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1.
Eukaryotic ribosome biogenesis involves ∼200 assembly factors, but how these contribute to ribosome maturation is poorly understood. Here, we identify a network of factors on the nascent 60S subunit that actively remodels preribosome structure. At its hub is Rsa4, a direct substrate of the force-generating ATPase Rea1. We show that Rsa4 is connected to the central protuberance by binding to Rpl5 and to ribosomal RNA (rRNA) helix 89 of the nascent peptidyl transferase center (PTC) through Nsa2. Importantly, Nsa2 binds to helix 89 before relocation of helix 89 to the PTC. Structure-based mutations of these factors reveal the functional importance of their interactions for ribosome assembly. Thus, Rsa4 is held tightly in the preribosome and can serve as a “distribution box,” transmitting remodeling energy from Rea1 into the developing ribosome. We suggest that a relay-like factor network coupled to a mechano-enzyme is strategically positioned to relocate rRNA elements during ribosome maturation.  相似文献   
2.
4-Phenylylboronic acid enhances the light emission from the horseradish peroxidase catalysed oxidation of luminol by hydrogen peroxide. Optimization studies showed that the greatest enhancement was obtained using micromolar concentrations of the new enhancer. The largest degree of enhancement was found with the basic isoenzyme of horseradish peroxidase (Type VIA), and lesser degrees of enhancement were obtained with Type VII and Type IX horseradish peroxidase. The enhancer was also effective in the peroxidase catalysed oxidation of isoluminol by peroxide.  相似文献   
3.
A susceptibility gene on chromosome 18 and a parent-of-origin effect have been suggested for bipolar affective disorder (BPAD). We have studied 28 nuclear families selected for apparent unilineal transmission of the BPAD phenotype, by using 31 polymorphic markers spanning chromosome 18. Evidence for linkage was tested with affected-sib-pair and LOD score methods under two definitions of the affected phenotype. The affected-sib-pair analyses indicated excess allele sharing for markers on 18p within the region reported previously. The greatest sharing was at D18S37: 64% in bipolar and recurrent unipolar (RUP) sib pairs (P = .0006). In addition, excess sharing of the paternally, but not maternally, transmitted alleles was observed at three markers on 18q: at D18S41, 51 bipolar and RUP sib pairs were concordant for paternally transmitted alleles, and 21 pairs were discordant (P = .0004). The evidence for linkage to loci on both 18p and 18q was strongest in the 11 paternal pedigrees, i.e., those in which the father or one of the father's sibs is affected. In these pedigrees, the greatest allele sharing (81%; P = .00002) and the highest LOD score (3.51; θ = 0.0) were observed at D18S41. Our results provide further support for linkage of BPAD to chromosome 18 and the first molecular evidence for a parent-of-origin effect operating in this disorder. The number of loci involved, and their precise location, require further study.  相似文献   
4.
High Resolution Proton NMR Spectroscopy of Multiple Sclerosis Lesions   总被引:6,自引:1,他引:5  
Abstract: Tissue from postmortem multiple sclerosis and normal control brains was extracted with perchloric acid and analysed using proton NMR spectroscopy. The content of N -acetyl-derived groups (the sum of N -acetylaspartate, acetate, and N -acetylaspartylglutamate) was decreased in multiple sclerosis plaques compared with normal control white matter (mean, 4.36 vs. 6.64 µmol/g wet weight). In normal appearing white matter adjacent to plaques a corresponding decrease was seen, with no change in white matter distant from plaques. A decrease in the content of total creatine was observed in multiple sclerosis plaques in comparison with normal control white matter (mean, 4.64 vs. 6.56 µmol/g wet weight), which correlated strongly with the decrease in N -acetyl-derived groups. No changes in other metabolites such as total choline or myo -inositol were seen. The decreases in content of N -acetyl-derived groups are in agreement with observations from in vivo proton NMR spectroscopy in multiple sclerosis patients. The decrease in total creatine is in contrast to most of the observations made in vivo where total creatine is assumed to be unchanged and metabolite levels are often expressed as a total creatine ratio. The use of a total creatine ratio in vivo could lead to an underestimation of reductions in N -acetylaspartate and an apparent increase in other metabolites in the multiple sclerosis lesion.  相似文献   
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Seven small (3.2 to 5.2 m total length) whale sharks were observed suction feeding on patches of surface plankton in the Bay of La Paz within 1 km of shore and 2 km N of the phosphate dock at San Juan de la Costa, on 1–2 November 1993. The sharks were photographed and videotaped from the boat and by snorkelers in the water. When actively feeding the shark turned its head from side to side, part of the head was lifted out of the water, and the mouth opened and closed 7 to 28 times per minute (x=17, N=13). These suction gulps were synchronized with the opening and closing of the gill slits. This feeding behavior occurred only in the patchy areas of densely cloudy water, a layer 10 to 30 cm thick at the surface containing an immense concentration of copepods, 95% of which were identified as Acartia clausi. Remoras accompanying the whale sharks also fed on the plankton bloom. This revised version was published online in July 2006 with corrections to the Cover Date.  相似文献   
8.
