300 research outputs found
Curing Cholera: Pathogens, Places and Poverty in South Asia
No full textIn this paper I will seek to provide a new understanding of endemicity of disease in India. Through a study of cholera research in the twentieth century I will argue that disease and its endemicity has to be understood in biological factors as well as within a wider social and economic context. I will discuss the medical efforts at locating the causality of cholera from the nineteenth century in Indian climate, water bodies and human anatomy to show that cholera is no more a biological phenomena than water is an ecological or environmental problem. Both are essentially political and economic questions
Type I Interferons and the Development of Impaired Vascular Function and Repair in Human and Murine Lupus.
No full textPatients with systemic lupus erythematosus (SLE), an autoimmune disease of unclear etiology, have a greatly increased risk of developing premature atherosclerotic cardiovascular disease (CVD), independent of traditional vascular risk factors. While CVD is a major cause of mortality and morbidity in these patients, the exact mechanisms behind this increased vascular risk are unknown. SLE patients develop a profound imbalance of vascular damage and repair which is mediated by interferon (IFN)-α and, potentially, by other type I IFNs. This dissertation elucidates the molecular mechanisms by which IFN-α inhibits vascular repair mediated by endothelial progenitor cells (EPCs), and demonstrates that type I IFNs play a key role in the development of endothelial dysfunction in lupus-prone and non-lupus-prone mice in vivo. Using a gene expression array approach, we identified that IFN-α promotes antiangiogenic responses in EPCs through repression of IL-1 signaling and of vascular endothelial growth factor. These effects are mediated through the JAK/STAT pathway. These transcriptional abnormalities are operational in vivo, as evidenced by vascular rarefaction observed in human lupus tissues. In murine studies, we identified that the lupus prone mouse strain New Zealand Black/New Zealand White F1 displays an abnormal vascular phenotype similar to human SLE. In the closely related NZM 2328 strain, we demonstrate that type I IFNs induce endothelial dysfunction, decreased neoangiogenesis and enhanced platelet activation. These deleterious effects on the vasculature mediated by type I IFNs were not secondary to lupus disease activity, gender or lupus prone phenotype. Furthermore, type I IFNs are also involved in atherosclerosis severity and acceleration of thrombosis in Apolipoprotein-E deficient mice, an atherosclerosis-prone mouse strain. Our results strongly suggest that type I IFNs play a vital role in the induction of endothelial dysfunction and aberrant vascular repair in lupus through the inhibition of important proangiogenic molecules. These results also indicate that type I IFNs may play a deleterious role in the vasculature in “idiopathic” atherosclerosis not related to systemic autoimmune diseases. These observations could also have important implications in the identification of therapeutic targets to prevent CVD and in the understanding on how microbial infections may trigger vascular damage.PhDImmunologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/86564/1/seththac_1.pd
Far eastern markets
No full textThesis (M.B.A.)--Boston University
PLEASE NOTE: page 115 appears to be missing from the thesis. Our determination is that this is the result of misnumbering by the author, and no substantive content is actually missing. If you are able to determine otherwise, please contact us
The Arab Avant-Garde: Musical Innovation in the Middle East
No full textIn the early nineteenth century, the term “avant-garde” began to capture greater semantic territory. Once purely a military phrase used to distinguish crack troops, it then assumed a high-ranking position within cultural expression, marking out art work that forged ahead and broke new ground. What can it mean to conjoin this French phrase with the word “Arab”? French forces, along with other imperial intruders, are no strangers to Arab terrain. The colonisation of Algeria, Tunisia, Morocco and Greater Syria followed in the wake of the brief Napoleonic “mission” to Egypt between 1798 and 1801. It was during this military foray that some of modern Europe’s most expansive data on Egyptian music was collected, information that comprised two whole volumes of Guillaume André Villoteau’s Description de l’Egypte. The Napoleonic campaign gathered not only military, but also cultural intelligence, if the two can be so easily separated
Distinct migratory and non-migratory ecotypes of an endemic New Zealand eleotrid (Gobiomorphus cotidianus) – implications for incipient speciation in island freshwater fish species
No full textBackground: Many postglacial lakes contain fish species with distinct ecomorphs. Similar evolutionary scenarios might be acting on evolutionarily young fish communities in lakes of remote islands. One process that drives diversification in island freshwater fish species is the colonization of depauperate freshwater environments by diadromous (migratory) taxa, which secondarily lose their migratory behaviour. The loss of migration limits dispersal and gene flow between distant populations, and, therefore, is expected to facilitate local morphological and genetic differentiation. To date, most studies have focused on interspecific relationships among migratory species and their non-migratory sister taxa. We hypothesize that the loss of migration facilitates intraspecific morphological, behavioural, and genetic differentiation between migratory and non-migratory populations of facultatively diadromous taxa, and, hence, incipient speciation of island freshwater fish species.
