Molecular Biology Commons^™

Modeling Of Dynamic Allostery In Proteins Enabled By Machine Learning, Mohsen Botlani-Esfahani

USF Tampa Graduate Theses and Dissertations

Regulation of protein activity is essential for normal cell functionality. Many proteins are regulated allosterically, that is, with spatial gaps between stimulation and active sites. Biological stimuli that regulate proteins allosterically include, for example, ions and small molecules, post-translational modifications, and intensive state-variables like temperature and pH. These effectors can not only switch activities on-and-off, but also fine-tune activities. Understanding the underpinnings of allostery, that is, how signals are propagated between distant sites, and how transmitted signals manifest themselves into regulation of protein activity, has been one of the central foci of biology for over 50 years. Today, the importance …

Quaternary Interactions And Supercoiling Modulate The Cooperative Dna Binding Of Agt, Manana Melikishvili, Michael G. Fried

Center for Structural Biology Faculty Publications

Human O⁶-alkylguanine-DNA alkyltransferase (AGT) repairs mutagenic O⁶-alkylguanine and O⁴-alkylthymine adducts in single-stranded and duplex DNAs. The search for these lesions, through a vast excess of competing, unmodified genomic DNA, is a mechanistic challenge that may limit the repair rate in vivo. Here, we examine influences of DNA secondary structure and twist on protein–protein interactions in cooperative AGT complexes formed on lesion-free DNAs that model the unmodified parts of the genome. We used a new approach to resolve nearest neighbor (nn) and long-range (lr) components from the ensemble-average cooperativity, ω_ave. We found …

Rational Drug Design Directed At Blocking The Initial Signaling Events In Lipopolysaccharide-Induced Sepsis., Christopher A. Tipton

Theses

Systemic Inflammatory Response Syndrome (SIRS) is classified as an immune system response to an infectious state. If left untreated, SIRS leads to sepsis, septic shock, end-organ dysfunction, and death. As a patient progresses through these stages, associations of acute respiratory distress, disseminated intravascular coagulation, and acute renal failure persist, resulting in millions of deaths annually. Lipopolysaccharide (LPS), a bacterial endotoxin, is released into the blood stream, triggering SIRS. LPS is found in the outer cell-wall of Gram-negative bacteria and is responsible for initiation of a devastating cytokine storm. One of the regions of LPS, lipid A, is a polyacylated glucosamine …

Discovering Antibacterial And Anti-Resistance Agents Targeting Multi-Drug Resistant Eskape Pathogens, Renee Fleeman

USF Tampa Graduate Theses and Dissertations

Antibiotic resistance has been a developing problem for mankind in recent decades and multi-drug resistant bacteria are now encountered that are resistant to all treatment options available. In 2014, the World Health Organization announced that this problem is driving us towards a “post-antibiotic era” that will change the face of modern medicine as we know it. If lack of novel antibiotic development and FDA approval continues, by the year 2050, 10 million people will die each year to an antimicrobial resistant bacterial infection. With lack of pharmaceutical industry involvement in developing novel antibiotics, the responsibility now lies within the academic …

The Chondrocyte Channelome: A Novel Ion Channel Candidate In The Pathogenesis Of Pectus Deformities, Anthony J. Asmar

Biological Sciences Theses & Dissertations

Costal cartilage is a type of rod-like hyaline cartilage connecting the ribs to the sternum. The chest wall deformities pectus excavatum (PE) and pectus carinatum (PC) involve displacement of the sternum causing a depression or protrusion of the chest. There is little knowledge about costal cartilage and pectus deformities with much of its understanding based on assumptions from articular cartilage. Chondrocytes are subjected to a constantly changing environment with fluctuations in pH and osmolarity. Ion channels detect these changes and in turn regulate proliferation, differentiation, and extracellular matrix production. Using ion channel qPCR arrays, we produced expression profiles for normal, …

