Biochemistry, Biophysics, and Structural Biology Commons^™

Mechanisms To Regulate Genes Encoding Clinically Relevant Multidrug Transporters At The Crossroads Of Antibiotic Resistance And Oxidative Stress Detection, Afsana Sabrin

LSU Doctoral Dissertations

Multiple Antibiotic Resistance Regulators (MarRs) are DNA binding proteins involved in bacterial survival and pathogenesis. My PhD dissertation focuses on a MarR homolog, OstR, which regulates genes encoding major multidrug transporters, a resistance-nodulation-division (RND) and an E. coli multidrug resistance B (EmrB) efflux pump homolog in Burkholderia thailandensis. The ostR gene is divergently oriented from genes encoding a hypothetical protein (Hyp) and an RND transporter and adjacent to a gene encoding an EmrB transporter. OstR binds to the promoters of each gene (K_d = 64.9 ± 8.0 nM, K_d = 126.1 ± 10.9 nM and K …

Integrated Molecular Characterization Of Lung Adenocarcinoma With Implications For Immunotherapy, Nicholas T. Gimbrone

USF Tampa Graduate Theses and Dissertations

This dissertation covers a variety of the genetic and molecular abnormalities of lung adenocarcinoma with an emphasis on STK11 loss and its implications on immunotherapy response. Given that lung cancer is the leading cancer killer, novel therapies are in great demand. In particular, immunotherapy has shown some of the most promise in the last decade but remains limited due to nearly 80% of patients not significantly responding. This dissertation aims to molecularly characterize lung adenocarcinoma while attempting to explain the reason why patients with STK11 loss do not respond to immunotherapy.

In the first chapter we discuss the relationship between …

High Expression Of Osm And Il-6 Are Associated With Decreased Breast Cancer Survival: Synergistic Induction Of Il-6 Secretion By Osm And Il-1Β, Ken Tawara, Hannah Scott, Jacqueline Emathinger, Cody Wolf, Dollie Lajoie, Danielle Hedeen, Laura Bond, Cheryl Jorcyk

Biomedical Research Institute Publications and Presentations

Chronic inflammation has been recognized as a risk factor for the development and maintenance of malignant disease. Cytokines such as interleukin-6 (IL-6), oncostatin M (OSM), and interleukin-1 beta (IL-1β) promote the development of both acute and chronic inflammation while promoting in vitro metrics of breast cancer metastasis. However, anti-IL-6 and anti-IL-1β therapeutics have not yielded significant results against solid tumors in clinical trials. Here we show that these three cytokines are interrelated in expression. Using the Curtis TCGA™ dataset, we have determined that there is a correlation between expression levels of OSM, IL-6, and IL-1β and reduced breast cancer patient …

Purification And Characterization Of A Nonspecific Lipid Transfer Protein 1 (Nsltp1) From Ajwain (Trachyspermum Ammi) Seeds, Meshal Nazeer, Humera Waheed, Maria Saeed, Saman Yousuf Ali, M. Iqbal Choudhary, Zaheer Ul-Haq, Aftab Ahmed

Pharmacy Faculty Articles and Research

Ajwain (Trachyspermum ammi) belongs to the family Umbelliferae, is commonly used in traditional, and folk medicine due to its carminative, stimulant, antiseptic, diuretic, antihypertensive, and hepatoprotective activities. Non-specific lipid transfer proteins (nsLTPs) reported from various plants are known to be involved in transferring lipids between membranes and in plants defense response. Here, we describe the complete primary structure of a monomeric non-specific lipid transfer protein 1 (nsLTP1), with molecular weight of 9.66 kDa, from ajwain seeds. The nsLTP1 has been purified by combination of chromatographic techniques, and further characterized by mass spectrometry, and Edman degradation. The ajwain nsLTP1 …

Molecular Rotation In 3 Dimensions At An Air/Water Interface Using Femtosecond Time Resolved Sum Frequency Generation, Yi Rao, Yuqin Qian, Gang-Hua Deng, Ashlie Kinross, Nicholas J. Turro, Kenneth B. Eisenthal

Chemistry and Biochemistry Faculty Publications

This paper presents the first study of the rotations of rigid molecules in 3 dimensions at the air/water interface, using the femtosecond time resolved sum frequency generation (SFG) technique. For the purpose of this research, the aromatic dye molecule C153 was chosen as an example of a molecule having two functional groups that are SFG active, one being the hydrophilic −−C==O group and the other the hydrophobic −−CF₃ group. From polarized SFG measurements, the orientations of the two chromophores with respect to the surface normal were obtained. On combining these results with the known relative orientation of the two …

Parp1 Is A Versatile Factor In The Regulation Of Mrna Stability And Decay, Elena A. Matveeva, Lein F. Mathbout, Yvonne N. Fondufe-Mittendorf

