Molecular Biology Commons^™

Loss Of Carnitine Palmitoyltransferase 1a Reduces Docosahexaenoic Acid-Containing Phospholipids And Drives Sexually Dimorphic Liver Disease In Mice, Mikala M. Zelows, Corissa Cady, Nikitha Dharanipragada, Anna E. Mead, Zachary A. Kipp, Evelyn A. Bates, Venkateshwari Varadharajan, Rakhee Banerjee, Se-Hyung Park, Nathan R. Shelman, Harrison A. Clarke, Tara R. Hawkinson, Terrymar Medina, Ramon C. Sun, Todd A. Lydic, Terry D. Hinds, Jr., J. Mark Brown, Samir Softic, Gregory A. Graf, Robert N. Helsley

Saha Cardiovascular Research Center Faculty Publications

Background and aims: Genome and epigenome wide association studies identified variants in carnitine palmitoyltransferase 1a (CPT1a) that associate with lipid traits. The goal of this study was to determine the role of liver-specific CPT1a on hepatic lipid metabolism.

Approach and results: Male and female liver-specific knockout (LKO) and littermate controls were placed on a low-fat or high-fat diet (60% kcal fat) for 15 weeks. Mice were necropsied after a 16 h fast, and tissues were collected for lipidomics, matrix-assisted laser desorption ionization mass spectrometry imaging, kinome analysis, RNA-sequencing, and protein expression by immunoblotting. Female LKO mice had increased serum alanine …

Natural Remedies To Combat Aberrant Hallmark Signatures Including Altered Glycosylation In Oral Carcinoma, Kruti A. Mehta, Jayendra B. Patel, Prabhudas S. Patel

Research Symposium

Background: Tobacco associated oral cancers remain a major concern in India with higher incidence and mortality making it an Indian-centric burning issue. To combat this dreadful disease, we investigated effects of certain natural compounds on the hallmark signatures including glycosylation transcripts levels in oral carcinoma.

Methods: The tongue carcinoma cells- SAS cells were treated with tobacco compounds, natural compounds and Cisplatin. RNA was isolated from the cells and converted to cDNA. RT-qPCR was performed to evaluate expression levels of various genes.

Results: The treatment of tobacco compounds resulted in similar pattern of altered makers (ST3GAL1, NEU3, FUT5, FUT6, MMP2, BCL2) …

Dpyd Pathogenic Variants Associated With Fluoropyrimidines Toxicity, Diana Cristina Pérez-Ibave, Noé Israel Oliva-García, Irasema Ramos-Martínez, Francisco Javier Villarreal Alvarado, Valeria Jimena Gómez Ordaz, Jonatán Isaí Cortes Alfaro, Carlos Horacio Burciaga-Flores, Juan Francisco González-Guerrero, Oscar Vidal-Gutiérrez, Maria De Lourdes Garza-Rodriguez

Research Symposium

Background: Genetic variants in dihydropyrimidine dehydrogenase gene (DPYD) coding for the key enzyme (DPD) of fluoropyrimidines (FPs) catabolism. DPYD contributes to the development of severe FPs-related toxicity, and pathogenic DPYD variants detection reduces side effects and complications associated with FP-toxicity. The allelic frequency of these variants in the Mexican population is currently unknown.

Methods: The study was carried out at the Centro Universitario Contra el Cáncer (CUCC) of the Universidad Autónoma de Nuevo León (UANL) in Monterrey México. Genomic DNA was isolated from 154 subjects using the QIAamp DNA Blood Midi kit (QIAGEN) following the manufacturer's recommendations. We …

Hiv-1 Vpu Protein Forms Stable Oligomers In Aqueous Solution Via Its Transmembrane Domain Self-Association, Saman Majeed, Lan Dang, Md Majharul Islam, Olamide Ishola, Peter P Borbat, Steven J Ludtke, Elka R Georgieva

