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Institution

University of Kiel

EducationKiel, Germany
About: University of Kiel is a education organization based out in Kiel, Germany. It is known for research contribution in the topics: Population & Transplantation. The organization has 27816 authors who have published 57114 publications receiving 2061802 citations. The organization is also known as: Christian Albrechts University & Christian-Albrechts-Universität zu Kiel.


Papers
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Journal ArticleDOI
16 Nov 2000-Oncogene
TL;DR: The results show that Bcl-XL can protect pancreatic cancer cells from CD95- and TRAIL-mediated apoptosis, and in these epithelial tumour cells the mitochondrially mediated ‘type II’ pathway of apoptosis induction is not only operative regarding the CD95 system but also regarding the TRAIL system.
Abstract: In this study we sought to clarify the role of the proapoptotic potential of mitochondria in the death pathway emanating from the TRAIL (APO-2L) and CD95 receptors in pancreatic carcinoma cells. We focused on the role of the Bcl-2 family member Bcl-XL, using three pancreatic carcinoma cell lines as a model system, two of which have high (Panc-1, PancTuI) and one has low (Colo357) Bcl-XL expression. In these cell lines, the expression of Bcl-XL correlated with sensitivity to apoptosis induced by TRAIL or anti-CD95. Flow cytometric analysis revealed cell surface expression of TRAIL-R1 and TRAIL-R2 on PancTuI and Colo357, and TRAIL-R2 on Panc-1 cells. In Colo357 cells retrovirally transduced with Bcl-XL, caspase-8 activation in response to treatment with TRAIL or anti-CD95 antibody was not different from parental cells and EGFP-transfected controls, however, apoptosis was completely suppressed as measured by the mitochondrial transmembrane potential deltapsim, caspase-3 activity (PARP cleavage) and DNA-fragmentation. Inhibition of Bcl-XL function by overexpression of Bax or administration of antisense oligonucleotides against Bcl-XL mRNA resulted in sensitization of Panc-1 cells to TRAIL and PancTuI cells to anti-CD95 antibody-induced cell death. The results show that Bcl-XL can protect pancreatic cancer cells from CD95- and TRAIL-mediated apoptosis. Thus, in these epithelial tumour cells the mitochondrially mediated 'type II' pathway of apoptosis induction is not only operative regarding the CD95 system but also regarding the TRAIL system.

286 citations

Journal ArticleDOI
TL;DR: Mechanisms for the GBA1 gene's association with increased synucleinopathy risk are explored and a loss in lysosomal acid–β‐glucosidase enzyme activity underlies Gaucher disease.
Abstract: Objective: Heterozygous mutations in the GBA1 gene elevate the risk of Parkinson disease and dementia with Lewy bodies; both disorders are characterized by misprocessing of a-synuclein (SNCA). A loss in lysosomal acid-beta-glucosidase enzyme (GCase) activity due to biallelic GBA1 mutations underlies Gaucher disease. We explored mechanisms for the gene's association with increased synucleinopathy risk. Methods: We analyzed the effects of wild-type (WT) and several GBA mutants on SNCA in cellular and in vivo models using biochemical and immunohistochemical protocols. Results: We observed that overexpression of all GBA mutants examined (N370S, L444P, D409H, D409V, E235A, and E340A) significantly raised human SNCA levels to 121 to 248 of vector control (p = 20), we recorded an age-dependent rise of endogenous Snca in hippocampal membranes (125 vs WT at 52 weeks; p = 0.019). In young Gaucher disease mice (V394Lgba+/+//prosaposinps-null//ps-transgene), which demonstrate neurological dysfunction after age 10 weeks (GCase activity, <= 10%), we recorded no significant change in endogenous Snca levels at 12 weeks of age. However, enhanced neuronal ubiquitin signals and axonal spheroid formation were already present. The latter changes were similar to those seen in three week-old cathepsin D-deficient mice. Interpretation: Our results demonstrate that GBA mutants promote SNCA accumulation in a dose-and time-dependent manner, thereby identifying a biochemical link between GBA1 mutation carrier status and increased synucleinopathy risk. In cell culture models, this gain of toxic function effect can be mitigated by rapamycin. Loss in GCase activity did not immediately raise SNCA concentrations, but first led to neuronal ubiquitinopathy and axonal spheroids, a phenotype shared with other lysosomal storage disorders. ANN NEUROL 2011;69:940-953

286 citations

Journal ArticleDOI
Norihiro Kato, Marie Loh1, Marie Loh2, Marie Loh3  +253 moreInstitutions (73)
TL;DR: The trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry finds genetic variants at 12 new loci to be associated with blood pressure, providing new evidence for the role of DNA methylation in blood pressure regulation.
Abstract: We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10(-11) to 5.0 × 10(-21)). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 × 10(-6)). Our results provide new evidence for the role of DNA methylation in blood pressure regulation.

286 citations

Journal ArticleDOI
A. Rohr1, K. Lüddecke1, Stephan Drusch1, M.J. Müller1, R.v. Alvensleben1 
TL;DR: Food manufacturers have gained credibility from 1997 to 2002 although still on a low level, and two segments of consumers emerged, i.e. price-sensitive and safety-sensitive consumers.

286 citations

Journal ArticleDOI
TL;DR: In this article, the diversity and distribution of sulfate-reducing bacteria in cold seeps were investigated. But the authors focused on the presence of methanotrophic archaea, which can be identified by specific biomarker lipids and 16S rDNA analysis.
Abstract: Cold seep environments such as sediments above outcropping hydrate at Hydrate Ridge (Cascadia margin off Oregon) are characterized by methane venting, high sulfide fluxes caused by the anaerobic oxidation of methane, and the presence of chemosynthetic communities. Recent investigations showed that another characteristic feature of cold seeps is the occurrence of methanotrophic archaea, which can be identified by specific biomarker lipids and 16S rDNA analysis. This investigation deals with the diversity and distribution of sulfate-reducing bacteria, some of which are directly involved in the anaerobic oxidation of methane as syntrophic partners of the methanotrophic archaea. The composition and activity of the microbial communities at methane vented and nonvented sediments are compared by quantitative methods including total cell counts, fluorescence in situ hybridization (FISH), bacterial production, enzyme activity, and sulfate reduction rates. Bacteria involved in the degradation of particulate organic carbon (POC) are as active and diverse as at other productive margin sites of similar water depths. The availability of methane supports a two orders of magnitude higher microbial biomass (up to 9.6 2 10 10 cells cm m 3 ) and sulfate reduction rates (up to 8 w mol cm m 3 d m 1 ) in hydrate-bearing sediments, as well as a high bacterial diversity, especially in the group of i -proteobacteria including members of the branches Desulfosarcina/Desulfococcus , Desulforhopalus , Desulfobulbus , and Desulfocapsa . Most of the diversity of sulfate-reducing bacteria in hydrate-bearing sediments comprises seep-endemic clades, which share only low similarities with previously cultured bacteria.

286 citations


Authors

Showing all 28103 results

NameH-indexPapersCitations
Stefan Schreiber1781233138528
Jun Wang1661093141621
William J. Sandborn1621317108564
Jens Nielsen1491752104005
Tak W. Mak14880794871
Annette Peters1381114101640
Severine Vermeire134108676352
Peter M. Rothwell13477967382
Dusan Bruncko132104284709
Gideon Bella129130187905
Dirk Schadendorf1271017105777
Neal L. Benowitz12679260658
Thomas Schwarz12370154560
Meletios A. Dimopoulos122137171871
Christian Weber12277653842
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Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
2023197
2022421
20212,760
20202,643
20192,556
20182,247