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2023

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Articles 361 - 390 of 402

Full-Text Articles in Biochemistry

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 …


Suppressing Hepatic Ugt1a1 Increases Plasma Bilirubin, Lowers Plasma Urobilin, Reorganizes Kinase Signaling Pathways And Lipid Species And Improves Fatty Liver Disease, Evelyn A. Bates, Zachary A. Kipp, Genesee J. Martinez, Olufunto O. Badmus, Mangala M. Soundarapandian, Donald Foster, Mei Xu, Justin F. Creeden, Jennifer R. Greer, Andrew J. Morris, David E. Stec, Terry D. Hinds Jr. Jan 2023

Suppressing Hepatic Ugt1a1 Increases Plasma Bilirubin, Lowers Plasma Urobilin, Reorganizes Kinase Signaling Pathways And Lipid Species And Improves Fatty Liver Disease, Evelyn A. Bates, Zachary A. Kipp, Genesee J. Martinez, Olufunto O. Badmus, Mangala M. Soundarapandian, Donald Foster, Mei Xu, Justin F. Creeden, Jennifer R. Greer, Andrew J. Morris, David E. Stec, Terry D. Hinds Jr.

Markey Cancer Center Faculty Publications

Several population studies have observed lower serum bilirubin levels in patients with non-alcoholic fatty liver disease (NAFLD). Yet, treatments to target this metabolic phenotype have not been explored. Therefore, we designed an N-Acetylgalactosamine (GalNAc) labeled RNAi to target the enzyme that clears bilirubin from the blood, the UGT1A1 glucuronyl enzyme (GNUR). In this study, male C57BL/6J mice were fed a high-fat diet (HFD, 60%) for 30 weeks to induce NAFLD and were treated subcutaneously with GNUR or sham (CTRL) once weekly for six weeks while continuing the HFD. The results show that GNUR treatments significantly raised plasma bilirubin levels and …


The Link Between Intracellular Calcium Signaling And Exosomal Pd-L1 In Cancer Progression And Immunotherapy, Rakibul Alam, Mizanur Rahman, Zhiguo Li Jan 2023

The Link Between Intracellular Calcium Signaling And Exosomal Pd-L1 In Cancer Progression And Immunotherapy, Rakibul Alam, Mizanur Rahman, Zhiguo Li

Markey Cancer Center Faculty Publications

Exosomes are small membrane vesicles containing microRNA, RNA, DNA fragments, and proteins that are transferred from donor cells to recipient cells. Tumor cells release exo- somes to reprogram the factors associated with the tumor microenvironment (TME) causing tu- mor metastasis and immune escape. Emerging evidence revealed that cancer cell-derived exosomes carry immune inhibitory molecule program death ligand 1 (PD-L1) that binds with re- ceptor program death protein 1 (PD-1) and promote tumor progression by escaping immune response. Currently, some FDA-approved monoclonal antibodies are clinically used for cancer treatment by blocking PD-1/PD-L1 interaction. Despite notable treatment outcomes, some pa- tients show …


Genome-Wide Investigation Of Snrk2 Gene Family In Two Jute Species: Corchorus Olitorius And Corchorus Capsularis, Borhan Ahmed, Fakhrul Hasan, Anika Tabassum, Rasel Ahmed, Rajnee Hassan, Ruhul Amin, Mobashwer Alam Jan 2023

Genome-Wide Investigation Of Snrk2 Gene Family In Two Jute Species: Corchorus Olitorius And Corchorus Capsularis, Borhan Ahmed, Fakhrul Hasan, Anika Tabassum, Rasel Ahmed, Rajnee Hassan, Ruhul Amin, Mobashwer Alam

Department of Biochemistry: Faculty Publications

Background Sucrose non-fermenting-1 (SNF1)-related protein kinase 2 (SnRK2), a plant-specifc serine/threonine kinase family, is associated with metabolic responses, including abscisic acid signaling under biotic and abiotic stresses. So far, no information on a genome-wide investigation and stress-mediated expression profling of jute SnRK2 is available. Recent whole-genome sequencing of two Corchorus species prompted to identify and characterize this SnRK2 gene family.