Faculty, Staff and Students Publications

We report our findings on the assembly of the HIV-1 protein Vpu into soluble oligomers. Vpu is a key HIV-1 protein. It has been considered exclusively a single-pass membrane protein. Previous observations show that this protein forms stable oligomers in aqueous solution, but details about these oligomers still remain obscure. This is an interesting and rather unique observation, as the number of proteins transitioning between soluble and membrane embedded states is limited. In this study we made use of protein engineering, size exclusion chromatography, cryoEM and electron paramagnetic resonance (EPR) spectroscopy to better elucidate the nature of the soluble oligomers. …

Protocol For Optimizing Production And Quality Control Of Infective Ecohiv Virions, Hammodah Rawhi Hammodah Alfar, Daphne N. Pariser, Harry Chanzu, Smita Joshi, Daniёlle M. Coenen, Joshua Lykins, Kanakanagavalli Shravani Prakhya, Mary Jane Potash, Wei Chao, Jennifer Kelschenbach, David J. Volsky, Kelly Metcalf-Pate

Saha Cardiovascular Research Center Faculty Publications

EcoHIV is a model of HIV infection that recapitulates aspects of HIV-1 pathology in mice. However, there are limited published protocols to guide EcoHIV virion production. Here, we present a protocol for producing infective EcoHIV virions and essential quality controls. We describe steps for viral purification, titering, and multiple techniques to analyze infection efficacy. This protocol produces high infectivity in C57BL/6 mice which will aid investigators in generating preclinical data.

Prenylated Stilbenoids As Paclitaxel Adjuvants In Triple-Negative Breast Cancer Treatment, Sepideh Mohammadhosseinpour

Student Theses and Dissertations

Triple-negative breast cancer (TNBC), the most fatal breast cancer subtype, lacks three main receptors (the human epidermal growth factor 2 receptor (ERBB2, formerly HER2), estrogen (ER) and progesterone (PR) receptors) and represents about 15% of all breast tumors. The most common treatment for TNBC is chemotherapy, being paclitaxel one of the most prescribed drugs. One of the main issues of paclitaxel is its high level of toxicity to non-cancerous cells and the development of paclitaxel resistance in the TNBC cells. Adjuvant therapy has been proposed as an alternative approach to increase the efficacy of a drug or circumvent drug resistance. …

Modeling Biphasic, Non-Sigmoidal Dose-Response Relationships: Comparison Of Brain- Cousens And Cedergreen Models For A Biochemical Dataset, Venkat D. Abbaraju, Tamaraty L. Robinson, Brian P. Weiser

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Biphasic, non-sigmoidal dose-response relationships are frequently observed in biochemistry and pharmacology, but they are not always analyzed with appropriate statistical methods. Here, we examine curve fitting methods for “hormetic” dose-response relationships where low and high doses of an effector produce opposite responses. We provide the full dataset used for modeling, and we provide the code for analyzing the dataset in SAS using two established mathematical models of hormesis, the Brain-Cousens model and the Cedergreen model. We show how to obtain and interpret curve parameters such as the ED50 that arise from modeling, and we discuss how curve parameters might change …

Study Of Polytopic Membrane Protein Topological Organization As A Function Of Membrane Lipid Composition, Takefumi Morizumi, Kyumhyuk Kim, Hai Li, Elena G Govorunova, Oleg A Sineshchekov, Yumei Wang, Lei Zheng, Éva Bertalan, Ana-Nicoleta Bondar, Azam Askari, Leonid S Brown, John L Spudich, Oliver P Ernst

Faculty, Staff and Student Publications

Kalium channelrhodopsin 1 from Hyphochytrium catenoides (HcKCR1) is a light-gated channel used for optogenetic silencing of mammalian neurons. It selects K+ over Na+ in the absence of the canonical tetrameric K+ selectivity filter found universally in voltage- and ligand-gated channels. The genome of H. catenoides also encodes a highly homologous cation channelrhodopsin (HcCCR), a Na+ channel with >100-fold larger Na+ to K+ permeability ratio. Here, we use cryo-electron microscopy to determine atomic structures of these two channels embedded in peptidiscs to elucidate structural foundations of their dramatically different cation selectivity. Together with structure-guided mutagenesis, we show that K+ versus Na+ …

