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THE INFLUENCE OF MEMBRANE CHOLESTEROL-RELATED SHEAR STRESS MECHANOSENSITIVITY ON NEUTROPHIL FLOW BEHAVIORZhang, Xiaoyan 01 January 2012 (has links)
Hypercholesterolemia is a dominant risk factor for a variety of cardiovascular diseases and involves a chronic inflammatory component in which neutrophil activity plays a critical role. Recently, fluid shear stress mechanotransduction has been established as a control mechanism that regulates the activity of neutrophils by reducing the formation of pseudopods and the surface expression of CD18 integrins, thereby rendering these cells rounded, deformable, and non-adhesive. This is critical for maintaining a healthy circulation, because chronically activated neutrophils not only release excess cytotoxic and degradative agents but also exhibit a reduced efficiency to pass through the small vessels of the microcirculation leading to increased microvascular resistance. We hypothesized that aberrant neutrophil mechanosensitivity to fluid shear stress due to the altered blood environment (i.e., excess plasma cholesterol) is a contributing factor for elevated hemodynamic resistance in the microcirculation associated with hypercholesterolemia. For this purpose, the present work firstly showed that the sensitivity of neutrophils to fluid shear stress depends on the cholesterol-dependent fluidity of the cell membrane, and that, in the face of hypercholesterolemia, the neutrophil mechanosensitivity highly correlated with the plasma levels of free cholesterol. The second part of this project demonstrated that, when subjected to shear stress fields, leukocyte suspensions exhibited transient (within 10 min of flow onset) time-dependent reductions in their apparent viscosity. Moreover, shear-induced changes in viscosity of cell suspensions were influenced by disturbances of membrane cholesterol and fluidity in a fashion similar to that for shear-induced pseudopod retraction. Finally, the third part of this work provided evidence that neutrophils played a role in hypercholesterolemia-related impairment of flow recovery response to transient ischemia. In conclusion, results of the current work provided the first evidence that cholesterol is an important component of the neutrophil mechanotransducing capacity and impaired neutrophil shear mechanotransduction may disturb the blood flow rheology, leading to elevations in the apparent viscosity as well as in the resistance. This cholesterol-linked perturbation may be a contributing factor for the pathologic microcirculation associated with hypercholesterolemia.
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Molecular Phylogeny of Poa L. sensu lato (Poaceae) with a Focus on West Asian SpeciesAmiri, Neda January 2016 (has links)
Poa L., is known as a highly diverse cosmopolitan genus with taxonomic difficulties that includes unknown species and species with uncertain affinities mainly in West Asia and North Africa. Poa also exhibits a close relationship with two West Asian genera, Eremopoa Roshev. and Oreopoa H. Scholz & Parolly. This study was conducted to: 1) fill the gap of information on the affinities between Poa species with an emphasis on West Asian Poa; 2) revise and evaluate the accuracy of traditional infrageneric classification of West Asian Poa; and 3) clarify the relationship between Poa and two allied genera of Poaceae Barnhart, Eremopoa and Oreopoa. DNA molecular evidence from present phylogenetic analyses of West Asian species of Poa, Eremopoa and Oreopoa, resulted in some great findings as follow: I) Poa caucasica Trin., which is currently assigned to subsection Nivicolae of section Poa from subgenus Poa resolved as a unique new distinct lineage within Poa. II), New treatments are suggested for Poa densa Troitsky, Poa masenderana Freyn & Sint., Poa cenisia All., Poa psychrophila Boiss. & Heldr. and Poa lipskyi. III) Three unclassified species of Poa pseudobulbosa, Poa diversifolia and Poa aitchisonii are assigned here to subgenus Poa and supersection Poa. IV), The present molecular evidence supports inclusion of Eremopoa in Poa and confirms reduction of Eremopoa to a level of subgenus of Poa. V) Present phylogenetic analyses also indicate that monotypic genus Oreopoa H. Scholz & Parolly is part of Poa. These findings require an urgent modification in subgeneric and sectional classification of the genus Poa.
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