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Sökning: WFRF:(Bridge J.)

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1.
  • Jones, Gregory T., et al. (författare)
  • Meta-Analysis of Genome-Wide Association Studies for Abdominal Aortic Aneurysm Identifies Four New Disease-Specific Risk Loci
  • 2017
  • Ingår i: Circulation Research. - 0009-7330 .- 1524-4571. ; 120:2, s. 341-
  • Tidskriftsartikel (refereegranskat)abstract
    • Rationale: Abdominal aortic aneurysm (AAA) is a complex disease with both genetic and environmental risk factors. Together, 6 previously identified risk loci only explain a small proportion of the heritability of AAA. Objective: To identify additional AAA risk loci using data from all available genome-wide association studies. Methods and Results: Through a meta-analysis of 6 genome-wide association study data sets and a validation study totaling 10 204 cases and 107 766 controls, we identified 4 new AAA risk loci: 1q32.3 (SMYD2), 13q12.11 (LINC00540), 20q13.12 (near PCIF1/MMP9/ZNF335), and 21q22.2 (ERG). In various database searches, we observed no new associations between the lead AAA single nucleotide polymorphisms and coronary artery disease, blood pressure, lipids, or diabetes mellitus. Network analyses identified ERG, IL6R, and LDLR as modifiers of MMP9, with a direct interaction between ERG and MMP9. Conclusions: The 4 new risk loci for AAA seem to be specific for AAA compared with other cardiovascular diseases and related traits suggesting that traditional cardiovascular risk factor management may only have limited value in preventing the progression of aneurysmal disease.
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  • Pérez-González, P.G.P., et al. (författare)
  • Improving the identification of high-z Herschel sources with position priors and optical/NIR and FIR/mm photometric redshifts
  • 2010
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 518:Article Number: L15
  • Tidskriftsartikel (refereegranskat)abstract
    • We present preliminary results about the detection of high redshift (U)LIRGs in the Bullet cluster field by the PACS and SPIRE instruments within the Herschel Lensing Survey (HLS) Program. We describe in detail a photometric procedure designed to recover robust fluxes and deblend faint Herschel sources near the confusion noise. The method is based on the use of the positions of Spitzer/MIPS 24 mu m sources as priors. Our catalogs are able to reliably (5 sigma) recover galaxies with fluxes above 6 and 10 mJy in the PACS 100 and 160 mu m channels, respectively, and 12 to 18 mJy in the SPIRE bands. We also obtain spectral energy distributions covering the optical through the far-infrared/millimeter spectral ranges of all the Herschel detected sources, and analyze them to obtain independent estimations of the photometric redshift based on either stellar population or dust emission models. We exemplify the potential of the combined use of Spitzer position priors plus independent optical and IR photometric redshifts to robustly assign optical/NIR counterparts to the sources detected by Herschel and other (sub-)mm instruments.
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  • Rex, M., et al. (författare)
  • The far-infrared/submillimeter properties of galaxies located behind the Bullet cluster
  • 2010
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 518:Article Number: L13
  • Tidskriftsartikel (refereegranskat)abstract
    • The Herschel Lensing Survey (HLS) takes advantage of gravitational lensing by massive galaxy clusters to sample a population of high-redshift galaxies which are too faint to be detected above the confusion limit of current far-infrared/submillimeter telescopes. Measurements from 100-500 mu m bracket the peaks of the far-infrared spectral energy distributions of these galaxies, characterizing their infrared luminosities and star formation rates. We introduce initial results from our science demonstration phase observations, directed toward the Bullet cluster (1E0657-56). By combining our observations with LABOCA 870 mu m and AzTEC 1.1 mm data we fully constrain the spectral energy distributions of 19 MIPS 24 mu m-selected galaxies which are located behind the cluster. We find that their colors are best fit using templates based on local galaxies with systematically lower infrared luminosities. This suggests that our sources are not like local ultra-luminous infrared galaxies in which vigorous star formation is contained in a compact highly dust-obscured region. Instead, they appear to be scaled up versions of lower luminosity local galaxies with star formation occurring on larger physical scales.
