Biochemistry Commons^™

Protein Oxidation In Aging And Alzheimer’S Disease Brain, Rukhsana Sultana, D. Allan Butterfield

Markey Cancer Center Faculty Publications

Proteins are essential molecules that play crucial roles in maintaining cellular homeostasis and carrying out biological functions such as catalyzing biochemical reactions, structural proteins, immune response, etc. However, proteins also are highly susceptible to damage by reactive oxygen species (ROS) and reactive nitrogen species (RNS). In this review, we summarize the role of protein oxidation in normal aging and Alzheimer’s disease (AD). The major emphasis of this review article is on the carbonylation and nitration of proteins in AD and mild cognitive impairment (MCI). The oxidatively modified proteins showed a strong correlation with the reported changes in brain structure, carbohydrate …

Predicting The Pathway Involvement Of Metabolites Based On Combined Metabolite And Pathway Features, Erik D. Huckvale, Hunter N. B. Moseley

Markey Cancer Center Faculty Publications

A major limitation of most metabolomics datasets is the sparsity of pathway annotations for detected metabolites. It is common for less than half of the identified metabolites in these datasets to have a known metabolic pathway involvement. Trying to address this limitation, machine learning models have been developed to predict the association of a metabolite with a “pathway category”, as defined by a metabolic knowledge base like KEGG. Past models were implemented as a single binary classifier specific to a single pathway category, requiring a set of binary classifiers for generating the predictions for multiple pathway categories. This past approach …

Homeobox A10: Regulator Of Pancreatic Cancer Progression And Survival, Sophia G. Kisling

Theses & Dissertations

Pancreatic ductal adenocarcinoma (PDAC) has one of the lowest incidence rates among all major cancers, yet it is disproportionally responsible for 8% of all cancer deaths. This high death rate is primarily attributed to the immunosuppressive tumor microenvironment and a lack of clinically relevant molecular targets. However, the underlying biology responsible for these poor outcomes remains obscure. To facilitate improved management of PDAC, an in-depth understanding of the molecular player(s) involved in PDAC aggressiveness is needed. Therefore, we analyzed the transcriptomic profiles of PDAC patients with long- and short-term survival and performed gene set enrichment analysis (GSEA), identifying a novel …

Targeting Lifr/C-Myc/Ddx21 Axis To Overcome Docetaxel Resistance In Prostate Cancer, Sushanta Halder

Theses & Dissertations

Resistance to chemotherapy poses a significant challenge in the treatment of advanced-stage prostate cancer (PCa), specifically with chemotherapy drugs like docetaxel (Doce), which is often employed after the failure of hormone therapy. However, 50-90% of PCa patients develop resistance to docetaxel within three years of post-chemo treatment, compounded by serious adverse side effects necessitating dose reductions. Various strategies are being investigated to address this issue, including identifying new therapeutic targets or mechanisms, developing novel combination therapies, and optimizing dosing regimens. In particular, our research is focused on uncovering the underlying mechanisms of resistance to docetaxel, such as the activation of …

Mucins: Drivers Of Cancer Cell And Microenvironment Crosstalk In Pancreatic Cancer, Xiaoqi Li

Theses & Dissertations

Mucins facilitate the pancreatic cancer (PC) initiation, progression, and metastasis. Among mucins, MUC4 has been reported to inhibit lymphokine-activated cell killing and induce the apoptosis of cytotoxic T-cells. Counterintuitively, MUC4 expression is upregulated by multiple T-cell-secreted cytokines, such as IFN-γ, IL-17, and stroma-secreted factors like retinoic acid. Previously, we have identified that nuclear receptor coactivator 3 (NCOA3) regulates the MUC1 and MUC4 expression by increasing chromatin accessibility and maintaining protein stability. However, the comprehensive crosstalk mediated by MUC4 in cancer cells and T-cells and how its upstream regulator, NCOA3, modifies the cancer cell-intrinsic behavior is still elusive. Here, we show …

