Mechanism of adaptation of an atypical alkaline p-nitrophenyl phosphatase from the archaeon Halobacterium salinarum at low-water environments

Enzymes suspended in organic solvents represent a versatile system for studying the involvement of water in catalytic properties and their flexibility in adapting to different environmental conditions. The extremely halophilic alkaline p-nitrophenylphosphate phosphatase from the archaeon Halobacterium salinarum was solubilized in an organic medium consisting of reversed micelles of hexadecyltrimethylammoniumbromide in cyclohexane, with 1-butanol as cosurfactant. Hydrolysis of p-nitrophenylphosphate was nonlinear with time when the enzyme was microinjected into reversed micelles that contained substrate. These data are consistent with a kinetic model in which the enzyme is irreversibly converted from an initial form to a final stable form during the first seconds of the encapsulation process. The model features a rate constant (k) for that transition and separate hydrolysis rates, v(1) and v(2), for the two forms of the enzyme. The enzyme conversion may be governed by the encapsulation process.     

Galanin in Alzheimer disease

Galanin (GAL) and GAL receptors (GALR) are overexpressed in limbic brain regions associated with cognition in Alzheimer disease (AD). The functional consequences of this overexpression are unclear. Because GAL inhibits cholinergic transmission and restricts long-term potentiation in the hippocampus, GAL overexpression may exacerbate clinical features of AD. In contrast, GAL expression increases in response to neuronal injury, and galaninergic hyperinnervation prevents the decreased production of protein phosphatase 1 subtype mRNAs in cholinergic basal forebrain neurons in AD. Thus, GAL may also be neuroprotective for AD. Further elucidation of GAL activity in selectively vulnerable brain regions will help gauge the therapeutic potential of GALR ligands for the treatment of AD.     

Polymorphisms in Endothelin System Genes,Arsenic Levels and Obesity Risk

Background/Objectives

Obesity has been linked to morbidity and mortality through increased risk for many chronic diseases. Endothelin (EDN) system has been related to endothelial function but it can be involved in lipid metabolism regulation: Receptor type A (EDNRA) activates lipolysis in adipocytes, the two endothelin receptors mediate arsenic-stimulated adipocyte dysfunction, and endothelin system can regulate adiposity by modulating adiponectin activity in different situations and, therefore, influence obesity development. The aim of the present study was to analyze if single nucleotide polymorphisms (SNPs) in the EDN system could be associated with human obesity.

Subjects/Methods

We analyzed two samples of general-population-based studies from two different regions of Spain: the VALCAR Study, 468 subjects from the area of Valencia, and the Hortega Study, 1502 subjects from the area of Valladolid. Eighteen SNPs throughout five genes were analyzed using SNPlex.

Results

We found associations for two polymorphisms of the EDNRB gene which codifies for EDN receptor type B. Genotypes AG and AA of the rs5351 were associated with a lower risk for obesity in the VALCAR sample (p=0.048, OR=0.63) and in the Hortega sample (p=0.001, OR=0.62). Moreover, in the rs3759475 polymorphism, genotypes CT and TT were also associated with lower risk for obesity in the Hortega sample (p=0.0037, OR=0.66) and in the VALCAR sample we found the same tendency (p=0.12, OR=0.70). Furthermore, upon studying the pooled population, we found a stronger association with obesity (p=0.0001, OR=0.61 and p=0.0008, OR=0.66 for rs5351 and rs3759475, respectively). Regarding plasma arsenic levels, we have found a positive association for the two SNPs studied with obesity risk in individuals with higher arsenic levels in plasma: rs5351 (p=0.0054, OR=0.51) and rs3759475 (p=0.009, OR=0.53)

Conclusions

Our results support the hypothesis that polymorphisms of the EDNRB gene may influence the susceptibility to obesity and can interact with plasma arsenic levels.     

Novel non-nucleoside human cytomegalovirus inhibitors based upon TSAO nucleoside derivatives: structure-activity relationships

TSAO derivatives are a unique group of potent and highly specific inhibitors of HIV-1 replication. We have recently reported 4'-ureido TSAO derivatives that are devoid of anti-HIV-1 activity, but inhibit human cytomegalovirus with an activity comparable to that of Ganciclovir. We herein report the synthesis and biological evaluation of novel 4'-ureido TSAO derivatives in order to evaluate the structural features required for anti-HCMV activity. Interestingly, these studies revealed that the compounds may inhibit HCMV at the DNA polymerase step via a non-nucleoside mechanism.     

Dietary oleic acid and adipocyte lipolytic activity in culture

Although various studies have noted fatty-acid-mediated regulation of adipocyte lipolysis, determining the isolated effect of a single fatty acid is more difficult. We examined the influence of dietary oleic acid on adipose cell lipolytic activity and the tissue fat content independently of the variation in other dietary fatty acids. We fed 48 rats with six diets designed so that the oleic acid content was not correlated with the content of any other fatty acid and studied the lipolytic activity and fatty acid content of the tissues. There were no differences in the weight of the animals after the diet. The muscle fat content and the epinephrine-stimulated lipolytic activity varied significantly according to the dietary levels of oleic acid and the tissues, showing a dose-dependent behavior of the dietary oleic acid concentration. The results of this study show that diets rich in oleic acid have a beneficial effect on the regulation of lipid metabolism and body weight homeostasis.     

Effectiveness of Low‐Cost Planting Techniques for Improving Water Availability to Olea europaea Seedlings in Degraded Drylands

Reforestation projects in semiarid lands often yield poor results. Water scarcity, poor soil fertility, and structure strongly limit the survival and growth of planted seedlings in these areas. At two experimental semiarid sites, we evaluated a variety of low‐cost planting techniques in order to increase water availability to plants. Treatments included various combinations of traditional planting holes; water‐harvesting microcatchments; stone or plastic mulches; small waterproof sheets to increase water harvesting; dry wells; buried clay pots; and deep irrigation. Some of these treatments were also combined with addition of composted biosolids. Waterproof sheets significantly enhanced water harvesting (43%) and soil moisture in the planting hole (40%), especially for low‐intensity rainfall events. Treatment effects on the survival and growth of Olea europaea seedlings varied between experimental sites. At the most water‐limited site, clay pots, and dry wells improved seedling survival, while no treatment enhanced seedling growth. At the least water‐stressed site, the application of composted sludge significantly improved seedling growth. We conclude that nutrient‐mediated stress is subordinate to water stress in arid and semiarid environments, and we suggest modifications on the microsite scale to address these limiting conditions in Mediterranean drylands .