Liu Lin. / "January 2006." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2006. / Includes bibliographical references (p. 117-135). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese.

Submitted by Lucas Benites Doretto (lucasbdoretto@gmail.com) on 2019-02-01T13:11:58Z No. of bitstreams: 1 Doretto_2018.pdf: 4650233 bytes, checksum: 9bea19edf8684552c0f36f3b98fe9df8 (MD5) / Approved for entry into archive by ROSANGELA APARECIDA LOBO null (rosangelalobo@btu.unesp.br) on 2019-02-01T18:19:44Z (GMT) No. of bitstreams: 1 doretto_lb_me_bot.pdf: 4650233 bytes, checksum: 9bea19edf8684552c0f36f3b98fe9df8 (MD5) / Made available in DSpace on 2019-02-01T18:19:44Z (GMT). No. of bitstreams: 1 doretto_lb_me_bot.pdf: 4650233 bytes, checksum: 9bea19edf8684552c0f36f3b98fe9df8 (MD5) Previous issue date: 2018-12-20 / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / As células tronco são classificadas em dois grandes grupos de acordo com sua origem e capacidade de diferenciação. Células tronco embrionárias (CTE) são originadas do zigoto, e podem ser classificadas como totipotentes, isto é, capazes de originar um indivíduo inteiro, ou pluripotentes, quando originam os três folhetos embrionários (ecto, meso e endoderme). As células tronco adultas (CTA) são as células tronco encontradas nos tecidos fetais e adultos; classificadas como uni, oligo ou multipotentes dependendo da variedade de tecidos originados a partir delas. Marcadores de células tronco, como antígenos de superfície específicos, fatores de trancrição como OCT4 e NANOG são expressos em CTE e algumas CTA, mas são rapidamente reprimidos à medida que as células se diferenciam. O presente trabalho tem como objetivo identificar marcadores de células tronco e com isso, os efeitos do hormônio endócrino Fsh e do fator parácrino GDNF na atividade proliferativa e gênica dessas populações de células e também de células de Sertoli. Foi observado que os marcadores Pou5f3 e Gfra1a são principalmente expressos em espermatogônias tronco indiferenciadas e que sua expressão reduz significativamente sob efeito do recombinante zebrafish Fsh. Por outro lado, genes como o igf3, nanos3 e nanog tiveram sua expressão aumentada significativamente. O recombinante humano GDNF não altera significativamente a expressão desses genes, porém estimula a proliferação de espermatogônias tipo Aund e Adiff e células de Sertoli associadas. Logo, conclui-se que o rzfFsh atua de maneira endócrina na diferenciação de espermatogônias tronco Pou5f3+ e Gfra1a+ via células de Sertoli, visto que seu receptor é principalmente expresso em cistos indiferenciados. O rhGDNF, que por sua vez é expresso em células germinativas, estimula a proliferação de Aund e Adiff e células de Sertoli associadas através de seu receptor Gfra1a, expresso em ambas populações. / 2016/12101-4

No two individuals are identical. This is true at the genetic level and at the phenotypic level. One of the traits that varies between populations is toxicant susceptibility: some individuals are sensitive to the effects of environmental chemical exposure, and others are resistant. This body of work aims to address the impact of genomic copy number variants (CNV)--large (>1 Kb) duplications or deletions across the genome--on the toxicant-susceptibility phenotype. Herein copy number variants were characterized across three commonly used laboratory strains of zebrafish (Danio rerio) and mRNA expression phenotypes were identified in the same strains. It was found that males and females have only a 14% overlap in differentially expressed mRNA transcripts across three common laboratory strains, congruent with the growing body of work identifying sex- and strain-specific phenotypes in zebrafish. Furthermore, identified were two strain-specific response quantitative trait loci (QTL) that explain about a third of the variation in susceptibility to PCB and tested the response QTL using targeted CRISPR-Cas9 editing of the CNV involved. Overall, this body of work defines CNV and mRNA expression variation across zebrafish strains, identifies CNV causal in the PCB-susceptibility phenotype, and confirms the PCB-susceptibility QTL using targeted genomic editing.

The zebrafish is rapidly becoming a vital tool in studies of genetic disease. Use of the zebrafish embryo as an experimental model combines the efficiency of techniques specific to invertebrates with the human applicability of vertebrate studies, along with a number of other advantages such as optical transparency and high spawn number. Sequencing maps and mutant screen data are available, and gene ontology annotation is progressing. Furthermore, a number of highly important projects are underway to expand the utility of the zebrafish still further (eg. Mutant screens and TILLING projects; see (Lieschke and Currie, 2007) for review). As such the zebrafish has become a vital model organism for study of a variety of genetic defects, toxicology and pharmacological screens etc. These papers trace the development of zebrafish embryos as a model organism for both genetic disease and, as part of this, the development of a relatively high throughput approach to analysing relative levels of apoptosis. The first paper describes the fmr1 gene family in zebrafish (fmr1, and its orthologs fxr1 and fxr2). This paper includes a phylogenetic analysis of the gene family that demonstrates the high conservation between human and zebrafish, in the context of Drosophila. We then describe expression of the genes in the embryo (using in situ hybridisation) and adult (using real time pcr). The conclusions are that the zebrafish is an appropriate model in which to study Fragile X Mental Retardation genetic disease. The second paper builds upon this conclusion and further establishes the appropriateness of the model by recapitulating elements of the disease that had already been modelled in other model organisms. The research is validated using a number of controls. We describe a number of original findings that extended the body of knowledge regarding pharmacological rescue of the FMRP loss phenotypes. A craniofacial phenotype is identified, the first such discovery in a model of Fragile X syndrome. These findings are a vital step toward understanding the pathway from gene, to molecular phenotype, to cellular morphology, to gross morphology. As part of these studies, we found it necessary to analyse apoptosis. The technique developed to facilitate this analysis is described in our third paper. Given the highly stochastic nature of the apoptotic patterns we developed a method to take full advantage of the characteristics of zebrafish embryos, primarily their transparency and availability in large numbers. As the zebrafish becomes more widely accepted as a model for a diverse range of scientific questions, the development of such a technique is doubly important given the necessity of a cheap, reliable and simple generalizable method of analysing processes affecting cell viability in fish. This has clear importance for pharmacological studies, but is also a long overdue addition to the battery of controls available for highly invasive techniques such as microinjection, in which apoptosis is regularly found among its non specific effects. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1311173 / Thesis (Ph.D.) -- University of Adelaide, School of Molecular and Biomedical Science, 2008

No description available.

Thesis (Ph.D.)--Hong Kong University of Science and Technology, 2007. / Includes bibliographical references (leaves 213-239). Also available in electronic version.

Thèse de doctorat : Sciences de la vie et de la santé : Tours : 2008. / Titre provenant de l'écran-titre.

Thèse de doctorat : Sciences du vivant. Biologie du développement : Strasbourg 1 : 2007. / Thèse soutenue sur un ensemble de travaux. Titre provenant de l'écran-titre. Bibliogr. 20 p.

The entire thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file; a non-technical public abstract appears in the public.pdf file. Title from PDF of title page (University of Missouri--Columbia, viewed on January 20, 2010). Thesis advisor: Dr. Anand Chandrasekhar. Includes bibliographical references.

Thesis (Ph. D., Neuroscience)--University of Idaho, October 2009. / Major professor: Deborah L. Stenkamp. Includes bibliographical references. Also available online (PDF file) by subscription or by purchasing the individual file.