Identifying The Molecular Determinants Of Lung Metastatic Adaptation In Prostate Cancer, Grace M. Waldron

Theses & Dissertations

Prostate cancer (PC) stands as the primary diagnosed cancer in men in the US at approximately 299,010 cases in 2024 and ranks second globally, posing a significant public health challenge. Clinical presentations vary widely, from indolent to aggressive forms, necessitating stage-specific treatment regimens. Understanding its metastatic nature is critical due to the impact of cancer cell dissemination on disease morbidity, with bone and visceral organs serving as key sites of metastasis. Despite bone metastasis being the most common site for metastasis, visceral metastases at sites such as the liver and lungs correlate with poorer survival, emphasizing the role of microenvironmental …

A Study Of The Effects Of An Amino Acid Residue On The Thermal Stability Of A Collagen Triple Helix In Varied Sequence Context, Ph, And Ionic Strength Of The Buffer, Zhenxun Xu

Theses and Dissertations

Collagen mimetic peptides are used broadly for collagen research and biomedical applications. Unlike the synthetic peptides obtained by solid phase chemical synthesis, recombinant peptides have more than 100 amino acid residues in length and are expressed in E. coli using designed genes. These longer peptides can offer improved, more native-like functions of native collagen for biomedical applications. One major challenge is the intrinsically low stability of native collagen, which has a melting temperature just above the physiological temperature of the organism. To understand how to enhance the thermostability of the peptides, I investigated the effects of amino acid sequences on …

Understanding The Non-Canonical Regulation Of Srebp In Aspergillus Fumigatus, Muhammad Abubakar Khan

Dartmouth College Ph.D Dissertations

Aspergillus fumigatus is an opportunistic fungal pathogen causing invasive pulmonary aspergillosis (IPA), with high mortality rates in immunocompromised individuals. Adaptation to the hypoxic microenvironment of IPA is crucial for fungal virulence. The transcription factor SrbA, a Sterol Regulatory Element-Binding Protein (SREBP) homolog, plays a key role in this hypoxic response and regulates genes involved in hypoxic growth, sterol biosynthesis, and azole resistance, making it an attractive therapeutic target.

However, SrbA activation in A. fumigatus lacks critical components of the canonical SREBP pathway, such as SCAP, Site-1 protease (S1P), and Site-2 protease (S2P). Instead, the rhomboid protease RbdB, signal peptide peptidase …

Incorporating Solvent Effects In Dft: Insights From Cation Exchange In Faujasites, An T. Ta, Ayoub Daouli, R. Seaton Ullberg, Eric Fonseca, Vanessa Proust, Agnès Grandjean, Richard G. Hennig, Hans Conrad Zur Loye, Michael Badawi, Simon R. Phillpot

Faculty Publications

Zeolites are versatile materials renowned for their extra-framework cation exchange capabilities, with applications spanning diverse fields, including nuclear waste treatment. While detailed experimental characterization offers valuable insight, density functional theory (DFT) proves particularly adept at investigating ion exchange in zeolites, owing to its atomic and electronic resolution. However, the prevalent occurrence of zeolitic ion exchange in aqueous environments poses a challenge to conventional DFT modeling, traditionally conducted in a vacuum. This study seeks to enhance zeolite modeling by systematically evaluating predictive differences across varying degrees of aqueous solvent inclusion. Specifically focusing on monovalent cation exchange in Na-X zeolites, we explore …

Fiddler Crab Gut Microbiomes As An Indicator For Eutrophication Due To Waste-Water Contamination In Estuaries, Madison L. Geraci

Honors Theses

Estuaries are unique biogeochemical zones in coastal systems that provide a myriad of ecological functions: providing habitat for critically important fishery species, diverse species of plants and animals, and contributing to nutrient cycling. Estuaries are vulnerable to anthropogenic stressors as they are intersections between marine and terrestrial communities and are often the hotspot of coastal development and activity. Estuarine sediments act as repositories for anthropogenic contaminants, including excess nutrient runoffs and waste-water pollution that can cause states of eutrophication. Microorganisms are sensitive to these environmental changes, presenting a unique opportunity of being useful bioindicators of environmental stress. Isolating microorganisms from …