Results: Microchemical analyses of otolith isotopes (Sr-88, Ba-137 and Ca-43) differentiated migratory and non-migratory stocks of the New Zealand endemic Gobiomorphus cotidianus McDowall (Eleotridae). Samples were taken from two rivers, one lake and two geographically-separated outgroup locations. Meristic analyses of oculoscapular lateral line canals documented a gradual reduction of these structures in the non-migratory populations. Amplified fragment length polymorphism (AFLP) fingerprints revealed considerable genetic isolation between migratory and non-migratory populations. Temporal differences in reproductive timing (migratory = winter spawners, non-migratory = summer spawners; as inferred from gonadosomatic indices) provide a prezygotic reproductive isolation mechanism between the two ecotypes.
Conclusion: This study provides a holistic look at the role of diadromy in incipient speciation of island freshwater fish species. All four analytical approaches (otolith microchemistry, morphology, spawning timing, population genetics) yield congruent results, and provide clear and independent evidence for the existence of distinct migratory and non-migratory ecotypes within a river in a geographically confined range. The morphological changes within the non-migratory populations parallel interspecific patterns observed in all non-migratory New Zealand endemic Gobiomorphus species and other derived gobiid taxa, a pattern suggesting parallel evolution. This study indicates, for the first time, that distinct ecotypes of island freshwater fish species may be formed as a consequence of loss of migration and subsequent diversification. Therefore, if reproductive isolation persists, these processes may provide a mechanism to facilitate speciation
Reinventing (with) theory in rhetoric and writing studies: essays in honor of Sharon Crowley
No full textIncludes bibliographical references and index.Scholarship that takes up and extends the practices of inventive theorizing characterized by Crowley's work. Showing that theory is a continual rhetorical process that is indispensable for understanding situations and their potential significance--and a means of persuasion. Includes a foreword, afterword, and interview with Crowley.--Provided by publisher.The fallacy of reason / Dawn Penich-Thacker -- A brief etiology of violence: the logic of identity and the metaphysics of presence / Judy Holiday -- Toward a working theory of institutional rhetorics / Ryan Skinnell -- The sophist as mentor: Sharon Crowley's rhetoric as a theory and practice of mentoring / William Lalicker, James C. McDonald, and Susan Wyche -- Reflections on being against audience with Sharon and others / Victor J. Vitanza -- Ludic rhetorics: theories of play in rhetoric and writing / Joshua Daniel-Wariya -- Unhurried conversations: writing center models for ideological intervention / Joshua C. Hilst and Rebecca Disrud -- No body is disinterested: the discursive materiality of composition in the university / Kirsti Cole -- Once more with feeling / Jennifer Lin LeMesurier -- Theory building in the rhetoric of health & medicine / J. Blake Scott and Catherine C. Gouge -- Victimless leather: toward a new materialist ethics of invention / Jason Barrett-Fox and Geoffrey Clegg -- Corporeal rhetoric as embodied action: composing in/through bodily motion / Bre Garrett -- Rhetorical futurity, or desiring theory / Kendall Gerdes -- Black religion matters: African American prophecy as a theoretical frame for rhetorical interpretation, invention, and critique / David G. Holmes -- When queers listen / Timothy Oleksiak -- Rhetoric in dimness / Matthew Heard -- Afterword: feeling and historiography / Debra Hawhee
Lipoprotein X Causes Renal Disease in LCAT Deficiency.
