Biochemistry Commons^™

Alopecia As An Early Clinical Marker For Azathioprine Induced Myelosuppression: A Case Report, Nilanjana Dutta , Final Year Mbbs, Dr. M Suresh Babu , Professor, Dr. Subramanian Ramaswamy , Professor, Dr. Mahabaleshwar Mamadapur , Assistant Professor

Digital Journal of Clinical Medicine

Azathioprine is a pro-drug and is metabolized by the TPMT enzyme in the body. In South Asians, Azathioprine is known to cause alopecia and bone marrow suppression in patients with TPMT enzyme deficiency. In India, the prevalence of TPMT mutation varies from 1.2- 10%. A new mutation was detected in 2014, NUDT15 whose incidence varies from 8.5-16%. Patients with mutation in both TPMT and NUDT15 develop myelosuppression faster. In our case, alopecia manifested as the first clinical feature of Azathioprine myelosuppression. Physicians need to recognize early clinical clues (alopecia) to avoid the impending development of myelosuppression and to look for …

Mechanistic Analysis Of Four-Way Dna Junctions And Cytokine-Binding Aptamers For Therapeutic Interventions, Roaa S. Mahmoud

Theses and Dissertations

DNA is inherently dynamic and topologically diverse and can fold into many different structures. Besides the canonical Watson-Crick structure, other higher-order structures such as G-quadruplexes (G4), i-motifs (iM), and four-way DNA junctions are possible. Although these high-order DNA structures are known to form transiently, they are important due to the crucial roles they play in many cellular processes including DNA replication, recombination, and repair. Among these DNA structures, 4-way junctions (also known as Holliday junctions, HJ) which are formed during the repair of double-strand DNA breaks (DSBs) and interact with proteins have garnered significant attention due to their central role …

Synthesis And Biophysical Analysis Of Modified Cell-Penetrating Peptides, Joel Mitchell

Theses and Dissertations (Comprehensive)

Cell-penetrating peptides (CPPs) are a family of peptides that have the ability to penetrate biological membranes. They were discovered in the late 1980s and have been the topic of many studies. Much of the interest in CPPs has been due to their ability to translocate biological membranes, and the possibility that they could offer a novel drug delivery method by conjugation to biologically active molecules. Linear CPPs can be modified to form cyclic structures. This change in structure has been observed to enhance the stability and penetrative ability of the CPPs which have been studied. The current thesis focuses on …

Novel Photobase Generators For Photoinduced Polymerization And Ph Regulation, Shupei Yu

Dissertations

Photochemistry encompasses the investigation of chemical processes instigated by light absorption. As important branches of photochemistry, photosensitive and optical materials have attracted extensive research interests in both academia and industry. Photosensitive and optical materials are composed of polymers / small molecules with photo-responsive properties. These materials not only can absorb light in the desired energy spectrum, but also exhibit chemical / physical reactions, which can be applied to different fields such as photoredox, photo-heat, phototherapy, solar cells, diodes, etc. Among them, photobase generators (PBGs) are a series of photosensitive compounds, which absorb the incident light, then release the basic species …

Reducing Food Scarcity: The Benefits Of Urban Farming, S.A. Claudell, Emilio Mejia

Journal of Nonprofit Innovation

Urban farming can enhance the lives of communities and help reduce food scarcity. This paper presents a conceptual prototype of an efficient urban farming community that can be scaled for a single apartment building or an entire community across all global geoeconomics regions, including densely populated cities and rural, developing towns and communities. When deployed in coordination with smart crop choices, local farm support, and efficient transportation then the result isn’t just sustainability, but also increasing fresh produce accessibility, optimizing nutritional value, eliminating the use of ‘forever chemicals’, reducing transportation costs, and fostering global environmental benefits.

