A peculiarity of metal-poor stars with planets ?

Stars with planets at intermediate metallicities ([-0.7,-0.2] dex) exhibit properties that differ from the general field stars. Thirteen stars with planets reported in this metallicity range belong to the thick disc, while only one planet have been detected among stars of the thin disc. Although this statistics is weak, it contradicts the known correlation between the presence of planet and metallicity. We relate this finding to the specific property of the thin disc in this metallicity range, where stars are shown to rotate around the Galaxy faster than the Sun. Their orbital parameters are conveniently explained if they are contaminants coming from the outer Galactic disc, as a result of radial mixing. This must be considered together with the fact that metal-rich stars ([Fe/H]>+0.1 dex) found in the solar neighbourhood, which are the hosts of most of the detected planets, are suspected of being wanderers from the inner Galactic disc. It is then questionned why stars that originate in the inner and outer thin disc show respectively the highest and lowest rate of detected planets. It is suggested that the presence of giant planets might be primarily a function of a parameter linked to galactocentric radius, but not metallicity. Combined with the existing radial metallicity gradient, then radial mixing explains the correlation at high metallicity observed locally, but also the peculiarity found at low metallicity, which cannot be accounted for by a simple correlation between metallicity and planet probability.Comment: 4 pages, 2 figures, accepted for publication in A&

Modelling a high-mass red giant observed by CoRoT

The G6 giant HR\,2582 (HD\,50890) was observed by CoRoT for approximately 55 days. Mode frequencies are extracted from the observed Fourier spectrum of the light curve. Numerical stellar models are then computed to determine the characteristics of the star (mass, age, etc...) from the comparison with observational constraints. We provide evidence for the presence of solar-like oscillations at low frequency, between 10 and 20\,$\mu$Hz, with a regular spacing of $(1.7\pm0.1)\mu$Hz between consecutive radial orders. Only radial modes are clearly visible. From the models compatible with the observational constraints used here, We find that HR\,2582 (HD\,50890) is a massive star with a mass in the range (3--\,5\,$M_{\odot}$), clearly above the red clump. It oscillates with rather low radial order ($n$ = 5\,--\,12) modes. Its evolutionary stage cannot be determined with precision: the star could be on the ascending red giant branch (hydrogen shell burning) with an age of approximately 155 Myr or in a later phase (helium burning). In order to obtain a reasonable helium amount, the metallicity of the star must be quite subsolar. Our best models are obtained with a mixing length significantly smaller than that obtained for the Sun with the same physical description (except overshoot). The amount of core overshoot during the main-sequence phase is found to be mild, of the order of 0.1\,$H_{\rm p}$.Comment: Accepted in A&

The evolutionary dynamics of extrachromosomal DNA in human cancers

Oncogene amplification on extrachromosomal DNA (ecDNA) is a common event, driving aggressive tumor growth, drug resistance and shorter survival. Currently, the impact of nonchromosomal oncogene inheritance-random identity by descent-is poorly understood. Also unclear is the impact of ecDNA on somatic variation and selection. Here integrating theoretical models of random segregation, unbiased image analysis, CRISPR-based ecDNA tagging with live-cell imaging and CRISPR-C, we demonstrate that random ecDNA inheritance results in extensive intratumoral ecDNA copy number heterogeneity and rapid adaptation to metabolic stress and targeted treatment. Observed ecDNAs benefit host cell survival or growth and can change within a single cell cycle. ecDNA inheritance can predict, a priori, some of the aggressive features of ecDNA-containing cancers. These properties are facilitated by the ability of ecDNA to rapidly adapt genomes in a way that is not possible through chromosomal oncogene amplification. These results show how the nonchromosomal random inheritance pattern of ecDNA contributes to poor outcomes for patients with cancer

Personalized recurrence risk assessment following the birth of a child with a pathogenic de novo mutation

Following the diagnosis of a paediatric disorder caused by an apparently de novo mutation, a recurrence risk of 1–2% is frequently quoted due to the possibility of parental germline mosaicism; but for any specific couple, this figure is usually incorrect. We present a systematic approach to providing individualized recurrence risk. By combining locus-specific sequencing of multiple tissues to detect occult mosaicism with long-read sequencing to determine the parent-of-origin of the mutation, we show that we can stratify the majority of couples into one of seven discrete categories associated with substantially different risks to future offspring. Among 58 families with a single affected offspring (representing 59 de novo mutations in 49 genes), the recurrence risk for 35 (59%) was decreased below 0.1%, but increased owing to parental mixed mosaicism for 5 (9%)—that could be quantified in semen for paternal cases (recurrence risks of 5.6–12.1%). Implementation of this strategy offers the prospect of driving a major transformation in the practice of genetic counselling

Frequency and Prognostic Impact of ALK Amplifications and Mutations in the European Neuroblastoma Study Group (SIOPEN) High-Risk Neuroblastoma Trial (HR-NBL1).

