23rd Annual Graduate Student Research Symposium

The annual Graduate Research Symposium brings together graduate and professional students from diverse backgrounds. This signature annual event promotes communication and interaction among students comprising the top-notch graduate programs offered at Washington University in St. Louis. Through the symposium, students gain an opportunity to present their research to a broad audience of students, faculty, and community members with diverse academic backgrounds.

Our students at Washington University do wonderful work in a diverse range of graduate programs. However, it is not often that a Comparative Literature student would be found sharing his or her work with a Chemistry student, or a Biomedical Engineering student conversing with a Psychology and Brain Science Student. Each time a new acquaintance is made, the other is often curious to know a bit about you and what you do. Effectively giving a concise overview of one’s work is a valuable skill students will rely on not just in their graduate work, but also in their careers. This symposium provides a unique platform to encourage dialogue among students and faculty from across the university. It encourages intellectual discussion of one’s’ work and provides opportunities for networking and collaboration throughout the conversation surrounding the most current research here at Washington University.

In preparation for this year’s symposium, the GSS held a workshop led by Dr. Karen Olson and fellow student Cynthia Holland. The workshop focused on effective communication to broad audiences and creating a captivating research poster for all viewers.

This year’s Graduate Student Research Symposium benefits from the collaborative efforts of numerous graduate student groups: the Graduate Student Senate (GSS), Association of Graduate Engineering Students (AGES), and the Graduate Professional Council (GPC). The hard work and dedication of these groups make the Symposium possible.  In addition, the event would not be possible without the continued generous support of the Graduate School of Arts and Sciences. We hope that the 23rd year of the annual Graduate Research Symposium is a truly cinematic presentation of the work these hardworking students do each day.


Schedule of Events

2:00 pm – 4:00 pm

Poster Presentations & Judging throughout Crowder Courtyard

4:00-5:00 pm

Awards Ceremony in Bryan Cave Moot Courtroom

 

 Awards Ceremony

Welcome

Ninecia Scott and Brice Albert; Co-Chairs, Graduate Research Symposium

Introduction

Melissa Budelier; Graduate Student

Remarks

Jose Moron-Concepcion, Ph.D.

Presentation of the Awards

Daniel Mulrow, Anna Franklin, Marta Stojanovic, Caleb Boyd, Carmen Toro, Graham Zulu;

Graduate Research Symposium Committee Members

Closing & Thanks

Ninecia Scott and Brice Albert; Co-Chairs, Graduate Research Symposium


2018 Graduate Research Symposium Presenters

Engineering:

ENG-1            Gabriela Espinosa       Biomedical Engineering

ENG-2            Kristina Maxwell        Biomedical Engineering

ENG-3            Amrita Nishtala           Biomedical Engineering

ENG-4            Ben Sumlin                 Energy, Environmental, and Chemical Engineering

ENG-5            Yvonne Afriyie            Mechanical Engineering & Material Sciences

ENG-6            Ke Song                      Mechanical Engineering & Material Sciences

 

Humanitites:

HUM-1                       Yuqi Li                         Anthropology

HUM-2                       Lindsay Sheedy          Art History and Archaeology

HUM-3                       Anothai Kaewkaen     Comparative Literature

 

Professional:

PRO-1             Allison Poehler            Public Health

PRO-2             Roger Wong                Public Health Sciences

PRO-3             Zhao Yingnan             Law

 

Sciences:

SCI-1              Tabbetha Bohac          Chemistry

SCI-2              Chia-Hsin Chen          Chemistry

SCI-3              Robert Marti               Chemistry

SCI-4              Michael West              Chemistry

SCI-5              Brian Earley                Developmental Biology

SCI-6              Rich Li                    Developmental, Regenerative, and Stem Cell Biology

SCI-7              Catherine Lipovsky Developmental, Regenerative, and Stem Cell Biology

SCI-8              Sean Yu                      Informatics

SCI-9              Michal Skowyra          Molecular Cell Biology

SCI-10            Nina Beri                     Molecular Genetics and Genomics

SCI-11            Hannah Frye               Neuroscience

SCI-12            Samantha Powers        Plant and Microbial Biosciences

SCI-13            Kelsey Meinerz           Physics

SCI-14            Seyed Motahari           Physics

 

Social Sciences:

SOC-1             Lamesse Eldesouky    Psychology and Brain Sciences

SOC-2             Jessica Nicosia Psychology and Brain Sciences


Abstracts

Engineering:

ENG-1 Gabriela Espinosa, Biomedical Engineering

Hemodynamic Perturbations Alter the Mechanical Properties of Chick Dorsal Aorta in Development

“Perturbations to embryonic hemodynamics are known to adversely affect key cardiovascular developmental processes.  Vitelline vein ligation (VVL) is a model of reduced placental blood flow commonly used to induce cardiac defects in chick development.  Arteries begin maturation in the same time frame, but their response to these hemodynamic interventions is unknown.  We hypothesize that changes to the hemodynamic environment result in structural and mechanical alterations to the developing dorsal aorta (DA).  We measured the heart rate and blood velocity in the DA of control and VVL chick embryos at embryonic days (E) 3-10.  We also used immunofluorescence to characterize aortic dimensions, degree of fiber orientation, and percent quantities of elastin, collagen, and cells at E6, 8, and 10.  Aortic rings from E8 and E10 embryos were used for opening angle measurements, stress relaxation tests, and cyclic tensile mechanical tests.  We found that blood velocity is significantly reduced immediately post-surgery and E10, but comparable to controls at the intervening time points.  At E10, we found that VVL DAs show a substantial decrease in elastin content and increase in opening angle.  Stress relaxation and cyclic loading data were analyzed using a quasi-linear viscoelastic model.  These reveal an increase in peak stress, elastic modulus, and hysteresis in E10 VVL rings as compared to controls.  These results show that decreased blood flow impairs elastic fiber development, resulting in altered viscoelastic properties of the DA.  Future work will incorporate these results into a model of arterial growth and development.”

