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171.
172.
Mulugu S Bai W Fridy PC Bastidas RJ Otto JC Dollins DE Haystead TA Ribeiro AA York JD 《Science (New York, N.Y.)》2007,316(5821):106-109
Inositol pyrophosphates are a diverse group of high-energy signaling molecules whose cellular roles remain an active area of study. We report a previously uncharacterized class of inositol pyrophosphate synthase and find it is identical to yeast Vip1 and Asp1 proteins, regulators of actin-related protein-2/3 (ARP 2/3) complexes. Vip1 and Asp1 acted as enzymes that encode inositol hexakisphosphate (IP6) and inositol heptakisphosphate (IP7) kinase activities. Alterations in kinase activity led to defects in cell growth, morphology, and interactions with ARP complex members. The functionality of Asp1 and Vip1 may provide cells with increased signaling capacity through metabolism of IP6. 相似文献
173.
Hegde SS Vetting MW Roderick SL Mitchenall LA Maxwell A Takiff HE Blanchard JS 《Science (New York, N.Y.)》2005,308(5727):1480-1483
Fluoroquinolones are gaining increasing importance in the treatment of tuberculosis. The expression of MfpA, a member of the pentapeptide repeat family of proteins from Mycobacterium tuberculosis, causes resistance to ciprofloxacin and sparfloxacin. This protein binds to DNA gyrase and inhibits its activity. Its three-dimensional structure reveals a fold, which we have named the right-handed quadrilateral beta helix, that exhibits size, shape, and electrostatic similarity to B-form DNA. This represents a form of DNA mimicry and explains both its inhibitory effect on DNA gyrase and fluoroquinolone resistance resulting from the protein's expression in vivo. 相似文献
174.
Changelian PS Flanagan ME Ball DJ Kent CR Magnuson KS Martin WH Rizzuti BJ Sawyer PS Perry BD Brissette WH McCurdy SP Kudlacz EM Conklyn MJ Elliott EA Koslov ER Fisher MB Strelevitz TJ Yoon K Whipple DA Sun J Munchhof MJ Doty JL Casavant JM Blumenkopf TA Hines M Brown MF Lillie BM Subramanyam C Shang-Poa C Milici AJ Beckius GE Moyer JD Su C Woodworth TG Gaweco AS Beals CR Littman BH Fisher DA Smith JF Zagouras P Magna HA Saltarelli MJ Johnson KS Nelms LF Des Etages SG Hayes LS Kawabata TT 《Science (New York, N.Y.)》2003,302(5646):875-878
Because of its requirement for signaling by multiple cytokines, Janus kinase 3 (JAK3) is an excellent target for clinical immunosuppression. We report the development of a specific, orally active inhibitor of JAK3, CP-690,550, that significantly prolonged survival in a murine model of heart transplantation and in cynomolgus monkeys receiving kidney transplants. CP-690,550 treatment was not associated with hypertension, hyperlipidemia, or lymphoproliferative disease. On the basis of these preclinical results, we believe JAK3 blockade by CP-690,550 has potential for therapeutically desirable immunosuppression in human organ transplantation and in other clinical settings. 相似文献
175.
Cyclooxygenase (COX) inhibitors and the intestine 总被引:1,自引:0,他引:1
Little D Jones SL Blikslager AT 《Journal of veterinary internal medicine / American College of Veterinary Internal Medicine》2007,21(3):367-377
Nonsteroidal anti-inflammatory drugs (NSAIDs) have long been used for the treatment of pain and inflammation because of their inhibitory effects on cyclooxygenase (COX). For almost as long as NSAIDs have been in use, multiple adverse effects have been noted. Assessment of many of these adverse effects have been complicated because of the discovery of multiple splice variants of the cox gene, and a greater array of COX inhibitors, especially the COX-2 selective inhibitors have become available. Some of these adverse effects cannot be readily explained by the effect of these drugs on COX. This has sparked a new field of investigation into the COX-independent effects of the COX inhibitors. The major noncyclooxygenase targets of the COX inhibitors of particular relevance to inflammation and the gastrointestinal tract are phosphatidylinositol 3'-kinase Akt signaling, uncoupling of oxidative phosphorylation, PPARgamma, nuclear factor KB, mitogen activated protein kinases, and heat shock proteins. 相似文献
176.
Disaster damage levels are matched to county‐level nonprofit activity indicators. Using dynamic panel‐data estimation, nonprofit net assets (and nonprofit revenue to a lesser extent) defined at this local level are found to be positively correlated with disaster event damage levels, consistent with a post‐disaster giving mechanism. Magnitudes are relatively small, suggesting a distributed downstream flow of benefits to local nonprofits from larger national organizations. Furthermore, disaster damage at a lag is associated with only minor increases in the count of local nonprofit organizations at the county level. The relative impacts of assets and nonprofit counts in particular indicate that existing nonprofits have the established credibility and networks to be reliable conduits for post‐disaster asset flows. If local nonprofits are an indicator of regional social capital, the findings suggest that disasters reveal the resilience of social capital structures in the face of crisis along the focal dimension of nonprofit activity. 相似文献
177.
Clarisse Boulenger Alain J. Crivelli Fabien Charrier Jean‐Marc Roussel Eric Feunteun Anthony Acou 《Ecology of Freshwater Fish》2016,25(2):281-294
As a key parameter in the management of fish populations, individual growth rate (GR) variations were examined in the European eel (Anguilla anguilla; > 150 mm) using extensive mark–recapture surveys in the lotic habitats of two small rivers of western France: the Frémur, supposed to be saturated, and at the same latitude, the Oir with densities fivefold lower than those of the Frémur. In both systems, generalised linear models were used to test whether spatiotemporal factors such as dominant habitat type or local density affect GR variability. In the presumed unsaturated system, the Oir, GR variability is mainly explained by a set of habitat suitability drivers (density, dominant habitat type). In the Frémur, GRs appear independent of differences in habitat density or productivity. Below saturation, an increase in density will decrease the GR through intraspecific competition. At saturation, intraspecific competition reaches such high levels that regardless of eel density and productivity, the resources available by individual are similar throughout the system. In these circumstances, the effect of density on growth was presumed undetectable. Despite these contrasted results, mean GRs observed in both catchments were closed (~20 mm·year?1). This is an unexpected result as GR is expected to be higher in unsaturated systems. This similarity could be explained by the difference between the two systems in terms of: (i) sex ratio (the Frémur is dominated by male, whereas the female is dominant in the Oir), (ii) habitat type distribution or (iii) possible interspecific competition (important salmonid populations in the Oir). 相似文献
178.
179.
Jideani VA Nkama I Agbo EB Jideani IA 《Plant foods for human nutrition (Dordrecht, Netherlands)》2001,56(1):23-36
The objective of research was to conduct a survey related to the production process for fura. Fura is a staple food for the Fulanis and Hausas. The single most important cereal grain for fura production is millet. A significant difference exists among respondents on the variety of millet chosen for fura production. A significantly greater proportion (p=0.05) indicated that `gero' is the variety in common use. Spices are indispensable as an ingredient in fura production with ginger being the single most important spice (p=0.01). The traditional pounding method for processing millet into flour is still very much used. The implication of this is highlighted and a possible solution of optimizing fura production process is recommended. Strictly speaking, fura is distributed with a minimum of packaging. The choice of suitable package provided protection during a generally short shelf-life and for local distribution. With increasing influence of advertising upon customers, small food processing enterprises making fura will have to improve the packaging and preservation of their products if they are to survive the competition. 相似文献
180.