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Articles 1 - 30 of 457

Full-Text Articles in Biochemical Phenomena, Metabolism, and Nutrition

Mitochondrial Aspects Of Neuronal Pathology In Triple-Transgenic Alzheimer’S Disease Mice, John Zachary Cavendish Jan 2021

Mitochondrial Aspects Of Neuronal Pathology In Triple-Transgenic Alzheimer’S Disease Mice, John Zachary Cavendish

Graduate Theses, Dissertations, and Problem Reports

Alzheimer’s disease (AD) is a fatal, progressive neurodegenerative disease afflicting millions of people in the United States alone and is the only one of the top leading causes of morbidity and mortality with no effective disease-modifying therapies. It is the most common form of dementia, affecting one in three people over the age of 85. While the hallmarks of the disease include accumulation of beta-amyloid-based extracellular plaques and hyperphosphorylated tau-based intracellular neurofibrillary tangles, treatment strategies centered on removing or mitigating these components of AD have all failed in humans. Mitochondrial dysfunction has been increasingly recognized as an early and ...


Proceedings Of The 3rd International Evolutionary Health Conference, Lynda Frassetto, Pedro Bastos, Filipe Brito, Emily C. Deans Md, Dan Pardi, Angelo Rossiello Oct 2019

Proceedings Of The 3rd International Evolutionary Health Conference, Lynda Frassetto, Pedro Bastos, Filipe Brito, Emily C. Deans Md, Dan Pardi, Angelo Rossiello

Journal of Evolution and Health

No abstract provided.


Genetic Rescue Of Fragile X Syndrome Links Fmrp Deficiency To Codon Optimality-Dependent Rna Destabilization, Huan Shu, Elisa Donnard, Botao Liu, Joel D. Richter Oct 2019

Genetic Rescue Of Fragile X Syndrome Links Fmrp Deficiency To Codon Optimality-Dependent Rna Destabilization, Huan Shu, Elisa Donnard, Botao Liu, Joel D. Richter

University of Massachusetts Medical School Faculty Publications

Fragile X syndrome (FXS) is caused by inactivation of FMR1 gene and loss of its encoded product the RNA binding protein FMRP, which generally represses translation of its target transcripts in the brain. In mouse models of FXS (i.e., Fmr1 knockout animals; Fmr1 KO), deletion of Cpeb1, which encodes a translational activator, mitigates nearly all pathophysiologies associated with the disorder. Here we reveal unexpected wide-spread dys-regulation of RNA abundance in Fmr1 KO brain cortex and its rescue to normal levels in Fmr1/Cpeb1 double KO mice. Alteration and restoration of RNA levels are the dominant molecular events that drive ...


Pheochromocytoma – Clinical Manifestations, Diagnosis And Current Perioperative Management, Maria Manea, Dragos R. Marcu, Ovidiu G. Bratu, Ana M. Stanescu, Anca Pantea Stoian, Mihnea A. Gaman, Camelia C. Diaconu Oct 2019

Pheochromocytoma – Clinical Manifestations, Diagnosis And Current Perioperative Management, Maria Manea, Dragos R. Marcu, Ovidiu G. Bratu, Ana M. Stanescu, Anca Pantea Stoian, Mihnea A. Gaman, Camelia C. Diaconu

Journal of Mind and Medical Sciences

Pheochromocytoma is a neuroendocrine tumor characterized by the excessive production of catecholamines (epinephrine, norepinephrine, and dopamine). The diagnosis is suspected due to hypertensive paroxysms, associated with vegetative phenomena, due to the catecholaminergic hypersecretion. Diagnosis involves biochemical tests that reveal elevated levels of catecholamine metabolites (metanephrine and normetanephrine). Functional imaging, such as 123I-metaiodobenzylguanidine scintigraphy (123I-MIBG), has increased specificity in identifying the catecholamine-producing tumor and its metastases. The gold-standard treatment for patients with pheochromocytoma is represented by the surgical removal of the tumor. Before surgical resection, it is important to optimize blood pressure and intravascular volume in order to avoid negative hemodynamic ...


