| 1. |
- 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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| 2. |
- Söderström, Pär-Anders, et al.
(författare)
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Interaction position resolution simulations and in-beam measurements of the AGATA HPGe detectors
- 2011
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Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 638:1, s. 96-109
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Tidskriftsartikel (refereegranskat)abstract
- The interaction position resolution of the segmented HPGe detectors of an AGATA triple cluster detector has been studied through Monte Carlo simulations and in an in-beam experiment. A new method based on measuring the energy resolution of Doppler-corrected γ-ray spectra at two different target to detector distances is described. This gives the two-dimensional position resolution in the plane perpendicular to the direction of the emitted γ-ray. The γ-ray tracking was used to determine the full energy of the γ-rays and the first interaction point, which is needed for the Doppler correction. Five different heavy-ion induced fusion-evaporation reactions and a reference reaction were selected for the simulations. The results of the simulations show that the method works very well and gives a systematic deviation of in the FWHM of the interaction position resolution for the γ-ray energy range from 60 keV to 5 MeV. The method was tested with real data from an in-beam measurement using a 30Si beam at 64 MeV on a thin 12C target. Pulse-shape analysis of the digitized detector waveforms and γ-ray tracking was performed to determine the position of the first interaction point, which was used for the Doppler corrections. Results of the dependency of the interaction position resolution on the γ-ray energy and on the energy, axial location and type of the first interaction point, are presented. The FWHM of the interaction position resolution varies roughly linearly as a function of γ-ray energy from 8.5 mm at 250 keV to 4 mm at 1.5 MeV, and has an approximately constant value of about 4 mm in the γ-ray energy range from 1.5 to 4 MeV.
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| 3. |
- Maguire, K., et al.
(författare)
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A statistical analysis of circumstellar material in Type Ia supernovae
- 2013
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 436:1, s. 222-240
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Tidskriftsartikel (refereegranskat)abstract
- A key tracer of the elusive progenitor systems of Type Ia supernovae (SNe Ia) is the detection of narrow blueshifted time-varying Na I D absorption lines, interpreted as evidence of circumstellar material surrounding the progenitor system. The origin of this material is controversial, but the simplest explanation is that it results from previous mass-loss in a system containing a white dwarf and a non-degenerate companion star. We present new single-epoch intermediate-resolution spectra of 17 low-redshift SNe Ia taken with XShooter on the European Southern Observatory Very Large Telescope. Combining this sample with events from the literature, we confirm an excess (similar to 20 per cent) of SNe Ia displaying blueshifted narrow Na I D absorption features compared to redshifted Na I D features. The host galaxies of SNe Ia displaying blueshifted absorption profiles are skewed towards later-type galaxies, compared to SNe Ia that show no Na I D absorption and SNe Ia displaying blueshifted narrow Na I D absorption features have broader light curves. The strength of the Na I D absorption is stronger in SNe Ia displaying blueshifted Na I D absorption features than those without blueshifted features, and the strength of the blueshifted Na I D is correlated with the B - V colour of the SN at maximum light. This strongly suggests the absorbing material is local to the SN. In the context of the progenitor systems of SNe Ia, we discuss the significance of these findings and other recent observational evidence on the nature of SN Ia progenitors. We present a summary that suggests that there are at least two distinct populations of normal, cosmologically useful SNe Ia.
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| 4. |
- Motte, F., et al.
(författare)
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Initial highlights of the HOBYS key program, the Herschel imaging survey of OB young stellar objects
- 2010
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 518, s. L77-
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Tidskriftsartikel (refereegranskat)abstract
- We present the initial highlights of the HOBYS key program, which are based on Herschel images of the Rosette molecular complex and maps of the RCW120 H II region. Using both SPIRE at 250/350/500 mu m and PACS at 70/160 mu m or 100/160 mu m, the HOBYS survey provides an unbiased and complete census of intermediate-to high-mass young stellar objects, some of which are not detected by Spitzer. Key core properties, such as bolometric luminosity and mass (as derived from spectral energy distributions), are used to constrain their evolutionary stages. We identify a handful of high-mass prestellar cores and show that their lifetimes could be shorter in the Rosette molecular complex than in nearby low-mass star-forming regions. We also quantify the impact of expanding H II regions on the star formation process acting in both Rosette and RCW 120.
