Conformational Regulation of Cell Surface Receptor Proteolysis

Hayward, Amanda Nicole ProQuest Dissertations & Theses University of Minn 2019 해외박사(DDOD)

Cell surface receptors can commonly undergo ectodomain shedding to modulate signaling pathways and cell contacts. To date, there are over 400 proteins that serve diverse functions on the cell surface that are predicted to undergo ectodomain shedding, and the shedding rates are commonly modulated in diseases such as cancer and inflammation. However, validating targets and understanding shedding regulation has been difficult due to a lack of control of proteolysis-inducing stimuli and unknown fates of cleavage products. Therefore, we built tools to help progress the field forward in understanding as well as investigated two cell surface receptors. The development of technology and tools to study proteolytically sensitive proteins is ongoing. Herein, two different tools that aid in the identification and study of mechanically sensitive proteins are described. We utilized HUH-tags to covalently link single-stranded DNA to target proteins of interest for single molecule force spectroscopy studies. We then developed an assay called SNAPS to identify switch-like proteins and screen for modulation of proteolysis by drugs. The SNAPS assay has innumerous applications in biotechnology and assessment of potential therapeutics, a few are described herein. We also investigated the biological impact of proteolysis on dystroglycan, an essential protein that forms a bridge between the extracellular matrix (ECM) and actin cytoskeleton. Proteolysis of dystroglycan is enhanced in disease states such as cancer, yet the biological impact of its proteolysis has not been elucidated. Moreover, there are muscular dystrophy disease-related mutations that map to the region where dystroglycan is cleaved by matrix metalloproteases (MMPs), but how they contribute to the mechanism of pathogenesis is not known. We have shown that disease mutations within the proteolysis domain of dystroglycan impact the overall conformation and stability of this domain, resulting in an increased in MMP cleavage. Proteolysis also has an impact on cell migration and cell morphology, suggesting that it may contribute to muscular dystrophy disease pathogenesis. Lastly, we turned our attention to Polycystin-1, a 7-pass transmembrane protein that is predicted to act as a mechanosensitive unit with Polycystin-2 in primary cilia. Its putative shedding is predicted to be functionally different than dystroglycan's; instead of having a buried proteolysis site, its extracellular juxtamembrane region is proposed to involve dissociation of two non-covalently linked subunits. We investigated several disease-related mutations within its domain and performed initial tests for studying Polycystin-1 in the context of cultured cells.

Students' initial impressions of teaching effectiveness

Hayward, Pamela Ann University of Illinois at Urbana-Champaign 2000 해외박사(DDOD)

To discover what instructor's behaviors leave an impression on students on the first day of class, University of Illinois students were surveyed at the end of the first class on instructor attributes they feel make an impact. Later, students at Lake Superior State University listened to audio tapes of these classes and wrote descriptions of instructor's behaviors. Responses related to an instructor's Communicative Competence were most frequently mentioned when participants were asked to write down their first impressions of the instructor. A factor analysis of the instructional attributes the students rated revealed four factors: Concern for Students, Communicative Competence, Expectations, and Benefit. A regression analysis revealed the Communicative Competence factor had the greatest influence on teaching effectiveness. In analyzing the attributes which students rank ordered the attributes most important to them, the following attributes were identified as most important: “instructor will teach at an appropriate level,” “instructor has a good command of the subject material,” and “instructor makes ideas clear.” The attributes most frequently ranked relatively unimportant were: “instructor seems nice,” “course will help me develop career skills,” and “instructor seems friendly.&rdquo. In the Lake Superior State University tape analysis of the instructors, almost two-thirds of the positive comments received by the most effective instructors were related to Concern for Students. Almost two-thirds of the negative comments for the most effective instructors were related to Communicative Competence. More than two-thirds of the positive comments received by the least effective instructors were related to Concern for Students. Almost three-fourths of the negative comments for the least effective instructors were related to Communicative Competence. Based on these results, the most important finding is that most student open-ended comments regarding their instructors on the first day of class, whether elicited at the end of class or when instructed to stop a tape when an instructor did something that affected their impression, focused on Communicative Competence. Although students did make numerous comments about instructor Concern for Students, Communicative Competence behaviors seem more closely related to evaluations, especially negative evaluations.

