13 results on '"McNair, Elizabeth"'
Search Results
2. Microglia either promote or restrain TRAIL-mediated excitotoxicity caused by Aβ1−42 oligomers.
- Author
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Zou, Jian, McNair, Elizabeth, DeCastro, Sagan, Lyons, Scott P., Mordant, Angie, Herring, Laura E., Vetreno, Ryan P., and Coleman Jr, Leon G.
- Subjects
- *
MACROPHAGE colony-stimulating factor , *TRAIL protein , *ALZHEIMER'S disease , *DEATH receptors , *DESIGNER drugs - Abstract
Background: Alzheimer's disease (AD) features progressive neurodegeneration and microglial activation that results in dementia and cognitive decline. The release of soluble amyloid (Aβ) oligomers into the extracellular space is an early feature of AD pathology. This can promote excitotoxicity and microglial activation. Microglia can adopt several activation states with various functional outcomes. Protective microglial activation states have been identified in response to Aβ plaque pathology in vivo. However, the role of microglia and immune mediators in neurotoxicity induced by soluble Aβ oligomers is unclear. Further, there remains a need to identify druggable molecular targets that promote protective microglial states to slow or prevent the progression of AD. Methods: Hippocampal entorhinal brain slice culture (HEBSC) was employed to study mechanisms of Aβ1−42 oligomer-induced neurotoxicity as well as the role of microglia. The roles of glutamate hyperexcitation and immune signaling in Aβ-induced neurotoxicity were assessed using MK801 and neutralizing antibodies to the TNF-related apoptosis-inducing ligand (TRAIL) respectively. Microglial activation state was manipulated using Gi-hM4di designer receptor exclusively activated by designer drugs (DREADDs), microglial depletion with the colony-stimulating factor 1 receptor (CSF1R) antagonist PLX3397, and microglial repopulation (PLX3397 withdrawal). Proteomic changes were assessed by LC-MS/MS in microglia isolated from control, repopulated, or Aβ-treated HEBSCs. Results: Neurotoxicity induced by soluble Aβ1−42 oligomers involves glutamatergic hyperexcitation caused by the proinflammatory mediator and death receptor ligand TRAIL. Microglia were found to have the ability to both promote and restrain Aβ-induced toxicity. Induction of microglial Gi-signaling with hM4di to prevent pro-inflammatory activation blunted Aβ neurotoxicity, while microglial depletion with CSF1R antagonism worsened neurotoxicity caused by Aβ as well as TRAIL. HEBSCs with repopulated microglia, however, showed a near complete resistance to Aβ-induced neurotoxicity. Comparison of microglial proteomes revealed that repopulated microglia have a baseline anti-inflammatory and trophic phenotype with a predicted pathway activation that is nearly opposite that of Aβ-exposed microglia. mTORC2 and IRF7 were identified as potential targets for intervention. Conclusion: Microglia are key mediators of both protection and neurodegeneration in response to Aβ. Polarizing microglia toward a protective state could be used as a preventative strategy against Aβ-induced neurotoxicity. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
3. Grammatical patterns in the linguistic ecology of Griffin, Georgia
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McNair Elizabeth DuPree
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Griffin, Georgia -- Social aspects ,Grammaticality (Linguistics) -- Analysis ,Linguistic geography -- Analysis ,Languages and linguistics - Abstract
Qualitative findings of local grammatical variables are displayed and patterns of change over apparent time from a sample that is one hundred years deep is described and these patterns to trends found in other researchers' work is compared. Factors that influence patterns of change and stability include salience, settlement history, grammaticalization and social variables.
- Published
- 2005
4. Social networks and linguistic evolution: A brief case study
- Author
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McNair, Elizabeth DuPree
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Linguistic geography -- Analysis ,Linguistic analysis (Linguistics) ,Languages and linguistics - Abstract
Several ways in which the combination of internal and external ecologies plays an important role in development of new varieties of white English since the seventeenth century are demonstrated. The successful features are not necessarily those that improve a dialect, but rather the features that are used by people in certain kinds of contacts.
