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Articles 421 - 450 of 466
Full-Text Articles in Biochemistry, Biophysics, and Structural Biology
Long-Term Clinicopathological Characteristics Of Alpacas Naturally Infected With Bovine Viral Diarrhea Virus Type Ib, D. Bedenice, Edward J. Dubovi, Clayton Kelling, Jamie N Henningson, Christina L. Topliff, N. Parry
Long-Term Clinicopathological Characteristics Of Alpacas Naturally Infected With Bovine Viral Diarrhea Virus Type Ib, D. Bedenice, Edward J. Dubovi, Clayton Kelling, Jamie N Henningson, Christina L. Topliff, N. Parry
School of Veterinary and Biomedical Sciences: Faculty Publications
Background: Substantial bovine viral diarrhea virus (BVDV)-related production losses in North American alpaca herds have been associated with BVDV type Ib infection.
Objectives: To classify and differentiate the long-term clinicopathological characteristics of BVDV type Ib infection of al- paca crias, after natural virus exposure. We hypothesized that persistently infected (PI) alpacas specifically demonstrate growth retardation, clinicopathological evidence of opportunistic infections, and early mortality.
Animals: Thirty-five crias naturally exposed to BVDV (18 acute, 3 chronic, 14 PIs), and 19 healthy cohort controls of 5 northeastern alpaca farms were prospectively evaluated over 2 years (September 2005–September 2008).
Methods: Observational cohort-control study.
Results: …
Gender Differences In Cns Autoimmunity Induced By Mimicry Epitope For Plp 139–151 In Sjl Mice, Chandirasegara Massilamany, Sivasubramani Thulasingam, David Steffen, Jay Reddy
Gender Differences In Cns Autoimmunity Induced By Mimicry Epitope For Plp 139–151 In Sjl Mice, Chandirasegara Massilamany, Sivasubramani Thulasingam, David Steffen, Jay Reddy
Jay Reddy Publications
Development of multiple sclerosis (MS) is more prevalent in females than in males, but the underlying mechanisms are not clear. Microbial infections have been suspected as triggers of MS and it is not known whether gender differences in reactivity to environmental antigens contribute to the disease pathogenesis. We demonstrated that ACA 83–95, a mimicry epitope from Acanthamoeba castellanii for proteolipid protein (PLP) 139–151, induces clinical signs of encephalomyelitis in both male and female SJL mice. Conversely ACA 83–95-induced effector cells from males fail to induce disease in female mice. Although we found no gender differences in the frequencies of antigen-specific …
Rnai Screening Reveals Requirement For Host Cell Secretory Pathway In Infection By Diverse Families Of Negative-Strand Rna Viruses, Debasis Panda, Anshuman Das, Phat X. Dinh, Sakthivel Subramaniam, Debasis Nayak, Nicholas J. Barrows, James L. Pearson, Jesse Thompson, David L. Kelly, Istvan Ladunga, Asit K. Pattnaik
Rnai Screening Reveals Requirement For Host Cell Secretory Pathway In Infection By Diverse Families Of Negative-Strand Rna Viruses, Debasis Panda, Anshuman Das, Phat X. Dinh, Sakthivel Subramaniam, Debasis Nayak, Nicholas J. Barrows, James L. Pearson, Jesse Thompson, David L. Kelly, Istvan Ladunga, Asit K. Pattnaik
School of Veterinary and Biomedical Sciences: Faculty Publications
Negative-strand (NS) RNA viruses comprise many pathogens that cause serious diseases in humans and animals. Despite their clinical importance, little is known about the host factors required for their infection. Using vesicular stomatitis virus (VSV), a prototypic NS RNA virus in the family Rhabdoviridae, we conducted a human genomewide siRNA screen and identified 72 host genes required for viral infection. Many of these identified genes were also required for infection by two other NS RNA viruses, the lymphocytic choriomeningitis virus of the Arenaviridae family and human parainfluenza virus type 3 of the Paramyxoviridae family. Genes affecting different stages of …
Consensus-Based Reporting Standards For Diagnostic Test Accuracy Studies For Paratuberculosis In Ruminants, Ian A. Gardner, Søren S. Nielsen, Richard J. Wittington, Michael T. Collins, Douwe Bakker, Beth Harris, Srinand Sreevatsan, Jason E. Lombard, Raymond Sweeney, David R. Smith, Jerrie Gavalchin, Shigetoshi Eda
