Digital Commons Network^™

Characterizing The Expression Of The Sphingosine 1-Phosphate Pathway In Injury And Post-Traumatic Fibrosis, Nicole Cubbage

Masters Theses, 2020-current

Following injury, tissue repair allows for the restoration of the architecture and function of the injured tissue, while tissue replacement is characterized by severely damaged or non-regenerable tissue that is repaired by the laying down of extensive connective tissue, also known as fibrosis. The fibrotic process should be arrested at its early stage to have the greatest impact on preventing or reversing associate sequelae and promoting the regeneration of normal tissue. Sphingosine 1-phosphate (S1P), a metabolic product of cell membrane sphingolipids, has emerged as a pathway that may be involved in fibrosis. Most of S1P’s actions are mediated through the …

Role Of Dunc-13 Isoforms In Alcohol Sensitivity In Drosophila, Makenzie Havard

Honors Theses

Functional alcohol tolerance is an adaptation made by the nervous system to high doses of alcohol, and is seen by a significant reduction in sensitivity to this drug. This tolerance is a significant contributing factor in the progression to Alcohol Use Disorders. A major goal of alcohol research is to understand how alcohol induces this tolerance. Dunc13 is a presynaptic active zone protein essential in synaptic vesicle docking and priming. Alcohol binds to the C1 domain of Dunc13 at physiological concentrations, which inhibits Dunc13 from binding Diacylglycerol. This inhibition is predicted to reduce Dunc13 activity and presynaptic activity. Yet, genetically …

Casi: A Framework For Cross-Timepoint Analysis Of Single-Cell Rna Sequencing Data, Yizhuo Wang, Christopher R Flowers, Michael Wang, Xuelin Huang, Ziyi Li

Faculty, Staff and Student Publications

Single-cell RNA sequencing (scRNA-seq) technology has been widely used to study the differences in gene expression at the single cell level, providing insights into the research of cell development, differentiation, and functional heterogeneity. Various pipelines and workflows of scRNA-seq analysis have been developed but few considered multi-timepoint data specifically. In this study, we develop CASi, a comprehensive framework for analyzing multiple timepoints' scRNA-seq data, which provides users with: (1) cross-timepoint cell annotation, (2) detection of potentially novel cell types emerged over time, (3) visualization of cell population evolution, and (4) identification of temporal differentially expressed genes (tDEGs). Through comprehensive simulation …

Modulation Of The Blood-Brain Barrier By Sigma-1r Activation, Eugen Brailoiu, Jeffrey L Barr, Hailey N Wittorf, Saadet Inan, Ellen M Unterwald, Gabriela Cristina Brailoiu

Faculty, Staff and Student Publications

Sigma non-opioid intracellular receptor 1 (Sigma-1R) is an intracellular chaperone protein residing on the endoplasmic reticulum at the mitochondrial-associated membrane (MAM) region. Sigma-1R is abundant in the brain and is involved in several physiological processes as well as in various disease states. The role of Sigma-1R at the blood-brain barrier (BBB) is incompletely characterized. In this study, the effect of Sigma-1R activation was investigated in vitro on rat brain microvascular endothelial cells (RBMVEC), an important component of the blood-brain barrier (BBB), and in vivo on BBB permeability in rats. The Sigma-1R agonist PRE-084 produced a dose-dependent increase in mitochondrial calcium, …

Effect Of Methyl Jasmonate And Ga3 On Canola (Brassica Napus L) Growth, Antioxidants Activity, And Nutrient Concentration Cultivated In Salt-Affected Soils, Subhan Danish, Sundas Sana, Muhammad Baqir Hussain, Khadim Dawar, Hesham S Almoallim, Mohammad Javed Ansari, Misbah Hareem, Rahul Datta

Faculty, Staff and Student Publications

Salinity stress is a significant challenge in agricultural production. When soil contains high salts, it can adversely affect plant growth and productivity due to the high concentration of soluble salts in the soil water. To overcome this issue, foliar applications of methyl jasmonate (MJ) and gibberellic acid (GA3) can be productive amendments. Both can potentially improve the plant's growth attributes and flowering, which are imperative in improving growth and yield. However, limited literature is available on their combined use in canola to mitigate salinity stress. That's why the current study investigates the impact of different levels of MJ (at concentrations …

