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Full-Text Articles in Biochemistry, Biophysics, and Structural Biology

A Look At Gene Control: Tracking The Ccnd1 Gene, Bryan Anders Jan 2020

A Look At Gene Control: Tracking The Ccnd1 Gene, Bryan Anders

Mahurin Honors College Capstone Experience/Thesis Projects

Cancer occurs when the cell does not properly control its own cell cycle. It then replicates in an out of control fashion leading to the death of various organs and then the demise of the organism as a whole. As it seems to have always been a problem for cell-based life, certain safeguards against cancer have been evolved over time. One such method comes in the form of prevention via cyclin proteins, which are encoded from cyclin genes. The gene that is the focus of this research is the CCND1, or cyclin D1, gene that controls the progression through various …


Hormonal Regulation Of Glycine Decarboxylase And Its Metabolic Outcomes, Ruta Milind Jog Jan 2020

Hormonal Regulation Of Glycine Decarboxylase And Its Metabolic Outcomes, Ruta Milind Jog

Wayne State University Dissertations

The amino acid glycine is involved in generation of multiple critical metabolites including glutathione, heme, and creatinine. Interestingly, in both humans and rodents, circulating glycine levels are significantly reduced in obesity, glucose intolerance, type II diabetes and non-alcoholic fatty liver disease. The glycine cleavage system is the predominant glycine degradation pathway in humans. The rate-limiting enzyme of glycine cleavage system is glycine decarboxylase (GLDC), and loss-of-function mutations of GLDC cause hyperglycinemia. Here, we show that GLDC gene expression is upregulated in livers of mouse models of diabetes and diet-induced obesity as well as in the fasted state in normal animals. …


Molecular And Functional Characterization Of Α-Galactosyl Epitopes In Trypanosoma Cruzi, Uriel Ortega Rodriguez Jan 2020

Molecular And Functional Characterization Of Α-Galactosyl Epitopes In Trypanosoma Cruzi, Uriel Ortega Rodriguez

Open Access Theses & Dissertations

Trypanosoma cruzi, the causative agent of Chagas disease (CD) currently affects 6-7 million people across the world. Currently, only two drugs, benznidazole and nifurtimox, are available for treatment of CD and they are highly toxic and less effective in the chronic stage of the disease. Specific biomarkers for diagnosis and follow-up of treatment do not exist in the clinical settings. following chemotherapy, patients take approximately 10-20 years to exhibit negative seroconversion with the conventional serology assays. Moreover, there is no vaccine available to prevent or treat CD. T. cruzi contains a complex cell surface consisting of several classes of glycoconjugates …


Meta-Analysis Comparing Watchmantm And Amplatzer Devices For Stroke Prevention In Atrial Fibrillation, Indranill Basu Ray, Dibbendhu Khanra, Sumit Shah, Sudhanva Char, Xiaoming Jia, Wilson Lam, Nilesh Mathuria, Mehdi Razavi, Bhavna Jain, Dhanunjaya Lakkireddy, Saibal Kar, Andrea Natale, Adedayo Adeboye, John Lynn Jefferies, Sripal Bangalore, Samuel Asirvatham, Mohammad Saeed Jan 2020

Meta-Analysis Comparing Watchmantm And Amplatzer Devices For Stroke Prevention In Atrial Fibrillation, Indranill Basu Ray, Dibbendhu Khanra, Sumit Shah, Sudhanva Char, Xiaoming Jia, Wilson Lam, Nilesh Mathuria, Mehdi Razavi, Bhavna Jain, Dhanunjaya Lakkireddy, Saibal Kar, Andrea Natale, Adedayo Adeboye, John Lynn Jefferies, Sripal Bangalore, Samuel Asirvatham, Mohammad Saeed

Faculty, Staff and Students Publications

Background: For patients with atrial fibrillation who are at high risk for bleeding or who cannot tolerate oral anticoagulation, left atrial appendage (LAA) closure represents an alternative therapy for reducing risk for thromboembolic events.

Objectives: To compare the efficacy and safety of the Amplatzer and WatchmanTM LAA closure devices.

Methods: A meta-analysis was performed of studies comparing the safety and efficacy outcomes of the two devices. The Newcastle-Ottawa Scale was used to appraise study quality.

