Everyday, human beings engage in prosocial behaviors, which are behaviors intended to benefit others. These include simple acts, such as holding doors for others, and costlier behaviors, such as donating money. Even young children help, share with, and comfort others. To gain insight into why human beings engage in prosociality from such an early age, it is critical to examine individual variability in children’s prosocial behavior. That is, why are some children more prosocial than others? One factor that may influence prosociality is social anhedonia, which is the reduced capacity to experience pleasure from social interactions. Adults with high social anhedonia are less prosocial; however, no work has explored if children’s capacity to experience pleasure from social interactions motivates their prosociality. The current work develops a measure of social anhedonia in early childhood and examines if variability in the capacity to experience pleasure from social interactions is related to children’s tendency to engage in prosocial behavior. To explore this question, parents of 4- to 8-year-olds report their child’s prosociality. They also report their child’s social anhedonia using the Child Social Anhedonia Scale, which I created based on a questionnaire assessing adulthood social anhedonia. This work is ongoing, but an analysis of 134 participants (57 females) revealed a significant negative correlation between children’s social anhedonia and prosociality, r=-0.32, p<0.001. This finding suggests that children who are less likely to experience pleasure from social interactions are also less prosocial, implying that perhaps enjoying social interactions serves as a motivation for children’s prosociality. This study is the first step in understanding the relation between pleasure from social interactions and children’s prosocial behavior. Future studies could further examine if this relationship is causal.

Inpatient hypoglycemic events less than 50 mg/dL are prevalent among hospitalized patients and can lead to poor health outcomes, including increased mortality. Some studies indicate that among hospitalized patients, older individuals, patients with co-morbidities, and those who are admitted to intensive care units are the most common inpatient populations to suffer from hypoglycemic events. Studies also suggest that inpatient hypoglycemic events are more often medication attributable in contrast to physiologic causes. The aims of this quantitative study are to: 1) determine the root causes that lead to hypoglycemic events in the hospital setting, 2) describe patterns in chart documentation related to hypoglycemic events, and 3) identify measures to attain effective prevention of hypoglycemia. Specifically, this study examines the time range between the hypoglycemic event measurement and the blood glucose measurement prior to the event to determine if tighter glycemic control results in improved patient outcomes, the use and documentation of rescue medications after a hypoglycemic event, and the presence of dietary intake charting in the medical record prior to the hypoglycemic event. We collaborated with the glycemic team at a local medical center to collect data drawn from patient medical records. Patient medical records were selected if they had experienced a hypoglycemic event less than 50 mg/dL between March 2017 and June 2017. Analysis used descriptive measures to identify patterns and inconsistencies in the data derived from the medical charts related to potential root causes of hypoglycemia. Using a systematic approach to identify the root cause of inpatient hypoglycemia informs future development of tools and policies to reduce the incidence of inpatient hypoglycemia in the future and improve patient outcomes. The expected results of this study attributes the hypoglyemic events to infrequent and inaccurate diet intake documentation, and longer time intervals between blood glucose monitoring. 

Research has shown that drinking motives (or reasons for consuming alcohol) are strong predictors of alcohol use; moreover, enhancement and social motives are among the strongest predictors of alcohol use. Given limited research to date, the purpose of the current study is to examine how drinking motives relate to drinking alone and also to drinking with friends. College student drinkers ages 18-24 were recruited for an ongoing study. To be eligible, participants had to report alcohol use two or more days a week and one or more occasions of heavy episodic drinking in the last two weeks. Baseline data on alcohol use, drinking motives, and drinking context were used for the current analyses (N = 292 to date; 52% female, 71% Caucasian, mean age = 20.17 years). Participants were asked to report how often they drank alone and with friends on a scale from “never” to “daily or almost daily.” In addition, they were asked to report motives for drinking on each of five subscales using response options from “almost never/never” to “almost always/always." The current study will use regression analyses to test associations with four of the subscales: coping-anxiety, coping-depression, enhancement, and social motives. We hypothesize that higher coping motives will be associated with being more likely to report drinking alone and with friends. Additionally, we hypothesize that higher social and enhancement motives will be associated with being less likely to report drinking alone and more likely to report drinking with friends. Results from this study will provide a better understanding of why people decide to drink and in which different social contexts, thus providing valuable information to guide interventions on how to better incorporate drinking motives and social context.

