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  • 1
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    Losartan, an AT1 antagonist, prevents aortic aneurysm in a mouse model of Marfan syndrome (2006)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2006-04-08
    Description: Aortic aneurysm and dissection are manifestations of Marfan syndrome (MFS), a disorder caused by mutations in the gene that encodes fibrillin-1. Selected manifestations of MFS reflect excessive signaling by the transforming growth factor-beta (TGF-beta) family of cytokines. We show that aortic aneurysm in a mouse model of MFS is associated with increased TGF-beta signaling and can be prevented by TGF-beta antagonists such as TGF-beta-neutralizing antibody or the angiotensin II type 1 receptor (AT1) blocker, losartan. AT1 antagonism also partially reversed noncardiovascular manifestations of MFS, including impaired alveolar septation. These data suggest that losartan, a drug already in clinical use for hypertension, merits investigation as a therapeutic strategy for patients with MFS and has the potential to prevent the major life-threatening manifestation of this disorder.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1482474/" 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/PMC1482474/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Habashi, Jennifer P -- Judge, Daniel P -- Holm, Tammy M -- Cohn, Ronald D -- Loeys, Bart L -- Cooper, Timothy K -- Myers, Loretha -- Klein, Erin C -- Liu, Guosheng -- Calvi, Carla -- Podowski, Megan -- Neptune, Enid R -- Halushka, Marc K -- Bedja, Djahida -- Gabrielson, Kathleen -- Rifkin, Daniel B -- Carta, Luca -- Ramirez, Francesco -- Huso, David L -- Dietz, Harry C -- K08 HL067056/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2006 Apr 7;312(5770):117-21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute and Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16601194" target="_blank"〉PubMed〈/a〉
    Keywords: Adrenergic beta-Antagonists/administration & dosage/therapeutic use ; Angiotensin II Type 1 Receptor Blockers/administration & dosage/*therapeutic use ; Animals ; Antibodies/immunology ; Aorta/pathology ; Aortic Aneurysm/etiology/*prevention & control ; *Disease Models, Animal ; Elastic Tissue/pathology ; Female ; Losartan/administration & dosage/*therapeutic use ; Lung/pathology ; Lung Diseases/drug therapy/pathology ; Marfan Syndrome/complications/*drug therapy/metabolism/pathology ; Mice ; Microfilament Proteins/genetics ; Mutation ; Neutralization Tests ; Pregnancy ; Pregnancy Complications/drug therapy ; Propranolol/administration & dosage/therapeutic use ; Pulmonary Alveoli/pathology ; Receptor, Angiotensin, Type 1/metabolism ; Signal Transduction ; Transforming Growth Factor beta/antagonists & inhibitors/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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  • 2
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    Human lineage-specific amplification, selection, and neuronal expression of DUF1220 domains (2006)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2006-09-02
    Description: Extreme gene duplication is a major source of evolutionary novelty. A genome-wide survey of gene copy number variation among human and great ape lineages revealed that the most striking human lineage-specific amplification was due to an unknown gene, MGC8902, which is predicted to encode multiple copies of a protein domain of unknown function (DUF1220). Sequences encoding these domains are virtually all primate-specific, show signs of positive selection, and are increasingly amplified generally as a function of a species' evolutionary proximity to humans, where the greatest number of copies (212) is found. DUF1220 domains are highly expressed in brain regions associated with higher cognitive function, and in brain show neuron-specific expression preferentially in cell bodies and dendrites.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Popesco, Magdalena C -- Maclaren, Erik J -- Hopkins, Janet -- Dumas, Laura -- Cox, Michael -- Meltesen, Lynne -- McGavran, Loris -- Wyckoff, Gerald J -- Sikela, James M -- AA11853/AA/NIAAA NIH HHS/ -- New York, N.Y. -- Science. 2006 Sep 1;313(5791):1304-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Human Medical Genetics, University of Colorado at Denver and Health Sciences Center, Aurora, CO 80045, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16946073" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; *Biological Evolution ; Brain/*metabolism ; Cognition ; Exons ; *Gene Amplification ; Gene Dosage ; Gene Duplication ; Gene Expression ; Genome, Human ; Humans ; Macaca mulatta/genetics ; Mice ; Molecular Sequence Data ; Neocortex/metabolism ; Neurons/*metabolism ; Pan troglodytes/genetics ; Phylogeny ; Polymerase Chain Reaction ; *Protein Structure, Tertiary ; Proteins/*chemistry/genetics ; Rats ; *Selection, 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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  • 3
