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Nicholas Dean

Bio: Nicholas Dean is an academic researcher. The author has contributed to research in topics: Virus & Virulence. The author has an hindex of 1, co-authored 1 publications receiving 245 citations.
Topics: Virus, Virulence

Papers
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Journal ArticleDOI
TL;DR: A role for endogenously expressed Trp1 in regulating a Ca2-selective current activated upon Ca2+ store depletion is supported.
Abstract: SPECIFIC AIMTo determine whether host selenium (Se) deficiency can induce changes in the genome of a replicating influenza virus such that a normally mild virus converts into a more virulent strain and to characterize such genomic changes.PRINCIPAL FINDINGS1. Replication of a mild strain of influenza virus in Se-deficient mice results in a novel virulent strain that causes severe lung pathology even when passed into Se-adequate miceSe-deficient mice developed much more severe lung pathology postinfection with influenza virus than Se-adequate infected mice. To determine whether host factors or viral factors were responsible for the increased pathogenicity of influenza virus that had replicated in Se-deficient mice, a passage experiment was performed. We infected groups of Se-adequate and Se-deficient mice with influenza A/Bangkok/1/79 (H3N2). At 5 days postinfection, the mice were killed and virus was recovered from the lungs. Five separate isolates from each group of mice were used to inoculate five indiv...

262 citations


Cited by
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Journal ArticleDOI
TL;DR: The key electrophysiological features of I(CRAC) and other store-operated Ca(2+) currents and how they are regulated are described, and recent advances that have shed insight into the molecular mechanisms involved in this ubiquitous and vital Ca( 2+) entry pathway are considered.
Abstract: In electrically nonexcitable cells, Ca2+ influx is essential for regulating a host of kinetically distinct processes involving exocytosis, enzyme control, gene regulation, cell growth and prolifera...

2,248 citations

Journal ArticleDOI
TL;DR: This review summarizes and analyzes the recent data from genetic, physiological, cellular, and morphological studies that have addressed the signaling mechanisms involved in the regulation of both the paracellular and transcellular transport pathways.
Abstract: The microvascular endothelial cell monolayer localized at the critical interface between the blood and vessel wall has the vital functions of regulating tissue fluid balance and supplying the essential nutrients needed for the survival of the organism. The endothelial cell is an exquisite "sensor" that responds to diverse signals generated in the blood, subendothelium, and interacting cells. The endothelial cell is able to dynamically regulate its paracellular and transcellular pathways for transport of plasma proteins, solutes, and liquid. The semipermeable characteristic of the endothelium (which distinguishes it from the epithelium) is crucial for establishing the transendothelial protein gradient (the colloid osmotic gradient) required for tissue fluid homeostasis. Interendothelial junctions comprise a complex array of proteins in series with the extracellular matrix constituents and serve to limit the transport of albumin and other plasma proteins by the paracellular pathway. This pathway is highly regulated by the activation of specific extrinsic and intrinsic signaling pathways. Recent evidence has also highlighted the importance of the heretofore enigmatic transcellular pathway in mediating albumin transport via transcytosis. Caveolae, the vesicular carriers filled with receptor-bound and unbound free solutes, have been shown to shuttle between the vascular and extravascular spaces depositing their contents outside the cell. This review summarizes and analyzes the recent data from genetic, physiological, cellular, and morphological studies that have addressed the signaling mechanisms involved in the regulation of both the paracellular and transcellular transport pathways.

1,575 citations

Journal ArticleDOI
TL;DR: The relationships between selenium intake/status and health, or risk of disease, are complex but require elucidation to inform clinical practice, to refine dietary recommendations, and to develop effective public health policies.
Abstract: This review covers current knowledge of selenium in the environment, dietary intakes, metabolism and status, functions in the body, thyroid hormone metabolism, antioxidant defense systems and oxidative metabolism, and the immune system. Selenium toxicity and links between deficiency and Keshan disease and Kashin-Beck disease are described. The relationships between selenium intake/status and various health outcomes, in particular gastrointestinal and prostate cancer, cardiovascular disease, diabetes, and male fertility, are reviewed, and recent developments in genetics of selenoproteins are outlined. The rationale behind current dietary reference intakes of selenium is explained, and examples of differences between countries and/or expert bodies are given. Throughout the review, gaps in knowledge and research requirements are identified. More research is needed to improve our understanding of selenium metabolism and requirements for optimal health. Functions of the majority of the selenoproteins await characterization, the mechanism of absorption has yet to be identified, measures of status need to be developed, and effects of genotype on metabolism require further investigation. The relationships between selenium intake/status and health, or risk of disease, are complex but require elucidation to inform clinical practice, to refine dietary recommendations, and to develop effective public health policies.

1,034 citations

Journal ArticleDOI
TL;DR: The present review summarizes the most pertinent recent evidence regarding the structural and functional properties of TRP channels, focusing on the regulation and physiology of mammalian TRPs.

732 citations

Journal ArticleDOI
TL;DR: Influenza (or “flu”) leads to the hospitalization of more than 200,000 people yearly and results in 36,000 deaths from flu or flu-related complications in the United States.
Abstract: Influenza (or “flu”) leads to the hospitalization of more than 200,000 people yearly and results in 36,000 deaths from flu or flu-related complications in the United States ([15][1]), striking both the elderly and infant populations particularly hard ([24][2]). Two members of the

490 citations