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81.
A strain of the fungus Beauveria bassiana (Balsamo) Vuillemin (Deuteromycota: Hyphomycetes) isolated from varroa mites, Varroa destructor Anderson & Trueman (Acari: Varroidae), was used to treat honey bees, Apis mellifera L. (Hymenoptera: Apidae), against varroa mites in southern France. Fungal treatment caused a significant increase in the percentage of infected varroa mites compared with control treatments in two field experiments. In the first experiment, hives were treated with a formulation containing 0.37 g of B. bassiana conidia per hive and in the second experiment with a dose of 1.0 g of conidia per hive. The percentage of infected varroa mites also increased in the nontreated (control) hives, suggesting a movement of conidia, probably via bee drift, among the hives. Mite fall was significantly higher among treated hives compared with control hives on the sixth and eighth days after treatment in the first experiment. These days correspond to previously published data on the median survivorship of mites exposed to that fungal solate. The interaction of treatment and date was significant in the second experiment with respect to mite fall. Increases in colony-forming unit (cfu) density per bee were observed in all treatments but were significantly higher among bees from treated hives than control hives for at least a week after treatment. The relationship between cfu density per bee and proportion infected was modeled using a sigmoid curve. High levels of infection (>80%) were observed for cfu density per bee as low as 5 x 102 per bee, but the cfu density in hives treated with 0.37 g generally dropped below this level less than a week after treatment. 相似文献
82.
The reaction-diffusion system of the neuromuscular junction has been modeled in 3D using the finite element package FEtk. The numerical solution of the dynamics of acetylcholine with the detailed reaction processes of acetylcholinesterases and nicotinic acetylcholine receptors has been discussed with the reaction-determined boundary conditions. The simulation results describe the detailed acetylcholine hydrolysis process, and reveal the time-dependent interconversion of the closed and open states of the acetylcholine receptors as well as the percentages of unliganded/monoliganded/diliganded states during the neuro-transmission. The finite element method has demonstrated its flexibility and robustness in modeling large biological systems. 相似文献
83.
Sangild PT Malo C Schmidt M Petersen YM Elnif J Holst JJ Buddington RK 《American journal of physiology. Regulatory, integrative and comparative physiology》2007,293(6):R2179-R2184
Exogenous glucagon-like peptide 2 (GLP-2) prevents intestinal atrophy and increases nutrient absorption in term newborn pigs receiving total parenteral nutrition (TPN). We tested the hypothesis that the immature intestine of fetuses and preterm neonates has a diminished nutrient absorption response to exogenous GLP-2. This was accomplished using catheterized fetal pigs infused for 6 days (87-91% of gestation) with GLP-2 (25 nmol.kg(-1).day(-1) iv; n = 7) or saline (n = 7), and cesarean-delivered preterm pigs (92% of gestation) that received TPN with GLP-2 (25 nmol.kg(-1).day(-1) iv; n = 8) or saline (n = 7) for 6 days after birth. Responses to GLP-2 were assessed by measuring intestinal dimensions, absorption of nutrients (glucose, leucine, lysine, proline) by intact tissues and brush border membrane vesicles, and abundance of sodium-glucose cotransporter mRNA. Infusion of GLP-2 increased circulating GLP-2 levels in fetuses, but did not increase intestinal mass or absorption of nutrients by intact tissues and brush border membrane vesicles, except for lysine. Administration of exogenous GLP-2 to preterm TPN-fed pigs similarly did not increase rates of nutrient absorption, yet nutrient absorption capacities of the entire small intestine tended to increase (+10-20%, P < 0.10) compared with TPN alone due to increased intestinal mass (+30%, P < 0.05). GLP-2 infusion did not increase sodium-glucose cotransporter-1 mRNA abundance in fetuses or postnatal preterm pigs. Hence, the efficacy of exogenous GLP-2 to improve nutrient absorption by the intestine of fetal and preterm pigs is limited compared with term pigs and more mature animals and humans. 相似文献
84.
Teng M Johnson MD Thomas C Kiel D Lakis JN Kercher T Aytes S Kostrowicki J Bhumralkar D Truesdale L May J Sidelman U Kodra JT Jørgensen AS Olesen PH de Jong JC Madsen P Behrens C Pettersson I Knudsen LB Holst JJ Lau J 《Bioorganic & medicinal chemistry letters》2007,17(19):5472-5478
Following our previous publication describing the biological profiles, we herein describe the structure-activity relationships of a core set of quinoxalines as the hGLP-1 receptor agonists. The most potent and efficacious compounds are 6,7-dichloroquinoxalines bearing an alkyl sulfonyl group at the C-2 position and a secondary alkyl amino group at the C-3 position. These findings serve as a valuable starting point for the discovery of more drug-like small molecule agonists for the hGLP-1 receptor. 相似文献
85.
