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Iron Acquisition Strategies Employed By Staphylococcus Lugdunensis, Jeremy R. Brozyna 2016 The University of Western Ontario

Iron Acquisition Strategies Employed By Staphylococcus Lugdunensis, Jeremy R. Brozyna

Electronic Thesis and Dissertation Repository

Iron is crucial for many cellular processes including DNA synthesis and respiration. The majority of iron in mammals is in heme within hemoproteins, inside cells, or transported through circulation by the glycoprotein transferrin, which constitutes the greatest iron source in serum. Limiting iron availability is an important facet of nutritional immunity to help prevent infection.

Staphylococcus lugdunensis is a human skin commensal and opportunistic pathogen capable of causing a variety of infections, including particularly aggressive endocarditis. It is an emerging pathogen with elevated virulence compared to other species of coagulase-negative staphylococci. The versatility of S. lugdunensis to infect multiple niches ...


Modeling And Analysis Of Germ Layer Formations Using Finite Dynamical Systems, Alexander Garza, Megan Eberle, Eric A. Eager 2016 University of Wisconsin-La Crosse

Modeling And Analysis Of Germ Layer Formations Using Finite Dynamical Systems, Alexander Garza, Megan Eberle, Eric A. Eager

Spora: A Journal of Biomathematics

The development of an embryo from a fertilised egg to a multicellular organism proceeds through numerous steps, with the formation of the three germ layers (endoderm, mesoderm, ectoderm) being one of the first. In this paper we study the mesendoderm (the tissue that collectively gives rise to both mesoderm and endoderm) gene regulatory network for two species, \textit{Xenopus laevis} and the axolotl (\textit{Ambystoma mexicanum}) using Boolean networks. We find that previously-established bistability found in these networks can be reproduced using this Boolean framework, provided that some assumptions used in previously-published differential equations models are relaxed. We conclude by ...


Cal And Magi Pdz Protein Regulation Of Crfr1 And 5-Ht2ar Trafficking And Signaling, Maha Mahmoud Hammad 2016 The University of Western Ontario

Cal And Magi Pdz Protein Regulation Of Crfr1 And 5-Ht2ar Trafficking And Signaling, Maha Mahmoud Hammad

Electronic Thesis and Dissertation Repository

PDZ (PSD95/Disc Large/Zona Occludens) domain-containing proteins are scaffolding proteins that play important roles in regulating the activity of G protein-coupled receptors. Corticotropin Releasing Factor Receptor 1 (CRFR1) and Serotonin 2A Receptor (5-HT2AR) are two GPCRs that are commonly associated with mental disorders. Both receptors also contain a class I PDZ-binding motif at the carboxyl terminal tail. In the first chapter, we investigate the effects of CAL (CFTR-associated ligand) on regulating the trafficking and signaling of CRFR1. We demonstrate a role for CAL in inhibiting CRFR1 endocytosis, cell surface expression, and CRF-mediated ERK1/2 signaling via the ...


P-Rex1 Promotes Resistance To Vegf/Vegfr-Targeted Therapy In Prostate Cancer, Hira Lal Goel, Bryan M. Pursell, Leonard D. Shultz, Dale L. Greiner, Rolf A. Brekken, Craig W. Vander Kooi, Arthur M. Mercurio 2016 University of Massachusetts Medical School

P-Rex1 Promotes Resistance To Vegf/Vegfr-Targeted Therapy In Prostate Cancer, Hira Lal Goel, Bryan M. Pursell, Leonard D. Shultz, Dale L. Greiner, Rolf A. Brekken, Craig W. Vander Kooi, Arthur M. Mercurio

Arthur M. Mercurio

Autocrine VEGF signaling is critical for sustaining prostate and other cancer stem cells (CSCs), and it is a potential therapeutic target, but we observed that CSCs isolated from prostate tumors are resistant to anti-VEGF (bevacizumab) and anti-VEGFR (sunitinib) therapy. Intriguingly, resistance is mediated by VEGF/neuropilin signaling, which is not inhibited by bevacizumab and sunitinib, and it involves the induction of P-Rex1, a Rac GEF, and consequent Rac1-mediated ERK activation. This induction of P-Rex1 is dependent on Myc. CSCs isolated from the PTEN(pc-/-) transgenic model of prostate cancer exhibit Rac1-dependent resistance to bevacizumab. Rac1 inhibition or P-Rex1 downregulation increases ...


