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Characterization And Manipulation Of O-Glcnacylation In Granulosa Cells Of Bovine Ovarian Antral Follicles, Abigail Marie Maucieri 2022 University of Vermont

Characterization And Manipulation Of O-Glcnacylation In Granulosa Cells Of Bovine Ovarian Antral Follicles, Abigail Marie Maucieri

Graduate College Dissertations and Theses

Glucose is widely recognized as the preferred energy substrate for metabolism by granulosa cells (GCs). Yet in most cells, 2-5% of glucose is shunted through the hexosamine biosynthesis pathway (HBP) for O-linked N-acetylglucosaminylation (O-GlcNAcylation). O-GlcNAcylation is an evolutionarily-conserved, post-translational process that modifies serine and threonine residues on a variety of proteins. O-GlcNAcylation is also considered a nutrient sensor that can regulate cellular processes such as metabolism, signal transduction, and proliferation. In this respect, O-GlcNAcylation may be similar to, and possibly mediate, AMP-activated protein kinase (AMPK) signaling and its nutrient-sensing actions. However, the occurrence of O-GlcNAcylation and its relative importance to ...


Purification And Initial Biochemical Characterization Of Atp:Cob(I)Alamin Adenosyltransferase (Eutt) Enzyme Of Salmonella Enterica, Nicole R. Buan, Jorge C. Escalante-Semerena 2021 University of Nebraska-Lincoln

Purification And Initial Biochemical Characterization Of Atp:Cob(I)Alamin Adenosyltransferase (Eutt) Enzyme Of Salmonella Enterica, Nicole R. Buan, Jorge C. Escalante-Semerena

Biochemistry -- Faculty Publications

ATP:cob(I)alamin adenosyltransferase (EutT) of Salmonella enterica was overproduced and enriched to ~70% homogeneity, and its basic kinetic parameters were determined. Abundant amounts of EutT protein were produced, but all of it remained insoluble. Soluble active EutT protein (~70% homogeneous) was obtained after treatment with detergent. Under conditions in which cobalamin (Cbl) was saturating, Km(ATP) = 10 μM, kcat = 0.03 s1, and Vmax = 54.5 nM min1. Similarly, under conditions in which MgATPwas saturating,Km(Cbl)= 4.1μM, kcat = 0.06 s1, andVmax= 105 nM min1 ...


Covid-19 In Silico Drug With Zingiber Officinale Natural Product Compound Library Targeting The Mpro Protein, Renadya Maulani Wijaya, Muhammad Aldino Hafidzhah, Viol Dhea Kharisma, Arif Nur Muhammad Ansori, Arli Aditya Parikesit 2021 Department of Bioinformatics, School of Life Sciences, Indonesia International Institute for Life Sciences (i3L), Jakarta 13210, Indonesia

Covid-19 In Silico Drug With Zingiber Officinale Natural Product Compound Library Targeting The Mpro Protein, Renadya Maulani Wijaya, Muhammad Aldino Hafidzhah, Viol Dhea Kharisma, Arif Nur Muhammad Ansori, Arli Aditya Parikesit

Makara Journal of Science

Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a worldwide pandemic. Ginger (Zingiber officinale) is a rhizome, which is commonly used for culinary and medicinal purposes. In Indonesia, ginger is taken as traditional medicine by processing it into a drink known as jamu. The present study aimed to assess and evaluate the bioactive compounds in ginger that can be used in drug design for treating COVID-19. The crystal structure of the SARS-CoV-2 main protease (Mpro) was generated from a protein sequence database, i.e., Protein Data Bank, and the bioactive ...


