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Articles 2641 - 2670 of 6985

Full-Text Articles in Biochemistry

Insights Into Nucleic Acid-Platinum(Ii) Compound Interactions And Structural Impacts, Supuni Duneeshya Kamal Thalalla Gamage Jan 2019

Insights Into Nucleic Acid-Platinum(Ii) Compound Interactions And Structural Impacts, Supuni Duneeshya Kamal Thalalla Gamage

Wayne State University Dissertations

With the discovery of cisplatin in the 1960s, it has been widely studied as a precursor for anticancer drug development. Despite its effectiveness against certain cancers, clinical usage of cisplatin is restricted by a number of side effects and resistance. In the past decade, scientists have been exploring biologically important ligands such as sugar derivatives in the hope of overcoming such challenges. Attachment of a sugar moiety could facilitate lower accumulation of platinum drugs in the body as well as enhance cellular uptake. In this study, a carbohydrate-linked cisplatin analog, cis-dichlorido[(2-β-D-glucopyranosidyl)propane-1,3-diammine]platinum (5) has been studied. The aim was to evaluate …

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Functional Characterization Of Accessory Proteins And Novel Activities In Direct And Indirect Trna Aminoacylation, Udumbara Menike Rathnayake Jan 2019

Functional Characterization Of Accessory Proteins And Novel Activities In Direct And Indirect Trna Aminoacylation, Udumbara Menike Rathnayake

Wayne State University Dissertations

Indirect tRNA aminoacylation is essential for most bacteria and archaea, particularly when these species do not have genes encoding asparaginyl- and/or glutaminyl-tRNA synthetase (AsnRS and GlnRS). In the absence of AsnRS, the first step in Asn-tRNAAsn synthesis involves misacylation of tRNAAsn with aspartate to produce Asp-tRNAAsn; this reaction is catalyzed by a non-discriminating aspartyl-tRNA synthetase (ND-AspRS). Subsequently, in bacteria, an amidotransferase called GatCAB converts Asp-tRNAAsn to Asn-tRNAAsn. An analogous, two-step processes exist to produce Gln-tRNAGln. In this case, a non-discriminating glutamyl-tRNA synthetase (ND-GluRS) misacylates tRNAGln to produce Glu-tRNAGln, which is then converted to Gln-tRNAGln by GatCAB. The central hub of …

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The Fallacy Of Defensive Protection For Traditional Knowledge, Margo A. Bagley Jan 2019

The Fallacy Of Defensive Protection For Traditional Knowledge, Margo A. Bagley

Faculty Articles

Proponents of databases as defensive protection posit that having sources of traditional knowledge easily accessible to, and searchable by, examiners during the prosecution process should minimize the grant of patents covering traditional knowledge, and avoid the problems such erroneously granted patents may produce. Some countries, such as India, which support an international sui generis positive protection instrument, also support the use of traditional knowledge databases, as the two approaches are not mutually exclusive. India's CSIR, which created and maintains the TKDL, asserts that the database has thwarted the grant of scores of patents in IP offices across the globe, although …

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Computational Design And Production Of Levansucrase With Increased Thermostability, Methus Klaewkla Jan 2019

Computational Design And Production Of Levansucrase With Increased Thermostability, Methus Klaewkla

Chulalongkorn University Theses and Dissertations (Chula ETD)

Levansucrase is a carbohydrate-modifying enzyme that catalyzes hydrolysis of sucrose and transfructosylation of a fructosyl unit of sucrose to produce levan and levan-type fructooligosaccharides (LFOs). Due to their various beneficial properties such as low viscosity and non-toxicity. Levan and LFOs have potential applications in many industries such as prebiotics in food industries and anti-tumor agents in pharmaceutical industries. Previous study found that the Y246S mutant of Bacillus licheniformis RN-01 levansucrase (Oligosaccharide Producing Levansucrase, OPL) could effectively produce LFOs, but its thermostability is limited at high temperature. In this study, molecular dynamics (MD) and computational protein design were used to design …

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Naturally Derived Compounds As Preventatives Of Proteinopathies, Lois Mendez Jan 2019

