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  • 1
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    Biodiversity and biogeography of phages in modern stromatolites and thrombolites (2008)
    Nature Publishing Group (NPG)
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    Publication Date: 2008-03-04
    Description: Viruses, and more particularly phages (viruses that infect bacteria), represent one of the most abundant living entities in aquatic and terrestrial environments. The biogeography of phages has only recently been investigated and so far reveals a cosmopolitan distribution of phage genetic material (or genotypes). Here we address this cosmopolitan distribution through the analysis of phage communities in modern microbialites, the living representatives of one of the most ancient life forms on Earth. On the basis of a comparative metagenomic analysis of viral communities associated with marine (Highborne Cay, Bahamas) and freshwater (Pozas Azules II and Rio Mesquites, Mexico) microbialites, we show that some phage genotypes are geographically restricted. The high percentage of unknown sequences recovered from the three metagenomes (〉97%), the low percentage similarities with sequences from other environmental viral (n = 42) and microbial (n = 36) metagenomes, and the absence of viral genotypes shared among microbialites indicate that viruses are genetically unique in these environments. Identifiable sequences in the Highborne Cay metagenome were dominated by single-stranded DNA microphages that were not detected in any other samples examined, including sea water, fresh water, sediment, terrestrial, extreme, metazoan-associated and marine microbial mats. Finally, a marine signature was present in the phage community of the Pozas Azules II microbialites, even though this environment has not been in contact with the ocean for tens of millions of years. Taken together, these results prove that viruses in modern microbialites display biogeographical variability and suggest that they may be derived from an ancient community.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Desnues, Christelle -- Rodriguez-Brito, Beltran -- Rayhawk, Steve -- Kelley, Scott -- Tran, Tuong -- Haynes, Matthew -- Liu, Hong -- Furlan, Mike -- Wegley, Linda -- Chau, Betty -- Ruan, Yijun -- Hall, Dana -- Angly, Florent E -- Edwards, Robert A -- Li, Linlin -- Thurber, Rebecca Vega -- Reid, R Pamela -- Siefert, Janet -- Souza, Valeria -- Valentine, David L -- Swan, Brandon K -- Breitbart, Mya -- Rohwer, Forest -- England -- Nature. 2008 Mar 20;452(7185):340-3. doi: 10.1038/nature06735. Epub 2008 Mar 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, San Diego State University, San Diego, California 92182, USA. cdesnues@yahoo.fr〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18311127" target="_blank"〉PubMed〈/a〉
    Keywords: Bacteriophages/classification/genetics/*isolation & purification/*physiology ; Bahamas ; *Biodiversity ; Capsid/chemistry ; Computational Biology ; DNA, Viral/analysis/genetics ; *Ecosystem ; Fresh Water/microbiology/virology ; Genome, Viral/genetics ; Genomics ; *Geography ; Geologic Sediments/microbiology/virology ; Mexico ; Molecular Sequence Data ; Phylogeny ; Proteome/metabolism ; Seawater/microbiology/virology ; *Water Microbiology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 2
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    Bone-marrow adipocytes as negative regulators of the haematopoietic microenvironment (2009)
    Nature Publishing Group (NPG)
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    Publication Date: 2009-06-12
    Description: Osteoblasts and endothelium constitute functional niches that support haematopoietic stem cells in mammalian bone marrow. Adult bone marrow also contains adipocytes, the number of which correlates inversely with the haematopoietic activity of the marrow. Fatty infiltration of haematopoietic red marrow follows irradiation or chemotherapy and is a diagnostic feature in biopsies from patients with marrow aplasia. To explore whether adipocytes influence haematopoiesis or simply fill marrow space, we compared the haematopoietic activity of distinct regions of the mouse skeleton that differ in adiposity. Here we show, by flow cytometry, colony-forming activity and competitive repopulation assay, that haematopoietic stem cells and short-term progenitors are reduced in frequency in the adipocyte-rich vertebrae of the mouse tail relative to the adipocyte-free vertebrae of the thorax. In lipoatrophic A-ZIP/F1 'fatless' mice, which are genetically incapable of forming adipocytes, and in mice treated with the peroxisome proliferator-activated receptor-gamma inhibitor bisphenol A diglycidyl ether, which inhibits adipogenesis, marrow engraftment after irradiation is accelerated relative to wild-type or untreated mice. These data implicate adipocytes as predominantly negative regulators of the bone-marrow microenvironment, and indicate that antagonizing