Interdisciplinary – Page 35 – UROP Spring Symposium 2021

Interdisciplinary

Midfacial Defects with Ectopic Cartilages through Ectopic X Chromosome Inactivation by Enhanced Bone Morphogenic Protein Signaling

Craniofacial defects have affected some humans from birth, running rampant without many methods to lessen the impact. We aim to explore potential solutions to the phenomenon using model mice. We recently reported that transgenic mice with enhanced bone morphogenic protein (BMP) signaling in neural crest cells induced midfacial defects along with ectopic cartilages in the face but not in trunk neural crest cells (NCCs). Here, we hypothesized that enhanced BMP signaling in NCCs formed ectopic cartilages, resulting in midfacial defects. Single-cell RNA sequencing identified candidate genes that may be involved in the ectopic cartilage formation. Among them, Xist, a central component of X chromosome inactivation, is our focus because it was significantly increased in cranial NCCs from mutant mice but not in trunk NCCs from mutant mice. That led us to the idea that ectopic X chromosome inactivation by increased Xist is responsible for the ectopic cartilages in the face since Xist is not increased in trunk NCCs, and ectopic cartilages did not form in the trunk. To analyze that, we counted inactivated X chromosomes of cranial and trunk NCCs, allowing us to analyze how they impacted ectopic cartilage formation. Female cells normally inactivate one of two X chromosomes in a nucleus. Here, we showed that some of the cranial NCCs from mutant mice have two inactivated X chromosomes in a nucleus, which means ectopic X chromosome inactivation. Moreover, trunk NCCs from both control and mutant mice did not have two inactivated X chromosomes in a nucleus as we expected. Our preliminary results indicated that cranial NCCs from mutant mice have ectopic X chromosome inactivation, and trunk NCCs from mutant mice did not have ectopic X chromosome inactivation. That outcome supports that ectopic X chromosome inactivation in the cranial region is partially responsible for ectopic cartilage formation. That area could be a target for clinical treatment of the ailment. Considering the increased Xist in mutant mice, an inhibitor would be ideal for treatment, allowing X chromosome inactivation.

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NeuroInsight: A novel toolbox to study the mechanisms of epileptic seizures

Millions of Americans suffer from epileptic seizures that result in a temporary loss of consciousness. The majority of our understanding of neural dynamics during seizures is based on extracellular recordings, with intracellular neuronal recordings not yet possible in patients. Here, we create a toolbox – called NeuroInsight – that can allow for the decoding of estimated intracellular potentials based only on extracellular single neuron recordings. NeuroInsight’s algorithms can approximate the intracellular membrane potential of neurons and identify periods of excessive depolarization that may correlate with increased seizure likelihood. We streamline the analysis process by including multiple built in visualization tools. Furthermore, the isolation quality of sorted single units can be evaluated with two included metrics. This novel toolbox has the promise to be an important resource for both clinicians and researchers studying the mechanisms of multiple forms of epilepsy.

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Effects of temporomandibular joint disorder in chewing cycle

Temporomandibular joint disorders (TMJD) are a series of disorders that affect the joint articulating the mandible and the skull, which is responsible for jaw movement. Abnormal jaw movement and abnormal temporomandibular joint (TMJ) shape are typical symptoms in TMJD patients. It is yet unknown whether abnormal TMJ movement is a result of the alterations in the TMJ in TMJD. In this study, we will use Evc2 mutant mice, which bears TMJ in abnormal shape, to understand if abnormal joint shape may lead to abnormal jaw movement. Currently, video of one mutant mouse, which has its Evc2 gene deleted in neural crest derived tissues, and one control mouse were taken to analyze jaw movement. After tracking fiducial markers planted in the mice with a program called XMALab onto a 3D coordinate plane for four consistent chews, we discovered a difference in chewing pattern between the mutant mouse and the control mouse by looking at the distance between the mandible and the skull in the duration of its chewing. We found that while the control mouse clearly had two types of chewing patterns, the mutant mouse only had a scattered chewing pattern with one noticeable type of chewing pattern. The chewing range of the mutant mouse was approximately half of that of the chewing range of the control mouse. Possible explanations of this is that the mutant mouse possibly is not physically capable of moving the jaw to do two cycles or the mouse could be in possible pain, preventing the two chewing patterns we saw in control. There is a notable difference in the chewing patterns between the control mouse and the mutant mouse, indicating that abnormal TMJ impacts chewing cycle.

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The evolution of bone shape in chimpanzees and gorillas

One important factor in understanding how locomotor behavior and anatomy interact is bone shape. While the effects of interspecies locomotor differences on bone shape are understood, less is known about the effects of locomotor changes across an individual’s lifetime on bone shape. This study seeks to understand the effects of locomotor changes across lifespans of non-human apes on bone shape. We predict that bone cross sections will be rounder in shape during periods of high arboreal locomotion, because bones are stressed along multiple axes when climbing, while bones will be more elliptical in shape during periods of high terrestrial locomotion, because movement will be mostly along a forward-moving axis. Cross sectional bone data was collected from the Hamann-Todd Osteological Collection and the Harvard Museum of Comparative Zoology. The femur, humerus, radius, and tibia of Pan troglodytes (n=70), Gorilla gorilla (n=46), and Pongo (n=22) were scanned at the 25%, 50%, and 75% bone lengths using a peripheral quantitative computed tomography (pQCT) scanner. Images were analyzed using BoneJ and ImageJ to collect cross-sectional properties and linear distances along the longest and shortest cross-sectional axes. Data was analyzed using ANCOVAs to test differences in linear measurements across species at different ages. Linear regressions will also be used to assess differences in patterns of change throughout lifetimes. The study is ongoing and data is still being collected, so no results have been found yet. This study will increase our understanding of bone’s responsiveness to locomotion across development and can be applied to the discovery of locomotor patterns of fossil apes.