Consensus-Based Reporting Standards For Diagnostic Test Accuracy Studies For Paratuberculosis In Ruminants, Ian A. Gardner, Søren S. Nielsen, Richard J. Wittington, Michael T. Collins, Douwe Bakker, Beth Harris, Srinand Sreevatsan, Jason E. Lombard, Raymond Sweeney, David R. Smith, Jerrie Gavalchin, Shigetoshi Eda
School of Veterinary and Biomedical Sciences: Faculty Publications
The Standards for Reporting of Diagnostic Accuracy (STARD) statement was developed to encourage complete and transparent reporting of key elements of test accuracy studies in human medicine. The statement was motivated by widespread evidence of bias in test accuracy studies and the finding that incomplete or absent reporting of items in the STARD checklist was associated with overly optimistic estimates of test performance characteristics. Although STARD principles apply broadly, specific guidelines do not exist to account for unique considerations in livestock studies such as herd tests, potential use of experimental challenge studies, a more diverse group of testing purposes and …
Genome-Wide Ribosome Profiling Reveals Complex Translational Regulation In Response To Oxidative Stress, Maxim V. Gerashchenko, Alexei V. Lobanov, Vadim N. Gladyshev
Genome-Wide Ribosome Profiling Reveals Complex Translational Regulation In Response To Oxidative Stress, Maxim V. Gerashchenko, Alexei V. Lobanov, Vadim N. Gladyshev
Department of Biochemistry: Faculty Publications
Information on unique and coordinated regulation of transcription and translation in response to stress is central to the understanding of cellular homeostasis. Here we used ribosome profiling coupled with next-generation sequencing to examine the interplay between transcription and translation under conditions of hydrogen peroxide treatment in Saccharomyces cerevisiae. Hydrogen peroxide treatment led to a massive and rapid increase in ribosome occupancy of short upstream ORFs, including those with non-AUG translational starts, and of the N-terminal regions of ORFs that preceded the transcriptional response. In addition, this treatment induced the synthesis of N-terminally extended proteins and elevated stop codon read-through …
Reduced Utilization Of Selenium By Naked Mole Rats Due To A Specific Defect In Gpx1 Expression, Marina V. Kasaikina, Alexei V. Lobanov, Mikalai I. Malinouski, Byung Cheon Lee, Javier Seravalli, Dmitri E. Fomenko, Anton A. Turanov, Lydia Finney, Stefan Vogt, Thomas J. Park, Richard A. Miller, Dolph L. Hatfield, Vadim N. Gladyshev
Reduced Utilization Of Selenium By Naked Mole Rats Due To A Specific Defect In Gpx1 Expression, Marina V. Kasaikina, Alexei V. Lobanov, Mikalai I. Malinouski, Byung Cheon Lee, Javier Seravalli, Dmitri E. Fomenko, Anton A. Turanov, Lydia Finney, Stefan Vogt, Thomas J. Park, Richard A. Miller, Dolph L. Hatfield, Vadim N. Gladyshev
Department of Biochemistry: Faculty Publications
Naked mole rat (MR) Heterocephalus glaber is a rodent model of delayed aging because of its unusually long life span (>28 years). It is also not known to develop cancer. In the current work, tissue imaging by x-ray fluorescence microscopy and direct analyses of trace elements revealed low levels of selenium in the MR liver and kidney, whereas MR and mouse brains had similar selenium levels. This effect was not explained by uniform selenium deficiency because methionine sulfoxide reductase activities were similar in mice and MR. However, glutathione peroxidase activity was an order of magnitude lower inMRliver and kidney …
A 4-Selenocysteine, 2-Selenocysteine Insertion Sequence (Secis) Element Methionine Sulfoxide Reductase From Metridium Senile Reveals A Non-Catalytic Function Of Selenocysteines, Byung Cheon Lee, Alexey V. Lobanov, Stefano M. Marino, Alaattin Kaya, Javier Seravalli, Dolph L. Hatfield, Vadim N. Gladyshev
A 4-Selenocysteine, 2-Selenocysteine Insertion Sequence (Secis) Element Methionine Sulfoxide Reductase From Metridium Senile Reveals A Non-Catalytic Function Of Selenocysteines, Byung Cheon Lee, Alexey V. Lobanov, Stefano M. Marino, Alaattin Kaya, Javier Seravalli, Dolph L. Hatfield, Vadim N. Gladyshev
