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Molecular Mechanism Of Damage-Associated Molecular Patterns In Association With Acute Hepatopancreatic Necrosis Disease Resistance Of Heat Stressed-Shrimp Penaeus Vannamei, Supitcha Wanvimonsuk

Chulalongkorn University Theses and Dissertations (Chula ETD)

Non-lethal heat shock (NLHS) is known to enhance resistance to acute hepatopancreatic necrosis disease caused by Vibrio parahaemolyticus (VPAHPND) in the Pacific white shrimp Penaeus vannamei. Generally, cell damage induced by stresses leads to the release of damage-associated molecular patterns (DAMPs), molecules that act as endogenous danger signals to promote immune response. The first part of this research aims to study molecular mechanism of DAMPs that can enhance innate immunity upon NLHS treatment on VPAHPND resistance. We identified and characterized the candidate NLHS-induced DAMP that can activate innate immune responses against VPAHPND. The candidate DAMP genes were retrieved from the …

Type-B Energetic Processes And Their Associated Scientific Implications, James Weifu Lee

Chemistry & Biochemistry Faculty Publications

Recently, our work has identified two thermodynamically distinct types (A and B) of energetic processes naturally occurring on Earth. Type-A energy processes such as the classical heat engines, ATP hydrolysis, and many of the known chemical, electrical, and mechanical processes apparently follow well the second law of thermodynamics; Type-B energy processes, for example, the newly discovered thermotropic function that isothermally utilizes environmental heat energy to do useful work in driving ATP synthesis, follow the first law of thermodynamics (conservation of mass and energy) but do not have to be constrained by the second law, owing to its special asymmetric functions. …

A Look Into Alzheimer’S Disease—Interventions At The Molecular Level, Priscila Feliciano Nieves

Honors Undergraduate Theses

There are puzzle pieces to the cure for Alzheimer’s Disease (AD), and such can emerge by inspecting the biomolecular interactions and their effects on neuronal cells. The upcoming presented literature review will cover the molecular changes caused by AD pathological progression, explore the relationship between non-AD molecules and AD molecules in the body, and analyze potential contributing factors in AD. In addition, the information to be provided will highlight medicinal alternatives respective to a particular stage in AD.

Investigation Of Dna Hybridization In Localized Systems In Close Proximity, Ashley M. Sewsankar

Honors Undergraduate Theses

Hybridization of two or more DNA or RNA strands is well documented for the process taking place with all strands free in solution or when one strand is immobilized on a substrate. This study contributes to the investigation of the hybridization process when two single DNA strands (ssDNA) are in close proximity. We took advantage of an X sensor in which hybridization of four DNA strands enables the formation of a DNA four-way junction (crossover or X) structure. We immobilized multiple layers of crossover structures to study its hybridization being triggered by short ssDNA coming from solution and further investigate …

Peripheral And Central Glucose Flux In Type I Diabetes, Jelena Anna Juras

Theses and Dissertations--Neuroscience

Diabetes is a complex metabolic disorder, of which high blood glucose concentration is the primary hallmark. Type I diabetes mellitus (T1DM) is characterized by the lack of insulin production, due to a poorly understood autoinflammatory cascade. In the words of historian Barnett “Diabetes may no longer be a death sentence, but for more and more people in the 21st century, it will become a life sentence”, making it the focal point of many research groups. It is estimated that around 20 million individuals worldwide live with T1DM.

Effects of long-term chronically elevated blood glucose are not only seen in micro/macro-vascular …

Building Tools For Improved Modulation Of The Human Gabaa Receptor, A Central Nervous System Target For The Treatment Of Anxiety, Garrett Edward Zinck

Theses and Dissertations--Pharmacy

In the U.S., anxiety is recognized as an increasing range of mentally and physically debilitating psychiatric health disorders with significant economic repercussions. Over the last 20 years, several novel anti-anxiety therapies have entered the drug development pipeline, but none have made it to market.

The work in this dissertation focused on structurally modifying valerenic acid (VA), a structurally unique carboxylated sesquiterpene acid found in Valeriana officinalis. VA is putatively reported to have allosteric modulatory activity of the human GABA_A receptor, a ligand-gated ion channel responsible for attenuating neurotransmissions. Structural modeling of VA’s GABA_A receptor interaction suggests that …

Apoe Genotype And Cerebral Glucose Metabolism: A Multi-Omics Approach, Holden C. Williams