 

ENG-2 Kristina Maxwell, Biomedical Engineering

Miniature bioreactors for parallel differentiation of diabetic patient induced pluripotent stem cells to insulin-producing β cells in 3D

“Strategies for generating β-like cells from human pluripotent stem cells, including induced pluripotent stem cells (iPSCs), have been recently reported. These stem cell-derived β (SC-β) cells display many of the same features as β cells from adults, including similar gene expression and the ability to secrete insulin in response to glucose. A major application of this technology is generation of β cells from patient iPSCs for study of β cell stress and failure in disease models. However, current differentiation approaches have limited feasibility for studying multiple patient-derived SC-β cells due to culture vessel size and format. We differentiated patient-derived iPSCs into SC-β cells from patients with multiple forms of diabetes in a miniaturized 5-mL bioreactor. This culture format is up to 60x smaller than previous reports while maintaining 3D cell culture in suspension and is in a multi-well format facilitating parallel differentiation of several iPSC lines. We compared the differentiation of iPSCs from patients with Wolfram Syndrome (WS) and non-diabetics (ND) to SC-β cells and observed that WS SC-β cells had reduced insulin secretion and ability to respond to glucose compare to ND SC-β cells. The expression of several β cell genes, including NKX6-1, MAFA, KCNK3, and INS, were lower in WS SC-β cells while markers associated with ER stress, including CHOP, BiP, ATF6, and PERK, were higher. WS SC-β cells also responded to ER stress induced with thapsigargin treatment. Overall, WS SC-β cells had reduced expression of β cell markers and function and increased markers of stress compared to ND SC-β cells.”

 

ENG-3 Amrita Nishtala, Biomedical Engineering

Chronic Nerve Interfacing Utilizing Graft-Embedded Regenerative Electrodes

“Peripheral nervous system (PNS) injuries in humans often lead to incomplete functional recovery. Existing peripheral nerve repair techniques such as inter-positional grafting and end-to-side neurorrhaphy fall short in regaining loss of function. Double end-to-side neurorrhaphy, or “jump graft”, has gained recent traction as it offers an expedited route of functional recovery over traditional nerve repair methods. In this study, the jump graft technique is combined with customized macrosieve electrodes to assess multiple parameters of neuro-regeneration in the rat sciatic nerve. The study consists of three experimental groups (nerve graft only (GO), nerve graft inside a silicone tube (G+C), and nerve graft inside a silicone conduit with a sieve electrode (S)), with four animal subjects each. Neuro-regeneration was quantified with functional assessments via needle electrode-based electromyography (EMG) and evoked muscle force measurements. Histological responses of nerve transections were also gathered to quantify axon numbers through the areas proximal and distal to the injured segment. Chronically implanted macrosieve electrodes demonstrated successful and independent recruitment of motor nerve fibers and induction of selective muscle activation in independent muscle groups in the lower limb. This suggests strong axon sprouting through the graft nerve and preservation of existing functional axons in the PNS, yielding new approaches to achieving a stable and high selectivity interface to peripheral nerve tissue.”

 

ENG-4 Ben Sumlin, Energy, Environmental, and Chemical Engineering

A Novel Mie Theory Inversion Technique for Retrieving the Complex Refractive Index from Optical Measurements

“Mie theory is a powerful tool that can accurately calculate the scattering and absorption behavior of an aerosol particle with any radial symmetry, such as spheres and long cylinders, and whose diameter is on the order of the wavelength of incident light. However, the complex refractive index m=n+ik is often the unknown parameter in aerosol optics studies and is a vital parameter for climate modeling and satellite retrieval algorithms. Mie theory equations take m as an input, therefore recovering it from measurements presents an inverse problem which is confounded by the multidimensional parameter space the equations require.

Since m cannot be measured directly, a method to determine the refractive index from experimental data is needed. We present a novel, visual method to determine m from optical measurements by identifying intersections of scattering and absorption contour maps in n-k space. This method allows arbitrary curves to be treated geometrically and algebraically, eliminating the need to develop complicated analytic expressions for the contours. The minimum inputs are scattering, absorption, particle size, and wavelength, however, this can lead to an improperly constrained problem, with multiple valid values of refractive index that will reproduce the measured parameters. This can be fully constrained by measuring an additional independent parameter, such as the backscattering efficiency.

This inversion method is presented in the context of The Python Mie Scattering package, or PyMieScatt. This package is open-source, fully documented, and available to the community, allowing research groups to bypass the step of developing their own Mie theory software.”

