| 311. |
- Puschmann, Andreas, et al.
(författare)
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Heterozygous PINK1 p.G411S increases risk of Parkinson's disease via a dominant-negative mechanism
- 2017
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Ingår i: Brain. - : Oxford University Press (OUP). - 1460-2156 .- 0006-8950. ; 140:1, s. 98-117
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Tidskriftsartikel (refereegranskat)abstract
- SEE GANDHI AND PLUN-FAVREAU DOI101093/AWW320 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: It has been postulated that heterozygous mutations in recessive Parkinson's genes may increase the risk of developing the disease. In particular, the PTEN-induced putative kinase 1 (PINK1) p.G411S (c.1231G>A, rs45478900) mutation has been reported in families with dominant inheritance patterns of Parkinson's disease, suggesting that it might confer a sizeable disease risk when present on only one allele. We examined families with PINK1 p.G411S and conducted a genetic association study with 2560 patients with Parkinson's disease and 2145 control subjects. Heterozygous PINK1 p.G411S mutations markedly increased Parkinson's disease risk (odds ratio = 2.92, P = 0.032); significance remained when supplementing with results from previous studies on 4437 additional subjects (odds ratio = 2.89, P = 0.027). We analysed primary human skin fibroblasts and induced neurons from heterozygous PINK1 p.G411S carriers compared to PINK1 p.Q456X heterozygotes and PINK1 wild-type controls under endogenous conditions. While cells from PINK1 p.Q456X heterozygotes showed reduced levels of PINK1 protein and decreased initial kinase activity upon mitochondrial damage, stress-response was largely unaffected over time, as expected for a recessive loss-of-function mutation. By contrast, PINK1 p.G411S heterozygotes showed no decrease of PINK1 protein levels but a sustained, significant reduction in kinase activity. Molecular modelling and dynamics simulations as well as multiple functional assays revealed that the p.G411S mutation interferes with ubiquitin phosphorylation by wild-type PINK1 in a heterodimeric complex. This impairs the protective functions of the PINK1/parkin-mediated mitochondrial quality control. Based on genetic and clinical evaluation as well as functional and structural characterization, we established p.G411S as a rare genetic risk factor with a relatively large effect size conferred by a partial dominant-negative function phenotype.
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| 312. |
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| 313. |
- Salami, H., et al.
(författare)
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Spectroscopic observations, spin-orbit functions, and coupled-channel deperturbation analysis of data on the A (1)Sigma(+)(u) and b (3)Pi(u) states of Rb-2
- 2009
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Ingår i: Physical Review A (Atomic, Molecular and Optical Physics). - 1050-2947. ; 80:2
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Tidskriftsartikel (refereegranskat)abstract
- We present experimentally derived potential curves and spin-orbit interaction functions for the strongly perturbed A (1)Sigma(+)(u) and b (3)Pi(u) states of the rubidium dimer. The results are based on laser-induced fluorescence and optical-optical double-resonance polarization spectroscopy measurements combined with earlier laser-induced fluorescence data. We used an analytic potential (Hannover form) incorporated in a discrete variable representation of the Hamiltonian matrix for numerical energy-level calculation. A previous vibrational assignment of the A levels is confirmed, and very probable vibrational assignment for the b levels is also obtained. Currently, the rms residual of our fit is 0.053 cm(-1) as compared to the typical experimental uncertainties that are estimated to be 0.005 cm(-1). Fitted diagonal and off-diagonal spin-orbit functions are obtained and compared with ab initio calculations by all electrons and effective core pseudopotential methods. Analysis of the computational results yields an explanation for the ubiquitous single minima in these spin-orbit functions, which can be represented approximately by Morse-type functions.
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| 314. |
- Ampatzoglou, A., et al.
(författare)
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Effects of increased wholegrain consumption on immune and inflammatory markers in healthy low habitual wholegrain consumers.
- 2016
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Ingår i: European Journal of Nutrition. - : Springer Science and Business Media LLC. - 1436-6207 .- 1436-6215. ; 55:1, s. 183-195
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Tidskriftsartikel (refereegranskat)abstract
- Wholegrain (WG) consumption is associated with reduced risk of cardiovascular disease, but clinical data on inflammation and immune function is either conflicting or limited. The objective of this study was to assess the impact of increasing WG consumption to at least 80 g/day on markers of inflammation and glucose metabolism and on phenotypic and functional aspects of the immune system, in healthy, middle-aged adults with low habitual WG intake. Subjects consumed a diet high in WG (> 80 g/day) or low in WG (
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| 315. |
- Ampatzoglou, A., et al.
