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Initial Characterization Of A Conserved Active Site Residue For The Cdc34 Ubiquitin Conjugating Enzyme, Arvin Akoopie 2014 University of Nevada, Las Vegas

Initial Characterization Of A Conserved Active Site Residue For The Cdc34 Ubiquitin Conjugating Enzyme, Arvin Akoopie

Theses

Ubiquitin-conjugating enzymes (E2s) covalently modify protein substrates with ubiquitins. The active site cysteine residues on E2s are essential for catalyzing the transfer of ubiquitin from the E2 active site onto the protein substrate, however there is a limited amount of information available concerning additional active site residues for E2s that may also participate in catalysis. Cdc34 is an essential E2 that has merited the lion’s share of attention for biochemical analysis of the E2 family. Previous phylogenetic analysis of Cdc34 amino acid sequences has identified an invariably conserved histidine residue close to the active site cysteine in the primary ...


Aminoglycoside-Induced Sensitization Of Cancer Cells And Development Of Carbohydrate-Containing Drugs, Michael F. Cuccarese 2014 Northeastern University

Aminoglycoside-Induced Sensitization Of Cancer Cells And Development Of Carbohydrate-Containing Drugs, Michael F. Cuccarese

Chemistry Dissertations

Modern drug discovery requires that synthesis of compounds with unique structures and properties is performed in concert with in-depth research on the biological event being targeted. The synergy of these two components of drug discovery generates the meaningful data necessary for a hypothesis-driven approach toward novel therapeutics. Herein, research is presented that pertains both to the study of biological activity, as well as the development of novel synthetic methods.

While the bactericidal effects of aminoglycosides are well understood, their therapeutic potential in human cells is emerging. Herein, a novel use of this class of compounds in cancer therapy is described ...


Pop2: A Potential Regulator Of Hmt1-Catalyzed Arginine Methylation In Yeast, Celeste Excell 2014 Utah State University

Pop2: A Potential Regulator Of Hmt1-Catalyzed Arginine Methylation In Yeast, Celeste Excell

All Graduate Theses and Dissertations

Protein arginine methylation is an important post-translational modification that is vital in regulating various cellular processes such as gene transcription, cell signaling, and RNA processing. Protein arginine methyltransferases (PRMTs) are responsible for performing this important modification. PRMT1 (protein arginine methyltransferase 1) and Hmt1 (hnRNP methyltransferase 1) are the predominant PRMTs in humans and yeast, respectively. Despite growing momentum in this field, relatively little is understood about PRMT regulation. Further work discovering how PRMTs are regulated will greatly advance our understanding of diseases where PRMTs have been implicated, such as heart disease, viral pathogenesis, and cancer.

It has been discovered that ...


Optimizing The Expression Of Nitronate Monooxygenase In E. Coli, Jennifer Hernandez 2014 Georgia State University

Optimizing The Expression Of Nitronate Monooxygenase In E. Coli, Jennifer Hernandez

Georgia State Undergraduate Research Conference

No abstract provided.


Molecular Dynamic Employment Regarding The Broad Specificity Of D-Arginine Dehydrogenase With D-Amino Acids, Charles Adeniran 2014 Georgia State University

Molecular Dynamic Employment Regarding The Broad Specificity Of D-Arginine Dehydrogenase With D-Amino Acids, Charles Adeniran

Georgia State Undergraduate Research Conference

No abstract provided.


Investigating Mitochondrial Protein Trafficking In Crithidia Fasciculata, Jeremiah Arnold 2014 Georgia State University

Investigating Mitochondrial Protein Trafficking In Crithidia Fasciculata, Jeremiah Arnold

Georgia State Undergraduate Research Conference

No abstract provided.


