| 1. |
- Aspholm, Marina, et al.
(författare)
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SabA is the H. pylori hemagglutinin and is polymorphic in binding to sialylated glycans.
- 2006
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Ingår i: PLoS pathogens. - : Public Library of Science (PLoS). - 1553-7374 .- 1553-7366. ; 2:10
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Tidskriftsartikel (refereegranskat)abstract
- Adherence of Helicobacter pylori to inflamed gastric mucosa is dependent on the sialic acid-binding adhesin (SabA) and cognate sialylated/fucosylated glycans on the host cell surface. By in situ hybridization, H. pylori bacteria were observed in close association with erythrocytes in capillaries and post-capillary venules of the lamina propria of gastric mucosa in both infected humans and Rhesus monkeys. In vivo adherence of H. pylori to erythrocytes may require molecular mechanisms similar to the sialic acid-dependent in vitro agglutination of erythrocytes (i.e., sialic acid-dependent hemagglutination). In this context, the SabA adhesin was identified as the sialic acid-dependent hemagglutinin based on sialidase-sensitive hemagglutination, binding assays with sialylated glycoconjugates, and analysis of a series of isogenic sabA deletion mutants. The topographic presentation of binding sites for SabA on the erythrocyte membrane was mapped to gangliosides with extended core chains. However, receptor mapping revealed that the NeuAcalpha2-3Gal-disaccharide constitutes the minimal sialylated binding epitope required for SabA binding. Furthermore, clinical isolates demonstrated polymorphism in sialyl binding and complementation analysis of sabA mutants demonstrated that polymorphism in sialyl binding is an inherent property of the SabA protein itself. Gastric inflammation is associated with periodic changes in the composition of mucosal sialylation patterns. We suggest that dynamic adaptation in sialyl-binding properties during persistent infection specializes H. pylori both for individual variation in mucosal glycosylation and tropism for local areas of inflamed and/or dysplastic tissue.
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| 2. |
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| 3. |
- Bugaytsova, Jeanna, et al.
(författare)
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pH regulated H. pylori adherence : implications for persistent infection and disease
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Helicobacter pylori’s BabA adhesin binds strongly to gastric mucosal ABH/Leb glycans on the stomach epithelium and overlying mucus, materials continuously shed into the acidic gastric lumen. Here we report that this binding is acid labile, acid inactivation is fully reversible; and acid lability profiles vary with BabA sequence and correlate with disease patterns. Isogenic H. pylori strains from the gastric antrum and more acidic corpus were identified that differed in acid lability of receptor binding and in sequence near BabA’s carbohydrate binding domain. We propose that reversible acid inactivation of receptor binding helps H. pylori avoid clearance by mucosal shedding, and that strain differences in acid lability affect tissue tropism and the spectrum of associated gastric diseases.
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| 4. |
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| 5. |
- Garcia-Closas, Montserrat, et al.
(författare)
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Heterogeneity of breast cancer associations with five susceptibility loci by clinical and pathological characteristics
- 2008
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Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 4:4, s. e1000054-
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Tidskriftsartikel (refereegranskat)abstract
- A three-stage genome-wide association study recently identified single nucleotide polymorphisms (SNPs) in five loci (fibroblast growth receptor 2 (FGFR2), trinucleotide repeat containing 9 (TNRC9), mitogen-activated protein kinase 3 K1 (MAP3K1), 8q24, and lymphocyte-specific protein 1 (LSP1)) associated with breast cancer risk. We investigated whether the associations between these SNPs and breast cancer risk varied by clinically important tumor characteristics in up to 23,039 invasive breast cancer cases and 26,273 controls from 20 studies. We also evaluated their influence on overall survival in 13,527 cases from 13 studies. All participants were of European or Asian origin. rs2981582 in FGFR2 was more strongly related to ER-positive (per-allele OR (95%CI) = 1.31 (1.27-1.36)) than ER-negative (1.08 (1.03-1.14)) disease (P for heterogeneity = 10(-13)). This SNP was also more strongly related to PR-positive, low grade and node positive tumors (P = 10(-5), 10(-8), 0.013, respectively). The association for rs13281615 in 8q24 was stronger for ER-positive, PR-positive, and low grade tumors (P = 0.001, 0.011 and 10(-4), respectively). The differences in the associations between SNPs in FGFR2 and 8q24 and risk by ER and grade remained significant after permutation adjustment for multiple comparisons and after adjustment for other tumor characteristics. Three SNPs (rs2981582, rs3803662, and rs889312) showed weak but significant associations with ER-negative disease, the strongest association being for rs3803662 in TNRC9 (1.14 (1.09-1.21)). rs13281615 in 8q24 was associated with an improvement in survival after diagnosis (per-allele HR = 0.90 (0.83-0.97). The association was attenuated and non-significant after adjusting for known prognostic factors. Our findings show that common genetic variants influence the pathological subtype of breast cancer and provide further support for the hypothesis that ER-positive and ER-negative disease are biologically distinct. Understanding the etiologic heterogeneity of breast cancer may ultimately result in improvements in prevention, early detection, and treatment.
