An estimated 20.6 million people live with Human Immunodeficiency Virus (HIV) in Eastern and Southern Africa. In 2012, the World Health Organization (WHO) announced Option B+ which adopts a single, universal regiment to both treat HIV-infected pregnant women and prevent mother-to-child transmission of HIV. Unlike other HIV treatment options, Option B+ is a lifelong provision of antiretroviral therapy (ART) for all HIV-positive pregnant women regardless of their immune status or viral load. However, I hypothesize that the implementation of prolonged HIV treatment (Option B+) may pose a substantial financial burden for women in very resource poor settings, which could ultimately decrease ART adherence--resulting in no change or even an increase in maternal transmission. This research will examine how economically accessible Option B+ is for expecting mothers in different populations across Eastern and Southern Africa. I am statistically evaluating the cost of ART in relation to household income, living expenses, and cost of childcare at the national level. Future research will use this data to examine maternal transmission risk in relation to economic accessibility, and identify how conceptual frameworks of HIV healthcare are implemented in varied resource settings.

Combination therapies currently used to treat malaria in Subsaharan Africa have declined in efficacy owing to partner-drug resistance in the Plasmodium falciparum parasite, contributing to stalling rates in the decline of malaria disease since 2015. Amodiaquine (AQ) is a partner drug used in combination with artesunate (AS) as a first-line malaria treatment in 24 Subsaharan African countries. AQ is also distributed intermittently to children without malaria in the Sahel subregion of Subsaharan Africa as part of a seasonal malaria chemoprevention (SMC) drug package, increasing parasite exposure to AQ in 9 countries, 8 of which also utilize AS-AQ combination therapy. Using data compiled by the Worldwide Antimalarial Resistance Network and the World Health Organization, I examine the prevalence of polymorphisms in P. falciparum pfcrt and pfmdr1 genes associated with parasite resistance to AQ treatment. I will compare data for countries in the Sahel where AS-AQ therapy and SMC are administered, and for neighboring countries where only AS-AQ is used. A test showing a statistically greater prevalence of polymorphisms in countries utilizing SMC compared to those which do not would suggest that there may be a link between use of SMC and AQ resistance in those countries. It is hoped that the results of the study may be used to further efforts to understand malaria treatment resistance.

Seasonal and weather change on humans have countless effects on mood, sleep, and diet. Seasonal affective disorder, also known as SAD, is a seasonally linked mood and behavior disorder that typically lasts for four months, starting in the autumn. Similar to depression, SAD involves symptoms of lowered mood, energy loss, fatigue and some atypical symptoms such as hypersomnia, and increased appetite and eating. SAD may have a genetic factor related to serotonin metabolism and melatonin secretion, and rates of autumn-winter SAD may increase with latitude because of the increased seasonal differences in daylight hours. Due to genetic variations among certain ethnic groups, SAD may also disproportionately affect populations who are genetically from southern climates but were raised in northern climates. Yet it is not known how prevalent SAD symptoms were historically in populations adapted to northern climates, and what cultural traditions, if any, these cultures may have evolved in response to SAD. To answer this question, I have conducted a systematic search of ethnographies available through the Human Relations Area Files (HRAF) database. The HRAF databases have indexed and coded ethnographic knowledge across over 400 cultures. I examine the prevalence and traditions of SAD in the indexed ethnographies, and apply these insights to current migrant populations in northern latitudes that may experience SAD.