L-Carnitine Supplementation: A Potential Treatment For Cancer Cachexia, Aaron Kwong, Obaidullah Khan, Katrina Fleming, Sina Moshiri, Muhammad Hashmi 2014 McMaster University

L-Carnitine Supplementation: A Potential Treatment For Cancer Cachexia, Aaron Kwong, Obaidullah Khan, Katrina Fleming, Sina Moshiri, Muhammad Hashmi

The Meducator

Cachexia is a paraneoplastic syndrome that exhibits rampant muscle wasting, unintentional weight loss, fatigue, weakness, and overall loss of appetite, none of which can be abated by an increase in caloric intake. Metabolic derailment by cachexia is so severe in cancer patients that it can shorten lifetime expectancy and lead to death before the course of treatment is finished. Etiology may involve proinflammatory cytokines, but the abnormal loss of muscle, protein, and fat suggests an underlying metabolic dysfunction that contributes to cachexia. Previous research has shown reduction of L-carnitine in cachectic patients and chemotherapy-induced damage to the L-carnitine transport system ...


Determinants Of The Magnitude Of Training Mediated Muscle Hypertrophy, Cameron Mitchell 2014 McMaster University

Determinants Of The Magnitude Of Training Mediated Muscle Hypertrophy, Cameron Mitchell

Open Access Dissertations and Theses

Chronic resistance training leads to muscle hypotrophy in a wide range of populations however most resistance training studies are relatively small in sample size

Three studies were conducted to better understand the sources of this variability. The first study employed a unilateral resistance training model to test the effects of relative training load and volume on the magnitude of hypertrophy and strength gains. This study showed that high relative training loads were no better than low training loads at inducing muscle hypertrophy provided that each set was performed to the point of muscular exhaustion. In agreement with previous finding, strength ...


Redox Regulation Of Protein Translation In Eukaryotes, Maxim Gerashchenko 2014 University of Nebraska - Lincoln

Redox Regulation Of Protein Translation In Eukaryotes, Maxim Gerashchenko

Theses and Dissertations in Biochemistry

Gene expression may be controlled at multiple levels, e.g., through genomic architecture, transcription and translation. In the current work, we focused on regulation of protein synthesis. Historically, the investigation of the regulation of gene expression at the level of translation lagged behind the transcriptional control because of the lack of accessible high-throughput methods. Our research has begun with the finding of the use of alternative non-AUG start codon in thioredoxin-glutathione reductase (TGR), a selenoprotein involved in redox control during male reproduction. The use of this codon, CUG, relies on the Kozak consensus sequence and ribosomal scanning mechanism. However, the ...


Detection, Characterization And Evolution Of Internal Repeats In Chitinases Of Known 3-D Structure, Manigandan Sivaji, Vinoth Sadasivam, Jayabalan Narayanasamy, Selvaraj Samuel, Chuanzhu Fan 2014 Wayne State University

Detection, Characterization And Evolution Of Internal Repeats In Chitinases Of Known 3-D Structure, Manigandan Sivaji, Vinoth Sadasivam, Jayabalan Narayanasamy, Selvaraj Samuel, Chuanzhu Fan

Biological Sciences Faculty Research Publications

Chitinase proteins have evolved and diversified almost in all organisms ranging from prokaryotes to eukaryotes. During evolution, internal repeats may appear in amino acid sequences of proteins which alter the structural and functional features. Here we deciphered the internal repeats from Chitinase and characterized the structural similarities between them. Out of 24 diverse Chitinase sequences selected, six sequences (2CJL, 2DSK, 2XVP, 2Z37, 3EBV and 3HBE) did not contain any internal repeats of amino acid sequences. Ten sequences contained repeats of length <50, and the remaining 8 sequences contained repeat length between 50 and 100 residues. Two Chitinase sequences, 1ITX and 3SIM, were found to be structurally similar when analyzed using secondary structure of Chitinase from secondary and 3-Dimensional structure database of Protein Data Bank. Internal repeats of 3N17 and 1O6I were also involved in the ligand-binding site of those Chitinase proteins, respectively. Our analyses enhance our understanding towards the identification of structural characteristics of internal repeats in Chitinase proteins.