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| 5. |
- Nicholl, M., et al.
(författare)
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Slowly fading super-luminous supernovae that are not pair-instability explosions
- 2013
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 502:7471, s. 346-
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Tidskriftsartikel (refereegranskat)abstract
- Super-luminous supernovae(1-4) that radiate more than 1044 ergs per second at their peak luminosity have recently been discovered in faint galaxies at redshifts of 0.1-4. Some evolve slowly, resembling models of 'pair-instability' supernovae(5,6). Such models involve stars with original masses 140-260 times that of the Sun that now have carbon-oxygen cores of 65-130 solar masses. In these stars, the photons that prevent gravitational collapse are converted to electron-positron pairs, causing rapid contraction and thermonuclear explosions. Many solar masses of Ni-56 are synthesized; this isotope decays to Fe-56 via Co-56, powering bright light curves(7,8). Such massive progenitors are expected to have formed from metal-poor gas in the early Universe(9). Recently, supernova 2007bi in a galaxy at redshift 0.127 (about 12 billion years after the Big Bang) with a metallicity one-third that of the Sun was observed to look like a fading pair-instability supernova(1,10). Here we report observations of two slow-to-fade super-luminous supernovae that show relatively fast rise times and blue colours, which are incompatible with pair-instability models. Their late-time light-curve and spectral similarities to supernova 2007bi call the nature of that event into question. Our early spectra closely resemble typical fast-declining super-luminous supernovae(2,11,12), which are not powered by radio-activity. Modelling our observations with 10-16 solar masses of magnetar-energized(13,14) ejecta demonstrates the possibility of a common explosion mechanism. The lack of unambiguous nearby pair-instability events suggests that their local rate of occurrence is less than 6 x 10(-6) times that of the core-collapse rate.
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| 6. |
- Furberg, Helena, et al.
(författare)
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Genome-wide meta-analyses identify multiple loci associated with smoking behavior
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 42:5, s. 134-441
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Tidskriftsartikel (refereegranskat)abstract
- Consistent but indirect evidence has implicated genetic factors in smoking behavior1,2. We report meta-analyses of several smoking phenotypes within cohorts of the Tobacco and Genetics Consortium (n = 74,053). We also partnered with the European Network of Genetic and Genomic Epidemiology (ENGAGE) and Oxford-GlaxoSmithKline (Ox-GSK) consortia to follow up the 15 most significant regions (n > 140,000). We identified three loci associated with number of cigarettes smoked per day. The strongest association was a synonymous 15q25 SNP in the nicotinic receptor gene CHRNA3 (rs1051730[A], b = 1.03, standard error (s.e.) = 0.053, beta = 2.8 x 10(-73)). Two 10q25 SNPs (rs1329650[G], b = 0.367, s. e. = 0.059, beta = 5.7 x 10(-10); and rs1028936[A], b = 0.446, s. e. = 0.074, beta = 1.3 x 10(-9)) and one 9q13 SNP in EGLN2 (rs3733829[G], b = 0.333, s. e. = 0.058, P = 1.0 x 10(-8)) also exceeded genome-wide significance for cigarettes per day. For smoking initiation, eight SNPs exceeded genome-wide significance, with the strongest association at a nonsynonymous SNP in BDNF on chromosome 11 (rs6265[C], odds ratio (OR) = 1.06, 95% confidence interval (Cl) 1.04-1.08, P = 1.8 x 10(-8)). One SNP located near DBH on chromosome 9 (rs3025343[G], OR = 1.12, 95% Cl 1.08-1.18, P = 3.6 x 10(-8)) was significantly associated with smoking cessation.
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| 7. |
- Men'shchikov, A., et al.
