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Articles 601 - 630 of 758
Full-Text Articles in Biochemistry, Biophysics, and Structural Biology
A Tale Of Two Regulators : Characterization Of The Novel Transcription Factor Abmr And The Small Non-Coding Rna Mcr11 In Mycobacterium Tuberculosis, Roxanne Candice Girardin
A Tale Of Two Regulators : Characterization Of The Novel Transcription Factor Abmr And The Small Non-Coding Rna Mcr11 In Mycobacterium Tuberculosis, Roxanne Candice Girardin
Legacy Theses & Dissertations (2009 - 2024)
Genes of unknown function make up nearly one third of Mtb’s genome (Cole,
Influence Of The Pre-Initiation Complex On Mediator Recruitment In Saccharomyces Cerevisiae, Elisabeth Rose Knoll
Influence Of The Pre-Initiation Complex On Mediator Recruitment In Saccharomyces Cerevisiae, Elisabeth Rose Knoll
Legacy Theses & Dissertations (2009 - 2024)
The Mediator complex plays a central, highly conserved role in eukaryotic transcription by RNA Polymerase II (Pol II) by stimulating the cooperative assembly of a pre-initiation complex (PIC) and recruitment of Pol II for gene activation. Mediator recruitment has generally been ascribed to sequence-specific activators engaging subunits from the tail module which in turn function to recruit the middle and head for complete assembly at the UAS. Mediator subunits of the middle and head then bridge the enhancer to connect with the PIC at the core promoter. It is reported that Mediator recruitment at the UAS preferentially occurs at SAGA-dependent, …
The Role Of The Mediator Transcriptional Co-Activator Complex And Promoter Dependence In Ty1 Retrotransposition In Saccharomyces Cerevisiae, Alicia Salinero
The Role Of The Mediator Transcriptional Co-Activator Complex And Promoter Dependence In Ty1 Retrotransposition In Saccharomyces Cerevisiae, Alicia Salinero
Legacy Theses & Dissertations (2009 - 2024)
Retrotransposons are mobile genetic elements that replicate via an RNA intermediary and constitute a significant portion of most eukaryotic genomes. Saccharomyces cerevisiae has been invaluable to retrotransposon research due to the presence of an active retroelement known as Ty1. The mobility of Ty1 is regulated both positively and negatively by numerous host factors, including several subunits of the Mediator transcriptional co-activator complex. The Mediator core complex is organized into genetically and structurally defined head, middle, and tail modules, along with a transiently associated kinase module. We show that with the exception of the kinase module, deletion of non-essential subunits from …
Effects Of Antibiotic Treatment On The Expression Of Hepatic And Intestinal Cytochrome P450, Bruno Pereira De Carvalho
Effects Of Antibiotic Treatment On The Expression Of Hepatic And Intestinal Cytochrome P450, Bruno Pereira De Carvalho
Legacy Theses & Dissertations (2009 - 2024)
Expression of metabolic enzymes Cytochrome P450 (CYP) is highly affected by drugs, diseases, age and gender. The Intestinal microflora has been suggested to play a role in regulating CYP expression and antibiotic treatments would lead to changes in level and composition of microbiota in mouse gut. This study aims to analyze CYP expression changes in the liver and small intestine resulted from the reduction of intestinal microflora by antibiotics. Impacts on bile acid signaling were also analyzed for a better comprehension of the mechanisms involved in this modulation. Female C57BL/6J mice (9- to 13-week old) were treated with ampicillin (AMP) …
Further Development Of Raman Spectroscopy For Body Fluid Investigation : Forensic Identification, Limit Of Detection, And Donor Characterization, Claire K. Muro
