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981.
Cantin LD Magnuson S Gunn D Barucci N Breuhaus M Bullock WH Burke J Claus TH Daly M Decarr L Gore-Willse A Hoover-Litty H Kumarasinghe ES Li Y Liang SX Livingston JN Lowinger T Macdougall M Ogutu HO Olague A Ott-Morgan R Schoenleber RW Tersteegen A Wickens P Zhang Z Zhu J Zhu L Sweet LJ 《Bioorganic & medicinal chemistry letters》2007,17(10):2869-2873
Modulation of cAMP levels has been linked to insulin secretion in preclinical animal models and in humans. The high expression of PDE-10A in pancreatic islets suggested that inhibition of this enzyme may provide the necessary modulation to elicit increased insulin secretion. Using an HTS approach, we have identified quinoline-based PDE-10A inhibitors as insulin secretagogues in vitro. Optimized compounds were evaluated in vivo where improvements in glucose tolerance and increases in insulin secretion were measured. 相似文献
982.
983.
Teepe AG Loprete DM He Z Hoggard TA Hill TW 《Fungal genetics and biology : FG & B》2007,44(6):554-562
The calC2 mutation in Aspergillus nidulans causes hypersensitivity to Calcofluor White, along with other drug sensitivities that indicate a defect in cell wall integrity. We have cloned CalC by complementation, isolating the A. nidulans orthologue of protein kinase C (PkcA). The pkcA allele of the calC2 strain contains a mutation predicted to introduce a charged arginine residue in place of neutral glycine at a conserved site located immediately beside the C1B regulatory domain. Both PkcA and calC2 map to the same region of chromosome VIII. A PkcA::GFP chimera localizes to hyphal apices and growing septa, as well as to the conidiogenous apices of phialides, indicating a role for PkcA in polarized cell wall growth. These observations support the hypothesis that the role of PkcA in A. nidulans, is comparable to that played by Pkc1p in the Saccharomyces cerevisiae cell wall integrity pathway. 相似文献
984.
985.
Revell TK Dunbar SG 《Comparative biochemistry and physiology. Part A, Molecular & integrative physiology》2007,148(2):393-398
One of the proposed ecological functions of sleep is to conserve energy. The majority of studies that support this theory have been done on endothermic animals whose body temperatures drop during sleep due to the reduced neurological control of thermoregulation. In the present study, we examined typical temperatures to which the Desert Iguana, Dipsosaurus dorsalis, is exposed to in the field and found that mean high temperatures ranged from 24-58 degrees C throughout the active portion of the year. We also examined the ecological savings that sleep could provide for this ectothermic iguana using a closed system respirometer. We found that laboratory-acclimated iguanas are able to save significantly more (27.6%) energy by sleeping than by being awake and that field iguanas also had significant savings of energy (69.1%) while asleep. However, iguanas could save more energy by remaining awake at cooler temperatures than by sleeping at warmer temperatures. In addition, we found no correlation for time of night with metabolic rate. Our study supports the hypothesis that one potential function of sleep is to conserve energy. 相似文献
986.
987.
988.
989.
Idell S Allen T Chen S Koenig K Mazar A Azghani A 《American journal of physiology. Lung cellular and molecular physiology》2007,293(1):L25-L32
High levels of adenosine can be measured from the lungs of asthmatics, and it is well recognized that aerosolized 5'AMP, the precursor of adenosine, elicits robust bronchoconstriction in patients with this disease. Characterization of mice with elevated adenosine levels secondary to the loss of adenosine deaminase (ADA) expression, the primary metabolic enzyme for adenosine, further support a role for this ubiquitous mediator in the pathogenesis of asthma. To begin to identify pathways by which adenosine can alter airway tone, we examined adenosine-induced bronchoconstriction in four mouse lines, each lacking one of the receptors for this nucleoside. We show, using direct measures of airway mechanics, that adenosine can increase airway resistance and that this increase in resistance is mediated by binding the A(1) receptor. Further examination of this response using pharmacologically, surgically, and genetically manipulated mice supports a model in which adenosine-induced bronchoconstriction occurs indirectly through the activation of sensory neurons. 相似文献
990.
Smith TR Clark AJ Napier R Taylor PC Thompson AJ Marsh A 《Bioconjugate chemistry》2007,18(4):1355-1359
We prepare a biotinylated conjugate of the ubiquitous plant hormone (S)-(+)-abscisic acid via an acyl hydrazone linkage at the C4' position and demonstrate in vivo cleavage of the otherwise stable acyl hydrazone linkage using LC-MS2. As part of a wider chemical genomic study, biological activity of the conjugate was assessed using standard epidermal peel and gravimetric transpiration assays, showing significant activity but at a level lower than the unconjugated hormone. When deuterated samples of the conjugate were fed to the plant, however, it was apparent by LC-MS2 experiments that significant levels of hydrolysis of the acyl hydrazone had taken place, contrary to in vitro stability assays in artificial sap. We conclude that abscisic acid is liberated in sufficient quantities to account for the observed physiological response and that LC-MS2 monitoring of conjugates is a simple and practical method by which such events may be assessed, whether in plants or other organisms. 相似文献