Ameliorative effect of tannic acid on hypermethioninemia-induced oxidative and nitrosative damage in rats: biochemical-based evidences in liver,kidney, brain,and serum

We investigated the ability of tannic acid (TA) to prevent oxidative and nitrosative damage in the brain, liver, kidney, and serum of a rat model of acute hypermethioninemia. Young Wistar rats were divided into four groups: I (control), II (TA 30 mg/kg), III (methionine (Met) 0.4 g/kg + methionine sulfoxide (MetO) 0.1 g/kg), and IV (TA/Met + MetO). Rats in groups II and IV received TA orally for seven days, and rats of groups I and III received an equal volume of water. After pretreatment with TA, rats from groups II and IV received a single subcutaneous injection of Met + MetO, and were euthanized 3 h afterwards. In specific brain structures and the kidneys, we observed that Met + MetO led to increased reactive oxygen species (ROS), nitrite, and lipid peroxidation levels, followed by a reduction in thiol content and antioxidant enzyme activity. On the other hand, pretreatment with TA prevented both oxidative and nitrosative damage. In the serum, Met + MetO caused a decrease in the activity of antioxidant enzymes, which was again prevented by TA pretreatment. In contrast, in the liver, there was a reduction in ROS levels and an increase in total thiol content, which was accompanied by a reduction in catalase and superoxide dismutase activities in the Met + MetO group, and pretreatment with TA was able to prevent only the reduction in catalase activity. Conclusively, pretreatment with TA has proven effective in preventing oxidative and nitrosative changes caused by the administration of Met + MetO, and may thus represent an adjunctive therapeutic approach for treatment of hypermethioninemia.

     

Simple Mechanisms Can Explain Social Learning in Domestic Dogs (Canis familiaris)

Recent studies have suggested that domestic dogs (Canis familiaris) engage in highly complex forms of social learning. Here, we critically assess the potential mechanisms underlying social learning in dogs using two problem‐solving tasks. In a classical detour task, the test dogs benefited from observing a demonstrator walking around a fence to obtain a reward. However, even inexperienced dogs did not show a preference for passing the fence at the same end as the demonstrator. Furthermore, dogs did not need to observe a complete demonstration by a human demonstrator to pass the task. Instead, they were just as successful in solving the problem after seeing a partial demonstration by an object passing by at the end of the fence. In contrast to earlier findings, our results suggest that stimulus enhancement (or affordance learning) might be a powerful social learning mechanism used by dogs to solve such detour problems. In the second task, we examined whether naïve dogs copy actions to solve an instrumental problem. After controlling for stimulus enhancement and other forms of social influence (e.g. social facilitation and observational conditioning), we found that dogs’ problem solving was not influenced by witnessing a skilful demonstrator (either an unknown human, a conspecific or the dog’s owner). Together, these results add to evidence suggesting that social learning may often be explained by relatively simple (but powerful) mechanisms.     

The effects of periodized concurrent and aerobic training on oxidative stress parameters, endothelial function and immune response in sedentary male individuals of middle age

The vascular endothelium plays a key role in arterial wall homeostasis by preventing atherosclerotic plaque formation. A primary causal factor of endothelial dysfunction is the reactive oxygen species. Aerobic exercise is ascribed as an important adjuvant therapy in endothelium‐dependent cardiovascular disease. However, little is known about the effects of concurrent (aerobic + strength) training on that. For a comparison of the effects of aerobic and concurrent physical training on endothelial function, oxidative stress parameters and the immunoinflammatory activity of monocytes/macrophages, 20 adult male volunteers of middle age were divided into a concurrent training (CT) programme group and an aerobic training group. The glutathione disulphide to glutathione ratio (GSSG/GSH) and plasma lipoperoxide (LPO) levels, as well as flow‐mediated dilation (FMD), monocyte/macrophage functional activity (zymosan phagocytosis), body lipid profiles, aerobic capacity (maximal oxygen uptake) and strength parameters (one‐repetition maximum test), were measured before and after the exercise training programmes. The CT exhibited reduced acute effects of exercise on the GSSG/GSH ratio, plasma LPO levels and zymosan phagocytosis. The CT also displayed improved lipid profiles, glycaemic control, maximal oxygen uptake and one‐repetition maximum test values. In both the aerobic training and the CT, training improved the acute responses to exercise, as inferred from a decrease in the GSSG/GSH ratios. The aerobic sessions did not alter basal levels of plasma LPO or macrophage phagocytic activity but improved FMD values as well as lipid profiles and glycaemic control. In summary, both training programmes improve systemic redox status and antioxidant defences. However, the aerobic training was more efficient in improving FMD in the individuals studied. Copyright © 2011 John Wiley & Sons, Ltd.     

