VictorJuiz/thesis huggingface dataset:
Structural and Functional Characterization of FOXO3a in Transcription and Apoptosis
Keywords: FOXO3a
NMR
CBP/p300
p53
Apoptosis
Transcription

Forkhead box Class O (FOXO), one subfamily of the Forkhead box (Fox) family, which is featured by the Forkhead (FH) DNA-binding domain, includes four human transcription factors: FOXO1, FOXO3a, FOXO4, and FOXO6. The tumor suppressor FOXO3a is involved in multiple physiological and pathological processes, such as breast cancer and acute myeloid leukemia, and is related to human longevity. It plays essential role in metabolism, cell cycle arrest, DNA repair, and apoptosis. Besides the FH domain, FOXO3a contains three other regions (CR1-3), conserved within FOXO subfamily. It specifically binds a consensus Forkhead response element (FRE) DNA sequence through the FH domain, and recruits transcriptional coactivator CBP/p300 to activate gene transcription. FOXO3a functions through interacting with other proteins as well. FOXO3a binds p53 through the FH domain and the CR3 region, which are also engaged in an intramolecular interaction, and the solution structure of the former one was determined. This intramolecular interaction regulates coactivator recruitment and is disrupted by FRE DNA. A novel transactivation domain (TAD) CR2C was identified in addition to the known TAD CR3, both of which promiscuously associate with the KIX domain of CBP/p300 in equilibrium between two conformational states, the structures of which were determined by NMR spectroscopy. These two TADs of FOXO3a form additional multivalent binding to the TAZ1 and TAZ2 domains of CBP/p300, further increasing the promiscuity and complexity of the interaction. The coactivator recruitment is modulated by AMPK phosphorylation, which enhances the multivalent interaction between FOXO3a and CBP/p300, and thus the transactivation. These results indicate the significance of intrinsically disordered regions (IDRs) of FOXO3a in transcriptional activation and protein interaction, provide insight of the role of FOXO3a in gene transcription and apoptosis under various conditions, and potentially contribute to the cancer therapy.
Chemical, Isotopic, and Textural Characteristics of Diamond Crystals and Their Mineral Inclusions from A154 South (Northwest Territories), Lynx (Quebec), and Kelsey Lake (Colorado): Implications for Growth Histories and Different Mantle Environments
Keywords: diamond
mantle
carbon isotope
garnet
chromite
diopside
craton
nitrogen
secondary ion mass spectrometry
cathodoluminescence

Parcels of diamond crystals from the A154 South kimberlite diatreme, Northwest Territories (n=281), and the Lynx kimberlite dyke, Quebec (n=6598) were examined in terms of colour, size, morphology, and UV fluorescence (A154 South samples only). A subset of stones from each parcel (A154 South: n=60, Lynx: n=20) were cut and polished to expose internal zonation and mineral inclusions. Exposed primary mineral inclusions were quantitatively analyzed for major elements by EMPA. Diamond crystals from the Kelsey Lake kimberlite diatreme, Colorado (n=20), were cut into plates and analyzed for nitrogen aggregation states by FTIR. Twelve of these stones were then analyzed with further subsets from A154 South (n=18) and Lynx (n=16) for carbon isotope ratios and nitrogen abundances by SIMS. Every diamond crystal cut and polished had its internal zonation imaged with CL. Mineral inclusion data from A154 South and Lynx show that the mantle keel of the Slave craton is slightly less depleted than that of the Superior craton, and both are less depleted than those of the Kaapvaal and Siberian cratons. Equilibration conditions plot on hotter geothermal gradients (surface heat flows ~42 mW/m2) than for those of typical Archean cratons (≤40 mW/m2). Equilibration temperatures (~1150-1250°C) are ~100-200°C hotter than previously reported from Kelsey Lake (~1020°C). Kelsey Lake and A154 South samples have carbon isotope ratios and nitrogen contents typical of most diamond populations worldwide. Diamond crystals from Lynx are entirely different, consisting of mostly Type II diamond with δ13C (vs. PDB) values from approximately -3.6 ‰ to +1.7 ‰. These 13C-enriched samples are suggested to be the result of extreme Rayleigh fractionation of diamond from a carbonate fluid and possibly input of carbon sourced from subducted abiotic oceanic crust. Also notable is that growth trends (δ13C-[NT]) for most of the samples studied show little or no consistency with published fractionation models.
All is One: Towawrd a Spirtual Whole Life Education based on an Inner Life Curriculum
Keywords: Higher Self Yoga
Eastern Philosophy
Inner Life Wisdom
Self-transformation
Expansion of Aware Consciousness
Whole Life Education
Spirituality
Spiritual Heart
Spiritual Practices
Spiritual Whole Life Living
Agni Yoga
Theosophy
Western Intellectual Mind
African Philosophy
Egyptian Philosophy
North American Aboriginal Spirituality

