HIV-1 infection of microglial cells in a reconstituted humanized mouse model and identification of compounds that selectively reverse HIV latency.

Most studies of HIV latency focus on the peripheral population of resting memory T cells, but the brain also contains a distinct reservoir of HIV-infected cells in microglia, perivascular macrophages, and astrocytes. Studying HIV in the brain has been challenging, since live cells are difficult to recover from autopsy samples and primate models of SIV infection utilize viruses that are more myeloid-tropic than HIV due to the expression of Vpx. Development of a realistic small animal model would greatly advance studies of this important reservoir and permit definitive studies of HIV latency. When radiation or busulfan-conditioned, immune-deficient NSG mice are transplanted with human hematopoietic stem cells, human cells from the bone marrow enter the brain and differentiate to express microglia-specific markers. After infection with replication competent HIV, virus was detected in these bone marrow-derived human microglia. Studies of HIV latency in this model would be greatly enhanced by the development of compounds that can selectively reverse HIV latency in microglial cells. Our studies have identified members of the CoREST repression complex as key regulators of HIV latency in microglia in both rat and human microglial cell lines. The monoamine oxidase (MAO) and potential CoREST inhibitor, phenelzine, which is brain penetrant, was able to stimulate HIV production in human microglial cell lines and human glial cells recovered from the brains of HIV-infected humanized mice. The humanized mice we have developed therefore show great promise as a model system for the development of strategies aimed at defining and reducing the CNS reservoir

Topological Superconductor Sn4Au: A first principle study

Topological semimetals such as Weyl or Dirac semimetal with superconductivity have emerged as a new class of topological materials to realize and study Majorana Fermion in its intrinsic form. This article reports the Density Functional Theory (DFT) calculated bulk electronic band structure of recently discovered topological superconductor candidate Sn4Au. This study is further extended to the calculation of Z2 invariants. The Fermi surfaces corresponding to the bands which are responsible for non-trivial band topology along with the surface states are also mapped. The complete study suggests that Sn4Au is a topological semimetal. On Sn4Au, it is the first report in the literature showing the non-trivial band topology based on first-principle calculations.Comment: 19 Pages Text + Figs: SUST - Special issue: Superconductivity Research in Indi

Weak Antilocalization and topological edge states in PdSn4_4

Here we report, the successful synthesis of single crystals of topological semimetal (TSM) candidate, PdSn$_4$ using the self-grown route. The synthesized crystal is well characterized through X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), and X-ray photoelectron spectroscopy (XPS). Detailed Rietveld analysis of the powder XRD pattern of PdSn$_4$ confirmed the same to crystallize in the Aea2 space group instead of reported Ccce. A large magnetoresistance (MR) along with Subnikov-de Haas oscillations have been observed in magnetotransport measurements at 2K. The presence of a weak antilocalization (WAL) effect in synthesized PdSn$_4$ crystal is confirmed and analyzed using Hikami Larkin Nagaoka (HLN) formalism, being applied on magnetoconductivity of the same at the low magnetic field. An extended Kohler rule is implemented on MR data, to determine the role of the scattering process and temperature-dependent carrier density on transport phenomenon in PdSn$_4$. Further, the non-trivial band topology and presence of edge states are shown through density functional theory (DFT) based theoretical calculations. All calculations are performed considering the Aea2 space group symmetry. The calculated Z2 invariants suggest the presence of weak topological insulating properties in PdSn$_4$. Clear evidence of topological edge states at the $\Gamma$ point is visible in calculated edge state spectra. This is the first report on PdSn$_4$, showing the presence of SdH oscillation in magneto transport measurement.Comment: 26 PAGES TEXT + FIGS. REVISED J. APPL. PHYS. 202

