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  • 1
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    Genetic selection of peptide inhibitors of biological pathways (1999)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1999-07-27
    Description: Genetic selections were used to find peptides that inhibit biological pathways in budding yeast. The peptides were presented inside cells as peptamers, surface loops on a highly expressed and biologically inert carrier protein, a catalytically inactive derivative of staphylococcal nuclease. Peptamers that inhibited the pheromone signaling pathway, transcriptional silencing, and the spindle checkpoint were isolated. Putative targets for the inhibitors were identified by a combination of two-hybrid analysis and genetic dissection of the target pathways. This analysis identified Ydr517w as a component of the spindle checkpoint and reinforced earlier indications that Ste50 has both positive and negative roles in pheromone signaling. Analysis of transcript arrays showed that the peptamers were highly specific in their effects, which suggests that they may be useful reagents in organisms that lack sophisticated genetics as well as for identifying components of existing biological pathways that are potential targets for drug discovery.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Norman, T C -- Smith, D L -- Sorger, P K -- Drees, B L -- O'Rourke, S M -- Hughes, T R -- Roberts, C J -- Friend, S H -- Fields, S -- Murray, A W -- P41-RR11823/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 1999 Jul 23;285(5427):591-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physiology, University of California, San Francisco, CA 94143-0444, USA. tnorman@microbia.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10417390" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Calcium-Calmodulin-Dependent Protein Kinases/metabolism ; Fungal Proteins/metabolism ; G1 Phase ; Galactose/metabolism ; Lipoproteins/metabolism ; Micrococcal Nuclease ; Mitosis ; Molecular Sequence Data ; Peptide Library ; Peptides/genetics/metabolism/*pharmacology ; Pheromones/*metabolism ; Protein Binding ; Protein-Serine-Threonine Kinases ; Protein-Tyrosine Kinases ; Saccharomyces cerevisiae/cytology/genetics/*metabolism ; *Saccharomyces cerevisiae Proteins ; *Selection, Genetic ; *Signal Transduction ; Spindle Apparatus/drug effects/*metabolism ; Transcription, Genetic
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 2
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    Diversity and complexity in DNA recognition by transcription factors (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-05-16
    Description: Sequence preferences of DNA binding proteins are a primary mechanism by which cells interpret the genome. Despite the central importance of these proteins in physiology, development, and evolution, comprehensive DNA binding specificities have been determined experimentally for only a few proteins. Here, we used microarrays containing all 10-base pair sequences to examine the binding specificities of 104 distinct mouse DNA binding proteins representing 22 structural classes. Our results reveal a complex landscape of binding, with virtually every protein analyzed possessing unique preferences. Roughly half of the proteins each recognized multiple distinctly different sequence motifs, challenging our molecular understanding of how proteins interact with their DNA binding sites. This complexity in DNA recognition may be important in gene regulation and in the evolution of transcriptional regulatory networks.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2905877/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2905877/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Badis, Gwenael -- Berger, Michael F -- Philippakis, Anthony A -- Talukder, Shaheynoor -- Gehrke, Andrew R -- Jaeger, Savina A -- Chan, Esther T -- Metzler, Genita -- Vedenko, Anastasia -- Chen, Xiaoyu -- Kuznetsov, Hanna -- Wang, Chi-Fong -- Coburn, David -- Newburger, Daniel E -- Morris, Quaid -- Hughes, Timothy R -- Bulyk, Martha L -- R01 HG003985/HG/NHGRI NIH HHS/ -- R01 HG003985-01/HG/NHGRI NIH HHS/ -- R01 HG003985-02/HG/NHGRI NIH HHS/ -- R01 HG003985-03/HG/NHGRI NIH HHS/ -- New York, N.Y. -- Science. 2009 Jun 26;324(5935):1720-3. doi: 10.1126/science.1162327. Epub 2009 May 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Banting and Best Department of Medical Research, University of Toronto, Toronto, ON M5S 3E1, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19443739" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs ; Amino Acid Sequence ; Animals ; Base Sequence ; Binding Sites ; DNA/chemistry/*metabolism ; Electrophoretic Mobility Shift Assay ; Gene Expression Regulation ; Gene Regulatory Networks ; Humans ; Mice ; Protein Array Analysis ; Protein Binding ; Protein Structure, Tertiary ; Recombinant Fusion Proteins/chemistry/metabolism ; Transcription Factors/*chemistry/*metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
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    Extensive diversity of Ig-superfamily proteins in the immune system of insects (2005)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2005-08-20
