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Articles 181 - 198 of 198

Full-Text Articles in Medical Molecular Biology

Carhsp1 Is Required For Effective Tumor Necrosis Factor Alpha Mrna Stabilization And Localizes To Processing Bodies And Exosomes, Jason R. Pfeiffer, Bethany L. Mcavoy, Ryan E. Fecteau, Kristen M. Deleault, Seth A. Brooks Nov 2010

Carhsp1 Is Required For Effective Tumor Necrosis Factor Alpha Mrna Stabilization And Localizes To Processing Bodies And Exosomes, Jason R. Pfeiffer, Bethany L. Mcavoy, Ryan E. Fecteau, Kristen M. Deleault, Seth A. Brooks

Dartmouth Scholarship

Tumor necrosis factor alpha (TNF-α) is a critical mediator of inflammation, and its production is tightly regulated, with control points operating at nearly every step of its biosynthesis. We sought to identify uncharacterized TNF-α 3' untranslated region (3'UTR)-interacting proteins utilizing a novel screen, termed the RNA capture assay. We identified CARHSP1, a cold-shock domain-containing protein. Knockdown of CARHSP1 inhibits TNF-α protein production in lipopolysaccharide (LPS)-stimulated cells and reduces the level of TNF-α mRNA in both resting and LPS-stimulated cells. mRNA stability assays demonstrate that CARHSP1 knockdown decreases TNF-α mRNA stability from a half-life (t(1/2)) of 49 min to a t(1/2) …

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Molecular And Therapeutic Implications Of Notch1 Signaling In Pediatric T-Cell Acute Lymphoblastic Leukemia, Amanda Larson Gedman Jan 2010

Molecular And Therapeutic Implications Of Notch1 Signaling In Pediatric T-Cell Acute Lymphoblastic Leukemia, Amanda Larson Gedman

Wayne State University Dissertations

T-cell acute lymphoblastic leukemia (T-ALL) accounts for 15% of pediatric ALL cases and is associated with early relapse and inferior outcome. The poorer prognosis of T-ALL compared to B-precursor ALL may in part reflect the lack of unique features on which to base therapy. NOTCH1 mutations are of particular interest since these were reported in 37-71% of T-ALLs. The prognostic value of NOTCH1 mutations remains controversial as both favorable and unfavorable associations were reported, whereas in other studies, there were no associations between NOTCH1 mutations and treatment outcome. We explored the impact of mutations in NOTCH1, FBW7 and PTEN on …

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Imaging Spontaneous Mmtvneu Transgenic Murine Mammary Tumors: Targeting Metabolic Activity Versus Genetic Products., Mathew L Thakur, Devakumar Devadhas, Kaijun Zhang, Richard G Pestell, Chenguang Wang, Peter Mccue, Eric Wickstrom Jan 2010

Imaging Spontaneous Mmtvneu Transgenic Murine Mammary Tumors: Targeting Metabolic Activity Versus Genetic Products., Mathew L Thakur, Devakumar Devadhas, Kaijun Zhang, Richard G Pestell, Chenguang Wang, Peter Mccue, Eric Wickstrom

Department of Radiology Faculty Papers

INTRODUCTION: Despite the great strides made in imaging breast cancer (BC) in humans, the current imaging modalities miss up to 30% of BC, do not distinguish malignant lesions from benign ones, and require histologic examinations for which invasive biopsy must be performed. Annually in the United States, approximately 5.6 million biopsies find benign lesions. More than 50% of human BCs overexpress cyclin D1, and all BCs exhibit VPAC1 oncogene products. Together, these gene products may provide an excellent biomarker for the early and accurate detection of BC. We have evaluated 4 biologically active peptide analogs that have high affinity for …

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Molecular Mechanism Of Tetraspanin Cd9 Mediated Cell Motility, Jayaprakash Kotha May 2007

Molecular Mechanism Of Tetraspanin Cd9 Mediated Cell Motility, Jayaprakash Kotha

Theses and Dissertations (ETD)

