[Truncated abstract] The placenta forms a barrier regulating the transfer of gases, nutrients and wastes between the mother and the developing conceptus, and also produces hormones affecting both the fetus and the mother. This barrier is formed by the differentiation of the outer layer of the blastocyst- the trophoblast- to facilitate implantation and subsequent invasion of the uterus. The trophoblast consists of an underlying proliferative pool of cytotrophoblasts, which differentiate to replenish the overlying continuous, multi-nucleated syncytiotrophoblast that forms the barrier between the mother and fetus. Moreover, the location of the syncytiotrophoblast directly in contact with the maternal circulation suggests an endothelial role for the trophoblast regulating blood flow, thrombosis and immune cell adhesion. Disruption to the function of the human trophoblast may result in preeclampsia, a maternally manifested disorder of pregnancy characterised by hypertension and proteinurea. Blood flow to preeclamptic placentae is reduced and the cytotrophoblast pool is diminished; however the exact cause (or causes) remains elusive. Many potential causes are hypothesised, including endothelial damage, premature remodelling of maternal spiral arteries, increased oxidative stress and impaired trophoblast differentiation and apoptosis. Caspase-14 is an unusual caspase in that it is not involved in apoptosis. Furthermore, it possesses a limited, predominantly epithelial, tissue distribution. In the epidermis, caspase-14 is expressed in the apical differentiating layers. Here it cleaves profilaggrin to stabilise intracellular keratin intermediate filaments, and indirectly provides natural hydration and UV protection to the corneocytes. Thus, caspase-14 is vital to the maintenance of the barrier function of the skin. ... As differentiation-associated genes were elevated in the absence of caspase-14, this implies that caspase-14 suppresses biochemical trophoblast differentiation. The cytoskeletal keratin network was also examined following RNA Interference. The synthesis of cytokeratin 18 was significantly enhanced after caspase-14 suppression during BeWo differentiation, linking caspase-14 with keratin homeostasis. Therefore caspase-14 suppresses trophoblast differentiation, potentially through modulation of the cytoskeletal keratin filament network. The precise mechanism remains to be elucidated, however the identification of pathways regulated by caspase-14 advances our knowledge of trophoblast differentiation and potential causes of disorders of pregnancy. In summary, caspase-14 appears to be involved in the suppression of differentiation in the human trophoblast. As disorders of pregnancy such as preeclampsia often feature disturbed differentiation and a diminished cytotrophoblast pool, a greater understanding of caspase-14 biology in the human placenta could lead potential therapies for various disorders of pregnancy.

Thesis (Ph. D.)--University of Virginia, 2007. / Includes bibliographical references. Also available online through Digital Dissertations.

Diss. (sammanfattning) Stockholm : Karol. inst., 2002. / Härtill 5 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2004. / Härtill 4 uppsatser.

Diss. (sammanfattning) Uppsala : Sveriges lantbruksuniv. / Härtill 4 uppsatser.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 4 uppsatser.

Thesis (Ph.D.) -- Mississippi State University. Department of Biochemistry and Molecular Biology. / Title from title screen. Includes bibliographical references.

Thesis (Ph.D.)--University of Alabama at Birmingham, 2007. / Title from first page of PDF file (viewed on June 25, 2009). Includes bibliographical references.

Thesis (Ph.D.) -- University of Texas Southwestern Medical Center at Dallas, 2006. / Partial embargo. Vita. Bibliography: 128-131.

Thesis (MSc (Plant Biotechnology))--University of Stellenbosch, 2010. / ABSTRACT: Nitric Oxide (NO) is an essential bioregulatory molecule in plant growth, development, and tolerance against biotic and abiotic stresses. In legume root nodules, abiotic stresses impose restraint on metabolic capacity of bacteria and cause oxidative damage to cellular macromolecules, leading to inhibition of nitrogenase activity. In this study, the primary aim was to determine the influence of NO signaling on cysteine protease activity in soybean (Glycine. max [L] Merr) root nodules. Intact plants were treated with a NO donor, diethylenetriamine/nitric oxide adjunct (DETA/NO), 8-(4-chlorophenylthio)-[CPT]- cGMP, sorbitol and sodium chloride (NaCl). The root nodule cysteine protease activity was measured using the chromogenic substrate N-benzoil-L-p-nitroanilide (L-BAPNA). The results demonstrated NO as acting both as a protection against programmed cell death (PCD) at low exogenously applied NO concentrations, or as inducing PCD through regulating the cysteine proteases activity in root nodules when NO is applied at elevated concentrations. In the root nodules, the activity of cysteine protease is regulated either through cyclic guanosine monophosphate (cGMP)-dependent during abiotic stress or cGMP-independent pathways during normal root nodule development. The purpose of this research was to highlight the importance of NO in cell signaling and cysteine protease activity in legume root nodules. We also focused on the effect of abiotic stress on two maize genotypes as well as the influence of abiotic stress on cysteine protease activity in the abiotic stress-sensitive maize genotype than the tolerant genotype. The study suggests that cysteine protease activity can be used as early screen to identify abiotic stress-sensitive/tolerant maize genotype upon exposure to abiotic stress. / AFRIKAANSE OPSOMMING: Geen Afrikaanse opsomming beskikbaar. / National Research Foundation