 

ENG-5 Yvonne Afriyie, Mechanical Engineering & Materials Science

Structural Dependence of Aluminum Oxide Thin Films on Starting Precursor and Annealing Temperature

“Aluminum is an ideal metal for solution-processed oxide dielectric thin films because it can form polymerized hydroxo networks in aqueous solution and dense amorphous oxide dielectrics by various synthesis routes. Conventional synthesis techniques such as Atomic layer deposition (ALD) and metal-organic chemical vapor deposition (MOCVD) are not the most economical methods for fabrication of these dielectric thin films because they require high operational cost and present limitations in large surface area applications1.  Solution deposition technique presents itself as a more cost-saving synthesis route and is ideal for large surface area fabrication. The behavior of the structural evolution of these thin films remain an enigma, therefore this project seeks to understand the evolution of the local structure of aluminum oxide based thin films as a function of annealing temperature.

Aluminum oxide (AlxOy) thin films prepared from aqueous solution-deposited cluster precursors have been proposed for use in devices such as high-k dielectrics in thin film transistors2.  The films are fabricated from four different aluminum oxide precursor clusters, spin-coated on a substrate and annealed at temperatures ranging 230◦C to 900◦C. The films in the mid temperature range of 300◦C to 700◦C are amorphous due to the lack of long range order. This lack of long range order complicates the analysis of the thin films by conventional diffraction means; however solid-state nuclear magnetic resonance (ssNMR) can be used to determine the structure of these materials in the amorphous domain. ssNMR yields important information regarding the aluminum metal coordination.”

 

ENG-6 Ke Song, Mechanical Engineering & Materials Science

Musculoskeletal Models with Generic and Subject-Specific Geometry Estimate Joint Biomechanics Differently in Pathomorphologic Hips

“Developmental dysplasia of the hip (DDH) is a disease characterized by deformed hip bone geometry, abnormal joint loading, and joint degeneration at an early age. Human hip biomechanics (e.g. joint reaction forces, JRF) during routine activities may be indicative of the DDH etiology; but as they are difficult to measure in vivo, musculoskeletal models are commonly used to estimate their values. Most studies on healthy population scaled models with a generic geometry to match each individual, but such approach might be less accurate to represent deformed joints. Model accuracy may be improved by adding subject-specific geometry from medical images, yet computational burden could make models less practical. To find a balance between accuracy and complexity, we compared models with generic vs. subject-specific geometry, and investigated their effects on hip biomechanical estimates for both DDH individuals and healthy controls. We created 3 increasingly complex models using 3D pelvis geometry reconstructed from CT images, then estimated hip JRFs and muscle forces during walking from each model. The highly subject-specific models (with CT-based hip joint locations and fine-tuned muscle paths) estimated different hip JRFs (p≤0.033) and muscle forces vs. less specific models, with considerable effects for DDH individuals while less so for controls. In contrast, incrementally specific models (with pelvis scaled using CT images but no subject-specific geometry) showed no difference vs. generic models. Including highly specific geometric details may thus be necessary for models to reliably estimate joint biomechanics in DDH hips, and potentially for other joint deformity diseases.”

 

 

Humanities:

HUM-1 Yuqi Li, Anthropology

New Technologies Help Investigate Silk Road Irrigation Systems

“Irrigation technologies were fundamental to the desert communities living along the heartland of the Silk Road in China’s Xinjiang region. However, archaeologists know very little about the irrigation technologies in this region, particularly for the Han to Jin dynasties (ca. 200-400 AD), the formative period of the Silk Road. The majority of the known irrigation systems dating to this period were constructed by the Han dynasty to sustain its rule of Xinjiang. Only a few were likely built by the locals, but research on them is limited to simple morphological descriptions, far from enough to reveal the hydraulic considerations behind their designs.

In this study, I combine satellite remote sensing, drone-based surveys, 3D hydraulic modeling, sediment analysis, and other conventional archaeological methods to tackle the two major problems associated with the study of ancient irrigation technologies in Xinjiang, the scarcity of known sites associated with the local populations and a lack of in-depth analysis of known sites. My discovery and analysis of the irrigation system at MGK in central Xinjiang reveals that the local populations were capable to build sophisticated irrigation systems during the formative period of the Silk Road. Compared with the irrigation systems introduced by the Han dynasty, the system at MGK required much lower labor and resource investment, had lower impact on the local ecology, and better matched with the local populations’ agro-pastoralist lifestyle. This a result suggests a necessity to reevaluate the local populations’ technological contribution to the formation and persistence of the Silk Road.”

 

HUM-2 Lindsay Sheedy, Art History and Archeology

Rembrandt’s Three Crosses: Art History. Technology. Imagination.

 “As its title suggests, my project explores the intersections between art history, technology, and imagination in a case study of Rembrandt van Rijn’s print, Three Crosses, which depicts Christ crucified between two thieves as crowds of people despair at the base of the titular crosses. This project began as a small research assignment for a recent exhibition at the Mildred Lane Kemper Art Museum and has since spilled over into the work that I am doing for an innovative new course entitled Digital Art Historian. My work aims to elucidate Rembrandt’s artistic processes and to highlight his skill as a storyteller by visualizing the changes that he made to Three Crosses over the course of ten years, in which he re-worked the scene on his copper plate at least four times. The Kemper’s impression of Three Crosses, which is without question one of the most important prints in the collection, represents the fourth and final stage of Rembrandt’s reimagining of the scene of Christ’s crucifixion. By using programs such as Photoshop, I transform the first state of the print into the fourth state. This visualization allows us to see, through a series of overlapping layers, how Rembrandt radically transformed the scene over the course of his ten-year meditation on the subject. In presenting this project at the GRS, my goal is to share not only my own work but also to introduce attendees to a star work in the Kemper collection and share the fruits of an innovative new course.”

