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Articles 2251 - 2280 of 13229

Full-Text Articles in Biochemistry, Biophysics, and Structural Biology

Use Of Foreign Edna Tracers To Resolve Site- And Time-Specific Edna Distributions In Natural Streams, Braden A. Herman Jan 2023

Use Of Foreign Edna Tracers To Resolve Site- And Time-Specific Edna Distributions In Natural Streams, Braden A. Herman

Cal Poly Humboldt theses and projects

Substantial uncertainty in how to interpret eDNA observations motivates a need for a technique to effectively and efficiently measure of system- and time-specific eDNA distributions. Using a technique to robustly calibrate eDNA dynamics in a given system would improve established eDNA methods such as presence and absence and has the potential to refine estimates of organism abundance using eDNA concentration that are less well understood. Particles of eDNA are present in a wide variety of size and type resulting in varying transport dynamics, persistence, decay, among others. This variation likely makes eDNA transport more complex than that of conservative tracers …


Identification And Functional Characterization Of Mads-Box Proteins And Ccos Involved In Carotenoid Metabolism In Durian Durio Zibethinus L. Pulps, Kittiya Tantisuwanichkul Jan 2023

Identification And Functional Characterization Of Mads-Box Proteins And Ccos Involved In Carotenoid Metabolism In Durian Durio Zibethinus L. Pulps, Kittiya Tantisuwanichkul

Chulalongkorn University Theses and Dissertations (Chula ETD)

Durian (Durio zibethinus L.), known as the "King of fruits," holds significant economic importance in Thailand. Apart from its unique odor and sweet taste, durian pulp exhibits a yellow color, which is an important aspect of fruit quality. Carotenoids are essential compounds responsible for the yellow, orange, and red coloration in many fruits and vegetables. During durian fruit development and ripening processes, its pulp changes from white to yellow due to increased carotenoid accumulation. The carotenoid biosynthetic pathway, responsible for carotenoid production, is controlled by ethylene. However, the mechanism underlying this process in durian fruit is still unknow. Notably, the …


Tissue And Sex-Dependent Regulation Of Innate Immunity And Rna Editing In Mice, Kelsey R. Kendrick Jan 2023

Tissue And Sex-Dependent Regulation Of Innate Immunity And Rna Editing In Mice, Kelsey R. Kendrick

Graduate Theses/Dissertations

Inflammation occurs as a result of insult or infection within the body. Individual cells respond to inflammation by upregulating genes that help mediate the immune response, such as ADAR1. ADAR1 helps regulate the immune response but also catalyzes a process called RNA editing. RNA editing alters the sequence of select mRNAs to alter the encoded proteins. The result is altered function of the encoded protein, which is often beneficial for the cell. Our goal was to determine how inflammation affects the function of ADAR1. Since we know that the effects of inflammation vary between different organs and sexes, we examined …


Role Of Grb2 Intracellular Localization In Progesterone Receptor Positive Breast Cancer, Nattamolphan Wittayavimol Jan 2023

Role Of Grb2 Intracellular Localization In Progesterone Receptor Positive Breast Cancer, Nattamolphan Wittayavimol

Chulalongkorn University Theses and Dissertations (Chula ETD)

Progesterone receptor (PR) extranuclear signaling mediates mainly through PR polyproline domain (PPD) interaction with SH3 domain of cytoplasmic signaling molecules. PR-PPD interfered with Grb2-SOS binding through SH3 interaction resulting in decreased cell proliferation and correlates with a good prognosis in PR positive breast cancer. Grb2 is a key adaptor molecule and expressed in both nucleus and cytoplasm. We hypothesized that change in Grb2 localization alters PR transcription resulting in better clinical outcomes in PR positive breast cancer. BT-474 breast cancer cells expressing inducible Grb2-SV402x (nuclear Grb2, nuGrb2) or Grb2-MYR (membrane Grb2, memGrb2) were constructed. MemGrb2-BT-474 showed higher levels of PR …


