3,332 research outputs found
The human fetal adrenal cortex and the window of sexual differentiation
No full textUnderstanding normal development is fundamental to appreciating postnatal morphology, physiology and, in some instances, pathophysiology. Developmental biology tends to interrogate models in nonprimate species, for instance the mouse, where genetic manipulation gives privileged insight into the function of particular genes. Some human developmental processes, as occur in the adrenal gland, are not faithfully reproduced in these rodent models, yet have an impact on the pathophysiology and treatment of endocrine disorders, such as congenital adrenal hyperplasia. In this setting, in vitro research of normal human development complements clinical investigation of patients born with congenital disorder
Commonalities in the endocrinology of stem cell biology and organ regeneration (In special issue: Stem cells and progenitors in organ maintenance, regeneration and replacement: the role of hormones and growth factors in health and disease)
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Embryonic stem cells to beta-cells by understanding pancreas development
Full text linkInsulin injections treat but do not cure Type 1 diabetes (T1DM). The success of islet transplantation suggests cell replacement therapies may offer a curative strategy. However, cadaver islets are of insufficient number for this to become a widespread treatment. To address this deficiency, the production of beta-cells from pluripotent stem cells offers an ambitious far-sighted opportunity. Recent progress in generating insulin-producing cells from embryonic stem cells has shown promise, highlighting the potential of trying to mimic normal developmental pathways. Here, we provide an overview of the current methodology that has been used to differentiate stem cells toward a beta-cell fate. Parallels are drawn with what is known about normal development, especially regarding the human pancrea
The adrenal cortex and sexual differentiation during early human development
No full textHuman sexual differentiation is a critical process whereby a strict dimorphism is established that enables future reproductive success as phenotypic males and females. Significant components of this differentiation pathway unfold during the first three months of gestation when they are sensitive to disruption by abnormal hormonal influences. Excessive exposure of female development to androgens in conditions such as congenital adrenal hyperplasia causes virilization. However, recently we have suggested that female development normally takes place in the presence of low, yet significant, levels of androgen, implying a need for strict regulation to avoid virilization and the potential for a biological role of androgens in females that has not been fully elucidated. Here, we review androgen-dependent male differentiation of the external genitalia in humans, and link this to current understanding of female development and steroidogenesis in the developing adrenal cortex
Weighing up beta-cell mass in mice and humans: self-renewal, progenitors or stem cells? (In special issue: Stem cells and progenitors in organ maintenance, regeneration and replacement: the role of hormones and growth factors in health and disease)
No full textUnderstanding how beta-cells maintain themselves in the adult pancreas is important for prioritizing strategies aimed at ameliorating or ideally curing different forms of diabetes. There has been much debate over whether beta-cell proliferation, as a means of self-renewal, predominates over the existence and differentiation of a pancreatic stem cell or progenitor cell population. This article describes the two opposing positions based largely on research in laboratory rodents and its extrapolation to humans
Age-specific changes in sex steroid biosynthesis and sex development
No full textNormal male sex development requires the SRY gene on the Y chromosome, the regression of Mullerian structures via anti-Mullerian hormone (AMH) signalling, the development of the Wolffian duct system into normal male internal genital structures consequent to testosterone secretion by the testicular Leydig cells, and finally, sufficient activation of testosterone to dihydrotestosterone by 5alpha-reductase. All these events take place during weeks 8-12 of gestation, a narrow window of sexual differentiation. Recent studies in human fetal development have demonstrated the early fetal expression of the adrenocorticotrophic hormone (ACTH) receptor and all steroidogenic components necessary for the biosynthesis of cortisol. These findings provide compelling evidence for the assumed pathogenesis of congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency, diminished feedback to the pituitary due to glucocorticoid deficiency, subsequent ACTH excess, and up-regulation of adrenal androgen production with subsequent virilization. Another CAH variant, P450 oxidoreductase deficiency, manifests with 46,XX disorder of sex development (DSD), i.e., virilized female genitalia, despite concurrently low circulating androgens. This CAH variant illustrates the existence of an alternative pathway toward the biosynthesis of active androgens in humans which is active in human fetal life only. Thus CAH teaches important lessons from nature, providing privileged insights into the window of human sexual differentiation, and particularly highlighting the importance of steroidogenesis in the process of human sexual differentiatio
