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  • 1
    Publication Date: 2013-08-21
    Description: Mammals harbour a complex gut microbiome, comprising bacteria that confer immunological, metabolic and neurological benefits. Despite advances in sequence-based microbial profiling and myriad studies defining microbiome composition during health and disease, little is known about the molecular processes used by symbiotic bacteria to stably colonize the gastrointestinal tract. We sought to define how mammals assemble and maintain the Bacteroides, one of the most numerically prominent genera of the human microbiome. Here we find that, whereas the gut normally contains hundreds of bacterial species, germ-free mice mono-associated with a single Bacteroides species are resistant to colonization by the same, but not different, species. To identify bacterial mechanisms for species-specific saturable colonization, we devised an in vivo genetic screen and discovered a unique class of polysaccharide utilization loci that is conserved among intestinal Bacteroides. We named this genetic locus the commensal colonization factors (ccf). Deletion of the ccf genes in the model symbiont, Bacteroides fragilis, results in colonization defects in mice and reduced horizontal transmission. The ccf genes of B. fragilis are upregulated during gut colonization, preferentially at the colonic surface. When we visualize microbial biogeography within the colon, B. fragilis penetrates the colonic mucus and resides deep within crypt channels, whereas ccf mutants are defective in crypt association. Notably, the CCF system is required for B. fragilis colonization following microbiome disruption with Citrobacter rodentium infection or antibiotic treatment, suggesting that the niche within colonic crypts represents a reservoir for bacteria to maintain long-term colonization. These findings reveal that intestinal Bacteroides have evolved species-specific physical interactions with the host that mediate stable and resilient gut colonization, and the CCF system represents a novel molecular mechanism for symbiosis.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3893107/" 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/PMC3893107/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lee, S Melanie -- Donaldson, Gregory P -- Mikulski, Zbigniew -- Boyajian, Silva -- Ley, Klaus -- Mazmanian, Sarkis K -- DK078938/DK/NIDDK NIH HHS/ -- GM007616/GM/NIGMS NIH HHS/ -- GM099535/GM/NIGMS NIH HHS/ -- P01 DK091222/DK/NIDDK NIH HHS/ -- R01 DK078938/DK/NIDDK NIH HHS/ -- R01 GM099535/GM/NIGMS NIH HHS/ -- R21 DK083633/DK/NIDDK NIH HHS/ -- England -- Nature. 2013 Sep 19;501(7467):426-9. doi: 10.1038/nature12447. Epub 2013 Aug 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, California 91125, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23955152" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bacterial Proteins/genetics/metabolism ; Bacteroides/*classification/genetics/growth & development/*physiology ; Bacteroides fragilis/genetics/growth & development/metabolism ; Colon/microbiology ; Conserved Sequence/genetics ; Evolution, Molecular ; Female ; Gastrointestinal Tract/*microbiology ; Gene Deletion ; Genes, Bacterial/genetics ; Germ-Free Life ; Intestinal Mucosa/microbiology ; Male ; Metagenome/*physiology ; Mice ; Polysaccharides/metabolism ; Species Specificity ; Symbiosis/genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2012-07-06
    Description: Most leukocytes can roll along the walls of venules at low shear stress (1 dyn cm-2), but neutrophils have the ability to roll at tenfold higher shear stress in microvessels in vivo. The mechanisms involved in this shear-resistant rolling are known to involve cell flattening and pulling of long membrane tethers at the rear. Here we show that these long tethers do not retract as postulated, but instead persist and appear as 'slings' at the front of rolling cells. We demonstrate slings in a model of acute inflammation in vivo and on P-selectin in vitro, where P-selectin-glycoprotein-ligand-1 (PSGL-1) is found in discrete sticky patches whereas LFA-1 is expressed over the entire length on slings. As neutrophils roll forward, slings wrap around the rolling cells and undergo a step-wise peeling from the P-selectin substrate enabled by the failure of PSGL-1 patches under hydrodynamic forces. The 'step-wise peeling of slings' is distinct from the 'pulling of tethers' reported previously. Each sling effectively lays out a cell-autonomous adhesive substrate in front of neutrophils rolling at high shear stress during inflammation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3433404/" 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/PMC3433404/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sundd, Prithu -- Gutierrez, Edgar -- Koltsova, Ekaterina K -- Kuwano, Yoshihiro -- Fukuda, Satoru -- Pospieszalska, Maria K -- Groisman, Alex -- Ley, Klaus -- EB02185/EB/NIBIB NIH HHS/ -- R01 EB002185/EB/NIBIB NIH HHS/ -- England -- Nature. 