Crystallography on Curved Surfaces

We study static and dynamical properties that distinguish two dimensional crystals constrained to lie on a curved substrate from their flat space counterparts. A generic mechanism of dislocation unbinding in the presence of varying Gaussian curvature is presented in the context of a model surface amenable to full analytical treatment. We find that glide diffusion of isolated dislocations is suppressed by a binding potential of purely geometrical origin. Finally, the energetics and biased diffusion dynamics of point defects such as vacancies and interstitials is explained in terms of their geometric potential.Comment: 12 Pages, 8 Figure

Элитарная языковая личность: опыт моделирования (на материале русского эпистолярия ХХ?ХХ? вв.)

Исследование выполнено в рамках лингвоперсонологического и дискурсоориентированного подходов с опорой на последние достижения в области функциональной и коммуникативной стилистики, когнитивной лингвистики, лингвокультурологии, жанроведения и прагмалингвистики. В качестве эмпирической базы выступают частные письма представителей русской творческой интеллигенции - художника, оперного певца, композитора, патриарха, поэтов, публицистов, ученых, актеров, в большинстве своем не изученные в лингвистическом отношении. Работу отличает динамический аспект рассмотрения заявленной проблема-тики на протяжении значительного исторического периода - ХХ-ХХI вв. Сказанное определяет актуальность статьи. Цель исследования - создание инварианта языковой личности, принадлежащей элитарному типу речевой культуры. В связи с этим используются такие методы, как прием моделирования, коммуникативно-прагматический и сопоставительный анализ. В результате осуществленного исследования на основе определенных дискурсивных параметров создана модельная элитарная языковая личность, особенности коммуникативного поведения которой эксплицируются в конкретных ситуациях личностно ориентированного эпистолярного общения. В качестве вывода приводится перечень инвариантных свойств обозначенного типа языковой личности: рефлексивность сознания, особенно заметная в ситуациях осмысления роли творца в социуме, высокий уровень коммуникативной компетентности и риторического мастерства, открытость дискурсивных проявлений

Elasticity Theory and Shape Transitions of Viral Shells

Recently, continuum elasticity theory has been applied to explain the shape transition of icosahedral viral capsids - single-protein-thick crystalline shells - from spherical to buckled/faceted as their radius increases through a critical value determined by the competition between stretching and bending energies of a closed 2D elastic network. In the present work we generalize this approach to capsids with non-icosahedral symmetries, e.g., spherocylindrical and conical shells. One key new physical ingredient is the role played by nonzero spontaneous curvature. Another is associated with the special way in which the energy of the twelve topologically-required five-fold sites depends on the background local curvature of the shell in which they are embedded. Systematic evaluation of these contributions leads to a shape phase diagram in which transitions are observed from icosahedral to spherocylindrical capsids as a function of the ratio of stretching to bending energies and of the spontaneous curvature of the 2D protein network. We find that the transition from icosahedral to spherocylindrical symmetry is continuous or weakly first-order near the onset of buckling, leading to extensive shape degeneracy. These results are discussed in the context of experimentally observed variations in the shapes of a variety of viral capsids.Comment: 53 pages, 17 figure

Rhesus TRIM5α disrupts the HIV-1 capsid at the inter-hexamer interfaces

TRIM proteins play important roles in the innate immune defense against retroviral infection, including human immunodeficiency virus type-1 (HIV-1). Rhesus macaque TRIM5α (TRIM5αrh) targets the HIV-1 capsid and blocks infection at an early post-entry stage, prior to reverse transcription. Studies have shown that binding of TRIM5α to the assembled capsid is essential for restriction and requires the coiled-coil and B30.2/SPRY domains, but the molecular mechanism of restriction is not fully understood. In this study, we investigated, by cryoEM combined with mutagenesis and chemical cross-linking, the direct interactions between HIV-1 capsid protein (CA) assemblies and purified TRIM5αrh containing coiled-coil and SPRY domains (CC-SPRYrh). Concentration-dependent binding of CC-SPRYrh to CA assemblies was observed, while under equivalent conditions the human protein did not bind. Importantly, CC-SPRYrh, but not its human counterpart, disrupted CA tubes in a non-random fashion, releasing fragments of protofilaments consisting of CA hexamers without dissociation into monomers. Furthermore, such structural destruction was prevented by inter-hexamer crosslinking using P207C/T216C mutant CA with disulfide bonds at the CTD-CTD trimer interface of capsid assemblies, but not by intra-hexamer crosslinking via A14C/E45C at the NTD-NTD interface. The same disruption effect by TRIM5αrh on the inter-hexamer interfaces also occurred with purified intact HIV-1 cores. These results provide insights concerning how TRIM5α disrupts the virion core and demonstrate that structural damage of the viral capsid by TRIM5α is likely one of the important components of the mechanism of TRIM5α-mediated HIV-1 restriction. © 2011 Zhao et al

