A Subarcsecond Companion to the T Tauri Star AS 353B

Adaptive optics imaging of the bright visual T Tauri binary AS 353 with the Subaru Telescope shows that it is a hierarchical triple system. The secondary component, located 5.6" south of AS 353A, is resolved into a subarcsecond binary, AS 353Ba and Bb, separated by 0.24". Resolved spectroscopy of the two close components shows that both have nearly identical spectral types of about M1.5. Whereas AS 353A and Ba show clear evidence for an infrared excess, AS 353Bb does not. We discuss the possible role of multiplicity in launching the large Herbig-Haro flow associated with AS 353A.Comment: AASTeXv5.0, 21 pages, 5 figures, Astronomical Journal, in pres

A Single-Year Cosmic Ray Event at 5410 BCE Registered in C-14 of Tree Rings

The annual C-14 data in tree rings is an outstanding proxy for uncovering extreme solar energetic particle (SEP) events in the past. Signatures of extreme SEP events have been reported in 774/775 CE, 992/993 CE, and similar to 660 BCE. Here, we report another rapid increase of C-14 concentration in tree rings from California, Switzerland, and Finland around 5410 BCE. These C-14 data series show a significant increase of similar to 6 parts per thousand in 5411-5410 BCE. The signature of C-14 variation is very similar to the confirmed three SEP events and points to an extreme short-term flux of cosmic ray radiation into the atmosphere. The rapid C-14 increase in 5411/5410 BCE rings occurred during a period of high solar activity and 60 years after a grand C-14 excursion during 5481-5471 BCE. The similarity of our C-14 data to previous events suggests that the origin of the 5410 BCE event is an extreme SEP event.Peer reviewe

An Instruction on the In Vivo Shell-Less Chorioallantoic Membrane 3-Dimensional Tumor Spheroid Model

The traditional shell chicken chorioallantoic membrane (CAM) model has been used extensively in cancer research to study tumor growth and angiogenesis. Here we present a combined in vivo tumor spheroid and shell-less CAM three-dimensional model for use in quantitative and qualitative analysis. With this model, the angiogenic and tumorigenic environments can be generated locally without exogenous growth factors. This physiological model offers a stable, static and flat environment that features a large working area and wider field of view useful for imaging and biomedical engineering applications. The short experimental time frame allows for rapid data acquisition, screening and validation of biomedical devices. The method and application of this shell-less model are discussed in detail, providing a useful tool for biomedical engineering research

Euphol, a tetracyclic triterpene, from Euphorbia tirucalli induces autophagy and sensitizes temozolomide cytotoxicity on glioblastoma cells

Glioblastoma (GBM) is the most frequent and aggressive type of brain tumor. There are limited therapeutic options for GBM so that new and effective agents are urgently needed. Euphol is a tetracyclic triterpene alcohol, and it is the main constituent of the sap of the medicinal plant Euphorbia tirucalli. We previously identified anti-cancer activity in euphol based on the cytotoxicity screening of 73 human cancer cells. We now expand the toxicological screening of the inhibitory effect and bioactivity of euphol using two additional glioma primary cultures. Euphol exposure showed similar cytotoxicity against primary glioma cultures compared to commercial glioma cells. Euphol has concentration-dependent cytotoxic effects on cancer cell lines, with more than a five-fold difference in the IC50 values in some cell lines. Euphol treatment had a higher selective cytotoxicity index (0.64-3.36) than temozolomide (0.11-1.13) and reduced both proliferation and cell motility. However, no effect was found on cell cycle distribution, invasion and colony formation. Importantly, the expression of the autophagy-associated protein LC3-II and acidic vesicular organelle formation were markedly increased, with Bafilomycin A1 potentiating cytotoxicity. Finally, euphol also exhibited antitumoral and antiangiogenic activity in vivo, using the chicken chorioallantoic membrane assay, with synergistic temozolomide interactions in most cell lines. In conclusion, euphol exerted in vitro and in vivo cytotoxicity against glioma cells, through several cancer pathways, including the activation of autophagy-associated cell death. These findings provide experimental support for further development of euphol as a novel therapeutic agent for GBM, either alone or in combination chemotherapy.The work was supported by the Amazonia Fitomedicamentos (FITO05/2012) Ltda. and Barretos Cancer Hospital, all from Brazil

Combination of adenoviral virotherapy and temozolomide chemotherapy eradicates malignant glioma through autophagic and apoptotic cell death in vivo