Result We identifed seven SnRK2 genes of each of Corchorus olitorius (Co) and C. capsularis (Cc) genomes, with similar physico-molecular properties and sub-group patterns of other models and related crops. In both species, the SnRK2 gene …


Oligogalactolipid Production During Cold Challenge Is Conserved In Early Diverging Lineages, Allison C. Barnes, Jennifer L. Myers, Samantha M. Surber, Zhikai Liang, Jeffrey P. Mower, James Schnable, Rebecca Roston Jan 2023

Oligogalactolipid Production During Cold Challenge Is Conserved In Early Diverging Lineages, Allison C. Barnes, Jennifer L. Myers, Samantha M. Surber, Zhikai Liang, Jeffrey P. Mower, James Schnable, Rebecca Roston

Department of Biochemistry: Faculty Publications

Oligogalactolipid production is a response to severe cold in many land plant lineages. It occurs during times of membrane damage and can be reproduced in multiple species by cytosolic acidification.

Severe cold, defined as a damaging cold beyond acclimation temperatures, has unique responses, but the signaling and evolution of these responses are not well understood. Production of oligogalactolipids, which is triggered by cytosolic acidification in Arabidopsis (Arabidopsis thaliana), contributes to survival in severe cold. Here, we investigated oligogalactolipid production in species from bryophytes to angiosperms. Production of oligogalactolipids differed within each clade, suggesting multiple evolutionary origins of severe …


A Facile Strategy For The Fabrication Of Cell-Laden Porous Alginate Hydrogels Based On Two-Phase Aqueous Emulsions, Wen Xue, Donghee Lee, Yunfan Kong, Mitchell Kuss, Ying Huang, Taesung Kim, Soonkyu Chung, Andrew T. Dudley, Seung-Hyun Ro, Bin Duan Jan 2023

A Facile Strategy For The Fabrication Of Cell-Laden Porous Alginate Hydrogels Based On Two-Phase Aqueous Emulsions, Wen Xue, Donghee Lee, Yunfan Kong, Mitchell Kuss, Ying Huang, Taesung Kim, Soonkyu Chung, Andrew T. Dudley, Seung-Hyun Ro, Bin Duan

Department of Biochemistry: Faculty Publications

Porous alginate (Alg) hydrogels possess many advantages as cell carriers. However, current pore generation methods require either complex or harsh fabrication processes, toxic components, or extra purification steps, limiting the feasibility and affecting the cellular survival and function. In this study, a simple and cell-friendly approach to generate highly porous cell-laden Alg hydrogels based on two-phase aqueous emulsions is reported. The pre-gel solutions, which contain two immiscible aqueous phases of Alg and caseinate (Cas), are cross-linked by calcium ions. The porous structure of the hydrogel construct is formed by subsequently removing the Cas phase from the ion-cross-linked Alg hydrogel. Those …


Structural Basis Of Dna Binding By The Whib-Like Transcription Factor Whib3 In Mycobacterium Tuberculosis, Tao Wan, Magdaléna Horová, Vimmy Khetrapal, Shanren Li, Camden Jones, Andrew Schacht, Xinghui Sun, Limei Zhang Jan 2023

Structural Basis Of Dna Binding By The Whib-Like Transcription Factor Whib3 In Mycobacterium Tuberculosis, Tao Wan, Magdaléna Horová, Vimmy Khetrapal, Shanren Li, Camden Jones, Andrew Schacht, Xinghui Sun, Limei Zhang

Department of Biochemistry: Faculty Publications

Mycobacterium tuberculosis (Mtb) WhiB3 is an iron–sulfur cluster-containing transcription factor belonging to a subclass of the WhiB-Like (Wbl) family that is widely distributed in the phylum Actinobacteria. WhiB3 plays a crucial role in the survival and pathogenesis of Mtb. It binds to the conserved region 4 of the principal sigma factor (σA4) in the RNA polymerase holoenzyme to regulate gene expression like other known Wbl proteins in Mtb. However, the structural basis of how WhiB3 coordinates with σA4 to bind DNA and regulate transcription is unclear. Here we determined crystal structures …


Akkermansia Muciniphila And Its Membrane Protein Ameliorates Intestinal Inflammatory Stress And Promotes Epithelial Wound Healing Via Crebh And Mir‑143/145, Henry Wade, Kaichao Pan, Qihua Duan, Szczepan Kaluzny, Ekta Pandey, Linda Fatumoju, Viswanathan Saraswathi, Rongxue Wu, Edward N. Harris, Qiaozhu Su Jan 2023

