Craniofacial malformations arise from developmental defects in the head, face, and neck and account for one third of congenital defects at birth. Clinical phenotypes such as DiGeorge Syndrome, the most common microdeletion condition, illustrate a developmental link between cardiovascular and craniofacial morphogenesis. Moreover, recent fate mapping studies in mice and zebrafish support this notion through identification of a multipotent progenitor in the cardiopharyngeal field that gives rise to the heart, branchiomeric muscles, and pharyngeal arch (PA) arteries. NKX2-5 is a key cardiac transcription factor associated with human congenital heart disease and mouse models of Nkx2-5 deficiency highlight critical roles in cardiac development. In zebrafish, nkx2.5 and nkx2.7 are paralogous genes in the NK4 family expressed in cardiomyocytes and PAs. Despite the shared cellular origins of cardiac and craniofacial tissues, the function of NK4 factors in head and neck patterning has not been elucidated. Here, we demonstrate that Nkx2.7 serves as a previously unappreciated, crucial regulator of craniofacial muscle and cartilage formation. Our studies reveal a unique requirement for nkx2.7 in PA1- and PA2-derived branchiomeric muscle and cartilage elements for which nkx2.5 cannot compensate. Moreover, molecular evolutionary analysis of NK4 genes reveals that nkx2.5 and nkx2.7 are ohnologs resulting from two rounds of vertebrate whole genome duplications with an early split between them, underscoring the concept that these genes play independent roles during development. The distinct mechanistic function of nkx2.7 is elucidated by cell counting experiments that uncover the requirement of nkx2.7 in specification of PA1 and PA2 branchiomeric muscle progenitors. Furthermore, single cell RNA-sequencing performed on microdissected PA tissues from wild-type and nkx2.7-/- embryos identifies decreased expression of the ventral neural crest gene signature essential for cartilage and jaw joint morphogenesis. Together, our studies shed light on an evolutionarily conserved, unique function of Nkx2.7 in vertebrate craniofacial development and have the potential to advance our understanding of the etiologies and therapeutic interventions for patients with congenital deformities of the head and neck.

The purpose of this study was to develop and describe a model for the enhancement of self-concept of people with oculocutaneous albinism based on the experience of the participants. The need to conduct the study was triggered by the researcher’s long-term interaction with people with oculocutaneous albinism, and observation that they are still stigmatised and marginalised by the community. A purposive sample of fifteen participants, consisting of twelve females and three males with oculocutaneous albinism, aged between 18 and 48, participated in the study. The study was conducted in urban and semi-urban areas around the Gauteng Province in South Africa. The study had two theory generative objectives, namely to identify the main concepts of the model from the findings, and to describe the model structure and process. A theory generative, qualitative, explorative, descriptive and contextual research design was used to achieve these objectives. Chinn and Kramer’s (1995:92) four steps of theory-generation were used, namely concept analysis, construction of theoretical relationships, description of the model, and development of guidelines to operationalise the model.Concept analysis involved identification, definition and classification of the concepts to develop the model. In-depth, phenomenological interviews were conducted to explore the participants’ experience. Data analysis and interpretation revealed three main themes from the findings: the participants’ perception of the self; experience with the external environment, and expression of need for development and growth. The main concepts deducted from the findings were “self-concept” and “enhancement” hence “A model for enhancement of self-concept of people with albinism”. Construction of theoretical relationships entailed using deductive reasoning to describe the interaction between the concepts of the model. Description of the model entailed visually portraying and describing the structure and process of the model, as well as evaluating it. Developing guidelines to operationalise the model entailed describing practical strategies to assist health professionals to enhance the self-concept of people with oculocutaneous albinism. / Health Studies / D. Litt. et Phil. (Health Studies)