Further Development Of Raman Spectroscopy For Body Fluid Investigation : Forensic Identification, Limit Of Detection, And Donor Characterization, Claire K. Muro
Legacy Theses & Dissertations (2009 - 2024)
The challenges to forensic body fluid analysis have placed limitations on the type of information that investigators can acquire and how that information can be collected. In recent years, Raman spectroscopy has proven itself useful for characterizing body fluids. In 2008, a large-scale investigation was undertaken to explore the use of Raman spectroscopy as a means of identifying body fluids. This work resulted in multidimensional Raman spectroscopic signatures for the five main body fluids: semen, peripheral blood, saliva, vaginal fluid, and sweat. These studies were incredibly successful and created the foundation for years of continued research. Accordingly, the studies included …
Structural Characterization Of The Interactions Of Nicotinamide And Analogs With Human Sirt6 By Saturation Transfer Difference (Std) Nmr And Site Directed Mutagenesis, Beatriz Elena Bolivar-Vega
Structural Characterization Of The Interactions Of Nicotinamide And Analogs With Human Sirt6 By Saturation Transfer Difference (Std) Nmr And Site Directed Mutagenesis, Beatriz Elena Bolivar-Vega
Legacy Theses & Dissertations (2009 - 2024)
The allosteric regulation of SIRT6 by nicotinamide (NAM), along with the growing evidence of this enzyme's key role in the immune response, prompted the mechanistic study of SIRT6 inhibition by pyrazinamide (PZA) and analogs. In our current study, PZA, an analog of NAM, was revealed to have a modest modulatory effect on SIRT6, an enzyme that regulates the NF-κB signaling pathway at the transcriptional level (a relevant pathway to inflammation). Similarly, the analogs of PZA, 5-Cl PZA, 5-MeO PZA, and POA exhibited a modulatory effect against SIRT6 in our in vitro studies, enabling identification of a potential new target for …
Benzylideneoxymorphone: A New Lead For Development Of Bifunctional Mu/Delta Opioid Receptor Ligands, Jason R. Healy, Padmavani Bezawada, Nicholas W. Griggs, Andrea L. Devereaux, Rae Reiko Matsumoto, John R. Traynor, Christopher W. Cunningham
Benzylideneoxymorphone: A New Lead For Development Of Bifunctional Mu/Delta Opioid Receptor Ligands, Jason R. Healy, Padmavani Bezawada, Nicholas W. Griggs, Andrea L. Devereaux, Rae Reiko Matsumoto, John R. Traynor, Christopher W. Cunningham
Faculty Publications & Research of the TUC College of Pharmacy
Opioid analgesic tolerance remains a considerable drawback to chronic pain management. The finding that concomitant administration of delta opioid receptor (DOR) antagonists attenuates the development of tolerance to mu opioid receptor (MOR) agonists has led to interest in producing bifunctional MOR agonist/DOR antagonist ligands. Herein, we present 7-benzylideneoxymorphone (6, UMB 246) displaying MOR partial agonist/DOR antagonist activity, representing a new lead for designing bifunctional MOR/DOR ligands.
Detoxification Of Mitochondrial Oxidants And Apoptotic Signaling Are Facilitated By Thioredoxin-2 And Peroxiredoxin-3 During Hyperoxic Injury, Benjamin J. Forred, Darwin R. Daugaard, Brianna K. Titus, Ryan R. Wood, Miranda J. Floen, Michelle L. Booze, Peter F. Vitiello
Detoxification Of Mitochondrial Oxidants And Apoptotic Signaling Are Facilitated By Thioredoxin-2 And Peroxiredoxin-3 During Hyperoxic Injury, Benjamin J. Forred, Darwin R. Daugaard, Brianna K. Titus, Ryan R. Wood, Miranda J. Floen, Michelle L. Booze, Peter F. Vitiello
School of Veterinary and Biomedical Sciences: Faculty Publications