Akkermansia Muciniphila And Its Membrane Protein Ameliorates Intestinal Inflammatory Stress And Promotes Epithelial Wound Healing Via Crebh And Mir‑143/145, Henry Wade, Kaichao Pan, Qihua Duan, Szczepan Kaluzny, Ekta Pandey, Linda Fatumoju, Viswanathan Saraswathi, Rongxue Wu, Edward N. Harris, Qiaozhu Su

Department of Biochemistry: Faculty Publications

Background The intestinal epithelial barrier is the interface for interaction between gut microbiota and host metabolic systems. Akkermansia muciniphila (A. muciniphila) is a key player in the colonic microbiota that resides in the mucus layer, whose abundance is selectively decreased in the faecal microbiota of inflammatory bowel disease (IBD) patients. This study aims to investigate the regulatory mechanism among A. muciniphila, a transcription factor cAMPresponsive element-binding protein H (CREBH), and microRNA-143/145 (miR-143/145) in intestinal inflammatory stress, gut barrier integrity and epithelial regeneration.

Methods A novel mouse model with increased colonization of A muciniphila in the intestine of CREBH knockout …


Factors Influencing Instructors’ Adoption And Continued Use Of Computing Science Technologies: A Case Study In The Context Of Cell Collective, Changsoo Song, Resa M. Helikar, Wendy M. Smith, Tomáš Helikar Jan 2023

Factors Influencing Instructors’ Adoption And Continued Use Of Computing Science Technologies: A Case Study In The Context Of Cell Collective, Changsoo Song, Resa M. Helikar, Wendy M. Smith, Tomáš Helikar

Department of Biochemistry: Faculty Publications

Acquiring computational modeling and simulation skills has become ever more critical for students in life sciences courses at the secondary and tertiary levels. Many modeling and simulation tools have been created to help instructors nurture those skills in their classrooms. Understanding the factors that may motivate instructors to use such tools is crucial to improve students’ learning, especially for having authentic modeling and simulation learning experiences. This study designed and tested a decomposed technology acceptance model in which the perceived usefulness and perceived ease of use constructs are split between the teaching and learning sides of the technology to examine …


Conformal Electrodeposition Of Antimicrobial Hydrogels Formed By Self-Assembled Peptide Amphiphiles, Gervasio Zaldivar, Jiachen Feng, Leonardo Lizarraga, Yafan Yu, Luana De Campos, Kelly Mari Pires De Oliveira, Kurt Piepenbrink, Martin Conda-Sheridan, Mario Tagliazucchi Jan 2023

Conformal Electrodeposition Of Antimicrobial Hydrogels Formed By Self-Assembled Peptide Amphiphiles, Gervasio Zaldivar, Jiachen Feng, Leonardo Lizarraga, Yafan Yu, Luana De Campos, Kelly Mari Pires De Oliveira, Kurt Piepenbrink, Martin Conda-Sheridan, Mario Tagliazucchi

Department of Biochemistry: Faculty Publications

The colonization of biomedical surfaces by bacterial biofilms is concerning because these microorganisms display higher antimicrobial resistance in biofilms than in liquid cultures. Developing antimicrobial coatings that can be easily applied to medically-relevant complex-shaped objects, such as implants and surgical instruments, is an important and challenging research direction. This work reports the preparation of antibacterial surfaces via the electrodeposition of a conformal hydrogel of self-assembling cationic peptide-amphiphiles (PAs). Hydrogels of three PAs are electrodeposited: C16K2, C16K3, and C18K2, where Cn is an alkyl chain of n methylene …


Genetic Control Of Photoprotection And Photosystem Ii Operating Efficiency In Plants, Seema Sahay, Marcin Grzybowski, James Schnable, Katarzyna Głowacka Jan 2023

Genetic Control Of Photoprotection And Photosystem Ii Operating Efficiency In Plants, Seema Sahay, Marcin Grzybowski, James Schnable, Katarzyna Głowacka

Department of Biochemistry: Faculty Publications

• Photoprotection against excess light via nonphotochemical quenching (NPQ) is indispensable for plant survival. However, slow NPQ relaxation under low light conditions can decrease yield of field-grown crops up to 40%.