Naturally Derived Compounds As Preventatives Of Proteinopathies, Lois Mendez

Open Access Theses & Dissertations

Neurodegenerative diseases, such as Parkinson’s disease (PD), afflict millions worldwide. Of greater concern is the fact that a main risk factor this disease is aging and the baby boomer population is now reaching a geriatric age. Despite the active research in this area, little progress has been made in the development of therapeutic strategies and furthering of our understanding in pinpointing the causal events that onset these disease processes. Our lab has focused on studying the protein homeostasis of key biomarkers in neurodegenerative diseases and examining whether natural compounds can act as neuro-protectants and, thus, attenuate the pathology that ensues …

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Amino Acids Profiling For The Diagnosis Of Metabolic Disorders, Yana Sandlers Jan 2019

Amino Acids Profiling For The Diagnosis Of Metabolic Disorders, Yana Sandlers

Chemistry Faculty Publications

Inborn errors of metabolism (IEM) represent a group of inherited diseases in which genetic defect leads to the block on a metabolic pathway, resulting in a single enzyme dysfunction. As a downstream consequence of the residual or full loss of the enzymatic activity, there is an accumulation of toxic metabolites in the proximity of the metabolic block and/or a deficiency of an essential metabolic product which leads to the clinical presentation of the disease. While individually IEMs are rare, a collectively estimated incidence of metabolic inherited disorders is 1:800. The genetic basis of IEMs can involve abnormalities such as point …

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Unintended Consequences Of Dna Analysis Delays In North Carolina, Pamela Cook Woodard Jan 2019

Unintended Consequences Of Dna Analysis Delays In North Carolina, Pamela Cook Woodard

Walden Dissertations and Doctoral Studies

The processing of DNA recovered from felony crime scenes often causes delays in trials of up to 3 years, calling into question defendants' rights to a speedy trial. Using Lewin's force field analysis as the theoretical framework, the purpose of this quantitative, comparative study was to compare the processing and reporting of results related to DNA testing in 4 states. Survey data were collected from state bar members (n=137), members of a professional law organization (n=149), and members of a state DNA laboratory (n=20). The purpose of this quantitative, comparative study was to determine whether these variables (interagency communications, staff …

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Toward An Enzyme-Coupled, Bioorthogonal Platform For Methyltransferases: Probing The Specificity Of Methionine Adenosyltransferases, Tyler D. Huber Jan 2019

Toward An Enzyme-Coupled, Bioorthogonal Platform For Methyltransferases: Probing The Specificity Of Methionine Adenosyltransferases, Tyler D. Huber

Theses and Dissertations--Pharmacy

Methyl group transfer from S-adenosyl-l-methionine (AdoMet) to various substrates including DNA, proteins, and natural products (NPs), is accomplished by methyltransferases (MTs). Analogs of AdoMet, bearing an alternative S-alkyl group can be exploited, in the context of an array of wild-type MT-catalyzed reactions, to differentially alkylate DNA, proteins, and NPs. This technology provides a means to elucidate MT targets by the MT-mediated installation of chemoselective handles from AdoMet analogs to biologically relevant molecules and affords researchers a fresh route to diversify NP scaffolds by permitting the differential alkylation of chemical sites vulnerable to NP MTs that are unreactive to …

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Elucidating A Common Mechanism Of Proteasome Impairment In Neurodegenerative Disease And Its Pharmacological Intervention, Tiffany Ann Thibaudeau Jan 2019

Elucidating A Common Mechanism Of Proteasome Impairment In Neurodegenerative Disease And Its Pharmacological Intervention, Tiffany Ann Thibaudeau

Graduate Theses, Dissertations, and Problem Reports (ETD)

Proteostasis is maintained by several systems in the cell including the ubiquitin-proteasome system (UPS), chaperones, chaperone-mediated autophagy, and macroautophagy. The UPS is the principle route for the degradation of intracellular misfolded, damaged, or unneeded cellular proteins and has a critical role essential every cell process, including: cell cycle progression, transcriptional regulation, genome integrity, apoptosis, immune responses, and neuronal plasticity. When the efficiency of protein degradation is perturbed, misfolded and damaged protein aggregates can accumulate to toxic levels and cause neuronal dysfunction, which may underlie many neurodegenerative diseases. It is widely appreciated that soluble oligomers of misfolded proteins (e.g. Aβ, Alzheimer’s; …

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Screening Of Human Serum/Plasma Using Vibrational Spectroscopy For Early Disease Diagnostics And Therapeutic Drug Monitoring, Drishya Rajan Parachalil [Thesis] Jan 2019

