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261.
Adipocytes have been studied with increasing intensity as a result of the emergence of obesity as a serious public health problem and the realization that adipose tissue serves as an integrator of various physiological pathways. In particular, their role in calorie storage makes adipocytes well suited to the regulation of energy balance. Adipose tissue also serves as a crucial integrator of glucose homeostasis. Knowledge of adipocyte biology is therefore crucial for understanding the pathophysiological basis of obesity and metabolic diseases such as type 2 diabetes. Furthermore, the rational manipulation of adipose physiology is a promising avenue for therapy of these conditions. 相似文献
262.
Wang J Soisson SM Young K Shoop W Kodali S Galgoci A Painter R Parthasarathy G Tang YS Cummings R Ha S Dorso K Motyl M Jayasuriya H Ondeyka J Herath K Zhang C Hernandez L Allocco J Basilio A Tormo JR Genilloud O Vicente F Pelaez F Colwell L Lee SH Michael B Felcetto T Gill C Silver LL Hermes JD Bartizal K Barrett J Schmatz D Becker JW Cully D Singh SB 《Nature》2006,441(7091):358-361
Bacterial infection remains a serious threat to human lives because of emerging resistance to existing antibiotics. Although the scientific community has avidly pursued the discovery of new antibiotics that interact with new targets, these efforts have met with limited success since the early 1960s. Here we report the discovery of platensimycin, a previously unknown class of antibiotics produced by Streptomyces platensis. Platensimycin demonstrates strong, broad-spectrum Gram-positive antibacterial activity by selectively inhibiting cellular lipid biosynthesis. We show that this anti-bacterial effect is exerted through the selective targeting of beta-ketoacyl-(acyl-carrier-protein (ACP)) synthase I/II (FabF/B) in the synthetic pathway of fatty acids. Direct binding assays show that platensimycin interacts specifically with the acyl-enzyme intermediate of the target protein, and X-ray crystallographic studies reveal that a specific conformational change that occurs on acylation must take place before the inhibitor can bind. Treatment with platensimycin eradicates Staphylococcus aureus infection in mice. Because of its unique mode of action, platensimycin shows no cross-resistance to other key antibiotic-resistant strains tested, including methicillin-resistant S. aureus, vancomycin-intermediate S. aureus and vancomycin-resistant enterococci. Platensimycin is the most potent inhibitor reported for the FabF/B condensing enzymes, and is the only inhibitor of these targets that shows broad-spectrum activity, in vivo efficacy and no observed toxicity. 相似文献
263.
Goldraij A Kondo K Lee CB Hancock CN Sivaguru M Vazquez-Santana S Kim S Phillips TE Cruz-Garcia F McClure B 《Nature》2006,439(7078):805-810
Pollen-pistil interactions are crucial for controlling plant mating. For example, S-RNase-based self-incompatibility prevents inbreeding in diverse angiosperm species. S-RNases are thought to function as specific cytotoxins that inhibit pollen that has an S-haplotype that matches one of those in the pistil. Thus, pollen and pistil factors interact to prevent mating between closely related individuals. Other pistil factors, such as HT-B, 4936-factor and the 120 kDa glycoprotein, are also required for pollen rejection but do not contribute to S-haplotype-specificity per se. Here we show that S-RNase is taken up and sorted to a vacuolar compartment in the pollen tubes. Antibodies to the 120 kDa glycoprotein label the compartment membrane. When the pistil does not express HT-B or 4936-factor, S-RNase remains sequestered, unable to cause rejection. Similarly, in wild-type pistils, compatible pollen tubes degrade HT-B and sequester S-RNase. We suggest that S-RNase trafficking and the stability of HT-B are central to S-specific pollen rejection. 相似文献
264.
Stream denitrification across biomes and its response to anthropogenic nitrate loading 总被引:11,自引:0,他引:11
Mulholland PJ Helton AM Poole GC Hall RO Hamilton SK Peterson BJ Tank JL Ashkenas LR Cooper LW Dahm CN Dodds WK Findlay SE Gregory SV Grimm NB Johnson SL McDowell WH Meyer JL Valett HM Webster JR Arango CP Beaulieu JJ Bernot MJ Burgin AJ Crenshaw CL Johnson LT Niederlehner BR O'Brien JM Potter JD Sheibley RW Sobota DJ Thomas SM 《Nature》2008,452(7184):202-205
Anthropogenic addition of bioavailable nitrogen to the biosphere is increasing and terrestrial ecosystems are becoming increasingly nitrogen-saturated, causing more bioavailable nitrogen to enter groundwater and surface waters. Large-scale nitrogen budgets show that an average of about 20-25 per cent of the nitrogen added to the biosphere is exported from rivers to the ocean or inland basins, indicating that substantial sinks for nitrogen must exist in the landscape. Streams and rivers may themselves be important sinks for bioavailable nitrogen owing to their hydrological connections with terrestrial systems, high rates of biological activity, and streambed sediment environments that favour microbial denitrification. Here we present data from nitrogen stable isotope tracer experiments across 72 streams and 8 regions representing several biomes. We show that total biotic uptake and denitrification of nitrate increase with stream nitrate concentration, but that the efficiency of biotic uptake and denitrification declines as concentration increases, reducing the proportion of in-stream nitrate that is removed from transport. Our data suggest that the total uptake of nitrate is related to ecosystem photosynthesis and that denitrification is related to ecosystem respiration. In addition, we use a stream network model to demonstrate that excess nitrate in streams elicits a disproportionate increase in the fraction of nitrate that is exported to receiving waters and reduces the relative role of small versus large streams as nitrate sinks. 相似文献
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Summary Energy transfer from the second excited state of spirobifluorene is examined by polarization spectroscopy. Evidence against spiroconjugation and evidence in favor of a coulombic mechanism is reviewed and discussed. This coulombic interaction is categorized as an intramolecular energy transfer caused by the extrinsic factors of the Weber nomenclature. 相似文献
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270.
Herron BJ Liddell RA Parker A Grant S Kinne J Fisher JK Siracusa LD 《Nature genetics》2005,37(11):1210-1212
Stratifin (Sfn, also called 14-3-3sigma) is highly expressed in differentiating epidermis and mediates cell cycle arrest. Sfn is repressed in cancer, but its function during development is uncharacterized. We identified an insertion mutation in the gene Sfn in repeated epilation (Er) mutant mice by positional cloning. Er/+ mice expressed a truncated Sfn protein, which probably contributes to the defects in Er/Er and Er/+ epidermis and to cancer development in Er/+ mice. 相似文献