2012 Aug 16;488(7411):399-403. doi: 10.1038/nature11248.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Inflammation Biology, La Jolla Institute for Allergy and Immunology, La Jolla, California 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22763437" target="_blank"〉PubMed〈/a〉
    Keywords: Adhesiveness ; Animals ; Antigens, CD/metabolism ; Cell Adhesion ; Cell Adhesion Molecules/metabolism ; E-Selectin/metabolism ; Inflammation/immunology/metabolism/pathology ; Intercellular Adhesion Molecule-1/metabolism ; *Leukocyte Rolling ; Lymphocyte Function-Associated Antigen-1/metabolism ; Membrane Glycoproteins/metabolism ; Mice ; Mice, Inbred C57BL ; Microvessels/metabolism ; Neutrophils/*cytology/immunology/*metabolism ; P-Selectin/metabolism ; *Shear Strength ; Th1 Cells/cytology/immunology ; Venules/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 3
    Keywords: CELLS ; ENDOTHELIAL-CELLS ; CELL ; Germany ; IN-VIVO ; MODEL ; MODELS ; VIVO ; MICE ; LIGAND ; FAMILY ; CONTRAST ; BINDING ; treatment ; MOLECULE ; ALPHA ; ACID ; GLYCOPROTEIN ; ADHESION ; MUSCLE ; FRAGMENTS ; LECTIN ; INTERACTS ; P-SELECTIN ; CHILDREN ; TNF-ALPHA ; inflammation ; C-type lectin ; NEUTROPHILS ; FAMILIES ; RESIDUES ; DEFICIENT MICE ; carbohydrate structures ; GLYCOPROTEINS ; INTEGRINS ; function ; in vivo ; FRAGMENT ; ENDOTHELIAL-CELL ; carbohydrate ; ACID-RESIDUES ; GLYCOPROTEIN LIGAND-1 ; HIGH ENDOTHELIAL VENULES ; LYMPHOCYTE RECIRCULATION ; ROLLING IN-VIVO ; TYROSINE SULFATION
    Abstract: L-selectin belongs to the C-type lectin family of glycoproteins and is constitutively expressed on most leukocytes. L-selectin mediates leukocyte rolling in inflamed microvessels and high endothelial venules (HEV) via binding to specific carbohydrate structures on selectin ligands. Previous studies using sialidase treatment suggested a role of sialic acid residues in L-selectin-dependent rolling. To investigate the role of the alpha 2,3-sialyltransferase (ST3Gal)-IV on L-selectin ligand activity in vivo, we studied leukocyte rolling in inflamed venules of the cremaster muscle and in Peyer's patch HEV of ST3Gal-IV-deficient mice and littermate control mice. In cremaster muscle venules with or without TNF-alpha treatment, L-selectin-dependent rolling was almost completely abolished in ST3Gal-IV-/- mice. In both models, L-selectin interacts with P-selectin glycoprotein ligand-1 (PSGL-1) presented by adherent leukocytes and leukocyte fragments, but not with endothelial L-selectin ligands. In contrast, L-selectin-dependent rolling in Peyer's patch HEV, which is mediated by unknown endothelial L-selectin ligands, was not impaired in the absence of ST3Gal-IV. Our in vivo data show that PSGL-1, the molecule responsible for L-selectin-mediated leukocyte interactions in inflammation, is dependent on ST3Gal-IV, while alpha 2,3-sialylation by ST3Gal-IV is not necessary for L-selectin ligand activity on high endothelial cells of Peyer's patch HEV
    Type of Publication: Journal article published
    PubMed ID: 17111351
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  • 4
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  125. Kongress der Deutschen Gesellschaft für Chirurgie; 20080422-20080425; Berlin; DOC08dgch8813 /20080416/
    Publication Date: 2008-04-14
    Keywords: ddc: 610
    Language: German
    Type: conferenceObject
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  • 5
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  24. Jahrestagung der Deutschen Gesellschaft für Arterioskleroseforschung; 20100318-20100320; Blaubeuren; DOC10dgaf15 /20110323/
    Publication Date: 2011-03-23
