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Thesis advisor: Eranthie Weerapana / Reactive oxygen species (ROS) modulate protein function through cysteine oxidation. Identifying protein targets of ROS can provide insight into uncharacterized ROS-regulated pathways especially within ROS generating organelles such as the mitochondria. There are several known examples of mitochondrial cysteine targets that alter protein and pathway activity resulting in pathological effects. Several chemoproteomic workflows, including ABPP and OxICAT, can be used to identify sites of cysteine oxidation. However, determining ROS targets localized within subcellular regions and ROS hotspots remains challenging with existing workflows. Here, we present combined cysteine- monitoring chemoproteomic platforms (isoTOP-ABPP and OxICAT) with mitochondrial enrichment (organelle isolation and proximity labeling) to monitor cysteine oxidation events within the mitochondria. First, we profile redox- sensitive cysteines under exogenous and endogenous peroxide in isolated mitochondria using isoTOP-ABPP and OxICAT. Next, we introduce PL-OxICAT which combines enzymatic proximity labeling (PL) (TurboID/APEX) and OxICAT to monitor localized cysteine oxidation events within subcellular compartments such as the mitochondrial matrix and intermembrane space as well as ROS hotspots. Together, these platforms further hone our ability to monitor cysteine oxidation events within specific subcellular locations and ROS hotspots and provide a deeper understanding of the protein targets of endogenous and exogenous ROS. / Thesis (PhD) — Boston College, 2022. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.

Past research demonstrates that participants who label themselves as ‘victims' experience worse trauma-related outcomes than those who label themselves as ‘survivors.' Self-labeling in trauma research is typically measured using a dichotomous measure where participants choose either victim or survivor, but this construct may be better conceived as more continuous. The current study assessed self-labeling as a possible continuous construct and explored its predictive validity. To capture self-labeling as a continuous construct, we created and utilized a new scale, the Trauma Self-Labeling Measure. Two hundred eleven participants completed a battery of questionnaires to measure self-labeling and four trauma-related outcomes: posttraumatic stress symptoms (PTSS), depression, anxiety, and resilience. When tested on the continuous trauma self-labeling measure, an overwhelming number of participants chose in-between victim and survivor (78.9%) which suggests self-labeling is better assessed using a continuous measure than dichotomous. However, correlation analyses revealed that the continuous self-labeling measure was not significantly correlated to the four trauma-related outcomes, whereas the dichotomous self-labeling, continuous victim, and continuous survivor measures were. When conducting post-hoc analyses, we found an unexpected positive correlation between the continuous victim and survivor self-labeling measures. This unexpected positive correlation suggests that self-labeling is not a singular construct, as previously assumed, but rather is composed of separate victim and survivor constructs. In conclusion, the current study provides the first empirical evidence to support the idea that self-labeling is more continuous than dichotomous and composed of two separate constructs of victim and survivor.

Glycans are macromolecules that contain several classes. Glycans can play an important role in biological activities. Studying the cell surface glycans can provide a very powerful way to understand the fundamental process. Also it could help to regulate expected cell response. Thus it is very necessary to have a method to detect cell- surface glycans efficiently. An efficient method for glycan detection is necessary. Metabolic glycan labeling and chemoenzymatic glycan labeling are most commonly used. Chemoenzymatic glycan labeling is a rapid and sensitive method which also has high specificity. This method can be applied in both vitro and vivo. However the availability of unnatural sugar nucleotides functioned by bioorthogonal groups is the main limitation for chemoenzymatic labeling. In this thesis, UDP-GlcNAc and UDP-GalNAc derivatives were prepared for further chemoenzymatic labeling by using chemoenzymatic synthesis method.