Role Of Chronic Stress-Induced Neuroinflammation In Rodent Locus Coeruleus Physiology And Anxiety-Like Behaviors, Arthur Anthony Alfonso Reyes

Graduate School of Biomedical Sciences Theses and Dissertations

The locus coeruleus (LC), the primary site of brain norepinephrine (NE), is a key anatomical brain region implicated in the stress response. Stress is a neuroendocrine physiologic response to a stressor that promotes organism survival through adaptive change and restoration of homeostasis. The central stress response, which drives behavioral and physiological change, is primarily mediated by activating the hypothalamic-pituitary-adrenal (HPA) axis. While advantageous in the short term, chronic stress exposure can lead to HPA axis and LC dysregulation, which are thought to contribute to the etiology of anxiety disorders. Previous studies demonstrate the effects of acute stress in increasing LC …

Sequential Absorption Of Two Photons Creates A Bistable Form Of Rubyacr Responsible For Its Strong Desensitization, Oleg A Sineshchekov, Elena G Govorunova, Hai Li, Yumei Wang, John L Spudich

Faculty, Staff and Student Publications

Channelrhodopsins with red-shifted absorption, rare in nature, are highly desired for optogenetics because light of longer wavelengths more deeply penetrates biological tissue. RubyACRs (Anion ChannelRhodopsins), a group of four closely related anion-conducting channelrhodopsins from thraustochytrid protists, are the most red-shifted channelrhodopsins known with absorption maxima up to 610 nm. Their photocurrents are large, as is typical of blue- and green-absorbing ACRs, but they rapidly decrease during continuous illumination (desensitization) and extremely slowly recover in the dark. Here, we show that long-lasting desensitization of RubyACRs results from photochemistry not observed in any previously studied channelrhodopsins. Absorption of a second photon by …

Elucidating The Impact Of Sos-Response Timing In On Escherichia Coli Survival Following Treatment With Fluoroquinolone Topoisomerase Inhibitors, Stephanie Schofield

Honors Scholar Theses

Antibiotic treatment failure is a public health crisis, with a 2019 report stating that roughly 35,000 deaths occur in the United States yearly due to bacterial infections that are unresponsive to antibiotics (1). One complication in the treatment of bacterial infection is antibiotic persistence which further compromises our battle to effectively treat infection. Bacterial persisters can exist in clonal bacterial cultures and can tolerate antibiotic treatment by undergoing reversible phenotypic changes. They can survive drug concentrations that their genetically identical kin cannot. Some persisters remain in a slow growing state and are difficult to target with current antibiotics. A specific …

The Involvement Of Ubiquitin In Med13 Cyclin C Degradation Following Cellular Stress, Ayesha Gurnani, Brittany Friedson, Katrina Cooper

Rowan-Virtua Research Day

The Cdk8 Kinase Module is a dissociable regulator of cellular stress response genes, with degradation of its components Med13 and cyclin C eventually determining cell fate decisions such as engaging cell survival or cell death mechanisms. We aimed to explore the roles of ubiquitin in degradation of the Cdk8 Kinase Module following nitrogen starvation, with respect to the potential involvement of deubiquitinating enzyme Doa4, lysine linkage at position K63, and E2 ubiquitin conjugating enzymes Ubc4 and Ubc5. We utilized Western blot analysis to observe nitrogen starvation-induced degradation of Med13-HA in wild-type, doa4 mutant, and K63R yeast strains; degradation of cyclin …

Identifying Co-Factors That Drive Tra-1 Activator Function, Jibran Imtiaz, Yongquan Shen, Ronald Ellis

Rowan-Virtua Research Day

Gli proteins are involved in cell fate determination, proliferation, and patterning in many species and are major effectors of Hedgehog (Hh) signaling. There are three Gli proteins in humans, and mutations or errors in their regulation lead to a variety of developmental disorders or cancer. However, the mechanisms by which they interact with co-factors are poorly understood. We are analyzing co-factors of Gli proteins using TRA-1 in Caenorhabditis nematodes. The TRA-1 zinc fingers are structurally like those of other Gli proteins, and TRA-1 can be cleaved like other Gli proteins to form a repressor. However, its function has changed during …

Effect Of Temperature On The Microbiome Of A Laboratory Reared Colony Of Haemaphysalis Longicornis Ticks, Brianna Mitchell

Poster Presentations

Honors research poster.

