X-Ray Crystallography of CUG-Containing RNA Constructs with and Without Small Molecules Could Help Develop Therapeutic Agents to Alleviate Myotonic Dystrophy Symptoms at a Molecular Level

Presenter: Irina Rapoport

Mentor: Andy Berglund

AM Poster Presentation

Poster 37

Myotonic dystrophy is the most common form of adult-onset muscular dystrophy. DM type 1 is caused by aberrantly expanded CTG repeats in the 3’ untranslated region of the DMPK gene. Upon transcription, toxic RNA CUG repeats are formed, which sequester Mbnl proteins, causing abnormal splicing in cells. Some of these abnormal splicing events have been shown to lead to the disease symptoms. Small molecules that release Mbnl sequestration from the toxic RNA could alleviate disease symptoms. I am crystallizing CUG-containing RNA constructs with and without small molecules. Crystal structures would provide direct evidence of where and how the small molecules bind the toxic RNA. Before crystallography, the RNA is deprotected, purified by HPLC, resuspended in buf- fer and annealed. Using Natrix crystallization screens, I test a wide array of conditions for crystal formations. Then, I scale up and vary the most favorable conditions to obtain bigger crystals. Two different RNA constructs, containing three CUG repeats, have crystal- lized well without small molecules under several conditions. A third RNA construct, with two CUG repeats, formed crystals with a small molecule called JFA12046. To screen for additional small molecules with the ability to disrupt the MBNL-CUG complex, we are running competitive electrophoretic mobility shift assays. Long-term, efficiently designed small molecules could be used as therapeutic agents to treat myotonic dystrophy and other diseases with similar molecular mechanisms.

Altered Lung Development in Growth Restricted Offspring from Hypertensive Pregnant Rats

Presenter : Alice Rear

Mentor : Jeffrey Gilbert

Major : Biology and Human Physiology

Poster 37

Recent studies suggest that angiogenic dysregulation in utero impairs fetal pulmonary vascular development and arrests normal alveolarization, potentially contributing to the pathogenesis of bronchopulmonary dysplasia (BPD). Since reduced utero-placental perfusion (RUPP) induced hypertension is associated with angiogenic imbalance (soluble fms-like tyrosine kinase-1, sFlt-1; and vascular endothelial growth factor, VEGF) in the maternal circulation and amniotic fluid, we hypothesized it would result in abnormal alveolarization, diminished pulmonary vascular development, and impaired VEGF signaling in the fetal rat lung. Fetal lung tissue and amniotic fluid were collected on day 19 of gestation from RUPP and normal pregnancies (NP). A second cohort delivered pups that were weighed at birth and lungs were collected at 10 weeks of age. Fetuses from RUPP pregnancies were smaller at day 19 (2.1 vs. 2.6 g; P<0.05) of gestation and at birth (6.1 vs. 6.7 g; P<0.05) than NP offspring. Preliminary data suggests that RUPP offspring may have reduced (20% decrease) pulmonary vascularity and alveolar simplification (45% decrease in alveolar space) when compared to normal pregnant controls. VEGF receptor-2 was decreased (48%; P< 0.05) in the lungs of day 19 RUPP offspring. These data suggest that chronic placental insufficiency has detrimental effects on the developing pulmonary vasculature and alveoli, and support the hypoth- esis that angiogenic imbalance in utero may play an important role in the pathogenesis of BPD

Exposure to perchlorate affects differentiating germ cells in teleost fish

Presenter: Nathaniel Earp

Mentor: William Cresko

Poster: 37

Major: Human Physiology 

Perchlorate is a widespread contaminant in the environment. We have found that perchlorate has masculinizing effects on threespine stickleback, Gasterosteus aculeatus. The mechanism of this masculinization is unknown. Our previous studies found that during development female stickleback show increased proliferation of undifferentiated primordial germ cells (PGC) followed by a larger wave of apoptosis compared to male stickleback. We hypothesize that perchlorate treated stickleback will show a decrease in total number of PGCs compared to control fish. To test our hypothesis, stickleback of 15 and 20 days post fertilization (dpf) – a critical time for primary sexual differentiation– were grown from fertilization to the end of the experiment in 10 or 100 ppm perchlorate treated medium or control medium with no perchlorate. Stickleback were sectioned and stained with hematoxylin and eosin, and visualized by light microscope. Total number of PGCs were counted and characterized as either pre-meiotic or meiotic based on morphology of the PGC and nucleus. Perchlorate treated fish show a significant decrease (27.6%) in total number of PGCs compared to controls. Furthermore, control stickleback showed a decrease in total number of PGCs from 15 dpf to 20 dpf, presumably due to female germ cell apoptosis, while perchlorate treated stickleback did not show this decrease. These findings are consistent with perchlorate’s masculinizing effect. We are further investigating the effects of perchlorate on total PGC count in zebrafish, Danio rerio, as perchlorate has been shown to have a feminizing effect on zebrafish, giving us an opportunity to explore the basic mechanisms underlying the reproductive abnormalities caused by perchlorate. Our findings contribute to understanding mechanisms of perchlorate induced reproductive abnormalities in vertebrates, and to better understand the underlying process of sex determination in two divergent teleosts.