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| 6. |
- Greiwe, Ansgar, et al.
(författare)
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Erfassung der Hauptreflektordeformation eines Radioteleskops durch UAV-gestützte Nahbereichsphotogrammetrie
- 2020
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Ingår i: Publikationen der Deutschen Gesellschaft für Photogrammetrie, Fernerkundung und Geoinformation e.V. ; :29, s. 346-357
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Konferensbidrag (refereegranskat)abstract
- Deformationen am Hauptreflektor eines Radioteleskops verursachen systematische Abweichungen in den Messungen und führen zu einer Verfälschung der abgeleiteten globalen Position und somit zu einem verzerrten Netzmaßstab im globalen geodätischen Bezugsrahmen. Um diese Systematiken zu minimieren, ist ein stabiler bzw. modellierbarer Strahlengang über den gesamten Arbeitsbereich des Teleskops notwendig. Zur messtechnischen Erfassung des Hauptreflektors konventioneller Radioteleskope werden gegenwärtig häufig Laserscanner verwendet, die eine Einzelpunktgenauigkeit von wenigen Millimetern erreichen. Für diesen Beitrag wurde erstmals das elevationsabhängige Verformungsverhalten eines modernen, kompakten VGOS-spezifizierten VLBI-Radioteleskops photogrammetrisch untersucht. Um den Hauptreflektor des Teleskops in mehreren Neigungen zu erfassen, erfolgte die photogrammetrische Datenerhebung durch ein Unmanned Aircraft Vehicle (UAV) als Sensorplattform für eine leichtgewichtige Kompaktkamera. Im Rahmen der Untersuchungen wurde eine Einzelpunktgenauigkeit von ca. 50 μm in 21 unterschiedlichen Bildverbänden erreicht.
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| 7. |
- Greiwe, Ansgar, et al.
(författare)
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Erfassung von Hauptreflektordeformationen an VGOS-Teleskopen mittels UAS
- 2020
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Ingår i: Photogrammetrie - Laserscanning - Optische 3D-Messtechnik: Beiträge der 19. Oldenburger 3D-Tage 2020. - 9783879076888
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Konferensbidrag (refereegranskat)abstract
- Das Verfahren zur Interferometrie auf langen Basislinien (VLBI) zählt zu den geodätischen Raumtechniken, die zur Realisierung eines erdfesten- als auch eines sternenfesten geodätischen Bezugssystems herangezogen werden. Messtechnische Untersuchungen von Hauptreflektoren konventioneller VLBI-Radioteleskope weisen ein elevationsabhängiges Eigenverformungsverhalten auf, die zu einer Variation der Brennweite von z.T. mehreren Zentimetern führt. Unkompensiert führen diese systematischen Verformungen zu einer Verzerrung der geschätzten Stationskoordinate, die u.U. den globalen Netzmaßstab verfälscht. Um das elevationsabhängige Verformungsverhalten eines kompakten 13 m VLBI-Radioteleskops zu untersuchen, werden für die Datenerhebung Messungen an diskreten Punkten auf dem Hauptreflektor in den unterschiedlichen Elevationsstellungen verwendet. Die geforderte Messgenauigkeit liegt hierbei unter 1 mm. Der naheliegende Einsatz der Nahbereichsphotogrammetrie per Kran wird hierbei durch die jeweilige Neigung des Hauptreflektors erschwert. Aus diesem Grunde wurde die Erfassung der Aufnahmen erstmals mit einem UAV und einer geeigneten Kamera durchgeführt. Im vorliegenden Beitrag werden das Messkonzept, die verwendete Kamera, erreichte Genauigkeiten und das Ergebnis der elevationsabhängigen Deformation vorgestellt.
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| 8. |
- Ishijima, Nozomi, et al.
