908 resultados para G-coupled protein receptors


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The processes that govern the predictability of decadal variations in the North Atlantic meridional overturning circulation (MOC) are investigated in a long control simulation of the ECHO-G coupled atmosphere–ocean model. We elucidate the roles of local stochastic forcing by the atmosphere, and other potential ocean processes, and use our results to build a predictive regression model. The primary influence on MOC variability is found to come from air–sea heat fluxes over the Eastern Labrador Sea. The maximum correlation between such anomalies and the variations in the MOC occurs at a lead time of 2 years, but we demonstrate that the MOC integrates the heat flux variations over a period of 10 years. The corresponding univariate regression model accounts for 74.5% of the interannual variability in the MOC (after the Ekman component has been removed). Dense anomalies to the south of the Greenland-Scotland ridge are also shown to precede the overturning variations by 4–6 years, and provide a second predictor. With the inclusion of this second predictor the resulting regression model explains 82.8% of the total variance of the MOC. This final bivariate model is also tested during large rapid decadal overturning events. The sign of the rapid change is always well represented by the bivariate model, but the magnitude is usually underestimated, suggesting that other processes are also important for these large rapid decadal changes in the MOC.

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In the last decade, there has been renewed interest in biologically active peptides in fields like allergy, autoimmume diseases and antibiotic therapy. Mast cell degranulating peptides mimic G-protein receptors, showing different activity levels even among homologous peptides. Another important feature is their ability to interact directly with membrane phospholipids, in a fast and concentration-dependent way. The mechanism of action of peptide HR1 on model membranes was investigated comparatively to other mast cell degranulating peptides (Mastoparan, Eumenitin and Anoplin) to evidence the features that modulate their selectivity. Using vesicle leakage, single-channel recordings and zeta-potential measurements, we demonstrated that HR1 preferentially binds to anionic bilayers, accumulates, folds, and at very low concentrations, is able to insert and create membrane spanning ion-selective pores. We discuss the ion selectivity character of the pores based on the neutralization or screening of the peptides charges by the bilayer head group charges or dipoles. (C) 2009 Elsevier Inc. All rights reserved.

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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

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In the present study we have investigated the effects of heat acclimation on brain and hepatic Hsp70 protein levels and body temperature of broiler chickens in response to gradual heat stress. Two groups of broilers were raised up to 47 days of age under distinct temperature conditions: thermoneutral (TN, according to bird age) or hot environmental (HS, 31-33°C). At 46 days of age, the birds reared at high ambient temperature were transferred to thermoneutrality conditions. After 18 h, these birds and the birds reared at thermoneutral temperature were submitted to gradual heat stress in a climatic chamber so that environment temperature was increased from 28 to 40ºC at a rate of 2ºC/h. Colonic temperature was measured using a thermometer sensor probe at each two hours, and hepatic and brain tissues were collected immediately after slaughter in order to assess Hsp70 protein level by Western blotting analysis. The colonic temperatures of birds reared at high temperature increased steeply during the first 2 h of heat stress (1.06ºC/h) and more slowly thereafter (0.59ºC/h). Broilers reared at thermoneutral temperature showed a small increase in the first 4 h of heat stress (0.18ºC/h) and then colonic temperature increased sharply (0.72ºC/h). Nevertheless, both groups presented similar final colonic temperature by the end of the stress period. Hsp70 levels (ng Hsp70 µg total protein-1) did not change in the liver or brain of the birds reared at high temperature. on the other hand, both liver and brain Hsp70 levels increased significantly during heat stress in the animals reared at thermoneutrality, with a higher expression of this peptide in brain tissue.

