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Gidalevitz T Ben-Zvi A Ho KH Brignull HR Morimoto RI 《Science (New York, N.Y.)》2006,311(5766):1471-1474
Numerous human diseases are associated with the chronic expression of misfolded and aggregation-prone proteins. The expansion of polyglutamine residues in unrelated proteins is associated with the early onset of neurodegenerative disease. To understand how the presence of misfolded proteins leads to cellular dysfunction, we employed Caenorhabditis elegans polyglutamine aggregation models. Here, we find that polyglutamine expansions disrupted the global balance of protein folding quality control, resulting in the loss of function of diverse metastable proteins with destabilizing temperature-sensitive mutations. In turn, these proteins, although innocuous under normal physiological conditions, enhanced the aggregation of polyglutamine proteins. Thus, weak folding mutations throughout the genome can function as modifiers of polyglutamine phenotypes and toxicity. 相似文献
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Yu L Babzien M Ben-Zvi I DiMauro LF Doyuran A Graves W Johnson E Krinsky S Malone R Pogorelsky I Skaritka J Rakowsky G Solomon L Wang XJ Woodle M Yakimenko V Biedron SG Galayda JN Gluskin E Jagger J Sajaev V Vasserman I 《Science (New York, N.Y.)》2000,289(5481):932-935
A high-gain harmonic-generation free-electron laser is demonstrated. Our approach uses a laser-seeded free-electron laser to produce amplified, longitudinally coherent, Fourier transform-limited output at a harmonic of the seed laser. A seed carbon dioxide laser at a wavelength of 10.6 micrometers produced saturated, amplified free-electron laser output at the second-harmonic wavelength, 5.3 micrometers. The experiment verifies the theoretical foundation for the technique and prepares the way for the application of this technique in the vacuum ultraviolet region of the spectrum, with the ultimate goal of extending the approach to provide an intense, highly coherent source of hard x-rays. 相似文献
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6beta-Hydroxy-delta(1)-tetrahydrocannabinol, a metabolite of delta(1)-tetrahydrocannabinol has been synthesized from delta(6)-tetrahydrocannabinol. It shows high tetrahydrocannabinol-type activity in rhesus monkeys. The implications of this funding are discussed. 相似文献
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