Roles Of Progesterone Signaling On Dna Repair And Cell Survival In Ovarian Cancer Cells, Pattarasiri Rangsrikitphoti Jan 2023

Roles Of Progesterone Signaling On Dna Repair And Cell Survival In Ovarian Cancer Cells, Pattarasiri Rangsrikitphoti

Chulalongkorn University Theses and Dissertations (Chula ETD)

Every year over 300,000 women worldwide are diagnosed with ovarian cancer and half of these patients die from this disease. The symptoms of ovarian cancer are very general and often confused with other common female diseases making ovarian cancer a challenging disease to diagnose and treat. Platinum-based chemotherapy, including cisplatin, stands as the first-line treatment for ovarian cancer. However, chemotherapy resistance remains a continuing problem, contributing to a high mortality rate. Progesterone receptor (PR) signaling has been implicated in various aspects of ovarian cancer biology. Clinical studies show a positive correlation between PR expression, improved patient survival and cisplatin response, …


Natural Variation In Temperature-Modulated Immunity To Pseudomonas Syringae Pv. Tomato (Pst Dc3000) In Arabidopsis Thaliana Plants, Christina A. M. Rossi Jan 2023

Natural Variation In Temperature-Modulated Immunity To Pseudomonas Syringae Pv. Tomato (Pst Dc3000) In Arabidopsis Thaliana Plants, Christina A. M. Rossi

Theses and Dissertations (Comprehensive)

Studies conducted on the model plant-pathogen system Arabidopsis thaliana-Pseudomonas syringae pv. tomato (Pst) showed that elevated temperature suppresses the pathogen-induced production of salicylic acid (SA), which is a key plant defence hormone. This increased host vulnerability at higher temperatures is due to downregulated expression of CALMODULIN BINDING PROTEIN 60-LIKE G (CBP60g) and SYSTEMIC ACQUIRED RESISTANCE DEFICIENT 1 (SARD1), which encode master regulators of SA production. Collectively, these previous studies only focused on one natural accession of Arabidopsis called Columbia-0 (Col-0). However, the intraspecific variation in Arabidopsis immunity phenotypes under elevated temperature remains unknown. To fill this critical knowledge gap, my …


Exploring The Membrane Protein And Peptide Interactions Of Mitochondrial And Bacterial Lipid Systems, George Saudan Jan 2023

Exploring The Membrane Protein And Peptide Interactions Of Mitochondrial And Bacterial Lipid Systems, George Saudan

Theses and Dissertations (Comprehensive)

This study aims to expand the understanding of interactions between membrane lipids and proteins, and relate it to their biological functions in two experimental systems. The first system focuses on the interaction and conformation of a membrane protein Uncoupling Protein 4 (UCP4) in mitochondrial inner membrane lipids, in the absence and presence of cardiolipin; a lipid specific to mitochondrial inner membranes. The second system considers the interaction and conformation of a cell penetrating peptide, Penetratin, which can interact with both mammalian and bacterial cells. A N- and C-termini protected form of this 16-meric peptide (Pen2) was used to explore its …


Investigation Of Mechanical Regulation On Stat3 Activity And Mmp Production, Jaxson R. Libby Jan 2023

Investigation Of Mechanical Regulation On Stat3 Activity And Mmp Production, Jaxson R. Libby

Honors Theses and Capstones

Transcription factor, STAT3, is inappropriately expressed in cancer cells, and has contrasting activation in 2D versus 3D microenvironments. 2D plates are often used for drug screening and do not always recapitulate in vivo responses. To combat inaccurate 2D drug studies, a 3D hydrogel was created to support the growth of cancer cells into a tumor-like environment. The hydrogel consists of a biocompatible dextran homopolysaccharide, cell adhesion RGD sequences, and crosslinker MMP labile peptides. A pH dependent reaction couples the RGD sequences to dextran then the polymers are crosslinked into a gel. Crosslinking is accomplished using terminal cysteine peptide sequences, allowing …