Results: Six studies encompassing 614 patients were included in the meta-analysis. Overall event rates were low for both devices. No significant differences between the …


Spironolactone In Pulmonary Arterial Hypertension: Results Of A Cross-Over Study, Zeenat Safdar, Adaani Frost, Arya Basant, Anita Deswal, E O'Brian Smith, Mark Entman Jan 2020

Spironolactone In Pulmonary Arterial Hypertension: Results Of A Cross-Over Study, Zeenat Safdar, Adaani Frost, Arya Basant, Anita Deswal, E O'Brian Smith, Mark Entman

Faculty, Staff and Students Publications

The renin–angiotensin–aldosterone system is implicated in the pathophysiology of pulmonary arterial hypertension. We undertook this study to determine the effects of spironolactone, a mineralocorticoid receptor blocker, on collagen metabolism in pulmonary arterial hypertension patients. After obtaining institutional review board approval and informed consent, 42 pulmonary arterial hypertension patients were prospectively enrolled and 35 patients completed the 16-week randomized double-blinded crossover clinical trial. Subjects received 50 mg spironolactone or placebo and at the end of week 8, treatment arm was switched. Circulating levels of collagen biomarkers, brain natriuretic peptide, and aldosterone levels were measured, and six-minute walk distance, liver function tests, …


Pregnancy And Lactation In A 67-Year-Old Elderly Gravida Following Donor Oocyte, Leila Magistrado, Mary C Tolcher, Anju Suhag, Sonal Zambare, Kjersti M Aagaard Jan 2020

Pregnancy And Lactation In A 67-Year-Old Elderly Gravida Following Donor Oocyte, Leila Magistrado, Mary C Tolcher, Anju Suhag, Sonal Zambare, Kjersti M Aagaard

Faculty, Staff and Students Publications

There is limited data on the anticipated perinatal course among gravidae in their sixth and seventh decades. Our objective was to describe the relatively uncomplicated prenatal, intrapartum, and postpartum course of a 67-year-old essential primigravida. Briefly, our patient conceived a singleton pregnancy via IVF with donor oocytes, then presented at 13 6/7 weeks of gestation to initiate prenatal care. Her medical history was significant for chronic hypertension, hyperlipidemia, and obesity. Her cardiac function was monitored throughout pregnancy, and she delivered at 36 1/7 weeks by cesarean for a decline in left ventricular function with mitral regurgitation. Her intrapartum and postpartum …


Aromatase Inhibitors Plus Weight Loss Improves The Hormonal Profile Of Obese Hypogonadal Men Without Causing Major Side Effects, Georgia Colleluori, Rui Chen, Christie G Turin, Francesca Vigevano, Clifford Qualls, Biju Johnson, Sanjay Mediwala, Dennis T Villareal, Reina Armamento-Villareal Jan 2020

Aromatase Inhibitors Plus Weight Loss Improves The Hormonal Profile Of Obese Hypogonadal Men Without Causing Major Side Effects, Georgia Colleluori, Rui Chen, Christie G Turin, Francesca Vigevano, Clifford Qualls, Biju Johnson, Sanjay Mediwala, Dennis T Villareal, Reina Armamento-Villareal

Faculty, Staff and Students Publications

Objective: In obese men, the increased expression of the aromatase enzyme in adipose tissue leads to high conversion of androgens to estrogens contributing to hypogonadotropic hypogonadism (HHG). Our objective is to evaluate efficacy and safety of weight loss (WL) plus aromatase inhibitor (AI) therapy in severely obese men with HHG. We hypothesize that AI+WL will be more effective as compared to WL alone in improving the hormonal profile, thus muscle strength and symptoms of HHG (primary outcomes), with no significant adverse effects on lean mass, metabolic profile, and bone mineral density (secondary outcomes).

Design: Randomized double-blind placebo-controlled pilot trial.

Methods: …


The Vimentin Rod Domain Blocks P-Selectin-P-Selectin Glycoprotein Ligand 1 Interactions To Attenuate Leukocyte Adhesion To Inflamed Endothelium, Fong Wilson Lam, Cameron August Brown, Christian Valladolid, Dabel Cynthia Emebo, Timothy Gerald Palzkill, Miguel Angel Cruz Jan 2020

The Vimentin Rod Domain Blocks P-Selectin-P-Selectin Glycoprotein Ligand 1 Interactions To Attenuate Leukocyte Adhesion To Inflamed Endothelium, Fong Wilson Lam, Cameron August Brown, Christian Valladolid, Dabel Cynthia Emebo, Timothy Gerald Palzkill, Miguel Angel Cruz