Screening Of Human Serum/Plasma Using Vibrational Spectroscopy For Early Disease Diagnostics And Therapeutic Drug Monitoring, Drishya Rajan Parachalil [Thesis]

Doctoral

Analysis of analytes present in the blood stream can potentially deliver crucial information on patient health and indicate the presence of numerous pathologies. Existing clinical techniques for this analysis can, however, be costly and time-consuming. The potential of Raman spectroscopic analysis of human plasma and/or serum for diagnostic purposes has been widely investigated and, increasingly, its feasibility for clinical translation has been explored. However, as the concentration of many analytes in plasma/serum is relatively low, to date such analysis has commonly been performed on air-dried drops deposited on substrates, leading to inhomogeneity and inconsistencies. This study explores the potential of …

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Effects Of Hydrogen Synthesis Inhibition On Changes Of Bioproduct Contents In Cyanobacterium Synechocystis Sp. Pcc 6803, Nannaphat Sukkasam Jan 2019

Effects Of Hydrogen Synthesis Inhibition On Changes Of Bioproduct Contents In Cyanobacterium Synechocystis Sp. Pcc 6803, Nannaphat Sukkasam

Chulalongkorn University Theses and Dissertations (Chula ETD)

Cyanobacteria have an ability to convert carbon dioxide and solar light to bioproducts. Synechocystis sp. PCC 6803 is the laboratory model strain of cyanobacteria with known metabolism and biochemistry. NADPH is one of the essential electron carriers and coenzymes required for various cellular metabolism including the production of bioproducts. [NiFe]-Hydrogenase consumes NADPH to produce hydrogen gas which considerably the loss of metabolic energy. Thus, the elimination of [NiFe]-hydrogenase would increase NADPH level in the cell and might increase the accumulation of bioproducts. In this work, hoxY and hoxH genes (encoding the two catalysis subunits of [NiFe]-hydrogenase) were inactivated. The inactivation …

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Anti-Tumor Activities Of Auricularia Polytricha Extracts In Hepatocellular Carcinoma Cell Line (Hepg2) And Breast Cancer Cell Lines (Mcf-7 And Mda-Mb-231), Sunita Nilkhet Jan 2019

Anti-Tumor Activities Of Auricularia Polytricha Extracts In Hepatocellular Carcinoma Cell Line (Hepg2) And Breast Cancer Cell Lines (Mcf-7 And Mda-Mb-231), Sunita Nilkhet

Chulalongkorn University Theses and Dissertations (Chula ETD)

Cancer is the disease that happens to occur in a high number of new cases each year. Even the choice of treatment is developing, but the adverse effects on cancer therapeutic drugs still challenging. To investigate the antitumor activities of Auricularia polytricha (AP) mushroom extract and active compounds, human cancer cell lines such as Hepatocellcular (HepG2) and Breast cancer cell lines (MCF-7 and MDA-MB-231) were interested. The crude hexane extract of AP (APH) and crude ethanol extract of AP (APE) were prepared by maceration and Soxhlet extraction, respectively. Both APE and APH were investigated for their compound compositions by GC-MS. …

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Biomass Yield In A Genetically Diverse Miscanthus Sinensis Germplasm Panel Evaluated At Five Locations Revealed Individuals With Exceptional Potential, Lindsay V. Clark, Maria S. Dwiyanti, Kossonou G. Anzoua, Joe E. Brummer, Bimal Kumar Ghimire, Katarzyna Glowacka, Megan Hall, Kweon Heo, Xiaoli Jin, Alexander E. Lipka, Junhua Peng, Toshihiko Yamada, Ji Hye Yoo, Chang Yeon Yu, Hua Zhao, Stephen P. Long, Erik J. Sacks Jan 2019

Biomass Yield In A Genetically Diverse Miscanthus Sinensis Germplasm Panel Evaluated At Five Locations Revealed Individuals With Exceptional Potential, Lindsay V. Clark, Maria S. Dwiyanti, Kossonou G. Anzoua, Joe E. Brummer, Bimal Kumar Ghimire, Katarzyna Glowacka, Megan Hall, Kweon Heo, Xiaoli Jin, Alexander E. Lipka, Junhua Peng, Toshihiko Yamada, Ji Hye Yoo, Chang Yeon Yu, Hua Zhao, Stephen P. Long, Erik J. Sacks

