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- Van Deerlin, Vivian M, et al.
(författare)
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Common variants at 7p21 are associated with frontotemporal lobar degeneration with TDP-43 inclusions
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:3, s. 234-239
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Tidskriftsartikel (refereegranskat)abstract
- Frontotemporal lobar degeneration (FTLD) is the second most common cause of presenile dementia. The predominant neuropathology is FTLD with TAR DNA-binding protein (TDP-43) inclusions (FTLD-TDP). FTLD-TDP is frequently familial, resulting from mutations in GRN (which encodes progranulin). We assembled an international collaboration to identify susceptibility loci for FTLD-TDP through a genome-wide association study of 515 individuals with FTLD-TDP. We found that FTLD-TDP associates with multiple SNPs mapping to a single linkage disequilibrium block on 7p21 that contains TMEM106B. Three SNPs retained genome-wide significance following Bonferroni correction (top SNP rs1990622, P = 1.08 x 10(-11); odds ratio, minor allele (C) 0.61, 95% CI 0.53-0.71). The association replicated in 89 FTLD-TDP cases (rs1990622; P = 2 x 10(-4)). TMEM106B variants may confer risk of FTLD-TDP by increasing TMEM106B expression. TMEM106B variants also contribute to genetic risk for FTLD-TDP in individuals with mutations in GRN. Our data implicate variants in TMEM106B as a strong risk factor for FTLD-TDP, suggesting an underlying pathogenic mechanism.
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- Thompson, Paul M., et al.
(författare)
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The ENIGMA Consortium : large-scale collaborative analyses of neuroimaging and genetic data
- 2014
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Ingår i: BRAIN IMAGING BEHAV. - : Springer Science and Business Media LLC. - 1931-7557 .- 1931-7565. ; 8:2, s. 153-182
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Tidskriftsartikel (refereegranskat)abstract
- The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, ENIGMA studies have analyzed neuroimaging data from over 12,826 subjects. In addition, data from 12,171 individuals were provided by the CHARGE consortium for replication of findings, in a total of 24,997 subjects. By meta-analyzing results from many sites, ENIGMA has detected factors that affect the brain that no individual site could detect on its own, and that require larger numbers of subjects than any individual neuroimaging study has currently collected. ENIGMA's first project was a genome-wide association study identifying common variants in the genome associated with hippocampal volume or intracranial volume. Continuing work is exploring genetic associations with subcortical volumes (ENIGMA2) and white matter microstructure (ENIGMA-DTI). Working groups also focus on understanding how schizophrenia, bipolar illness, major depression and attention deficit/hyperactivity disorder (ADHD) affect the brain. We review the current progress of the ENIGMA Consortium, along with challenges and unexpected discoveries made on the way.
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- Ferrari, Raffaele, et al.
(författare)
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Frontotemporal dementia and its subtypes: a genome-wide association study.
- 2014
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Ingår i: Lancet Neurology. - 1474-4465. ; 13:7, s. 686-699
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Tidskriftsartikel (refereegranskat)abstract
- Frontotemporal dementia (FTD) is a complex disorder characterised by a broad range of clinical manifestations, differential pathological signatures, and genetic variability. Mutations in three genes-MAPT, GRN, and C9orf72-have been associated with FTD. We sought to identify novel genetic risk loci associated with the disorder.
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- Gomez, L. F., et al.
(författare)
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Shapes and vorticities of superfluid helium nanodroplets
- 2014
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 345:6199, s. 906-909
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Tidskriftsartikel (refereegranskat)abstract
- Helium nanodroplets are considered ideal model systems to explore quantum hydrodynamics in self-contained, isolated superfluids. However, exploring the dynamic properties of individual droplets is experimentally challenging. In this work, we used single-shot femtosecond x-ray coherent diffractive imaging to investigate the rotation of single, isolated superfluid helium-4 droplets containing ~108 to 1011 atoms. The formation of quantum vortex lattices inside the droplets is confirmed by observing characteristic Bragg patterns from xenon clusters trapped in the vortex cores. The vortex densities are up to five orders of magnitude larger than those observed in bulk liquid helium. The droplets exhibit large centrifugal deformations but retain axially symmetric shapes at angular velocities well beyond the stability range of viscous classical droplets.
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- Gallagher, Michael D., et al.
