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Browsing by Author "Huang, Tao"

Now showing 1 - 3 of 3
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    Mechanism of sphingosine 1-phosphate clearance from blood
    Kharel, Yugesh; Huang, Tao; Salamon, Anita; Harris, Thurl E.; Santos, Webster L.; Lynch, Kevin R. (Portland Press, 2020-03-06)
    The interplay of sphingosine 1-phosphate (S1P) synthetic and degradative enzymes as well as S1P exporters creates concentration gradients that are a fundamental to S1P biology. Extracellular S1P levels, such as in blood and lymph, are high relative to cellular S1P. The blood-tissue S1P gradient maintains endothelial integrity while local S1P gradients influence immune cell positioning. Indeed, the importance of S1P gradients was recognized initially when the mechanism of action of an S1P receptor agonist used as a medicine for multiple sclerosis was revealed to be inhibition of T-lymphocytes’ recognition of the high S1P in efferent lymph. Furthermore, the increase in erythrocyte S1P in response to hypoxia influences oxygen delivery during high altitude acclimatization. However, understanding of how S1P gradients are maintained is incomplete. For example, S1P is synthesized but is only slowly metabolized by blood yet circulating S1P turns over quickly by an unknown mechanism. Prompted by the counterintuitive observation that blood S1P increases markedly in response to inhibition S1P synthesis (by sphingosine kinase 2 (SphK2)), we studied mice wherein several tissues were made deficient in either SphK2 or S1P degrading enzymes. Our data reveal a mechanism whereby S1P is de-phosphorylated at the hepatocyte surface and the resulting sphingosine is sequestered by SphK phosphorylation and in turn degraded by intracellular S1P lyase. Thus, we identify the liver as the primary site of blood S1P clearance and provide an explanation for the role of SphK2 in this process. Our discovery suggests a general mechanism whereby S1P gradients are shaped.
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    Reforming Industrial Design Education in Mainland China for Sustainability
    Huang, Tao (Virginia Tech, 2007-04-09)
    Industrial Design in China seldom addresses the issue of sustainability in mass production. Failure to incorporate sustainable design as a core principle will result in long term environmental and economic loss for both business and society. This research studies the current Industrial Design educational system in Mainland China and proposes a new educational framework to engage sustainability as a design objective. This study adopts the philosophical perspectives of constructivism, sustainable design theory, critical pedagogy, and systems thinking. Literature related to sustainability is collected and organized and overlaid with educational constraints identified through the interviews with educators, students, and practitioners of Industrial Design in four major cities of Mainland China. Using the grounded theory approach, from these two sources a new educational framework is proposed. The educational framework categorizes courses in a four year undergraduate Industrial Design educational program into four domains: ecological literacy, artistic, technological, and professional. Suggestions for the appropriate timeline, content, and pedagogical approaches for curriculum are also provided. The proposed framework was then critically reviewed Chinese educators that served as feedback for the final proposition.
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    Saccharomyces cerevisiae as a platform for assessing sphingolipid lipid kinase inhibitors
    Kharel, Yugesh; Agah, Sayeh; Huang, Tao; Mendelson, Anna J.; Eletu, Oluwafunmilayo T.; Barkey-Bircannl, Peter; Gesualdil, James; Smith, Jeffrey S.; Santos, Webster L.; Lynch, Kevin R. (PLOS, 2018-04-19)
    Successful medicinal chemistry campaigns to discover and optimize sphingosine kinase inhibitors require a robust assay for screening chemical libraries and for determining rank order potencies. Existing assays for these enzymes are laborious, expensive and/or low throughput. The toxicity of excessive levels of phosphorylated sphingoid bases for the budding yeast, Saccharomyces cerevisiae, affords an assay wherein inhibitors added to the culture media rescue growth in a dose-dependent fashion. Herein, we describe our adaptation of a simple, inexpensive, and high throughput assay for assessing inhibitors of sphingosine kinase types 1 and 2 as well as ceramide kinase and for testing enzymatic activity of sphingosine kinase type 2 mutants. The assay was validated using recombinant enzymes and generally agrees with the rank order of potencies of existing inhibitors.