GASP XXIII: a jellyfish galaxy as an astrophysical laboratory of the baryonic cycle

© 2019. The American Astronomical Society. All rights reserved. With MUSE, Chandra, VLA, ALMA, and UVIT data from the GASP program, we study the multiphase baryonic components in a jellyfish galaxy (JW100) with a stellar mass 3.2 × 1011 M o hosting an active galactic nucleus (AGN). We present its spectacular extraplanar tails of ionized and molecular gas, UV stellar light, and X-ray and radio continuum emission. This galaxy represents an excellent laboratory to study the interplay between different gas phases and star formation and the influence of gas stripping, gas heating, and AGNs. We analyze the physical origin of the emission at different wavelengths in the tail, in particular in situ star formation (related to Hα, CO, and UV emission), synchrotron emission from relativistic electrons (producing the radio continuum), and heating of the stripped interstellar medium (ISM; responsible for the X-ray emission). We show the similarities and differences of the spatial distributions of ionized gas, molecular gas, and UV light and argue that the mismatch on small scales (1 kpc) is due to different stages of the star formation process. We present the relation Hα-X-ray surface brightness, which is steeper for star-forming regions than for diffuse ionized gas regions with a high [O i]/Hα ratio. We propose that ISM heating due to interaction with the intracluster medium (either for mixing, thermal conduction, or shocks) is responsible for the X-ray tail, observed [O i] excess, and lack of star formation in the northern part of the tail. We also report the tentative discovery in the tail of the most distant (and among the brightest) currently known ULX, a pointlike ultraluminous X-ray source commonly originating in a binary stellar system powered by either an intermediate-mass black hole or a magnetized neutron star

GASP XXIII: A jellyfish galaxy as an astrophysical laboratory of the baryonic cycle

With MUSE, Chandra, VLA, ALMA and UVIT data from the GASP programme we study the multiphase baryonic components in a jellyfish galaxy (JW100) with a stellar mass 3.2 X 10^{11} M_sun hosting an AGN. We present its spectacular extraplanar tails of ionized and molecular gas, UV stellar light, X-ray and radio continuum emission. This galaxy represents an excellent laboratory to study the interplay between different gas phases and star formation, and the influence of gas stripping, gas heating, and AGN. We analyze the physical origin of the emission at different wavelengths in the tail, in particular in-situ star formation (related to Halpha, CO and UV emission), synchrotron emission from relativistic electrons (producing the radio continuum) and heating of the stripped interstellar medium (ISM) (responsible for the X-ray emission). We show the similarities and differences of the spatial distributions of ionized gas, molecular gas and UV light, and argue that the mismatch on small scales (1kpc) is due to different stages of the star formation process. We present the relation Halpha--X-ray surface brightness, which is steeper for star-forming regions than for diffuse ionised gas regions with high [OI]/Halpha ratio. We propose that ISM heating due to interaction with the intracluster medium (either for mixing, thermal conduction or shocks) is responsible for the X-ray tail, the observed [OI]-excess and the lack of star formation in the northern part of the tail. We also report the tentative discovery in the tail of the most distant (and among the brightest) currently known ULX, a point-like ultraluminous X-ray source commonly originating in a binary stellar system powered either by an intermediate-mass black hole or a magnetized neutron star.Comment: accepted for publication in Ap

ARTICLEAssociation of the CHEK2 c.1100delC variant, radiotherapy, and systemic treatment with contralateral breast cancer risk and breast cancer-specific survival

Aim To assessed the associations of CHEK2 c.1100delC, radiotherapy, and systemic treatment with CBC risk and BCSS. Methods Analyses were based on 82,701 women diagnosed with a first primary invasive BC including 963 CHEK2 c.1100delC carriers; median follow-up was 9.1 years. Differential associations with treatment by CHEK2 c.1100delC status were tested by including interaction terms in a multivariable Cox regression model. A multi-state model was used for further insight into the relation between CHEK2 c.1100delC status, treatment, CBC risk and death. Results There was no evidence for differential associations of therapy with CBC risk by CHEK2 c.1100delC status. The strongest association with reduced CBC risk was observed for the combination of chemotherapy and endocrine therapy [HR (95% CI): 0.66 (0.55–0.78)]. No association was observed with radiotherapy. Results from the multi-state model showed shorter BCSS for CHEK2 c.1100delC carriers versus non-carriers also after accounting for CBC occurrence [HR (95% CI): 1.30 (1.09–1.56)]. Conclusion Systemic therapy was associated with reduced CBC risk irrespective of CHEK2 c.1100delC status. Moreover, CHEK2 c.1100delC carriers had shorter BCSS, which appears not to be fully explained by their CBC risk

