Project description:Filoviruses infect a wide range of cell types with the exception of lymphocytes. The intracellular proteins cathepsin B and L, two-pore channel 1 and 2, and bona fide receptor Niemann–Pick Disease C1 (NPC1) are essential for the endosomal phase of cell entry. However, earlier steps of filoviral infection remain poorly characterized. Numerous plasma membrane proteins have been implicated in attachment but it is still unclear which ones are sufficient for productive entry. To define a minimal set of host factors required for filoviral glycoprotein-driven cell entry, we screened twelve cell lines and identified the nonlymphocytic cell line SH-SY5Y to be specifically resistant to filovirus infection. Heterokaryons of SH-SY5Y cells fused to susceptible cells were susceptible to filoviruses, indicating that SH-SY5Y cells do not express a restriction factor but lack an enabling factor critical for filovirus entry. However, all tested cell lines expressed functional intracellular factors. Global gene expression profiling of known cell surface entry factors and protein expression levels of analyzed attachment factors did not reveal any correlation between susceptibility and expression of a specific host factor. Using binding assays with recombinant filovirus glycoprotein, we identified cell attachment as the step impaired in filovirus entry in SH-SY5Y cells. Individual overexpression of attachment factors T-cell immunoglobulin and mucin domain 1 (TIM-1), Axl, Mer, or dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) rendered SH-SY5Y cells susceptible to filovirus glycoprotein-driven transduction. Our study reveals that a lack of attachment factors limits filovirus entry and provides direct experimental support for a model of filoviral cell attachment where host factor usage at the cell surface is highly promiscuous.
Project description:Primary objectives: The primary objective is to investigate circulating tumor DNA (ctDNA) via deep sequencing for mutation detection and by whole genome sequencing for copy number analyses before start (baseline) with regorafenib and at defined time points during administration of regorafenib for treatment efficacy in colorectal cancer patients in terms of overall survival (OS).
Primary endpoints: circulating tumor DNA (ctDNA) via deep sequencing for mutation detection and by whole genome sequencing for copy number analyses before start (baseline) with regorafenib and at defined time points during administration of regorafenib for treatment efficacy in colorectal cancer patients in terms of overall survival (OS).
Project description:Gene expression was determined for Male accessory gland and testes in different members of the Anopheles gambiae complex, including An. gambiae (Savannah, MRA-762), An. coluzzii (Mopti) [2], An. arabiensis [3], An. merus [4] and An. quadriannalatus [5. All the mosquito stocks were obtained from the Malaria Research and Reference Reagent Resource Center (MR4) in Atlanta (https://www.beiresources.org/Catalog/BEIVectors/MRA-762.aspx). References: 1. MR4 wild stocks information. Access Jenuary 2018. (Kisumu) https://www.beiresources.org/Catalog/BEIVectors/MRA-762.aspx 2. MR4 wild stocks information. Access Jenuary 2018. (Mopti) https://www.beiresources.org/Catalog/BEIVectors/MRA-763.aspx 3. MR4 wild stocks information. Access Jenuary 2018. (arabiensis) https://www.beiresources.org/Catalog/BEIVectors/MRA-856.aspx 4. MR4 wild stocks information. Access Jenuary 2018. (merus) https://www.beiresources.org/Catalog/BEIVectors/MRA-1156.aspx 5. MR4 wild stocks information. Access Jenuary 2018. (quadriannulatus) https://www.beiresources.org/Catalog/BEIVectors/MRA-1155.aspx
Project description:The project compares the production of plant biomass degrading enzymes by Podospora anserina during growth on different feed stocks.
Project description:Viruses in the Ebolavirus and Marburgvirus genera (family Filoviridae) have been associated with large outbreaks of hemorrhagic fever in human and nonhuman primates. The first documented cases occurred in primates over 45 years ago, but the amount of virus genetic diversity detected within bat populations, which have recently been identified as potential reservoir hosts, suggests that the filoviruses are much older. Here, detailed Bayesian coalescent phylogenetic analyses are performed on 97 whole-genome sequences, 55 of which are newly reported, to comprehensively examine molecular evolutionary rates and estimate dates of common ancestry for viruses within the family Filoviridae. Molecular evolutionary rates for viruses belonging to different species range from 0.46 × 10(-4) nucleotide substitutions/site/year for Sudan ebolavirus to 8.21 × 10(-4) nucleotide substitutions/site/year for Reston ebolavirus. Most recent common ancestry can be traced back only within the last 50 years for Reston ebolavirus and Zaire ebolavirus species and suggests that viruses within these species may have undergone recent genetic bottlenecks. Viruses within Marburg marburgvirus and Sudan ebolavirus species can be traced back further and share most recent common ancestors approximately 700 and 850 years before the present, respectively. Examination of the whole family suggests that members of the Filoviridae, including the recently described Lloviu virus, shared a most recent common ancestor approximately 10,000 years ago. These data will be valuable for understanding the evolution of filoviruses in the context of natural history as new reservoir hosts are identified and, further, for determining mechanisms of emergence, pathogenicity, and the ongoing threat to public health.
| S-EPMC3571414 | biostudies-literature
Project description:Pooled whole genome sequencing of Pacific cod spawning stocks