The intent of this thesis is to understand how we as educators and learners in our Western system of education can bridge and heal the fundamental principles of a constructed divide embedded in our consciousness that continues to be reproduced in our Western academy. The primary goal is to make visible this divide that is based on the intellectualization of Western education in the absence of spiritual aspirations, thus revealing the potential of spiritual transformation within the academy and our everyday lives. In my literature-based thesis research I explored, analyzed and discussed two bodies of literature: the historical intellectualization of Western education on the one hand, and, on the other, Eastern Philosophy with the emphasis on Higher Self Yoga, African Philosophy and North American Aboriginal Spirituality. I investigated these bodies of literature employing a research paradigm that has its foundation in a spiritual ontology and epistemology. I analyzed my findings using such methodologies as appreciative inquiry, content analysis and textual analysis, including anti-colonial and indigenous knowledges theoretical frameworks. I found that the synthesis and integration of the inner life wisdom revealed in the three philosophies is an integral component fundamental toward a whole life vision of education, an educative vision that has the potential to serve as a catalyst to open the gates for life-enhancing change in the academy and our everyday lives. Change implies becoming aware of our true origin, who we truly are, and what our intrinsic purpose is. Change implies becoming aware of humanity’s accelerated transition toward a higher level of spiritual planetary consciousness, a spiritual evolution as an inner quest of unity with nature, the larger human community, the universe, and the divine Source itself. Change implies whole life educational processes, inclusive of the unfoldment of inner life wisdom, the authority of the human spirit, and the sense of divinity, as useful bridging work in healing the divide in our aware consciousness and our educational institutions. Whole life change needs to be the responsibility of academic education, as well our self-responsibility of realizing ourselves as citizen of the world living within one-world consciousness. All is one.
Attrition from Child/Youth Mental Health Treatment: The Role of Child Symptoms
Keywords: child mental health
service use
treatment drop out
attrition
mental health symptoms

This study examined the associations between social adversity, barriers-to-care (logistical obstacles, wait-time) and participation in children’s mental health treatment. The theoretical role of child symptoms (impact on the child, family burden) was addressed. Records were obtained for 1,963 parents who had accessed community-based care for their child (3-17 years). Data were collected as part of a provincial (Ontario, Canada) screening and outcome measurement initiative. The data were analyzed using multivariate logistic regression. Children with behavioural problems were at increased risk for attrition from treatment (OR=1.47, p < 0.001). The effect held upon controlling for age, gender, and co-morbid emotional symptoms; however, it was explained by child functional impairment. Similar effects were not found for the impact of symptoms on the family. Dropout was greater for adolescents (OR=1.43, p < 0.01) than younger children. Disadvantaged youth were more likely to drop out than more advantaged clients (OR=1.86, p < 0.001). Perceptions of difficulties in attending treatment were associated with a decreased risk (OR=0.89, p < 0.001). The adversity and service relationships were not mediated by child behavioural symptoms, functioning, or family burden. Waiting for care did not influence parent decisions to participate. Moderation analyses showed effects for adversity, service obstacles, emotional symptoms, functional impairment, and family burden for clients with behavioural problems. These children were more likely to drop out if they were socially disadvantaged, or had functional impairment at intake to services. However, completion was more likely for co-morbid children, and parental reports of burden. Families were also willing to overcome access difficulties in order to continue with treatment. There were few findings for children without behavioural problems. The results suggest a focus on other constructs, such as parent cognitions, that may link adversity and barriers with participation. The effects for symptoms as a moderator, suggests different levels of service provision based on sub-types of children. Efforts to engage “high-risk” clients are necessary. On the other hand, resources for intensive services would be appropriate for clients with more severe problems.
At the Bottom: Migrant Workers in the South Korean Long-term Care Market
Keywords: migrant workers
long-term care provision