Extensive Ribosome And Rf2 Rearrangements During Translation Termination, Egor Svidritskiy, Gabriel Demo, Anna B. Loveland, Chen Xu, Andrei A. Korostelev Sep 2019

Extensive Ribosome And Rf2 Rearrangements During Translation Termination, Egor Svidritskiy, Gabriel Demo, Anna B. Loveland, Chen Xu, Andrei A. Korostelev

Open Access Articles

Protein synthesis ends when a ribosome reaches an mRNA stop codon. Release factors (RFs) decode the stop codon, hydrolyze peptidyl-tRNA to release the nascent protein, and then dissociate to allow ribosome recycling. To visualize termination by RF2, we resolved a cryo-EM ensemble of E. coli 70S*RF2 structures at up to 3.3 A in a single sample. Five structures suggest a highly dynamic termination pathway. Upon peptidyl-tRNA hydrolysis, the CCA end of deacyl-tRNA departs from the peptidyl transferase center. The catalytic GGQ loop of RF2 is rearranged into a long beta-hairpin that plugs the peptide tunnel, biasing a nascent ...


Co-Option Of The Gibbon-Specific Lava Retrotransposon In Dna Repair Pathways, Mariam Okhovat, Kimberly A. Nevonen, Brett Davis, Pryce S. Michener, Samantha Ward, Mark Milhaven, Lana Harshman, Ajuni Sohota, Rachel J. O’Neill, Nadav Ahituv, Krishna R. Veeramah, Lucia Carbone Sep 2019

Co-Option Of The Gibbon-Specific Lava Retrotransposon In Dna Repair Pathways, Mariam Okhovat, Kimberly A. Nevonen, Brett Davis, Pryce S. Michener, Samantha Ward, Mark Milhaven, Lana Harshman, Ajuni Sohota, Rachel J. O’Neill, Nadav Ahituv, Krishna R. Veeramah, Lucia Carbone

University of Massachusetts Medical School Faculty Publications

Transposable elements (TEs) can shape gene regulation networks by being co-opted as enhancers. However, the contribution of lineage-specific TE insertions to recent adaptations remains poorly understood. Gibbons present a suitable model to study these contributions, as they have evolved many distinct traits, including heavily rearranged genomes and a novel TE called LAVA. The LAVA retrotransposon is still active in the gibbon genome and is thought to have contributed to evolution of gibbon-specific traits. In this study, we characterized fixed and polymorphic LAVA insertions across multiple gibbon genomes and found that 10% of all LAVA elements overlap chromatin states associated with ...


High-Fat Diet In A Mouse Insulin-Resistant Model Induces Widespread Rewiring Of The Phosphotyrosine Signaling Network, Antje Dittmann, Norman J. Kennedy, Nina L. Soltero, Nader Morshed, Miyeko D. Mana, Omer H. Yilmaz, Roger J. Davis, Forest M. White Aug 2019

High-Fat Diet In A Mouse Insulin-Resistant Model Induces Widespread Rewiring Of The Phosphotyrosine Signaling Network, Antje Dittmann, Norman J. Kennedy, Nina L. Soltero, Nader Morshed, Miyeko D. Mana, Omer H. Yilmaz, Roger J. Davis, Forest M. White

Open Access Articles

Obesity-associated type 2 diabetes and accompanying diseases have developed into a leading human health risk across industrialized and developing countries. The complex molecular underpinnings of how lipid overload and lipid metabolites lead to the deregulation of metabolic processes are incompletely understood. We assessed hepatic post-translational alterations in response to treatment of cells with saturated and unsaturated free fatty acids and the consumption of a high-fat diet by mice. These data revealed widespread tyrosine phosphorylation changes affecting a large number of enzymes involved in metabolic processes as well as canonical receptor-mediated signal transduction networks. Targeting two of the most prominently affected ...


Alternative Splicing Regulates Stochastic Nlrp3 Activity, Florian Hoss, James L. Mueller, Francisca Rojas Ringeling, Juan F. Rodriguez-Alcazar, Rebecca Brinkschulte, Gerald Seifert, Rainer Stahl, Lori Broderick, Chris D. Putnam, Richard D. Kolodner, Stefan Canzar, Matthias Geyer, Hal M. Hoffman, Eicke Latz Jul 2019

Alternative Splicing Regulates Stochastic Nlrp3 Activity, Florian Hoss, James L. Mueller, Francisca Rojas Ringeling, Juan F. Rodriguez-Alcazar, Rebecca Brinkschulte, Gerald Seifert, Rainer Stahl, Lori Broderick, Chris D. Putnam, Richard D. Kolodner, Stefan Canzar, Matthias Geyer, Hal M. Hoffman, Eicke Latz

Open Access Articles

Leucine-rich repeat (LRR) domains are evolutionarily conserved in proteins that function in development and immunity. Here we report strict exonic modularity of LRR domains of several human gene families, which is a precondition for alternative splicing (AS). We provide evidence for AS of LRR domain within several Nod-like receptors, most prominently the inflammasome sensor NLRP3. Human NLRP3, but not mouse NLRP3, is expressed as two major isoforms, the full-length variant and a variant lacking exon 5. Moreover, NLRP3 AS is stochastically regulated, with NLRP3 exon 5 lacking the interaction surface for NEK7 and hence loss of activity. Our data thus ...