Mitochondria play a fundamental role in the regulation of cell death during accumulation of oxidants. High concentrations of atmospheric oxygen (hyperoxia), used clinically to treat tissue hypoxia in premature newborns, is known to elicit oxidative stress and mitochondrial injury to pulmonary epithelial cells. A consequence of oxidative stress in mitochondria is the accumulation of peroxides which are detoxified by the dedicated mitochondrial thioredoxin system. This system is comprised of the oxidoreductase activities of peroxiredoxin-3 (Prx3), thioredoxin-2 (Trx2), and thioredoxin reductase-2 (TrxR2). The goal of this study was to understand the role of the mitochondrial thioredoxin system and mitochondrial injuries during …
Maternal Inflammation At Mid-Gestation In Pregnant Rats Impairs Fetal Muscle Growth And Development At Term, C. N. Cadaret, K. A. Beede, E. M. Merrick, T. L. Barnes, J. D. Loy, D. T. Yates
Maternal Inflammation At Mid-Gestation In Pregnant Rats Impairs Fetal Muscle Growth And Development At Term, C. N. Cadaret, K. A. Beede, E. M. Merrick, T. L. Barnes, J. D. Loy, D. T. Yates
School of Veterinary and Biomedical Sciences: Faculty Publications
Intrauterine growth restriction (IUGR) is a leading cause of perinatal morbidity and mortality. Low birth weight resulting from preterm birth and/or IUGR is an underlying factor in 60–80% of perinatal death worldwide, and is particularly common in developing countries (UNICEF, 2008). Furthermore, studies have linked IUGR and the associated fetal malnutrition to increased incidence of metabolic syndrome in adult life (Barker et al., 1993; Godfrey and Barker, 2000). The “thrifty phenotype hypothesis” developed by David Barker (Hales et al., 1991) states that IUGR-associated fetal malnutrition forces the fetus to spare nutrients by altering tissue-specific metabolism in order to survive. In …
A Parapoxviral Virion Protein Targets The Retinoblastoma Protein To Inhibit Nf-Κb Signaling, Ponnuraj Nagendraprabhu, Sushil Khatiwada, Sabal Chaulagain, Gustavo A. Delhon, Daniel L. Rock
A Parapoxviral Virion Protein Targets The Retinoblastoma Protein To Inhibit Nf-Κb Signaling, Ponnuraj Nagendraprabhu, Sushil Khatiwada, Sabal Chaulagain, Gustavo A. Delhon, Daniel L. Rock
School of Veterinary and Biomedical Sciences: Faculty Publications
Poxviruses have evolved multiple strategies to subvert signaling by Nuclear Factor κB (NF-κB), a crucial regulator of host innate immune responses. Here, we describe an orf virus (ORFV) virion-associated protein, ORFV119, which inhibits NF-κB signaling very early in infection (≤30 min post infection). ORFV119 NF-κB inhibitory activity was found unimpaired upon translation inhibition, suggesting that virion ORFV119 alone is responsible for early interference in signaling. A C-terminal LxCxE motif in ORFV119 enabled the protein to interact with the retinoblastoma protein (pRb) a multifunctional protein best known for its tumor suppressor activity. Notably, experiments using a recombinant virus containing an ORFV119 …
การคัดกรองและการประยุกต์เครื่องหมายไมโครแซทเทลไลท์เพื่อการวิเคราะห์ความหลากหลายทางพันธุกรรมของนกกระเรียนพันธุ์ไทย Grus Antigone Sharpii Blanford, 1895 ในสภาพกรงเลี้ยง, รังสินี สันคม
Chulalongkorn University Theses and Dissertations (Chula ETD)
Grus antigone sharpii จัดเป็นนกกระเรียนที่เคยสูญพันธุ์ไปจากธรรมชาติของประเทศไทย การเพาะเลี้ยงและขยายพันธุ์นกกระเรียนในกรงเลี้ยงเป็นขั้นตอนสำคัญที่สามารถเพิ่มจำนวนประชากรเพื่อนำไปปล่อยคืนสู่ธรรมชาติในอนาคตได้ โดยสิ่งสำคัญที่ต้องคำนึงถึงคือความหลากหลายทางพันธุกรรม โดยเฉพาะอย่างยิ่งในกลุ่มของพ่อแม่พันธุ์ตั้งต้น ในการศึกษาครั้งนี้มีวัตถุประสงค์เพื่อคัดกรองเครื่องหมายไมโครแซทเทลไลท์จำนวน 28 ตำแหน่ง ซึ่งเป็นไพรเมอร์ที่เคยใช้ศึกษาในนกกระเรียน G. americana และนกกระเรียน Anthropoides paradisea เพื่อใช้วิเคราะห์ความหลากหลายทางพันธุกรรมของนกกระเรียนพันธุ์ไทยจากสวนสัตว์เปิดเขาเขียว (KKOZ, n = 11) และสถานีวิจัยเพาะเลี้ยงนกน้ำบางพระ (BB, n = 17) จังหวัดชลบุรี ผลการศึกษาพบว่าไพรเมอร์ทั้ง 28 คู่สามารถเพิ่มปริมาณไมโครแซทเทลไลท์ดีเอ็นเอของนกกระเรียนพันธุ์ไทยได้ แต่มีเพียง 22 คู่ที่แสดงความเป็น polymorphism และมีตำแหน่งไมโครแซทเทลไลท์ที่ปรากฏค่า linkage disequilibrium 8 ตำแหน่ง การเบี่ยงเบนออกจากสมดุล Hardy-Weinberg พบที่โลคัส Gram8 และ Gpa38 ซึ่งเป็นผลมาจาก null allele และการเพิ่มขึ้นของอัลลีลแบบ heterozygous ตามลำดับ จากการวิเคราะห์ค่าความหลากหลายทางพันธุกรรมพบว่า ค่าเฉลี่ยของ expected และ observed heterozygosity มีค่าเท่ากับ 0.63 และ 0.69 ค่า inbreeding coefficient มีค่าเท่ากับ -0.100 ซึ่งแสดงว่านกกระเรียนมีความหลากหลายทางพันธุกรรมค่อนข้างสูง และเกิด inbreeding น้อย นอกจากนี้ยังพบว่านกกระเรียนจาก KKOZ และ BB มีความแตกต่างทางพันธุกรรมต่ำ (FST = 0.035) และไม่มีการแยกออกเป็นกลุ่มประชากรย่อย (K = 1) จากผลการศึกษาครั้งนี้บ่งบอกได้ว่านกกระเรียนพันธุ์ไทยจาก 2 พื้นที่การศึกษาน่าจะเหมาะสมที่จะใช้เป็นพ่อแม่พันธุ์เพื่อเพิ่มจำนวนประชากรในกรงเลี้ยงให้มากขึ้น และสามารถนำไปปล่อยคืนสู่พื้นที่ชุ่มน้ำตามธรรมชาติในอนาคตได้
Differential Precipitation And Solubilisation Of Proteins, Barry J. Ryan, Gemma K. Kinsella
Differential Precipitation And Solubilisation Of Proteins, Barry J. Ryan, Gemma K. Kinsella
Books/Book Chapters/ Proceedings
Differential protein precipitation is a rapid and economical step in protein purification and is based on exploiting the inherent physicochemical properties of the polypeptide. Precipitation of recombinant proteins, lysed from the host cell, is commonly used to concentrate the protein of choice before further polishing steps with more selective purification columns (e.g., His-Tag, Size Exclusion, etc.). Recombinant proteins can also precipitate naturally as inclusion bodies due to various influences during overexpression in the host cell. Although this phenomenon permits easier initial separation from native proteins, these inclusion bodies must carefully be differentially solubilized so as to reform functional, correctly folded …
Biochemical And Molecular Assessment Of Toxicity Of Primaquine Metabolites On Erythrocytes, Jagrati Jain
Biochemical And Molecular Assessment Of Toxicity Of Primaquine Metabolites On Erythrocytes, Jagrati Jain
Electronic Theses and Dissertations
The 8-aminoquinoline (8AQ) antimalarial drug primaquine (PQ) is the only drug for prevention of malaria relapse. Moreover, PQ also has gametocytocidal activity against Plasmodium falciparum. However, clinical use of PQ has been limited due to its hemolytic toxicity, especially in glucose-6-phosphate dehydrogenase deficient (G6PDd) individuals. Phenolic and quinone metabolites generated via cytochrome P450-dependent pathways appear to be responsible for hemolytic effects of PQ. However, the mechanism for the hemolytic toxicity of PQ is still poorly understood. To explore the mechanism, targets, and pathways for toxicity of PQ, normal and G6PDd human erythrocytes were treated with the potential hemotoxic metabolites of …
Nucleic Acid Clamp-Mediated Transcriptional And Translational Modulation Of Oncogenes Via The Stabilization Of G-Quadruplexes, Taisen Hao
Electronic Theses and Dissertations
G-quadruplexes (G4s) are non-canonical secondary nucleic acid structures that exit in various biologically important regions within a cell, such as the promoters of DNA, 5’-Untranslated regions (UTR) of mRNA and telomeres. These secondary structures tend to cluster around 1 kb from transcriptional start sites across all human chromosomes in addition to at telomeric regions. Extensive efforts from many research groups have been dedicated to targeting G4s in oncogenic promoters, telomeres, and 5’-UTRs with traditional small molecules. However, most small molecules recognizing multiple G4s raising potential issues in terms of utilizing these small molecules clinically. Therefore, we developed a novel nucleic …