Imaging Features Of Primary Intracranial Sarcoma With Dicer1 Mutation: A Multicenter Case Series, Rami W Eldaya, Richard J Fagan, Samir A Dagher, Angshumoy Roy, Sonika Dahyia, Gregory N Fuller, Max Wintermark, Matthew S Parsons, Thierry A G M Huisman

Faculty, Staff and Student Publications

Primary intracranial sarcoma, DICER1-mutant, is a rare, recently described entity in the fifth edition of the WHO Classification of CNS Tumors. Given the entity's rarity and recent description, imaging data on primary intracranial sarcoma, DICER1-mutant, remains scarce. In this multicenter case series, we present detailed multimodality imaging features of primary intracranial sarcoma, DICER1-mutant, with emphasis on the appearance of the entity on MR imaging. In total, 8 patients were included. In all 8 patients, the lesion demonstrated blood products on T1WI. In 7 patients, susceptibility-weighted imaging was obtained and demonstrated blood products. Primary intracranial sarcoma, DICER1-mutant, …

Downregulation Of Mirlet7 Mirna Family Promotes Tc17 Differentiation And Emphysema Via De-Repression Of Rorγt, Phillip A Erice, Xinyan Huang, Matthew J Seasock, Matthew J Robertson, Hui-Ying Tung, Melissa A Perez-Negron, Shivani L Lotlikar, David B Corry, Farrah Kheradmand, Antony Rodriguez

Faculty, Staff and Students Publications

Environmental air irritants including nanosized carbon black (nCB) can drive systemic inflammation, promoting chronic obstructive pulmonary disease (COPD) and emphysema development. The let-7 microRNA (Mirlet7 miRNA) family is associated with IL-17-driven T cell inflammation, a canonical signature of lung inflammation. Recent evidence suggests the Mirlet7 family is downregulated in patients with COPD, however, whether this repression conveys a functional consequence on emphysema pathology has not been elucidated. Here, we show that overall expression of the Mirlet7 clusters, Mirlet7b/Mirlet7c2 and Mirlet7a1/Mirlet7f1/Mirlet7d, are reduced in the lungs and T cells of smokers with emphysema as well as in mice with …

Clearing The Light Path: Proteoglycans And Their Important Roles In The Lens And Cornea, Mary Ann Stepp, A. Sue Menko

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Some of the earliest studies of glycans were performed on mammalian corneas and lenses with many of the key concepts we currently recognize as being fundamental to our understanding of basic cell biology arising from these studies. Proteoglycans and their GAG side chains are essential components of the ECM of the lens capsule. They also are present in the anterior corneal epithelial basement membrane and the posterior (Decemet's) basement membrane, and they organize collagen fiber diameters and spacing in the corneal stroma to maintain stromal clarity. Studies using genetically engineered mice and characterization of spontaneously arising mutations in genes controlling …

Correction: Horne Et Al White Matter Correlates Of Domain-Specific Working Memory, Autumn Horne, Junhua Ding, Tatiana T Schnur, Randi C Martin

Faculty, Staff and Student Publications

In the original publication [...].

Optimization Of The Antifungal Properties Of The Bacterial Peptide Entv By Variant Analysis, Shantanu Guha, Shane A Cristy, Giuseppe Buda De Cesare, Melissa R Cruz, Michael C Lorenz, Danielle A Garsin

Faculty, Staff and Student Publications

Fungal resistance to commonly used medicines is a growing public health threat, and there is a dire need to develop new classes of antifungals. We previously described a peptide produced by Enterococcus faecalis, EntV, that restricts Candida albicans to a benign form rather than having direct fungicidal activity. Moreover, we showed that one 12-amino acid (aa) alpha helix of this peptide retained full activity, with partial activity down to the 10aa alpha helix. Using these peptides as a starting point, the current investigation sought to identify the critical features necessary for antifungal activity and to screen for new variants …

Exome Sequencing Implicates Ancestry-Related Mendelian Variation At Syne1 In Childhood-Onset Essential Hypertension, Ian Copeland, Edmond Wonkam-Tingang, Monesha Gupta-Malhotra, S Shahrukh Hashmi, Yixing Han, Aarti Jajoo, Nancy J Hall, Paula P Hernandez, Natasha Lie, Dan Liu, Jun Xu, Jill Rosenfeld, Aparna Haldipur, Zelene Desire, Zeynep H Coban-Akdemir, Daryl A Scott, Qing Li, Hsiao-Tuan Chao, Ana M Zaske, James R Lupski, Dianna M Milewicz, Sanjay Shete, Jennifer E Posey, Neil A Hanchard