• Using semi-high-throughput assay, we quantified the kinetics of NPQ and photosystem II operating efficiency (ΦPSII) in a replicated field trial of more than 700 maize (Zea mays) genotypes across 2 yr. Parametrized kinetics data were used to conduct genome-wide association studies.

• For six candidate genes involved in NPQ and ΦPSII kinetics in maize the loss of function alleles of orthologous genes in Arabidopsis (Arabidopsis thaliana) …


Advancements In Computational Modelling Of Biological Systems: Seventh Annual Sysmod Meeting, Bhanwar Lal Puniya, Andreas Dräger Jan 2023

Advancements In Computational Modelling Of Biological Systems: Seventh Annual Sysmod Meeting, Bhanwar Lal Puniya, Andreas Dräger

Department of Biochemistry: Faculty Publications

The Computational Modelling of Systems Biology (SysMod) Community of Special Interest (COSI) convenes annually at the Intelligent Systems for Molecular Biology (ISMB) conference to facilitate knowledge dissemination and exchange of research findings on systems modelling from interdisciplinary domains. The SysMod meeting 2022 was held in a hybrid mode in Madison, Wisconsin, spanning a 1-day duration centred on modelling techniques, applications, and single-cell technology implementations. The meeting showcased innovative approaches to modelling biological systems using cell-specific and multiscale modelling, multiomics data integration, and novel tools to develop systems models using single-cell and multiomics technology. The meeting also recognized outstanding research by …


Identification Of A Dna Polymerase Alpha Gene Sequence In Thermomyces Lanuginosus Fungus, Nathan Williams Jan 2023

Identification Of A Dna Polymerase Alpha Gene Sequence In Thermomyces Lanuginosus Fungus, Nathan Williams

Honors Program Theses

With cell growth being the main focus of our research, we chose to study DNA polymerase alpha. DNA polymerase alpha is likely to be involved in cell growth as it is the enzyme that starts DNA replication. Control of this enzyme might lead to decreased cell growth in cancer or increased cell growth in damaged spinal cord tissue. We chose the thermophilic fungus Thermomyces lanuginosus for the study of the enzyme due to the ability to compare the enzyme’s activity during fungal growth at different temperatures. Thermomyces exhibits rapid growth at high temperatures and slow growth at low temperatures. Studying …


Assessing The Biocatalytic Promiscuity Of Pep- Transformations For Geminal-Difluorination, Eloy Jose Torres Garcia Jan 2023

Assessing The Biocatalytic Promiscuity Of Pep- Transformations For Geminal-Difluorination, Eloy Jose Torres Garcia

Theses and Dissertations (Comprehensive)

Fluorine is the most electronegative chemical element and can drastically change molecular properties, such as drug pharmacokinetics and agrochemical half-life. Although a great deal of progress is occurring in synthetic methods to access various organofluorines, these methods struggle with harsh conditions and limited substrate scope. Biocatalytic approaches offer the potential to access organofluorines that are difficult or impossible with the current methodology. Phosphoenolpyruvate (PEP) is a central metabolite and biosynthetic precursor for diverse molecules. Phosphoenol pyruvate mutase (Ppm) catalyses the interconversion of Phosphonopyruvate (PnPy) to Phosphoenolpyruvate (PEP). This research successfully expressed and …


Engineering And Characterizing Proteins: A Dual Study On Canine P53 Protein And Cyan Thermal Protein, Dhruv B. Sitapara Jan 2023

Engineering And Characterizing Proteins: A Dual Study On Canine P53 Protein And Cyan Thermal Protein, Dhruv B. Sitapara

Graduate Theses/Dissertations

This research aims to explore protein development and characterization, focusing on a dual study of canine p53 protein and cyan thermal protein. For the canine p53 protein, the goal is to comprehend its structure to better understand a key component of canine cancers. This multi-step process involved expressing the canine p53 DNA-binding domain in E. coli and purifying it through affinity and ion-exchange chromatography. The purified protein was studied to test the binding of canine p53 protein to human DNA sequences using Surface Plasmon Resonance (SPR) experiments and an Electrophoretic Mobility Shift Assay (EMSA), visualized with a SYBR-safe stain. The …


Development Of Multivalent Dna-Peptide Nucleosome Mimetics And Multi-Domain Protein Inhibitors That Directly Or Indirectly Target The E3 Ligase Uhrf1, Li Gu Jan 2023