Haemaphysalis longicornis is a species of tick native to eastern Asia, including eastern China, Japan, eastern Russia, and Korea. To date, it has invaded and has now established its existence in Australia, New Zealand, and several of the Pacific Islands. This species of tick has recently been introduced to the United States, having a confirmed sighting in November 2017 on a sheep farm in New Jersey and since establishing populations in 18 states along the east coast and Appalachia. Based on the existing locations of H. longicornis in its native regions, as well as in the United …

Immunomodulatory Effects Of Resolvin D2 In A Model Of Infection, Prem Yugandhar Kadiyam Sundarasivarao

Graduate School of Biomedical Sciences Theses and Dissertations

Dysregulated hyperinflammatory host immune response to underlying bacterial infections is a characteristic of sepsis. In sepsis, bacteria often trigger abnormal hyperinflammatory responses which can cause multiple organ failure and if sustained can lead to an immunosuppressive phase where the host is susceptible to secondary infections caused by opportunistic bacteria like Pseudomonas aeruginosa (P. aeruginosa). In our studies, we used a 2-hit model of cecal ligation and puncture (CLP) followed by P. aeruginosa secondary lung infection to investigate cellular and molecular mechanisms in the beneficial action of resolvin D2 (RvD2). Resolvins of the D-series are a group of fatty acids known …

Spatial Metabolomics Reveals Glycogen As An Actionable Target For Pulmonary Fibrosis, Lindsey R. Conroy, Harrison A. Clarke, Derek B. Allison, Samuel Santos Valenca, Qi Sun, Tara R. Hawkinson, Lyndsay E. A. Young, Juanita E. Ferreira, Autumn V. Hammonds, Jaclyn B. Dunne, Robert J. Mcdonald, Kimberly J. Absher, Brittany Dong, Ronald C. Bruntz, Kia H. Markussen, Jelena A. Juras, Warren J. Alilain, Jinze Liu, Matthew S. Gentry, Peggi M. Angel, Christopher M. Waters, Ramon C. Sun

Saha Cardiovascular Research Center Faculty Publications

Matrix assisted laser desorption/ionization imaging has greatly improved our understanding of spatial biology, however a robust bioinformatic pipeline for data analysis is lacking. Here, we demonstrate the application of high- dimensionality reduction/spatial clustering and histopathological annotation of matrix assisted laser desorption/ionization imaging datasets to assess tissue metabolic heterogeneity in human lung diseases. Using metabolic features identified from this pipeline, we hypothesize that metabolic channeling between glycogen and N-linked glycans is a critical metabolic process favoring pulmonary fibrosis progression. To test our hypothesis, we induced pulmonary fibrosis in two different mouse models with lysosomal glycogen utilization deficiency. Both mouse models displayed …

The Effects Of Specialized Pro-Resolving Mediator Lipoxin A4 On Pseudomonas Aeruginosa Biofilms And Interactions With Monocytes, Julianne M. Thornton

Graduate School of Biomedical Sciences Theses and Dissertations

Pseudomonas aeruginosa (P. aeruginosa) is an opportunistic pathogen known as a major cause of hospital-acquired secondary infections, commonly causing chronic respiratory infections in immunocompromised individuals, especially those with cystic fibrosis, and often found in wound infections. P. aeruginosa uses the quorum sensing pathway to readily form protective biofilms, which reduce the efficacy of antibiotics and access by host immune cells to eradicate the pathogen. Specialized pro-resolving mediators (SPMs) are lipids endogenously produced by the host immune response to infection to aid in infection resolution. One SPM, Lipoxin A4 (LxA4), has been shown to be a robust quorum sensing inhibitor.