In neuroblastoma (NB), the ALK receptor tyrosine kinase can be constitutively activated through activating point mutations or genomic amplification. We studied ALK genetic alterations in high-risk (HR) patients on the HR-NBL1/SIOPEN trial to determine their frequency, correlation with clinical parameters, and prognostic impact. Diagnostic tumor samples were available from 1,092 HR-NBL1/SIOPEN patients to determine ALK amplification status (n = 330), ALK mutational profile (n = 191), or both (n = 571). Genomic ALK amplification (ALKa) was detected in 4.5% of cases (41 out of 901), all except one with MYCN amplification (MNA). ALKa was associated with a significantly poorer overall survival (OS) (5-year OS: ALKa [n = 41] 28% [95% CI, 15 to 42]; no-ALKa [n = 860] 51% [95% CI, 47 to 54], [P < .001]), particularly in cases with metastatic disease. ALK mutations (ALKm) were detected at a clonal level (> 20% mutated allele fraction) in 10% of cases (76 out of 762) and at a subclonal level (mutated allele fraction 0.1%-20%) in 3.9% of patients (30 out of 762), with a strong correlation between the presence of ALKm and MNA (P < .001). Among 571 cases with known ALKa and ALKm status, a statistically significant difference in OS was observed between cases with ALKa or clonal ALKm versus subclonal ALKm or no ALK alterations (5-year OS: ALKa [n = 19], 26% [95% CI, 10 to 47], clonal ALKm [n = 65] 33% [95% CI, 21 to 44], subclonal ALKm (n = 22) 48% [95% CI, 26 to 67], and no alteration [n = 465], 51% [95% CI, 46 to 55], respectively; P = .001). Importantly, in a multivariate model, involvement of more than one metastatic compartment (hazard ratio [HR], 2.87; P < .001), ALKa (HR, 2.38; P = .004), and clonal ALKm (HR, 1.77; P = .001) were independent predictors of poor outcome. Genetic alterations of ALK (clonal mutations and amplifications) in HR-NB are independent predictors of poorer survival. These data provide a rationale for integration of ALK inhibitors in upfront treatment of HR-NB with ALK alterations

Personalized recurrence risk assessment following the birth of a child with a pathogenic de novo mutation

Following the diagnosis of a paediatric disorder caused by an apparently de novo mutation, a recurrence risk of 1-2% is frequently quoted due to the possibility of parental germline mosaicism; but for any specific couple, this figure is usually incorrect. We present a systematic approach to providing individualized recurrence risk. By combining locus-specific sequencing of multiple tissues to detect occult mosaicism with long-read sequencing to determine the parent-of-origin of the mutation, we show that we can stratify the majority of couples into one of seven discrete categories associated with substantially different risks to future offspring. Among 58 families with a single affected offspring (representing 59 de novo mutations in 49 genes), the recurrence risk for 35 (59%) was decreased below 0.1%, but increased owing to parental mixed mosaicism for 5 (9%)-that could be quantified in semen for paternal cases (recurrence risks of 5.6-12.1%). Implementation of this strategy offers the prospect of driving a major transformation in the practice of genetic counselling

Changes in cortical cytoskeletal and extracellular matrix gene expression in prostate cancer are related to oncogenic ERG deregulation

Abstract Background The cortical cytoskeleton network connects the actin cytoskeleton to various membrane proteins, influencing cell adhesion, polarity, migration and response to extracellular signals. Previous studies have suggested changes in the expression of specific components in prostate cancer, especially of 4.1 proteins (encoded by EPB41 genes) which form nodes in this network. Methods Expression of EPB41L1, EPB41L2, EPB41L3 (protein: 4.1B), EPB41L4B (EHM2), EPB41L5, EPB49 (dematin), VIL2 (ezrin), and DLG1 (summarized as „cortical cytoskeleton" genes) as well as ERG was measured by quantitative RT-PCR in a well-characterized set of 45 M0 prostate adenocarcinoma and 13 benign tissues. Hypermethylation of EPB41L3 and GSTP1 was compared in 93 cancer tissues by methylation-specific PCR. Expression of 4.1B was further studied by immunohistochemistry. Results EPB41L1 and EPB41L3 were significantly downregulated and EPB41L4B was upregulated in cancer tissues. Low EPB41L1 or high EPB41L4B expression were associated with earlier biochemical recurrence. None of the other cortical cytoskeleton genes displayed expression changes, in particular EPB49 and VIL2, despite hints from previous studies. EPB41L3 downregulation was significantly associated with hypermethylation of its promoter and strongly correlated with GSTP1 hypermethylation. Protein 4.1B was detected most strongly in the basal cells of normal prostate epithelia. Its expression in carcinoma cells was similar to the weaker one in normal luminal cells. EPB41L3 downregulation and EPB41L4B upregulation were essentially restricted to the 22 cases with ERG overexpression. Expression changes in EPB41L3 and EPB41L4B closely paralleled those previously observed for the extracellular matrix genes FBLN1 and SPOCK1, respectively. Conclusions Specific changes in the cortical cytoskeleton were observed during prostate cancer progression. They parallel changes in the expression of extracellular matrix components and all together appear to be associated with oncogenic ERG overexpression. We hypothesize that these alterations may contribute to the increased invasivity conferred to prostate cancer cells by ERG deregulation.</p

