ASTE Simultaneous HCN(4-3) and HCO+(4-3) Observations of the Two Luminous Infrared Galaxies NGC 4418 and Arp 220

We report the results of HCN(J=4-3) and HCO+(J=4-3) observations of two luminous infrared galaxies (LIRGs), NGC 4418 and Arp 220, made using the Atacama Submillimeter Telescope Experiment (ASTE). The ASTE wide-band correlator provided simultaneous observations of HCN(4-3) and HCO+(4-3) lines, and a precise determination of their flux ratios. Both galaxies showed high HCN(4-3) to HCO+(4-3) flux ratios of >2, possibly due to AGN-related phenomena. The J = 4-3 to J = 1-0 transition flux ratios for HCN (HCO+) are similar to those expected for fully thermalized (sub-thermally excited) gas in both sources, in spite of HCN's higher critical density. If we assume collisional excitation and neglect an infrared radiative pumping process, our non-LTE analysis suggests that HCN traces gas with significantly higher density than HCO+. In Arp 220, we separated the double-peaked HCN(4-3) emission into the eastern and western nuclei, based on velocity information. We confirmed that the eastern nucleus showed a higher HCN(4-3) to HCN(1-0) flux ratio, and thus contained a larger amount of highly excited molecular gas than the western nucleus.Comment: 21 pages, 4 figures, accepted for publication in PASJ (Vol.62, No.1, 2010 Feb 25 issue

Identification of amino acid residues participating in the energy coupling and proton transport of Streptomyces coelicolor A3(2) H+-pyrophosphatase

AbstractThe H+-translocating inorganic pyrophosphatase is a proton pump that hydrolyzes inorganic pyrophosphate. It consists of a single polypeptide with 14–17 transmembrane domains (TMs). We focused on the third quarter region of Streptomyces coelicolor A3(2) H+-pyrophosphatase, which contains a long conserved cytoplasmic loop. We assayed 1520 mutants for pyrophosphate hydrolysis and proton translocation, and selected 34 single-residue substitution mutants with low substrate hydrolysis and proton-pump activities. We also generated 39 site-directed mutant enzymes and assayed their activity. The mutation of 5 residues in TM10 resulted in low energy-coupling efficiencies, and mutation of conserved residues Thr409, Val411, and Gly414 showed neither hydrolysis nor pumping activity. The mutation of six, five, and four residues in TM11, 12, and 13, respectively, gave a negative effect. Phe388, Thr389, and Val396 in cytoplasmic loop i were essential for efficient H+ translocation. Ala436 and Pro560 in the periplasmic loops were critical for coupling efficiency. These low-efficiency mutants showed dysfunction of the energy-conversion and/or proton-translocation activity. The energy efficiency was increased markedly by the mutation of two and six residues in TM9 and 12, respectively. These results suggest that TM10 is involved in enzyme function, and that TM12 regulate the energy-conversion efficiency. H+-pyrophosphatase might involve dynamic linkage between the hydrophilic loops and TMs through the central half region of the enzyme

Lung Cancer Risk and Genetic Polymorphisms in DNA Repair Pathways: A Meta-Analysis

Genetic variations in DNA repair genes are thought to modulate DNA repair capacity and are suggested to be related to lung cancer risk. We conducted a meta-analysis of epidemiologic studies on the association between genetic polymorphisms in both base excision repair and nucleotide excision repair pathways, and lung cancer. We found xeroderma pigmentosum complementation group A (XPA) G23A (odds ratio (OR) = 0.76, 95% confidence interval (CI) = 0.61–0.94), 8-oxoguanine DNA glycosylase 1 (OGG1) Ser326Cys (OR = 1.22, 95% CI = 1.02–1.45), and excision repair cross-complementing group 2 (ERCC2) Lys751Gln (OR = 1.27, 95% CI = 1.10–1.46) polymorphisms were associated with lung cancer risk. Considering the data available, it can be conjectured that if there is any risk association between a single SNP and lung cancer, the risk fluctuation will probably be minimal. Advances in the identification of new polymorphisms and in high-throughput genotyping techniques will facilitate the analysis of multiple genes in multiple DNA repair pathways. Therefore, it is likely that the defining feature of future epidemiologic studies will be the simultaneous analysis of large samples of cases and controls

A Search for Molecular Gas toward a BzK-selected Star-forming Galaxy at z = 2.044

