Biochemistry, Biophysics, and Structural Biology Commons^™

Novel Roles Of The Blm Syndrome Dna Helicase In Genome Maintenance And Mitochondrial Regulation, Brian B. Rodemoyer

USF Tampa Graduate Theses and Dissertations

Bloom syndrome (BS) is an extremely rare autosomal recessive genetic disorder caused by defects in the BLM gene. Patients with BS display a broad phenotypic spectrum including abnormally short stature, microcephaly, sun sensitivity, insulin resistance, perpetual oxidative stress, and a ~300-fold greater propensity for developing cancer than the general population. As such, BS patients typically do not live past their 20’s. The BLM gene encodes the BLM helicase, a member of the highly conserved RecQ family of 3’ to 5’ DNA helicases. Most of our cellular understanding of BLM is through its role in DNA damage repair through the homologous …

Twenty-Year Survival Following Lung Transplantation, John James Miggins, Ross M Reul, Spencer Barrett, Abbas Rana, Ahmed Alnajar, Jordan Dunson, Alexis Shafii, Puneet Garcha, John Goss, Gabriel Loor

Faculty, Staff and Students Publications

BACKGROUND: Lung transplantation median survival has seen improvements due to recognition of short-term survival factors but continues to trail behind other solid organs due to limited understanding of long-term survivorship. Given the creation of the United Network for Organ Sharing (UNOS) database in 1986, it was difficult to accrue data on long-term survivors until recently. This study characterizes factors impacting lung transplant survival beyond 20 years, conditional to 1-year survival.

METHODS: Lung transplant recipients listed in UNOS from 1987 to 2002 who survived to 1 post-transplant year were reviewed. Kaplan-Meier and adjusted Cox regression analyses were performed at 20 and …

Withaferin A And Immune Checkpoint Blocker Therapy For The Treatment Of Non-Small Cell Lung Cancer, Roukiah Khalil

USF Tampa Graduate Theses and Dissertations

Lung cancer is the first cause of cancer-related deaths in both men and women with an overall five-year survival rate of 28%. Although immune checkpoint blockers (ICBs) are currently FDA-approved for the treatment of non-small cell lung cancer (NSCLC), only 17-20% of patients achieve durable responses by the induction of immunologic memory. The lack of response in most patients can be attributed to the tumor-intrinsic or tumor-extrinsic immune resistance mechanisms. A biomarker of importance is the Programmed Death Ligand-1 (PD-L1), as higher PD-L1 expression is usually associated with a better response to ICBs. Although studies have attempted to combine ICBs …

Anesthetic Considerations For Cardiac Tamponade After Internal Jugular Central Line Placement During Trauma Resuscitation: A Case Report, Kevin M Chen, Jamal Hasoon, Anvinh Nguyen

Faculty, Staff and Students Publications

Numerous complications are associated with central venous catheters. Among them, cardiac tamponade is a rare but well-documented catastrophic complication. A 22-year-old healthy male presented with Code 1 trauma resulting from gunshot wounds in the abdomen. Upon examination, he was found to have a large pericardial fluid collection, a large right supraclavicular hematoma, and significant amount of bilateral pleural effusions secondary to extraluminal placement of the right internal jugular central line during resuscitation. After repairing the internal jugular injury and draining the pericardial fluid, the patient was transferred from the intensive care unit to the regular hospital floor. However, 15 days …

Biochemical Markers Of Liver Toxicity Among Coal Mine Workers Of Punjab, Pakistan Suffering From Hcv, Aima Iram Batool, Asma Noreen, Naima Huma Naveed, Iram Inayat, Muhammad Fayyaz Ur Rehman, Fariha Idrees, Muhammad Ali Kanwal, Syeda Humaira Jabeen, Hakim Bibi

Journal of Bioresource Management

Hepatitis C is among the leading hepatic disorders in current period through which about 3 % world population has been anguish among them 170 million were diagnosed as persistent carriers. A great range of alteration in liver biochemical parameters were found to be allied with HCV infestation. Current study was designed to evaluate the extent of HCV mediated abnormalities in liver biochemical markers which includes ALT (alanine aminotransferase), AST (Aspartate transaminase), ALP (Alkaline Phosphatase) and serum bilirubin. The study was conducted on coal miners of Punjab province, Pakistan. HCV was primarily diagnosed through one step rapid test device after which …

Regulation Of The Wnt/Wingless Receptor Lrp6/Arrow By The Deubiquitylating Complex Usp46, Zachary T. Spencer

