| 1. |
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| 2. |
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| 3. |
- Lis, D. C., et al.
(författare)
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Herschel/HIFI discovery of interstellar chloronium (H2Cl+)
- 2010
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 521:1
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Tidskriftsartikel (refereegranskat)abstract
- We report the first detection of chloronium, H_2Cl^+, in the interstellar medium, using the HIFI instrument aboard the Herschel Space Observatory. The 2_12-1_01 lines of ortho-H\_2^35Cl^+ and ortho-H\_2^37Cl^+ are detected in absorption towards NGC 6334I, and the 1_11-0_00 transition of para-H\_2^35Cl^+ is detected in absorption towards NGC 6334I and Sgr B2(S). The H_2Cl^+ column densities are compared to those of the chemically-related species HCl. The derived HCl/H_2Cl^+ column density ratios, ~1-10, are within the range predicted by models of diffuse and dense photon dominated regions (PDRs). However, the observed H_2Cl^+ column densities, in excess of 10^13 cm^-2, are significantly higher than the model predictions. Our observations demonstrate the outstanding spectroscopic capabilities of HIFI for detecting new interstellar molecules and providing key constraints for astrochemical models.
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| 4. |
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| 5. |
- Ceccarelli, C., et al.
(författare)
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Herschel spectral surveys of star- forming regions Overview of the 555-636 GHz range
- 2010
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 521, s. L22-
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Tidskriftsartikel (refereegranskat)abstract
- High resolution line spectra of star-forming regions are mines of information: they provide unique clues to reconstruct the chemical, dynamical, and physical structure of the observed source. We present the first results from the Herschel key project " Chemical HErschel Surveys of Star forming regions", CHESS. We report and discuss observations towards five CHESS targets, one outflow shock spot and four protostars with luminosities bewteen 20 and 2 x 105 L similar to : L1157-B1, IRAS 16293-2422, OMC2-FIR4, AFGL 2591, and NGC 6334I. The observations were obtained with the heterodyne spectrometer HIFI on board Herschel, with a spectral resolution of 1 MHz. They cover the frequency range 555-636 GHz, a range largely unexplored before the launch of the Herschel satellite. A comparison of the five spectra highlights spectacular differences in the five sources, for example in the density of methanol lines, or the presence./absence of lines from S-bearing molecules or deuterated species. We discuss how these differences can be attributed to the different star-forming mass or evolutionary status.
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| 6. |
- Codella, C., et al.
(författare)
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The CHESS spectral survey of star forming regions : Peering into the protostellar shock L1157-B1. I. Shock chemical complexity
- 2010
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 518, s. L112-
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Tidskriftsartikel (refereegranskat)abstract
- We present the first results of the unbiased survey of the L1157-B1 bow shock, obtained with HIFI in the framework of the key program Chemical HErschel Survey of Star forming regions (CHESS). The L1157 outflow is driven by a low-mass Class 0 protostar and is considered the prototype of the so-called chemically active outflows. The bright blue-shifted bow shock B1 is the ideal laboratory for studying the link between the hot (~1000-2000 K) component traced by H2 IR-emission and the cold (~10-20 K) swept-up material. The main aim is to trace the warm gas chemically enriched by the passage of a shock and to infer the excitation conditions in L1157-B1. A total of 27 lines are identified in the 555-636 GHz region, down to an average 3σ level of 30 mK. The emission is dominated by CO(5-4) and H2O(110-101) transitions, as discussed by Lefloch et al. in this volume. Here we report on the identification of lines from NH3, H2CO, CH3OH, CS, HCN, and HCO+. The comparison between the profiles produced by molecules released from dust mantles (NH3, H2CO, CH3OH) and that of H2O is consistent with a scenario in which water is also formed in the gas-phase in high-temperature regions where sputtering or grain-grain collisions are not efficient. The high excitation range of the observed tracers allows us to infer, for the first time for these species, the existence of a warm (≥200 K) gas component coexisting in the B1 bow structure with the cold and hot gas detected from ground. Herschel is an ESA space observatory with science instruments provided by European-led principal Investigator consortia and with important participation from NASA.Table 1 is only available in electronic form at http://www.aanda.org
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| 7. |
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| 8. |
- Gretarsdottir, Solveig, et al.