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    Symbiotic bacteria direct expression of an intestinal bactericidal lectin (2006)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2006-08-26
    Description: The mammalian intestine harbors complex societies of beneficial bacteria that are maintained in the lumen with minimal penetration of mucosal surfaces. Microbial colonization of germ-free mice triggers epithelial expression of RegIIIgamma, a secreted C-type lectin. RegIIIgamma binds intestinal bacteria but lacks the complement recruitment domains present in other microbe-binding mammalian C-type lectins. We show that RegIIIgamma and its human counterpart, HIP/PAP, are directly antimicrobial proteins that bind their bacterial targets via interactions with peptidoglycan carbohydrate. We propose that these proteins represent an evolutionarily primitive form of lectin-mediated innate immunity, and that they reveal intestinal strategies for maintaining symbiotic host-microbial relationships.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2716667/" 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/PMC2716667/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cash, Heather L -- Whitham, Cecilia V -- Behrendt, Cassie L -- Hooper, Lora V -- R01 DK070855/DK/NIDDK NIH HHS/ -- R01 DK070855-01/DK/NIDDK NIH HHS/ -- T32-AI007520/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2006 Aug 25;313(5790):1126-30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Immunology, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA. Lora.Hooper@UTSouthwestern.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16931762" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, Neoplasm/*metabolism/pharmacology ; Bacteria/growth & development/*immunology ; Biomarkers, Tumor/*metabolism/pharmacology ; Chitin/metabolism ; Colony Count, Microbial ; Germ-Free Life ; Gram-Positive Bacteria/immunology/metabolism ; Homeostasis ; Humans ; *Immunity, Innate ; Immunity, Mucosal ; Intestine, Small/*microbiology ; Lectins, C-Type/*metabolism ; Ligands ; Listeria monocytogenes/ultrastructure ; Mice ; Oligonucleotide Array Sequence Analysis ; Paneth Cells/immunology/*metabolism ; Peptidoglycan/chemistry/*metabolism ; Protein Structure, Tertiary ; Proteins/genetics/*metabolism/pharmacology ; Recombinant Proteins/metabolism ; Secretory Vesicles/metabolism ; Symbiosis
    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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    Dissecting the functions of the mammalian clock protein BMAL1 by tissue-specific rescue in mice (2006)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2006-11-25
    Description: The basic helix-loop-helix (bHLH)-Per-Arnt-Sim (PAS) domain transcription factor BMAL1 is an essential component of the mammalian circadian pacemaker. Bmal1-/- mice lose circadian rhythmicity but also display tendon calcification and decreased activity, body weight, and longevity. To investigate whether these diverse functions of BMAL1 are tissue-specific, we produced transgenic mice that constitutively express Bmal1 in brain or muscle and examined the effects of rescued gene expression in Bmal1-/- mice. Circadian rhythms of wheel-running activity were restored in brain-rescued Bmal1-/- mice in a conditional manner; however, activity levels and body weight were lower than those of wild-type mice. In contrast, muscle-rescued Bmal1-/- mice exhibited normal activity levels and body weight yet remained behaviorally arrhythmic. Thus, Bmal1 has distinct tissue-specific functions that regulate integrative physiology.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3756687/" 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/PMC3756687/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McDearmon, Erin L -- Patel, Kush N -- Ko, Caroline H -- Walisser, Jacqueline A -- Schook, Andrew C -- Chong, Jason L -- Wilsbacher, Lisa D -- Song, Eun J -- Hong, Hee-Kyung -- Bradfield, Christopher A -- Takahashi, Joseph S -- P50 MH074924/MH/NIMH NIH HHS/ -- R01 ES005703/ES/NIEHS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2006 Nov 24;314(5803):1304-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Department of Neurobiology and Physiology, Northwestern University, Evanston, IL 60208, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17124323" target="_blank"〉PubMed〈/a〉
