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INDIVIDUAL ATTITUDES, SOCIAL NORMS, DEVIANCE, AND CONTRACEPTIVE USE IN BURKINA FASO
Get PDFBackground:
Research has demonstrated that shifting family planning-related social norms to create supportive environments can improve free, informed, and voluntary contraceptive choice. However, questions remain around whether addressing social norms alone is sufficient since women’s attitudes are an important factor in decision-making, and deviants who go against social norms could represent examples of women exerting agency. In this dissertation, I explore the environments associated with family planning-related social norms and examine the relationship between those norms, individual attitudes, and modern contraceptive use.
Methods:
Data came from the Performance Monitoring for Action (PMA) survey. I utilized cross-sectional data to measure community social norms and panel data to explore the relationship between norms, attitudes, and contraceptive use. I used responses to questions on three family planning-related attitudes to operationalize the measurement of social norms. I used nested Likelihood Ratio tests to explore the environments related to collective and perceived norms (Aim 1). Next, I used panel data and mixed multilevel logistic regressions to compare the individual associations between collective and perceived norms and modern contraceptive use (Aim 2) and then to investigate the relationship between personal attitudes, collective and perceived norms toward extramarital family planning, and contraception use and to identify the effect of deviance on contraceptive use (Aim 3).
Results:
Collective and perceived norms frequently were discordant in communities, and the sociodemographic correlates of positive and negative norms differed by whether norms were operationalized as collective or perceived. Their operationalization, the attitudes used to construct the norms, and the studied population impacted the relationship between norms and contraceptive use. Finally, collective norms toward extramarital family planning were more influential in the decision to use a contraceptive method than individual attitudes, and positive deviance was not associated with a change in the strength of the effect of individual attitudes on contraceptive decision-making.
Conclusion:
Findings confirmed previous social norms research, which demonstrated a relationship between collective social norms and contraceptive use. Programs that aim to increase voluntary and informed contraceptive use should ensure that community norms create environments where women feel comfortable deciding to use a contraceptive method if they so choose
INQUIRING MINDS WISH TO KNOW ESSAYS ON SOCIETY, SCIENCE, AND THE HUMAN EXPERIENCE
No full textStories are important. What stories we tell, who we tell them to, and how we tell them shape our worlds. Everywhere you look, from the stars to the cityscape, and in every topic, from the mundane to the taboo, there are stories.
Without intending to, I spent three years writing mostly about social taboos. Amongst those taboos I found things that are lovely, enticing, and funny. The topics in the pieces collected here include mental health, grief, death, body modification, abortion, and alcohol. Even the milder essays include topics that would once have been taboo, like being a woman in the trades.
Stories are an act of love. You have to fall in love with what you are writing about to produce the writing. And there is so much in this lifetime to fall in love with. This collection of essays, articles, and a script, is my attempt to show you a few
REGULATION OF CELLULAR STRESSES IN YEAST CELLS BY CALCINEURIN
Get PDFCalcineurin is a conserved Ca2+/calmodulin-dependent protein phosphatase. Originally identified for its abundant expression neurons, calcineurin has a well-defined role in activating T-cells and the adaptive immune response. Two inhibitors of calcineurin, FK506 and cyclosporin A, are immune-suppressive drugs. Due to its conserved nature, calcineurin has been well studied in yeasts, with identified roles in ion homeostasis, cell wall integrity, and ER stress. Pathogenic yeasts rely on calcineurin for successful survival, invasion, and proliferation in host tissues. Furthermore, calcineurin also enables tolerance of antifungal drugs. Due to its key function in both pathogenicity and drug tolerance, calcineurin is an ideal target to control invasive fungal infections. Therefore, it is imperative to better understand the roles calcineurin plays in the fungal cell.
In Chapter Two, I present published work in which I adapt a transposon mutagenesis screen developed in the lab. Complex pools of transposon insertion mutants in the pathogen Candida glabrata were treated with the calcineurin inhibitor FK506 to screen for genetic stresses that force reliance on calcineurin. I found that calcineurin plays compensatory roles in a variety of endomembrane and vesicle trafficking mutants. Calcineurin enables cells to tolerate stresses in the ER caused by inhibition of N-glycosylation and GPI-anchor biosynthesis. Calcineurin regulates expression of a supplemental set of genes encoding cell wall enzymes that mediate stresses to the cell wall.
