Investigating the role of the extracellular matrix (ECM) on pluripotent stem cell differentiation towards retinal lineages

PhD ThesisHuman pluripotent stem cells (hPSCs) can be differentiated into retinal organoids to study inherited and age related retinal dystrophies, to screen new drugs and to use them as replacement tissues. Published evidence suggests that retinal pigmented epithelium (RPE) and decellularised extracellular matrix (ECM) from RPE and neural retina contain several ECM molecules that are important for retinal development and synaptic formation between various cell types. To date, there has been limited detailed analysis of ECM components distribution during human retinal ontogenesis and the functional importance of several components is poorly understood. In this study, the expression of key ECM components in adult mouse and monkey retina, developing and adult human retina and hPSC-derived retinal organoids was studied. The results demonstrate that different ECM components have distinct distribution patterns throughout the adult retina of different species and a well conserved expression pattern between adult and developing human retinae. Furthermore, the expression of ECM components examined in retinal organoids was found to recapitulate at large human retinal development in vivo. The functional role of ECM on the differentiation of hPSC-derived retinal organoids was investigated either via blocking the action of two ECMs: cluster of differentiation 44 (CD44) and interphotoreceptor matrix proteoglycan 1 (IMPG1) in the organoids or via supplementation of culture media with RPE conditioned medium, decellularised ECM of neural retina or RPE. The findings indicate that IMPG1 and CD44 play an important role on photoreceptor development, their inner and outer segments, connecting cilia and IPM formation; with IMPG1 acting earlier and having more significant effect than CD44. All three supplements enhanced the light response in retinal organoids suggesting a beneficial effect of ECM on the development and function of hPSC-derived retinal organoids. Together, the study highlights a conserved expression of ECMs between human adult and developing retinae and retinal organoids as well as an important role for ECM in retinal development in vitro.King Abdulaziz University, Saudi Arabi

Torture, text and the reformulation of spiritual identity in old English religious verse

The Introduction to this thesis includes a brief discussion of various understandings of what torture is, and a statement of the definition of torture adopted for the purposes of this study. Torture, as it is examined in this study, is not so much an act of violence as it is a violent process; that is, torture is a means, not an end in itself, and torture always presupposes intent and causality. Chapter One provides the historical and legal contexts for later literary and theoretical discussions of torture. This chapter is divided into two parts, the first dealing with instances of torture which appear in Anglo-Saxon historical records, and the second dealing with legal codes which are concerned with torture. In the course of this chapter it becomes apparent that torture as a public act serves as a document of sorts, sometimes recording and sometimes interpreting political realities. Any study of torture must be grounded in an understanding of pain, and Chapter Two is concerned with the nature of pain, and with its relationship to torture. The paradox of pain is that it is universal and at the same time isolating and inexpressible. In Chapter Two, a close examination of the language and structure of The Dream of the Rood serves to illustrate that the Anglo-Saxons understood this paradox. The graphic and sometimes almost loving detail with which the poet describes the passion of Christ functions as a language "of weapons and wounds", and helps to convey, in some measure, the almost incommunicable nature of intense physical pain. Chapter Three explores the way in which torture acts may function as language acts, and the necessarily public nature of such performative language. This chapter begins with a discussion of linguistic theories concerning pragmatics and performative language acts. Then, drawing upon textual examples from such Old English sources as Elene, Juliana and Daniel, this chapter examines how torture may be construed as a form of language, and how the performative nature of an act of torture articulates that act's context of power and politics in the culture at large

Tilters with windmills--the coevolution of the appropriate technology movement in America

Thesis (Sc. D.)--Massachusetts Institute of Technology, Dept. of Political Science, 1988.Bibliography: v. 2, leaves 478-489.by Craig Adams Decker, Jr.Sc.D

Random patterns? : orderly disorder in contemporary narrative

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal

Annual Report of the Board of Regents of the Smithsonian Institution, showing the operations, expenditures, and condition of the Institution to July, 1897.

Annual Report of the Smithsonian Institution. 14 Apr. HD 575 (pts. 1-3), 55-2, v78-79 (pts. 1 and 2), 2308p. [3706-3708] Research related to the American Indian

Science handbook

2000 handbook for the faculty of Scienc

Science handbook

2000 handbook for the faculty of Scienc

Science handbook

2002 handbook for the faculty of Scienc

Science handbook

2003 handbook for the faculty of Scienc