Wind and nebula of the M33 variable GR290 (WR/LBV)

Context: GR290 (M33/V532=Romano's Star) is a suspected post-LBV star located in M33 galaxy that shows a rare Wolf-Rayet spectrum during its minimum light phase. In spite of many studies, its atmospheric structure, its circumstellar environment and its place in the general context of massive stars evolution is poorly known. Aims: Detailed study of its wind and mass loss, and study of the circumstellar environment associated to the star. Methods: Long-slit spectra of GR290 were obtained during its present minimum luminosity phase with the GTC together with contemporaneous BVRI photometry. The data were compared with non-LTE model atmosphere synthetic spectra computed with CMFGEN and with CLOUDY models for ionized interstellar medium regions. Results: The current $m_V=18.8$ mag, is the faintest at which this source has ever been observed. The non-LTE models indicate effective temperature $T_{eff}$=27-30 kK at radius $R_{2/3}$=27-21 Rsun and mass loss rate $\dot{M}=1.5\times10^{-5}$ Msun yr$^{-1}$. The terminal wind speed $V_\infty$=620 ${\rm km~s^{-1}}$ is faster than ever before recorded while the current luminosity $L_*=(3.1-3.7)\times 10^5$ Lsun is the lowest ever deduced. It is overabundant in He and N and underabundant in C and O. It is surrounded by an unresolved compact HII region with dimensions $\leq$4 pc, from where H-Balmer, HeI lines and [OIII] and [NII] are detected. In addition, we find emission from a more extended interstellar medium (ISM) region which appears to be asymmetric, with a larger extent to the East (16-40 pc) than to the West. Conclusions: In the present long lasting visual minimum, GR290 is in a lower bolometric luminosity state with higher mass loss rate. The nearby nebular emission seems to suggest that the star has undergone significant mass loss over the past $10^4-10^5$ years and is nearing the end stages of its evolution.Comment: submitted to A&A, 12 pages, 9 figures, 7 table

GR 290 (Romano's Star): 2. Light history and evolutionary state

We have built the historical light curve of the luminous variable GR 290 back to 1901, from old observations of the star found in several archival plates of M 33. These old recordings together with published and new data show that for at least half a century the star was in a low luminosity state, with B ~18. After 1960, five large variability cycles of visual luminosity were recorded. The amplitude of the oscillations was seen increasing towards the 1992-1994 maximum, then decreasing during the last maxima. The recent light curve indicates that the photometric variations have been quite similar in all the bands, and that the B-V color index has been constant within +/-0.1 m despite the 1.5m change of the visual luminosity. The spectrum of GR 290 at the large maximum of 1992-94, was equivalent to late-B type, while, during 2002-2014, it has varied between WN10h-11h near the visual maxima to WN8h-9h at the luminosity minima. We have detected, during this same period, a clear anti-correlation between the visual luminosity, the strength of the HeII 4686 A emission line, the strength of the 4600-4700 A lines blend and the spectral type. From a model analysis of the spectra collected during the whole 2002-2014 period we find that the Rosseland radius R_{2/3}, changed between the minimum and maximum luminosity phases by a factor of 3, while T_eff varied between about 33,000 K and 23,000 K. The bolometric luminosity of the star was not constant, but increased by a factor of ~1.5 between minimum and maximum luminosity, in phase with the apparent luminosity variations. In the light of current evolutionary models of very massive stars, we find that GR 290 has evolved from a ~60 M_Sun progenitor star and should have an age of about 4 million years. We argue that it has left the LBV stage and is moving to a Wolf-Rayet stage of late nitrogen spectral type.Comment: Accepted on The Astronomical Journal, 10 figures. Replaced because the previous uploaded file was that without the final small corrections requested by the refere

Migraine and psychiatric comorbidity: a review of clinical findings.