CD9, a member of the tetraspanin superfamily of proteins participates in the regulation of cell adhesive functions such as cell migration. The mechanisms underlying CD9 mediated cell migration are not known. In the current study, we investigated the molecular basis for the CD9 promoted cell migration. Our findings show that the phosphatidylinositol-3 kinase (PI-3K) inhibitors, wortamannin and LY294002 inhibited CD9 promoted cell motility in Chinese hamster ovary (CHO) cells. In contrast, inhibitors targeting protein kinase C or mitogen-activated protein kinase had no effect on CD9 driven CHO cell motility. Furthermore, inhibition of PI-3K activity in CHO cells by dominant/negative PI-3K …

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Cpg Hypomethylation In A Large Domain Encompassing The Embryonic Β-Like Globin Genes In Primitive Erythrocytes, Mei Hsu, Rodwell R. Mabaera, Christopher H. Lowrey, David I. K. Martin, Steven Fiering Apr 2007

Cpg Hypomethylation In A Large Domain Encompassing The Embryonic Β-Like Globin Genes In Primitive Erythrocytes, Mei Hsu, Rodwell R. Mabaera, Christopher H. Lowrey, David I. K. Martin, Steven Fiering

Dartmouth Scholarship

There is little evidence addressing the role of CpG methylation in transcriptional control of genes that do not contain CpG islands. This is reflected in the ongoing debate about whether CpG methylation merely suppresses retroelements or if it also plays a role in developmental and tissue-specific gene regulation. The genes of the β-globin locus are an important model of mammalian developmental gene regulation and do not contain CpG islands. We have analyzed the methylation status of regions in the murine β-like globin locus in uncultured primitive and definitive erythroblasts and other cultured primary and transformed cell types. A large (∼20-kb) …

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Binding Of Internalized Receptors To The Pdz Domain Of Gipc/Synectin Recruits Myosin Vi To Endocytic Vesicles, Samia N. Naccache, Tama Hasson, Arie Horowitz Aug 2006

Binding Of Internalized Receptors To The Pdz Domain Of Gipc/Synectin Recruits Myosin Vi To Endocytic Vesicles, Samia N. Naccache, Tama Hasson, Arie Horowitz

Dartmouth Scholarship

Myosin VI (myo6) is the only actin-based molecular motor that translocates along actin filaments toward the minus end. Myo6 participates in two steps of endocytic trafficking; it is recruited to both clathrin-coated pits and to ensuing uncoated endocytic vesicles (UCV). Although there is evidence suggesting that the PDZ adaptor protein GIPC/synectin is involved in the association of myo6 with UCV, the recruitment mechanism is unknown. We show that GIPC/synectin is required for both internalization of cell surface receptors and for coupling of myo6 to UCV. This coupling occurs via a mechanism wherein engagement of the GIPC/synectin PDZ domain by C …

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Sqt1, Which Encodes An Essential Wd Domain Protein Of Saccharomyces Cerevisiae, Suppresses Dominant-Negative Mutations Of The Ribosomal Protein Gene Qsr1., Dominic P. Eisinger, Frederick A. Dick, Elke Denke, Bernard L. Trumpower Sep 1997

Sqt1, Which Encodes An Essential Wd Domain Protein Of Saccharomyces Cerevisiae, Suppresses Dominant-Negative Mutations Of The Ribosomal Protein Gene Qsr1., Dominic P. Eisinger, Frederick A. Dick, Elke Denke, Bernard L. Trumpower

Dartmouth Scholarship

QSR1 is an essential Saccharomyces cerevisiae gene, which encodes a 60S ribosomal subunit protein required for joining of 40S and 60S subunits. Truncations of QSR1 predicted to encode C-terminally truncated forms of Qsr1p do not substitute for QSR1 but do act as dominant negative mutations, inhibiting the growth of yeast when expressed from an inducible promoter. The dominant negative mutants exhibit a polysome profile characterized by 'half-mer' polysomes, indicative of a subunit joining defect like that seen in other qsr1 mutants (D. P. Eisinger, F. A. Dick, and B. L. Trumpower, Mol. Cell. Biol. 17:5136-5145, 1997.) By screening a high-copy …