 

HUM-3 Anothai Kaewkaen, Comparative Literature

Psychoanalyzing “Mae Bia”: Both Beyond & Deeper Into the Sex Scenes

“In the popular 1987 Thai novel “Mae Bia,” a pair of adulterous lovers is stalked by a mysterious cobra. Conventional Thai scholarship has largely interpreted the novel in moralizing terms and the cobra as the enforcer of traditional family values and sexual propriety. However, these views are not only ahistorical, but fail to consider the broader context in which the snake appears and its complicated relationship with the main characters. Accepting the text’s own invitation to probe underlying psychological dimensions, this paper reads “Mae Bia” through feminist and Freudian lenses, as well as in relation with such texts as “Oedipus Rex” and “Hamlet.” In doing so, it demonstrates how the novel can be alternatively understood (beyond the sex scenes) as an interrogation of nationalistic identity politics and (deeper into the sex scenes) both an Oedipal drama and a tale of female sexual liberation.”

 

 

Professional:

PRO-1 Allison Poehler, Law

A Profile of Emergency Department Super Users for Sexually Transmitted Infection Care         

Introduction: STIs remain prevalent in urban populations and are commonly diagnosed and treated in emergency departments (EDs). However, the burden of STI-care on urban EDs is not well understood. The burden of care for super users, or patients making more than one visit, is not well understood. Methods: A retrospective study of patients seeking acute care for STI-related complaints at four EDs in in St. Louis, MO, from January 2012 to May 2016 was conducted. ED patients evaluated for Chlamydia trachomatis (Ct) and Neisseria gonorrhoeae (GC) infection by nucleic acid amplification testing or who had a STI diagnosis code were examined. Patient demographics, testing rates, and STI prevalence were characterized. Results: A total of 40,126 visits were made by 27,233 patients. Twenty-five percent (n=6,921) were super users. Super users made 49% (n=19,814) of all visits. Super users were majority African American (93%) females (81%) with a median age of 23.7 years. Thirty-nine percent of super user visits were paid by Medicaid and 38% were self-pay. Female super users were more likely to have positive tests for Ct (p>.001) and Gc (p>.001) than female single users. Male super users were also more likely to have positive tests for Ct (p=.004) and Gc (p=.001) than male single users. Conclusion: A large number of visits made for STI care to these EDs are made by frequent users, and the infection rates are higher in this group. Further analysis is needed to elucidate factors that influence infection status of single users and super users.”

 

PRO-2 Roger Wong, Public Health Sciences

Racial Differences in Alzheimer’s Disease Risk Within the United States         

Background: Although Alzheimer’s disease (AD) was identified more than 100 years ago, inequalities continue to persist as prior research has indicated an increased risk for racial minorities. Despite extensive support for this disparity, there is no research that has compared AD risk among all U.S. racial groups. Objectives:
This study examined racial differences in AD risk among older adults in the U.S. Methods: Data were retrieved from the National Healthy and Aging Trends Study, a longitudinal panel study that surveys a nationally representative sample of Medicare beneficiaries age 65 or older. The sample included 8,124 individuals who self-identified as White, African American, Hispanic, or Asian. Cox models were used to analyze the influence of sociodemographics, health, and lifestyle behaviors on racial differences in AD risk. Results: Approximately 6.1% of the sample developed a new AD diagnosis during the study, with an average diagnosed age of 81.7 years. Compared to White older adults, AD risk was highest among Hispanics (Hazard Ratio [HR]=1.86, p<.001) and African Americans (HR=1.38, p<.01), while Asians exhibited the lowest risk (HR=0.72, p=.48) when controlling for age and gender. Racial differences in AD risk was marginally reduced after controlling for sociodemographics, health, and lifestyle behaviors. Conclusions: Findings support previous research suggesting an elevated risk for AD among Hispanics and African Americans. Health professionals and policymakers should consider targeting health and lifestyle behaviors as potential areas to reduce inequalities in AD. Future research is needed to explore risk in other racial minority groups including American Indians and Pacific Islanders.”

 

PRO-3 Zhao Yingnan, Law

Do We Really Know Dworkin’s “One-Right-Answer” Thesis?          

“The “one-right-answer” thesis is Dworkin’s theoretical reply to Hart’s seminal opinion, “open texture”. This thesis means judges could provide the single right answer to legal issues, even if they are faced with hard cases. Getting to know the definite meaning of this thesis, hard cases and the objectivity of law should be taken into consideration. Through this consideration, there is logical consistency between what Dworkin called “Legal Principles Thesis” and “Constructive Interpretation”. Besides, the objectivity of law is dependent on the inner moral sense of judges, which guarantees the availability of “the single right answer”. Critical Legal Studies and Legal Positivists have misunderstood the definite meaning of objectivity in Dworkin’s sense, which has both legal and moral implications.”

