The presence of tag, however, shifted the temperature of thermal

The presence of tag, however, shifted the temperature of thermal inactivation as well as the thermal denaturation curve towards lower temperatures. Despite somewhat

lower thermal stability, the fusion protein is considered a better candidate for crystallization than the wild-type one due to a more negative value of its second optical virial coefficient. (C) 2009 Elsevier Inc. All rights reserved.”
“A 57-year-old woman reports increasing symptoms of painful paresthesias in both legs for the past 18 months. Physical examination reveals impaired position sense and vibration sense. The serum vitamin B-12 level is 205 pg per milliliter (151.2 pmol selleck chemicals per liter), which is above the lower end of the laboratory reference range. The hemato-crit is 42%, with a mean corpuscular volume of 96 fl. The serum methylmalonic acid level is 3600 nmol per liter (normal level, <400), and the serum homocysteine level 49.1 mu mol per liter (normal level, <14). How should this patient be further evaluated and treated?”
“A unique feature of retroviruses is the packaging of two copies of their genome, noncovalently linked at their 5′ ends. In vitro,

dimerization AZD5153 solubility dmso of human immunodeficiency virus type 2 (HIV-2) RNA occurs by interaction of a self-complementary sequence exposed in the loop of stem-loop 1 (SL-1), also termed the dimer initiation Farnesyltransferase site (DIS). However, in virions, HIV-2 genome dimerization does not depend on the DIS. Instead, a palindrome located within the packaging signal (Psi) is the essential motif for genome dimerization. We reported previously that a mutation within Psi decreasing genome dimerization and packaging also resulted in a reduced proportion of mature particles (A. L’Hernault, J. S. Greatorex, R. A. Crowther, and A. M. Lever, Retrovirology 4:90, 2007). In this study, we investigated

further the relationship between HIV-2 genome dimerization, particle maturation, and infectivity by using a series of targeted mutations in SL-1. Our results show that disruption of a purine-rich ((392)-GGAG-(395)) motif within Psi causes a severe reduction in genome dimerization and a replication defect. Maintaining the extended SL-1 structure in combination with the (392)-GGAG-(395) motif enhanced packaging. Unlike that of HIV-1, which can replicate despite mutation of the DIS, HIV-2 replication depends critically on genome dimerization rather than just packaging efficiency. Gag processing was altered in the HIV-2 dimerization mutants, resulting in the accumulation of the MA-CA-p2 processing intermediate and suggesting a link between genome dimerization and particle assembly. Analysis of revertant SL-1 mutant viruses revealed that a compensatory mutation in matrix (70TI) could rescue viral replication and partially restore genome dimerization and Gag processing.

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