(författare)
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Genome-wide association study identifies a sequence variant within the DAB2IP gene conferring susceptibility to abdominal aortic aneurysm
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 42:8, s. 71-692
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Tidskriftsartikel (refereegranskat)abstract
- We performed a genome-wide association study on 1,292 individuals with abdominal aortic aneurysms (AAAs) and 30,503 controls from Iceland and The Netherlands, with a follow-up of top markers in up to 3,267 individuals with AAAs and 7,451 controls. The A allele of rs7025486 on 9q33 was found to associate with AAA, with an odds ratio (OR) of 1.21 and P = 4.6 x 10(-10). In tests for association with other vascular diseases, we found that rs7025486[A] is associated with early onset myocardial infarction (OR = 1.18, P = 3.1 x 10(-5)), peripheral arterial disease (OR = 1.14, P = 3.9 x 10(-5)) and pulmonary embolism (OR = 1.20, P = 0.00030), but not with intracranial aneurysm or ischemic stroke. No association was observed between rs7025486[A] and common risk factors for arterial and venous diseases-that is, smoking, lipid levels, obesity, type 2 diabetes and hypertension. Rs7025486 is located within DAB2IP, which encodes an inhibitor of cell growth and survival.
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| 9. |
- Heid, Iris M, et al.
(författare)
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Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 949-960
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Tidskriftsartikel (refereegranskat)abstract
- Waist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body mass index (comprising up to 77,167 participants), following up 16 loci in an additional 29 studies (comprising up to 113,636 subjects). We identified 13 new loci in or near RSPO3, VEGFA, TBX15-WARS2, NFE2L3, GRB14, DNM3-PIGC, ITPR2-SSPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9 × 10⁻⁹ to P = 1.8 × 10⁻⁴⁰) and the known signal at LYPLAL1. Seven of these loci exhibited marked sexual dimorphism, all with a stronger effect on WHR in women than men (P for sex difference = 1.9 × 10⁻³ to P = 1.2 × 10⁻¹³). These findings provide evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions.
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| 10. |
- Lefloch, B., et al.
(författare)
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The CHESS spectral survey of star forming regions : Peering into the protostellar shock L1157-B1. II. Shock dynamics
- 2010
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 518, s. L113-
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Tidskriftsartikel (refereegranskat)abstract
- Context. The outflow driven by the low-mass class 0 protostar L1157 is the prototype of the so-called chemically active outflows. The bright bowshock B1 in the southern outflow lobe is a privileged testbed of magneto-hydrodynamical (MHD) shock models, for which dynamical and chemical processes are strongly interdependent. Aims: We present the first results of the unbiased spectral survey of the L1157-B1 bowshock, obtained in the framework of the key program “Chemical HErschel Surveys of star forming regions” (CHESS). The main aim is to trace the warm and chemically enriched gas and to infer the excitation conditions in the shock region. Methods: The CO 5-4 and o-H2O 110-101 lines have been detected at high-spectral resolution in the unbiased spectral survey of the HIFI-band 1b spectral window (555-636 GHz), presented by Codella et al. in this volume. Complementary ground-based observations in the submm window help establish the origin of the emission detected in the main-beam of HIFI and the physical conditions in the shock. Results: Both lines exhibit broad wings, which extend to velocities much higher than reported up to now. We find that the molecular emission arises from two regions with distinct physical conditions : an extended, warm (100 K), dense (3 × 105 cm-3) component at low-velocity, which dominates the water line flux in Band 1; a secondary component in a small region of B1 (a few arcsec) associated with high-velocity, hot (>400 K) gas of moderate density ((1.0-3.0) × 104 cm-3), which appears to dominate the flux of the water line at 179μm observed with PACS. The water abundance is enhanced by two orders of magnitude between the low- and the high-velocity component, from 8 × 10-7 up to 8 × 10-5. The properties of the high-velocity component agree well with the predictions of steady-state C-shock models. Herschel is an ESA space observatory with science instruments provided by European-led Principal Investigator consortia and with important participation from NASA.
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| 11. |
- Speliotes, Elizabeth K., et al.
(författare)
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Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 937-948
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and ~2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 × 10−8), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.
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| 12. |
- Vastel, C., et al.
