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121.
Ahmed Alagha Edelmiro Moman Mauro F.A. Adamo Kevin B. Nolan Anthony J. Chubb 《Bioorganic & medicinal chemistry letters》2009,19(15):4213-4216
Acetylsalicylic acid (aspirin) is an effective long-term prophylaxis of thrombotic events such as heart attacks and strokes. It covalently inhibits prostaglandin-H-synthase by interacting with Arg120 or Tyr385 at the active site allowing delivery of its acetyl group to Ser530. However the structure has not been optimized to fit the active site. We have designed acetylsalicylate analogues with an additional carboxylate substituent which allows simultaneous interaction with Arg120 and Tyr385 whilst positioning the acetyl group in close proximity to Ser530. One of these, an ester derivative which unlike acetylsalicylic acid is non-acidic, may act as useful lead compound for further exploitation of this approach. 相似文献
122.
Giordano Simonetta Sorbo Sergio Adamo Paola Basile Adriana Spagnuolo Valeria Cobianchi Rosa Castaldo 《Plant Ecology》2004,170(1):1-14
In the present study epiphytic bryophytes were employed as a model system in an integrated way both as bioindicators at species, population and community levels and as bioaccumulators of airborne trace elements. Twenty sites with Quercus ilex trees were chosen in a Mediterranean area both in urban and natural locations, with an altitude ranging from 0 to about 500 m a.s.l., in coastal and inland areas (Campania, Italy). Data on the presence of species, cover values and phenology were recorded for each site and the Index of Atmospheric Purity (IAP) was calculated. The data matrix of frequency/cover × species was analysed by multivariate methods. Data obtained clearly show that in urban sites the number of species and IAP values are lower, and that acrocarpous mosses and vegetative reproduction occur more frequently. Contents of trace elements (Al, As, Cd, Co, Cr, Cu, Fe, Mn, Mo, Ni, Pb, Ti, V, Zn) were measured in four species and concentrations were normalised to the soil pattern by calculating the Enrichment Factor (EF). The results show the large contribution of resuspended soil particles to the chemical composition of the analysed bryophytes. All the examined species were enriched in Cd, Cu and Zn, and in some cases showed high EF for Pb. The differences among epiphytic bryophyte vegetation are discussed in order to evaluate suspected alterations due to human impact and/or environmental change. 相似文献
123.
T E Graham K B Adamo J Shearer I Marchand B Saltin 《Journal of applied physiology》2001,90(3):873-879
We examined the net catabolism of two pools of glycogen, proglycogen (PG) and macroglycogen (MG), in human skeletal muscle during exercise. Male subjects (n = 21) were assigned to one of three groups. Group 1 exercised 45 min at 70% maximal O(2) uptake (VO(2 max)) and had muscle biopsies at rest, 15 min, and 45 min. Group 2 exercised at 85% VO(2 max) to exhaustion (45.4 +/- 3.4 min) and had biopsies at rest, 10 min, and exhaustion. Group 3 performed three 3-min bouts of exercise at 100% VO(2 max) separated by 6 min of rest. Biopsies were taken at rest and after each bout. Group 1 had small MG and PG net glycogenolysis rates (ranging from 3.8 +/- 1.0 to 2.4 +/- 0.6 mmol glucosyl units. kg(-1). min(-1)) that did not change over time. In group 2, the MG glycogenolysis rate remained low and unchanged over time, whereas the PG rate was initially elevated (11.3 +/- 2.3 mmol glucosyl units. kg(-1). min(-1)) and declined (P < or = 0.05) with time. During the first 10 min, PG concentration ([PG]) declined (P < or = 0.05), whereas MG concentration ([MG]) did not. Similarly, in group 3, in both the first and the second bouts of exercise [PG] declined (P < or = 0.05) and [MG] did not, although by the end of the second exercise period the [MG] was lower (P < or = 0.05) than the rest level. The net catabolic rates for PG in the first two exercises were 22.6 +/- 6.8 and 21.8 +/- 8.2 mmol glucosyl units. kg(-1). min(-1), whereas the corresponding values for MG were 17.6 +/- 6.0 and 10.8 +/- 5.6. The MG pool appeared to be more resistant to mobilization, and, when activated, its catabolism was inhibited more rapidly than that of PG. This suggests that the metabolic regulation of the two pools must be different. 相似文献
124.
Adamo SA 《Animal behaviour》1999,57(1):117-124
Animals should increase their present reproductive output if their chances for future reproduction are low. However, an animal's ability to make this adjustment may be constrained by the physiological mechanisms mediating the response. To examine this hypothesis, I infected 2- and 5-week-old female crickets, Acheta domesticus, with either a pathogen (the bacterium Serratia marcescens) that induces antimicrobial immune responses, or a parasite (larvae of the parasitoid fly, Ormia ochracea) that induces an encapsulation immune response. Females of both age groups infected with bacteria laid more eggs the day after injection than did saline-injected crickets. A similar increase was elicited by injecting components of the bacterial cell wall (lipopolysaccharides). The bacteria-induced increase in egg laying (1) was not the result of physical stress, (2) did not appear to be a nonspecific response to the infection, and (3) was probably not mediated by octopamine. Females did not increase egg laying when infested with O. ochracea, even though this parasitoid invariably kills its host. Injections of Sephadex beads, which induced an immune response similar to that created by the parasitoids, also had no effect on egg laying. These results are consistent with the hypotheses that crickets can increase egg laying in response to infection and that increased egg output correlates with the activation of some, but not all, immune responses. Copyright 1999 The Association for the Study of Animal Behaviour. 相似文献
125.