Department of Biochemistry: Faculty Publications
Selenocysteine (Sec) residues occur in thiol oxidoreductase families, and functionally characterized selenoenzymes typically have a single Sec residue used directly for redox catalysis. However, how new Sec residues evolve and whether non-catalytic Sec residues exist in proteins is not known. Here, we computationally identified several genes with multiple Sec insertion sequence (SECIS) elements, one of which was a methionine-Rsulfoxide reductase (MsrB) homolog from Metridium senile that has four in-frame UGA codons and two nearly identical SECIS elements. One of the UGA codons corresponded to the conserved catalytic Sec or Cys in MsrBs, whereas the three other UGA codons evolved recently …
Escherichia Coli Thioredoxin-Like Protein Ybbn Contains An Atypical Tetratricopeptide Repeat Motif And Is A Negative Regulator Of Groel, Jiusheng Lin, Mark A. Wilson
Escherichia Coli Thioredoxin-Like Protein Ybbn Contains An Atypical Tetratricopeptide Repeat Motif And Is A Negative Regulator Of Groel, Jiusheng Lin, Mark A. Wilson
Department of Biochemistry: Faculty Publications
Many proteins contain a thioredoxin (Trx)-like domain fused with one or more partner domains that diversify protein function by the modular construction of new molecules. The Escherichia coli protein YbbN is a Trx-like protein that contains a C-terminal domain with low homology to tetratricopeptide repeat motifs. YbbN has been proposed to act as a chaperone or co-chaperone that aids in heat stress response andDNAsynthesis. We report the crystal structure of YbbN, which is an elongated molecule with a mobile Trx domain and four atypical tetratricopeptide repeat motifs. The Trx domain lacks a canonical CXXC active site architecture and is not …
Defining A Relationship Between Dietary Fatty Acids And The Cytochrome P450 System In A Mouse Model Of Fatty Liver Disease, Monika Gonzalez, Whitney Sealls, Elliot D. Jesch, M. Julia Brosnan, Istvan Ladunga, Xinxin Ding, Paul N. Black, Concetta C. Dirusso
Defining A Relationship Between Dietary Fatty Acids And The Cytochrome P450 System In A Mouse Model Of Fatty Liver Disease, Monika Gonzalez, Whitney Sealls, Elliot D. Jesch, M. Julia Brosnan, Istvan Ladunga, Xinxin Ding, Paul N. Black, Concetta C. Dirusso
Department of Biochemistry: Faculty Publications
Liver-specific ablation of cytochrome P450 reductase in mice (LCN) results in hepatic steatosis that can progress to steatohepatitis characterized by inflammation and fibrosis. The specific cause of the fatty liver phenotype is poorly understood but is hypothesized to result from elevated expression of genes encoding fatty acid synthetic genes. Since expression of these genes is known to be suppressed by polyunsaturated fatty acids, we performed physiological and genomics studies to evaluate the effects of dietary linoleic and linolenic fatty acids (PUFA) or arachidonic and decosahexaenoic acids (HUFA) on the hepatic phenotypes of control and LCN mice by comparison with a …
Functional Diversification Of Thylakoidal Processing Peptidases In Arabidopsis Thaliana, Shih-Chi Hsu, Joshua K. Endow, Nicholas J. Ruppel, Rebecca Roston, Amy J. Baldwin, Kentaro Inoue
Functional Diversification Of Thylakoidal Processing Peptidases In Arabidopsis Thaliana, Shih-Chi Hsu, Joshua K. Endow, Nicholas J. Ruppel, Rebecca Roston, Amy J. Baldwin, Kentaro Inoue
Department of Biochemistry: Faculty Publications
Thylakoidal processing peptidase (TPP) is responsible for removing amino-terminal thylakoid-transfer signals from several proteins in the thylakoid lumen. Three TPP isoforms are encoded by the nuclear genome of Arabidopsis thaliana. Previous studies showed that one of them termed plastidic type I signal peptidase 1 (Plsp1) was necessary for processing three thylakoidal proteins and one protein in the chloroplast envelope in vivo. The lack of Plsp1 resulted in seedling lethality, apparently due to disruption of proper thylakoid development. The physiological roles of the other two TPP homologs remain unknown. Here we show that the three A. thaliana TPP isoforms …