Faculty, Staff and Student Publications

Childhood-onset essential hypertension (COEH) is an uncommon form of hypertension that manifests in childhood or adolescence and, in the United States, disproportionately affects children of African ancestry. The etiology of COEH is unknown, but its childhood onset, low prevalence, high heritability, and skewed ancestral demography suggest the potential to identify rare genetic variation segregating in a Mendelian manner among affected individuals and thereby implicate genes important to disease pathogenesis. However, no COEH genes have been reported to date. Here, we identify recessive segregation of rare and putatively damaging missense variation in the spectrin domain of spectrin repeat containing nuclear envelope …

Towards A Remote Patient Monitoring Platform For Comprehensive Risk Evaluations For People With Diabetic Foot Ulcers, Gozde Cay, M G Finco, Jason Garcia, Jill L Mcnitt-Gray, David G Armstrong, Bijan Najafi

Center on Aging Staff Publications

Diabetic foot ulcers (DFUs) significantly affect the lives of patients and increase the risk of hospital stays and amputation. We suggest a remote monitoring platform for better DFU care. This system uses digital health metrics (scaled from 0 to 10, where higher scores indicate a greater risk of slow healing) to provide a comprehensive overview through a visual interface. The platform features smart offloading devices that capture behavioral metrics such as offloading adherence, daily steps, and cadence. Coupled with remotely measurable frailty and phenotypic metrics, it offers an in-depth patient profile. Additional demographic data, characteristics of the wound, and clinical …

Protein Oxidation In Aging And Alzheimer’S Disease Brain, Rukhsana Sultana, D. Allan Butterfield

Markey Cancer Center Faculty Publications

Proteins are essential molecules that play crucial roles in maintaining cellular homeostasis and carrying out biological functions such as catalyzing biochemical reactions, structural proteins, immune response, etc. However, proteins also are highly susceptible to damage by reactive oxygen species (ROS) and reactive nitrogen species (RNS). In this review, we summarize the role of protein oxidation in normal aging and Alzheimer’s disease (AD). The major emphasis of this review article is on the carbonylation and nitration of proteins in AD and mild cognitive impairment (MCI). The oxidatively modified proteins showed a strong correlation with the reported changes in brain structure, carbohydrate …

Researching Covid To Enhance Recovery (Recover) Pediatric Study Protocol: Rationale, Objectives And Design, Rachel S. Gross, Tanayott Thaweethai, Erika B. Rosenzweig, James Chan, Lori B. Chibnik, Mine S. Cicek, Amy J. Elliott, Valerie J. Flaherman, Andrea S. Foulkes, Margot Gage Witvliet, Richard Gallagher, Maria Laura Gennaro, Terry L. Jernigan, Elizabeth W. Karlson, Stuart D. Katz, Patricia A. Kinser, Lawrence C. Kleinman, Michelle F. Lamendola-Essel, Joshua D. Milner, Sindhu Mohandas, Praveen C. Mudumbi, Jane W. Newburger, Kyung E. Rhee, Amy L. Salisbury, Jessica N. Snowden, Cheryl R. Stein, Melissa S. Stockwell, Kelan G. Tantisira, Tamara Bradford, Et Al

School of Medicine Faculty Publications

Importance The prevalence, pathophysiology, and long-term outcomes of COVID-19 (post-acute sequelae of SARS-CoV-2 [PASC] or “Long COVID”) in children and young adults remain unknown. Studies must address the urgent need to define PASC, its mechanisms, and potential treatment targets in children and young adults. Observations We describe the protocol for the Pediatric Observational Cohort Study of the NIH’s REsearching COVID to Enhance Recovery (RECOVER) Initiative. RECOVER-Pediatrics is an observational meta-cohort study of caregiver-child pairs (birth through 17 years) and young adults (18 through 25 years), recruited from more than 100 sites across the US. This report focuses on two of …

Endotrophin, A Key Marker And Driver For Fibroinflammatory Disease, Kim Henriksen, Federica Genovese, Alexander Reese-Petersen, Laurent P Audoly, Kai Sun, Morten A Karsdal, Philipp E Scherer