Imagine Doris, who is …

Structural Basis For Dna Proofreading, Gina Buchel, Ashok Nayak, Karl Herbine, Azadeh Sarfallah, Viktoriia Sokolova, Angelica Zamudio-Ochoa, Dmitry Temiakov

Department of Biochemistry and Molecular Biology Faculty Papers

DNA polymerase (DNAP) can correct errors in DNA during replication by proofreading, a process critical for cell viability. However, the mechanism by which an erroneously incorporated base translocates from the polymerase to the exonuclease site and the corrected DNA terminus returns has remained elusive. Here, we present an ensemble of nine high-resolution structures representing human mitochondrial DNA polymerase Gamma, Polγ, captured during consecutive proofreading steps. The structures reveal key events, including mismatched base recognition, its dissociation from the polymerase site, forward translocation of DNAP, alterations in DNA trajectory, repositioning and refolding of elements for primer separation, DNAP backtracking, and displacement …

Developing Regulated Crispr Systems To Control Bacterial Microbiomes, Gregory M. Pellegrino

Electronic Thesis and Dissertation Repository

Changes to the human microbiome’s composition and metabolome are associated with numerous diseases and alterations to xenobiotic metabolism. As such, targeting the human microbiome is an increasingly popular option for therapeutic interventions. However, traditional therapies that target the microbiome such as antibiotics lack specificity, which can affect the beneficial species of the microbiome and cause adverse health outcomes such as the rise of antimicrobial-resistant bacteria. Therefore, the research and development of specific, targeted antimicrobial therapies is crucial to effectively treating microbiome dysbioses.
CRISPR and CRISPRi provide easily modifiable, RNA-guided mechanisms mediated by the Cas9 or dCas9 enzymes to induce sequence-specific …

On The Anti-Adipogenic Function Of Collagen Triple Helix Repeat-Containing Protein 1, Matthew E. Siviski

Electronic Theses and Dissertations

Adipogenesis is regulated by the coordinated activity of adipogenic transcription factors, including PPAR-gamma (PPARG) and C/EBP alpha (CEBPA). Thus, dysregulated adipogenesis predisposes adipose tissues to adipocyte hypertrophy and hyperplasia. We have previously reported that mice possessing a homozygous null gene mutation in collagen triple helix repeat-containing protein 1 (CTHRC1) have increased adiposity compared to wildtype mice, supporting the concept that CTHRC1 regulates body composition. Herein, we investigated the anti-adipogenic activity of CTHRC1. Using 3T3-L1 preadipocytes, we showed significantly reduced adipogenic differentiation in the presence of CTHRC1 commensurate to marked suppression of Cebpa and Pparg gene expression. In addition, CTHRC1 increased …

Mutational Analysis Of The Nitrogenase Carbon Monoxide Protective Protein Cown Reveals That A Conserved C‑Terminal Glutamic Acid Residue Is Necessary For Its Activity, Dustin L. Willard, Joshuah J. Arellano, Mitch Underdahl, Terrence M. Lee, Avinash S. Ramaswamy, Gabriella Fumes, Agatha Kliman, Emily Y. Wong, Cedric P. Owens

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Nitrogenase is the only enzyme that catalyzes the reduction of nitrogen gas into ammonia. Nitrogenase is tightly inhibited by the environmental gas carbon monoxide (CO). Many nitrogen fixing bacteria protect nitrogenase from CO inhibition using the protective protein CowN. This work demonstrates that a conserved glutamic acid residue near the C-terminus of Gluconacetobacter diazotrophicus CowN is necessary for its function. Mutation of the glutamic acid residue abolishes both CowN’s protection against CO inhibition and the ability of CowN to bind to nitrogenase. In contrast, a conserved C-terminal cysteine residue is not important for CO protection by CowN. Overall, this work …

Role Of Prmt5 In Ulk1-Mediated Autophagy And Breast Cancer Therapy, Charles Brobbey

MUSC Theses and Dissertations

PRMT5 (Protein arginine methyltransferase 5) is the predominant type II PRMT that monomethylates and symmetrically dimethylates arginine residues of histone and none- histone proteins to regulate diverse cellular processes. PRMT5 overexpression has been implicated in tumorigenesis and other diseases and has gained trac1on as a poten1al an1tumor target with some of its inhibitors being tested in clinical trials. Despite the well- established an1tumor effect of PRMT5 inhibitors, how the efficacy of these inhibitors is regulated is unexplored. We show in this study that autophagy blockage enhances cellular sensi1vity to PRMT5 inhibitor in triple nega1ve breast cancer cells. Both gene1c deple1on …