    Description: The extensive somatic diversification of immune receptors is a hallmark of higher vertebrates. However, whether molecular diversity contributes to immune protection in invertebrates is unknown. We present evidence that Drosophila immune-competent cells have the potential to express more than 18,000 isoforms of the immunoglobulin (Ig)-superfamily receptor Down syndrome cell adhesion molecule (Dscam). Secreted protein isoforms of Dscam were detected in the hemolymph, and hemocyte-specific loss of Dscam impaired the efficiency of phagocytic uptake of bacteria, possibly due to reduced bacterial binding. Importantly, the molecular diversity of Dscam transcripts generated through a mechanism of alternative splicing is highly conserved across major insect orders, suggesting an unsuspected molecular complexity of the innate immune system of insects.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Watson, Fiona L -- Puttmann-Holgado, Roland -- Thomas, Franziska -- Lamar, David L -- Hughes, Michael -- Kondo, Masahiro -- Rebel, Vivienne I -- Schmucker, Dietmar -- 1RO1-NS46747-01/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2005 Sep 16;309(5742):1874-8. Epub 2005 Aug 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cancer Biology, Dana Farber Cancer Institute, Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16109846" target="_blank"〉PubMed〈/a〉
    Keywords: *Alternative Splicing ; Amino Acid Sequence ; Animals ; Animals, Genetically Modified ; Brain/metabolism ; Cell Adhesion Molecules ; Cell Line ; Drosophila Proteins/chemistry/*genetics/*immunology/metabolism ; Drosophila melanogaster/*genetics/*immunology/metabolism ; Escherichia coli/immunology/metabolism ; Fat Body/metabolism ; Hemocytes/immunology/*metabolism ; Hemolymph/chemistry ; Immunity, Innate ; Immunoglobulins/chemistry ; Insects/chemistry/genetics ; Molecular Sequence Data ; Neurons/metabolism ; Oligonucleotide Array Sequence Analysis ; Phagocytosis ; Protein Isoforms/chemistry/genetics/metabolism ; Protein Structure, Tertiary ; RNA Interference ; Receptors, Immunologic/immunology/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 4
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    The kinase domain of titin controls muscle gene expression and protein turnover (2005)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2005-04-02
    Description: The giant sarcomeric protein titin contains a protein kinase domain (TK) ideally positioned to sense mechanical load. We identified a signaling complex where TK interacts with the zinc-finger protein nbr1 through a mechanically inducible conformation. Nbr1 targets the ubiquitin-associated p62/SQSTM1 to sarcomeres, and p62 in turn interacts with MuRF2, a muscle-specific RING-B-box E3 ligase and ligand of the transactivation domain of the serum response transcription factor (SRF). Nuclear translocation of MuRF2 was induced by mechanical inactivity and caused reduction of nuclear SRF and repression of transcription. A human mutation in the titin protein kinase domain causes hereditary muscle disease by disrupting this pathway.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lange, Stephan -- Xiang, Fengqing -- Yakovenko, Andrey -- Vihola, Anna -- Hackman, Peter -- Rostkova, Elena -- Kristensen, Jakob -- Brandmeier, Birgit -- Franzen, Gereon -- Hedberg, Birgitta -- Gunnarsson, Lars Gunnar -- Hughes, Simon M -- Marchand, Sylvie -- Sejersen, Thomas -- Richard, Isabelle -- Edstrom, Lars -- Ehler, Elisabeth -- Udd, Bjarne -- Gautel, Mathias -- G0200496(63216)/Medical Research Council/United Kingdom -- G0300213/Medical Research Council/United Kingdom -- PG/03/049/15364/British Heart Foundation/United Kingdom -- New York, N.Y. -- Science. 2005 Jun 10;308(5728):1599-603. Epub 2005 Mar 31.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Muscle Signalling and Development, Randall Division, King's College London, London SE1 1UL, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15802564" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Amino Acid Substitution ; Animals ; Catalytic Domain ; Cell Line ; Cell Nucleus/metabolism ; Connectin ; *Gene Expression Regulation ; Heat-Shock Proteins/metabolism ; Humans ; Ligands ; Mice ; Mice, Inbred C3H ; Molecular Sequence Data ; Muscle Proteins/*chemistry/genetics/*metabolism ; Muscle, Skeletal/*metabolism ; Muscular Diseases/genetics ; Mutation ; Myocytes, Cardiac/*metabolism ; Protein Binding ; Protein Conformation ; Protein Kinases/*chemistry/genetics/*metabolism ; Protein Structure, Tertiary ; Proteins/metabolism ; Rats ; Respiratory Insufficiency/genetics/metabolism ; Sarcomeres/metabolism ; Serum Response Factor/metabolism ; Signal Transduction ; Two-Hybrid System Techniques ; Ubiquitin-Protein Ligases/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 5
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    GTBP, a 160-kilodalton protein essential for mismatch-binding activity in human cells (1995)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1995-06-30