 

 

Sciences:

SCI-1 Tabbetha Bohac, Chemistry

Synthesis and Biological Activity of Siderophores from Human Pathogenic A. baumannii

“The rise of antibiotic resistance is driving exploration of non-canonical antibiotic approaches, including neutralization of virulence factors. Siderophores are small iron (III) chelators required for pathogen virulence. Highly pathogenic A. baumannii excretes at least three siderophores during infection. Production of multiple siderophores seems redundant and costly, but must provide a fitness advantage. We aim to elucidate the benefit of producing siderophore cocktails through the chemical synthesis of natural siderophores, rationally designed analogs, and chemical probes. The synthesis and biological activity of several A. baumannii siderophores will be presented.”

 

SCI-2 Chia-Hsin Chen, Chemistry

Characterization of 13CO2 chemisorption on solid amine modified SBA15

“Increased concentrations of atmospheric CO2, largely from fossil fuel combustion, contribute to global climate change. Solid adsorbents such as amine-grafted SBA15 are proposed to replace existing aqueous amine technology for reducing CO2 emissions due to its lower regeneration energy cost. Unlike aqueous amines, which have been extensively studied, the mechanism of CO2 adsorption in solid amine adsorbents is still ambiguous. Several factors such as the nature of the amines, humidity, partial pressure of CO2, and amine density can influence the CO2 reaction pathways. 13CO2 is chemisorbed by the amine groups, forming isotopically-enriched products of carbamate, carbamic acid, and/or bicarbonate.

Chemical shift assignment of CO2 products such as carbamate, carbamic acid, and bicarbonate is insufficient for peak assignment, due to the small differences in chemical shift of such species.13C{1H} CPMAS and 15N{1H} CPMAS of 13CO2 loaded solid amine SBA15 will be discussed. 15N{13C} rotational-echo double-resonance (REDOR) and the complementary experiment of 13C{15N} REDOR were performed to help with the assignments of the chemisorbed products in the 13C and 15N spectra. These experiments result in interesting conclusions regarding the types of chemisorbed products in this system, as will be discussed.”

 

SCI-3 Robert Marti, Chemistry

Carbon Dioxide Dynamics and Characterization of Metal-Organic Frameworks 

“Using in situ variable temperature NMR measurements, we can elucidate structural details of carbon dioxide inside the one-dimensional channels of Mg-MOF-74. Understanding dynamics is key to synthesizing better carbon dioxide adsorbents. In addition to gas dynamics, we studied the quadrupolar nucleus, aluminum, to track the solid-to-solid transformation of MIL-53(Al) from aluminum carbide.

 

SCI-4 Michael West, Chemistry

Modeling and Measuring Nuclear Spin Temperature in GaAs Using 75As OPNMR 

“Isolated nuclear spins and nuclear spin pairs manipulated by polarized light are a hot topic in the realm of quantum computing.  Irradiating direct-gap semiconductors with circularly polarized light leads to hyperpolarization of nuclear spin states through a series of mechanisms that are not fully understood.  The efficiency of these mechanisms, which can be indirectly inspected by having a measure of final nuclear spin polarization, have not been studied in great detail.  Optically pumped nuclear magnetic resonance (OPNMR) of quadrupolar nuclei has the unique capability of being able to measure spin temperature in the form of relative transition intensities.  Here, models for predicting spin temperature based on density matrix formalism (DMF) for two common modified NMR pulse sequences are derived.  Results on preliminary experiments are shown, and applications are discussed.”

 

SCI-5 Brian Earley, DBBS  (Developmental Biology)

The high zinc receptor HIZR-1 is also the cadmium receptor

“Exposure to the toxic metal cadmium is a global health problem causing substantial disease for humans and ecosystems. There is an urgent need to develop therapeutic strategies that target cadmium injury, but mechanisms of cadmium toxicity remain speculative. To understand how cells detect and respond to cadmium, I have analyzed a newly discovered cadmium-activated transcription factor using the genetically amenable model organism C. elegans.  HIZR-1 is a transcription factor that directly binds the High Zinc Activation DNA element to activate multiple zinc homeostasis genes in response to high dietary zinc and cadmium. Without HIZR-1, animals fail to activate zinc homeostasis genes, and HIZR-1-deficient animals are hypersensitive to high zinc toxicity. Interestingly, HIZR-1-deficient animals are not hypersensitive to cadmium toxicity.
I first determined the proportion of the cadmium response that depends on HIZR-1. I then established the functional consequences of the cadmium response by analyzing animals that lack cadmium-activated genes. HIZR-1-dependent genes did not protect animals from cadmium, while HIZR-1-independent genes protected animals from cadmium and other stressors. The nuclear receptor HIZR-1 functions as both the zinc and cadmium receptor mediating a major part of the response to cadmium. In addition, there is a HIZR-1 independent response to cadmium exposure analogous to the general stress response.
Cadmium exposure is a serious health hazard with no mechanistic treatment or therapeutic. These experiments establish 1) HIZR-1 as the cadmium receptor and 2) the functional significance of many cadmium response genes. The mechanisms described in these studies may suggest new treatments for detoxifying cadmium.”