The Salmon Connection: Alaska and Oregon

Presenter: Madison Kirby

Co-Presenter: Melanie Burke

Mentor: Mark Blaine, Journalism

Poster: 37

Major: Journalism

This poster draws parallels between Oregon and Alaska found in the reporting of Science and Memory, a climate change reporting project from the School of Journalism and Communication at the University of Oregon. Parallels such as the dusky geese migration, braided river systems, and salmon runs help localize the thinking and science behind climate change. Our line of inquiry followed questions about climate change in Cordova, Alaska, and their implications for our home base in Oregon. As journalists, our job is to report, but also to draw light to issues that the general public seems to know little about. With the ever-growing list of “climate-deniers” in the media and political world we found ourselves with a greater task at hand than we anticipated. Using a broad range of multimedia and multi-platform storytelling techniques and tools, we began a multiyear process of documenting attitudes and values in communities facing climate change.

Gender Socialization of Masculinity

Presenter: Alexis Skaw

Co-Presenters: April Wheeler, Brent Koekkoek

Faculty Mentor: Julie Heffernan

Presentation Type: Poster 37

Primary Research Area: Humanities

Major: Education

As soon as a child is born in the United States, they are assigned a sex in the male/female gender binary and gender socialization automatically begins. For boys, this means they will be taught to be tough, strong and control their emotions in order to enact masculinity. While much of this socialization occurs in the child’s home, it is also strongly enforced throughout social institutions. Sometimes this socialization is explicitly taught while other times
the lessons are implicitly engrained into traditions and practices. Schools, as social institutions, contribute to student’s socialization regarding gender, race and class. Our focus is on how gender socialization of masculinity, which can intersect with race and class, affects boys at different stages of their development. Hyper-masculinity, the exaggeration of masculinity which emphasizes aggressive and impulsive behavior, is associated with a breadth of emotional and physical ramifications. By pointing out the negative effects of hyper-masculinity, we hope to inspire teachers to enact pedagogy which encourages boys to explore non-gender conforming hobbies, sports, studies
and careers among other activities. By fostering an environment where students do not feel pressured to enact masculinity, boys will feel less burdened to become hyper-masculine and in turn, they can avoid situations which have negative effects on their mental and physical well-being.

Using Machine Learning for Source Detection at the First G-APD Cherenkov Telescope (FACT)

Presenter(s): Jacob Bieker – Physics, Computer and Information Science

Faculty Mentor(s): Tim Cohen

Poster 37

Oral Session 2S

Research Area: Physical Science

Funding: DAAD Research Internships in Science and Engineering (RISE)

Finding gamma-ray sources is of paramount importance for Imaging Air Cherenkov Telescopes (IACT). This study looks at using deep neural networks on data from the First G-APD Cherenkov Telescope (FACT) as a proof-of-concept of finding gamma-ray sources with deep learning for the upcoming Cherenkov Telescope Array (CTA). In this study, FACT’s individual photon level observation data from the last 5 years was used with convolutional neural networks to determine if one or more sources were present. The output from the neural networks were compared using the default method of finding sources as a baseline. The neural networks used various architectures to determine which architectures were most successful in finding sources. Neural networks offer a promising method for finding gamma-ray sources for IACTs. With further improvement and modifications, they offer a compelling method for source detection for the next generation of IACTs.

The Effect of Varying Reward Treatments on Performance and Learning Acquisition in Mice

Presenter(s): John Francis

Faculty Mentor(s): Paul Steffan & David McCormick

Poster 37

Session: Sciences

An animal’s ability to interpret and respond to environmental stimuli is highly variable, depending on factors such as the reward the animal receives for correctly responding to said stimuli. Using a more favorable reward is expected to positively influence motivation and performance of these animals in a specific behavioral task. The present study examined the effects of using a highly palatable caloric reward in lieu of standard water reward. It was hypothesized that a highly caloric reward solution would facilitate a faster rate of learning on animals completing a behavioral task involving detecting and responding to a correct auditory stimulus embedded within a series of distractor auditory stimuli. Mice were water-restricted and subjected to one of two reward treatment conditions upon correct licking behaviors during a target auditory tone. While the present study determined that a 10% sucrose solution has the capacity to act as a stimulus that promotes correct behavior due to its positive reinforcement properties, (d’ = 2.02), further experiments and larger sample sizes are required to fully quantify the efficacy of sucrose solution compared to traditional water rewards. By examining the effects of alternative reward treatments on performance in an auditory tone discrimination task, we can determine optimal treatment conditions in which mice learn most efficiently. These results could further elucidate the relationship between caloric intake, nutrition, and learning at large.