Investigating The Roles Of Δnp63 As A Suppressor Of Migration, Invasion, And Metastasis, Ramon E. Flores Gonzalez 2016 The University of Texas Graduate School of Biomedical Sciences at Houston

Investigating The Roles Of Δnp63 As A Suppressor Of Migration, Invasion, And Metastasis, Ramon E. Flores Gonzalez

UT GSBS Dissertations and Theses (Open Access)

Cancer is one of the leading causes of death and disease in the world. Considerable resources are spent to study and understand cancer, with the hope of developing new treatments and eventually cures that will help millions of people. Efforts to understand cancer are hindered by its inherent complexity and instability. Nonetheless, understanding the basics of tumor development and progression are the key to focused on studying the role of ΔNp63 in cancer, a p53 family member known to be involved in epithelial development, microRNA biogenesis, and stem cell maintenance. Using the strength of in vivo mouse models, we found ...


Inhibition Of Nuclear Factor-Kappa B Enhances The Tumor Growth Of Ovarian Cancer Cell Line Derived From A Low-Grade Papillary Serous Carcinoma In P53-Independent Pathway, Xue Xiao, Gong Yang, Peng Bai, Shunping Gui, Tri M. Bui Nguyen, +8 additional authors 2016 George Washington University

Inhibition Of Nuclear Factor-Kappa B Enhances The Tumor Growth Of Ovarian Cancer Cell Line Derived From A Low-Grade Papillary Serous Carcinoma In P53-Independent Pathway, Xue Xiao, Gong Yang, Peng Bai, Shunping Gui, Tri M. Bui Nguyen, +8 Additional Authors

Biochemistry and Molecular Medicine Faculty Publications

Background: NF-kB can function as an oncogene or tumor suppressor depending on cancer types. The role of NF-kB in low-grade serous ovarian cancer, however, has never been tested. We sought to elucidate the function of NF-kB in the low-grade serous ovarian cancer.

Methods: The ovarian cancer cell line, HOC-7, derived from a low-grade papillary serous carcinoma. Introduction of a dominant negative mutant, IkBαM, which resulted in decrease of NF-kB function in ovarian cancer cell lines. The transcription ability, tumorigenesis, cell proliferation and apoptosis were observed in derivative cell lines in comparison with parental cells.

Results: Western blot analysis indicated increased ...


Protein Kinase Mitogen-Activated Protein Kinase Kinase Kinase Kinase 4 (Map4k4) Promotes Obesity-Induced Hyperinsulinemia, Rachel J. Roth Flach, Laura V. Danai, Marina DiStefano, Mark Kelly, Lorena Garcia Menendez, Agata Jurczyk, Rohit B. Sharma, Dae Young Jung, Jong Hun Kim, Jason K. Kim, Rita Bortell, Laura C. Alonso, Michael P. Czech 2016 University of Massachusetts Medical School

Protein Kinase Mitogen-Activated Protein Kinase Kinase Kinase Kinase 4 (Map4k4) Promotes Obesity-Induced Hyperinsulinemia, Rachel J. Roth Flach, Laura V. Danai, Marina Distefano, Mark Kelly, Lorena Garcia Menendez, Agata Jurczyk, Rohit B. Sharma, Dae Young Jung, Jong Hun Kim, Jason K. Kim, Rita Bortell, Laura C. Alonso, Michael P. Czech

Open Access Articles

Previous studies revealed a paradox whereby mitogen-activated protein kinase kinase kinase kinase 4 (Map4k4) acted as a negative regulator of insulin sensitivity in chronically obese mice, yet systemic deletion of Map4k4 did not improve glucose tolerance. Here, we report markedly reduced glucose-responsive plasma insulin and C-peptide levels in whole body Map4k4-depleted mice (M4K4 iKO) as well as an impaired first phase of insulin secretion from islets derived from M4K4 iKO mice ex vivo After long-term high fat diet (HFD), M4K4 iKO mice pancreata also displayed reduced beta cell mass, fewer proliferating beta cells and reduced islet-specific gene mRNA expression compared ...


Cell And Molecular Biology : What We Know & How We Found Out (Second Edition, Sample Chapter), Gerald Bergtrom 2016 University of Wisconsin - Milwaukee

Cell And Molecular Biology : What We Know & How We Found Out (Second Edition, Sample Chapter), Gerald Bergtrom

Cell and Molecular Biology 2e i-Text

No abstract provided.


Cell And Molecular Biology : What We Know & How We Found It (Second Edition, An Annotated Itext), Gerald Bergtrom 2016 University of Wisconsin - Milwaukee

Cell And Molecular Biology : What We Know & How We Found It (Second Edition, An Annotated Itext), Gerald Bergtrom

Cell and Molecular Biology 2e i-Text

No abstract provided.