    Keywords: ARNTL Transcription Factors ; Animals ; Basic Helix-Loop-Helix Transcription Factors/genetics/*physiology ; Body Weight ; Brain/*metabolism ; Calcinosis ; Cell Cycle Proteins/genetics ; Chromosomes, Artificial, Bacterial ; *Circadian Rhythm ; Gene Expression ; Longevity ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; *Motor Activity ; Muscle, Skeletal/*metabolism ; Nuclear Proteins/genetics ; Organ Specificity ; Period Circadian Proteins ; Suprachiasmatic Nucleus/metabolism ; Tendons/pathology ; Transcription Factors/genetics
    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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    Single-Particle Measurements of Midlatitude Black Carbon and Light-Scattering Aerosols from the Boundary Layer to the Lower Stratosphere (2006)
    In:  Other Sources
    Details
    Publication Date: 2019-07-19
    Description: A single-particle soot photometer (SP2) was flown on a NASA WB-57F high-altitude research aircraft in November 2004 from Houston, Texas. The SP2 uses laser-induced incandescence to detect individual black carbon (BC) particles in an air sample in the mass range of approx.3-300 fg (approx.0.15-0.7 microns volume equivalent diameter). Scattered light is used to size the remaining non-BC aerosols in the range of approx.0.17-0.7 microns diameter. We present profiles of both aerosol types from the boundary layer to the lower stratosphere from two midlatitude flights. Results for total aerosol amounts in the size range detected by the SP2 are in good agreement with typical particle spectrometer measurements in the same region. All ambient incandescing particles were identified as BC because their incandescence properties matched those of laboratory-generated BC aerosol. Approximately 40% of these BC particles showed evidence of internal mixing (e.g., coating). Throughout profiles between 5 and 18.7 km, BC particles were less than a few percent of total aerosol number, and black carbon aerosol (BCA) mass mixing ratio showed a constant gradient with altitude above 5 km. SP2 data was compared to results from the ECHAM4/MADE and LmDzT-INCA global aerosol models. The comparison will help resolve the important systematic differences in model aerosol processes that determine BCA loadings. Further intercomparisons of models and measurements as presented here will improve the accuracy of the radiative forcing contribution from BCA.
    Keywords: Meteorology and Climatology
    Type: Journal of Geophysical Research Atmospheres (ISSN 0148-0227); 111
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    NASA TECHNICAL REPORTS
  • 6
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    A virulence locus of Pseudomonas aeruginosa encodes a protein secretion apparatus (2006)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2006-06-10
    Description: Bacterial pathogens frequently use protein secretion to mediate interactions with their hosts. Here we found that a virulence locus (HSI-I) of Pseudomonas aeruginosa encodes a protein secretion apparatus. The apparatus assembled in discrete subcellular locations and exported Hcp1, a hexameric protein that forms rings with a 40 angstrom internal diameter. Regulatory patterns of HSI-I suggested that the apparatus functions during chronic infections. We detected Hcp1 in pulmonary secretions of cystic fibrosis (CF) patients and Hcp1-specific antibodies in their sera. Thus, HSI-I likely contributes to the pathogenesis of P. aeruginosa in CF patients. HSI-I-related loci are widely distributed among bacterial pathogens and may play a general role in mediating host interactions.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2800167/" 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/PMC2800167/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mougous, Joseph D -- Cuff, Marianne E -- Raunser, Stefan -- Shen, Aimee -- Zhou, Min -- Gifford, Casey A -- Goodman, Andrew L -- Joachimiak, Grazyna -- Ordonez, Claudia L -- Lory, Stephen -- Walz, Thomas -- Joachimiak, Andrzej -- Mekalanos, John J -- AI21451/AI/NIAID NIH HHS/ -- AI26289/AI/NIAID NIH HHS/ -- GM074942/GM/NIGMS NIH HHS/ -- GM62414/GM/NIGMS NIH HHS/ -- P50 GM062414/GM/NIGMS NIH HHS/ -- P50 GM062414-02/GM/NIGMS NIH HHS/ -- U54 GM074942/GM/NIGMS NIH HHS/ -- U54 GM074942-04S2/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2006 Jun 9;312(5779):1526-30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16763151" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bacterial Proteins/*genetics/physiology/secretion ; Crystallography, X-Ray ; Cystic Fibrosis/complications/microbiology ; Humans ; Models, Molecular ; Protein Conformation ; Pseudomonas Infections/complications/microbiology ; Pseudomonas aeruginosa/*genetics/pathogenicity ; Rats ; Recombinant Fusion Proteins ; Sequence Alignment ; Virulence/genetics
