Ebola virus entry requires the cholesterol transporter Niemann-Pick C1

Infections by the Ebola and Marburg filoviruses cause a rapidly fatal haemorrhagic fever in humans for which no approved antivirals are available. Filovirus entry is mediated by the viral spike glycoprotein (GP), which attaches viral particles to the cell surface, delivers them to endosomes and catalyses fusion between viral and endosomal membranes. Additional host factors in the endosomal compartment are probably required for viral membrane fusion; however, despite considerable efforts, these critical host factors have defied molecular identification. Here we describe a genome-wide haploid genetic screen in human cells to identify host factors required for Ebola virus entry. Our screen uncovered 67 mutations disrupting all six members of the homotypic fusion and vacuole protein-sorting (HOPS) multisubunit tethering complex, which is involved in the fusion of endosomes to lysosomes, and 39 independent mutations that disrupt the endo/lysosomal cholesterol transporter protein Niemann-Pick C1 (NPC1). Cells defective for the HOPS complex or NPC1 function, including primary fibroblasts derived from human Niemann-Pick type C1 disease patients, are resistant to infection by Ebola virus and Marburg virus, but remain fully susceptible to a suite of unrelated viruses. We show that membrane fusion mediated by filovirus glycoproteins and viral escape from the vesicular compartment require the NPC1 protein, independent of its known function in cholesterol transport. Our findings uncover unique features of the entry pathway used by filoviruses and indicate potential antiviral strategies to combat these deadly agents.     

Interferon-γ links ultraviolet radiation to melanomagenesis in mice

Cutaneous malignant melanoma is a highly aggressive and frequently chemoresistant cancer, the incidence of which continues to rise. Epidemiological studies show that the major aetiological melanoma risk factor is ultraviolet (UV) solar radiation, with the highest risk associated with intermittent burning doses, especially during childhood. We have experimentally validated these epidemiological findings using the hepatocyte growth factor/scatter factor transgenic mouse model, which develops lesions in stages highly reminiscent of human melanoma with respect to biological, genetic and aetiological criteria, but only when irradiated as neonatal pups with UVB, not UVA. However, the mechanisms underlying UVB-initiated, neonatal-specific melanomagenesis remain largely unknown. Here we introduce a mouse model permitting fluorescence-aided melanocyte imaging and isolation following in vivo UV irradiation. We use expression profiling to show that activated neonatal skin melanocytes isolated following a melanomagenic UVB dose bear a distinct, persistent interferon response signature, including genes associated with immunoevasion. UVB-induced melanocyte activation, characterized by aberrant growth and migration, was abolished by antibody-mediated systemic blockade of interferon-γ (IFN-γ), but not type-I interferons. IFN-γ was produced by macrophages recruited to neonatal skin by UVB-induced ligands to the chemokine receptor Ccr2. Admixed recruited skin macrophages enhanced transplanted melanoma growth by inhibiting apoptosis; notably, IFN-γ blockade abolished macrophage-enhanced melanoma growth and survival. IFN-γ-producing macrophages were also identified in 70% of human melanomas examined. Our data reveal an unanticipated role for IFN-γ in promoting melanocytic cell survival/immunoevasion, identifying a novel candidate therapeutic target for a subset of melanoma patients.     

A closely packed system of low-mass, low-density planets transiting Kepler-11

When an extrasolar planet passes in front of (transits) its star, its radius can be measured from the decrease in starlight and its orbital period from the time between transits. Multiple planets transiting the same star reveal much more: period ratios determine stability and dynamics, mutual gravitational interactions reflect planet masses and orbital shapes, and the fraction of transiting planets observed as multiples has implications for the planarity of planetary systems. But few stars have more than one known transiting planet, and none has more than three. Here we report Kepler spacecraft observations of a single Sun-like star, which we call Kepler-11, that reveal six transiting planets, five with orbital periods between 10 and 47?days and a sixth planet with a longer period. The five inner planets are among the smallest for which mass and size have both been measured, and these measurements imply substantial envelopes of light gases. The degree of coplanarity and proximity of the planetary orbits imply energy dissipation near the end of planet formation.     

Xe对NO(X)微分截面和非弹性散射中的碰撞诱导旋转准直

本文对NO(X)-Xe碰撞系统在碰撞能量为519 cm^-1,测量了完全?-双峰分解的微分截面和碰撞引起的旋转准直力矩. 同时结合初始量子态选择,使用六极杆的非均质电场,借助量子态分辨的测量,利用(1+1'')共振增强的多光子电离和速度离子成像. 结果显示,微分截面以及偏振相关的微分截面均显示与从头算势能面上进行的量子力学散射计算[J. K?os etal. J. Chem. Phys. 137, 014312 (2012)]一致. 通过与准经典轨迹、硬壳势能的量子力学散射以及运动近端模型的比较,评估了势能对所测微分截面和碰撞引起的旋转准直力矩的影响.     