Department of Biochemistry: Faculty Publications

To breed improved biomass cultivars of Miscanthus ×giganteus, it will be necessary to select the highest‐yielding and best‐adapted genotypes of its parental species, Miscanthus sinensis and Miscanthus sacchariflorus. We phenotyped a diverse clonally propagated panel of 569 M. sinensis and nine natural diploid M. ×giganteus at one subtropical (Zhuji, China) and five temperate locations (Sapporo, Japan; Leamington, Ontario, Canada; Fort Collins, CO; Urbana, IL; and Chuncheon, Korea) for dry biomass yield and 14 yield‐component traits, in trials grown for 3 years. Notably, dry biomass yield of four Miscanthus accessions exceeded 80 Mg/ha in Zhuji, China, approaching …

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An Arabidopsis Protoplast Isolation Method Reduces Cytosolic Acidification And Activation Of The Chloroplast Stress Sensor Sensitive To Freezing 2, Allison C. Barnes, Christian G. Elowsky, Rebecca Roston Jan 2019

An Arabidopsis Protoplast Isolation Method Reduces Cytosolic Acidification And Activation Of The Chloroplast Stress Sensor Sensitive To Freezing 2, Allison C. Barnes, Christian G. Elowsky, Rebecca Roston

Department of Biochemistry: Faculty Publications

Chloroplasts adapt to freezing and other abiotic stresses in part by modifying their membranes. One key-remodeling enzyme is SENSITIVE TO FREEZING2 (SFR2). SFR2 is unusual because it does not respond to initial cold stress or cold acclimation, instead it responds during freezing conditions in Arabidopsis. This response has been shown to be sensitive to cytosolic acidification. The unique lipid products of SFR2 have also been detected in response to non-freezing stresses, but what causes SFR2 to respond in these stresses is unknown. Here, we investigate protoplast isolation as a representative of wounding stress. We show that SFR2 oligogalactolipid products accumulate …

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The Impact Of Household Biocides And Antibiotics On Aquatic Microbial Community Composition, Abdulaziz Saud M Alrashdi Jan 2019

The Impact Of Household Biocides And Antibiotics On Aquatic Microbial Community Composition, Abdulaziz Saud M Alrashdi

Dissertations, Master's Theses and Master's Reports

Triclosan (TCS) is antimicrobial agent that is used in a lot of consumer products, including toothpaste, liquid and bar soap, and cosmetics. TCS has been found in many lakes and rivers in the United States. However, The Food and Drug Administration (FDA) banned TCS recently and it will no longer be used in household products. Despite the recent ban, TCS is known to persist in the environment and may have long-term impacts. We conducted an experiment on using fresh water from three locations Houghton, Green Bay and the Huron Mountains. Our goals in the study is to assess the impact …

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Preparation Of A Perylenebisimide Acceptor With Serinol And Nonadecyl-Swallowtail Imides For Use In Molecular Rectification, Tarrah Frederick Jan 2019

Preparation Of A Perylenebisimide Acceptor With Serinol And Nonadecyl-Swallowtail Imides For Use In Molecular Rectification, Tarrah Frederick

Honors Theses

Several attempts were made to add 2-amino-1,3-propanediol to the acceptor perylene monoanhydride (PMA). The theoretical product, N-(10-nonadecyl)-N'-(1,3-dihydroxypropan-2-yl)perylene-3,4,9,10-bis(dicarboximide), is intended for use in unimolecular rectification because the perylenebisimide core is classified as a good acceptor due to its high electron affinity. Rectification usually utilizes donor-σ-acceptor molecules, whose localized orbitals permit electron transfer when placed between metal electrodes of asymmetric voltages. However, according to an “asymmetric rectification” analysis, an electron can pass from one electrode, through the LUMO of the acceptor, and then to the other electrode when said electrodes are held at certain voltages, and result in rectification if the acceptor …

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Carbon Dioxide Reduction Using Redox-Active Macrocyclic Catalysts, Dawson Kendall Buettner Jan 2019

Carbon Dioxide Reduction Using Redox-Active Macrocyclic Catalysts, Dawson Kendall Buettner

