Characteristics of melanomacrophage centers in the liver and spleen of the roach Rutilus rutilus (Cypriniformes: Cyprinidae) in Lake Kotokel during the Haff disease outbreak

Characteristics of morphology and number of melanomacrophage centers (MMCs) in the liver and spleen of the roach Rutilus rutilus and the amount of pigments in MMCs during the Haff disease outbreak and the death of fish in Lake Kotokel in relation to these parameters in the roach from Lake Baikal are described. Pathological changes in the microvasculature and parenchyma in the liver of the roach from Lake Kotokel were found. The area of melanomacrophage centers in the liver of the roach from this lake was significantly smaller, whereas the number and size of these centers in the spleen was significantly larger than in the roaches from Lake Baikal. Among the pigments studied, the strongest response to the content of this toxin in the water body was shown by hemosiderin. An increase in its amount in the spleen MMCs testifies to an enhanced degradation of erythrocytes and iron release, which may be caused by the damage of cells of the erythrocyte lineage by the toxin.     

Disentangling the Association between Statins,Cholesterol, and Colorectal Cancer: A Nested Case-Control Study

BackgroundSeveral prior studies have found an association between statin use and reduced risk of colorectal cancer. We hypothesized that these findings may be due to systematic bias and examined the independent association of colorectal cancer risk with statin use, serum cholesterol, and change in cholesterol concentration.ConclusionsAlthough the risk of colorectal cancer was lower in statin users versus nonusers, no difference was observed among those who continued versus discontinued statin therapy, suggesting the potential for indication bias. The association between decreased serum cholesterol and colorectal cancer risk suggests a cholesterol-lowering effect of undiagnosed malignancy. Clinical judgment should be used when considering causes of cholesterol reduction in patients, including those on statin therapy.     

Docking and molecular dynamics studies of peripheral site ligand–oximes as reactivators of sarin-inhibited human acetylcholinesterase

In the present work, we performed docking and molecular dynamics simulations studies on two groups of long-tailored oximes designed as peripheral site binders of acetylcholinesterase (AChE) and potential penetrators on the blood brain barrier. Our studies permitted to determine how the tails anchor in the peripheral site of sarin-inhibited human AChE, and which aminoacids are important to their stabilization. Also the energy values obtained in the docking studies corroborated quite well with the experimental results obtained before for these oximes.     

Inhibition of Autoimmune Diabetes in NOD Mice by miRNA Therapy

Autoimmune destruction of the pancreatic islets in Type 1 diabetes is mediated by both increased proinflammatory (Teff) and decreased regulatory (Treg) T lymphocytes resulting in a significant decrease in the Treg:Teff ratio. The non-obese diabetic (NOD) mouse is an excellent in vivo model for testing potential therapeutics for attenuating the decrease in the Treg:Teff ratio and inhibiting disease pathogenesis. Here we show for the first time that a bioreactor manufactured therapeutic consisting of a complex of miRNA species (denoted as TA1) can effectively reset the NOD immune system from a proinflammatory to a tolerogenic state thus preventing or delaying autoimmune diabetes. Treatment of NOD mice with TA1 resulted in a systemic broad-spectrum upregulation of tolerogenic T cell subsets with a parallel downregulation of Teff subsets yielding a dramatic increase in the Treg:Teff ratio. Moreover, the murine-derived TA1 was highly effective in the inhibition of allorecognition of HLA-disparate human PBMC. TA1 demonstrated dose-responsiveness and exhibited equivalent or better inhibition of allorecognition driven proliferation than etanercept (a soluble TNF receptor). These findings demonstrate that miRNA-based therapeutics can effectively attenuate or arrest autoimmune disease processes and may be of significant utility in a broad range of autoimmune diseases including Type 1 diabetes.     

The Consequences of Precipitation Seasonality for Mediterranean-Ecosystem Vegetation of South Africa

Globally, mediterranean-climate ecosystem vegetation has converged on an evergreen, sclerophyllous and shrubby growth form. The particular aspects of mediterranean-climate regions that contribute to this convergence include summer droughts and relatively nutrient-poor soils. We hypothesised that winter-precipitation implies stressful summer droughts and leaches soils due to greater water availability (i.e. balance between precipitation and potential evapotranspiration; P–PET) during cold periods. We conducted a comparative analysis of normalised difference vegetation indices (NDVI) and edaphic and climate properties across the biomes of South Africa. NDVI was strongly correlated with both precipitation and P–PET (r² = 0.8). There was no evidence, however, that winter-precipitation reduces NDVI in comparison to similar amounts of summer-precipitation. Base saturation (BS), a measure of soil leaching was, however, negatively related to P–PET (r² = 0.64). This led to an interaction between P–PET and BS in determining NDVI, indicating the existence of a trade-off between water availability and soil nutrients that enables NDVI to increase with precipitation, despite negative consequences for soil nutrient availability. The mechanism of this trade-off is suggested to be that water increases nutrient accessibility. This implies that along with nutrient-depauperate geologies and long periods of time since glaciation, the winter-precipitation may have contributed to the highly leached status of the soils. Since many of the ecophysiological characteristics of mediterranean-ecosystem flora are associated with low nutrient availabilities (e.g. evergreen foliage, sclerophylly, cluster roots), we conclude that mediterranean-climates promote convergence of growth-forms in these regions through high leaching capacity.     

Satellite DNA of the red flour beetle Tribolium castaneum--comparative study of satellites from the genus Tribolium

A highly abundant satellite DNA comprising 17% of the Tribolium castaneum (Insecta, Coleoptera) genome was cloned and sequenced. The satellite monomer is 360 bp long, has a high A+T content of 73%, and lacks significant internal substructures. The sequence variability is 3.6%, essentially due to random distribution of single-point mutations. The satellite is evenly distributed in the regions of centromeric heterochromatin of all 20 chromosomes, as shown by fluorescent in situ hybridization. Comparison of T. castaneum satellite with those from three different but congeneric species reveals the highest sequence similarity of 47.1% with the satellite from the sibling species Tribolium freemani. The phylogenetic relationships among Tribolium species deduced from satellite sequence agree with those based on karyological, chemotaxonomic, and hybridization data. This indicates a parallel in the divergence of satellites and some genetic and cytogenetic characters. Despite low mutual sequence similarity, which makes them species-specific, Tribolium satellites have a common structural characteristic: a block of about 95% A+T content, 20 to 42 bp long, flanked at one side by an inverted repeat which can potentially form a thermodynamically stable dyad structure. Since similar structural features are found in centromeric DNA of Saccharomyces cerevisiae and Chironomus pallidivittatus, their possible importance in centromere function may be inferred.