- Published
- 2005
5. Settlement patterns, cultural space, and linguistic evolution in the American south
- Author
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McNair, Elizabeth DuPree
- Subjects
Linguistic analysis (Linguistics) ,Languages and linguistics - Abstract
Linguistic contact equation of different regions of south varied greatly with African and European varieties in large plantations. Economic upheavals broke the institutional foundations, and linguistic geographies and life modes were renegotiated, resulting in distinct speech patterns.
- Published
- 2005
6. A sociolinguistic study of a southern mill town
- Author
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McNair, Elizabeth DuPree
- Subjects
Griffin, Georgia -- Social aspects ,Language and culture -- Analysis ,Sociolinguistics -- Analysis ,Languages and linguistics - Abstract
An investigation to determine how the language contact equation between two speech communities in Griffin has played out over the past century of dramatic economic cycles is presented. Language is acknowledged as an object that could reflect abstract structures that are difficult to observe directly, a multidimensional approach is implemented to present the data informed by linguistic, sociological, and statistical methods.
- Published
- 2005
7. Disciplinary Influences on the Professional Identity of Civil Engineering Students: Starting the Conversation
- Author
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Groen, Cassandra J., Simmons, Denise Rutledge, McNair, Elizabeth D., Civil and Environmental Engineering, Engineering Education, Institute for Creativity, Arts, and Technology (ICAT), and The Myers-Lawson School of Construction
- Abstract
As the discipline of civil engineering has evolved from an apprentice-based trade to a socially-engaged profession, the role of the civil engineer has responded to shifts within the ever-changing culture of society. These shifts and historical events have directly influenced what is considered to be valued civil engineering knowledge, behaviors, and practices that we teach to students during their undergraduate careers. As part of a larger grounded theory study that is currently being conducted by the authors, the purpose of this paper is two-fold. First, we present the topic of professional identity formation as heavily influenced by unique historical events that shape the civil engineering discipline. . To establish the connection between identity formation and the history of civil engineering, we interpret historical events as constituents that create a disciplinary identity that is communicated to and subjectively applied by students during their undergraduate careers. Second, we hope to promote and invoke conversations surrounding the relevancy of civil engineering professional identity formation in engineering education among our colleagues within the technical disciplines. Through this paper, we add to ongoing research exploring the professional formation of engineering identities and promote discussions surround this topic at the disciplinary level. While most research conducted on identity formation has been generalized to include all or most engineering disciplines, we focus our discussion solely on professional identity formation within the civil engineering discipline. To reinforce the relationship between the history of the civil engineering profession and students’ professional identity formation, we review the literature on these two areas of inquiry. In particular, we will frame our paper using the following key discussion points: 1) providing a brief overview of key historical events of civil engineering in the United States; 2) discussing the influence of this history on instructor pedagogies and student learning within civil engineering education; and 3) conceptualizing this learning process as a means of professional identity formation. From this work, we will begin to understand how major historical shifts within our discipline maintain the potential to impact its future as we educate the next generation of civil engineering students. To conclude this paper, we will introduce current research that is being conducted by the authors to further understand the nuances of professional identity formation in undergraduate civil engineering students and how instructors may help or hinder that development. Published version Yes, full paper (Peer reviewed?)
- Published
- 2016
8. Achieving What Gets Measured: Responsive and Reflective Learning Approaches and Strategies of First-Year Engineering Students
- Author
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Van Tyne, Natalie Christine Trehubets, Engineering Education, McNair, Elizabeth D., Mccord, Rachel, Soledad, Michelle Millete, and Knight, David B.