(författare)
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Ortho-to-para ratio of interstellar heavy water
- 2010
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 521:1, s. Article Number: L31 -
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Tidskriftsartikel (refereegranskat)abstract
- Context. Despite the low elemental deuterium abundance in the Galaxy, enhanced molecular D/H ratios have been found in the environments of low-mass star-forming regions, and in particular the Class 0 protostar IRAS 16293-2422. Aims. The CHESS (Chemical HErschel Surveys of Star forming regions) key program aims to study the molecular complexity of the interstellar medium. The high sensitivity and spectral resolution of the Herschel/HIFI instrument provide a unique opportunity to observe the fundamental 1(1,1)-0(0,0) transition of the ortho-D2O molecule, which is inaccessible from the ground, and determine the ortho-to-para D2O ratio. Methods. We detected the fundamental transition of the ortho-D2O molecule at 607.35 GHz towards IRAS 16293-2422. The line is seen in absorption with a line opacity of 0.62 +/- 0.11 (1 sigma). From the previous ground-based observations of the fundamental 1(1,0)-1(0,1) transition of para-D2O seen in absorption at 316.80 GHz, we estimate a line opacity of 0.26 +/- 0.05 (1 sigma). Results. We show that the observed absorption is caused by the cold gas in the envelope of the protostar. Using these new observations, we estimate for the first time the ortho-to-para D2O ratio to be lower than 2.6 at a 3 sigma level of uncertainty, which should be compared with the thermal equilibrium value of 2:1.
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| 13. |
- Walters, R G, et al.
(författare)
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A new highly penetrant form of obesity due to deletions on chromosome 16p11.2.
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 463:7281, s. 671-5
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Tidskriftsartikel (refereegranskat)abstract
- Obesity has become a major worldwide challenge to public health, owing to an interaction between the Western 'obesogenic' environment and a strong genetic contribution. Recent extensive genome-wide association studies (GWASs) have identified numerous single nucleotide polymorphisms associated with obesity, but these loci together account for only a small fraction of the known heritable component. Thus, the 'common disease, common variant' hypothesis is increasingly coming under challenge. Here we report a highly penetrant form of obesity, initially observed in 31 subjects who were heterozygous for deletions of at least 593 kilobases at 16p11.2 and whose ascertainment included cognitive deficits. Nineteen similar deletions were identified from GWAS data in 16,053 individuals from eight European cohorts. These deletions were absent from healthy non-obese controls and accounted for 0.7% of our morbid obesity cases (body mass index (BMI) >or= 40 kg m(-2) or BMI standard deviation score >or= 4; P = 6.4 x 10(-8), odds ratio 43.0), demonstrating the potential importance in common disease of rare variants with strong effects. This highlights a promising strategy for identifying missing heritability in obesity and other complex traits: cohorts with extreme phenotypes are likely to be enriched for rare variants, thereby improving power for their discovery. Subsequent analysis of the loci so identified may well reveal additional rare variants that further contribute to the missing heritability, as recently reported for SIM1 (ref. 3). The most productive approach may therefore be to combine the 'power of the extreme' in small, well-phenotyped cohorts, with targeted follow-up in case-control and population cohorts.
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| 14. |
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| 15. |
- Lango Allen, Hana, et al.
(författare)
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Hundreds of variants clustered in genomic loci and biological pathways affect human height.
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 467:7317, s. 832-8
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Tidskriftsartikel (refereegranskat)abstract
- Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P<0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.
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| 16. |
- Moustafa, J. S. E., et al.
(författare)
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Novel association approach for variable number tandem repeats (VNTRs) identifies DOCK5 as a susceptibility gene for severe obesity
- 2012
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 21:16, s. 3727-3738
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Tidskriftsartikel (refereegranskat)abstract
- Variable number tandem repeats (VNTRs) constitute a relatively under-examined class of genomic variants in the context of complex disease because of their sequence complexity and the challenges in assaying them. Recent large-scale genome-wide copy number variant mapping and association efforts have highlighted the need for improved methodology for association studies using these complex polymorphisms. Here we describe the in-depth investigation of a complex region on chromosome 8p21.2 encompassing the dedicator of cytokinesis 5 (DOCK5) gene. The region includes two VNTRs of complex sequence composition which flank a common 3975 bp deletion, all three of which were genotyped by polymerase chain reaction and fragment analysis in a total of 2744 subjects. We have developed a novel VNTR association method named VNTRtest, suitable for association analysis of multi-allelic loci with binary and quantitative outcomes, and have used this approach to show significant association of the DOCK5 VNTRs with childhood and adult severe obesity (P-empirical 8.9 10(8) and P 3.1 10(3), respectively) which we estimate explains approximate to 0.8 of the phenotypic variance. We also identified an independent association between the 3975 base pair (bp) deletion and obesity, explaining a further 0.46 of the variance (P-combined 1.6 10(3)). Evidence for association between DOCK5 transcript levels and the 3975 bp deletion (P 0.027) and both VNTRs (P-empirical 0.015) was also identified in adipose tissue from a Swedish family sample, providing support for a functional effect of the DOCK5 deletion and VNTRs. These findings highlight the potential role of DOCK5 in human obesity and illustrate a novel approach for analysis of the contribution of VNTRs to disease susceptibility through association studies.