Contribution Of Specific Amino Acids To Calcium-Dependent Dimerization Of Epithelial Cadherin, Xiaoyun Z. Howard
Contribution Of Specific Amino Acids To Calcium-Dependent Dimerization Of Epithelial Cadherin, Xiaoyun Z. Howard
Electronic Theses and Dissertations
Cadherins are calcium-dependent molecules that play essential roles in embryonic development, tissue morphogenesis, and cancer progression. Epithelial (E-) cadherin is present at adherens junctions, structures that are important for maintaining tissue integrity. At adherens junctions, cell–cell adhesion complexes are formed as clusters of cadherin dimers through strand-swapped dimerization between two interacting protomers from adherent cells. Recently, a number of studies of dimer formation of E-cadherin supported a two-step adhesive binding model. First, an inter-molecular initial encounter complex (X-dimer) forms at the linker region of the first two extracellular domains, EC1 and EC2. Next, strand-swap dimerization occurs via exchange or ''swap'' …
Biochemical, Structural, And Drug Design Studies Of Norovirus And Zika Virus Proteases, Ben Kuiper
Biochemical, Structural, And Drug Design Studies Of Norovirus And Zika Virus Proteases, Ben Kuiper
Wayne State University Dissertations
Noroviruses, which are the leading cause of acute gastroenteritis, cause an estimated 677 million infections and 213,000 deaths each year worldwide. Noroviruses are classified into seven genogroups (GI-GVII); GI, GII, and GIV have been shown to be infectious in humans. However, GII noroviruses cause the majority of outbreaks (89%). No pharmacologic treatment or vaccine currently exists to treat or prevent norovirus infections.
Recently, the development of a norovirus replicon system, a murine model of norovirus infection, and the development of a biochemical protease assay have allowed for the design and development of norovirus inhibitors. However, the replicon and biochemical assay …
Patholigical And Prognostic Role Of Mdig In Pancreatic Cancer, Srinivas Ashok Kumar
Patholigical And Prognostic Role Of Mdig In Pancreatic Cancer, Srinivas Ashok Kumar
Wayne State University Theses
Pancreatic cancer is a highly aggressive malignant disease having very limited therapeutic options that ultimately results in its poor prognosis. It is still elusive on the etiology and tumorigenic mechanisms of pancreatic cancer. In the present report, we provide evidence showing involvement of the mineral dust-induced gene (mdig) in the pathogenesis and prognosis of the pancreatic cancer. Using immunohistochemistry approach on human pancreatic cancer tissue microarray, we found differential expression of mdig in pancreatic adenocarcinoma and normal pancreas. Based on the staining intensities of mdig in these tissue samples, we found that 12% of the cancer tissues were strongly positive …
The Effect Of Acetylation Of Cytochrome C On Its Functions In Prostate Cancer, Viktoriia Bazylianska
The Effect Of Acetylation Of Cytochrome C On Its Functions In Prostate Cancer, Viktoriia Bazylianska
Wayne State University Theses
Prostate cancer is the second leading cause of cancer death among men in America. The progression of cancer goes along with the Warburg effect, a metabolic switch from depending primarily on mitochondrial respiration to glycolysis. In addition, cancer cells manage to evade apoptosis. Cell signaling, via posttranslational modifications (PTMs), is one of the most important means of regulation, and most commonly dysregulated in cancer. In prostate cancer, androgen signaling plays a crucial role in driving cell proliferation.