Theses and Dissertations--Physiology

Apolipoprotein E (APOE) is encoded by the APOE gene, present in humans as three main isoforms (E2, E3, and E4). E4 carriers face up to a 15-fold increased risk for developing late-onset Alzheimer’s disease (AD), while E2 carriers are protected. Understanding the risk conferred by E4 has been an extensive research focus for nearly three decades, but the exact mechanism has yet to be proven. Many studies have demonstrated attenuated roles of E4 in classical hallmarks of AD, notably amyloid processing and neurofibrillary formation, which normally present later in disease progression. How APOE influences hallmarks that present much earlier are …

A Study Of Cobalt (Iii) Oxide Nanoparticle Delivery Of Sirna Molecules Directed Against Signaling Intermediates Of The P2y2 Receptor, Rachel Blair Stroud

Graduate Theses/Dissertations

G protein-coupled receptors are evolutionarily ubiquitous sensors of extracellular signals, propagating intracellular signal cascades through heterotrimeric G proteins. P2Y₂ receptors are GPCRs which are activated by extracellular nucleotides to mediate signaling cascades via Gαq coupling. Many GPCRs are subject to a common mechanism for signal termination involving phosphorylation of the C-terminal tail followed by β-arrestin binding and subsequent endocytic internalization of the complex. This effect has been described for the P2Y₂ R in the 1321N1 astrocytoma cell line, and UTP-induced activation and desensitization profiles have been previously defined. There is need to develop molecular vehicles for safe and …

Function And Expression Of Ribonucleotide Reductase-Encoding Genes In Flavobacterium Johnsoniae, Hunter Scott Doheny

All Graduate Theses, Dissertations, and Other Capstone Projects

Ribonucleotide reductases (RNRs) are essential enzymes that are involved in DNA synthesis. While this makes them ideal targets for antiproliferative drugs, most known RNR targeting agents are nonspecific. This poses a problem when considering antimicrobials, but several groups of bacteria have RNRs that utilize unique mechanisms that could be exploited if fully understood. One such bacteria, Flavobacterium johnsoniae, has the gene for a class Id RNR with a novel activation mechanism. Class Id RNRs belong to the aerobic class I RNRs and seem to have a unique metallocofactor and activation mechanism involving superoxide and manganese. The goal of this research …

Antibacterial Activity Of Commiphora Molmol (Myrrha) Against The Yeast, Mohammad Hassan Alshehri

Selected Full-Text Master Theses 2021-

Commiphora molmol (myrrha) is widely used as a traditional medicine around the globe against inflammatory diseases. It is also considered to be effective as anti-fungal, anti-cancer and anti-oxidant agent. The minimum inhibitory concentration, bactericidal activity and heat stability of antibiotic component in myrrha oil extract has been investigated. The MIC was determined in nutrient free buffer and in nutrient rich peptone glucose buffer. The results showed that MIC was 0.6% in nutrient free buffer as no growth was shown by cells, whereas, in peptone glucose media a slight increase in cell count was seen. It can be concluded that it …

Multilevel Computational Investigation Into The Dynamics And Reaction Mechanisms Of Non-Heme Iron And 2-Oxoglutarate Dependent Enzymes, Shobhit Sanjeev Chaturvedi

Dissertations, Master's Theses and Master's Reports

Computational chemistry methods have been extensively applied to investigate biological systems. This dissertation utilizes a multilevel computational approach to explore the dynamics and reaction mechanisms of two groups of enzymes belonging to non-heme Fe(II) and 2-oxoglutarate (2OG) dependent superfamily – histone lysine demethylases from class 7 and ethylene forming enzyme (EFE). Chapter 2 uncovers the role of conformational dynamics in the substrate selectivity of histone lysine demethylases 7A and 7B. The molecular dynamics (MD) simulations of the two enzymes revealed the importance of linker flexibility and dynamics in relative orientations of the reader (PHD) and the catalytic (JmjC) domains. Chapter …

Further Investigation Of The Initiating Mechanism Of The Type I Collagen Glomerulopathy, Matthew James Freese

Graduate Theses/Dissertations

The progressive accumulation of collagen and other extracellular matrix proteins in the renal mesangium results in fibrosis, glomerulosclerosis, and eventual renal failure. Mice deficient in integrating α2(I) collagen into the type I collagen structure, termed Col1a2-deficient mice, model kidney fibrosis through the condition Type I Collagen Glomerulopathy, because homotrimeric type I collagen accumulates extracellularly in the mesangium of renal glomeruli. Accumulation of homotrimeric type I collagen compresses blood vessels in glomeruli, which reduces filtration, increases pressure, and results in fibrosis. Picrosirius red (PSR) staining was used on Col1a2 deficient and wildtype mice to evaluate collagen deposition. Histological evaluation and …

