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  • Mice  (49)
  • Aerospace Medicine  (36)
  • Earth Resources and Remote Sensing  (27)
  • 2020-2022
  • 2005-2009  (112)
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  • 2007  (112)
  • 1
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    Ketamine-induced loss of phenotype of fast-spiking interneurons is mediated by NADPH-oxidase (2007)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2007-12-08
    Description: Abuse of the dissociative anesthetic ketamine can lead to a syndrome indistinguishable from schizophrenia. In animals, repetitive exposure to this N-methyl-d-aspartate-receptor antagonist induces the dysfunction of a subset of cortical fast-spiking inhibitory interneurons, with loss of expression of parvalbumin and the gamma-aminobutyric acid-producing enzyme GAD67. We show here that exposure of mice to ketamine induced a persistent increase in brain superoxide due to activation in neurons of reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. Decreasing superoxide production prevented the effects of ketamine on inhibitory interneurons in the prefrontal cortex. These results suggest that NADPH oxidase may represent a novel target for the treatment of ketamine-induced psychosis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Behrens, M Margarita -- Ali, Sameh S -- Dao, Diep N -- Lucero, Jacinta -- Shekhtman, Grigoriy -- Quick, Kevin L -- Dugan, Laura L -- New York, N.Y. -- Science. 2007 Dec 7;318(5856):1645-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, Division of Geriatric Medicine, University of California San Diego, La Jolla, CA 92093-0746, USA. mbehrens@ucsd.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18063801" target="_blank"〉PubMed〈/a〉
    Keywords: Acetophenones/pharmacology ; Animals ; Brain/*drug effects/enzymology/metabolism ; Cells, Cultured ; Enzyme Activation ; Enzyme Inhibitors/pharmacology ; Glutamate Decarboxylase/metabolism ; Interneurons/*drug effects/enzymology/*metabolism ; Ketamine/*pharmacology ; Male ; Membrane Glycoproteins/*metabolism ; Mice ; Mice, Inbred C57BL ; NADPH Oxidase/*metabolism ; Oxidation-Reduction ; Parvalbumins/metabolism ; Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors/metabolism ; Superoxides/*metabolism ; Synaptic Transmission/drug effects ; Synaptosomes/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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    Seasonal Snow Extent and Snow Mass in South America Using SMMR and SSM/I Passive Microwave Data (1979-2003) (2007)
    In:  CASI
    Details
    Publication Date: 2018-06-06
    Description: Seasonal snow cover in South America was examined in this study using passive microwave satellite data from the Scanning Multichannel Microwave Radiometer (SMMR) on board the Nimbus-satellite and the Special Sensor Microwave Imagers (SSM/I) on board Defense Meteorological Satellite Program (DMSP) satellites. For the period from 1979-2003, both snow cover extent and snow depth (snow mass) were investigated during coldest months (May-September), primarily in the Patagonia area of Argentina and in Chile. Most of the seasonal snow in South America is in the Patagonia region of Argentina. Since winter temperatures in this region are often above freezing, the coldest winter month was found to be the month having the most extensive snow cover and also usually the month having the deepest snow cover as well. Sharp year-to-year differences were recorded using the passive microwave observations. The average snow cover extent for July, the month with the greatest average snow extent during the 25-year period of record, is 320,700 km(exp 2). In July of 1984, the average monthly snow cover was 701,250 km(exp 2) - the most extensive coverage observed between 1979 and 2003. However, in July of 1989, snow cover extent was only 120 km(exp 2). The 25-year period of record shows a sinusoidal like pattern, though there appears to be no obvious trend in either increasing or decreasing snow extent or snow mass between 1979 and 2003.
