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Articles 301 - 330 of 2025

Full-Text Articles in Biochemistry

Engineered Plga Nanofibers For Drug Delivery, Andrew Mancuso Feb 2023

Engineered Plga Nanofibers For Drug Delivery, Andrew Mancuso

Dissertations, Theses, and Capstone Projects

Poly-lactic-co-glycolic acid (PLGA) polymers are rapidly gaining momentum as a platform for next-generation drug delivery systems due to their ease and low cost of synthesis, favorable biocompatibility and biodegradability, and lack of toxicity. In particular, the application of drug-loaded PLGA nanofibers directly to a target tissue may represent a promising alternative to traditional routes of drug administration (e.g., oral, injectable) as they offer the potential to greatly improve bioavailability, increase efficacy, and reduce off-target toxicity. Furthermore, the use of such a system may potentially allow for greater flexibility in clinical drug development, by enabling the use of compounds which have …

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Development Opportunities And Technical Challenges Of Industrialization For Hydrogen Production From Bio-Ethanol Reforming, Xue Han, Hong He, Guojun Yue, Hailong Lin, Jinsong Liu, Bin Yu Jan 2023

Development Opportunities And Technical Challenges Of Industrialization For Hydrogen Production From Bio-Ethanol Reforming, Xue Han, Hong He, Guojun Yue, Hailong Lin, Jinsong Liu, Bin Yu

Bulletin of Chinese Academy of Sciences (Chinese Version)

Bio-ethanol reforming for hydrogen production, using renewable raw materials and adopting mature and efficient chemical processes, is an important source of green hydrogen supply to achieve the goals of carbon peaking and carbon neutrality. Bio-ethanol is a widely used substitute for fossil fuels. With the continuous progress of cellulosic ethanol technology in recent years, bio-ethanol will gradually break through the constraints of starch-based raw material supply. Based on the industrialization achievements of hydrogen production and bio-ethanol, bio-ethanol reforming can realize a rapid linkage with the existing hydrogen energy industry. However, the existence of a carbon-carbon signal bond in ethanol poses …

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Bitumen Aging—Laboratory Simulation Methods Used In Practice And Selected Directions Of Research On New Methods, Paweł Czajkowski, Andrzej Przyjazny, Grzegorz Boczkaj Jan 2023

Bitumen Aging—Laboratory Simulation Methods Used In Practice And Selected Directions Of Research On New Methods, Paweł Czajkowski, Andrzej Przyjazny, Grzegorz Boczkaj

Natural Sciences Publications

Changes in the properties of bitumen binders that occur as a result of aging have a huge impact on the durability of products produced from them. In particular, asphalt pavements, which constitute the most common use of petroleum bitumen, are susceptible to damage resulting from the increasing stiffness of the bitumen during its life cycle. Increased stiffness of asphalt pavements reduces the pavement resistance to low-temperature cracks and fatigue cracks, ultimately leading to the loss of their functional properties and the need for road repair. The rate of changes in bitumen properties is influenced by many factors, the most important …

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Dual Ionic Liquid-Functionalized Cellulosic Materials: Thermal, Mechanical And Conductive Properties, Elizabeth Mcgrew, Kevin M. Miller Phd Jan 2023

Dual Ionic Liquid-Functionalized Cellulosic Materials: Thermal, Mechanical And Conductive Properties, Elizabeth Mcgrew, Kevin M. Miller Phd

Posters-at-the-Capitol

Cellulose, an inexpensive and renewable biomacromolecule, represents an intriguing synthetic foundation for new materials with task-specific properties. Here, we wish to report a synthetic route for functionalizing cellulose with a side chain containing two ionic liquid functional groups using azide-alkyne ‘click’ cyclization strategy, followed by quaternization of the two resulting heterocycles (1,2,3-triazole and imidazole). Through this functionalization strategy, the resulting cellulosic materials exhibited significant softening, with several glass transition (Tg) values observed below room temperature, indicating the amorphous nature of the materials, with the Tg dependent on both the length of the side chain and the …

