Biochemistry, Biophysics, and Structural Biology Commons^™

Indicators Of Senescence And Their Relationship With The Antioxidant Response Element In Ovarian Cancer Cells—Toward A More Encompassing View Of Enzyme Activity Levels In Cells, Shaniqua Analycia Hayes

LSU Doctoral Dissertations

Enzymes and other related proteins are promising targets as biomarkers for cancer diagnostics, and it is therefore important to be able to quantify intracellular enzyme activity levels, not just presence of enzyme. Thus, there is a great need for the development of methods that offer spatiotemporal quantification of intracellular enzyme activity levels in respiring 2- and 3-dimensional cultures or their sample-processed variants. Previous studies have demonstrated that ß-gal is upregulated in senescence and in select ovarian cancers, and its expression/activity is upregulated when cells are under oxidative stress conditions. To that end, the primary goal of this work was to …

Atg8 Is Conserved Between Saccharomyces Cerevisiae And Psychrophilic, Polar-Collected Fungi, B. J. Ivory, H. M. Smith, E. Cabrera, M. R. Robinson, J. T. Sparks, A. Solem, J. I. Ishihara, H. Takahashi, M. Tsuji, V. A. Segarra

Osteopathic Medicine, Jerry M. Wallace School of

No abstract provided.

Examination Of Methylation Status And Occupancy Of Dna Methylation Modifying Proteins On Regulatory Regions Of The Dax-1 Gene, Caroline P. Riedstra

Master's Theses

Epigenetic modifications influence gene expression and thereby play a pivotal role in development and disease. Misregulation and mutations in the DAX-1 gene, or Dosage-Sensitive Sex Reversal, Adrenal Hypoplasia Congenita, Critical Region on the X chromosome, gene 1, have been implicated in Adrenal Hypoplasia Congenita (AHC) and Dosage Sensitive Sex Reversal (DSS). The orphan nuclear hormone receptor DAX-1 is expressed predominantly in tissues such as the testes, ovaries, breast, adrenal cortex, and lung. Critically, DAX-1 may serve as an indicator of aberrant growth in these tissues. Here we hypothesize that DAX-1 is epigenetically regulated, specifically in cancer cells, thereby reducing its …

Dynamics Of Protein-Dna Interactions Characterized By Atomic Force Microscopy, Yaqing Wang

Theses & Dissertations

This thesis describes the nanoscale studies of protein-DNA interactions with different complexities using atomic force microscopy (AFM). One of the systems deals with DNA replication rescue. To maintain the genetic integrity, replication machinery needs to minimize the error rate, repair the damages, and restart the stalled replication caused by the attacks from the environment and inside the cell. The stalled replication rescue is orchestrated by a series of proteins, for example, the DNA helicases PriA and RecG and the ssDNA binding protein (SSB).

We demonstrated that SSB stimulates the restart process in two aspects. First, SSB facilitates the binding of …

Fgfr4 Glycosylation And Processing In Cholangiocarcinoma Promote Cancer Signaling, Andrew J. Phillips

Theses & Dissertations

Cholangiocarcinoma is a cancer of cholangiocytes, or epithelial cells lining the biliary tract. It is associated with a poor prognosis and additional therapeutic treatments are needed to help patients affected by this disease. Fibroblast growth factor receptor 4 (FGFR4) is receptor tyrosine kinase that is involved in various physiologic and pathologic processes. TCGA analysis of thirty different tumor types showed the highest FGFR4 mRNA levels in cholangiocarcinoma. At the protein level, FGFR4 was observed in the majority of cholangiocarcinomas screened and, higher levels were associated with a poorer prognosis. FGFR4 is an N-linked glycosylated receptor tyrosine kinase that we show …

Fibroblast Growth Factor Receptor 4 And R4-Icd Increased Proliferation, Cell Survival And Metastasis In Cholangiocarcinoma, Yamnah Hafeji