Orientador: Renato Passini Junior / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-11-09T15:30:07Z (GMT). No. of bitstreams: 1 Jannini_AlexandreWolf_M.pdf: 3134011 bytes, checksum: 9cae7dc9e2202285b4be1b0a5ae92bb0 (MD5) Previous issue date: 2008 / Resumo: Introdução: A legislação não permite a interrupção da gestação em casos de malformações fetais incompatíveis com a vida extra-uterina, cabendo ao Poder Judiciário decidir quando há uma solicitação deste tipo. Objetivos: Investigar a opinião de Magistrados e membros do Ministério Público sobre o abortamento nos casos de malformações fetais incompatíveis com a vida extra-uterina, especialmente em relação à anencefalia. Método: Análise parcial de dados obtidos em duas pesquisas realizadas pelo Centro de Pesquisas em Saúde Reprodutiva de Campinas (CEMICAMP), que objetivaram estudar a opinião destes profissionais acerca do aborto induzido. Foram obtidos dados de 1493 Magistrados e 2614 Promotores de Justiça. Foi constituído um banco de dados com as informações de interesse das pesquisas originais, analisado com auxílio do programa estatístico SAS versão 9.02, envolvendo análise bivariada e múltipla, por regressão logística. Resultados: Para 78,5% dos Magistrados e 82,6% dos membros do Ministério Público, a interrupção da gestação deveria ser permitida nos casos de qualquer malformação fetal incompatível com a vida extra-uterina. Em casos de diagnóstico de anencefalia, estes valores foram de 79,2% e 84,1%, respectivamente. Na análise multivariada, as variáveis associadas à opinião dos pesquisados foram a religiosidade, importância da religião e das concepções religiosas pessoais sobre as respostas dadas, experiência de gravidez indesejada que resultou em aborto, sexo, estado marital e o fato de possuir filhos. Conclusões: A grande maioria dos Magistrados e membros do Ministério Público foi favorável ao abortamento nas hipóteses estudadas, sendo as variáveis ligadas à religião as que mais influenciaram seu posicionamento / Abstract: Introduction: In Brazil abortion in cases of fetal malformation or anencephaly is prohibited by law. Pregnant women who want to perform an abortion in such cases must seek for a judicial order. Objectives: Evaluate the opinion of brazilian magistrates and Prosecutors about abortion in cases of fetal malformation incompatible with life and anencephaly. Methodology: It was a partial data analysis from data obtained in two researchs carried out by Centro de Pesquisas em Saúde Reprodutiva de Campinas (CEMICAMP ), to evaluate the opinion and conduct of these professionals about induced abortion. There were data from 1453 Magistrates and 2614 Prosecutors. It was made a data bank with data from the original studies, that was processed and analyzed using the statistical package SAS version 9.02. Results: For 78.5% of the Magistrates and 82.6% of the Prosecutors abortion should be permitted in cases of severe fetal malformation incompatible with life. In cases of anencephaly abortion should be permitted for 79.2% of the Magistrates and for 84.1% of the Prosecutors. Religiosity, influence of religion and personal religious convictions among responses, experience with unwanted pregnancy that ended in abortion, gender, marital status and the fact of having children had shown, in multivariable analysis, association with the opinion about abortion in the hypothesis studied. Conclusion: The great majority of Magistrates and Prosecutors had a favorable opinion about abortion in both hypothesis evaluated. Variables associated with religion had the strongest association with the opinion about abortion in cases of fetal malformation and anencephaly.Abstract: Introduction: In Brazil abortion in cases of fetal malformation or anencephaly is prohibited by law. Pregnant women who want to perform an abortion in such cases must seek for a judicial order. Objectives: Evaluate the opinion of brazilian magistrates and Prosecutors about abortion in cases of fetal malformation incompatible with life and anencephaly. Methodology: It was a partial data analysis from data obtained in two researchs carried out by Centro de Pesquisas em Saúde Reprodutiva de Campinas (CEMICAMP ), to evaluate the opinion and conduct of these professionals about induced abortion. There were data from 1453 Magistrates and 2614 Prosecutors. It was made a data bank with data from the original studies, that was processed and analyzed using the statistical package SAS version 9.02. Results: For 78.5% of the Magistrates and 82.6% of the Prosecutors abortion should be permitted in cases of severe fetal malformation incompatible with life. In cases of anencephaly abortion should be permitted for 79.2% of the Magistrates and for 84.1% of the Prosecutors. Religiosity, influence of religion and personal religious convictions among responses, experience with unwanted pregnancy that ended in abortion, gender, marital status and the fact of having children had shown, in multivariable analysis, association with the opinion about abortion in the hypothesis studied. Conclusion: The great majority of Magistrates and Prosecutors had a favorable opinion about abortion in both hypothesis evaluated. Variables associated with religion had the strongest association with the opinion about abortion in cases of fetal malformation and anencephaly / Mestrado / Ciencias Biomedicas / Mestre em Tocoginecologia

Source: Dissertation Abstracts International, Volume: 69-10, Section: B, page: 6009. Adviser: Dorothy K. Waller. Includes bibliographical references.

Thesis (Ph.D.) -- McMaster University, 2001. / Includes bibliographical references (leaves 197-209). Also available via World Wide Web.