    Description: In atherosclerotic arteries, blood monocytes differentiate to macrophages in the presence of growth factors like macrophage colony-stimulation factor (MCSF) and chemokines like platelet factor 4 (CXCL4). To compare the gene expression signature of CXCL4-induced macrophages with MCSF-induced macrophages or macrophages polarized with IFN-gamma/LPS (M1) or IL-4 (M2), we cultured primary human peripheral blood monocytes for six days. mRNA expression was measured by Affymetrix gene chips and differences were analyzed by Local Pooled Error test, Profile of Complex Functionality and Gene Set Enrichment Analysis. 375 genes were differentially expressed between MCSF- and CXCL4-induced macrophages, 206 of them overexpressed in CXCL4 macrophages coding for genes implicated in the inflammatory/immune response, antigen processing/presentation, and lipid metabolism. CXCL4-induced macrophages overexpressed some M1 and M2 genes and the corresponding cytokines at the protein level, however, their transcriptome clustered with neither M1 nor M2 transcriptomes. They almost completely lost the ability to phagocytose zymosan beads. Genes linked to atherosclerosis were not consistently up- or downregulated. Scavenger receptors showed lower and cholesterol efflux transporters higher expression in CXCL4- than MCSF-induced macrophages, resulting in lower LDL content. We conclude that CXCL4 induces a unique macrophage transcriptome distinct from known macrophage types, defining a new macrophage differentiation that we propose to call M4.
    Keywords: ddc: 610
    Language: English
    Type: conferenceObject
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  • 6
    ISSN: 0168-9002
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Physics
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1420-9071
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Zusammenfassung Andauernde ACTH-Behandlung beeinflusst sowohl Vermeidungs- als auch Fehlerkomponenten im Zweiwahl-Y-Labyrinthtest. Die Einwirkungen waren von der Intensität des Elektroschocks wie auch von der Reaktionsfähigkeit der Tiere abhängig.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1573-9686
    Keywords: Physiological database ; Mathematical model ; Physiome: microcirculation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Technology
    Notes: Abstract Presented is a discussion of steps towards the creation of a database of the microcirculation encompassing anatomical and functional experimental data, and conceptual and computational models. The discussion includes issues of database utility, organization, data deposition, and linkage to other databases. The database will span levels from gene to tissue and will serve both research and educational purposes. © 1998 Biomedical Engineering Society. PAC98: 8745Ft, 8710+e, 0130Cc
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-2013
    Keywords: Microcirculation ; Blood rheology ; Leukocytes ; Capillary ; Bifurcation ; Network ; Topology ; Intravital microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Distribution of leukocytes in rat mesenteric microvessel networks was studied using intravital fluorescence video microscopy. A digital image analysis system was used to measure vessel diameters, flow velocities and leukocyte fluxes in 306 capillaries of 8 networks. Capillaries were defined as vessel segments connecting divergent to convergent branch points. Their topological position within the network was quantified by a generation number defined as the number of bifurcations between the capillary and the arteriole feeding the network. Proximal capillaries (generation numbers 4 and 5) were slightly but significantly smaller in diameter (8.9±0.4) μm, mean ± SEM) than distal ones (generation numbers 20 and 21, 10.1±0.4 μm). Average capillary flow velocity decreased markedly from 2.0±1.0 mm·s−1 in proximal to 0.41 ±0.06 mm·s−1 in distal capillaries. Average leukocyte concentration was 3.4±0.5·109 l−1 and thus significantly below systemic values (6.0·109 l−1) in proximal capillaries, and above in distal ones (11.7±2.6·109l−1). The analysis of flow and leukocyte flux partition at 138 bifurcations showed preferential distribution of leukocytes to the daughter capillary with higher flow rate. This suggests a tentative explanation for the observed leukocyte accumulation along the microvascular tree: due to their low fractional flow, proximal capillaries draw relatively leukocytepoor blood from the arteriole feeding the network; this leads to an increased leukocyte concentration in distal capillaries. As a consequence of the concomitant increase of capillary diameter with increasing generation number, leukocytes are preferentially flowing through larger capillaries and are excluded from small ones.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Weinheim : Wiley-Blackwell
    ISSN: 0570-0833
    Keywords: Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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