Piluso G Carella M D'Avanzo M Santinelli R Carrano EM D'Avanzo A D'Adamo AP Gasparini P Nigro V 《Human genetics》2003,112(2):124-130
FG syndrome (FGS, MIM 305450) is a rare X-linked recessive disorder comprising mental retardation and multiple malformations. Various families have been described to date, increasing our knowledge of the phenotype variability and making the clinical diagnosis complex, especially in sporadic patients. The first locus for FG syndrome (FGS1) was linked to chromosome region Xq12-q21.31, but other families have been excluded from this locus. The genetic heterogeneity of FG syndrome has been confirmed by analysis of an X chromosome inversion [inv(X)(q11q28)] in an affected boy and in his mentally retarded maternal uncle, suggesting that an additional locus for FG syndrome (FGS2, MIM 300321) is located at either Xq11 or Xq28. Recently, a third locus (FGS3) has been mapped to Xp22.3. We have identified and clinically characterized an Italian FG family, including 31 members with three affected males in two generations and two obligate carriers. We have excluded linkage to known FGS loci, whereas an extensive study of the whole X chromosome has yielded a maximum LOD score (Z(max)) of 2.66 (recombination fraction=0) for markers between DXS8113 and sWXD805. This new locus for FG syndrome corresponds to a region of approximately 4.6 Mb on the X chromosome. 相似文献
126.
Naro F De Arcangelis V Coletti D Molinaro M Zani B Vassanelli S Reggiani C Teti A Adamo S 《American journal of physiology. Cell physiology》2003,284(4):C969-C976
Cytoplasmic Ca2+concentration ([Ca2+]i) variation is akey event in myoblast differentiation, but the mechanism by which itoccurs is still debated. Here we show that increases of extracellular Ca2+ concentration ([Ca2+]o)produced membrane hyperpolarization and a concentration-dependent increase of [Ca2+]i due to Ca2+influx across the plasma membrane. Responses were not related toinositol phosphate turnover and Ca2+-sensing receptor.[Ca2+]o-induced[Ca2+]i increase was inhibited byCa2+ channel inhibitors and appeared to be modulated byseveral kinase activities. [Ca2+]i increasewas potentiated by depletion of intracellular Ca2+ storesand depressed by inactivation of the Na+/Ca2+exchanger. The response to arginine vasopressin (AVP), which inducesinositol 1,4,5-trisphosphate-dependent[Ca2+]i increase in L6-C5 cells, was notmodified by high [Ca2+]o. On the contrary,AVP potentiated the [Ca2+]i increase in thepresence of elevated [Ca2+]o. Other clones ofthe L6 line as well as the rhabdomyosarcoma RD cell line and thesatellite cell-derived C2-C12 line expressed similar responses to high[Ca2+]o, and the amplitude of the responseswas correlated with the myogenic potential of the cells. 相似文献
127.
The C-terminal segment of the loop between transmembrane helices 2 and 3 (A(L) region) of the plasma membrane Ca(2+) pump (PMCA) is not conserved in other P-ATPases. Part of this region, just upstream from the third transmembrane domain, has been associated with activation of the PMCA by acidic lipids. cDNAs coding for mutants of the Ca(2+) pump isoform h4xb with deletions in the A(L) region were constructed, and the proteins were successfully expressed in either COS or Chinese hamster ovary cells. Mutants with deletions in the segment 296-349 had full Ca(2+) transport activity, but deletions involving the segment of amino acids 350-356 were inactive suggesting that these residues are required for a functional PMCA. In the absence of calmodulin the V(max) of mutant d296-349 was similar to that of the recombinant wild type pump, but its K(0.5) for Ca(2+) was about 5-fold lower. The addition of calmodulin increased the V(max) and the apparent Ca(2+) affinity of both the wild type and d296-349 enzymes indicating that the activating effects of calmodulin were not affected by the deletion. At low concentrations of Ca(2+) and in the presence of saturating amounts of calmodulin, the addition of phosphatidic acid increased about 2-fold the activity of the recombinant wild type pump. In contrast, under these conditions phosphatidic acid did not significantly change the activity of mutant d296-349. Taken together these results suggest that (a) deletion of residues 296-349 recreates a form of PMCA similar to that resulting from the binding of acidic lipids at the A(L) region; (b) the A(L) region acts as an acidic lipid-binding inhibitory domain capable of adjusting the Ca(2+) affinity of the PMCA to the lipid composition of the membrane; and (c) the function of the A(L) region is independent of the autoinhibition by the C-terminal calmodulin-binding region. 相似文献
128.
129.
130.
The purpose of this study was to characterize the mechanisms by which glucose regulates IGF-I gene expression in rat C6 glioma cells and in rat GH3 pituitary adenoma cells. Glucose starvation for periods of 12 to 48 h decreased IGF-I mRNA levels. In contrast, there was no stimulation of IGF-I mRNA by medium glucose between 1 and 25 mM over a 24-h period. Studies with hexoses and glycolytic metabolites suggested that glucose metabolism was required to maintain IGF-I mRNA. Glucose starvation lowered IGF-I mRNA half-life in both C6 and GH3 cells. Protein synthesis inhibition lowered IGF-I mRNA by about 20% in glucose-fed C6 and GH3 cells, while potently increasing IGF-I mRNA in glucose-starved C6 cells and not altering IGF-I mRNA in glucose-starved GH3 cells. Our results suggest that in these tumor cells, IGF-I mRNA stability is reduced by glucose starvation, secondary to a deficiency in intracellular glucose metabolism. Ongoing protein synthesis is not required for this mRNA de-stabilizing effect in GH3 cells. Rather, in glucose-starved C6 cells, decreased IGF-I mRNA stability may result from the action of a labile protein. 相似文献