(författare)
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Filamentary structures and compact objects in the Aquila and Polaris clouds observed by Herschel
- 2010
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 518, s. L103-
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Tidskriftsartikel (refereegranskat)abstract
- Our PACS and SPIRE images of the Aquila Rift and part of the Polaris Flare regions, taken during the science demonstration phase of Herschel discovered fascinating, omnipresent filamentary structures that appear to be physically related to compact cores. We briefly describe a new multi-scale, multi-wavelength source extraction method used to detect objects and measure their parameters in our Herschel images. All of the extracted starless cores (541 in Aquila and 302 in Polaris) appear to form in the long and very narrow filaments. With its combination of the far-IR resolution and sensitivity, Herschel directly reveals the filaments in which the dense cores are embedded; the filaments are resolved and have deconvolved widths of similar to 35 '' in Aquila and similar to 59 '' in Polaris (similar to 9000 AU in both regions). Our first results of observations with Herschel enable us to suggest that in general dense cores may originate in a process of fragmentation of complex networks of long, thin filaments, likely formed as a result of an interplay between gravity, interstellar turbulence, and magnetic fields. To unravel the roles of the processes, one has to obtain additional kinematic and polarization information; these follow-up observations are planned.
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| 8. |
- Schneider, N., et al.
(författare)
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The Herschel view of star formation in the Rosette molecular cloud under the influence of NGC 2244
- 2010
-
Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 518, s. L83-
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Tidskriftsartikel (refereegranskat)abstract
- Context. The Rosette molecular cloud is promoted as the archetype of a triggered star-formation site. This is mainly due to its morphology, because the central OB cluster NGC 2244 has blown a circular-shaped cavity into the cloud and the expanding H II-region now interacts with the cloud. Aims. Studying the spatial distribution of the different evolutionary states of all star-forming sites in Rosette and investigating possible gradients of the dust temperature will help to test the "triggered star-formation" scenario in Rosette. Methods. We use continuum data obtained with the PACS (70 and 160 mu m) and SPIRE instruments (250, 350, 500 mu m) of the Herschel telescope during the science demonstration phase of HOBYS. Results. Three-color images of Rosette impressively show how the molecular gas is heated by the radiative impact of the NGC 2244 cluster. A clear negative temperature gradient and a positive density gradient (running from the H II-region/molecular cloud interface into the cloud) are detected. Studying the spatial distribution of the most massive dense cores (size scale 0.05 to 0.3 pc), we find an age-sequence (from more evolved to younger) with increasing distance to the cluster NGC 2244. No clear gradient is found for the clump (size-scale up to 1 pc) distribution. Conclusions. The existence of temperature and density gradients and the observed age-sequence imply that star formation in Rosette may indeed be influenced by the radiative impact of the central NGC 2244 cluster. A more complete overview of the prestellar and protostellar population in Rosette is required to obtain a firmer result.
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| 9. |
- Scott, Robert A., et al.
(författare)
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Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways
- 2012
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:9, s. 991-1005
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Tidskriftsartikel (refereegranskat)abstract
- Through genome-wide association meta-analyses of up to 133,010 individuals of European ancestry without diabetes, including individuals newly genotyped using the Metabochip, we have increased the number of confirmed loci influencing glycemic traits to 53, of which 33 also increase type 2 diabetes risk (q < 0.05). Loci influencing fasting insulin concentration showed association with lipid levels and fat distribution, suggesting impact on insulin resistance. Gene-based analyses identified further biologically plausible loci, suggesting that additional loci beyond those reaching genome-wide significance are likely to represent real associations. This conclusion is supported by an excess of directionally consistent and nominally significant signals between discovery and follow-up studies. Functional analysis of these newly discovered loci will further improve our understanding of glycemic control.
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| 10. |
- Dall'Ora, M., et al.