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Assembly And Regulation Of The Cd40 Receptor Complex In Human B Cells, Michelle R. Kuhné, Michael Robbins, John E. Hambor, Matthew F. Mackey, Yoko Kosaka, Toshihide Nishimura, Jason P. Gigley, Randolph J. Noelle, David M. Calderhead Jul 1997

Assembly And Regulation Of The Cd40 Receptor Complex In Human B Cells, Michelle R. Kuhné, Michael Robbins, John E. Hambor, Matthew F. Mackey, Yoko Kosaka, Toshihide Nishimura, Jason P. Gigley, Randolph J. Noelle, David M. Calderhead

Dartmouth Scholarship

CD40 is a member of the tumor necrosis factor (TNF) receptor superfamily. Studies with human B cells show that the binding of CD154 (gp39, CD40L) to CD40 recruits TNF receptor– associated factor 2 (TRAF2) and TRAF3 to the receptor complex, induces the downregulation of the nonreceptor-associated TRAFs in the cell and induces an increased expression of Fas on the cell surface. Combined signaling through the interluekin 4 receptor and CD40 induces an increased expression of Fas with a commensurate increase in the level of TRAF2, but not TRAF3, that is recruited to the receptor complex. In contrast, engagement of the …

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C-Terminal Truncations Of The Yeast Nucleoporin Nup145p Produce A Rapid Temperature-Conditional Mrna Export Defect And Alterations To Nuclear Structure., Thomas C. Dockendorff, Catherine V. Heath, Alan L. Goldstein, Christine A. Snay, C N. Cole Feb 1997

C-Terminal Truncations Of The Yeast Nucleoporin Nup145p Produce A Rapid Temperature-Conditional Mrna Export Defect And Alterations To Nuclear Structure., Thomas C. Dockendorff, Catherine V. Heath, Alan L. Goldstein, Christine A. Snay, C N. Cole

Dartmouth Scholarship

A screen for temperature-sensitive mutants of Saccharomyces cerevisiae defective in nucleocytoplasmic trafficking of poly(A)+ RNA has identified an allele of the NUP145 gene, which encodes an essential nucleoporin. NUP145 was previously identified by using a genetic synthetic lethal screen (E. Fabre, W. C. Boelens, C. Wimmer, I. W. Mattaj, and E. C. Hurt, Cell 78:275-289, 1994) and by using a monoclonal antibody which recognizes the GLFG family of vertebrate and yeast nucleoporins (S. R. Wente and G. Blobel, J. Cell Biol. 125:955-969, 1994). Cells carrying the new allele, nup145-10, grew at 23 and 30 degrees C but were unable to …

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Distinct Cis-Acting Elements Mediate Clock, Light, And Developmental Regulation Of The Neurospora Crassa Eas (Ccg-2) Gene., Deborah Bell-Pedersen, Jay C. Dunlap, Jennifer J. Loros Feb 1996

Distinct Cis-Acting Elements Mediate Clock, Light, And Developmental Regulation Of The Neurospora Crassa Eas (Ccg-2) Gene., Deborah Bell-Pedersen, Jay C. Dunlap, Jennifer J. Loros

Dartmouth Scholarship

The Neurospora crassa eas (ccg-2) gene, which encodes a fungal hydrophobin, is transcriptionally regulated by the circadian clock. In addition, eas (ccg-2) is positively regulated by light and transcripts accumulate during asexual development. To sort out the basis of this complex regulation, deletion analyses of the eas (ccg-2) promoter were carried out to localize the cis-acting elements mediating clock, light, and developmental control. The primary sequence determinants of a positive activating clock element (ACE) were found to reside in a 45-bp region, just upstream from the TATA box. Using a novel unregulated promoter/reporter system developed for this study, we show …

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Transactivation Of The Moloney Murine Leukemia Virus And T-Cell Receptor Beta-Chain Enhancers By Cbf And Ets Requires Intact Binding Sites For Both Proteins., Wanwen Sun, Barbara J. Graves, Nancy A. Speck Aug 1995