For more than a century, Drosophila melanogaster (fruit flies) have been an invaluable and versatile tool to further our understanding of cell signaling and survival mechanisms. To this day, they continue to shed light on the endogenous pathways that cancer cells can hijack in order to proliferate, metastasize, and recur following remission. The molecular conservation of these pathways invites parallels between the germline stem cells in D. melanogaster and the cancer stem-like cells in human carcinoma. In the same way that a tumor can relapse following a period of dormancy, Drosophila germline stem cells are capable of repopulating their niche after insult from Ionizing Radiation (IR). Utilizing this powerful model, we have conducted a small molecule drug screen of 512 compounds that we have narrowed down to eight candidate drugs that appear to increase cell death in Drosophila germline stem cells. Having already characterized the wild type Drosophila germline stem cell response to IR-induced DNA damage, we  probed how drug treatment and gene knockdown affected the germline stem cells' ability to recover from insult. Previous work in the Ruohola-Baker Lab has demonstrated the critical importance of the mechanistic target of rapamycin (mTOR) and the Tie receptor pathways in regulating regeneration after insult in the Drosophila germline. The Tuberous Sclerosis Complex (TSC), a heterodimer comprised of Tsc1 and Tsc2, is a known negative regulator of mTOR. Additionally, the Tie receptor is central to anti-apoptotic signal transduction in the Drosophila ovary. We have screened four candidate drugs to see if they effectively increase stem cell death in Tsc1-knockdown and Tie-null flies, in order to ascertain whether our drugs affect stem cell survival mechanisms through mTOR and/or Tie signaling. Our findings may shed light onto how to mitigate the quiescent threat of tumor relapse.

Cancer stem cells are thought to play a role in relapses and metastasis in numerous cancers. The inability of traditional cancer therapies, such as chemotherapy, to eradicate these cancer stem cells prompted a search for small molecules that induced apoptosis in cancer stem cells. Drosophila germline stem cells can be used as a model system to emulate cancer stem cells. Upon irradiation, Drosophila germline stem cells are able to survive apoptosis through a molecular signal released by the apoptotic daughter cells via the TIE receptor. We have conducted an in vivo drug screen of 512 compounds in Drosophila melanogaster to find drugs that would disrupt this protective mechanism and induce apoptosis. In particular, Camptothecin, NSC 125197, and NSC 127458 were effective in killing germline stem cells. To test the effect of the small molecules we fed female flies the compound for 3 days, dissected and fixed the ovaries and stained for an apoptosis marker, activated caspase, and the GSC marker, adducin. We quantified the effect of the drug by analyzing the number of germline stem cells and caspase signaling on a confocal microscope. Through this system we aim to find potentially new, and more powerful anti-cancer drugs that can affect cancer stem cells. Future directions include attempting to understand the mechanism of action of these apoptotic compounds in hopes that they might be useful in the fight against cancer stem cells.

It is not fully known what controls signal preference in branched signal transduction pathways. One hypothesis is that the configuration and orientation of receptors determines signal preference. We are investigating this hypothesis in the context of the Tie2 receptor pathway which has downstream signaling involved in cell survival via Akt, migration via Dok-R, and sprouting via FAK, among other branches. We are using computer designed protein tools, short-armed claw trimers and nanocages, conjugated to F domains of the canonical Tie2 ligand angiopoietin 1 in our investigation. We have shown that short-armed claw trimers with three conjugated F domains do not yield increased phosphorylation of Akt, suggesting that more than three receptors must cluster together for signal activation. The nanocages are multivalent, for they have multiple F domains conjugated to them. We have different valency nanocages with different percentages of F domain conjugation. We are using these different valency nanocages to investigate which valency is optimal for receptor activation. We have shown that higher valency nanocages yield increased phosphorylation of Akt. We predict that higher valency nanocages cluster more Tie2 receptors together in a specific conformation. Thus, we show a positive correlation between Tie2 clustering and the phosphorylation of Akt due to Tie2 activation. Now we will investigate combination conjugations of F domain and integrin binders to the nanocages as well as other branches of the Tie2 pathway: Dok-R corresponding to wound healing ability and FAK corresponding to tube formation ability. This work has potential to help generate therapeutic compounds for wound healing.