(författare)
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TMEM106B is a genetic modifier of frontotemporal lobar degeneration with C9orf72 hexanucleotide repeat expansions
- 2014
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Ingår i: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 0001-6322 .- 1432-0533. ; 127:3, s. 407-418
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Tidskriftsartikel (refereegranskat)abstract
- Hexanucleotide repeat expansions in chromosome 9 open reading frame 72 (C9orf72) have recently been linked to frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis, and may be the most common genetic cause of both neurodegenerative diseases. Genetic variants at TMEM106B influence risk for the most common neuropathological subtype of FTLD, characterized by inclusions of TAR DNA-binding protein of 43 kDa (FTLD-TDP). Previous reports have shown that TMEM106B is a genetic modifier of FTLD-TDP caused by progranulin (GRN) mutations, with the major (risk) allele of rs1990622 associating with earlier age at onset of disease. Here, we report that rs1990622 genotype affects age at death in a single-site discovery cohort of FTLD patients with C9orf72 expansions (n = 14), with the major allele correlated with later age at death (p = 0.024). We replicate this modifier effect in a 30-site international neuropathological cohort of FTLD-TDP patients with C9orf72 expansions (n = 75), again finding that the major allele associates with later age at death (p = 0.016), as well as later age at onset (p = 0.019). In contrast, TMEM106B genotype does not affect age at onset or death in 241 FTLD-TDP cases negative for GRN mutations or C9orf72 expansions. Thus, TMEM106B is a genetic modifier of FTLD with C9orf72 expansions. Intriguingly, the genotype that confers increased risk for developing FTLD-TDP (major, or T, allele of rs1990622) is associated with later age at onset and death in C9orf72 expansion carriers, providing an example of sign epistasis in human neurodegenerative disease.
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- Huang, Z. Y., et al.
(författare)
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DETECTION OF MULTIPLE BIPOLAR FLOWS IN NGC 7027 WITH SUBMILLIMETER ARRAY
- 2010
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Ingår i: Astrophysical Journal. - 1538-4357 .- 0004-637X. ; 722:1, s. 273-280
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Tidskriftsartikel (refereegranskat)abstract
- Highly collimated multiple bipolar flows are detected with a 3 '' resolution in the HCO+ (J = 3-2) and HCN (J = 3-2) lines in the young planetary nebula NGC 7027 with the Submillimeter Array. The HCO+ and HCN flows coincide in location and velocity with compact and fast CO flows detected with similar to 6 '' resolutions with other millimeter arrays. The equatorial molecular torus of NGC 7027 is captured in HCO+ emission in the present observations. The HCO+ emission also closely follows the H-2 emission, indicating that the present observations probe the photon-dominated region of the molecular envelope of NGC 7027.
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| 14. |
- Karlsson, Magnus, et al.
(författare)
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Inferior physical performance tests in 10,998 men in the MrOS study is associated with recurrent falls
- 2012
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Ingår i: Age and Ageing. - : Oxford University Press (OUP). - 0002-0729 .- 1468-2834. ; 41:6, s. 740-746
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Tidskriftsartikel (refereegranskat)abstract
- Background: recurrent fallers are at especially high risk for injuries. Objective: to study whether tests of physical performance are associated with recurrent falls. Subjects: a total of 10,998 men aged 65 years or above. Methods: questionnaires evaluated falls sustained 12 months preceding testing of grip strength, timed stand, 6-m walk and 20-cm narrow walk test. Means with 95% confidence interval (95% CI) are reported. P < 0.01 is a statistically significant difference. Results: in comparison to both occasional fallers and non-fallers, recurrent fallers performed more poorly on all the physical ability tests (all P < 0.001). A score below -2 standard deviations (SDs) in the right-hand grip strength test was associated with an odds ratio of 2.4 (95% CI 1.7, 3.4) for having had recurrent falls compared with having had no fall and of 2.0 (95% CI 1.3, 3.4) for having had recurrent falls compared with having had an occasional fall. Conclusion: low performance in physical ability tests are in elderly men associated with recurrent falls.
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- Tambyah, Paul A, et al.
(författare)
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Safety and immunogenicity of two different doses of a Vero cell-derived, whole virus clade 2 H5N1 (A/Indonesia/05/2005) influenza vaccine.