Jnk And Cardiometabolic Dysfunction, Siobhan M. Craige, Kai Chen, Robert M. Blanton, John F. Keaney Jr., Shashi Kant Jul 2019

Jnk And Cardiometabolic Dysfunction, Siobhan M. Craige, Kai Chen, Robert M. Blanton, John F. Keaney Jr., Shashi Kant

Open Access Articles

Cardiometabolic syndrome (CMS) describes the cluster of metabolic and cardiovascular diseases that are generally characterized by impaired glucose tolerance, intra-abdominal adiposity, dyslipidemia, and hypertension. CMS currently affects more than 25% of the world's population and the rates of diseases are rapidly rising. These CMS conditions represent critical risk factors for cardiovascular diseases including atherosclerosis, heart failure, myocardial infarction, and peripheral artery disease (PAD). Therefore, it is imperative to elucidate the underlying signaling involved in disease onset and progression. The c-Jun N-terminal Kinases (JNKs) are a family of stress signaling kinases that have been recently indicated in CMS. The purpose ...


A Receptor Of The Immunoglobulin Superfamily Regulates Adaptive Thermogenesis, Carmen Hurtado Del Pozo, Randall H. Friedline, Hye Lim Noh, Jason K. Kim, Ann Marie. Schmidt Jul 2019

A Receptor Of The Immunoglobulin Superfamily Regulates Adaptive Thermogenesis, Carmen Hurtado Del Pozo, Randall H. Friedline, Hye Lim Noh, Jason K. Kim, Ann Marie. Schmidt

Open Access Articles

Exquisite regulation of energy homeostasis protects from nutrient deprivation but causes metabolic dysfunction upon nutrient excess. In human and murine adipose tissue, the accumulation of ligands of the receptor for advanced glycation end products (RAGE) accompanies obesity, implicating this receptor in energy metabolism. Here, we demonstrate that mice bearing global- or adipocyte-specific deletion of Ager, the gene encoding RAGE, display superior metabolic recovery after fasting, a cold challenge, or high-fat feeding. The RAGE-dependent mechanisms were traced to suppression of protein kinase A (PKA)-mediated phosphorylation of its key targets, hormone-sensitive lipase and p38 mitogen-activated protein kinase, upon beta-adrenergic receptor stimulation-processes ...


Control Of Antiviral Innate Immune Response By Protein Geranylgeranylation, Shigao Yang, Zhaozhao Jiang, Katherine A. Fitzgerald, Donghai Wang Jul 2019

Control Of Antiviral Innate Immune Response By Protein Geranylgeranylation, Shigao Yang, Zhaozhao Jiang, Katherine A. Fitzgerald, Donghai Wang

Katherine A. Fitzgerald

The mitochondrial antiviral signaling protein (MAVS) orchestrates host antiviral innate immune response to RNA virus infection. However, how MAVS signaling is controlled to eradicate virus while preventing self-destructive inflammation remains obscure. Here, we show that protein geranylgeranylation, a posttranslational lipid modification of proteins, limits MAVS-mediated immune signaling by targeting Rho family small guanosine triphosphatase Rac1 into the mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs) at the mitochondria-ER junction. Protein geranylgeranylation and subsequent palmitoylation promote Rac1 translocation into MAMs upon viral infection. MAM-localized Rac1 limits MAVS' interaction with E3 ligase Trim31 and hence inhibits MAVS ubiquitination, aggregation, and activation. Rac1 also facilitates ...