We present a search for CO(3-2) emission in SDF-26821, a BzK-selected star-forming galaxy (sBzK) at z = 2.044, using the 45-m telescope of the Nobeyama Radio Observatory and the Nobeyama Millimeter Array. We do not detect significant emission and derive 2 \sigma limits: the CO luminosity of L'CO < 3.1 x 10^10 K km s^{-1} pc^{-2}, the ratio of far-infrared luminosity to CO luminosity of L_FIR/L'CO > 57 Lsun (K km s^{-1} pc^{-2})^{-1}, and the molecular gas mass of M_H2 < 2.5 x 10^10 Msun, assuming a velocity width of 200 km s^{-1} and a CO-to-H2 conversion factor of alpha_CO=0.8 Msun (K km s^{-1} pc^{-2})^{-1}. The ratio of L_FIR/L'CO, a measure of star formation efficiency (SFE), is comparable to or higher than the two z ~ 1.5 sBzKs detected in CO(2-1) previously, suggesting that sBzKs can have a wide range of SFEs. Comparisons of far-infrared luminosity, gas mass, and stellar mass among the sBzKs suggest that SDF-26821 is at an earlier stage of forming stars with a similar SFE and/or more efficiently forming stars than the two z ~ 1.5 sBzKs. The higher SFEs and specific star formation rates of the sBzKs compared to local spirals are indicative of the difference in star formation modes between these systems, suggesting that sBzKs are not just scaled-up versions of local spirals.Comment: 4 pages, 4 figures, Accepted for publication in PAS

Methylenetetrahydrofolate reductase polymorphisms and interaction with smoking and alcohol consumption in lung cancer risk: a case-control study in a Japanese population

<p>Abstract</p> <p>Background</p> <p>Cigarette smoking is an established risk factor of lung cancer development while the current epidemiological evidence is suggestive of an increased lung cancer risk associated with alcohol consumption. Dietary folate, which is present in a wide range of fresh fruits and vegetables, may be a micronutrient that has a beneficial impact on lung carcinogenesis. Methylenetetrahydrofolate reductase (MTHFR) plays a crucial role in regulating folate metabolism, which affects both DNA synthesis/repair and methylation. We examined if smoking or alcohol consumption modify associations between <it>MTHFR </it>polymorphisms and lung cancer risk.</p> <p>Methods</p> <p>We evaluated the role of the <it>MTHFR </it>C677T (rs1801133) and A1298C (rs1801131) polymorphisms in a case-control study comprised of 462 lung cancer cases and 379 controls in a Japanese population. Logistic regression was used to assess the adjusted odds ratios (OR) and 95% confidence intervals (95% CI).</p> <p>Results</p> <p>The TT genotype of the C677T polymorphism was significantly associated with an increased risk of lung cancer (OR = 2.27, 95% CI = 1.42 - 3.62, P < 0.01) while the A1298C polymorphism was not associated with lung cancer risk. The minor alleles of both polymorphisms behaved in a recessive fashion. The highest risks were seen for 677TT-carriers with a history of smoking or excessive drinking (OR = 6.16, 95% CI = 3.48 - 10.9 for smoking; OR = 3.09, 95% CI = 1.64 - 5.81 for drinking) compared with C-carriers without a history of smoking or excessive drinking, but no interactions were seen. The 1298CC genotype was only associated with increased risk among non-smokers (P < 0.05), and smoking was only associated with increased risks among 1298A-carriers (P < 0.01), but no significant interaction was seen. There was a synergistic interaction between the A1298C polymorphism and drinking (P < 0.05). The highest risk was seen for the CC-carriers with excessive drinking (OR = 7.24, 95% CI = 1.89 - 27.7) compared with the A-carriers without excessive drinking).</p> <p>Conclusions</p> <p>The C677T polymorphism was significantly associated with lung cancer risk. Although the A1298C polymorphism was not associated with lung cancer risk, a significant interaction with drinking was observed. Future studies incorporating data on folate intake may undoubtedly lead to a more thorough understanding of the role of the <it>MTHFR </it>polymorphisms in lung cancer development.</p

Nicotine Induces Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor by α1 Nicotinic Acetylcholine Receptor–Mediated Activation in PC9 Cells