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The guava seed protein isolate ( PI) was obtained from the protein precipitation belonging to the class of the gluteline (Ip 4.5). The conditions for the preparation of the PI were determined by both the solubility curve and simultaneous thermogravimetry-differential thermal analysis (TG-DTA): pH 11.5, absence of NaCl and whiteners and T=( 25 +/- 3) degrees C. Under these conditions a yield of 77.0 +/- 0.4%, protein content of 94.2 +/- 0.3, ashes 0.50 +/- 0.05% and thermal stability, T= 200 degrees C, were obtained. The TG-DTA curves and the PI emulsification capacity study showed the presence of hydrophobic microdomains at pH 11.5 and 3.0 suggesting a random coil protein conformation and, to pH 10.0, an open protein conformation. The capacity of emulsification (CE), in the absence of NaCl, was verified for: 1 - pH 3.0 and 8.5, using the IP extracted at pH 10.0 and 11.5, CE >= 343 +/- 5 g of emulsified oil/g of protein; 2 - pH 6.60 just for the PI obtained at pH 11.5, CE >= 140 +/- 8 g of emulsified oil/g of protein.

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The effect of Haemonchus contortus infection in sheep fed with a moderate and high protein content diet was evaluated in two breeds of sheep. Forty-eight Ile de France and Santa Ines lambs were maintained indoors since birth, in worm-free conditions. The lambs were allocated after weaning in four groups of six animals per breed, which were either infected or remain uninfected and given access to either a moderately or highly metabolizable protein diet. The moderately and highly metabolizable protein diets were calculated to supply 75 and 129 g metabolizable protein per kg of dry matter (MP/kg DM), respectively. The infection consisted of a trickle infection with 300 infective larvae, three times a week, for 12 weeks. Significant differences were observed for mast cell, globule leukocyte and eosinophil counts in the abomasal mucosa of the infected groups compared to the control of both breeds (P < 0.05), regardless of the diet supplied. Significantly higher IgA anti-L5 antibody was detected in the infected Santa Ines groups than in the infected Ile de France groups (P < 0.05). Increased metabolizable protein supply resulted in larger body weight gain and higher packed cell volumes for both breeds (P < 0.05). Both breeds showed an increased ability to withstand the pathophysiological effects of H. contortus infection when given access to the highly metabolizable protein diet. However, increased metabolizable protein supply resulted in reduced worm burdens in Santa Ines lambs but not in the Ile de France lambs (P < 0.05). The present results show that the increase in protein content in growing lamb diets may benefit resistance and resilience to gastrointestinal parasites but that these benefits may vary among breeds. (c) 2005 Elsevier B.V. All rights reserved.

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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

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The scattering of ortho-positronium (Ps) by H-2 has been investigated using a three-Ps-state (Ps(1s,2s, 2p)H-2(X (1)Sigma(g)(+))) coupled-channel model and using the Born approximation for higher excitations and ionization of Ps and B (1)Sigma(u)(+) and b (3)Sigma(u)(+) excitations of H-2. We employ a recently proposed time-reversal-symmetric non-local electron-exchange model potential. We present a calculational scheme for solving the body-frame fixed-nuclei coupled-channel scattering equations for Ps-H-2, which simplifies the numerical solution technique considerably. Ps ionization is found to have the leading contribution to target-elastic and all target-inelastic processes. The total cross sections at low and medium energies are in good agreement with experiment.

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This study investigated the consequences of intrauterine protein restriction on the gastrointestinal tract and particularly on the gene expression and activity of intestinal disaccharidases in the adult offspring. Wistar rat dams were fed isocaloric diets containing 6% protein (restricted, n = 8) or 17% protein (control, n = 8) throughout gestation. Male offspring (n = 5-8 in each group) were evaluated at 3 or 16 weeks of age. Maternal protein restriction during pregnancy produced offspring with growth restriction from birth (5.7 ± 0.1 vs 6.3 ± 0.1 g; mean ± SE) to weaning (42.4 ± 1.3 vs 49.1 ± 1.6 g), although at 16 weeks of age their body weight was similar to control (421.7 ± 8.9 and 428.5 ± 8.5 g). Maternal protein restriction also increased lactase activity in the proximal (0.23 ± 0.02 vs 0.15 ± 0.02), medial (0.30 ± 0.06 vs 0.14 ± 0.01) and distal (0.43 ± 0.07 vs 0.07 ± 0.02 U·g-1·min-1) small intestine, and mRNA lactase abundance in the proximal intestine (7.96 ± 1.11 vs 2.38 ± 0.47 relative units) of 3-week-old offspring rats. In addition, maternal protein restriction increased sucrase activity (1.20 ± 0.02 vs 0.91 ± 0.02 U·g-1·min-1) and sucrase mRNA abundance (4.48 ± 0.51 vs 1.95 ± 0.17 relative units) in the duodenum of 16-week-old rats. In conclusion, the present study shows for the first time that intrauterine protein restriction affects gene expression of intestinal enzymes in offspring.