Premature infants are commonly born with an inability to feed properly from their mother’s breast, and enteral (tube) feeding is often too stressful on the still-growing body of a premature infant. A recent intervention called Oropharyngeal Colostrum (OPC) administration aims to safely and effectively strengthen the infant’s digestive and immune system, shortening the time to safe enteral feeding. Colostrum, the milk produced right after delivery, is exceptionally high in antibodies and proteins necessary for an infant’s development, and contains an even higher concentration of protective bodies after delivery of a susceptible premature newborn. With OPC administration, colostrum is swabbed on the infant’s cheek or tongue in small amounts on a regular schedule. When the colostrum comes in contact with the tissue in the mouth, the antibodies are taken in and boost the baby’s immune system, heightening resistance to common infections suffered by premature infants, especially in the gastrointestinal region. In 2018, the Lactation Program of the Hospital de la Madre y el Niño (HMN) in Formosa, Argentina began administering OPC to all infants admitted to the Neonatal Intensive Care Unit who were born <35 weeks gestational age and whose mothers consented to the procedure. This research will examine average time to enteral feeding among 400 premature infants administered OPC between 2018-2019. Differences are examined in average time to enteral feeding by gestational age, sex, Apgar score, birth weight, and colostrum administration. The data will be used to determine what characteristics in premature infants cause the most obstacles to enteral feeding. Results will be compared to other studies of time to enteral feeding with and without OPC administration. Results will be shared with the HMN administrators to inform them of the efficacy of the program.

Members of the LGBT+ community have long been wanting accurate representation on the big screen. Following the outlawing of “sexual perversion” by the Hollywood Production Code of 1930, homosexuality of any form was only allowed if the character was shown as a villain so as not to encourage their behavior. Traces of this restriction still remain today. Bisexual people in particular are even more problematic with their onscreen images often being either negative or absent completely. This is true even of films created by and for members of the LGBT+ community. To illustrate the pervasiveness of these issues, my research has taken a critical look at four films, Gray Matters, Imagine Me & You, I Can’t Think Straight, and Kyss Mig (Kiss Me), that have bisexual themes and have been celebrated for providing LGBT+ characters with rare happy endings. My project is titled “Happy Endings for Whom?” because I argue that these films perpetuate narratives tying bisexuality with deception and infidelity that are harmful to bisexual people and other members of the LGBT+ community. To do so I break down the plot structures and how the main characters are described and portrayed (ex: Who are the heroes? Villains? How do they identify?). The goal of my research is to expose the power structures that exist within media about and for members of the LGBT+ community and encourage individuals to be more thoughtful audience members and content creators. 

As the 2020 presidential election is fast approaching, per our democratic process, Americans will soon be held responsible to fulfill, arguably, their most important political right. Elections are thought of by many as both a mechanism of accountability and a measurement of performance. Although fair elections are a necessity to uphold democracy, it is essential to recognize that this belief is a misconception. The result of a political election is predominantly decided by the culmination of individual voters making decisions based upon their backgrounds, experiences, and beliefs. To examine this notion further, it is our goal to address the question: How does obtaining a college education affect political voting patterns? To accomplish this task, we have obtained data from the American National Election Survey (ANES). The data includes over 50,000 survey responses, ranging in years from 1948 to 2016, covering topics that include, but are not limited to, wealth, background, beliefs, ethnicity, age, gender, and socio-economic status. With this data, we have performed a regression analysis that is weighted and uses the Taylor Series adjustments to compute design-consistent standard errors. Through our research, it can be seen that the trends reveal a widening gap between educational attainment and party affiliation. Furthermore, those with higher education hold more leftward leaning beliefs, and in turn, are more likely vote Democrat when compared to those with less education. Lastly, the trends over-time reveal a dramatic shift; as, non-college-educated Americans used to primarily be Democrat, while college-educated Americans were mostly Republican. We feel that this no longer holds. This research has implications to demonstrate the importance, or lack of importance, of higher education in terms of the effect and influence it has on real life decisions, which in our case is voting patterns for presidential elections.

Civil religion, or the religion of the nation as a whole, is comprised of historically and religiously derived symbols and rituals, all of which contribute to an underlying and overarching ideal for American society rooted in sacrifice and commitment. This paper argues that during the Vietnam War, the Vietnam Veterans Against the War (VVAW) Coalition violated norms of civil religion, contributing to a decline and fragmentation of American civil religion and providential thought. Using Jon Ebel’s G.I. Messiahs: Soldiering, War, and American Civil Religion as a foundational text for the analysis of the intersections between the VVAW and American civil religiosity, the symbolic soldier, and providential thought, this paper concludes that the VVAW’s aims to “bring the war home” brought American civilians face to face with the atrocities of war, reminded Americans that involvement in war is hardly honorable (let alone innocent), and contributed to both a decline in providential thought and engagement in civil religion.