The …

Med13 Degradation Defines A New Receptor-Mediated Autophagy Pathway Activated By Nutrient Deprivation, Sara E. Hanley

Graduate School of Biomedical Sciences Theses and Dissertations

Cells are exposed to an enormous amount of diverse extracellular cues but have a limited arsenal of weapons for protecting and maintaining homeostasis. To overcome these restrictions, nature has engineered proteins that have multiple functions. The pleiotropy of using one protein to carry out a variety of functions allows cells to rapidly execute tailored responses to a diverse set of signals. The Cdk8 kinase module (CKM) is a conserved detachable unit of the Mediator complex predominantly known for its role in transcriptional regulation. The CKM is composed of four proteins, the scaffolding proteins Med13 and Med12, as well as the …

Lipid Nanoparticle-Mediated Mrna Delivery In Lung Fibrosis, Matteo Massaro, Suhong Wu, Gherardo Baudo, Haoran Liu, Scott Collum, Hyunho Lee, Cinzia Stigliano, Victor Segura-Ibarra, Harry Karmouty-Quintana, Elvin Blanco

Faculty, Staff and Student Publications

mRNA delivery enables the specific synthesis of proteins with therapeutic potential, representing a powerful strategy in diseases lacking efficacious pharmacotherapies. Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease characterized by excessive extracellular matrix (ECM) deposition and subsequent alveolar remodeling. Alveolar epithelial type 2 cells (AEC2) and fibroblasts represent important targets in IPF given their role in initiating and driving aberrant wound healing responses that lead to excessive ECM deposition. Our objective was to examine a lipid nanoparticle (LNP)-based mRNA construct as a viable strategy to target alveolar epithelial cells and fibroblasts in IPF. mRNA-containing LNPs measuring ∼34 nm had …

Anterior And Posterior Tongue Regions And Taste Papillae: Distinct Roles And Regulatory Mechanisms With An Emphasis On Hedgehog Signaling And Antagonism., Archana Kumari, Charlotte M. Mistretta

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Sensory receptors across the entire tongue are engaged during eating. However, the tongue has distinctive regions with taste (fungiform and circumvallate) and non-taste (filiform) organs that are composed of specialized epithelia, connective tissues, and innervation. The tissue regions and papillae are adapted in form and function for taste and somatosensation associated with eating. It follows that homeostasis and regeneration of distinctive papillae and taste buds with particular functional roles require tailored molecular pathways. Nonetheless, in the chemosensory field, generalizations are often made between mechanisms that regulate anterior tongue fungiform and posterior circumvallate taste papillae, without a clear distinction that highlights …

Loss Of Peroxiredoxin Iv Protects Mice From Azoxymethane/Dextran Sulfate Sodium-Induced Colorectal Cancer Development, Pratik Thapa, Hong Jiang, Na Ding, Yanning Hao, Aziza Alshahrani, Eun Young Lee, Junichi Fujii, Qiou Wei

Markey Cancer Center Faculty Publications

Peroxiredoxin IV (Prx4), a typical two-cysteine-containing member of the peroxidase family, functions as an antioxidant to maintain cellular redox homeostasis through the reduction of reactive oxygen species (ROS) via cycles of oxidation–reduction reactions. Under oxidative stress, all Prxs including Prx4 are inactivated as their catalytic cysteines undergo hyperoxidation, and hyperoxidized two-cysteine Prxs can be exclusively repaired and revitalized through the reduction cycle catalyzed by sulfiredoxin (Srx). Previously, we showed that Prx4 is a preferred substrate of Srx, and knockout of Srx in mice leads to resistance to azoxymethane/dextran sulfate sodium (AOM/DSS)-induced colon carcinogenesis. To further understand the significance of the …

Ferric Chloride-Induced Arterial Thrombosis And Sample Collection For 3d Electron Microscopy Analysis, Smita Joshi, Alexis N. Smith, Kanakanagavalli Shravani Prakhya, Hammodah Rawhi Hammodah Alfar, Joshua Lykins, Ming Zhang, Irina D. Pokrovskaya, Maria A. Aronova, Richard D. Leapman, Brian Storrie, Sidney W. Whiteheart

