8 research outputs found

    The Gelatinase Biosynthesis‐Activating Pheromone binds and stabilizes the FsrB membrane protein in Enterococcus faecalis quorum sensing

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    Quorum‐sensing mechanisms regulate gene expression in response to changing cell‐population density detected through pheromones. In Enterococcus faecalis, Fsr quorum sensing produces and responds to the gelatinase biosynthesis‐activating pheromone (GBAP). Here we establish that the enterococcal FsrB membrane protein has a direct role connected with GBAP by showing that GBAP binds to purified FsrB. Far‐UV CD measurements demonstrated a predominantly α‐helical protein exhibiting a small level of conformational flexibility. Fivefold (400 ÎŒm) GBAP stabilised FsrB (80 ÎŒm) secondary structure. FsrB thermal denaturation in the presence and absence of GBAP revealed melting temperatures of 70.1 and 60.8 °C, respectively, demonstrating GBAP interactions and increased thermal stability conferred by GBAP. Addition of GBAP also resulted in tertiary structural changes, confirming GBAP binding

    HHIPL1, a Gene at the 14q32 Coronary Artery Disease Locus, Positively Regulates Hedgehog Signaling and Promotes Atherosclerosis

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    The research leading to these results has received funding from the European Union Seventh Framework Programme FP7/2007–2013 under grant agreement number HEALTH-F2-2013–601456, a Transatlantic Networks of Excellence Award (12CVD02) from The Leducq Foundation and the British Heart Foundation (SP/18/8/33620) as a partner of the European Research Area Network on Cardiovascular Diseases (ERA-CVD) druggable-MI-genes (01KL1802) and supported by the UK National Institute for Health Research (NIHR) Leicester Biomedical Research Centre. Dr Samani is a UK NIHR Senior Investigator. Drs Morris, Ye, and Webb are funded by the British Heart Foundation (SP/16/4/32697).Peer reviewedPublisher PD

    Status and prospects for renewable energy using wood pellets from the southeastern United States

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    The ongoing debate about costs and benefits of wood-pellet based bioenergy production in the southeastern United States (SE USA) requires an understanding of the science and context influencing market decisions associated with its sustainability. Production of pellets has garnered much attention as US exports have grown from negligible amounts in the early 2000s to 4.6 million metric tonnes in 2015. Currently, 98% of these pellet exports are shipped to Europe to displace coal in power plants. We ask, ‘How is the production of wood pellets in the SE USA affecting forest systems and the ecosystem services they provide?’ To address this question, we review current forest conditions and the status of the wood products industry, how pellet production affects ecosystem services and biodiversity, and what methods are in place to monitor changes and protect vulnerable systems. Scientific studies provide evidence that wood pellets in the SE USA are a fraction of total forestry operations and can be produced while maintaining or improving forest ecosystem services. Ecosystem services are protected by the requirement to utilize loggers trained to apply scientifically based best management practices in planning and implementing harvest for the export market. Bioenergy markets supplement incomes to private rural landholders and provide an incentive for forest management practices that simultaneously benefit water quality and wildlife and reduce risk of fire and insect outbreaks. Bioenergy also increases the value of forest land to landowners, thereby decreasing likelihood of conversion to nonforest uses. Monitoring and evaluation are essential to verify that regulations and good practices are achieving goals and to enable timely responses if problems arise. Conducting rigorous research to understand how conditions change in response to management choices requires baseline data, monitoring, and appropriate reference scenarios. Long-term monitoring data on forest conditions should be publicly accessible and utilized to inform adaptive management

    Characterisation of HHIPL1, a Coronary Artery Disease Associated Gene

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    Genome-wide association studies (GWAS) have produced many single nucleotide polymorphisms (SNPs) significantly associated with coronary artery disease (CAD) in humans. The variant rs10139550 is a CAD-associated SNP within the HHIPL1 gene. HHIPL1 (hedgehog interacting protein-like 1) is an uncharacterised protein that has homology with the hedgehog (HH) antagonist Hedgehog Interacting Protein (HHIP). This thesis aimed to characterise HHIPL1 within HH signalling pathway. This thesis also aimed to identify causal variants in HHIPL1 and link them to human smooth muscle cell phenotypes. This is based on previous work in the same laboratory using murine models that linked HHIPL1, smooth muscle cell phenotypes, and CAD. A luciferase assay linked to GLI protein expression in murine Shh-LIGHT2 cells determined the function of HHIPL1 in HH signalling. GLI proteins are transcription factors in the HH pathway. In silico analysis and co-immunoprecipitation studies examined HHIPL1 binding to the HH ligand, sonic hedgehog (SHH). An association study determined if the lead SNP rs10139550 and SNPs in a 100kb area surrounding this variant were significantly associated with human umbilical artery smooth muscle cell phenotypes. Expression analysis determined if there was any link between HHIPL1 variants and altered expression of HHIPL1. Results of binding studies were suggestive of HHIPL1 binding to SHH. HHIPL1 was found to be a positive modulator of full-length SHH, but a negative modulator with the biologically active SHH-N. No variants were found to be in genome-wide significance with the smooth muscle cell phenotypes studied. One variant was significant at an analysis-wide threshold, but was deemed a false positive. Expression analysis showed no significant difference in HHIPL1 expression. This study characterises a novel modulator in hedgehog signalling and informs future investigation to further define HHIPL1 binding partners and dynamics, and causal variants in coronary artery disease.</p

    Teaching Bioeconomics

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    Bioeconomics is a relatively young field that uses an expanded microeconomics to examine animal behavior, human behavior, and animal and human social institutions. A voluminous literature is rapidly accumulating. There are as yet no standard textbooks, but there are several excellent books and/or articles that can be used in combination with videos and other aids to make a course that students will enjoy and that teachers can use to advance the frontiers of scholarship in economics and biology. Copyright Springer 2005altruism, conflict, cooperation, evolution, game theory, institutions, rationality,
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