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Mechanistic Insights Into Mftr-Dependent Regulation Of The Redox Cofactor Mycofactocin, Aigera Mendauletova Jan 2023

Mechanistic Insights Into Mftr-Dependent Regulation Of The Redox Cofactor Mycofactocin, Aigera Mendauletova

Electronic Theses and Dissertations

Organic redox cofactors are essential for life. While classic flavins and nicotinamides are widely distributed across all domains of life, nature has also evolved niche cofactors in subsets of life domains. For example, in Actinobacteria, coenzyme F420 is commonly used in place of flavin mononucleotide in enzymes associated with carbon fixation and oxidation of secondary alcohols. The importance of niche cofactors has long been recognized however, detailed understanding about their biosynthesis and physiological uses has been lagging. One class of niche cofactors is derived from ribosomally synthesized and posttranslationally modified peptides (RiPPs). To achieve their mature form, the genetically …

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Post-Translational Modification Of Proteins Via Ambient Air Pollutants And Endogenous Reactive Species, Rachel Lauren Davey Jan 2023

Post-Translational Modification Of Proteins Via Ambient Air Pollutants And Endogenous Reactive Species, Rachel Lauren Davey

Electronic Theses and Dissertations

Proteins can react with reactive oxygen species (ROS) and reactive nitrogen species (RNS) to form post-translational modifications (PTMs), which can affect protein structure and function. The formation of 3-nitrotyrosine (NTyr) and dityrosine (DiTyr) upon reaction of proteins with ROS/RNS are two common PTMs studied due to their stability and irreversibility, as well as their ability to enhance the allergenicity of pollen allergens upon formation. Many common techniques used to study the formation of these PTMs can reliably detect the PTMs but can only provide semi-quantitative information due to many assumptions and limitations. In Chapter 2 we present an analysis of …

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Novel Application Of Graphene Oxide In Conjunction With Dna Binding Dcas9 For Detecting Antibiotic Resistance Genes, Langley Williams Jan 2023

Novel Application Of Graphene Oxide In Conjunction With Dna Binding Dcas9 For Detecting Antibiotic Resistance Genes, Langley Williams

Mahurin Honors College Capstone Experience/Thesis Projects

The frequent emergence of antibiotic resistance genes poses a stumbling block to prompt treatment of pathogen-originating diseases and therefore spurs the demand for a simple, rapid diagnostic device that can outcompete the time and cost of traditional methods such as PCR and cell culturing. The proposed method for detecting pathogenic DNA utilizes the binding properties of deactivated CRISPR-associated protein9 (dCas9) complexed with fluorescein-labeled single-guide RNA (sgRNA) and the fluorescence quenching properties previously demonstrated in graphene oxide (GO). For our assay, we designed sgRNAs to target specific 20 nucleotide sequences extracted from the tetracycline resistance (tetM) gene sequence and covalently modified …

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Chemistry And Public Policy: Equipping Advocates, Herbert R. Fynewever, I. Bos, C. Demlow, G. Fulkerson Jan 2023

Chemistry And Public Policy: Equipping Advocates, Herbert R. Fynewever, I. Bos, C. Demlow, G. Fulkerson

Summer Research

No abstract provided.

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Identification Of Rickettsia Prowazekii Methionine Aminopeptidase Inhibitors And Development Of Thermal Shift Assays For Burkholderia Pseudomallei Ispf And Sars-Cov-2 3cl Protease, Ishpriya Sharma Jan 2023

Identification Of Rickettsia Prowazekii Methionine Aminopeptidase Inhibitors And Development Of Thermal Shift Assays For Burkholderia Pseudomallei Ispf And Sars-Cov-2 3cl Protease, Ishpriya Sharma

