Collagen aggregation phenomena

Three processes by which tropocollagen units associate to yield highly specific aggregates have been examined. From the temperature coefficients of the amounts aggregated it is concluded that the complex “native” aggregation is endothermic, whereas both end-to-end and lateral aggregation are exothermic. These results combined with additional information lead to the conclusion that “native” aggregation is an entropy-driven process in which hydrophobic bonding plays the dominant role. In contrast the reactions producing the lateral aggregate and the aggregate in which end-to-end bonding is dominant are electrostatically governed.     

Activation of turkey erythrocyte adenylate cyclase and blocking of the catecholamine-stimulated GTPase by guanosine 5'-(gamma-thio) triphosphate.

By SDS-polyacrylamide gel electrophoresis, mitochondrial proteins having covalently-bound flavin were analyzed. Mitochondria were prepared from the liver of rat injected with radioactive riboflavin. Radioactivity was found to be associated with four protein components. Their subunit molecular weights were 91,000, 72,000, 60,000 and 44,000. The first two components exhibited yellowish fluorescence on a gel under ultraviolet illumination. The component of the highest molecular weight seems to be a new protein containing covalently-bound flavin.     

Correlations between Nitrate Reduction, Protein Synthesis and Malate Accumulation

The reduction of nitrate in leaves establishes an ‘excess’ of cations in the tissue which is rapidly neutralized by the synthesis of malate. Malate synthesized in nitrate-containing leaves accumulates while malate synthesized in nitrate-depleted leaves disappears gradually. The levels of nitrate reductasc and malate synthesis change similarly during leaf growth. Good correlation was also found between the rate of protein synthesis and the rale of malate synthesis. Stoichiometric relation between the amount of nitrate reduced and malate accumulated may be observed in short-term experiments.     

Novel phenylamino acetamide derivatives as potent and selective kappa opioid receptor agonists

A novel series of phenylamino acetamide derivatives was synthesized. These amides were shown to be potent and selective kappa opioid receptor agonists.     

Inhibition of predation by Bdellovibrio bacteriovorus and Micavibrio aeruginosavorus via host cell metabolic activity in the presence of carbohydrates

Bdellovibrio bacteriovorus and Micavibrio aeruginosavorus are highly motile Gram-negative predatory bacteria with the potential of being used as biocontrol agents or living antibiotics. It was suggested previously that sugar-binding proteins play a role in M. aeruginosavorus and B. bacteriovorus host specificity and predator-prey interactions. The effect of carbohydrates on predation was reexamined in this study. It was demonstrated that the presence of carbohydrates could indeed block predation. However, further investigation demonstrated that inhibition of predation was due to medium acidification by the metabolic activity of the host and not to a blocking of a putative sugar-binding protein. The data presented here might be of value when storing, growing, and cultivating predatory bacteria, as well as when considering environmental conditions that might influence predation in the field.     

Protection of Human Pancreatic Islets from Lipotoxicity by Modulation of the Translocon

Type 2 diabetes is characterized by peripheral insulin resistance and pancreatic beta cell dysfunction. Elevated free fatty acids (FFAs) may impair beta cell function and mass (lipotoxicity). Altered calcium homeostasis may be involved in defective insulin release. The endoplasmic reticulum (ER) is the major intracellular calcium store. Lipotoxicity induces ER stress and in parallel an ER calcium depletion through unknown ER calcium leak channels. The main purposes of this study is first to identify one of these channels and secondly, to check the opportunity to restore beta cells function (i.e., insulin secretion) after pharmacological inhibition of ER calcium store depletion. We investigated the functionality of translocon, an ER calcium leak channel and its involvement on FFAs-induced alterations in MIN6B1 cells and in human pancreatic islets. We evidenced that translocon acts as a functional ER calcium leak channel in human beta cells using anisomycin and puromycin (antibiotics), respectively blocker and opener of this channel. Puromycin induced a significant ER calcium release, inhibited by anisomycin pretreatment. Palmitate treatment was used as FFA model to induce a mild lipotoxic effect: ER calcium content was reduced, ER stress but not apoptosis were induced and glucose induced insulin secretion was decreased in our beta cells. Interestingly, translocon inhibition by chronic anisomycin treatment prevented dysfunctions induced by palmitate, avoiding reticular calcium depletion, ER stress and restoring insulin secretion. Our results provide for the first time compelling evidence that translocon actively participates to the palmitate-induced ER calcium leak and insulin secretion decrease in beta cells. Its inhibition reduces these lipotoxic effects. Taken together, our data indicate that TLC may be a new potential target for the treatment of type 2 diabetes.     

Adolescent Sexual and Reproductive Health Services and Implications for the Provision of Voluntary Medical Male Circumcision: Results of a Systematic Literature Review

Background

Voluntary medical male circumcision (VMMC) is a critical HIV prevention tool. Since 2007, sub-Saharan African countries with the highest prevalence of HIV have been mobilizing resources to make VMMC available. While implementers initially targeted adult men, demand has been highest for boys under age 18. It is important to understand how male adolescents can best be served by quality VMMC services.

Methods and Findings

A systematic literature review was performed to synthesize the evidence on best practices in adolescent health service delivery specific to males in sub-Saharan Africa. PubMed, Scopus, and JSTOR databases were searched for literature published between January 1990 and March 2014. The review revealed a general absence of health services addressing the specific needs of male adolescents, resulting in knowledge gaps that could diminish the benefits of VMMC programming for this population. Articles focused specifically on VMMC contained little information on the adolescent subgroup. The review revealed barriers to and gaps in sexual and reproductive health and VMMC service provision to adolescents, including structural factors, imposed feelings of shame, endorsement of traditional gender roles, negative interactions with providers, violations of privacy, fear of pain associated with the VMMC procedure, and a desire for elements of traditional non-medical circumcision methods to be integrated into medical procedures. Factors linked to effective adolescent-focused services included the engagement of parents and the community, an adolescent-friendly service environment, and VMMC counseling messages sufficiently understood by young males.

Conclusions

VMMC presents an opportune time for early involvement of male adolescents in HIV prevention and sexual and reproductive health programming. However, more research is needed to determine how to align VMMC services with the unique needs of this population.     

Discovery of a series of aminopiperidines as novel iNOS inhibitors

Nitric oxide (NO), a mediator of various physiological and pathophysiological processes, is synthesized by three isozymes of nitric oxide synthase (NOS). Potential candidate clinical drugs should be devoid of inhibitory activity against endothelial NOS (eNOS), since eNOS plays an important role in maintaining normal blood pressure and flow. A new series of aminopiperidines as potent inhibitors of iNOS were identified from a HTS lead. From this study, we identified compound 33 as a potent iNOS inhibitor, with >25-fold selectivity over eNOS and 16-fold selectivity over nNOS.