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排序方式: 共有5746条查询结果,搜索用时 15 毫秒
941.
Morgan-Kiss RM Chan LK Modla S Weber TS Warner M Czymmek KJ Hanson TE 《Photosynthesis research》2009,99(1):11-21
Green sulfur bacteria (GSB) rely on the chlorosome, a light-harvesting apparatus comprised almost entirely of self-organizing
arrays of bacteriochlorophyll (BChl) molecules, to harvest light energy and pass it to the reaction center. In Chlorobaculum tepidum, over 97% of the total BChl is made up of a mixture of four BChl c homologs in the chlorosome that differ in the number and identity of alkyl side chains attached to the chlorin ring. C. tepidum has been reported to vary the distribution of BChl c homologs with growth light intensity, with the highest degree of BChl c alkylation observed under low-light conditions. Here, we provide evidence that this functional response at the level of the
chlorosome can be induced not only by light intensity, but also by temperature and a mutation that prevents phototrophic thiosulfate
oxidation. Furthermore, we show that in conjunction with these functional adjustments, the fraction of cellular volume occupied
by chlorosomes was altered in response to environmental conditions that perturb the balance between energy absorbed by the
light-harvesting apparatus and energy utilized by downstream metabolic reactions. 相似文献
942.
943.
Siobhan M. Abeyesinghe Morven A. McLeman Rachael C. Owen Claire E. McMahon Christopher M. Wathes 《Behavioural processes》2009,81(1):1-13
Social relationships in domestic fowl are commonly assumed to rely on social recognition and its pre-requisite, discrimination of group-mates. If this is true, then the unnatural physical and social environments in which commercial laying hens are typically housed, when compared with those in which their progenitor species evolved, may compromise social function with consequent implications for welfare. Our aims were to determine whether adult hens can discriminate between unique pairs of familiar conspecifics, and to establish the most appropriate method for assessing this social discrimination. We investigated group-mate discrimination using two learning tasks in which there was bi-directional exchange of visual, auditory and olfactory information. Learning occurred in a Y-maze task (p < 0.003; n = 7/8) but not in an operant key-pecking task (p = 0.001; n = 1/10). A further experiment with the operant-trained hens examined whether failure was specific to the group-mate social discrimination or to the response task. Learning also failed to occur in this familiar/unfamiliar social discrimination task (p = 0.001; n = 1/10). Our findings demonstrate unequivocally that adult laying hens kept in small groups, under environmental conditions more consistent with those in which sensory capacities evolved, can discriminate group members: however, appropriate methods to demonstrate discrimination are crucial. 相似文献
944.
945.
Kirk D. Robarge Shirley A. Brunton Georgette M. Castanedo Yong Cui Michael S. Dina Richard Goldsmith Stephen E. Gould Oivin Guichert Janet L. Gunzner Jason Halladay Wei Jia Cyrus Khojasteh Michael F.T. Koehler Karen Kotkow Hank La Rebecca L. LaLonde Kevin Lau Leslie Lee Derek Marshall James C. Marsters Minli Xie 《Bioorganic & medicinal chemistry letters》2009,19(19):5576-5581
SAR for a wide variety of heterocyclic replacements for a benzimidazole led to the discovery of functionalized 2-pyridyl amides as novel inhibitors of the hedgehog pathway. The 2-pyridyl amides were optimized for potency, PK, and drug-like properties by modifications to the amide portion of the molecule resulting in 31 (GDC-0449). Amide 31 produced complete tumor regression at doses as low as 12.5 mg/kg BID in a medulloblastoma allograft mouse model that is wholly dependent on the Hh pathway for growth and is currently in human clinical trials, where it is initially being evaluated for the treatment of BCC. 相似文献
946.
Mark J. Ammirati Kim M. Andrews David D. Boyer Anne M. Brodeur Dennis E. Danley Shawn D. Doran Bernard Hulin Shenping Liu R. Kirk McPherson Stephen J. Orena Janice C. Parker Jana Polivkova Xiayang Qiu Carolyn B. Soglia Judith L. Treadway Maria A. VanVolkenburg Donald C. Wilder David W. Piotrowski 《Bioorganic & medicinal chemistry letters》2009,19(7):1991-1995
A series of 4-substituted proline amides was synthesized and evaluated as inhibitors of dipeptidyl pepdidase IV for the treatment of type 2 diabetes. (3,3-Difluoro-pyrrolidin-1-yl)-[(2S,4S)-(4-(4-pyrimidin-2-yl-piperazin-1-yl)-pyrrolidin-2-yl]-methanone (5) emerged as a potent (IC50 = 13 nM) and selective compound, with high oral bioavailability in preclinical species and low plasma protein binding. Compound 5, PF-00734200, was selected for development as a potential new treatment for type 2 diabetes. 相似文献
947.