Oxidation Alters The Architecture Of The Phenylalanyl-Trna Synthetase Editing Domain To Confer Hyperaccuracy, Pooja Srinivas, Rebecca E. Steiner, Ian J. Pavelich, Ricardo Guerrera-Ferreira, Puneet Juneja, Michael Ibba, Christine M. Dunham 2021 Emory University

Oxidation Alters The Architecture Of The Phenylalanyl-Trna Synthetase Editing Domain To Confer Hyperaccuracy, Pooja Srinivas, Rebecca E. Steiner, Ian J. Pavelich, Ricardo Guerrera-Ferreira, Puneet Juneja, Michael Ibba, Christine M. Dunham

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

High fidelity during protein synthesis is accomplished by aminoacyl-tRNA synthetases (aaRSs). These enzymes ligate an amino acid to a cognate tRNA and have proofreading and editing capabilities that ensure high fidelity. Phenylalanyl-tRNA synthetase (PheRS) preferentially ligates a phenylalanine to a tRNAPhe over the chemically similar tyrosine, which differs from phenylalanine by a single hydroxyl group. In bacteria that undergo exposure to oxidative stress such as Salmonella enterica serovar Typhimurium, tyrosine isomer levels increase due to phenylalanine oxidation. Several residues are oxidized in PheRS and contribute to hyperactive editing, including against mischarged Tyr-tRNAPhe, despite these oxidized residues not being ...


Improving Healthspan Through Patient-Derived Artificial Organs From Induced Pluripotent Stem Cells And Two-Photon Polymerization, Connor Espenshade 2021 University of Pennsylvania

Improving Healthspan Through Patient-Derived Artificial Organs From Induced Pluripotent Stem Cells And Two-Photon Polymerization, Connor Espenshade

Protocols and Reports

Senescence, from the shortening of telomeres, accumulation of mutations, epigenetic hypomethylation, and other causes, begins an eventual cycle of decline in every patient. Stem cells disappear as a function of age, which in turn impairs cellular replication. Moreover, when fully differentiated cells are induced back into induced pluripotent stem cells (iPSCs), they not only revert to a state of pre-differentiation, but also to a younger cellular age. Their aging clocks turn back: their telomeres become longer and DNA methylation reverts back to an earlier age. It should therefore be possible to use iPSCs to replace the missing stem cells from ...


60. Epfl Genes And Their Role In Flower Development In Arabidopsis Thaliana, Rachael Deboe 2021 University of Tennessee, Knoxville

60. Epfl Genes And Their Role In Flower Development In Arabidopsis Thaliana, Rachael Deboe

EURēCA: Exhibition of Undergraduate Research and Creative Achievement

Flowers are composed of four floral organ types: sepals, petals, stamens, and a pistil. In Arabidopsis thaliana, the ERECTA family leucine rich repeat receptor like kinases (LRR-RLKs) have been shown to regulate plant morphology. Epidermal Patterning Factor-Like (EPFL) genes encode for small secretory proteins that are ligands for ERECTA Family (ERf) receptors. It is suspected that EPFL’s act as a signal to coordinate proper lateral organ number, patterning, and spacing. ERf mutants have significant defects in flower development, including difficulty forming anther lobes and pistils, yet little is known about how individual EPFL ligands contribute to ERf signaling. In ...


Targeting The Cdk6 Dependence Of Ph+ Acute Lymphoblastic Leukemia, Patrizia Porazzi, Marco De Dominici, Joseph Salvino, Bruno Calabretta 2021 Thomas Jefferson University

Targeting The Cdk6 Dependence Of Ph+ Acute Lymphoblastic Leukemia, Patrizia Porazzi, Marco De Dominici, Joseph Salvino, Bruno Calabretta