Mammalian Cytochrome c (Cytc) is a multifunctional protein involved in cellular life and death decision. It is an essential component of the electron …
Fam129b, A Novel Adherent Junction Protein, Forms A Complex With Keap1, Fatme Ali Hachem
Fam129b, A Novel Adherent Junction Protein, Forms A Complex With Keap1, Fatme Ali Hachem
Wayne State University Theses
FAM129B/Minerva, a protein implicated in melanoma cell invasion, has been shown to suppress TNFα induced apoptosis in cancer cells (Song, Evans & Evans (2010), JBC 286, 10201-09), thus contributing to the survival of metastatic cells. KEAP1, a substrate recognition molecule for the CUL3 E3 ubiquitin ligase, plays a central role in the activation of the TNFα pathway. We wish to test the hypothesis that the up-regulation of FAM129B in cancer cells suppresses apoptosis by sequestering KEAP1, thus preventing its participation in the apoptotic pathway. The first step is to demonstrate that FAM129B and KEAP1 form a complex. We have cloned …
Development Of Student Data Visualization Tool, Adaption Of Clostridium Difficile Toxin A Into Protein Delivery Vehicle, And Elucidation Of Tcdc Mechanism Of Toxin Control, Adam Boyden
Wayne State University Theses
Advancing student success in higher education is of paramount importance, and is in need for a tool that visualizes student data in a longitudinal manner. Student Circos plots achieve this by plotting student data in circular plots, depicting the timeline and grades for students selected by demographic or performance information. Cellular delivery of exogenous proteins is a bountiful area of research. However, most current systems have limited in vivo applications and most lack cellular specificity. By adapting Toxin A from Clostridium difficile, the goal was to create a cell specific protein delivery vehicle that would be robust in vivo. However, …
Human Cytomegalovirus Cytoplasmic Virion Assembly Complex: Structure In Vivo And Role Of Pul103 In Its Biogenesis, Ma Christina Raye Lim
Human Cytomegalovirus Cytoplasmic Virion Assembly Complex: Structure In Vivo And Role Of Pul103 In Its Biogenesis, Ma Christina Raye Lim
Wayne State University Theses
Human Cytomegalovirus (HCMV) is a linear, double stranded DNA virus that causes severe disease in the immunocompromised, and is one of the common cause of congenital disease. Antivirals that are currently available for treatment target the DNA replication of the virus cycle, and are highly toxic. Finding new drug targets, such as proteins responsible for virion assembly and egress, would help to alleviate the disease burden.
