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51.
52.
The scale of the human immunodeficiency virus (HIV)/AIDS epidemic has exceeded all expectations since its identification 20 years ago. Globally, an estimated 36 million people are currently living with HIV, and some 20 million people have already died, with the worst of the epidemic centred on sub-Saharan Africa. But just as the spread of HIV has been greater than predicted, so too has been its impact on social capital, population structure and economic growth. Responding to AIDS on a scale commensurate with the epidemic is a global imperative, and the tools for an effective response are known. Nothing less than a sustained social mobilization is necessary to combat one of the most serious crises facing human development. 相似文献
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Zaugg CE Spaniol M Kaufmann P Bellahcene M Barbosa V Tolnay M Buser PT Krähenbühl S 《Cellular and molecular life sciences : CMLS》2003,60(4):767-775
Carnitine is essential for mitochondrial metabolism of long-chain fatty acids and thus for myocardial energy production. Accordingly, carnitine deficiency can be associated with cardiomyopathy. To better understand this disease, we determined myocardial function and energy metabolism in a rat model of carnitine deficiency. Carnitine deficiency was induced by a 3- or 6-week diet containing N-trimethyl-hydrazine-3-propionate, reducing cardiac and plasma carnitine by 70-85%. Myocardial function was investigated in isolated isovolumic heart preparations. Carnitine-deficient hearts showed left ventricular systolic dysfunction, reduced contractile reserve, and a blunted frequency-force relationship independently of the substrate used (glucose or palmitate). After glycogen depletion, palmitate could not sustain myocardial function. Histology and activities of carnitine palmitoyl transferase, citrate synthase, and cytochrome c oxidase were unaltered. Thus, as little as 3-6 weeks of systemic carnitine deficiency can lead to abnormalities in myocardial function. These abnormalities are masked by endogenous glycogen and are not accompanied by structural alterations of the myocardium or by altered activities of important mitochondrial enzymes. 相似文献
55.
Ceci M Gaviraghi C Gorrini C Sala LA Offenhäuser N Marchisio PC Biffo S 《Nature》2003,426(6966):579-584
The assembly of 80S ribosomes requires joining of the 40S and 60S subunits, which is triggered by the formation of an initiation complex on the 40S subunit. This event is rate-limiting for translation, and depends on external stimuli and the status of the cell. Here we show that 60S subunits are activated by release of eIF6 (also termed p27BBP). In the cytoplasm, eIF6 is bound to free 60S but not to 80S. Furthermore, eIF6 interacts in the cytoplasm with RACK1, a receptor for activated protein kinase C (PKC). RACK1 is a major component of translating ribosomes, which harbour significant amounts of PKC. Loading 60S subunits with eIF6 caused a dose-dependent translational block and impairment of 80S formation, which were reversed by expression of RACK1 and stimulation of PKC in vivo and in vitro. PKC stimulation led to eIF6 phosphorylation, and mutation of a serine residue in the carboxy terminus of eIF6 impaired RACK1/PKC-mediated translational rescue. We propose that eIF6 release regulates subunit joining, and that RACK1 provides a physical and functional link between PKC signalling and ribosome activation. 相似文献
56.
Pellegata NS Dieguez-Lucena JL Joensuu T Lau S Montgomery KT Krahe R Kivelä T Kucherlapati R Forsius H de la Chapelle A 《Nature genetics》2000,25(1):91-95
Specialized collagens and small leucine-rich proteoglycans (SLRPs) interact to produce the transparent corneal structure. In cornea plana, the forward convex curvature is flattened, leading to a decrease in refraction. A more severe, recessively inherited form (CNA2; MIM 217300) and a milder, dominantly inherited form (CNA1; MIM 121400) exist. CNA2 is a rare disorder with a worldwide distribution, but a high prevalence in the Finnish population. The gene mutated in CNA2 was assigned by linkage analysis to 12q (refs 4, 5), where there is a cluster of several SLRP genes. We cloned two additional SLRP genes highly expressed in cornea: KERA (encoding keratocan) in 12q and OGN (encoding osteoglycin) in 9q. Here we report mutations in KERA in 47 CNA2 patients: 46 Finnish patients are homozygous for a founder missense mutation, leading to the substitution of a highly conserved amino acid; and one American patient is homozygous for a mutation leading to a premature stop codon that truncates the KERA protein. Our data establish that mutations in KERA cause CNA2. CNA1 patients had no mutations in these proteoglycan genes. 相似文献
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Hobmayer B Rentzsch F Kuhn K Happel CM von Laue CC Snyder P Rothbächer U Holstein TW 《Nature》2000,407(6801):186-189
59.
Ernst Gäumann 《Cellular and molecular life sciences : CMLS》1945,1(5):153-157
Summary For the initiation of an epidemic with a tendency to become wide-spread, various conditions must be fulfilled in the vegetable kingdom. Factors which can lead to such an epidemic are the same as in epidemic diseases in humans and concern the host, causative agents and environmental factors. 相似文献
60.
Temporal trends of perfluoroalkyl substances (PFASs) have been determined in the blood samples from several countries globally including a female population in Sweden recently, yet little is known about the time trends in the blood levels of these compounds in Swedish male populations over recent years. In this study, the fourteen target PFASs consisted of four perfluorosulfonates (PFSAs) and ten perfluorocarboxylates (PFCAs) in the whole blood samples, collected from 153 Swedish elderly men during the period between 2008 and 2010, were analyzed via ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). As the dominant PFASs contaminants in the blood samples, perfluorooctane sulfo- nate (PFOS) showed the highest geometric mean (GM) at 8.5 ng/mL, ranging from 1.7 to 29 ng/mL, while blood perfluorooctanoic acid (PFOA) contained the GM of 1.8 ng/mL, ranging from 0.35 to 6.4 ng/mL. Both the levels of these two compounds were lower than those determined in the blood samples of Swedish elderly pop- ulations derived from the late 1990s. According to the temporal trend analysis, over the three years, the blood levels of PFOS in Swedish male populations declined 16 % per annum, while those of perfluoroundecanoic acid (PFUnDA) increased 6.1% per annum, which were con- sistent with those reported previously for the populations from other countries. 相似文献