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Engineering ,First Year ,ComputingMilieux_COMPUTERSANDEDUCATION ,Reflection ,Learning Strategies - Abstract
Background: Engineering students who achieve academic success during their first year may later disengage from challenging course material in their upper-level courses, due to perceived differences between their expectations and values and those of their degree programs. In the extreme, academic disengagement can lead to attrition. Purpose: The purpose of this study is to better understand the learning approaches and strategies used by first-year engineering students. Research questions were as follows: How do first-year engineering students describe their learning approaches and strategies? How do first-year engineering students customize their learning strategies among their courses? How do first-year engineering students employ reflection as part of their learning strategies? Design/Method: I employed both qualitative and quantitative methods to collect and analyze data, using an explanatory design approach consisting of two surveys and a set of semi-structured interviews between survey administrations. The interview data from a purposive sample of survey participants were coded using a priori, pattern and comparative coding. The survey data were analyzed for medians and interquartile ranges in order to identify trends in reflective learning strategies among courses. Results: One notable finding was the fact that many interviewees stated that their overall purpose for studying was to achieve high grades by preparing for tests (a surface-level approach), and yet the learning strategies that they used reflected a deeper engagement with their course material than one would expect from students whose singular focus was on grades. Certain strategies were similar for both technical and non-technical courses, while others were dissimilar. There are also ways to combine the surface and deep learning strategies sequentially. They need not be mutually exclusive. Conclusions: The results of this study will provide educators with a starting point for the development of guided practice in meaningful learning strategies to encourage a greater engagement with learning. Both educators and administrators should be amenable to measures that would improve their students' chances for success, by providing guidance in how to learn as well as what to learn. Several recommendations are given for future studies, such as the relationships among reflection, metacognition, and critical thinking, and the integration of meaningful learning strategies into technically overloaded engineering degree curricula. Doctor of Philosophy I chose to study the learning approaches and strategies of first-year engineering students. The term "learning strategies" refers to study habits, but learning strategies also involve choices about how to study based on goals, motivation, and available resources. My results will provide professors and instructors with insights that they can use to help their students learn more effectively and find deeper meaning in their course material, by guiding them in how to learn as well as what to learn. Knowing how to learn is a lifelong skill. First-year engineering students have a special need to know how to learn in order to be better prepared for a more challenging workload in their upper level engineering courses. Prior studies have shown that students most often leave an engineering program during their first or second year due to inadequate academic preparation in prior years. If we are to help engineering these students to improve their learning approaches and strategies, we first need to know what approaches and strategies they currently use. My data came from two surveys that were given at the end of each of two introductory engineering courses to a group of approximately 1,200 students, and from interviews with fifteen students who had also completed the surveys. I was trying to learn more about how these students customized their learning strategies among their courses, and how they used reflection to discover the meaning behind what they are learning. One of the most interesting findings was the fact that many interviewees stated that their overall purpose for studying was to achieve high grades by preparing for tests (a surface-level approach), and yet the learning strategies that they used reflected a deeper engagement with their course material than one would expect from students whose only focus was on grades. This combination of different learning approaches was more common in engineering, science and mathematics courses than in humanities or social science courses. This dissertation also contains a three-part class assignment, given at the beginning, middle, and end of a first-year engineering course, in which students reflect on their progress in learning one or more skills that they had identified at the beginning of the course. Implications arising from my study are directed at researchers, administrators, faculty, and students, respectively, as well as opportunities for further work in this aspect of higher education. Opportunities for further studies include the relationship between reflection and critical thinking, and methods for incorporating guided practice in learning strategies into engineering degree programs that currently contain too much technical content.