Faculty, Staff and Students Publications

Acute inflammation begins with leukocyte P-selectin glycoprotein ligand-1 (PSGL-1) binding to P-selectin on inflamed endothelium and platelets. In pathologic conditions, this process may contribute to secondary organ damage, like sepsis-induced liver injury. Therefore, developing novel therapies to attenuate inflammation may be beneficial. We previously reported that recombinant human vimentin (rhVim) binds P-selectin to block leukocyte adhesion to endothelium and platelets. In this study, we used SPOT-peptide arrays to identify the rod domain as the active region within rhVim that interacts with P-selectin. Indeed, recombinant human rod domain of vimentin (rhRod) binds to P-selectin with high affinity, with in silico modeling …


Acute Lymphoblastic Leukemia Presenting Initially As Spinal Cord Compression: When Chemotherapy Alone Is Enough, Albert Jang, Kallie N Kram, Scott N Berger, Mahmoud R Gaballa, Lee B Lu, David R Dunaway, Courtney N Miller-Chism Jan 2020

Acute Lymphoblastic Leukemia Presenting Initially As Spinal Cord Compression: When Chemotherapy Alone Is Enough, Albert Jang, Kallie N Kram, Scott N Berger, Mahmoud R Gaballa, Lee B Lu, David R Dunaway, Courtney N Miller-Chism

Faculty, Staff and Students Publications

Spinal cord compression (SCC) is a rare initial presentation and complication of acute lymphoblastic leukemia (ALL) with nearly all reported cases occurring in the pediatric population. We report a 38-year-old previously healthy man who presented with acute on chronic lower back pain, gait instability, urinary retention, and severe thrombocytopenia. Radiologic examination revealed two soft tissue masses of the thoracic spine associated with compression fractures causing spinal canal narrowing and cord compression. Bone marrow biopsy confirmed the diagnosis of ALL. Immediate initiation of high-dose corticosteroids and systemic chemotherapy resolved the patient's symptoms without radiation therapy or surgical intervention. After two courses …


Characterizing Glycosaminoglycan And Glycosaminoglycan-Oligo Interactions With Cancer Stem Cells And Their Regulators, Rahaman Navaz Gangji Jan 2020

Characterizing Glycosaminoglycan And Glycosaminoglycan-Oligo Interactions With Cancer Stem Cells And Their Regulators, Rahaman Navaz Gangji

Theses and Dissertations

Tumor metastasis and recurrence account for more than 90% of cancer-associated deaths and are thought to occur due to a small subpopulation of neoplastic cells known as cancer stem cells (CSCs). Because CSCs are resistant to conventional chemotherapy, there is a critical need to develop CSC-targeting agents. Microenvironmental components, especially glycosaminoglycans (GAGs), play a key role in regulating CSC phenotype. GAGs such as heparan sulfate (HS) interact with hundreds of proteins and influence a variety of biological processes including tumor proliferation, angiogenesis, metastasis and stem cell biology.

Recently, the Desai and Patel laboratories have demonstrated that a hexasaccharide form of …


Single-Nuclei Rna-Seq On Human Retinal Tissue Provides Improved Transcriptome Profiling, Qingnan Liang, Rachayata Dharmat, Leah Owen, Akbar Shakoor, Yumei Li, Sangbae Kim, Albert Vitale, Ivana Kim, Denise Morgan, Shaoheng Liang, Nathaniel Wu, Ken Chen, Margaret M Deangelis, Rui Chen Dec 2019

Single-Nuclei Rna-Seq On Human Retinal Tissue Provides Improved Transcriptome Profiling, Qingnan Liang, Rachayata Dharmat, Leah Owen, Akbar Shakoor, Yumei Li, Sangbae Kim, Albert Vitale, Ivana Kim, Denise Morgan, Shaoheng Liang, Nathaniel Wu, Ken Chen, Margaret M Deangelis, Rui Chen

Faculty, Staff and Students Publications

Single-cell RNA-seq is a powerful tool in decoding the heterogeneity in complex tissues by generating transcriptomic profiles of the individual cell. Here, we report a single-nuclei RNA-seq (snRNA-seq) transcriptomic study on human retinal tissue, which is composed of multiple cell types with distinct functions. Six samples from three healthy donors are profiled and high-quality RNA-seq data is obtained for 5873 single nuclei. All major retinal cell types are observed and marker genes for each cell type are identified. The gene expression of the macular and peripheral retina is compared to each other at cell-type level. Furthermore, our dataset shows an …


Examining Multiple Cellular Pathways At Once Using Multiplex Hextuple Luciferase Assaying, Alejandro Sarrion-Perdigones, Lyra Chang, Yezabel Gonzalez, Tatiana Gallego-Flores, Damian W Young, Koen J T Venken Dec 2019

Examining Multiple Cellular Pathways At Once Using Multiplex Hextuple Luciferase Assaying, Alejandro Sarrion-Perdigones, Lyra Chang, Yezabel Gonzalez, Tatiana Gallego-Flores, Damian W Young, Koen J T Venken