A Kras-Directed Transcriptional Silencing Pathway That Mediates The Cpg Island Methylator Phenotype, Ryan W. Serra, Minggang Fang, Sung Mi Park, Lloyd Hutchinson, Michael R. Green 2014 University of Massachusetts Medical School

A Kras-Directed Transcriptional Silencing Pathway That Mediates The Cpg Island Methylator Phenotype, Ryan W. Serra, Minggang Fang, Sung Mi Park, Lloyd Hutchinson, Michael R. Green

Program in Molecular Medicine Publications and Presentations

Approximately 70% of KRAS-positive colorectal cancers (CRCs) have a CpG island methylator phenotype (CIMP) characterized by aberrant DNA hypermethylation and transcriptional silencing of many genes. The factors involved in, and the mechanistic basis of, CIMP is not understood. Among the CIMP genes are the tumor suppressors p14(ARF), p15(INK4B), and p16(INK4A), encoded by the INK4-ARF locus. In this study, we perform an RNA interference screen and identify ZNF304, a zinc-finger DNA-binding protein, as the pivotal factor required for INK4-ARF silencing and CIMP in CRCs containing activated KRAS. In KRAS-positive human CRC cell lines and tumors, ZNF304 is bound ...


Endocytosis And Vacuolar Degradation Of The Yeast Cell Surface Glucose Sensors Rgt2 And Snf3, Adhiraj Roy, Jeong-Ho Kim 2014 Himmelfarb Health Sciences Library, The George Washington University

Endocytosis And Vacuolar Degradation Of The Yeast Cell Surface Glucose Sensors Rgt2 And Snf3, Adhiraj Roy, Jeong-Ho Kim

Biochemistry and Molecular Medicine Faculty Publications

Sensing and signaling the presence of extracellular glucose is crucial for the yeast Saccharomyces cerevisiae because of its fermentative metabolism, characterized by high glucose flux through glycolysis. The yeast senses glucose through the cell surface glucose sensors Rgt2 and Snf3, which serve as glucose receptors that generate the signal for induction of genes involved in glucose uptake and metabolism. Rgt2 and Snf3 detect high and low glucose concentrations, respectively, perhaps due to their different affinities for glucose. Here, we provide evidence that cell surface levels of glucose sensors are regulated by ubiquitination and degradation. The glucose sensors are removed from ...


Systems Thinking With Biology Models, Joseph Dauer 2014 University of Nebraska - Lincoln

Systems Thinking With Biology Models, Joseph Dauer

DBER Speaker Series

The recent AAAS call to improve undergraduate biology education suggested university instruction should focus on teaching core concepts like matter and energy, evolution, and systems and core competences like quantitative reasoning, modeling and integrating disciplines. My research has focused on how undergraduate biology students organize their knowledge of biological systems and how they reason about the myriad interactions and potential outcomes inherent to these systems. I will report ongoing research into students’ model construction during an introductory biology course and during clinical interviews 2 years after the course. My colleagues and I have found students’ models change dramatically in both ...


An Improved Predictive Recognition Model For Cys2-His2 Zinc Finger Proteins, Ankit Gupta, Ryan G. Christensen, Heather A. Bell, Mathew Goodwin, Ronak Y. Patel, Manishi Pandey, Metewo Selase Enuameh, Amy L. Rayla, Cong Zhu, Stacey Thibodeau-Beganny, Michael H. Brodsky, J. Keith Joung, Scot A. Wolfe, Gary D. Stormo 2014 University of Massachusetts Medical School

An Improved Predictive Recognition Model For Cys2-His2 Zinc Finger Proteins, Ankit Gupta, Ryan G. Christensen, Heather A. Bell, Mathew Goodwin, Ronak Y. Patel, Manishi Pandey, Metewo Selase Enuameh, Amy L. Rayla, Cong Zhu, Stacey Thibodeau-Beganny, Michael H. Brodsky, J. Keith Joung, Scot A. Wolfe, Gary D. Stormo