Saha Cardiovascular Research Center Faculty Publications

Cardiovascular diseases are a leading cause of mortality and morbidity worldwide. Aberrant thrombosis is a common feature of systemic conditions like diabetes and obesity, and chronic inflammatory diseases like atherosclerosis, cancer, and autoimmune diseases. Upon vascular injury, usually the coagulation system, platelets, and endothelium act in an orchestrated manner to prevent bleeding by forming a clot at the site of the injury. Abnormalities in this process lead to either excessive bleeding or uncontrolled thrombosis/insufficient antithrombotic activity, which translates into vessel occlusion and its sequelae. The FeCl3-induced carotid injury model is a valuable tool in probing how thrombosis initiates and progresses …

Gasdermin D Deficiency In Vascular Smooth Muscle Cells Ameliorates Abdominal Aortic Aneurysm Through Reducing Putrescine Synthesis, Jianing Gao, Yanghui Chen, Huiqing Wang, Xin Li, Ke Li, Yangkai Xu, Xianwei Xie, Yansong Guo, Nana Yang, Xinhua Zhang, Dong Ma, Hong S. Lu, Ying H. Shen, Yong Liu, Jifeng Zhang, Y. Eugene Chen, Alan Daugherty, Dao Wen Wang, Lemin Zheng

Saha Cardiovascular Research Center Faculty Publications

Abdominal aortic aneurysm (AAA) is a common vascular disease associated with significant phenotypic alterations in vascular smooth muscle cells (VSMCs). Gasdermin D (GSDMD) is a pore-forming effector of pyroptosis. In this study, the role of VSMC-specific GSDMD in the phenotypic alteration of VSMCs and AAA formation is determined. Single-cell transcriptome analyses reveal Gsdmd upregulation in aortic VSMCs in angiotensin (Ang) II-induced AAA. VSMC-specific Gsdmd deletion ameliorates Ang II-induced AAA in apolipoprotein E (ApoE)−/− mice. Using untargeted metabolomic analysis, it is found that putrescine is significantly reduced in the plasma and aortic tissues of VSMC-specific GSDMD deficient mice. High putrescine levels …

Identification Of Novel Biosynthetic Gene Clusters Encoding For Polyketide/Nrps-Producing Chemotherapeutic Compounds From Marine-Derived Streptomyces Hygroscopicus From A Marine Sanctuary, Hannah Ruth Flaherty

Honors Theses and Capstones

Nearly one out of six deaths in 2020, around ten million people, were caused by cancer, making it a leading cause of death worldwide (WHO, 2022). This major public health issue, in addition to the rise of multidrug-resistant (MDR) pathogens, provides a high demand for the discovery of new pharmaceutical drugs to be used clinically to treat these conditions. The Streptomyces genus accounts to produce 39% of all microbial metabolites currently approved for human health, indicating its potential as an important species to study for antimicrobial and anticancer agents. The long linear genome of Streptomyces contains specialized sequences known as …

Characterizing Cellular Injury And Inflammation With Aldob-/-Mouse Model Of Mafld, Andy Rashid

All Master's Theses

Metabolic-associated fatty liver disease (MAFLD) affects 1 in 3 people in the US and is a healthcare burden on the order of billions of dollars. MAFLD is characterized by pathological lipid accumulation in the liver, excess production of triglycerides and cholesterol, and export of LDL particles that raise serum lipid levels. These metabolic perturbations can lead to the development of liver fibrosis, chronic inflammation, and insulin resistance. Diagnosing MAFLD prior to fibrosis is crucial for successful intervention and prevention of advanced liver disease and other metabolic complications. Fructose-1Phospahte (F1P) accumulation from fructose overconsumption can drive hepatic lipogenesis and MAFLD progression. …

The Link Between Intracellular Calcium Signaling And Exosomal Pd-L1 In Cancer Progression And Immunotherapy, Rakibul Alam, Mizanur Rahman, Zhiguo Li