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Identification of novel genetic drivers of pediatric tumors

Cancer-causing processes such as smoking and exposure to UV-light leave behind unique mutational signatures among the DNA of cancer patients. The analysis of mutational signatures in raw tumor data to produce/solidify a diagnosis would greatly benefit cancer patients and help streamline their prognosis. My project deals with the analysis of variant data obtained from tumor samples in order to determine which mutational signatures are present, utilizing technologies such as deconstructSigs, siglasso, and quadratic programming, as well as the well-established COSMIC mutational signatures.

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Resin Optimization and Organism Toxicity for iTIE (in situ Toxicity Identification Evaluation)

Toxicity Identification Evaluation (TIE) is a laboratory bioassay developed by the USEPA and used for assessing sites with multiple chemical contaminants. To determine the predominating environmental stressors and primary toxicity concerns at these sites, this method physically and chemically fractionates various compounds from water samples in a laboratory setting. However, the method is resource-intensive and does not require in situ toxicity analysis, which limits the results’ ecological realism. To improve the effectiveness and validity of assessments at sites with multiple contaminants, the in situ Toxicity Identification Evaluation (iTIE) has been developed to separate and expose fractionated waters to organisms directly within the field by use of resin adsorption technology. Specific resins are used for target removal of ammonia, heavy metals, polar organic, and nonpolar organic contaminants of concern from site water prior to organism exposure within chambers in the iTIE unit. The purpose of this study is to inform specific amendments to the iTIE prototype and to optimize the effectiveness of resins by ensuring that they cause no adverse effects to test organisms. In laboratory toxicity experiments, cladoceran Daphnia magna larva were exposed to each of the resins and analyzed for reproduction. Results suggest that the tested resins cause no significantly toxic effects. Using this supporting information, resin optimization for the iTIE system can reduce costs for future ecotoxicological assessments and impact management decisions by identification of the primary contaminants of concern in a site with multiple stressors.

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Investigating the exposure of nonhuman primates on an elevational gradient to contemporary climate change

My research investigates the impacts of anthropogenic climate change on primates and their environments. To accomplish this, I compiled fourteen years of weather data from the Cabang Panti Research Station in Gunung Palung National Park, Indonesia. Specifically, I used R computing software to organize, analyze, and visualize trends in temperature and precipitation over time. Results have shown upward trends in average temperature and corresponding increases in precipitation, although the magnitude of these trends differs across forest types. Integrating these results with additional datasets on primate abundance and food availability will be valuable for anthropological and ecological studies, as well as primate conservation.

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Transcription of Historical Archival Letters from UM’s Excavations in Egypt

In the 1910s and 1920s, Professor Francis W. Kelsey, Chairman of the Department of Latin at UM, brought a collection of papyrus from the hands of dealers and his friends in Egypt back to the US. His goal was to make papyrus manuscripts available to American scholars. My work is to read and transcribe around 30 letters between Professor Kelsey and Dr. Askren, one of his friends and colleagues in Egypt. After the reading, I learned a lot about the details during the dealing process. The current supply of papyri was coming mainly from the ruins of ancient villages and fellahs would exploit the mounds with papyri as an agricultural fertilizer. The research aims to share this kind of information relevant to researchers working with the papyrus collection and other objects stored at the Kelsey Museum of Archaeology, as well as anyone who is curious about the collecting process.

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Transcription of Historical Archival Letters from UM’s Excavations in Egypt

In the 1910s and -20s, Prof. Francis Kelsey of the University of Michigan kept close contact with Dr. David L. Askren to acquire ancient papyri and other artifacts in Egypt and the Middle East. The research focuses on the letters exchanged between Dr. Kelsey, Dr. Askren, and other associates with whom they communicated. The purpose of the project is to transcribe all of the available letters and make them easily accessible. Scans of the paper copies are used, and they are transcribed via Google Docs. The data will be collected and stored in a shared drive. The current main objective is to transcribe as many letters as possible. Eventually, the letters will be organized chronologically and published online. Biweekly meetings ensure the quality and accuracy of transcriptions. The letters have never been analyzed as a corpus from a chronological and material perspective. With a chronological analysis, we expect to discover new information on the University of Michigan’s collection houses in the Kelsey Museum, and of Cairo and other Middle Eastern related objects, as well as uncover patterns in Dr. Kelsey’s and Dr. Askren’s acquisitions of these artifacts. The University of Michigan has one of the most prestigious collections of ancient objects, papyri and archival documents from Roman Egypt in the world, and the Askren letters are important documentation of these material stored in Hatcher, the Bentley, and the Kelsey Museum of Archaeology. When the letters are transcribed and posted, graduate students, instructors, or other faculty could use the letters in their own papers or research. These letters will also be very beneficial to researchers around the world.

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A New Narrative on Live Performance in Classical Era Movie Theaters

Live vaudeville performance that played alongside film showings was an affordable and popular form of entertainment for many Americans prior to the 1930’s. When the Great Depression hit in 1929, many sources put forward the narrative that companies gave up on vaudeville and live performances and never looked back. Our team’s research suggests that this narrative is not the case as we look at evidence relating to the perspective of theater managers, company executives, and other influential individuals in relation to the continuation and production of vaudeville in the 1930’s. We have examined articles from entertainment magazines from this time period and have built upon a database cataloging many live acts and performances using Variety show bills from the early 1930’s. Our research, so far, suggests that rather than vaudeville and live performance coming to an abrupt and definitive end, it would continue to fall and re-emerge several times throughout the 1930’s and beyond. Our research concerning the uncertainty and wavering popularity of vaudeville and live performance provides us with more insight into the motivations and nature of the entertainment industry during this time period, especially considering the economic state of the United States during the Great Depression.

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