 

SCI-6 Rich Li, DBBS (Developmental, Regenerative, Stem Cell Biology)

Differential Wnt-Mediated Programming and Arrhythmogenesis In Right Versus Left Ventricles           

“Several inherited arrhythmias primarily affect the right ventricle, including Brugada syndrome and arrhythmogenic cardiomyopathy, however the molecular basis of this chamber predilection is not well understood. Right and left ventricular cardiomyocytes derive from distinct progenitor populations. Here, we show that Hrt2, a gene associated with Brugada syndrome, is a direct target of Wnt signaling in the right ventricle and Notch signaling in the left ventricle. Perturbations of Wnt and Notch signaling during development and in the adult lead to chamber-specific transcriptional effects on Hrt2 expression associated with distinct binding patterns to Hrt2 enhancers. Differential enhancer binding is present at early developmental stages when the signaling pathways are active and persists into adulthood. Consistent with chamber-specific regulation, mice deficient in Wnt transcriptional activity dysregulate only a small fraction of transcripts in common between ventricles. Wnt target genes important for cellular electrophysiology are differentially regulated, resulting in perturbed cardiac conduction and cellular electrophysiological parameters only within the right ventricle. Ex vivo and in vivo physiologic stimulation of the right ventricle is sufficient to induce ventricular tachycardia in Wnt transcriptionally inactive hearts, while left ventricular stimulation has no effect. Taken together, these data delineate mechanisms underlying ventricular-specific arrhythmia susceptibility due to embryonic programming.”

 

SCI-7 Catherine Lipovsky, DBBS (Developmental, Regenerative, Stem Cell Biology)

Notch Activation Predisposes to Atrial Arrhythmias in Mice

“Notch signaling programs cardiac conduction during development, then becomes quiescent in adult cardiomyocytes. We have previously shown Notch signaling is reactivated in adult atrial cardiomyocytes following cardiac injury. To model an injury response and determine effects of Notch signaling on atrial electrophysiology, we transiently activated Notch signaling within adult myocardium using a doxycycline-inducible genetic system (iNICD). These mice have no structural defects, yet develop sinus bradycardia, frequent sinus pauses, and pacing-induced supraventricular tachycardia when stimulated near the pulmonary veins, which taken together are indicative of an electrically remodeled arrhythmogenic substrate. Furthermore, we have shown that Notch activation within the adult heart leads to right atrial chamber changes in cardiac electrophysiology and gene expression that persist even one year after a short pulse of Notch signaling activation. Together, these phenotypes resemble a model of murine Sick Sinus Syndrome, which is known in humans to predispose to Atrial Fibrillation (AF). AF is the most common arrhythmia, yet despite its prevalence, our knowledge of the molecular mechanism(s) underlying its pathology remain limited. What is becoming increasingly clear is that each cardiac chamber represents a distinct transcriptional unit that has a differential response to injury signals. Supporting this idea, preliminary data indicate that Notch signaling in the left atrium (LA) affects the expression of genes important for cardiac electrophysiology that are implicated in AF, but are different than those affected in the right atrium (RA) of the exact same heart, suggesting that injury-induced Notch signaling may play a role in left atrial arrhythmogenesis.”

 

SCI-8 Sean Yu, Informatics

Treatment Regimen Clustering and Characterization for Acute Myocardial Infarction Cohort in MIMIC-III dataset

“Clinical quality improvement is an ongoing endeavor to ensure that safe, effective, equitable, and timely care is delivered. Clinical quality is commonly measured through quality measures, many of which assess whether particular actions was taken for particular cohorts. Because quality measures are used to adjust financial reimbursements for value-focused federal programs, quality measures are becoming ever more important in healthcare. However, healthcare organizations and clinicians often find these measurements burdensome, expensive, inaccurate, and indifferent to the complexity of care delivery. Thus, the motivation for this project was to investigate novel methods for assessing clinical quality – in particular, clinical practice variation. As precision medicine implores us to treat clinically different patients differently, research on clinical variation suggests that patients with similar patient factors (age, gender, ethnicity, past diagnoses, etc.) ought to be subject to similar treatment regimens. To this end, Acute Myocardial Infarction cohort and their data were extracted from MIMIC-III, an open dataset of deidentified health data. Medication data was translated into pharmaceutical class data using RxNORM. A similarity score between treatment regimens was constructed using a modified Needleman-Wunsch algorithm that uses the Jaccard Index. Agglomerative hierarchical clustering using Ward’s criterion was used to discover subtypes of treatment regimen. Each cluster was characterized by a single consensus regimen through a Multivariate Profile Hidden Markov Model. Using patient factors as input, and treatment regimen cluster membership as output, a decision tree was constructed. Heterogenous leaves of the decision tree present potential opportunities for quality improvement.”