The Gastrointestinal-Brain-Microbiota Axis: A Promising Therapeutic Target For Ischemic Stroke, Jian-Zhuang Li Jan 2023

The Gastrointestinal-Brain-Microbiota Axis: A Promising Therapeutic Target For Ischemic Stroke, Jian-Zhuang Li

Faculty, Staff and Student Publications

Ischemic stroke is a highly complex systemic disease characterized by intricate interactions between the brain and gastrointestinal tract. While our current understanding of these interactions primarily stems from experimental models, their relevance to human stroke outcomes is of considerable interest. After stroke, bidirectional communication between the brain and gastrointestinal tract initiates changes in the gastrointestinal microenvironment. These changes involve the activation of gastrointestinal immunity, disruption of the gastrointestinal barrier, and alterations in gastrointestinal microbiota. Importantly, experimental evidence suggests that these alterations facilitate the migration of gastrointestinal immune cells and cytokines across the damaged blood-brain barrier, ultimately infiltrating the ischemic brain. …


Multiscale Molecular Modeling Studies Of The Dynamics And Catalytic Mechanisms Of Iron(Ii)- And Zinc(Ii)-Dependent Metalloenzymes, Sodiq O. Waheed Jan 2023

Multiscale Molecular Modeling Studies Of The Dynamics And Catalytic Mechanisms Of Iron(Ii)- And Zinc(Ii)-Dependent Metalloenzymes, Sodiq O. Waheed

Dissertations, Master's Theses and Master's Reports

Enzymes are biological systems that aid in specific biochemical reactions. They lower the reaction barrier, thus speeding up the reaction rate. A detailed knowledge of enzymes will not be achievable without computational modeling as it offers insight into atomistic details and catalytic species, which are crucial to designing enzyme-specific inhibitors and impossible to gain experimentally. This dissertation employs advanced multiscale computational approaches to study the dynamics and reaction mechanisms of non-heme Fe(II) and 2-oxoglutarate (2OG) dependent oxygenases, including AlkB, AlkBH2, TET2, and KDM4E, involved in DNA and histone demethylation. It also focuses on Zn(II) dependent matrix metalloproteinase-1 (MMP-1), which helps …


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 …


Interactions Of Amyloid Peptides With Lipid Membranes, Yanxing Yang Dec 2022

Interactions Of Amyloid Peptides With Lipid Membranes, Yanxing Yang

Dissertations

The aggregation of amyloid proteins into fibrils is a hallmark of several diseases including Alzheimer’s (AD), Parkinson’s, and Type II diabetes. This aggregation process involves the formation of small size oligomers preceding the formation of insoluble fibrils. Recent studies have shown that these oligomers are more likely to be responsible for cell toxicity than fibrils. A possible mechanism of toxicity involves the interaction of oligomers with the cell membrane compromising its integrity. In particular, oligomers may form pore-like structures in the cell membrane affecting its permeability or they may induce lipid loss via a detergent-like effect. This dissertation aims to …


Angiogenic Supports For Microvascular Engineering, Zain Siddiqui Dec 2022

Angiogenic Supports For Microvascular Engineering, Zain Siddiqui

Dissertations

Ischemic tissue disease is caused by a lack of circulation / blood supply to tissue. This can be treated by introducing a number of angiogenic (pro-blood vessel forming) factors into the tissue. This work presents strategies for ischemic tissue treatment utilizing a novel proangiogenic self-assembling peptide hydrogel platform. To demonstrate the utility of this platform, its use alone as an angiogenic therapeutic (both alone as a self-assembling hydrogel and with two-component systems), and its ability to vascularize implants is explored. Due to these angiogenic scaffolds demonstrating efficacy to regenerate microvasculature, this work evaluates diseases that can be treated by the …