Molecular and Cellular Biochemistry Faculty Publications

PARP1 is an abundant nuclear protein with many pleiotropic functions involved in epigenetic and transcriptional controls. Abundance of mRNA depends on the balance between synthesis and decay of a particular transcript. PARP1 binds RNA and its depletion results in increased expression of genes involved in nonsense-mediated decay, suggesting that PARP1 might be involved in mRNA stability. This is of interest considering RNA binding proteins play key roles in post-transcriptional processes in all eukaryotes. We tested the direct impact of PARP1 and PARylation on mRNA stability and decay. By measuring the half-lives of two PARP1-mRNA targets we found that the half-lives …

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 …

Living, Learning, And Leading At Linfield College, Kelsey Bruce

Student Engagement Posters

Kelsey Bruce discusses student engagement at Linfield College with regard to leadership through student/faculty collaborative research with Dr. Megan Bestwick, speech and debate, and the Linfield Residence Life team.

Global Biochemical And Structural Analysis Of The Type Iv Pilus From The Gram-Positive Bacterium Streptococcus Sanguinis, Jamie-Lee Berry, Ishwori Gurung, Jan Haug Anonsen, Ingrid Spielman, Elliot Harper, Alexander M. J. Hall, Vivianne J. Goosens, Claire Raynaud, Michael Koomey, Nicolas Biais, Steve Matthews, Vladimir Pelicic

Publications and Research

Type IV pili (Tfp) are functionally versatile filaments, widespread in prokaryotes, that belong to a large class of filamentous nanomachines known as type IV filaments (Tff). Although Tfp have been extensively studied in several Gram-negative pathogens where they function as key virulence factors, many aspects of their biology remain poorly understood. Here, we performed a global biochemical and structural analysis of Tfp in a recently emerged Gram-positive model, Streptococcus sanguinis. In particular, we focused on the five pilins and pilin-like proteins involved in Tfp biology in S. sanguinis. We found that the two major pilins, PilE1 and PilE2, (i) follow …

Molecular Relatedness Of Two Distinct Type Iv Crispr-Associated (Cas) Proteins, Matt Armbrust

Research on Capitol Hill

CRISPR-Cas systems are prokaryotic adaptive immune systems. Bacteria use CRISPR systems as a defense against foreign nucleic acid invasion such as phage infection.

Total Reflection X-Ray Fluorescence, Martina Schmeling

Chemistry: Faculty Publications and Other Works

Total reflection X-ray fluorescence (TXRF) spectrometry is a non-destructive and surface sensitive multi-element analytical method based on energy dispersive X-ray fluorescence spectrometry with detection limits in the lower picogram range. It utilizes the total reflection of the primary X-ray beam at or below the critical angle of incidence. At this angle, the fluorescence intensity is substantially enhanced for samples present as small granular residue or as thin homogenous layer deposited at the surface of a thick substrate. Generally, two types of application exist: micro- and trace-analysis as well as surface and thin-layer analysis. For micro- and traceanalysis, a small amount …

Targeted Therapy For The Future: The Use Of Novel Antimicrobial Peptides Against P. Aeurginosa, Matthew Froid

UNO Student Research and Creative Activity Fair

Pathogenic bacteria, such as the gram-negative bacterium Pseudomonas aeruginosa, are becoming resistant to our current arsenal of antibiotics at an alarming rate. P. aeruginosa is a leading cause of nosocomial acquired infections and is a primary co-morbidity in patients with compromised immune systems. One potential source of new antibiotic agents is antimicrobial peptides. Antimicrobial peptides (AMPs) are small proteins, and some have shown a high degree of efficacy and broad-spectrum activity against both Gram-positive and Gram-negative bacteria. An experimental AMP that has been developed by Dr. Wang at UNMC, DASamp2, has shown to be effective against virulent bacteria, including P. …

Data Analytics Pipeline For Rna Structure Analysis Via Shape, Quinn Nelson

UNO Student Research and Creative Activity Fair

Coxsackievirus B3 (CVB3) is a cardiovirulent enterovirus from the family Picornaviridae. The RNA genome houses an internal ribosome entry site (IRES) in the 5’ untranslated region (5’UTR) that enables cap-independent translation. Ample evidence suggests that the structure of the 5’UTR is a critical element for virulence. We probe RNA structure in solution using base-specific modifying agents such as dimethyl sulfate as well as backbone targeting agents such as N-methylisatoic anhydride used in Selective 2’-Hydroxyl Acylation Analyzed by Primer Extension (SHAPE). We have developed a pipeline that merges and evaluates base-specific and SHAPE data together with statistical analyses that provides confidence …

