| 1. |
- Dengjel, Joern, et al.
(författare)
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Identification of Autophagosome-associated Proteins and Regulators by Quantitative Proteomic Analysis and Genetic Screens
- 2012
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Ingår i: Molecular & Cellular Proteomics. - 1535-9476 .- 1535-9484. ; 11:3
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Tidskriftsartikel (refereegranskat)abstract
- Autophagy is one of the major intracellular catabolic pathways, but little is known about the composition of autophagosomes. To study the associated proteins, we isolated autophagosomes from human breast cancer cells using two different biochemical methods and three stimulus types: amino acid deprivation or rapamycin or concanamycin A treatment. The autophagosome- associated proteins were dependent on stimulus, but a core set of proteins was stimulus- independent. Remarkably, proteasomal proteins were abundant among the stimulus- independent common autophagosome- associated proteins, and the activation of autophagy significantly decreased the cellular proteasome level and activity supporting interplay between the two degradation pathways. A screen of yeast strains defective in the orthologs of the human genes encoding for a common set of autophagosome- associated proteins revealed several regulators of autophagy, including subunits of the retromer complex. The combined spatiotemporal proteomic and genetic data sets presented here provide a basis for further characterization of autophagosome biogenesis and cargo selection.
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| 2. |
- Dittmann, Tobias, et al.
(författare)
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The EcoQO on Mercury and Organohalogens in CoastalBird Eggs -Report on the Pilot Study 2008 – 2010
- 2011
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- On the one hand the coastal areas of the North Sea hold important breeding populations of marinebirds but on the other hand these areas are also under pressure from pollution with environmentalchemicals. Due to biomagnification effects through the food chain, the bird egg is an ideal matrixto get a consistent and reliable picture of the pollutant level of the marine environment over timeand space.With this report, we are pleased to give, for the first time, a North-Sea-wide overviewabout the spatial patterns of mercury and organochlorine pollution in coastal bird eggs, presentingdata from Oystercatcher, Common Tern and Arctic Tern in the period 2008-2010. We are able toshow how the recently defined Ecological Quality Objectives (EcoQOs) for these substances incoastal bird eggs have been fulfilled in the different parts of the North Sea. This report aims toprovide input for the further development of EcoQOs in the North Sea area and for their potentialrole in the implementation of the EU Marine Strategy Directive.We would like to thank all those who contributed to the report by coordinating andorganizing the field sampling, by participating in workshops and providing funding for theproject. A large part of the work was carried out in the framework of the long establishedTrilateral Monitoring and Assessment Program (TMAP) of the Trilateral Wadden SeaCooperation which provided resources and data for the Wadden Sea sites. A cooperation withinstitutes in Belgium, Norway, Sweden and the UK made it possible to extend the monitoring ofpollutants from the Wadden Sea to the entire North Sea. This was achieved thanks to theenormous commitment of many colleagues.We hope to be able to continue this fruitful cooperation in the future with the aim tofurther support the protection of the North Sea ecosystem with integrated approaches.
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| 3. |
- Dossus, Laure, et al.
(författare)
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Tumor necrosis factor (TNF)-α, soluble TNF receptors and endometrial cancer risk : the EPIC study
- 2011
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Ingår i: International Journal of Cancer. - Geneve : International union against cancer. - 0020-7136 .- 1097-0215. ; 129:8, s. 2032-2037
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Tidskriftsartikel (refereegranskat)abstract
- Chronic inflammation has been hypothesized to play a role in endometrial cancer development. Tumor necrosis factor-α (TNF-α), one of the major pro-inflammatory cytokines, has also been implicated in endometrial physiology. We conducted a case-control study nested within the European prospective investigation into cancer and nutrition (EPIC) to examine the association of TNF-α and its two soluble receptors (sTNFR1 and sTNFR2) with endometrial cancer risk. Two-hundred-seventy cases and 518 matched controls were analyzed using conditional logistic regression. All statistical tests were two-sided. We observed an increased risk of endometrial cancer among women in the highest versus lowest quartile of TNF-α (odds ratio [OR]: 1.73, 95% CI: 1.09-2.73, Ptrend = 0.01), sTNFR1 (OR: 1.68, 95% CI: 0.99-2.86, Ptrend = 0.07) and sTNFR2 (OR: 1.53, 95%CI: 0.92-2.55, Ptrend = 0.03) after adjustment for body-mass-index, parity, age at menopause and previous postmenopausal hormone therapy use. Further adjustments for estrogens and C-peptide had minor effect on risk estimates. Our data show that elevated prediagnostic concentrations of TNF-α and its soluble receptors are related to a higher risk of endometrial cancer, particularly strong in women diagnosed within 2 years of blood donation. This is the first study of its kind and therefore deserves replication in further prospective studies.
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| 4. |
- Meyer-Schwesinger, Catherine, et al.
(författare)
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Nephrotic Syndrome and Subepithelial Deposits in a Mouse Model of Immune-Mediated Anti-Podocyte Glomerulonephritis.
- 2011
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Ingår i: Journal of immunology (Baltimore, Md. : 1950). - : The American Association of Immunologists. - 1550-6606 .- 0022-1767. ; 187:6, s. 3218-3229
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Tidskriftsartikel (refereegranskat)abstract
- Subepithelial immune complex deposition in glomerular disease causes local inflammation and proteinuria by podocyte disruption. A rat model of membranous nephropathy, the passive Heymann nephritis, suggests that Abs against specific podocyte Ags cause subepithelial deposit formation and podocyte foot process disruption. In this study, we present a mouse model in which a polyclonal sheep anti-mouse podocyte Ab caused subepithelial immune complex formation. Mice developed a nephrotic syndrome with severe edema, proteinuria, hypoalbuminemia, and elevated cholesterol and triglycerides. Development of proteinuria was biphasic: an initial protein loss was followed by a second massive increase of protein loss beginning at approximately day 10. By histology, podocytes were swollen. Electron microscopy revealed 60-80% podocyte foot process effacement and subepithelial deposits, but no disruption of the glomerular basement membrane. Nephrin and synaptopodin staining was severely disrupted, and podocyte number was reduced in anti-podocyte serum-treated mice, indicating severe podocyte damage. Immunohistochemistry detected the injected anti-podocyte Ab exclusively along the glomerular filtration barrier. Immunoelectron microscopy localized the Ab to podocyte foot processes and the glomerular basement membrane. Similarly, immunohistochemistry localized mouse IgG to the subepithelial space. The third complement component (C3) was detected in a linear staining pattern along the glomerular basement membrane and in the mesangial hinge region. However, C3-deficient mice were not protected from podocyte damage, indicating a complement-independent mechanism. Twenty proteins were identified as possible Ags to the sheep anti-podocyte serum by mass spectrometry. Together, these data establish a reproducible model of immune-mediated podocyte injury in mice with subepithelial immune complex formation.
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| 5. |
- Aad, G., et al.
(författare)
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- 2012
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swepub:Mat__t (refereegranskat)
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| 6. |
- Aad, G., et al.
(författare)
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- 2013
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swepub:Mat__t (refereegranskat)
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| 7. |
- Aad, G., et al.
(författare)
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- 2012
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Tidskriftsartikel (refereegranskat)
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| 8. |
- Aad, G., et al.
(författare)
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- 2012
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Tidskriftsartikel (refereegranskat)
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| 9. |
- Aad, G., et al.
(författare)
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- 2012
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swepub:Mat__t (refereegranskat)
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| 10. |
- Aad, G., et al.
(författare)
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- 2012
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Tidskriftsartikel (refereegranskat)
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