Conditionally replicative adenoviruses (CRAds) represent a novel treatment strategy for malignant glioma. Recent studies suggest that the cytopathic effect elicited by these vectors is mediated through autophagy, a form of programmed cell death. Likewise, temozolomide (TMZ), a chemotherapeutic agent used for the treatment of malignant gliomas, also triggers autophagic cell death. In this study, we examined the potential to combine the two treatments in the setting of experimental glioma. In vitro, pretreatment with TMZ followed by CRAd-Surivin-pk7 enhanced cytotoxicity against a panel of glioma cell lines. Western blot analysis showed increased expression of BAX and p53, decreased expression of BCL2 and elevated level of APG5. Treatment with TMZ followed by CRAd-Survivin-pk7 (CRAd-S-pk7) led to a significant over-expression of autophagy markers, acidic vesicular organelles and light-chain 3 (LC3). These results were further evaluated in vivo, in which 90% of the mice with intracranial tumours were long-term survivors (>100 days) after treatment with TMZ and CRAd-S-pk7 (P<0.01). Analysis of tumours ex vivo showed expression of both LC3 and cleaved Caspase-3, proving that both autophagy and apoptosis are responsible for cell death in vivo. These results suggest that combination of chemovirotherapy offers a powerful tool against malignant glioma and should be further explored in the clinical setting

Spatially Resolved 3 um Spectroscopy of IRAS 22272+5435: Formation and Evolution of Aliphatic Hydrocarbon Dust in Proto-Planetary Nebula

We present medium-resolution 3 um spectroscopy of the carbon-rich proto-planetary nebula IRAS 22272+5435. Spectroscopy with the Subaru Telescope adaptive optics system revealed a spatial variation of hydrocarbon molecules and dust surrounding the star. The ro-vibrational bands of acetylene (C2H2) and hydrogen cyanide (HCN) at 3.0 um are evident in the central star spectra. The molecules are concentrated in the compact region near the center. The 3.3 and 3.4 um emission of aromatic and aliphatic hydrocarbons is detected at 600--1300 AU from the central star. The separation of spatial distribution between gas and dust suggests that the small hydrocarbon molecules are indeed the source of solid material, and that the gas leftover from the grain formation is being observed near the central star. The intensity of aliphatic hydrocarbon emission relative to the aromatic hydrocarbon emission decreases with distance from the central star. The spectral variation is well matched to that of a laboratory analog thermally annealed with different temperatures. We suggest that either the thermal process after the formation of a grain or the variation in the temperature in the dust-forming region over time determines the chemical composition of the hydrocarbon dust around the proto-planetary nebula.Comment: 14 pages, 7 figures, Accepted for publication in the Astrophyical Journa

Autophagy Interplay with Apoptosis and Cell Cycle Regulation in the Growth Inhibiting Effect of Resveratrol in Glioma Cells

Prognosis of patients with glioblastoma (GBM) remains very poor, thus making the development of new drugs urgent. Resveratrol (Rsv) is a natural compound that has several beneficial effects such as neuroprotection and cytotoxicity for several GBM cell lines. Here we evaluated the mechanism of action of Rsv on human GBM cell lines, focusing on the role of autophagy and its crosstalk with apoptosis and cell cycle control. We further evaluated the role of autophagy and the effect of Rsv on GBM Cancer Stem Cells (gCSCs), involved in GBM resistance and recurrence. Glioma cells treated with Rsv was tested for autophagy, apoptosis, necrosis, cell cycle and phosphorylation or expression levels of key players of these processes. Rsv induced the formation of autophagosomes in three human GBM cell lines, accompanied by an upregulation of autophagy proteins Atg5, beclin-1 and LC3-II. Inhibition of Rsv-induced autophagy triggered apoptosis, with an increase in Bax and cleavage of caspase-3. While inhibition of apoptosis or autophagy alone did not revert Rsv-induced toxicity, inhibition of both processes blocked this toxicity. Rsv also induced a S-G2/M phase arrest, accompanied by an increase on levels of pCdc2(Y15), cyclin A, E and B, and pRb (S807/811) and a decrease of cyclin D1. Interestingly, this arrest was dependent on the induction of autophagy, since inhibition of Rsv-induced autophagy abolishes cell cycle arrest and returns the phosphorylation of Cdc2(Y15) and Rb(S807/811), and levels of cyclin A, and B to control levels. Finally, inhibition of autophagy or treatment with Rsv decreased the sphere formation and the percentage of CD133 and OCT4-positive cells, markers of gCSCs. In conclusion, the crosstalk among autophagy, cell cycle and apoptosis, together with the biology of gCSCs, has to be considered in tailoring pharmacological interventions aimed to reduce glioma growth using compounds with multiple targets such as Rsv