Biophysical Factors Affecting Habitat Suitability For Crassostrea Virginica, Jason D. Tilley

Dissertations

Oyster reefs provide a variety of important ecosystem services. However, the mortality rate of eastern oyster, Crassostrea virginica, the dominant species that produces oyster reefs in the northern Gulf of Mexico, is increasing at an alarming rate due to a variety of abiotic and biological factors. I examined how biophysical factors, including the less-studied fatty acid profiles of the suspended particulate matter on which oysters feed, influenced morphometric condition of C. virginica.

I sampled suspended particulate matter (SPM) and oysters in-situ in the western Mississippi Sound, which historically supported the majority of oyster production in Mississippi waters. Sampling …

Effects Of Dimerization On The Deacylase Activities Of Human Sirt2., Jie Yang, Nathan I Nicely, Brian P Weiser

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

Human sirtuin isoform 2 (SIRT2) is an NAD+-dependent enzyme that functions as a lysine deacetylase and defatty-acylase. Here, we report that SIRT2 readily dimerizes in solution and in cells and that dimerization affects its ability to remove different acyl modifications from substrates. Dimerization of recombinant SIRT2 was revealed with analytical size exclusion chromatography and chemical cross-linking. Dimerized SIRT2 dissociates into monomers upon binding long fatty acylated substrates (decanoyl-, dodecanoyl-, and myristoyl-lysine). However, we did not observe dissociation of dimeric SIRT2 in the presence of acetyl-lysine. Analysis of X-ray crystal structures led us to discover a SIRT2 double mutant (Q142A/E340A) that …

Diaryl Oxazoles As Cleavable Linkers For Drug Discovery Platforms, Elizabeth Taggart

Honors Theses

Within the field of medicine and pharmacology, discovering small molecule or biologic based molecules with therapeutic potential is a difficult task. Current methods involve individually screening hundreds of compounds on a potential target biomolecule, and recent technologies have explored peptide encoded libraries (PELs) as a means of making this screening process more high-throughput. These libraries produce a large number of small molecule drug candidates each conjugated to a unique peptide fragment, functioning as a barcode. Analysis of PELs requires the capture of hit small molecules and the subsequent release of their peptide tags; however, current approaches are limited in their …

Synthesis Of Bacterial Glycerophospholipids For Biomembrane Model Studies: A Means To Advanced Biofuels, Felix Adulley

Electronic Theses and Dissertations

To reduce reliance on fossil fuels, sustainable biofuels are being pursued, especially advanced biofuels like 1-butanol that have higher energy content and greater compatibility with existing infrastructure than ethanol. A persistent challenge is the yield-limiting toxicity of biofuels and process solvents, such as tetrahydrofuran, to the microbes that ferment biomass into biofuel. The cell membrane is a focal point of toxicity, and understanding how it interacts with fuels and solvents is key to improving yield. Phospholipid bilayers are the core of biomembranes, and model biomembranes of defined composition provide the ideal platform for biophysical studies. To this end, glycerophospholipids characteristic …

Flavonol Glucosylation: A Structural Investigation Of The Flavonol Specific 3-O Glucosyltransferase Cp3gt, Aaron S. Birchfield

Electronic Theses and Dissertations

Flavonoid glycosyltransferases (GTs), enzymes integral to plant ecological responses and human pharmacology, necessitate rigorous structural elucidation to decipher their mechanistic function and substrate specificity, particularly given their role in the biotransformation of diverse pharmacological agents and natural products. This investigation delved into a comprehensive exploration of the flavonol 3-O GT from Citrus paradisi (Cp3GT), scrutinizing the impact of a c-terminal c-myc/6x histidine tag on its enzymatic activity and substrate specificity, and successfully achieving its purification to apparent homogeneity. This established a strong foundation for potential future crystallographic and other structure/function analyses. Through the strategic implementation of site-directed mutagenesis, a thrombin …