Program in Gene Function and Expression Publications and Presentations

Cys2-His2 zinc finger proteins (ZFPs) are the largest family of transcription factors in higher metazoans. They also represent the most diverse family with regards to the composition of their recognition sequences. Although there are a number of ZFPs with characterized DNA-binding preferences, the specificity of the vast majority of ZFPs is unknown and cannot be directly inferred by homology due to the diversity of recognition residues present within individual fingers. Given the large number of unique zinc fingers and assemblies present across eukaryotes, a comprehensive predictive recognition model that could accurately estimate the DNA-binding specificity of any ZFP based on ...


Role Of Hepatitis C Virus Inducted Osteopontin In Epithelial To Mesenchymal Transition, Migration, And Invasion Of Hepatocytes, Jawed Iqbal, Steven McRae, Thi Mai, Krishna Banaudha, Mehuli Sarkar-Dutta, Gulam Waris 2014 Himmelfarb Health Sciences Library, The George Washington University

Role Of Hepatitis C Virus Inducted Osteopontin In Epithelial To Mesenchymal Transition, Migration, And Invasion Of Hepatocytes, Jawed Iqbal, Steven Mcrae, Thi Mai, Krishna Banaudha, Mehuli Sarkar-Dutta, Gulam Waris

Biochemistry and Molecular Medicine Faculty Publications

Osteopontin (OPN) is a secreted phosphoprotein which has been linked to tumor progression and metastasis in a variety of cancers including hepatocellular carcinoma (HCC). Previous studies have shown that OPN is upregulated during liver injury and inflammation. However, the role of OPN in hepatitis C virus (HCV)-induced liver disease pathogenesis is not known. In this study, we determined the induction of OPN, and then investigated the effect of secreted forms of OPN in epithelial to mesenchymal transition (EMT), migration and invasion of hepatocytes. We show the induction of OPN mRNA and protein expression by HCV-infection. Our results also demonstrate ...


Non-Synonymous Variations In Cancer And Their Effects On The Human Proteome: Workflow For Ngs Data Biocuration And Proteome-Wide Analysis Of Tcga Data, Charles Cole, Konstantinos Krampis, Konstantinos Karagiannis, Jonas Almeida, William J. Faison, Mona Motwani, Quan Wan, Anton Golikov, Yang Pan, Vahan Simonyan, Raja Mazumder 2014 Himmelfarb Health Sciences Library, The George Washington University

Non-Synonymous Variations In Cancer And Their Effects On The Human Proteome: Workflow For Ngs Data Biocuration And Proteome-Wide Analysis Of Tcga Data, Charles Cole, Konstantinos Krampis, Konstantinos Karagiannis, Jonas Almeida, William J. Faison, Mona Motwani, Quan Wan, Anton Golikov, Yang Pan, Vahan Simonyan, Raja Mazumder

Biochemistry and Molecular Medicine Faculty Publications

Background

Next-generation sequencing (NGS) technologies have resulted in petabytes of scattered data, decentralized in archives, databases and sometimes in isolated hard-disks which are inaccessible for browsing and analysis. It is expected that curated secondary databases will help organize some of this Big Data thereby allowing users better navigate, search and compute on it.

Results

To address the above challenge, we have implemented a NGS biocuration workflow and are analyzing short read sequences and associated metadata from cancer patients to better understand the human variome. Curation of variation and other related information from control (normal tissue) and case (tumor) samples will ...