Perceiving Whites as gatekeepers of the American dream: The interplay of hierarchy-enhancing beliefs, status, opportunity, and identity

Hayward, Craig Leonard University of California, Irvine 2001 해외박사(DDOD)

Change in the ethnic composition of the United States has led to an increased need for research that describes and explains intergroup attitudes. In a pair of studies, beliefs about ethnic groups were examined via an adjective checklist and a contextualized measure of ethnic group preference. Social identity theory and system justification theory provided a theoretical framework for the investigations. In the first study social dominance orientation, socioeconomic status, and acculturation were measured in a sample of 333 undergraduates from six ethnic groups (African Americans, Chinese Americans, Korean-Americans, Mexican Americans, Vietnamese Americans, and White Americans). These variables were related to ingroup bias, interethnic attitudes, stereotypes, and group preference. Mexican Americans were found to have the highest levels of ingroup bias and to produce the most negative descriptions of White Americans. Some support was found the system justification hypothesis, but only among Vietnamese Americans. Study 2 replicated and extended Study 1 with an emphasis upon attitudes toward White Americans. Ethnic identity, group status, self-esteem, social dominance orientation, and beliefs about economic opportunity were related to the conceptions of White Americans that were held by a sample of 225 Chinese American, Vietnamese American, Mexican American, and White American undergraduates. Beliefs about opportunity were found to be associated with more positive and less negative views of Whites. Additionally, beliefs about opportunity mediated the relationship between ethnic group membership and negative views of Whites. Ethnic identity was higher and self-esteem was lower for members of low status groups (i.e., Mexican and Vietnamese Americans). System justification was not supported in Study 2. Ethnic identity was unrelated to self esteem. Tables of common descriptions of each group are presented. Possible psychological, cultural, and historical reasons for these relationships are discussed.

The heart of the matter: Transforming the lives of students through relationships

Hayward, Randy B University of Pennsylvania 2011 해외박사(DDOD)

My investigation addresses the following research question: How does Marvin L. Winans Academy of Performing Arts (WAPA) foster the development of relational trust? A large body of research demonstrates that school reform efforts tend to be successful when trust and trusting relationships exist within the school community, that trusting relationships among various stakeholders (primarily students and staff) help students to be both academically and socially fit, and that those relationships help foster social capital, which supports success in and out of school. As a researcher practitioner I set out to sample students' perceptions of WAPA practices that could have led to its becoming a rare success story among Detroit high schools with predominately African American populations. Qualitative data were obtained from a series of one-on-one interviews with students. Among other topics, students were asked about their school experience before and after attending Winans Academy, and about their relationships with school faculty and staff. Positive perceptions and outlook appeared to correlate with students' belief that other members of the school community cared about them, respected them and trusted them. Students were also able to name specific practices at Winans Academy' that supported their view of a caring community, such as access to staff, opportunities for casual conversation with staff, and policies and practices that foster strong personal identity and a sense of belonging, such as a school creed and uniform. One may conclude from the findings that Winans Academy has succeeded in building relational trust through thoughtful practices implemented by a caring principal and staff. These practices may serve as a starting point for turning around other troubled urban schools.

States and Group Rights: Legal Pluralism and the Decentralization of Judicial Power

Hayward, Emma ProQuest Dissertations & Theses University of Penn 2019 해외박사(DDOD)

When do states decentralize judicial power to ethnic and religious minority groups? This dissertation presents a theory to explain why states are willing to undertake significant transfers of power by lending their support to ascriptive, group-based law. It begins with a literature review of scholarship in comparative politics and public law, both of which argue, for different reasons, that because the judiciary is vital to the state's coercive apparatus, property rights regime, and governing functions, we should not expect states to decentralize judicial power. Yet over half of the world's states choose to officially engage with legal pluralism by delegating power to group-based law.