Transactivation Of The Moloney Murine Leukemia Virus And T-Cell Receptor Beta-Chain Enhancers By Cbf And Ets Requires Intact Binding Sites For Both Proteins., Wanwen Sun, Barbara J. Graves, Nancy A. Speck

Dartmouth Scholarship

The Moloney murine leukemia virus (Mo-MLV) enhancer contains binding sites (LVb and LVc) for the ets gene family of proteins and a core site that binds the polyomavirus enhancer-binding protein 2/core-binding factor (cbf) family of proteins. The LVb and core sites in the Mo-MLV enhancer contribute to its constitutive activity in T cells. All three binding sites (LVb, LVc, and core) are required for phorbol ester inducibility of the Mo-MLV enhancer. Adjacent binding sites for the ets and cbf proteins likewise constitute a phorbol ester response element within the human T-cell receptor beta-chain (TCR beta) enhancer and contribute to constitutive …

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Cooperative Binding Of Ets-1 And Core Binding Factor To Dna., David Wotton, Jacques Ghysdael, Shuwen Wang, Nancy A. Speck, Michael J. Owen Jan 1994

Cooperative Binding Of Ets-1 And Core Binding Factor To Dna., David Wotton, Jacques Ghysdael, Shuwen Wang, Nancy A. Speck, Michael J. Owen

Dartmouth Scholarship

Two phorbol ester-inducible elements (beta E2 and beta E3) within the human T-cell receptor beta gene enhancer each contain consensus binding sites for the Ets and core binding factor (CBF) transcription factor families. Recombinant Ets-1 and purified CBF bound individually to beta E2 and beta E3, in which the Ets and core sites are directly adjacent. In this report, we show that CBF and Ets-1 bind together to beta E2 and beta E3 and that Ets-1-CBF-DNA complexes are favored over the binding of either protein alone to beta E2. Formation of Ets-1-CBF-DNA complexes increased the affinity of Ets-1-DNA interactions and …

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Indistinguishable Nuclear Factor Binding To Functional Core Sites Of The T-Cell Receptor Delta And Murine Leukemia Virus Enhancers., Juan M. Redondo, Jeffrey L. Pfohl, Cristina Hernandez-Munain, Shuwen Wang, Nancy A. Speck, Michael S. Krangel Nov 1992

Indistinguishable Nuclear Factor Binding To Functional Core Sites Of The T-Cell Receptor Delta And Murine Leukemia Virus Enhancers., Juan M. Redondo, Jeffrey L. Pfohl, Cristina Hernandez-Munain, Shuwen Wang, Nancy A. Speck, Michael S. Krangel

Dartmouth Scholarship

We have previously shown that the delta E3 site is an essential element for transcriptional activation by the human T-cell receptor (TCR) delta enhancer and identified two factors, NF-delta E3A and NF-delta E3C, that bound to overlapping core (TGTGGTTT) and E-box motifs within delta E3. In this study, we show that protein binding to the core motif is necessary but not sufficient for transcriptional activation by the delta E3 element. In contrast, protein binding to the E-box motif does not contribute significantly to enhancer activity. A similar core motif present within the enhancers of T-cell-tropic murine retroviruses has been shown …

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The Influence Of Antimicrobial Use On Bacterial Resistance, James T. Griffith Jun 1992

The Influence Of Antimicrobial Use On Bacterial Resistance, James T. Griffith

Walden Dissertations and Doctoral Studies

Antimicrobial resistance is becoming an increasingly serious problem accompanied by relatively few studies examining the relationship between use and resistance. The present study undertakes a twenty year analysis of antimicrobial production and factors affecting antimicrobial use for a particular microorganism (Stp. faecalis)/antimicrobial agent (Cephalothin) combination. The period is inclusive of the market introduction of the agent and considerate of prescribing practices to the present time. The accumulated data reveal that there is indeed a relationship between total drug availability (medicinal, agricultural) and increased antimicrobial resistance. The data also suggest that national (or global) use changes would likely have a long …

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Purification Of Core-Binding Factor, A Protein That Binds The Conserved Core Site In Murine Leukemia Virus Enhancers., Shuwen W. Wang, Nancy A. Speck Jan 1992