Beta1 Integrin- And Jnk-Dependent Tumor Growth Upon Hypofractionated Radiation, Aejaz Sayeed, Huimin Lu, Qin Liu, David Deming Ii, Alexander Duffy, Peter McCue, Adam P. Dicker, Roger J. Davis, Dmitry Gabrilovich, Ulrich Rodeck, Dario C. Altieri, Lucia R. Languino 2016 Thomas Jefferson University

Beta1 Integrin- And Jnk-Dependent Tumor Growth Upon Hypofractionated Radiation, Aejaz Sayeed, Huimin Lu, Qin Liu, David Deming Ii, Alexander Duffy, Peter Mccue, Adam P. Dicker, Roger J. Davis, Dmitry Gabrilovich, Ulrich Rodeck, Dario C. Altieri, Lucia R. Languino

Open Access Articles

Radiation therapy is an effective cancer treatment modality although tumors invariably become resistant. Using the transgenic adenocarcinoma of mouse prostate (TRAMP) model system, we report that a hypofractionated radiation schedule (10 Gy/day for 5 consecutive days) effectively blocks prostate tumor growth in wild type (beta1wt /TRAMP) mice as well as in mice carrying a conditional ablation of beta1 integrins in the prostatic epithelium (beta1pc-/- /TRAMP). Since JNK is known to be suppressed by beta1 integrins and mediates radiation-induced apoptosis, we tested the effect of SP600125, an inhibitor of c-Jun amino-terminal kinase (JNK) in the TRAMP model system. Our results ...


Computational Modeling Of Allosteric Stimulation Of Nipah Virus Host Binding Protein, Priyanka Dutta 2016 University of South Florida

Computational Modeling Of Allosteric Stimulation Of Nipah Virus Host Binding Protein, Priyanka Dutta

Graduate Theses and Dissertations

Nipah belongs to the family of paramyxoviruses that cause numerous fatal diseases in humans and farm animals. There are no FDA approved drugs for Nipah or any of the paramyxoviruses. Designing antiviral therapies that are more resistant to viral mutations require understanding of molecular details underlying infection. This dissertation focuses on obtaining molecular insights into the very first step of infection by Nipah. Such details, in fact, remain unknown for all paramyxoviruses. Infection begins with the allosteric stimulation of Nipah virus host binding protein by host cell receptors. Understanding molecular details of this stimulation process have been challenging mainly because ...


Trimethylated Lysine 4 At Histone 3 Shows The Same Circadian Rhythm At Promoters Of Diversely-Expressed Genes In Chlamydomonas Reinhardtii, Robyn M. Wilson 2016 Western Kentucky University

Trimethylated Lysine 4 At Histone 3 Shows The Same Circadian Rhythm At Promoters Of Diversely-Expressed Genes In Chlamydomonas Reinhardtii, Robyn M. Wilson

Masters Theses & Specialist Projects

Circadian clocks are biochemical mechanisms that allow eukaryotic and some prokaryotic organisms to coordinate their physiology with daily environmental changes. It enables organisms to increase their fitness by taking advantage of beneficial environmental conditions while also avoiding or restricting certain sensitive processes during harsh conditions. Similarly, post-translational histone modifications allow eukaryotic organisms to regulate gene expression in response to environmental or developmental factors. Some post-translational modifications of histones are associated with active transcription while others are associated with repressed transcription depending upon the location, type and degree of modification. Trimethylation of lysine 4 on the N-terminal tail of histone H3 ...


Multiplexed Detection Of Double-Stranded Pathogenic Dna With Engineered Zinc Finger Proteins, Juhwa Kim 2016 Western Kentucky University

Multiplexed Detection Of Double-Stranded Pathogenic Dna With Engineered Zinc Finger Proteins, Juhwa Kim

Masters Theses & Specialist Projects

The development of a new technology for the detection of doublestranded (ds) DNA enables multiple biomedical applications including identifying multiple pathogens simultaneously. We previously employed colorimetric SEquence-Enabled Reassembly with TEM-1 β-lacatamase (SEER-LAC) to detect specific bacterial DNA sequence. SEER-Lac consists of the two inactive β-lactamase fragments which of each attached to a zinc finger protein (ZFP) would reassemble into an active full-length enzyme upon ZFPs binding to its target DNA. Here, we engineered two pairs of ZFPs which of each recognizes shiga toxin in E. coli O157 and staphylococcal enterotoxin B in Staphylococus Aureus, respectively. Biotin was simply conjugated to ...