Necroptosis is a lytic and immunogenic form of programmed cell death (PCD), characterized by pro-inflammatory cytokine production and the release of intracellular molecules, including cell-associated antigens. This form of death occurs after RIPK3, Receptor-Interacting Protein Kinase 3, activation. RIPK3 is a cell death regulator that promotes necroptosis. Previous studies have shown that necroptotic cells can promote maturation of antigen presenting cells (APCs) and are capable of priming antigen-specific CD8+ T cell responses. Understanding the downstream immunogenic effects of necroptosis allows for implicative applications within the field of tumor immunology. Previous work has shown that necroptotic NIH-3T3 fibroblasts produce inflammatory cytokines and chemokines, contributing to their immunogenicity. To recapitulate the immunogenic nature of 3T3s, we evaluated inflammatory chemokine and cytokine production via ELISA (enzyme-linked immunosorbent assay), quantifying these productions through antibodies and color-change, from necroptotic tumor cell line supernatants, including B16.F10 melanoma and LL/2 adenocarcinoma cells. Surprisingly, our results did not show significant chemokine or cytokine production from necroptotic tumor cells, suggesting that anti-tumor effects are not from signals derived from the tumor micro-environment (TME). This suggests that other forms of signaling downstream of RIPK3 activation, such as upregulation of non-chemokine transcriptional programs, could be the source of inflammatory signal production by necroptotic tumor cells. Further actions include RNA sequencing of necroptotic cancer cell lines to differentiate global changes between apoptotic and necroptotic forms of cell death, to provide unbiased analysis of transcriptional changes. With evidence of T cell-mediated immunity and the immunogenic nature of necroptosis, induction of this form of cell death within the TME will activate anti-tumor immune responses, potentially controlling tumor growth and contributing to the field of immunotherapy.

Diet, lifestyle, and environment can influence an individual’s behavior and brain function through epigenetic mechanisms. The Lattemann lab is investigating the effect that one factor, high fat diets, has on epigenetic regulation in hippocampus a key area for learning, memory and cognition. Previously, the lab determined that rats fed high fat diets exhibited increased sucrose motivation, and this behavioral effect was later linked to stearic and palmitic fatty acids explicitly. It was also shown that high fat, high sugar diets are associated with impaired place memory in rats. Most recently, the lab has analyzed hippocampal chromatin from rats fed high stearic and palmitic acid diets and is in the process of determining the effect of these diets on histone modifications. Histones regulate gene expression by binding to DNA: modifications to these histones influence how readily the DNA is transcribed, and how the gene expressed. These modifications are being screened for using Western blot analysis. In addition to screening for modifications in histones, the Lattemann lab also directly analyzed DNA for the expression of target genes. This screening procedure included measuring expression of candidate histone-target genes using PCR, and ChIP-Seq (Chromatin Immunoprecipitation and unbiased gene screening) assays. By locating histone modifications and quantitating the expression of hippocampal candidate genes, the lab has provided an epigenetic explanation for the behavioral effect of the diets, and a possible molecular mechanism by which the diets can induce this effect.

Ethics and diversity are critical components of engineering training and practice, but most undergraduate engineering programs do not address these issues in-depth. We describe the design and implementation of a novel curriculum that allows early engineering students to explore the interplay of diversity and ethics in an engineering context. Although upper-division bioethics courses may also address this relationship, we chose to implement this curriculum in a large, introductory course. We intend to provide an accessible opportunity for early engineering students, particularly underrepresented students interested in engineering, to engage with this material early and to impress upon a broad audience that diversity and ethics are critical topics in engineering. Engaging these students in meaningful discussion about the intersecting roles of diversity and ethics in bioengineering enables them to apply course competencies to their future engineering practice. Our learning objectives include: (1) Summarize key case studies regarding diversity-related ethics in STEM, (2) Identify how cultural concepts of race, gender, sexuality, and disability have shaped scientific thought (and vice versa) through history, (3) Critically evaluate literature regarding ethics and diversity in bioengineering, (4) Analyze how engineers handle implicit bias during research and design processes, and (5) Propose approaches to promote ethics and diversity in engineering practice. Course activities cover the importance of diversity and ethics competency in engineering; historic and current case studies of diversity-related ethical issues and how historical perceptions and contexts still influence modern scientific thinking and engineering design; advocacy and representation of minorities in engineering; evidence supporting the value of inclusive teaching and diverse teams; and best practices for advocacy and representation of diverse peoples in engineering. We assess the effectiveness of these teaching innovations through student surveys, student performance on assignments, and instructor observations. Additional supporting data is provided by excerpts of student work.