The purpose of this study was to develop and describe a model for the enhancement of self-concept of people with oculocutaneous albinism based on the experience of the participants. The need to conduct the study was triggered by the researcher’s long-term interaction with people with oculocutaneous albinism, and observation that they are still stigmatised and marginalised by the community. A purposive sample of fifteen participants, consisting of twelve females and three males with oculocutaneous albinism, aged between 18 and 48, participated in the study. The study was conducted in urban and semi-urban areas around the Gauteng Province in South Africa. The study had two theory generative objectives, namely to identify the main concepts of the model from the findings, and to describe the model structure and process. A theory generative, qualitative, explorative, descriptive and contextual research design was used to achieve these objectives. Chinn and Kramer’s (1995:92) four steps of theory-generation were used, namely concept analysis, construction of theoretical relationships, description of the model, and development of guidelines to operationalise the model.Concept analysis involved identification, definition and classification of the concepts to develop the model. In-depth, phenomenological interviews were conducted to explore the participants’ experience. Data analysis and interpretation revealed three main themes from the findings: the participants’ perception of the self; experience with the external environment, and expression of need for development and growth. The main concepts deducted from the findings were “self-concept” and “enhancement” hence “A model for enhancement of self-concept of people with albinism”. Construction of theoretical relationships entailed using deductive reasoning to describe the interaction between the concepts of the model. Description of the model entailed visually portraying and describing the structure and process of the model, as well as evaluating it. Developing guidelines to operationalise the model entailed describing practical strategies to assist health professionals to enhance the self-concept of people with oculocutaneous albinism. / Health Studies / D. Litt. et Phil. (Health Studies)

Morphogenesis is the fundamental and remarkable biological process that produces elaborate and diverse tissues and organs from simple groups of cells, which can happen on timescales as short as minutes or as long as days. One of the biggest challenges in understanding morphogenesis is the gap between our knowledge of the molecular-scale activities of genes and proteins, and the large-scale behaviors of cells and tissues. To fill this gap, a complete understanding of both biochemical and mechanical factors involved in morphogenesis is needed. Morphogenesis is naturally a mechanical process in which tissues are physically sculpted by mechanical stress, strain, and movements of cells that are induced by these genetic and molecular programs. However, many of the mechanical factors involved in morphogenesis remain poorly understood partially due to the strong coupling of mechanical factors and biological factors, the active responses of living tissues to the environment, and the lack of experimental methods to study the mechanics of tissues in vivo. Epithelial tissues play crucial roles in shaping early embryos and are widely spread in mature animals to serve as boundaries and barriers. They are robust tissues that not only support the structure of embryos and organs, but also actively change shape and structure, displaying a fluid behavior during morphogenesis. Contractile tension and cell-cell adhesion are thought to be the main mechanical factors involved in epithelial tissue morphogenesis, but how the balance between these two determines epithelial tissue mechanics remains unclear. To build a fundamental understanding of the mechanical mechanisms underlying epithelial tissue morphogenesis, this dissertation studies the germband epithelial tissue in the early Drosophila melanogaster embryo and addresses two important open questions in the field of mechanics in morphogenesis: (1) what mechanical factors are involved in the morphogenesis of epithelial tissues; (2) how does a cell control these factors to tune tissue mechanical behaviors. In this dissertation, we developed a systematic, quantitative, in vivo experimental approach to explore mechanics of epithelial tissue morphogenesis in the Drosophila embryo by integrating molecular genetics approaches, live confocal fluorescence imaging, and quantitative image analysis. Combining our experimental studies in the Drosophila embryo with our collaborators’ theoretical modeling approaches, we showed that the shapes and alignment of cells within tissues can help us understand and predict epithelial tissue mechanical behaviors, such as tissue fluidity, during morphogenesis and how defects in these processes can result in abnormalities in embryo shape. We also observed that the Drosophila germband tissue transitions from more solid-like to more fluid-like behavior to help accommodate dramatic tissue flows during convergent extension, which indicates that the mechanical properties of developing tissues might be tuned during morphogenetic events. To elucidate molecular mechanisms underlying how tissue mechanical properties may be regulated during morphogenesis, this dissertation explores the role of cell-cell adhesion in controlling epithelial tissue mechanics. By systematically modulating cell-cell adhesion levels in the Drosophila germband tissue and combining live imaging and quantitative image analysis, we studied the effects of cell-cell adhesion levels on cellular and tissue behaviors. We found biphasic dependencies of cell rearrangements, cell shape, and tissue fluidity on cell-cell adhesion levels, which are surprisingly linked to each other by cell patterns in the tissue. In particular, tissues comprising cells with either lower or higher cell-cell adhesion levels tend to rearrange faster and show cell patterns indicating more fluid-like tissue behaviors. Further studies suggested that cell-cell adhesion works with cytoskeletal molecules to achieve these effects. The experimental approaches developed for exploring mechanics in 2-D in the Drosophila germband epithelial tissue are expanded upon in order to investigate germband tissue mechanics in 3-D. These approaches are also used to study mechanics in the inner ear round window membrane of the guinea pig for clinical application. This dissertation advances our understanding of mechanics of epithelial tissue morphogenesis in vivo and provides a practical, quantitative, and appealing platform for exploring mechanics in living tissues during morphogenesis. This helps fill the gap in our knowledge of molecular-scale activities and tissue-level behaviors, provides insight into building tissues with precise shapes and structures in the lab, and sheds light on human diseases associated with improper regulation of tissue mechanics such as birth defects, aberrant wound healing, and cancer metastasis.