Department of Cancer Biology Faculty Papers

Ph+ ALL is a poor-prognosis leukemia subtype driven by the BCR-ABL1 oncogene, either the p190-or the p210-BCR/ABL isoform in a 70:30 ratio. Tyrosine Kinase inhibitors (TKIs) are the drugs of choice in the therapy of Ph+ ALL. In combination with standard chemotherapy, TKIs have markedly improved the outcome of Ph+ ALL, in particular if this treatment is followed by bone marrow transplantation. However, resistance to TKIs develops with high frequency, causing leukemia relapse that results in <5-year overall survival. Thus, new therapies are needed to address relapsed/TKI-resistant Ph+ ALL. We have shown that expression of cell cycle regulatory kinase CDK6, but not of the highly related CDK4 kinase, is required for the proliferation and survival of Ph+ ALL cells. Comparison of leukemia suppression induced by treatment with the clinically-approved dual CDK4/6 inhibitor palbociclib versus CDK6 silencing revealed that the latter treatment was markedly more effective, probably reflecting inhibition of CDK6 kinase-independent effects. Thus, we developed CDK4/6-targeted proteolysis-targeting chimeras (PROTACs) that preferentially degrade CDK6 over CDK4. One compound termed PROTAC YX-2-107, which degrades CDK6 by recruiting the Cereblon ubiquitin ligase, markedly suppressed leukemia burden in mice injected with de novo or TKI-resistant Ph+ ALL. The effect of PROTAC YX-2-107 was comparable or superior to that of palbociclib. The development of CDK6-selective PROTACs represents an effective strategy to exploit the “CDK6 dependence” of Ph+ ALL cells while sparing a high proportion of normal hematopoietic progenitors that depend on both CDK6 and CDK6 for their survival. In combination with other agents, CDK6-selective PROTACs may be valuable components of chemotherapy-free protocols for the therapy of Ph+ ALL and other CDK6-dependent hematological malignancies.


Machine Learning And Solvation Theory For Drug Discovery, Lieyang Chen 2021 The Graduate Center, City University of New York

Machine Learning And Solvation Theory For Drug Discovery, Lieyang Chen

Dissertations, Theses, and Capstone Projects

Drug discovery is a notoriously expensive and time-consuming process; hence, developing computational methods to facilitate the discovery process and lower the associated costs is a long-sought goal of computational chemists. Protein-ligand binding, which provides the physical and chemical basis for the mechanism of action of most drugs, occurs in an aqueous environment, and binding affinity is determined not only by atomic interactions between the protein and ligand but also by changes in their interactions with surrounding water molecules that occur upon binding. Thus, a quantitative understanding of the roles water molecules play in the protein-ligand binding process is an essential ...


Don't Sell Them Short, There's More To Bacterial Natural Products Than Antibiotics, Alison Clare Domzalski 2021 The Graduate Center, City University of New York

Don't Sell Them Short, There's More To Bacterial Natural Products Than Antibiotics, Alison Clare Domzalski

Dissertations, Theses, and Capstone Projects

Recent genomic studies of microbiomes have revealed an overwhelming number of biosynthetic genes of unknown function. Most of these “cryptic” biosynthetic genes are not expressed in laboratory monocultures of individual microbes. Thus, there remains tremendous untapped potential for natural products discovery. Here we employ mixed microbial culture (MMC) as a simple yet powerful approach to awaken cryptic biosynthetic gene clusters. Our preliminary studies demonstrated that arrays of metabolites could be induced in MMCs upon environmental cues, such as surface adhesion. Using this system, we have screened, identified, and isolated bioactive bacterial metabolites, which were characterized structurally and biologically. Of the ...


Tools And Strategies For The Patterning Of Bioactive Molecules And Macromolecules, Daniel J. Valles 2021 The Graduate Center, City University of New York

Tools And Strategies For The Patterning Of Bioactive Molecules And Macromolecules, Daniel J. Valles

Dissertations, Theses, and Capstone Projects

Hypersurface Photolithography (HP) is a printing method for fabricating structures and patterns composed of soft materials bound to solid surfaces and with ~1 micrometer resolution in the x, y, and z dimensions. This platform leverages benign, low intensity light to perform photochemical surface reactions with spatial and temporal control of irradiation, and, as a result, is particularly useful for patterning delicate organic and biological material. In particular, surface- initiated controlled radical polymerizations can be leveraged to create arbitrary polymer and block- copolymer brush patterns. Chapter 1 will review the advances in instrumentation architectures from our group that have made these ...