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  • Jones, Suzy, 1988, et al. (författare)
  • Overdensities of SMGs around WISE-selected, ultraluminous, high-redshift AGNs
  • 2017
  • Ingår i: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 469:4, s. 4565-4577
  • Tidskriftsartikel (refereegranskat)abstract
    • We investigate extremely luminous dusty galaxies in the environments around Wide-field Infrared Survey Explorer (WISE)-selected hot dust-obscured galaxies (Hot DOGs) and WISE/radio-selected active galactic nuclei (AGNs) at average redshifts of z = 2.7 and 1.7, respectively. Previous observations have detected overdensities of companion submillimetre-selected sources around 10 Hot DOGs and 30 WISE/radio AGNs, with overdensities of similar to 2-3 and similar to 5-6, respectively. We find that the space densities in both samples to be overdense compared to normal star-forming galaxies and submillimetre galaxies (SMGs) in the Submillimetre Common-User Bolometer Array 2 (SCUBA-2) Cosmology Legacy Survey (S2CLS). Both samples of companion sources have consistent mid-infrared (mid-IR) colours and mid-IR to submm ratios as SMGs. The brighter population around WISE/radio AGNs could be responsible for the higher overdensity reported. We also find that the star formation rate densities are higher than the field, but consistent with clusters of dusty galaxies. WISE-selected AGNs appear to be good signposts for protoclusters at high redshift on arcmin scales. The results reported here provide an upper limit to the strength of angular clustering using the two-point correlation function. Monte Carlo simulations show no angular correlation, which could indicate protoclusters on scales larger than the SCUBA-2 1.5-arcmin scale maps.
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  • Grätz, Lukas, et al. (författare)
  • NanoBiT‐ and NanoBiT/BRET‐based assays allow the analysis of binding kinetics of Wnt‐3a to endogenous Frizzled 7 in a colorectal cancer model
  • 2023
  • Ingår i: British Journal of Pharmacology. - : John Wiley & Sons. - 0007-1188 .- 1476-5381.
  • Tidskriftsartikel (refereegranskat)abstract
    •   Background and PurposeWnt binding to Frizzleds (FZD) is a crucial step that leads to the initiation of signalling cascades governing multiple processes during embryonic development, stem cell regulation and adult tissue homeostasis. Recent efforts have enabled us to shed light on Wnt–FZD pharmacology using overexpressed HEK293 cells. However, assessing ligand binding at endogenous receptor expression levels is important due to differential binding behaviour in a native environment. Here, we study FZD paralogue, FZD7, and analyse its interactions with Wnt-3a in live CRISPR-Cas9-edited SW480 cells typifying colorectal cancer.Experimental ApproachSW480 cells were CRISPR-Cas9-edited to insert a HiBiT tag on the N-terminus of FZD7, preserving the native signal peptide. These cells were used to study eGFP-Wnt-3a association with endogenous and overexpressed HiBiT-FZD7 using NanoBiT/bioluminescence resonance energy transfer (BRET) and NanoBiT to measure ligand binding and receptor internalization.Key ResultsWith this new assay the binding of eGFP-Wnt-3a to endogenous HiBiT-FZD7 was compared with overexpressed receptors. Receptor overexpression results in increased membrane dynamics, leading to an apparent decrease in binding on-rate and consequently in higher, up to 10 times, calculated Kd. Thus, measurements of binding affinities to FZD7 obtained in overexpressed cells are suboptimal compared with the measurements from endogenously expressing cells.Conclusions and ImplicationsBinding affinity measurements in the overexpressing cells fail to replicate ligand binding affinities assessed in a (patho)physiologically relevant context where receptor expression is lower. Therefore, future studies on Wnt–FZD7 binding should be performed using receptors expressed under endogenous promotion.
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7.
  • Kyle, Jennifer E., et al. (författare)
  • Interpreting the lipidome : bioinformatic approaches to embrace the complexity
  • 2021
  • Ingår i: Metabolomics. - : Springer-Verlag New York. - 1573-3882 .- 1573-3890. ; 17:6
  • Forskningsöversikt (refereegranskat)abstract
    • BACKGROUND: Improvements in mass spectrometry (MS) technologies coupled with bioinformatics developments have allowed considerable advancement in the measurement and interpretation of lipidomics data in recent years. Since research areas employing lipidomics are rapidly increasing, there is a great need for bioinformatic tools that capture and utilize the complexity of the data. Currently, the diversity and complexity within the lipidome is often concealed by summing over or averaging individual lipids up to (sub)class-based descriptors, losing valuable information about biological function and interactions with other distinct lipids molecules, proteins and/or metabolites.AIM OF REVIEW: To address this gap in knowledge, novel bioinformatics methods are needed to improve identification, quantification, integration and interpretation of lipidomics data. The purpose of this mini-review is to summarize exemplary methods to explore the complexity of the lipidome.KEY SCIENTIFIC CONCEPTS OF REVIEW: Here we describe six approaches that capture three core focus areas for lipidomics: (1) lipidome annotation including a resolvable database identifier, (2) interpretation via pathway- and enrichment-based methods, and (3) understanding complex interactions to emphasize specific steps in the analytical process and highlight challenges in analyses associated with the complexity of lipidome data.