(författare)
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THE TYPE IIP SUPERNOVA 2012aw IN M95 : HYDRODYNAMICAL MODELING OF THE PHOTOSPHERIC PHASE FROM ACCURATE SPECTROPHOTOMETRIC MONITORING
- 2014
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 787:2, s. 139-
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Tidskriftsartikel (refereegranskat)abstract
- We present an extensive optical and near-infrared photometric and spectroscopic campaign of the Type IIP supernova SN 2012aw. The data set densely covers the evolution of SN 2012aw shortly after the explosion through the end of the photospheric phase, with two additional photometric observations collected during the nebular phase, to fit the radioactive tail and estimate the Ni-56 mass. Also included in our analysis is the previously published Swift UV data, therefore providing a complete view of the ultraviolet-optical-infrared evolution of the photospheric phase. On the basis of our data set, we estimate all the relevant physical parameters of SN 2012aw with our radiation-hydrodynamics code: envelope mass M-env similar to 20 M-circle dot, progenitor radius R similar to 3 x 10(13) cm (similar to 430 R-circle dot), explosion energy E similar to 1.5 foe, and initial Ni-56 mass similar to 0.06 M-circle dot. These mass and radius values are reasonably well supported by independent evolutionary models of the progenitor, and may suggest a progenitor mass higher than the observational limit of 16.5 +/- 1.5 M-circle dot of the Type IIP events.
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| 11. |
- Escott-Price, Valentina, et al.
(författare)
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Gene-Wide Analysis Detects Two New Susceptibility Genes for Alzheimer's Disease
- 2014
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:6, s. e94661-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and 48,466 controls. Principal Findings: In addition to earlier reported genes, we detected genome-wide significant loci on chromosomes 8 (TP53INP1, p = 1.4x10(-6)) and 14 (IGHV1-67 p = 7.9x10(-8)) which indexed novel susceptibility loci. Significance: The additional genes identified in this study, have an array of functions previously implicated in Alzheimer's disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimer's disease.
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| 12. |
- Haas, Brian J., et al.
(författare)
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De novo transcript sequence reconstruction from RNA-seq using the Trinity platform for reference generation and analysis
- 2013
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Ingår i: Nature Protocols. - : Springer Science and Business Media LLC. - 1754-2189 .- 1750-2799. ; 8:8, s. 1494-1512
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Tidskriftsartikel (refereegranskat)abstract
- De novo assembly of RNA-seq data enables researchers to study transcriptomes without the need for a genome sequence; this approach can be usefully applied, for instance, in research on 'non-model organisms' of ecological and evolutionary importance, cancer samples or the microbiome. In this protocol we describe the use of the Trinity platform for de novo transcriptome assembly from RNA-seq data in non-model organisms. We also present Trinity-supported companion utilities for downstream applications, including RSEM for transcript abundance estimation, R/Bioconductor packages for identifying differentially expressed transcripts across samples and approaches to identify protein-coding genes. In the procedure, we provide a workflow for genome-independent transcriptome analysis leveraging the Trinity platform. The software, documentation and demonstrations are freely available from http://trinityrnaseq.sourceforge.net. The run time of this protocol is highly dependent on the size and complexity of data to be analyzed. The example data set analyzed in the procedure detailed herein can be processed in less than 5 h.
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| 13. |
- Nicholl, M., et al.
(författare)
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Superluminous supernovae from PESSTO
- 2014
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 444:3, s. 2096-2113
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Tidskriftsartikel (refereegranskat)abstract
- We present optical spectra and light curves for three hydrogen-poor superluminous supernovae followed by the Public ESO Spectroscopic Survey of Transient Objects (PESSTO). Time series spectroscopy from a fewdays aftermaximum light to 100 d later shows them to be fairly typical of this class, with spectra dominated by Ca II, MgII, FeII, and Si II, which evolve slowly over most of the post-peak photospheric phase. We determine bolometric light curves and apply simple fitting tools, based on the diffusion of energy input by magnetar spin-down, Ni-56 decay, and collision of the ejecta with an opaque circumstellar shell. We investigate how the heterogeneous light curves of our sample (combined with others from the literature) can help to constrain the possible mechanisms behind these events. We have followed these events to beyond 100-200 d after peak, to disentangle host galaxy light from fading supernova flux and to differentiate between the models, which predict diverse behaviour at this phase. Models powered by radioactivity require unrealistic parameters to reproduce the observed light curves, as found by previous studies. Both magnetar heating and circumstellar interaction still appear to be viable candidates. A large diversity is emerging in observed tail-phase luminosities, with magnetar models failing in some cases to predict the rapid drop in flux. This would suggest either that magnetars are not responsible, or that the X-ray flux from the magnetar wind is not fully trapped. The light curve of one object shows a distinct rebrightening at around 100 d after maximum light. We argue that this could result either from multiple shells of circumstellar material, or from a magnetar ionization front breaking out of the ejecta.