Faculty, Staff and Student Publications

Our overview covers several key areas related to recent results obtained for collagen type VI and endotrophin (ETP). (1) An introduction to the history of ETP, including how it was identified, how it is released, and its function and potential receptors. (2) An introduction to the collagen family, with a focus on what differentiates collagen type VI from an evolutionary standpoint. (3) An overview of collagen type VI, the 6 individual chains (COL6A1, A2, A3, A4, A5, and A6), their differences and similarities, as well as their expression profiles and function. (4) A detailed analysis of COL6A3, including the cleaved …

Single Extracellular Vesicle Imaging And Computational Analysis Identifies Inherent Architectural Heterogeneity, Kshipra S Kapoor, Seoyun Kong, Hikaru Sugimoto, Wenhua Guo, Vivek Boominathan, Yi-Lin Chen, Sibani Lisa Biswal, Tanguy Terlier, Kathleen M Mcandrews, Raghu Kalluri

Faculty, Staff and Student Publications

Evaluating the heterogeneity of extracellular vesicles (EVs) is crucial for unraveling their complex actions and biodistribution. Here, we identify consistent architectural heterogeneity of EVs using cryogenic transmission electron microscopy (cryo-TEM), which has an inherent ability to image biological samples without harsh labeling methods while preserving their native conformation. Imaging EVs isolated using different methodologies from distinct sources, such as cancer cells, normal cells, immortalized cells, and body fluids, we identify a structural atlas of their dominantly consistent shapes. We identify EV architectural attributes by utilizing a segmentation neural network model. In total, 7,576 individual EVs were imaged and quantified by …

Histone Demethylase Kdm5 Regulates Cardiomyocyte Maturation By Promoting Fatty Acid Oxidation, Oxidative Phosphorylation, And Myofibrillar Organization, Manisha Deogharia, Leslye Venegas-Zamora, Akanksha Agrawal, Miusi Shi, Abhinav K Jain, Kevin J Mchugh, Francisco Altamirano, Ali J Marian, Priyatansh Gurha

Faculty, Staff and Student Publications

Aims: Human pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) provide a platform to identify and characterize factors that regulate the maturation of CMs. The transition from an immature foetal to an adult CM state entails coordinated regulation of the expression of genes involved in myofibril formation and oxidative phosphorylation (OXPHOS) among others. Lysine demethylase 5 (KDM5) specifically demethylates H3K4me1/2/3 and has emerged as potential regulators of expression of genes involved in cardiac development and mitochondrial function. The purpose of this study is to determine the role of KDM5 in iPSC-CM maturation.

Methods and results: KDM5A, B, and C proteins were mainly expressed …

Identification Of Potent Pan-Ephrin Receptor Kinase Inhibitors Using Dna-Encoded Chemistry Technology, Chandrashekhar Madasu, Zian Liao, Sydney E Parks, Kiran L Sharma, Kurt M Bohren, Qiuji Ye, Feng Li, Murugesan Palaniappan, Zhi Tan, Fei Yuan, Chad J Creighton, Suni Tang, Ramya P Masand, Xiaoming Guan, Damian W Young, Diana Monsivais, Martin M Matzuk

Faculty, Staff and Students Publications

EPH receptors (EPHs) are highly sought-after drug targets owing to their essential roles in maintaining appropriate cellular functions in both physiological and disease conditions. However, limited potency and specificity pose significant obstacles to the development of small-molecule inhibitors for EPHs. Here, using high-throughput DNA-encoded chemical library screenings, we developed potent and selective inhibitors of the EPH receptor kinase family. Our results also emphasize the therapeutic potential of our EPH inhibitors in cancer and endometriosis, a global health concern that causes chronic pain and often leads to infertility in women. This study showcases the robust pipeline of using DNA-encoded chemistry technology …

Data Normalization For Addressing The Challenges In The Analysis Of Single-Cell Transcriptomic Datasets, Raquel Cuevas-Diaz Duran, Haichao Wei, Jiaqian Wu

Faculty, Staff and Student Publications

BACKGROUND: Normalization is a critical step in the analysis of single-cell RNA-sequencing (scRNA-seq) datasets. Its main goal is to make gene counts comparable within and between cells. To do so, normalization methods must account for technical and biological variability. Numerous normalization methods have been developed addressing different sources of dispersion and making specific assumptions about the count data.

