Plasma Membrane-Associated Restriction Factors and Their Counteraction by HIV-1 Accessory Proteins.

The plasma membrane is a site of conflict between host defenses and many viruses. One aspect of this conflict is the host's attempt to eliminate infected cells using innate and adaptive cell-mediated immune mechanisms that recognize features of the plasma membrane characteristic of viral infection. Another is the expression of plasma membrane-associated proteins, so-called restriction factors, which inhibit enveloped virions directly. HIV-1 encodes two countermeasures to these host defenses: The membrane-associated accessory proteins Vpu and Nef. In addition to inhibiting cell-mediated immune-surveillance, Vpu and Nef counteract membrane-associated restriction factors. These include BST-2, which traps newly formed virions at the plasma membrane unless counteracted by Vpu, and SERINC5, which decreases the infectivity of virions unless counteracted by Nef. Here we review key features of these two antiviral proteins, and we review Vpu and Nef, which deplete them from the plasma membrane by co-opting specific cellular proteins and pathways of membrane trafficking and protein-degradation. We also discuss other plasma membrane proteins modulated by HIV-1, particularly CD4, which, if not opposed in infected cells by Vpu and Nef, inhibits viral infectivity and increases the sensitivity of the viral envelope glycoprotein to host immunity

The use of direct geometry spectrometers in molecular spectroscopy

The advantages and disadvantages of the use of direct geometry spectrometers for molecular spectroscopy and catalysis studies are described. We show that both direct and indirect geometry INS spectrometers are important tools for the study of industrially relevant areas such as catalysis, proton conductors and gas separation. We propose a novel hybrid instrument, Cerberus, that would offer high sensitivity and high-to-reasonable resolution across the entire 'mid-infrared' spectral range that would effectively advance research in these areas

Delays in diagnosis of young women with symptomatic cervical cancer in England: an interview-based study

Background: Diagnosis may be delayed in young females with cervical cancer because of a failure to recognise symptoms. Aim: To examine the extent and determinants of delays in diagnosis of young females with symptomatic cervical cancer. Design and setting: A national descriptive study of time from symptoms to diagnosis of cervical cancer and risk factors for delay in diagnosis at all hospitals diagnosing cervical cancer in England. Method: One-hundred and twenty-eight patients <30 years with a recent diagnosis of cervical cancer were interviewed. Patient delay was defined as ?3 months from symptom onset to first presentation and provider delay as ? 3 months from first presentation to diagnosis. Results: Forty (31%) patients had presented symptomatically: 11 (28%) delayed presentation. Patient delay was more common in patients <25 than patients aged 25–29 (40% versus 15%, P = 0.16). Vaginal discharge was more common among patients who delayed presentation than those who did not; many reported not recognising this as a possible cancer symptom. Provider delay was reported by 24/40 (60%); in some no report was found in primary care records of a visual inspection of the cervix and some did not re-attend after the first presentation for several months. Gynaecological symptoms were common (84%) among patients who presented via screening. Conclusions: Young females with cervical cancer frequently delay presentation, and not recognising symptoms as serious may increase the risk of delay. Delay in diagnosis after first presentation is also common. There is some evidence that UK guidelines for managing young females with abnormal bleeding are not being followed

Downmodulation of CCR7 by HIV-1 Vpu Results in Impaired Migration and Chemotactic Signaling within CD4+ T Cells

SummaryThe chemokine receptor CCR7 plays a crucial role in the homing of central memory and naive T cells to peripheral lymphoid organs. Here, we show that the HIV-1 accessory protein Vpu downregulates CCR7 on the surface of CD4+ T cells. Vpu and CCR7 were found to specifically interact and colocalize within the trans-Golgi network, where CCR7 is retained. Downmodulation of CCR7 did not involve degradation or endocytosis and was strictly dependent on Vpu expression. Stimulation of HIV-1-infected primary CD4+ T cells with the CCR7 ligand CCL19 resulted in reduced mobilization of Ca2+, reduced phosphorylation of Erk1/2, and impaired migration toward CCL19. Specific amino acid residues within the transmembrane domain of Vpu that were previously shown to be critical for BST-2 downmodulation (A14, A18, and W22) were also necessary for CCR7 downregulation. These results suggest that BST-2 and CCR7 may be downregulated via similar mechanisms

Magnetoresistance in Mn pyrochlore: electrical transport in a low carrier density ferromagnet

We discuss magnetotransport in a low density electron gas coupled to spin fluctuations near and above a ferromagnetic transition. Provided the density is low enough ($n \lesssim 1/\xi^{3}(T)$, with $\xi(T)$ the ferromagnetic correlation length), spin polarons form in an intermediate temperature regime above $T_c$. Both in the spin polaron regime, and in the itinerant regime nearer $T_c$, the magnetoresistance is large. We propose that this provides a good model for ``colossal'' magnetoresistance in the pyrochlore Tl$_{2-x}$Sc$_x$Mn$_2$O$_7$, fundamentally different from the mechanism in the perovskite manganites such as La$_{1-x}$Sr$_x$MnO$_3$.Comment: 4 pages, LaTex, + 3 figure