marrow adipogenesis may enhance haematopoietic recovery in clinical bone-marrow transplantation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2831539/" 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/PMC2831539/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Naveiras, Olaia -- Nardi, Valentina -- Wenzel, Pamela L -- Hauschka, Peter V -- Fahey, Frederic -- Daley, George Q -- DP1 OD000256/OD/NIH HHS/ -- DP1 OD000256-01/OD/NIH HHS/ -- R01 DK059279/DK/NIDDK NIH HHS/ -- R01 DK059279-06/DK/NIDDK NIH HHS/ -- R01 DK070055/DK/NIDDK NIH HHS/ -- R01 DK070055-01/DK/NIDDK NIH HHS/ -- T32- HL -7623/HL/NHLBI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2009 Jul 9;460(7252):259-63. doi: 10.1038/nature08099. Epub 2009 Jun 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Pediatric Hematology/Oncology, Children's Hospital Boston and Dana Farber Cancer Institute, Massachusetts 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19516257" target="_blank"〉PubMed〈/a〉
    Keywords: Adipocytes/cytology/drug effects/*physiology ; Adipogenesis/drug effects ; Adiposity/physiology ; Animals ; Benzhydryl Compounds ; Bone Marrow Cells/*cytology/*metabolism ; Bone Marrow Transplantation ; Cell Line ; Epoxy Compounds/pharmacology ; Femur ; *Hematopoiesis/drug effects ; Hematopoietic Stem Cells/cytology/metabolism ; Homeostasis ; Mice ; Mice, Inbred C57BL ; Osteogenesis ; Spine/cytology/metabolism ; Stromal Cells ; Tail ; Thorax ; Tibia
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 3
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    Early-warning signals for critical transitions (2009)
    Nature Publishing Group (NPG)
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    Publication Date: 2009-09-04
    Description: Complex dynamical systems, ranging from ecosystems to financial markets and the climate, can have tipping points at which a sudden shift to a contrasting dynamical regime may occur. Although predicting such critical points before they are reached is extremely difficult, work in different scientific fields is now suggesting the existence of generic early-warning signals that may indicate for a wide class of systems if a critical threshold is approaching.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Scheffer, Marten -- Bascompte, Jordi -- Brock, William A -- Brovkin, Victor -- Carpenter, Stephen R -- Dakos, Vasilis -- Held, Hermann -- van Nes, Egbert H -- Rietkerk, Max -- Sugihara, George -- England -- Nature. 2009 Sep 3;461(7260):53-9. doi: 10.1038/nature08227.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Environmental Sciences, Wageningen University, PO Box 47, 6700 AA Wageningen, The Netherlands. marten.scheffer@wur.nl〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19727193" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Asthma/physiopathology ; Climate ; *Ecosystem ; Eutrophication ; Extinction, Biological ; Humans ; *Models, Biological ; *Models, Economic ; Seizures/physiopathology ; Stochastic Processes
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 4
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    Surface hydrophobin prevents immune recognition of airborne fungal spores (2009)
    Nature Publishing Group (NPG)
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    Publication Date: 2009-08-29
    Description: The air we breathe is filled with thousands of fungal spores (conidia) per cubic metre, which in certain composting environments can easily exceed 10(9) per cubic metre. They originate from more than a hundred fungal species belonging mainly to the genera Cladosporium, Penicillium, Alternaria and Aspergillus. Although these conidia contain many antigens and allergens, it is not known why airborne fungal microflora do not activate the host innate immune cells continuously and do not induce detrimental inflammatory responses following their inhalation. Here we show that the surface layer on the dormant conidia masks their recognition by the immune system and hence prevents immune response. To explore this, we used several fungal members of the airborne microflora, including the human opportunistic fungal pathogen Aspergillus fumigatus, in in vitro assays with dendritic cells and alveolar macrophages and in in vivo murine experiments. In A. fumigatus, this surface 'rodlet layer' is composed of hydrophobic RodA protein covalently bound to the conidial cell wall through glycosylphosphatidylinositol-remnants. RodA extracted from conidia of A. fumigatus was immunologically inert and did not induce dendritic cell or alveolar macrophage maturation and activation, and failed to activate helper T-cell immune responses in vivo. The removal of this surface 'rodlet/hydrophobin layer' either chemically (using hydrofluoric acid), genetically (DeltarodA mutant) or biologically (germination) resulted in conidial morphotypes inducing immune activation. All these observations show that the hydrophobic rodlet layer on the conidial cell surface immunologically silences airborne moulds.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Aimanianda, Vishukumar -- Bayry, Jagadeesh -- Bozza, Silvia -- Kniemeyer, Olaf -- Perruccio, Katia -- Elluru, Sri Ramulu -- Clavaud, Cecile -- Paris, Sophie -- Brakhage, Axel A -- Kaveri, Srini V -- Romani, Luigina -- Latge, Jean-Paul -- England -- Nature. 2009 Aug 27;460(7259):1117-21. doi: 10.1038/nature08264.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Unite des Aspergillus, Institut Pasteur, Paris F-75015, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19713928" target="_blank"〉PubMed〈/a〉