IntroductionNicotine, the major component among the 4000 identified chemicals in cigarette smoke, binds to nicotinic acetylcholine receptors (nAChRs) on non–small-cell lung cancer (NSCLC) cells and regulates cellular proliferation by activating mitogen-activated protein kinases [AQ: MAPK has been expanded to mitogen-activated protein kinases. Please approve.]and PI3K/Akt pathways. In patients with smoking-related lung cancer who continue smoking, the anticancer effect of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) is weaker than that in nonsmokers; however, the precise reason for this difference remains unclear. We investigated the role of α1 nAChR subunit in this phenomenon.MethodsWe screened for α1 nAChR mRNA in three NSCLC cell lines and analyzed the protein in resected primary NSCLC tissues. We used Western blot and RNA interference (siRNA) methodology to confirm the results.ResultsWe determined that α1 nAChR plays an essential role in nicotine-induced cell signaling and nicotine-induced resistance to EGFR-TKI. In addition, we showed that silencing of α1 nAChR subunit in NSCLC may suppress the nicotine-induced resistance to EGFR-TKI.ConclusionsThese results further implicate nicotine in lung carcinogenesis, and suggest that α1 nAChR may be a biomarker for EGFR-TKI treatment and also a personalizing target molecule for patients with smoking-related lung cancer

Molecular Gas Properties in the Host Galaxy of GRB 080207

We present the results of CO(1–0) and CO(4–3) observations of the host galaxy of a long-duration gamma-ray burst GRB 080207 at z = 2.0858 by using the Karl G. Jansky Very Large Array and the Atacama Large Millimeter/submillimeter Array. The host is detected in CO(1–0) and CO(4–3), becoming the first case for a gamma-ray burst (GRB) host with more than two CO transitions detected combined with CO(2–1) and CO(3–2) in the literature. Adopting a metallicity-dependent CO-to-H2 conversion factor, we derive a molecular gas mass of M gas = 8.7 × 1010 M ⊙, which places the host in a sequence of normal star-forming galaxies in an M gas–star formation rate (SFR) plane. A modified blackbody fit to the far-infrared–millimeter photometry results in a dust temperature of 37 K and a dust mass of M dust = 1.5 × 108 M ⊙. The spatially resolved CO(4–3) observations allow us to examine the kinematics of the host. The CO velocity field shows a clear rotation and is reproduced by a rotation-dominated disk model with a rotation velocity of 350 km s‑1 and a half-light radius of 2.4 kpc. The CO spectral line energy distribution derived from the four CO transitions is similar to that of starburst galaxies, suggesting a high excitation condition. Comparison of molecular gas properties between the host and normal (main-sequence) galaxies at similar redshifts shows that they share common properties such as gas mass fraction, gas depletion timescale, gas-to-dust ratio, location in the M gas–SFR (or surface density) relation, and kinematics, suggesting that long-duration GRBs can occur in normal star-forming environments at z ∼ 2

Millimeter Interferometric HCN(1-0) and HCO+(1-0) Observations of Luminous Infrared Galaxies

We present the results on millimeter interferometric observations of four luminous infrared galaxies (LIRGs), Arp 220, Mrk 231, IRAS 08572+3915, and VV 114, and one Wolf-Rayet galaxy, He 2-10, using the Nobeyama Millimeter Array (NMA). Both the HCN(1-0) and HCO+(1-0) molecular lines were observed simultaneously and their brightness-temperature ratios were derived. High-quality infrared L-band (2.8-4.1 micron) spectra were also obtained for the four LIRGs to better constrain their energy sources deeply buried in dust and molecular gas. When combined with other LIRGs we have previously observed with NMA, the final sample comprised nine LIRGs (12 LIRGs' nuclei) with available interferometric HCN(1-0) and HCO+(1-0) data-sufficient to investigate the overall trend in comparison with known AGNs and starburst galaxies. We found that LIRGs with luminous buried AGN signatures at other wavelengths tend to show high HCN(1-0)/HCO+(1-0) brightness-temperature ratios as seen in AGN-dominated galaxies, while the Wolf-Rayet galaxy He 2-10 displays a small ratio. An enhanced HCN abundance in the interstellar gas surrounding a strongly X-ray-emitting AGN, as predicted by some chemical calculations, is a natural explanation of our results.Comment: 43 pages, 11 figures, accepted for publication in Astronomical Journal. Higher resolution version is available at http://optik2.mtk.nao.ac.jp/~imanishi/Paper/HCN2/HCN2.pd