    Keywords: Earth Resources and Remote Sensing
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    NASA TECHNICAL REPORTS
  • 3
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    Effect Of Spaceflight On Microbial Gene Expression And Virulence: Preliminary Results From Microbe Payload Flown On-Board STS-115 (2007)
    In:  Other Sources
    Details
    Publication Date: 2019-07-19
    Description: Human presence in space, whether permanent or temporary, is accompanied by the presence of microbes. However, the extent of microbial changes in response to spaceflight conditions and the corresponding changes to infectious disease risk is unclear. Previous studies have indicated that spaceflight weakens the immune system in humans and animals. In addition, preflight and in-flight monitoring of the International Space Station (ISS) and other spacecraft indicates the presence of opportunistic pathogens and the potential of obligate pathogens. Altered antibiotic resistance of microbes in flight has also been shown. As astronauts and cosmonauts live for longer periods in a closed environment, especially one using recycled water and air, there is an increased risk to crewmembers of infectious disease events occurring in-flight. Therefore, understanding how the space environment affects microorganisms and their disease potential is critically important for spaceflight missions and requires further study. The goal of this flight experiment, operationally called MICROBE, is to utilize three model microbial pathogens, Salmonella typhimurium, Pseudomonas aeruginosa, and Candida albicans to examine the global effects of spaceflight on microbial gene expression and virulence attributes. Specifically, the aims are (1) to perform microarray-mediated gene expression profiling of S. typhimurium, P. aeruginosa, and C. albicans, in response to spaceflight in comparison to ground controls and (2) to determine the effect of spaceflight on the virulence potential of these microorganisms immediately following their return from spaceflight using murine models. The model microorganisms were selected as they have been isolated from preflight or in-flight monitoring, represent different degrees of pathogenic behavior, are well characterized, and have sequenced genomes with available microarrays. In particular, extensive studies of S. typhimurium by the Principal Investigator, Dr. Nickerson, using ground-based analog systems demonstrate important changes in the genotypic, phenotypic, and virulence characteristics of this pathogen resulting from exposure to a flight-like environment (i.e. modeled microgravity).
    Keywords: Aerospace Medicine
    Type: NASA HRP Investigators'' Workshop; Feb 12, 2007 - Feb 14, 2007; United States
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  • 4
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    The genomic landscapes of human breast and colorectal cancers (2007)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2007-10-13
    Description: Human cancer is caused by the accumulation of mutations in oncogenes and tumor suppressor genes. To catalog the genetic changes that occur during tumorigenesis, we isolated DNA from 11 breast and 11 colorectal tumors and determined the sequences of the genes in the Reference Sequence database in these samples. Based on analysis of exons representing 20,857 transcripts from 18,191 genes, we conclude that the genomic landscapes of breast and colorectal cancers are composed of a handful of commonly mutated gene "mountains" and a much larger number of gene "hills" that are mutated at low frequency. We describe statistical and bioinformatic tools that may help identify mutations with a role in tumorigenesis. These results have implications for understanding the nature and heterogeneity of human cancers and for using personal genomics for tumor diagnosis and therapy.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wood, Laura D -- Parsons, D Williams -- Jones, Sian -- Lin, Jimmy -- Sjoblom, Tobias -- Leary, Rebecca J -- Shen, Dong -- Boca, Simina M -- Barber, Thomas -- Ptak, Janine -- Silliman, Natalie -- Szabo, Steve -- Dezso, Zoltan -- Ustyanksky, Vadim -- Nikolskaya, Tatiana -- Nikolsky, Yuri -- Karchin, Rachel -- Wilson, Paul A -- Kaminker, Joshua S -- Zhang, Zemin -- Croshaw, Randal -- Willis, Joseph -- Dawson, Dawn -- Shipitsin, Michail -- Willson, James K V -- Sukumar, Saraswati -- Polyak, Kornelia -- Park, Ben Ho -- Pethiyagoda, Charit L -- Pant, P V Krishna -- Ballinger, Dennis G -- Sparks, Andrew B -- Hartigan, James -- Smith, Douglas R -- Suh, Erick -- Papadopoulos, Nickolas -- Buckhaults, Phillip -- Markowitz, Sanford D -- Parmigiani, Giovanni -- Kinzler, Kenneth W -- Velculescu, Victor E -- Vogelstein, Bert -- CA 43460/CA/NCI NIH HHS/ -- CA 57345/CA/NCI NIH HHS/ -- CA109274/CA/NCI NIH HHS/ -- CA112828/CA/NCI NIH HHS/ -- CA121113/CA/NCI NIH HHS/ -- CA62924/CA/NCI NIH HHS/ -- GM070219/GM/NIGMS NIH HHS/ -- GM07309/GM/NIGMS NIH HHS/ -- P30-CA43703/CA/NCI NIH HHS/ -- RR017698/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 2007 Nov 16;318(5853):1108-13. Epub 2007 Oct 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Ludwig Center for Cancer Genetics and Therapeutics and Howard Hughes Medical Institute at Johns Hopkins Kimmel Cancer Center, Baltimore, MD 21231, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17932254" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Breast Neoplasms/*genetics/metabolism ; Cell Line ; Chromosome Mapping ; Colorectal Neoplasms/*genetics/metabolism ; Computational Biology ; DNA, Neoplasm ; Databases, Genetic ; Genes, Neoplasm ; Genome, Human ; Humans ; Metabolic Networks and Pathways/genetics ; Mice ; Mutation ; Neoplasm Proteins/genetics/metabolism ; Sequence Analysis, DNA
    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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    The after-hours mutant reveals a role for Fbxl3 in determining mammalian circadian period (2007)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2007-04-28
    Description: By screening N-ethyl-N-nitrosourea-mutagenized animals for alterations in rhythms of wheel-running activity, we identified a mouse mutation, after hours (Afh). The mutation, a Cys(358)Ser substitution in Fbxl3, an F-box protein with leucine-rich repeats, results in long free-running rhythms of about 27 hours in homozygotes. Circadian transcriptional and translational oscillations are attenuated in Afh mice. The Afh allele significantly affected Per2 expression and delayed the rate of Cry protein degradation in Per2::Luciferase tissue slices. Our in vivo and in vitro studies reveal a central role for Fbxl3 in mammalian circadian timekeeping.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Godinho, Sofia I H -- Maywood, Elizabeth S -- Shaw, Linda -- Tucci, Valter -- Barnard, Alun R -- Busino, Luca -- Pagano, Michele -- Kendall, Rachel -- Quwailid, Mohamed M -- Romero, M Rosario -- O'neill, John -- Chesham, Johanna E -- Brooker, Debra -- Lalanne, Zuzanna -- Hastings, Michael H -- Nolan, Patrick M -- MC_U105170643/Medical Research Council/United Kingdom -- MC_U142684172/Medical Research Council/United Kingdom -- MC_U142684173/Medical Research Council/United Kingdom -- MC_U142684175/Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2007 May 11;316(5826):897-900. Epub 2007 Apr 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Medical Research Council (MRC) Mammalian Genetics Unit, Harwell, Oxfordshire OX11 0RD, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17463252" target="_blank"〉PubMed〈/a〉
    Keywords: ARNTL Transcription Factors ; Amino Acid Sequence ; Amino Acid Substitution ; Animals ; Basic Helix-Loop-Helix Transcription Factors/genetics/metabolism ; CLOCK Proteins ; COS Cells ; Cell Cycle Proteins/genetics/metabolism ; Cercopithecus aethiops ; *Circadian Rhythm/genetics ; Crosses, Genetic ; Cryptochromes ; F-Box Proteins/*genetics/*physiology ; Female ; Flavoproteins/genetics/metabolism ; Gene Expression Regulation ; Liver/metabolism ; Lung/metabolism ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C3H ; Molecular Sequence Data ; Nuclear Proteins/genetics/metabolism ; Period Circadian Proteins ; *Point Mutation ; Suprachiasmatic Nucleus/metabolism ; Trans-Activators/genetics/metabolism ; Transcription Factors/genetics/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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  • 6
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    Promotion of tissue inflammation by the immune receptor Tim-3 expressed on innate immune cells (2007)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2007-11-17
    Description: CD4+ T helper 1 (TH1) cells are important mediators of inflammation and are regulated by numerous pathways, including the negative immune receptor Tim-3. We found that Tim-3 is constitutively expressed on cells of the innate immune system in both mice and humans, and that it can synergize with Toll-like receptors. Moreover, an antibody agonist of Tim-3 acted as an adjuvant during induced immune responses, and Tim-3 ligation induced distinct signaling events in T cells and dendritic cells; the latter finding could explain the apparent divergent functions of Tim-3 in these cell types. Thus, by virtue of differential expression on innate versus adaptive immune cells, Tim-3 can either promote or terminate TH1 immunity and may be able to influence a range of inflammatory conditions.