A seed’s successful transition to a seedling depends on the suitability of the surrounding environment. All plants need water, sunlight, favorable temperatures, and soil nutrients to survive. On top of these essentials, interactions with other organisms through competition, herbivory, or disease may also have an impact. The goal of this study is to assess which factors influence tree germination in Washington’s temperate forests. Are there essentials without which seeds fail to complete the pivotal transition between embryo and tree? This question was explored using data collected since 2014 in a 25.6 hectare plot located in the Gifford Pinchot National Forest (WA). The dominant trees here, including Western hemlock and Douglas fir, were the focus species of this study. Forty seed traps distributed throughout the plot collected falling tree seeds so that they could later be identified to species and counted in the lab. Germinants and seedlings were recorded within a square meter adjacent to each seed trap, along with environmental factors such as soil moisture and sun exposure. Regression analyses were used to assess whether germination rates (the proportion of seeds that successfully germinated) were influenced by environmental factors, other organisms, seed densities, or year. While analyses and data collection are ongoing, results thus far indicate a negligible role for soil moisture and sunlight in germination. On the other hand, the presence of other vegetation decreased germination, while the presence of nurse logs increased it. Germination is an important and delicate life stage for every tree, and through their influence on it environmental factors may shape the species composition of these communities. Identifying relevant factors may also provide some ability to anticipate how these trees will respond to the warmer and drier conditions expected to define climate change in the Pacific Northwest.

Wound healing is an essential physiological process that repairs damaged tissues through a collaboration of molecular and cellular events.  For a wound to heal properly, hemostasis (blood clotting), inflammatory, proliferative, and maturation phases must occur sequentially at specific times and at optimal levels.  I’ve been using the fruit fly Drosophila melanogaster as a model organism to study wound healing and the potential role of a family of six growth factors called Imaginal Disc Growth Factors (IDGFs). IDGFs are related to human chitinase-like proteins, which are upregulated in cancer and other diseases associated with inflammation; their function, however, is not yet understood.  We hope to gain some insight by studying their role in wound healing in the Drosophila wing imaginal disc, a larval tissue that will become the adult wing.  Using a method called in situ hybridization, which reveals the patterns of RNA localization in fixed tissue, I found that while IDGFs are normally expressed in wing imaginal discs, their expression is immediately turned off upon wounding.  However, using transgenic fly strains that have IDGF2 and IDGF6 proteins tagged with a green fluorescent protein and an extended culture assay that allowed me to track protein expression over time, I found that IDGFs are upregulated at the wound sites after several hours.  Combining these observations, I hypothesize that IDGFs are first turned off in the hemostasis phase and later are upregulated in the inflammatory or proliferative phase, when new tissue begins to form.  To determine the cell types, cellular dynamics, and precise timing of IDGF upregulation, I will use confocal live imaging and label cell types that are known to be involved in wound healing, such as hemocytes.  These studies will contribute to our understanding of the genes that regulate tissue healing after mechanical injury.

Understanding how extracellular environments facilitate the differentiation of stem cells holds much promise for the field of regenerative medicine. Non-muscle myosin II (NMII) plays an important role in cell morphology and also generates forces that alfter biochemical signalling. It has been shown that the activity of NMII controls mechanoreceptors and integrins facilitating stem cell fate. More specifically, mechanotransduction of transcriptional coactivators YAP/TAZ facilitate differentiation of mesenchymal stem cells (MSCs). YAP and TAZ are responsible for upregulating genes associated with stem cell differentiation. Under external stresses mesenchymal stem cells differentiate into osteocytes whereas softer extracellular conditions favor the differentiation into adipocytes through mechanotransduction of YAP and TAZ.To further explore the role of physical forces determining the fate of stem cells, we used a computationally designed self-assembling homo-polymer called 2E01, generated by the Institute for Protein Design (IPD). Mechanical stress and the physical activity of NMII can be mimicked by controlled expression of the length of the E01 protein fiber. We introduced the 2E01 gene under a doxycycline-inducible promoter into the AAVS1 "safe harbor" locus of the induced pluripotent stem cells (iPSC). Expression of the E01 fiber in iPSCs lead to changes in colony morphology and subsequent differentiation of those cells, suggesting that changing the morphology of cells can change their fate. I want to see if I can use the 2E01 fiber as a tool to accelerate differentiation from IPSCs to neuronal cells and cardiomyocytes. In addition, we expressed 2E01 in mesenchymal stem cells, a cell type currently used in lab, and observed the activity of YAP and TAZ as an indicator of differentiation. Utilization of the 2E01 fiber could be benefical to the field of regenerative medicine as a directed agent of physical manipulation towards desired stem cell fate.

