Body mass and prostatic cancer: a prospective study.

Previous studies have suggested that increased body mass is associated with an increased risk of prostatic cancer, but these studies have been limited by the fact that they were based on a few simple measurements such as height and weight. Similar results were found in a prospective study of the incidence of prostatic cancer in a cohort of Japanese men born in 1900-19 and living in Hawaii. Further evaluation of the extensive anthropomorphic measurements made in this cohort suggested that the association between measures of body mass and prostatic cancer might be accounted for more by lean tissue than by fat tissue. There was a significant positive association of the risk of prostatic cancer with area of muscle in the arm but not with area of fat in the arm. Further research is needed on the biological mechanisms of carcinogenesis that may be related to both lean and fat tissue and the development of prostatic cancer.     

Effect of thyroid hormones on acid cholesterol ester hydrolase activity in rat liver,heart and epididymal fat pads

The regulation of acid cholesterol ester hydrolase activity by thyroid hormones was studied in subcellular fractions from rat liver, heart, and epididymal fat pads; hydrolase activity was determined at pH 5 with a glycerol-dispersed cholesterol oleate substrate preparation. Acid cholesterol ester hydrolase activity was decreased in liver preparations from thyroidectomized rats relative to activity in livers from euthyroid control rats. Administration of triidothyronine to either euthyroid or hypothyroid (thyroidectomized) rats resulted in an increase in acid cholesterol ester hydrolase activity in liver preparations. Similar effects of thyroidectomy and the administration of triiodothyronine on acid cholesterol ester hydrolase activity were observed with fat pad preparations. In contrast, no effect of thyroid hormones was observed on acid cholesterol ester hydrolase activity in heart. These results suggest that thyroid hormones may regulate the catabolism of serum lipoproteins, in part, by alterations in lysosomal acid cholesterol ester hydrolase activity in liver and epididymal fat pads.     

Bicluster pattern of codon context usages between flavivirus and vector mosquito Aedes aegypti: relevance to infection and transcriptional response of mosquito genes

The mosquito Aedes aegypti is the primary vector of dengue virus (DENV) infection in most of the subtropical and tropical countries. Besides DENV, yellow fever virus (YFV) is also transmitted by A. aegypti. Susceptibility of A. aegypti to West Nile virus (WNV) has also been confirmed. Although studies have indicated correlation of codon bias between flaviviridae and their animal/insect hosts, it is not clear if codon sequences have any relation to susceptibility of A. aegypti to DENV, YFV and WNV. In the current study, usages of codon context sequences (codon pairs for neighboring amino acids) of the vector (A. aegypti) genome as well as the flaviviral genomes are investigated. We used bioinformatics methods to quantify codon context bias in a genome-wide manner of A. aegypti as well as DENV, WNV and YFV sequences. Mutual information statistics was applied to perform bicluster analysis of codon context bias between vector and flaviviral sequences. Functional relevance of the bicluster pattern was inferred from published microarray data. Our study shows that codon context bias of DENV, WNV and YFV sequences varies in a bicluster manner with that of specific sets of genes of A. aegypti. Many of these mosquito genes are known to be differentially expressed in response to flaviviral infection suggesting that codon context sequences of A. aegypti and the flaviviruses may play a role in the susceptible interaction between flaviviruses and this mosquito. The bias in usages of codon context sequences likely has a functional association with susceptibility of A. aegypti to flaviviral infection. The results from this study will allow us to conduct hypothesis-driven tests to examine the role of codon context bias in evolution of vector–virus interactions at the molecular level.     

The DNA Damage Response and Checkpoint Adaptation in Saccharomyces cerevisiae: Distinct Roles for the Replication Protein A2 (Rfa2) N-Terminus

In response to DNA damage, two general but fundamental processes occur in the cell: (1) a DNA lesion is recognized and repaired, and (2) concomitantly, the cell halts the cell cycle to provide a window of opportunity for repair to occur. An essential factor for a proper DNA-damage response is the heterotrimeric protein complex Replication Protein A (RPA). Of particular interest is hyperphosphorylation of the 32-kDa subunit, called RPA2, on its serine/threonine-rich amino (N) terminus following DNA damage in human cells. The unstructured N-terminus is often referred to as the phosphorylation domain and is conserved among eukaryotic RPA2 subunits, including Rfa2 in Saccharomyces cerevisiae. An aspartic acid/alanine-scanning and genetic interaction approach was utilized to delineate the importance of this domain in budding yeast. It was determined that the Rfa2 N-terminus is important for a proper DNA-damage response in yeast, although its phosphorylation is not required. Subregions of the Rfa2 N-terminus important for the DNA-damage response were also identified. Finally, an Rfa2 N-terminal hyperphosphorylation-mimetic mutant behaves similarly to another Rfa1 mutant (rfa1-t11) with respect to genetic interactions, DNA-damage sensitivity, and checkpoint adaptation. Our data indicate that post-translational modification of the Rfa2 N-terminus is not required for cells to deal with “repairable” DNA damage; however, post-translational modification of this domain might influence whether cells proceed into M-phase in the continued presence of unrepaired DNA lesions as a “last-resort” mechanism for cell survival.