The Identification Of Small Molecule Inhibitors To Candida Albicans Phosphatidylserine Synthase, Yue Zhou

Doctoral Dissertations

Candida albicans phosphatidylserine (PS) synthase, encoded by the CHO1 gene, has been identified as a potential drug target for new antifungals against systemic candidiasis due to its importance in virulence, absence in the host and conservation among fungal pathogens. This dissertation is focused on the identification of inhibitors for this membrane enzyme. Cho1 has two substrates: cytidyldiphosphate-diacylglycerol (CDP-DAG) and serine. Previous studies identified a conserved CDP-alcohol phosphotransferase (CAPT) binding motif present within Cho1, and here we revealed that mutations in all but one conserved amino acid within the CAPT motif resulted in decreased Cho1. For serine, we have predicted a …

Characterization Of Lignin Structural Variability And The Associated Application In Genome Wide Association Studies, Nathan D. Bryant

Doctoral Dissertations

Poplar (Populus sp.) is a promising biofuel feedstock due to advantageous features such as fast growth, the ability to grow on marginal land, and relatively low lignin content. However, there is tremendous variability associated with the composition of biomass. Understanding this variability, especially in lignin, is crucial to developing and implementing financially viable, integrated biorefineries. Although lignin is typically described as being comprised of three primary monolignols (syringyl, guaiacyl, p-hydroxyphenyl), it is a highly irregular biopolymer that can incorporate non-canonical monolignols. It is also connected by a variety of interunit linkages, adding to its complexity. Secondary cell wall …

A Cancer-Specific Study On The Differentially Expressed Protein-Protein Interactions Of Fumarate Hydratase, Sydney Lac

Dissertations & Theses (Open Access)

Fumarate hydratase (FH) is an enzyme used in the Krebs Cycle to convert fumarate to malate, and it is controlled by the FH gene. In this paper, we will investigate its role in Uterine Corpus Endometrial Carcinoma (UCEC) and how FH-deficient cells affect tumorigenesis. It is well-established that FH has been extensively studied in connection with renal cell carcinoma, skin and uterine leiomyomas, pheochromocytoma, and paraganglioma. However, we aim to construct an interaction network of significant genes related to the FH gene under conditions of FH deficiency in the Kreb Cycle. Creating an interactive network that illustrates the interconnectedness of …

Biochemical And Kinetic Analysis Of Phosphofructokinase In The Eukaryotic Human Pathogen Entamoeba Histolytica, Jin Cho

All Dissertations

Entamoeba histolytica is a water- and food-borne intestinal parasite that causes amoebiasis and liver abscess in ~100 million people each year leading to ~100,000 deaths. This amitochondriate parasite lacks many metabolic pathways including the tricarboxylic acid cycle and oxidative phosphorylation, and cannot synthesize purines, pyrimidines, or most amino acids. As a result, E. histolytica is presumed to rely on its modified pyrophosphate (PP_i)-dependent glycolytic pathway for ATP production during growth on glucose. This pathway relies on a PP_i-dependent rather than ATP-dependent phosphofructokinase (PFK) and thus has a net production of three ATP per glucose. However, in …

The Discovery Of Diverse Picophytoplankton Populations In The Columbia And Willamette Rivers Using Flow Cytometry, Kylee Brevick

Chemistry Undergraduate Departmental Honors Theses

As important primary producers, picophytoplankton determine the flow of carbon and energy in aquatic ecosystems. Picocyanobacteria are one picophytoplankton group known to be dominant in oceans and lakes, but they are still poorly understood in river systems. This project examined picophytoplankton communities in two distinct river systems: the Columbia and Willamette Rivers in Portland, Oregon. I aimed to characterize and quantify the picophytoplankton populations in the context of the environmental conditions of the two rivers. I used flow cytometry to detect cells based on their relative size and pigment fluorescence. I sampled nearly weekly for ten months to capture population …

