Bidirectional lipid droplet velocities are controlled by differential binding strengths of HCV Core DII protein

Host cell lipid droplets (LD) are essential in the hepatitis C virus (HCV) life cycle and are targeted by the viral capsid core protein. Core-coated LDs accumulate in the perinuclear region and facilitate viral particle assembly, but it is unclear how mobility of these LDs is directed by core. Herein we used two-photon fluorescence, differential interference contrast imaging, and coherent anti-Stokes Raman scattering microscopies, to reveal novel core-mediated changes to LD dynamics. Expression of core protein’s lipid binding domain II (DII-core) induced slower LD speeds, but did not affect directionality of movement on microtubules. Modulating the LD binding strength of DII-core further impacted LD mobility, revealing the temporal effects of LD-bound DII-core. These results for DII-core coated LDs support a model for core-mediated LD localization that involves core slowing down the rate of movement of LDs until localization at the perinuclear region is accomplished where LD movement ceases. The guided localization of LDs by HCV core protein not only is essential to the viral life cycle but also poses an interesting target for the development of antiviral strategies against HCV

Research, Monitoring, and Evaluation of Fish and Wildlife Restoration Projects in the Columbia River Basin: Lessons Learned and Suggestions for Large- Scale Monitoring Programs

El ano 2006 representa en dos sentidos una fecha critica para la cuenca del Rio Columbia y para los esfuerzos de recuperacion del salmon y la trucha arcoiris en la region Pacifico Noroeste: el 25 aniversario de la creacion del Consejo para la Conservacion y Poder del Noroeste y el 10 degree aniversario de la enmienda al Acto de Poder del Noroeste, que formaliza el arbitraje cientifico del Programa de Pesca y Vida Silvestre de dicho consejo, asi como de sus proyectos individuales. Durante la ultima decada, los autores del presente trabajo fungieron como arbitros de estos proyectos. Los esfuerzos de recuperacion en el Rio Columbia constituyen una iniciativa muy importante en cuanto a la rehabilitacion de pesquerias y ecosistemas. En este articulo se examinan algunas lecciones aprendidas durante el proceso de revision de investigacion, monitoreo y evaluacion de proyectos y su repercusion sobre el avance del conocimiento (manejo adaptativo) en el Programa de Pesca y Vida Silvestre de la Cuenca del Rio Columbia, uno de los programas de recuperacion mas ambiciosos y de mas largo plazo en los Estados Unidos de Norteamerica.The year 2006 marked two milestones in the Columbia River Basin and the Pacific Northwest region's efforts to rebuild its once great salmon and steelhead runs -- the 25th anniversary of the creation of the Northwest Power and Conservation Council and the 10th anniversary of an amendment to the Northwest Power Act that formalized scientific peer review of the council's Fish and Wildlife Program and its varied individual projects. The authors of this article served as peer reviewers in the last decade. Restoration efforts in the Columbia River constitute a massive long-term attempt at fisheries and ecosystem restoration. In this article we examine some of the lessons we learned in reviewing the research, monitoring, and evaluation efforts of projects and their effects on advancing knowledge (i.e., adaptive management) in the Columbia River Basin Fish and Wildlife Program, one of the most ambitious and expensive long-term ecological restoration programs in the United States.Keywords: Restoration, Monitoring, Fishery Management, Columbia River BasinKeywords: Restoration, Monitoring, Fishery Management, Columbia River Basi

A decade of acoustic thermometry in the North Pacific Ocean

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94643/1/jgrc11250.pd

The Atacama Cosmology Telescope: a measurement of the primordial power spectrum

We present constraints on the primordial power spectrum of adiabatic fluctuations using data from the 2008 Southern Survey of the Atacama Cosmology Telescope (ACT). The angular resolution of ACT provides sensitivity to scales beyond \ell = 1000 for resolution of multiple peaks in the primordial temperature power spectrum, which enables us to probe the primordial power spectrum of adiabatic scalar perturbations with wavenumbers up to k \simeq 0.2 Mpc^{-1}. We find no evidence for deviation from power-law fluctuations over two decades in scale. Matter fluctuations inferred from the primordial temperature power spectrum evolve over cosmic time and can be used to predict the matter power spectrum at late times; we illustrate the overlap of the matter power inferred from CMB measurements (which probe the power spectrum in the linear regime) with existing probes of galaxy clustering, cluster abundances and weak lensing constraints on the primordial power. This highlights the range of scales probed by current measurements of the matter power spectrum.Comment: 10 pages, 5 figures, submitted to Ap

Mutation D816V Alters the Internal Structure and Dynamics of c-KIT Receptor Cytoplasmic Region: Implications for Dimerization and Activation Mechanisms

The type III receptor tyrosine kinase (RTK) KIT plays a crucial role in the transmission of cellular signals through phosphorylation events that are associated with a switching of the protein conformation between inactive and active states. D816V KIT mutation is associated with various pathologies including mastocytosis and cancers. D816V-mutated KIT is constitutively active, and resistant to treatment with the anti-cancer drug Imatinib. To elucidate the activating molecular mechanism of this mutation, we applied a multi-approach procedure combining molecular dynamics (MD) simulations, normal modes analysis (NMA) and binding site prediction. Multiple 50-ns MD simulations of wild-type KIT and its mutant D816V were recorded using the inactive auto-inhibited structure of the protein, characteristic of type III RTKs. Computed free energy differences enabled us to quantify the impact of D816V on protein stability in the inactive state. We evidenced a local structural alteration of the activation loop (A-loop) upon mutation, and a long-range structural re-organization of the juxta-membrane region (JMR) followed by a weakening of the interaction network with the kinase domain. A thorough normal mode analysis of several MD conformations led to a plausible molecular rationale to propose that JMR is able to depart its auto-inhibitory position more easily in the mutant than in wild-type KIT and is thus able to promote kinase mutant dimerization without the need for extra-cellular ligand binding. Pocket detection at the surface of NMA-displaced conformations finally revealed that detachment of JMR from the kinase domain in the mutant was sufficient to open an access to the catalytic and substrate binding sites

HIV infection of non-dividing cells: a divisive problem

Understanding how lentiviruses can infect terminally differentiated, non-dividing cells has proven a very complex and controversial problem. It is, however, a problem worth investigating, for it is central to HIV-1 transmission and AIDS pathogenesis. Here I shall attempt to summarise what is our current understanding for HIV-1 infection of non-dividing cells. In some cases I shall also attempt to make sense of controversies in the field and advance one or two modest proposals

The Drosophila melanogaster Genetic Reference Panel

A major challenge of biology is understanding the relationship between molecular genetic variation and variation in quantitative traits, including fitness. This relationship determines our ability to predict phenotypes from genotypes and to understand how evolutionary forces shape variation within and between species. Previous efforts to dissect the genotype–phenotype map were based on incomplete genotypic information. Here, we describe the Drosophila melanogaster Genetic Reference Panel (DGRP), a community resource for analysis of population genomics and quantitative traits. The DGRP consists of fully sequenced inbred lines derived from a natural population. Population genomic analyses reveal reduced polymorphism in centromeric autosomal regions and the X chromosome, evidence for positive and negative selection, and rapid evolution of the X chromosome. Many variants in novel genes, most at low frequency, are associated with quantitative traits and explain a large fraction of the phenotypic variance. The DGRP facilitates genotype–phenotype mapping using the power of Drosophila genetics