Bauer Ketones 23 And 24 From Echinacea Paradoxa Var. Paradoxa Inhibit Lipopolysaccharide-Induced Nitric Oxide, Prostaglandin E2 And Cytokines In Raw264.7 Mouse Macrophages, Xiaozhu Zhang, Ludmila Rizshsky, Catherine C. Hauck, Luping Qu, Mark P. Widrlechner, Basil J. Nikolau, Patricia A. Murphy, Diane F. Birt 2016 Iowa State University

Bauer Ketones 23 And 24 From Echinacea Paradoxa Var. Paradoxa Inhibit Lipopolysaccharide-Induced Nitric Oxide, Prostaglandin E2 And Cytokines In Raw264.7 Mouse Macrophages, Xiaozhu Zhang, Ludmila Rizshsky, Catherine C. Hauck, Luping Qu, Mark P. Widrlechner, Basil J. Nikolau, Patricia A. Murphy, Diane F. Birt

Basil Nikolau

Among the nine Echinacea species, E. purpurea, E. angustifolia and E. pallida, have been widely used to treat the common cold, flu and other infections. In this study, ethanol extracts of these three Echinaceaspecies and E. paradoxa, including its typical variety, E. paradoxa var. paradoxa, were screened in lipopolysaccharide (LPS)-stimulated macrophage cells to assess potential anti-inflammatory activity. E. paradoxa var. paradoxa, rich in polyenes/polyacetylenes, was an especially efficient inhibitor of LPS-induced production of nitric oxide (NO), prostaglandin E2 (PGE2), interleukin-1 beta (IL-1β) and interleukin-6 (IL-6) by 46%, 32%, 53% and 26%, respectively, when tested at 20 μg ...


Inhibition Of Lentivirus Replication By Aqueous Extracts Of Prunella Vulgaris, Melinda A. Brindley, Mark P. Widrlechner, Joe-Ann McCoy, Patricia A. Murphy, Catherine C. Hauck, Ludmila Rizshsky, Basil J. Nikolau, Wendy Maury 2016 University of Iowa

Inhibition Of Lentivirus Replication By Aqueous Extracts Of Prunella Vulgaris, Melinda A. Brindley, Mark P. Widrlechner, Joe-Ann Mccoy, Patricia A. Murphy, Catherine C. Hauck, Ludmila Rizshsky, Basil J. Nikolau, Wendy Maury

Basil Nikolau

Background
Various members of the mint family have been used historically in Chinese and Native American medicine. Many of these same family members, including Prunella vulgaris, have been reported to have anti-viral activities. To further characterize the anti-lentiviral activities of P. vulgaris, water and ethanol extractions were tested for their ability to inhibit equine infectious anemia virus (EIAV) replication.

Results
Aqueous extracts contained more anti-viral activity than did ethanol extracts, displaying potent anti-lentiviral activity against virus in cell lines as well as in primary cell cultures with little to no cellular cytotoxicity. Time-of-addition studies demonstrated that the extracts were effective ...


Identification Of Light-Independent Inhibition Of Human Immunodeficiency Virus-1 Infection Through Bioguided Fractionation Of Hypericum Perforatum, Wendy Maury, Jason P. Price, Melinda A. Brindley, ChoonSeok Oh, Jeffrey D. Neighbors, David F. Wiemer, Nickolas Wills, Susan L. Carpenter, Catherine C. Hauck, Patricia A. Murphy, Mark P. Widrlechner, Kathleen Delate, Ganesh Kumar, George A. Kraus, Ludmila Rizshsky, Basil J. Nikolau 2016 University of Iowa

Identification Of Light-Independent Inhibition Of Human Immunodeficiency Virus-1 Infection Through Bioguided Fractionation Of Hypericum Perforatum, Wendy Maury, Jason P. Price, Melinda A. Brindley, Choonseok Oh, Jeffrey D. Neighbors, David F. Wiemer, Nickolas Wills, Susan L. Carpenter, Catherine C. Hauck, Patricia A. Murphy, Mark P. Widrlechner, Kathleen Delate, Ganesh Kumar, George A. Kraus, Ludmila Rizshsky, Basil J. Nikolau

Basil Nikolau

Background
Light-dependent activities against enveloped viruses in St. John's Wort (Hypericum perforatum) extracts have been extensively studied. In contrast, light-independent antiviral activity from this species has not been investigated.

Results
Here, we identify the light-independent inhibition of human immunodeficiency virus-1 (HIV-1) by highly purified fractions of chloroform extracts of H. perforatum. Both cytotoxicity and antiviral activity were evident in initial chloroform extracts, but bioassay-guided fractionation produced fractions that inhibited HIV-1 with little to no cytotoxicity. Separation of these two biological activities has not been reported for constituents responsible for the light-dependent antiviral activities. Antiviral activity was associated with more ...