- Published
- 2022
9. Engaging with the Invisible: STS Groundwork in an Electrical and Computer Engineering Department
- Author
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Patrick, Annie Yong, Science and Technology Studies, Wisnioski, Matthew, Downey, Gary L., McNair, Elizabeth D., Schenk, Todd, and Hester, Rebecca
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Participatory approaches ,Science, Technology and Society (STS) ,Interventionist methodologies - Abstract
This dissertation is a study of groundwork in Engaged Science, Technology, and Society (STS) research. Engaged STS scholars reframe STS knowledge and move it beyond the traditional scope and boundaries of the field. They use various methods such as critical participation, making and doing, situated interventions, and experimentation to critically engage with their fields of study. These scholars have evaluated their work within the context of the disciplinary outsider, described their use of high-level pragmatic frameworks, and used the arts to bring critical social issues to the public eye. Yet, when I decided to use STS engagement methods to bring visibility to the lesser-known communities in the Bradley Department of Electrical and Computer Engineering (ECE) at Virginia Tech, I found a lack of work documenting the groundwork and experience of engagement. I could not locate groundwork regarding negotiation, designing the most appropriate intervention, collaboration strategies, or confronting my fears and doubts about being in the field. Therefore, in this dissertation, I identify and examine my engagement experience in three interventions within the ECE department to bring visibility to the groundwork of STS engagement. The limited-series podcast Engineering Visibility was a platform to bring visibility to the less dominant communities in the ECE department. Highlighting the experiences of women in engineering, the first-generation student, inclusion and diversity, and the non-traditional student fostered a shared identity and sense of belonging within the ECE department. On the ground, this project examined the need to protect participants' visibility through invisibility. Interventionist Protectivity conceptualizes how I combined trust, accountability, and social awareness to protect my participants' from social scrutiny. The second project was a seminar titled "Expand Your ECE Career." The seminar exposed students to a "broader range of careers" by challenging the traditional ideas of success. The seminar featured four ECE alumni with successful careers in law, finance, and fashion entrepreneurship. Additionally, this intervention pointed out the inadequacies of traditional forms of project assessment. I describe how I measured intervention success through other assessment methods such as "assessment per mobility." The last project was a data-driven white paper that translated the care work of the undergraduate academic career advisors and framed it to be understood by the ECE faculty. The care work done by the academic advisors was underappreciated in its connection to undergraduate student success. On the ground, I discussed the importance of identifying the advisors and the faculty's social construction to create an intervention that translated the advisors' work to be valued by the faculty. Lastly, I conclude with a discussion summarizing the overall lessons learned from the three interventions and discussing my experience of engagement. My engaged STS experience is discussed through my framing of the concept of self-confrontation and the work of avoiding the term of STS being deemed as useful. Doctor of Philosophy This dissertation is a study of groundwork in engaged Science, Technology, and Society (STS) research. Recent advances such as critical participation, making and doing, and situated intervention are reframing boundaries between knowledge and action in STS, offering scholars new approaches for improving scientific and technological communities. When I attempted to utilize these theories and methods in a culture change project, however, I found a lack of scholarship documenting the experience of engagement. How does one design the most appropriate intervention? What strategies are required to collaborate and negotiate? How do engaged scholars confront their fears and doubts in their communities and concerning the knowledge they bring back to STS? These groundwork questions confront both novice and seasoned STS scholars and are crucial to successful engaged scholarship, but they rarely are documented and analyzed. Utilizing a matters-of-care framework and self-reflective methods, I describe how and why I sought to change the culture of a large engineering department by making visible unseen and sometimes under-appreciated stakeholders. To do so, I created three interventions: a limited-series podcast to showcase the diversity of experiences in the department, an alternative-career seminar to redefine what counted as success in engineering, and a data-driven white paper to showcase the indispensable care work of academic advisors. I analyzed these projects' construction, application, and outcomes to highlight the complexities and significance of groundwork for STS engagement.
- Published
- 2022
10. Twelve Tales of Engineering in the 'Real World:' Narratives of Newcomers' Agency in Transitions to Engineering Work
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Gewirtz, Christopher Aaron, Engineering Education, Paretti, Marie C., Vinsel, Lee, Case, Jennifer Margaret, and McNair, Elizabeth D.
