Cardiovascular disease and diabetes have been and are currently associated with obesity. Understanding the connections between obesity, lipid droplets and these diseases is crucial to ameliorating their recurrence and the six hundred thousand people that are affected yearly. The roundworm C. elegans serve as a model for genetic and physiological regulation of lipid metabolism. A previous study by our lab identified numerous proteins that localized to C. elegans lipid droplets. One of these, ldp-1 (F22F7.1) shows similarity to a mammalian lipid droplet protein called CGI-49. Because the analysis of lipid droplet quantity and localization is crucial to understanding the physiological mechanisms of fat storage, we intended to determine if knocking down the gene encoding ldp-1 had any effect on fat accumulation. To determine the phenotypic effects of knockdown of ldp-1, the study used both Nile Red and Bodipy staining, and the process of RNAi. Analysis of the staining found that neither the intensity, nor the quantity of lipid droplets was affected by the knockdown of the gene ldp-1 when compared to wild type C. elegant. Thus, ldp-1 is not required for proper fat accumulation in well-fed young adult staged C. elegans.

The plant hormone auxin plays a role in nearly every aspect of plant growth and development. Auxin facilitates interactions between two protein families: the transcriptional repressor Aux/IAA family and the auxin receptor TIR1/AFB family. TIR1/AFB proteins act as the substrate recognition subunit of SCF ubiquitin ligase complexes. SCF^TIR1/AFB-auxin-Aux/IAA interactions lead to ubiquitination and degradation of Aux/IAA proteins, allowing transcription of auxin-responsive genes. Each of these protein families is comprised of many functionally distinct members, allowing auxin to drive numerous developmental responses in plants. This complex network can be decomposed and signaling dynamics of individual pairs of TIR1/AFB and fluorescently-labelled Aux/IAA proteins can be measured in a yeast synthetic system using time-lapse flow cytometry. This dynamic analysis can give insight into the behavior of developmental networks in planta. However, of the six TIR1/AFB genes in the model plant Arabidopsis thaliana, only TIR1 and AFB2 induce degradation of Aux/IAAs in yeast. We aim to engineer a variant of AFB5 that is functional in this synthetic system, as AFB5 is known to be the target of many agriculturally important herbicides, but little is known about its role in development. We hypothesize that AFB5 is non-functional in yeast because it cannot form an SCF complex with the native yeast proteins. This is potentially caused by the extended N-terminus of AFB5 or the sequence divergence within AFB5’s SCF binding domain. To test these hypotheses, several N-terminal truncations of AFB5 and chimeric AFB5 proteins with the SCF binding domain replaced by that of AFB2 or TIR1 will be individually tested for their ability to induce degradation of Aux/IAAs in yeast. Functional variants will allow identification of key AFB5-regulated Aux/IAAs and associated developmental networks. Additionally, this work will guide engineering and allow functional characterization of the remaining Arabidopsis AFB genes and AFB genes from other plant species.

The position of leaves around a stem (phyllotaxy) impacts a plant’s yield, pollination conditions, and light harvesting abilities. Auxin plays a critical role in establishing phyllotaxy. Expressing sequence variants of the auxin-regulated protein IAA28 in the plant Arabidopsis thaliana led to changes in phyllotaxy, specifically in the angles between flowers along the inflorescence bolt. Normally, the IAA28 protein binds and represses AUXIN RESPONSE FACTOR (ARF) transcription factors. When auxin is present, the IAA28 protein is degraded, initiating organogenesis. I am currently using three strategies to characterize an IAA28 knockout mutant (iaa28-ko) to better understand IAA28’s role in phyllotaxy. Loss of IAA28 is reported to cause a number of phenotypes by Wang and Guo, but phyllotactic patterning has not been characterized. My first goal is to quantify phyllotaxy by using a measuring device made in the Nemhauser Lab to measure the divergence angle between siliques. I hypothesize that the divergence angles measured in iaa28-ko plants will be smaller than the wild type. My second goal is to determine the change in auxin patterning in iaa28-ko mutants by using plants expressing an auxin reporter called DR5::Venus. Because the iaa28-ko mutant is reported to have more lateral roots, and lateral root initiation requires auxin, I hypothesize a higher expression of DR5::Venus in the iaa28-ko root and inflorescence meristem than in the control. Finally, I will test the functional conservation of BIF4, the putative maize ortholog of IAA28. To determine if BIF4 is functionally similar to IAA28, I will use Agrobacterium-mediated transformation to express BIF4 in an iaa28-ko plant. I hypothesize that the BIF4 protein will fill in the role of IAA28 in the auxin pathway, rescuing the mutant. By understanding the underlying mechanisms that control the phyllotaxy of Arabidopsis, we can learn how to apply similar engineering strategies in other plants.