Graduate Research Theses & Dissertations

There is a crucial need for new antibacterial agents to combat the increase in antibiotic resistance. Methionine aminopeptidase (MetAp) is an enzyme that removes the amino-terminal methionine residue from newly synthesized proteins, an important step in the maturation of proteins. As such, MetAp is a target for the development of antibacterial and anticancer agents. One such bacterial target is Rickettsia prowazekii (Rp), the causative agent of epidemic typhus. To discover new inhibitors of RpMetAp1, the MMV Malaria Box, which is a collection of 400 compounds with drug-like and probe-like compounds, was screened using a high throughput fluorescence-based RpMetAp1 enzyme inhibition …

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Structure–Activity Relationship Studies On 6-Chloro-1-Phenylbenzazepines Leads To The Identification Of A New Dopamine D1 Receptor Antagonist, Rajan Giri, Hari K. Namballa, Vishwashiv Emogaje, Wayne W. Harding Jan 2023

Structure–Activity Relationship Studies On 6-Chloro-1-Phenylbenzazepines Leads To The Identification Of A New Dopamine D1 Receptor Antagonist, Rajan Giri, Hari K. Namballa, Vishwashiv Emogaje, Wayne W. Harding

Publications and Research

The 1-phenylbenzazepine template has yielded a number of D1R-like ligands, which, though useful as pharmacological tools, have significant drawbacks in terms of selectivity versus D5R as well as pharmacokinetic behavior. A number of 1-phenylbenzazepines contain a 6-chloro functional group, but extensive SAR studies around the 6-chloro-1-phenylbenzazepine framework have not been reported in the literature. To further understand the tolerance of the 6-chloro-1-phenylbenzazepine template for various substituent groups towards affinity and selectivity at D1R, we synthesized two series of analogs with structural variations at the C-7, C-8, N-3, C-3′ and C-4′ positions. The series 2 analogs differed from …

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Isotopic Evidence For Sources Of Dissolved Carbon And The Role Of Organic Matter Respiration In The Fraser River Basin, Canada, Britta M. Voss, Timothy I. Eglinton, Bernhard Peucker-Ehrenbrink, Valier Galy, Susan Q. Lang, Cameron Mcintyre, Robert G.M. Spencer, Ekaterina Bulygina, Zhaohui Aleck Wang, Katherine A. Guay Jan 2023

Isotopic Evidence For Sources Of Dissolved Carbon And The Role Of Organic Matter Respiration In The Fraser River Basin, Canada, Britta M. Voss, Timothy I. Eglinton, Bernhard Peucker-Ehrenbrink, Valier Galy, Susan Q. Lang, Cameron Mcintyre, Robert G.M. Spencer, Ekaterina Bulygina, Zhaohui Aleck Wang, Katherine A. Guay

OES Faculty Publications

Sources of dissolved and particulate carbon to the Fraser River system vary significantly in space and time. Tributaries in the northern interior of the basin consistently deliver higher concentrations of dissolved organic carbon (DOC) to the main stem than other tributaries. Based on samples collected near the Fraser River mouth throughout 2013, the radiocarbon age of DOC exported from the Fraser River does not change significantly across seasons despite a spike in DOC concentration during the freshet, suggesting modulation of heterogeneous upstream chemical and isotopic signals during transit through the river basin. Dissolved inorganic carbon (DIC) concentrations are highest in …

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Development And Biological Evaluation Of Selective Small-Molecule Inhibitors Of The Human Cytochrome P450 1b1, Austin Hachey Jan 2023

Development And Biological Evaluation Of Selective Small-Molecule Inhibitors Of The Human Cytochrome P450 1b1, Austin Hachey

Theses and Dissertations--Chemistry

The human cytochrome P450 1B1 (CYP1B1) is an emerging target for small- molecule therapeutics. Several solid tumors overexpress CYP1B1 to the degree that it has been referred to as a universal tumor antigen. Conversely, its expression is low in healthy tissues. CYP1B1 may drive tumorigenesis through promoting the formation of reactive toxins from environmental pollutants or from endogenous hormone substrates. Additionally, the expression of CYP1B1 in tumors is associated with resistance to several common chemotherapies and with poor prognoses in cancer patients. However, inhibiting CYP1B1 with small molecules has been demonstrated in cellular and murine model systems to reverse this …