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Workplace Transitions ,Engineering Practice ,Identity Development ,Critical Pedagogy - Abstract
Reports that call for change in engineering education date back to the Mann report (1918), but more recent reports like "The Engineer of 2020" (NAE, 2004), and "Lean Engineering Education," (Flumerfelt et al., 2015) describe the need for engineers who are creative leaders, who have sustainability and ethics skills. Two narrative threads emerge from these reports: that engineering education does not adequately prepare engineers with the skills needed for industry, and that preparation for industry is imperative in order to address problems in society. However, these threads conflict with research from engineering education, science and technology studies, and higher education. There may not be a gap between school and work (Modestino, Shoag and Balance, 2016), and if there is one, it might be a socio-cultural gap that is unreasonable for universities to accept the full responsibility of narrowing. More problematic is that establishing "preparation-for-work" as the purpose for education threatens the goal of preparing students for life outside of work and does not necessarily prepare them to act towards benefit for society. The goal of this study was to critique these narratives using narratives of newcomer engineers' lived experiences. I had two research questions: 1) Who are new engineers asked to be at work? 2) Who do new engineers choose to be in response? I answered these by constructing and analyzing narratives of 12 newcomer engineers, based on interviews collected as part of the Capstone to Work study (Paretti et al., 2021). Using the figured worlds framework of identity development (Holland et al., 1998), I investigated the structures of work, which constrained who newcomers could become, and newcomers' agency, which they used to improvise identities within those constraints. The structures of engineering work that I examined required newcomers to acclimate to ongoing practices at their companies, which did not conform to newcomers' expectations of creative engineering work. Newcomers were objectified: their value and identity was often defined in terms of how much money they made for their company. They were alienated: their engineering problems were rarely defined in terms of their societal impact. The faced sexism: they were denied respectable identities based on gender. In response, some newcomers sought the identity of "asset" for their companies. Other newcomers sought new jobs that would give them opportunities for creativity, growth or societal benefit. And some newcomers worked to create opportunities at their jobs to be who they wanted: leaders, engineers working for environmental benefit, whole persons outside and inside of work. The results of this study suggest limitations of preparation narratives: They do not account for objectification, alienation, and sexism that newcomers face. Engineers also may unfortunately be prepared with stereotypes that do not match the realities of engineering work. This study suggests that we need to educate engineers in a way that recognizes them as human and prepares them for these realities. It also shows us that socio-technical change requires change at the structural level and cannot be limited to changes in education. Doctor of Philosophy Reports like "The Engineer of 2020", and "Lean Engineering Education," describe the need for engineers who are creative leaders, and who have sustainability and ethics skills. Engineering education researchers and practitioners use these preparation narratives to justify their funding to grant-awarding institutions, to develop research agendas, and to align their education efforts with these national calls. Two threads emerge from typical preparation narratives: that engineering education does not adequately prepare engineers with the skills needed for industry, and that preparation for industry is necessary for engineering to address societal problems. These, however, conflict with research from engineering education, science and technology studies, and higher education. If there is a gap between school and work, it might be a socio-cultural gap that is unreasonable for universities to accept the full responsibility of narrowing. More problematic is that establishing "preparation-for-work" as the primary purpose of education threatens the goal of preparing students for life outside of work and does not necessarily prepare them to act towards benefit for society. This study critiques these narratives by referring to newcomer engineers' lived experiences and identity development. I had two research questions: 1) Who are new engineers asked to be at work? 2) Who do new engineers choose to be in response? I answered these by constructing and analyzing narratives of 12 newcomer engineers, based on interviews collected as part of the Capstone to Work study. Using the figured worlds framework of identity development, I investigated the structures of work, which constrained who newcomers could become, and newcomers' agency in becoming different kinds of engineers within those constraints. Newcomers were generally required to acclimate to ongoing practices at their companies, which did not conform to their expectations of creative engineering work. Newcomers were objectified: their value and identity was often defined in terms of how much money they made for their company. They were alienated: their engineering problems were rarely defined in terms of their societal impact. The faced sexism: they were denied respectable identities based on gender. In response, some newcomers sought the identity of "asset" for their companies. Other newcomers sought new jobs that would give them opportunities for creativity, growth or societal benefit. And some newcomers worked to create opportunities at their jobs to be who they wanted. The results of this study suggest limitations of preparation narratives: they do not account for objectification, alienation, and sexism that newcomers face. Engineers also may unfortunately be prepared with stereotypes that do not match the realities of engineering work. Engineers should be educated in a way that recognizes them as human and prepares them for the realities of work. The study also confirms that efforts for socio-technical change cannot be limited to educational changes, because of structural constraints.