Production Of Biofuel Using Magnetic Nanocatalyst Zno-Ni0.5zn0.5fe2o4-Fe2o3: A Mini-Review Of Recent Studies, Nida Ziafat Miss, Majid Mahmood Dec 2022

Production Of Biofuel Using Magnetic Nanocatalyst Zno-Ni0.5zn0.5fe2o4-Fe2o3: A Mini-Review Of Recent Studies, Nida Ziafat Miss, Majid Mahmood

Journal of Bioresource Management

As conventional fossil fuels are becoming limited, it is critical to find alternative clean and renewable energy sources. Biodiesel is a degradable and renewable form of fuel made up of long-chain fatty acid esters that can be generated from either plants or animals. It is a mixture of long-chain alkyl esters made through a transesterification reaction with alcohol and catalyst. Due to the high cost of petroleum, the concept of biofuel production as an alternative source has increased in recent years. The present mini-review summarizes some recent studies on alternative methods for the production of biofuel. The review concludes that …


Phytochemical Constituents, Haematological Activities And Gc-Ms Analysis Of Isolated Oil Of Rosary Pea (Abrus Precatorius) In Wistar Rat Fed With High Lipid Diet, Osaro Iyekowa, Opara V Ndubuisi Dec 2022

Phytochemical Constituents, Haematological Activities And Gc-Ms Analysis Of Isolated Oil Of Rosary Pea (Abrus Precatorius) In Wistar Rat Fed With High Lipid Diet, Osaro Iyekowa, Opara V Ndubuisi

Tanzania Journal of Science

The study is aimed at investigating the phytochemical constituents and haematological activities of the isolated oil in Wistar rat fed with high lipid diet. Powdered leaves of Abrus precatorious were extracted and phytochemical screening was done according to prescribed standard methods, while vacuum liquid chromatography (VLC) was adopted for oil isolation of the crude extract and characterized by gas chromatography-mass spectrometry (GC-MS). Thirty adult Wistar rats were randomly arranged into six groups (A, B, C, D, E and F) and treated under certain conditions. Haematological analyses were performed according to standard procedures. Saponins, alkaloids, terpenoids, flavonoids and glycosides were present. …


Determination Of Sugars, Amino Acids, Ph And Alcohol In Bamboo Beverage From Southern Highlands, Tanzania, Lilian D Kaale Dec 2022

Determination Of Sugars, Amino Acids, Ph And Alcohol In Bamboo Beverage From Southern Highlands, Tanzania, Lilian D Kaale

Tanzania Journal of Science

The amounts of sugars and amino acids play significant roles in defining the fermentation process and quantifying the alcohol levels in beverages, while pH affects the biological stability, colour, oxidation rate, and protein stability of alcoholic beverages. This study investigated the sugar content, amino acids, alcohol levels, and pH of bamboo beverage from Tanzania's southern highlands. During storage, the sugars significantly decreased (p < 0.05), especially when kept at room temperature from 52.96 to 0.00 (source 1), 53.35 to 0.00 (source 2) and 53.57 to 0.00 (source 3) g/L for fructose, from 47.93 to 14.78 (source 1), 47.23 to 14.91 (source 2) and 47.61 to 14.77 (source 3) g/L for glucose, and from 0.40 to 0.00 (source 1), 0.36 to 0.00 (source 2) and 0.37 to 0.00 (source 3) g/L for sucrose after six days of storage. A total of 15 amino acids were determined from the bamboo beverage with tyrosine being the most prevalent (597.68 mg/L for source 1, 599.44 mg/L for source 2 and 597.83 mg/L for source 3), followed by valine (261.13 mg/L for source 1, 261.24 mg/L for source 2 and 262.54 mg/L for source 3), threonine (76.69 mg/L for source 1, 76.91 mg/L for source 2 and 77.13 mg/L for source 3), and serine (66.37 mg/L for source 1, 67.23 mg/L for source 2 and 66.68 mg/L for source 3). After six days of storage at room temperature, there was a significant decrease in pH from 4.04 to 3.63. Alcohol content ranged from 3.11 to 9.05% v/v at the room temperature storage. These results might facilitate the optimal use of bamboo beverages, which have been neglected due to lack of scientific information such as amino acid and sugar levels. Keywords:    Bamboo beverage, ulanzi, amino acids, sugars, alcohol content.