Theses & Dissertations

Fibroblast growth factor receptor 4 (FGFR4) is over-expressed in many cancers, including cholangiocarcinoma (CCA). FGFR4 is activated by fibroblast growth factor ligand 19 (FGF19) and plays a critical role in CCA progression. An intracellular cleaved product of FGFR4, referred as R4-ICD (FGFR4 intracellular domain) is also overexpressed in CCA. However, the specific role of R4-ICD in CCA is unknown. In this study, we hypothesized that FGFR4 and R4-ICD play a role in cell proliferation, cell survival and metastasis in CCA. To test this, FGFR4 and R4-ICD were cloned into a cholangiocarcinoma cell line (HuCCT-1) that does not endogenously express FGFR4. …

Niche Partitioning And Utilization Of Different Nitrogen Sources By Marine Cyanobacteria Synechococcus, Angel Bui, Anne W. Thompson

McNair Symposium

The Cyanobacterium Synechococcus plays a major role in the ocean’s biochemical processes and is responsible for a significant amount of primary production, especially around coastal areas. Synechococcus has a wide geographical distribution that includes both polar and high-nutrient waters. Within the genus, there are defined subpopulations that are ecologically distinct that allow them to niche partition the dynamic oceans. To further explore niche partitioning of Synechococcus, this project combines a bioinformatic and culture-based approach. I examined data along the North Pacific Subtropical Front (NSPF) to analyze the community structure. This analysis demonstrated that a particular ecotype identified as clade II …

Cd40l And Tnf-Alpha Levels After Traumatic Injury, Queen Revollido, Martin Schreiber

McNair Symposium

The biomarkers CD40 ligand and TNF-alpha are proteins that exhibit proinflammatory and prothrombotic effects. A small clinical study has shown that soluble CD40 ligand may have a role in early coagulopathy and inflammatory complications in severely injured patients. It is known that a CD40 ligand increases the production of cytokines such as TNF-alpha, thus, the current study aims to investigate the kinetics of these biomarkers and the extent of upregulation after traumatic injury. Frozen samples collected from baseline, 8, 24, and 48 hours after admission will be used. CD40 ligand and TNF-alpha levels will be quantified using Luminex that will …

High Altitude Ballooning As A Platform For Measuring Ozone Uptake Over Agricultural Landscapes, Thomas Sykora, Mark Potosnak

DePaul Discoveries

Measuring plant health is a key aspect in maximizing crop outputs. One often overlooked risk to crop fields is damage caused by stomatal ozone uptake; measuring this uptake is an important tool in understanding crop losses. Traditional methods for measuring plant ozone uptake are prohibitively expensive and rely on equipment that cannot easily be moved. Here, we propose high-altitude weather ballooning as a cost-effective alternative for measuring ozone uptake on a regional (~10 km) spatial scale. Ozonesounde data was obtained with weather balloons launched from the National Oceanic and Atmospheric Administration research station in Boulder, Colorado. This data was then …

Decoding The Roles Of Astrocytes And Hedgehog Signaling In Medulloblastoma, Terence Teixeira Duarte, Silvia Aparecida Teixeira, Luis Gonzalez-Reyes, Rui Manuel Reis

Publications and Research

The molecular evolution of medulloblastoma is more complex than previously imagined, as emerging evidence suggests that multiple interactions between the tumor cells and components of the tumor microenvironment (TME) are important for tumor promotion and progression. The identification of several molecular networks within the TME, which interact with tumoral cells, has provided new clues to understand the tumorigenic roles of many TME components as well as potential therapeutic targets. In this review, we discuss the most recent studies regarding the roles of astrocytes in supporting sonic hedgehog (SHH) subgroup medulloblastoma (MB) and provide an overview of MB progression through SHH …

On The Relationship Of Diabetes And Sleep Apnea: Evolution And Epigenetics, Nancy Wilson

