| 11. |
- Klimek, L, et al.
(author)
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Use of biologicals in allergic and type-2 inflammatory diseases during the current COVID-19 pandemic: Position paper of Ärzteverband Deutscher Allergologen (AeDA)A, Deutsche Gesellschaft für Allergologie und Klinische Immunologie (DGAKI)B, Gesellschaft für Pädiatrische Allergologie und Umweltmedizin (GPA)C, Österreichische Gesellschaft für Allergologie und Immunologie (ÖGAI)D, Luxemburgische Gesellschaft für Allergologie und Immunologie (LGAI)E, Österreichische Gesellschaft für Pneumologie (ÖGP)F in co-operation with the German, Austrian, and Swiss ARIA groupsG, and the European Academy of Allergy and Clinical Immunology (EAACI)H
- 2020
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In: Allergologie select. - 2512-8957. ; 4, s. 53-68
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Journal article (peer-reviewed)
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| 12. |
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| 14. |
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| 15. |
- Matricardi, PM, et al.
(author)
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EAACI Molecular Allergology User's Guide
- 2016
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In: Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology. - : Wiley. - 1399-3038. ; 2727 Suppl 23, s. 1-250
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Journal article (peer-reviewed)
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| 16. |
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| 17. |
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| 18. |
- Budczies, Jan, et al.
(author)
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Comparative metabolomics of estrogen receptor positive and estrogen receptor negative breast cancer : alterations in glutamine and beta-alanine metabolism
- 2013
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In: Journal of Proteomics. - : Lippincott Williams & Wilkins. - 1874-3919 .- 1876-7737. ; 94, s. 279-288
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Journal article (peer-reviewed)abstract
- UNLABELLED: Molecular subtyping of breast cancer is necessary for therapy selection and mandatory for all breast cancer patients. Metabolic alterations are considered a hallmark of cancer and several metabolic drugs are currently being investigated in clinical trials. However, the dependence of metabolic alterations on breast cancer subtypes has not been investigated on -omics scale. Thus, 204 estrogen receptor positive (ER+) and 67 estrogen receptor negative (ER-) breast cancer tissues were investigated using GC-TOFMS based metabolomics. 19 metabolites were detected as altered in a predefined training set (2/3 of tumors) and could be validated in a predefined validation set (1/3 of tumors). The metabolite changes included increases in beta-alanine, 2-hydroyglutarate, glutamate, xanthine and decreases in glutamine in the ER- subtype. Beta-alanine demonstrated the strongest change between ER- and ER+ breast cancer (fold change=2.4, p=1.5E-20). In a correlation analysis with genome-wide expression data in a subcohort of 154 tumors, we found a strong negative correlation (Spearman R=-0.62) between beta-alanine and 4-aminobutyrate aminotransferase (ABAT). Immunohistological analysis confirmed down-regulation of the ABAT protein in ER- breast cancer. In a Kaplan-Meier analysis of a large external expression data set, the ABAT transcript was demonstrated to be a positive prognostic marker for breast cancer (HR=0.6, p=3.2E-15).BIOLOGICAL SIGNIFICANCE: It is well-known for more than a decade that breast cancer exhibits distinct gene expression patterns depending on the molecular subtype defined by estrogen receptor (ER) and HER2 status. Here, we show that breast cancer exhibits distinct metabolomics patterns depending on ER status. Our observation supports the current view of ER+ breast cancer and ER- breast as different diseases requiring different treatment strategies. Metabolic drugs for cancer including glutaminase inhibitors are currently under development and tested in clinical trials. We found glutamate enriched and glutamine reduced in ER- breast cancer compared to ER+ breast cancer and compared to normal breast tissues. Thus, metabolomics analysis highlights the ER- subtype as a preferential target for glutaminase inhibitors. For the first time, we report on a regulation of beta-alanine catabolism in cancer. In breast cancer, ABAT transcript expression was variable and correlated with ER status. Low ABAT transcript expression was associated with low ABAT protein expression and high beta-alanine concentration. In a large external microarray cohort, low ABAT expression shortened recurrence-free survival in breast cancer, ER+ breast cancer and ER- breast cancer.
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| 19. |
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| 20. |
- Kleine, Barbara I., et al.
(author)
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Mineralogical controls on metamorphic fluid flow in metabasaltic sills from Islay, Scotland
- 2016
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In: Lithos. - : Elsevier BV. - 0024-4937 .- 1872-6143. ; 248, s. 22-39
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Journal article (peer-reviewed)abstract
- In this study we show that mineralogy was the primary control of metamorphic fluid flow in the well-studied metabasaltic sills in the SW Scottish Highlands. Here, basaltic sills have been partially carbonated by H2O-CO2 fluids at greenschist facies conditions. This has led to mineral zonation with carbonate-poor sill interiors separated from carbonate-rich sill margins by reaction fronts. Although deformation set the stage for metamorphic fluid flow in the SW Scottish Highlands by causing the preferred alignment of mineral grains, metamorphic fluid flow was not coupled with active deformation but occurred later utilizing the pre-existing mineral alignment as a means of accessing the sill interiors. The sills which were studied were partially carbonated with well-preserved reaction fronts. They were selected because (atypically for the SW Scottish Highlands) they are mineralogically heterogeneous making them ideal for a study of mineralogical controls of metamorphic fluid flow. Their mineralogical heterogeneity reflects chemical heterogeneity arising from magmatic flow differentiation and spilitization, which occurred before greenschist facies metamorphism. Magmatic flow differentiation resulted in parts of the sill containing large crystals with no preferred alignment. Large (up to 3 cm) plagioclase phenocrysts were concentrated in the sill interior whereas large (up to 1 cm) amphibole (after pyroxene) grains formed cumulate layers close to the sill margins. These large randomly oriented crystals were replaced by an interface-coupled dissolution-precipitation mechanism. Replacement is constant volume and with hydration and carbonation affecting the cores of these minerals while the rims are remained intact and unaltered. This finding points to intro-granular metamorphic fluid flow. In contrast inter-granular metamorphic fluid flow was facilitated by mineral alignment on different scales. Pre-metamorphic spilitization, produced layers of epidote called segregations, whereas regional deformation caused preferred alignment mainly of amphibole and chlorite. Epidote undergoes a series of volume changes during greenschist facies metamorphism. This created porosity which produced preferred pathways for metamorphic fluids affecting the advancement of fluid-driven reaction fronts. Preferred alignment of amphibole and chlorite also affected the advancement of reaction fronts. In this case, fluid flow was preferentially parallel to the foliation. In both cases, inter-granular metamorphic fluid flow utilized a pre-existing fabric albeit on different scales. These results show intra-granular metamorphic fluid flow in unfoliated rock and inter-granular metamorphic fluid flow in foliated rock. In both cases metamorphic fluid flow occurred after deformation controlled by pre-existing mineralogical heterogeneities, such as grain composition and shape anisotropy as well as preferred alignment of mineral grains.
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