The Role Of Pyruvate Dehydrogenase And Acetyl-Coenzyme A Synthetase In Fatty Acid Synthesis In Developing Arabidopsis Seeds, Jinshan Ke, Robert H. Behal, Stephanie L. Back, Basil J. Nikolau, Eve S. Wurtele, David J. Oliver 2016 Iowa State University

The Role Of Pyruvate Dehydrogenase And Acetyl-Coenzyme A Synthetase In Fatty Acid Synthesis In Developing Arabidopsis Seeds, Jinshan Ke, Robert H. Behal, Stephanie L. Back, Basil J. Nikolau, Eve S. Wurtele, David J. Oliver

Basil Nikolau

Acetyl-coenzyme A (acetyl-CoA) formed within the plastid is the precursor for the biosynthesis of fatty acids and, through them, a range of important biomolecules. The source of acetyl-CoA in the plastid is not known, but two enzymes are thought to be involved: acetyl-CoA synthetase and plastidic pyruvate dehydrogenase. To determine the importance of these two enzymes in synthesizing acetyl-CoA during lipid accumulation in developing Arabidopsis seeds, we isolated cDNA clones for acetyl-CoA synthetase and for the ptE1α- and ptE1β-subunits of plastidic pyruvate dehydrogenase. To our knowledge, this is the first reported acetyl-CoA synthetase sequence from a plant source. The Arabidopsis ...


Somatostatin Receptors Signal Through Efa6a-Arf6 To Activate Phospholipase D In Clonal Β-Cells, Justin A. Grodnitzky, Nasser Syed, Michael J. Kimber, Tim A. Day, Julie G. Donaldson, Walter H. Hsu 2016 Iowa State University

Somatostatin Receptors Signal Through Efa6a-Arf6 To Activate Phospholipase D In Clonal Β-Cells, Justin A. Grodnitzky, Nasser Syed, Michael J. Kimber, Tim A. Day, Julie G. Donaldson, Walter H. Hsu

Michael J. Kimber

Somatostatin (SS) is a peptide hormone that inhibits insulin secretion in β-cells by activating its Gi/o-coupled receptors. Our previous work indicated that a βγ-dimer of Gi/o coupled to SS receptors can activate phospholipase D1 (PLD1) (Cheng, H., Grodnitzky, J. A., Yibchok-anun, S., Ding, J., and Hsu, W. H. (2005) Mol. Pharmacol. 67, 2162–2172). The aim of the present study was to elucidate the mechanisms underlying SS-induced PLD activation. We demonstrated the presence of ADP-ribosylation factor Arf1 and Arf6 in clonal β-cells, HIT-T15. We also determined that the activation of PLD1 was mediated through Arf6 ...


Functional Characterization Of Recombinant Interleukin (Il)-17a/F1 In The Japanese Pufferfish (Takifugu Rubripes), Jun-ichi Hikima Dr., Koshin Mihara, Shun Maekawa, Han-Ching Wang, Takashi Aoki, Tomoya Kono, Masahiro Sakai 2016 University of Miyazaki, Faculty of Agriculture

Functional Characterization Of Recombinant Interleukin (Il)-17a/F1 In The Japanese Pufferfish (Takifugu Rubripes), Jun-Ichi Hikima Dr., Koshin Mihara, Shun Maekawa, Han-Ching Wang, Takashi Aoki, Tomoya Kono, Masahiro Sakai

2nd International Conference of Fish & Shellfish Immunology

No abstract provided.


Intrinsic Disorder Where You Least Expect It: The Incidence And Functional Relevance Of Intrinsic Disorder In Enzymes And The Protein Data Bank, Shelly Deforte 2016 University of South Florida

Intrinsic Disorder Where You Least Expect It: The Incidence And Functional Relevance Of Intrinsic Disorder In Enzymes And The Protein Data Bank, Shelly Deforte

Graduate Theses and Dissertations

Intrinsically disordered proteins (IDPs) and intrinsically disordered protein regions (IDPRs) exist as interconverting conformational ensembles, without a single fixed three-dimensional structure in vivo. The focus in the literature up to this point has been primarily on IDPs that are mostly or entirely disordered. Therefore, we have an incomplete understanding of the incidence and functional relevance of IDPRs in proteins that have regions of both order and disorder. This work explores these populations, by examining IDPRs in the Protein Data Bank (PDB) and in enzymes. By applying disorder prediction methods combined with an analysis of missing regions in crystal structure data ...


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