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| 14. |
- van der Harst, Pim, et al.
(författare)
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Seventy-five genetic loci influencing the human red blood cell
- 2012
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 492:7429, s. 369-375
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Tidskriftsartikel (refereegranskat)abstract
- Anaemia is a chief determinant of global ill health, contributing to cognitive impairment, growth retardation and impaired physical capacity. To understand further the genetic factors influencing red blood cells, we carried out a genome-wide association study of haemoglobin concentration and related parameters in up to 135,367 individuals. Here we identify 75 independent genetic loci associated with one or more red blood cell phenotypes at P < 10(-8), which together explain 4-9% of the phenotypic variance per trait. Using expression quantitative trait loci and bioinformatic strategies, we identify 121 candidate genes enriched in functions relevant to red blood cell biology. The candidate genes are expressed preferentially in red blood cell precursors, and 43 have haematopoietic phenotypes in Mus musculus or Drosophila melanogaster. Through open-chromatin and coding-variant analyses we identify potential causal genetic variants at 41 loci. Our findings provide extensive new insights into genetic mechanisms and biological pathways controlling red blood cell formation and function.
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| 15. |
- Gal-Yam, Avishay, et al.
(författare)
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A Wolf-Rayet-like progenitor of SN 2013cu from spectral observations of a stellar wind
- 2014
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 509:7501, s. 471-
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Tidskriftsartikel (refereegranskat)abstract
- The explosive fate of massive Wolf-Rayet stars(1) (WRSs) is a key open question in stellar physics. An appealing option is that hydrogen-deficient WRSs are the progenitors of some hydrogen-poor supernova explosions of types IIb, Ib and Ic (ref. 2). A blue object, having luminosity and colours consistent with those of some WRSs, has recently been identified in pre-explosion images at the location of a supernova of type Ib (ref. 3), but has not yet been conclusively determined to have been the progenitor. Similar work has so far only resulted in non-detections(4). Comparison of early photometric observations of type Ic supernovae with theoretical models suggests that the progenitor stars had radii of less than 1012 centimetres, as expected for some WRSs(5). The signature of WRSs, their emission line spectra, cannot be probed by such studies. Here we report the detection of strong emission lines in a spectrum of type IIb supernova 2013cu (iPTF13ast) obtained approximately 15.5 hours after explosion (by 'flash spectroscopy', which captures the effects of the supernova explosion shock breakout flash on material surrounding the progenitor star). We identify Wolf-Rayet-like wind signatures, suggesting a progenitor of the WN(h) subclass (those WRSs with winds dominated by helium and nitrogen, with traces of hydrogen). The extent of this dense wind may indicate increased mass loss from the progenitor shortly before its explosion, consistent with recent theoretical predictions(6).
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| 16. |
- Hantke, Max F., et al.
(författare)
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High-throughput imaging of heterogeneous cell organelles with an X-ray laser
- 2014
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Ingår i: Nature Photonics. - : Springer Science and Business Media LLC. - 1749-4885 .- 1749-4893. ; 8:12, s. 943-949
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Tidskriftsartikel (refereegranskat)abstract
- We overcome two of the most daunting challenges in single-particle diffractive imaging: collecting many high-quality diffraction patterns on a small amount of sample and separating components from mixed samples. We demonstrate this on carboxysomes, which are polyhedral cell organelles that vary in size and facilitate up to 40% of Earth's carbon fixation. A new aerosol sample-injector allowed us to record 70,000 low-noise diffraction patterns in 12 min with the Linac Coherent Light Source running at 120 Hz. We separate different structures directly from the diffraction data and show that the size distribution is preserved during sample delivery. We automate phase retrieval and avoid reconstruction artefacts caused by missing modes. We attain the highest-resolution reconstructions on the smallest single biological objects imaged with an X-ray laser to date. These advances lay the foundations for accurate, high-throughput structure determination by flash-diffractive imaging and offer a means to study structure and structural heterogeneity in biology and elsewhere.
