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.     

Nutrients are assimilated efficiently by Lymantria dispar caterpillars from the mature leaves of trees in the Salicaceae

The efficient aquisition of nutrients from leaves by insect herbivores increases their nutrient assimilation rates and overall fitness. Caterpillars of the gypsy moth (Lymantria dispar L.) have high protein assimilation efficiencies (PAE) from the immature leaves of trees such as red oak (Quercus rubra) and sugar maple (Acer saccharum) (71–81%) but significantly lower PAE from their mature leaves (45–52%). By contrast to this pattern, both PAE and carbohydrate assimilation efficiencies (CAE) remain high for L. dispar larvae on the mature leaves of poplar (Populus alba × Populus tremula) grown in greenhouse conditions. The present study tests two alternative hypotheses: (i) outdoor environmental stresses cause decreased nutrient assimilation efficiencies from mature poplar leaves and (ii) nutrients in the mature leaves of trees in the poplar family (Salicaceae) remain readily available for L. dispar larvae. When poplar trees are grown in ambient outdoor conditions, PAE and CAE remain high (approximately 75% and 78%, respectively) in L. dispar larvae, in contrast to the first hypothesis. When larvae feed on the mature leaves of species in the Salicaceae [aspen (Populus tremuloides), cottonwood (Populus deltoides), willow (Salix nigra) and poplar], PAE and CAE also remain high (68–76% and 72–92%, respectively), consistent with the second hypothesis. Larval growth rates are strongly associated with protein assimilation rates, and more strongly associated with protein assimilation rates than with carbohydrate assimilation rates. It is concluded that tree species in the Salicaceae are relatively high‐quality host plants for L. dispar larvae, in part, because nutrients in their mature leaves remain readily available.     

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.