615 research outputs found
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
Analyse und ein Gewinnungsverfahren des Americiums im Kernbrennstoffzyklus des Druckwasserreaktors
Effect of remobinant granulocyte-macrophage colony stimulating factor (GM-CSF) on leukopenia in AIDS
Three-dimensional structure of the M-MuLV CA protein on a lipid monolayer: a general model for retroviral capsid assembly
Strain and rupture of HIV-1 capsids during uncoating
Viral replication in HIV-1 relies on a fullerene-shaped capsid to transport genetic material deep into the nucleus of an infected cell. Capsid stability is linked to the presence of cofactors, including inositol hexakisphosphates (IP6) that bind to pores found in the capsid. Using extensive all-atom molecular dynamics simulations of HIV-1 cores imaged from cryo-electron tomography (cryoET) in intact virions, which contain IP6 and a ribonucleoprotein complex, we find markedly striated patterns of strain on capsid lattices. The presence of these cofactors also increases rigidity of the capsid. Conformational analysis of capsid proteins (CA) show CA accommodates strain by locally flexing away from structures resolved using X-ray crystallography and cryo-ET. Then, cryo-ET of HIV-1 cores undergoing endogenous reverse transcription demonstrates that lattice strain increases in the capsid prior to mechanical failure and that the capsid ruptures by crack propagation along regions of high strain. These results uncover HIV-1 capsid properties involved in their critical disassembly process
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
Corporate Security Responsibility: Towards a Conceptual Framework for a Comparative Research Agenda
The political debate about the role of business in armed conflicts has increasingly raised expectations as to governance contributions by private corporations in the fields of conflict prevention, peace-keeping and postconflict peace-building. This political agenda seems far ahead of the research agenda, in which the negative image of business in conflicts, seen as fuelling, prolonging and taking commercial advantage of violent conflicts,still prevails. So far the scientific community has been reluctant to extend the scope of research on ‘corporate social responsibility’ to the area of security in general and to intra-state armed conflicts in particular. As a consequence, there is no basis from which systematic knowledge can be generated about the conditions and the extent to which private corporations can fulfil the role expected of them in the political discourse. The research on positive contributions of private corporations to security amounts to unconnected in-depth case studies of specific corporations in specific conflict settings. Given this state of research, we develop a framework for a comparative research agenda to address the question: Under which circumstances and to what extent can private corporations be expected to contribute to public security
Monte Carlo Simulations of HIV Capsid Protein Homodimer
Capsid protein (CA) is the building block of virus coats. To help understand how the HIV CA proteins self-organize into large assemblies of various shapes, we aim to computationally evaluate the binding affinity and interfaces in a CA homodimer. We model the N- and C-terminal domains (NTD and CTD) of the CA as rigid bodies and treat the five-residue loop between the two domains as a flexible linker. We adopt a transferrable residue-level coarse-grained energy function to describe the interactions between the protein domains. In seven extensive Monte Carlo simulations with different volumes, a large number of binding/unbinding transitions between the two CA proteins are observed, thus allowing a reliable estimation of the equilibrium probabilities for the dimeric vs monomeric forms. The obtained dissociation constant for the CA homodimer from our simulations, 20–25 μM, is in reasonable agreement with experimental measurement. A wide range of binding interfaces, primarily between the NTDs, are identified in the simulations. Although some observed bound structures here closely resemble the major binding interfaces in the capsid assembly, they are statistically insignificant in our simulation trajectories. Our results suggest that although the general purpose energy functions adopted here could reasonably reproduce the overall binding affinity for the CA homodimer, further adjustment would be needed to accurately represent the relative strength of individual binding interfaces
Intelligence within BAOR and NATO's Northern Army Group
During the Cold War the UK's principal military role was its commitment to the North Atlantic Treaty Organisation (NATO) through the British Army of the Rhine (BAOR), together with wartime command of NATO's Northern Army Group. The possibility of a surprise attack by the numerically superior Warsaw Pact forces ensured that great importance was attached to intelligence, warning and rapid mobilisation. As yet we know very little about the intelligence dimension of BAOR and its interface with NATO allies. This article attempts to address these neglected issues, ending with the impact of the 1973 Yom Kippur War upon NATO thinking about warning and surprise in the mid-1970s. It concludes that the arrangements made by Whitehall for support to BAOR from national assets during crisis or transition to war were - at best - improbable. Accordingly, over the years, BAOR developed its own unique assets in the realm of both intelligence collection and special operations in order to prepare for the possible outbreak of conflict
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