Association of the CHEK2 c.1100delC variant, radiotherapy, and systemic treatment with contralateral breast cancer risk and breast cancer-specific survival

Background: Breast cancer (BC) patients with a germline CHEK2 c.1100delC variant have an increased risk of contralateral BC (CBC) and worse BC-specific survival (BCSS) compared to non-carriers.Aim: To assessed the associations of CHEK2 c.1100delC, radiotherapy, and systemic treatment with CBC risk and BCSS.Methods: Analyses were based on 82,701 women diagnosed with a first primary invasive BC including 963 CHEK2 c.1100delC carriers; median follow-up was 9.1 years. Differential associations with treatment by CHEK2 c.1100delC status were tested by including interaction terms in a multivariable Cox regression model. A multi-state model was used for further insight into the relation between CHEK2 c.1100delC status, treatment, CBC risk and death. Results: There was no evidence for differential associations of therapy with CBC risk by CHEK2 c.1100delC status. The strongest association with reduced CBC risk was observed for the combination of chemotherapy and endocrine therapy [HR (95% CI): 0.66 (0.55-0.78)]. No association was observed with radiotherapy.Results from the multi-state model showed shorter BCSS for CHEK2 c.1100delC carriers versus non-carriers also after accounting for CBC occurrence [HR (95% CI): 1.30 (1.09-1.56)].Conclusion: Systemic therapy was associated with reduced CBC risk irrespective of CHEK2 c.1100delC status. Moreover, CHEK2 c.1100delC carriers had shorter BCSS, which appears not to be fully explained by their CBC risk.Peer reviewe

Polygenic Risk Scores for Prediction of Breast Cancer and Breast Cancer Subtypes

Stratification of women according to their risk of breast cancer based on polygenic risk scores (PRSs) could improve screening and prevention strategies. Our aim was to develop PRSs, optimized for prediction of estrogen receptor (ER)-specific disease, from the largest available genome-wide association dataset and to empirically validate the PRSs in prospective studies. The development dataset comprised 94,075 case subjects and 75,017 control subjects of European ancestry from 69 studies, divided into training and validation sets. Samples were genotyped using genome-wide arrays, and single-nucleotide polymorphisms (SNPs) were selected by stepwise regression or lasso penalized regression. The best performing PRSs were validated in an independent test set comprising 11,428 case subjects and 18,323 control subjects from 10 prospective studies and 190,040 women from UK Biobank (3,215 incident breast cancers). For the best PRSs (313 SNPs), the odds ratio for overall disease per 1 standard deviation in ten prospective studies was 1.61 (95%CI: 1.57-1.65) with area under receiver-operator curve (AUC) = 0.630 (95%CI: 0.628-0.651). The lifetime risk of overall breast cancer in the top centile of the PRSs was 32.6%. Compared with women in the middle quintile, those in the highest 1% of risk had 4.37- and 2.78-fold risks, and those in the lowest 1% of risk had 0.16- and 0.27-fold risks, of developing ER-positive and ER-negative disease, respectively. Goodness-of-fit tests indicated that this PRS was well calibrated and predicts disease risk accurately in the tails of the distribution. This PRS is a powerful and reliable predictor of breast cancer risk that may improve breast cancer prevention programs.NovartisEli Lilly and CompanyAstraZenecaAbbViePfizer UKCelgeneEisaiGenentechMerck Sharp and DohmeRocheCancer Research UKGovernment of CanadaArray BioPharmaGenome CanadaNational Institutes of HealthEuropean CommissionMinistère de l'Économie, de l’Innovation et des Exportations du QuébecSeventh Framework ProgrammeCanadian Institutes of Health Researc

Genome-wide association study identifies 32 novel breast cancer susceptibility loci from overall and subtype-specific analyses.

