Discovery of possible molecular counterparts to the infrared Double Helix Nebula in the Galactic center

We have discovered two molecular features at radial velocities of -35 km/s and 0 km/s toward the infrared Double Helix Nebula (DHN) in the Galactic center with NANTEN2. The two features show good spatial correspondence with the DHN. We have also found two elongated molecular ridges at these two velocities distributed vertically to the Galactic plane over 0.8 degree. The two ridges are linked by broad features in velocity and are likely connected physically with each other. The ratio between the 12CO J=2-1 and J=1-0 transitions is 0.8 in the ridges which is larger than the average value 0.5 in the foreground gas, suggesting the two ridges are in the Galactic center. An examination of the K band extinction reveals a good coincidence with the CO 0 km/s ridge and is consistent with a distance of 8 +/-2 kpc. We discuss the possibility that the DHN was created by a magnetic phenomenon incorporating torsional Alfv\'en waves launched from the circumnuclear disk (Morris, Uchida & Do 2006) and present a first estimate of the mass and energy involved in the DHN.Comment: 32 pages, 23 figures, Accepted by Ap

Tetraspanin (TSP-17) Protects Dopaminergic Neurons against 6-OHDA-Induced Neurodegeneration in <i>C. elegans</i>

Parkinson's disease (PD), the second most prevalent neurodegenerative disease after Alzheimer's disease, is linked to the gradual loss of dopaminergic neurons in the substantia nigra. Disease loci causing hereditary forms of PD are known, but most cases are attributable to a combination of genetic and environmental risk factors. Increased incidence of PD is associated with rural living and pesticide exposure, and dopaminergic neurodegeneration can be triggered by neurotoxins such as 6-hydroxydopamine (6-OHDA). In C. elegans, this drug is taken up by the presynaptic dopamine reuptake transporter (DAT-1) and causes selective death of the eight dopaminergic neurons of the adult hermaphrodite. Using a forward genetic approach to find genes that protect against 6-OHDA-mediated neurodegeneration, we identified tsp-17, which encodes a member of the tetraspanin family of membrane proteins. We show that TSP-17 is expressed in dopaminergic neurons and provide genetic, pharmacological and biochemical evidence that it inhibits DAT-1, thus leading to increased 6-OHDA uptake in tsp-17 loss-of-function mutants. TSP-17 also protects against toxicity conferred by excessive intracellular dopamine. We provide genetic and biochemical evidence that TSP-17 acts partly via the DOP-2 dopamine receptor to negatively regulate DAT-1. tsp-17 mutants also have subtle behavioral phenotypes, some of which are conferred by aberrant dopamine signaling. Incubating mutant worms in liquid medium leads to swimming-induced paralysis. In the L1 larval stage, this phenotype is linked to lethality and cannot be rescued by a dop-3 null mutant. In contrast, mild paralysis occurring in the L4 larval stage is suppressed by dop-3, suggesting defects in dopaminergic signaling. In summary, we show that TSP-17 protects against neurodegeneration and has a role in modulating behaviors linked to dopamine signaling

Star Forming Dense Cloud Cores in the TeV {\gamma}-ray SNR RX J1713.7-3946

RX J1713.7-3946 is one of the TeV {\gamma}-ray supernova remnants (SNRs) emitting synchrotron X rays. The SNR is associated with molecular gas located at ~1 kpc. We made new molecular observations toward the dense cloud cores, peaks A, C and D, in the SNR in the 12CO(J=2-1) and 13CO(J=2-1) transitions at angular resolution of 90". The most intense core in 13CO, peak C, was also mapped in the 12CO(J=4-3) transition at angular resolution of 38". Peak C shows strong signs of active star formation including bipolar outflow and a far-infrared protostellar source and has a steep gradient with a r^{-2.2$\pm$0.4} variation in the average density within radius r. Peak C and the other dense cloud cores are rim-brightened in synchrotron X rays, suggesting that the dense cloud cores are embedded within or on the outer boundary of the SNR shell. This confirms the earlier suggestion that the X rays are physically associated with the molecular gas (Fukui et al. 2003). We present a scenario where the densest molecular core, peak C, survived against the blast wave and is now embedded within the SNR. Numerical simulations of the shock-cloud interaction indicate that a dense clump can indeed survive shock erosion, since shock propagation speed is stalled in the dense clump. Additionally, the shock-cloud interaction induces turbulence and magnetic field amplification around the dense clump that may facilitate particle acceleration in the lower-density inter-clump space leading to the enhanced synchrotron X rays around dense cores.Comment: 22 pages, 7 figures, to accepted in The Astrophysical Journal. A full color version with higher resolution figures is available at http://www.a.phys.nagoya-u.ac.jp/~sano/ApJ10/ms_sano.pd