Enzymatic Defects Underlying Hereditary Glutamate Cysteine Ligase Deficiency Are Mitigated By Association Of The Catalytic And Regulatory Subunits, Melanie Neely Willis, Yilin Liu, Ekaterina I. Biterova, Melanie A. Simpson, Heejeong Kim, Jaekwon Lee, Joseph J. Barycki
Enzymatic Defects Underlying Hereditary Glutamate Cysteine Ligase Deficiency Are Mitigated By Association Of The Catalytic And Regulatory Subunits, Melanie Neely Willis, Yilin Liu, Ekaterina I. Biterova, Melanie A. Simpson, Heejeong Kim, Jaekwon Lee, Joseph J. Barycki
Department of Biochemistry: Faculty Publications
Glutamate cysteine ligase (GCL) deficiency is a rare autosomal recessive trait that compromises
production of glutathione, a critical redox buffer and enzymatic cofactor. Patients have markedly
reduced levels of erythrocyte glutathione, leading to hemolytic anemia and in some cases,
impaired neurological function. Human glutamate cysteine ligase is a heterodimer comprised of a
catalytic (GCLC) and a regulatory subunit (GCLM), which catalyzes the initial rate limiting step
in glutathione production. Four clinical missense mutations have been identified within GCLC:
Arg127Cys, Pro158Leu, His370Leu, and Pro414Leu. Here, we have evaluated the impacts of
these mutations on enzymatic function in vivo and in vitro …
The Lyr Protein Mzm1 Functions In The Insertion Of The Rieske Fe/S Protein In Yeast Mitochondria, Aaron Atkinson, Pamela Smith, Jennifer L. Fox, Tie-Shong Cui, Oleh Khalimonchuk, Dennis R. Winge
The Lyr Protein Mzm1 Functions In The Insertion Of The Rieske Fe/S Protein In Yeast Mitochondria, Aaron Atkinson, Pamela Smith, Jennifer L. Fox, Tie-Shong Cui, Oleh Khalimonchuk, Dennis R. Winge
Department of Biochemistry: Faculty Publications
The assembly of the cytochrome bc1 complex in Saccharomyces cerevisiae is shown to be conditionally dependent on a novel factor, Mzm1. Cells lacking Mzm1 exhibit a modest bc1 defect at 30°C, but the defect is exacerbated at elevated temperatures. Formation of bc1 is stalled in mzm1 Δ cells at a late assembly intermediate lacking the Rieske iron-sulfur protein Rip1. Rip1 levels are markedly attenuated in mzm1 Δ cells at elevated temperatures. Respiratory growth can be restored in the mutant cells by the overexpression of the Rip1 subunit. Elevated levels of Mzm1 enhance the stabilization of Rip1 through …
Rpir Homologues May Link Staphylococcus Aureus Rnaiii Synthesis And Pentose Phosphate Pathway Regulation, Yefei Zhu, Nandakumar Madayiputhiya, Marat R. Sadykov, Nandakumar Madayiputhiya, Thanh T. Luong, Rosmarie Gaupp, Chia Y. Lee, Greg Somerville
Rpir Homologues May Link Staphylococcus Aureus Rnaiii Synthesis And Pentose Phosphate Pathway Regulation, Yefei Zhu, Nandakumar Madayiputhiya, Marat R. Sadykov, Nandakumar Madayiputhiya, Thanh T. Luong, Rosmarie Gaupp, Chia Y. Lee, Greg Somerville
Department of Biochemistry: Faculty Publications
Staphylococcus aureus is a medically important pathogen that synthesizes a wide range of virulence determinants. The synthesis of many staphylococcal virulence determinants is regulated in part by stress-induced changes in the activity of the tricarboxylic acid (TCA) cycle. One metabolic change associated with TCA cycle stress is an increased concentration of ribose, leading us to hypothesize that a pentose phosphate pathway (PPP)-responsive regulator mediates some of the TCA cycle-dependent regulatory effects. Using bioinformatics, we identified three potential ribose-responsive regulators that belong to the RpiR family of transcriptional regulators. To determine whether these RpiR homologues affect PPP activity and virulence determinant …
In Vivo Liver Endocytosis Followed By Purification Of Liver Cells By Liver Perfusion, Sandhya Gopalakrishnan, Edward N. Harris
In Vivo Liver Endocytosis Followed By Purification Of Liver Cells By Liver Perfusion, Sandhya Gopalakrishnan, Edward N. Harris
Department of Biochemistry: Faculty Publications