    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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    Structure of a DNA glycosylase searching for lesions (2006)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2006-02-25
    Description: DNA glycosylases must interrogate millions of base pairs of undamaged DNA in order to locate and then excise one damaged nucleobase. The nature of this search process remains poorly understood. Here we report the use of disulfide cross-linking (DXL) technology to obtain structures of a bacterial DNA glycosylase, MutM, interrogating undamaged DNA. These structures, solved to 2.0 angstrom resolution, reveal the nature of the search process: The protein inserts a probe residue into the helical stack and severely buckles the target base pair, which remains intrahelical. MutM therefore actively interrogates the intact DNA helix while searching for damage.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Banerjee, Anirban -- Santos, Webster L -- Verdine, Gregory L -- F32 GM067380/GM/NIGMS NIH HHS/ -- GM044853/GM/NIGMS NIH HHS/ -- R01 CA100742/CA/NCI NIH HHS/ -- R01 GM044853/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2006 Feb 24;311(5764):1153-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16497933" target="_blank"〉PubMed〈/a〉
    Keywords: *Base Pairing ; Binding Sites ; Cross-Linking Reagents ; Crystallography, X-Ray ; DNA/*chemistry/metabolism ; *DNA Damage ; DNA Glycosylases/*chemistry/*metabolism ; Geobacillus stearothermophilus/*enzymology ; Guanine/*analogs & derivatives/analysis/metabolism ; Hydrogen Bonding ; Models, Molecular ; Nucleic Acid Conformation ; Oligodeoxyribonucleotides/chemistry/metabolism ; Protein Conformation ; Protein Structure, Secondary
    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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  • 8
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    Prion-induced amyloid heart disease with high blood infectivity in transgenic mice (2006)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2006-07-11
    Description: We investigated extraneural manifestations in scrapie-infected transgenic mice expressing prion protein lacking the glycophosphatydylinositol membrane anchor. In the brain, blood, and heart, both abnormal protease-resistant prion protein (PrPres) and prion infectivity were readily detected by immunoblot and by inoculation into nontransgenic recipients. The titer of infectious scrapie in blood plasma exceeded 10(7) 50% infectious doses per milliliter. The hearts of these transgenic mice contained PrPres-positive amyloid deposits that led to myocardial stiffness and cardiac disease.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1820586/" 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/PMC1820586/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Trifilo, Matthew J -- Yajima, Toshitaka -- Gu, Yusu -- Dalton, Nancy -- Peterson, Kirk L -- Race, Richard E -- Meade-White, Kimberly -- Portis, John L -- Masliah, Eliezer -- Knowlton, Kirk U -- Chesebro, Bruce -- Oldstone, Michael B A -- 5R01HL66424-04/HL/NHLBI NIH HHS/ -- AGO4342/PHS HHS/ -- NS041219-05/NS/NINDS NIH HHS/ -- P01 AG004342/AG/NIA NIH HHS/ -- New York, N.Y. -- Science. 2006 Jul 7;313(5783):94-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Viral-Immunobiology Laboratory, Departments of Molecular and Integrative Neurosciences and Infectology, Scripps Research Institute, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16825571" target="_blank"〉PubMed〈/a〉
    Keywords: Amyloid/*analysis ; Amyloidosis/blood/etiology/*pathology/physiopathology ; Animals ; Blotting, Western ; Cardiac Catheterization ; Coronary Vessels/chemistry/pathology ; Disease Models, Animal ; Glycosylphosphatidylinositols ; Heart Diseases/blood/etiology/*pathology/physiopathology ; Heart Function Tests ; Immunohistochemistry ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Microcirculation/chemistry/pathology ; Myocardial Contraction ; Myocardium/*chemistry/*pathology ; PrPC Proteins/chemistry ; PrPSc Proteins/*analysis/blood ; Scrapie/blood/*pathology/physiopathology ; Staining and Labeling ; Time Factors
    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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  • 9
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    Exogenous induction of cerebral beta-amyloidogenesis is governed by agent and host (2006)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2006-09-23
