Neuropeptide Y (NPY)-induced feeding behavior in female rats: comparison with human NPY ([Met17]NPY), NPY analog ([norLeu4]NPY) and peptide YY

Porcine neuropeptide Y (pNPY) administered into the third ventricle of the brain is known to elicit a powerful feeding response in steroid-treated ovariectomized and intact male rats. The present study compared the effects of pNPY and 3 structurally related peptides, human NPY (hNPY), an analog of NPY (NPY-A, [norLeu4]NPY) and peptide YY (PYY) on feeding behavior in intact female rats. Intraventricular administration of pNPY, hNPY, NPY-A and PYY over a dose range of 0.5 to 10 micrograms evoked feeding behavior to a varying extent. Cumulative food intake during 60 and 120 min was increased in a dose-related fashion at 0.5 and 2.0 microgram for the 4 peptides. Whereas the 10-micrograms dose of pNPY evoked a feeding response smaller than that seen after 2 micrograms, the responses to either 10 micrograms hNPY or 10 micrograms PYY were similar to that seen after 2 micrograms. The effects of these peptides on the time spent eating were quite different: while pNPY increased the time spent eating, this effect was not dose-related, whereas hNPY, NPY-A and PYY produced dose-related increments in the time spent eating. The most dramatic increment in local eating rate was observed after 2.0 micrograms pNPY, with lesser increments seen after 2.0 microgram hNPY and NPY-A. This increased local eating was apparently responsible for the highest cumulative food intake observed. These results demonstrate that (a) 2 micrograms pNPY is equally effective in stimulating feeding behavior in intact female rats as it is in steroid-primed ovariectomized female and intact male rats.(ABSTRACT TRUNCATED AT 250 WORDS)     

Apposite insulin-like growth factor (IGF) receptor glycosylation is critical to the maintenance of vascular smooth muscle phenotype in the presence of factors promoting osteogenic differentiation and mineralization

Vascular calcification is strongly linked with increased morbidity and mortality from cardiovascular disease. Vascular calcification is an active cell-mediated process that involves the differentiation of vascular smooth muscle cells (VSMCs) to an osteoblast-like phenotype. Several inhibitors of this process have been identified, including insulin-like growth factor-I (IGF-I). In this study, we examined the role of the IGF receptor (IGFR) and the importance of IGFR glycosylation in the maintenance of the VSMC phenotype in the face of factors known to promote osteogenic conversion. IGF-I (25 ng/ml) significantly protected VSMCs from β-glycerophosphate-induced osteogenic differentiation (p < 0.005) and mineral deposition (p < 0.01). Mevalonic acid depletion (induced by 100 nm cerivastatin) significantly inhibited these IGF protective effects (p < 0.01). Mevalonic acid depletion impaired IGFR processing, decreased the expression of mature IGFRs at the cell surface, and inhibited the downstream activation of Akt and MAPK. Inhibitors of N-linked glycosylation (tunicamycin, deoxymannojirimycin, and deoxynojirimycin) also markedly attenuated the inhibitory effect of IGF-I on β-glycerophosphate-induced mineralization (p < 0.05) and activation of Akt and MAPK. These results demonstrate that alterations in the glycosylation of the IGFR disrupt the ability of IGF-I to protect against the osteogenic differentiation and mineralization of VSMCs by several interrelated mechanisms: decreased IGFR processing, reduced IGFR cell-surface expression, and reduced downstream signaling via the Akt and MAPK pathways. IGF-I thus occupies a critical position in the maintenance of normal VSMC phenotype and protection from factors known to stimulate vascular calcification.     

Central leptin gene therapy blocks ovariectomy-induced adiposity

Objective: In this study, we tested the hypothesis that insufficiency of leptin restraint in the hypothalamus is responsible for promoting weight gain and adiposity after ovariectomy (ovx). Whether increasing leptin transgene expression can overcome the diminution in leptin restraint was evaluated in ovx rats. Research Methods and Procedures: Enhanced leptin or green fluorescent protein (GFP; control) transgene expression was induced by a single intracerebroventricular injection of recombinant adeno‐associated viral vector encoding either leptin gene (rAAV‐lep) or GFP gene (rAAV‐GFP; control) in acutely and chronically ovx rats. Body weight and food intake responses were monitored weekly. White adipose tissue (WAT) mass and serum levels of WAT‐derived hormones, leptin, and adiponectin were analyzed at termination of the experiments. Results and Discussion: An increase in leptin transgene expression in the hypothalamus initiated soon after ovx blocked hyperphagia and body weight gain and markedly suppressed WAT mass and adipokines, leptin, and adiponectin. Similar suppression of weight gain and adiposity and serum leptin and adiponectin levels after intracerebroventricular rAAV‐lep injection in chronically ovx rats were observed concomitant with unchanged daily food intake. These findings are consistent with the hypothesis that in the absence of ovarian steroids, the existent insufficiency of leptin restraint at the hypothalamic level can be overcome with ectopic leptin expression, thereby reinstating central control on weight and adiposity.     

Identification of Proteins Secreted by Malaria Parasite into Erythrocyte using SVM and PSSM profiles

Background  

Malaria parasite secretes various proteins in infected RBC for its growth and survival. Thus identification of these secretory proteins is important for developing vaccine/drug against malaria. The existing motif-based methods have got limited success due to lack of universal motif in all secretory proteins of malaria parasite.     