 

SCI-9 Michal Skowyra, DBBS Molecular Cell Biology

Triggered recruitment of ESCRT machinery promotes endolysosomal repair

“Endosomes and lysosomses comprise the endolysosomal network and function to sort, recycle, and degrade various substances from inside and outside the cell. Endolysosomes can be damaged by many materials that transit through them, such as incoming pathogens, particulates such as mineral crystals or pathogenic protein aggregates, or molecules that intercalate into and destabilize the lipid bilayer. Terminally damaged compartments are degraded by a form of selective autophagy known as lysophagy, which is triggered by recruitment of cytosolic damage sensors such as galectins to abnormally exposed lumenal glycans on the injured organelles. However, mechanisms that repair salvageable organelles and maintain endolysosomal integrity are poorly understood. Here we found that the Endosomal Sorting Complex Required for Transport (ESCRT) machinery, known to facilitate budding and fission on endolysosomes, also plays an essential role in their repair. Using peptide reagents that accumulate within acidic endolysosomes and selectively trigger their disruption, we show that ESCRTs are rapidly recruited to acutely injured organelles via a pathway requiring calcium and ESCRT-activating factors. This response was especially prominent on compartments damaged by silica crystals. By imaging fluorescently-tagged ESCRT proteins in combination with ratiometric pH sensors and fluorogenic reporters of lysosomal proteolytic activity, we demonstrate that ESCRTs responded to small perforations in endolysosomal membranes and enabled compartments to recover from limited damage. ESCRTs thus provide a defense against endolysosomal damage that is likely to be relevant in physiological and pathological contexts where membrane integrity has been compromised.”

 

SCI-10 Nina Beri, DBBS Molecular Genetics and Genomics

The Role of lncRNA-PELI1 in Non-Hodgkin Lymphoma Pathogenesis

“Long non-coding RNAs (lncRNAs) act as transcriptional regulators, scaffolds, and signaling modulators in development, immune response, and oncogenesis. Our -omics study of >100 human Non-Hodgkin Lymphoma (NHL) and normal B cell samples revealed altered expression of lncRNAs in NHL. LncRNAs have not been characterized in NHL or B cells, and there are few guidelines for functional prediction. To address this gap, we developed a novel computational approach: Correlative Recurrent Expression of Predicted Elements (CREPE) to identify lncRNAs that regulate key NHL pathways. CREPE integrates differential and correlative expression, cell-type specificity, subcellular localization, and local enhancer and 3D genome interaction landscapes to calculate a rankable score for prediction of potential function, including 1) transcriptional regulation via lncRNA transcript, 2) enhancer-associated regulation, and 3) scaffold/modulator cytoplasmic function. CREPE identified several lncRNAs that may regulate NHL oncogenes and modulate B-cell receptor signaling. Here, we highlight one of these, a predicted transcriptional regulatory lncRNA, AC074289.1, which is spliced, localized to the nucleus, and highly expressed in NHL samples. Transcript levels of this lncRNA positively and specifically correlate with a proximal protein-coding gene, PELI1, but not with two other neighboring genes, VSP54 and UGP2.  PELI1 encodes an E3 ubiquitin ligase that is involved in NF-KB signaling and may increase the activity of the lymphoma oncoprotein BCL6. Functional studies of AC074289.1, including CRISPR KO and KD, are ongoing. By defining new mechanisms of gene deregulation in lymphoma, we expect to provide previously unrecognized therapeutic targets and novel approaches to NHL therapy.”

 

SCI-11 Hannah Frye, Neuroscience

Characterization of a cornichon homolog-3 (CNIH3) knockdown mouse model and its effects on post-synaptic density proteins within the hippocampus

“In a 2016 genome-wide association study comparing non-dependent and dependent opioid misusers, the strongest genetic correlation with dependence risk was single nucleotide polymorphisms (SNPs) in the gene encoding for cornichon family AMPA receptor auxiliary protein 3 (CNIH3). However, the underlying role of CNIH3 SNPs on opioid dependence remains unknown. The dependence protective SNPs are limited to non-coding regions of CNIH3, implying the SNPs may alter gene expression levels. To model effects of reduced CNIH3 gene expression, we created a CNIH3 knockdown (KD) mouse line. Mice bearing the KD gene express 50% less CNIH3 compared to wildtype levels. Beta-galactosidase staining for the gene’s lacZ cassette reveals strong expression of CNIH3 in the hippocampus, a region associated with AMPA receptor (AMPAR) dependent memory and learning. Biochemically, hippocampal AMPARs are decreased at the post-synaptic density (PSD) in CNIH3 KD male mice. The PSD is a dense matrix of synaptic proteins at the post-synaptic membrane which anchors neurotransmitter receptors to the membrane. A decrease in AMPARs at the PSD may affect synapse morphology and AMPAR-dependent contextual learning and memory. CNIH3 KD results in a decrease in the synaptic scaffolding protein PSD-95 at the PSD in both sexes, but preliminary data indicates no significant change in the number of dendritic synapses. Future studies will investigate effects of CNIH3 KD on contextual memory and learning and determine if the effects seen in CNIH3 KD are reversed with hippocampus-targeted viral overexpression.”

 

SCI-12 Samantha Powers, DBBS (Plant and Microbial Biosciences)

Investigating the Role of Protein Multimerization in ARF Transcription Factor Activity

“The hormone auxin plays a crucial role in nearly every aspect of plant growth and development by controlling cell expansion and division. In plants, the AUXIN RESPONSE FACTOR (ARF) family of
transcription factors regulates auxin-responsive gene expression and exhibit nuclear localization in regions of high auxin responsiveness; however, our data suggest that activating ARF proteins form biomolecular condensates in the cytoplasm of tissues with decreased auxin responsiveness, suggesting a model in which ARF nucleo-cytoplasmic partitioning plays a role in mediating cellular competence for auxin response. We have identified roles for the intrinsically disordered middle region and electrostatic PB1 domain of ARF proteins in driving the formation of these condensates. Mutation of a single lysine residue within the PB1 domain is sufficient to allow ARF localization to the nucleus in all tissue types, resulting in morphological defects and altered transcriptional auxin responsiveness in the plant. In combination, these data suggest a model in which ARF nuclear-cytoplasmic partitioning is sufficient to regulate auxin transcriptional responsiveness in different tissues of the plant.”