    Description: Protein aggregation is an established pathogenic mechanism in Alzheimer's disease, but little is known about the initiation of this process in vivo. Intracerebral injection of dilute, amyloid-beta (Abeta)-containing brain extracts from humans with Alzheimer's disease or beta-amyloid precursor protein (APP) transgenic mice induced cerebral beta-amyloidosis and associated pathology in APP transgenic mice in a time- and concentration-dependent manner. The seeding activity of brain extracts was reduced or abolished by Abeta immunodepletion, protein denaturation, or by Abeta immunization of the host. The phenotype of the exogenously induced amyloidosis depended on both the host and the source of the agent, suggesting the existence of polymorphic Abeta strains with varying biological activities reminiscent of prion strains.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Meyer-Luehmann, Melanie -- Coomaraswamy, Janaky -- Bolmont, Tristan -- Kaeser, Stephan -- Schaefer, Claudia -- Kilger, Ellen -- Neuenschwander, Anton -- Abramowski, Dorothee -- Frey, Peter -- Jaton, Anneliese L -- Vigouret, Jean-Marie -- Paganetti, Paolo -- Walsh, Dominic M -- Mathews, Paul M -- Ghiso, Jorge -- Staufenbiel, Matthias -- Walker, Lary C -- Jucker, Mathias -- NS45357/NS/NINDS NIH HHS/ -- RR-00165/RR/NCRR NIH HHS/ -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2006 Sep 22;313(5794):1781-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cellular Neurology, Hertie-Institute for Clinical Brain Research, University of Tubingen, D-72076 Tubingen, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16990547" target="_blank"〉PubMed〈/a〉
    Keywords: Aged ; Aged, 80 and over ; Aging ; Alzheimer Disease/metabolism ; Amyloid beta-Peptides/*administration & dosage/*analysis/chemistry/pharmacology ; Amyloid beta-Protein Precursor/*administration & dosage/pharmacology ; Amyloidosis/*metabolism/pathology ; Animals ; Brain/pathology ; Brain Chemistry ; Brain Diseases/*metabolism/pathology ; Female ; Hippocampus/*chemistry/pathology ; Humans ; Male ; Mice ; Mice, Transgenic ; Protein Denaturation ; Time Factors ; Tissue Extracts
    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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  • 10
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    Differential targeting of Gbetagamma-subunit signaling with small molecules (2006)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2006-04-22
    Description: G protein betagamma subunits have potential as a target for therapeutic treatment of a number of diseases. We performed virtual docking of a small-molecule library to a site on Gbetagamma subunits that mediates protein interactions. We hypothesized that differential targeting of this surface could allow for selective modulation of Gbetagamma subunit functions. Several compounds bound to Gbetagamma subunits with affinities from 0.1 to 60 muM and selectively modulated functional Gbetagamma-protein-protein interactions in vitro, chemotactic peptide signaling pathways in HL-60 leukocytes, and opioid receptor-dependent analgesia in vivo. These data demonstrate an approach for modulation of G protein-coupled receptor signaling that may represent an important therapeutic strategy.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bonacci, Tabetha M -- Mathews, Jennifer L -- Yuan, Chujun -- Lehmann, David M -- Malik, Sundeep -- Wu, Dianqing -- Font, Jose L -- Bidlack, Jean M -- Smrcka, Alan V -- GM60286/GM/NIGMS NIH HHS/ -- HL-T3207949/HL/NHLBI NIH HHS/ -- HL080706/HL/NHLBI NIH HHS/ -- K05-DA00360/DA/NIDA NIH HHS/ -- R01 CA132317/CA/NCI NIH HHS/ -- R01 GM054597/GM/NIGMS NIH HHS/ -- R01 GM054597-09/GM/NIGMS NIH HHS/ -- R01 HL080706/HL/NHLBI NIH HHS/ -- R01 HL080706-10/HL/NHLBI NIH HHS/ -- R01 HL080706-11/HL/NHLBI NIH HHS/ -- T32DA07232/DA/NIDA NIH HHS/ -- New York, N.Y. -- Science. 2006 Apr 21;312(5772):443-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology and Physiology, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16627746" target="_blank"〉PubMed〈/a〉
    Keywords: Analgesics/pharmacology ; Animals ; Binding Sites ; Binding, Competitive ; Cell Line ; Computer Simulation ; Cyclohexanes/chemistry/*metabolism/*pharmacology ; Drug Evaluation, Preclinical/*methods ; Enzyme-Linked Immunosorbent Assay ; G-Protein-Coupled Receptor Kinase 2 ; GTP-Binding Protein alpha Subunits/metabolism ; GTP-Binding Protein beta Subunits/chemistry/*metabolism ; GTP-Binding Protein gamma Subunits/chemistry/*metabolism ; HL-60 Cells ; Humans ; Isoenzymes/metabolism ; Mice ; Mice, Inbred ICR ; Mitogen-Activated Protein Kinases/metabolism ; Molecular Structure ; Morphine/pharmacology ; N-Formylmethionine Leucyl-Phenylalanine/metabolism ; Peptide Library ; Peptides/*metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; Phospholipase C beta ; Protein Binding ; Protein Interaction Mapping ; *Signal Transduction ; Software ; Structure-Activity Relationship ; Type C Phospholipases/metabolism ; Xanthenes/chemistry/*metabolism/*pharmacology ; beta-Adrenergic Receptor Kinases/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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