Role of obesity, weight gain, physical activity, and polymorphisms in the mTOR pathway and the risk of renal cell carcinoma

The interplay between obesity, physical activity, weight gain and genetic variants in mTOR pathway have not been studied in renal cell carcinoma (RCC). We examined the associations between obesity, weight gain, physical activity and RCC risk. We also analyzed whether genetic variants in the mTOR pathway could modify the association. Incident renal cell carcinoma cases and healthy controls were recruited from the University of Texas MD Anderson Cancer Center in Houston, Texas. Cases and controls were frequency-matched by age (±5 years), ethnicity, sex, and county of residence. Epidemiologic data were collected via in-person interview. A total of 577 cases and 593 healthy controls (all white) were included. One hundred ninety-two (192) SNPs from 22 genes were available and their genotyping data were extracted from previous genome-wide association studies. Logistic regression and regression spline were performed to obtain odds ratios. Obesity at age 20, 40, and 3 years prior to diagnosis/recruitment, and moderate and large weight gain from age 20 to 40 were each significantly associated with increased RCC risk. Low physical activity was associated with a 4.08-fold (95% CI: 2.92-5.70) increased risk. Five single nucleotide polymorphisms (SNPs) were significantly associated with RCC risk and their cumulative effect increased the risk by up to 72% (95% CI: 1.20-2.46). Strata specific effects for weight change and genotyping cumulative groups were observed. However, no interaction was suggested by our study. In conclusion, energy balance related risk factors and genetic variants in the mTOR pathway may jointly influence susceptibility to RCC. ^

Association between sugar-sweetened beverages and both gestational weight gain and gestational diabetes

This cross-sectional study aimed at evaluating the association between sugar sweetened beverage (SSB) consumption and both excessive gestational weight gain (EGWG) and gestational diabetes mellitus (GDM). The study was conducted in the postpartum units of Memorial Hermann Hospital, Lyndon Baines Johnson General Hospital, the University of Texas Medical Branch at Galveston General Hospital, and the University of Texas at Brownsville Hospital. Between June 2009 and September 2010, women between the ages of 18 and 49 years with singleton pregnancies who delivered an infant born at 37 weeks of gestation or later were approached. Descriptive, univariate and multivariate analysis were employed in our study using the Statistical Analysis System (SAS) software version 9.1 (SAS Institute Inc. Cary, North Carolina). Our investigation did not find statistically significant associations between SSBs and EGWG. Our study reported no evidence of an association between SSBs and GDM except for sports drinks. However, the estimate of this association was deemed very imprecise. In conclusion, our study did not find strong provide strong support for the hypothesis that high consumption of SSBs increases the risk of EGWG or GDM. ^

Gain-of-function of the p53R172H mutation in a mouse model of Li -Fraumeni syndrome

Missense mutations in the p53 tumor-suppressor gene are the most common alterations of p53 in somatic tumors and in patients with Li-Fraumeni syndrome. p53 missense mutations occur in the DNA binding region and disrupt the ability of p53 to activate transcription. In vitro studies have shown that some p53 missense mutants have a gain-of-function or dominant-negative activity. ^ The p53 175 Arg-to-His (p53 R175H) mutation in humans has been shown to have dominant-negative and gain-of-function properties in vitro. This mutation is observed in the germline of individuals with Li-Fraumeni syndrome. To accurately model Li-Fraumeni syndrome and to examine the mechanistic nature of a gain-of-function missense mutation on in vivo tumorigenesis, we generated and characterized a mouse with the corresponding mutation, p53 R172H. p53R172H homozygous and heterozygous mice developed similar tumor spectra and survival curves as p53 −/− and p53+/− mice, respectively. However, tumors in p53+/R172H mice metastasized to various organs with high frequency, suggesting a gain-of-function phenotype by p53R172H in vivo. Mouse embryonic fibroblasts (MEFs) from p53R172H mice also showed gain-of-function phenotypes in cell proliferation, DNA synthesis, and transformation potential, while cells from p53+/− and p53−/− mice did not. ^ To mechanistically characterize the gain-of-function phenotype of the p53R172H mutant, the role of p53 family members, p63 and p73, was analyzed. Disruption of p63 and p73 by siRNAs in p53 −/− MEFs increased transformation potential and reinitiated DNA synthesis to levels observed in p53R172H/R172H cells. Additionally, p63 and p73 were bound and functionally inactivated by p53R172H in metastatic p53 R172H tumor-derived cell lines, indicating a role for the p53 family members in the gain-of-function phenotype. This study provides in vivo evidence for the gain-of-function effect of p53 missense mutations and more accurately models the Li-Fraumeni syndrome. ^

(Table 1) Attenuation coefficient of lateral propagating light in sea ice, southern Beaufort Sea

The attenuation property of a lateral propagating light (LPL) in sea ice was measured using an artificial lamp in the Canadian Arctic during the 2007/2008 winter. A measurement method is proposed and applied whereby a recording instrument is buried in the sea ice and an artificial lamp is moved across the instrument. The apparent attenuation coefficient µ(lamda) for the lateral propagating light is obtained from the measured logarithmic relative variation rate. With the exception of blue and red lights, the attenuation coefficient changed little with wavelength, but changed considerably with depth. The vertical decrease of the attenuation coefficient was found to be correlated with salinity: the greater the salinity, the greater the attenuation coefficient. A clear linear relation of salinity and the lateral attenuation coefficient with R2 = 0.939 exists to address the close correlation of the attenuation of LPL with the scattering from the brine. The observed attenuation coefficient of LPL is much larger than that of the vertical propagation light, which we speculate to be caused by scattering. Part of this scattered component is transmitted out of the sea ice from the upper and lower surfaces.

(Table 2) Similarity Indexes (Pearson's correlation coefficient) of the silicoflagellate assemblages of IODP Exp302

The silicoflagellate and ebridian assemblages in early middle Eocene Arctic cores obtained by IODP Expedition 302 (ACEX) were studied in order to decipher the paleoceanography of the upper water column. The assemblages in Lithologic Unit 2 (49.7-45.1 Ma), one of the biosiliceous intervals, were usually endemic as compared to the assemblages that occurred outside of the Arctic Ocean. The presence of these endemic assemblages is probably due to a unique environmental setting, controlled by the degree of mixing between the low-salinity Arctic waters and relatively high salinity waters supplied from outside the Arctic Ocean, such as the Atlantic and possibly the Western Siberian Sea. Using the basin-to-basin fractionation model, the early middle Eocene Arctic Ocean corresponds to an estuarine circulation type, which includes the modern-day Black Sea. The abundant down-core occurrence of ebridians strongly suggests the past presence of low-salinity waters, and may indicate that low oxygen concentrations prevailed in the euphotic layer, on the basis of the ecology of the modern ebridian Hermesinum adriaticum.