Interfacial Interactions Between Engineered Nanoplastics And Biological Systems: Towards An Atomic And Molecular Understanding Of Plastics- Driven Cellular Dyshomeostasis, Afroz Karim

Open Access Theses & Dissertations

The persistent presence of micro (nano) plastics in our environment has raised concerns regarding potential health risks associated with human exposure. With the extensive use of plastic materials and the widespread consumption of plastic-contaminated food items, two types of microplastics, polystyrene (PS) and polymethylmethacrylate (PMMA), have attracted increased attention. While the adverse effects of microplastics on animals and marine life have been extensively studied, their potential impact on human health remains largely unexplored. Specifically, the interaction between microplastics and biomolecules within the human body and their effect on human health have yet to be comprehensively investigated. This dissertation study focuses …

Biochemical Analyses Of Udgx-A Crosslinking Uracil-Dna Glycosylase, Chuan Liang

All Dissertations

DNA base damage is common due to exposure to various endogenous and exogenous factors. To repair the base lesions, such as uracil from cytosine deamination, enzymes from the uracil-DNA glycosylase (UDG) superfamily are critical, which can recognize the damaged base and initiate the base excision repair (BER) pathway. There used to be six families of proteins identified in the UDG superfamily until a new member, UDGX, was found in Mycobacterium smegmatis, which is a unique DNA-crosslinking UDG. In this dissertation work, a series of biochemical analyses of the newly found UDGX are performed, including the analyses of structures, functions, …

Characterization Of The Effects Of The Pyrazolopyrimidine Inhibitor Grassofermata (Nav-2729) In The Eukaryotic Pathogen Trypanosoma Brucei, Kristina Marie Parman

All Dissertations

The protozoan pathogen, Trypanosoma brucei, is the causative agent of sleeping sickness in humans and nagana in livestock in sub-Saharan Africa. T. brucei cycles between tsetse fly and mammalian hosts, and it is adapted to survive in diverse host tissues. Variant Surface Glycoprotein (VSG) plays a key role in immune evasion in the mammalian host. The VSG membrane anchor requires two myristates, 14-carbon saturated fatty acids (FAs) that are scarce in the host. T. brucei can synthesize FAs de novo, but also readily takes up exogenous FAs, despite lacking homologs to fatty acid uptake proteins found in other …

Growth, Yield, And Photosynthetic Dry Matter Remobilization Response Of Barley To Plant Growth Promoting Rhizobacteria (Pgpr) And Nitrogen, Abazar Abbasi, Shahram Mehri, Hossein Solimanzadeh, Saeid Alipour

The Philippine Agricultural Scientist

A two-year factorial experiment based on a randomized complete block design with three replicates was carried out on barley cultivar LB-IRAN at the research farm of the Islamic Azad University, Ardabil, Iran, during the cropping years of 2019–2021, in order to survey the impact of plant growth-promoting rhizobacteria (PGPR) and nitrogen fertilizer on growth, yield, and remobilization of photosynthetic dry matter in barley. The first factor included five nitrogen levels: 0 (control), 25, 50, 75, 100 kg/ha net nitrogen; the second factor contained grain inoculations with four bacteria: no inoculation (control), Azotobacter chroococcum race 5, Azospirillum lipoferum race of, and …

Amyloid Fibrils Of Human Fgf-1 Induced By Different Detergents, Zeina Ismael Ibrahem Alraawi

Graduate Theses and Dissertations

Nature achieves molecular self-assembly through the ordered growth of nanoscale building blocks with high efficiency to fabricate macromolecular architectures. One example of self- assembly is peptides folding onto protein is one of the most astounding biological self-assembly processes. When proteins aggregate to form amyloid fibers, the secondary structure of the protein converts from its native state to a cross-beta-sheet. Fibroblast growth factors (FGFs) possess an essential role in neuronal survival during development. In addition, they are involved in neural stem cell (NSC) proliferation. Fibroblast growth factors (FGFs) are well known to be synthesized in the central nervous system (CNS) and …