Honors Theses

The current energy crisis experienced by society today is in desperate need of a solution. Through carbon dioxide (CO2) reduction, we can reduce the amount of greenhouse gas that is warming our planet as well as create a source of renewable energy. Significant challenges currently inhibit the reduction of CO2 to more desirable products. Current limitations can be addressed through the design and synthesis of more efficient catalysts that are selective, durable, and operate close to the target thermodynamic potential of CO2 reduction. In this work, three redox-active macrocyclic ligands have been synthesized and studied for the development of potential …

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Cullin-3 Dependent Deregulation Of Actn1 Represents A New Pathogenic Mechanism In Nemaline Myopathy, Jordan Blondelle, Kavya Tallapaka, Jane T. Seto, Majid Ghassemian, Madison Clark, Jenni M. Laitila, Adam Bournazos, Jeffrey Singer, Stephan Lange Jan 2019

Cullin-3 Dependent Deregulation Of Actn1 Represents A New Pathogenic Mechanism In Nemaline Myopathy, Jordan Blondelle, Kavya Tallapaka, Jane T. Seto, Majid Ghassemian, Madison Clark, Jenni M. Laitila, Adam Bournazos, Jeffrey Singer, Stephan Lange

Biology Faculty Publications and Presentations

Nemaline myopathy is a congenital neuromuscular disorder characterized by muscle weakness, fiber atrophy, and presence of nemaline bodies within myofibers. However, understanding of the underlying pathomechanisms is lacking. Recently, mutations in KBTBD13, KLHL40, and KLHL41, three substrate adaptors for the E3 ubiquitin ligase Cullin-3, have been associated with early-onset nemaline myopathies. We hypothesized that deregulation of Cullin-3 and its muscle protein substrates may be responsible for disease development. Using Cullin-3–knockout mice, we identified accumulation of non-muscle α-actinins (ACTN1 and ACTN4) in muscles of these mice, which we also observed in patients with mutations in KBTBD13. Our …

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Mutations Of Fus Cause Aggregation Of Rna Binding Proteins, Disruptions In Protein Synthesis, And Dysregulation Of Nonsense Mediated Decay, Marisa Elizabeth Kamelgarn Jan 2019

Mutations Of Fus Cause Aggregation Of Rna Binding Proteins, Disruptions In Protein Synthesis, And Dysregulation Of Nonsense Mediated Decay, Marisa Elizabeth Kamelgarn

Theses and Dissertations--Toxicology and Cancer Biology

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by motor neuron death and subsequent muscle atrophy. Approximately 15% of ALS cases are inheritable, and mutations in the Fused in Sarcoma (FUS) gene contribute to approximately 5% of these cases, as well as about 2% of sporadic cases. FUS performs a diverse set of cellular functions, including being a major regulator of RNA metabolism. FUS undergoes liquid- liquid phase transition in vitro, allowing for its participation in stress granules and RNA transport granules. Phase transition also contributes to the formation of cytoplasmic inclusions found in the …

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Molecular Level Comparison Of Water Extractives Of Maple And Oak With Negative And Positive Ion Esi Ft-Icr Mass Spectrometry, Zhongqi He, Rachel L. Sleighter, Patrick G. Hatcher, Shasha Liu, Fengchang Wu, Haixuan Zou, O. Modesto Olanya Jan 2019

Molecular Level Comparison Of Water Extractives Of Maple And Oak With Negative And Positive Ion Esi Ft-Icr Mass Spectrometry, Zhongqi He, Rachel L. Sleighter, Patrick G. Hatcher, Shasha Liu, Fengchang Wu, Haixuan Zou, O. Modesto Olanya

Chemistry & Biochemistry Faculty Publications

Soluble extractives in wood function to protect living trees from destructive agents and also contribute to wood color and fragrance. Some extractive components have biological activities with medical applications. They also play important roles in wood processing and related applications. To increase the knowledge of wood chemistry, maple and oak were extracted by water. Ultraviolet/visible (UV/vis) spectroscopy indicated the presence of a phenolic compound, resorcinol, in maple extractives having higher molecular mass and more aromatic components than oak extractives. Negative and positive electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (ESI FT-ICR-MS) identified thousands of formulas in the two …

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Condensation And Polymerization Explain The Humification Of Lignin Into Aliphatic And Aromatic Structures In Soil, Patrick G. Hatcher, Hongmei Chen, Seyyedhadi Khatami, Derek C. Waggoner Jan 2019

