A global lipid map defines a network essential for Zika virus replication

Zika virus (ZIKV), an arbovirus of global concern, remodels intracellular membranes to form replication sites. How ZIKV dysregulates lipid networks to allow this, and consequences for disease, is poorly understood. Here, we perform comprehensive lipidomics to create a lipid network map during ZIKV infection. We find that ZIKV significantly alters host lipid composition, with the most striking changes seen within subclasses of sphingolipids. Ectopic expression of ZIKV NS4B protein results in similar changes, demonstrating a role for NS4B in modulating sphingolipid pathways. Disruption of sphingolipid biosynthesis in various cell types, including human neural progenitor cells, blocks ZIKV infection. Additionally, the sphingolipid ceramide redistributes to ZIKV replication sites, and increasing ceramide levels by multiple pathways sensitizes cells to ZIKV infection. Thus, we identify a sphingolipid metabolic network with a critical role in ZIKV replication and show that ceramide flux is a key mediator of ZIKV infection

A global lipid map defines a network essential for Zika virus replication.

Zika virus (ZIKV), an arbovirus of global concern, remodels intracellular membranes to form replication sites. How ZIKV dysregulates lipid networks to allow this, and consequences for disease, is poorly understood. Here, we perform comprehensive lipidomics to create a lipid network map during ZIKV infection. We find that ZIKV significantly alters host lipid composition, with the most striking changes seen within subclasses of sphingolipids. Ectopic expression of ZIKV NS4B protein results in similar changes, demonstrating a role for NS4B in modulating sphingolipid pathways. Disruption of sphingolipid biosynthesis in various cell types, including human neural progenitor cells, blocks ZIKV infection. Additionally, the sphingolipid ceramide redistributes to ZIKV replication sites, and increasing ceramide levels by multiple pathways sensitizes cells to ZIKV infection. Thus, we identify a sphingolipid metabolic network with a critical role in ZIKV replication and show that ceramide flux is a key mediator of ZIKV infection

A global lipid map defines a network essential for Zika virus replication

Zika virus (ZIKV) remodels intracellular membranes for replication, but the role of different lipid types for infection and disease is unclear. Here, the authors perform lipidomics, show perturbation of the lipid network during ZIKV infection and show that ceramides are important for ZIKV infection

A global lipid map defines a network essential for Zika virus replication

AbstractZika virus (ZIKV), an arbovirus of global concern, remodels intracellular membranes to form replication sites. How ZIKV dysregulates lipid networks to allow this, and consequences for disease, is poorly understood. Here, we performed comprehensive lipidomics to create a lipid network map during ZIKV infection. We found that ZIKV significantly alters host lipid composition, with the most striking changes seen within subclasses of sphingolipids. Ectopic expression of ZIKV NS4B protein resulted in similar changes, demonstrating a role for NS4B in modulating sphingolipid pathways. Disruption of sphingolipid biosynthesis in various cell types, including human neural progenitor cells, blocked ZIKV infection. Additionally, the sphingolipid ceramide redistributes to ZIKV replication sites and increasing ceramide levels by multiple pathways sensitizes cells to ZIKV infection. Thus, we identify a sphingolipid metabolic network with a critical role in ZIKV replication and show that ceramide flux is a key mediator of ZIKV infection

A global lipid map defines a network essential for Zika virus replication.

Zika virus (ZIKV), an arbovirus of global concern, remodels intracellular membranes to form replication sites. How ZIKV dysregulates lipid networks to allow this, and consequences for disease, is poorly understood. Here, we perform comprehensive lipidomics to create a lipid network map during ZIKV infection. We find that ZIKV significantly alters host lipid composition, with the most striking changes seen within subclasses of sphingolipids. Ectopic expression of ZIKV NS4B protein results in similar changes, demonstrating a role for NS4B in modulating sphingolipid pathways. Disruption of sphingolipid biosynthesis in various cell types, including human neural progenitor cells, blocks ZIKV infection. Additionally, the sphingolipid ceramide redistributes to ZIKV replication sites, and increasing ceramide levels by multiple pathways sensitizes cells to ZIKV infection. Thus, we identify a sphingolipid metabolic network with a critical role in ZIKV replication and show that ceramide flux is a key mediator of ZIKV infection

On the Use of Phylogeny-Based Tests to Detect Association between Quantitative Traits and Haplotypes