This thesis explores Korean-Chinese migrant workers’ local experiences of the global phenomenon of international migration of care labour, focusing on how the care labour of migrant workers is being constructed through the intertwined social and political processes in South Korea’s shifting long-term care sector for the elderly. The thesis uses a qualitative case study method and relies on data collected through participant observation, interviews, and textual analysis during field research between November 2009 and May 2010. The analysis is based on a global economy of care framework, which understands care work as being made of products that are socially and politically constructed in the global processes. My study findings illuminate the roles and relations of the state, the employers, and the workers in producing a huge migrant workforce in South Korea’s segregated elder care labour market. The policy analysis at the intersection of elder care, labour market, and immigration policies shows that, over the last decade, the South Korean government has significantly reconstructed the boundaries of elder care work through the expansion of publicly-funded programmes for the elderly and the institutionalisation of care work in those programmes. In the institutionalisation process, the government’s ignorance about the care work performed in the private care sector has resulted in different regulations and working conditions for care workers in the publicly-funded versus the private sector. My empirical findings highlight how employers’ search for ‘cheap’ and ‘flexible’ labour and older female migrants’ disadvantageous status in the labour market have placed these workers in the less regulated private sector and their pay and working conditions at the bottom of hierarchical elder care workforce. In advocating for migrant care workers’ labour rights, this thesis challenges the current discriminative employment practices and the government’s lack of protection and regulation of care work in the private sector.
Seeking Connectivity: An Analysis of Relationships of Power from Staff Nurses' Perspectives
Keywords: nurse
power
relations
empowerment

Nurse empowerment is a well-researched area of nursing practice yet the quality of work environments continue to be eroded, and interactions between nurses and nurse managers continue to be fragile. Power is integral to empowerment, yet the exercise of power between nurses and their managers have been under-investigated in the nurse empowerment literature. To advance our knowledge in the empowerment literature, the study explored the process of how power is exercised in nurse-manager relationships in the hospital setting. Strauss and Corbin’s (1998) grounded theory methodology informed the study. Multiple qualitative fieldwork methods were utilized to collect data on staff nurses about how the manager’s role affected their ability to do their work. The researcher conducted semi-structured interviews and participant observations with 26 participants on three units within a tertiary hospital in Western Canada. Seeking connectivity was the basic social process in which nurses strive to connect with their manager to create a workable partnership in the provision of quality patient care while responding to the demands in the organizational context. Conditions, actions, and consequences formed the theory of seeking connectivity as an extension of nurse empowerment theory. The overarching finding is that the manager plays a critical role in modifying the work environment for nurses and as such, nurses seek connection with their manager to accomplish their work. Institutional policies and practices combined in various ways to influence nurses’ thinking and shaped their actions. The first pattern of the process was characterized by the absence of meaningful engagement with the manager. Power was held over nurses restricting discussions with the manager, and nurses employed a variety of resistance strategies. In the second pattern of the process when managers provided guidance, advocated for nurses, and engaged nurses as collaborators, nurses were better able to problem solve and make decisions with the manager to positively influence patient outcomes. The theory of seeking connectivity is the explanatory framework emerging from the study that reveals how power is exercised in social relations between nurses and managers. Seeking connectivity is a recursive process that continues to evolve. The results of this study advance nurse empowerment primarily from a structural perspective and secondarily from a critical social perspective, suggesting nurses’ perceptions and abilities shape their work role and are foundational to promoting change through collective action. Study implications for research, practice and policy are addressed.
Assessment for Early Cardiovascular Risk in Pediatric Rheumatic Disease
Keywords: rheumatic disease
pediatrics
atherosclerosis
vascular function
lipids

Objectives: 1) Evaluate the risk of atherosclerosis in rheumatic disease compared to healthy controls; 2) Assess the lipid profile of children with systemic lupus erythematosus (SLE) at presentation before treatment with corticosteroids; 3) Compare the lipid profiles of children with juvenile dermatomyositis (JDM), systemic juvenile idiopathic arthritis (SJIA), and SLE; 4) Evaluate the extent of early atherosclerosis in children with JDM, SJIA, and SLE; 5) Investigate the progression of early markers of atherosclerosis in children with SLE. Methods. The methods include a systematic review, a cross sectional study of serum lipid levels of a cohort of children with SLE, an analysis of the first time point of a prospective study of cardiovascular disease risk factors and vascular function measures of a cohort of children with JDM, and SJIA, and SLE and a longitudinal study of vascular function measures of a prospective study of a cohort of children with SLE. Results. Our systematic review demonstrated that carotid intima media thickness (CIMT), a surrogate marker of early atherosclerosis, was significantly increased in rheumatic disease populations. We found that newly diagnosed children with SLE before corticosteroid treatment exhibited a pattern of dyslipoproteinemia of increased triglycerides and depressed HDL-cholesterol. When we measured the lipid profiles in children with the rheumatic diseases of JDM, SJIA, and SLE, one third of children had at least one abnormal lipid value. The most common abnormalities were found for total cholesterol and triglyceride levels and most often in children with JDM. One quarter of all patients were found to have insulin resistance. Lastly, when we considered the effects of treatment in children with SLE, we found that improvement in CIMT was possible and it correlated with a higher cumulative dose of prednisone over the study period. Conclusions. Early markers of atherosclerosis in pediatric rheumatic disease are important for determining the risk of these children in developing heart disease as young adults. Chronic inflammation plays a significant role and should be considered an important predictor of premature atherosclerosis.
Detergents as Membrane-mimetic Media for Structural Characterization of Membrane Proteins
Keywords: membrane proteins
detergents
protein folding
peptides
designed proteins
spectroscopy
transmembrane segments
detergent-protein interactions