Assisted evolution enables HIV-1 to overcome a high trim5α-imposed genetic barrier to rhesus macaque tropism

Diversification of antiretroviral factors during host evolution has erected formidable barriers to cross-species retrovirus transmission. This phenomenon likely protects humans from infection by many modern retroviruses, but it has also impaired the development of primate models of HIV-1 infection. Indeed, rhesus macaques are resistant to HIV-1, in part due to restriction imposed by the TRIM5α protein (rhTRIM5α). Initially, we attempted to derive rhTRIM5α-resistant HIV-1 strains using two strategies. First, HIV-1 was passaged in engineered human cells expressing rhTRIM5α. Second, a library of randomly mutagenized capsid protein (CA) sequences was screened for mutations that reduced rhTRIM5α sensitivity. Both approaches identified several individual mutations in CA that reduced rhTRIM5α sensitivity. However, neither approach yielded mutants that were fully resistant, perhaps because the locations of the mutations suggested that TRIM5α recognizes multiple determinants on the capsid surface. Moreover, even though additive effects of various CA mutations on HIV-1 resistance to rhTRIM5α were observed, combinations that gave full resistance were highly detrimental to fitness. Therefore, we employed an 'assisted evolution' approach in which individual CA mutations that reduced rhTRIM5α sensitivity without fitness penalties were randomly assorted in a library of viral clones containing synthetic CA sequences. Subsequent passage of the viral library in rhTRIM5α-expressing cells resulted in the selection of individual viral species that were fully fit and resistant to rhTRIM5α. These viruses encoded combinations of five mutations in CA that conferred complete or near complete resistance to the disruptive effects of rhTRIM5α on incoming viral cores, by abolishing recognition of the viral capsid. Importantly, HIV-1 variants encoding these CA substitutions and SIVmac239 Vif replicated efficiently in primary rhesus macaque lymphocytes. These findings demonstrate that rhTRIM5α is difficult to but not impossible to evade, and doing so should facilitate the development of primate models of HIV-1 infection

A one-mutation mathematical model can explain the age incidence of acute myeloid leukemia with mutated nucleophosmin (NPM1)

Acute myeloid leukemia with mutated NPM1 gene and aberrant cytoplasmic expression of nucleophosmin (NPMc+acute myeloid leukemia) shows distinctive biological and clinical features. Experimental evidence of the oncogenic potential of the nucleophosmin mutant is, however, still lacking, and it is unclear whether other genetic lesion(s), e.g. FLT3 internal tandem duplication, cooperate with NPM1 mutations in acute myeloid leukemia development. An analysis of age-specific incidence, together with mathematical modeling of acute myeloid leukemia epidemiology, can help to uncover the number of genetic events needed to cause leukemia. We collected data on age at diagnosis of acute myeloid leukemia patients from five European Centers in Germany, The Netherlands and Italy, and determined the age-specific incidence of AML with mutated NPM1 (a total of 1,444 cases) for each country. Linear regression of the curves representing age-specific rates of diagnosis per year showed similar slopes of about 4 on a double logarithmic scale. We then adapted a previously designed mathematical model of hematopoietic tumorigenesis to analyze the age incidence of acute myeloid leukemia with mutated NPM1 and found that a one-mutation model can explain the incidence curve of this leukemia entity. This model fits with the hypothesis that NPMc+acute myeloid leukemia arises from an NPM1 mutation with haploinsufficiency of the wild-type NPM1 allele

Structure of a Novel Shoulder-to-Shoulder p24 Dimer in Complex with the Broad-Spectrum Antibody A10F9 and Its Implication in Capsid Assembly

10.1371/journal.pone.0061314PLoS ONE84