Identification Of Small Molecule Enzyme Inhibitors As Broad-Spectrum Anthelmintics, Rahul Tyagi, Elfawal A. Mostafa, Scott A. Wildman, Jon Helander, Christina A. Bulman, Judy Sakanari, Bruce A. Rosa, Paul J. Brindley, James W. Janetka, Raffi V. Aroian, Makedonka Mitreva Jun 2019

Identification Of Small Molecule Enzyme Inhibitors As Broad-Spectrum Anthelmintics, Rahul Tyagi, Elfawal A. Mostafa, Scott A. Wildman, Jon Helander, Christina A. Bulman, Judy Sakanari, Bruce A. Rosa, Paul J. Brindley, James W. Janetka, Raffi V. Aroian, Makedonka Mitreva

Open Access Articles

Targeting chokepoint enzymes in metabolic pathways has led to new drugs for cancers, autoimmune disorders and infectious diseases. This is also a cornerstone approach for discovery and development of anthelmintics against nematode and flatworm parasites. Here, we performed omics-driven knowledge-based identification of chokepoint enzymes as anthelmintic targets. We prioritized 10 of 186 phylogenetically conserved chokepoint enzymes and undertook a target class repurposing approach to test and identify new small molecules with broad spectrum anthelmintic activity. First, we identified and tested 94 commercially available compounds using an in vitro phenotypic assay, and discovered 11 hits that inhibited nematode motility. Based on ...


Extreme Events Reveal An Alimentary Limit On Sustained Maximal Human Energy Expenditure, Caitlin Thurber, Lara R. Dugas, Cara Ocobock, Bryce Carlson, John R. Speakman, Herman Pontzer Jun 2019

Extreme Events Reveal An Alimentary Limit On Sustained Maximal Human Energy Expenditure, Caitlin Thurber, Lara R. Dugas, Cara Ocobock, Bryce Carlson, John R. Speakman, Herman Pontzer

Publications and Research

The limits on maximum sustained energy expenditure are unclear but are of interest because they constrain reproduction, thermoregulation, and physical activity. Here, we show that sustained expenditure in humans, measured as maximum sustained metabolic scope (SusMS), is a function of event duration. We compiled measurements of total energy expenditure (TEE) and basal metabolic rate (BMR) from human endurance events and added new data from adults running ~250 km/week for 20 weeks in a transcontinental race. For events lasting 0.5 to 250+ days, SusMS decreases curvilinearly with event duration, plateauing below 3× BMR. This relationship differs from that of ...


Lithium-Induced Chronic Kidney Disease In A Pediatric Patient, Neena Gupta, Meghan Gibson, Ellen C. Wallace Jun 2019

Lithium-Induced Chronic Kidney Disease In A Pediatric Patient, Neena Gupta, Meghan Gibson, Ellen C. Wallace

Pediatric Publications and Presentations

Lithium-induced nephropathy usually manifests in adulthood as it develops slowly after many years of cumulative exposure. There is very limited information available in pediatric patients. Renal function monitoring and timely intervention is the key in preventing lithium-induced chronic kidney disease in these patients. We report a case of a 14-year-old boy who was on lithium for almost 9 years for his complex psychiatric illness. He presented with increased urinary frequency and nocturia. His serum creatinine increased to 1.15 mg/dL (estimated glomerular filtration rate or eGFR 53 ml/min/1.73 m(2)) from a baseline of 0.78 ...


Control Of Antiviral Innate Immune Response By Protein Geranylgeranylation, Shigao Yang, Zhaozhao Jiang, Katherine A. Fitzgerald, Donghai Wang May 2019

Control Of Antiviral Innate Immune Response By Protein Geranylgeranylation, Shigao Yang, Zhaozhao Jiang, Katherine A. Fitzgerald, Donghai Wang

Open Access Articles

The mitochondrial antiviral signaling protein (MAVS) orchestrates host antiviral innate immune response to RNA virus infection. However, how MAVS signaling is controlled to eradicate virus while preventing self-destructive inflammation remains obscure. Here, we show that protein geranylgeranylation, a posttranslational lipid modification of proteins, limits MAVS-mediated immune signaling by targeting Rho family small guanosine triphosphatase Rac1 into the mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs) at the mitochondria-ER junction. Protein geranylgeranylation and subsequent palmitoylation promote Rac1 translocation into MAMs upon viral infection. MAM-localized Rac1 limits MAVS' interaction with E3 ligase Trim31 and hence inhibits MAVS ubiquitination, aggregation, and activation. Rac1 also facilitates ...