In Chapter Three I describe an ongoing, unpublished study of the regulation of ceramide synthesis in the model yeast Saccharomyces cerevisiae. The redundant ceramide synthase (CerS) proteins are regulated by calcineurin and CK2. Excess ceramide is damaging to biological membranes. Therefore, we have developed a hypothesis that a key function of calcineurin is to attenuate the cytotoxic accumulation of ceramide during ER stress. I as well as former graduate students in the lab demonstrate that accumulation of ceramides is toxic to the cell, while chemical inhibition of ceramide synthesis protects cell viability. Genetic mutation of CerS and the deletion of effector genes CKA2 and SVF1 eliminates calcineurin regulation of cell fate. Finally, we demonstrate that calcineurin directly dephosphorylates CerS proteins in ER stress, establishing a likely mechanism of regulation
On the Diagnosis and Generalization of Compositional Visual Reasoning
Get PDFComputer vision is not only about recognizing visual signals, but also rea- soning over perceived visual elements. This ability, termed visual reasoning, is typically studied by multimodal tasks like visual question answering and image captioning. Thanks to recent developments in multimodal vision-and- language, we are closer to achieving visual reasoning than ever. However, more efforts are still required, in order to build visual reasoning systems that are robust, interpretable and generalizable.
In this dissertation, I present my efforts towards visual reasoning, through both model diagnosis and enhancements. In the first part, I diagnose existing visual question answering models, including the end-to-end models and com- positional models, and show the advantage of the latter. In the second part, I dive deeper into compositional models, proposing techniques for enhancing them with improved performance on real-world images. In the third part, I generalize visual reasoning onto a different task, image captioning, introduc- ing a new setting of the task that requires strong reasoning to summarize and compare groups of images. With this dissertation, I showcase the advantages and disadvantages of compositional visual reasoning methods, which should be pursued in conjunction with non-compositional end-to-end models
Investigating the Impact of Confinement on Collectively Migrating Cancer Cells
No full textCancer metastasis is responsible for over 90% of all cancer-related deaths. The metastatic cascade is a multifaceted and complex biological process in which tumor cells acquire phenotypic changes enabling them to migrate from a primary tumor and traverse diverse physiological hurdles to form new metastases in distant tissues and organs. Classical depictions of the metastatic cascade portray single tumor cells departing from a primary tumor and embarking on an arduous journey to form new metastatic colonies. While this depiction is partly true, it fails to consider the contribution of collectively migrating circulating tumor cell (CTC) clusters in tumor invasion, progression, and metastasis. Collectively migrating CTC clusters have been detected in the blood of lung cancer patients, have demonstrated increased resistance to chemotherapeutics, and exhibit a high correlation to poor patient prognosis, thereby suggesting the critical contribution of collective migration in tumor cell dissemination and metastatic spread.