Faculty, Staff and Students Publications

Sensitive simultaneous assessment of multiple signaling pathways within the same cells requires orthogonal reporters that can assay over large dynamic ranges. Luciferases are such genetically encoded candidates due to their sensitivity, versatility, and cost-effectiveness. We expand luciferase multiplexing in post-lysis endpoint luciferase assays from two to six. Light emissions are distinguished by a combination of distinct substrates and emission spectra deconvolution. All six luciferase reporter units are stitched together into one plasmid facilitating delivery of all reporter units through a process we termed solotransfection, minimizing experimental errors. We engineer a multiplex hextuple luciferase assay to probe pathway fluxes through five …


Residues And Residue Pairs Of Evolutionary Importance Differentially Direct Signaling Bias Of D2 Dopamine Receptors, María E Terrón-Díaz, Sara J Wright, Melina A Agosto, Olivier Lichtarge, Theodore G Wensel Dec 2019

Residues And Residue Pairs Of Evolutionary Importance Differentially Direct Signaling Bias Of D2 Dopamine Receptors, María E Terrón-Díaz, Sara J Wright, Melina A Agosto, Olivier Lichtarge, Theodore G Wensel

Faculty, Staff and Students Publications

The D2 dopamine receptor and the serotonin 5-hydroxytryptamine 2A receptor (5-HT2A) are closely-related G-protein–coupled receptors (GPCRs) from the class A bioamine subfamily. Despite structural similarity, they respond to distinct ligands through distinct downstream pathways, whose dysregulation is linked to depression, bipolar disorder, addiction, and psychosis. They are important drug targets, and it is important to understand how their bias toward G-protein versus β-arrestin signaling pathways is regulated. Previously, evolution-based computational approaches, difference Evolutionary Trace and Evolutionary Trace–Mutual information (ET-Mip), revealed residues and residue pairs that, when switched in the D2 receptor to the corresponding residues from 5-HT2A, altered ligand potency …


Ultrafast Two-Photon Imaging Of A High-Gain Voltage Indicator In Awake Behaving Mice, Vincent Villette, Mariya Chavarha, Ivan K Dimov, Jonathan Bradley, Lagnajeet Pradhan, Benjamin Mathieu, Stephen W Evans, Simon Chamberland, Dongqing Shi, Renzhi Yang, Benjamin B Kim, Annick Ayon, Abdelali Jalil, François St-Pierre, Mark J Schnitzer, Guoqiang Bi, Katalin Toth, Jun Ding, Stéphane Dieudonné, Michael Z Lin Dec 2019

Ultrafast Two-Photon Imaging Of A High-Gain Voltage Indicator In Awake Behaving Mice, Vincent Villette, Mariya Chavarha, Ivan K Dimov, Jonathan Bradley, Lagnajeet Pradhan, Benjamin Mathieu, Stephen W Evans, Simon Chamberland, Dongqing Shi, Renzhi Yang, Benjamin B Kim, Annick Ayon, Abdelali Jalil, François St-Pierre, Mark J Schnitzer, Guoqiang Bi, Katalin Toth, Jun Ding, Stéphane Dieudonné, Michael Z Lin

Faculty, Staff and Students Publications

Optical interrogation of voltage in deep brain locations with cellular resolution would be immensely useful for understanding how neuronal circuits process information. Here, we report ASAP3, a genetically encoded voltage indicator with 51% fluorescence modulation by physiological voltages, submillisecond activation kinetics, and full responsivity under two-photon excitation. We also introduce an ultrafast local volume excitation (ULoVE) method for kilohertz-rate two-photon sampling in vivo with increased stability and sensitivity. Combining a soma-targeted ASAP3 variant and ULoVE, we show single-trial tracking of spikes and subthreshold events for minutes in deep locations, with subcellular resolution and with repeated sampling over days. In the …


Alzheimer's And Amyloid Beta: Amyloidogenicity And Tauopathy Via Dyshomeostatic Interactions Of Amyloid Beta, Jordan Tillinghast Dec 2019

Alzheimer's And Amyloid Beta: Amyloidogenicity And Tauopathy Via Dyshomeostatic Interactions Of Amyloid Beta, Jordan Tillinghast