Dartmouth College Ph.D Dissertations

The evolutionarily conserved Wnt/Wingless signal transduction pathway is critical for the proper development of all animals and implicated in numerous diseases in adulthood. Upon binding of the Wnt/Wingless ligand, a cascade of events culminates in inactivation of the destruction complex, a negative regulator of the pathway, and the subsequent formation of singalosomes which mediate pathway activation. A critical component of signalosome formation is the Wnt/Wingless receptor LRP6/Arrow. Upon canonical pathway activation, LRP6/Arrow undergoes activation via phosphorylation by several kinases and complexes with another Wnt/Wingless receptor Frizzled, along with several cytoplasmic components. While many studies have investigated the regulatory mechanisms of …

Putrescine Detected In Strains Of Staphylococcus Aureus, Javier Seravalli, Frank Portugal

Department of Biochemistry: Faculty Publications

Most forms of life, including the archaea, bacteria, and eukaryotes synthesize the polyamine putrescine. Although putrescine is widely distributed, several Gram-positive bacteria, including Staphylococcus aureus (S. aureus), appear to be the exceptions. We report here that strains of S. aureus can produce the polyamine putrescine, as well as the derivative N-acetyl-putrescine. Three strains of S. aureus from the American Type Culture Collection (ATCC), one strain listed in the National Center for Biotechnology Information (NCBI) database, whose genomic sequence is well defined, and well as eight strains from S. aureus-induced brain abscesses of individual patients from multiple …

Investigating The Activity Of Alternative Warheads For Targeted Covalent Inhibition Of The Inhibitor Vertebrate Lysozyme Protein From Pseudomonas Aeruginosa, Katie Hambrick

Master of Science in Chemical Sciences Theses

Pseudomonas aeruginosa (P. aeruginosa) is a Gram-negative bacterium that causes blood and lung infections in hospital environments due to its ability to survive on improperly sterilized medical equipment. P. aeruginosa has developed several multi-drug resistance mechanisms that make it very difficult to treat with current antibiotics.¹ This presents the need for a new class of antibiotics that cannot be overcome by P. aeruginosa’s mechanisms of resistance.

The primary goal of this project was to develop a small library of inhibitors that could later be incorporated into lead compounds for novel antibiotic drug discovery. One of P. …

Quantitative Risk Assessment Of Oocyst Versus Bradyzoite Foodborne Transmission Of Toxoplasma Gondii In Brazil, Sophie Zhu, Elizabeth Vanwormer, Beatriz Martínez-López, Lílian Maria Garcia Bahia-Oliveira, Renato Augusto Damatta, Pedro Souto Rodrigues, Karen Shapiro

School of Veterinary and Biomedical Sciences: Faculty Publications

Toxoplasma gondii is a globally distributed zoonotic protozoan parasite. Infection with T. gondii can cause congenital toxoplasmosis in developing fetuses and acute outbreaks in the general population, and the disease burden is especially high in South America. Prior studies found that the environmental stage of T. gondii, oocysts, is an important source of infection in Brazil; however, no studies have quantified this risk relative to other parasite stages. We developed a Bayesian quantitative risk assessment (QRA) to estimate the relative attribution of the two primary parasite stages (bradyzoite and oocyst) that can be transmitted in foods to people in …

Exploring Strain Variation And Bacteriophage Predation In The Gut Microbiome Of Ciona Robusta, Celine Grace F. Atkinson

USF Tampa Graduate Theses and Dissertations

Current microbiome studies have shown that the maintenance of homeostasis betweenmicrobial populations (e.g. bacteria, viruses) and the host immune system (e.g. innate immune molecules) is necessary for balancing health and disease outcomes within the host. These studies most often utilize vertebrate models; however, research in this field can benefit from diverse model systems that facilitate our ability to conduct experiments to identify phylogenically conserved rules influencing homeostasis in the gut of animals. The Dishaw has developed the use of a filter-feeding marine invertebrate chordate, Ciona robusta, to model such fundamental interactions[1]–[6]. While most biological diversity and functional contribution within microbiomes …

Downregulation Of Fkbp5 Promotes Atrial Arrhythmogenesis, Xiaolei Wang, Jia Song, Yue Yuan, Luge Li, Issam Abu-Taha, Jordi Heijman, Liang Sun, Shokoufeh Dobrev, Markus Kamler, Liang Xie, Xander H T Wehrens, Frank T Horrigan, Dobromir Dobrev, Na Li

Faculty, Staff and Students Publications

BACKGROUND: Atrial fibrillation (AF), the most common arrhythmia, is associated with the downregulation of

METHODS: Right atrial samples from patients with AF were used to assess the protein levels of FKBP5. A cardiomyocyte-specific FKBP5 knockdown mouse model was established by crossbreeding