Il-18 Polymorphisms Contribute To Hepatitis B Virus-Related Cirrhosis And Hepatocellular Carcinoma Susceptibility In Chinese Population: A Case-Control Study., Zhi-Jun Dai, Xing-Han Liu, Meng Wang, Yan Guo, Wenge Zhu, Xiao Li, Shuai Lin, Tian Tian, Kang Liu, Yi Zheng, Peng Xu, Tianbo Jin, Xiaopeng Li

Biochemistry and Molecular Medicine Faculty Publications

IL-18 polymorphisms influence the transcriptional activity of the IL-18 gene and associated with various diseases. However, their relationships with hepatitis B virus-related liver diseases had not reached a consensus. So we conducted this case-control study with a view to clarifying the association. We included four groups: healthy controls, chronic hepatitis B virus (CHB) carriers, liver cirrhosis (LC) and hepatocellular carcinoma (HCC) groups with each group of 250 persons. Odd ratios (ORs) and 95% confidence intervals (95%CIs) with or without adjustment were calculated. Haplotype analysis was also performed. The results showed people carrying rs187238 CG genotype had a lower risk of …

Safety And Potential Efficacy Of Gemfibrozil As A Supportive Treatment For Children With Late Infantile Neuronal Ceroid Lipofuscinosis And Other Lipid Storage Disorders., Kyeongsoon Kim, Hynda K Kleinman, Hahn-Jun Lee, Kalipada Pahan

Biochemistry and Molecular Medicine Faculty Publications

Neuronal Ceroid Lipofuscinosis (NCL), also known as Batten disease, is a group of genetically distinct lysosomal disorders that mainly affect the central nervous system, resulting in progressive motor and cognitive decline primarily in children. Multiple distinct genes involved in the metabolism of lipids have been identified to date with various mutations in this family of diseases. There is no cure for these diseases but some new therapeutic approaches have been tested that offer more hope than the standard palliative care. Many of the therapeutic advances require invasive procedures but some progress in slowing the disease has been found and more …

Microarray Analysis Of Aging-Associated Immune System Alterations In The Rostral Ventrolateral Medulla Of F344 Rats, Sivasai Balivada, Chanran Ganta, Yongqing Zhang, Hitesh Pawar, Richard Ortiz, Kevin Becker, Arshad Khan, Michael Kenney

Selected Works Temporary Series

The rostral ventrolateral medulla (RVLM) is an area of the brain stem that contains diverse neural substrates that are involved in systems critical for physiological function. There is evidence that aging affects some neural substrates within the RVLM, although age-related changes in RVLM molecular mechanisms are not well established. The goal of the present study was to characterize the transcriptomic profile of the aging RVLM and to test the hypothesis that aging is associated with altered gene expression in the RVLM, with an emphasis on immune system associated gene transcripts. RVLM tissue punches from young, middle-aged, and aged F344 rats …

Microarray Analysis Of Aging-Associated Immune System Alterations In The Rostral Ventrolateral Medulla Of F344 Rats, Balivada, Chanran Ganta, Yongqing Zhang, Hitesh Pawar, Richard Ortiz, Kevin Becker, Arshad Khan, Michael Kenney

Departmental Papers (Biology)

The rostral ventrolateral medulla (RVLM) is an area of the brain stem that contains diverse neural substrates that are involved in systems critical for physiological function. There is evidence that aging affects some neural substrates within the RVLM, although age-related changes in RVLM molecular mechanisms are not well established. The goal of the present study was to characterize the transcriptomic profile of the aging RVLM and to test the hypothesis that aging is associated with altered gene expression in the RVLM, with an emphasis on immune system associated gene transcripts. RVLM tissue punches from young, middle-aged, and aged F344 rats …

A Lipid Binding Structure And Functional Analysis Of Human Arv1, Jessie Lee Cunningham

Graduate School of Biomedical Sciences Theses and Dissertations

Metabolic Syndrome (MetS) is a combination of risk factors that can over time increase the probability of developing diseases, including cardiovascular disease, type 2 diabetes, non-alcoholic fatty liver disease (NAFLD), and non-alcoholic steatohepatitis (NASH). Acyl-coenzyme-A: cholesterol O-acyl transferase related enzyme required for viability-1, abbreviated as Arv1, is an evolutionarily conserved putative lipid binding protein. Several studies have implicated hArv1 as a critical regulator of lipid transport and trafficking.