Breast cancer susceptibility variants frequently show heterogeneity in associations by tumor subtype1-3. To identify novel loci, we performed a genome-wide association study including 133,384 breast cancer cases and 113,789 controls, plus 18,908 BRCA1 mutation carriers (9,414 with breast cancer) of European ancestry, using both standard and novel methodologies that account for underlying tumor heterogeneity by estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 status and tumor grade. We identified 32 novel susceptibility loci (P < 5.0 × 10-8), 15 of which showed evidence for associations with at least one tumor feature (false discovery rate < 0.05). Five loci showed associations (P < 0.05) in opposite directions between luminal and non-luminal subtypes. In silico analyses showed that these five loci contained cell-specific enhancers that differed between normal luminal and basal mammary cells. The genetic correlations between five intrinsic-like subtypes ranged from 0.35 to 0.80. The proportion of genome-wide chip heritability explained by all known susceptibility loci was 54.2% for luminal A-like disease and 37.6% for triple-negative disease. The odds ratios of polygenic risk scores, which included 330 variants, for the highest 1% of quantiles compared with middle quantiles were 5.63 and 3.02 for luminal A-like and triple-negative disease, respectively. These findings provide an improved understanding of genetic predisposition to breast cancer subtypes and will inform the development of subtype-specific polygenic risk scores

GASP. XXII. The Molecular Gas Content of the JW100 Jellyfish Galaxy at z ∼ 0.05: Does Ram Pressure Promote Molecular Gas Formation?

Within the GASP survey, aimed at studying the effect of the ram-pressure stripping on the star formation quenching in cluster galaxies, we analyze here ALMA observations of the jellyfish galaxy JW100. We find an unexpected large amount of molecular gas (∼ 2.5 × 10 10 M), 30% of which is located in the stripped gas tail out to ∼35 kpc from the galaxy center. The overall kinematics of molecular gas is similar to the one shown by the ionized gas, but for clear signatures of double components along the stripping direction detected only out to 2 kpc from the disk. The line ratio r 21 has a clumpy distribution and in the tail can reach large values (≥ 1), while its average value is low (0.58 with a 0.15 dispersion). All these evidence strongly suggest that the molecular gas in the tail is newly born from stripped HI gas or newly condensed from stripped diffuse molecular gas. The analysis of interferometric data at different scales reveals that a significant fraction (∼ 40%) of the molecular gas is extended over large scales (≥ 8 kpc) in the disk, and this fraction becomes predominant in the tail (∼ 70%). By comparing the molecular gas surface density with the star formation rate surface density derived from the Hα emission from MUSE data, we find that the depletion time on 1 kpc scale is particularly large (5 − 10 Gyr) both within the ram-pressure disturbed region in the stellar disk, and in the complexes along the tail

Role of VEGF-D and VEGFR-3 in developmental lymphangiogenesis, a chemicogenetic study in Xenopus tadpoles

The importance of the lymphangiogenic factor VEGF-D and its receptor VEGFR-3 in early lymphatic development remains largely unresolved. We therefore investigated their role in Xenopus laevis tadpoles, a small animal model allowing chemicogenetic dissection of developmental lymphangiogenesis. Single morpholino antisense oligo knockdown of xVEGF-D did not affect lymphatic commitment, but transiently impaired lymphatic endothelial cell (LEC) migration. Notably, combined knockdown of xVEGF-D with xVEGF-C at suboptimal morpholino concentrations resulted in more severe migration defects and lymphedema formation than the corresponding single knockdowns. Knockdown of VEGFR-3 or treatment with the VEGFR-3 inhibitor MAZ51 similarly impaired lymph vessel formation and function and caused pronounced edema. VEGFR-3 silencing by morpholino knockdown, MAZ51 treatment, or xVEGF-C/D double knockdown also resulted in dilation and dysfunction of the lymph heart. These findings document a critical role of VEGFR-3 in embryonic lymphatic development and function, and reveal a previously unrecognized modifier role of VEGF-D in the regulation of embryonic lymphangiogenesis in frog embryos.status: publishe

A genetic Xenopus laevis tadpole model to study lymphangiogenesis

Lymph vessels control fluid homeostasis, immunity and metastasis. Unraveling the molecular basis of lymphangiogenesis has been hampered by the lack of a small animal model that can be genetically manipulated. Here, we show that Xenopus tadpoles develop lymph vessels from lymphangioblasts or, through transdifferentiation, from venous endothelial cells. Lymphangiography showed that these lymph vessels drain lymph, through the lymph heart, to the venous circulation. Morpholino-mediated knockdown of the lymphangiogenic factor Prox1 caused lymph vessel defects and lymphedema by impairing lymphatic commitment. Knockdown of vascular endothelial growth factor C (VEGF-C) also induced lymph vessel defects and lymphedema, but primarily by affecting migration of lymphatic endothelial cells. Knockdown of VEGF-C also resulted in aberrant blood vessel formation in tadpoles. This tadpole model offers opportunities for the discovery of new regulators of lymphangiogenesis.status: publishe