| 1. |
- Tragante, Vinicius, et al.
(författare)
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Gene-centric Meta-analysis in 87,736 Individuals of European Ancestry Identifies Multiple Blood-Pressure-Related Loci.
- 2014
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297. ; 94:3, s. 349-360
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Tidskriftsartikel (refereegranskat)abstract
- Blood pressure (BP) is a heritable risk factor for cardiovascular disease. To investigate genetic associations with systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), and pulse pressure (PP), we genotyped ∼50,000 SNPs in up to 87,736 individuals of European ancestry and combined these in a meta-analysis. We replicated findings in an independent set of 68,368 individuals of European ancestry. Our analyses identified 11 previously undescribed associations in independent loci containing 31 genes including PDE1A, HLA-DQB1, CDK6, PRKAG2, VCL, H19, NUCB2, RELA, HOXC@ complex, FBN1, and NFAT5 at the Bonferroni-corrected array-wide significance threshold (p < 6 × 10(-7)) and confirmed 27 previously reported associations. Bioinformatic analysis of the 11 loci provided support for a putative role in hypertension of several genes, such as CDK6 and NUCB2. Analysis of potential pharmacological targets in databases of small molecules showed that ten of the genes are predicted to be a target for small molecules. In summary, we identified previously unknown loci associated with BP. Our findings extend our understanding of genes involved in BP regulation, which may provide new targets for therapeutic intervention or drug response stratification.
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| 2. |
- Aad, G., et al.
(författare)
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- 2012
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swepub:Mat__t (refereegranskat)
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| 3. |
- Bellenguez, Celine, et al.
(författare)
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Genome-wide association study identifies a variant in HDAC9 associated with large vessel ischemic stroke
- 2012
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 44:3, s. 141-328
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Tidskriftsartikel (refereegranskat)abstract
- Genetic factors have been implicated in stroke risk, but few replicated associations have been reported. We conducted a genome-wide association study (GWAS) for ischemic stroke and its subtypes in 3,548 affected individuals and 5,972 controls, all of European ancestry. Replication of potential signals was performed in 5,859 affected individuals and 6,281 controls. We replicated previous associations for cardioembolic stroke near PITX2 and ZFHX3 and for large vessel stroke at a 9p21 locus. We identified a new association for large vessel stroke within HDAC9 (encoding histone deacetylase 9) on chromosome 7p21.1 (including further replication in an additional 735 affected individuals and 28,583 controls) (rs11984041; combined P = 1.87 x 10(-11); odds ratio (OR) = 1.42, 95% confidence interval (CI) = 1.28-1.57). All four loci exhibited evidence for heterogeneity of effect across the stroke subtypes, with some and possibly all affecting risk for only one subtype. This suggests distinct genetic architectures for different stroke subtypes.
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| 4. |
- Brown, James Benedict, 1982-, et al.
(författare)
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Let Loose the Loganberries of War : Making Noise and Occupying Space in Govanhill
- 2010
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Ingår i: Field. - : Sheffield School of Architecture. - 1755-0068. ; 3:1, s. 125-131
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Tidskriftsartikel (refereegranskat)abstract
- In the early hours of Tuesday 7 August 2001 approximately two hundred and fifty police officers - including mounted officers and an aerial surveillance unit - converged on Calder Street in the Glasgow neighbourhood of Govanhill. Accompanied by eight sheriff's officers bearing court orders for eviction, they had come to bring to an end the longest public occupation of a civic building in British history. For the previous 135 days up to seventy local residents at a time had occupied a building described by Historic Scotland as 'an architecturally and historically important part of the city’s history ... particularly important culturally in that until recently they offered a valued and distinctive facility open to all members of the community.'2 It took almost twenty hours to evict the protesters and seal the building with steel shutters. By late evening a crowd of approximately 200 people had gathered on the streets outside. Eggs, flour bombs and fruit were thrown at police officers, and the air was thick with the overpowering stench of garlic powder, three catering-sized tubs of which had been emptied around the building to confuse sniffer dogs sent into to locate the last of the protesters.
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| 5. |
- Brown, Michael R, et al.
(författare)
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Microphysics of Cosmic Plasmas : Hierarchies of Plasma Instabilities from MHD to Kinetic
- 2014. - 1
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Ingår i: Microphysics of cosmic plasmas. - Boston : Springer. - 9781489974129 - 9781489974136 ; , s. 281-307
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Bokkapitel (refereegranskat)abstract
- In this article, we discuss the idea of a hierarchy of instabilities that can rapidly couple the disparate scales of a turbulent plasma system. First, at the largest scale of the system, L, current carrying flux ropes can undergo a kink instability. Second, a kink instability in adjacent flux ropes can rapidly bring together bundles of magnetic flux and drive reconnection, introducing a new scale of the current sheet width, ℓ, perhaps several ion inertial lengths (δ i ) across. Finally, intense current sheets driven by reconnection electric fields can destabilize kinetic waves such as ion cyclotron waves as long as the drift speed of the electrons is large compared to the ion thermal speed, v D ≫v i . Instabilities such as these can couple MHD scales to kinetic scales, as small as the proton Larmor radius, ρ i .
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| 6. |
- Hepburn, Lucy, et al.
