A registry for exposure and population health in the Altai region affected by fallout from the Semipalatinsk nuclear test site

A registry of the rural population in the Altai region exposed to fallout from nuclear tests at the Semipalatinsk test site (STS) was established more than four decades after the first Soviet nuclear explosion on August 29, 1949. Information about individuals living in an exposed and a control area was collected using all available local sources, such as kolkhoz documentation, school registries, medical treatment records and interviews with residents. As a result, a database comprising an exposed group of 39 179 individuals from 53 Altai region villages, 6769 external and 3303 internal controls was compiled. For several settlements, effective dose estimates reached the level of 1.5 Sv, while the average effective dose estimate in the exposed group was 340 mSv. Dosimetric data, vital status information and health records gathered at rayon and village medical facilities are held in the registry. Cause-of-death information for deceased residents is obtained from death registration forms archived at the Altai region vital statistics office. At present, a follow-up of approximately 40% of the population exposed in 1949 has been done. More will be added by searching for migrants to the larger towns of the Altai region, i.e. Barnaul, Rubtsovsk and Biisk. In order to assess the influence of radiation exposure, analytical studies with a case-control design for stomach and lung cancer are currently being prepared. The number of known cases is sufficient to detect an odds ratio of 1.5 at the 95% confidence level. Epidemiological studies in populations affected by fallout from STS may be equally important to the atomic bomb survivors’ study for the direct quantification of radiation effects. The range of exposure rates experienced will extend the acute high-dose-rate findings from Hiroshima/Nagasaki towards acute and protracted lower exposures, which are more relevant for radiation protection issues. Received: 3 March 1999 / Accepted in revised form: 8 June 1999     

Homologs of the Genes for Receptor-Like Kinase Proteins Conferring Plant Resistance to Pathogens: Resistance Gene Homologs in Solanum Species

Direct amplification of the genomic DNA from cultivated and wild Solanum species was used to synthesize three groups of NBS-LRR homologs of the genes which encode the pathogen-recognizing receptor-like serine/threonine kinases (RLK): (1) the NBS-kinase regions homologous to the arabidopsis RPS2 gene, the tobacco N gene, and the flax L6 gene (the corresponding GenBank accession nos. U14158, U15605, and U27081); (2) full-size sequences homologous to the Pto gene of Lycopersicon pimpinellifolium (AF220602); and (3) LRR regions homologous to potato genesGpa2/Rx1 (AJ249449 and AJ011801) and the tomato gene Mi1 (AF091048). The nucleotide and deduced amino acid sequences of the cloned fragments of the genes and pseudogenes were compared to the already known genes and their homologs within the family Solanaceae.     

Pancreatic Islet Survival and Engraftment Is Promoted by Culture on Functionalized Spider Silk Matrices

Transplantation of pancreatic islets is one approach for treatment of diabetes, however, hampered by the low availability of viable islets. Islet isolation leads to disruption of the environment surrounding the endocrine cells, which contributes to eventual cell death. The reestablishment of this environment is vital, why we herein investigated the possibility of using recombinant spider silk to support islets in vitro after isolation. The spider silk protein 4RepCT was formulated into three different formats; 2D-film, fiber mesh and 3D-foam, in order to provide a matrix that can give the islets physical support in vitro. Moreover, cell-binding motifs from laminin were incorporated into the silk protein in order to create matrices that mimic the natural cell environment. Pancreatic mouse islets were thoroughly analyzed for adherence, necrosis and function after in vitro maintenance on the silk matrices. To investigate their suitability for transplantation, we utilized an eye model which allows in vivo imaging of engraftment. Interestingly, islets that had been maintained on silk foam during in vitro culture showed improved revascularization. This coincided with the observation of preserved islet architecture with endothelial cells present after in vitro culture on silk foam. Selected matrices were further evaluated for long-term preservation of human islets. Matrices with the cell-binding motif RGD improved human islet maintenance (from 36% to 79%) with preserved islets architecture and function for over 3 months in vitro. The islets established cell-matrix contacts and formed vessel-like structures along the silk. Moreover, RGD matrices promoted formation of new, insulin-positive islet-like clusters that were connected to the original islets via endothelial cells. On silk matrices with islets from younger donors (<35 year), the amount of newly formed islet-like clusters found after 1 month in culture were almost double compared to the initial number of islets added.     