Senior Honors Theses

This paper reviews functions of Amyloid-β (Aβ) in healthy individuals compared to the consequences of aberrant Aβ in Alzheimer’s disease (AD). As extraneuronal Aβ accumulation and plaque formation are characteristics of AD, it is reasonable to infer a pivotal role for Aβ in AD pathogenesis. Establishing progress of the disease as well as the mechanism of neurodegeneration from AD have proven difficult (Selkoe, 1994). This thesis provides evidence suggesting the pathogenesis of AD is due to dysfunctional neuronal processes involving Aβ’s synaptic malfunction, abnormal interaction with tau, and disruption of neuronal homeostasis. Significant evidence demonstrates that AD symptoms are partially …


Structural Basis Of Amino Acid Surveillance By Higher-Order Trna-Mrna Interactions, Shuang Li, Zhaoming Su, Jean Lehmann, Vassiliki Stamatopoulou, Nikoleta Giarimoglou, Frances E Henderson, Lixin Fan, Grigore D Pintilie, Kaiming Zhang, Muyuan Chen, Steven J Ludtke, Yun-Xing Wang, Constantinos Stathopoulos, Wah Chiu, Jinwei Zhang Dec 2019

Structural Basis Of Amino Acid Surveillance By Higher-Order Trna-Mrna Interactions, Shuang Li, Zhaoming Su, Jean Lehmann, Vassiliki Stamatopoulou, Nikoleta Giarimoglou, Frances E Henderson, Lixin Fan, Grigore D Pintilie, Kaiming Zhang, Muyuan Chen, Steven J Ludtke, Yun-Xing Wang, Constantinos Stathopoulos, Wah Chiu, Jinwei Zhang

Faculty, Staff and Students Publications

Amino acid availability in Gram-positive bacteria is monitored by T-box riboswitches. T-boxes directly bind tRNAs, assess their aminoacylation state, and regulate the transcription or translation of downstream genes to maintain nutritional homeostasis. Here, we report cocrystal and cryo-EM structures of Geobacillus kaustophilus and Bacillus subtilis T-box-tRNA complexes, detailing their multivalent, exquisitely selective interactions. The T-box forms a U-shaped molecular vise that clamps the tRNA, captures its 3' end using an elaborate 'discriminator' structure, and interrogates its aminoacylation state using a steric filter fashioned from a wobble base pair. In the absence of aminoacylation, T-boxes clutch tRNAs and form a continuously …


Bipolar Fresh Osteochondral Allograft Transplantation And Joint Reconstruction For Patellar And Trochlear Cartilage Defects, Omid Jalali, Zachary Vredenburgh, John Prodromo, Neilen Benvegnu, George Frederick Rick Hatch Dec 2019

Bipolar Fresh Osteochondral Allograft Transplantation And Joint Reconstruction For Patellar And Trochlear Cartilage Defects, Omid Jalali, Zachary Vredenburgh, John Prodromo, Neilen Benvegnu, George Frederick Rick Hatch

Faculty, Staff and Students Publications

Patellar instability is a debilitating condition, and trauma due to the dislocations may severely damage the articular cartilage of the patellofemoral joint. The lack of healing capacity of cartilage makes treatment of such lesions challenging. In young patients, preservation of native bone and cartilage is a priority, and therefore arthroplasty procedures should be avoided even in relatively larger lesions. Fresh osteochondral allografting has been described for these difficult and complex cases, with recent studies showing promising results. In this surgical technique, we describe the use of bipolar osteochondral allografts of the patella and trochlea and patellofemoral joint reconstruction for large …


Defining The Layers Of A Sensory Cilium With Storm And Cryoelectron Nanoscopy, Michael A Robichaux, Valencia L Potter, Zhixian Zhang, Feng He, Jun Liu, Michael F Schmid, Theodore G Wensel Nov 2019

Defining The Layers Of A Sensory Cilium With Storm And Cryoelectron Nanoscopy, Michael A Robichaux, Valencia L Potter, Zhixian Zhang, Feng He, Jun Liu, Michael F Schmid, Theodore G Wensel

Faculty, Staff and Students Publications

Primary cilia carry out numerous signaling and sensory functions, and defects in them, "ciliopathies," cause a range of symptoms, including blindness. Understanding of their nanometer-scale ciliary substructures and their disruptions in ciliopathies has been hindered by limitations of conventional microscopic techniques. We have combined cryoelectron tomography, enhanced by subtomogram averaging, with superresolution stochastic optical reconstruction microscopy (STORM) to define subdomains within the light-sensing rod sensory cilium of mouse retinas and reveal previously unknown substructures formed by resident proteins. Domains are demarcated by structural features such as the axoneme and its connections to the ciliary membrane, and are correlated with molecular …


The Role Of Atypical Protein Kinase C In Colorectal Cancer Cells Carcinogenesis, S M Anisul Islam Nov 2019

