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.     

Genome sequence of enterohaemorrhagic Escherichia coli O157:H7

The bacterium Escherichia coli O157:H7 is a worldwide threat to public health and has been implicated in many outbreaks of haemorrhagic colitis, some of which included fatalities caused by haemolytic uraemic syndrome. Close to 75,000 cases of O157:H7 infection are now estimated to occur annually in the United States. The severity of disease, the lack of effective treatment and the potential for large-scale outbreaks from contaminated food supplies have propelled intensive research on the pathogenesis and detection of E. coli O157:H7 (ref. 4). Here we have sequenced the genome of E. coli O157:H7 to identify candidate genes responsible for pathogenesis, to develop better methods of strain detection and to advance our understanding of the evolution of E. coli, through comparison with the genome of the non-pathogenic laboratory strain E. coli K-12 (ref. 5). We find that lateral gene transfer is far more extensive than previously anticipated. In fact, 1,387 new genes encoded in strain-specific clusters of diverse sizes were found in O157:H7. These include candidate virulence factors, alternative metabolic capacities, several prophages and other new functions--all of which could be targets for surveillance.     

Creating, moving and merging Dirac points with a Fermi gas in a tunable honeycomb lattice

Dirac points are central to many phenomena in condensed-matter physics, from massless electrons in graphene to the emergence of conducting edge states in topological insulators. At a Dirac point, two energy bands intersect linearly and the electrons behave as relativistic Dirac fermions. In solids, the rigid structure of the material determines the mass and velocity of the electrons, as well as their interactions. A different, highly flexible means of studying condensed-matter phenomena is to create model systems using ultracold atoms trapped in the periodic potential of interfering laser beams. Here we report the creation of Dirac points with adjustable properties in a tunable honeycomb optical lattice. Using momentum-resolved interband transitions, we observe a minimum bandgap inside the Brillouin zone at the positions of the two Dirac points. We exploit the unique tunability of our lattice potential to adjust the effective mass of the Dirac fermions by breaking inversion symmetry. Moreover, changing the lattice anisotropy allows us to change the positions of the Dirac points inside the Brillouin zone. When the anisotropy exceeds a critical limit, the two Dirac points merge and annihilate each other-a situation that has recently attracted considerable theoretical interest but that is extremely challenging to observe in solids. We map out this topological transition in lattice parameter space and find excellent agreement with ab initio calculations. Our results not only pave the way to model materials in which the topology of the band structure is crucial, but also provide an avenue to exploring many-body phases resulting from the interplay of complex lattice geometries with interactions.     

Sparse Bayesian vector autoregressions in huge dimensions

We develop a Bayesian vector autoregressive (VAR) model with multivariate stochastic volatility that is capable of handling vast dimensional information sets. Three features are introduced to permit reliable estimation of the model. First, we assume that the reduced-form errors in the VAR feature a factor stochastic volatility structure, allowing for conditional equation-by-equation estimation. Second, we apply recently developed global–local shrinkage priors to the VAR coefficients to cure the curse of dimensionality. Third, we utilize recent innovations to sample efficiently from high-dimensional multivariate Gaussian distributions. This makes simulation-based fully Bayesian inference feasible when the dimensionality is large but the time series length is moderate. We demonstrate the merits of our approach in an extensive simulation study and apply the model to US macroeconomic data to evaluate its forecasting capabilities.     

Molecular structure of the chick cerebellar kainate-binding subunit of a putative glutamate receptor

Kainate receptors mediate some of the excitatory transactions carried out in the central nervous system by the neurotransmitter glutamate. They are involved in neurotoxicity, possibly in neurodegenerative disorders and it has been suggested that they have a role in long-term potentiation. Kainate receptors are present both on neuronal and glial cell membranes where they regulate the gating of a voltage-independent ion channel. Nothing is known about their molecular structure. Taking advantage of the unusually high abundance of 3H-kainate binding sites in the chick cerebellum, we have isolated an oligomeric protein that displays a pharmacological profile similar to that of a kainate receptor, and have demonstrated, using the monoclonal antibody IX-50, that this protein is composed of a single polypeptide of Mr 49,000 which harbours the specific kainate recognition site. The structure of this kainate binding protein (KBP) is also of interest because of its exclusive cerebellar localization on Bergmann glial membrane in close proximity to established glutamatergic synapses. We now report the isolation of the complementary DNA containing the complete coding region of the kainate binding protein. The predicted structure of the mature protein has four putative transmembrane domains with a topology analogous to that found in the superfamily of ligand-gated ion channels. This raises the possibility, that kainate binding protein may form part of an ion channel and may be a subunit of a kainate subtype of glutamate receptor.     

Happy centenary, photon

One hundred years ago Albert Einstein introduced the concept of the photon. Although in the early years after 1905 the evidence for the quantum nature of light was not compelling, modern experiments--especially those using photon pairs--have beautifully confirmed its corpuscular character. Research on the quantum properties of light (quantum optics) triggered the evolution of the whole field of quantum information processing, which now promises new technology, such as quantum cryptography and even quantum computers.     

Transverse and longitudinal variation in woody riparian vegetation along a montane river

This study explores how the relationship between flow and riparian vegetation varies along a montane river. We mapped occurrence of woody riparian plant communities along 58 km of the San Miguel River in southwestern Colorado. We determined the recurrence interval of inundation for each plant community by combining step-backwater hydraulic modeling at 4 representative reaches with Log-Pearson analysis of 4 stream gaging stations. Finally, we mapped bottomland surficial geology and used a Geographic Information System to overlay the coverages of geology and vegetation. Plant communities were distinctly arrayed along the hydrologic gradient. The Salix exigua Nuttall (sandbar willow) community occurred mostly on surfaces with a recurrence interval of inundation shorter than 2.2 years; the Betula occidentalis Hooker (river birch) community peaked on sites with recurrence intervals of inundation between 2.2 and 4.6 years. The hydrologic position occupied by communities dominated by Populus angustifolia James (narrowleaf cottonwood) was strongly related to age of trees and species composition of understory shrubs. The fraction of riparian vegetation on surfaces historically inundated by the river decreased in the upstream direction from almost 100% near Uravan to <50% along the South Fork of the San Miguel River. In upstream reaches much of the physical disturbance necessary to maintain riparian vegetation is provided by valley-side processes including debris flows, floods from minor tributaries, landslides, and beaver activity. Where valley-side processes are important, prediction of riparian vegetation change based on alterations of river flow will be incomplete.