Undergraduate Honors Theses

This thesis gives an overview of the relationship between diabetes, sleep apnea, obesity, and heart disease. It then addresses evidence that the traditional understanding of this relationship is incomplete or misleading. In the process, there is a brief discussion of the evolutionary rationale for the development and retention of sleep apnea in light of blood sugar dysregulation, as an adaptive mechanism in response to environmental stressors, followed by a brief overview of the general concepts of epigenetics. Finally, this paper presents the results of a literature search on the epigenetic marks and changes in gene expression found in sleep apnea …

Bioactive Recombinant Human Oncostatin M For Nmr-Based Screening In Drug Discovery, Olga A. Mass, Joseph Tuccinardi, Luke Woodbury, Cody L. Wolf, Bri Grantham, Kelsey Holdaway, Xinzhu Pu, Matthew D. King, Don L. Warner, Cheryl L. Jorcyk, Lisa R. Warner

Biomedical Research Institute Publications and Presentations

Oncostatin M (OSM) is a pleiotropic, interleukin-6 family inflammatory cytokine that plays an important role in inflammatory diseases, including inflammatory bowel disease, rheumatoid arthritis, and cancer progression and metastasis. Recently, elevated OSM levels have been found in the serum of COVID-19 patients in intensive care units. Multiple anti-OSM therapeutics have been investigated, but to date no OSM small molecule inhibitors are clinically available. To pursue a high-throughput screening and structure-based drug discovery strategy to design a small molecule inhibitor of OSM, milligram quantities of highly pure, bioactive OSM are required. Here, we developed a reliable protocol to produce highly pure …

Quantifying Phosphatidylethanol From Blood Samples, James V. Defrancesco, Majid Afshar

Chemistry: Faculty Publications and Other Works

Disclosed herein is a method for quantifying phosphatidylethanol (“ PEth ”), direct ethanol biomarker, from a blood sample using gas chromatography mass spectrometry. The method disclosed herein is useful for diagnosing acute and chronic alcohol abuse.

Pgc1Α Is Required For The Renoprotective Effect Of Lncrna Tug1 In Vivo And Links Tug1 With Urea Cycle Metabolites, Li Li, Jianyin Long, Koki Mise, Daniel L Galvan, Paul A Overbeek, Lin Tan, Shwetha V Kumar, Wai Kin Chan, Phillip L Lorenzi, Benny H Chang, Farhad R Danesh

Faculty, Staff and Students Publications

lncRNA taurine-upregulated gene 1 (Tug1) is a promising therapeutic target in the progression of diabetic nephropathy (DN), but the molecular basis of its protection remains poorly understood. Here, we generate a triple-mutant diabetic mouse model coupled with metabolomic profiling data to interrogate whether Tug1 interaction with peroxisome proliferator-activated receptor gamma coactivator 1α (PGC1α) is required for mitochondrial remodeling and progression of DN in vivo. We find that, compared with diabetic conditional deletion of Pgc1α in podocytes alone (db/db; Pgc1αPod-f/f), diabetic Pgc1α knockout combined with podocyte-specific Tug1 overexpression (db/db; TugPodTg; Pgc1αPod-f/f) reverses the protective phenotype of …

Identification Of Fluoxetine-Sert Interactions And Apo-Sert Studies Via Crosslinking Mass Spectrometry, Elizabeth Castellano

Electronic Theses and Dissertations

The serotonin transporter (SERT) is a member of the neurotransmitter sodium symporter family of transporters. SERT controls the magnitude and duration of serotonergic neurotransmission by facilitating the reuptake of serotonin back into the pre-synaptic neuron and is thus a target for antidepressants. Selective serotonin re-uptake inhibitors (SSRIs) such as fluoxetine, are commonly prescribed to treat depression. SSRIs act by blocking reuptake and prolonging serotonin signaling. However, significant problems regarding selectivity and mechanisms of action of these drugs remain unresolved. The structures of SERT and related transporters have been determined and serve as useful structural models. However, they are typically mutated …