- Published
- 2021
11. Transdisciplinarity on Paper: How do interdisciplinary faculty translate university initiatives into the classroom?
- Author
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Ozkan, Desen Sevi, Engineering Education, Bairaktarova, Diana, McNair, Elizabeth D., Matusovich, Holly M., and Salado Diez, Alejandro
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organizational change ,interdisciplinarity ,curriculum design ,engineering education ,archival data - Abstract
University-level transdisciplinary initiatives have become prevalent as institutions reorient disciplines around complex problems that are relevant to society. Transdisciplinary research initiatives, like those of interdisciplinarity in the previous decade, are reinforced by federal funding agencies because of their potential to yield technological innovation, and in turn, economic growth. However, the sustained development of transdisciplinary or interdisciplinary curriculum design remains limited due to the multiple competing factors that govern the curriculum. This dissertation research focuses on the implementation of the transdisciplinary initiative as it pertains to interdisciplinary curriculum design. I use public institutional documents to trace the transdisciplinary institutional initiative as it is enacted at different university levels and interviews to understand the initiatives in practice, drawing from administrators, faculty, and staff experiences as they develop interdisciplinary courses. Many university-level initiatives that purport transdisciplinary and interdisciplinary education fall short in their implementation because of academic structures that directly or indirectly inhibit sustainable interdisciplinary curricula. Instead, administrative organizations like the Registrar's Office, Office of Integrated General Education, and Transdisciplinary Initiative Office develop networks and artifacts that connect faculty who have experience bypassing academic structures with faculty who seek out these forms of institutional support. These emergent practices are an adaptation to the university system rather than a proactive measure that facilitates the large-scale structural change claimed by university-level transdisciplinary initiatives. This study contributes to the understanding of potential long-term implications through the examination of interrelated university initiatives as they exist through metrics and incentives provided by the upper administration and experiences of faculty and staff in developing interdisciplinary courses. Doctor of Philosophy There is a trend in universities across the United States of implementing initiatives that incentivize departments to focus their research and teaching on complex problems that span different disciplines. These initiatives are attractive to potential university donors due to their perceived societal relevance and reinforced by external funding agencies because of their potential to yield technological innovation. These initiatives can be short-lived, however, as they seek to disrupt the traditional university structure. The purpose of this study is to examine how faculty and staff translate and negotiate the complex university structures and initiatives as they design interdisciplinary courses. I use public institutional documents to trace the transdisciplinary institutional initiative as it is enacted at different university levels and interviews to understand the initiatives in practice, drawing from administrators, faculty, and staff experiences as they develop interdisciplinary courses. The findings show that even for faculty and staff working to create interdisciplinary classes in alignment with these initiatives, they are faced with challenges as the initiatives are limited in their structural reorientation. Instead, mid-tier administrative organizations have developed networks and artifacts that connect those who have experience bypassing academic structures with those who express interest in following their lead. This study includes a discussion of broader socio-political and economic factors that contextualizes layers of faculty and staff experiences, administrator perspectives, and the university's public messaging through the historical legacies of academia, the economy, and society at large.
- Published
- 2020
12. Organization and Retention in Research Groups in Graduate Engineering Departments
- Author
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Crede, Erin Dawne, Engineering Education, Borrego, Maura Jenkins, McNair, Elizabeth D., Fuller, Ted, and Lohani, Vinod K.