(författare)
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Increased Whole Grain Consumption Does Not Affect Blood Biochemistry, Body Composition, or Gut Microbiology in Healthy, Low-Habitual Whole Grain Consumers
- 2015
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Ingår i: Journal of Nutrition. - : Elsevier BV. - 1541-6100 .- 0022-3166. ; 145:2, s. 215-221
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Tidskriftsartikel (refereegranskat)abstract
- Background: Whole-grain (WG) foods have been suggested to reduce the risk of cardiovascular disease, but studies are inconsistent and effects on cardiovascular risk markers are not clear. Objective: The objective of this study was to assess the impact of increasing WG consumption to at least 80 g/d on overall dietary intake, body composition, blood pressure (BP), blood lipids, blood glucose, gastrointestinal microbiology, and gastrointestinal symptoms in healthy, middle-aged adults with habitual WG intake 80 g/d) or low in WG[
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| 316. |
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| 317. |
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| 318. |
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| 319. |
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| 320. |
- Fairchild, Ian J., et al.
(författare)
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Tonian-Cryogenian boundary sections of Argyll, Scotland
- 2018
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Ingår i: Precambrian Research. - : Elsevier BV. - 0301-9268 .- 1872-7433. ; 319, s. 37-64
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Tidskriftsartikel (refereegranskat)abstract
- The Tonian-Cryogenian System boundary is to be defined at a GSSP (Global Boundary Stratigraphic Section and Point) beneath the first evidence of widespread glaciation. A candidate lies within the Dalradian Supergroup of Scotland and Ireland, which is least deformed and metamorphosed in Argyll, western Scotland. We present new stratigraphic profiles and interpretations from the Isle of Islay and the Garvellach Islands, update the chemostratigraphy of the Appin Group Tonian carbonates underlying the thick (ca. 1 km) glacigenic Port Askaig Formation (PAF) and demonstrate an environmental transition at the contact. The Appin Group forms a regionally extensive, > 4 km-thick, succession of limestones, shales and sandstones deposited on a marine shelf. On Islay, the upper part of the lithostratigraphy has been clarified by measuring and correlating two sections containing distinctive stratigraphic levels including molar tooth structure, oolite, stromatolitic dolomite and intraclastic microbial mounds. Significantly deeper erosion at the unconformity at the base of the overlying PAF is demonstrated in the southern section. Carbonate facies show a gradual decline in delta C-13(VPDB) from +5 to + 2 parts per thousand upwards. In NE Garbh Eileach (Garvellach Islands), a continuously exposed section of Appin Group carbonates, 70 m thick, here designated the Garbh Eileach Formation (GEF), lies conformably beneath the PAF. The GEF and the GEF-PAF boundary relationships are re -described with new sedimentological logs, petrological and stable isotope data. Interstratified limestone and dolomicrosparite with delta C-13 of -4 to -7 parts per thousand (a feature named the Garvellach anomaly, replacing the term Islay anomaly) are overlain by dolomite in which the isotope signature becomes weakly positive (up to +1 parts per thousand) upwards. Shallow subtidal conditions become peritidal upwards, with evidence of wave and storm activity. Gypsum pseudomorphs and subaerial exposure surfaces are common near the top of the GEF. The basal diamictite (D1) of the PAF is rich in carbonate clasts similar to slightly deeper water parts of the underlying succession. D1 is typically several metres thick with interstratified sandstone and conglomerate, but dies out laterally. Scattered siliciclastic coarse sandstone to pebble conglomerate with dropstones associated with soft -sediment deformation is interbedded with carbonate below and above D1. Dolomite beds with derived intraclasts and gypsum pseudomorphs are found above D1 (or equivalent position, where Dl is absent). Published and new Sr isotope studies, including successive leach data, demonstrate primary Tonian Sr-87/Sr-86 values of 0.7066-0.7069 on Islay, decreasing to 0.7064-0.7066 in the younger GEF limestones on the Garvellachs, with 1700-2700 ppm Sr. Other typically Tonian characteristics of the carbonates are the Sr-rich nature of limestones, molar tooth structure, and dolomitized peritidal facies with evidence of aridity. Seabed surveys suggesting uniformly-dipping strata and shallow borehole core material illustrate the potential for extending the Tonian record offshore of the Garvellachs. A candidate Tonian-Cryogenian GSSP is proposed on Garbh Eileach within the smooth delta C-13 profile at the cross-over to positive delta C-13 signatures, 4 m below the first occurrence of ice-rafted sediment and 9 m below the first diamictite. Although lacking radiometric constraints or stratigraphically significant biotas or biomarkers, the Scottish succession has a thick and relatively complete sedimentary record of glaciation, coherent carbon and strontium chemostratigraphy, lateral continuity of outcrops and 100% exposure at the proposed boundary interval.
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