Development Of Multivalent Dna-Peptide Nucleosome Mimetics And Multi-Domain Protein Inhibitors That Directly Or Indirectly Target The E3 Ligase Uhrf1, Li Gu

University of the Pacific Theses and Dissertations

UHRF1 is an E3 ubiquitin ligase and a key epigenetic regulator establishing a crosstalk between DNA methylation and histone modification. Despite the important biochemical role of UHRF1 in cells, its overexpression has been found in almost all primary cancer types including breast cancer, lung cancer and so on. Numerous evidence indicates a strong link between tumorigenesis and UHRF1 overexpression, supporting its potential as a universal biomarker for cancer. However, UHRF1 is “yet-to-be drugged” and no highly potent chemical probes have been developed to target UHRF1 to date. In this study, we proposed two drug design approaches for UHRF1. The first …


Concentrated Wastewater Treatment Using A Ferric Iron-Dosed Anaerobic Upflow Sludge Blanket Reactor For Recovery Of Phosphorus And Ammonium, Carley E. Shingleton Jan 2023

Concentrated Wastewater Treatment Using A Ferric Iron-Dosed Anaerobic Upflow Sludge Blanket Reactor For Recovery Of Phosphorus And Ammonium, Carley E. Shingleton

Graduate Theses, Dissertations, and Problem Reports (ETD)

This study evaluated the performance of a novel, ferric iron-dosed anaerobic bioreactor to recover two separate nutrient products from concentrated wastewaters -- phosphorus as vivianite (Fe3(PO4)2×8H2O) and an ammonium-containing effluent with low organics. A bench-scale upflow anaerobic sludge blanket (UASB) reactor fed with a synthetic wastewater (458.0 mg/L total organic carbon, 282.7 mg/L ammonium, and 84.4 mg/L phosphate) was dosed with a ferric chloride solution at an org. C/Fe3+ molar ratio ~17.5 to facilitate organic carbon oxidation coupled to iron reduction. The reactor design allowed natural settling of vivianite to its …


Investigating The Role Of Nudt7-Mediated Peroxisomal Coa Degradation In The Regulation Of Hepatic Coa Levels And Lipid Metabolism, Schuyler Dan Adams Vickers Jan 2023

Investigating The Role Of Nudt7-Mediated Peroxisomal Coa Degradation In The Regulation Of Hepatic Coa Levels And Lipid Metabolism, Schuyler Dan Adams Vickers

Graduate Theses, Dissertations, and Problem Reports (ETD)

Coenzyme A (CoA) is a crucial cofactor required to support many essential metabolic processes, including fatty acid oxidation and synthesis, the TCA cycle, and bile acid synthesis. In order to support the proper functioning of these pathways, CoA levels within the cell must be properly regulated. The regulation of CoA levels is achieved through a balance between CoA synthesis and CoA degradation. While the regulation of CoA synthesis has been extensively characterized, the degradation of CoA has received less attention. As such, the contribution of CoA degradation to the regulation of metabolism is poorly understood. NUDT7 is a CoA-specific Nudix …


Heat Shock Protein 90 (Hsp90) System In Health And Disease., Daniella Munezero Jan 2023

Heat Shock Protein 90 (Hsp90) System In Health And Disease., Daniella Munezero

Graduate Theses, Dissertations, and Problem Reports (ETD)

Cells rely on heat shock proteins (HSP) to facilitate and regulate the folding of the substrate proteins into their native state, and degradation if misfolding cannot be prevented. HSP90, a member of the HSP family, is a potential target for treatment of cancer and neurodegenerative diseases. Unfortunately, several clinical trials for cancer treatment have been discontinued due to cell toxicity accompanying HSP90 inhibition. HSP90 has four distinct but structurally similar paralogs. HSP90 inhibitors target all the paralogs despite increasing proof of functional differences among the paralogs. Understanding the in vivo function of HSP90 and the role played by each paralog …


Gestational Vulnerability To Ozone Air Pollution - A Placental Story, Vishnupriya Alavala, Sarah Brent, Russell Hunter, Matthew J. Campen, Andrew Ottens Jan 2023

Gestational Vulnerability To Ozone Air Pollution - A Placental Story, Vishnupriya Alavala, Sarah Brent, Russell Hunter, Matthew J. Campen, Andrew Ottens

Undergraduate Research Posters

About 99% of the global population resides in areas with air pollution surpassing World Health Organization standards. Air pollution is associated with adverse neonatal health outcomes such as low fetal birth weight and an increased risk for maternal pre-eclampsia. A particularly reactive air pollutant is ozone, which forms reactive oxygen species that induce cellular damage. Research exists on the dispersion of reactive oxygen species through the bloodstream leading to fetal vulnerability during pregnancy, specifically via the placenta. Yet, placental and fetal development is a temporal process with varied susceptibility to negative gestational outcomes.