Three Lc-Ms Plant Metabolomics Studies Of Hop (Humulus) Species: Wild H. Neomexicanus, Drought Stress, And Agricultural Terroir, Taylan Morcol 2021 The Graduate Center, City University of New York

Three Lc-Ms Plant Metabolomics Studies Of Hop (Humulus) Species: Wild H. Neomexicanus, Drought Stress, And Agricultural Terroir, Taylan Morcol

Dissertations, Theses, and Capstone Projects

The hop plant (Humulus L., Cannabaceae) is a dioecious, perennial, twining vine with a long history of human use. Nowadays, hop plants are generally grown for their inflorescences (“cones”), which are used in brewing for their phytochemical metabolites. Many of these metabolites are involved in plant stress response and communication. Genetics and environment are two major factors that affect plant metabolism. In three separate metabolomics studies, this project examined the effects of both genetic and environmental factors on hop phytochemistry.

In the first study, 23 hop genotypes were grown in two different locations in the Pacific Northwest region of the ...


Conserved Regions Mediate Interactions Between Canonical Nox Domains, Akua Acheampong 2021 Kennesaw State University

Conserved Regions Mediate Interactions Between Canonical Nox Domains, Akua Acheampong

Symposium of Student Scholars

NAPDH oxidase (NOXes) are membrane-bound enzymes that generate reactive oxygen species (ROS) that play a role in immune response and signaling. Misregulation of NOXes is implicated in various human pathologies. NOXes contain a catalytic core comprised of a heme-containing transmembrane (TM) domain and a cytoplasmic dehydrogenase (DH) domain that binds FAD and NADPH. Several conserved regions at the interface of the TM and DH domains in eukaryotic NOXes have been suggested to mediate enzyme function and activity. In 2017, researchers successfully purified SpNox, a bona fide NOX homolog from Streptococcus pneumoniae and verified its NOX properties. SpNox’s robust activity ...


Effects Of Osmotic Stress Induced By Polyethylene Glycol (Peg) 6000 And Mannitol On Seed Germination And Seedling Growth Of Durum Wheat, Ratiba Bousba, Rabah Bounar, Narimene Sedrati, Randa Lakhal, Chourouk Hamla, Malika Rached-Kanouni 2021 Department of Biology and Ecology, Faculty of Natural Sciences and Life, University Mentouri Brothers Constantine 1, Algeria.

Effects Of Osmotic Stress Induced By Polyethylene Glycol (Peg) 6000 And Mannitol On Seed Germination And Seedling Growth Of Durum Wheat, Ratiba Bousba, Rabah Bounar, Narimene Sedrati, Randa Lakhal, Chourouk Hamla, Malika Rached-Kanouni

Journal of Bioresource Management

Seed germination is generally the critical step in seed establishment and thus the determination of successful crop production. This study was focused at examination of the biochemical and germination parameters effected by low water potential which was generated by polyethylene glycol (PEG) 6000 and mannitol, related to drought stress and growth of Waha durum wheat genotype. Two tests were carried out in a growth chamber; the first comprises seed germination into Petri dishes in the presence of different concentrations of the two osmoticums (0, 5, 10, 15 and 20 % of PEG6000 and mannitol). The second test was carried out in ...


Insights Into Halophilic Microbial Adaptation: Analysis Of Integrons And Associated Genomic Structures And Characterization Of A Nitrilase In Hypersaline Environments, Sarah Sonbol 2021 American University in Cairo

Insights Into Halophilic Microbial Adaptation: Analysis Of Integrons And Associated Genomic Structures And Characterization Of A Nitrilase In Hypersaline Environments, Sarah Sonbol

Theses and Dissertations

Hypersaline environments are extreme habitats that can be exploited as biotechnological resources. Here, we characterized a nitrilase (NitraS-ATII) isolated from Atlantis II Deep brine pool. It showed higher thermal stability and heavy metal tolerance compared to a closely related nitrilase.

We also studied integrons in halophiles and hypersaline environments. Integrons are genetic platforms in which an integron integrase (IntI) mediates the excision and integration of gene cassettes at specific recombination sites. In order to search for integrons in halophiles and hypersaline metagenomes, we used a PCR-based approach, in addition to different bioinformatics tools, mainly IntegronFinder.

We found that integrons and ...