(författare)
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A Spaetzle-like role for nerve growth factor beta in vertebrate immunity to Staphylococcus aureus
- 2014
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 346:6209, s. 641-646
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Tidskriftsartikel (refereegranskat)abstract
- Many key components of innate immunity to infection are shared between Drosophila and humans. However, the fly Toll ligand Spaetzle is not thought to have a vertebrate equivalent. We have found that the structurally related cystine-knot protein, nerve growth factor β (NGFβ), plays an unexpected Spaetzle-like role in immunity to Staphylococcus aureus infection in chordates. Deleterious mutations of either human NGFβ or its high-affinity receptor tropomyosin-related kinase receptor A (TRKA) were associated with severe S. aureus infections. NGFβ was released by macrophages in response to S. aureus exoproteins through activation of the NOD-like receptors NLRP3 and NLRP4 and enhanced phagocytosis and superoxide-dependent killing, stimulated proinflammatory cytokine production, and promoted calcium-dependent neutrophil recruitment. TrkA knockdown in zebrafish increased susceptibility to S. aureus infection, confirming an evolutionarily conserved role for NGFβ-TRKA signaling in pathogen-specific host immunity.
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| 7. |
- Johnson, Toby, et al.
(författare)
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Blood Pressure Loci Identified with a Gene-Centric Array.
- 2011
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 1537-6605 .- 0002-9297. ; 89:6
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Tidskriftsartikel (refereegranskat)abstract
- Raised blood pressure (BP) is a major risk factor for cardiovascular disease. Previous studies have identified 47 distinct genetic variants robustly associated with BP, but collectively these explain only a few percent of the heritability for BP phenotypes. To find additional BP loci, we used a bespoke gene-centric array to genotype an independent discovery sample of 25,118 individuals that combined hypertensive case-control and general population samples. We followed up four SNPs associated with BP at our p < 8.56 × 10(-7) study-specific significance threshold and six suggestively associated SNPs in a further 59,349 individuals. We identified and replicated a SNP at LSP1/TNNT3, a SNP at MTHFR-NPPB independent (r(2) = 0.33) of previous reports, and replicated SNPs at AGT and ATP2B1 reported previously. An analysis of combined discovery and follow-up data identified SNPs significantly associated with BP at p < 8.56 × 10(-7) at four further loci (NPR3, HFE, NOS3, and SOX6). The high number of discoveries made with modest genotyping effort can be attributed to using a large-scale yet targeted genotyping array and to the development of a weighting scheme that maximized power when meta-analyzing results from samples ascertained with extreme phenotypes, in combination with results from nonascertained or population samples. Chromatin immunoprecipitation and transcript expression data highlight potential gene regulatory mechanisms at the MTHFR and NOS3 loci. These results provide candidates for further study to help dissect mechanisms affecting BP and highlight the utility of studying SNPs and samples that are independent of those studied previously even when the sample size is smaller than that in previous studies.
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| 8. |
- Kaya, Sarp, et al.
(författare)
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Highly Compressed Two-Dimensional Form of Water at Ambient Conditions
- 2013
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 3
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Tidskriftsartikel (refereegranskat)abstract
- The structure of thin-film water on a BaF2(111) surface under ambient conditions was studied using x-ray absorption spectroscopy from ambient to supercooled temperatures at relative humidity up to 95%. No hexagonal ice-like structure was observed in spite of the expected templating effect of the lattice-matched (111) surface. The oxygen K-edge x-ray absorption spectrum of liquid thin-film water on BaF2 exhibits, at all temperatures, a strong resemblance to that of high-density phases for which the observed spectroscopic features correlate linearly with the density. Surprisingly, the highly compressed, high-density thin-film liquid water is found to be stable from ambient (300 K) to supercooled (259 K) temperatures, although a lower-density liquid would be expected at supercooled conditions. Molecular dynamics simulations indicate that the first layer water on BaF2(111) is indeed in a unique local structure that resembles high-density water, with a strongly collapsed second coordination shell.
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| 9. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 10. |
- Lindström, Tom, et al.
(författare)
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Rapid shifts in dispersal behavior on an expanding range edge
- 2013
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 110:33, s. 13452-13456
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Tidskriftsartikel (refereegranskat)abstract
- Dispersal biology at an invasion front differs from that of populations within the range core, because novel evolutionary and ecological processes come into play in the nonequilibrium conditions at expanding range edges. In a world where species range limits are changing rapidly, we need to understand how individuals disperse at an invasion front. We analyzed an extensive dataset from radio-tracking invasive cane toads (Rhinella marina) over the first 8 y since they arrived at a site in tropical Australia. Movement patterns of toads in the invasion vanguard differed from those of individuals in the same area postcolonization. Our model discriminated encamped versus dispersive phases within each toads movements and demonstrated that pioneer toads spent longer periods in dispersive mode and displayed longer, more directed movements while they were in dispersive mode. These analyses predict that overall displacement per year is more than twice as far for toads at the invasion front compared with those tracked a few years later at the same site. Studies on established populations (or even those a few years postestablishment) thus may massively underestimate dispersal rates at the leading edge of an expanding population. This, in turn, will cause us to underpredict the rates at which invasive organisms move into new territory and at which native taxa can expand into newly available habitat under climate change.
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