The idea of busy culture permeates college campuses nationwide and describes the trend of students engaging in less leisure activities and more time spent in academic and professional devotions: a trend which in our experience is reflected in the culture of University of Washington. There is little research exploring the nature and consequences of busy culture on college campuses. To address this gap in the literature, the purpose of this study is to better understand UW undergraduate students’ own perceptions of being busy, and how they see busyness as impacting their academic experience and overall well-being. We conducted four focus groups with eight to ten participants per group, with two trained student facilitators. These focus groups explored topics including what students consider “busy,” and how busyness functions in their life. Qualitative analyses looked for emergent definitions of busyness that are consistent across students, and seeked to understand if motivations and perceived consequences of busyness are similar, or different among different students. We discussed these patterns in the context of existing literature on social norms and student stress and refine hypotheses about busyness to better inform future research. We also considered how these results can contribute to improved student programming to enhance the student experience at UW.

In many plant species, temperature and herbivory have been shown to affect photosynthetic rates, and thus, capacity for growth. However, few studies have looked at  the combined effects of temperature and herbivory on plant performance. This is important, as increases in temperature and rates of herbivory are predicted to coincide with climate change. To address this issue, Lupinus latifolius, a perennial plant native to the western coast of the United States, was studied. L. latifolius was chosen because it is a nitrogen-fixer, and it can facilitate the growth of other plant species in disturbed habitat. As such, observing how L. latifolius responds to future conditions we expect with climate change can provide insight about how plant communities will respond in the future. In this experiment, two growth chambers were used, and L. latifolius plants were placed in one of four treatment groups. The treatment groups were organized so the combined effects of temperature and herbivory could be compared to the standalone effects of temperature and herbivory. For the herbivory treatments, grasshoppers were used. MultispeQ, a portable plant-phenotyping instrument, was used to capture photosynthetic parameters and relative chlorophyll. Certain morphological traits, such as plant height and leaf mass per area (LMA), were also measured. I expect that higher temperatures will result in higher photosynthetic rates, but that herbivory will have a larger negative impact on photosynthesis. As a result, lower photosynthetic rates are likely to be observed under increased temperature and herbivory. T tests and ANOVA were conducted to determine whether differences between treatments are statistically significant. By conducting this research, we can gain a better understanding of how changes in temperature and herbivory rates associated with climate change can interact to affect plant performance and health.

Studies have shown disparities in environmental justice as manifest by the variation of air pollution exposure based on race and socioeconomic status (SES) on a national scale. This study focused on determining whether a similar association exists in Washington. I hypothesized that in areas where people of color are the majority residents, exposure to air pollution as measured in PM2.5, will be higher. I also hypothesized that there would be a higher average concentration of PM2.5 in low-income areas. PM2.5 are solid particles with a diameter smaller than 2.5 micrometers. In this cross-sectional study, I used linear regression and analysis of variance to evaluate my hypotheses where I treated income as a continuous variable and majority residency by race as a categorical variable. Overall, I found a negative association between PM2.5 and income, which supports the hypothesis. I estimated that PM2.5 is expected to decrease by 0.03 µg/m3 on average per 10,000 dollars increase in income [95% CI: -0.032, -0.02.8]. I controlled for urbanity and education. When I considered effect modification, I found that the negative association was not present in rural areas. In descriptive analyses, I considered four different racial categories (White, Black, Latinos, and Asian). I observed that for areas where black people are the majority, the PM2.5 exposure is the highest, with a mean of 6.86 µg/m3 [95% CI: 6.82, 6.87], with a maximum of 7.65 µg/m3 and a minimum of 6.06 µg/m3. In comparison, in areas where white people are the majority population, the mean was 6.12 µg/m3 [95% CI: 6.11, 6.13], with a maximum of 8.12 µg/m3 and a minimum of 3.54 µg/m3. I conclude that there is a disparity in air quality based on ethnicity and SES in Washington State. Directly or indirectly, environmental injustice contributes a greater risk of health issues and diseases.