Condensation And Polymerization Explain The Humification Of Lignin Into Aliphatic And Aromatic Structures In Soil, Patrick G. Hatcher, Hongmei Chen, Seyyedhadi Khatami, Derek C. Waggoner

Chemistry & Biochemistry Faculty Publications

Soil organic matter (SOM) constitutes a global reservoir of carbon that is more than twice that of either atmospheric carbon or aquatic carbon; however, the manner in which it forms from degraded plant biomass is poorly understood. Some have recently questioned whether plant biomass is involved directly in SOM formation and suggest that it is microbial carbon that constitutes the main source of stable SOM. Such a view implies that above and below ground plant biomass is rapidly decomposed and mineralized. This view contrasts significantly with traditional ones that involve the transformation of plant biomass to recalcitrant humic materials fueled …

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Treatment Of Plastic Wastes Using Plasma Gasification Technology, Zachary Homolka Jan 2019

Treatment Of Plastic Wastes Using Plasma Gasification Technology, Zachary Homolka

Honors Program: Senior Projects (Public)

Plasma gasification (PG) complements traditional recycling when applied to contaminated or mixed plastics. Without PG these plastics cost recyclers more to process than they are worth on the market, and sometimes they are landfilled or incinerated instead of being recycled. Plasma gasification can take plastic not suitable for traditional recycling and break it down into high-quality syngas for use in electricity generation, chemical manufacturing, or hydrogen production. The technology can be implemented without changing the behavior of consumers, which is a major advantage over attempting to decrease contamination or reduce use of low-value plastic. Due to high capital requirements and …

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Novel Methods For The Inactivation Of Cruzain For The Prevention And Treatment Of Chagas Disease, Veronica Gonzalez Jan 2019

Novel Methods For The Inactivation Of Cruzain For The Prevention And Treatment Of Chagas Disease, Veronica Gonzalez

Open Access Theses & Dissertations

Chagas Disease, also known as American Trypanosomiasis, is endemic to Latin American and is gradually making its way to other countries. The disease is caused by Trypanosoma cruzi, a protozoan parasite that causes lesions and inflammation of organs including the heart, esophagus, and colon. Over 30% of people infected will develop heart disease which can be fatal if untreated. While no vaccine is yet available, research is currently being conducted in finding new treatments for the disease. One target is an enzyme that is believed to help the progression of the disease. Cruzain, a cysteine protease expressed as a pro-enzyme, …

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Potential Of Nanoscale Elements To Control Fusarium Wilt Disease In Tomato (Solanum Lycopersicum), Enhance Macronutrient Use Efficiency, And Increase Its Yield, Ishaq Olarewaju Adisa Jan 2019

Potential Of Nanoscale Elements To Control Fusarium Wilt Disease In Tomato (Solanum Lycopersicum), Enhance Macronutrient Use Efficiency, And Increase Its Yield, Ishaq Olarewaju Adisa

Open Access Theses & Dissertations

Nanotechnology has a great potential in ensuring food production, security and safety globally. Over the past decade, research on the use of nanomaterials to supply nutrient elements and protect plants from pest and diseases has significantly increased. Tomato (Solanum lycopersicum) is one of the most consumed vegetables in the world and United State is one of its largest producers globally generating billions of dollars annually in revenue.. Tomato plants are affected worldwide by Fusarium wilt caused by Fusarium oxysporum f. sp. Lycopersici. There is growing concern about excessive use of conventional pesticides in controlling Fusarium and other diseases in tomato …

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Protein Templated Silver Nanoclusters, Greyson Keel Jan 2019

Protein Templated Silver Nanoclusters, Greyson Keel

Honors Theses

Nanoclusters are smaller than their nanoparticle counterparts and have unique properties. Most research has been done on gold nanoclusters, but silver nanoclusters are said to be more robust. During the process of trying to create nanoclusters, several methods in the procedure were changed when gathering data: determining a successful silver concentration, working with the correct buffer, mixing gold and silver metals together, observing the effects of pH, and finding a good reducing agent. After experimenting with those changes, a successful protocol was adapted and modified from literature (Journal of Materials Chemistry, 2011, 21, 11205-11212) to produce the protein-templated Ag clusters. …

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Unravelling The D1r-D2r Heteromer, Margaret M. Champion Jan 2019