Detection of water in jet fuel using layer-by-layer thin film coated long period grating sensor

The quantitative measurement of jet fuel additives in the field is of interest to the Air Force. The “smart nozzle” project was designed as a state-of-the-art diagnostics package attached to a single-point refueling nozzle for assessing key fuel properties as the fuel is dispensed. The objective of the work was to show proof of concept that a layer-by-layer thin film and long period grating fibers could be used to detect the presence of water in jet fuel. The data for the nafion/PDMA film and a long period grating fiber is a combination capable of quantitative measurement of water in kerosene. The average response (spectral loss wavelength shift) to the kerosene sample ranged from −6.0 for 15 ppm to −126.5 for 60 ppm water. The average calculated value for the check standard was 21.71 and ranged from 21.25 to 22.00 with a true value of 22.5 ppm water. Potential interferences were observed and are judged to be insignificant in real samples.     

Kinetics and mechanism of the reaction of propylene oxide with chlorine atoms and hydroxy radicals

The kinetics and mechanism of gas‐phase propylene oxide (PPO) reactions were studied in a 142‐L reaction chamber by long‐path Fourier transform infrared spectroscopy at atmospheric pressure and 298 K. Rate coefficients for the reaction of PPO with ozone (O₃), chlorine atoms (Cl), and hydroxyl radicals (OH) were measured using the relative rate technique. Product yields of acetic acid, acetic formic anhydride, formic acid, and carbon monoxide were determined for the following reactions: PPO with Cl both in the presence and absence of NO, PPO with OH and NO, methyl acetate with Cl both in the presence and absence of NO, and ethyl formate with Cl both in the presence and absence of NO. The measured rate coefficients for PPO with O₃, Cl, and OH are <3.5 × 10^?21 cm³ molecule^?1 s^?1, (3.0 ± 0.7) × 10^?11 cm³ molecule^?1 s^?1, and (3.0 ± 1.0) × 10^?13 cm³ molecule^?1 s^?1, respectively. The carbon balance for the products measured ranged from 10% (for OH + PPO) to 100% (for Cl + methyl acetate in the absence of NO). The mechanistic and atmospheric implications of these measurements are discussed. © 2011 Wiley Periodicals, Inc. Int J Chem Kinet 43: 507–521, 2011     

Voltage-controlled optical switch in planar nematic liquid crystal film

This study presents an integrated device that consists of a directional coupler and an electro-optic switch. The device is designed to include a nematic liquid crystal cell, comprising a grating-like electrode. Applying the appropriate voltage to the cell yields a periodically distributed refractive index. An incident polarized beam will couple to an adjacent channel if it is parallel to the channel. The coupling efficiency is controlled by applied voltage. An obliquely injected polarized beam will be reflected and refracted in the channel, and propagated along a curved path. The route of the beam can be controlled by applying the voltage. A multiport routing was achieved for voltage modulation. In addition, the distribution of refractive index is also investigated by employing conoscopic technique experimentally and numerically.     

Synthesis of Structurally Varied 1,3‐Disiloxanediols and Their Activity as Anion‐Binding Catalysts

A series of new 1,3‐disiloxanediols has been synthesized, including naphthyl‐substituted and unsymmetrical siloxanes, and demonstrated as a new class of anion‐binding catalysts. In the absence of anions, diffusion‐ordered spectroscopy (DOSY) displays self‐association of 1,3‐disiloxanediols through hydrogen‐bonding interactions. Binding constants determined for 1,3‐disiloxanediol catalysts indicate strong hydrogen‐bonding and anion‐binding abilities with unsymmetrical siloxanes displaying different hydrogen‐bonding abilities for each silanol group.     

Combined Helmholtz equation-least squares method for reconstructing acoustic radiation from arbitrarily shaped objects

A combined Helmholtz equation-least squares (CHELS) method is developed for reconstructing acoustic radiation from an arbitrary object. This method combines the advantages of both the HELS method and the Helmholtz integral theory based near-field acoustic holography (NAH). As such it allows for reconstruction of the acoustic field radiated from an arbitrary object with relatively few measurements, thus significantly enhancing the reconstruction efficiency. The first step in the CHELS method is to establish the HELS formulations based on a finite number of acoustic pressure measurements taken on or beyond a hypothetical spherical surface that encloses the object under consideration. Next enough field acoustic pressures are generated using the HELS formulations and taken as the input to the Helmholtz integral formulations implemented through the boundary element method (BEM). The acoustic pressure and normal component of the velocity at the discretized nodes on the surface are then determined by solving two matrix equations using singular value decomposition (SVD) and regularization techniques. Also presented are in-depth analyses of the advantages and limitations of the CHELS method. Examples of reconstructing acoustic radiation from separable and nonseparable surfaces are demonstrated.