University of Maryland Biotechnology Institute

About: University of Maryland Biotechnology Institute is a based out in . It is known for research contribution in the topics: Gene & Population. The organization has 1565 authors who have published 2458 publications receiving 171434 citations. The organization is also known as: UMBI.

From individuals to population densities: searching for the intermediate scale of nontrivial determinism

Abstract: The degree of stochasticity or determinism in the dynamics of ecological systems varies with sampling scale. We propose the application of a determinism test from nonlinear data analysis to describe this variation and to identify a characteristic length scale at which to average spatiotemporal systems. Specifically, we investigate the spatial scale at which to aggregate individuals into densities in a system that combines demographic noise with local density-dependent interactions. The proposed approach is applied to the dynamics of a spatial and individual-based predator-prey model. The selected spatial scale is smaller than the one obtained by a previously proposed method whose similarities and differences we discuss. Two models, the simplest candidates for approximating the dynamics of densities at the selected scale, are examined: a predator-prey system of differential equations that ignores the local nature of the dynamics, and an extension of it that adds demographic noise. These approximations perform poorly, failing to capture broad statistical features of the predator and prey fluctuations. These findings indicate that spatial factors are nonnegligible at the selected intermediate scale of aggregation. Thus, predator-prey systems and other oscillatory ecological systems may display a dynamic regime at an intermediate scale of aggregation in which local interactions are still important. We discuss the type of model needed to approximate population densities in this dynamic regime.

A Live Attenuated Vaccine for Lassa Fever Made by Reassortment of Lassa and Mopeia Viruses

Abstract: Lassa virus (LASV) and Mopeia virus (MOPV) are closely related Old World arenaviruses that can exchange genomic segments (reassort) during coinfection. Clone ML29, selected from a library of MOPV/LASV (MOP/LAS) reassortants, encodes the major antigens (nucleocapsid and glycoprotein) of LASV and the RNA polymerase and zinc-binding protein of MOPV. Replication of ML29 was attenuated in guinea pigs and nonhuman primates. In murine adoptive-transfer experiments, as little as 150 PFU of ML29 induced protective cell-mediated immunity. All strain 13 guinea pigs vaccinated with clone ML29 survived at least 70 days after LASV challenge without either disease signs or histological lesions. Rhesus macaques inoculated with clone ML29 developed primary virus-specific T cells capable of secreting gamma interferon in response to homologous MOP/LAS and heterologous MOPV and lymphocytic choriomeningitis virus. Detailed examination of two rhesus macaques infected with this MOPV/LAS reassortant revealed no histological lesions or disease signs. Thus, ML29 is a promising attenuated vaccine candidate for Lassa fever.

Extracellular HIV-1 Tat Protein Up-Regulates the Expression of Surface CXC-Chemokine Receptor 4 in Resting CD4+ T Cells

Abstract: Here we report that synthetic HIV-1 Tat protein, immobilized on a solid substrate, up-regulates the surface expression of the CXC-chemokine receptor 4 (CXCR4), but not of the CC-chemokine receptor 5 in purified populations of primary resting CD4+ T cells. The Tat-mediated increase of CXCR4 occurred in a well-defined range of concentrations (1–10 nM of immobilized Tat) and time period (4–8 h postincubation). Moreover, the increase of CXCR4 was accompanied by an increased entry of the HXB2 T cell line-tropic (X4-tropic), but not of the BaL macrophage-tropic strain of HIV-1. The ability of Tat to up-regulate CXCR4 expression was abrogated by the protein synthesis inhibitor cycloheximide, clearly indicating the requirement of de novo synthesis. As Tat protein is actively released by HIV-1 infected cells, our data indicate a potentially important role for extracellular Tat in rendering bystander CD4+ T cells more susceptible to infection with X4-tropic HIV-1 isolates.

Structural basis for peptidoglycan binding by peptidoglycan recognition proteins

Abstract: Peptidoglycan (PGN) recognition proteins (PGRPs) are pattern-recognition receptors of the innate immune system that bind and, in some cases, hydrolyze bacterial PGNs. We determined the crystal structure, at 2.30-A resolution, of the C-terminal PGN-binding domain of human PGRP-Iα in complex with a muramyl tripeptide representing the core of lysine-type PGNs from Gram-positive bacteria. The peptide stem of the ligand is buried at the deep end of a long binding groove, with N-acetylmuramic acid situated in the middle of the groove, whose shallow end can accommodate a linked N-acetylglucosamine. Although most interactions are with the peptide, the glycan moiety also seems to be essential for specific recognition by PGRPs. Conservation of key PGN-contacting residues shows that all PGRPs employ this basic PGN-binding mode. The structure pinpoints variable residues that likely mediate discrimination between lysine- and diaminopimelic acid-type PGNs. We also propose a mechanism for PGN hydrolysis by Zn2+-containing PGRPs.