In vivo, metastatic cancer cells must travel through 3-dimensional (3D) fiber-, pore-, and channel-like tracks to form metastases, and these 3D tracks can range from a highly confining 3 m in width to a less confining 30 m in width, and between 100 m and 600 m in length. To recapitulate this environment for in vitro studies, we utilized bioengineering principles and a novel polydimethylsiloxane (PDMS) microfluidic system equipped with an array of confining microchannel through which cells migrate. Using this system, we can directly observe and probe the mechanisms by which cancer cells migrate collectively in confining spaces. Our findings suggest a mechanism whereby confinement of collectively migrating tumor cells leads to elevated RhoA activity and myosin IIA (MIIA) contractility resulting in leader cell dissociations from collectively migrating tumor cell strands. Furthermore, our studies indicate that nuclear dynamics are tightly implicated in this process. Collective cell migration into confining microchannels promotes linker of nucleoskeleton and cytoskeleton (LINC) complex-facilitated leader cell nuclear area expansion. This increase in leader cell nuclear area triggers the cPLA2 signaling pathway promoting downstream RhoA activity, myosin II contractility, and leader cell dissociations from collective strands
Psychosocial factors and HIV care engagement among adolescents and young adults living with HIV in Akwa Ibom and Cross River states, Nigeria
Get PDFAdolescents and young adults ages 15-24 are a priority population for HIV epidemic control in sub-Saharan Africa given their lower engagement across the HIV care cascade. Currently, there is limited understanding of the extent to which existing measures of social support are salient in this population and whether social support protects against HIV care disengagement over time. To address this gap, this dissertation research uses quantitative and qualitative data to explore psychosocial factors related to HIV care engagement in a sample of adolescents and young adults living with HIV in southeastern Nigeria. Chapter 4 explores the construct validity of the Medical Outcomes Study Social Support Survey (MOS-SSS) and examines its relationships with conceptually related psychosocial factors. Analyses yielded mixed findings, with some evidence for good model fit, and weaker-than-expected associations with depression symptoms and social isolation. Chapter 5 uses social support scores calculated in Chapter 4 and examines social support as a hypothesized protective factor against HIV care disengagement using longitudinal data, finding that social support did not predict HIV care disengagement over time in primary analyses. Secondarily, Chapter 5 examines three other psychosocial factors – social isolation, internalized stigma, and positive ART beliefs – finding that all three measures acted as risk or protective factors against HIV care disengagement. Chapter 6 expands on Chapter 5 by using qualitative data to explore a subset of participants’ lived experiences and sense of self while navigating their first year of HIV care. Participants described complicated experiences including feelings of isolation and concerns about disrupted future goals when learning their status, navigating HIV care largely in isolation, and a restored sense of normalcy upon connecting with others living with HIV and role models for a positive future. Taken together, this research furthers our understanding of social support measurement in a high priority population for HIV epidemic control, identifies potentially modifiable predictors of HIV care engagement for consideration in future research, and adds to a growing body of literature about experiences of isolation, difference, and re-establishing normalcy as salient elements of navigating life with HIV globally
CYTOPLASMIC ACCUMULATION AND PLASMA MEMBRANE ASSOCIATION OF ANILLIN AND ECT2 PROMOTE CONFINED MIGRATION AND INVASION
No full textCells migrating in confinement experience mechanical challenges whose consequences on cell migration machinery remain only partially understood. Here, we demonstrate that a pool of the cytokinesis regulatory protein anillin is retained during interphase in the cytoplasm of different cell types. Confinement induces recruitment of cytoplasmic anillin to plasma membrane at the poles of migrating cells, which is further enhanced upon nuclear envelope (NE) rupture(s). Rupture events also enable the cytoplasmic egress of predominantly nuclear RhoGEF Ect2. Anillin and Ect2 redistributions scale with microenvironmental stiffness and confinement, and are observed in confined cells in vitro and in invading tumor cells in vivo. Anillin, which binds actomyosin at the cell poles, and Ect2, which activates RhoA, cooperate additively to promote myosin II contractility, and promote efficient invasion and extravasation. Overall, our work provides a mechanistic understanding of how cytokinesis regulators mediate RhoA/ROCK/myosin II-dependent mechanoadaptation during confined migration and invasive cancer progression.
In addition to mesenchymal of bleb-based migration, cells can utilize a third migration mode in confing channel, which used water intake at the cell front and water extrusion at the cell rear to propel the cell forward, called osmotic engine migration (OEM). This water influx and efflux is facilitated by aquaporins and Na+/H+ exchanger (NHE1) at the leading edge and volume-regulated anion channel LRRC8A (SWELL1) at the trailing edge. Through mass spectrometry and co-immunoprecipitation, we discovered a novel interaction between SWELL1 and calponin-2, a mechanosensitive myosin regulator and actin stabilizer
THE ROLE OF N-TERMINAL PHOSPHORYLATION OF DGK-θ
Get PDFDiacylglycerol kinases (DGKs) are lipid kinases that mediate the phosphorylation of diacylglycerol (DAG) leading to the production of phosphatidic acid (PtdOH). In this dissertation, we first developed a new enzyme activity assay for DGKs which utilizes fluorescent labeled NBD-DAG (1-Oleoyl-2-[12-[(7-nitro-2-1,3-benzoxadiazol-4-yl) amino] dodecanoyl]-sn-Glycero-3-diacylglycerol) to quantify the DGK-catalyzed conversion of NBD-DAG to NBD-PtdOH.