The self-orientation of mammalian cells in optical tweezers - the importance of the nucleus
No full textHere we present the first evidence showing that eukaryotic cells can be stably trapped in a single focused Gaussian beam with an orientation that is defined by the nucleus. A mammalian eukaryotic cell (in suspension) is trapped and is re-oriented in the focus of a linearly polarized Gaussian beam with a waist of dimension smaller than the radius of the nucleus. The cell reaches a position relative to the focus that is dictated by the nucleus and nuclear components. Our studies illustrate that the force exerted by the optical tweezers at locations within the cell can be predicted theoretically; the data obtained in this way is consistent with the experimental observations
Expression profiles of SF-1, DAX1, and CYP17 in the human fetal adrenal gland: potential interactions in gene regulation
No full textCytochrome P450 17?-hydroxylase/17–20 lyase (P450C17) is a critical branchpoint enzyme for steroid hormone biosynthesis. During human gestation, P450C17 is required for the production of dehydroepiandrostenedione sulfate by the fetal adrenal cortex and for testicular production of androgens that mediate male sexual differentiation. In this study, we investigate the regulation of the human CYP17 gene by two orphan nuclear receptors, steroidogenic factor 1 (SF-1) and DAX1. In human embryos, SF-1 and DAX1 are expressed throughout the developing adrenal cortex from its inception at 33 days post conception (dpc). In contrast, P450C17 expression, which commences between 41 and 44 dpc, is limited to the fetal zone. The 5'-flanking region of the human CYP17 gene contains three functional SF-1 elements that collectively mediate a ?25-fold induction of promoter activity by SF-1. In constructs containing all three functional SF-1 elements, DAX1 inhibited this activation by ?55%. In the presence of only one or two SF-1 elements, DAX1 inhibition was lost even though SF-1 transactivation persisted. These data suggest that efficient repression of SF-1-mediated activation of the human CYP17 gene by DAX1 requires multiple SF-1 elements. Opposing effects of SF-1 and DAX1 may fine tune the differential responses of various SF-1 target genes in different endocrine tissues
Facing the Future: the Changing Shape of Academic Skills Support at Bournemouth University
No full textThis paper explores the potential impact of changes to higher education in England on student expectations, engagement, lifestyles and diversity, and outlines implications for the development of digital literacy within academic skills support at Bournemouth University (BU). We will investigate how tackling resource constraints with organisational change can also enable efficient, centralised provision of support materials that utilise networks to overcome the risk of fragmented support for digital literacy. We will also look at how changing delivery modes for support can accommodate changing student lifestyles whilst tackling a weakness of centralised support for digital literacy: that it can become detached from the student’s subject-focused academic practice. Finally we will explore how involving students in developing support can help us to face changes to student expectations and engagement whilst ensuring that materials are authentic and speak to learners in their own voice
Hearing Faces and Seeing Voices: The Integration and Interaction of Face and Voice Processing
Full text linkCognitive understanding of voice recognition has borrowed much from the area of face processing, both in terms of the theoretical framework within which results are interpreted, and the methodology used to assess performance. A considerable body of research now exists to suggest that voice recognition may proceed in parallel with face recognition, and that the two pathways may combine to inform person recognition. However, rather than being independent or equivalent, these parallel pathways appear to interact to reveal interesting interference effects. The present paper reviews a series of studies that focus on a considerable and growing literature. The vulnerability of voice processing will be explored relative to face processing, and the interaction of these two pathways will be examined with reference to broader theoretical frameworks for person recognition
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