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2023

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Articles 391 - 402 of 402

Full-Text Articles in Biochemistry

Analyzing The Impact Of Zip Subfamily Ii Mutations On The Zinc And Iron Transport Of Zupt From Escherichia Coli, Bradley Vandecar Jan 2023

Analyzing The Impact Of Zip Subfamily Ii Mutations On The Zinc And Iron Transport Of Zupt From Escherichia Coli, Bradley Vandecar

Wayne State University Theses

The disfunction or misregulation of the ZIP family of metal ion transporters has been linked to a plethora of diseases and cancers in humans. Zn2+ is the primary substrate for ZIPs and is transported through the M1 metal binding site, though this activity is stimulated through the binding of Fe2+ in the M2 metal binding site. The members of ZIP Subfamily II are predicted to have an inactive M2 site due to the lack of Fe2+ transport and from a previously generated homology model. This work utilizes homology modelling, whole cell metal ion uptake assays, and growth studies in minimal …

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In Silico Drug Discovery For Sars-Cov-2 Papain-Like Protease, Olivia Haskin Jan 2023

In Silico Drug Discovery For Sars-Cov-2 Papain-Like Protease, Olivia Haskin

Wayne State University Theses

SARS-CoV-2 Papain-like protease is an essential viral protein for viral replication. In our lab, we hypothesize that successful inhibition of this protease will stop viral replication and allow for clearance of the infection by the host. The work described here aimed to design and execute an in silico drug discovery workflow for successfully selecting PLpro inhibitors from the Mcule purchasable compound database. This work reports such a workflow and nine potential compounds for in vitro testing. This work also describes structural activity relationship analysis of a proprietary set of PLpro inhibitors synthesized by medicinal chemistry collaborators and makes recommendations for …

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Cup Is Essential For Oskar Mrna Translational Repression During Early Drosophila Oogenesis, Livia V. Bayer, Samantha Milano, Stephen K. Formel, Harpreet Kaur, Rishi Ravichandran, Juan A. Cambeiro, Lizaveta Slinko, Irina E. Catrina, Diana P. Bratu Jan 2023

Cup Is Essential For Oskar Mrna Translational Repression During Early Drosophila Oogenesis, Livia V. Bayer, Samantha Milano, Stephen K. Formel, Harpreet Kaur, Rishi Ravichandran, Juan A. Cambeiro, Lizaveta Slinko, Irina E. Catrina, Diana P. Bratu

Publications and Research

Study of the timing and location for mRNA translation across model systems has begun to shed light on molecular events fundamental to such processes as intercellular communication, morphogenesis, and body pattern formation. In D. melanogaster, the posterior mRNA determinant, oskar, is transcribed maternally but translated only when properly localized at the oocyte’s posterior cortex. Two effector proteins, Bruno1 and Cup, mediate steps of oskar mRNA regulation. The current model in the field identifies Bruno1 as necessary for Cup’s recruitment to oskar mRNA and indispensable for oskar’s translational repression. We now report that this Bruno1-Cup interaction leads …

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C-Glycopyranosyl Aldehydes: Emerging Chiral Synthons In Organic Synthesis, Sandeep Kumar, Vinod Khatri, Priyanka Mangla, Rajni Johar Chhatwal, Virinder S. Parmar, Ashok K. Prasad Jan 2023

C-Glycopyranosyl Aldehydes: Emerging Chiral Synthons In Organic Synthesis, Sandeep Kumar, Vinod Khatri, Priyanka Mangla, Rajni Johar Chhatwal, Virinder S. Parmar, Ashok K. Prasad

Publications and Research

Herein, we have summarized the vast array of synthetic processes that have been developed for the synthesis of C-glycopyranosyl aldehydes and diverse C-glycoconjugates derived from them by covering the literature reported from 1979 to 2023. Notwithstanding its challenging chemistry, C-glycosides are considered stable pharmacophores and are used as important bioactive molecules. The discussed synthetic methodologies to access C-glycopyranosyl aldehydes take advantage of seven key intermediates, viz. allene, thiazole, dithiane, cyanide, alkene, and nitromethane. Furthermore, the integration of complex C-glycoconjugates derived from varied C-glycopyranosyl aldehydes involves nucleophilic addition/substitution, reduction, condensation, oxidation, cyclo condensation, coupling, and …

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Molecular Mechanism Behind The Safe Immunostimulatory Effect Of Withania Somnifera, Kriti Kalpana, Shen Yap, Moriya Tsuji, Akira Kawamura Jan 2023