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8.
  • Melinder, Jens, 1977-, et al. (författare)
  • The Lyα Reference Sample. XIV. Lyα Imaging of 45 Low-redshift Star-forming Galaxies and Inferences on Global Emission
  • 2023
  • Ingår i: Astrophysical Journal Supplement Series. - 0067-0049 .- 1538-4365. ; 266:1
  • Tidskriftsartikel (refereegranskat)abstract
    • We present Lyα imaging of 45 low-redshift star-forming galaxies observed with the Hubble Space Telescope. The galaxies have been selected to have moderate to high star formation rates (SFRs) using far-ultraviolet (FUV) luminosity and Hα equivalent width criteria, but no constraints on Lyα luminosity. We employ a pixel stellar continuum fitting code to obtain accurate continuum-subtracted Lyα, Hα, and Hβ maps. We find that Lyα is less concentrated than FUV and optical line emission in almost all galaxies with significant Lyα emission. We present global measurements of Lyα and other quantities measured in apertures designed to capture all of the Lyα emission. We then show how the escape fraction of Lyα relates to a number of other measured quantities (mass, metallicity, star formation, ionization parameter, and extinction). We find that the escape fraction is strongly anticorrelated with nebular and stellar extinction, weakly anticorrelated with stellar mass, but no conclusive evidence for correlations with other quantities. We show that Lyα escape fractions are inconsistent with common dust extinction laws, and discuss how a combination of radiative transfer effects and clumpy dust models can help resolve the discrepancies. We present an SFR calibration based on Lyα luminosity, where the equivalent width of Lyα is used to correct for nonunity escape fraction, and show that this relation provides a reasonably accurate SFR estimate. We also show stacked growth curves of Lyα for the galaxies that can be used to find aperture loss fractions at a given physical radius.
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  • Puschnig, Johannes, et al. (författare)
  • The Lyman Alpha Reference Sample : XI. Efficient turbulence-driven Lyα escape and an analysis of IR, CO, and [C II]158 μm
  • 2020
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 644
  • Tidskriftsartikel (refereegranskat)abstract
    • Context. Lyman-alpha (Ly alpha) is the brightest emission line in star-forming galaxies. However, its interpretation in terms of physical properties is hampered by the resonant nature of Ly alpha photons. In order to remedy this complicated situation, the Lyman Alpha Reference Sample (LARS) was defined, enabling the study of Ly alpha production and escape mechanisms in 14 local star-forming galaxies.Aims. With this paper, we complement our efforts and study the global dust and (molecular) gas content as well as the properties of gas associated with photon-dominated regions. We aim to characterize the interstellar medium of LARS galaxies, allowing us to relate these newly derived properties to quantities relevant for Ly alpha escape.Methods. We observed LARS galaxies with Herschel, SOFIA, the IRAM 30m telescope, and APEX, targeting far-infrared (FIR) continuum and emission lines of [C II]158 mu m, [O I]63 mu m, [O III]88 mu m, and low-J CO lines. Using Bayesian methods we derived dust model parameters and estimated the total gas masses for all LARS galaxies, taking into account a metallicity-dependent gas-to-dust ratio. Star formation rates were estimated from FIR, [C II]158 mu m, and [O I]63 mu m luminosities.Results. LARS covers a wide dynamic range in the derived properties, with FIR-based star formation rates from similar to 0.5-100 M-circle dot yr(-1), gas fractions between similar to 15-80%, and gas depletion times ranging from a few hundred megayears up to more than ten gigayears. The distribution of LARS galaxies in the Sigma(gas) versus Sigma(SFR) (Kennicutt-Schmidt plane) is thus quite heterogeneous. However, we find that LARS galaxies with the longest gas depletion times, that is, relatively high gas surface densities (Sigma(gas)) and low star formation rate densities (Sigma(SFR)), have by far the highest Ly alpha escape fraction. A strong approximately linear relation is found between the Ly alpha escape fraction and the total gas (HI+H-2) depletion time. We argue that the Ly alpha escape in those galaxies is driven by turbulence in the star-forming gas that shifts the Ly alpha photons out of resonance close to the places where they originate. We further report on an extreme [C II]158 mu m excess in LARS 5, corresponding to similar to 14 +/- 3% of the FIR luminosity, which probably is the most extreme [C II]-to-FIR ratio observed in a galaxy (without active nucleus) to date.