Membrane proteins are essential cellular components, responsible for a wide variety of biological functions. In order to better understand such aspects of cell activity, researchers have pursued detailed structural analysis of this class of proteins. Because of the complexities in isolating and studying membrane proteins in their native environment, detergents are often employed as a membrane mimetic media. This thesis examines several features of transmembrane (TM) protein structure and folding in detergents through which we are able to gain insights into membrane protein folding, as well as explore the suitability of detergents as membrane-mimetic environments. We first compare the helix-helix association of a series of model TM sequences in a native bilayer to the corresponding association in a detergent environment. We find that while various classes of helix-helix interaction motifs are preserved in detergents, alterations in detergent solvation may, in turn, lead to altered association affinity. We further explore this phenomenon through investigation of the consequences of the insertion of a strongly polar residue into a TM segment. In these studies we find a correlation between sequence-dependent alterations in detergent solvation and predicted in vivo folding. We also extend such analyses to a variety of detergents and native TM segments, finding that native secondary structure, as it occurs in the context of a full-length protein, is generally well preserved in a variety of detergents. Finally, we assess the determinants of membrane protein folding using two-transmembrane segment constructs, in the process optimizing expression, production and characterization techniques for a diverse range of transmembrane protein sequences. Overall this thesis finds that, detergents are capable of solubilizing membrane proteins in a form suitable for in-depth structural characterization that may not be feasible in other environments. Thus, as an approximation of a native membrane, detergents are able to preserve certain features of membrane proteins such as helix-helix association and native secondary structure.
The Adaptive Role of Neuronal Nitric Oxide Synthase in Maintaining Oxygen Homeostasis during Acute Anemia
Keywords: Anemia
Hypoxia
Hemoglobin
Neuronal nitric oxide synthase
Cardiovascular
Knockout mice
Hypoxia-inducible factor
S-nitrosylation

Mammals are well adapted to respond to changes in ambient oxygen concentration (O2) by activating homeostatic physiological and cellular responses which maintain cell function and survival. Although anemia has been associated with increased mortality in a number of clinical settings, surprisingly little is known about how anemia affects tissue PO2 and hypoxia signaling. Because nitric oxide synthases (NOSs) figure prominently in the cellular response to acute hypoxia, we define the effects of NOS deficiency in acute anemia. Unlike wildtype (WT), endothelial NOS (eNOS) and inducible NOS (iNOS) deficient mice, only neuronal NOS (nNOS) deficient mice (nNOS-/-) demonstrated increased mortality during acute anemia. With respect to global tissue O2 delivery, anemia did not increase cardiac output (CO) or reduce systemic vascular resistance (SVR) in nNOS -/- mice. At the cellular level, anemia increased expression of HIF-1α and HIF-responsive mRNA levels (EPO, VEGF, GLUT1, PDK) in the brain of WT, but not nNOS-/- mice. These date suggest that nNOS contributed to cardiovascular and cellular mechanisms which maintain oxygen homeostasis in anemia. To confirm the physiological relevance of these findings in a whole animal model of anemia, we utilized transgenic animals which express a reporter HIF-α(ODD)-luciferase chimeric protein. Using this model, we confirmed that nNOS is essential for anemia-induced increases in HIF-α protein stability in vivo in real-time whole animal images and brain tissue. With respect to the mechanism, nNOS-derived NO is known to affect S-nitrosylation of specific proteins, which may interfere with HIF-α and von Hippal Lindau protein (pVHL) interaction. Utilizing the biotin switch assay, we demonstrated that anemia caused a time-dependent increase in S-nitrosylation of pVHL in brain tissue from WT but not nNOS-/- mice. In addition, anemia also leads to a decrease in S-nitrosoglutathione (GSNO) reductase protein expression, an important enzyme responsible for de-nitrosylation of proteins. The combination of increased nNOS expression and decreased GSNO reductase expression would favor prolonged S-nitrosylation of proteins during anemia. These findings identify nNOS effects on the HIF/pVHL signaling pathway as critically important in the physiological responses to anemia in vivo. By contrast, after exposure to acute hypoxia, nNOS-/- mice survived longer, retained the ability to regulate CO and SVR, and increased brain HIF-α protein levels and HIF-responsive mRNA transcripts. This comparative assessment provided essential mechanistic insight into the unexpected and striking difference between anemia and hypoxia. Understanding the adaptive responses to acute anemia will help to define novel therapeutic strategies for anemic patients.