MAIN BODY: The selection of a normalization method has a direct impact on downstream analysis, for example differential gene expression and cluster identification. Thus, the objective of this review is to guide the reader in making an informed decision on the most …

Hormonal Basis Of Brain Fog In Cancer Treatment, Yuan Pan, Jian Hu

Faculty, Staff and Student Publications

The cognitive side effects of cancer treatment are common, but no targeted therapy exists yet to treat or prevent such neurological sequelae. We explore the role of hormones as mediators between cancer therapy and cognitive impairment, discussing potential future directions.

Serine Deamination By Human Serine Racemase Synergizes With Antibiotics To Curtail The Replication Of Chlamydia Trachomatis, Patricia D. Mott, Arnold H. Zea, Jamiya Lewis, Oygul Mirzalieva, Ashok A. Aiyar

School of Medicine Faculty Publications

The obligate intracellular bacterium, Chlamydia trachomatis, has evolved to depend on its human host for many metabolites, including most amino acids and three of the four nucleotides. Given this, it is not surprising that depletion of a single amino acid in the host cell growth medium blocks chlamydial replication. Paradoxically, supra-normal levels of some amino acids also block productive replication of Chlamydia. Here, we have determined how elevated serine levels, generated by exogenous supplementation, impede chlamydial inclusion development and reduce the generation of infectious progeny. Our findings reveal that human serine racemase, which is broadly expressed in multiple tissues, potentiates …

Ras G-Domains Allosterically Contribute To The Recognition Of Lipid Headgroups And Acyl Chains, Neha Arora, Huanwen Mu, Hong Liang, Wenting Zhao, Yong Zhou

Faculty, Staff and Student Publications

Mutant RAS are major contributors to cancer and signal primarily from nanoclusters on the plasma membrane (PM). Their C-terminal membrane anchors are main features of membrane association. However, the same RAS isoform bound to different guanine nucleotides spatially segregate. Different RAS nanoclusters all enrich a phospholipid, phosphatidylserine (PS). These findings suggest more complex membrane interactions. Our electron microscopy-spatial analysis shows that wild-types, G12V mutants, and membrane anchors of isoforms HRAS, KRAS4A, and KRAS4B prefer distinct PS species. Mechanistically, reorientation of KRAS4B G-domain exposes distinct residues, such as Arg 135 in orientation state 1 (OS1) and Arg 73/Arg 102 in OS2, …

Metaplastic Regeneration In The Mouse Stomach Requires A Reactive Oxygen Species Pathway, Zhi-Feng Miao, Jing-Xu Sun, Xuan-Zhang Huang, Shi Bai, Min-Jiao Pang, Jia-Yi Li, Han-Yu Chen, Qi-Yue Tong, Shi-Yu Ye, Xin-Yu Wang, Xiao-Hai Hu, Jing-Ying Li, Jin-Wei Zou, Wen Xu, Jun-Hao Yang, Xi Lu, Jason C Mills, Zhen-Ning Wang

Faculty, Staff and Students Publications

In pyloric metaplasia, mature gastric chief cells reprogram via an evolutionarily conserved process termed paligenosis to re-enter the cell cycle and become spasmolytic polypeptide-expressing metaplasia (SPEM) cells. Here, we use single-cell RNA sequencing (scRNA-seq) following injury to the murine stomach to analyze mechanisms governing paligenosis at high resolution. Injury causes induced reactive oxygen species (ROS) with coordinated changes in mitochondrial activity and cellular metabolism, requiring the transcriptional mitochondrial regulator Ppargc1a (Pgc1α) and ROS regulator Nf2el2 (Nrf2). Loss of the ROS and mitochondrial control in Ppargc1a-/- mice causes the death of paligenotic cells through ferroptosis. Blocking the cystine transporter SLC7A11(xCT), which …

Successful Application Of Craniosacral Therapy In A Case Of Acute Ptosis Following A Covid-19 Infection., Efterpi Rompoti

Journal of Transformative Touch

This case study offers a unique insight on the effectiveness of CranioSacral therapy (CST) in a 49 year old woman experiencing an acute stage of a viral infection (Covid-19) causing a partial left Oculomotor nerve palsy. A CST glial/Cerebrospinal Fluid (CSF) specific protocol was utilised over 2 consecutive days. The patient recovered fully after 5 days. The results of this particular case can open up the possibility of utilising CST more widely in treating cranial nerve palsies following a viral infection to support the healing process and the functional restoration.