Markey Cancer Center Faculty Publications

Exosomes are small membrane vesicles containing microRNA, RNA, DNA fragments, and proteins that are transferred from donor cells to recipient cells. Tumor cells release exo- somes to reprogram the factors associated with the tumor microenvironment (TME) causing tu- mor metastasis and immune escape. Emerging evidence revealed that cancer cell-derived exosomes carry immune inhibitory molecule program death ligand 1 (PD-L1) that binds with re- ceptor program death protein 1 (PD-1) and promote tumor progression by escaping immune response. Currently, some FDA-approved monoclonal antibodies are clinically used for cancer treatment by blocking PD-1/PD-L1 interaction. Despite notable treatment outcomes, some pa- tients show …

Development Of A Chemical Biology Approach To Uncover The Influence Of Sequence Variations On Ces1 Activity In Live Cells, Samuel James Knebel

Masters Theses

Drug metabolism is the biochemical process of modifying drugs to detoxify and remove them through enzymatic transformations. These biotransformation’s occur primarily in the liver and are critical to understanding how pharmaceutical compounds are chemically altered inside the human body. Human carboxylesterases (CESs) catalyze the hydrolysis of esters, amides, thioesters, and carbamates. CES-mediated hydrolysis plays an important role in the metabolism of many drugs including the first FDA approved antiviral treatment for COVID-19, remdesivir (Veklury), the seizure control medication rufinamide (Banzel), and the flu antiviral drug oseltamivir (Tamiflu). CES activity is known to be influenced by a variety of factors including …

The Gastrointestinal-Brain-Microbiota Axis: A Promising Therapeutic Target For Ischemic Stroke, Yan-Hao Wei, Ren-Tang Bi, Yan-Mei Qiu, Chun-Lin Zhang, Jian-Zhuang Li, Ya-Nan Li, Bo Hu

Faculty, Staff and Student Publications

Ischemic stroke is a highly complex systemic disease characterized by intricate interactions between the brain and gastrointestinal tract. While our current understanding of these interactions primarily stems from experimental models, their relevance to human stroke outcomes is of considerable interest. After stroke, bidirectional communication between the brain and gastrointestinal tract initiates changes in the gastrointestinal microenvironment. These changes involve the activation of gastrointestinal immunity, disruption of the gastrointestinal barrier, and alterations in gastrointestinal microbiota. Importantly, experimental evidence suggests that these alterations facilitate the migration of gastrointestinal immune cells and cytokines across the damaged blood-brain barrier, ultimately infiltrating the ischemic brain. …

Therapies For Mitochondrial Disorders, Kayli Sousa Smyth, Anne Mulvihill

SURE Journal: Science Undergraduate Research Experience Journal

Mitochondria are cytoplasmic, double-membrane organelles that synthesise adenosine triphosphate (ATP). Mitochondria contain their own genome, mitochondrial DNA (mtDNA), which is maternally inherited from the oocyte. Mitochondrial proteins are encoded by either nuclear DNA (nDNA) or mtDNA, and both code for proteins forming the mitochondrial oxidative phosphorylation (OXPHOS) complexes of the respiratory chain. These complexes form a chain that allows the passage of electrons down the electron transport chain (ETC) through a proton motive force, creating ATP from adenosine diphosphate (ADP). This study aims to explore current and prospective therapies for mitochondrial disorders (MTDS). MTDS are clinical syndromes coupled with abnormalities …

T-Cell Antigen Receptors In Multiple Sclerosis, Lisa Lanée Keyes Jones

Biomedical Sciences Theses & Dissertations

Multiple Sclerosis (MS) is T-cell mediated autoimmune disease characterized by inflammation, demyelination, and degeneration of axons in the brain and spinal cord. A T cell-mediated immune response in MS is directed against myelin components and possibly other antigens in genetically susceptible individuals and is triggered by a viral infection. The T-cell antigen receptor (TCR) on T cells is responsible for antigen recognition and determines specificity. Our overall hypothesis is to determine whether clonally expanded T cells in patients with MS recognize viral or self-antigens and to determine whether molecular mimicry is involved in the development of the disease. To study …