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Anderson, Ana C -- Anderson, David E -- Bregoli, Lisa -- Hastings, William D -- Kassam, Nasim -- Lei, Charles -- Chandwaskar, Rucha -- Karman, Jozsef -- Su, Ee W -- Hirashima, Mitsuomi -- Bruce, Jeffrey N -- Kane, Lawrence P -- Kuchroo, Vijay K -- Hafler, David A -- R01 AI067544/AI/NIAID NIH HHS/ -- R01 AI067544-01A2/AI/NIAID NIH HHS/ -- R56 AI067544/AI/NIAID NIH HHS/ -- R56 AI067544-01A1/AI/NIAID NIH HHS/ -- R56 AI067544-02/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2007 Nov 16;318(5853):1141-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Molecular Immunology, Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18006747" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, CD11b/immunology ; Astrocytes/immunology ; Central Nervous System Neoplasms/immunology ; Dendritic Cells/immunology ; Encephalomyelitis, Autoimmune, Experimental/immunology ; Galectins/immunology ; Glioblastoma/immunology ; Humans ; Immunity, Innate ; Inflammation Mediators/*immunology ; Lipopolysaccharides/immunology ; Macrophages/immunology ; Membrane Proteins/biosynthesis/*immunology ; Mice ; Microglia/immunology ; Multiple Sclerosis/immunology ; Rats ; Receptors, Immunologic/biosynthesis/*immunology ; Receptors, Virus/biosynthesis/*immunology ; Signal Transduction ; T-Lymphocytes/immunology ; Th1 Cells/*immunology ; Toll-Like Receptors
    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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    Immunization by avian H5 influenza hemagglutinin mutants with altered receptor binding specificity (2007)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2007-08-11
    Description: Influenza virus entry is mediated by the receptor binding domain (RBD) of its spike, the hemagglutinin (HA). Adaptation of avian viruses to humans is associated with HA specificity for alpha2,6- rather than alpha2,3-linked sialic acid (SA) receptors. Here, we define mutations in influenza A subtype H5N1 (avian) HA that alter its specificity for SA either by decreasing alpha2,3- or increasing alpha2,6-SA recognition. RBD mutants were used to develop vaccines and monoclonal antibodies that neutralized new variants. Structure-based modification of HA specificity can guide the development of preemptive vaccines and therapeutic monoclonal antibodies that can be evaluated before the emergence of human-adapted H5N1 strains.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2367145/" 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/PMC2367145/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yang, Zhi-Yong -- Wei, Chih-Jen -- Kong, Wing-Pui -- Wu, Lan -- Xu, Ling -- Smith, David F -- Nabel, Gary J -- Z99 AI999999/Intramural NIH HHS/ -- New York, N.Y. -- Science. 2007 Aug 10;317(5839):825-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health, Building 40, Room 4502, Mailstop Code MSC-3005, 40 Convent Drive, Bethesda, MD 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17690300" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies, Monoclonal/immunology ; Antibodies, Viral/immunology ; Carbohydrate Conformation ; Cell Line ; Female ; Genes, Viral ; Hemagglutination Inhibition Tests ; Hemagglutinin Glycoproteins, Influenza Virus/*genetics/*immunology/metabolism ; Humans ; Influenza A Virus, H5N1 Subtype/*genetics/*immunology/metabolism ; Influenza Vaccines/immunology ; Mice ; Mice, Inbred BALB C ; Molecular Sequence Data ; *Mutation ; Neutralization Tests ; Receptors, Virus/*metabolism ; Sialic Acids/*metabolism ; Vaccination
    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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    Localization of a stable neural correlate of associative memory (2007)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2007-09-01
    Description: Do learning and retrieval of a memory activate the same neurons? Does the number of reactivated neurons correlate with memory strength? We developed a transgenic mouse that enables the long-lasting genetic tagging of c-fos-active neurons. We found neurons in the basolateral amygdala that are activated during Pavlovian fear conditioning and are reactivated during memory retrieval. The number of reactivated neurons correlated positively with the behavioral expression of the fear memory, indicating a stable neural correlate of associative memory. The ability to manipulate these neurons genetically should allow a more precise dissection of the molecular mechanisms of memory encoding within a distributed neuronal network.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Reijmers, Leon G -- Perkins, Brian L -- Matsuo, Naoki -- Mayford, Mark -- 5-74653/PHS HHS/ -- 57368/PHS HHS/ -- New York, N.Y. -- Science. 2007 Aug 31;317(5842):1230-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell Biology, 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/17761885" target="_blank"〉PubMed〈/a〉
    Keywords: Amygdala/cytology/*physiology ; Animals ; Brain Mapping ; Conditioning (Psychology) ; Extinction, Psychological ; Fear ; Genes, fos ; Learning ; *Memory ; *Mental Recall ; Mice ; Mice, Transgenic ; Nerve Net/*physiology ; Neuronal Plasticity ; Neurons/*physiology