No full textHuman familial lecithin:cholesterol acyltransferase (LCAT) deficiency (FLD) is characterized by low HDL, accumulation of an abnormal cholesterol-rich multilamellar particle called lipoprotein-X (LpX) in plasma, and renal disease. The aim of our study was to determine if LpX is nephrotoxic and to gain insight into the pathogenesis of FLD renal disease. We administered a synthetic LpX, nearly identical to endogenous LpX in its physical, chemical and biologic characteristics, to wild-type and Lcat-/- mice. Our in vitro and in vivo studies demonstrated an apoA-I and LCAT-dependent pathway for LpX conversion to HDL-like particles, which likely mediates normal plasma clearance of LpX. Plasma clearance of exogenous LpX was markedly delayed in Lcat-/- mice, which have low HDL, but only minimal amounts of endogenous LpX and do not spontaneously develop renal disease. Chronically administered exogenous LpX deposited in all renal glomerular cellular and matrical compartments of Lcat-/- mice, and induced proteinuria and nephrotoxic gene changes, as well as all of the hallmarks of FLD renal disease as assessed by histological, TEM, and SEM analyses. Extensive in vivo EM studies revealed LpX uptake by macropinocytosis into mouse glomerular endothelial cells, podocytes, and mesangial cells and delivery to lysosomes where it was degraded. Endocytosed LpX appeared to be degraded by both human podocyte and mesangial cell lysosomal PLA2 and induced podocyte secretion of pro-inflammatory IL-6 in vitro and renal Cxl10 expression in Lcat-/- mice. In conclusion, LpX is a nephrotoxic particle that in the absence of Lcat induces all of the histological and functional hallmarks of FLD and hence may serve as a biomarker for monitoring recombinant LCAT therapy. In addition, our studies suggest that LpX-induced loss of endothelial barrier function and release of cytokines by renal glomerular cells likely plays a role in the initiation and progression of FLD nephrosis
The Detrimental Effects of IFN-α on Vasculogenesis in Lupus Are Mediated by Repression of IL-1 Pathways: Potential Role in Atherogenesis and Renal Vascular Rarefaction
No full textAbstract
Systemic lupus erythematosus (SLE) is characterized by increased vascular risk due to premature atherosclerosis independent of traditional risk factors. We previously proposed that IFN-α plays a crucial role in premature vascular damage in SLE. IFN-α alters the balance between endothelial cell apoptosis and vascular repair mediated by endothelial progenitor cells (EPCs) and myeloid circulating angiogenic cells (CACs). In this study, we demonstrate that IFN-α promotes an antiangiogenic signature in SLE and control EPCs/CACs, characterized by transcriptional repression of IL-1α and β, IL-1R1, and vascular endothelial growth factor A, and upregulation of IL-1R antagonist and the decoy receptor IL-1R2. IL-1β promotes significant improvement in the functional capacity of lupus EPCs/CACs, therefore abrogating the deleterious effects of IFN-α. The beneficial effects from IL-1 are mediated, at least in part, by increases in EPC/CAC proliferation, by decreases in EPC/CAC apoptosis, and by preventing the skewing of CACs toward nonangiogenic pathways. IFN-α induces STAT2 and 6 phosphorylation in EPCs/CACs, and JAK inhibition abrogates the transcriptional antiangiogenic changes induced by IFN-α in these cells. Immunohistochemistry of renal biopsies from patients with lupus nephritis, but not anti-neutrophil cytoplasmic Ab-positive vasculitis, showed this pathway to be operational in vivo, with increased IL-1R antagonist, downregulation of vascular endothelial growth factor A, and glomerular and blood vessel decreased capillary density, compared with controls. Our study introduces a novel putative pathway by which type I IFNs may interfere with vascular repair in SLE through repression of IL-1–dependent pathways. This could promote atherosclerosis and loss of renal function in this disease.</jats:p
Synthesis of Cholesterol Analogues Bearing BODIPY Fluorophores by Suzuki or Liebeskind–Srogl Cross‐Coupling and Evaluation of Their Potential for Visualization of Cholesterol Pools
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