Adipocyte Acly Facilitates Dietary Carbohydrate Handling To Maintain Metabolic Homeostasis In Females, Sully Fernandez, John M. Viola, Annmarie Torres, Martina Wallace, Sophie Trefely, Steven Zhao, Hayley C. Affronti, Jivani M. Gengatharan, David A. Guertin, Nathaniel W. Snyder, Christian M. Metallo, Kathryn E. Wellen May 2019

Adipocyte Acly Facilitates Dietary Carbohydrate Handling To Maintain Metabolic Homeostasis In Females, Sully Fernandez, John M. Viola, Annmarie Torres, Martina Wallace, Sophie Trefely, Steven Zhao, Hayley C. Affronti, Jivani M. Gengatharan, David A. Guertin, Nathaniel W. Snyder, Christian M. Metallo, Kathryn E. Wellen

Open Access Articles

Sugars and refined carbohydrates are major components of the modern diet. ATP-citrate lyase (ACLY) is upregulated in adipocytes in response to carbohydrate consumption and generates acetyl-coenzyme A (CoA) for both lipid synthesis and acetylation reactions. Here, we investigate the role of ACLY in the metabolic and transcriptional responses to carbohydrates in adipocytes and unexpectedly uncover a sexually dimorphic function in maintaining systemic metabolic homeostasis. When fed a high-sucrose diet, Acly(FAT-/-) females exhibit a lipodystrophy-like phenotype, with minimal fat accumulation, insulin resistance, and hepatic lipid accumulation, whereas Acly(FAT-/-) males have only mild metabolic phenotypes. We find that ACLY is ...


Post Lumbar-Puncture Headache Experience In A Community Hospital (Peach) Study, Melissa Kessel, Caroline Knight, Robert Stein May 2019

Post Lumbar-Puncture Headache Experience In A Community Hospital (Peach) Study, Melissa Kessel, Caroline Knight, Robert Stein

Maine Medical Center

Introduction:

Post lumbar puncture (LP) headaches have been reported to occur in 10 to 30% of patients . The incidence of post-LP headaches at Pen Bay Medical Center (PBMC) was unknown prior to this study. This study was undertaken to attempt to understand the local experience with this procedural complication.


The Effect Of Glucosamine, Chondroitin And Harpagophytum Procumbens On Femoral Hyaline Cartilage Thickness In Patients With Knee Osteoarthritis– An Mri Versus Ultrasonography Study, Florentin Ananu Vreju, Paulina Lucia Ciurea, Anca Rosu, Beatrice Andreea Chisalau, Cristina Dorina Parvanescu, Sineta Cristina Firulescu, Adina Turcu Stiolica, Andreea Lili Barbulescu, Stefan Cristian Dinescu, Cristiana Iulia Dumitrescu, Roxana Mihaela Dumitrascu, Cristina Criveanu, Lucretiu Radu, Mihai Tusaliu, Daniela Dumitrescu Apr 2019

The Effect Of Glucosamine, Chondroitin And Harpagophytum Procumbens On Femoral Hyaline Cartilage Thickness In Patients With Knee Osteoarthritis– An Mri Versus Ultrasonography Study, Florentin Ananu Vreju, Paulina Lucia Ciurea, Anca Rosu, Beatrice Andreea Chisalau, Cristina Dorina Parvanescu, Sineta Cristina Firulescu, Adina Turcu Stiolica, Andreea Lili Barbulescu, Stefan Cristian Dinescu, Cristiana Iulia Dumitrescu, Roxana Mihaela Dumitrascu, Cristina Criveanu, Lucretiu Radu, Mihai Tusaliu, Daniela Dumitrescu

Journal of Mind and Medical Sciences

Background: the evaluation of cartilage thickness has become possible with new techniques such as musculoskeletal ultrasonography (US) and magnetic resonance imagining (MRI), making the evaluation of the treatment response and the progression of the disease more accurate. Objective: to evaluate the efficacy of a Symptomatic Slow Acting Drug for Osteoarthritis using both US and MRI for measuring cartilage thickness at baseline and after 1 year. Methods: The study included the clinical evaluation of 20 patients at baseline, at 6 and 12 months as well as imaging exams (US and MRI) at baseline and after 1 year. Measurements were performed in ...


