| 1. |
- Rosendahl, J, et al.
(författare)
-
Genome-wide association study identifies inversion in the CTRB1-CTRB2 locus to modify risk for alcoholic and non-alcoholic chronic pancreatitis
- 2018
-
Ingår i: Gut. - : BMJ. - 1468-3288 .- 0017-5749. ; 67:10, s. 1855-1863
-
Tidskriftsartikel (refereegranskat)abstract
- Alcohol-related pancreatitis is associated with a disproportionately large number of hospitalisations among GI disorders. Despite its clinical importance, genetic susceptibility to alcoholic chronic pancreatitis (CP) is poorly characterised. To identify risk genes for alcoholic CP and to evaluate their relevance in non-alcoholic CP, we performed a genome-wide association study and functional characterisation of a new pancreatitis locus.Design1959 European alcoholic CP patients and population-based controls from the KORA, LIFE and INCIPE studies (n=4708) as well as chronic alcoholics from the GESGA consortium (n=1332) were screened with Illumina technology. For replication, three European cohorts comprising 1650 patients with non-alcoholic CP and 6695 controls originating from the same countries were used.ResultsWe replicated previously reported risk loci CLDN2-MORC4, CTRC, PRSS1-PRSS2 and SPINK1 in alcoholic CP patients. We identified CTRB1-CTRB2 (chymotrypsin B1 and B2) as a new risk locus with lead single-nucleotide polymorphism (SNP) rs8055167 (OR 1.35, 95% CI 1.23 to 1.6). We found that a 16.6 kb inversion in the CTRB1-CTRB2 locus was in linkage disequilibrium with the CP-associated SNPs and was best tagged by rs8048956. The association was replicated in three independent European non-alcoholic CP cohorts of 1650 patients and 6695 controls (OR 1.62, 95% CI 1.42 to 1.86). The inversion changes the expression ratio of the CTRB1 and CTRB2 isoforms and thereby affects protective trypsinogen degradation and ultimately pancreatitis risk.ConclusionAn inversion in the CTRB1-CTRB2 locus modifies risk for alcoholic and non-alcoholic CP indicating that common pathomechanisms are involved in these inflammatory disorders.
|
|
| 2. |
- Kmiecik, M., et al.
(författare)
-
Spin-alignment and g-factor Measurement of the I=12+ Isomer in 192Pb Produced in the Relativistic-energy Fragmentation of a 238U Beam
- 2010
-
Ingår i: European Physical Journal A. Hadrons and Nuclei. - : Springer Science and Business Media LLC. - 1434-6001. ; 45:2, s. 153-158
-
Tidskriftsartikel (refereegranskat)abstract
- The feasibility of measuring g-factors using the TDPAD method applied to high-energy, heavy fragmentation products is explored. The 2623 keV I-pi = 12(+) isomer in Pb-192 with tau = 1.57 mu s has been produced using the fragmentation of a 1 A GeV U-238 beam. The results presented demonstrate for the first time that such heavy nuclei produced in a fragmentation reaction with a relativistic beam are sufficiently well spin-aligned. Moreover, the rather large value of the alignment, 28(10)% of the maximum possible, is preserved during the separation process allowing the determination of magnetic moments. The measured values of the lifetime, tau = 1.54(9) mu s, and the g-factor, g = -0.175(20), agree with the results of previous investigations using fusion-evaporation reactions.
|
|
| 3. |
- Zhukova, Nataliya, et al.
(författare)
-
WNT activation by lithium abrogates TP53 mutation associated radiation resistance in medulloblastoma
- 2014
-
Ingår i: Acta neuropathologica communications. - : Springer Science and Business Media LLC. - 2051-5960. ; 2
-
Tidskriftsartikel (refereegranskat)abstract
- TP53 mutations confer subgroup specific poor survival for children with medulloblastoma. We hypothesized that WNT activation which is associated with improved survival for such children abrogates TP53 related radioresistance and can be used to sensitize TP53 mutant tumors for radiation. We examined the subgroup-specific role of TP53 mutations in a cohort of 314 patients treated with radiation. TP53 wild-type or mutant human medulloblastoma cell-lines and normal neural stem cells were used to test radioresistance of TP53 mutations and the radiosensitizing effect of WNT activation on tumors and the developing brain. Children with WNT/TP53 mutant medulloblastoma had higher 5-year survival than those with SHH/TP53 mutant tumours (100% and 36.6%±8.7%, respectively (p<0.001)). Introduction of TP53 mutation into medulloblastoma cells induced radioresistance (survival fractions at 2Gy (SF2) of 89%±2% vs. 57.4%±1.8% (p<0.01)). In contrast, beta-catenin mutation sensitized TP53 mutant cells to radiation (p<0.05). Lithium, an activator of the WNT pathway, sensitized TP53 mutant medulloblastoma to radiation (SF2 of 43.5%±1.5% in lithium treated cells vs. 56.6±3% (p<0.01)) accompanied by increased number of gammaH2AX foci. Normal neural stem cells were protected from lithium induced radiation damage (SF2 of 33%±8% for lithium treated cells vs. 27%±3% for untreated controls (p=0.05). Poor survival of patients with TP53 mutant medulloblastoma may be related to radiation resistance. Since constitutive activation of the WNT pathway by lithium sensitizes TP53 mutant medulloblastoma cells and protect normal neural stem cells from radiation, this oral drug may represent an attractive novel therapy for high-risk medulloblastomas.
|
|
| 4. |
|
|
| 5. |
- Lach, Stefan, et al.
(författare)
-
Metal-Organic Hybrid Interface States of A Ferromagnet/Organic Semiconductor Hybrid Junction as Basis For Engineering Spin Injection in Organic Spintronics
- 2012
-
Ingår i: Advanced Functional Materials. - : Wiley. - 1616-301X .- 1616-3028. ; 22:5, s. 989-997
-
Tidskriftsartikel (refereegranskat)abstract
- Electrons in organic semiconductors (OSC) possess remarkably long spin relaxation times. Hybrid spintronic devices that combine OSC with ferromagnetic (FM) substrates are therefore expected to provide a route to devices with improved and new functionalities. A crucial role is played by the FM-OSC interface which governs the spin injection into the OSC. Using spin-resolved photoelectron spectroscopy and ab initio calculations we study here such possible injection channels in metal phthalocyanines (MPc). We report the first direct observation of the successful engineering of different spin-selective hybrid interface states at the Fermi level of a FM-OSC hybrid junction only by changing the central metal atom of a MPc. Our results demonstrate that tailoring the chemical interaction at the FM-OSC interface is a promising way to modify the spin injection channels and thus the spin injection capability.
|
|