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Modulatory Effects Of Deacetylated Sialic Acids (A Sugar Residue) In Nk-Mediated Cytotoxicity And Targeted Therapy By Receptor Tyrosine Kinase Inhibitors, Mathias Tawiah Anim Jan 2023

Modulatory Effects Of Deacetylated Sialic Acids (A Sugar Residue) In Nk-Mediated Cytotoxicity And Targeted Therapy By Receptor Tyrosine Kinase Inhibitors, Mathias Tawiah Anim

Electronic Theses and Dissertations

The complex nature of the biology of cancer is still an unraveling science, yielding several biomarkers that have served as molecular targets for detection and treatment of the disease. How sugars, glycans, play a role has remained relatively uninvestigated. Sialic acid (Sia), a sugar residue on the surface of cells, has been identified as a hallmark of cancer and its progression. Sialic acid can be highly functionalized, but we became interested in acetylated Sias. This functional group is modulated by Sialate O- acetylesterase (encoded by the gene SIAE) and Sialate O-acetyltransferase (encoded by CASD1), enzymes that play a crucial role …

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Design Of Block Copolymer With Tunable Hydrophobic/Hydrophilic/Fluorophilic Interactions, Tatiane De Fatima Dutra Jan 2023

Design Of Block Copolymer With Tunable Hydrophobic/Hydrophilic/Fluorophilic Interactions, Tatiane De Fatima Dutra

Theses, Dissertations and Culminating Projects

Block copolymers (BCP) with balanced interactions and their resultant bulk-phase self-assembly have become increasingly important in advancing nanotechnology, separation, and energy applications. However, a few reports have addressed the synthesis challenge and bulk-phase self-assembly of such triblock copolymers. This thesis presents a facile route for preparing triblock copolymer via controlled radical and organocatalytic ring-opening polymerization that allows precise control over the incorporation of individual moieties in resultant polymer, responsible for balanced hydrophilic, hydrophobic/lipophilic, and fluorophilic interactions. Synthesized polymer with suggested self-assembled 2D lamellar nanostructure exhibits high-temperature stability. The long-term goal of this work is to selectively use this polymer class …

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A Computational Study Of The Copper-Catalyzed Trifluoromethylation Of Boronic Acids, Kevin Nyhuis Jan 2023

A Computational Study Of The Copper-Catalyzed Trifluoromethylation Of Boronic Acids, Kevin Nyhuis

Theses, Dissertations and Culminating Projects

This work is a computational study of a reaction mechanism for the trifluoromethylation of boronic acids. Three steps of the proposed reaction mechanism are studied, •CF3 addition to a copper catalyst center, base promoted transmetalation between copper and aryl boronic acid, and bond forming reductive elimination in which the CF3 and aryl substituent form a bond. Limited information is known about this mechanism. This study uses computational methods to attempt to elucidate the mechanism and provide the groundwork for potential improvement. Quantum chemical methods in conjunction with tight-binding based conformational sampling methods are used to investigate the possible …

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Investigating The Roles Of Active Site Residues K59, K119 And E168 In M. Tuberculosis Indole-3-Glycerol Phosphate Synthase, Maryum M. Bhatti Jan 2023

Investigating The Roles Of Active Site Residues K59, K119 And E168 In M. Tuberculosis Indole-3-Glycerol Phosphate Synthase, Maryum M. Bhatti

Theses, Dissertations and Culminating Projects

Tuberculosis (TB) is a disease that is caused by a bacteria called Mycobacterium tuberculosis and primarily attacks the lungs but can spread to other areas of the body as well. TB can develop resistance to drugs that may be used to cure the disease. Multidrug resistant TB is especially a growing issue as it does not respond to the two most powerful anti-TB drugs, isoniazid and rifampicin. For this reason, finding new ways to target TB are critically needed. One possible way to do this is to target the enzymes in the tryptophan biosynthetic pathway of M. tuberculosis. Studies have …