Exercise Rescues Gene Pathways Involved In Vascular Expansion And Promotes Functional Angiogenesis In Subcutaneous White Adipose Tissue, So Yun Min, Heather Learnard, Shashi Kant, Olga Gaelikman, Raziel Rojas-Rodriguez, Tiffany Desouza, Anand Desai, John F. Keaney Jr., Silvia Corvera, Siobhan M. Craige Apr 2019

Exercise Rescues Gene Pathways Involved In Vascular Expansion And Promotes Functional Angiogenesis In Subcutaneous White Adipose Tissue, So Yun Min, Heather Learnard, Shashi Kant, Olga Gaelikman, Raziel Rojas-Rodriguez, Tiffany Desouza, Anand Desai, John F. Keaney Jr., Silvia Corvera, Siobhan M. Craige

Open Access Articles

Exercise mitigates chronic diseases such as diabetes, cardiovascular diseases, and obesity; however, the molecular mechanisms governing protection from these diseases are not completely understood. Here we demonstrate that exercise rescues metabolically compromised high fat diet (HFD) fed mice, and reprograms subcutaneous white adipose tissue (scWAT). Using transcriptomic profiling, scWAT was analyzed for HFD gene expression changes that were rescued by exercise. Gene networks involved in vascularization were identified as prominent targets of exercise, which led us to investigate the vasculature architecture and endothelial phenotype. Vascular density in scWAT was found to be compromised in HFD, and exercise rescued this defect ...


Severe Anion Gap Metabolic Acidosis Associated With Initiation Of A Very Low-Carbohydrate Diet., Sijan Basnet, Niranjan Tachamo, Salik Nazir, Rashmi Dhital, Asad Jehangir, Anthony Donato Apr 2019

Severe Anion Gap Metabolic Acidosis Associated With Initiation Of A Very Low-Carbohydrate Diet., Sijan Basnet, Niranjan Tachamo, Salik Nazir, Rashmi Dhital, Asad Jehangir, Anthony Donato

Reading Hospital Internal Medicine Residency

Low carbohydrate diets have been popularized as an effective solution for weight loss. Although rare, life-threatening anion gap metabolic acidosis has been reported in patients on these diets. We present a case of a 31-year-old man with atypical symptoms of chest pain and shortness of breath found to have severe metabolic acidosis after starting low carbohydrate diet for a week.


Nutritional Management Of Pediatric Patients With Short Bowel Syndrome, Melissa Henry Apr 2019

Nutritional Management Of Pediatric Patients With Short Bowel Syndrome, Melissa Henry

Undergraduate Research Symposium

Short Bowel Syndrome (SBS) and associated nutritional deficiencies result from massive bowel resection. The most common causes of SBS are necrotizing enterocolitis and intestinal atresia, but the condition may be caused by any condition that results in necrotic bowel tissue. Significant research exists regarding the nutritional management of these patients in the immediate post-operative period via total parenteral nutrition and regarding the transition to enteral nutrition for short-term management. Other nutritional and psychological research shows that oral feeding should be the long-term goal for these patients due to the psychological and social benefits of oral feeding. In the long-term management ...


Role Of Serum Biomarkers In Early Detection Of Non-Alcoholic Steatohepatitis And Fibrosis In West Virginian Children, Komal Sodhi, Lucas Bracero, Andrew S. Feyh, Alexandra Nichols, Krithika Srikanthan, Tariq M. Latif, Deborah L. Preston, Joseph I. Shapiro, Yoram Elitsur Apr 2019

Role Of Serum Biomarkers In Early Detection Of Non-Alcoholic Steatohepatitis And Fibrosis In West Virginian Children, Komal Sodhi, Lucas Bracero, Andrew S. Feyh, Alexandra Nichols, Krithika Srikanthan, Tariq M. Latif, Deborah L. Preston, Joseph I. Shapiro, Yoram Elitsur

Joseph I Shapiro MD

Background: Obesity, an epidemic among West Virginia children, as well as insulin resistance (IR), is wellestablished contributors to nonalcoholic steatohepatitis (NASH). Progression of NASH can lead to hepatic fibrosis and cirrhosis, making early detection imperative. The standard for diagnosing NASH is histologically via liver biopsy, which is highly invasive and generally contraindicated in children. By studying serum biomarkers associated with NASH, we aim to identify high risk children who can benefit from a less invasive, alternative approach to the early detection of NASH.

Methods: Seventy one children were prospectively recruited and divided into 3 groups: normal weight without IR (control ...