HCMV remodels the host cell to form a structure called the cytoplasmic virion assembly complex (cVAC), a site of virion maturation and egress. The first objective of this work is to study the structure …
Determination Of The Direct Protein-Protein Interactions In The Drosophila Sin3a Complex, Ian Moore
Determination Of The Direct Protein-Protein Interactions In The Drosophila Sin3a Complex, Ian Moore
Wayne State University Theses
The proteins that comprise the Drosophila SIN3 220 and SIN3 187 complexes are currently known. Limited information with regard to interacting complex member proteins has been described. Much of these data are results of high-throughput investigations, and there have been no studies done to reconstitute all direct interactions within the complex. The unique C-terminal region of the SIN3 220 isoform was used to test for interactions with other complex proteins using the bacterial expression system. Additionally, the region of Caf1-55 necessary for interaction with SIN3 in vivo was identified using a truncation mutant. The results of this work identified novel …
Differential Activation Of Dead Box Rna Helicases Rhlb And Rhle By Hfq/Srnas And Their Target Mrnas, Amit Kumar
Differential Activation Of Dead Box Rna Helicases Rhlb And Rhle By Hfq/Srnas And Their Target Mrnas, Amit Kumar
Wayne State University Theses
Number of small RNA (sRNA) gene regulators have mounted in E. coli over the years whereas the number of validated protein partners has not changed considerably. Hfq has remained the only well studied global regulatory partner of sRNAs in E. coli. However, direct or indirect involvement of other protein partners has always been speculated. Study from Blasi lab has shown that CsdA, one of the five DEAD-box RNA helicases of E. coli, is required for the DsrA mediated upregulation of rpoS under cold stress condition. Previous study from our lab has identified two other DEAD-box RNA helicases, RhlB and RhlE, …
Fam129b Phosphorylation And Its Effect On Membrane Localization In Confluent Hela Cells, Lakshmi Thompil Somasekharan
Fam129b Phosphorylation And Its Effect On Membrane Localization In Confluent Hela Cells, Lakshmi Thompil Somasekharan
Wayne State University Theses
Phosphorylation and de-phosphorylation of many proteins is a key regulator of cellular life. It maintains cellular activity through an array of signaling pathways like cell division, proliferation and growth. However, Overexpression or mutations by the constitutive activation of phosphorylation machinery disrupt the balance in the cell, driving the inappropriate activation or deactivation of the cellular processes it controls. FAM129B is a protein whose activity is partly maintained by phosphorylation and dephosphorylation at the six serine residues at the C-terminal. FAM129B is expressed highly in many forms of cancer and its main function is to suppress apoptosis and enhances cancer cell …
Design, Synthesis And Analysis Of Potential Photo-Activatable Cathepsin K Inhibitors, Khalin Evania Nisbett
Design, Synthesis And Analysis Of Potential Photo-Activatable Cathepsin K Inhibitors, Khalin Evania Nisbett
Wayne State University Theses
Abstract
DESIGN, SYNTHESIS AND ANALYSIS OF POTENTIAL PHOTO-ACTIVATABLE CATHEPSIN K INHIBITORS
by
KHALIN NISBETT
May 2017
Advisor: Dr. Jeremy Kodanko
Major: Chemistry
Degree: Master of Science
Tightly regulated cysteine CA proteases play a major role in maintaining the homeostasis within cells. Subsequently, when these proteases are dysregulated and mislocalized they disrupt healthy cell dynamics and contribute to many life-threatening pathologies such arteriosclerosis, osteoporosis and cancer. As such many pharmaceutical companies and research teams are highly interested in these proteases as targets. One emergent strategy is the spatiotemporal control of biological processes. In relation to this, a series of spatiotemporally controlled …
Elucidating Structure, Function, And Small Molecular Interactions Of Human Immunodeficiency Virus And Chikungunya Virus, Kristin Nicole Slater
Elucidating Structure, Function, And Small Molecular Interactions Of Human Immunodeficiency Virus And Chikungunya Virus, Kristin Nicole Slater
Wayne State University Theses
Abstract HIV-1:
Human immunodeficiency virus-1 (HIV-1) is a widespread, incurable retrovirus known to cause
immunodeficiency and a shortened life span. Despite successful treatment methods, HIV-1
frequently mutates, resulting in antiviral resistance. Many therapies target the HIV-1 protease
(PR), which is responsible for cleaving the viral polyprotein essential for its life cycle. HIV-1 PR
often evades treatment by way of mutations and less commonly through residue insertions. We
have identified a clinical isolate with a five residue insertion between residues 28 and 29.