Sabbir Ahmed Imran Shahid Sachin Dhanani Caroline P. Owen 《Bioorganic & medicinal chemistry letters》2009,19(16):4698-4701
We report the synthesis and biochemical evaluation of a range of 4-sulfonated derivatives of 4-hydroxybenzyl imidazole which has been targetted against the two components of 17α-hydroxylase/17,20-lyase (P-45017α), namely, 17α-hydroxylase (17α-OHase) and 17,20-lyase (lyase). The results from the biochemical testing suggest that the compounds synthesised are highly potent inhibitors possessing excellent selectivity towards the lyase component. 相似文献
948.
Robert O. Hughes John K. Walker D. Joseph Rogier Steve E. Heasley Rhadika M. Blevis-Bal Alan G. Benson E. Jon Jacobsen Jerry W. Cubbage Yvette M. Fobian Dafydd R. Owen John N. Freskos John M. Molyneaux David L. Brown Brad A. Acker Todd M. Maddux Mike B. Tollefson Joseph B. Moon Brent V. Mischke Jeanne M. Rumsey Yi Zheng Ying Yu 《Bioorganic & medicinal chemistry letters》2009,19(17):5209-5213
We describe efforts to improve the pharmacokinetic profile of the aminopyridopyrazinone class of PDE5 inhibitors. These efforts led to the discovery of 3-[(trans-4-hydroxycyclohexyl)amino]-7-(6-methoxypyridin-3-yl)-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2(1H)-one, a potent and selective inhibitor of PDE5 with an excellent PK profile. 相似文献
949.
Maheshinie Rajapaksha Jack F. Eichler Jan Hajduch David E. Anderson Kenneth L. Kirk James G. Bann 《Protein science : a publication of the Protein Society》2009,18(1):17-23
The binding of the Bacillus anthracis protective antigen (PA) to the host cell receptor is the first step toward the formation of the anthrax toxin, a tripartite set of proteins that include the enzymatic moieties edema factor (EF), and lethal factor (LF). PA is cleaved by a furin‐like protease on the cell surface followed by the formation of a donut‐shaped heptameric prepore. The prepore undergoes a major structural transition at acidic pH that results in the formation of a membrane spanning pore, an event which is dictated by interactions with the receptor and necessary for entry of EF and LF into the cell. We provide direct evidence using 1‐dimensional 13C‐edited 1H NMR that low pH induces dissociation of the Von‐Willebrand factor A domain of the receptor capillary morphogenesis protein 2 (CMG2) from the prepore, but not the monomeric full length PA. Receptor dissociation is also observed using a carbon‐13 labeled, 2‐fluorohistidine labeled CMG2, consistent with studies showing that protonation of His‐121 in CMG2 is not a mechanism for receptor release. Dissociation is likely caused by the structural transition upon formation of a pore from the prepore state rather than protonation of residues at the receptor PA or prepore interface. 相似文献
950.
Linda J.S. Allen Curtis L. Wesley Robert D. Owen Douglas G. Goodin David Koch Colleen B. Jonsson Yong-Kyu Chu J.M. Shawn Hutchinson Robert L. Paige 《Journal of theoretical biology》2009,260(4):510-522
New habitat-based models for spread of hantavirus are developed which account for interspecies interaction. Existing habitat-based models do not consider interspecies pathogen transmission, a primary route for emergence of new infectious diseases and reservoirs in wildlife and man. The modeling of interspecies transmission has the potential to provide more accurate predictions of disease persistence and emergence dynamics. The new models are motivated by our recent work on hantavirus in rodent communities in Paraguay. Our Paraguayan data illustrate the spatial and temporal overlaps among rodent species, one of which is the reservoir species for Jabora virus and others which are spillover species. Disease transmission occurs when their habitats overlap. Two mathematical models, a system of ordinary differential equations (ODE) and a continuous-time Markov chain (CTMC) model, are developed for spread of hantavirus between a reservoir and a spillover species. Analysis of a special case of the ODE model provides an explicit expression for the basic reproduction number, , such that if , then the pathogen does not persist in either population but if , pathogen outbreaks or persistence may occur. Numerical simulations of the CTMC model display sporadic disease incidence, a new behavior of our habitat-based model, not present in other models, but which is a prominent feature of the seroprevalence data from Paraguay. Environmental changes that result in greater habitat overlap result in more encounters among various species that may lead to pathogen outbreaks and pathogen establishment in a new host. 相似文献