Apoptotic Effect Of Bortezomib On Pancreatic Islet Cells In Stz-Induced Diabetic Rats, Çiğdem Ekin, Neslihan Tekin Karacaer, Mehtap Tarhan Karaoğlan, Ibrahim Örün, Kamile Öztürk Dec 2022

Apoptotic Effect Of Bortezomib On Pancreatic Islet Cells In Stz-Induced Diabetic Rats, Çiğdem Ekin, Neslihan Tekin Karacaer, Mehtap Tarhan Karaoğlan, Ibrahim Örün, Kamile Öztürk

Makara Journal of Health Research

Background: This study aimed to investigate the possible apoptotic role of bortezomib (BMZ) on pancreatic islets of streptozotocin (STZ)-induced diabetic rats.

Methods: Sprague-Dawley rats were divided into groups that were administered BMZ alone or in combination with STZ. To evaluate the effect of BMZ on the development of diabetes, blood glucose levels were measured regularly in the animals. Islet cell viability was determined by staining the islets with fluorescein diacetate and propidium iodide. Expression of the Bcl-2 and bax genes was determined in islet cells by quantitative real-time polymerase chain reaction.

Results: Administering STZ-induced hyperglycemia in the …


Hiv-Tat Exacerbates The Actions Of Atazanavir, Efavirenz, And Ritonavir On Cardiac Ryanodine Receptor (Ryr2), Imam Abdulrahman Bin Faisal University, Chengju Tian, Sean R. Bidasee, Zachary L. Venn, Evan Schroder, Nick Y. Palermo, Mohammad Alshabeeb, Benson J. Edagwa, Jason J. Payne, Keshoer R. Bidasee Dec 2022

Hiv-Tat Exacerbates The Actions Of Atazanavir, Efavirenz, And Ritonavir On Cardiac Ryanodine Receptor (Ryr2), Imam Abdulrahman Bin Faisal University, Chengju Tian, Sean R. Bidasee, Zachary L. Venn, Evan Schroder, Nick Y. Palermo, Mohammad Alshabeeb, Benson J. Edagwa, Jason J. Payne, Keshoer R. Bidasee

Department of Biochemistry: Faculty Publications

The incidence of sudden cardiac death (SCD) in people living with HIV infection (PLWH), especially those with inadequate viral suppression, is high and the reasons for this remain incompletely characterized. The timely opening and closing of type 2 ryanodine receptor (RyR2) is critical for ensuring rhythmic cardiac contraction–relaxation cycles, and the disruption of these processes can elicit Ca2+ waves, ventricular arrhythmias, and SCD. Herein, we show that the HIV protein Tat (HIVTat: 0–52 ng/mL) and therapeutic levels of the antiretroviral drugs atazanavir (ATV: 0–25,344 ng/mL), efavirenz (EFV: 0–11,376 ng/mL), and ritonavir (RTV: 0–25,956 ng/mL) bind to and modulate the …


Therapies For Mitochondrial Disorders, Kayli Sousa Smyth, Anne Mulvihill Dec 2022

Therapies For Mitochondrial Disorders, Kayli Sousa Smyth, Anne Mulvihill

SURE Journal: Science Undergraduate Research Experience Journal

Mitochondria are cytoplasmic, double-membrane organelles that synthesise adenosine triphosphate (ATP). Mitochondria contain their own genome, mitochondrial DNA (mtDNA), which is maternally inherited from the oocyte. Mitochondrial proteins are encoded by either nuclear DNA (nDNA) or mtDNA, and both code for proteins forming the mitochondrial oxidative phosphorylation (OXPHOS) complexes of the respiratory chain. These complexes form a chain that allows the passage of electrons down the electron transport chain (ETC) through a proton motive force, creating ATP from adenosine diphosphate (ADP). This study aims to explore current and prospective therapies for mitochondrial disorders (MTDS). MTDS are clinical syndromes coupled with abnormalities …