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Arginine-178 Is An Essential Residue For Itpa Function, Nicholas E. Burgis, Caitlin April, Kandise Vanwormer Jan 2023

Arginine-178 Is An Essential Residue For Itpa Function, Nicholas E. Burgis, Caitlin April, Kandise Vanwormer

Chemistry and Biochemistry Faculty Publications

The inosine triphosphate pyrophosphatase (ITPA) enzyme plays a critical cellular role by removing noncanonical nucleoside triphosphates from nucleotide pools. One of the first pathological ITPA mutants identified is R178C (rs746930990), which causes a fatal infantile encephalopathy, termed developmental and epileptic encephalopathy 35 (DEE 35). The accumulation of noncanonical nucleotides such as inosine triphosphate (ITP), is suspected to affect RNA and/or interfere with normal nucleotide function, leading to development of DEE 35. Molecular dynamics simulations have shown that the very rare R178C mutation does not significantly perturb the overall structure of the protein, but results in a high level of structural …

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Impact Of Sample Conditions On Dna Phosphodiester Backbone Bi/Bii Conformational Equilibrium Dynamics, Autumn C. Pilarski Jan 2023

Impact Of Sample Conditions On Dna Phosphodiester Backbone Bi/Bii Conformational Equilibrium Dynamics, Autumn C. Pilarski

Graduate Theses/Dissertations

DNA damage, such as single base lesions and mismatches, is highly prevalent within cells. If these DNA damage events are not repaired, they could lead to mutations and thus disease and cancer. Intricate repair mechanisms are in place to fix these damage events, one such being Base Excision Repair (BER) and associated enzyme: Thymine DNA Glycosylase (TDG). The first step of this repair process, recognition of the lesion by TDG, is not well understood. The following thesis presents results to better understand the fundamental biophysical question of how a DNA lesion within a mismatch context is recognized in a million …

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Investigating Visinin-Like Protein 1 And Ubiquitinated Visinin-Like Protein 1 As Mild Traumatic Brain Injury Biomarkers, Yueming Wu Jan 2023

Investigating Visinin-Like Protein 1 And Ubiquitinated Visinin-Like Protein 1 As Mild Traumatic Brain Injury Biomarkers, Yueming Wu

Theses and Dissertations--Chemistry

Traumatic brain injury (TBI) continues to be a significant cause of morbidity and mortality worldwide. Despite significant progress in understanding the complex pathophysiology of TBI, the underlying mechanisms remain poorly understood. The primary brain damage is acute and irreversible. However, secondary brain injuries often develop gradually over months to years, creating an opportunity for critical therapeutic interventions. In the past decade, research on TBI biomarkers has seen significant progress. This progress has been driven by the diverse nature of TBI pathologies and the challenges they present for evaluation, management, and prognosis. TBI biomarker proteins resulting from axonal, neuronal, or glial …

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Lead Induced Differences In Bone Properties In Osteocalcin +/+ And −/− Female Mice, G. Yildirim, W. C. Budell, O. Berezovska, S. Yagerman, S. S. Maliath, P. Mastrokostas, S. Tommasini, T. L. Dowd Jan 2023

Lead Induced Differences In Bone Properties In Osteocalcin +/+ And −/− Female Mice, G. Yildirim, W. C. Budell, O. Berezovska, S. Yagerman, S. S. Maliath, P. Mastrokostas, S. Tommasini, T. L. Dowd

Publications and Research

Lead (Pb) toxicity is a major health problem and bone is the major reservoir. Lead is detrimental to bone, affects bone remodelingand is associated with elderly fractures. Osteocalcin (OC) affects bone remodeling, improves fracture resistance and decreases with age and in some diseases. The effect of lead in osteocalcin depleted bone is unknown and of interest. We compared bone mineral properties of control and Pb exposed (from 2 to 6 months) femora from female adult C57BL6 OC+/+ and OC−/− mice using Fourier Transform Infrared Imaging (FTIRI), Micro-computed tomography (uCT), bone biomechanical measurements and serum turnover markers (P1NP, CTX). Lead significantly …