    Description: DNA mismatch recognition and binding in human cells has been thought to be mediated by the hMSH2 protein. Here it is shown that the mismatch-binding factor consists of two distinct proteins, the 100-kilodalton hMSH2 and a 160-kilodalton polypeptide, GTBP (for G/T binding protein). Sequence analysis identified GTBP as a new member of the MutS homolog family. Both proteins are required for mismatch-specific binding, a result consistent with the finding that tumor-derived cell lines devoid of either protein are also devoid of mismatch-binding activity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Palombo, F -- Gallinari, P -- Iaccarino, I -- Lettieri, T -- Hughes, M -- D'Arrigo, A -- Truong, O -- Hsuan, J J -- Jiricny, J -- New York, N.Y. -- Science. 1995 Jun 30;268(5219):1912-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Istituto di Ricerche di Biologia Molecolare P. Angeletti, Pomezia, Italy.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7604265" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Base Composition ; Base Sequence ; Cloning, Molecular ; Colorectal Neoplasms ; *DNA Repair/genetics ; DNA, Neoplasm/*metabolism ; DNA-Binding Proteins/chemistry/genetics/*metabolism ; HeLa Cells ; Humans ; Molecular Sequence Data ; Molecular Weight ; Nucleic Acid Heteroduplexes/*metabolism ; Sequence Analysis ; Tumor Cells, Cultured
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 6
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    Reverse transcriptase motifs in the catalytic subunit of telomerase (1997)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1997-04-25
    Description: Telomerase is a ribonucleoprotein enzyme essential for the replication of chromosome termini in most eukaryotes. Telomerase RNA components have been identified from many organisms, but no protein component has been demonstrated to catalyze telomeric DNA extension. Telomerase was purified from Euplotes aediculatus, a ciliated protozoan, and one of its proteins was partially sequenced by nanoelectrospray tandem mass spectrometry. Cloning and sequence analysis of the corresponding gene revealed that this 123-kilodalton protein (p123) contains reverse transcriptase motifs. A yeast (Saccharomyces cerevisiae) homolog was found and subsequently identified as EST2 (ever shorter telomeres), deletion of which had independently been shown to produce telomere defects. Introduction of single amino acid substitutions within the reverse transcriptase motifs of Est2 protein led to telomere shortening and senescence in yeast, indicating that these motifs are important for catalysis of telomere elongation in vivo. In vitro telomeric DNA extension occurred with extracts from wild-type yeast but not from est2 mutants or mutants deficient in telomerase RNA. Thus, the reverse transcriptase protein fold, previously known to be involved in retroviral replication and retrotransposition, is essential for normal chromosome telomere replication in diverse eukaryotes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lingner, J -- Hughes, T R -- Shevchenko, A -- Mann, M -- Lundblad, V -- Cech, T R -- AG11728/AG/NIA NIH HHS/ -- New York, N.Y. -- Science. 1997 Apr 25;276(5312):561-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO 80309-0215, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9110970" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Binding Sites ; Catalysis ; Chromosomes/metabolism ; DNA, Fungal/metabolism ; DNA-Binding Proteins ; Euplotes/*enzymology ; Evolution, Molecular ; Fungal Proteins/chemistry/metabolism ; Genes, Fungal ; Genes, Protozoan ; Molecular Sequence Data ; Protein Conformation ; *Rna ; RNA, Fungal/metabolism ; RNA, Protozoan/metabolism ; RNA-Directed DNA Polymerase/*chemistry/metabolism ; Saccharomyces cerevisiae/enzymology ; Saccharomyces cerevisiae Proteins ; Sequence Alignment ; Telomerase/*chemistry/genetics/isolation & purification/metabolism ; Telomere/metabolism ; Templates, Genetic
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 7
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    Turbofan Noise Reduction Associated With Increased Bypass Nozzle Flow (2005)
    In:  CASI
    Details
    Publication Date: 2018-06-02
    Description: An advanced 22-in. scale model turbofan, typical of a current-generation aircraft engine design by GE Aircraft Engines, was tested in NASA Glenn Research Center s 9- by 15- Foot Low-Speed Wind Tunnel to explore the far-field acoustic effects of an increased bypass nozzle area at simulated aircraft speeds of takeoff, approach, and landing. The wind-tunnel-scale model consisted of the bypass stage fan, stators, and nacelle (including the fan exit nozzle) of a typical turbofan. This fan-stage test was part of the NASA Glenn Fan Broadband Source Diagnostic Test, second entry, which acquired aeroacoustic results over a range of test conditions. A baseline nozzle was selected, and the nozzle area was chosen for maximum performance at sea-level conditions. Two additional nozzles were also tested--one with a 5.4-percent increase in nozzle area over the baseline nozzle (sized for design point conditions), corresponding to a 5-percent increase in fan weight flow, and another nozzle with a 10.9-percent increase in nozzle area over the baseline nozzle (sized for maximum weight flow at sea-level conditions), corresponding to a 7.5 percent increase in fan weight flow. Measured acoustic benefits with increased nozzle area were very encouraging, showing overall sound power level reductions of 2 dB or more (left graph) while the stage adiabatic efficiency (right graph) and thrust (final graph) actually increased by several percentage points. These noise-reduction benefits were seen to include both rotor-interaction tones and broadband noise, and were evident throughout the range of measured sideline angles.