Exosomal-Long Non-Coding Rnas Journey In Colorectal Cancer: Evil And Goodness Faces Of Key Players, Nehal I. Rizk, Ahmed I. Abulsoud, Mohamed M. Kamal, Dina H. Kassem, Nadia M. Hamdy

Pharmacy

Exosomes are nano-vesicles (NVs) secreted by cells and take part in cell-cell communications. Lately, these exosomes were proved to have dual faces in cancer. Actually, they can contribute to carcinogenesis through epithelial-mesenchymal transition (EMT), angiogenesis, metastasis and tumor microenvironment (TME) of various cancers, including colorectal cancer (CRC). On the other hand, they can be potential targets for cancer treatment. CRC is one of the most frequent tumors worldwide, with incidence rates rising in the recent decades. In its early stage, CRC is asymptomatic with poor treatment outcomes. Therefore, finding a non-invasive, early diagnostic biomarker tool and/or suitable defender to combat …

Sources And Therapeutic Strategies Of Mesenchymal Stem Cells In Regenerative Medicine, Mohamed M. Kamal, Dina H. Kassem

Pharmacy

During the past decade, mesenchymal stem cells (MSCs) have made their mark as a potential weapon in regenerative medicine. Since their first isolation by Friedenstein in the late 1970s of the last century, MSCs have opened new avenues in the field of regenerative medicine. The main fascination about MSCs lies in their ease of isolation and large ex vivo expansion capacity, as well as demonstrated multipotency and immunomodulatory activities. Basically, several reports have proved that MSCs isolated from different sources possess different characteristics and potentials. In addition, the mechanisms by which these cells can help regenerate tissues and treat several …

Protumorigenic Effects Of Mixed Lineage Kinase Domain-Like Protein In Cholangiocarcinoma Cells, Nattaya Duangthim

Chulalongkorn University Theses and Dissertations (Chula ETD)

Cholangiocarcinoma (CCA), a heterogeneous malignancy of bile duct system, has the highest incidence in Thailand. CCA is one of the leading causes of death which has low 5-year survival rate from 5% to 10% in advanced stages due to the difficulty of diagnosis in early stage and lack of effective therapies. Therefore, understanding the molecular mechanisms and pathogenesis of CCA development and progression is urgently needs and will lead to the development of novel therapeutic targets and strategies. Mixed lineage kinase domain-like (MLKL) was identified as a key effector in a novel regulated necrosis or necroptosis pathway. Recently studies have …

Characterizing The Relationship Of Lgl1 And Akt In Migration Of Murine Neural Stem And Progenitor Cells, Natalie Pedicino

Cal Poly Humboldt theses and projects

Asymmetric cell division and migration are critical for neural stem cell differentiation and brain development. When these processes are dysregulated in neural progenitor cells (NPCs), developmental defects and diseases like glioma can result. Lgl1 is a tumor suppressor gene that was first characterized in Drosophila neuroblasts (Strand et al., 1994). It is best known for its regulation of asymmetric cell division through its association with the Par complex. The PI3K/AKT signaling cascade is involved in cellular migration and is also regulated by Par signaling. Unpublished data from the Sprowles laboratory suggests a potential role of Lgl1 in migration and other …

Ero1Α Promotes Tumorigenesis In Egfr Driven Nsclc, Brennan D. Johnson

Graduate Theses, Dissertations, and Problem Reports (ETD)

Non-Small Cell Lung Cancer (NSCLC) is a pulmonary malignancy most commonly associated with smoking, or exposure to asbestos or Radon. Approximately, 1.6 Million deaths occur each year due to lung cancer. Lung Cancer is categorized by two main types, Small Cell Lung Cancer (SCLC) and NSCLC. NSCLC accounts for approximately 85% of all lung cancer cases and is subdivided into three sub-categories: Adenocarcinoma, the most common and leading cause of death in the United States; Squamous Cell Carcinoma (SCC), and Large Cell Carcinoma. Though NSCLC treatment regimens have shown increasing clinical benefit over the last two decades with targeted therapies. …

Amelioration Of Mitochondrial Bioenergetic Dysfunction In Diabetes Mellitus: Delving Into Specialized And Non-Specific Therapeutics For The Ailing Heart, Andrya Jean Durr

Graduate Theses, Dissertations, and Problem Reports (ETD)

Morbidity and mortality of the diabetic population is influenced by many confounding factors, but cardiovascular disease (CVD), remains the leading cause of death. Mitochondrial dysfunction is central in the development of cardiac contractile dysfunction, with decreased mitochondrial bioenergetic function, increased dependence on free fatty acid utilization, and a decrease in glucose utilization having been shown to contribute to contractile dysfunction. Strategies targeting the amelioration of mitochondrial bioenergetic function are attractive for limiting diabetes-induced heart failure, and preserving health-span. The goals of this dissertation were to assess two mitochondrial-centric approaches for the amelioration of mitochondrial and cardiac contractile dysfunction in diabetes …