Experiences of Low Socioeconomic Community College Students Anticipating Transition to a 4-Year University

Hayward, Richard Walden University ProQuest Dissertations & Theses 2020 해외박사(DDOD)

Elevated maternal corticosterone alters offspring development, physiology and behavior in quail

Hayward, Lisa Shelby University of Washington 2004 해외박사(DDOD)

Within the last decade, a large body of literature has accumulated documenting the deposition of maternal androgens into egg yolk and their consequences for offspring. However, little is known about the transfer of maternal glucocorticoids into yolk and their effects on offspring. Here I show that high plasma corticosterone in a laying bird corresponds to high corticosterone in the yolk of her eggs. I then demonstrate that elevated yolk corticosterone has a range of effects on offspring development and adult phenotype. Female quail from selected for heightened plasma corticosterone response to capture and restraint lay eggs with higher yolk corticosterone than quail selected for a low plasma corticosterone response. This difference in yolk corticosterone concentration is particularly interesting given that baseline corticosterone levels do not differ between the two lines. Experimentally elevating plasma corticosterone in laying quail increased corticosterone concentration in the yolk of their eggs. Chicks that hatched from eggs laid by females implanted with corticosterone grew more slowly than controls, and showed higher plasma corticosterone response to capture and restraint as adults. To determine whether the effects of elevated maternal corticosterone were mediated by transfer of the steroid itself to yolk, yolk corticosterone concentration was manipulated directly. Male, but not female, chicks that hatched from eggs injected with corticosterone grew more slowly than controls, and female, but not male, offspring showed a decreased corticosterone response as adults. Finally, eggs were injected with corticosterone and chick performance in a maze, and adult expression of anxiety behavior were quantified to investigate the effects of elevated yolk corticosterone on cognitive ability and behavior. Chicks from eggs injected with corticosterone completed the maze faster than controls on the first trial. However, control chicks improved in their second trial to become as fast at completing the maze as the corticosterone chicks. There was no effect of corticosterone treatment on anxiety behavior in adults. Thus, I show that high maternal corticosterone is transferred to avian egg yolk and that it has lasting effects on offspring development and adult phenotype. Future studies are needed to understand the role of maternal corticosterone in yolk within an ecological context.

Searching for Meaning: New Methods, Measures, and Modeling Approaches in the Sociology of Religion

Hayward, George M ProQuest Dissertations & Theses The University of 2020 해외박사(DDOD)

This dissertation uses a combination of new measures and modeling approaches in the sociology of religion to advance our understanding of three substantive topics. In the first chapter, I use data from the National Study of Youth and Religion (NSYR) to answer the question of how a multidimensional model of religiosity fits an adolescent and young adult sample. Additionally, this chapter considers multiple ways to build longitudinal models of these dimensions over time, and ultimately uses autoregressive latent trajectory models to show that each of these dimensions are predicted over time, sometimes in different ways, by their prior values, individuals’ background characteristics, and life course changes during the transition to adulthood. In the second chapter, I explore another dimension of religiosity: religious knowledge. This relatively understudied topic has long lacked ample measures, though the recent Pew Religious Knowledge Survey (2010) provides a rich set of religious knowledge questions, thus allowing for a fresh evaluation of this topic and assessment of these new measures. Accordingly, this chapter proposes and tests a multidimensional model of religious knowledge and provides support for a model spanning several religious traditions with twenty-four indicators. As an external validity check and application to personal religiosity, this chapter shows that knowledge of one’s own religion is correlated with two different dimensions of personal religiosity.Finally, the third chapter in this dissertation takes on a broader question: what can internet search data tell us about the dynamics of the U.S. religious landscape? Using Google search data from 2004 to 2019, this paper examines the trends in online searches for world religions, other religions, conventional religious terms, and a host of quasi-religious, spiritual, and areligious terms. The results show that, while terms related to institutional religion tend to be declining in popularity, many terms related to minority religious traditions and terms related to general spirituality are increasing in popularity. Nevertheless, searches for institutional religion still dominate the overall volume of religious searching. Comparisons with data from the General Social Survey suggest that internet search data can serve as a reasonable proxy for societal interest.