Arterial spin labeling é uma técnica completamente não invasiva que permite o monitoramento quantitativo da perfusão cerebral e, juntamente com outras técnicas de ressonância magnética, tem se estabelecido como uma excelente ferramenta para estudos relacionados à hemodinâmica e problemas vasculares cerebrais. Dentre as possíveis implementações da técnica, a abordagem contínua, combinada a uma bobina de marcação dedicada, apresenta algumas vantagens com relação à relação sinal-ruído e à deposição de potência de RF. No presente trabalho, estas vantagens foram exploradas na implementação de uma metodologia que permite a obtenção de mapas quantitativos de fluxo sanguíneo cerebral, bem como dos territórios vasculares das principais artérias suprindo o cérebro. Os resultados obtidos em humanos e animais revelam a robustez e aplicabilidade da técnica em estudos da hemodinâmica cerebral. Aplicações em hipertensão comprovam que a técnica é capaz de fornecer informações que podem auxiliar na compreensão de diferentes patologias. A implementação da variante dinâmica da técnica ASL demonstra a versatilidade da metodologia fornecendo ferramentas para uma maior compreensão das características espaciais e temporais da hemodinâmica cerebral. Os resultados demonstram isto tanto em condições de fluxo sanguíneo basal como em hiperemia causada por estímulos funcionais. / Arterial spin labeling techniques allow to obtain quantitative maps of perfusion non-invasively. Along with other MRI techniques, it has proven useful for diagnosis of a variety of cerebrovascular diseases. Amongst the available basic implementations, the continuous approach employing a dedicated labeling RF coil has the advantages of presenting high signal-to-noise ratio and lower RF power deposition. In the present work, these advantages were explored in order to implement a methodology to obtain quantitative maps of cerebral blood flow and the vascular territories of the major cerebral feeding arteries. Human and animal results reveal the robustness and applicability of the technique in cerebral hemodynamic studies. Applications in hypertension show that the technique can provide complimentary information to improve the understanding of neurovascular diseases. The dynamic ASL technique shows the method versatility for studying the spatial and temporal characteristics of cerebral hemodynamics. The results unravel that both under basal and functional hyperemia conditions.

A hipertensão arterial é uma doença que aflinge mais de um quarto da população adulta mundial e mais da metade da população idosa. Ela é o principal fator de risco para doenças cerebrovasculares e o segundo fator de risco, após idade, para os acidentes vasculares cerebrais (AVC) hemorrágico e isquêmico. É também a principal causa de declínio cognitivo e demência, incluindo a doença de Alzheimer. A hipertensão causa remodelamento vascular e modifica os mecanismos de regulação do fluxo sangüíneo cerebral, incluindo a hiperemia funcional, a autoregulação cerebrovascular e a regulação endotelial. Portanto, pesquisas contínuas sobre os efeitos da hipertensão na função cerebrovascular são cruciais para o desenvolvimento de terapias preventivas que objetivam minimizar os riscos de desenvolvimento de doenças cerebrovasculares. No presente estudo, a perfusão cerebral de um importante modelo experimental de hipertensão, o rato SHR (do inglês spontaneously hypertensive rat), foi avaliada utilizando as técnicas de arterial spin labeling (ASL), que permitem a quantificação não-invasiva da perfusão. Utilizando o método de ASL contínua, o fluxo sangüíneo cerebral foi quantificado para todo o cérebro do rato sob condições de normocapnia e hipercapnia. Resistência cerebrovascular aumentada e reatividade vascular ao CO2 reduzida foram observadas em SHR adultos, confirmando que a hipertensão leva à redução progressiva da capacidade de dilatação da vasculatura cerebral. A técnica de ASL dinâmica permitiu medir o fluxo sangüíneo cerebral funcional evocado por estimulação somatosensorial. Além de apresentarem resposta hemodinâmica positiva à estimulação, os ratos hipertensos também apresentaram resposta hemodinâmica negativa em áreas circundantes àquelas ativadas positivamente. Foi mostrado que esse resultado está relacionado com um efeito puramente hemodinâmico causado pela pressão arterial elevada e pela reserva vascular alterada do SHR. Experimentos farmacológicos mostraram diferenças na modulação do acoplamento neurovascular de SHR quando comparado com rato normotenso. Além disso, SHR submetidos à oclusão temporária da artéria cerebral média apresentaram maior volume da lesão isquêmica e do edema cerebral, redução severa da massa corporal e déficits neurológicos piores do que ratos normotensos. Esses resultados estão relacionados à autoregulação cerebral alterada e ao desenvolvimento prejudicado da circulação colateral em SHR. Em suma, os achados do presente estudo mostraram que a hipertensão resulta em reserva vascular prejudicada, acoplamento neurovascular alterado e piores conseqüências a um AVC isquêmico. / Hypertension is a disease that afflicts more than a quarter of the general population and more than half of the elderly population. It is the most important modifiable risk factor for cerebrovascular diseases and the second most important risk factor, after age, for hemorrhagic and ischemic stroke. It is a leading cause of cognitive decline and dementia, including the Alzheimer\'s disease. Hypertension causes vascular remodeling and modifies the intricate mechanisms of cerebral blood flow (CBF) regulation, including functional hyperemia, cerebrovascular autoregulation, and endothelial regulation. For all of the above, continued research on the effects of hypertension on cerebrovascular function is a crucial step in the design of preventive therapies aimed at minimizing the risk of development of cerebrovascular disease. In the present work, cerebral perfusion of an important experimental model of hypertension, the spontaneously hypertensive rat (SHR), was evaluated using the arterial spin labeling (ASL) techniques, which allow non-invasive quantification of perfusion. Using continuous ASL, CBF was quantified for the whole rat brain under normocapnic and hypercapnic conditions. Increased cerebrovascular resistance and decreased vascular reactivity to CO2 were observed in adult SHR, confirming that hypertension leads to reduced compliance of the cerebral vasculature. The dynamic ASL technique allowed the measurement of functional CBF evoked by somatosensorial stimulation. Hypertensive rats not only showed positive hemodynamic response to stimulation, but also negative hemodynamic response in areas surrounding the positively activated areas. It was shown to be related to a purely hemodynamic effect caused by high blood pressure and impaired vascular reserve of the SHR. Pharmacological experiments showed differences on modulation of the neurovascular coupling in SHR when compared to normotensive rats. Moreover, hypertensive rats subjected to temporary middle cerebral artery occlusion had larger ischemic lesion volume and brain edema, severe decrease in body weight and worse neurological deficits, when compared to normotensive rats. These results are related to the altered cerebral autoregulation and impaired collateral circulation development in SHR. Taken together, the findings of the present work show that hypertension results in impaired vascular reserve, which is related to altered neurovascular coupling and worse stroke outcome.

