927 resultados para Edward W. Said


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Chlamydia trachomatis infection (chlamydia) is the most common notifiable bacterial sexually transmitted infection (STI) worldwide. In the United States of America (USA) in 2009, 1,244,180 cases of chlamydia were reported to the Centers for Disease Control and Prevention (CDC), the largest number of cases ever reported to CDC for any notifiable disease [1]. It has been estimated, from population prevalence surveys, that approximately 2 % of sexually active adults aged 18–44 years old in the UK [2] and 2.2 % (CI, 1.8–2.8 %) of the US population aged 14–39 years [3] are infected with chlamydia. This level of prevalence in the USA translates into an estimated 2,291,000 (95 % confidence interval, CI, 1,857,000–2,838,000) chlamydia infections each year [3]. Globally, the World Health Organization (WHO) estimates that there are about 92 million new cases of chlamydia each year [4].

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Myosin B (MyoB) is one of the two short class XIV myosins encoded in the Plasmodium genome. Class XIV myosins are characterized by a catalytic "head," a modified "neck," and the absence of a "tail" region. Myosin A (MyoA), the other class XIV myosin in Plasmodium, has been established as a component of the glideosome complex important in motility and cell invasion, but MyoB is not well characterized. We analyzed the properties of MyoB using three parasite species as follows: Plasmodium falciparum, Plasmodium berghei, and Plasmodium knowlesi. MyoB is expressed in all invasive stages (merozoites, ookinetes, and sporozoites) of the life cycle, and the protein is found in a discrete apical location in these polarized cells. In P. falciparum, MyoB is synthesized very late in schizogony/merogony, and its location in merozoites is distinct from, and anterior to, that of a range of known proteins present in the rhoptries, rhoptry neck or micronemes. Unlike MyoA, MyoB is not associated with glideosome complex proteins, including the MyoA light chain, myosin A tail domain-interacting protein (MTIP). A unique MyoB light chain (MLC-B) was identified that contains a calmodulin-like domain at the C terminus and an extended N-terminal region. MLC-B localizes to the same extreme apical pole in the cell as MyoB, and the two proteins form a complex. We propose that MLC-B is a MyoB-specific light chain, and for the short class XIV myosins that lack a tail region, the atypical myosin light chains may fulfill that role.

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The brain cholecystokinin-B/gastrin receptor (CCK-BR) is a major target for drug development because of its postulated role in modulating anxiety, memory, and the perception of pain. Drug discovery efforts have resulted in the identification of small synthetic molecules that can selectively activate this receptor subtype. These drugs include the peptide-derived compound PD135,158 as well as the nonpeptide benzodiazepine-based ligand, L-740,093 (S enantiomer). We now report that the maximal level of receptor-mediated second messenger signaling that can be achieved by these compounds (drug efficacy) markedly differs among species homologs of the CCK-BR. Further analysis reveals that the observed differences in drug efficacy are in large part explained by single or double aliphatic amino acid substitutions between respective species homologs. This interspecies variability in ligand efficacy introduces the possibility of species differences in receptor-mediated function, an important consideration when selecting animal models for preclinical drug testing. The finding that even single amino acid substitutions can significantly affect drug efficacy prompted us to examine ligand-induced signaling by a known naturally occurring human CCK-BR variant (glutamic acid replaced by lysine in position 288; 288E → K). When examined using the 288E → K receptor, the efficacies of both PD135,158 and L-740,093 (S) were markedly increased compared with values obtained with the wild-type human protein. These observations suggest that functional variability resulting from human receptor polymorphisms may contribute to interindividual differences in drug effects.

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National Highway Traffic Safety Administration, Office of Driver and Pedestrian Programs, Washington, D.C.

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"Report of Senator Edward W. Brooke, 'United States foreign assistance for Haiti', April 1974": p. 73-120.

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Mode of access: Internet.

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Mode of access: Internet.

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National Highway Traffic Safety Administration, Washington, D.C.

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National Highway Traffic Safety Administration, Washington, D.C.

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National Highway Traffic Safety Administration, Manpower Development Division, Washington, D.C.

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National Highway Traffic Safety Administration, Washington, D.C.

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National Highway Traffic Safety Administration, Washington, D.C.

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National Highway Traffic Safety Administration, Washington, D.C.