86 research outputs found

    Development of habitat inventory techniques for rapidly assessing impacts of forest management practices on deer

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    To research selected aspects of deer resource dynamics that have been identified as key components in the redefinition and/or implementation of deer management strategic plans and programs in northern New York

    An Index to Assess the Sensitivity of Gulf of Mexico Species to Changes in Estuarine Salinity Regimes

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    An index of biological sensitivity to changes in freshwater inflow was developed for 44 species in 22 Gulf of Mexico estuaries for adult and juvenile life stages of fishes and macroinvertebrates. The BioSalinity Index (BSI) provides an innovative approach to quantify estuary-specific sensitivity of organisms to changes in estuarine salinity regimes based upon our knowledge of species salinity habitat preferences, the availability of this preferred habitat, and the relative abundance and distribution of species in time and space. We found that a significant difference exists between adult and juvenile life stage sensitivity, with juveniles exhibiting a lower sensitivity to salinity changes than adults, and that a considerable disparity exists in species-specific sensitivities among Gulf estuaries. Likewise, when the full complement of 44 species-level BSIs are averaged, marked differences in assemblage-wide sensitivity are evident across estuaries. The availability of preferred salinity habitat had a greater influence on the BSI for estuarine species than did their relative abundance and temporal distribution. The BSI was applied by members of a 1995 Gulf of Mexico freshwater inflow workshop to identify a subset of estuaries which appear more sensitive to freshwater inflow changes and are candidates for further study

    Sewers as a Source and Sink of Chlorinated-Solvent Groundwater Contamination, Marine Corps Recruit Depot, Parris Island, South Carolina

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    2010 S.C. Water Resources Conferences - Science and Policy Challenges for a Sustainable Futur

    The Application of Topmodel to Assess Mercury Fluxes in the McTier Creek Watershed

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    2008 S.C. Water Resources Conference - Addressing Water Challenges Facing the State and Regio

    Abnormal Trafficking of Endogenously Expressed BMPR2 Mutant Allelic Products in Patients with Heritable Pulmonary Arterial Hypertension

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    More than 200 heterozygous mutations in the type 2 BMP receptor gene, BMPR2, have been identified in patients with Heritable Pulmonary Arterial Hypertension (HPAH). More severe clinical outcomes occur in patients with BMPR2 mutations by-passing nonsense-mediated mRNA decay (NMD negative mutations). These comprise 40% of HPAH mutations and are predicted to express BMPR2 mutant products. However expression of endogenous NMD negative BMPR2 mutant products and their effect on protein trafficking and signaling function have never been described. Here, we characterize the expression and trafficking of an HPAH-associated NMD negative BMPR2 mutation that results in an in-frame deletion of BMPR2 EXON2 (BMPR2ΔEx2) in HPAH patient-derived lymphocytes and in pulmonary endothelial cells (PECs) from mice carrying the same in-frame deletion of Exon 2 (Bmpr2 (ΔEx2/+) mice). The endogenous BMPR2ΔEx2 mutant product does not reach the cell surface and is retained in the endoplasmic reticulum. Moreover, chemical chaperones 4-PBA and TUDCA partially restore cell surface expression of Bmpr2ΔEx2 in PECs, suggesting that the mutant product is mis-folded. We also show that PECs from Bmpr2 (ΔEx2/+) mice have defects in the BMP-induced Smad1/5/8 and Id1 signaling axis, and that addition of chemical chaperones restores expression of the Smad1/5/8 target Id1. These data indicate that the endogenous NMD negative BMPRΔEx2 mutant product is expressed but has a folding defect resulting in ER retention. Partial correction of this folding defect and restoration of defective BMP signaling using chemical chaperones suggests that protein-folding agents could be used therapeutically in patients with these NMD negative BMPR2 mutations

    Two Gα i1 Rate-Modifying Mutations Act in Concert to Allow Receptor-Independent, Steady-State Measurements of RGS Protein Activity

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    RGS proteins are critical modulators of G protein-coupled receptor (GPCR) signaling given their ability to deactivate Gα subunits via “GTPase-accelerating protein” (GAP) activity. Their selectivity for specific GPCRs makes them attractive therapeutic targets. However, measuring GAP activity is complicated by slow GDP release from Gα and lack of solution-phase assays for detecting free GDP in the presence of excess GTP. To overcome these hurdles, we developed a Gαi1 mutant with increased GDP dissociation and decreased GTP hydrolysis, enabling detection of GAP activity using steady-state GTP hydrolysis. Gαi1(R178M/A326S) GTPase activity was stimulated 6~12 fold by RGS proteins known to act on Gαi subunits, and not affected by those unable to act on Gαi, demonstrating that the Gα/RGS domain interaction selectivity was not altered by mutation. Gαi1(R178M/A326S) interacted with RGS proteins with expected binding specificity and affinities. To enable non-radioactive, homogenous detection of RGS protein effects on Gαi1(R178M/A326S), we developed a Transcreener® fluorescence polarization immunoassay based on a monoclonal antibody that recognizes GDP with greater than 100-fold selectivity over GTP. Combining Gαi1(R178M/A326S) with a homogenous, fluorescence-based GDP detection assay provides a facile means to explore the targeting of RGS proteins as a new approach for selective modulation of GPCR signaling
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