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| 17. |
- Palmer, Nicholette D, et al.
(författare)
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A genome-wide association search for type 2 diabetes genes in African Americans.
- 2012
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Ingår i: PloS one. - San Francisco : Public Library of Science (PLoS). - 1932-6203. ; 7:1, s. e29202-
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Tidskriftsartikel (refereegranskat)abstract
- African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations.
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| 18. |
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| 19. |
- Carvalho, F. A., et al.
(författare)
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Transient Inability to Manage Proteobacteria Promotes Chronic Gut Inflammation in TLR5-Deficient Mice
- 2012
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Ingår i: Cell Host & Microbe. - : Elsevier BV. - 1931-3128. ; 12:2, s. 139-152
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Tidskriftsartikel (refereegranskat)abstract
- Colitis results from breakdown of homeostasis between intestinal microbiota and the mucosal immune system, with both environmental and genetic influencing factors. Flagellin receptor TLR5-deficient mice (T5KO) display elevated intestinal proinflammatory gene expression and colitis with incomplete penetrance, providing a genetically sensitized system to study the contribution of microbiota to driving colitis. Both colitic and noncolitic T5KO exhibited transiently unstable microbiotas, with lasting differences in colitic T5KO, while their noncolitic siblings stabilized their microbiotas to resemble wild-type mice. Transient high levels of proteobacteria, especially enterobacteria species including E. coli, observed in close proximity to the gut epithelium were a striking feature of colitic microbiota. A Crohn's disease-associated E. coli strain induced chronic colitis in T5KO, which persisted well after the exogenously introduced bacterial species had been eliminated. Thus, an innate immune deficiency can result in unstable gut microbiota associated with low-grade inflammation, and harboring proteobacteria can drive and/or instigate chronic colitis.
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| 20. |
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| 21. |
- Szatkiewicz, JP, et al.
(författare)
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Copy number variation in schizophrenia in Sweden
- 2014
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Ingår i: Molecular psychiatry. - : Springer Science and Business Media LLC. - 1476-5578 .- 1359-4184. ; 19:7, s. 762-773
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Tidskriftsartikel (refereegranskat)
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| 22. |
- Walters, S., et al.
(författare)
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Breast cancer survival and stage at diagnosis in Australia, Canada, Denmark, Norway, Sweden and the UK, 2000-2007 : a population-based study
- 2013
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 108:5, s. 1195-1208
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Tidskriftsartikel (refereegranskat)abstract
- Background: We investigate whether differences in breast cancer survival in six high-income countries can be explained by differences in stage at diagnosis using routine data from population-based cancer registries. Methods: We analysed the data on 257 362 women diagnosed with breast cancer during 2000-7 and registered in 13 population-based cancer registries in Australia, Canada, Denmark, Norway, Sweden and the UK. Flexible parametric hazard models were used to estimate net survival and the excess hazard of dying from breast cancer up to 3 years after diagnosis. Results: Age-standardised 3-year net survival was 87-89% in the UK and Denmark, and 91-94% in the other four countries. Stage at diagnosis was relatively advanced in Denmark: only 30% of women had Tumour, Nodes, Metastasis (TNM) stage I disease, compared with 42-45% elsewhere. Women in the UK had low survival for TNM stage III-IV disease compared with other countries. Conclusion: International differences in breast cancer survival are partly explained by differences in stage at diagnosis, and partly by differences in stage-specific survival. Low overall survival arises if the stage distribution is adverse (e. g. Denmark) but stage-specific survival is normal; or if the stage distribution is typical but stage-specific survival is low (e. g. UK). International differences in staging diagnostics and stage-specific cancer therapies should be investigated.
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