Machine Learning And Protein Allostery, Sian Xiao, Gennady M. Verkhivker, Peng Tao Dec 2022

Machine Learning And Protein Allostery, Sian Xiao, Gennady M. Verkhivker, Peng Tao

Mathematics, Physics, and Computer Science Faculty Articles and Research

The fundamental biological importance and complexity of allosterically regulated proteins stem from their central role in signal transduction and cellular processes. Recently, machine-learning approaches have been developed and actively deployed to facilitate theoretical and experimental studies of protein dynamics and allosteric mechanisms. In this review, we survey recent developments in applications of machine-learning methods for studies of allosteric mechanisms, prediction of allosteric effects and allostery-related physicochemical properties, and allosteric protein engineering. We also review the applications of machine-learning strategies for characterization of allosteric mechanisms and drug design targeting SARS-CoV-2. Continuous development and task-specific adaptation of machine-learning methods for protein allosteric …


Surveillance Of Antimicrobial Resistance In Veterinary Medicine In The United States: Current Efforts, Challenges, And Opportunities, Juliana M. Ruzante, Beth Harris, Paul Plummer, Raissa R. Raineri, John Dustin Loy, Megan Jacob, Orhan Sahin, Amanda J. Kreuder Dec 2022

Surveillance Of Antimicrobial Resistance In Veterinary Medicine In The United States: Current Efforts, Challenges, And Opportunities, Juliana M. Ruzante, Beth Harris, Paul Plummer, Raissa R. Raineri, John Dustin Loy, Megan Jacob, Orhan Sahin, Amanda J. Kreuder

School of Veterinary and Biomedical Sciences: Faculty Publications

Antimicrobial resistance (AMR) is a global problem facing human, animal, plant, and environmental health by threatening our ability to effectively treat bacterial infections with antimicrobials. In the United States, robust surveillance efforts exist to collect, analyze, and disseminate AMR data in human health care settings. These tools enable the development of effective infection control methods, the detection of trends, and provide the evidence needed to guide stewardship efforts to reduce the potential for emergence and further spread of AMR. However, in veterinary medicine, there are currently no known equivalent tools. This paper reviews efforts to reduce the potential for emergence …


Compatibility Of Crude Oil Blends─Processing Issues Related To Asphaltene Precipitation, Methods Of Instability Prediction─A Review, Krzysztof Bambinek, Andrzej Przyjazny, Grzegorz Boczkaj Dec 2022

Compatibility Of Crude Oil Blends─Processing Issues Related To Asphaltene Precipitation, Methods Of Instability Prediction─A Review, Krzysztof Bambinek, Andrzej Przyjazny, Grzegorz Boczkaj

Natural Sciences Publications

Processing crude oil of variable composition, especially due to the need to process crude oil blends obtained from various sources, presents a tremendous process challenge. This is mainly due to the destabilization of the colloidal system manifested mostly by the precipitation of the asphaltene fraction. The precipitation of asphaltenes from crude oil is a serious problem during extraction, transport, and processing. In the latter case, engineers and scientists have spent a lot of time determining what mechanisms are conducive to the occurrence of this phenomenon. On the one hand, there was a scientific curiosity about the principles of the nanoworld …


Arginine Methylation Of The Pgc-1Α C‑Terminus Is Temperature- Dependent, Meryl Mendoz, Mariel Mendoza, Tiffany Lubrino, Sidney Briski, Immaculeta Osuji, Janielle Cuala, Brendan Ly, Ivan Ocegueda, Harvey Peralta, Benjamin A. Garcia, Cecilia Zurita-Lopez Dec 2022