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An experiment was conducted to examine the influence of dietary protein and immunisation on parasite establishment and pathogenesis of Haemonchus placei in calves. Four groups of 4-6-month-old worm-free calves (n=4) were given a low protein diet (LP) containing 213 g crude protein (CP) per head per day or a high-protein diet (HP) containing 469 g per head per day CP. Five weeks later, calves in one of the two groups of each dietary treatment were given 50 000 H. placei infective larvae (L(3)). Twenty-five days later, infection in these groups was terminated by dosing with oxfendazole, This immunisation process was repeated 4 days later. Four days after termination of the second immunisation all calves were challenged with 100 000 L(3). Five weeks later, all calves were slaughtered for abomasal worm counts. Worm establishment was lower in the immunised groups; however, only the HP-I group showed a significant reduction (P < 0.05). All calves gained weight during the first 13 week period, and after challenge the non-immunised groups lost weight, independent of the level of protein in the diet (P < 0.05), Packed cell volume values for all treatments only dropped after challenge (P < 0.05) and the HP-immunised group presented values significantly higher when compared with the other treatments, All calves were hypoproteinaemic and hypoalbuminaemic at the end of the experiment, regardless of the treatment. Immunised calves showed a normocytic normochromic anaemia, while the non-immunised groups presented a microcytic normochromic anaemia.

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Protein is one of the limiting factors in animal production, and the knowledge of protein requirements by livestock is crucial for the success of a commercial animal raising enterprise. Thirty-four castrated lambs, 17 of them F1 Ideal x lie de France wool lambs and the remaining ones were Santa Ines hair lambs, with homogeneous initial BW, were used in the experiment. Five animals from each genotype were slaughtered in the beginning of the experimental period and used as reference. Diets (D) were composed of concentrate mix (C) and Cynodon sp. c.v. Tifton 85 hay (R), combined in three different ratios: D1 =60CAOR; D2=40C:60R and D3=20C:80R. Animals of each group of three lambs, that showed simultaneously an initial BW of 20 +/- 0.14 kg at the beginning of the dietary regimen, were slaughtered when one of them reached 35 kg, what always happened to be the one fed with D1. Net requirements for BW gain in wool lamb, fleece-free, ranged from 101 to 110 g of protein/kg BW, and for hair lamb ranged from 1 10 to 118 g of protein/kg BW. Net protein requirements for wool production ranged from 634 to 642 g/kg of produced wool. Hair lambs presented a 7.8-9.5% higher estimated net protein requirements than wool lambs, according to BW and daily weight gain (DG). Total net protein requirements for Santa Ines and wool lambs, with 30 kg of initial B W and an approximate 200 g mean DG, were 48.5 and 45.4 g/day, respectively. Metabolizable protein requirements for Santa Ines and wool lambs, with 20 kg of initial BW and an approximate 200 g mean DG were 59.4 g and 76.5 -/day, respectively. Net protein requirements for wool production was 64g/100g of produced wool. Thus, under the conditions of this experiment, it is concluded that hair lambs showed a higher concentration of protein in the body, more efficient use of the ingested protein and a consequent additional BW gain when fed isoproteic diets as compared to F1 Ideal x Ile de France wool lambs. (c) 2006 Elsevier B.V All rights reserved.