A Noncoding Rna Modulator Potentiates Phenylalanine Metabolism In Mice, Yajuan Li, Zhi Tan, Yaohua Zhang, Zhao Zhang, Qingsong Hu, Ke Liang, Yao Jun, Youqiong Ye, Yi-Chuan Li, Chunlai Li, Lan Liao, Jianming Xu, Zhen Xing, Yinghong Pan, Sujash S Chatterjee, Tina K Nguyen, Heidi Hsiao, Sergey D Egranov, Nagireddy Putluri, Cristian Coarfa, David H Hawke, Preethi H Gunaratne, Kuang-Lei Tsai, Leng Han, Mien-Chie Hung, George A Calin, Fares Namour, Jean-Louis Guéant, Ania C Muntau, Nenad Blau, V Reid Sutton, Manuel Schiff, François Feillet, Shuxing Zhang, Chunru Lin, Liuqing Yang

Faculty, Staff and Students Publications

The functional role of long noncoding RNAs (lncRNAs) in inherited metabolic disorders, including phenylketonuria (PKU), is unknown. We demonstrated that the mouse lncRNA Pair and human HULC associate with phenylalanine hydroxylase (PAH). Pair-knockout mice exhibited excessive blood phenylalanine, musty odor, hypopigmentation, growth retardation, and progressive neurological symptoms including seizures, which faithfully models human PKU. HULC depletion led to reduced PAH enzymatic activities in human induced pluripotent stem cell (hiPSC)-differentiated hepatocytes. Mechanistically, HULC modulated the enzymatic activities of PAH by facilitating PAH-substrate and PAH-cofactor interactions. To develop a therapeutic strategy for restoring liver lncRNAs, we designed GalNAc-tagged lncRNA mimics that …

Hydrodynamic Characteristics Of The Shortfin Mako Shark (Isurus Oxyrinchus) For Two Caudal Fin Morphologies, Matthew C. Rodriguez

Electronic Theses and Dissertations

No abstract provided.

Mucinomics: A Bioinformatic Analysis Of Snail Mucins, And Their Function, Maxwell B. Mcdermott

Theses and Dissertations

This thesis outlines the current research on secreted snail mucus, highlighting the potential of this biopolymer, and also demonstrates a research strategy to fulfill the unmet need of examining the hierarchical structures that lead to the enormous biological and chemical diversity of snail mucus genes.

Application Of Artificial Intelligence And Machine Learning In Chemistry, Niraj Verma

Chemistry Theses and Dissertations

In the last four years, I have been exposed to various topics in scientific research under the supervision of Dr. Kraka in the CATCO group. Numerous involved chemistry projects were undertaken to gain an understanding of the basic laws of nature involving vibrational spectroscopy, molecular acidity, and catalysts based on transition metals for halogen chemistry. The insights from computational chemistry were then applied to model and predict various complicated problems in chemistry via artificial intelligence. With the help of classical artificial intelligence, the non-covalent interactions governing the properties of proteins and water properties were analyzed. Significant improvements were made in …

A Multi-Approach And Multi-Scale Platform To Model Cd4+ T Cells Responding To Infections, Kenneth Y. Wertheim, Bhanwar Lal Puniya, Alyssa La Fleur, Ab Rauf Shah, Matteo Barberis, Tomáš Helikar

Department of Biochemistry: Faculty Publications

Immune responses rely on a complex adaptive system in which the body and infections interact at multiple scales and in different compartments. We developed a modular model of CD4+ T cells, which uses four modeling approaches to integrate processes at three spatial scales in different tissues. In each cell, signal transduction and gene regulation are described by a logical model, metabolism by constraint-based models. Cell population dynamics are described by an agent-based model and systemic cytokine concentrations by ordinary differential equations. A Monte Carlo simulation algorithm allows information to flow efficiently between the four modules by separating the time scales. …