DNA polymerase (Pol) proofreading and mismatch repair (MMR) cooperatively guard against DNA replication errors and cancer. Defects in these activities produce “mutator” phenotypes characterized by elevated levels of base-substitutions and frameshifts. The clinical significance of these mutator mutations is noted in how POLE exonuclease domain mutations have been found in both colorectal and endometrial cancers. Haploid yeast with combined defects in Pol and MMR rapidly go extinct, in a process termed error-induced extinction (EEX). Organisms adapt by duplicating their genome without dividing (polyploidization) or by lowering their mutation rate via antimutator mutations. In evolution experiments with haploid mutators that display a synthetic-sick phenotype due to Pol ε proofreading and MMR defects we found that polyploids routinely beat out antimutator mutants. Although whether these results would hold true for diploids was unknown, so to investigate whether polyploids would arise in diploid strains, we did similar evolution experiments with Pol ε proofreading and MMR deficient diploids. After passaging about 200 generations, we found the vast majority of cultures had remained diploid. We then measured mutation rates of isolates from these cultures and repeatedly found antimutator phenotypes. Whole genome sequencing of independent isolates from each culture revealed various POL2 mutations in many of those that had suppressed mutation rates. Thus, spontaneous antimutator alleles and polyploidization rescues haploid and diploid cells from EEX with markedly different efficiencies. Differences in the relative frequency of each escape mechanism may reflect the nature of the mutator alleles, the starting ploidy of the cells, or the magnitude of the initial mutation rate. Our findings in diploids suggest that mutator cancer cells near the edge of error-induced extinction may similarly be under selection for spontaneous antimutator mutations and polyploidization.

Historically, the dominant culture in fraternities and sororities has been heteronormative. Prior studies have found members of the Greek system have higher levels of intolerance towards those in the LGBTQ+ community than those outside of the Greek system. There is little data about the effectiveness of educational initiatives on LGBTQ+ literacy, awareness and acceptance in the Greek system. Thus, we set out to determine the effectiveness of an educational intervention to promote LGBTQ+ literacy and attitudes among new fraternity and sorority members at the University of Washington. To do this, we administered surveys to incoming fraternity (n=383) and sorority (n=208) members to assess literacy, awareness and acceptance before and after a standardized presentation on LGBTQ+ issues developed with content experts from Seattle Children’s Hospital. Post-intervention, significantly more participants reporting knowing that there are more than two genders compared to thinking there are only two genders or feeling unsure. More participants correctly defined the acronym LGBTQ after the intervention than before, and significantly more understood the distinction between gender and sex. More participants understood the definition of heteronormative, pansexual and had an improved understanding of the difference between transgender and cisgender post-intervention. Participants’ level of anxiety about their own sexuality did not change from pre- to post-intervention, but after the intervention, participants rated the Greek System as more inclusive of LGBTQ+. After the intervention, participants reported feeling significantly more prepared if a friend approached them to reveal that they are LGBTQ+. In conclusion, an educational intervention resulted in an increase in LGBTQ+ literacy and self-reports of awareness and acceptance of LGBTQ peers among incoming Greek system at a large public university. Further research can determine if this intervention would be similarly effective in different geographic regions, private university settings and potentially help with academic success and wellbeing.