To addressing this gap, our laboratory utilized …


Engineering Ph-Dependent Antibody Interactions Through Introduction Of Linked Protonation Equibria Within The Antigen Binding Interface Or Linked Oligomeric Interfaces, Tosha Laughlin Jan 2023

Engineering Ph-Dependent Antibody Interactions Through Introduction Of Linked Protonation Equibria Within The Antigen Binding Interface Or Linked Oligomeric Interfaces, Tosha Laughlin

Graduate Research Theses & Dissertations

Antibodies are widely applied as affinity reagents across a variety of fields, due to their high affinity and specificity. While high affinity across a range of conditions is useful for many applications, the ability to modulate affinity with environmental conditions (e.g., pH) opens new opportunities for antibody applications. This dissertation focuses on exploring the impact of an antibody’s interface size on engineered pH dependence, as well as exploring engineered pH-dependence through perturbing oligomerization equilibria that are linked to target binding. An anti-maltose binding protein (MBP) Fab 7O antibody fragment was used as a large protein-protein interface model to explore a …


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 …


Evaluating The Contribution Of Adjacent Charges On The Observed Ph-Dependent Binding Profile For A Vhh/Antigen Interaction With A Linked Histidine Protonation Equilibria, Kiruthika Arulmoly Jan 2023

Evaluating The Contribution Of Adjacent Charges On The Observed Ph-Dependent Binding Profile For A Vhh/Antigen Interaction With A Linked Histidine Protonation Equilibria, Kiruthika Arulmoly

Graduate Research Theses & Dissertations

pH dependent protein-protein interactions are of great importance for various biological processes. In addition, the generation of engineered pH-dependent therapeutic antibodies opens opportunities for the extension of therapeutic half-life, thereby reducing drug dosage or frequency of administration, as well as providing pH-dependent targeting, such as the tumor microenvironment. Engineering pH-dependent antibody-antigen interaction is mostly achieved through the incorporation of ionizable residues within the antigen binding interface. These ionizable residues must undergo a change in environment upon forming a protein-protein complex, which causes a change in the ionizable group’s pKa value. This coupled protonation equilibria is responsible for the observed pH-dependent …


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 …


The Role Of Cadherins And Ryk On Metastasis And Invasion In Triple Negative Breast Cancer Cell Model: Hs578t/Hs578ts(I)8, Ibis Iser Jan 2023

The Role Of Cadherins And Ryk On Metastasis And Invasion In Triple Negative Breast Cancer Cell Model: Hs578t/Hs578ts(I)8, Ibis Iser

Electronic Theses and Dissertations

Breast cancer is a major cause of death among women in European and North American countries, even with improved methods for diagnosis and therapy. The mortality of breast cancer is mainly due to the migration of the primary tumor to distinct sites in the body and is very common in triple negative breast cancer (TNBC). This type of breast cancer affects younger woman and has a high recurrence rate. Unfortunately, TNBC is extremely difficult to control because of the absence of specific targets for treatment. Therefore, our research aim is to discover new therapeutic targets and identify novel approaches for …


Food Waste Storage Gaseous Emissions Detection And Quantification Using Infrared Spectroscopy, Ryley A. Burton-Tauzer Jan 2023

Food Waste Storage Gaseous Emissions Detection And Quantification Using Infrared Spectroscopy, Ryley A. Burton-Tauzer

Cal Poly Humboldt theses and projects

A growing interest in sustainable waste management and the implementation of new policies have prompted a shift towards alternative resource recovery methods for organic waste, including food waste. To effectively assess alternative food waste treatment scenarios, it is important to evaluate the life cycle impacts associated with each scenario. The storage phase of food waste, encompassing its accumulation in kitchens, and storage in bins for collection and transportation, has been overlooked as a source of greenhouse gases in previous studies. This investigation aimed to identify the greenhouse gases emitted during the initial five-day period of low-oxygen storage. An open dynamic …