International audienceWith the increasing availability of genetic data, several SNPs in a candidate gene can be combined into haplotypes to test for association with a quantitative trait. When the number of SNPs increases, the number of haplotypes can become very large and there is a need to group them together. The use of the phylogenetic relationships between haplotypes provides a natural and efficient way of grouping. Moreover, it allows us to identify disease or quantitative trait-related loci. In this article, we describe ALTree-q, a phylogeny-based approach to test for association between quantitative traits and haplotypes and to identify putative quantitative trait nucleotides (QTN). This study focuses on ALTree-q association test which is based on one-way analyses of variance (ANOVA) performed at the different levels of the tree. The statistical properties (type-one error and power rates) were estimated through simulations under different genetic models and were compared to another phylogeny-based test, TreeScan, (Templeton, 2005) and to a haplotypic omnibus test consisting in a one-way ANOVA between all haplotypes. For dominant and additive models ALTree-q is usually the most powerful test whereas TreeScan performs better under a recessive model. However, power depends strongly on the recurrence rate of the QTN, on the QTN allele frequency, and on the linkage disequilibrium between the QTN and other markers. An application of the method on Thrombin Activatable Fibronolysis Inhibitor Antigen levels in European and African samples confirms a possible association with polymorphisms of the CPB2 gene and identifies several QTN

Agricultural Research Bulletins, Nos. 413-447

Volume 32, Bulletins 413-447. (413) What Does the Iowa Farmer Want from Radio Market News?; (414) Estimate of the Volume of Farm Dwelling Construction in Iowa; (415) Retail Lumber Establishment and Farm Dwelling Construction in Iowa; (416) Farm Rental Practices and Problems in the Midwest; (417) How Do Iowa Farmers Obtain and Use Market News?; (418) Incomplete Block Designs with Blocks of Two Plots; (419) Economic Efficiency in Pasture Production and Improvement in Southern Iowa; (420) Load Characteristics of Southeastern Iowa Farms Using Electric Ranges; (421) Objective Grade Specifications for Slaughter Barrow and Gilt Carcasses; (422) Comparison of Costs of Service and Self-Service Methods in Retail Meat Departments; (423) Costs, Returns and Capital Requirements for Soil-Conserving Farming on Rented Farms in Western Iowa; (424) Crop Response Surfaces and Economic Optima in Fertilizer Use; (425) Resource Returns and Productivity Coefficients in Selected Farming Areas of Iowa, Montana and Alabama; (426) Optimum Combinations of Competitive Crops at Particular Locations (Applications of Linear Programming: 1); (427) Application of Input-Output Analysis to a Simple Model Emphasizing Agriculture (A Study of the Interdependence of Agriculture and Other Sectors of the National Economy; (428) Farm Size Adjustments in Iowa and Cost Economies in Crop Production for Farms of Different Sizes; (429) Costs and Returns for Soil-Conserving Systems of Farming on Ida-Monona Soils in Iowa; (430) Population Change and Net Migration in the North Central States, 1940-1950; (431) Economic Instability and Choices Involving Income and Risk in Livestock and Poultry Production; (432) Relationships Between Lard Production Methods, Volumes of Production, Costs and Characteristics of Lard Produced in Selected Packing Plants; (433) Marginal Productivity of Resources and Imputation of Shares for Cash and Share Rented Farms; (434) Nutrition of 9-, 10-, and 11-Year-Old Public School Children in Iowa, Kansas and Ohio; (435) Optimum Allocation of Resources Between Pasture Improvement and Other Opportunities on Southern Iowa Farms; (436) Physical and Mathematical Theories of the Tile and Ditch Drainage and their Usefulness in Design; (437) Optimum Combinations of Livestock Enterprises and Management Practices on Farms Including Supplementary Dairy and Poultry Enterprises (An Application of Linear Programming); (438) Application of Expectation Models to Livestock and Crop Prices and Products; (439) Combinations of Rotations and Fertilization to Maximize Crop Profits on Farms in North-Central Iowa (An Application of Linear Programming); (440) Optimum Farm Plans for Beginning Farmers on Tama-Muscatine Soils; (441) Production Functions, Isoquants, Isoclines and Economic Optima in Corn Fertilization for Experiments with Two and Three Variable Nutrients; (442) Least-Cost Rations and Optimum Marketing Weights for Broilers; (443) Least-Cost Rations and Optimum Marketing Weights for Turkeys; (444) Milk Production Functions, Hay/Grain Substitution Rates and Economic Optima in Dairy Cow Rations; (445) Analysis of the Efficiencies of Alternative Farm Leasing Arrangements (An Application of Linear Programming); (446) Effects of the USDA Corn Storage Program on Corn Carryover Stocks and Corn Utilization; (447) Uncertainty, Expectations and Investment Decisions for a Sample of Central Iowa Farmers</p