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In five male cirrhotic patients (Child A) and in four age- and sex-matched healthy control subjects, whole-body protein turnover was measured using a single oral dose of N-15-glycine as a tracer and urinary ammonia as end product. Subjects were studied in the fasting and feeding state, with different levels of protein and energy intake. The patients were underweight and presented lower plasma transthyretin and retinol-binding protein levels. When compared with controls, the kinetic studies showed patients to be hypometabolic in the fasting (Do) state and with the control diet [D-1 = (0.85 g of protein/154 kJ). kg(-1). day(-1)]. However, when corrected by body weight, the kinetic differences between groups disappeared, whereas the N-retention in the feeding state showed better results for the patients due mainly to their efficient breakdown decrease. When fed high-level protein or energy diets [D-2 = (0.9 g protein/195 kJ) and D-3 = (1.56 g protein/158 kJ). kg(-1). day(-1)], the patients showed D-0 = D-1 = D-2 < D-3 for N-flux and (D-0 = D-1) < D-3 (D-2 is intermediary) for protein synthesis. Thus, the present data suggest that the remaining mass of the undernourished mild cirrhotic patients has fairly good protein synthesis activity and also that protein, rather than energy intake, would be the limiting factor for increasing their whole-body protein synthesis.

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The objective of the present study was to investigate the effects of dietary macronutrient ratio on energy metabolism and on skeletal muscle mRNA expression of avian uncoupling protein (UCP), thought to be implicated in thermogenesis in birds. Broiler chickens from 2 to 6 weeks of age received one of three isoenergetic diets containing different macronutrient ratios (low-lipid (LL) 30 v. 77 g lipid/kg-, low-protein (LP) 125 v. 197 g crude protein (N X 6.25)/kg; low-carbohydrate (LC) 440 v. 520 g carbohydrate/kg). LP chickens were characterised by significantly lower body weights and food intakes compared with LL and LC chickens (-47 and -38% respectively) but similar heat production/kg metabolic body weight, as measured by indirect calorimetry, in the three groups. However, heat production/g food ingested was higher in animals receiving the LP diet (+41%, P<0.05). These chickens also deposited 57% less energy as protein (P<0.05) and 33% more as fat. No significant differences in energy and N balances were detected between LL and LC chickens. The diets with the higher fat contents (i.e. The LP and LC diets) induced slightly but significantly higher relative expressions of avian UCP mRNA in gastrocnemius muscle, measured by reverse transcription-polymerase chain reaction, than the LL diet (88 and 90 v. 78% glyceraldehyde-3-phosphate dehydrogenase respectively, P<0.05). Our present results are consistent with the recent view that UCP homologues could be involved in the regulation of lipid utilisation as fuel substrate and provide evidence that the macronutrient content of the diet regulates energy metabolism and especially protein and fat deposition.

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

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The oxidative process of LDL particles generates molecules which are structurally similar to platelet-activating factor (PAF), and some effects of oxidized LDL (oxLDL) have been shown to be dependent on PAF receptor (PAFR) activation. In a previous study, we showed that PAFR is required for upregulation of CD36 and oxLDL uptake. In the present study we analyzed the molecular mechanisms activated by oxLDL in human macrophages and the contribution of PAFR to this response. Human adherent monocytes/macrophages were stimulated with oxLDL. Uptake of oxLDL and CD36 expression were determined by flow cytometry; MAP kinases and Akt phosphorylation by Western blot; IL-8 and MCP-1 concentration by ELISA and mRNA expression by real-time PCR. To investigate the participation of the PI3K/Akt pathway, G alpha i-coupled protein or PAFR, macrophages were treated with LY294002, pertussis toxin or with the PAFR antagonists WEB2170 and CV3988, respectively before addition of oxLDL. It was found that the addition of oxLDL to human monocytes/macrophages activates the PI3K/Akt pathway which in turn activates the MAPK (p38 and JNK). Phosphorylation of Akt requires the engagement of PAFR and a G alpha i-coupled protein. The upregulation of CD36 protein and the uptake of oxLDL as well as the IL-8 production are dependent on PI3K/Akt pathway activation. The increased CD36 protein expression is dependent on PAFR and G alpha i-coupled protein. Transfection studies using HEK 293t cells showed that oxLDL uptake occurs with either PAFR or CD36, but IL-8 production requires the co-transfection of both PAFR and CD36. These findings show that PAFR has a pivotal role in macrophages response to oxLDL and suggest that pharmacological intervention at the level of PAFR activation might be beneficial in atherosclerosis.