Open cluster candidates in the VVVX area: VVVX CL 076 and CL 077

We are reporting some basic parameters of two newly discovered clusters, VVVX CL 076 and CL 077, recently discovered in the galactic disk area covered by the VISTA Variables in the Via Lactea eXtended (VVVX) ESO Public Survey. The preliminary analysis shows that both clusters are young and relatively close to the Sun.Peer reviewedFinal Published versio

La chimiohyperthermie intrapéritonéale (CHIP) dans les cancers ovariens

RésuméLe cancer de l’ovaire reste, en France, la quatrième cause de décès par cancer chez la femme. Il s’agit d’une maladie souvent diagnostiquée à un stade évolué avec carcinose péritonéale (CP) et dont l’histoire naturelle est marquée par des récidives essentiellement péritonéales et l’acquisition d’un profil de chimiorésistance. Malgré les nombreuses lignes de chimiothérapie systémique et les chirurgies de cytoréduction (CCR), le pronostic de ces récidives reste sombre. Depuis plus de 20ans, plusieurs équipes spécialisées ont développé un traitement combiné des CP, associant une chirurgie de cytoréduction complète à une chimiohyperthermie intrapéritonéale (CHIP). Cette thérapeutique a une large place dans le traitement des CP d’origine non gynécologiques. Le rationnel pour une utilisation de la CHIP dans le traitement des CP d’origine ovarienne est important. D’une part, 3 études prospectives randomisées ont démontré la supériorité de l’utilisation de la chimiothérapie intrapéritonéale (sans hyperthermie) par rapport à la chimiothérapie systémique sur des patientes sélectionnées. D’autre part, des études rétrospectives et cas-témoins évaluant la CHIP font état de données de survie encourageantes, en particulier en cas de récidive chimiorésistante. Néanmoins, la morbidité et la mortalité associées doivent appeler à une sélection rigoureuse des patientes éligibles, et à une prise en charge multidisciplinaire dans des centres spécialisés. L’évaluation de la CHIP doit se faire par le moyen d’études randomisées à différents stades évolutifs : 1re ligne, consolidation, récidives qu’elles soient chimiorésistantes ou chimiosensibles. Plusieurs études européennes sont en cours.SummaryOvarian cancer remains the fourth leading cause of cancer death in women in France. It is all too often diagnosed at an advanced stage with peritoneal carcinomatosis (PC), but remains confined to the peritoneal cavity throughout much of its natural history. Because of cellular selection pressure over time, most tumor recurrences eventually develop resistance to systemic platinum. Options for salvage therapy include alternative systemic chemotherapies and further cytoreductive surgery (CRS), but the prognosis remains poor. Over the past two decades, a new therapeutic approach to PC has been developed that combines CRS with hyperthermic intraperitoneal chemotherapy (HIPEC). This treatment strategy has already been shown to be effective in non-gynecologic carcinomatosis in numerous reports. There is a strong rationale for the use of HIPEC for PC of ovarian origin. On the one hand, three prospective randomized trials have demonstrated the superiority of intraperitoneal chemotherapy (without hyperthermia) in selected patients compared to systemic chemotherapy. Moreover, retrospective studies and case-control studies of HIPEC have reported encouraging survival data, especially when used to treat chemoresistant recurrence. However, HIPEC has specific morbidity and mortality; this calls for very careful selection of eligible patients by a multidisciplinary team in specialized centers. HIPEC needs to be evaluated by means of randomized trials for ovarian cancer at different developmental stages: as first line therapy, as consolidation, and for chemoresistant recurrence. Several European Phase III studies are currently ongoing

Deriving metallicities from calcium triplet spectroscopy in combination with near-infrared photometry

Context. When they are established with sufficient precision, the ages, metallicities and kinematics of Galactic globular clusters (GGCs) can shed much light on the dynamical and chemical evolution of the Galactic halo and bulge. While the most fundamental way of determining GC abundances is by means of high-resolution spectroscopy, in practice this method is limited to only the brighter stars in the nearest and less reddened objects. This restriction has, over the years, led to the development of a large number of techniques that measure the overall abundance indirectly from parameters that correlate with overall metallicity. One of the most efficient methods is measuring the equivalent width (EW) of the calcium II triplet (CaT) at λ ≈ 8500 Å in red giants, which are corrected for the luminosity and temperature effects using the V magnitude differences from the horizontal branch (HB). Aims. We establish a similar method in the near-infrared (NIR), by combining the power of the differential magnitudes technique with the advantages of NIR photometry to minimize differential reddening effects. Methods. We used the Ks magnitude difference between the star and the reddest part of the HB (RHB) or of the red clump (RC) to generate reduced equivalent widths (rEW) from previously presented datasets. Then we calibrated these rEW against three previously reported different metallicity scales; one of which we corrected using high-resolution spectroscopic metallicities. Results. We calculated the calibration relations for the two datasets and the three metallicity scales and found that they are approximately equivalent, with almost negligible differences. We compared our NIR calibrations with the corresponding optical ones, and found them to be equivalent, which shows that the luminosity-corrected rEW using the Ks magnitude is compatible with the one obtained from the V magnitude. We then used the metallicities obtained from the calibration to investigate the internal metallicity distributions of the GCs. Conclusions. We have established that the ([Fe/H]:rEW) relation is independent of the magnitude used for the luminosity correction and find that the calibration relations change only slightly for different metallicity scales. The CaT technique using NIR photometry is thus a powerful tool to derive metallicities. In particular, it can be used to study the internal metallicity spread of a GC. We confirm the presence of at least two metallicity populations in NGC 6656 and find that several other GCs present peculiar metallicity distributions

Premenopausal endogenous oestrogen levels and breast cancer risk: a meta-analysis.

