High-contrast imaging constraints on gas giant planet formation - The Herbig Ae/Be star opportunity

Planet formation studies are often focused on solar-type stars, implicitly considering our Sun as reference point. This approach overlooks, however, that Herbig Ae/Be stars are in some sense much better targets to study planet formation processes empirically, with their disks generally being larger, brighter and simply easier to observe across a large wavelength range. In addition, massive gas giant planets have been found on wide orbits around early type stars, triggering the question if these objects did indeed form there and, if so, by what process. In the following I briefly review what we currently know about the occurrence rate of planets around intermediate mass stars, before discussing recent results from Herbig Ae/Be stars in the context of planet formation. The main emphasis is put on spatially resolved polarized light images of potentially planet forming disks and how these images - in combination with other data - can be used to empirically constrain (parts of) the planet formation process. Of particular interest are two objects, HD100546 and HD169142, where, in addition to intriguing morphological structures in the disks, direct observational evidence for (very) young planets has been reported. I conclude with an outlook, what further progress we can expect in the very near future with the next generation of high-contrast imagers at 8-m class telescopes and their synergies with ALMA.Comment: Accepted by Astrophysics and Space Science as invited short review in special issue about Herbig Ae/Be stars; 12 pages incl. 5 figures, 2 tables and reference

Eclipses by circumstellar material in the T Tauri star AA Tau. II. Evidence for non-stationary magnetospheric accretion

We report the results of a synoptic study of the photometric and spectroscopic variability of the classical T Tauri star AA Tau on timescales ranging from a few hours to several weeks. Emission lines show both infall and outflow signatures and are well reproduced by magnetospheric accretion models with moderate mass accretion rates and high inclinations. The veiling shows variations that indicate the presence of 2 rotationally modulated hot spots corresponding to the two magnetosphere poles. It correlates well with the HeI line flux, with B-V and the V excess flux. We have indications of a time delay between the main emission lines and veiling, the lines formed farther away preceding the veiling changes. The time delay we measure is consistent with accreted material propagating downwards the accretion columns at free fall velocity from a distance of about 8 Rstar. We also report periodic radial velocity variations of the photospheric spectrum which might point to the existence of a 0.02 Msun object orbiting the star at a distance of 0.08 AU. During a few days, the variability of the system was strongly reduced and the line fluxes and veiling severely depressed. We argue that this episode of quiescence corresponds to the temporary disruption of the magnetic configuration at the disk inner edge. The radial velocity variations of inflow and outflow diagnostics in the Halpha profile yield further evidence for large scale variations of the magnetic configuration on a timescale of a month. These results may provide the first clear evidence for large scale instabilities developping in T Tauri magnetospheres as the magnetic field lines are twisted by differential rotation between the star and the inner disk.Comment: 25 pages, Astron. Astrophys., in pres

Transcription Profiling of Epstein-Barr Virus Nuclear Antigen (EBNA)-1 Expressing Cells Suggests Targeting of Chromatin Remodeling Complexes

The Epstein-Barr virus (EBV) encoded nuclear antigen (EBNA)-1 regulates virus replication and transcription, and participates in the remodeling of the cellular environment that accompanies EBV induced B-cell immortalization and malignant transformation. The putative cellular targets of these effects of EBNA-1 are largely unknown. To address this issue we have profiled the transcriptional changes induced by short- and long-term expression of EBNA-1 in the EBV negative B-cell lymphoma BJAB. Three hundred and nineteen cellular genes were regulated in a conditional transfectant shortly after EBNA-1 induction while a ten fold higher number of genes was regulated upon continuous EBNA-1 expression. Promoter analysis of the differentially regulated genes demonstrated a significant enrichment of putative EBNA-1 binding sites suggesting that EBNA-1 may directly influence the transcription of a subset of genes. Gene ontology analysis of forty seven genes that were consistently regulated independently on the time of EBNA-1 expression revealed an unexpected enrichment of genes involved in the maintenance of chromatin architecture. The interaction network of the affected gene products suggests that EBNA-1 may promote a broad rearrangement of the cellular transcription landscape by altering the expression of key components of chromatin remodeling complexes

Parkin Deficiency Delays Motor Decline and Disease Manifestation in a Mouse Model of Synucleinopathy

In synucleinopathies, including Parkinson's disease, partially ubiquitylated α-synuclein species phosphorylated on serine 129 (PS129-α-synuclein) accumulate abnormally. Parkin, an ubiquitin-protein ligase that is dysfunctional in autosomal recessive parkinsonism, protects against α-synuclein-mediated toxicity in various models

Reactionary and reparative dentin formation after pulp capping: Hydrogel vs. Dycal