The Role Of Atypical Protein Kinase C In Colorectal Cancer Cells Carcinogenesis, S M Anisul Islam

USF Tampa Graduate Theses and Dissertations

Colorectal cancer (CRC) is the third most common malignancy and the fourth most common cause of cancer-related death worldwide. CRC is a life-threatening disease due to therapy-resistant cancerous cells. The exact mechanisms of cell growth, survival, metastasis and inter & intracellular signaling pathways involved in CRC are still a significant challenge. Moreover, the treatment of metastatic CRC considered palliative for many years aimed for an improved life, with little hope of a cure, highlighting the need for developing novel targeted therapy for CRC. Hence, investigating new molecular mechanism(s) that lead to colorectal carcinogenesis may give insight into the therapeutic target. …


The Essential Role Of Carbon Metabolism In The Virulence Of Cryptococcus Neoformans, Mara Weigner Oct 2019

The Essential Role Of Carbon Metabolism In The Virulence Of Cryptococcus Neoformans, Mara Weigner

Senior Honors Theses

Cryptococcus neoformans infections are a major cause of meningoencephalitis in immunosuppressed patients worldwide. Inhaled as spores or desiccated yeast cells, C. neoformans can undergo metabolic changes in response to the new host environment that allow it to cross the blood brain barrier and cause deadly central nervous system (CNS) infections. Nutrient acquisition, and specifically carbon metabolism, is critical for survival and proliferation within the host. Notably, efficient carbon metabolism is necessary to produce the polysaccharide capsule, which is arguably C. neoformans’ most important and well-studied virulence factor. As such, a better understanding of carbon acquisition and regulation is essential for …


Creating A Molecular Map Of The Pediatric Lung, Quinlen F. Marshall Sep 2019

Creating A Molecular Map Of The Pediatric Lung, Quinlen F. Marshall

Forum Lectures

The newborn lung undergoes vast biochemical and physiological changes during adaptation from the intrauterine to the extrauterine environment. Lung morphogenesis continues from birth into early childhood, mediated by dynamic gene expression and a diversity of pulmonary cell types that exhibit remarkable heterogeneity. (Whitsett, JA. et al. Physiol. Rev, 2019). Surprisingly, few studies have solely focused on human lung development during this critical period, and many current studies of lung maturation rely on adult, murine, or diseased samples, limiting their insights and applicability to longitudinal pediatric lung development. Understanding the molecular and physiological nuances of pulmonary development has important clinical relevance, …


Advances In Gene Ontology Utilization Improve Statistical Power Of Annotation Enrichment, Eugene Waverly Hinderer Iii, Robert M. Flight, Rashmi Dubey, James N. Macleod, Hunter N. B. Moseley Aug 2019

Advances In Gene Ontology Utilization Improve Statistical Power Of Annotation Enrichment, Eugene Waverly Hinderer Iii, Robert M. Flight, Rashmi Dubey, James N. Macleod, Hunter N. B. Moseley

Maxwell H. Gluck Equine Research Center Faculty Publications

Gene-annotation enrichment is a common method for utilizing ontology-based annotations in gene and gene-product centric knowledgebases. Effective utilization of these annotations requires inferring semantic linkages by tracing paths through edges in the ontological graph, referred to as relations. However, some relations are semantically problematic with respect to scope, necessitating their omission or modification lest erroneous term mappings occur. To address these issues, we created the Gene Ontology Categorization Suite, or GOcats—a novel tool that organizes the Gene Ontology into subgraphs representing user-defined concepts, while ensuring that all appropriate relations are congruent with respect to scoping semantics. Here, we demonstrate the …


Temporal Gene Expression Of Mesenchymal Cells In The Pediatric Lung, Quinlen F. Marshall, Soumyaroop Bhattacharya, Gautam Bandyopadhyay, Ravi Misra, Thomas Mariani, Gloria Pryhuber Aug 2019

Temporal Gene Expression Of Mesenchymal Cells In The Pediatric Lung, Quinlen F. Marshall, Soumyaroop Bhattacharya, Gautam Bandyopadhyay, Ravi Misra, Thomas Mariani, Gloria Pryhuber

Chemistry Student Work

INTRODUCTION: The newborn lung undergoes vast biochemical and physiological changes during adaptation from the intrauterine to the extrauterine environment. Lung morphogenesis continues from birth into early childhood, mediated by dynamic gene expression and a diversity of pulmonary cell types (Whitsett, JA. et al. Physiol. Rev, 2019). Murine models demonstrate that pulmonary mesenchymal cells exhibit remarkable heterogeneity in function and morphology during development, however, confirmation of their role is lacking in human neonates and early childhood (Guo, M. et al. Nat. Comm, 2019). In addition, many current human genomic studies of lung maturation suffer from limited sample size, limiting …