Role Of Serum Biomarkers In Early Detection Of Non-Alcoholic Steatohepatitis And Fibrosis In West Virginian Children, Komal Sodhi, Lucas Bracero, Andrew S. Feyh, Alexandra Nichols, Krithika Srikanthan, Tariq M. Latif, Deborah L. Preston, Joseph I. Shapiro, Yoram Elitsur Apr 2019

Role Of Serum Biomarkers In Early Detection Of Non-Alcoholic Steatohepatitis And Fibrosis In West Virginian Children, Komal Sodhi, Lucas Bracero, Andrew S. Feyh, Alexandra Nichols, Krithika Srikanthan, Tariq M. Latif, Deborah L. Preston, Joseph I. Shapiro, Yoram Elitsur

Joseph I Shapiro MD

Background: Obesity, an epidemic among West Virginia children, as well as insulin resistance (IR), is wellestablished contributors to nonalcoholic steatohepatitis (NASH). Progression of NASH can lead to hepatic fibrosis and cirrhosis, making early detection imperative. The standard for diagnosing NASH is histologically via liver biopsy, which is highly invasive and generally contraindicated in children. By studying serum biomarkers associated with NASH, we aim to identify high risk children who can benefit from a less invasive, alternative approach to the early detection of NASH.

Methods: Seventy one children were prospectively recruited and divided into 3 groups: normal weight without IR (control ...


Role Of Serum Biomarkers In Early Detection Of Diabetic Cardiomyopathy In The West Virginian Population, Adam Shaver, Alexandra Nichols, Ellen A. Thompson, Amrita Mallick, Nandini Manne, Shanmuga Sundaram, Joseph I. Shapiro Md, Komal Sodhi Apr 2019

Role Of Serum Biomarkers In Early Detection Of Diabetic Cardiomyopathy In The West Virginian Population, Adam Shaver, Alexandra Nichols, Ellen A. Thompson, Amrita Mallick, Nandini Manne, Shanmuga Sundaram, Joseph I. Shapiro Md, Komal Sodhi

Joseph I Shapiro MD

Objectives: Diabetic cardiomyopathy (DCM) is an established complication of diabetes mellitus. In West Virginia, the especially high incidence of diabetes and heart failure validate the necessity of developing new strategies for earlier detection of DCM. Since most DCM patients remain asymptomatic until the later stages of the disease when the fibrotic complications become irreversible, we aimed to explore biomarkers that can identify early-stage DCM.

Methods: The patients were grouped into 4 categories based on clinical diabetic and cardiac parameters: Control, Diabetes (DM), Diastolic dysfunction (DD), and Diabetes with diastolic dysfunction (DM+DD), the last group being the preclinical DCM group ...


Role Of Serum Biomarkers In Early Detection Of Diabetic Cardiomyopathy In The West Virginian Population, Adam Shaver, Alexandra Nichols, Ellen A. Thompson, Amrita Mallick, Nandini Manne, Shanmuga Sundaram, Joseph I. Shapiro Md, Komal Sodhi Apr 2019

Role Of Serum Biomarkers In Early Detection Of Diabetic Cardiomyopathy In The West Virginian Population, Adam Shaver, Alexandra Nichols, Ellen A. Thompson, Amrita Mallick, Nandini Manne, Shanmuga Sundaram, Joseph I. Shapiro Md, Komal Sodhi

Komal Sodhi

Objectives: Diabetic cardiomyopathy (DCM) is an established complication of diabetes mellitus. In West Virginia, the especially high incidence of diabetes and heart failure validate the necessity of developing new strategies for earlier detection of DCM. Since most DCM patients remain asymptomatic until the later stages of the disease when the fibrotic complications become irreversible, we aimed to explore biomarkers that can identify early-stage DCM.

Methods: The patients were grouped into 4 categories based on clinical diabetic and cardiac parameters: Control, Diabetes (DM), Diastolic dysfunction (DD), and Diabetes with diastolic dysfunction (DM+DD), the last group being the preclinical DCM group ...


Role Of Serum Biomarkers In Early Detection Of Non-Alcoholic Steatohepatitis And Fibrosis In West Virginian Children, Komal Sodhi, Lucas Bracero, Andrew S. Feyh, Alexandra Nichols, Krithika Srikanthan, Tariq M. Latif, Deborah L. Preston, Joseph I. Shapiro, Yoram Elitsur Apr 2019

Role Of Serum Biomarkers In Early Detection Of Non-Alcoholic Steatohepatitis And Fibrosis In West Virginian Children, Komal Sodhi, Lucas Bracero, Andrew S. Feyh, Alexandra Nichols, Krithika Srikanthan, Tariq M. Latif, Deborah L. Preston, Joseph I. Shapiro, Yoram Elitsur

Komal Sodhi

Background: Obesity, an epidemic among West Virginia children, as well as insulin resistance (IR), is wellestablished contributors to nonalcoholic steatohepatitis (NASH). Progression of NASH can lead to hepatic fibrosis and cirrhosis, making early detection imperative. The standard for diagnosing NASH is histologically via liver biopsy, which is highly invasive and generally contraindicated in children. By studying serum biomarkers associated with NASH, we aim to identify high risk children who can benefit from a less invasive, alternative approach to the early detection of NASH.