The liver is the metabolic center of the mammalian body and serves as a filter for the blood. The basic architecture of the liver is illustrated in figure 1 in which more than 85% of the liver mass is composed of hepatocytes and the remaining 15% of the cellular mass is composed of Kupffer cells (KCs), stellate cells (HSCs), and sinusoidal endothelial cells (SECs). SECs form the blood vessel walls within the liver and contain specialized morphology called fenestrae within in the cytoplasm. Fenestration of the cytoplasm is the appearance of holes (˜100 μm) within the cells so that the …
Synthesis, Biochemical And Molecular Modelling Studies Of Antiproliferative Azetidinones Causing Microtubule Disruption And Mitotic Catastrophe, Niamh O'Boyle, Miriam Carr, Lisa M. Greene, Niall O. Keely, Andrew Js Knox, Thomas Mccabe, David G. Lloyd, Daniela M. Zisterer, Mary J. Meegan
Synthesis, Biochemical And Molecular Modelling Studies Of Antiproliferative Azetidinones Causing Microtubule Disruption And Mitotic Catastrophe, Niamh O'Boyle, Miriam Carr, Lisa M. Greene, Niall O. Keely, Andrew Js Knox, Thomas Mccabe, David G. Lloyd, Daniela M. Zisterer, Mary J. Meegan
Articles
The structure-activity relationships of antiproliferative β-lactams, focusing on modifications at the 4-position of the β-lactam ring, is described. Synthesis of this series of compounds was achieved utilizing the Staudinger and Reformatsky reactions. The antiproliferative activity was assessed in MCF-7 cells, where the 4-(4-ethoxy)phenyl substituted compound 26 displayed the most potent activity with an IC50 value of 0.22 μM. The mechanism of action was demonstrated to be by inhibition of tubulin. Cell exposure to combretastatin A-4 and 26 led to arrest of MCF-7 cells in the G2/M phase of the cell cycle and induction of apoptosis. Additionally, mitotic catastrophe for …
Lead Identification Of Β-Lactam And Related Imine Inhibitors Of The Molecular Caperone Heat Shock Protein 90, Niamh O'Boyle, Andrew Js Knox, Trevor P. Price, D. Clive Williams, Daniela M. Zisterer, David G. Lloyd, Mary J. Meegan
Lead Identification Of Β-Lactam And Related Imine Inhibitors Of The Molecular Caperone Heat Shock Protein 90, Niamh O'Boyle, Andrew Js Knox, Trevor P. Price, D. Clive Williams, Daniela M. Zisterer, David G. Lloyd, Mary J. Meegan
Articles
Heat shock protein 90 is an emerging target for oncology therapeutics. Inhibitors of this molecular chaperone, which is responsible for the maintenance of a number of oncogenic proteins, have shown promise in clinical trials and represent a new and exciting area in the treatment of cancer. Heat shock protein 90 inhibitors have huge structural diversity, and here we present the identification of inhibitors based on β-lactam and imine templates. β-Lactam 5 and imines 12 and 18 exhibit binding to heat shock protein 90-α with IC50 values of 5.6 μM, 14.5 μM and 22.1 μM respectively. The binding affinity displayed …
Glucosamine-Induced Insulin Resistance In Primary Rat Hepatocytes And The Role Of Selenium As An Insulin Mimetic, Sandhya N. Adiyodi Veetil
Glucosamine-Induced Insulin Resistance In Primary Rat Hepatocytes And The Role Of Selenium As An Insulin Mimetic, Sandhya N. Adiyodi Veetil
Dissertations
Type 2 diabetes is mediated by insulin resistance, the inability of insulin to elicit a normal biological response in insulin responsive tissues. Several cellular models have been utilized to determine the mechanism of induction of insulin resistance but questions remain unanswered. One model, implicates the products of the Hexosamine Biosynthetic Pathway (HBP) in the induction of insulin resistance under hyperglycemia. The major end product of HBP, UDP-GlcNAc, is the substrate for O-GlcNAc transferase, an enzyme that catalyzes the O-GlcNAcylation of numerous proteins. This modification may play a role in induction of insulin resistance and thus needs to be evaluated in …
Molecular, Cellular And Systemic Effects Of Atrazine On The Xenopus Laevis Tadpole, Renee Maryanne Zaya
Molecular, Cellular And Systemic Effects Of Atrazine On The Xenopus Laevis Tadpole, Renee Maryanne Zaya