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Development Of Novel Cellular Assay Model And Therapeutic Deep Eutectic Solvents To Optimize The Activity Of Anticancer Agents, Nizam Uddin Jan 2023

Development Of Novel Cellular Assay Model And Therapeutic Deep Eutectic Solvents To Optimize The Activity Of Anticancer Agents, Nizam Uddin

Electronic Theses and Dissertations

Multidrug resistance (MDR) is the major burden behind chemotherapeutic treatment failure. It is the principal mechanism by which cancer cells evade chemotherapeutic treatment. As a result, aggressive cancer cells survive and continue uncontrolled cell division. Multidrug resistance affects survival rate of almost all types of cancer patients and death toll rises at an alarming rate. There are seven different mechanisms for evolving MDR. The most common mechanism in efflux activity of overexpressed ABC transporters. MRP1 is a prominent ABC transporter that pumps out a wide variety of anticancer drugs from the cells and thereby reduces intracellular drug concentrations and develops …

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The Affect Of Dha Concentration On Lipid Membrane Fluidity, Elise Rezabeck Jan 2023

The Affect Of Dha Concentration On Lipid Membrane Fluidity, Elise Rezabeck

Williams Honors College, Honors Research Projects

My proposed project will be creating large unilaminar vesicles with varying concentrations of DHA in the vesicles. The diffusion in and out of these vesicles will be tracked by using singular lipid molecules. These singular lipid molecules will be tagged with fluorescence and viewed using an internal reflection fluorescence microscope. The data collected over the course of this project will then be analyzed using Matlab. The result of the project will be to find the specific lipid diffusion constant of these unilaminar vesicles. The relationship between the concentration of DHA and lipid diffusion and membrane fluidity will be found as …

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Multilevel Computational Investigation Into The Catalytic Mechanisms Of Matrix Metalloproteinase-1 And Fat Mass And Obesity-Associated Enzyme, Ann Varghese Jan 2023

Multilevel Computational Investigation Into The Catalytic Mechanisms Of Matrix Metalloproteinase-1 And Fat Mass And Obesity-Associated Enzyme, Ann Varghese

Dissertations, Master's Theses and Master's Reports

Enzymes are biological macromolecules, typically proteins, that efficiently accelerate the rate of chemical reactions. Their remarkable catalytic power plays a vital role in essential processes across all kingdoms of life. Nowadays, computational chemistry methods provide valuable insights into enzymatic functions aiding our understanding of biological processes and providing advancements in fields such as biomedical sciences, biomimetic catalysis, drug design and biotechnology. This dissertation employs multilevel computational chemistry methods to investigate the structure-function relationships and the catalytic mechanisms of two metalloenzymes -Zn(II)-dependent matrix metalloproteinase-1 (MMP-1) and non-heme Fe(II)/2-oxoglutarate (2OG) dependent fat-mass and obesity-associated (FTO) enzyme. Chapter 2 explores the role of …

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A Monoadduct Generating Ru(Ii) Complex Induces Ribosome Biogenesis Stress And Is A Molecular Mimic Of Phenanthriplatin, Richard Joseph Mitchell, Sarah M. Kriger, Alexander D. Fenton, Dmytro Havrylyuk, Ankit Pandeya, Yang Sun, Tami Smith, Jason E. Derouchey, David K. Heidary, Edith C. Glazer Jan 2023

A Monoadduct Generating Ru(Ii) Complex Induces Ribosome Biogenesis Stress And Is A Molecular Mimic Of Phenanthriplatin, Richard Joseph Mitchell, Sarah M. Kriger, Alexander D. Fenton, Dmytro Havrylyuk, Ankit Pandeya, Yang Sun, Tami Smith, Jason E. Derouchey, David K. Heidary, Edith C. Glazer