Methods: Seventy one children were prospectively recruited and divided into 3 groups: normal weight without IR (control ...


Changes In Mitochondrial Protein Expression In Human Cd4 + T Cells During The Initiation And Progression Of Diabetes, Alanna Keady Apr 2019

Changes In Mitochondrial Protein Expression In Human Cd4 + T Cells During The Initiation And Progression Of Diabetes, Alanna Keady

Health Sciences Student Work

Introduction: Chronic sterile inflammation that underlies obesity can promote unhealthy cellular changes eventually leading to a decline in metabolic health and type-2 diabetes. Dysregulation of cellular processes during the initiation and progression of obesity can impair inflammatory homeostasis leading to a proinflammatory Th17 cytokine profile by CD4 + Tcells. Our ongoing research efforts are to understand the mechanistic link between the changes in a cellular housekeeping process known as autophagy and the regulation of Th17 cytokines in obese non diabetic and diabetic subjects. Methods: We assessed cellular protein expression and colocalization using immunoblotting, immunofluorescence, flow cytometry and ELISA assays. Results: We ...


Characterizing Aft1/2-Grx3/4 Interaction And The Role Of Bol2 During Iron Regulation In Saccharomyces Cerevisiae, William Rivers Apr 2019

Characterizing Aft1/2-Grx3/4 Interaction And The Role Of Bol2 During Iron Regulation In Saccharomyces Cerevisiae, William Rivers

Senior Theses

Iron dysregulation has been linked to a variety of human diseases, such as anemia, Friedreich’s ataxia, X-linked sideroblastic anemia, sideroblastic-like microcytic anemia, and myopathy. Thus, it is vitally important to understand the mechanisms for regulating intracellular iron. Here, we use fluorescence microscopy techniques in live cells to study interactions of the yeast proteins Grx3/4, Aft1/2, and Bol2, which have been shown to be involved in turning off iron import when the cell has adequate iron. Modified versions of genes encoding these proteins have been incorporated into several yeast backgrounds to use fluorescence to monitor interactions under varying ...


The Pharmabiotic For Phenylketonuria: Development Of A Novel Therapeutic, Chloé Elizabeth Lebegue Apr 2019

The Pharmabiotic For Phenylketonuria: Development Of A Novel Therapeutic, Chloé Elizabeth Lebegue

Senior Theses

Phenylketonuria, now known as phenylalanine hydroxylase (PAH) deficiency, is a genetic disorder of metabolism affecting approximately one in every 15,000 infants born in the United States. Patients have nonfunctional PAH enzyme secondary to one or more genetic mutations. The enzyme deficit results in destructive supraphysiologic blood phenylalanine levels upon consumption of the essential dietary amino acid phenylalanine. Current standards of care mitigate signs and symptoms of the disorder, but do not approach a cure. The methods for creating a prototype pharmabiotic as an innovative treatment strategy for PAH deficiency are described herein.

DNA molecular cloning techniques were utilized to ...


Supervised Dimension Reduction For Large-Scale "Omics" Data With Censored Survival Outcomes Under Possible Non-Proportional Hazards, Lauren Spirko-Burns, Karthik Devarajan Mar 2019

Supervised Dimension Reduction For Large-Scale "Omics" Data With Censored Survival Outcomes Under Possible Non-Proportional Hazards, Lauren Spirko-Burns, Karthik Devarajan

COBRA Preprint Series

The past two decades have witnessed significant advances in high-throughput ``omics" technologies such as genomics, proteomics, metabolomics, transcriptomics and radiomics. These technologies have enabled simultaneous measurement of the expression levels of tens of thousands of features from individual patient samples and have generated enormous amounts of data that require analysis and interpretation. One specific area of interest has been in studying the relationship between these features and patient outcomes, such as overall and recurrence-free survival, with the goal of developing a predictive ``omics" profile. Large-scale studies often suffer from the presence of a large fraction of censored observations and potential ...