BACKGROUND: Many of the established risk factors for breast cancer implicate circulating hormone levels in the aetiology of the disease. Increased levels of postmenopausal endogenous oestradiol (E2) have been found to increase the risk of breast cancer, but no such association has been confirmed in premenopausal women. We carried out a meta-analysis to summarise the available evidence in women before the menopause. METHODS: We identified seven prospective studies of premenopausal endogenous E2 and breast cancer risk, including 693 breast cancer cases. From each study we extracted odds ratios of breast cancer between quantiles of endogenous E2, or for unit or s.d. increases in (log transformed) E2, or (where odds ratios were unavailable) summary statistics for the distributions of E2 in breast cancer cases and unaffected controls. Estimates for a doubling of endogenous E2 were obtained from these extracted estimates, and random-effect meta-analysis was used to obtain a pooled estimate across the studies. RESULTS: Overall, we found weak evidence of a positive association between circulating E2 levels and the risk of breast cancer, with a doubling of E2 associated with an odds ratio of 1.10 (95% CI: 0.96, 1.27). CONCLUSION: Our findings are consistent with the hypothesis of a positive association between premenopausal endogenous E2 and breast cancer risk

mRNA Display Selection of an Optimized MDM2-Binding Peptide That Potently Inhibits MDM2-p53 Interaction

p53 is a tumor suppressor protein that prevents tumorigenesis through cell cycle arrest or apoptosis of cells in response to cellular stress such as DNA damage. Because the oncoprotein MDM2 interacts with p53 and inhibits its activity, MDM2-p53 interaction has been a major target for the development of anticancer drugs. While previous studies have used phage display to identify peptides (such as DI) that inhibit the MDM2-p53 interaction, these peptides were not sufficiently optimized because the size of the phage-displayed random peptide libraries did not cover all of the possible sequences. In this study, we performed selection of MDM2-binding peptides from large random peptide libraries in two stages using mRNA display. We identified an optimal peptide named MIP that inhibited the MDM2-p53 and MDMX-p53 interactions 29- and 13-fold more effectively than DI, respectively. Expression of MIP fused to the thioredoxin scaffold protein in living cells by adenovirus caused stabilization of p53 through its interaction with MDM2, resulting in activation of the p53 pathway. Furthermore, expression of MIP also inhibited tumor cell proliferation in a p53-dependent manner more potently than DI. These results show that two-stage, mRNA-displayed peptide selection is useful for the rapid identification of potent peptides that target oncoproteins

A massive helium star with a sufficiently strong magnetic field to form a magnetar

Magnetars are highly magnetized neutron stars; their formation mechanism is unknown. Hot helium-rich stars with spectra dominated by emission lines are known as Wolf-Rayet stars. We observe the binary system HD 45166 using spectropolarimetry, finding that it contains a Wolf-Rayet star with a mass of 2 solar masses and a magnetic field of 43 kilogauss. Stellar evolution calculations indicate that this component will explode as a type Ib or IIb supernova, and the strong magnetic field favors a magnetar remnant. We propose that the magnatized Wolf-Rayet star formed by the merger of two lower mass helium stars.Comment: Published in Science on the 18 August 2023. Radial velocities, spectra, and software available in: https://zenodo.org/record/8042656 ESO press release: www.eso.org/public/news/eso231

Infrared photometry and CaT spectroscopy of globular cluster M 28 (NGC 6626)

Recent studies show that the inner Galactic regions host genuine bulge globular clusters, but also halo intruders, complex remnants of primordial building blocks, and objects likely accreted during major merging events. In this study we focus on the properties of M 28, a very old and massive cluster currently located in the Galactic bulge. We analysed wide-field infrared photometry collected by the VVV survey, VVV proper motions, and intermediate-resolution spectra in the calcium triplet range for 113 targets in the cluster area. Our results in general confirm previous estimates of the cluster properties available in the literature. We find no evidence of differences in metallicity between cluster stars, setting an upper limit of Delta[Fe/H]<0.08 dex to any internal inhomogeneity. We confirm that M 28 is one of the oldest objects in the Galactic bulge (13-14 Gyr). From this result and the literature data, we find evidence of a weak age-metallicity relation among bulge globular clusters that suggests formation and chemical enrichment. In addition, wide-field density maps show that M 28 is tidally stressed and that it is losing mass into the general bulge field. Our study indicates that M 28 is a genuine bulge globular cluster, but its very old age and its mass loss suggest that this cluster could be the remnant of a larger structure, possibly a primeval bulge building block.Comment: Accepted for publication in Astronomy & Astrophysic

Single-Molecule characterization of oligomerization kinetics and equilibria of the tumor suppressor p53

The state of oligomerization of the tumor suppressor p53 is an important factor in its various biological functions. It has a well-defined tetramerization domain, and the protein exists as monomers, dimers and tetramers in equilibrium. The dissociation constants between oligomeric forms are so low that they are at the limits of measurement by conventional methods in vitro. Here, we have used the high sensitivity of single-molecule methods to measure the equilibria and kinetics of oligomerization of full-length p53 and its isolated tetramerization domain, p53tet, at physiological temperature, pH and ionic strength using fluorescence correlation spectroscopy (FCS) in vitro. The dissociation constant at 37°C for tetramers dissociating into dimers for full-length p53 was 50 ± 7 nM, and the corresponding value for dimers into monomers was 0.55 ± 0.08 nM. The half-lives for the two processes were 20 and 50 min, respectively. The equivalent quantities for p53tet were 150 ± 10 nM, 1.0 ± 0.14 nM, 2.5 ± 0.4 min and 13 ± 2 min. The data suggest that unligated p53 in unstressed cells should be predominantly dimeric. Single-molecule FCS is a useful procedure for measuring dissociation equilibria, kinetics and aggregation at extreme sensitivity