380 research outputs found
P17-09. Immunization with a single HIV-1 envelope sequence can generate CD8+ T lymphocytes capable of recognizing multiple variant forms of envelope
Background: The ability of CD8+ T lymphocytes to recognize a diversity of mutant forms of an HIV epitope is of central importance in the immune containment of this virus. The present studies were pursued to determine the mechanism employed by CD8+ T lymphocytes to recognize mutant viruses. In particular, we sought to determine whether mutant sequences are recognized by distinct CD8+ T lymphocyte populations or whether individual clonal populations of CD8+ T lymphocytes recognize a diversity of mutant sequences. Methods: We employed flow cytometry, Vβ repertoire analysis, and CDR3 sequencing methodologies to characterize the clonal diversity of CD8+ T lymphocytes that recognize variant forms of the HIV-1 envelope (Env) p41A epitope generated after infection by SHIV-89.6P or elicited by HIV-1 89.6P Env immunization of Mamu-A*01+ rhesus monkeys. To evaluate the capacity of the CD8+ T lymphocytes to recognize genetically diverse isolates of HIV-1, we employed a series of tetramers constructed with variants of the p41A epitope of HIV-1 Env. To define which T cell receptor mediated the recognition of each specific variant p41A, we isolated variant p41A-specific CD8+ T lymphocyte populations and analyzed the expression of 46 Vβ families and subfamilies genes. We then determined the precise clones employed for the recognition of each variant epitope peptide through CDR3 sequencing. Results: In both the infected and the vaccinated monkeys, we observed clonotypes capable of recognizing the majority of the variant epitope peptides. Conclusion: These data show that exposure to a single HIV-1 Env sequence can generate clonotypes capable of recognizing multiple variant forms of HIV-1 Env. Such Env-specific CD8+ T lymphocytes should be able to confer potent, effective protection against a diverse spectrum of circulating viruses
Electron-phonon coupling and superconductivity in -MoB as a function of pressure
We have studied the lattice dynamics, electron-phonon coupling, and
superconducting properties of -MoB, as a function of applied
pressure, within the framework of density functional perturbation theory using
a mixed-basis pseudopotential method. We found that phonon modes located along
the AH, HL, and LA high-symmetry paths exhibit large phonon linewidths
and contribute significantly to the electron-phonon coupling constant. Although
linewidths are particularly large for the highest-frequency optical phonon
modes (dominated by B vibrations), their contribution to the electron-phonon
coupling constant is marginal. The latter is largely controlled by the acoustic
low-frequency modes of predominantly Mo character. It was observed that at a
pressure of ~GPa, where -MoB forms, the phonon-mediated pairing
falls into the strong-coupling regime, and the estimate for the superconducting
critical temperature agrees well with experimental observations. When
further increasing the applied pressure, a reduction of is predicted,
which correlates with a hardening of the acoustic low-frequency phonon modes
and a decrease of the electron-phonon coupling parameter.Comment: Updated and accepted for publication versio
Non-adiabatic effects in the phonon dispersion of Mg 1--x Al x B 2
Superconducting MgB shows an E zone center phonon, as measured
by Raman spectroscopy, that is very broad in energy and temperature dependent.
The Raman shift and lifetime show large differences with the values elsewhere
in the Brillouin Zone measured by Inelastic X-ray Scattering (IXS), where its
dispersion can be accounted for by standard harmonic phonon theory, adding only
a moderate electron-phonon coupling. Here we show that the effects rapidly
disappear when electron-phonon coupling is switched off by Al substitution on
the Mg sites. Moreover, using IXS with very high wave-vector resolution in
MgB, we can follow the dispersion connecting the Raman and the IXS signal,
in agreement with a theory using only electron-phonon coupling but without
strong anharmonic terms. The observation is important in order to understand
the effects of electron-phonon coupling on zone center phonons modes in
MgB, but also in all metals characterized by a small Fermi velocity in a
particular direction, typical for layered compounds
A first-principles study of superconductivity on RbH by doping without applied pressure
The structural, electronic, lattice dynamics, electron-phonon coupling, and
superconducting properties of the alkali-metal hydride RbH, metalized through
electron-doping by the construction of the solid-solution RbSrH,
are systematically analyzed as a function of Sr-content within the framework of
density functional perturbation and Migdal-Eliashberg theories, taking into
account the effect of zero-point energy contribution by the quasi-harmonic
approximation. For the entire studied range of Sr-content, steady increments of
the electron-phonon coupling constant and the superconducting critical
temperature are found with progressive alkaline-earth metal content through
electron-doping, reaching the values of and ~K
with =0.1(0). The steady rise of such quantities as a function of
Sr-content is consequence of the metallization of the hydride as an increase of
density of states at the Fermi level is observed, as well as the softening of
the phonon spectrum, mainly coming from H-optical modes. Our results indicate
that electron-doping on metal-hydrides is an encouraging alternative to look
for superconductivity without applied pressure.Comment: 8 pages, 6 figure
OA05-06 LB. First-in-human Phase 1 safety and immunigenicity of an adenovirus serotype 26 HIV-1 vaccine vector
VPS29 Is Not an Active Metallo-Phosphatase but Is a Rigid Scaffold Required for Retromer Interaction with Accessory Proteins
VPS29 is a key component of the cargo-binding core complex of retromer, a protein assembly with diverse roles in transport of receptors within the endosomal system. VPS29 has a fold related to metal-binding phosphatases and mediates interactions between retromer and other regulatory proteins. In this study we examine the functional interactions of mammalian VPS29, using X-ray crystallography and NMR spectroscopy. We find that although VPS29 can coordinate metal ions Mn2+ and Zn2+ in both the putative active site and at other locations, the affinity for metals is low, and lack of activity in phosphatase assays using a putative peptide substrate support the conclusion that VPS29 is not a functional metalloenzyme. There is evidence that structural elements of VPS29 critical for binding the retromer subunit VPS35 may undergo both metal-dependent and independent conformational changes regulating complex formation, however studies using ITC and NMR residual dipolar coupling (RDC) measurements show that this is not the case. Finally, NMR chemical shift mapping indicates that VPS29 is able to associate with SNX1 via a conserved hydrophobic surface, but with a low affinity that suggests additional interactions will be required to stabilise the complex in vivo. Our conclusion is that VPS29 is a metal ion-independent, rigid scaffolding domain, which is essential but not sufficient for incorporation of retromer into functional endosomal transport assemblies
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