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| 17. |
- Hennemann, M., et al.
(författare)
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Herschel observations of embedded protostellar clusters in the Rosette molecular cloud
- 2010
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 518, s. L84-
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Tidskriftsartikel (refereegranskat)abstract
- The Herschel OB young stellar objects survey (HOBYS) has observed the Rosette molecular cloud, providing an unprecedented view of its star formation activity. These new far-infrared data reveal a population of compact young stellar objects whose physical properties we aim to characterise. We compiled a sample of protostars and their spectral energy distributions that covers the near-infrared to submillimetre wavelength range. These were used to constrain key properties in the protostellar evolution, bolometric luminosity, and envelope mass and to build an evolutionary diagram. Several clusters are distinguished including the cloud centre, the embedded clusters in the vicinity of luminous infrared sources, and the interaction region. The analysed protostellar population in Rosette ranges from 0.1 to about 15 M-circle dot with luminosities between 1 and 150 L-circle dot, which extends the evolutionary diagram from low-mass protostars into the high-mass regime. Some sources lack counterparts at near-to mid-infrared wavelengths, indicating extreme youth. The central cluster and the Phelps & Lada 7 cluster appear less evolved than the remainder of the analysed protostellar population. For the central cluster, we find indications that about 25% of the protostars classified as Class I from near-to mid-infrared data are actually candidate Class 0 objects. As a showcase for protostellar evolution, we analysed four protostars of low-to intermediate-mass in a single dense core, and they represent different evolutionary stages from Class 0 to Class I. Their mid-to far-infrared spectral slopes flatten towards the Class I stage, and the 160 to 70 mu m flux ratio is greatest for the presumed Class 0 source. This shows that the Herschel observations characterise the earliest stages of protostellar evolution in detail.
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| 18. |
- Ho, Joshua W. K., et al.
(författare)
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Comparative analysis of metazoan chromatin organization
- 2014
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 512:7515, s. 449-U507
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Tidskriftsartikel (refereegranskat)abstract
- Genome function is dynamically regulated in part by chromatin, which consists of the histones, non-histone proteins and RNA molecules that package DNA. Studies in Caenorhabditis elegans and Drosophila melanogaster have contributed substantially to our understanding of molecular mechanisms of genome function in humans, and have revealed conservation of chromatin components and mechanisms(1-3). Nevertheless, the three organisms have markedly different genome sizes, chromosome architecture and gene organization. On human and fly chromosomes, for example, pericentric heterochromatin flanks single centromeres, whereas worm chromosomes have dispersed heterochromatin-like regions enriched in the distal chromosomal 'arms', and centromeres distributed along their lengths(4,5). To systematically investigate chromatin organization and associated gene regulation across species, we generated and analysed a large collection of genome-wide chromatin data sets from cell lines and developmental stages in worm, fly and human. Here we present over 800 new data sets from our ENCODE and modENCODE consortia, bringing the total to over 1,400. Comparison of combinatorial patterns of histone modifications, nuclear lamina-associated domains, organization of large-scale topological domains, chromatin environment at promoters and enhancers, nucleosome positioning, and DNA replication patterns reveals many conserved features of chromatin organization among the three organisms. We also find notable differences in the composition and locations of repressive chromatin. These data sets and analyses provide a rich resource for comparative and species-specific investigations of chromatin composition, organization and function.
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| 19. |
- Koettgen, Anna, et al.