Purification Of Core-Binding Factor, A Protein That Binds The Conserved Core Site In Murine Leukemia Virus Enhancers., Shuwen W. Wang, Nancy A. Speck

Dartmouth Scholarship

The Moloney murine leukemia virus causes thymic leukemias when injected into newborn mice. A major genetic determinant of the thymic disease specificity of the Moloney virus genetically maps to two protein binding sites in the Moloney virus enhancer, the leukemia virus factor b site and the adjacent core site. Point mutations introduced into either of these sites significantly shifts the disease specificity of the Moloney virus from thymic leukemia to erythroleukemia (N. A. Speck, B. Renjifo, E. Golemis, T. Frederickson, J. Hartley, and N. Hopkins, Genes Dev. 4:233-242, 1990). We have purified several polypeptides that bind to the core site …

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Interleukin-2-Triggered Raf-1 Expression, Phosphorylation, And Associated Kinase Activity Increase Through G1 And S In Cd3-Stimulated Primary Human T Cells., Antanina Zmuidzinas, Harvey J. Mamon, Thomas M. Roberts, Kendall A. Smith May 1991

Interleukin-2-Triggered Raf-1 Expression, Phosphorylation, And Associated Kinase Activity Increase Through G1 And S In Cd3-Stimulated Primary Human T Cells., Antanina Zmuidzinas, Harvey J. Mamon, Thomas M. Roberts, Kendall A. Smith

Dartmouth Scholarship

To gain further insight into the role of Raf-1 in normal cell growth, c-raf-1 mRNA expression, Raf-1 protein production, and Raf-1-associated kinase activity in normal human T cells were analyzed. In contrast to the constitutive expression of Raf-1 in continuously proliferating cell lines, c-raf-1 mRNA and Raf-1 protein levels were barely detectable in freshly isolated G0 T lymphocytes. Previous work with fibroblasts has suggested that Raf-1 plays a signaling role in the G0-G1 phase transition. In T cells, triggering via the T-cell antigen receptor (TCR)-CD3 complex (TCR/CD3) resulted in an approximately fourfold increase in c-raf-1 mRNA. In addition, the promotion …

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Neurospora Crassa Clock-Controlled Genes Are Regulated At The Level Of Transcription., Jennifer J. Loros, Jay C. Dunlap Jan 1991

Neurospora Crassa Clock-Controlled Genes Are Regulated At The Level Of Transcription., Jennifer J. Loros, Jay C. Dunlap

Dartmouth Scholarship

Although an extensive number of biological processes are under the daily control of the circadian biological clock, little is known about how the clock maintains its regulatory networks within a cell. An important aspect of this temporal control is the daily control of gene expression. Previously we identified two morning-specific genes that are regulated by the clock through daily control of gene expression (J. Loros, S. Denome, and J.C. Dunlap, Science 243:385-388, 1989). We have now introduced a method for transcriptional analysis in Neurospora crassa and used this nuclear run-on procedure to show that regulation of mRNA abundance for these …

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Identification Of A Complex Associated With Processing And Polyadenylation In Vitro Of Herpes Simplex Virus Type 1 Thymidine Kinase Precursor Rna., Fang Zhang, Charles N. Cole Sep 1987

Identification Of A Complex Associated With Processing And Polyadenylation In Vitro Of Herpes Simplex Virus Type 1 Thymidine Kinase Precursor Rna., Fang Zhang, Charles N. Cole

Dartmouth Scholarship

Cleavage and polyadenylation of substrate RNAs containing the herpes simplex virus type 1 (HSV-1) thymidine kinase (tk) gene polyadenylation signal region were examined in HeLa cell nuclear extract. 3'-End RNA processing was accurate and efficient and required ATP and Mg2+. Cleavage, but not polyadenylation, occurred in the presence of EDTA or when ATP was replaced with 3' dATP (cordycepin) or AMP(CH2)PP, a nonhydrolyzable analog of ATP. Processing in vitro and in vivo showed the same signal element requirements: a series of substrates containing linker scanning, internal deletion, and small insertion mutations was processed with the same relative efficiencies and at …

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