Unlike humans, zebrafish and salamanders can regenerate entire bony appendages following amputation. This unique regenerative potential may reflect key differences in osteoprogenitor activation and regulation. Here, we used cross-species transcriptomics and single-cell combinatorial indexing RNA sequencing (sci-RNA seq) to 1) identify genes dissimilarly expressed during rat and zebrafish bone regeneration, and 2) determine which cell populations in zebrafish expressed these genes. We modified a previously developed bioinformatics pipeline to include dynamic time warping (DTW) and a robust similarity metric (DTW distance) to quantify gene expression similarity. We analyzed publicly available microarray datasets for zebrafish caudal fin regeneration and rat marrow ablation-induced bone regeneration to determine dissimilarly expressed genes during regeneration. The 30 most similarly expressed genes were enriched with genes of known skeletal function. Of the 30 most dissimilarly expressed genes, 11 were upregulated in zebrafish while downregulated in rat. The most dissimilarly expressed gene during bone regeneration in rat and zebrafish was f13a1b. We performed sci-RNA seq of the regenerating zebrafish caudal fin to investigate these genes at single-cell resolution, identifying what cell types are present in the regenerating fin and how their gene expression varies. f13a1b is expressed within osteoblasts, epidermal, and mesenchymal cells in the regenerating fin. Within the osteoblasts, further clustering identified cycling and non-cycling osteoblasts, pre-osteoblasts (col10a1+), and early-osteoblasts (sp7+). f13a1b expression is enriched in two of the osteoprogenitor populations and less abundant in the later stages of osteoblast differentiation (pre-osteoblasts and early osteoblasts). In conclusion, we have performed comparative transcriptomics to elucidate genes that are upregulated in zebrafish relative to rats and determined the involvement of these genes at single-cell resolution in the regenerating zebrafish caudal fin. Genes upregulated during zebrafish bone regeneration may provide drug targets to improve bone regeneration in humans and a better understanding of the molecular pathways driving appendage regeneration.

The Davis lab is focused on understanding the pathogenic cellular mechanisms causing Parkinson’s disease and other aging-associated neurodegenerative diseases.We are currently researching how GBA affects extracellular vesicle aggregate protein propagation that increases the advancement of Parkinson’s disease. My own research in the lab is focused around the effects of GBA mutations on ceramide metabolism, a lipid in extracellular membranes, and how ceramide levels affect the propagation of Parkinson’s disease. I will use a GBAdel Drosophila model with Carmofur to increase Ceramide levels and determine if any visible changes in extracellular vesicles can be seen. I will also use a neuronal model created from Parkinson’s disease patients to look at and characterize vesicles when ceramide levels are changed. Through these two models I will be able to analyze and determine if variation in ceramide metabolism levels are due to GBAdel and how ceramide levels affect extracellular vesicles related to Parkinson’s disease. GBA is known to encode for GCase, an enzyme that hydrolyzes glucosylceramide into its parts, glucose and ceramide, since GBA directly allows for the creation of ceramide, it is reasonable to believe a mutation in GBA would affect ceramide levels in a Parkinson’s patient. It is also reasonable to assume that changes in ceramide levels will correlate with the aiding of Parkinson propagation, due to ceramide’s role in extracellular vesicle creationWe are using a fruit fly model based on a genetic risk factor for Parkinson’s disease, and a human neuronal model derived from Parkinson’s disease patients with genetic risk factors for this disease. We are currently investigating how this risk factor may influence faster propagation of pathogenic protein aggregation throughout the brain. We hope to identify new possible therapeutic targets to slow or stop neurodegeneration in Parkinson’s disease, where currently only symptomatic treatment exists.

Parkinson’s disease (PD) is a common neurodegenerative disorder that is caused by the death of dopamine-secreting neurons in the midbrain. The onset of symptoms such as progressively worsening tremors, movement difficulty, and dementia are thought to be caused by protein aggregates called Lewy bodies, mitochondrial defects, and neuroinflammation. Mutations in the GBA gene, one of the genes responsible for PD symptoms, accounts for 5-10% of all PD cases. It codes for the enzyme glucocerebrosidase which breaks down the lipid glucosylceramide. Expression of GBA in muscle cells reduces protein aggregation in the head and GBA is found in extracellular vesicles (EV). Similarly, expression in the midgut partially reduces protein aggregation in the head. Our goal is to determine if GBA expressed in the midgut can travel in EVs. We have developed a GBA mutant fly model that features symptoms similar to human PD – neurodegeneration, shortened lifespan, motor deficits, and increased protein aggregation. Flies were bred and crossed to the correct genotype, collected and frozen, and processed for analysis. To ensure that GBA is not expressed elsewhere to prevent confounding, we use an Npc1b promoter with the GAL4/UAS system, since the Npc1b gene is only expressed in the midgut. Protein is quantified following gel electrophoresis and western blots. We expect to find GBA in EVs which would help confirm that GBA traveling in EVs is responsible for the reduction in protein aggregation. This is potentially an important feature for the development of treatments for PD, as understanding what causes protein aggregation is a key step in eliminating or reducing it to prevent PD.