Circulating cell-free DNA as a predictive marker for distant metastasis of hepatitis C virus-related hepatocellular carcinoma

In a previous study, we showed that levels of cell-free DNA (cfDNA) were significantly higher in sera of patients with hepatocellular carcinoma (HCC) associated with hepatitis C virus (HCV) than in sera of non-HCC patients with HCV. To confirm this finding, we analysed serum cfDNA levels in a cohort of 96 patients with HCV-related HCC and in 100 HCV carriers without known HCC. Again we found that serum cfDNA levels were significantly higher in HCC patients than in HCV carriers (115.9±98.3 vs 34.4±40.4 ng ml−1 (mean±s.d.), P<0.0001). Of 87 eligible patients who underwent curative hepatectomy, those with a high cfDNA level had a significantly shorter overall survival (OS) time than those in whom the cfDNA level was not high. Cox proportional hazards model showed the cfDNA level to be an independent prognostic factor for OS and cancer recurrence in distant organs. Our results suggest that the serum cfDNA level reflects the metastatic potential of HCV-related HCC and that it can be a useful predictive biomarker for distant metastasis after curative surgery

C. elegans rrf-1 Mutations Maintain RNAi Efficiency in the Soma in Addition to the Germline

Gene inactivation through RNA interference (RNAi) has proven to be a valuable tool for studying gene function in C. elegans. When combined with tissue-specific gene inactivation methods, RNAi has the potential to shed light on the function of a gene in distinct tissues. In this study we characterized C. elegans rrf-1 mutants to determine their ability to process RNAi in various tissues. These mutants have been widely used in RNAi studies to assess the function of genes specifically in the C. elegans germline. Upon closer analysis, we found that two rrf-1 mutants carrying different loss-of-function alleles were capable of processing RNAi targeting several somatically expressed genes. Specifically, we observed that the intestine was able to process RNAi triggers efficiently, whereas cells in the hypodermis showed partial susceptibility to RNAi in rrf-1 mutants. Other somatic tissues in rrf-1 mutants, such as the muscles and the somatic gonad, appeared resistant to RNAi. In addition to these observations, we found that the rrf-1(pk1417) mutation induced the expression of several transgenic arrays, including the FOXO transcription factor DAF-16. Unexpectedly, rrf-1(pk1417) mutants showed increased endogenous expression of the DAF-16 target gene sod-3; however, the lifespan and thermo-tolerance of rrf-1(pk1417) mutants were similar to those of wild-type animals. In sum, these data show that rrf-1 mutants display several phenotypes not previously appreciated, including broader tissue-specific RNAi-processing capabilities, and our results underscore the need for careful characterization of tissue-specific RNAi tools

THE NEUTRAL INTERSTELLAR GAS TOWARD SNR W44: CANDIDATES FOR TARGET PROTONS IN HADRONIC γ-RAY PRODUCTION IN A MIDDLE-AGED SUPERNOVA REMNANT