    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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    An X chromosome gene, WTX, is commonly inactivated in Wilms tumor (2007)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2007-01-06
    Description: Wilms tumor is a pediatric kidney cancer associated with inactivation of the WT1 tumor-suppressor gene in 5 to 10% of cases. Using a high-resolution screen for DNA copy-number alterations in Wilms tumor, we identified somatic deletions targeting a previously uncharacterized gene on the X chromosome. This gene, which we call WTX, is inactivated in approximately one-third of Wilms tumors (15 of 51 tumors). Tumors with mutations in WTX lack WT1 mutations, and both genes share a restricted temporal and spatial expression pattern in normal renal precursors. In contrast to biallelic inactivation of autosomal tumor-suppressor genes, WTX is inactivated by a monoallelic "single-hit" event targeting the single X chromosome in tumors from males and the active X chromosome in tumors from females.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rivera, Miguel N -- Kim, Woo Jae -- Wells, Julie -- Driscoll, David R -- Brannigan, Brian W -- Han, Moonjoo -- Kim, James C -- Feinberg, Andrew P -- Gerald, William L -- Vargas, Sara O -- Chin, Lynda -- Iafrate, A John -- Bell, Daphne W -- Haber, Daniel A -- P01-CA101942/CA/NCI NIH HHS/ -- R37 CA054358/CA/NCI NIH HHS/ -- R37 CA054358-17/CA/NCI NIH HHS/ -- R37-CA058596/CA/NCI NIH HHS/ -- T32-CA009216/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2007 Feb 2;315(5812):642-5. Epub 2007 Jan 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Massachusetts General Hospital Cancer Center, Harvard Medical Center, Boston, MA 02114, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17204608" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Proteins, Signal Transducing ; Alleles ; Amino Acid Sequence ; Animals ; Cell Line ; Chromosome Deletion ; Chromosomes, Human, X/*genetics ; Female ; Gene Expression ; *Gene Silencing ; *Genes, Wilms Tumor ; Heterozygote ; Humans ; In Situ Hybridization, Fluorescence ; Kidney/embryology/metabolism ; Kidney Neoplasms/*genetics ; Male ; Mice ; Mice, Inbred C57BL ; Molecular Sequence Data ; Mutation ; Point Mutation ; Tumor Suppressor Proteins/chemistry/*genetics/physiology ; Wilms Tumor/*genetics ; beta Catenin/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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  • 10
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    Anti-inflammatory activity of human IgG4 antibodies by dynamic Fab arm exchange (2007)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2007-09-18
    Description: Antibodies play a central role in immunity by forming an interface with the innate immune system and, typically, mediate proinflammatory activity. We describe a novel posttranslational modification that leads to anti-inflammatory activity of antibodies of immunoglobulin G, isotype 4 (IgG4). IgG4 antibodies are dynamic molecules that exchange Fab arms by swapping a heavy chain and attached light chain (half-molecule) with a heavy-light chain pair from another molecule, which results in bispecific antibodies. Mutagenesis studies revealed that the third constant domain is critical for this activity. The impact of IgG4 Fab arm exchange was confirmed in vivo in a rhesus monkey model with experimental autoimmune myasthenia gravis. IgG4 Fab arm exchange is suggested to be an important biological mechanism that provides the basis for the anti-inflammatory activity attributed to IgG4 antibodies.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉van der Neut Kolfschoten, Marijn -- Schuurman, Janine -- Losen, Mario -- Bleeker, Wim K -- Martinez-Martinez, Pilar -- Vermeulen, Ellen -- den Bleker, Tamara H -- Wiegman, Luus -- Vink, Tom -- Aarden, Lucien A -- De Baets, Marc H -- van de Winkel, Jan G J -- Aalberse, Rob C -- Parren, Paul W H I -- New York, N.Y. -- Science. 2007 Sep 14;317(5844):1554-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Sanquin Research-AMC Landsteiner Laboratory, Department of Immunopathology, Plesmanlaan 125, 1066 CX Amsterdam, the Netherlands.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17872445" target="_blank"〉PubMed〈/a〉
    Keywords: Allergens/immunology ; Animals ; Antibodies, Bispecific/immunology ; Antibodies, Monoclonal/immunology ; Antigens, CD20/immunology ; Antigens, Plant ; Autoantibodies/immunology ; Glycoproteins/immunology ; Humans ; Immunoglobulin Constant Regions/chemistry ; Immunoglobulin Fab Fragments/*chemistry/*immunology/metabolism ; Immunoglobulin G/*chemistry/*immunology/metabolism ; Immunoglobulin Heavy Chains ; Macaca mulatta ; Mice ; Mutation ; Myasthenia Gravis, Autoimmune, Experimental/immunology/prevention & control ; Protein Processing, Post-Translational ; Receptor, Epidermal Growth Factor/immunology ; Receptors, Cholinergic/immunology
    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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