Plants respond to environmental changes by changing their growth patterns. For plants to continue to grow throughout their lives, they are constantly undergoing cell fate determination—how the plant determines the specific fate of new cells they are generating. One example of this is the development of roots that emerge from the primary root, called lateral roots. The number and spacing of lateral roots determine the overall root structure, which determines how well the plant takes advantage of resources in its environment. Auxin is a plant hormone involved in many aspects of growth and development, including the regulation of lateral root production. Using data from an experiment where mRNAs were sequenced from single cells isolated from roots, the Nemhauser Lab identified specific genes that may be active during lateral root development. My research question is: are these genes targets of auxin signaling? To test this, I will use quantitative RT-PCR to measure expression of the candidate genes in wild type and in plants that are deficient in the auxin response pathway. Genes that are targets of auxin should show lower expression levels in the mutants relative to wild type. The more we understand about how cell fate determination occurs in lateral roots, the more we can understand the underlying mechanisms by which plants arrive at their final root structure. Our understanding can then guide engineering or breeding projects, allowing optimal root growth that could drastically increase plant survivability and yield.

Surgical palliation/repair of congenital heart defects is associated with significant morbidity and mortality. During the majority of cardiac surgeries, the patient is placed on cardiopulmonary bypass (CPB) in order to minimize ischemic damage while the heart is being operated on. Exposure to CPB results in systemic inflammation and multi-organ dysfunction that is especially severe in neonatal and pediatric patients. Particularly, brain damage resulting in developmental and cognitive disorders have emerged as major concerns in this group of patients due to its negative impact on the patient’s quality of life. Therapeutic intervention is currently limited as the mechanism how the systemic inflammatory response links to brain damage remains unclear. It is hypothesized that CPB-activated immune cells could infiltrate into tissues, releasing intracellular contents that cause tissue injuries. In order to understand how the brain – specifically the neuronal and glial cells – responds to secretory proteins from CPB-activated monocytes, we exposed differentiated neuronal cells (dSY5Y) and glial cells (U118) to conditioned media from either control static or CPB-mimicking sheared monocytes (THP-1). Quantitative polymerase chain reaction was performed to quantify potential changes of various target genes. The data suggested that chemokine C-C-motif ligand 2 (CCL2), chemokine CXC motif ligand 11 (CXCL11), chitinase-3-like protein 1 (CHI3L1), S100 calcium binding protein B (S100B) and interleukin-1-beta (IL1b) were significantly upregulated in both dSY5Y and U118 cells cultured in conditioned media from sheared monocytes compared to the static control. This is the first step to understand the mechanism of interaction between the brain and the activated immune system after CPB so that novel targets could later be identified for therapeutic development. 

Can parenting styles offset the effects of neighborhood disadvantage on child life-course trajectories? Much research indicates that children raised in an economically disadvantaged neighborhood face a greater risk of high school dropout or expulsion, low-wage employment, and incarceration. Yet not all youths raised in disadvantaged neighborhoods follow this trajectory, and success stories abound. This study examines how low-income parents’ childrearing strategies positively or negatively affect the life-course trajectories of at-risk youth. Using the Denver Youth Survey (DYS), a nationally representative, longitudinal sample of high risk youth, I intend to test whether parents’ childrearing strategies affect young adults’ academic accomplishment, income, job type, and criminal record. I hypothesize that positive parenting, defined as monitoring, control, and warmth towards the child, is associated with a reduced likelihood of youths experiencing impediments to socio-economic mobility. As an alternative hypothesis, I test whether impulsivity of the child mediates the association between parenting style and positive life-course outcomes. In doing so, I aim to contribute to the intersecting literature on life-course theory, child developmental psychology, and criminology, as well as provide evidence to aid the development of policy assisting at-risk youths overcome their disadvantaged circumstances.