Stellar Structure and Evolution: Deductions from Hipparcos

During the last decade, the understanding of fine features of the structure and evolution of stars has become possible as a result of enormous progress made in the acquisition of high-quality observational and experimental data and of new developments and refinements in the theoretical description of stellar plasmas. The confrontation of high-quality observations with sophisticated stellar models has allowed many aspects of the theory to be validated, and several characteristics of stars relevant to Galactic evolution and cosmology to be inferred. This paper is a review of the results of recent studies undertaken in the context of the Hipparcos mission, taking benefit of the high-quality astrometric data it has provided. Successes are discussed, as well as the problems that have arisen and suggestions proposed to solve them. Future observational and theoretical developments expected and required in the field are also presented.Comment: 56 pages, including 9 figures, Ann. Rev. Astron. Astrophys. Vol. 38, September 2000 (in press

NLTE line formation of Fe for late-type stars. I. Standard stars with 1D and <3D> model atmospheres

We investigate departures from LTE in the line formation of Fe for a number of well-studied late-type stars in different evolutionary stages. A new model of Fe atom was constructed from the most up-to-date theoretical and experimental atomic data available so far. Non-local thermodynamic equilibrium (NLTE) line formation calculations for Fe were performed using 1D hydrostatic MARCS and MAFAGS-OS model atmospheres, as well as the spatial and temporal average stratifications from full 3D hydrodynamical simulations of stellar convection computed using the Stagger code. It is shown that the Fe I/Fe II ionization balance can be well established with the 1D and mean 3D models under NLTE including calibrated inelastic collisions with H I calculated from the Drawin's (1969) formulae. Strong low-excitation Fe I lines are very sensitive to the atmospheric structure; classical 1D models fail to provide consistent excitation balance, particularly so for cool metal-poor stars. A better agreement between Fe I lines spanning a range of excitation potentials is obtained with the mean 3D models. Mean NLTE metallicities determined for the standard stars using the 1D and mean 3D models are fully consistent. Also, the NLTE spectroscopic effective temperatures and gravities from ionization balance agree with that determined by other methods, e.g., infrared flux method and parallaxes, if one of the stellar parameters is constrained independently.Comment: accepted for publication in MNRA

Formation of Galactic Systems in Light of the Magnesium Abundance in Field Stars: The Thick Disk

The space velocities and Galactic orbital elements of stars calculated from the currently available high-accuracy observations in our summary catalog of spectroscopic magnesium abundances in dwarfs and subgiants in the solar neighborhood are used to identify thick-disk objects. The relative magnesium abundances in thick-disk stars are shown to lie within the range 0.0<[Mg/Fe]<0.5 and to decrease with increasing metallicity starting from [Fe/H]=-1.0. This is interpreted as evidence for a longer duration of the star formation process in the thick disk. We have found vertical gradients in metallicity (grad_Z[Fe/H]=-0.13\pm 0.04 kpc^{-1}) and relative magnesium abundance (grad_Z [Mg/Fe]=0.06\pm 0.02 kpc^{-1}), which can be present in the subsystem only in the case of its formation in a slowly collapsing protogalaxy. The large spread in relative magnesium abundance (-0.3<[Mg/Fe]<0.5) in the stars of the metal-poor "tail" of the thick disk which constitute 8% of the subsystem, can be explained in terms of their formation inside isolated interstellar clouds that interacted weakly with the matter of a single protogalactic cloud. We have found a statistically significant negative radial gradient in relative magnesium abundance in the thick disk (grad_R [Mg/Fe]=-0.03\pm 0.01 kpc^{-1}) instead of the expected positive gradient. The smaller perigalactic orbital radii and the higher eccentricities for magnesium-richer stars, which among other stars, are currently located in a small volume of the Galactic space near the Sun are assumed to be responsible for the gradient inversion. A similar but statistically less significant inversion is also observed in the subsystem for the radial metallicity gradient.Comment: Accepted for 2005, Astronomy Letters, Vol. 31, No. 8, P.515-527; 14 pages, 6 figure