Migraine is an extremely common disorder. The underlying mechanisms of this chronic illness interspersed with acute symptoms appear to be increasingly complex. An important aspect of migraine heterogeneity is comorbidity with other neurological diseases, cardiovascular disorders, and psychiatric illnesses. Depressive disorders are among the leading causes of disability worldwide according to WHO estimation. In this review, we have mainly considered the findings from general population studies and studies on clinical samples, in adults and children, focusing on the association between migraine and psychiatric disorders (axis I of the DSM), carried over after the first classification of IHS (1988). Though not easily comparable due to differences in methodology to reach diagnosis, general population studies generally indicate an increased risk of affective and anxiety disorders in patients with migraine, compared to non-migrainous subjects. There would also be a trend towards an association of migraine with bipolar disorder, but not with substance abuse/dependence. With respect to migraine subtypes, comorbidity mainly involves migraine with aura. Patients suffering from migraine, however, show a decreased risk of developing affective and anxiety disorders compared to patients with daily chronic headache. It would also appear that psychiatric disorders prevail in patients with chronic headache and substance use than in patients with simple migraine. The mechanisms underlying migraine psychiatric comorbidity are presently poorly understood, but this topic remains a priority for future research. Psychiatric comorbidity indeed affects migraine evolution, may lead to chronic substance use, and may change treatment strategies, eventually modifying the outcome of this important disorder

A fine physical map of the CACNA1A gene region on 19p13.1-p13.2 chromosome

The P/Q-type Ca(2+) channel alpha(1A) subunit gene (CACNA1A) was cloned on the short arm of chromosome 19 between the markers D19S221 and D19S179 and found to be responsible for Episodic Ataxia type 2, Familial Hemiplegic Migraine and Spinocerebellar Ataxia type 6. This region was physically mapped by 11 cosmid contigs spanning about 1. 4Mb, corresponding to less than 70% of the whole region. The cosmid contig used to characterize the CACNA1A gene accounted only for the coding region of the gene lacking, therefore, the promoter and possible regulation regions. The present study improves the physical map around and within the CACNA1A by giving a complete cosmid or BAC contig coverage of the D19S221-D19S179 interval. A number of new STSs, whether polymorphic or not, were characterized and physically mapped within this region. Four ESTs were also assigned to cosmids belonging to specific contigs

Effects of PCSK9 inhibitors on HDL cholesterol efflux and serum cholesterol loading capacity in familial hypercholesterolemia subjects: a multi-lipid-center real-world evaluation

Proprotein convertase subtilisin/kexin type 9 (PCSK9), beyond regulating LDL cholesterol (LDL-c) plasma levels, exerts several pleiotropic effects by modulating lipid metabolism in extrahepatic cells such as macrophages. Macrophage cholesterol homeostasis depends on serum lipoprotein functions, including the HDL capacity to promote cell cholesterol efflux (CEC) and the serum capacity to promote cell cholesterol loading (CLC). The aim of this observational study was to investigate the effect of PCSK9 inhibitors (PCSK9-i) treatment on HDL-CEC and serum CLC in patients with familial hypercholesterolemia (FH). 31 genetically confirmed FH patients were recruited. Blood was collected and serum isolated at baseline and after 6 months of PCSK9-i treatment. HDL-CEC was evaluated through the main pathways with a radioisotopic cell-based assay. Serum CLC was assessed fluorimetrically in human THP-1 monocyte-derived macrophages. After treatment with PCSK9-i, total cholesterol and LDL-c significantly decreased (−41.6%, p < 0.0001 and −56.7%, p < 0.0001, respectively). Total HDL-CEC was not different between patients before and after treatment. Conversely, despite no changes in HDL-c levels between the groups, ABCG1 HDL-CEC significantly increased after treatment (+22.2%, p < 0.0001) as well as HDL-CEC by aqueous diffusion (+7.8%, p = 0.0008). Only a trend towards reduction of ABCA1 HDL-CEC was observed after treatment. PCSK9-i significantly decreased serum CLC (−6.6%, p = 0.0272). This effect was only partly related to the reduction of LDL-c levels. In conclusion, PCSK9-i treatment significantly increased HDL-CEC through ABCG1 and aqueous diffusion pathways and reduced the serum CLC in FH patients. The favorable effect of PCSK9-i on functional lipid profile could contribute to the cardiovascular benefit of these drugs in FH patients