We present an analysis of the interstellar medium (ISM) toward the γ-ray supernova remnant (SNR) W44. We used NANTEN2 12CO(J = 2-1) and 12CO(J = 1-0) data and Arecibo H I data in order to identify the molecular and atomic gas in the SNR. We confirmed that the molecular gas is located in the SNR shell with a primary peak toward the eastern edge of the shell. We newly identified high-excitation molecular gas along the eastern shell of the SNR in addition to the high-excitation broad gas previously observed inside the shell; the line intensity ratio between the 12CO(J = 2-1) and 12CO(J = 1-0) transitions in these regions is greater than ~1.0, suggesting a kinetic temperature of 30 K or higher, which is most likely due to heating by shock interaction. By comparing the ISM with γ-rays, we find that target protons of hadronic origin are dominated by molecular protons of average density around 200 cm–3, where the possible contribution of atomic protons is 10% or less. This average density is consistent with the recent discovery of the low-energy γ-rays suppressed in 50 MeV-10 GeV as observed with AGILE and Fermi. The γ-ray spectrum differs from place to place in the SNR, suggesting that the cosmic-ray (CR) proton spectrum significantly changes within the middle-aged SNR perhaps due to the energy-dependent escape of CR protons from the acceleration site. We finally derive a total CR proton energy of ~1049 erg, consistent with the SN origin of the majority of the CRs in the Galaxy

Antifungal activity of amphotericin B conjugated to nanosized magnetite in the treatment of paracoccidioidomycosis

This study reports on in vitro and in vivo tests that sought to assess the antifungal activity of a newly developed magnetic carrier system comprising amphotericin B loaded onto the surface of pre-coated (with a double-layer of lauric acid) magnetite nanoparticles. The in vitro tests compared two drugs; i.e., this newly developed form and free amphotericin B. We found that this nanocomplex exhibited antifungal activity without cytotoxicity to human urinary cells and with low cytotoxicity to peritoneal macrophages. We also evaluated the efficacy of the nanocomplex in experimental paracoccidioidomycosis. BALB/c mice were intratracheally infected with Paracoccidioides brasiliensis and treated with the compound for 30 or 60 days beginning the day after infection. The newly developed amphotericin B coupled with magnetic nanoparticles was effective against experimental paracoccidioidomycosis, and it did not induce clinical, biochemical or histopathological alterations. The nanocomplex also did not induce genotoxic effects in bone marrow cells. Therefore, it is reasonable to believe that amphotericin B coupled to magnetic nanoparticles and stabilized with bilayer lauric acid is a promising nanotool for the treatment of the experimental paracoccidioidomycosis because it exhibited antifungal activity that was similar to that of free amphotericin B, did not induce adverse effects in therapeutic doses and allowed for a reduction in the number of applications

Suppression of mRNAs Encoding Tegument Tetraspanins from Schistosoma mansoni Results in Impaired Tegument Turnover

Schistosomes express a family of integral membrane proteins, called tetraspanins (TSPs), in the outer surface membranes of the tegument. Two of these tetraspanins, Sm-TSP-1 and Sm-TSP-2, confer protection as vaccines in mice, and individuals who are naturally resistant to S. mansoni infection mount a strong IgG response to Sm-TSP-2. To determine their functions in the tegument of S. mansoni we used RNA interference to silence expression of Sm-tsp-1 and Sm-tsp-2 mRNAs. Soaking of parasites in Sm-tsp dsRNAs resulted in 61% (p = 0.009) and 74% (p = 0.009) reductions in Sm-tsp-1 and Sm-tsp-2 transcription levels, respectively, in adult worms, and 67%–75% (p = 0.011) and 69%–89% (p = 0.004) reductions in Sm-tsp-1 and Sm-tsp-2 transcription levels, respectively, in schistosomula compared to worms treated with irrelevant control (luciferase) dsRNA. Ultrastructural morphology of adult worms treated in vitro with Sm-tsp-2 dsRNA displayed a distinctly vacuolated and thinner tegument compared with controls. Schistosomula exposed in vitro to Sm-tsp-2 dsRNA had a significantly thinner and more vacuolated tegument, and morphology consistent with a failure of tegumentary invaginations to close. Injection of mice with schistosomula that had been electroporated with Sm-tsp-1 and Sm-tsp-2 dsRNAs resulted in 61% (p = 0.005) and 83% (p = 0.002) reductions in the numbers of parasites recovered from the mesenteries four weeks later when compared to dsRNA-treated controls. These results imply that tetraspanins play important structural roles impacting tegument development, maturation or stability