Producing pure and well behaved bispecific antibodies (bsAbs) on a large scale for preclinical and clinical testing is a challenging task. Here, we describe a new strategy for making monovalent bispecific heterodimeric IgG antibodies in mammalian cells. We applied an electrostatic steering mechanism to engineer antibody light chain-heavy chain (LC-HC) interface residues in such a way that each LC strongly favors its cognate HC when two different HCs and two different LCs are co-expressed in the same cell to assemble a functional bispecific antibody. We produced heterodimeric IgGs from transiently and stably transfected mammalian cells. The engineered heterodimeric IgG molecules maintain the overall IgG structure with correct LC-HC pairings, bind to two different antigens with comparable affinity when compared with their parental antibodies, and retain the functionality of parental antibodies in biological assays. In addition, the bispecific heterodimeric IgG derived from anti-HER2 and anti-EGF receptor (EGFR) antibody was shown to induce a higher level of receptor internalization than the combination of two parental antibodies. Mouse xenograft BxPC-3, Panc-1, and Calu-3 human tumor models showed that the heterodimeric IgGs strongly inhibited tumor growth. The described approach can be used to generate tools from two pre-existent antibodies and explore the potential of bispecific antibodies. The asymmetrically engineered Fc variants for antibody-dependent cellular cytotoxicity enhancement could be embedded in monovalent bispecific heterodimeric IgG to make best-in-class therapeutic antibodies.  相似文献   
9.
DNA strand transfer protein alpha (STP alpha) from meiotic Saccharomyces cerevisiae cells promotes homologous pairing of DNA without any nucleotide cofactor in the presence of yeast single-stranded DNA binding protein. This gene (DNA strand transferase 1, DST1) encodes a 309-amino-acid protein with a predicted molecular mass of 34,800 Da. The STP alpha protein level is constant in both mitotic and meiotic cells, but during meiosis the polypeptide is activated by an unknown mechanism, resulting in a large increase in its specific activity. A dst1::URA3/dst1::URA3 mutant grows normally in mitotic media; however, meiotic cells exhibit a greatly reduced induction of both DNA strand transfer activity and intragenic recombination between his1 heteroalleles. Spore viability is normal. These results suggest that DST1 is required for much of the observed induction of homologous recombination in S. cerevisiae during meiosis but not for normal sporulation.  相似文献   
10.
Biogenic production of cyanide and its application to gold recovery   总被引:1,自引:0,他引:1  
Chromobacterium violaceum is a cyanogenic (cyanide-producing) microorganism. Cyanide is used on an industrial scale to complex and recover gold from ores or concentrates of ores bearing the precious metal. A potentially useful approach in gold mining operations could be to produce cyanide biologically in relatively small quantities at the ore surface. In this study, C. violaceum grown in nutrient broth formed a biofilm and could complex and solubilize 100% of the gold on glass test slides within 4–7 days. Approximately 50% of the cyanide-recoverable gold could be mobilized from a biooxidized sulfidic-ore concentrate. Complexation of cyanide in solution by gold appeared to have a beneficial effect on cell growth — viable cell counts were nearly two orders of magnitude greater in the presence of gold-coated slides or biooxidized ore substrates than in their absence. C. violaceum was cyanogenic when grown in alternative feedstocks. When grown in a mineral salt solution supplemented with 13.3% v/v swine fecal material (SFM), cells exhibited pigmentation and suspended cell concentrations comparable to cultures grown in nutrient broth. Glycine supplements stimulated production of cyanide in 13.3% v/v SFM. In contrast, glycine was inhibitory when added at the time of inoculation in the more concentrated SFM, decreasing cell numbers and reducing ultimate bulk-solution cyanide concentrations. However, aeration and addition of glycine to stationary phase cells grown on 13.3% v/v SFM anaerobically resulted in rapid production and high concentrations (up to 38 mg l−1) of cyanide. This indicates that biogenesis of cyanide may be supported in remote areas using locally produced and inexpensive agricultural feedstocks in place of commercial media. Journal of Industrial Microbiology & Biotechnology (2001) 26, 134–139. Received 06 June 2000/ Accepted in revised form 30 September 2000  相似文献   
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