(författare)
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Genome-wide association analyses identify 18 new loci associated with serum urate concentrations
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:2, s. 145-154
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Tidskriftsartikel (refereegranskat)abstract
- Elevated serum urate concentrations can cause gout, a prevalent and painful inflammatory arthritis. By combining data from >140,000 individuals of European ancestry within the Global Urate Genetics Consortium (GUGC), we identified and replicated 28 genome-wide significant loci in association with serum urate concentrations (18 new regions in or near TRIM46, INHBB, SEMBT1, TMEM171, VEGFA, BAZ1B, PRKAG2, STC1, HNF4G, A1CF, ATXN2, UBE2Q2, IGF1R, NFAT5, MAF, HLF, ACVR1B-ACVRL1 and B3GNT4). Associations for many of the loci were of similar magnitude in individuals of non-European ancestry. We further characterized these loci for associations with gout, transcript expression and the fractional excretion of urate. Network analyses implicate the inhibins-activins signaling pathways and glucose metabolism in systemic urate control. New candidate genes for serum urate concentration highlight the importance of metabolic control of urate production and excretion, which may have implications for the treatment and prevention of gout.
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| 20. |
- Köttgen, Anna, et al.
(författare)
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New loci associated with kidney function and chronic kidney disease
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:5, s. 376-384
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Tidskriftsartikel (refereegranskat)abstract
- Chronic kidney disease (CKD) is a significant public health problem, and recent genetic studies have identified common CKD susceptibility variants. The CKDGen consortium performed a meta-analysis of genome-wide association data in 67,093 individuals of European ancestry from 20 predominantly population-based studies in order to identify new susceptibility loci for reduced renal function as estimated by serum creatinine (eGFRcrea), serum cystatin c (eGFRcys) and CKD (eGFRcrea < 60 ml/min/1.73 m2; n = 5,807 individuals with CKD (cases)). Follow-up of the 23 new genome-wide–significant loci (P < 5 × 10−8) in 22,982 replication samples identified 13 new loci affecting renal function and CKD (in or near LASS2, GCKR, ALMS1, TFDP2, DAB2, SLC34A1, VEGFA, PRKAG2, PIP5K1B, ATXN2, DACH1, UBE2Q2 and SLC7A9) and 7 loci suspected to affect creatinine production and secretion (CPS1, SLC22A2, TMEM60, WDR37, SLC6A13, WDR72 and BCAS3). These results further our understanding of the biologic mechanisms of kidney function by identifying loci that potentially influence nephrogenesis, podocyte function, angiogenesis, solute transport and metabolic functions of the kidney.
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| 21. |
- Lawler, S. M., et al.
(författare)
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The debris disc of solar analogue tau Ceti : Herschel observations and dynamical simulations of the proposed multiplanet system
- 2014
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 444:3, s. 2665-2675
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Tidskriftsartikel (refereegranskat)abstract
- tau Ceti is a nearby, mature G-type star very similar to our Sun, with a massive Kuiper Belt analogue and possible multiplanet system that has been compared to our Solar system. We present Herschel Space Observatory images of the debris disc, finding the disc is resolved at 70 mu m and 160 mu m, and marginally resolved at 250 mu m. The Herschel images and infrared photometry from the literature are best modelled using a wide dust annulus with an inner edge between 1 and 10 au and an outer edge at similar to 55 au, inclined from face-on by 35 degrees +/- 10 degrees, and with no significant azimuthal structure. We model the proposed tightly packed planetary system of five super-Earths and find that the innermost dynamically stable disc orbits are consistent with the inner edge found by the observations. The photometric modelling, however, cannot rule out a disc inner edge as close to the star as 1 au, though larger distances produce a better fit to the data. Dynamical modelling shows that the five-planet system is stable with the addition of a Neptune or smaller mass planet on an orbit outside 5 au, where the radial velocity data analysis would not have detected a planet of this mass.
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| 22. |
- Scalzo, R. A., et al.