Dissertations
Atrazine is one of the two most commonly used herbicides in the US and it is the most studies are among the first to link physiological effects of atrazine to changes in tissue and gene expression in Xenopus laevis tadpoles. These studies provide the groundwork for future studies into the mechanisms behind responses to chemical stressors generating data resulting in a better understanding of how these chemicals affect us all. commonly found herbicide in ground water. As a result, a great deal of attention has been placed on its use and safety. It has also been implicated to play a …
Conformation And Ion Transport Of Neuronal Uncoupling Proteins: Ucp2, Ucp4, And Ucp5, Tuan Hoang
Conformation And Ion Transport Of Neuronal Uncoupling Proteins: Ucp2, Ucp4, And Ucp5, Tuan Hoang
Theses and Dissertations (Comprehensive)
Located in the inner mitochondrial membrane of brown adipose tissue, uncoupling protein -1 (UCP1) dissipates the proton electrochemical gradient, causing reduction in the rate of ATP synthesis, and generates heat by non-shivering thermogenesis. Three other UCP homologs (UCP2, UCP4 and UCP5), expressed in neurons, are suggested to have potential roles in the function and protection of the central nervous system (CNS). Up to date, structural information for UCPs still remains limited. Extensive biochemical studies on UCP2 have provided adequate evidence for its participation in proton and anion transport. So far, no functional studies in proteoliposome systems have been performed on …
Novel Roles For The Transcriptional Repressor Prdm1 In Human Natural Killer Cells And Identification Of An Inhibitor Of Its Interacting Methyltransferase G9a, Matthew Adams Smith
Novel Roles For The Transcriptional Repressor Prdm1 In Human Natural Killer Cells And Identification Of An Inhibitor Of Its Interacting Methyltransferase G9a, Matthew Adams Smith
USF Tampa Graduate Theses and Dissertations
The studies presented within this dissertation provide the first description of PRDM1 (also known as Blimp-1 or PRDI-BF1) function in natural killer cells. NK cells are major effectors of the innate immune response via antigen-independent cytotoxicity and link to the adaptive immune response through cytokine release. Molecular mechanisms mediating NK activation are relatively well-studied; however, much less is known about the mechanisms that restrain activation.
In the first study, the transcriptional repressor PRDM1 is shown to be a critical negative regulator of NK function. Microarray analysis was used to characterize transcriptional changes associated with cytokine-mediated activation. PRDM1 is expressed at …
The Role Of Brca1 Domains And Motifs In Tumor Suppression, Aneliya Velkova
The Role Of Brca1 Domains And Motifs In Tumor Suppression, Aneliya Velkova
USF Tampa Graduate Theses and Dissertations
Individuals that carry deleterious mutations in the breast and ovarian cancer susceptibility gene 1 (BRCA1) have much more elevated risk to develop breast and/or ovarian cancer than the individuals from the general population. The BRCA1 gene product has been implicated in several aspects of the DNA damage response, but its biochemical function in these processes has remained elusive. In order to probe BRCA1 functions we conducted a yeast two-hybrid screening to identify interacting partners to a conserved motif (Motif 6) in the central region of BRCA1. In this dissertation, we report the identification of the actin-binding protein Filamin A (FLNA) …
Probing Molecules In Confined Space, Carissa Marie Vetromile
Probing Molecules In Confined Space, Carissa Marie Vetromile
USF Tampa Graduate Theses and Dissertations
Despite the plethora of information regarding cellular crowding and its importance on modulating protein function the effects of confinement on biological molecules are often overlooked when investigating their physiological function. Recently however, the encapsulation of biomolecules in solid state matrices (NafionTM, sol-gels, zirconium phosphate,etc.) has increased in importance as a method for examining protein conformation and dynamics in confined space as well as novel applications in biotechnology. Biotechnological applications include, but are not limited to, bioremediation, biosensors, biocatalysts, etc. In order to better utilize solid state materials as substrates for biological molecules an understanding of the effects of encapsulation on …