Detailed structural and topological analysis of SnBi2Te4 single crystal

We report herein the successful synthesis of the topological material SnBi2Te4 in single-crystal form. Phase purity and unidirectional growth are evident from X-ray diffraction (XRD) patterns acquired from a powdered sample and a crystal flake. The crystalline morphology has also been visualized by acquiring a field-emission scanning electron microscope (FESEM) image. The crystal has been thoroughly characterized by means of Raman spectroscopy and X ray photoelectron spectroscopy (XPS) measurements. The topological properties of SnBi2Te4 have been probed through magneto-transport measurements. SnBi2Te4 has been found to exhibit a small but non-saturating magneto-resistance (MR) up to 12 T. The low-field magnetoconductivity (MC) of SnBi2Te4 at 2 K can be well explained through the Hikami Larkin Nagaoka (HLN) formalism, which confirms the presence of a weak anti-localization (WAL) effect in its crystal. Moreover, the non-trivial topological character has been evidenced through first-principles calculations using density functional theory (DFT), with and without spin-orbit coupling (SOC) protocols. A significant change in the bulk electronic band structure is observed upon the inclusion of SOC parameters, signifying the topological properties of SnBi2Te4. Its topological non-trivial character has also been verified through the calculation of Z2 invariants and the surface states spectrum in the (111) plane.Comment: 24 Pages TEXT + Figs: J. Phys. Chem. Solid

A Candidate Subspecies Discrimination System Involving a Vomeronasal Receptor Gene with Different Alleles Fixed in M. m. domesticus and M. m. musculus

Assortative mating, a potentially efficient prezygotic reproductive barrier, may prevent loss of genetic potential by avoiding the production of unfit hybrids (i.e., because of hybrid infertility or hybrid breakdown) that occur at regions of secondary contact between incipient species. In the case of the mouse hybrid zone, where two subspecies of Mus musculus (M. m. domesticus and M. m. musculus) meet and exchange genes to a limited extent, assortative mating requires a means of subspecies recognition. We based the work reported here on the hypothesis that, if there is a pheromone sufficiently diverged between M. m. domesticus and M. m. musculus to mediate subspecies recognition, then that process must also require a specific receptor(s), also sufficiently diverged between the subspecies, to receive the signal and elicit an assortative mating response. We studied the mouse V1R genes, which encode a large family of receptors in the vomeronasal organ (VNO), by screening Perlegen SNP data and identified one, Vmn1r67, with 24 fixed SNP differences most of which (15/24) are nonsynonymous nucleotide substitutions between M. m. domesticus and M. m. musculus. We observed substantial linkage disequilibrium (LD) between Vmn1r67 and Abpa27, a mouse salivary androgen-binding protein gene that encodes a proteinaceous pheromone (ABP) capable of mediating assortative mating, perhaps in conjunction with its bound small lipophilic ligand. The LD we observed is likely a case of association rather than residual physical linkage from a very recent selective sweep, because an intervening gene, Vmn1r71, shows significant intra(sub)specific polymorphism but no inter(sub)specific divergence in its nucleotide sequence. We discuss alternative explanations of these observations, for example that Abpa27 and Vmn1r67 are coevolving as signal and receptor to reinforce subspecies hybridization barriers or that the unusually divergent Vmn1r67 allele was not a product of fast positive selection, but was derived from an introgressed allele, possibly from Mus spretus

Development of a SiPM Camera for a Schwarzschild-Couder Cherenkov Telescope for the Cherenkov Telescope Array

We present the development of a novel 11328 pixel silicon photomultiplier (SiPM) camera for use with a ground-based Cherenkov telescope with Schwarzschild-Couder optics as a possible medium-sized telescope for the Cherenkov Telescope Array (CTA). The finely pixelated camera samples air-shower images with more than twice the optical resolution of cameras that are used in current Cherenkov telescopes. Advantages of the higher resolution will be a better event reconstruction yielding improved background suppression and angular resolution of the reconstructed gamma-ray events, which is crucial in morphology studies of, for example, Galactic particle accelerators and the search for gamma-ray halos around extragalactic sources. Packing such a large number of pixels into an area of only half a square meter and having a fast readout directly attached to the back of the sensors is a challenging task. For the prototype camera development, SiPMs from Hamamatsu with through silicon via (TSV) technology are used. We give a status report of the camera design and highlight a number of technological advancements that made this development possible.Comment: 8 pages, 5 figures, In Proceedings of the 34th International Cosmic Ray Conference (ICRC2015), The Hague, The Netherlands. All CTA contributions at arXiv:1508.0589