RESULTS: FKBP5 protein levels were lower in the atrial lysates of patients with paroxysmal AF or long-lasting persistent (chronic) AF. Cardiomyocyte-specific knockdown mice exhibited increased AF inducibility and duration compared with control mice. Enhanced AF susceptibility in cardiomyocyte-specific knockdown mice was associated with the development of action potential alternans and spontaneous Ca

CONCLUSIONS: This is the first study to …

Type Iv Pilus-Mediated Inhibition Of Acinetobacter Baumannii Biofilm Formation By Phenothiazine Compounds, Nam Vo, Benjamin S. Sidner, Yafan Yu, Kurt H. Piepenbrink

Department of Biochemistry: Faculty Publications

Infections by pathogenic Acinetobacter species represent a significant burden on the health care system, despite their relative rarity, due to the difficulty of treating infections through oral antibiotics. Multidrug resistance is commonly observed in clinical Acinetobacter infections and multiple molecular mechanisms have been identified for this resistance, including multidrug efflux pumps, carbapenemase enzymes, and the formation of bacterial biofilm in persistent infections. Phenothiazine compounds have been identified as a potential inhibitor of type IV pilus production in multiple Gram-negative bacterial species. Here, we report the ability of two phenothiazines to inhibit type IV pilus-dependent surface (twitching) motility and biofilm formation …

Effect Of Dual Inhibition Of Atypical Pkc Signaling And Pi3k/Akt Signaling On Cell Viability And Apoptosis In Clear Cell Renal Cell Carcinoma (Ccrcc)., Khandker M. Khalid

USF Tampa Graduate Theses and Dissertations

Renal Cell Carcinoma (RCC) is the most common type of kidney cancer (85%); 75% of the cases involve conventional clear cell RCC (ccRCC). The choice of treatments recommended for clear cell carcinoma and non-clear cell carcinoma include partial nephrectomy (Stage I), radical nephrectomy (Stages II and III), and chemotherapy (stage IV). Phosphatidylinositol-3-kinase (PI3K) inhibitors can be a viable candidate in the chemotherapy of ccRCC because the PI3K/Akt pathway is frequently activated in RCC. Hence, PI3K inhibitors like Alpelisib (BYL719) can be chosen as a treatment. In addition, aPKCs (PKC-ί and PKC ζ) are overexpressed in most cancer cells, and they …

An Improved Reporter Identifies Ruxolitinib As A Potent And Cardioprotective Camkii Inhibitor, Oscar E Reyes Gaido, Nikoleta Pavlaki, Jonathan M Granger, Olurotimi O Mesubi, Bian Liu, Brian L Lin, Alan Long, David Walker, Joshua Mayourian, Kate L Schole, Chantelle E Terrillion, Lubika J Nkashama, Mohit M Hulsurkar, Lauren E Dorn, Kimberly M Ferrero, Richard L Huganir, Frank U Müller, Xander H T Wehrens, Jun O Liu, Elizabeth D Luczak, Vassilios J Bezzerides, Mark E Anderson

Faculty, Staff and Students Publications

Ca2+/calmodulin-dependent protein kinase II (CaMKII) hyperactivity causes cardiac arrhythmias, a major source of morbidity and mortality worldwide. Despite proven benefits of CaMKII inhibition in numerous preclinical models of heart disease, translation of CaMKII antagonists into humans has been stymied by low potency, toxicity, and an enduring concern for adverse effects on cognition due to an established role of CaMKII in learning and memory. To address these challenges, we asked whether any clinically approved drugs, developed for other purposes, were potent CaMKII inhibitors. For this, we engineered an improved fluorescent reporter, CaMKAR (CaMKII activity reporter), which features superior sensitivity, kinetics, and …

Institutional And Individual Approaches To Change In Undergraduate Stem Education: Two Framework Analyses, Stephanie B. Feola

USF Tampa Graduate Theses and Dissertations

The overarching goal of this dissertation is to examine institutional change initiatives in STEM and to understand the impact of engaging with a specific change strategy on a biochemistry educator’s instructional practice. Institutional change initiatives involve executing an intentional strategy to influence teaching practices within a specific institution. This research investigates NSF-funded change initiatives at three public research universities that were focused on encouraging the adoption of evidenced-based instructional practices (EBIPs) by STEM faculty. As part of an effort to understand how the three institutions approached this task, framework analysis was performed using the initiative’s annual reports to NSF. Further …

Raw Diffraction Data For 1tel-Aa-Vwa (Sumo), Wwpdb Id: 7n1o, Moriah H. Mathis, Braydan D. Bezzant, Diana T. Ramírez, Supeshala D. Nawarathnage, Tzanko I. Doukov, James Moody

ScholarsArchive Data

This X-ray diffraction dataset was collected on October 21Oct2020 at SSRL Beamline BL9-2. The crystal was of Batch 1 1TEL-AA-vWa (SUMO) The solved structure used frames 1-999 and has been deposited in the wwPDB under the PDB ID 7N1O. This data can be readily processed using XDS, AutoProc, CCP4, HKL2000/3000, or other crystallographic X-ray diffraction data processing software. The files have a human-readable header but are otherwise binary.

