Pelo ist ein evolutionär konserviertes Gen, das in diversen Spezies charakterisiert wurde. In der Maus führt der Verlust von Pelo zu embryonaler Letalität in frühen Postimplantationsstadien. In vitro Studien mit Pelo-null Blastocysten haben gezeigt, dass PELO möglicherweise eine Rolle bei der Regulation des Zellzyklus oder der Selbsterneuerung der pluripotenten Embryonaler Stammzellen (Embryonic Stem Cells, ESCs) spielt. In der vorliegenden Arbeit sollte die molekulare Rolle von PELO bei der Selbsterneuerung und bei der Differenzierung von ESCs und Keimbahnstammzellen mit Hilfe eines konditionalen Pelo Knockout-Mausmodels in Kombination mit in vitro sowie in vivo Experimenten untersucht werden. Im ersten Teil der Arbeit konnten wir zeigen, dass PELO für die Selbsterneuerung von ESCs oder deren Differenzierung in die drei Keimblätter nicht notwendig ist, jedoch unabdingbar ist für die Differenzierung des extraembryonalen Endoderms (ExEn). Im Umkehrschluss wird durch die Überexpression von Pelo in ESCs das Programm zur Differenzierung des ExEn`s aktiviert. Auf molekularer Ebene konnten wir zeigen, dass die beeinträchtigte Differenzierung des ExEn`s in Pelo-defizienten Embryoidkörpern (Embryonic Bodies, EBs) aus einer reduzierten Aktivität des Bone Morphogenetic Proteins (BMP) resultiert. Dieses Ergebnis wurde durch weitere Experimente bestätigt, die gezeigt haben, dass Pelo-defiziente Zellen durch Behandlung mit BMP4 in das ExEn differenzieren können. In vivo Studien haben gezeigt, dass Pelo-null Embryonen am Tag 6.5 (E6.5) das ExEn besitzen, jedoch an E7.5 versterben. Dies lässt vermuten, dass PELO nicht für die Induktion der Entwicklung des ExEn`s notwendig ist, sondern vielmehr für dessen Erhaltung oder abschließende Differenzierung in das funktionelle viszerale Endoderm, das den Embryo mit Wachstumsfaktoren für die weitere Entwicklung versorgt. Zudem ist PELO notwendig für die BMP-Aktivierung zu Beginn der somatischen Zellreprogrammierung. Der Verlust von PELO beeinträchtigt die Reprogrammierung zur induzierten Pluripotenz. Außerdem konnten wir die konservierte Funktion von PELO im Qualitätskontrollmechanismus der RNA in murinen ESCs feststellen. Im zweiten Teil der Arbeit haben wir demonstriert, dass die Pelo-Expression essentiell für die Erhaltung der männlichen Fertilität und Spermatogenese ist. Der Verlust von Pelo während der Entwicklung von männlichen Keimzellen in Mäusen hat gezeigt, dass PELO für die Selbsterneuerung und Erhaltung der Spermatogonialen Stammzellen (Spermatogonial Stem Cells, SSCs) notwendig ist, jedoch für die Entwicklung der späteren Spermatogenesestadien sowie die Spermienfunktion erlässlich ist. Insgesamt zeigen unsere Studien die molekulare Rolle(n) von PELO in der frühen Embryonalentwicklung der Maus und bei der männlichen Fertilität auf. Unsere Ergebnisse geben Hinweise auf Ursachen von Defekten, die mit dem PELO Verlust zusammenhängen.