The Role Of Mdm2 In Estrogen-Mediated Breast Cancer Cell Proliferation, Angelika Brekman
The Role Of Mdm2 In Estrogen-Mediated Breast Cancer Cell Proliferation, Angelika Brekman
Dissertations, Theses, and Capstone Projects
Estrogen signaling is important in breast cancer development and progression. Mdm2, a negative regulator of the p53 tumor suppressor, is often over-expressed in estrogen receptor positive breast cancers. To study the role of Mdm2 in the estrogen-mediated breast cancer cell proliferation, we examined the effect of estrogen on the p53-Mdm2 pathway in estrogen receptor positive and p53 wild-type MCF-7 breast cancer cells. Estrogen-mediated increase in cell proliferation correlated with increased Mdm2, but no concomitant decrease in the p53 protein level. Blocking Mdm2 expression with inducible shRNA inhibited estrogen-mediated cell proliferation and colony formation in soft agar. Mdm2 knockdown in the …
Changes In Apparent Molar Water Volume And Dkp Solubility Yield Insights On The Hofmeister Effect, Daryl K. Eggers, A. Y. Payumo, R. M. Huijon, D. D. Mansfield, L. M. Belk, A. K. Bui, A. E. Knight
Changes In Apparent Molar Water Volume And Dkp Solubility Yield Insights On The Hofmeister Effect, Daryl K. Eggers, A. Y. Payumo, R. M. Huijon, D. D. Mansfield, L. M. Belk, A. K. Bui, A. E. Knight
Faculty Publications, Chemistry
This study examines the properties of a 4 × 2 matrix of aqueous cations and anions at concentrations up to 8.0 M. The apparent molar water volume, as calculated by subtracting the mass and volume of the ions from the corresponding solution density, was found to exceed the molar volume of ice in many concentrated electrolyte solutions, underscoring the nonideal behavior of these systems. The solvent properties of water were also analyzed by measuring the solubility of diketopiperazine (DKP) in 2.000 M salt solutions prepared from the same ion combinations. Solution rankings for DKP solubility were found to parallel the …
The Specific Role Of The Mll Cxxc Domain In Mll Fusion Protein Function, Laurie Ellen Risner
The Specific Role Of The Mll Cxxc Domain In Mll Fusion Protein Function, Laurie Ellen Risner
Dissertations
The MLL gene was first identified because it is involved in chromosome translocations which produce novel fusion proteins that cause leukemia. The CXXC domain of MLL is a cysteine rich DNA binding domain with specificity for binding unmethylated CpG-containing DNA. The CXXC domain is retained in oncogenic MLL fusions, and is absolutely required for the fusions to cause leukemia. This project explored the role of the CXXC domain by introducing structure-informed point mutations within the MLL CXXC domain that disrupt DNA binding, and by performing domain swap experiments in which different CXXC domains from other proteins, including DNMT1, CGBP and …
Role Of Non-Coding Rna Nc4 In Mll And Cyp33 Mediated Regulation Of Hoxc8, Jessica Arvindbhai Solanki
Role Of Non-Coding Rna Nc4 In Mll And Cyp33 Mediated Regulation Of Hoxc8, Jessica Arvindbhai Solanki
Dissertations
MLL or Mixed Lineage Leukemia gene is clinically known for its involvement in genetic translocation with more than 70 different partners identified each giving rise to a highly leukemogenic fusion protein. With a poor prognosis of MLL related leukemia, an investigation into its role during hematopoiesis has been a very active field of research. In order to design strategies to combat the MLL leukemia, it becomes essential to delineate the molecular mechanisms behind the function of MLL wild type protein. Wild type MLL is a transcriptional maintenance protein from the Trithorax Group (TrxG) that resides in complex with other chromatin …
Wee1 Is A Biological Target Of The Mir-17-92 Cluster In Leukemia, Sonia Susan Olikara