Development Of A Sonically Powered Biodegradable Nanogenerator For Bone Regeneration, Avi Patel May 2019

Development Of A Sonically Powered Biodegradable Nanogenerator For Bone Regeneration, Avi Patel

Honors Scholar Theses

Background: Reconstruction of bone fractures and defects remains a big challenge in orthopedic surgery. While regenerative engineering has advanced the field greatly using a combination of biomaterial scaffolds and stem cells, one matter of difficulty is inducing osteogenesis in these cells. Recent works have shown electricity’s ability to promote osteogenesis in stem cell lines when seeded in bone scaffolds; however, typical electrical stimulators are either (a) externally housed and require overcomplex percutaneous wires be connected to the implanted scaffold or (b) implanted non-degradable devices which contain toxic batteries and require invasive removal surgeries.

Objective: Here, we establish a biodegradable, piezoelectric …


The Role Of Ros In The Progression And Treatment Of Castration-Resistant Prostate Cancer, Dannah R. Miller May 2019

The Role Of Ros In The Progression And Treatment Of Castration-Resistant Prostate Cancer, Dannah R. Miller

Theses & Dissertations

Prostate cancer is the second leading cause of cancer-related deaths in U.S. men, primarily due to the development of castration-resistant (CR) prostate cancer (PCa), of which there are no effective treatment options. Reactive oxygen species (ROS) plays a critical role in prostate carcinogenesis, including the progression of the CR PCa phenotype. ROS regulates both cell proliferation and apoptosis; a moderate increase in ROS can promote proliferation; however, a substantial rise in ROS levels will result in apoptosis. Oxidase p66Shc is elevated in clinical PCa cells and has been associated with a metastatic phenotype of CR PCa cells, promoting PCa cell …


One Amino Acid Change Of Angiotensin Ii Diminishes Its Effects On Abdominal Aortic Aneurysm, Ya Wang, Yinchuan Xu, Congqing Wu, Hongguang Xia, Yingchao Wang, Jinliang Nan, Jinghai Chen, Hong Yu, Wei Zhu, Peng Shi, Alan Daugherty, Hong S. Lu, Jian'an Wang May 2019

One Amino Acid Change Of Angiotensin Ii Diminishes Its Effects On Abdominal Aortic Aneurysm, Ya Wang, Yinchuan Xu, Congqing Wu, Hongguang Xia, Yingchao Wang, Jinliang Nan, Jinghai Chen, Hong Yu, Wei Zhu, Peng Shi, Alan Daugherty, Hong S. Lu, Jian'an Wang

Saha Cardiovascular Research Center Faculty Publications

Angiotensin (Ang) A is formed by the decarboxylation of the N terminal residue of AngII. The present study determined whether this one amino acid change impacted effects of AngII on abdominal aortic aneurysm (AAA) formation in mice. Computational analyses implicated that AngA had comparable binding affinity to both AngII type 1 and 2 receptors as AngII. To compare effects of these two octapeptides in vivo, male low-density lipoprotein receptor (Ldlr) or apolipoprotein E (Apoe) deficient mice were infused with either AngII or AngA (1 μg/kg/min) for 4 weeks. While AngII infusion induced AAA consistently in …


Serum Anti Mullerian Hormone And Renalase Levels In Predicting The Risk Of Preeclampsia, Zehra Jamil, Sana Shahid, Erum Baig, Rida Ahmad, Faryal Subhani, Syeda Sadia Fatima Mar 2019

Serum Anti Mullerian Hormone And Renalase Levels In Predicting The Risk Of Preeclampsia, Zehra Jamil, Sana Shahid, Erum Baig, Rida Ahmad, Faryal Subhani, Syeda Sadia Fatima

Department of Biological & Biomedical Sciences

Objective: The aim of the study was to explore the association of serum AMH and Renalase with the risk of preeclampsia thereby assessing them as screening tools, reducing the risk of gravid consequences of preeclampsia.
Materials and Methods: This cross-sectional study recruited n = 95 pregnant women between 14 and 32 gestational weeks. They were categorized as a) women with gestational hypertension (n = 45); b) women with pre-eclampsia (n = 20) and c) normotensive pregnant women (n = 30) according to the ACOG criteria. Anthropometrics data and blood and urine samples were collected. AMH and Renalase levels were measured …