Exploring The Impact Of High-Temperature Stress On Physiological, Anatomical, Molecular, Productive, And Quality Parameters In Diverse Olive Cultivars, Bassam F. Alowaiesh, Taghreed S. Alnusaire

The Philippine Agricultural Scientist

Olive (Olea europaea L.) is one of the most important horticultural crops in Saudi Arabia. High temperatures are typical in most regions during the summer season. This study explored the effect of high temperatures on diverse olive cultivars (Manzanillo, Chemlali, and Picual) grown in three different geographical locations in Saudi Arabia (Sakaka, Basita, and Al-Qurayyat). Sakaka region was classified as a hot region, while the Basita and Al-Qurayyat regions were characterized by relatively mild or low temperatures. Genotypic components were assessed by studying Amplified Fragment Length Polymorphism (AFLP) molecular markers and physiological, anatomical, productive, and oil quality parameters. The …

Characterization Of Human Fibroblast Growth Factor 2 Variant To Determine Effects On Structure, Stability, And Cell Proliferation, Ryan Layes

Graduate Theses and Dissertations

Fibroblast growth factors (FGFs) are a family of cell signaling proteins conserved across multiple species. Each individual FGF elicits different cellular functions including, but not limited to, proliferation, migration, differentiation, angiogenesis, and wound healing. One of the most studied members, fibroblast growth factor 2 (FGF2), has demonstrated substantial wound healing capacity in a wide range of tissues including skeletal, muscular, neural, respiratory, epithelial, and cardiovascular. This ability makes FGF2 a potential therapeutic for a wide range of conditions and injuries. However, due to a short half-life at room temperature, therapeutic use of FGF2 is limited. It has been demonstrated that …

Liquid Chromatography Mass Spectrometry Method Development For The Determination Of Β–Defensins In Bovine Milk, Elisha Ogbebor

Masters Theses & Specialist Projects

Bovine mastitis is caused by a wide range of pathogens which results in a substantial economic loss for the dairy cattle livestock industry. β-defensins are a part of the innate immune system and act as the first line of defense against mastitis in bovine. β-defensins (~6- 10kDa) are antimicrobial peptides that contain about 28 to 67 amino acids, the presence of six cysteine residues results in their three disulfide bonds and a β-sheet structure. A few β- defensins have been identified in cows based on the site of occurrence and time of expression in tissue, but not in milk. A …

Quantifying The Role Of Water Quality On Nitrogen Cycling In A Trophic Estuary, Kayla Gonzalez-Boy

Symposium of Student Scholars

Jobos Bay Estuary is an intertidal, tropical estuary located in southern Puerto Rico. The estuary covers about 12 km² and has a variety of habitats, such as seagrass beds, mangroves, mud flats, and coral reefs, which play important roles in sediment trapping and water quality maintenance. Seagrasses also serve as nursery and feeding grounds and provide shelter for macrofauna. Currently, the role of seagrasses and water quality on nitrogen (N) cycling in trophic estuaries is not well constrained. Understanding variations in sediment-based effects on N cycling rates and transformations, and how they are associated with water quality, is an …

Chemical Composition, Mineral Profile, Anti-Bacterial, And Wound Healing Properties Of Snail Slime Of Helix Aspersa Müller, Marouane Aouji, Amine Rkhaila, Bouchra Bouhaddioui, Malak Zirari, Hala Harifi, Youness Taboz, Lalla Aicha Lrhorfi, Rachid Bengueddour

BioMedicine

Mucus is a substance made by snails that serves a variety of purposes and is increasingly employed in the medical and cosmetic industries. It includes bioactive compounds with a range of biological characteristics that could be useful in the treatment of particular issues. This study assessed the wound-healing efficiency, antibacterial activity, chemical and mineral composition of Helix aspersa Müller slime. Inductively Coupled Argon Plasma Atomic Emission Spectrometry (ICP-OES) was used for mineral analysis, while Gas chromatography coupled to mass spectrometry (GC-MS) analysis was used for chemical characterization. The findings showed that the H. aspersa Müller slime had inhibitory activity on …