International audienceBackgroundAfter indirect capping, injured odontoblasts generate reactionary dentin, whereas after direct capping of a pulp exposure pulp, cells stimulate the formation of reparative dentin. The aim of this study was to evaluate and compare the effects of two direct capping agents on pulp tissue reactions: Hydrogel (a bovine serum albumin (BSA)/glutaraldehyde,) and Dycal (a calcium hydroxide-based capping agent).MethodsIn 6-week-old male Sprague–Dawley rats, occlusal cavities were drilled in the first maxillary molars, and the pulps were exposed. In one of the groups, 24 right molars were capped with Hydrogel (G1), whereas in the other group 24 M were capped with Dycal (G2). After 1 to 4 weeks, the rats were anaesthetized intraperitoneally (six rats per group) and perfused intracardiacally with 4 % paraformaldehyde fixative. Maxillary molar’s blocks were demineralized with a 4.13 % EDTA solution, embedded in paraffin, and the sections were histologically stained. Measurements of the thickness of reactionary dentin and area of inflammation were measured with ImageJ software. Results were compared with Kruskal Wallis and Mann Whitney U tests at p = 0.05.ResultsOne week after Dycal capping, a statistically significant large number of aggregates of pulp cells enlightened pulpal inflammation compared to Hydrogel. At 2–3 weeks, reactionary dentin formation was increased at the periphery of the pulp chamber. After 4 weeks, a dentinal bridge sealed partially the pulp exposure, while tunnel defects persisting across reparative osteodentin. In contrast, 1 week after Hydrogel capping, inflammation was barely detectable. Hydrogel induced the massive apposition of reactionary dentin at the pulp periphery, and reparative dentin was developing within the pulp. The degradation of Hydrogel releases glutaraldehyde acting on pulp cells as a fixative and consequently favoring BSA bioactivity.ConclusionAfter Hydrogel capping, nemosis stimulates pulp mineralization, improving reactionary and reparative dentin formation. In contrast, the highly alkaline compound Dycal produced inflammation within the pulp. The differences between the two capping agents suggest that Hydrogel might present some clinical advantages over Dycal

Apoptosis and TRAF-1 cleavage in Epstein-Barr virus-positive nasopharyngeal carcinoma cells treated with doxorubicin combined with a farnesyl-transferase inhibitor.

Epstein-Barr virus (EBV)-associated nasopharyngeal carcinomas (NPC) are much more sensitive to chemotherapy than other head and neck carcinomas. Spectacular regressions are frequently observed after induction chemotherapy. However, these favorable responses are difficult to predict and often of short duration. So far there have been only few experiments to investigate the mechanisms which underline the cytotoxic effects of anti-neoplastic drugs against NPC cells. In addition, these studies were performed almost entirely on EBV-negative cell lines therefore not truly representative of NPC cells. For the first time, we have used two EBV-positive NPC tumor lines derived from a North African (C15) and a Chinese (C666-1) patient as in vitro targets for a panel of anti-neoplastic agents. Doxorubicin, taxol and in a lesser extent cis-platinum efficiently inhibited NPC cell proliferation at clinically relevant concentrations, but all three agents failed to induce apoptosis. However, massive apoptosis of C15 cells was achieved when doxorubicin (1 microM) was combined with a farnesyl-transferase inhibitor, BIM 2001 (5 microM). Moreover, this apoptotic process was associated with a caspase-dependent early cleavage of the TNF-receptor associated factor 1 (TRAF-1) molecule, a signaling adaptor which is specifically expressed in latently EBV-infected cells. TRAF-1 cleavage might become a useful indicator of chemo-induced apoptosis in EBV-associated NPCs

Pathogenic prions deviate PrPC signaling in neuronal cells and impair A-beta clearance

International audienceThe subversion of the normal function exerted by the cellular prion protein (PrP C) in neurons by pathogenic prions is assumed to have a central role in the pathogenesis of transmissible spongiform encephalopathies. Using two murine models of prion infection, the 1C11 neuronal cell line and neurospheres, we document that prion infection is associated with the constitutive activation of signaling targets normally coupled with PrP C , including the Fyn kinase, the mitogen-associated protein kinases ERK1/2 and the CREB transcription factor. PrP C-dependent signaling overactivation in infected cells is associated with the recruitment of p38 and JNK stress-associated kinases. Downstream from CREB, prion-infected cells exhibit reduced activity of the matrix metalloprotease (MMP)-9. As MMP-9 catalyzes the degradation of the amyloid A-beta peptide, the decrease in MMP-9 activity in prion-infected cells causes a significant impairment of the clearance of A-beta, leading to its accumulation. By exploiting two 1C11-infected clones accumulating high or moderate levels of prions, we show that the prion-induced changes are correlated with the level of infectivity. Of note, a dose-dependent increase in A-beta levels was also found in the cerebrospinal fluid of mice inoculated with these infected clones. By demonstrating that pathogenic prions trigger increases in A-beta levels through the deviation of PrP C signaling, our data argue that A-beta may exacerbate prion-induced toxicity

Human tumor virus utilizes exosomes for intercellular communication

The Epstein–Barr virus (EBV) latent membrane protein 1 (LMP1) is expressed in multiple human malignancies and has potent effects on cell growth. It has been detected in exosomes and shown to inhibit immune function. Exosomes are small secreted cellular vesicles that contain proteins, mRNAs, and microRNAs (miRNAs). When produced by malignant cells, they can promote angiogenesis, cell proliferation, tumor-cell invasion, and immune evasion. In this study, exosomes released from nasopharyngeal carcinoma (NPC) cells harboring latent EBV were shown to contain LMP1, signal transduction molecules, and virus-encoded miRNAs. Exposure to these NPC exosomes activated the ERK and AKT signaling pathways in the recipient cells. Interestingly, NPC exosomes also contained viral miRNAs, several of which were enriched in comparison with their intracellular levels. LMP1 induces expression of the EGF receptor in an EBV-negative epithelial cell line, and exosomes produced by these cells also contain high levels of EGF receptor in exosomes. These findings suggest that the effects of EBV and LMP1 on cellular expression also modulate exosome content and properties. The exosomes may manipulate the tumor microenvironment to influence the growth of neighboring cells through the intercellular transfer of LMP1, signaling molecules, and viral miRNAs