ASTE 12^{12}CO(J=J=3--2) Survey of Elliptical Galaxies

We report $^{12}$CO($J=$3--2) observations of 15 nearby elliptical galaxies carried out with the ASTE telescope. Thirteen were selected without regard to the presence of other tracers of cold interstellar matter. CO emission was detected from three of the galaxies, two of which are undetected by IRAS at 100 microns, suggesting that cold ISM may be present in more ellipticals than previously thought. The molecular gas masses range from $2.2 \times 10^6$ to $4.3 \times 10^8$ $M_\odot$. The ratio of the CO(3--2) and (1--0) lines, $R_{31}$, has a lower value for elliptical galaxies than for spiral galaxies except for NGC 855, for which the value is close to the mean for spirals. The molecular gas in NGC 855 has a mean density in the range 300 -- 1000 cm$^{-3}$ adopting a temperature range of 15 -- 100 K.Comment: 6 pages, 3 figures, Accepted for publication in PAS

Milliarcsecond-Scale Structure in the Gamma-Ray Loud Quasar PKS 1622-297

We have made a high-resolution VLBI observation of the gamma-ray loud quasar PKS 1622-297 with the HALCA spacecraft and ground radio telescopes at 5 GHz in 1998 February, almost three years after the source exhibited a spectacular GeV gamma-ray flare. The source shows an elongated structure toward the west on the parsec scale. The visibility data are well modeled by three distinct components; a bright core and two weaker jet components. Comparison with previous observations confirms that the jet components have an apparent superluminal motion up to 12.1 h^{-1}c, with the inner jet components having lower superluminal speeds. We apply the inverse Compton catastrophe model and derive a Doppler factor, \delta, of 2.45, which is somewhat lower than that of other gamma-ray loud active galactic nuclei (AGNs), suggesting the source was in a more quiescent phase at the epoch of our observation. As an alternative probe of the sub-parsec scale structure, we also present the results from multi-epoch ATCA total flux monitoring, which indicate the presence of persistent intraday variability consistent with refractive interstellar scintillation. We examine the gamma-ray emission mechanism in the light of these observations.Comment: 10 pages, 6 figures, 3 tables, to appear in PASJ, Vol.58, No.

TFPI-2 is a putative tumor suppressor gene frequently inactivated by promoter hypermethylation in nasopharyngeal carcinoma

<p>Abstract</p> <p>Background</p> <p>Epigenetic silencing of tumor suppressor genes play important roles in NPC tumorgenesis. Tissue factor pathway inhibitor-2 (TFPI-2), is a protease inhibitor. Recently, <it>TFPI-2 </it>was suggested to be a tumor suppressor gene involved in tumorigenesis and metastasis in some cancers. In this study, we investigated whether <it>TFPI-2 </it>was inactivated epigenetically in nasopharyngeal carcinoma (NPC).</p> <p>Methods</p> <p>Transcriptional expression levels of <it>TFPI-2 </it>was evaluated by RT-PCR. Methylation status were investigated by methylation specific PCR and bisulfate genomic sequencing. The role of <it>TFPI-2 </it>as a tumor suppressor gene in NPC was addressed by re-introducing <it>TFPI-2 </it>expression into the NPC cell line CNE2.</p> <p>Results</p> <p><it>TFPI-2 </it>mRNA transcription was inactivated in NPC cell lines. <it>TFPI-2 </it>was aberrantly methylated in 66.7% (4/6) NPC cell lines and 88.6% (62/70) of NPC primary tumors, but not in normal nasopharyngeal epithelia. <it>TFPI-2 </it>expression could be restored in NPC cells after demethylation treatment. Ectopic expression of TFPI-2 in NPC cells induced apoptosis and inhibited cell proliferation, colony formation and cell migration.</p> <p>Conclusions</p> <p>Epigenetic inactivation of <it>TFPI-2 </it>by promoter hypermethylation is a frequent and tumor specific event in NPC. <it>TFPI-2 </it>might be considering as a putative tumor suppressor gene in NPC.</p

Integrative Genome Comparison of Primary and Metastatic Melanomas

A cardinal feature of malignant melanoma is its metastatic propensity. An incomplete view of the genetic events driving metastatic progression has been a major barrier to rational development of effective therapeutics and prognostic diagnostics for melanoma patients. In this study, we conducted global genomic characterization of primary and metastatic melanomas to examine the genomic landscape associated with metastatic progression. In addition to uncovering three genomic subclasses of metastastic melanomas, we delineated 39 focal and recurrent regions of amplification and deletions, many of which encompassed resident genes that have not been implicated in cancer or metastasis. To identify progression-associated metastasis gene candidates, we applied a statistical approach, Integrative Genome Comparison (IGC), to define 32 genomic regions of interest that were significantly altered in metastatic relative to primary melanomas, encompassing 30 resident genes with statistically significant expression deregulation. Functional assays on a subset of these candidates, including MET, ASPM, AKAP9, IMP3, PRKCA, RPA3, and SCAP2, validated their pro-invasion activities in human melanoma cells. Validity of the IGC approach was further reinforced by tissue microarray analysis of Survivin showing significant increased protein expression in thick versus thin primary cutaneous melanomas, and a progression correlation with lymph node metastases. Together, these functional validation results and correlative analysis of human tissues support the thesis that integrated genomic and pathological analyses of staged melanomas provide a productive entry point for discovery of melanoma metastases genes

Epigenetics of human cutaneous melanoma: setting the stage for new therapeutic strategies

Cutaneous melanoma is a very aggressive neoplasia of melanocytic origin with constantly growing incidence and mortality rates world-wide. Epigenetic modifications (i.e., alterations of genomic DNA methylation patterns, of post-translational modifications of histones, and of microRNA profiles) have been recently identified as playing an important role in melanoma development and progression by affecting key cellular pathways such as cell cycle regulation, cell signalling, differentiation, DNA repair, apoptosis, invasion and immune recognition. In this scenario, pharmacologic inhibition of DNA methyltransferases and/or of histone deacetylases were demonstrated to efficiently restore the expression of aberrantly-silenced genes, thus re-establishing pathway functions. In light of the pleiotropic activities of epigenetic drugs, their use alone or in combination therapies is being strongly suggested, and a particular clinical benefit might be expected from their synergistic activities with chemo-, radio-, and immuno-therapeutic approaches in melanoma patients. On this path, an important improvement would possibly derive from the development of new generation epigenetic drugs characterized by much reduced systemic toxicities, higher bioavailability, and more specific epigenetic effects

Observation and Analysis of Model Lipid Raft Deformation Dynamics Induced by Lipoprotein–Gold Nanorod-based Devices to Manipulate Phase Transition of Lipid Bilayer

Lipid rafts, which are complexes that form on cholesterol-rich areas of cell membranes, play key roles as gates for the distribution of information between the inner and outer spaces of living cells. The physical and biological properties of lipid rafts have been investigated, but the engineering of lipid rafts remains a difficult subject. We developed a lipoprotein–gold nanorod nanodevice to control the formation/deformation of model lipid rafts. The nanodevice attached to the liquid order (Lo) phase region, selectively removed cholesterol from the Lo domain, and induced the Lo-to-solid order (So) phase transition. In this study, we analyzed the phase transition induced by the nanodevice. We found that the domain boundary gradually collapsed and that a local two-phase mixture was induced. Local instability resulted in domain incursion into other domains, and protrusions were torn to form small domains with the characteristics of two phases. The two different domains grouped together to form a non-circular So domain on giant unilamellar vesicles. Close observation of the non-equilibrium process of phase transition may lead to the design of strategies for external lipid raft manipulation methodology using biological macromolecules and/or nanoparticles