 

SCI-13 Kelsey Meinerz, Physics

Investigating Confounds In Quantifying Molecular Oxygen Concentration (pO2) via Magnetic Resonance Relaxation of Water 1H Spins

“Tumor hypoxia is closely linked with resistance to radiotherapy and chemotherapy, and increased angiogenesis and metastasis. A noninvasive method to map in vivo tissue oxygen tension, pO2, would aid in diagnosis and treatment planning. Magnetic resonance (MR) holds promise for mapping tissue pO2 because, in principle, the measured 1H longitudinal relaxation rate constant of tissue water, R1, is directly proportional to tissue pO2. Herein, we use cross-linked bovine serum albumin (x-BSA; a tissue surrogate/mimic) and “high resolution” NMR spectroscopy to: (i) characterize/quantify the effects of physiologic confounds to the R1-based pO2 measurement (temperature, pH, and macromolecule concentration) and (ii) directly quantify the R1 vs pO2 relationship. Our data show that temperature, pH, and macromolecular concentration changes affect the R1 measurement and must therefore be either mitigated in vivo or, incorporated into a model that accounts for such effects.”

 

SCI-14 Seyed Motahari, Physics

Modeling Pulling Force Generation By Ensembles of Polymerizing Actin Filaments 


“Actin polymerization in yeast is the primary mechanism for overcoming the large turgor pressure that opposes clathrin-mediated endocytosis. While generation of pushing forces by actin polymerization is fairly well understood, it is not clear how actin polymerization produces pulling forces. Previous work using a finite element approach has suggested that continuous spatial variation of the polymerization rate can generate pulling forces. We extend this work by performing calculations on a discrete system of actin filaments with all subunits explicitly treated. We stochastically simulate growing arrays of up to 200 semiflexible actin filaments in a square network, where each filament interacts with the membrane via an interaction potential that has both attractive and repulsive components. The crucial protein Sla2, which binds actin filaments to the membrane, is assumed to contribute a strongly attractive component to the potential. The polymerization and depolymerization rates depend on the filament-membrane gap. We model the elasticity of the actin network by linear springs connecting adjacent filaments to each other. The inner filaments of the array are taken to correspond to a Sla2 patch. They are thus bound more strongly to the membrane, and grow more slowly. The simulation results show that the outer filaments push on the membrane, while the inner filaments pull on it. We calculate the total pulling force as a function of several model parameters, including the potential depths, the free filament on- and off-rates, the numbers of fast- and slow-growing filaments, the filament tip stiffness, and the network rigidity.”

 

 

Social Sciences:

SOC-1 Lamesse Eldesouky, Psychology and Brain Sciences

Appearing Warm vs. Competence: Expressive Suppression is Differentially Predicted by Impression Management Goals

“Expressive suppression, the hiding of emotional expression, is harmful for social relationships. Interestingly, research suggests that people often use suppression for a social reason – wanting to make certain impressions on others. However, impression management is a broad construct and people can be motivated to make a variety of impressions. Thus, in the current study we investigated how suppression is differentially motivated by specific impression management goals: appear warm vs. competent. We conducted an experiment in which undergraduates (N = 160; 70% women) pursued one of four goals in a mock job interview): appear warm, appear competent, act natural (control), or feel calm (a comparison goal). Following the interview, they reported on their suppression use. We found that those instructed to appear warm or feel calm suppressed their emotions significantly less than those told to appear competent; these effects were stronger for men than for women. Our findings demonstrate that while impression management goals may broadly motivate suppression, suppression is not used to make all kinds of impressions. They also show that impression management goals may have a greater impact on men’s suppression use than women.”

 

SOC-2 Jessica Nicosia, Psychological & Brain Sciences

Age-Related Slowing from an Upcoming Explicit Recognition Decision on Implicit Speeded Word Pronunciation              

“Speeded word pronunciation is a relatively simple task that maps orthographic patterns onto phonological patterns, and has been viewed as relatively devoid of attention demanding strategic processes.  In the present study, we investigated the influence of an upcoming recognition decision on this simple pronunciation task.  Thirty-six young and 36 older adults performed two different tasks.  In the standard implicit priming task, each participant studied a list of 10 high- and 10 low-frequency words and then pronounced the old words intermixed with a set of new words aloud.  Standard repetition priming effects, which were larger for low-frequency words than high-frequency words, were found for both young and older adults.  In the second task, participants again studied a list of (new) high- and low-frequency words.  The only difference in the second task is that participants made old/new recognition decisions on each trial after pronouncing the word aloud.  Results indicated that older adults showed disproportionate slowing in their response times to pronounce the words when they additionally had to make a recognition judgment afterwards, as compared to when they only had to pronounce the items.  Furthermore, compared to the standard implicit task, word frequency effects in pronunciation were attenuated in older adults, and when participants made recognition decisions on each trial.  These results were not due to age-related differences in recognition memory performance.  The results suggest that older adults have difficulty tuning to the constraints of a simple implicit task, without contamination from an upcoming explicit decision.”