Transitions Between The Steps Of Group Iic Intron Forward And Reverse Splicing And Integration Into Dna, Claire Mae Smathers

Graduate Theses, Dissertations, and Problem Reports (ETD)

Group II introns are ancient ribozymes capable of self-excision and mobility into new genomic locations. As the ancestors of both the eukaryotic spliceosome and eukaryotic retroelements, these simple RNA machines serve as excellent models for understanding the mechanisms of both gene splicing and retroelement activity in eukaryotes. Although group II introns have been studied for decades, knowledge of the most unique and arguably evolutionarily relevant class of group II introns, IIC, is limited. Our knowledge is especially limited in terms of understanding how IIC introns mediate the transition between the two transesterification steps of forward splicing and reverse splicing into …

Getting To The Root Cause: The Genetic Underpinnings Of Root System Architecture And Rhizodeposition In Sorghum, Farren Smith

Graduate Theses, Dissertations, and Problem Reports (ETD)

Plants are some of the most diverse organisms on earth, consisting of more than 350,000 different species. To understand the underlying processes that contributed to plant diversification, it is fundamental to identify the genetic and genomic components that facilitated various adaptations over evolutionary history. Most studies to date have focused on the underlying controls of above-ground traits such as grain and vegetation; however, little is known about the “hidden half” of plants. Root systems comprise half of the total plant structure and provide vital functions such as anchorage, resource acquisition, and storage of energy reserves. The execution of these key …

Determining The Effects Of Chemical Exposure On Hepatocyte Mitochondrial Networks And Cell Viability, Bethany Eaton

All Master's Theses

Mitochondria are cellular organelles that are becoming more recently studied. One of their main functions is the production of energy through cellular respiration, which is crucial to cell life. However, they are also associated with numerous disease states. It is hypothesized that reactive oxygen species (ROS), largely produced in mitochondria, induce oxidative stress and affect mitochondrial morphology along with cell viability. This study compares chemical exposure of menadione, an ROS producer, and phthalates (plasticizers) on two mouse hepatocyte cell lines to determine the effects they have on mitochondrial morphology and cell viability. Three experiments were performed to analyze the effects …

Development Of Novel Pyridazine Derivatives And Drug Delivery Systems Against Dengue, Janae A. Culmer

College of Graduate Studies: Theses & Dissertations

The lack of approved vaccines, medications and treatment regimens has significantly contributed to the rapid spread of mosquito-borne viruses such as Dengue and Zika virus. The complex immunopathology of these viruses presents limitations for the development and implementation of a definitive, safe and effective approach to combat infections.Previous research has demonstrated that vector control strategies such as the elimination of larval habitats, larviciding with insecticides, the use of biological agents and the application of adulticides have been unsuccessful in the reduction of viral transmission leading to the need for the continued development of antivirals. This research proposes an approach for …

Epigenetic Buffering In Introduced House Sparrows, M. Ellesse Lauer

College of Graduate Studies: Theses & Dissertations

Epigenetic buffering, as an environmentally induced increase in variance of epigenetic states that increases phenotypic variation to buffer populations against decreased fitness, may be a factor that resolves the genetic paradox of introduced species. DNA methylation is a molecular mechanism that could facilitate epigenetic buffering by changing in response to environmental stress. Therefore, epigenetic buffering can be detected through increased variance in DNA methylation in novel or heterogeneous environments. Introduced house sparrows (Passer domesticus) have well-documented phenotypic changes with low genetic diversity, high epigenetic diversity, and high variance in DNA methylation that provide a characteristic signature of epigenetic buffering. …

Biomimetic Synthesis Of Palladium Nanoparticles For Catalytic Application, Emily A. Groover

College of Graduate Studies: Theses & Dissertations

The synthesis of palladium nanoparticles (Pd NPs) using materials-directed peptides is a novel, nontoxic approach which exerts a high level of control over the particle size and shape. This biomimetic technique is environmentally benign, featuring nonhazardous ligands and ambient conditions. Nanoparticles are extremely reactive catalysts, boasting a large surface-to-volume ratio when compared to their bulk counterparts. The rational design of these nanoparticles using peptides has been very successful in aqueous environments, but no research has been done to apply it in organic systems. As such, the biomimetic synthesis of Pd NPs in an organic system is here investigated, with ethanol …

Investigating The Main Protease (Mpro) Of Sars-Cov-2 As A Potential Drug Target, Valerie Giovina Pascetta

