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- Cheng, THT, et al.
(författare)
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Meta-analysis of genome-wide association studies identifies common susceptibility polymorphisms for colorectal and endometrial cancer near SH2B3 and TSHZ1
- 2015
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 5, s. 17369-
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Tidskriftsartikel (refereegranskat)abstract
- High-risk mutations in several genes predispose to both colorectal cancer (CRC) and endometrial cancer (EC). We therefore hypothesised that some lower-risk genetic variants might also predispose to both CRC and EC. Using CRC and EC genome-wide association series, totalling 13,265 cancer cases and 40,245 controls, we found that the protective allele [G] at one previously-identified CRC polymorphism, rs2736100 near TERT, was associated with EC risk (odds ratio (OR) = 1.08, P = 0.000167); this polymorphism influences the risk of several other cancers. A further CRC polymorphism near TERC also showed evidence of association with EC (OR = 0.92; P = 0.03). Overall, however, there was no good evidence that the set of CRC polymorphisms was associated with EC risk and neither of two previously-reported EC polymorphisms was associated with CRC risk. A combined analysis revealed one genome-wide significant polymorphism, rs3184504, on chromosome 12q24 (OR = 1.10, P = 7.23 × 10−9) with shared effects on CRC and EC risk. This polymorphism, a missense variant in the gene SH2B3, is also associated with haematological and autoimmune disorders, suggesting that it influences cancer risk through the immune response. Another polymorphism, rs12970291 near gene TSHZ1, was associated with both CRC and EC (OR = 1.26, P = 4.82 × 10−8), with the alleles showing opposite effects on the risks of the two cancers.
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- Pastorello, A., et al.
(författare)
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The evolution of luminous red nova AT 2017jfs in NGC 4470
- 2019
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Ingår i: Astronomy and Astrophysics. - : EDP SCIENCES S A. - 0004-6361 .- 1432-0746. ; 625
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Tidskriftsartikel (refereegranskat)abstract
- We present the results of our photometric and spectroscopic follow-up of the intermediate-luminosity optical transient AT 2017jfs. At peak, the object reaches an absolute magnitude of M-g = 15.46 +/- 0.15 mag and a bolometric luminosity of 5.5 x 10(41) erg s(-1). Its light curve has the double-peak shape typical of luminous red novae (LRNe), with a narrow first peak bright in the blue bands, while the second peak is longer-lasting and more luminous in the red and near-infrared (NIR) bands. During the first peak, the spectrum shows a blue continuum with narrow emission lines of H and Fe II. During the second peak, the spectrum becomes cooler, resembling that of a K-type star, and the emission lines are replaced by a forest of narrow lines in absorption. About 5 months later, while the optical light curves are characterized by a fast linear decline, the NIR ones show a moderate rebrightening, observed until the transient disappears in solar conjunction. At these late epochs, the spectrum becomes reminiscent of that of M-type stars, with prominent molecular absorption bands. The late-time properties suggest the formation of some dust in the expanding common envelope or an IR echo from foreground pre-existing dust. We propose that the object is a common-envelope transient, possibly the outcome of a merging event in a massive binary, similar to NGC4490-2011OT1.
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- Melandri, A., et al.
(författare)
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GRB171010A/SN 2017htp : a GRB-SN at z=0.33
- 2019
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 490:4, s. 5366-5374
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Tidskriftsartikel (refereegranskat)abstract
- The number of supernovae known to be connected with long-duration gamma-ray bursts (GRBs) is increasing and the link between these events is no longer exclusively found at low redshift (z less than or similar to 0.3) but is well established also at larger distances. We present a new case of such a liaison at z = 0.33 between GRB171010A and SN 2017htp. It is the second closest GRB with an associated supernova of only three events detected by Fermi-LAT. The supernova is one of the few higher redshift cases where spectroscopic observations were possible and shows spectral similarities with the well-studied SN 1998bw, having produced a similar Ni mass (M-Ni = 0.33 +/- 0.02 M-circle dot) with slightly lower ejected mass (M-ej = 4.1 +/- 0.7 M-circle dot) and kinetic energy (E-K = 8.1 +/- 2.5 x 10(51) erg). The host-galaxy is bigger in size than typical GRB host galaxies, but the analysis of the region hosting the GRB revealed spectral properties typically observed in GRB hosts and showed that the progenitor of this event was located in a very bright H II region of its face-on host galaxy, at a projected distance of similar to 10 kpc from its galactic centre. The star-formation rate (SFRGRB similar to 0.2 M-circle dot yr(-1)) and metallicity (12 + log(O/H) similar to 8.15 +/- 0.10) of the GRB star-forming region are consistent with those of the host galaxies of previously studied GRB-SN systems.
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- Izzo, L., et al.