Serum antioxidant enzyme activity in Parkinson's disease

Summary The activities of superoxide dismutase (SOD; EC 1.15.1.1) and glutathione peroxidase (GSHP_x; EC 1.11.1.9.), the enzymes that metabolize the superoxide anion and hydrogen peroxide, respectively, were measured in serum from healthy subjects and patients with Parkinson's disease (PD). The activities of SOD and GSHP_x in patients with PD were higher than those in normal healthy individuals. These results suggest that the increased activities of these enzymes could be due to oxidative stress in the initial stages of this disease.     

Terrigenous sediment-dominated reef platform infilling: an unexpected precursor to reef island formation and a test of the reef platform size–island age model in the Pacific

Low-lying coral reef islands are considered highly vulnerable to climate change, necessitating an improved understanding of when and why they form, and how the timing of formation varies within and among regions. Several testable models have been proposed that explain inter-regional variability as a function of sea-level history and, more recently, a reef platform size model has been proposed from the Maldives (central Indian Ocean) to explain intra-regional (intra-atoll) variability. Here we present chronostratigraphic data from Pipon Island, northern Great Barrier Reef (GBR), enabling us to test the applicability of existing regional island evolution models, and the platform size control hypothesis in a Pacific context. We show that reef platform infilling occurred rapidly (~4–5 mm yr⁻¹) under a “bucket-fill” type scenario. Unusually, this infilling was dominated by terrigenous sedimentation, with platform filling and subsequent reef flat formation complete by ~5000 calibrated years BP (cal BP). Reef flat exposure as sea levels slowly fell post highstand facilitated a shift towards intertidal and subaerial-dominated sedimentation. Our data suggest, however, a lag of ~1500 yr before island initiation (at ~3200 cal BP), i.e. later than that reported from smaller and more evolutionarily mature reef platforms in the region. Our data thus support: (1) the hypothesis that platform size acts to influence the timing of platform filling and subsequent island development at intra-regional scales; and (2) the hypothesis that the low wooded islands of the northern GBR conform to a model of island formation above an elevated reef flat under falling sea levels.

     

Short‐term and long‐term effects of acute kidney injury in chronic kidney disease patients: A longitudinal analysis

We use data from an ongoing cohort study of chronic kidney patients at Salford Royal NHS Foundation Trust, Greater Manchester, United Kingdom, to investigate the influence of acute kidney injury (AKI) on the subsequent rate of change of kidney function amongst patients already diagnosed with chronic kidney disease (CKD). We use a linear mixed effects modelling framework to enable estimation of both acute and chronic effects of AKI events on kidney function. We model the fixed effects by a piece‐wise linear function with three change‐points to capture the acute changes in kidney function that characterise an AKI event, and the random effects by the sum of three components: a random intercept, a stationary stochastic process with Matérn correlation structure, and measurement error. We consider both multivariate Normal and multivariate t versions of the random effects. For either specification, we estimate model parameters by maximum likelihood and evaluate the plug‐in predictive distributions of the random effects given the data. We find that following an AKI event the average long‐term rate of decline in kidney function is almost doubled, regardless of the severity of the event. We also identify and present examples of individual patients whose kidney function trajectories diverge substantially from the population‐average.     

Aflatoxin B1 effect on beta-D-galactosidase in some starter cultures.

Six starter cultures were examined for their ability to induce beta-D-Galactosidase activity. The maximum (713 x 10(-4) units/ml) and minimum (140 x 10(-4) units/ml) enzyme activity was shown by Lactobacillus bulgaricus and Streptomyces thermophilus, respectively. The maximum inhibition by aflatoxin B1 of induction and activity of enzyme in vitro was observed at 60 micrograms/ml in all cultures. However, low levels of the toxin stimulated induction of the enzyme in Streptococcus lactis and S. thermophilus.     

ACC Deaminase-Containing Bacillus subtilis Reduces Stress Ethylene-Induced Damage and Improves Mycorrhizal Colonization and Rhizobial Nodulation in Trigonella foenum-graecum Under Drought Stress

This study was aimed at protecting Trigonella plants by reducing stress ethylene levels through ACC (1-aminocyclopropane-1-carboxylic acid) deaminase-containing Bacillus subtilis (LDR2) and promoting plant growth through improved colonization of beneficial microbes like Ensifer meliloti (Em) and Rhizophagus irregularis (Ri) under drought stress. A plant growth-promoting rhizobacterium strain possessing high levels of ACC deaminase characterized as B. subtilis was selected. Application of this strain considerably protected Trigonella plants under severe drought stress conditions; this protection was correlated with reduced levels of ACC (responsible for generation of stress ethylene). The experiment consisted of eight inoculation treatments with different combinations of ACC deaminase-containing rhizobacteria LDR2, Ri, and Em under three water regimes. The tripartite combination of LDR2 + Ri + Em acted synergistically to induce protective mechanisms against decreased soil water availability in Trigonella plants and improved plant weight by 56 % with lower ACC concentration (39 % less than stressed noninoculated plants) under severe drought conditions. Drought-induced changes in biochemical markers like reduced chlorophyll concentration, increased proline content, and higher lipid peroxidation were monitored and clearly indicated the protective effects of LDR2 under drought stress. Under drought conditions, apart from alleviating ethylene-induced damage, LDR2 enhanced nodulation and arbuscular mycorrhizal fungi colonization in the plants resulting in improved nutrient uptake and plant growth.