Sequential synthesis and methylation of phosphatidylethanolamine promote lipid droplet biosynthesis and stability in tissue culture and in vivo

Triacylglycerols are stored in eukaryotic cells within lipid droplets (LD). The LD core is enwrapped by a phospholipid monolayer with phosphatidylcholine (PC), the major phospholipid, and phosphatidylethanolamine (PE), a minor component. We demonstrate that the onset of LD formation is characterized by a change in cellular PC, PE, and phosphatidylserine (PS). With induction of differentiation of 3T3-L1 fibroblasts into adipocytes, the cellular PC/PE ratio decreased concomitant with LD formation, with the most pronounced decline between confluency and day 5. The mRNA for PS synthase-1 (forms PS from PC) and PS decarboxylase (forms PE from PS) increased after day 5. Activity and protein of PE N-methyltransferase (PEMT), which produces PC by methylation of PE, are absent in 3T3-L1 fibroblasts but were induced at day 5. High fat challenge induced PEMT expression in mouse adipose tissue. PE, produced via PS decarboxylase, was the preferred substrate for methylation to PC. A PEMT-GFP fusion protein decorated the periphery of LD. PEMT knockdown in 3T3-L1 adipocytes correlated with increased basal triacylglycerol hydrolysis. Pemt(-/-) mice developed desensitization against adenosine-mediated inhibition of basal hydrolysis in adipose tissue, and adipocyte hypotrophy was observed in Pemt(-/-) animals on a high fat diet. Knock-out of PEMT in adipose tissue down-regulated PS synthase-1 mRNA, suggesting coordination between PE supply and converting pathways during LD biosynthesis. We conclude that two consecutive processes not previously related to LD biogenesis, (i) PE production via PS and (ii) PE conversion via PEMT, are implicated in LD formation and stability.     

The yeast Cbk1 kinase regulates mRNA localization via the mRNA-binding protein Ssd1

The mRNA-binding protein Ssd1 is a substrate for the Saccharomyces cerevisiae LATS/NDR orthologue Cbk1, which controls polarized growth, cell separation, and cell integrity. We discovered that most Ssd1 localizes diffusely within the cytoplasm, but some transiently accumulates at sites of polarized growth. Cbk1 inhibition and cellular stress cause Ssd1 to redistribute to mRNA processing bodies (P-bodies) and stress granules, which are known to repress translation. Ssd1 recruitment to P-bodies is independent of mRNA binding and is promoted by the removal of Cbk1 phosphorylation sites. SSD1 deletion severely impairs the asymmetric localization of the Ssd1-associated mRNA, SRL1. Expression of phosphomimetic Ssd1 promotes polarized localization of SRL1 mRNA, whereas phosphorylation-deficient Ssd1 causes constitutive localization of SRL1 mRNA to P-bodies and causes cellular lysis. These data support the model that Cbk1-mediated phosphorylation of Ssd1 promotes the cortical localization of Ssd1-mRNA complexes, whereas Cbk1 inhibition, cellular stress, and Ssd1 dephosphorylation promote Ssd1-mRNA interactions with P-bodies and stress granules, leading to translational repression.     

Cotrimoxazole enhances the in vitro susceptibility of Coccidioides posadasii to antifungals

The aim of the present study was to evaluate the effect of cotrimoxazole on the in vitro susceptibility of Coccidioides posadasii strains to antifungals. A total of 18 strains of C. posadasii isolated in Brazil were evaluated in this study. The assays were performed in accordance with the Clinical and Laboratory Standards Institute guidelines and the combinations were tested using the checkerboard method. The minimum inhibitory concentrations were reduced by 11, 2.4, 4.3 and 3.5 times for amphotericin B, itraconazole, fluconazole and voriconazole, respectively. Moreover, it was seen that cotrimoxazole itself inhibited C. posadasii strains in vitro. The impairment of folic acid synthesis may be a potential antifungal target for C. posadasii.     

Expanding the body mass range: associations between BMR and tissue morphology in wild type and mutant dwarf mice (<Emphasis Type="Italic">David</Emphasis> mice)

We sought to identify associations of basal metabolic rate (BMR) with morphological traits in laboratory mice. In order to expand the body mass (BM) range at the intra-strain level, and to minimize relevant genetic variation, we used male and female wild type mice (C3HeB/FeJ) and previously unpublished ENU-induced dwarf mutant littermates (David mice), covering a body mass range from 13.5 g through 32.3 g. BMR was measured at 30°C, mice were killed by means of CO₂ overdose, and body composition (fat mass and lean mass) was subsequently analyzed by dual X-ray absorptiometry (DEXA), after which mice were dissected into 12 (males) and 10 (females) components, respectively. Across the 44 individuals, 43% of the variation in the basal rates of metabolism was associated with BM. The latter explained 47% to 98% of the variability in morphology of the different tissues. Our results demonstrate that sex is a major determinant of body composition and BMR in mice: when adjusted for BM, females contained many larger organs, more fat mass, and less lean mass compared to males. This could be associated with a higher mass adjusted BMR in females. Once the dominant effects of sex and BM on BMR and tissue mass were removed, and after accounting for multiple comparisons, no further significant association between individual variation in BMR and tissue mass emerged. Electronic supplementary material Supplementary material is available in the online version of this article at and is accessible for authorized users.