(författare)
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Signatures of a jet cocoon in early spectra of a supernova associated with a γ-ray burst
- 2019
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 565:7739, s. 324-
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Tidskriftsartikel (refereegranskat)abstract
- Long gamma-ray bursts are associated with energetic, broad-lined, stripped-envelope supernovae(1,2) and as such mark the death of massive stars. The scarcity of such events nearby and the brightness of the gamma-ray burst afterglow, which dominates the emission in the first few days after the burst, have so far prevented the study of the very early evolution of supernovae associated with gamma-ray bursts(3). In hydrogen-stripped supernovae that are not associated with gamma-ray bursts, an excess of high-velocity (roughly 30,000 kilometres per second) material has been interpreted as a signature of a choked jet, which did not emerge from the progenitor star and instead deposited all of its energy in a thermal cocoon(4). Here we report multi-epoch spectroscopic observations of the supernova SN 2017iuk, which is associated with the gamma-ray burst GRB 171205A. Our spectra display features at extremely high expansion velocities (around 115,000 kilometres per second) within the first day after the burst(5,6). Using spectral synthesis models developed for SN 2017iuk, we show that these features are characterized by chemical abundances that differ from those observed in the ejecta of SN 2017iuk at later times. We further show that the high-velocity features originate from the mildly relativistic hot cocoon that is generated by an ultra-relativistic jet within the gamma-ray burst expanding and decelerating into the medium that surrounds the progenitor star(7,8). This cocoon rapidly becomes transparent(9) and is outshone by the supernova emission, which starts to dominate the emission three days after the burst.
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| 13. |
- Law, PJ, et al.
(författare)
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Genome-wide association analysis implicates dysregulation of immunity genes in chronic lymphocytic leukaemia
- 2017
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8, s. 14175-
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Tidskriftsartikel (refereegranskat)abstract
- Several chronic lymphocytic leukaemia (CLL) susceptibility loci have been reported; however, much of the heritable risk remains unidentified. Here we perform a meta-analysis of six genome-wide association studies, imputed using a merged reference panel of 1,000 Genomes and UK10K data, totalling 6,200 cases and 17,598 controls after replication. We identify nine risk loci at 1p36.11 (rs34676223, P=5.04 × 10−13), 1q42.13 (rs41271473, P=1.06 × 10−10), 4q24 (rs71597109, P=1.37 × 10−10), 4q35.1 (rs57214277, P=3.69 × 10−8), 6p21.31 (rs3800461, P=1.97 × 10−8), 11q23.2 (rs61904987, P=2.64 × 10−11), 18q21.1 (rs1036935, P=3.27 × 10−8), 19p13.3 (rs7254272, P=4.67 × 10−8) and 22q13.33 (rs140522, P=2.70 × 10−9). These new and established risk loci map to areas of active chromatin and show an over-representation of transcription factor binding for the key determinants of B-cell development and immune response.
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- Cai, Y.-Z., et al.
(författare)
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The transitional gap transient AT 2018hso : new insights into the luminous red nova phenomenon
- 2019
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 632
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Tidskriftsartikel (refereegranskat)abstract
- Context. The absolute magnitudes of luminous red novae (LRNe) are intermediate between those of novae and supernovae (SNe), and show a relatively homogeneous spectro-photometric evolution. Although they were thought to derive from core instabilities in single stars, there is growing support for the idea that they are triggered by binary interaction that possibly ends with the merging of the two stars.Aims. AT 2018hso is a new transient showing transitional properties between those of LRNe and the class of intermediate-luminosity red transients (ILRTs) similar to SN 2008S. Through the detailed analysis of the observed parameters, our study supports that it actually belongs to the LRN class and was likely produced by the coalescence of two massive stars.Methods. We obtained ten months of optical and near-infrared photometric monitoring, and 11 epochs of low-resolution optical spectroscopy of AT 2018hso. We compared its observed properties with those of other ILRTs and LRNe. We also inspected the archival Hubble Space Telescope (HST) images obtained about 15 years ago to constrain the progenitor properties.Results. The light curves of AT 2018hso show a first sharp peak (reddening-corrected M-r = -13.93 mag), followed by a broader and shallower second peak that resembles a plateau in the optical bands. The spectra dramatically change with time. Early-time spectra show prominent Balmer emission lines and a weak [Ca II] doublet, which is usually observed in ILRTs. However, the strong decrease in the continuum temperature, the appearance of narrow metal absorption lines, the great change in the H alpha strength and profile, and the emergence of molecular bands support an LRN classification. The possible detection of a M-I similar to -8 mag source at the position of AT 2018hso in HST archive images is consistent with expectations for a pre-merger massive binary, similar to the precursor of the 2015 LRN in M101.Conclusions. We provide reasonable arguments to support an LRN classification for AT 2018hso. This study reveals growing heterogeneity in the observables of LRNe than has been thought previously, which is a challenge for distinguishing between LRNe and ILRTs. This suggests that the entire evolution of gap transients needs to be monitored to avoid misclassifications.
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| 24. |
- Barker, Abigail, et al.