An Investigation Of Protein Arginine Methyltransferase 1 Substrate Recognition Through Ribonucleoprotein Modifications, Isabella Beverly Lonardo

Undergraduate Honors Capstone Projects

Just as humans need to communicate with each other, our cells have a series of processes that allows them to communicate from one to another. Protein Arginine Methyltransferase I is an enzyme that helps mediate cellular communication by selectively binding to target proteins and performing chemistry that has broad-reaching downstream effects. However, the mechanisms that underly PRMT1 selectivity have yet to be elucidated. This study uses alterations to a series of known targets, called ribonucleoproteins, to identify some of the characteristics that govern recognition by the PRMT1 enzyme. I have made significant progress in the creation, expression, and purification of …

Tpm^Ph Derivative Of Tungsten; Hydrogen-Bonding In 7-Coordinate Cation Complex, Olivia Ryon Simcox

Undergraduate Honors Thesis Collection

Tpm^Ph, or tris(3-phenylpyrazolyl)methane reacts with tungsten hexacarbonyl to form the ligand-metal complex tris(3-phenylpyrazolyl)methane tungsten tricarbonyl, or Tpm^PhW(CO)3. The further complexes of Tpm^PhW(CO)3 and Tpm^PhMo(CO)3 are not known. This project aims to explore how the addition of a phenyl substituent to the pyrazole ring on Tpm impacts the synthesis of [Tpm^PhW(CO)3I]+X– and [Tpm^PhW(CO)3H]+X–. The inclusion of this phenyl substituent may impact the possible hydrogen bonding of then hydrogen contained in the carbon-hydrogen bond. This work aims to explore the extent of hydrogen-bonding of the carbon-hydrogen bond of the Tpm^Ph ligand in cationic metal complexes.

Development Of Selective Rna Aptamers For Kainate Receptors, Samantha Ingenito

Legacy Theses & Dissertations (2009 - 2024)

Ionotropic glutamate receptors (iGluRs) play a major role in mediating the excitatoryfunctions in the central nervous system (CNS). iGluRs are ligand-gated ion channels that are activated when glutamate binds to the extracellular ligand binding domain, thereby leading to the opening of the ion channels. Three subtypes of iGluRs include kainate receptors, α-amino-3- hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptors, and N-methyl-D-aspartate (NMDA) receptors. Abnormal and dysregulation of these receptors have cytotoxic effects for neurons and have been implicated in various neurological diseases. For instance, elevated expression of a key AMPA receptor subunit has been linked to conditions such as ALS, where cytotoxic levels …

Pipecolic Acid And Novel Insights Into Cerebral Malaria, Akua E. Mensah

Theses and Dissertations

Cerebral malaria (CM), a severe manifestation of Plasmodium infection, prompts our investigation into the nuanced role of pipecolic acid in its pathophysiology. To unravel the molecular intricacies, we conducted in vitro lysine labeling techniques of mice infected with P. berghei ANKA parasites, and human P. falciparum grown in vitro, aiming to discern the impact of Plasmodium on pipecolic acid production. Previous observations indicated an elevation in pipecolic acid levels correlating with neurological decline in children with CM. In our study, confirming elevated pipecolic acid presence in the plasma and brain tissues of CM patients and the animal model of CM, …

Chm116 Principles Of Chemistry Ii Lecture Slides, Leah S. Cohen, Probal Banerjee

Open Educational Resources

This file contains the lecture slides that are used in CHM116, Principles of Chemistry II.