Recent work using an Arv1 knock out (KO) mouse model have established a clear link between Arv1 function and the progression of MetS and NAFLD/NASH [unpublished data] [1]. Overall, studies show that …

Endocrine And Metabolic Effects Of Consuming Sugar-Sweetened Beverages: Preclinical And Clinical Studies", Peter Havel

Science Seminar Series

Peter J. Havel of the School of Veterinary Medicine at UC Davis will speak on his research on Endocrine and Metabolic Effects of Consuming Sugar-Sweetened Beverages: Preclinical and clinical studies at this Science Seminar Series lecture.

Approaching Undergraduate Research With Students Who Are Deaf And Hard-Of-Hearing, Austin U. Gehret, Jessica W. Trussell, Lea V. Michel

Journal of Science Education for Students with Disabilities

An undergraduate research experience can provide a unique opportunity for students to learn and grow as scientists; when positive, this experience is often transformative and motivates students to pursue science, technology, engineering and mathematics (STEM) graduate degrees or careers. Conversely, negative research experiences can sour a student’s opinion of research, propagate misconceptions of graduate school, and lead to attrition from STEM fields. Negative research experiences can be equally devastating for faculty mentors and may result in reluctance to mentor future research students. Using a mentoring approach that has traditionally translated to positive research experiences for hearing students may not be …

Functional Roles Of Matrix Metalloproteinases In Bone Metastatic Prostate Cancer, Jeremy S. Frieling

USF Tampa Graduate Theses and Dissertations

Skeletal metastasis is a lethal component of many advanced cancers including prostate, the second most common cancer among men. Patients whose prostate cancer is localized and detected early benefit from multiple treatment options ranging from active surveillance to radiation and surgery, resulting in a 5-year survival rate of nearly 100%. Unfortunately, the prognosis and survival for patients with advanced metastatic disease is much worse due to the highly aggressive nature of the disease and a paucity of treatment options. Understanding the mechanisms and interactions that occur between metastatic cancer cells and the bone will enable the future treatment landscape for …

Applied Drug Development And Combinatorial Strategies For Antimicrobial Treatment, Steven K. Lai Hing

Andrews Research Conference

Streptococcus mutans JH1140 is a strain of bacteria which produces a lantibiotic product, named mutacin 1140. Mutacin 1140 has been shown to be effective at inhibiting Gram-positive bacterial infections caused by Staphylococcus aureus and Streptococcus pneumoniae. Mutacin 1140 is a ribosomally synthesized peptide antibiotic that undergoes extensive posttranslational modifications (PTM). We have found that Mutacin 1140 and an aminoglycoside, Kanamycin, when combined together, act synergistically against Staphylococcus aureus. This was determined by performing serial kill curve dilution overlays on solid media, followed up with kill curve by microdilution plate, and most recently confirmed with kill curve CFU count plates …

Negative Regulation Of Haa1 By Casein Kinase I Protein Hrr25 In Saccharomyces Cerevisiae, Morgan Collins

LSU New Orleans Theses and Dissertations

Haa1 is a transcription factor that adapts Saccharomyces cerevisiae cells to weak organic acid stresses by activating the expression of various genes. How Haa1 is activated by weak acids is not clear. This study proposes that Hrr25 is an important regulator of cellular adaptation to weak acid stress by inhibiting Haa1 through phosphorylation. YRO2, one of the targets of Haa1, shows increase in expression during stationary phase. This increase is due to basal activity of Haa1 and another, unknown, transcription factor. This study proposes that Gsm1 is another transcription factor that regulates YRO2 expression in the stationary phase. Finally, …

Characterization Of Genes Involved In Phycobiliprotein Biosynthesis In Fremyella Diplosiphon And Thermosynechococcus Elongatus, Christina M. Kronfel