Honors Theses and Capstones

The rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the coronavirus disease 19 (COVID-19) pandemic has claimed the lives of roughly 6.2 million people worldwide as of May 2022. The virus’s main protease (M^pro ) has been identified as an attractive drug target due to the critical role it plays in the viral life cycle. The roughly 34 kDa M^pro cleaves functional viral polypeptides out of two long polyproteins at conserved cut sites, allowing them to fulfill their role in processes like transcription and replication. Here, we have studied the enzymatic activity …

Production And Biological Activities Of Oligo Pectin From Early Immature Fruit Of Durio Zibethinus L., Aunchiya Pitaksa

Chulalongkorn University Theses and Dissertations (Chula ETD)

Early immature durian (EID) fruits, 30-45 days after anthesis with 6-12 cm in length, are considered agricultural waste from cultivation. It is known that durian rinds of mature fruits contain pectin, but there have been no reports on the pectin content of early immature durian (EID) fruits. Therefore, the objective of this study was to determine the pectin content in EID fruits. We extracted pectin from EID fruits using distilled water at different temperatures (25°C, 50°C, and 75°C) for 1 h to investigate pectin content. Instrumental analyses, including X-ray diffraction (XRD) and Fourier Transform Infrared Spectrometer (FT-IR), confirmed the presence …

Anti-Neuroinflammatory Effects Of Auricularia Polytricha Extracts On Bisphenol A (Bpa)-Induced Microglial Cell Activation And Reduction Of Hippocampal Cell Damage, Chanin Sillapachaiyaporn

Chulalongkorn University Theses and Dissertations (Chula ETD)

Bisphenol A (BPA) is widely used in the production of polycarbonate plastics, it has been reported that BPA can activate neuroinflammation. Neuroinflammation is a brain pathology that involves the high levels of pro-inflammatory mediators, including tumor necrosis factor-alpha (TNF-α). An excessive TNF-α expression could result in neuronal cell death and subsequently lead to neurodegeneration. Auricularia polytricha (AP) is an edible mushroom with several medicinal properties. Herein, the anti-neuroinflammatory effects of AP extracts against BPA-induced BV2 microglial inflammation were investigated. Hexane (APH) and ethanol (APE) extracts of AP inhibited BPA-induced neuroinflammation in BV2 cells by reducing the expression of pro-inflammatory cytokines. …

Purification And Activity Assay Optimization Of Bacterial Catalase From Psychrobacter Koprana, Sydney Willis

Honors Program Theses

To date, catalase protein from bacterial species is not the most widely used commercial catalase. Catalase, the enzyme that breaks down hydrogen peroxide in most living organisms, is an invaluable enzyme in the food, agriculture, and pharmaceutical industries. In 2019, a novel species of a psychrotolerant bacterium was discovered in Cold Harbor, NY. This species, Psychrobacter koprana, exhibits highly active catalase. Preliminary data from activity assays demonstrates that P. koprana catalase has the same activity as commercially available catalase. After purification and activity assay optimization, the activity of this catalase has the potential to be more active than other easily …

Identifying The Role Of Cholesterol And The Cholesterol Transfer Protein, Ysp1-2, In Cell-Cell Fusion In Tetrahymena Thermophila, Natasha D. Kusibab

Honors Program Theses

A cell’s shape directly affects how it behaves as one’s structure directly correlates to its function. The shape of cells and organelles is driven in part by the lipid bilayer that makes up their membranes. The process by which cells systematically adjust the types of lipids in membranes to facilitate changes in membrane shape remain uncertain. In our research, we aimed to address this issue by studying the role of lipid transfer proteins in the ciliate, Tetrahymena thermophilia. Specifically, we focus on the process of cell-cell fusion during mating in Tetrahymena as this requires a drastic change in membrane shape …

Cryo-Em Structure Of Transmembrane Aaa+ Protease Ftsh In The Adp State, Wu Liu, Martien Schoonen, Tong Wang, Sean Mcsweeney, Qun Liu

Advanced Science Research Center

AAA+ proteases regulate numerous physiological and cellular processes through tightly regulated proteolytic cleavage of protein substrates driven by ATP hydrolysis. FtsH is the only known family of membrane-anchored AAA+ proteases essential for membrane protein quality control. Although a spiral staircase rotation mechanism for substrate translocation across the FtsH pore has been proposed, the detailed conformational changes among various states have not been clear due to absence of FtsH structures in these states. We report here the cryo-EM structure for Thermotoga maritima FtsH (TmFtsH) in a fully ADP-bound symmetric state. Comparisons of the ADP-state structure with its apo-state and a substrate-engaged …