Attempts for the in vitro differentiation of reconstituting human HSCs from ESCs have been unsuccessful as key factors of HSC specification remain unclear. Enforced HOXB4 expression can enhance haemopoietic differentiation of mouse and human ESCs and generate reconstituting HSCs from mouse ESCs. We have previously shown that HOXB4 can enhance haemopoietic differentiation of mouse ESCs in a paracrine manner. Microarray analysis identified a number of secreted factors upregulated by HOXB4 potentially mediating this paracrine effect. The aim of this study was to assess whether these factors alone and/or in combination can enhance the in vitro haemopoietic differentiation of mouse and human ESCs. We first developed a defined, serum and feeder-free protocol to test the effects of these secreted factors on haemopoietic differentiation. This defined protocol allowed us to compare the haemopoietic potential of mouse ESCs with the recently derived epiblast stem cells (EpiSCs), thought to be comparable to hESCs. Haemopoietic colony forming assay and flow cytometry analysis showed that serum-free conditions generated 8- 10 fold more CD144+CD41+ and c-Kit+CD41+ haemopoietic progenitor cells (HPCs) compared to serum conditions from both ESCs and EpiSCs, with ESCs giving the most significant increase. We then validated the panel of HOXB4 target genes by QRT-PCR and selected those increased in expression by at least 2.5-fold when HOXB4 was activated. We used this defined, serum-free protocol to assess the effects of our panel of secreted factors, FGF17, RSPO3 and APLN, on the haemopoietic differentiation of mouse ESCs. We demonstrated that FGF17 can mediate HOXB4 haemopoietic activity by enhancing the generation of c-Kit+ HPCs. On the other hand increasing concentrations of RSPO3 inhibited haemopoietic development by reducing the numbers of CD41+ and CD41+CD45+ HPCs, while, APLN did not have any effects on the haemopoietic activity of the cells. We finally used the secreted factors in human ESC and iPSC differentiation cultures. We observed differences in the activity of the tested factors not only between species but also between human cell lines. These results suggest that HOXB4 haemopoietic activity is partly mediated by paracrine signalling but more complex cell interactions are probably required for it to fully exert its effects. More importantly, HOXB4 regulatory pathways differ between mouse and human cells stressing the need for careful translation of data between the two species and more detailed analysis of key human haemopoietic factors for the successful generation of reconstituting HSCs.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第20609号 / 医博第4258号 / 新制||医||1023(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 高橋 淳, 教授 伊佐 正, 教授 影山 龍一郎 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

This descriptive study of the twenty regional Education Service Centers in Texas is an exploratory analysis of programs and services that promote school improvement. Data collected from each service center website enabled the researcher to determine which programs and services are available to school districts and also allowed the researcher to analyze the similarities and differences of the programs and services among the twenty ESCs. The study also compared the numbers of programs provided by each service center along with the number of school districts, schools, and students served by Education Service Centers. The data revealed that Education Service Centers serve different numbers of students and districts and they assist schools through a variety of special program support, state and federal funding issues, educator certification programs, and professional development training that are designed to support the teaching and learning process in school districts. Although the number of programs and services vary among the twenty Education Service Centers, they do provide similar programs and services that are effective and provide sustainable systemic support for school improvement throughout their region particularly when it comes to statewide initiatives and areas of federal and state compliance issues and the improvement of student achievement. Throughout the state, Education Service Centers prove to be a valuable resource to school districts seeking solutions from knowledgeable and experienced educational professionals. In conclusion, Education Service centers provide a variety of professional services that can assist superintendents, principals, teachers, paraprofessionals, and other district staff in assisting students throughout their district in achieving the highest possible levels of success in every aspect of the school day. However, it is highly critical that both school leaders and Education Service Centers communicate effectively with each other about the needs of the districts and the services that are available to promote school improvement.