Design, Synthesis, And Optimization Of Allosteric Inhibitors Of Hiv-1 Integrase, Krunal H. Patel

Dissertations

The human immunodeficiency virus type 1 (HIV-1) infection remains a global health crisis, necessitating the development of innovative antiviral strategies. During the integration step, HIV-1 integrase (IN) interacts with viral DNA and the cellular cofactor LEDGF/p75 to effectively integrate the reverse transcript into the host chromatin. Recently, a novel class of antiretroviral agents called Allosteric Inhibitors of HIV-1 Integrase (ALLINI) compounds has emerged as a promising avenue in the fight against HIV-1. While originally designed to inhibit IN-LEDGF/p75 interactions, these compounds have been shown to also impact late-stage viral maturation severely through IN multimerization. Induction of IN multimerization interferes with …

A Review Of Rheb Activation Of Mtorc1 And The Great Mystery Of One Missing Gef, Jack Gregory

Senior Honors Theses

The mTORC1 pathway is involved in the regulation of cell growth and translation. The pathway has a complex web of activators and inhibitors to activate mTORC1. mTORC1 is regulated via a small GTPase called Rheb, which interacts directly with mTORC1. This GTPase and its GTPase activating protein (GAP), TSC1/2, have been widely studied to understand how the variety of regulators of mTORC1 interact with these proteins. Despite this, the guanine nucleotide exchange factor (GEF) of Rheb has yet to be identified. This review broadly analyzes Rheb and mTORC1, their structures, regulations, and interactions, and explores the mystery of the missing …

Plant Model Of Α-Synucleinopathy: Expression Of Α-Synuclein A53t Variant In Hairy Root Cultures Leads To Proteostatic Stress And Dysregulation Of Iron Metabolism, Jasmina Kurepa, Kristen A. Bruce, Greg A. Gerhardt, Jan A. Smalle

Neurology Faculty Publications

Synucleinopathies, typified by Parkinson’s disease (PD), entail the accumulation of α- synuclein (αSyn) aggregates in nerve cells. Various αSyn mutants, including the αSyn A53T variant linked to early-onset PD, increase the propensity for αSyn aggregate formation. In addition to disrupting protein homeostasis and inducing proteostatic stress, the aggregation of αSyn in PD is associated with an imbalance in iron metabolism, which increases the generation of reactive oxygen species and causes oxidative stress. This study explored the impact of αSyn A53T expression in transgenic hairy roots of four medicinal plants (Lobelia cardinalis, Artemisia annua, Salvia miltiorrhiza, and Polygonum multiflorum). In all …

Genetics Of Lrg1 And Its Association With The Cardiometabolic Risk Traits In Mexican American Children And Adolescents, Aaron Rene Reyna

Theses and Dissertations

Leucine-rich alpha-2-glycoprotein 1 (LRG1) has become a major topic of research due to an increasing number of studies demonstrating its unique role in the pathogenesis of multiple human diseases including diabetes and cardiovascular disease. LRG1 has recently been identified as an adipokine, a signaling molecule secreted by adipose tissue. Furthermore, it has been correlated with intercellular signaling that promotes diet-induced hepatosteatosis and insulin resistance in mice. In this study, LRG1 serum concentrations were measured in a family-based cohort of 571 non-diabetic Mexican American children and adolescents aged 6-17 years old (mean age = 11.76 years and females = 48.2%) to …

Effects Of Nitrogen Or Phosphorus Depletion On Lipid Production In Bracteacoccus Sp. And Tetrastrum Sp., Cassandra J. Po

Theses and Dissertations

As global energy demands have risen in the past decades, various species of microalgae have been chosen and used as sources of lipids for third-generation biofuel. I selected two species of green microalgae, Bracteacoccus sp. and Tetrastrum sp., from isolates from South Texas to determine their potential as sources of biofuel. For comparison, Chlamydomonas reinhardtii was used as a model organism. To evaluate lipid productivity under different nutrient regimens, the microalgae were grown in nutrient-replete growth media until the population had reached the end of the logarithmic phase (roughly 14 days), and then transferred into growth media depleted of nitrogen …