A Cu2+ (S = 1/2) Kagom\'e Antiferromagnet: MgxCu4-x(OH)6Cl2

Spin-frustrated systems are one avenue for inducing macroscopic quantum states in materials. However, experimental realization of this goal has been difficult because of the lack of simple materials and, if available, the separation of the unusual magnetic properties arising from exotic magnetic states from behavior associated with chemical disorder, such as site mixing. Here we report the synthesis and magnetic properties of a new series of magnetically frustrated materials, MgxCu4-x(OH)6Cl2. Because of the substantially different ligand-field chemistry of Mg2+ and Cu2+, site disorder within the kagom\'e layers is minimized, as directly measured by X-ray diffraction. Our results reveal that many of the properties of these materials and related systems are not due to disorder of the magnetic lattice but rather reflect an unusual ground state.Comment: Accepted for publication in J. Am. Chem. Soc

What Does The Korringa Ratio Measure?

We present an analysis of the Korringa ratio in a dirty metal, emphasizing the case where a Stoner enhancement of the uniform susceptibilty is present. We find that the relaxation rates are significantly enhanced by disorder, and that the inverse problem of determining the bare density of states from a study of the change of the Knight shift and relaxation rates with some parameter, such as pressure, has rather constrained solutions, with the disorder playing an important role. Some preliminary applications to the case of chemical substitution in the Rb$_{3-x}$K$_x$C$_{60}$ family of superconductors is presented and some other relevant systems are mentioned.Comment: 849, Piscataway, New Jersey 08855 24 June 199

Discovery and Validation of Kepler-452b: A 1.6-Re Super Earth Exoplanet in the Habitable Zone of a G2 Star

We report on the discovery and validation of Kepler-452b, a transiting planet identified by a search through the 4 years of data collected by NASA's Kepler Mission. This possibly rocky 1.63$^{+0.23}_{-0.20}$ R$_\oplus$ planet orbits its G2 host star every 384.843$^{+0.007}_{0.012}$ days, the longest orbital period for a small (R$_p$ < 2 R$_\oplus$) transiting exoplanet to date. The likelihood that this planet has a rocky composition lies between 49% and 62%. The star has an effective temperature of 5757$\pm$85 K and a log g of 4.32$\pm$0.09. At a mean orbital separation of 1.046$^{+0.019}_{-0.015}$ AU, this small planet is well within the optimistic habitable zone of its star (recent Venus/early Mars), experiencing only 10% more flux than Earth receives from the Sun today, and slightly outside the conservative habitable zone (runaway greenhouse/maximum greenhouse). The star is slightly larger and older than the Sun, with a present radius of 1.11$^{+0.15}_{-0.09}$ R$_\odot$ and an estimated age of 6 Gyr. Thus, Kepler-452b has likely always been in the habitable zone and should remain there for another 3 Gyr.Comment: 19 pages, 16 figure

Phase diagram of a generalized Hubbard model applied to orbital order in manganites

The magnetic phase diagram of a two-dimensional generalized Hubbard model proposed for manganites is studied within Hartree-Fock approximation. In this model the hopping matrix includes anisotropic diagonal hopping matrix elements as well as off-diagonal elements. The antiferromagnetic (AF), ferromagnetic (F), canted (C) and paramagnetic (P) states are included in the analysis as possible phases. It is found that away from half-filling only the canted and F states may exist and AF and P states which are possible for the usual Hubbard model do not appear. This is because the F order has already developed for on-site repulsion U=0 due to the hopping matrix of the generalized model. When applied for manganites the orbital degree is described by a pseudospin. Thus our ``magnetic'' phase diagram obtained physically describes how orbital order changes with $U$ and with doping for manganites. Part of our results are consistent with other numerical calculations and some experiments.Comment: 5 eps figures; a note added, to appear in Phys. Rev.

Planetary Candidates Observed by Kepler VI: Planet Sample from Q1-Q16 (47 Months)

\We present the sixth catalog of Kepler candidate planets based on nearly 4 years of high precision photometry. This catalog builds on the legacy of previous catalogs released by the Kepler project and includes 1493 new Kepler Objects of Interest (KOIs) of which 554 are planet candidates, and 131 of these candidates have best fit radii <1.5 R_earth. This brings the total number of KOIs and planet candidates to 7305 and 4173 respectively. We suspect that many of these new candidates at the low signal-to-noise limit may be false alarms created by instrumental noise, and discuss our efforts to identify such objects. We re-evaluate all previously published KOIs with orbital periods of >50 days to provide a consistently vetted sample that can be used to improve planet occurrence rate calculations. We discuss the performance of our planet detection algorithms, and the consistency of our vetting products. The full catalog is publicly available at the NASA Exoplanet Archive.Comment: 18 pages, to be published in the Astrophysical Journal Supplement Serie