The formation of cysteine-linked dimers of BST-2/tetherin is important for inhibition of HIV-1 virus release but not for sensitivity to Vpu

<p>Abstract</p> <p>Background</p> <p>The Human Immunodeficiency virus type 1 (HIV-1) Vpu protein enhances virus release from infected cells and induces proteasomal degradation of CD4. Recent work identified BST-2/CD317 as a host factor that inhibits HIV-1 virus release in a Vpu sensitive manner. A current working model proposes that BST-2 inhibits virus release by tethering viral particles to the cell surface thereby triggering their subsequent endocytosis.</p> <p>Results</p> <p>Here we defined structural properties of BST-2 required for inhibition of virus release and for sensitivity to Vpu. We found that BST-2 is modified by N-linked glycosylation at two sites in the extracellular domain. However, N-linked glycosylation was not important for inhibition of HIV-1 virus release nor did it affect surface expression or sensitivity to Vpu. Rodent BST-2 was previously found to form cysteine-linked dimers. Analysis of single, double, or triple cysteine mutants revealed that any one of three cysteine residues present in the BST-2 extracellular domain was sufficient for BST-2 dimerization, for inhibition of virus release, and sensitivity to Vpu. In contrast, BST-2 lacking all three cysteines in its ectodomain was unable to inhibit release of wild type or Vpu-deficient HIV-1 virions. This defect was not caused by a gross defect in BST-2 trafficking as the mutant protein was expressed at the cell surface of transfected 293T cells and was down-modulated by Vpu similar to wild type BST-2.</p> <p>Conclusion</p> <p>While BST-2 glycosylation was functionally irrelevant, formation of cysteine-linked dimers appeared to be important for inhibition of virus release. However lack of dimerization did not prevent surface expression or Vpu sensitivity of BST-2, suggesting Vpu sensitivity and inhibition of virus release are separable properties of BST-2.</p

Ab initio calculations of neutrinoless ββ\beta \beta decay refine neutrino mass limits

Neutrinos are perhaps the most elusive known particles in the universe. We know they have some nonzero mass, but unlike all other particles, the absolute scale remains unknown. In addition, their fundamental nature is uncertain; they can either be their own antiparticles or exist as distinct neutrinos and antineutrinos. The observation of the hypothetical process of neutrinoless double-beta ($0\nu\beta\beta$) decay would at once resolve both questions, while providing a strong lead in understanding the abundance of matter over antimatter in our universe. In the scenario of light-neutrino exchange, the decay rate is governed by, and thereby linked to the effective mass of the neutrino via, the theoretical nuclear matrix element (NME). In order to extract the neutrino mass, if a discovery is made, or to assess the discovery potential of next-generation searches, it is essential to obtain accurate NMEs for all isotopes of experimental interest. However, two of the most important cases, $^{130}$Te and $^{136}$Xe, lie in the heavy region and have only been accessible to phenomenological nuclear models. In this work we utilize powerful advances in ab initio nuclear theory to compute NMEs from the underlying nuclear and weak forces driving this decay, including the recently discovered short-range component. We find that ab initio NMEs are generally smaller than those from nuclear models, challenging the expected reach of future ton-scale searches as well as claims to probe the inverted hierarchy of neutrino masses. With this step, ab initio calculations with theoretical uncertainties are now feasible for all isotopes relevant for next-generation $0\nu\beta\beta$ decay experiments.Comment: 5 pages, 3 figures, supplemental material include

Converged ab initio calculations of heavy nuclei

We propose a novel storage scheme for three-nucleon (3N) interaction matrix elements relevant for the normal-ordered two-body approximation used extensively in ab initio calculations of atomic nuclei. This scheme reduces the required memory by approximately two orders of magnitude, which allows the generation of 3N interaction matrix elements with the standard truncation of $E_{3\max}=28$, well beyond the previous limit of 18. We demonstrate that this is sufficient to obtain ground-state energies in $^{132}$Sn converged to within a few MeV with respect to the $E_{3\max}$ truncation. In addition, we study the asymptotic convergence behavior and perform extrapolations to the un-truncated limit. Finally, we investigate the impact of truncations made when evolving free-space 3N interactions with the similarity renormalization group. We find that the contribution of blocks with angular momentum $J_{\rm rel}>9/2$ is dominated by a basis-truncation artifact which vanishes in the large-space limit, so these computationally expensive components can be neglected. For the two sets of nuclear interactions employed in this work, the resulting binding energy of $^{132}$Sn agrees with the experimental value within theoretical uncertainties. This work enables converged ab initio calculations of heavy nuclei.Comment: 13 pages, 10 figure

Analytical investigation of magnetic field distributions around superconducting strips on ferromagnetic substrates