Unravelling The D1r-D2r Heteromer, Margaret M. Champion

Master's Theses and Doctoral Dissertations

Dopamine receptors D1R and D2R form a heterooligomeric complex with signaling properties distinct from the individual receptors. Aberrant expression of this protein-protein complex is linked to the etiology of various neuropsychiatric diseases. Formation of the D1R-D2R heteromer is thought to be dependent upon electrostatic interactions occurring between the carboxyl tail of D1R and the third intracellular loop of D2R. Using this interaction site as template, I synthesized several peptides designed to disrupt the minimal area of the D1R-D2R interaction interface and tested these using whole cell lysates of human brain tissue and dopamine receptor constructs. I report that a synthetic …

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Investigating Iron Metabolism In Subarachnoid Hemorrhage Patients, Alexander A. Maynard, Gardenia Pacheco Jan 2019

Investigating Iron Metabolism In Subarachnoid Hemorrhage Patients, Alexander A. Maynard, Gardenia Pacheco

Williams Honors College, Honors Research Projects

Subarachnoid hemorrhage (SAH) is a stroke characterized by bleeding into the subarachnoid space of the brain, typically resulting in high mortality rate.8 Delayed cerebral ischemia (DCI), characterized by vasospasms induced arterial constriction, occurs in roughly one third of the surviving patients.20 The development of DCI and neurodegeneration could be linked to metabolic pathology that occurs after SAH, specifically iron induced changes in redox status. The oxidized environment induced by iron has the potential to functionally affect the ferroxidase ceruloplasmin (Cp), which is linked to neurodegeneration.15 Global LC-MS based metabolomics data revealed alterations in metabolism in the CSF …

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Cloning The Vision Related G Protein Transducin For Live Cell Fluorescence Studies, Deanna M. Bowman Jan 2019

Cloning The Vision Related G Protein Transducin For Live Cell Fluorescence Studies, Deanna M. Bowman

Williams Honors College, Honors Research Projects

G coupled protein receptors (GCPR) are one of the largest families of receptors and mediate a variety of biological responses. Rhodopsin is the largest family and aids in sight, the α-subunit of the GCPR complex in extremely important to the activation and downstream signaling effects of GCPR. The α-subunit contains a small trans-domain portion and in this project the sequence of that portion will be inserted into a vector containing a fluorescent tag. These vectors will then be used to collect fluorescent cross correlation spectroscopy or FCCS data. The unit was cloned using assembly methods that include PCR and purification …

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Biochemical, Structural, And Drug Design Studies Of Aspartate Transcarbamoylase From Pseudomonas Aeruginosa And Staphylococcus Aureus, Chandni Patel Jan 2019

Biochemical, Structural, And Drug Design Studies Of Aspartate Transcarbamoylase From Pseudomonas Aeruginosa And Staphylococcus Aureus, Chandni Patel

Wayne State University Dissertations

Sepsis affects 1.7 million people in the United States every year and nearly 270,000 people die as a result. Sepsis is characterized by systemic inflammation from an infection leading to organ dysfunction and death. Multi-drug resistance in bacteria is increasing globally, and Pseudomonas aeruginosa and Staphylococcus aureus are notorious for their multi-drug resistance and pose a serious need for the development of new antibiotics. The levels of pyrimidines in blood are too low to sustain the growth of bacteria, so they must rely on pyrimidine biosynthesis. Previous studies have shown that a defect in several pyrimidine biosynthetic enzymes resulted in …

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Perturbation Of Energy Metabolism At The Center Of The Mechanism Of Action Of Valproate, Michael Ghassan Salsaa Jan 2019

Perturbation Of Energy Metabolism At The Center Of The Mechanism Of Action Of Valproate, Michael Ghassan Salsaa

Wayne State University Dissertations

Bipolar disorder (BD) is a common and debilitating psychiatric disorder. Valproic acid (VPA) is one of the major drugs used to treat BD patients. However, it is not universally effective and, in addition, causes severe side effects. Its mechanism of action is not known, which complicates efforts to develop more effective drugs. Studies have established that VPA perturbs metabolism, which is implicated in both the therapeutic mechanism of action of the drug as well as drug toxicity. However, the mechanism whereby VPA causes these perturbations is not understood. To address this knowledge gap, I investigated the acute and chronic effects …

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