Posttraumatic growth and disability: On happiness, positivity, and meaning

Hayward, H'Sien Harvard University 2013 해외박사(DDOD)

The field of psychology has traditionally focused on the deleterious effects of adversity to the exclusion of positive effects. However, a literature on positive sequelae of traumatic events has burgeoned over the past decade. The issue of whether individual's reports of positive changes are merely illusory self-enhancing biases or are reflective of objective, quantifiable change is perhaps the most contentious in the posttraumatic growth research at this time. This dissertation begins with a broad overview of the extant research on posttraumatic growth, then presents the evidence supporting each side of the validity debate. As the population studied in this dissertation is adults with traumatic-onset spinal cord injuries, a presentation of research that ties disability to the posttraumatic growth literature follows. Finally, the introductory chapter concludes with an argument for the importance of including a disability perspective in psychological science. Three papers follow, each taking up aspects of this relatively new focus on positive aspects of disability. The first paper lays the foundation for the work that follows by exploring the question of whether people with disabilities are, in fact, doing well. Establishing a baseline of subjective well-being would seem necessary before venturing into an exploration of how this happiness may have come to be. In a replication of a classic study, I find that indeed, people with spinal cord injuries report levels of happiness that are equal to both those of controls and lottery winners. In the second study, I use experimental and survey evidence collected over a span of eight-years to explore posttraumatic growth and its relationship to emotion regulation advances. Finally, Paper 3 takes an in-depth look at one of the critical components of posttraumatic growth, a sense of meaning in life, and its relationship to happiness. The concluding chapter outlines several limitations of this program of research, and provides directions for research that will carry it forward. Finally, it returns to the validity debate in the posttraumatic growth literature most broadly, making recommendations for future research that will shed light on this issue, and presenting reasons that resolution of this debate is important for academia, clinical practice, and society-at-large.

A hierarchy of disability: Attitudes of people with disabilities toward one another

Hayward, Katharine Anne University of California, Los Angeles 2005 해외박사(DDOD)

Previous studies indicate a hierarchy of acceptance for people with varying types of disability, where people with mental retardation or a psychiatric disability are least accepted compared to people with physical disabilities. However, research among people with disabilities assessing how they view others with disabilities is nearly nonexistent. Research conducted for this dissertation attempts to: (1) determine whether a hierarchy of acceptance of people with disabilities exists among those with disabilities, (2) describe factors contributing to it, and (3) describe attitudes of people with disabilities toward their own disability and self-identity as a disabled person. The conceptual framework for this study comprises theories of stigma, labeling, deviance, and social networks to provide a framework for understanding how stigma associated with disability affects how people with disabilities see themselves and how this affects the degree to which individuals with disabilities accept others with disabilities. Data were collected between April and December 2004 among college students with disabilities recruited from UCLA and UC Davis disability centers. Participants completed self-administered questionnaires available as printed versions or online that addressed their attitudes toward having a disability and toward others with disabilities. Several findings emerged from this study. One finding is the demonstration of a stable hierarchy of disability among people with disabilities that positions those with physical disabilities at the top and those with mental retardation or psychological disabilities at the bottom. Social distance did not vary by respondent's disability. Contact with others with disabilities was found to be significantly related to both disability identity and social distance, although the contact variable of significance differed in each case. Participants who knew more people with a disability had greater disability identity whereas those with no close friends with disabilities expressed greater social distance. Being male, having frequent contact with others with disabilities, knowing more individuals with disabilities, and having a higher number of friends is associated with an increased sense of disability identity. Being White, having a close friend with a disability, and a father who was college educated increased social acceptance of others with disabilities. Finally, disability identity and social distance were found to be significantly negatively related.