Wee1 Is A Biological Target Of The Mir-17-92 Cluster In Leukemia, Sonia Susan Olikara
Master's Theses
MicroRNAs are noncoding RNAs that bind to the 3' untranslated region of their mRNA targets, which causes downregulation of target gene expression. Previous studies have shown that the miR-17-92 cluster, which encodes six miRNAs, is overexpressed in leukemias arising from chromosomal translocations of the Mixed Lineage Leukemia (MLL) gene. In the present study, prediction algorithms identified WEE1, a kinase that inhibits cell cycle progression, as a possible target of five of the six miRNAs. Through luciferase reporter assays, we found that miR-17, miR-20a, and miR-18a specifically target nucleotides 465 to 487 of the 3' UTR of WEE1, while miR-19a and …
Notch-1 Specifically Activates Erk1/2 In Multiple Breast Cancer Subtypes, Allison Schuyler Rogowski
Notch-1 Specifically Activates Erk1/2 In Multiple Breast Cancer Subtypes, Allison Schuyler Rogowski
Master's Theses
Notch-1 is a cell fate regulatory protein and a potent breast oncogene. Notch-1 and its ligand Jagged-1 are over-expressed in human breast cancers that are associated with poor overall survival (Reedijk, Odorcic et al. 2005). Deregulated Notch signaling may contribute to tumorigenesis by increasing proliferation, inhibiting differentiation, and preventing apoptosis (Miele, Golde et al. 2006). The mitogen-activated protein kinase (MAPK) pathway is a critical cell signaling pathway that has been implicated in the development and progression of cancer (Hanahan and Weinberg 2000). Four major MAPK pathways are involved in both cell growth and apoptosis. The regulation of these pathways is …
A Study On The Biochemical And Cellular Effects Of Enviormental Tobacco Smoke On Adult And Developing Rat Brain Biochemistry, Brian Fuller
A Study On The Biochemical And Cellular Effects Of Enviormental Tobacco Smoke On Adult And Developing Rat Brain Biochemistry, Brian Fuller
Theses and Dissertations
Exposure to environmental tobacco smoke (ETS) has been recognized as a significant health risk for adults and children. In adults, ETS exposure has been linked to increased incidences of cardiovascular disease and dementia. In children, exposure has been linked to behavioral and cognitive deficits. Studies on the effects of ETS in the brain have been largely epidemiological, and have lacked a defined explanation of the molecular/biochemical effects of ETS. The present dissertation aims to test whether ETS exposure leads to altered biochemistry in the adult and developing mammalian brain. A rat ETS exposure model was employed to investigate changes at …
Synthesis, Linda H. Pardo, Linda H. Geiser, Mark E. Fenn, Charles T. Driscoll, Christine L. Goodale, Edith B. Allen, Jill S. Baron, Roland Bobbink, William D. Bowman, Christopher M. Clark, Bridget Emmett, Frank S. Gilliam, Tara Greaver, Sharon J. Hall, Erik A. Lilleskov, Lingli Liu, Jason A. Lynch, Knute Nadelhoffer, Steven S. Perakis, Molly J. Robin-Abbott, John L. Stoddard, Kathleen C. Weathers
Synthesis, Linda H. Pardo, Linda H. Geiser, Mark E. Fenn, Charles T. Driscoll, Christine L. Goodale, Edith B. Allen, Jill S. Baron, Roland Bobbink, William D. Bowman, Christopher M. Clark, Bridget Emmett, Frank S. Gilliam, Tara Greaver, Sharon J. Hall, Erik A. Lilleskov, Lingli Liu, Jason A. Lynch, Knute Nadelhoffer, Steven S. Perakis, Molly J. Robin-Abbott, John L. Stoddard, Kathleen C. Weathers
Biological Sciences Faculty Research
Human activity in the last century has led to a substantial increase in nitrogen (N) emissions and deposition. This N deposition has reached a level that has caused or is likely to cause alterations to the structure and function of many ecosystems across the United States. One approach for quantifying the level of pollution that would be harmful to ecosystems is the critical loads approach. The critical load is dei ned as the level of a pollutant below which no detrimental ecological effect occurs over the long term according to present knowledge.
The objective of this project was to synthesize …