    Keywords: Acoustics
    Type: Research and Technology 2004; NASA/TM-2005-213419
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  • 8
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    Derivation of Acoustic Criteria for the Cassini Spacecraft and Comparison with Flight Data (1999)
    In:  CASI
    Details
    Publication Date: 2019-07-13
    Description: Acoustic measurements from eight pre-Cassini Titan IV flights, and an acoustic test of a Cassini simulator and Titan payload fairing (PLF), were used to derive acoustic flight and test criteria for the Cassini spacecraft. The flight and ground test data were used or modified to account for the following factors: (a) noise-spike contamination of flight data, (b) spatial and flight-to-flight variations of flight data, (c) application of a thicker banier-blanket to the PLF for the Cassini mission, (d) effects of locating two Cassini assemblies, the Huygens Probe, and the High Gain Antenna (HGA), near the PLF, and (e) higher thrust of upgraded Titan solid rocket motors (SRMS) for the Cassini mission. An overall sound pressure level (OA SPL) of 145 dB was verified for the protoflight acoustic test criteria for the Cassini spacecraft. Cassini flight liftoff data showed an average OA SPL of 133 dB.
    Keywords: Acoustics
    Type: International Congress on Sound and Vibration; Jul 05, 1999 - Jul 08, 1999; Lyngby; Denmark
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    NASA TECHNICAL REPORTS
  • 9
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    Benefits of Swept and Leaned Stators for Fan Noise Reduction (1998)
    In:  CASI
    Details
    Publication Date: 2019-07-13
    Description: An advanced high bypass ratio fan model was tested in the NASA Lewis Research Center 9 x 15-Foot Low Speed Wind Tunnel. The primary focus of this test was to quantify the acoustic benefits and aerodynamic performance of sweep and lean in stator vane design. Three stator sets were used for this test series. A conventional radial stator was tested at two rotor-stator axial spacings. Additional stator sets incorporating sweep + lean, and sweep only were also tested. The hub axial location for the swept + lean, and sweep only stators corresponded to the location of the radial stator at the upstream rotor-stator spacing, while the tip axial location of these modified stators corresponded to the radial stator axial position at the downstream position. The acoustic results show significant reductions in both rotor-stator interaction noise and broadband noise beyond what could be achieved through increased axial spacing of the conventional, radial stator. Theoretical application of these results to acoustically quantify a fictitious 2-engine aircraft and flight path suggested that about 3 Effective Perceived Noise (EPN) dB could be achieved through incorporation of these modified stators. This reduction would represent a significant portion of the 6 EPNdB noise goal of the current NASA Advanced Subsonic Technology (AST) initiative relative to that of 1992 technology levels. A secondary result of this fan test was to demonstrate the ability of an acoustic barrier wall to block aft-radiated fan noise in the wind tunnel, thus revealing the acoustic structure of the residual inlet-radiated noise. This technology should prove valuable toward better understanding inlet liner design, or wherever it is desirable to eliminate aft-radiated noise from the fan acoustic signature.
    Keywords: Acoustics
    Type: NASA/TM-1998-208661 , NAS 1.15:208661 , AIAA Paper 99-0479 , E-11382 , Aerospace Sciences Meeting and Exhibit; Jan 11, 1999 - Jan 14, 1999; Reno, NV; United States
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  • 10
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    Vibroacoustic Analysis of Large Heat Rejection Radiators for Future Spacecraft (2006)
    In:  CASI
    Details
    Publication Date: 2019-07-13
    Description: Spacecraft structures such as antennas, solar arrays and radiator panels significantly respond to high acoustic levels seen at lift-off. Some future spacecraft may utilize nuclear electric propulsion that require large radiator panels to reject waste heat. A vibroacoustic assessment was performed for two different radiator panel designs. Results from the analysis of the two designs using different analytical approaches are presented and discussed.
    Keywords: Acoustics
    Type: Spacecraft and Launch Vehicle Dynamic Environment Workshop; Jun 21, 2005 - Jun 23, 2005; El Segundo, CA; United States
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    NASA TECHNICAL REPORTS
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