Stress-Induced Epinephrine Enhances Lactate Dehydrogenase A And Promotes Breast Cancer Stem-Like Cells, Bai Cui, Yuanyuan Luo, Pengfei Tian, Fei Peng, Jinxin Lu, Yongliang Yang, Qitong Su, Bing Liu, Jiachuan Yu, Xi Luo, Liu Yin, Wei Cheng, Fan An, Bin He, Dapeng Liang, Sijin Wu, Peng Chu, Luyao Song, Xinyu Liu, Huandong Luo, Binhua P. Zhou Mar 2019

Stress-Induced Epinephrine Enhances Lactate Dehydrogenase A And Promotes Breast Cancer Stem-Like Cells, Bai Cui, Yuanyuan Luo, Pengfei Tian, Fei Peng, Jinxin Lu, Yongliang Yang, Qitong Su, Bing Liu, Jiachuan Yu, Xi Luo, Liu Yin, Wei Cheng, Fan An, Bin He, Dapeng Liang, Sijin Wu, Peng Chu, Luyao Song, Xinyu Liu, Huandong Luo, Binhua P. Zhou

Molecular and Cellular Biochemistry Faculty Publications

Chronic stress triggers activation of the sympathetic nervous system and drives malignancy. Using an immunodeficient murine system, we showed that chronic stress–induced epinephrine promoted breast cancer stem-like properties via lactate dehydrogenase A–dependent (LDHA-dependent) metabolic rewiring. Chronic stress–induced epinephrine activated LDHA to generate lactate, and the adjusted pH directed USP28-mediated deubiquitination and stabilization of MYC. The SLUG promoter was then activated by MYC, which promoted development of breast cancer stem-like traits. Using a drug screen that targeted LDHA, we found that a chronic stress–induced cancer stem-like phenotype could be reversed by vitamin C. These findings demonstrated the critical importance of psychological …


Autophagic Flux Modulation By Wnt/Β-Catenin Pathway Inhibition In Hepatocellular Carcinoma, Lilia Turcios, Heather E. Chacon, Catherine Garcia, Pedro Eman, Virgilius Cornea, Jieyun Jiang, Brett T. Spear, Chunming Liu, David S. Watt, Francesc Marti, Roberto Gedaly Feb 2019

Autophagic Flux Modulation By Wnt/Β-Catenin Pathway Inhibition In Hepatocellular Carcinoma, Lilia Turcios, Heather E. Chacon, Catherine Garcia, Pedro Eman, Virgilius Cornea, Jieyun Jiang, Brett T. Spear, Chunming Liu, David S. Watt, Francesc Marti, Roberto Gedaly

Surgery Faculty Publications

Autophagy targets cellular components for lysosomal-dependent degradation in which the products of degradation may be recycled for protein synthesis and utilized for energy production. Autophagy also plays a critical role in cell homeostasis and the regulation of many physiological and pathological processes and prompts this investigation of new agents to effect abnormal autophagy in hepatocellular carcinoma (HCC). 2,5-Dichloro-N-(2-methyl-4-nitrophenyl) benzenesulfonamide (FH535) is a synthetic inhibitor of the Wnt/β-catenin pathway that exhibits anti-proliferative and anti-angiogenic effects on different types of cancer cells. The combination of FH535 with sorafenib promotes a synergistic inhibition of HCC and liver cancer stem cell proliferation, …


Clinical Features, Survival And Prognostic Factors Of Glycogen-Rich Clear Cell Carcinoma (Grcc) Of The Breast In The U.S. Population, Zhengqiu Zhou, Connor J. Kinslow, Hanina Hibshoosh, Hua Guo, Simon K. Cheng, Chunyan He, Matthew S. Gentry, Ramon C. Sun Feb 2019

Clinical Features, Survival And Prognostic Factors Of Glycogen-Rich Clear Cell Carcinoma (Grcc) Of The Breast In The U.S. Population, Zhengqiu Zhou, Connor J. Kinslow, Hanina Hibshoosh, Hua Guo, Simon K. Cheng, Chunyan He, Matthew S. Gentry, Ramon C. Sun

Molecular and Cellular Biochemistry Faculty Publications

The World Health Organization (WHO) defines glycogen-rich clear cell carcinoma (GRCC) of the breast as a carcinoma with glycogen accumulation in more than 90% of its tumor cells. Due to the rarity of this disease, its reported survival and clinical associations have been inconsistent due to reliance on case reports and limited case series. As a result, the prognostic implication of this cancer subtype remains unclear. Using the U.S. Surveillance, Epidemiology, and End Results (SEER) program database, we compared the incidence, demographics and prognostic factors of 155 cases of GRCC of the breast to 1,251,584 cases of other (non-GRCC) breast …