(författare)
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BabA-mediated adherence is a potentiator of the Helicobacter pylori type IV secretion system activity
- 2011
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Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 286:28, s. 25256-25264
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Tidskriftsartikel (refereegranskat)abstract
- Chronic infection of Helicobacter pylori in the stomach mucosa with translocation of the bacterial cytotoxin-associated gene A (CagA) effector protein via the cag-Type IV secretion system (TFSS) into host epithelial cells are major risk factors for gastritis, gastric ulcers, and cancer. The blood group antigen-binding adhesin BabA mediates the adherence of H. pylori to ABO/Lewis b (Le(b)) blood group antigens in the gastric pit region of the human stomach mucosa. Here, we show both in vitro and in vivo that BabA-mediated binding of H. pylori to Le(b) on the epithelial surface augments TFSS-dependent H. pylori pathogenicity by triggering the production of proinflammatory cytokines and precancer-related factors. We successfully generated Le(b)-positive cell lineages by transfecting Le(b)-negative cells with several glycosyltransferase genes. Using these established cell lines, we found increased mRNA levels of proinflammatory cytokines (CCL5 and IL-8) as well as precancer-related factors (CDX2 and MUC2) after the infection of Le(b)-positive cells with WT H. pylori but not with babA or TFSS deletion mutants. This increased mRNA expression was abrogated when Le(b)-negative cells were infected with WT H. pylori. Thus, H. pylori can exploit BabA-Le(b) binding to trigger TFSS-dependent host cell signaling to induce the transcription of genes that enhance inflammation, development of intestinal metaplasia, and associated precancerous transformations.
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| 9. |
- Javaheri, Anahita, et al.
(författare)
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Helicobacter pylori adhesin HopQ engages in a virulence-enhancing interaction with human CEACAMs
- 2017
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Ingår i: Nature Microbiology. - : NATURE PUBLISHING GROUP. - 2058-5276. ; 2:1
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Tidskriftsartikel (refereegranskat)abstract
- Helicobacter pylori specifically colonizes the human gastric epithelium and is the major causative agent for ulcer disease and gastric cancer development. Here, we identify members of the carcinoembryonic antigen-related cell adhesion molecule (CEACAM) family as receptors of H. pylori and show that HopQ is the surface-exposed adhesin that specifically binds human CEACAM1, CEACAM3, CEACAM5 and CEACAM6. HopQ-CEACAM binding is glycan-independent and targeted to the N-domain. H. pylori binding induces CEACAM1-mediated signalling, and the HopQ-CEACAM1 interaction enables translocation of the virulence factor CagA into host cells and enhances the release of pro-inflammatory mediators such as interleukin-8. Based on the crystal structure of HopQ, we found that a beta-hairpin insertion (HopQ-ID) in HopQ's extracellular 3+4 helix bundle domain is important for CEACAM binding. A peptide derived from this domain competitively inhibits HopQ-mediated activation of the Cag virulence pathway, as genetic or antibody-mediated abrogation of the HopQ function shows. Together, our data suggest the HopQ-CEACAM1 interaction to be a potentially promising novel therapeutic target to combat H. pylori-associated diseases.
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| 10. |
- Kickert, Conrad, et al.
(författare)
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Spatial dynamics of long-term urban retail decline in three transatlantic cities
- 2020
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Ingår i: Cities. - : Elsevier BV. - 0264-2751 .- 1873-6084. ; 107
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Tidskriftsartikel (refereegranskat)abstract
- This paper studies the effects of the centrality, connectivity and agglomeration of retail establishments on their long-term viability in three cities in the United States, United Kingdom and The Netherlands. As retail is declining in all three markets, there is a dearth of knowledge on the spatial patterns of this decline. This obstructs the substantiation of development decisions and public policy on urban retail retention and growth. Without knowing where stores are most at risk of closing, where can we decide to invest or divest? This paper uses a self-built dataset of store locations and store closures over the span of more than a century in the urban cores of Detroit, Michigan; Birmingham, England; and The Hague, The Netherlands. While taking different paths, all three cities have experienced significant retail decline over the past century. The probability of store closure over time is compared to the metric distance of stores to the retail center of gravity (centrality), store location along well-used streets as measured by their Choice value (connectivity), and the number of surrounding stores (agglomeration). These three comparisons are statistically analyzed using simple line regression, panel regression, and spatial autoregressive probit models. Across these models, store closure is most significantly affected by agglomeration, then by centrality, followed by connectivity. The significance of all three measures is strongest in The Hague, followed by Birmingham and Detroit – two cities that experienced large-scale urban renewal and socio-economic decline.
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