LSU New Orleans Theses and Dissertations

Cyanobacteria are photosynthetic organisms that efficiently capture light by utilizing the light-harvesting complexes called phycobilisomes. In many cyanobacteria, phycobilisomes are composed of an allophycocyanin core with phycocyanin and phycoerythrin (PE) rods radiating from the core. These phycobiliproteins have multiple bilin chromophores, such as phycoerythrobilin (PEB), covalently attached to specific cysteine (Cys) residues for efficient photosynthetic light capture. Chromophore ligation on phycobiliprotein subunits occurs through bilin lyase catalyzed reactions.

This study mainly focuses on characterizing the roles of enzymes that are involved in the biosynthetic pathway of the phycobiliproteins within two cyanobacteria Thermosynechococcus elongatus and Fremyella diplosiphon. A combination of molecular …

Identification Of Novel Nuclear Proteins Required For Meiotic Silencing By Unpaired Dna In Neurospora Crassa, Dilini Ralalage

Theses and Dissertations

A fundamental step that occurs during sexual reproduction is meiosis, which is a specialized type of cell division. During meiosis, pairs of chromosomes exchange genetic information via recombination. At this point, the genome is particularly susceptible to viruses and other foreign genetic invasions. Therefore, it is important to protect the genome to prevent the transmission of foreign genetic materials to the offspring. There are several mechanisms work together to protect host genome from foreign genetic materials. These are known as “genome defense mechanisms”.

The fungus Neurospora crassa is one of the best organisms for genome defense studies due to the …

The Impact Of The Mitochondrial Metabolism Of Induced Pluripotent Stem Cells Upon Differentiation, Stefanie T. Shahan

McKelvey School of Engineering Graduate Student Theses & Dissertations

Induced pluripotent stem cells (iPSCs) can be differentiated into any cell type found in the body. The derivation of a stem cell derived β cell (SC-β) capable of responding to glucose by secreting insulin was hugely significant for diabetes research and opened up the possibility of cell replacement therapy to combat this widespread disease (Pagliuca et al. 2014). The optimization of differentiation procedures such as this could improve yield, function, cost, and efficiency of a stem cell-derived product. Current approaches to improve differentiation are primarily focused on signal transduction pathways, while the metabolic state of the cells has received little …

Long Non-Coding Rna Profile In Mantle Cell Lymphoma Identifies A Functional Lncrna Ror1-As1 Associated With Ezh2/Prc2 Complex., Guangzhen Hu, Shiv K Gupta, Tammy P Troska, Asha Nair, Mamta Gupta

Biochemistry and Molecular Medicine Faculty Publications

Mantle cell lymphoma (MCL) is an aggressive B-cell lymphoma characterized by rapid disease progression. The needs for new therapeutic strategies for MCL patients call for further understanding on the molecular mechanisms of pathogenesis of MCL. Recently, long noncoding RNAs (lncRNAs) have been recognized as key regulators of gene expression and disease development, however, the role of lncRNAs in non-Hodgkin lymphoma and specifically in MCL is still unknown. Next generation RNA-sequencing was carried out on MCL patient samples along with normal controls and data was analyzed. As a result, several novel lncRNAs were found significantly overexpressed in the MCL samples with …

B7h6: A Cancer Biomarker For The Development Of Novel Immunotherapy Approaches, Mariana Phillips

Seton Hall University Dissertations and Theses (ETDs)

Cancer-based immunotherapy has led the evolution of biologics that can stimulate immune responses towards tumor eradication. The synthesis of small to intermediate size molecules with the targeting and effector functions of mAb may represent a novel class of immunotherapeutics that may overcome the limitations of their biological counterparts.Towards this objective, B7H6 has been identified as a protein ligand localized on the cell surface of transformed tumor cells. B7H6 binds specifically to the activating receptor NKp30, constitutively expressed on all resting and active NK cells. Upon ligand:receptor binding, B7H6 triggers NK cell activation and release of chemokines and pro-inflammatory cytokines such …