Conventional wisdom concerning labor migration in Southern Africa holds that cheap, migratory labor was necessary for the extraction of base metals and the profitability of colonial mining. The different geologic, political, economic, labor and domestic conditions of mines across the region has, as a result, been obscured. The deterministic view of labor migration within “cheap-labor theory” does not consider the individual reasons why workers and other migrants chose to migrate. As self-perception has become embedded in ideas of work-membership, able-bodiedness, and gender, specific historical analysis of urbanization in different contexts has become necessary. Using health data, colonial and mining company records, and anthropological accounts, along with secondary scholarship, this study addresses dependency relationships between urban black populations, native leaders and colonial and mining authorities. The hypothesis is that relationships of dependence may have translated into forms of citizenship that were not institutionally recognized or that may be antithetical to Western, liberal ideas of freedom. Assessing these relationships in the context of health offers an understanding for how individuals navigated issues of social and political change that are important for decision making in the fields of global and public health, and urban planning. Structural and institutional inequalities created by historical circumstances have resulted in the different quality of state membership experienced by marginalized communities. Understanding how membership and self-perception has been historically created is an essential element for deconstructing institutional and social barriers that contribute to global health inequalities in crucial ways.

Nearly all psychiatry residents in the United States take the Psychiatry Resident-In-Training Examination (PRITE).  The PRITE is a 300-question examination administered annually to psychiatry residents that covers a variety of important topics related to general psychiatry training. After each test administration, residency programs receive a detailed computer analysis of the test performance of their residents. The computer-generated analysis provides details for comparing residents across different training programs with a similar level of training. In recent years, the University of Washington Psychiatry Residency Program has consistently ranked below the 50th percentile on the PRITE in the area of forensic psychiatry across all years of residency training. In this study, the authors reviewed PRITE questions over multiple years that were categorized as focusing on forensic psychiatry. Each question was then coded for a specific sub-topic within forensic psychiatry. This research reveals the sub-topics identified as important in the PRITE. The authors, using the data collected, also identify areas in need of further instruction or emphasis in the psychiatry residency didactic curriculum and provide recommendations for psychiatry training to cover the identified sub-topics. 

Mathematics, in its own way, is a language, a new, and often abstract, way of viewing the world.  Through examining knot theory, we are able to contribute information to this rapidly expanding field of study, and apply our results to other research disciplines. A mathematical knot is a closed circle embedded into 3-dimensional space, where there exists crossings and regions. We examine the number of region crossing changes necessary to produce an alternating diagram, and define our new invariant as the region dealternating number. This property leads to an invariant, similar to the dealternating number, but offers new insight into the manipulation of knots. We expand our invariant under the connect sum theory to better understand the behavior of the region dealternating number. In particular, we apply the reasoning built for this invariant to prove that the (warping) span of any knot is at most 2, answering a previously unsolved question for warping span. We hope to continue to further these concepts and apply them to other families of knots and subsequent invariants. 

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorder characterized by social and communication deficits as well as restrictive/repetitive behaviors and interests (American Psychiatric Association, 2013). The broader autism phenotype (BAP) is a set of subclinical characteristics that are milder, but qualitatively similar to the defining features of ASDs and are most notably seen in first- and second-degree relatives of individuals with autism (Gerdts, Bernier, Dawson, & Estes, 2013; Ingersoll, Hopwood, Wainer, & Donnellan, 2011). The broader autism phenotype is thought to display the genetic liability to autism, and as BAP characteristics are only part of the total set of autistic deficits, they are thought to represent simpler components that may more easily be tied to underlying genetic causes. While comparisons of BAP traits in parents of simplex (one affected child) and multiplex (multiple affected children) families have potentially suggested different underlying genetic liabilities, there is no research to date comparing these traits in families with identified genetic events. Using the Simon Simplex Collection (SSC), this study looks to explore differences in phenotypic presentation of ASD-related traits by examining the rates of BAP characteristics within simplex families whose autism has been linked to either a de novo (spontaneous) CNV (large structural chromosomal change), a de novo SNV (single base pair change), an inherited event, or has been deemed idiopathic (unknown cause). Parent BAP levels are assessed via two measures, the Broad Autism Phenotype Questionnaire (BAPQ; Hurley, Losh, Parlier, Reznick, & Piven, 2007) and the Social Responsiveness Scale (SRS; Constantino & Gruber, 2005). Mothers and fathers within the four groups are compared on each of the five SRS subscales, the SRS total score, the three BAPQ subscales, and the BAPQ total score. Given the multiple independent and dependent variables, a multivariate analysis of variance (MANOVA) is used to compare scores across groups.