Ischemic heart disease in nuclear workers first employed at the Mayak PA in 1948-1972.

Following an earlier study of incidence and mortality of ischemic heart disease (IHD) published in 2010, a second analysis has been conducted based on an extended cohort and five additional years of follow-up. The cohort includes 18,763 workers, of whom 25% were females, first employed at the Mayak PA in 1948-1972 and followed up to the end of 2005. Some of these workers were exposed to external gamma rays only, and others were exposed to a mixture of external gamma-rays and internal alpha-particle radiation. A total of 6,134 cases and 2,629 deaths from IHD were identified in the study cohort. A statistically significant increasing trend was found with total external gamma-ray dose in IHD incidence (ERR/Gy 0.099; 95% CI: 0.045-0.153) after adjusting for non-radiation factors. This value reduced slightly when adjusting for internal liver dose. There was no statistically significant increase trend for internal liver dose in IHD incidence. These findings were consistent with an earlier study. New findings in IHD incidence revealed a statistically significant decrease in IHD incidence among workers exposed to external gamma-rays doses of 0.2-0.5 Gy in relation to the external doses below 0.2 Gy. This decreased risk is heavily influenced by female workers. This finding has never been reported in other studies, and the results should be treated with caution. The findings for IHD mortality are similar to those results in the earlier analysis; there was no statistically significant trend with external gamma-ray dose or for internal liver dose after adjustment for external dose. The risk estimates obtained from these analyses of IHD incidence and mortality in relation to external gamma-rays in the cohort of Mayak workers are generally compatible with those from other large occupational radiation worker studies and the Japanese atomic bomb survivors.

Oxidoreductive cellulose depolymerization by the enzymes cellobiose dehydrogenase and glycoside hydrolase 61.

Several members of the glycoside hydrolase 61 (GH61) family of proteins have recently been shown to dramatically increase the breakdown of lignocellulosic biomass by microbial hydrolytic cellulases. However, purified GH61 proteins have neither demonstrable direct hydrolase activity on various polysaccharide or lignacious components of biomass nor an apparent hydrolase active site. Cellobiose dehydrogenase (CDH) is a secreted flavocytochrome produced by many cellulose-degrading fungi with no well-understood biological function. Here we demonstrate that the binary combination of Thermoascus aurantiacus GH61A (TaGH61A) and Humicola insolens CDH (HiCDH) cleaves cellulose into soluble, oxidized oligosaccharides. TaGH61A-HiCDH activity on cellulose is shown to be nonredundant with the activities of canonical endocellulase and exocellulase enzymes in microcrystalline cellulose cleavage, and while the combination of TaGH61A and HiCDH cleaves highly crystalline bacterial cellulose, it does not cleave soluble cellodextrins. GH61 and CDH proteins are coexpressed and secreted by the thermophilic ascomycete Thielavia terrestris in response to environmental cellulose, and the combined activities of T. terrestris GH61 and T. terrestris CDH are shown to synergize with T. terrestris cellulose hydrolases in the breakdown of cellulose. The action of GH61 and CDH on cellulose may constitute an important, but overlooked, biological oxidoreductive system that functions in microbial lignocellulose degradation and has applications in industrial biomass utilization.

Stimulation of lignocellulosic biomass hydrolysis by proteins of glycoside hydrolase family 61: structure and function of a large, enigmatic family.

Currently, the relatively high cost of enzymes such as glycoside hydrolases that catalyze cellulose hydrolysis represents a barrier to commercialization of a biorefinery capable of producing renewable transportable fuels such as ethanol from abundant lignocellulosic biomass. Among the many families of glycoside hydrolases that catalyze cellulose and hemicellulose hydrolysis, few are more enigmatic than family 61 (GH61), originally classified based on measurement of very weak endo-1,4-beta-d-glucanase activity in one family member. Here we show that certain GH61 proteins lack measurable hydrolytic activity by themselves but in the presence of various divalent metal ions can significantly reduce the total protein loading required to hydrolyze lignocellulosic biomass. We also solved the structure of one highly active GH61 protein and find that it is devoid of conserved, closely juxtaposed acidic side chains that could serve as general proton donor and nucleophile/base in a canonical hydrolytic reaction, and we conclude that the GH61 proteins are unlikely to be glycoside hydrolases. Structure-based mutagenesis shows the importance of several conserved residues for GH61 function. By incorporating the gene for one GH61 protein into a commercial Trichoderma reesei strain producing high levels of cellulolytic enzymes, we are able to reduce by 2-fold the total protein loading (and hence the cost) required to hydrolyze lignocellulosic biomass.

The "clinic" medical-dosimetric database of Mayak production association workers: structure, characteristics and prospects of utilization.

To study early (deterministic) and long-term effects of radiation exposure, the "Clinic" medical-dosimetric database for the Mayak Production Association worker cohort has been established at the Southern Urals Biophysics Institute (SUBI). This paper describes the principles of organization, structure and prospects of future utilization of this database.