published_or_final_version / Public Health / Master / Master of Public Health

Conventionally, efforts of combating climate change mainly focus on reducing emissions at production sources, such as factories, offices or other organizational-based entities. While this approach has served its purposes for years, the environmental impacts of consumer goods, which cause cross-border carbon emission are very difficult to be managed. This study investigated the feasibilities of an alternative solution to combat climate change using the concept of product carbon footprint (PCF) labelling in Hong Kong. PCF describes the total set of greenhouse gases caused by a product over its whole life cycle, from raw material extraction to disposal. The concept of PCF is prevalent in regions such as Europe, Japan and Taiwan, where PCF information is shown as labels on products’ packaging to help consumers distinguish more eco-friendly products. These PCF labels, based on overseas pioneer experience, have shown enormous market potential and environmental benefits. Hong Kong has yet to establish such labelling system despite these benefits. The aim of the study is to investigate the feasibilities of introducing PCF labelling in Hong Kong and identify the opportunities and difficulties lie ahead. Five main types of feasibilities, namely technical, economic, legal, operational and scheduling feasibilities were considered in the study and in-depth review was carried out on each one. Literature review, questionnaire for general public and interviews with stakeholders were undertaken to understand existing PCF labelling schemes and obtain first-hand information from stakeholders of different perspectives. By analyzing the questionnaire and interview results, the study revealed that short-term feasibilities of introducing PCF labelling in Hong Kong is medium. Recommendations were made in accordance to each type of feasibilities to promote the wider adoption of PCF labelling in the future. / published_or_final_version / Environmental Management / Master / Master of Science in Environmental Management

Teenagers are not yet fully developed, creating their self-identity, full of aspiration, and exploring their world through sometimes harmless acts. While it has long been acknowledged that delinquency can lead to a life of crime, criminologists vary on whether a criminal disposition is caused by internal and/or external forces. Labeling theory suggests it could be the negative labels placed upon youth that could inhibit future aspirations more so than the delinquent acts themselves. Using data from the National Youth Survey, this study examines the influence of negative labeling by significant others on educational aspirations among youth with varying levels of educational achievement. These analyses use the third wave of the National Youth Survey dataset when the respondents were teenagers, aged 13-19, as well as the fifth wave, two years later, to examine the internalization of negative labels and the transformative effects on self-identity and educational aspirations. Ordinary Least Squares (OLS) regression models show statistically significant relationships between negative labeling by significant others (teachers, parents, and friends) and lowered educational aspirations net of delinquency. Specifically, negative labeling by teachers has the most profound effect upon low achievers, while negative labeling by parents and friends has the greatest impact on middle achievers. Implications are discussed.

The purpose of this study is to assess the need for menu labeling of calories based on the ability of food consumers to identify lower calorie options. By surveying consumers in Kentucky and Ohio and health professionals in Kentucky about their awareness of caloric content, basic nutrition knowledge and ability to choose lower calorie options, we can predict the potential benefit of menu labeling initiatives and the amount of education that will be necessary for consumers to effectively use menu labeling to make informed decisions on calorie intake. Through online surveys, it was determined that consumers were better able to predict calorie levels of foods at common quick serve restaurants, compared to health professionals. Health professionals are more knowledgeable about daily calorie requirements and more likely to change their quick serve food order with calorie labels. Health professionals and consumers dining out 3-5 times per month were better able to determine low calorie options and daily calorie requirements. These findings suggest that show that health professionals are in no better able to predict calorie levels at restaurants. Furthermore, nutrition education is necessary to aid in the use of menu calorie labeling for consumers.