Prospects for Gene Therapy of Epilepsy Using Calcium-Acivated Potassium Channel Vectors

Journal of Evolutionary Biochemistry and Physiology - Epilepsy is one of the widespread neurological human diseases, and nearly a third of patients are not completely relieved from epileptic...     

Collagen denaturation in spread monolayers at the air-water interface: Experiments and a possible model of the process

Spread monolayers of the fibril protein collagen were studied at the air-water interface in the presence of denaturants, urea and thiourea. The most prominent feature of spread collagen monolayers at the air-water interface is the ability to form supramolecular structures (fibrils), which themselves can form monolayers with collapse points of their own. The surface pressure isotherms of collagen monolayers have two “quasi-linear” centers, which are separated by a plateau and correspond to liquid-expanded and liquid-condensed states; this unique capability makes collagen different from other proteins. When in monolayer, collagen acquires the same level of structural organization as in the bulk. In the presence of denaturants, subphase characteristics of collagen monolayers change rapidly and irreversibly. Thiourea exerts more pronounced denaturing action on collagen monolayers than urea; this effect increases with exposure time and denaturant concentration. A hypothetical mechanism of thiourea-induced denaturation of fibril proteins is proposed according to which interactions between hydrophobic C=S groups of thiourea and nonpolar surface groups of the protein lead to reorientation of carbonyl groups to formation of intrinsic hydrogen bonds with NH₂-groups of thiourea eventually resulting in the rupture of intrinsic hydrogen bonds and denaturation of the protein.     

Immature stages of leaf beetles of the genera Octodonta and Pystosia (Coleoptera, Chrysomelidae, Hispinae) from Vietnam

The morphology of larvae and pupae of two leaf beetle species, Octodonta depressa Chap. and Pystosia dactyliferae Maulik, is described. Some aspects of their ecology are considered.     

Identification of cytotoxic,glutathione-reactive moieties inducing accumulation of reactive oxygen species via glutathione depletion

Reactive oxygen species (ROS) play an essential role in the survival and progression of cancer. Moderate oxidative stress drives proliferation, whereas high levels of ROS induce cytotoxicity. Compared to cancer cells, healthy cells often exhibit lower levels of oxidative stress. Elevation of cellular ROS levels by small molecules could therefore induce cancer-specific cytotoxicity. We have employed high-throughput phenotypic screening to identify inducers of ROS accumulation. We found 4,5-dihalo-2-methylpyridazin-3-one (DHMP) and 2,3,4,5(6)-tetrachloro-6(5)-methylpyridine (TCMP) moieties to strongly deplete GSH, to cause ROS accumulation and to induce cell death. Small molecules containing these fragments will most likely share the same properties and should therefore be carefully considered in the development of bioactive molecules.     

Identification of novel PDEδ interacting proteins

Prenylation is a post-translational modification that increases the affinity of proteins for membranes and mediates protein-protein interactions. The retinal rod rhodopsin-sensitive cGMP 3′,5′-cyclic phosphodiesterase subunit delta (PDEδ) is a prenyl binding protein that is essential for the shuttling of small GTPases between different membrane compartments and, thus, for their proper functioning. Although the prenylome comprises up to 2% of the mammalian proteome, only few prenylated proteins are known to interact with PDEδ. A proteome-wide approach was employed to map the PDEδ interactome among the prenylome and revealed RAB23, CDC42 and CNP as novel PDEδ interacting proteins. Moreover, PDEδ associates with the lamin A mutant progerin in a prenyl-dependent manner. These findings shed new light on the role of PDEδ in binding (and regulating) prenylated proteins in cells.