    Keywords: Adoptive Transfer ; Air Microbiology ; Allergens ; Animals ; Antigens, Fungal/chemistry/genetics/*immunology ; Antigens, Plant ; Aspergillus fumigatus/chemistry/immunology/physiology ; CD4-Positive T-Lymphocytes/immunology ; Cathepsins ; Cells, Cultured ; Dendritic Cells/cytology/immunology/transplantation ; Fungal Proteins ; Humans ; Hydrofluoric Acid/chemistry ; Immune System/immunology ; Lymphocyte Activation ; Macrophages, Alveolar/immunology ; Mice ; Mice, Inbred C57BL ; Spores, Fungal/chemistry/genetics/*immunology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 5
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    Cell-cycle restriction limits DNA damage and maintains self-renewal of leukaemia stem cells (2009)
    Nature Publishing Group (NPG)
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    Publication Date: 2009-01-06
    Description: Rare cells with the properties of stem cells are integral to the development and perpetuation of leukaemias. A defining characteristic of stem cells is their capacity to self-renew, which is markedly extended in leukaemia stem cells. The underlying molecular mechanisms, however, are largely unknown. Here we demonstrate that expression of the cell-cycle inhibitor p21 is indispensable for maintaining self-renewal of leukaemia stem cells. Expression of leukaemia-associated oncogenes in mouse haematopoietic stem cells (HSCs) induces DNA damage and activates a p21-dependent cellular response, which leads to reversible cell-cycle arrest and DNA repair. Activated p21 is critical in preventing excess DNA-damage accumulation and functional exhaustion of leukaemic stem cells. These data unravel the oncogenic potential of p21 and suggest that inhibition of DNA repair mechanisms might function as potent strategy for the eradication of the slowly proliferating leukaemia stem cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Viale, Andrea -- De Franco, Francesca -- Orleth, Annette -- Cambiaghi, Valeria -- Giuliani, Virginia -- Bossi, Daniela -- Ronchini, Chiara -- Ronzoni, Simona -- Muradore, Ivan -- Monestiroli, Silvia -- Gobbi, Alberto -- Alcalay, Myriam -- Minucci, Saverio -- Pelicci, Pier Giuseppe -- England -- Nature. 2009 Jan 1;457(7225):51-6. doi: 10.1038/nature07618.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Experimental Oncology at the IFOM-IEO Campus, European Institute of Oncology, IEO, 20141 Milan, Italy. andrea.viale@ifom-ieo-campus.it〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19122635" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Count ; *Cell Cycle/genetics ; Cell Division ; Core Binding Factor Alpha 2 Subunit/genetics/metabolism ; Cyclin-Dependent Kinase Inhibitor p21/deficiency/genetics/*metabolism ; *DNA Damage/genetics ; DNA Repair ; Fibroblasts ; Gene Expression Regulation, Neoplastic ; Leukemia/*pathology ; Mice ; Mice, Inbred C57BL ; Neoplastic Stem Cells/cytology/*pathology ; Oncogene Proteins, Fusion/genetics/metabolism ; Up-Regulation
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 6
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    Modulation of gene expression via disruption of NF-kappaB signaling by a bacterial small molecule (2008)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2008-06-21
    Description: The control of innate immune responses through activation of the nuclear transcription factor NF-kappaB is essential for the elimination of invading microbial pathogens. We showed that the bacterial N-(3-oxo-dodecanoyl) homoserine lactone (C12) selectively impairs the regulation of NF-kappaB functions in activated mammalian cells. The consequence is specific repression of stimulus-mediated induction of NF-kappaB-responsive genes encoding inflammatory cytokines and other immune regulators. These findings uncover a strategy by which C12-producing opportunistic pathogens, such as Pseudomonas aeruginosa, attenuate the innate immune system to establish and maintain local persistent infection in humans, for example, in cystic fibrosis patients.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kravchenko, Vladimir V -- Kaufmann, Gunnar F -- Mathison, John C -- Scott, David A -- Katz, Alexander Z -- Grauer, David C -- Lehmann, Mandy -- Meijler, Michael M -- Janda, Kim D -- Ulevitch, Richard J -- New York, N.Y. -- Science. 2008 Jul 11;321(5886):259-63. doi: 10.1126/science.1156499. Epub 2008 Jun 19.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Immunology and Microbial Sciences, Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18566250" target="_blank"〉PubMed〈/a〉