Markey Cancer Center Faculty Publications

Ruthenium complexes are often investigated as potential replacements for platinum-based chemotherapeutics in hopes of identifying systems with improved tolerability in vivo and reduced susceptibility to cellular resistance mechanisms. Inspired by phenanthriplatin, a non-traditional platinum agent that contains only one labile ligand, monofunctional ruthenium polypyridyl agents have been developed, but until now, few demonstrated promising anticancer activity. Here we introduce a potent new scaffold, based on [Ru(tpy)(dip)Cl]Cl (tpy = 2,20:60,200-terpyridine and dip = 4,7-diphenyl-1,10-phenanthroline) in pursuit of effective Ru(II )-based monofunctional agents. Notably, the extension of the terpyridine at the 40 position with an aromatic ring resulted in a molecule that …

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Polycomb Deficiency Drives A Foxp2-High Aggressive State Targetable By Epigenetic Inhibitors, Fan Chen, Aria Byrd, Jinpeng Liu, Robert M. Flight, Tanner Ducote, Kassandra J. Naughton, Xiulong Song, Abigail R Edgin, Alexsandr Lukyanchuk, Danielle T. Dixon, Christian M. Gosser, Dave-Preston Esoe, Rani Jayswal, Stuart H. Orkin, Hunter N. B. Moseley, Chi Wang, Christine Fillmore Brainson Jan 2023

Polycomb Deficiency Drives A Foxp2-High Aggressive State Targetable By Epigenetic Inhibitors, Fan Chen, Aria Byrd, Jinpeng Liu, Robert M. Flight, Tanner Ducote, Kassandra J. Naughton, Xiulong Song, Abigail R Edgin, Alexsandr Lukyanchuk, Danielle T. Dixon, Christian M. Gosser, Dave-Preston Esoe, Rani Jayswal, Stuart H. Orkin, Hunter N. B. Moseley, Chi Wang, Christine Fillmore Brainson

Markey Cancer Center Faculty Publications

Inhibitors of the Polycomb Repressive Complex 2 (PRC2) histone methyltransferase EZH2 are approved for certain cancers, but realizing their wider utility relies upon understanding PRC2 biology in each cancer system. Using a genetic model to delete Ezh2 in KRAS-driven lung adenocarcinomas, we observed that Ezh2 haplo-insufficient tumors were less lethal and lower grade than Ezh2 fully-insufficient tumors, which were poorly differentiated and metastatic. Using three-dimensional cultures and in vivo experiments, we determined that EZH2-deficient tumors were vulnerable to H3K27 demethylase or BET inhibitors. PRC2 loss/inhibition led to de-repression of FOXP2, a transcription factor that promotes migration and stemness, and FOXP2 …

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Cup Is Essential For Oskar Mrna Translational Repression During Early Drosophila Oogenesis, Livia V. Bayer, Samantha Milano, Stephen K. Formel, Harpreet Kaur, Rishi Ravichandran, Juan A. Cambeiro, Lizaveta Slinko, Irina E. Catrina, Diana P. Bratu Jan 2023

Cup Is Essential For Oskar Mrna Translational Repression During Early Drosophila Oogenesis, Livia V. Bayer, Samantha Milano, Stephen K. Formel, Harpreet Kaur, Rishi Ravichandran, Juan A. Cambeiro, Lizaveta Slinko, Irina E. Catrina, Diana P. Bratu

Publications and Research

Study of the timing and location for mRNA translation across model systems has begun to shed light on molecular events fundamental to such processes as intercellular communication, morphogenesis, and body pattern formation. In D. melanogaster, the posterior mRNA determinant, oskar, is transcribed maternally but translated only when properly localized at the oocyte’s posterior cortex. Two effector proteins, Bruno1 and Cup, mediate steps of oskar mRNA regulation. The current model in the field identifies Bruno1 as necessary for Cup’s recruitment to oskar mRNA and indispensable for oskar’s translational repression. We now report that this Bruno1-Cup interaction leads …

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C-Glycopyranosyl Aldehydes: Emerging Chiral Synthons In Organic Synthesis, Sandeep Kumar, Vinod Khatri, Priyanka Mangla, Rajni Johar Chhatwal, Virinder S. Parmar, Ashok K. Prasad Jan 2023