Molecular Mechanism Behind The Safe Immunostimulatory Effect Of Withania Somnifera, Kriti Kalpana, Shen Yap, Moriya Tsuji, Akira Kawamura

Publications and Research

Withania somnifera (L.) Dunal (family Solanaceae) is a medicinal plant known for, among many pharmacological properties, an immune boosting effect. Our recent study revealed that its key immunostimulatory factor is lipopolysaccharide of plant-associated bacteria. This is peculiar, because, although LPS can elicit protective immunity, it is an extremely potent pro-inflammatory toxin (endotoxin). However, W. somnifera is not associated with such toxicity. In fact, despite the presence of LPS, it does not trigger massive inflammatory responses in macrophages. To gain insights into the safe immunostimulatory effect of W. somnifera, we conducted a mechanistic study on its major phytochemical constituent, …

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Tcga Expression Analyses Of 10 Carcinoma Types Reveal Clinically Significant Racial Differences, Brian Lei, Xinyin Jiang, Anjana Saxena Jan 2023

Tcga Expression Analyses Of 10 Carcinoma Types Reveal Clinically Significant Racial Differences, Brian Lei, Xinyin Jiang, Anjana Saxena

Publications and Research

Epidemiological studies reveal disparities in cancer incidence and outcome rates between racial groups in the United States. In our study, we investigated molecular differences between racial groups in 10 carcinoma types. We used publicly available data from The Cancer Genome Atlas to identify patterns of differential gene expression in tumor samples obtained from 4112 White, Black/African American, and Asian patients. We identified race-dependent expression of numerous genes whose mRNA transcript levels were significantly correlated with patients’ survival. Only a small subset of these genes was differentially expressed in multiple carcinomas, including genes involved in cell cycle progression such as CCNB1 …

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Treponema Denticola Synthesizes C-Di-Amp And Encodes The Cdaa-Type Diadenylate Cyclase Cdaa, Claire R. O'Brien Jan 2023

Treponema Denticola Synthesizes C-Di-Amp And Encodes The Cdaa-Type Diadenylate Cyclase Cdaa, Claire R. O'Brien

Theses and Dissertations

Periodontitis is a form of oral disease characterized by dysbiosis of the oral microbiome, leading to inflammation, bone resorption, and in severe cases, entire tooth loss, affecting 42% of adults in the US. One of the bacteria most associated with periodontal disease progression is Treponema denticola (Td), an oral spirochete which inhabits the mouth in small quantities during health but which can dominate the biofilms that form during periodontal disease. The ability of Td to survive in a disease environment and contribute to the progression of disease requires the use of robust signaling networks. Analysis of Td cultures …

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Characterization Of The Clostridioides Difficile Glycosyl Hydrolase Ccsz, Brian Lowrance Jan 2023

Characterization Of The Clostridioides Difficile Glycosyl Hydrolase Ccsz, Brian Lowrance

Theses and Dissertations (Comprehensive)

Bacteria inhabit many of the harshest environments on Earth; persisting and thriving in conditions thought to be unsuitable for life. One common strategy to withstand these environments is the formation of a biofilm. Biofilm composition varies greatly, depending on the underlying community that produces it. Cellulose, a polymer consistently prevalent in biofilms, has been identified as a virulence factor in many pathogens and is suspected to be involved in pathogenesis by Clostridioides difficile. C. difficile is the #1 cause of hospital acquired diarrhea, which can range from mild to life-threatening infections. Biofilm formation is hypothesized to be involved in …

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Functional Residues Of Cjpata, Robert Lamont Jan 2023

Functional Residues Of Cjpata, Robert Lamont

Theses and Dissertations (Comprehensive)

Antibiotic resistance in pathogenic bacteria continues to challenge clinicians and threaten the lives of infected individuals. For this reason, new classes of antibiotics or new targets for antibiotic therapy are needed to circumvent this global health crisis. In Gram-negative bacteria, the enzymes peptidoglycan O-acetyltransferase A and B (PatA and PatB), are responsible for adding acetyl groups to the C-6 hydroxyl group of N-acetyl muramic acid (MurNAc) in peptidoglycan (PG). These acetyl groups are responsible for inhibiting the activity of lysozyme from host organisms that hydrolyze the β1-4 glycosidic linkage between MurNAc and N-acetylglucosamine (GlcNAc). The acetyl groups …

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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 …

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

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

Theses and Dissertations (Comprehensive)

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

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

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

Honors Program Theses

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

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