The eclipse of Epsilon Aurigae visible spectroscopy and ultraviolet activity

The preliminary results of the study of several high resolution spectrograms (lambda 3500 - lambda 7000 A), obtained at the Haute Provence Observatory (OHP) in France, at different epochs before, during and after the eclipse are reported. Some of these spectrograms are compared with corresponding IUE high resolution observations, in order to study the effects of the intrinsic UV activity, towards the longer wavelengths

Simultaneous targeting of Eph receptors in glioblastoma

Eph tyrosine kinase receptors are frequently overexpressed and functional in many cancers, and they are attractive candidates for targeted therapy. Here, we analyzed the expression of Eph receptor A3, one of the most up-regulated factors in glioblastoma cells cultured under tumorsphere-forming conditions, together with EphA2 and EphB2 receptors. EphA3 was overexpressed in up to 60% of glioblastoma tumors tested, but not in normal brain. EphA3 was localized in scattered areas of the tumor, the invasive ring, and niches near tumor vessels. EphA3 co-localized with macrophage/leukocyte markers, suggesting EphA3 expression on tumor-infiltrating cells of bone marrow origin. We took advantage of the fact that ephrinA5 (eA5) is a ligand that binds EphA3, EphA2 and EphB2 receptors, and used it to construct a novel targeted anti-glioblastoma cytotoxin. The eA5-based cytotoxin potently and specifically killed glioblastoma cells with an IC(50) of at least 10(−11) M. This and similar cytotoxins will simultaneously target different compartments of glioblastoma tumors while mitigating tumor heterogeneity

Taming the Invisible Monster: System Parameter Constraints for Epsilon Aurigae from the Far-Ultraviolet to the Mid-Infrared

We have assembled new Spitzer Space Telescope Infrared Array Camera observations of the mysterious binary star Epsilon Aurigae, along with archival far-ultraviolet to mid-infrared data, to form an unprecedented spectral energy distribution spanning three orders of magnitude in wavelength from 0.1 microns to 100 microns. The observed spectral energy distribution can be reproduced using a three component model consisting of a 2.2+0.9/-0.8 Msun F type post-asymptotic giant branch star, and a 5.9+/-0.8 Msun B5+/-1 type main sequence star that is surrounded by a geometrically thick, but partially transparent, disk of gas and dust. At the nominal HIPPARCOS parallax distance of 625 pc, the model normalization yields a radius of 135+/-5 Rsun for the F star, consistent with published interferometric observations. The dusty disk is constrained to be viewed at an inclination of i > 87 deg, and has effective temperature of 550+/-50 K with an outer radius of 3.8 AU and a thickness of 0.95 AU. The dust content of the disk must be largely confined to grains larger than ~10 microns in order to produce the observed gray optical-infrared eclipses and the lack of broad dust emission features in the archival Spitzer mid-infrared spectra. The total mass of the disk, even considering a potential gaseous contribution in addition to the dust that produces the observed infrared excess, is << 1 Msun. We discuss evolutionary scenarios for this system that could lead to the current status of the stellar components and suggests possibilities for its future evolution, as well as potential observational tests of our model.Comment: 13 pages, 3 figures. Accepted for publication in The Astrophysical Journal

Constitutive activation of the EGFR-STAT1 axis increases proliferation of meningioma tumor cells.

Background: Meningiomas are the most frequent primary brain tumors of the central nervous system. The standard of treatment is surgery and radiotherapy, but effective pharmacological options are not available yet. The well-characterized genetic background stratifies these tumors in several subgroups, thus increasing diversification. We identified epidermal growth factor receptor-signal transducer and activator of transcription 1 (EGFR-STAT1) overexpression and activation as a common identifier of these tumors. Methods: We analyzed STAT1 overexpression and phosphorylation in 131 meningiomas of different grades and locations by utilizing several techniques, including Western blots, qPCR, and immunocytochemistry. We also silenced and overexpressed wild-type and mutant forms of the gene to assess its biological function and its network. Results were further validated by drug testing. Results: STAT1 was found widely overexpressed in meningioma but not in the corresponding healthy controls. The protein showed constitutive phosphorylation not dependent on the JAK-STAT pathway. STAT1 knockdown resulted in a significant reduction of cellular proliferation and deactivation of AKT and ERK1/2. STAT1 is known to be activated by EGFR, so we investigated the tyrosine kinase and found that EGFR was also constitutively phosphorylated in meningioma and was responsible for the aberrant phosphorylation of STAT1. The pharmaceutical inhibition of EGFR caused a significant reduction in cellular proliferation and of overall levels of cyclin D1, pAKT, and pERK1/2. Conclusions: STAT1-EGFR-dependent constitutive phosphorylation is responsible for a positive feedback loop that causes its own overexpression and consequently an increased proliferation of the tumor cells. These findings provide the rationale for further studies aiming to identify effective therapeutic options in meningioma

A Rapid Robust Method for Subgrouping Non-NF2 Meningiomas According to Genotype and Detection of Lower Levels of M2 Macrophages in AKT1 E17K Mutated Tumours

The majority of meningiomas are grade I, but some grade I tumours are clinically more aggressive. Recent advances in the genetic study of meningiomas has allowed investigation into the influence of genetics on the tumour microenvironment, which is important for tumorigenesis. We have established that the endpoint genotyping method Kompetitive Allele Specific PCR (KASP™) is a fast, reliable method for the screening of meningioma samples into different non-NF2 mutational groups using a standard real-time PCR instrument. This genotyping method and four-colour flow cytometry has enabled us to assess the variability in the largest immune cell infiltrate population, M2 macrophages (CD45+HLA-DR+CD14+CD163+) in 42 meningioma samples, and to suggest that underlying genetics is relevant. Further immunohistochemistry analysis comparing AKT1 E17K mutants to WHO grade I NF2-negative samples showed significantly lower levels of CD163-positive activated M2 macrophages in meningiomas with mutated AKT1 E17K, signifying a more immunosuppressive tumour microenvironment in NF2 meningiomas. Our data suggested that underlying tumour genetics play a part in the development of the immune composition of the tumour microenvironment. Stratifying meningiomas by mutational status and correlating this with their cellular composition will aid in the development of new immunotherapies for patients.</jats:p