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retention ,mixed methods ,ComputingMilieux_COMPUTERSANDEDUCATION ,graduate education ,engineering research groups - Abstract
The purpose of this research project was to better understand the experiences of graduate students in internationally diverse research groups, and how these research groups and international diversity contributes to a student's intent to complete his or her graduate degree. This exploratory mixed methods research was conducted in three phases: (1) an ethnographic study of selected research groups in two engineering graduate departments, (2) development of a survey for students in graduate engineering students, and (3) administering the survey to graduate engineering students in research groups to verify the findings. In order to address the project aims, three smaller studies were initiated that address individual elements of graduate education, including: learning in research groups and international diversity, and retention in graduate engineering programs. The focus of the first study was to understand how and under what conditions research groups foster successful learning and professional development for graduate engineering students, and how these findings can be used to inform management of engineering research groups to optimize student learning, productivity, and intent to complete the degree. Key findings from the ethnographic analysis indicate that group size directly influences the mechanisms of student learning, as well as several elements common across research groups from different universities and academic departments, including: power distance and communication, access to resources, and role of the advisor. During the (second) integration phase of this mixed methods study, the nine months of ethnographically guided observations and interviews were used to develop a survey examining graduate engineering student retention. Findings from the ethnographic fieldwork yielded several themes, including: the role of international diversity, research group organization and climate, student self efficacy, and individual and group learning experiences. Final retention themes from the ethnographic analysis are presented along with a discussion of how these data were configured into instrument questions. A discussion of the final instrument is presented, including validity and reliability analysis, and how the final questions were integrated into themes to test hypotheses for future studies. This chapter also presents implications for mixed methods researchers interested in using qualitative methods to create new instruments. In the third and final stage of the research study, the survey developed in the second phase of the research study was administered to four universities across the United States. Data analysis focused on better understanding the differences in retention constructs by student nationality. Results from more than 600 engineering PhD students from 6 international regions enrolled in U.S. engineering graduate programs were examined to characterize demographic differences in participant responses for intention to complete the degree. Six constructs were found to be significant in predicting students' responses regarding their intention to complete their degree, including: expectations, climate, organization, project ownership, perception of value, and individual preferences. Taken together these constructs were able to explain 28 percent of the variation in student responses. Additionally, all six constructs showed significant differences with respect to a respondent's country or region or origin. These results are discussed in light of the implications for faculty members advising similarly diverse groups of students. In combination, these three studies represent a sequential exploratory mixed methods approach in which ethnographically guided observations and interviews were integrated into a quantitative instrument. Results of this study can be used to inform the organization and management of internationally diverse research groups to foster student development and ultimately increase retention. Ph. D.
- Published
- 2011
13. Loss of neuronal lysosomal acid lipase drives amyloid pathology in Alzheimer's disease.
- Author
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Barnett AM, Dawkins L, Zou J, McNair E, Nikolova VD, Moy SS, Sutherland GT, Stevens J, Colie M, Katemboh K, Kellner H, Damian C, DeCastro S, Vetreno RP, and Coleman LG Jr
- Abstract
Underlying drivers of late-onset Alzheimer's disease (LOAD) pathology remain unknown. However, multiple biologically diverse risk factors share a common pathological progression. To identify convergent molecular abnormalities that drive LOAD pathogenesis we compared two common midlife risk factors for LOAD, heavy alcohol use and obesity. This revealed that disrupted lipophagy is an underlying cause of LOAD pathogenesis. Both exposures reduced lysosomal flux, with a loss of neuronal lysosomal acid lipase (LAL). This resulted in neuronal lysosomal lipid (NLL) accumulation, which opposed Aβ localization to lysosomes. Neuronal LAL loss both preceded (with aging) and promoted (targeted knockdown) Aβ pathology and cognitive deficits in AD mice. The addition of recombinant LAL ex vivo and neuronal LAL overexpression in vivo prevented amyloid increases and improved cognition. In WT mice, neuronal LAL declined with aging and correlated negatively with entorhinal Aβ. In healthy human brain, LAL also declined with age, suggesting this contributes to the age-related vulnerability for AD. In human LOAD LAL was further reduced, correlated negatively with Aβ
1-42 , and occurred with polymerase pausing at the LAL gene. Together, this finds that the loss of neuronal LAL promotes NLL accumulation to impede degradation of Aβ in neuronal lysosomes to drive AD amyloid pathology., Competing Interests: Competing interests: The first and senior author are inventors on patent 5470.946.WO entitled: Targeting lysosomal lipid in Alzheimer’s disease. The first and senior author are inventors on patent 5470.946PR entitled: Targeting lysosomal lipid in Alzheimer’s disease.- Published
- 2024
- Full Text
- View/download PDF
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