Thesis (M.Phil. (Social Work))--University of Stellenbosch, 1984. / 367 leaves printed on single pages,preliminary pages i - xiv and numberd pages 1-351. Includes bibliography and 3 figures. Digitized at 600 dpi grayscale to pdf format (OCR), using a Bizhub 250 Konica Minolta Scanner. / Please refer to full text.

Human response to ionising radiation (IR) shows a wide variation. This is most clearly seen in the radiation-response of cells as measured by frequencies of chromosomal aberrations. Different frequencies of IR-induced aberrations can be conveniently observed in phytohaemagglutin-stimulated peripheral blood T-lymphocytes from both normal individuals and sporadic cancer cases, in either metaphase chromosomes or as micronuclei in the following cell cycle. Metaphase cells show frequent chromatid breaks, defined as chromatid discontinuities or terminal deletions, if irradiated in the G 2 -phase of the cell cycle. It has been shown that the frequency of chromatid breaks in cells from approximately 40% of sporadic breast cancer patients, are significantly higher than in groups of normal individuals. This suggests that elevated radiation-induced chromatid break frequency may be linked with susceptibility to breast cancer. It is known that chromatid breaks are initiated by a double strand break (DSB), but it appears that the two are linked only indirectly as repair kinetics for DSBs and chromatid breaks do not match. Therefore, the underlying causes of the wide variation in frequencies of chromatid breaks in irradiated T-lymphocytes from different normal individuals and from sporadic breast cancer cases are still unclear but it is unlikely to be linked directly to DSB rejoining. My research has focused on the mechanism through which chromatid breaks are formed from initial DSBs. The lack of a direct association suggested that a signalling process might be involved, connecting the initial DSB and resulting chromatid break. The signal model, suggested that the initial DSB is located within a chromatin loop that leads to an intra- or interchromatid rearrangement resulting in incomplete mis-joining of chromatin ends during the decatenation of chromatids during G 2 . It was therefore proposed that topoisomerase II alpha (topo IIα) might be involved, mainly because of its ability to incise DNA and its role in sister chromatid decatenation. During my PhD research I have used a strategy of altering topo II activity or expression and studying whether this alters IR-induced chromatid break frequency. The first approach involved cell lines that varied in topo IIα expression. The frequency of IR-induced chromatid breaks was found to correlate positively with topo IIα expression level, as measured in three different cell lines by immunoblotting, i.e. two cell lines with lower topo IIα expression exhibited lower chromatid break frequency. Topo II activity in these three cell lines was also estimated indirectly by the ability of a topo IIα poison to activate the G 2 /M checkpoint, and this related well with topo IIα expression. A second approach involved ‘knocking down’ topo IIα protein expression by silencing RNA (siRNA). Lowered topo IIα expression was confirmed by immunoblotting and polymerase chain reaction. SiRNA-lowered topo IIα expression correlated with a decreased IR-induced chromatid break frequency. In a third series of experiments cells were treated with ICRF-193, a topo IIα catalytic inhibitor. It was shown that inhibition of topo IIα also significantly reduced IR-induced chromatid breaks. I also showed that lowered chromatid break frequency was not due to cells with high chromatid break frequencies being blocked in G 2 as the mitotic index was not altered significantly in cells with lowered topo IIα expression or activity. These experiments show that topo IIα is involved in IR-induced chromatid break formation. The final experiments reported here attempted to show how topo II might be recruited in the process of forming IR-induced chromatid breaks. Hydrogen peroxide was used as a source of reactive oxygen species (reported to poison topo IIα) and it was shown that topo IIα under these conditions is involved in the entanglement of metaphase chromosomes and formation of chromatin ‘dots’ as well as chromatid breaks. Experiments using atomic force microscopy attempted to confirm these dots as excised chromatin loops. The possible role of topo IIα in both radiation- and hydrogen peroxide-induced primary DNA damage was also tested. It was shown that topo IIα does not affect radiation-induced DSBs, even though it does affect chromatid break frequency. Also, topo IIα does not affect hydrogen peroxide-induced DNA damage at low doses. The results support the idea that topo IIα is involved in the conversion of DSBs to chromatid breaks after both irradiation and treatment with hydrogen peroxide at a low concentrations. I have demonstrated that topo IIα is involved in forming IR-induced chromatid breaks, most likely by converting the initial DSBs into chromosomal aberrations as suggested by the signal model.

In The Deptford Trilogy, Robertson Davies uses the circus freaks and the Roman Catholic Saints who influence the main characters to illustrate the duality inherent in all human beings.