- 2012
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Ingår i: Vaccine. - : Elsevier. - 0264-410X .- 1873-2518. ; 30:2, s. 329-35
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Tidskriftsartikel (refereegranskat)abstract
- A successful vaccine development strategy for areas with clustered H5N1 events requires conduct of vaccine trials in potentially non-naïve subjects and evaluation of post-vaccination responsiveness. An open-label, randomized, phase I/II study therefore assessed the immunogenicity and safety of two different dose levels of an inactivated, non-adjuvanted, whole virus clade 2.1 (A/Indonesia/05/2005) H5N1 Vero cell-derived influenza vaccine in healthy adults (21-45 years) from a region where the virus has been circulating (Hong Kong) as well as Singapore. Subjects (N=110) were randomized 1:1 to receive two vaccinations with either 3.75 μg or 7.5 μg H5N1 haemagglutinin antigen 21 days apart. Safety, immunogenicity (microneutralization [MN] and single radial haemolysis [SRH] at baseline and post-vaccination) and cross-reactivity against a heterologous clade 1 strain (A/Vietnam/1203/2004) of the vaccine were assessed. Pre-existing immunity to the vaccine strain was 14% which is higher than previously reported for these regions. Two vaccinations with either vaccine formulation induced high seroprotection rates (MN titre ≥ 1:20) against the vaccine strain A/Indonesia/05/2005: 82.7% and 86.5% in the 3.75 μg and 7.5 μg dose groups. Seroconversion rates and fold increase exceeded the CPMP criterion of >40% and >2.5 for MN and SRH in both dose groups after the second vaccination, while the seroprotection rate in the 7.5 μg dose group determined by SRH was only marginally lower (69.2%) than the CPMP criterion of >70%. Thus, 11 of 12 CHMP criteria were fulfilled. A cross-reactive antibody response against the heterologous A/Vietnam/1203/2004 strain was demonstrated after the second vaccination (>21% by MN and ≥ 25% by SRH). Persistence of antibodies against the vaccine strain was also demonstrated 6 months after the first vaccination, indicating that a booster vaccination would be effective in those who have received two priming doses. No serious adverse events were reported. The H5N1 influenza vaccine against clade 2.1 strain A/Indonesia/05/2005 was well tolerated and immunogenic after two vaccinations, and induced a cross-neutralizing antibody response, with no dose effect.
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| 17. |
- Welp, U., et al.
(författare)
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Anisotropic phase diagram and superconducting fluctuations of single-crystalline SmFeAsO(0.85)F(0.15)
- 2011
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Ingår i: Physical Review B. Condensed Matter and Materials Physics. - 1098-0121 .- 1550-235X. ; 83:10, s. 100513-
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Tidskriftsartikel (refereegranskat)abstract
- We report on the specific-heat determination of the anisotropic phase diagram of single crystals of optimally doped SmFeAsO(1-x)F(x). In zero field, we find a clear cusplike anomaly in C/T with Delta C/T(c) = 24 mJ/mol K(2) at T(c) = 49.5 K. In magnetic fields along the c axis, pronounced superconducting fluctuations induce broadening and suppression of the specific-heat anomaly which can be described using three-dimensional lowest-Landau-level scaling with an upper critical field slope of -3.5 T/K and an anisotropy of Gamma = 8. The small value of Delta C/T(c) yields a Sommerfeld coefficient gamma similar to 8 mJ/mol K(2), indicating that SmFeAsO(1-x)F(x) is characterized by a modest density of states and strong coupling.
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| 18. |
- Yan, H., et al.
(författare)
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Photothermal-responsive [2]rotaxanes
- 2013
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Ingår i: RSC Advances. - : Royal Society of Chemistry (RSC). - 2046-2069. ; 3:7, s. 2341-2350
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Tidskriftsartikel (refereegranskat)abstract
- Three photothermal-responsive α-cyclodextrin-based [2]rotaxanes were prepared via the copper(i)-catalyzed azide-alkyne cycloaddition, in which the α-cyclodextrin ring was threaded onto the azobenzene dumbbell component. The difference between the three [2]rotaxanes are the length of the ethylene glycol repeating chains connected between the azobenzene and triazole units in the dumbbell components. The α-cyclodextrin rings in the [2]rotaxanes can be reversibly switched between the azobenzene unit and triazole/ethylene glycol unit driven by the trans-cis isomerization of the azobenzene unit. The trans-to-cis isomerization of the azobenzene unit under UV light irradiation (365 nm) leads the α-cyclodextrin ring moving to the triazole/ethylene glycol unit, while the cis-to-trans isomerization of the azobenzene unit under either visible light irradiation or heating enables the α-cyclodextrin ring shuttling back to the azobenzene station. The different ethylene glycol repeating chains in the [2]rotaxanes can affect (1) the isomerization rates of the azobenzene units, i.e. the longer the chain, the faster the isomerization rate, and (2) fluorescent quantum yields of the [2]rotaxanes, i.e. the longer the chain, the lower the fluorescent quantum yield. In addition, the quantum yields of the [2]rotaxanes were enhanced by UV light irradiation and decreased back upon visible light irradiation or heating at 65 °C. The current research provides a fundamental understanding of the working mechanism for photothermal-responsive [2]rotaxanes.
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