Influence of exogenous NO donator and variations in the Ca<Superscript>2+</Superscript> content on transport activity related to tonoplast proton pumps in ontogenesis and under hyperosmotic stress

The changes in transport activity of tonoplast proton pumps under the influence of exogenous NO donator and modulation of Ca²⁺ concentration jointly and separately were investigated at different stages of ontogenesis and under hyperosmotic stress. The results suggest that both exogenous NO donator and Ca²⁺ ions can influence the activity of transport processes related to tonoplast and this influence is especially evident in the period of growth and accumulation of metabolites. Under hyperosmotic stress, H⁺-pyrophosphatase plays a more important role than H⁺-ATPase: the activity of the former increases 2.3-fold compared to the control osmotic conditions, whereas the activity of H⁺-ATPase is practically unchanged. H⁺-pyrophosphatase was more responsive to the presence of exogenous NO donator and to variations in Ca²⁺ concentration. The effects of exogenous NO donator on tonoplast proton pumps depended on the concentration of Ca²⁺, which apparently can mediate NO action.     

Mechanisms of changes in human hemodynamics under the conditions of microgravity and prognosis of postflight orthostatic stability

The mechanisms of hemodynamic responses to orthostatic stresses and orthostatic stability (OS) of cosmonauts were studied before and after short-and long-term spaceflights (SFs) using orthostatic tests, as well as before, during, and after SFs using ultrasonic methods in tests with exposure to lower body negative pressure (LBNP). The capacitance and distensibility of the veins of the lower extremities were studied using occlusive air plethysmography before, during, and after SFs of different durations. A stay in microgravity has been proved to result in detraining of, mainly, the vascular mechanisms of compensating orthostatic perturbations. It has been established that the decrease in OS under the influence of microgravity is determined by a reduction of the vasoconstrictive ability of large blood vessels of the lower extremities; an increase in venous distensibility and capacitance of the legs; and an impairment of blood flow regulation, which leads to a cerebral blood flow deficit in orthostatic stresses, and of the initial individual OS before the flight. The results of preflight studies of hemodynamics by ultrasonic methods at LBNP and the data of orthostatic tests before SFs make it possible to predict the degree of decrease of OS after an SF proceeding in the normal mode. At the same time, the data of ultrasonic blood flow examination provide more a accurate estimation of OS and make it possible to assess the physiological reserves of hemodynamic regulation and to reveal the loss of regulation capacity even in cases where integrated indices (heart rate and blood pressure) are within the normal ranges.     

Possible involvement of DNA breaks in epigenetic regulation of cell differentiation

The review summarizes the authors’ and literature data on accumulation of DNA breaks in differentiating cells. Large 50-kb free DNA fragments were observed by several research teams in non-apoptotic insect, mammal, and plant cells. More intense DNA breakage was observed during maturation of spermatides, embryo development, and differentiation of myotubes, epidermal cells, lymphocytes, and neutrophils. In general, accumulation of DNA breaks in differentiating cells cannot be attributed to a decrease in the DNA repair efficiency. Poly(ADP)ribose synthesis often follows the DNA breakage in differentiating cells. We hypothesize that DNA fragmentation is an epigenetic tool for regulating the differentiation process. Scarce data on localization of the differentiation-associated DNA breaks indicate their preferable accumulation in specific DNA sequences including the nuclear matrix attachment sites. The same sites are degraded at early stages of apoptosis. Recent data on non-apoptotic function of caspases provide more evidence for possible existence of a DNA breakage mechanism in differentiating cells, resembling the initial stage of apoptosis. Excision of methylated cytosine and recombination are other possible explanations of the phenomenon. Elucidation of mechanisms of differentiation-induced DNA breaks appears to be a prospective research direction.     

