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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 ...


Apoε4 Lowers Energy Expenditure In Females And Impairs Glucose Oxidation By Increasing Flux Through Aerobic Glycolysis, Brandon C. Farmer, Holden C. Williams, Nicholas A. Devanney, Margaret A. Piron, Grant K. Nation, David J. Carter, Adeline E. Walsh, Rebika Khanal, Lyndsay E. A. Young, Jude C. Kluemper, Gabriela Hernandez, Elizabeth J. Allenger, Rachel Mooney, Lesley R. Golden, Cathryn T. Smith, J. Anthony Brandon, Vedant A. Gupta, Philip A. Kern, Matthew S. Gentry, Josh M. Morganti, Ramon C. Sun, Lance A. Johnson 2021 University of Kentucky

Apoε4 Lowers Energy Expenditure In Females And Impairs Glucose Oxidation By Increasing Flux Through Aerobic Glycolysis, Brandon C. Farmer, Holden C. Williams, Nicholas A. Devanney, Margaret A. Piron, Grant K. Nation, David J. Carter, Adeline E. Walsh, Rebika Khanal, Lyndsay E. A. Young, Jude C. Kluemper, Gabriela Hernandez, Elizabeth J. Allenger, Rachel Mooney, Lesley R. Golden, Cathryn T. Smith, J. Anthony Brandon, Vedant A. Gupta, Philip A. Kern, Matthew S. Gentry, Josh M. Morganti, Ramon C. Sun, Lance A. Johnson

Physiology Faculty Publications

BACKGROUND: Cerebral glucose hypometabolism is consistently observed in individuals with Alzheimer's disease (AD), as well as in young cognitively normal carriers of the Ε4 allele of Apolipoprotein E (APOE), the strongest genetic predictor of late-onset AD. While this clinical feature has been described for over two decades, the mechanism underlying these changes in cerebral glucose metabolism remains a critical knowledge gap in the field.

METHODS: Here, we undertook a multi-omic approach by combining single-cell RNA sequencing (scRNAseq) and stable isotope resolved metabolomics (SIRM) to define a metabolic rewiring across astrocytes, brain tissue, mice, and human subjects expressing APOE4.

RESULTS ...


The Nature Of Cofilin’S Severing Mechanism, Ethan Lester 2021 Yale University

The Nature Of Cofilin’S Severing Mechanism, Ethan Lester

The Yale Undergraduate Research Journal

Cofilin plays an essential role in regulating actin filament propagation through the cytoplasmic medium. Over the years, various studies have been conducted in an attempt to better understand the complex mechanism by which cofilin promotes filament severing and de-polymerization. Here, we have compiled information obtained from these studies in order to craft a more complete and succinct description of cofilin functionality. In particular, we review the precise structural and mechanical changes associated with cofilin-binding, and the subtle ways in which some of these structural changes may be interconnected.


Mutations In Several Auxin Biosynthesis Genes And Their Effects On Plant Phenotypes In Arabidopsis, Gabriela Hernandez, Lauren Huebner, Bethany Karlin Zolman 2021 University of Missouri-St. Louis

Mutations In Several Auxin Biosynthesis Genes And Their Effects On Plant Phenotypes In Arabidopsis, Gabriela Hernandez, Lauren Huebner, Bethany Karlin Zolman

Undergraduate Research Symposium

Auxins are important hormones in plants that regulate growth and development. Disruptions in the auxin biosynthesis pathway result in morphological changes in phenotypes in the model plant Arabidopsis thaliana, including differences in root and leaf formation. Mutations in the Tryptophan Aminotransferase of Arabidopsis (TAA1) and YUCCA (YUC4) genes interfere with the plant's ability to synthesize Indole-3-acetic acid (IAA), the primary auxin involved in plant development. IBR1 and IBR3 act in the multistep conversion of indole-3-butyric acid (IBA) to IAA. ILL2, IAR3, and ILR1 hydrolyze IAA-amino acid conjugates into free IAA. The goal of our study was to determine the ...


A Novel Approach For Characterizing The Ultra-Micro Size-Fraction Community, Abdullah Ahmed Salim, Priscilla Nicole Pineda, Isabella Alamilla, Andrew Dean Putt 2021 University of Tennessee, Knoxville

A Novel Approach For Characterizing The Ultra-Micro Size-Fraction Community, Abdullah Ahmed Salim, Priscilla Nicole Pineda, Isabella Alamilla, Andrew Dean Putt

EURēCA: Exhibition of Undergraduate Research and Creative Achievement

A Novel Approach for Characterizing the Ultra-Micro Size-Fraction Community

Students: Abdullah Salim, Priscilla Pineda, Isabella Alamilla

Mentors/Supervisors: Andrew Putt, Terry C. Hazen

ABSTRACT

The ultra-micro size-fraction (UMSF) are bacteria that can pass through the 0.2 µm pore membrane filters employed in environmental surveys. Despite being ubiquitous and having high metabolic activity, UMSF remain elusive and largely uncultured. Investigations of UMSF are skewed by difficulties in culturing and a lack of techniques for measuring UMSF biogeochemical signatures. This study measures surface stream UMSF community diversity, and community response to the addition of the synthetic pharmaceutical and cosmetic carbon product ...