(författare)
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The magma plumbing system for the 1971 Teneguía eruption on La Palma, Canary Islands
- 2015
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Ingår i: Contributions to Mineralogy and Petrology. - : Springer Science and Business Media LLC. - 0010-7999 .- 1432-0967. ; 170:5-6
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Tidskriftsartikel (refereegranskat)abstract
- The 1971 Teneguía eruption is the most recent volcanic event of the Cumbre Vieja rift zone on La Palma. The eruption produced basanite lavas that host xenoliths, which we investigate to provide insight into the processes of differentiation, assimilation and magma storage beneath La Palma. We compare our results to the older volcanomagmatic systems of the island with the aim to reconstruct the temporal development of the magma plumbing system beneath La Palma.The 1971 lavas are clinopyroxene-olivine-phyric basanites that contain augite, sodic-augite and Aluminium augite. Kaersutite cumulate xenoliths host olivine, clinopyroxene including sodic-diopside, and calcic-amphibole, whereas an analysed leucogabbro xenolith hosts plagioclase, sodic-augite-diopside, calcic-amphibole and hauyne. Mineral and mineral-melt thermobarometry indicate that clinopyroxene and plagioclase in the 1971 Teneguía lavas crystallised at 20 to 45 km depth, coinciding with clinopyroxene and calcic-amphibole crystallisation in the kaersutite cumulate xenoliths at 25 to 45 km and clinopyroxene, calcic-amphibole and plagioclase crystallisation in the leucogabbro xenolith at 30 to 50 km.Combined mineral chemistry and thermobarometry suggest that the magmas had already crystallised, differentiated and formed multiple crystal populations in the oceanic lithospheric mantle. Notably, the magmas that supplied the 1949 and 1971 events appear to have crystallised deeper than the earlier Cumbre Vieja magmas, which suggests progressive underplating beneath the Cumbre Vieja rift zone. In addition, the lavas and xenoliths of the 1971 event crystallised at a common depth, indicating a reused plumbing system and progressive recycling of Ocean Island plutonic complexes during subsequent magmatic activity.
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- Carracedo, M, et al.
(författare)
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Upregulated Autophagy in Calcific Aortic Valve Stenosis Confers Protection of Valvular Interstitial Cells
- 2019
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Ingår i: International journal of molecular sciences. - : MDPI AG. - 1422-0067. ; 20:6
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Tidskriftsartikel (refereegranskat)abstract
- Autophagy serves as a cell survival mechanism which becomes dysregulated under pathological conditions and aging. Aortic valve thickening and calcification causing left ventricular outflow obstruction is known as calcific aortic valve stenosis (CAVS). CAVS is a chronic and progressive disease which increases in incidence and severity with age. Currently, no medical treatment exists for CAVS, and the role of autophagy in the disease remains largely unexplored. To further understand the role of autophagy in the progression of CAVS, we analyzed expression of key autophagy genes in healthy, thickened, and calcified valve tissue from 55 patients, and compared them with nine patients without significant CAVS, undergoing surgery for aortic regurgitation (AR). This revealed a upregulation in autophagy exclusively in the calcified tissue of CAVS patients. This difference in autophagy between CAVS and AR was explored by LC3 lipidation in valvular interstitial cells (VICs), revealing an upregulation in autophagic flux in CAVS patients. Inhibition of autophagy by bafilomycin-A1 led to a decrease in VIC survival. Finally, treatment of VICs with high phosphate led to an increase in autophagic activity. In conclusion, our data suggests that autophagy is upregulated in the calcified tissue of CAVS, serving as a compensatory and pro-survival mechanism.
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- Timofeeva, Maria N, et al.
(författare)
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Recurrent Coding Sequence Variation Explains Only A Small Fraction of the Genetic Architecture of Colorectal Cancer.
- 2015
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Whilst common genetic variation in many non-coding genomic regulatory regions are known to impart risk of colorectal cancer (CRC), much of the heritability of CRC remains unexplained. To examine the role of recurrent coding sequence variation in CRC aetiology, we genotyped 12,638 CRCs cases and 29,045 controls from six European populations. Single-variant analysis identified a coding variant (rs3184504) in SH2B3 (12q24) associated with CRC risk (OR = 1.08, P = 3.9 × 10(-7)), and novel damaging coding variants in 3 genes previously tagged by GWAS efforts; rs16888728 (8q24) in UTP23 (OR = 1.15, P = 1.4 × 10(-7)); rs6580742 and rs12303082 (12q13) in FAM186A (OR = 1.11, P = 1.2 × 10(-7) and OR = 1.09, P = 7.4 × 10(-8)); rs1129406 (12q13) in ATF1 (OR = 1.11, P = 8.3 × 10(-9)), all reaching exome-wide significance levels. Gene based tests identified associations between CRC and PCDHGA genes (P < 2.90 × 10(-6)). We found an excess of rare, damaging variants in base-excision (P = 2.4 × 10(-4)) and DNA mismatch repair genes (P = 6.1 × 10(-4)) consistent with a recessive mode of inheritance. This study comprehensively explores the contribution of coding sequence variation to CRC risk, identifying associations with coding variation in 4 genes and PCDHG gene cluster and several candidate recessive alleles. However, these findings suggest that recurrent, low-frequency coding variants account for a minority of the unexplained heritability of CRC.
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