Nearly half of Americans live in earthquake prone areas. Many primary fault zones that host large earthquakes, such as the Cascadia, Alaska, and San Andreas fault zones, extend into the offshore regime. These offshore fault systems have been historically difficult to study due to challenges in observational techniques. Through the creation of an algorithm that uses geospatial analytical tools, this study seeks to identify seafloor faulting structures from data collected by high frequency multichannel acoustic methods. In doing so, we improve our capabilities of characterizing offshore fault zones. In addition, we examine these geospatial analytical methods for accuracy and explore the impact of data collection and post-processing procedures on associated errors. Data utilized subsists of bathymetric data collected in the Cascadia and South African regions, which are active and passive margins respectively. Methods for surface fault identification include visual inspection, as well as geospatial analytical methods consisting of the Bathymetric Position Index, slope, and aspect of surface morphology. Faults identified from surface morphology are compared to those identified using a coherence-based detection method from seismic reflection data. Surface expressed faults indicate high-amplitude and/or recent geologic deformation and can give insight into tectonic stress regimes and associated faulting hazards. An improved understanding of faulting hazards through efficient surface fault identification would aid in preparation and planning for earthquakes. Through the creation of this algorithm, our capabilities to accurately identify surface expressed faults in bathymetric datasets will be enhanced and thus our understanding of global tectonic processes and earthquake risks to population centers like those in the Pacific Northwest will be improved.

A graph is a collection of vertices and edges. In computer science, graphs are often called networks and form the basis for many data structures and search algorithms. A matching of a graph is a selection of edges that share no common endpoints. The set of all matchings of a graph forms a simplicial complex which we call the matching complex. We are interested in the relationship between a graph and its matching complex and have been exploring whether we can characterize all simplicial complexes that are matching complexes. What structure does the matching complex imply about the graph and vice versa? We have also been interested in connections between matching complexes and well-known simplicial complexes– in particular, two-dimensional Buchsbaum complexes. These have much more structure than simplicial complexes in general, so they lend themselves to interesting questions. How can we characterize all two-dimensional Buchsbaum complexes that are matching complexes? We have also developed an interest in sequences of graphs generated by taking repeated matching complexes. Understanding these sequences would allow us to categorize graphs using the matching operation. Which graphs go to the empty set after a finite number of iterated matchings? For what finite values does this occur? What common structure do these graphs have? Investigating these questions will allow us to categorize graphs and complexes using the matching operation. We hope to make connections between graphs or categories of graphs that would otherwise remain disconnected. In pursuing these queries not only are we seeking answers but a development of tools which can be applied to further exploration.

Postoperative pain is common and associated with adverse short and long-term outcomes. Previous studies have identified preoperative pain as a predictor of postoperative pain, but persistent preoperative pain in the breast in women undergoing surgery for breast cancer has not been well explored. This cross-sectional observational study aimed to (1) identify demographic and clinical characteristics associated with preoperative breast pain and (2) determine the relationship between occurrence and location of persistent preoperative pain (in the breast, elsewhere, or both locations) and acute postoperative pain outcomes in women undergoing surgery for breast cancer. The study leveraged clinical and patient-reported outcome data collected by the multinational registry PAIN OUT between January 2011 and December 2018. Subgroups of women were identified based on occurrence and location of persistent preoperative pain (i.e., no persistent preoperative pain, preoperative pain in the breast, preoperative pain elsewhere, preoperative pain in the breast and elsewhere). 1,883 women at 62 participating institutions, aged 62 ± 14 years, who underwent surgery for breast cancer provided data. Controlling for pertinent demographic, clinical, and pharmacological characteristics, the independent relationship between persistent preoperative pain and acute postoperative pain intensity was evaluated. In general, women with preoperative breast pain had a higher body mass index and higher prevalence of affective disorder and women with preoperative pain elsewhere were older, had more comorbidities and a higher prevalence of hypertension. Persistent preoperative breast pain occurrence was associated with more severe acute postoperative pain and pain interference. Controlling for covariates, women with persistent preoperative pain in the breast (with or without pain elsewhere) experienced more severe acute postoperative pain, particularly compared to patients without persistent preoperative pain. Preoperative identification and targeted intervention of these subgroups at risk for severe acute postoperative pain following breast surgery may eventually enhance the recovery trajectory for breast cancer patients.