Assessing Selective Plasmids For Bradyrhizobium Sp. Doa9 And Mesorhizobium Loti, Aiden J. Wilcox, Rebecca Meaney, Bogumil Karas 2021 Western University

Assessing Selective Plasmids For Bradyrhizobium Sp. Doa9 And Mesorhizobium Loti, Aiden J. Wilcox, Rebecca Meaney, Bogumil Karas

Undergraduate Student Research Internships Conference

No abstract provided.


The Cofactor Specificity Of Nqo2, Shujun Dong 2021 Western University

The Cofactor Specificity Of Nqo2, Shujun Dong

Undergraduate Student Research Internships Conference

NQO1 and NQO2 are closely related quinone reductases, which are FAD-linked enzymes that catalyze the 2-electron reduction of quinones. Whereas NQO1 has a well-defined role in cellular detoxification of quinones, NQO2’s function is less clear; it uses the conventional cofactors NADH/NADPH inefficiently compared to smaller nicotinamide cofactors, which are often present in low cellular amounts. This unique cofactor specificity suggests that NQO2 may have non-enzymatic functions, such as a role in intracellular signalling.

The goals of this research project include: 1) examining whether cofactor specificity is conserved in amniote NQO2 enzymes and 2) re-constructing ancient enzymes along the ...


Investigating Stop Codon Readthrough In Saccharomyces Cerevisiae, Amy Kwon 2021 Western University

Investigating Stop Codon Readthrough In Saccharomyces Cerevisiae, Amy Kwon

Undergraduate Student Research Internships Conference

Stop codon readthrough occurs via genetic and epigenetic mechanisms, resulting in a longer polypeptide chain at the C-terminus. Although these readthroughs may seem like an error made by translational mechanisms, evidence from yeast suggests that stop codon readthrough has an impact on various cellular processes. Readthrough has the potential to create genetic diversity, similar to RNA splicing, mRNA editing, and protein modification. The diversity created by translational readthrough may result in a beneficial change in phenotype, and thus have a role in evolution and adaptability. Translational readthrough is observed in organisms such as yeast and E. coli but may also ...


Synthesis Of Nucleotide Prodrugs As Potential Antiviral Agents, Mohammed Attaelmanan 2021 Western University

Synthesis Of Nucleotide Prodrugs As Potential Antiviral Agents, Mohammed Attaelmanan

Undergraduate Student Research Internships Conference

No abstract provided.


Investigating Dha Levels In Rat Brain Tissues In Relation To Maternal Thc Exposure Using Maldi-Ims, Aleksandra (Ola) Doktor 2021 Western University

Investigating Dha Levels In Rat Brain Tissues In Relation To Maternal Thc Exposure Using Maldi-Ims, Aleksandra (Ola) Doktor

Undergraduate Student Research Internships Conference

This research focuses on investigating whether maternal exposure to THC (tetrahydrocannabinol) has an effect on lowering DHA (Docosahexaenoic Acid) levels in female and male offspring, and if an omega-3 rich diet, containing DHA, is able to recover DHA levels following a THC caused deficiency. To study this, DHA levels in rat brain tissues from 21-Day-Old offspring were compared across four different groups of maternal rats, vehicle rats with a controlled diet (veh/ct), vehicle rats with an omega-3 rich diet (veh/n3), THC treated rats with a controlled diet (thc/ct), and THC treated rats with an omega-3 rich diet ...


Encirclement Of Moving Targets Using Noisy Range And Bearing Measurements, Cammy Peterson, Puneet Jain, Randal Beard 2021 Brigham Young University

Encirclement Of Moving Targets Using Noisy Range And Bearing Measurements, Cammy Peterson, Puneet Jain, Randal Beard

Faculty Publications

This paper presents theoretically justified controllers that use relative range and bearing measurements to steer a team of autonomous vehicles, operating without inertial position information, to circular trajectories around a constant-acceleration, constant-velocity, or stationary target. An extended Kalman filter is used to improve the noisy relative measurements and estimate the velocity of the moving target. These estimated values are used in the control laws to encircle constant-velocity moving targets. Lyapunov techniques are utilized to show that the vehicle will converge to the desired circular formations. Additionally, cooperating vehicles are shown to converge to a circular formation with equal temporal spacing ...


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