(författare)
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Early ultraviolet emission in the Type Ia supernova LSQ12gdj : No evidence for ongoing shock interaction
- 2014
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 445:1, s. 30-48
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Tidskriftsartikel (refereegranskat)abstract
- We present photospheric-phase observations of LSQ12gdj, a slowly declining, UV-bright Type Ia supernova. Classified well before maximum light, LSQ12gdj has extinction-corrected absolute magnitude M-B = -19.8, and pre-maximum spectroscopic evolution similar to SN 1991T and the super-Chandrasekhar-mass SN 2007if. We use ultraviolet photometry from Swift, ground-based optical photometry, and corrections from a near-infrared photometric template to construct the bolometric (1600-23 800 angstrom) light curve out to 45 d past B-band maximum light. We estimate that LSQ12gdj produced 0.96 +/- 0.07 M-circle dot of Ni-56, with an ejected mass near or slightly above the Chandrasekhar mass. As much as 27 per cent of the flux at the earliest observed phases, and 17 per cent at maximum light, is emitted bluewards of 3300 angstrom. The absence of excess luminosity at late times, the cutoff of the spectral energy distribution bluewards of 3000 angstrom and the absence of narrow line emission and strong Na I D absorption all argue against a significant contribution from ongoing shock interaction. However, similar to 10 per cent of LSQ12gdj's luminosity near maximum light could be produced by the release of trapped radiation, including kinetic energy thermalized during a brief interaction with a compact, hydrogen-poor envelope (radius < 10(13) cm) shortly after explosion; such an envelope arises generically in double-degenerate merger scenarios.
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| 23. |
- 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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| 24. |
- Stritzinger, M. D., et al.
(författare)
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Optical and near-IR observations of the faint and fast 2008ha-like supernova 2010ae
- 2014
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 561, s. A146-
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Tidskriftsartikel (refereegranskat)abstract
- A comprehensive set of optical and near-infrared (NIR) photometry and spectroscopy is presented for the faint and fast 2008ha-like supernova (SN) 2010ae. Contingent on the adopted value of host extinction, SN 2010ae reached a peak brightness of -13.8 > M-V > -15.3 mag, while modeling of the UVOIR light curve suggests it produced 0.003-0.007 M-circle dot of Ni-56, ejected 0.30-0.60 M-circle dot of material, and had an explosion energy of 0.04-0.30 x 10(51) erg. The values of these explosion parameters are similar to the peculiar SN 2008ha -for which we also present previously unpublished early phase optical and NIR light curves - and places these two transients at the faint end of the 2002cx-like SN population. Detailed inspection of the post-maximum NIR spectroscopic sequence indicates the presence of a multitude of spectral features, which are identified through SYNAPPS modeling to be mainly attributed to Co II. Comparison with a collection of published and unpublished NIR spectra of other 2002cx-like SNe, reveals that a Co II footprint is ubiquitous to this subclass of transients, providing a link to Type Ia SNe. A visual-wavelength spectrum of SN 2010ae obtained at +252 days past maximum shows a striking resemblance to a similar epoch spectrum of SN 2002cx. However, subtle differences in the strength and ratio of calcium emission features, as well as diversity among similar epoch spectra of other 2002cx-like SNe indicates a range of physical conditions of the ejecta, highlighting the heterogeneous nature of this peculiar class of transients.
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| 25. |
- Su, Zhan, et al.
(författare)
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Common variants at the MHC locus and at chromosome 16q24.1 predispose to Barrett's esophagus.
- 2012
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:10
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Tidskriftsartikel (refereegranskat)abstract
- Barrett's esophagus is an increasingly common disease that is strongly associated with reflux of stomach acid and usually a hiatus hernia, and it strongly predisposes to esophageal adenocarcinoma (EAC), a tumor with a very poor prognosis. We report the first genome-wide association study on Barrett's esophagus, comprising 1,852 UK cases and 5,172 UK controls in the discovery stage and 5,986 cases and 12,825 controls in the replication stage. Variants at two loci were associated with disease risk: chromosome 6p21, rs9257809 (Pcombined=4.09×10(-9); odds ratio (OR)=1.21, 95% confidence interval (CI)=1.13-1.28), within the major histocompatibility complex locus, and chromosome 16q24, rs9936833 (Pcombined=2.74×10(-10); OR=1.14, 95% CI=1.10-1.19), for which the closest protein-coding gene is FOXF1, which is implicated in esophageal development and structure. We found evidence that many common variants of small effect contribute to genetic susceptibility to Barrett's esophagus and that SNP alleles predisposing to obesity also increase risk for Barrett's esophagus.
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