Raw Diffraction Data For 3tel-Hlx-Darpin (Sumo), Wwpdb Id: 7n2b, Supeshala D. Nawarathnage, Parag Laljibhai Gajjar, Derick R. Bunn, Cameron Stewart, Tzanko I. Doukov, James Moody

ScholarsArchive Data

This X-ray diffraction dataset was collected on October 21Oct2020 at SSRL Beamline BL9-2. The crystal was of 3TEL-hlx-DARPin (SUMO) The solved structure used frames 1-1799 and has been deposited in the wwPDB under the PDB ID 7N2B. This data can be readily processed using XDS, AutoProc, CCP4, HKL2000/3000, or other crystallographic X-ray diffraction data processing software. The files have a human-readable header but are otherwise binary.

Neuropharmacology Of Human [Tera2.Cl.Sp12] Stem Cell-Derived Neurons In Ultra-Long-Term Culture For Antiseizure Drug Discovery, Hamed Salmanzadeh, Ankita Poojari, Atefeh Rabiee, Benjamin D. Zeitlin, Robert F. Halliwell

School of Pharmacy Faculty Articles

Modeling the complex and prolonged development of the mammalian central nervous system in vitro remains a profound challenge. Most studies of human stem cell derived neurons are conducted over days to weeks and may or may not include glia. Here we have utilized a single human pluripotent stem cell line, TERA2.cl.SP12 to derive both neurons and glial cells and determined their differentiation and functional maturation over 1 year in culture together with their ability to display epileptiform activity in response to pro-convulsant agents and to detect antiseizure drug actions. Our experiments show that these human stem cells differentiate in vitro …

Ngr1 Binding To Reovirus Reveals An Unusual Bivalent Interaction And A New Viral Attachment Protein, Danica M Sutherland, Michael Strebl, Melanie Koehler, Olivia L Welsh, Xinzhe Yu, Liya Hu, Rita Dos Santos Natividade, Jonathan J Knowlton, Gwen M Taylor, Rodolfo A Moreno, Patrick Wörz, Zachery R Lonergan, Pavithra Aravamudhan, Camila Guzman-Cardozo, Sukhleen Kour, Udai Bhan Pandey, David Alsteens, Zhao Wang, B V Venkataram Prasad, Thilo Stehle, Terence S Dermody

Faculty, Staff and Students Publications

Nogo-66 receptor 1 (NgR1) binds a variety of structurally dissimilar ligands in the adult central nervous system to inhibit axon extension. Disruption of ligand binding to NgR1 and subsequent signaling can improve neuron outgrowth, making NgR1 an important therapeutic target for diverse neurological conditions such as spinal crush injuries and Alzheimer's disease. Human NgR1 serves as a receptor for mammalian orthoreovirus (reovirus), but the mechanism of virus-receptor engagement is unknown. To elucidate how NgR1 mediates cell binding and entry of reovirus, we defined the affinity of interaction between virus and receptor, determined the structure of the virus-receptor complex, and identified …

Examining Parent-Of-Origin Effects On Transcription And Rna Methylation In Mediating Aggressive Behavior In Honey Bees (Apis Mellifera), Sean T. Bresnahan, Ellen Lee, Lindsay Clark, Rong Ma, Michael P. Markey, Juliana Rangel, Christina M. Grozinger, Hongmei Li-Byarlay

Biochemistry and Molecular Biology Faculty Publications

Conflict between genes inherited from the mother (matrigenes) and the father (patrigenes) is predicted to arise during social interactions among offspring if these genes are not evenly distributed among offspring genotypes. This intragenomic conflict drives parent-specific transcription patterns in offspring resulting from parent-specific epigenetic modifications. Previous tests of the kinship theory of intragenomic conflict in honey bees (Apis mellifera) provided evidence in support of theoretical predictions for variation in worker reproduction, which is associated with extreme variation in morphology and behavior. However, more subtle behaviors – such as aggression – have not been extensively studied. Additionally, the canonical epigenetic mark …