This project aims to ground truth a statistical model created previously by our lab. The model predicts the characteristics of a hyper velocity impact of a projectile into both sea ice and water ice. We compared the modeling program’s simulated results with observed results from both 1.5 inch and 4 inch ice perpetrators on lab created water ice and naturally forming sea ice respectively and studying such characteristics such as peak ejection angle, maximum crater depth, and crater diameter. The experimental results are compared with the simulation presented by Koch 2017. We will apply both our experimental data and our simulation data in the design and creation of a two-stage penetration probe. The first stage is a hyper-velocity penetrator. The second stage is an aero-breaking probe that will use the plume created by the first stage to reduce its velocity before impacting the surface.

What drives change in populations of endangered species such as the northern spotted owl (Strix occidentalis caurina)? Despite northern spotted owl populations in Washington declining yearly, variability in year to year population performance suggests that understanding what facilitates a “good” year for this endangered species may improve management practices. It is possible that resource pulses, distinct increases in ephemeral resources occurring at infrequent time intervals, influence this variation. “Masting” is a type of resource pulse in terrestrial ecosystems characterized by large increases in seed or fruit production, which may raise abundance of small mammals that consume seed. For example, northern flying squirrels (Glaucomys sabrinus), have been found to respond positively to mast events from the previous autumn. Because northern flying squirrels are a primary prey item of S. occidentalis, constituting up to 81% of its diet by biomass, spotted owl numbers and seed masting events may be correlated. To elucidate this relationship, I used seed production data collected in Mt. Rainier National Park (MORA) since 2008 by the Hille Ris Lambers Lab, in conjunction with northern spotted owl demographic data from the National Park Service. An estimated 80,000 acres of suitable spotted owl habitat exist in MORA extending to altitudes of 4,800 feet, dominated by Psuedotsuga menziesii, three Abies species, Thuja plicata, and Tsuga heterophylla — trees which mast and may be consumed by small mammals. We hypothesize that a mast event will produce a resource pulse of seeds which may heighten flying squirrel abundance, resulting in increased northern spotted owl population two years after the seed mast event. This hypothesis predicts a positive correlation between seed production and adult northern spotted owl population two years post mast event. This study will improve knowledge of spotted owl population dynamics and potentially improve management protocol of Strix occidentalis caurina in MORA.

Protons take part in many important reactions such as redox, acid-base chemistry and biochemistry; however, the mechanisms for proton transfer and hydronium’s stabilization are less understood. Hydronium sequestered in 18-crown-6 ether (CE) has an unusually broad and intense vibrational absorbance (OH-feature) compared to bare hydronium. One environmental factor affecting this OH-feature is the range of hydrogen bonded geometries between the hydrogen atoms in hydronium and the oxygen atoms in the CE, which is sampled by the complex even in its ground vibrational state. The breadth of the OH-feature is attributed to changes of the OH stretch frequency of hydronium as it rattles within the CE, and to the CE distorting to accommodate the hydronium. Hydronium will donate a proton to diethyl ether in the binary complex, because the diethyl ether is a stronger base than water. However, when hydronium hydrogen bonds to three diethyl ether molecules in a ternary complex, all three hydrogen atoms in hydronium are pulled by the ether molecules preventing any one of the protons from transferring. The hydrogen bonded geometries we analyze involve complexes of hydronium with both simple ethers and cyclic CE molecules. The CE hydrogen bonds to all three of the hydrogen atoms in hydronium similarly to the ternary complex, thus the CE complex prevents proton transfer. We explore several other environmental factors, including increasing the rigidity of the CE by replacing carbon-carbon single bonds with carbon-carbon double bonds. This increase in CE rigidity reduces the rattling of the hydronium. We also explore the effects of reducing electron density on the oxygen atoms in the CE by replacing hydrogen atoms in the CE with fluorine atoms. Optimizations, frequencies and potential energy scans are made at the B3LYP level of theory using a 6-311G(2d,p) basis.