Palmer AM Grobbel B Brehm C Zimmermann PJ Buhr W Feth MP Holst HC Simon WA 《Bioorganic & medicinal chemistry》2007,15(24):7647-7660
A series of novel tetrahydroimidazo[2,1-a]isoquinolines was prepared based on a hetero Diels–Alder reaction between an enamine and 1,2,4-triazine as key step. A structure–activity relationship was established focussing on the influence of the substitution pattern in position 3 and 6 of the heterocycle on antisecretory activity, lipophilicity, and pKa value. Potent inhibitors of the gastric acid pump were identified. 相似文献
86.
87.
Walz HA Wierup N Vikman J Manganiello VC Degerman E Eliasson L Holst LS 《Cellular signalling》2007,19(7):1505-1513
cAMP signaling is important for the regulation of insulin secretion in pancreatic beta-cells. The level of intracellular cAMP is controlled through its production by adenylyl cyclases and its breakdown by cyclic nucleotide phosphodiesterases (PDEs). We have previously shown that PDE3B is involved in the regulation of nutrient-stimulated insulin secretion. Here, aiming at getting deeper functional insights, we have examined the role of PDE3B in the two phases of insulin secretion as well as its localization in the beta-cell. Depolarization-induced insulin secretion was assessed and in models where PDE3B was overexpressed [islets from transgenic RIP-PDE3B/7 mice and adenovirally (AdPDE3B) infected INS-1 (832/13) cells], the first phase of insulin secretion, occurring in response to stimulation with high K(+) for 5 min, was significantly reduced ( approximately 25% compared to controls). In contrast, in islets from PDE3B(-/-) mice the response to high K(+) was increased. Further, stimulation of isolated beta-cells from RIP-PDE3B/7 islets, using successive trains of voltage-clamped depolarizations, resulted in reduced Ca(2+)-triggered first phase exocytotic response as well as reduced granule mobilization-dependent second phase, compared to wild-type beta-cells. Using sub-cellular fractionation, confocal microscopy and transmission electron microscopy of isolated mouse islets and INS-1 (832/13) cells, we show that endogenous and overexpressed PDE3B is localized to insulin granules and plasma membrane. We conclude that PDE3B, through hydrolysis of cAMP in pools regulated by Ca(2+), plays a regulatory role in depolarization-induced insulin secretion and that the enzyme is associated with the exocytotic machinery in beta-cells. 相似文献
88.
89.
Trine Holst S?rensen Nicolaj Cruys-Bagger Michael Skovbo Windahl Silke Flindt Badino Kim Borch Peter Westh 《The Journal of biological chemistry》2015,290(36):22193-22202
We measured hydrolytic rates of four purified cellulases in small increments of temperature (10–50 °C) and substrate loads (0–100 g/liter) and analyzed the data by a steady state kinetic model that accounts for the processive mechanism. We used wild type cellobiohydrolases (Cel7A) from mesophilic Hypocrea jecorina and thermophilic Rasamsonia emersonii and two variants of these enzymes designed to elucidate the role of the carbohydrate binding module (CBM). We consistently found that the maximal rate increased strongly with temperature, whereas the affinity for the insoluble substrate decreased, and as a result, the effect of temperature depended strongly on the substrate load. Thus, temperature had little or no effect on the hydrolytic rate in dilute substrate suspensions, whereas strong temperature activation (Q10 values up to 2.6) was observed at saturating substrate loads. The CBM had a dual effect on the activity. On one hand, it diminished the tendency of heat-induced desorption, but on the other hand, it had a pronounced negative effect on the maximal rate, which was 2-fold larger in variants without CBM throughout the investigated temperature range. We conclude that although the CBM is beneficial for affinity it slows down the catalytic process. Cel7A from the thermophilic organism was moderately more activated by temperature than the mesophilic analog. This is in accord with general theories on enzyme temperature adaptation and possibly relevant information for the selection of technical cellulases. 相似文献
90.
Jason A Roberts Michael S Roberts Andrew Semark Andrew A Udy Carl MJ Kirkpatrick David L Paterson Matthew J Roberts Peter Kruger Jeffrey Lipman 《BMC anesthesiology》2011,11(1):1-7