Large Scale Dynamical Model Of Macrophage/Hiv Interactions, Matthew M. Froid

UNO Student Research and Creative Activity Fair

Properties emerge from the dynamics of large-scale molecular networks that are not discernible at the individual gene or protein level. Mathematical models - such as probabilistic Boolean networks - of molecular systems offer a deeper insight into how these emergent properties arise. Here, we introduce a non-linear, deterministic Boolean model of protein, gene, and chemical interactions in human macrophage cells during HIV infection. Our model is composed of 713 nodes with 1583 interactions between nodes and is responsive to 38 different inputs including signaling molecules, bacteria, viruses, and HIV viral particles. Additionally, the model accurately simulates the dynamics of over …

Alternative Nad(P)H Dehydrogenase And Alternative Oxidase: Proposed Physiological Roles In Animals, Allison Mcdonald, Dmytro V. Gospodaryov

Biology Faculty Publications

The electron transport systems in mitochondria of many organisms contain alternative respiratory enzymes distinct from those of the canonical respiratory system depicted in textbooks. Two of these enzymes, the alternative NADH dehydrogenase and the alternative oxidase, were of interest to a limited circle of researchers until they were envisioned as gene therapy tools for mitochondrial disease treatment. Recently, these enzymes were discovered in several animals. Here, we analyse the functioning of alternative NADH dehydrogenases and oxidases in different organisms. We propose that both enzymes ensure bioenergetic and metabolic flexibility during environmental transitions or other conditions which may compromise the operation …

Evaluation Of Soluble Tnf-Like Weak Inducer Of Apoptosis (Stweak) Levels To Predict Preeclampsia In Early Weeks Of Pregnancy, Sana Shahid, Erum Khalid, Syeda Sadia Fatima, Ghulam Mustafa Khan

Department of Biological & Biomedical Sciences

Introduction: Soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) is linked to endothelial dysfunction; a key factor in pre-eclamptic pathogenesis. This study aimed to compare sTWEAK levels during pregnancy to assess for its prognostic ability.
Materials and Methods: Sixty three high risk pregnant women were followed up from 12 weeks of gestation till term. Serum levels of sTWEAK and platelet derived growth factor (PlGF), blood pressure, serum glucose, uric acid, urea/creatinine and liver function tests were measured. Subjects were stratified according to the ACOG criteria as women who developed PE, or PIH or remained normotensive at term. A negative …

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 …

Arabinose Substitution Effect On Xylan Rigidity And Self-Aggregation, Utsab Shrestha, Sydney Smith, Sai Venkatesh Pingali, Hui Yang, Mai Zahran, Llyod Breunig, Liza Wilson, Daniel Cosgrove, Hugh O'Neill, Loukas Petridis

Publications and Research

Substituted xylans play an important role in the structure and mechanics of the primary cell wall of plants. Arabinoxylans (AX) consist of a xylose backbone substituted with arabinose, while glucuronoarabinoxylans (GAX) also contain glucuronic acid substitutions and ferulic acid esters on some of the arabinoses. We provide a molecular-level description on the dependence of xylan conformational, selfaggregation properties and binding to cellulose on the degree of arabinose substitution. Molecular dynamics simulations reveal fully solubilized xylans with a low degree of arabinose substitution (lsAX) to be stiffer than their highly substituted (hsAX) counterparts. Small-angle neutron scattering experiments indicate that both wild-type …

Total Synthesis Of Anticancer Agent Deoxypodophyllotoxin And Antiviral F4-4 Demonstrating The Utility Of The Intramolecular Styryl Diels-Alder (Isda) Reaction, Diana Isabel Saavedra Nova

Theses and Dissertations

The intramolecular styryl Diels – Alder (ISDA) reaction is a rare and unique [4+2] cycloaddition with potential in the syntheses of polycycles. Its utility is based on the formation of two rings and one stereocenter in a single step, making it an efficient method for the construction of lignan-type natural product targets. Detailed mechanistic studies with complex esters and the application to natural product synthesis has been limited due to drawbacks including the loss of aromaticity, producing slow reactivity, a potentially problematic thermal [1,3]-hydrogen shift, and electronic mismatch related to the substituents on the aryl functional groups. In this research, …

Escaping Death: Naloxone's Chemical Nature And Potential To Combat The Opioid Epidemic, Abigale Miller

Honors Program: Senior Projects (Public)

Naloxone is a life-saving drug with the ability to reverse an opioid overdose. As the opioid epidemic’s death toll rises, we can turn to Naloxone as a tool to combat the crisis. The epidemic, born of corruption, has a wide reach among the people of the United States, with especially firm grasps on middle-aged people, sufferers of chronic pain, white Americans and those living in the eastern portion of the country. Naloxone’s elegant design saves lives by effectively competing for a position on an opioid biding receptor in the brain to almost instantly end an overdose and restore normal breathing. …