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第18850号 / 医博第3961号 / 新制||医||1007(附属図書館) / 31801 / 京都大学大学院医学研究科医学専攻 / (主査)教授 山下 潤, 教授 吉村 長久, 教授 中畑 龍俊 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Dissertação (mestrado)—Universidade de Brasília, Instituto de Ciências Sociais, Departamento de Antropologia, Programa de Pós-Graduação em Antropologia Social, 2014. / Submitted by Ana Cristina Barbosa da Silva (annabds@hotmail.com) on 2015-02-05T17:17:22Z No. of bitstreams: 1 2014_IgorD’AvilaBaseggio.pdf: 2673609 bytes, checksum: 766d304035cede7ee90e93638853ca51 (MD5) / Approved for entry into archive by Ruthléa Nascimento(ruthleanascimento@bce.unb.br) on 2015-02-13T14:14:49Z (GMT) No. of bitstreams: 1 2014_IgorD’AvilaBaseggio.pdf: 2673609 bytes, checksum: 766d304035cede7ee90e93638853ca51 (MD5) / Made available in DSpace on 2015-02-13T14:14:49Z (GMT). No. of bitstreams: 1 2014_IgorD’AvilaBaseggio.pdf: 2673609 bytes, checksum: 766d304035cede7ee90e93638853ca51 (MD5) / Esta dissertação é resultado de trabalho etnográfico realizado em torno de um processo de transformação institucional na Escola Superior de Ciências da Saúde, ESCS, que seria transformada na chamada Universidade de Ciências da Saúde do Distrito Federal, UNISUS, a primeira universidade distrital especializada em ciências da saúde em Brasília. Com metodologia pedagógica diferente dos modelos disciplinares de ensino em medicina e com a realização de atividades pedagógicas nas unidades assistenciais do próprio sistema público de saúde local, a instituição parecia desafiar os modelos de gestão dos processos pedagógicos e de gestão política do ensino em saúde no contexto do Estado. Mapeou-se a arena política local na qual interagiram os atores institucionais envolvidos com o processo abordado e destacou-se conflitos e controvérsias em torno do Projeto UNISUS no contexto da participação social e no controle social da saúde pública no Distrito Federal. Ao longo da dissertação, explora-se as profundidades históricas, institucionais, pedagógicas e políticas atuantes no processo abordado, refletindo-se analiticamente sobre os mecanismos da democracia participativa na gestão da saúde pública, sobre a implementação de modelos diferentes de gestão pedagógica e administrativa e sobre a gestão ideológica dos processos institucionais, e atreladas à um processo institucional que se mostrou como expressão da transformação do ensino em medicina em um contexto mais amplo. ___________________________________________________________________________________ ABSTRACT / This dissertation results from an ethnographic fieldwork made around a process of institutional transformation at the Superior Health Sciences School, ESCS, which would be transformed in the University of Health Sciences of Distrito Federal, UNISUS, the first district university specialized in health sciences in Brasilia. Having a pedagogical approach different from the usual disciplinary models of medical training, and holding educational activities in the facilities of the local public health system, this institution seemed to challenge the pedagogical models and the political management of medical training in the context of the State. The local political arena was mapped. Therein, the institutional actors involved with the analyzed process interact, arousing controversies around UNISUS Project in the context of democratic representativeness and social control of public health in Distrito Federal. Throughout the study, historical, institutional, pedagogical and political depths are explored while it encourages a reflection on the mechanisms of democratic participation in public health management; on the ideological management; and on the implementation of different models of pedagogical management process, related to an institutional process which was an expression of the transformation of medical teaching in a broader context.

Sponsorship is an essential part of marketing communications within sports (Biscaia et al., 2014). Congruence, or the degree to which a sponsor and an event mesh, is one of the main factors influencing sponsorship memory accuracy (Evans, 2019). It is found that, within women’s sports, demand for research on how to maximize the efficiency of sponsorships exists.The research aims to find if sponsors and sponsees could look towards sponsorships with more external congruence to increase the value of the sponsorship to both the sponsor and sponsee. The study uses a survey to find correlations between the amount of external congruence and the degree to which sponsorship objectives are reached. The External Sponsorship Congruence Scale (ESCS), developed by Evans (2019), is used as a basis for measurement of external congruence. The key finding is that the perceived quality of a brand seems to correlate with having a sponsorship that is high in external congruence. Furthermore, both areas of brand awareness and brand image could possibly see some correlation to external congruence. However, those areas were not found to be statistically significant in this study. These findings are important to develop the concept of external congruence and find possible ways of measuring external congruence. For instance, it is found that the ESCS and its constructs seem to be useable in the field of women’s and niche sports. On a theoretical level, changes to the ESCS’s geographical congruence are proposed and a revised ESCS is presented. Moreover, managers within women’s and niche sports, as well as sponsors of those, can use the findings of this study to improve the chances of finding successful sponsorships.

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