Through molecular dynamics simulations we analyzed the protease protein structure and
determined that the residue insertion created a …
Primate Proteomic Composition Of Seminal Plasma And Prostate-Specific Transglutaminase Activity In Relation To Sexual Selection., Amanda M.C. Zielen
Primate Proteomic Composition Of Seminal Plasma And Prostate-Specific Transglutaminase Activity In Relation To Sexual Selection., Amanda M.C. Zielen
Electronic Theses and Dissertations
Humans (Homo sapiens), chimpanzees (Pan troglodytes), and gorillas (Gorilla gorilla) have diverse mating systems with varying levels of sperm competition. Several seminal plasma genes have been claimed to evolve under positive selection, while others are altered or lost. This study aims to identify biologically relevant differences among seminal plasma proteomes of primates in relation to mating systems and previous genomic studies. Seminal plasma from three individuals of each species were run in triplicate in shotgun liquid chromatography – tandem mass spectrometry (LC-MS/MS) and confirmed with Western blots. Over 7,000 peptides were identified across all …
Modeling The Binding Of Neurotransmitter Transporter Inhibitors With Molecular Dynamics And Free Energy Calculations, Bernandie Jean
Modeling The Binding Of Neurotransmitter Transporter Inhibitors With Molecular Dynamics And Free Energy Calculations, Bernandie Jean
Electronic Theses and Dissertations
The monoamine transporter (MAT) proteins responsible for the reuptake of the neurotransmitter substrates, dopamine, serotonin, and norepinephrine, are drug targets for the treatment of psychiatric disorders including depression, anxiety, and attention deficit hyperactivity disorder. Small molecules that inhibit these proteins can serve as useful therapeutic agents. However, some dopamine transporter (DAT) inhibitors, such as cocaine and methamphetamine, are highly addictive and abusable. Efforts have been made to develop small molecules that will inhibit the transporters and elucidate specific binding site interactions. This work provides knowledge of molecular interactions associated with MAT inhibitors by offering an atomistic perspective that can guide …
Investigating The Relationship Between Instructors’ Use Of Active Learning Strategies And Students’ Conceptual Understanding And Affective Changes In Introductory Biology: A Comparison Of Two Active-Learning Environments, Lacy M. Cleveland, Jeffrey T. Olimpo, Sue Dechenne-Peters
Investigating The Relationship Between Instructors’ Use Of Active Learning Strategies And Students’ Conceptual Understanding And Affective Changes In Introductory Biology: A Comparison Of Two Active-Learning Environments, Lacy M. Cleveland, Jeffrey T. Olimpo, Sue Dechenne-Peters
Biology: Faculty Publications
In response to calls for reform in undergraduate biology education, we conducted research examining how varying active-learning strategies impacted students’ conceptual understanding, attitudes, and motivation in two sections of a large-lecture introductory cell and molecular biology course. Using a quasi-experimental design, we collected quantitative data to compare participants’ conceptual understanding, attitudes, and motivation in the biological sciences across two contexts that employed different active-learning strategies and that were facilitated by unique instructors. Students participated in either graphic organizer/worksheet activities or clicker-based case studies. After controlling for demographic and presemester affective differences, we found that students in both active-learning environments displayed …
The Localization And Function Of Novel Tetrahymena Thermophila Cytoskeletal Genes Bbc29 And Bbc39, Emily K. Moore, Nicole C. Zanolli
The Localization And Function Of Novel Tetrahymena Thermophila Cytoskeletal Genes Bbc29 And Bbc39, Emily K. Moore, Nicole C. Zanolli
Undergraduate Research Symposium Posters
Ciliary function is known to play an important role in many human conditions, including chronic sinus and pulmonary diseases and problems with infertility. Cilia are cytoskeletal structures that protrude from the cell body to facilitate movement. Ciliary structure is conserved throughout eukaryotes, from unicellular to multicellular organisms, including humans. A clear understanding the proteins that compose cilia and how they interact with one another will increase our knowledge about important cytoskeletal elements. Because cilia are difficult to study in multicellular organisms, the unicellular eukaryote Tetrahymena thermophila serves as a useful model for the study of cytoskeletal genes, due to their …