Phylogenetically related Argentinean and Australian Escherichia coli O157 isolates are distinguished by virulence clades and alternative shiga toxin 1 and 2 prophages

Shiga toxigenic Escherichia coli O157 is the leading cause of hemolytic uremic syndrome (HUS) worldwide. The frequencies of stx genotypes and the incidences of O157-related illness and HUS vary significantly between Argentina and Australia. Locusspecific polymorphism analysis revealed that lineage I/II (LI/II) E. coli O157 isolates were most prevalent in Argentina (90%) and Australia (88%). Argentinean LI/II isolates were shown to belong to clades 4 (28%) and 8 (72%), while Australian LI/II isolates were identified as clades 6 (15%), 7 (83%), and 8 (2%). Clade 8 was significantly associated with Shiga toxin bacteriophage insertion (SBI) type stx2 (locus of insertion, argW) in Argentinean isolates (P<0.0001). In Argentinean LI/II strains, stx2 is carried by a prophage inserted at argW, whereas in Australian LI/II strains the argW locus is occupied by the novel stx1 prophage. In both Argentinean and Australian LI/II strains, stx2c is almost exclusively carried by a prophage inserted at sbcB. However, alternative q933- or q21-related alleles were identified in the Australian stx2c prophage. Argentinean LI/II isolates were also distinguished from Australian isolates by the presence of the putative virulence determinant ECSP_3286 and the predominance of motile O157:H7 strains. Characteristics common to both Argentinean and Australian LI/II O157 strains included the presence of putative virulence determinants (ECSP_3620, ECSP_0242, ECSP_2687, ECSP_2870, and ECSP_2872) and the predominance of the tir255T allele. These data support further understanding of O157 phylogeny and may foster greater insight into the differential virulence of O157 lineages. © 2012, American Society for Microbiology

Epigenetic Silencing of HIV-1 by the Histone H3 Lysine 27 Methyltransferase Enhancer of Zeste 2

Latent HIV proviruses are silenced as the result of deacetylation and methylation of histones located at the viral long terminal repeat (LTR). Inhibition of histone deacetylases (HDACs) leads to the reemergence of HIV-1 from latency, but the contribution of histone lysine methyltransferases (HKMTs) to maintaining HIV latency remains uncertain. Chromatin immunoprecipitation experiments using latently infected Jurkat T-cell lines demonstrated that the HKMT enhancer of Zeste 2 (EZH2) was present at high levels at the LTR of silenced HIV proviruses and was rapidly displaced following proviral reactivation. Knockdown of EZH2, a key component of the Polycomb repressive complex 2 (PRC2) silencing machinery, and the enzyme which is required for trimethyl histone lysine 27 (H3K27me3) synthesis induced up to 40% of the latent HIV proviruses. In contrast, there was less than 5% induction of latent proviruses following knockdown of SUV39H1, which is required for H3K9me3 synthesis. Knockdown of EZH2 also sensitized latent proviruses to external stimuli, such as T-cell receptor stimulation, and slowed the reversion of reactivated proviruses to latency. Similarly, cell populations that responded poorly to external stimuli carried HIV proviruses that were enriched in H3K27me3 and relatively depleted in H3K9me3. Treating latently infected cells with the HKMT inhibitor 3-deazaneplanocin A, which targets EZH2, led to the reactivation of silenced proviruses, whereas chaetocin and BIX01294 showed only minimal reactivation activities. These findings suggest that PRC2-mediated silencing is an important feature of HIV latency and that inhibitors of histone methylation may play a useful role in induction strategies designed to eradicate latent HIV pools