Suppression of Viral RNA Binding and the Assembly of Infectious Hepatitis C Virus Particles In Vitro by Cyclophilin Inhibitors

Nonstructural protein 5A (NS5A) of hepatitis C virus (HCV) is an indispensable component of the HCV replication and assembly machineries. Although its precise mechanism of action is not yet clear, current evidence indicates that its structure and function are regulated by the cellular peptidylprolyl isomerase cyclophilin A (CyPA). CyPA binds to proline residues in the C-terminal half of NS5A, in a distributed fashion, and modulates the structure of the disordered domains II and III. Cyclophilin inhibitors (CPIs), including cyclosporine (CsA) and its nonimmunosuppressive derivatives, inhibit HCV infection of diverse genotypes, both in vitro and in vivo. Here we report a mechanism by which CPIs inhibit HCV infection and demonstrate that CPIs can suppress HCV assembly in addition to their well-documented inhibitory effect on RNA replication. Although the interaction between NS5A and other viral proteins is not affected by CPIs, RNA binding by NS5A in cell culture-based HCV (HCVcc)-infected cells is significantly inhibited by CPI treatment, and sensitivity of RNA binding is correlated with previously characterized CyPA dependence or CsA sensitivity of HCV mutants. Furthermore, the difference in CyPA dependence between a subgenomic and a full-length replicon of JFH-1 was due, at least in part, to an additional role that CyPA plays in HCV assembly, a conclusion that is supported by experiments with the clinical CPI alisporivir. The host-directed nature and the ability to interfere with more than one step in the HCV life cycle may result in a higher genetic barrier to resistance for this class of HCV inhibitors.     

Eye size variation reflects habitat and daily activity patterns in colubrid snakes

The functioning of the vertebrate eye depends on its absolute size, which is presumably adapted to specific needs. Eye size variation in lidless and spectacled colubrid snakes was investigated, including 839 specimens belonging to 49 genera, 66 species and subspecies. Variations of adult eye diameters (EDs) in both absolute and relative terms between species were correlated with parameters reflecting behavioral ecology. In absolute terms, eye of arboreal species was larger than in terrestrial and semiaquatic species. For diurnal species, EDs of terrestrial species do not differ from semiaquatic species; for nocturnal species the ED of terrestrial species is larger than fossorial species but not different from semiaquatic species. In relative terms, ED did not differ significantly by habitat for diurnal species. Although the ED of terrestrial species is larger than fossorial species there were no differences for nocturnal species between semiaquatic and fossorial snakes. In contrast to other vertebrates studied to date, colubrid EDs in absolute and relative terms are larger in diurnal than in nocturnal species. These observations suggest that among colubrid snakes, eye size variation reflects adaptation to specific habitats, foraging strategies and daily activities, independently of phylogeny. J. Morphol. 2012. © 2012 Wiley Periodicals, Inc.     

Effect of menthol on human temperature sensitivity

Application of 1% methol, which, along with cold, activates specific thermosensitive ionic channels, changes the number of functioning cold receptors on the skin of the forearm similarly to the cold exposure test; however, it does not affect the number of heat receptors and does not significantly change the threshold of cold sensation. Group variants of responses to menthol that indicate individual differences in the sensitivity of skin receptors to the effects of methol and cold have been found. The results obtained give grounds to suggest that, from the variant of response to menthol (a decrease, increase, or absence of changes in the number of functioning cold receptors 5 min after menthol application), it is possible to predict specific features of response to cold.     

Reply to Hussey et al.: The requirement for accurate diet-tissue discrimination factors for interpreting stable isotopes in sharks

Carbon and nitrogen stable isotope analyses have improved our understanding of food webs and movement patterns of aquatic organisms. These techniques have recently been applied to diet studies of elasmobranch fishes, but isotope turnover rates and isotope diet–tissue discrimination are still poorly understood for this group. We performed a diet switch experiment on captive sandbar sharks (Carcharhinus plumbeus) as a model shark species to determine tissue turnover rates for liver, whole blood, and white muscle. In a second experiment, we subjected captive coastal skates (Leucoraja spp.) to serial salinity reductions to measure possible impacts of tissue urea content on nitrogen stable isotope values. We extracted urea from spiny dogfish (Squalus acanthias) white muscle to test for effects on nitrogen stable isotopes. Isotope turnover was slow for shark tissues and similar to previously published estimates for stingrays and teleost fishes with low growth rates. Muscle isotope data would likely fail to capture seasonal migrations or diet switches in sharks, while liver and whole blood would more closely reflect shorter term movement or shifts in diet. Nitrogen stable isotope values of skate blood and skate and dogfish white muscle were not affected by tissue urea content, suggesting that available diet–tissue discrimination estimates for teleost fishes with similar physiologies would provide accurate estimates for elasmobranchs.