C-Glycopyranosyl Aldehydes: Emerging Chiral Synthons In Organic Synthesis, Sandeep Kumar, Vinod Khatri, Priyanka Mangla, Rajni Johar Chhatwal, Virinder S. Parmar, Ashok K. Prasad

Publications and Research

Herein, we have summarized the vast array of synthetic processes that have been developed for the synthesis of C-glycopyranosyl aldehydes and diverse C-glycoconjugates derived from them by covering the literature reported from 1979 to 2023. Notwithstanding its challenging chemistry, C-glycosides are considered stable pharmacophores and are used as important bioactive molecules. The discussed synthetic methodologies to access C-glycopyranosyl aldehydes take advantage of seven key intermediates, viz. allene, thiazole, dithiane, cyanide, alkene, and nitromethane. Furthermore, the integration of complex C-glycoconjugates derived from varied C-glycopyranosyl aldehydes involves nucleophilic addition/substitution, reduction, condensation, oxidation, cyclo condensation, coupling, and …

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Molecular Mechanism Behind The Safe Immunostimulatory Effect Of Withania Somnifera, Kriti Kalpana, Shen Yap, Moriya Tsuji, Akira Kawamura Jan 2023

Molecular Mechanism Behind The Safe Immunostimulatory Effect Of Withania Somnifera, Kriti Kalpana, Shen Yap, Moriya Tsuji, Akira Kawamura

Publications and Research

Withania somnifera (L.) Dunal (family Solanaceae) is a medicinal plant known for, among many pharmacological properties, an immune boosting effect. Our recent study revealed that its key immunostimulatory factor is lipopolysaccharide of plant-associated bacteria. This is peculiar, because, although LPS can elicit protective immunity, it is an extremely potent pro-inflammatory toxin (endotoxin). However, W. somnifera is not associated with such toxicity. In fact, despite the presence of LPS, it does not trigger massive inflammatory responses in macrophages. To gain insights into the safe immunostimulatory effect of W. somnifera, we conducted a mechanistic study on its major phytochemical constituent, …

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Development Of A Chemical Biology Approach To Uncover The Influence Of Sequence Variations On Ces1 Activity In Live Cells, Samuel James Knebel Jan 2023

Development Of A Chemical Biology Approach To Uncover The Influence Of Sequence Variations On Ces1 Activity In Live Cells, Samuel James Knebel

Masters Theses

Drug metabolism is the biochemical process of modifying drugs to detoxify and remove them through enzymatic transformations. These biotransformation’s occur primarily in the liver and are critical to understanding how pharmaceutical compounds are chemically altered inside the human body. Human carboxylesterases (CESs) catalyze the hydrolysis of esters, amides, thioesters, and carbamates. CES-mediated hydrolysis plays an important role in the metabolism of many drugs including the first FDA approved antiviral treatment for COVID-19, remdesivir (Veklury), the seizure control medication rufinamide (Banzel), and the flu antiviral drug oseltamivir (Tamiflu). CES activity is known to be influenced by a variety of factors including …

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Bioanalytical Studies Of Disease Protein Profiles: Maldi-Tof Ms, Prajkta Satish Chivte Jan 2023

Bioanalytical Studies Of Disease Protein Profiles: Maldi-Tof Ms, Prajkta Satish Chivte

Graduate Research Theses & Dissertations

Coronavirus disease-2019 (COVID-19), which is caused by a novel coronavirus named severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has ravaged the world for the past 3 years. Even today, there still exists a need for rapid, accurate, economical and non-invasive diagnostic testing platforms that yield high specificity and sensitivity towards the constantly mutating SARS-CoV-2. Research has consistently indicated saliva to be a more amenable specimen type for early detection of SARS-CoV-2, compared to the oral and nasopharyngeal swabs. Considering the limitations and high demand of the existing COVID-19 testing platforms, this dissertation work studies used MALDI-ToF MS (matrix-assisted laser desorption/ionization-time of …

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