Diss. (sammanfattning) Stockholm : Karol. inst., 2004. / Härtill 5 uppsatser.

Thesis (Ph. D.)--University of Oregon, 2007. / Typescript. Includes vita and abstract. Includes bibliographical references (leaves 45-48). Also available online in Scholars' Bank; and in ProQuest, free to University of Oregon users.

Thesis (Ph. D.)--University of Washington, 1997. / Vita. Includes bibliographical references (leaves [78]-85).

Thesis (Ph. D.) -- University of Texas Southwestern Medical Center at Dallas, 2004. / Vita. Bibliography: 77-82.

Thesis (Ph. D.)--University of Wisconsin--Madison, 1956. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 66-69).

Thesis--University of Florida. / Description based on print version record. Typescript. Vita. Includes bibliographical references (leaves 67-69).

Thesis (Ph. D.)--Ohio State University, 2007. / Full text release at OhioLINK's ETD Center delayed at author's request

xiv, 81 p. : ill. (some col.) A print copy of this thesis is available through the UO Libraries. Search the library catalog for the location and call number. / Protein-protein interaction networks translate environmental inputs into specific physiological outputs. The signaling proteins in these networks require regulatory mechanisms to ensure proper molecular function. Two common regulatory features of signaling proteins are autoinhibition and ultrasensitivity. Autoinhibition locks the protein in an inactive state through cis interactions with a regulatory module until it is activated by a specific input signal. Ultrasensitivity, defined as steep activation after a threshold, allows cells to convert graded inputs into more switch-like outputs and can lead to complex decision making behaviors such as bistability. Although these mechanisms are common features of signaling proteins, their molecular origins are poorly understood. I used the Drosophila Pins protein, a regulator of spindle positioning in neuroblast cells, as a model to study the molecular origin and function of autoinhibition and ultrasensitivity. Pins and its binding partners. Gαi and Mud, form a signaling pathway required for coordinating spindle positioning with cellular polarity in Drosophila neuroblasts. I found Pins switches from an autoinhibited to an activate state by modular allostery. Gαi binding to the third of three GoLoco (GL) domains allows Pins to interact with the microtubule binding protein Mud. The GL3 region is required for autoinhibitoon, as amino acids upstream and within GL3 constitute this regulatory behavior. This autoinhibitory module is conserved in LGN, the mammalian Pins orthologue. I also demonstrated that Gαi activation of Pins is ultrasensitive. A Pins protein containing inactivating point mutations to GLs l and 2 exhibits non-ultrasensitive (graded) activation. Ultrasensitivity is required for Pins function in vivo as the graded Pins mutant fails to robustly orient the mitotic spindle. I considered two models for the source of ultrasensitivity in this pathway: cooperative or "decoy" Gai binding. I found ultrasensitivity arises from a decoy mechanism in which GLs 1 and 2 compete with the activating GL3 for the input, Gai. These findings suggest that molecular ultrasensitivity can be generated without cooperativity. This decoy mechanism is relatively simple, suggesting ultrasensitive responses can be evolved by the inclusion of domain repeats, a common feature observed in signaling proteins. This dissertation includes previously published and unpublished co-authored material. / Committee in charge: Tom Stevens, Chairperson, Chemistry; Kenneth Prehoda, Member, Chemistry; Christopher Doe, Member, Biology; Peter von Hippel, Member, Chemistry; Karen Guillemin, Outside Member, Biology

A recente explosão do conhecimento da genética molecular e o avanço da indústria da biotecnologia requerem que o público compreenda muitos conceitos da genética para a tomada de decisões sobre a pertinência do uso dessas novas ferramentas. Durante os últimos 30 anos a literatura educacional produziu conceitos e teorias para lidar com estas dificuldades, mas a maioria dos professores desconhece estas produções, principalmente porque os periódicos de referência são publicados em línguas estrangeiras (principalmente em inglês). Esta pesquisa-ação pretende preencher esta lacuna e foi baseada em testes que envolveram 283 estudantes de 12 a 15 anos de idade. Nela descrevemos as concepções dos estudantes sobre a localização e transmissão da informação genética antes e após a aplicação de uma seqüência didática elaborada especificamente para desenvolver estratégias metacognitivas de aprendizagem. As idéias dos estudantes foram colhidas por meio dos questionários e redações, nas quais os estudantes descrevem como imaginam ser o interior das células e dos gametas. Verificamos que as crianças do ensino fundamental possuem concepções semelhantes àquelas descritas para estudantes do ensino médio. A comparação das redações produzidas pelos estudantes antes e após a aplicação da seqüência didática permitiu verificar que o padrão mais comum de aprendizagem é sincrético, ou seja, as crianças tendem a distorcer as informações oferecidas pelo professor em virtude da existência de conhecimentos prévios. Por fim, a descrição e a documentação de seqüências didáticas planejadas a partir de conhecimentos produzidos na literatura educacional permitem o entendimento dos processos de transposição didática e a relação deste com a aprendizagem dos estudantes. / The recent knowledge explosion on the areas of genetics, molecular biology and biotechnology introduced many new concepts hard for common people to grasp in their decision-making processes. During the last 30 years or so the educational literature produced concepts and theories to cope with these difficulties but the vast majority of our elementary and highschool teachers remain unaware of them possibly because the available literature is written in foreign languages (mainly in English). The action-research here presented intends to fill this gap and was based on tests performed with 283 students aged 12 to 15. We describe their conceptions on the location and transmission of genetic information before and after the application of a didactic sequence specifically elaborated to develop metacognitive learning strategies. The students\' ideas were gathered by means of questionnaires and through essays describing how they imagine the interior of cells and germ-cells. We verified that children on basic educational level have conceptions very similar to those of students of middle-level education. The paired comparison of before and after essays suggests the existence of a common, syncretic learning standard. In plain language, the results indicate that previous informal knowledge of children tends to distort the formal information transmitted by their teachers. It is clear that the description and documentation of planned didactic sequences, available from the specialized literature, provide the understanding of the didactic transposition process and its relation with the students´ learning process.

Genome of S. pneumoniae contains only one copy of the gene coding eukaryotic type protein kinase StkP and corresponding phosphatase PhpP. These two enzymes form a functional signaling pair regulating cell division, which could be used in the future for the design of new bacteriostatic compounds. Not only kinase and phosphatase are important components of the system, but also other members of this pathway - specific substrates of these enzymes. The identification of the Ser/Thr phosphoproteom with a focus on the membrane fraction provided information not only about already known substrates such as LocZ, Jag and DivIVA but also about an unknown protein P15 with a molecular weight about 15 kDa. In this thesis the protein was identified as rhodanase (spr0595) by MS MALDI TOF. However, its subsequent deletion did not confirm it as a StkP/PhpP substrate. Therefore we investigated another substrate, protein FtsA, which has already been identified as a substrate of this kinase in a previous study (Beilharz et al., 2012). FtsA is an essential cell division protein that anchors FtsZ filaments into the membrane. Phosphorylation of this protein was detected on the Thr residue at position 404. Using phosphoablative substitution we found out, that Thr404 is indeed phosphorylated by protein kinase StkP, however, FtsA...