venues for the development of diagnosis and treatment approaches

Microbial Fuel Cells and Microbial Ecology: Applications in Ruminant Health and Production Research

Microbial fuel cell (MFC) systems employ the catalytic activity of microbes to produce electricity from the oxidation of organic, and in some cases inorganic, substrates. MFC systems have been primarily explored for their use in bioremediation and bioenergy applications; however, these systems also offer a unique strategy for the cultivation of synergistic microbial communities. It has been hypothesized that the mechanism(s) of microbial electron transfer that enable electricity production in MFCs may be a cooperative strategy within mixed microbial consortia that is associated with, or is an alternative to, interspecies hydrogen (H2) transfer. Microbial fermentation processes and methanogenesis in ruminant animals are highly dependent on the consumption and production of H2in the rumen. Given the crucial role that H2 plays in ruminant digestion, it is desirable to understand the microbial relationships that control H2 partial pressures within the rumen; MFCs may serve as unique tools for studying this complex ecological system. Further, MFC systems offer a novel approach to studying biofilms that form under different redox conditions and may be applied to achieve a greater understanding of how microbial biofilms impact animal health. Here, we present a brief summary of the efforts made towards understanding rumen microbial ecology, microbial biofilms related to animal health, and how MFCs may be further applied in ruminant research