Elucidating Mechanisms Of Proteasome Modulation By Small Molecules To Treat Neurodegenerative Diseases And Cancer, Janelle Joo Yee Chuah Jan 2023

Elucidating Mechanisms Of Proteasome Modulation By Small Molecules To Treat Neurodegenerative Diseases And Cancer, Janelle Joo Yee Chuah

Graduate Theses, Dissertations, and Problem Reports (ETD)

Maintaining protein homeostasis, or proteostasis, is crucial for cellular function, and protein degradation through the proteasome plays a pivotal role in this process. Dysregulation of the proteasome can lead to proteostasis collapse and has been linked to the development of neurodegenerative diseases and cancers. Neurodegenerative diseases often exhibit proteasome impairment, whereas proteasome upregulation is frequently observed in cancer. Although the use of proteasome inhibitors as a pharmaceutical approach has shown success in certain cancers, it has yet to demonstrate efficacy in neurodegenerative diseases due to the absence of drug-like small molecules capable of effectively reversing proteasome impairment and/or activating the …


Characterizing The Dynamic Localization Of Cmi In Early Drosophila Development, Asra Habibullah Jan 2023

Characterizing The Dynamic Localization Of Cmi In Early Drosophila Development, Asra Habibullah

Master's Theses

The COMPASS-like family of lysine methyltransferases, MLR/MLX complexes, are epigenetic regulators that are essential for normal development through the methylation of the fourth lysine residue on histone 3 (H3K4), a universal epigenetic mark associated with active transcription. This family of complexes is highly conserved from yeast to mammals and the genes encoding the human MLR complexes have been associated with various developmental diseases and cancers (Dingwall and Fagan, 2019). In D. melanogaster, the enzymatic methyltransferase core of this complex is composed of two proteins: Cara Mitad (Cmi, also known as Lpt) and Trithorax-related (Trr). Although these proteins have been shown …


Functional Characterization Of Pacific White Shrimp Litopenaeus Vannamei Heat Shock Protein 90 In Response To White Spot Syndrome Virus Infection, Warumporn Yingsunthonwattana Jan 2023

Functional Characterization Of Pacific White Shrimp Litopenaeus Vannamei Heat Shock Protein 90 In Response To White Spot Syndrome Virus Infection, Warumporn Yingsunthonwattana

Chulalongkorn University Theses and Dissertations (Chula ETD)

Heat shock proteins (HSPs) are host chaperones that can be used by viruses to facilitate various steps of viral infections. In this study, we found that Litopenaeus vannamei heat shock protein 90 (LvHSP90) is a viral-responsive protein, due to a significant transcriptional and translational upregulation following white spot syndrome virus (WSSV) infection. Suppression of LvHSP90 significantly reduced WSSV infection which was corresponded with significantly decreased expressions of viral genes, including the immediate-early genes and viral DNA polymerase. Conversely, injecting shrimp with WSSV that had been co-incubated with a recombinant LvHSP90 (rLvHSP90) promoted WSSV infection as evidenced by an increased cumulative …


Solubility And Anti-Cancer Efficiency Enhancement Of Phytochemicals By Complexation With Β-Cyclodextrin And Derivatives, Saba Ali Jan 2023

Solubility And Anti-Cancer Efficiency Enhancement Of Phytochemicals By Complexation With Β-Cyclodextrin And Derivatives, Saba Ali

Chulalongkorn University Theses and Dissertations (Chula ETD)

Phytochemicals, abundant in plants, showcase diverse pharmacological effects, with an increasing focus on their potential as anticancer agents. Three bioactive natural compounds with pharmaceutical potential are piperine (PP), oxyresveratrol (OXY), and tanshinone IIA (Tan IIA). However, these three phytochemicals have low water solubility and susceptibility to UV light degradation. To address this problem, we explored the potential of β -cyclodextrins (βCDs), renowned for their ability to enhance the solubility and stability of lipophilic drugs by encapsulating them within their molecular structure. Our focus centered on β-cyclodextrin (βCD) and its derivatives, including hydroxypropyl-β-cyclodextrin (HPβCD), dimethyl-β-cyclodextrin (DMβCD), and sulfobutylether-β-cyclodextrin (SBEβCD). In this …