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.


College Of Natural Sciences Newsletter, September 2021, College Of Natural Sciences 2021 South Dakota State University

College Of Natural Sciences Newsletter, September 2021, College Of Natural Sciences

College of Natural Sciences Newsletters and Reports

Volume 2, Issue 9.

Page 1 Dean's Message
Page 2 Awards and Recognition
Page 3 Student Clubs in Natural Science
Page 4 Media Coverage of CNS
Page 5 Hobo Day Festivities
Page 6 Open PRAIRIE Data; Grants Awarded in CNS
Page 7 One Day for State Recap


Conformation Of The Protein-Free Spliceosomal U2-U6 Snrna Complex And Remodeling By Mg2+ And Proteins, Huong Chu 2021 The Graduate Center, City University of New York

Conformation Of The Protein-Free Spliceosomal U2-U6 Snrna Complex And Remodeling By Mg2+ And Proteins, Huong Chu

Dissertations, Theses, and Capstone Projects

Splicing of precursor messenger RNA is an essential process in eukaryotes in which the non-coding regions (introns) are removed and coding regions (exons) ligated together to form a mature mRNA. This process is catalyzed by a multi-mega Dalton ribonucleoprotein complex called the spliceosome, which is assembled from five small nuclear ribonucleoproteins (snRNP) in the form of RNA-protein complexes (U1, U2, U4, U5 and U6) and hundreds of proteins. U2 and U6 small nuclear (sn)RNAs are the only snRNAs directly implicated in catalyzing the splicing of pre-mRNA, but assembly and rearrangement steps prior to catalysis require numerous proteins. Previous studies ...


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 ...


Study Of The Gain-Of-Function Mutant P53 And Parp1 In Triple-Negative Breast Cancer, Devon Lundine 2021 The Graduate Center, City University of New York

Study Of The Gain-Of-Function Mutant P53 And Parp1 In Triple-Negative Breast Cancer, Devon Lundine

Dissertations, Theses, and Capstone Projects

Cancer cells often lose expression of the p53 protein or express mutant forms of p53. Some of these mutant p53 proteins, called gain-of-function mutant p53, have gained oncogenic functions. Previously, our group observed mutant p53 R273H interacts with replicating DNA and upregulates the chromatin localization of several DNA replication factors including PCNA, MCM2-7, and PARP1 (termed the mtp53-PARP-MCM axis). In this thesis, we explore the contribution of mutant p53 and PARP1 in castration-resistant prostate cancer (mutant p53 P223L and V274F) and triple-negative breast cancer (mutant p53 R273H). In the castration-resistant prostate cancer cell line DU145, we examine two mutant p53 ...


Understanding The Influence Of Zinc On Grain Cadmium Accumulation And Bioaccessibility In Rice, Michael A. Tavarez 2021 The Graduate Center, City University of New York

Understanding The Influence Of Zinc On Grain Cadmium Accumulation And Bioaccessibility In Rice, Michael A. Tavarez

Dissertations, Theses, and Capstone Projects

The effect of cadmium and zinc on mineral concentrations in three cultivars of rice

Interactions between the essential mineral zinc (Zn) and the toxic heavy metal cadmium (Cd) play an important role in regulating transport of both minerals to rice grains. Understanding these interactions is crucial for limiting cadmium and increasing zinc transfer to the food chain. Previous studies on the matter have had conflicting results suggesting synergistic and antagonistic relationships between the minerals. The goal of this work was to identify the effect of external cadmium and zinc on the uptake and translocation of both minerals from roots to ...


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 ...


The Veiled Lady Fungus, Nick Parbhoo 2021 Kennesaw State University

The Veiled Lady Fungus, Nick Parbhoo

Symposium of Student Scholars

This semester I studied the Stinkhorn mushroom Phallus Indusiatus. The plan of this research is to develop a protocol for growing this fungus and using it in collaboration with research on it’s web-like properties of the unique veil produced by the fruiting body. This will be distributed to teams of engineers as well as NASA for Dr. Penick’s research. Due to logistics of receiving spores from across the world, we still have not been able to begin growing these mushrooms. However, I have described a protocol that we will follow in order to grow. The protocol contains detailed ...


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