Arginine Methylation Of The Pgc-1Α C‑Terminus Is Temperature- Dependent, Meryl Mendoz, Mariel Mendoza, Tiffany Lubrino, Sidney Briski, Immaculeta Osuji, Janielle Cuala, Brendan Ly, Ivan Ocegueda, Harvey Peralta, Benjamin A. Garcia, Cecilia Zurita-Lopez

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

We set out to determine whether the C-terminus (amino acids 481–798) of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α, UniProt Q9UBK2), a regulatory metabolic protein involved in mitochondrial biogenesis, and respiration, is an arginine methyltransferase substrate. Arginine methylation by protein arginine methyltransferases (PRMTs) alters protein function and thus contributes to various cellular processes. In addition to confirming methylation of the C-terminus by PRMT1 as described in the literature, we have identified methylation by another member of the PRMT family, PRMT7. We performed in vitro methylation reactions using recombinant mammalian PRMT7 and PRMT1 at 37, 30, 21, 18, and 4 °C. …


Dissecting Interactions Across Gene Regulatory Layers In C. Elegans, Morgan Taylor Dec 2022

Dissecting Interactions Across Gene Regulatory Layers In C. Elegans, Morgan Taylor

Biological Sciences Theses and Dissertations

The nematode Caenorhabditis elegans is a powerful tool for studying nervous system genetics. Though relatively simple compared to mammals, C. elegans boasts a remarkably well-conserved neuronal genome and proteome, and its utility in the characterization of neuronal genes has been well-established. However, gene expression is often controlled by complex interactions between multiple genes, and teasing apart the functions of individual genes within such networks remains a challenge. Dissecting these interaction networks is crucial in determining the multifaceted functions of important, conserved regulatory genes. Here we explore interactions between gene regulatory layers in the C. elegans nervous system, employing a synthetic …


Quantum Computations And Molecular Dynamics Simulations: From The Fundamentals Of Antimicrobial Resistance To Neurological Diseases, Angel Tamez Dec 2022

Quantum Computations And Molecular Dynamics Simulations: From The Fundamentals Of Antimicrobial Resistance To Neurological Diseases, Angel Tamez

Electronic Theses and Dissertations

Biophysical phenomena are modeled using a combination of quantum and classical methods to interpret and supplement three distinct and diverse problems in this dissertation. In the first project, decarboxylation reactions are ubiquitous across chemical and biological disciplines, yet the origin of non-catalytic solvent effects remains elusive. Specific solvent structure and energetics have not been well described for the monoanion of malonate, nor corrected from the gas-phase charge-assisted intramolecular hydrogen bond model known as “pseudochair”. In the aqueous phase, a low-lying energy conformer known as the “orthogonal conformation” is computed to be preferred by a three-water cluster of hydrogen bonding over …


Structural And Inhibitory Studies On (I)Two Mycobacterium Tuberculosis Enzymes Essential For Capsular Glucan Biosynthesis And Mrna Degradation: (Ii) Hantann Virus L-Protein Endonuclease Domain, Hettiarachchige Thilina D. Jayasinghe Dec 2022

Structural And Inhibitory Studies On (I)Two Mycobacterium Tuberculosis Enzymes Essential For Capsular Glucan Biosynthesis And Mrna Degradation: (Ii) Hantann Virus L-Protein Endonuclease Domain, Hettiarachchige Thilina D. Jayasinghe

Theses & Dissertations

Mycobacterium tuberculosis (Mtb) is the pathogenic bacterium species that causes Tuberculosis (TB). Understanding the major biosynthetic pathways responsible for cell viability is essential in developing new drugs against Mtb. The first two projects will reflect our approach in identifying inhibitors against Mtb GlgE, Mtb GpsI, and characterization of protein inhibitor interactions using X-ray crystallography.