    Keywords: 4-Butyrolactone/*analogs & derivatives/physiology ; Adult ; Animals ; Cyclic AMP Response Element-Binding Protein/metabolism ; Cystic Fibrosis/microbiology ; Female ; *Gene Expression Regulation ; Homoserine/*analogs & derivatives/physiology ; Humans ; I-kappa B Kinase/metabolism ; I-kappa B Proteins/metabolism ; Immunity, Innate ; Interferon-gamma/immunology ; Lipopolysaccharides/immunology ; Macrophage Activation ; Macrophages/*immunology/*metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Middle Aged ; NF-kappa B/*metabolism ; Phosphorylation ; Pseudomonas Infections/immunology/microbiology ; Pseudomonas aeruginosa/immunology/*pathogenicity/physiology ; *Signal Transduction ; Toll-Like Receptors/metabolism ; Transcription Factor RelA/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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  • 7
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    Oceanographic basis of the global surface distribution of Prochlorococcus ecotypes (2006)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2006-05-13
    Description: By using data collected during a continuous circumnavigation of the Southern Hemisphere, we observed clear patterns in the population-genetic structure of Prochlorococcus, the most abundant photosynthetic organism on Earth, between and within the three Southern Subtropical Gyres. The same mechanisms that were previously invoked to account for the vertical distribution of ecotypes at local scales accounted for the global (horizontal) patterns we observed. Basin-scale and seasonal variations in the structure and strength of vertical stratification provide a basis for understanding large-scale horizontal distribution in genetic and physiological traits of Prochlorococcus, and perhaps of marine microbial communities in general.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bouman, Heather A -- Ulloa, Osvaldo -- Scanlan, David J -- Zwirglmaier, Katrin -- Li, William K W -- Platt, Trevor -- Stuart, Venetia -- Barlow, Ray -- Leth, Ole -- Clementson, Lesley -- Lutz, Vivian -- Fukasawa, Masao -- Watanabe, Shuichi -- Sathyendranath, Shubha -- New York, N.Y. -- Science. 2006 May 12;312(5775):918-21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratorio de Procesos Oceanograficos y Clima, Departamento de Oceanografia, and Centro de Investigacion Oceanografica en el Pacifico Sur-Oriental, Universidad de Concepcion, Casilla 160-C, Concepcion, Chile. heather@profc.udec.cl〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16690867" target="_blank"〉PubMed〈/a〉
    Keywords: Atlantic Ocean ; Biomass ; Chlorophyll/analysis ; Climate ; Colony Count, Microbial ; *Ecosystem ; Flow Cytometry ; Indian Ocean ; Light ; Oceanography ; Pacific Ocean ; Phytoplankton/*genetics/*growth & development/physiology ; Polymerase Chain Reaction ; Prochlorococcus/classification/*genetics/*growth & development/physiology ; Seasons ; Seawater/*microbiology ; Temperature ; Vinyl Compounds/analysis
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 8
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    Ice record of delta13C for atmospheric CH4 across the Younger Dryas-Preboreal transition (2006)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2006-08-26
    Description: We report atmospheric methane carbon isotope ratios (delta13CH4) from the Western Greenland ice margin spanning the Younger Dryas-to-Preboreal (YD-PB) transition. Over the recorded approximately 800 years, delta13CH4 was around -46 per mil (per thousand); that is, approximately 1 per thousand higher than in the modern atmosphere and approximately 5.5 per thousand higher than would be expected from budgets without 13C-rich anthropogenic emissions. This requires higher natural 13C-rich emissions or stronger sink fractionation than conventionally assumed. Constant delta13CH4 during the rise in methane concentration at the YD-PB transition is consistent with additional emissions from tropical wetlands, or aerobic plant CH4 production, or with a multisource scenario. A marine clathrate source is unlikely.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schaefer, Hinrich -- Whiticar, Michael J -- Brook, Edward J -- Petrenko, Vasilii V -- Ferretti, Dominic F -- Severinghaus, Jeffrey P -- New York, N.Y. -- Science. 2006 Aug 25;313(5790):1109-12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉School of Earth and Ocean Sciences, University of Victoria, Post Office Box 3055, V8W 3P6, Canada. schaefeh@geo.oregonstate.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16931759" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Atmosphere ; Bacteria/metabolism ; Carbon Isotopes/analysis ; *Climate ; *Ecosystem ; Environment ; Greenland ; Ice/*analysis ; Methane/*analysis/metabolism ; Plants/metabolism ; Time
    Print ISSN: 0036-8075