Development Of A Synthetic Biomarker System For Early Detection Of Ischemic Stroke, Mason L. Matthies

Honors Thesis

Stroke, particularly Ischemic Stroke (IS) affects millions of individuals across the world each year . Current diagnostic methods like CT scans and MRI imaging have limitations in detecting minor IS due to the limited spatial resolution of the CT scan and the feasibility and access to MRIs warranting a more effective method of early detection. Natural biomarkers are currently ineffective in detecting IS prior to severe damage like rapid cell death (32,000 cells/sec) post arterial blockage because there is minimal amount of natural biomarkers expressed from minor cellular damage . Our proposed Synthetic Biomarker System (SBS) would solve this by …

Development, Validation, And Diagnostic Performance Of A Novel Radiomic Model For Predicting Prostate Cancer Recurrence, Linda M. Huynh

Theses & Dissertations

Multi-parametric magnetic resonance imaging (MP-MRI)-derived radiomics have been shown to capture sub-visual patterns for the quantitative characterization of prostate cancer (PC) phenotypes. The present dissertation seeks to develop, evaluate, and compare the performance of an MRI-derived radiomic model for the prediction of PC recurrence following definitive treatment with radical prostatectomy (RP).

MP-MRI was obtained from 339 patients who had a minimum of 2 years follow-up following RP at three institutions. The prostate was manually delineated as the region of interest and 924 radiomic features were extracted. All features were evaluated for stability via intraclass correlation coefficient (ICC) and image normalization …

Impact Of Nutritional Status And Placental Malaria Infection On Pregnancy Outcome In A Population Of Nigerian Maternal-Infant Dyads, Shirley F. Delair

Theses & Dissertations

Nigeria is the most populous country in Africa and accounts for one-quarter of the newborn mortality on the continent. Most newborn deaths are from prematurity (33%), infections (33%), and intrapartum complications (31%). Using an adapted analytical framework for the study of child survival in developing countries, this dissertation aimed to look at the pregnancy outcome of a population of Nigerian women and their offspring by looking at proximate determinants of health from nutritional status and environmental conditions. In Chapter 1, we characterized the micronutrients of the mother-infant dyads, looking specifically at concentrations of vitamin D and its metabolites. In Chapter …

Cognitive Control In Health And Disease: A Dynamic Approach To Mapping Oscillatory Activity Across The Lifespan, Mikki Schantell

Theses & Dissertations

Cognitive control is critical for flexibly adapting goal-directed behaviors to meet the demands of dynamically changing environments. The neural oscillatory dynamics serving cognitive control undergo changes across the lifespan, both in health and disease, with impairments in cognitive control functions being broadly implicated across a multitude of psychiatric disorders. Despite this, the trajectory of the population-level neural oscillatory dynamics supporting cognitive control across the lifespan remain poorly characterized, presenting challenges in fully understanding perturbations to these systems relative to one’s stage in neuronal maturation. Herein, we used the Eriksen flanker task during magnetoencephalographic (MEG) recording to map the neural oscillatory …

Unraveling The Role Of Gjb3 In Lung Adenocarcinoma, Swathi M. Priyanka

Theses & Dissertations

Lung cancer stands as a leading cause of cancer-related mortality worldwide, with small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC) comprising its primary categories. NSCLC, representing nearly 85% of cases, exhibits a 5-year survival rate of less than 21%. Among NSCLC subtypes, lung adenocarcinoma (LUAD) prevails as the most common, followed by squamous cell carcinoma and large cell carcinoma. Gap junctions are crucial for intercellular communication and cellular homeostasis maintenance, demonstrate altered expression patterns in various diseases, including cancer. Gap junction beta 3 (GJB3 or Connexin31) exhibits significant expression in both preclinical and clinical LUAD samples, prompting investigation into …

The Molecular Basis Of Maple Syrup Urine Disease, Chloe Jensen

Senior Honors Theses

Maple syrup urine disease (MSUD) is a rare metabolic disorder that is caused by mutations in the branched chain alpha keto acid dehydrogenase enzyme complex (BCKDC). There are three main genes, the BCKDHA, BCKDHB, and DBT, that affect the BCKDC, all contributing to the onset of the disease. MSUD causes encephalopathy, neural deficits, maple syrup scented urine, coma, and even death if not treated due to the aggregation of branched-chain amino acids (BCAAs). There is currently no known cure for patients with MSUD, but the condition can be managed to improve quality of life. This review serves to examine MSUD …