The complex-field approach is developed to derive analytical expressions of the magnetic field distributions around superconducting strips on ferromagnetic substrates (SC/FM strips). We consider the ferromagnetic substrates as ideal soft magnets with an infinite magnetic permeability, neglecting the ferromagnetic hysteresis. On the basis of the critical state model for a superconducting strip, the ac susceptibility $\chi_1'+i\chi_1''$ of a SC/FM strip exposed to a perpendicular ac magnetic field is theoretically investigated, and the results are compared with those for superconducting strips on nonmagnetic substrates (SC/NM strips). The real part $\chi_1'$ for $H_0/j_cd_s\to 0$ (where $H_0$ is the amplitude of the ac magnetic field, $j_c$ is the critical current density, and $d_s$ is the thickness of the superconducting strip) of a SC/FM strip is 3/4 of that of a SC/NM strip. The imaginary part $\chi_1''$ (or ac loss $Q$) for $H_0/j_cd_s<0.14$ of a SC/FM strip is larger than that of a SC/NM strip, even when the ferromagnetic hysteresis is neglected, and this enhancement of $\chi_1''$ (or $Q$) is due to the edge effect of the ferromagnetic substrate.Comment: 8 pages, 6 figures, submitted to Phys. Rev.

Protein processing characterized by a gel-free proteomics approach

We describe a method for the specific isolation of representative N-terminal peptides of proteins and their proteolytic fragments. Their isolation is based on a gel-free, peptidecentric proteomics approach using the principle of diagonal chromatography. We will indicate that the introduction of an altered chemical property to internal peptides holding a free α-N-terminus results in altered column retention of these peptides, thereby enabling the isolation and further characterization by mass spectrometry of N-terminal peptides. Besides pointing to changes in protein expression levels when performing such proteome surveys in a differential modus, protease specificity and substrate repertoires can be allocated since both are specified by neo-N-termini generated after a protease cleavage event. As such, our gel-free proteomics technology is widely applicable and amenable for a variety of proteome-driven protease degradomics research

Presence of a chiral soliton lattice in the chiral helimagnet MnTa3S6

Chiral helimagnetism was investigated in transition-metal intercalated dichalcogenide single crystals of MnTa3S6. Small-angle neutron scattering (SANS) experiments revealed the presence of harmonic chiral helimagnetic order, which was successfully detected as a pair of satellite peaks in the SANS pattern. The magnetization data are also supportive of the presence of chiral soliton lattice (CSL) phase in MnTa3S6. The observed features are summarized in the phase diagram of MnTa3S6, which is in strong contrast with that observed in other dichalcogenides such as CrNb3S6 and CrTa3S6. The presence of the remanent state provides tunable capability of the number of chiral solitons at zero magnetic field in the CSL system, which may be useful for memory device applications

Presence of a chiral soliton lattice in the chiral helimagnet MnTa3_{3}S6_{6}

Chiral helimagnetism was investigated in transition-metal intercalated dichalcogenide single crystals of MnTa$_3$S$_6$. Small-angle neutron scattering (SANS) experiments revealed the presence of harmonic chiral helimagnetic order, which was successfully detected as a pair of satellite peaks in the SANS pattern. The magnetization data are also supportive of the presence of chiral soliton lattice (CSL) phase in MnTa$_3$S$_6$. The observed features are summarized in the phase diagram of MnTa$_3$S$_6$, which is in strong contrast with that observed in other dichalcogenides such as CrNb$_3$S$_6$ and CrTa$_3$S$_6$. The presence of the remanent state provides tunable capability of the number of chiral solitons at zero magnetic field in the CSL system, which may be useful for memory device applications.Comment: 6 pages, 6 figure

Anti-self-dual Maxwell solutions on hyperk\"ahler manifold and N=2 supersymmetric Ashtekar gravity

Anti-self-dual (ASD) Maxwell solutions on 4-dimensional hyperk\"ahler manifolds are constructed. The N=2 supersymmetric half-flat equations are derived in the context of the Ashtekar formulation of N=2 supergravity. These equations show that the ASD Maxwell solutions have a direct connection with the solutions of the reduced N=2 supersymmetric ASD Yang-Mills equations with a special choice of gauge group. Two examples of the Maxwell solutions are presented.Comment: 9 page

Low-Rank Decompositions of Three-Nucleon Forces via Randomized Projections

Ab initio calculations for nuclei and nuclear matter are limited by the computational requirements of processing large data objects. In this work, we develop low-rank singular value decompositions for chiral three-nucleon interactions, which dominate these limitations. In order to handle the large dimensions in representing three-body operators, we use randomized decomposition techniques. We study in detail the sensitivity of different three-nucleon topologies to low-rank matrix factorizations. The developed low-rank three-nucleon interactions are benchmarked in Faddeev calculations of the triton and ab initio calculations of medium-mass nuclei. Exploiting low-rank properties of nuclear interactions will be particularly important for the extension of ab initio studies to heavier and deformed systems, where storage requirements will exceed the computational capacities of the most advanced high-performance-computing facilities.Comment: 7 pages, 4 figure