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  • 9
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    Mesoscale iron enrichment experiments 1993-2005: synthesis and future directions (2007)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2007-02-03
    Description: Since the mid-1980s, our understanding of nutrient limitation of oceanic primary production has radically changed. Mesoscale iron addition experiments (FeAXs) have unequivocally shown that iron supply limits production in one-third of the world ocean, where surface macronutrient concentrations are perennially high. The findings of these 12 FeAXs also reveal that iron supply exerts controls on the dynamics of plankton blooms, which in turn affect the biogeochemical cycles of carbon, nitrogen, silicon, and sulfur and ultimately influence the Earth climate system. However, extrapolation of the key results of FeAXs to regional and seasonal scales in some cases is limited because of differing modes of iron supply in FeAXs and in the modern and paleo-oceans. New research directions include quantification of the coupling of oceanic iron and carbon biogeochemistry.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Boyd, P W -- Jickells, T -- Law, C S -- Blain, S -- Boyle, E A -- Buesseler, K O -- Coale, K H -- Cullen, J J -- de Baar, H J W -- Follows, M -- Harvey, M -- Lancelot, C -- Levasseur, M -- Owens, N P J -- Pollard, R -- Rivkin, R B -- Sarmiento, J -- Schoemann, V -- Smetacek, V -- Takeda, S -- Tsuda, A -- Turner, S -- Watson, A J -- New York, N.Y. -- Science. 2007 Feb 2;315(5812):612-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉National Institute for Water and Atmospheric Research (NIWA) Centre for Chemical and Physical Oceanography, Department of Chemistry, University of Otago, Dunedin, New Zealand. pboyd@alkali.otago.ac.nz〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17272712" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Atmosphere ; Carbon/analysis/metabolism ; Carbon Dioxide ; Chlorophyll/analysis ; Climate ; Diatoms/growth & development ; *Ecosystem ; *Iron/analysis ; Oceans and Seas ; Phytoplankton/*growth & development/metabolism ; *Seawater ; Zooplankton/*growth & development
    Print ISSN: 0036-8075
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  • 10
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    Recapitulation of IVIG anti-inflammatory activity with a recombinant IgG Fc (2008)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2008-04-19
    Description: It is well established that high doses of monomeric immunoglobulin G (IgG) purified from pooled human plasma [intravenous immunoglobulin (IVIG)] confer anti-inflammatory activity in a variety of autoimmune settings. However, exactly how those effects are mediated is not clear because of the heterogeneity of IVIG. Recent studies have demonstrated that the anti-inflammatory activity of IgG is completely dependent on sialylation of the N-linked glycan of the IgG Fc fragment. Here we determine the precise glycan requirements for this anti-inflammatory activity, allowing us to engineer an appropriate IgG1 Fc fragment, and thus generate a fully recombinant, sialylated IgG1 Fc with greatly enhanced potency. This therapeutic molecule precisely defines the biologically active component of IVIG and helps guide development of an IVIG replacement with improved activity and availability.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2409116/" 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/PMC2409116/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Anthony, Robert M -- Nimmerjahn, Falk -- Ashline, David J -- Reinhold, Vernon N -- Paulson, James C -- Ravetch, Jeffrey V -- GM60938/GM/NIGMS NIH HHS/ -- R01 GM054045/GM/NIGMS NIH HHS/ -- R01 GM054045-11/GM/NIGMS NIH HHS/ -- R01 GM060938/GM/NIGMS NIH HHS/ -- R01 GM060938-09/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2008 Apr 18;320(5874):373-6. doi: 10.1126/science.1154315.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Molecular Genetics and Immunology, Rockefeller University, New York, NY 10021, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18420934" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anti-Inflammatory Agents, Non-Steroidal/administration & ; dosage/chemistry/*therapeutic use ; Arthritis, Experimental/drug therapy ; Autoimmune Diseases/*drug therapy ; Carbohydrate Conformation ; Galactose/chemistry ; Glycosylation ; Humans ; Immunoglobulin Fc Fragments/administration & ; dosage/*chemistry/metabolism/*therapeutic use ; Immunoglobulin G/administration & dosage/chemistry/metabolism/*therapeutic use ; Immunoglobulins, Intravenous/administration & dosage/*chemistry/*therapeutic use ; Mice ; Mice, Inbred C57BL ; Mice, Inbred NOD ; N-Acetylneuraminic Acid/chemistry ; Polysaccharides/chemistry ; Purpura, Thrombocytopenic, Idiopathic/drug therapy ; Receptors, Fc/metabolism ; Recombinant Proteins/chemistry/therapeutic use
    Print ISSN: 0036-8075
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