Understanding The Mechanism Of Glucose-Induced Relief Of Rgt1-Mediated Repression In Yeast, Adhiraj Roy, David Jouandot, Kyu Hong Cho, Jeong-Ho Kim 2014 Himmelfarb Health Sciences Library, The George Washington University

Understanding The Mechanism Of Glucose-Induced Relief Of Rgt1-Mediated Repression In Yeast, Adhiraj Roy, David Jouandot, Kyu Hong Cho, Jeong-Ho Kim

Biochemistry and Molecular Medicine Faculty Publications

The yeast Rgt1 repressor inhibits transcription of the glucose transporter (HXT) genes in the absence of glucose. It does so by recruiting the general corepressor complex Ssn6-Tup1 and the HXT corepressor Mth1. In the presence of glucose, Rgt1 is phosphorylated by the cAMP-activated protein kinase A (PKA) and dissociates from the HXT promoters, resulting in expression of HXT genes. In this study, using Rgt1 chimeras that bind DNA constitutively, we investigate how glucose regulates Rgt1 function. Our results show that the DNA-bound Rgt1 constructs repress expression of the HXT1 gene in conjunction with Ssn6-Tup1 and Mth1, and that this repression ...


Vibrational Spectroscopy: Disease Diagnostics And Beyond, Hugh J. Byrne, Kamila Ostrowska, Haq Nawaz, Jennifer Dorney, Aidan D. Meade, Franck Bonnier, Fiona M. Lyng 2014 Dublin Institute of Technology

Vibrational Spectroscopy: Disease Diagnostics And Beyond, Hugh J. Byrne, Kamila Ostrowska, Haq Nawaz, Jennifer Dorney, Aidan D. Meade, Franck Bonnier, Fiona M. Lyng

Books/Book Chapters

Summary

This chapter outlines some developments in the applications of vibrational spectroscopy for disease diagnostics and demonstrates how the applications of the spectroscopic techniques can be extended to the analysis and evaluation of disease aetiology and the mechanisms of interaction and the cellular and subcellular responses to, for example chemotherapeutic agents and nanoparticles. The primary emphasis is on Raman spectroscopy, although some examples are based on infrared absorption spectroscopy. The studies presented are chosen to illustrate how a range of multivariate analytical techniques can be employed to maximize the potential benefits of the complex spectral information obtained from tissue or ...


Development Of An Enzymatic Digestion Method To Probe The Sequence Specificity Of Carcinogen Adduction In Oligonucleotides, John M. Capece 2014 Northeastern University

Development Of An Enzymatic Digestion Method To Probe The Sequence Specificity Of Carcinogen Adduction In Oligonucleotides, John M. Capece

Chemistry Master's Theses

A carcinogen is defined as any substance, radiation, or radionucleotide that produces cancer through alteration of the metabolic processes in the cell or by directly damaging the cell's DNA. In cases where DNA is damaged, the carcinogen comes into contact with the DNA; the DNA performs a nucleophilic attack on the electrophilic carcinogen, which permanently binds the two. This reaction between carcinogens and DNA generally exhibits sequence selectivity, the recognition of which may be important in understanding their mutagenic activities. A method could be developed to measure the effectiveness of several different DNA repair pathways. Exposing bacterial plasmids to ...


Further Characterization Of A Secreted Lipase From The Human Pathogen Leishmania Donovani By Determining The Effect Of Various Metal Ions On Its Enzymatic Activity., Lana Hoertz 2014 Salve Regina University

Further Characterization Of A Secreted Lipase From The Human Pathogen Leishmania Donovani By Determining The Effect Of Various Metal Ions On Its Enzymatic Activity., Lana Hoertz

Pell Scholars and Senior Theses

Leishmania donovani, a protozoan parasite, is the causative agent of the often fatal disease visceral leishmaniasis. The current treatments available are minimal and toxic to the patient. It has been shown that these organisms exhibit lipolytic activity during their growth in vitro. Lipases are enzymes that are known to aid in the development and virulence of several pathogenic organisms such as Candida albicans and Staphylococcus warneri. Little information is known, however, about the role of lipases in Leishmania species. We hypothesize that lipase may play a part in Leishmania's ability to survive within the human host as well as ...


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