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  • Bridge, Joanna S., et al. (författare)
  • The Ly alpha Reference Sample. VIII. Characterizing Ly alpha Scattering in Nearby Galaxies
  • 2018
  • Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 852:1
  • Tidskriftsartikel (refereegranskat)abstract
    • We examine the dust geometry and Ly alpha scattering in the galaxies of the Lyman Alpha Reference Sample (LARS), a set of 14 nearby (0.02 < z < 0.2) Ly alpha-emitting and starbursting systems with Hubble Space Telescope Ly alpha, H alpha, and H beta imaging. We find that the global dust properties determined by line ratios are consistent with other studies, with some of the LARS galaxies exhibiting clumpy dust media, while others of them show significantly lower Ly alpha emission compared to their Balmer decrement. With the LARS imaging, we present Ly alpha/H alpha and H alpha/H beta maps with spatial resolutions as low as similar to 40 pc, and use these data to show that in most galaxies, the dust geometry is best modeled by three distinct regions: a central core where dust acts as a screen, an annulus where dust is distributed in clumps, and an outer envelope where Ly alpha photons only scatter. We show that the dust that affects the escape of Ly alpha is more restricted to the galaxies' central regions, while the larger Ly alpha halos are generated by scattering at large radii. We present an empirical modeling technique to quantify how much Ly alpha scatters in the halo, and find that this characteristic scattering distance correlates with the measured size of the Ly alpha halo. We note that there exists a slight anti-correlation between the scattering distance of Ly alpha and global dust properties.
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  • Romeo, Salvatore, et al. (författare)
  • Heterogeneous and Complex Rearrangements of Chromosome Arm 6q in Chondromyxoid Fibroma. Delineation of Breakpoints and Analysis of Candidate Target Genes.
  • 2010
  • Ingår i: American Journal of Pathology. - : Elsevier BV. - 1525-2191 .- 0002-9440. ; 177:3, s. 1365-1376
  • Tidskriftsartikel (refereegranskat)abstract
    • Chondromyxoid fibroma (CMF) is an uncommon benign cartilaginous tumor of bone usually occurring during the second decade of life. CMF is associated with recurrent rearrangements of chromosome bands 6p23-25, 6q12-15, and 6q23-27. To delineate further the role and frequency of the involvement of three candidate regions (6q13, 6q23.3 and 6q24) in the pathogenesis of CMF, we studied a group of 43 cases using a molecular cytogenetic approach. Fluorescence in situ hybridization with probe sets bracketing the putative breakpoint regions was performed in 30 cases. The expression level of nearby candidate genes was studied by immunohistochemistry and quantitative RT-PCR in 24 and 23 cases, respectively. Whole-genome copy number screening was performed by array comparative genomic hybridization in 16 cases. Balanced and unbalanced rearrangements of 6q13 and 6q23.3 occurred in six and five cases, respectively, and a hemizygous deletion in 6q24 was found in five cases. Two known tumor suppressor genes map to the latter region: PLAGL1 and UTRN. However, neither of these two genes nor BCLAF1 and COL12A1, respectively located in 6q23.3 and 6q13, showed altered expression. Therefore, although rearrangements of chromosomal regions 6q13, 6q23.3, and 6q24 are common in CMF, the complexity of the changes precludes the use of a single fluorescence in situ hybridization probe set as an adjunct diagnostic tool. These data indicate that the genetic alterations in CMF are heterogeneous and are likely a result of a cryptic rearrangement beyond the resolution level of combined binary ratio fluorescence in situ hybridization or a point mutation.
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