While there are considerable data regarding the physiological roles of DGKs, our understanding of the mechanisms involved, how post-translational modification such as phosphorylation regulate the enzymatic activity and membrane binding of the enzyme is more limited. This is especially true for the lone Type V DGK, DGK-θ. To figure out the role of phosphorylation on DGK-θ, we identified the phosphorylated sites on endogenous DGK-θ from mouse brains and found four sites: S15, S17, which we refer to phosphomotif-1 sites, and S22 and S26 which we refer to as phosphomotif-2 sites. This study focused on the roles of these phosphorylated sites on enzyme activity, membrane binding, thermal stability, and cellular half-life of DGK-θ. After generating a construct devoid of all non-catalytic phosphorylation sites (4A) we generated other constructs to mimic phosphorylation of these residues by mutating them to glutamate (E). Our data demonstrate that an increase in membrane affinity requires the phosphorylation of all four endogenous sites as the phosphomimetic 4E, but not other phosphomimietics, leads to a decrease in the KD of membrane binding. Further, 4E also shows an increase in basal activity, as well as an increase in the Syt1-induced activity compare to 4A. It is noteworthy, that these phosphorylations had no effect on the thermal stability or cellular half-life of this enzyme. Interestingly, when only one phosphorylation domain (phosphomotif-1 or phosphomotif-2) contained phosphomimetics (S15E/S17E or S22E/S26E), the basal activity is also increased but membrane binding was not affected. Furthermore, when only one residue in each domain mimicked an endogenous phosphorylated serine (S15E/S22E or S17E/S26E), the Syt1-induced activity as well as membrane binding affinity decreased relative to 4A. These results indicate that these endogenous phosphorylation sites contribute differentially to membrane binding and enzymatic activity
Oral History of Rahne Alexander
No full textThis oral history about transgender experience in Baltimore was recorded as part of Vintage T, a public humanities project led by Monica Stevens, Jamie Grace Alexander, and Rahne Alexander and sponsored by Sistas of the “T” and the Winston Tabb Special Collections Research Center. Vintage T was launched in 2023 to document and archive the perspectives, strategies, and personal histories of trans individuals in Baltimore, thereby preserving valuable traditions within trans communities
Systems Biology Modeling of Complex Cellular Signaling Networks in Human Diseases
Get PDFMany biological processes are regulated by complex chemical and molecular reaction networks formed by intracellular and intercellular signaling networks. Quantitatively characterizing the molecular control of these signaling networks is crucial to understanding the mechanisms of the related diseases and discovering therapeutic strategies targeting these networks. In this dissertation, I use mechanistic systems biology models of complex signaling networks and apply them in the context of peripheral arterial disease, cancer, and sickle cell disease to gain insight into their molecular mechanisms and investigate potential therapeutic strategies in silico.
Peripheral arterial disease affects the lives of hundreds of millions of patients worldwide. To investigate potential therapeutics that can promote the growth of stable vasculature, I construct systems biology models of the endothelial cell signaling pathways and the signaling network formed by them to obtain mechanistic understanding of the molecular control of vascular growth and stability. To address the limited antitumor efficacies and response rates of anti-angiogenic and immunomodulatory drugs in cancer and facilitate translational drug developments, I develop quantitative systems pharmacology models of angiogenesis-driven tumor growth and the cancer immune cycle. The models are used to simulate antitumor efficacies of drug combinations in pre-clinical models of cancer. In sickle cell disease, inadequate phagocytosis of sickle red blood cells (RBCs) by splenic macrophages can lead to life-threatening splenic sequestration crisis. I use a multi-physics approach to build an integrated signaling-biophysical model of the RBC phagocytosis informed by in vitro measurements of RBC phagocytosis to unravel the mechanistic control of this process and computationally investigate potential therapeutic strategies that can facilitate the controlled clearance of RBCs.
Systems biology models of complex biological signaling networks enable us to efficiently and quantitively investigate the molecular mechanisms and effects of perturbation. Hypotheses generated from in silico investigations using these models inform therapeutic discoveries for peripheral arterial disease, cancer, and sickle cell disease