The enzyme GlgE plays an essential role in the α-glucan biosynthesis pathway in Mtb cells. These α-glucans are one of the major structural units in the Mtb capsule. GlgE catalyzes the elongation of α-glucan by transferring maltose from maltose-1-phosphate (M1P) to the non-reducing end …


Characterization Of Ape1 And Dna G-Quadruplex Interaction In Transcription Regulation And Dna Damage Repair, Suravi Pramanik Dec 2022

Characterization Of Ape1 And Dna G-Quadruplex Interaction In Transcription Regulation And Dna Damage Repair, Suravi Pramanik

Theses & Dissertations

Human AP Endonuclease 1 (APE1) is the primary enzyme in the base excision repair (BER) pathway that repairs apurinic/apyrimidinic (AP) sites, the most frequently formed DNA lesions in the genome. Recently, through genome-wide mapping analysis, we have shown that APE1, as well as its post-translationally modified form, acetylated APE1 (AcAPE1), is enriched in the gene regulatory regions. The APE1/AcAPE1-enriched regions also harbor Guanine (G)-rich sequences that fold into DNA secondary structures called G-quadruplexes (G4s). Our lab has demonstrated a strong genome-wide correlation between the occurrence of G4 structures and the binding of APE1 and AcAPE1. However, it is unknown whether …


Novel Mechanisms Of Protein Kinase C Α Regulation And Function, Xinyue Li Dec 2022

Novel Mechanisms Of Protein Kinase C Α Regulation And Function, Xinyue Li

Theses & Dissertations

Protein kinase Cα (PKCα) is a member of the PKC family of serine/threonine kinases, which have been implicated in regulation of many cellular processes, including cell proliferation, differentiation, survival, and transformation. A large body of evidence from the Black laboratory and others support an anti-proliferative function of PKCα in normal epithelial tissues, including the intestinal mucosa and endometrial epithelium. PKCα is also tumor suppressive in epithelial cancers, such as colorectal cancer (CRC) and endometrial cancer (EC). However, a major obstacle to harnessing the tumor suppressive functions of PKCα to benefit patients is the widespread loss of PKCα expression in tumors. …


Metoprolol Disrupts Sterol Biosynthesis Through Inhibition Of 7-Dehydrocholesterol Reductase (Dhcr7), Luke B. Allen Dec 2022

Metoprolol Disrupts Sterol Biosynthesis Through Inhibition Of 7-Dehydrocholesterol Reductase (Dhcr7), Luke B. Allen

Theses & Dissertations

Cholesterol is essential for life. It is particularly important in the brain as it relies on de novo synthesis of cholesterol following the formation of the blood brain barrier (BBB). As such, disrupting sterol biosynthesis during neurodevelopment can have devastating outcomes. The most common post-lanosterol sterol biosynthesis disorder, Smith-Lemli-Opitz Syndrome, arises from a faulty DHCR7 enzyme. DHCR7 has also been shown to be inhibited by several psychotropic medications. Here we assess six beta-blockers and their effects on sterol biosynthesis in vitro. Two beta-blockers, metoprolol and nebivolol strongly inhibit DHCR7 in four separate in vitro models of both mouse and …


Dynamics Of Nucleosome Assembly Characterized By Atomic Force Microscopy, Tommy Stormberg Dec 2022

Dynamics Of Nucleosome Assembly Characterized By Atomic Force Microscopy, Tommy Stormberg

Theses & Dissertations

Nucleosomes are the basic repeating unit defining the assembly and function of chromatin. Understanding the fundamental mechanisms of nucleosome structure and dynamics is critical to elucidating the chromatin assembly process. This dissertation describes my work in elucidating the role of different factors that drive the nucleosome dynamics.

In my first study, we characterized, for the first time, the effect of sequence on nucleosome assembly. We then characterized the role of internucleosomal interactions, discovering a critical role internucleosomal interactions in the assembly of higher order structures.

Based on the previous study and literature regarding histone tails, we hypothesized the histone H4 …