We have mapped the northern area (30 × 20 ) of a Local Group spiral galaxy M33 in 12 CO(J = 1-0) line with the 45 m telescope at the Nobeyama Radio Observatory. Along with Hα and Spitzer 24 μm data, we have investigated the relationship between the surface density of molecular gas mass and that of star formation rate (SFR) in an external galaxy (Kennicutt-Schmidt law) with the highest spatial resolution (∼80 pc) to date, which is comparable to scales of giant molecular clouds (GMCs). At positions where CO is significantly detected, the SFR surface density exhibits a wide range of over four orders of magnitude, from Σ SFR 10 −10 to ∼10 −6 M yr −1 pc −2 , whereas the Σ H 2 values are mostly within 10-40 M pc −2 . The surface density of gas and that of SFR correlate well at an ∼1 kpc resolution, but the correlation becomes looser with higher resolution and breaks down at GMC scales. The scatter of the Σ SFR -Σ H 2 relationship in the ∼80 pc resolution results from the variety of star-forming activity among GMCs, which is attributed to the various evolutionary stages of GMCs and to the drift of young clusters from their parent GMCs. This result shows that the Kennicutt-Schmidt law is valid only in scales larger than that of GMCs, when we average the spatial offset between GMCs and star-forming regions, and their various evolutionary stages.

Neisseria gonorrhoeae strains with reduced susceptibility to cefixime (MICs, 0.25 to 0.5 g/ml) were isolated from male urethritis patients in Tokyo, Japan, in 2000 and 2001. The resistance to cephems including cefixime and penicillin was transferred to a susceptible recipient, N. gonorrhoeae ATCC 19424, by transformation of the penicillin-binding protein 2 gene (penA) that had been amplified by PCR from a strain with reduced susceptibility to cefixime (MIC, 0.5 g/ml). The sequences of penA in the strains with reduced susceptibilities to cefixime were different from those of other susceptible isolates and did not correspond to the reported N. gonorrhoeae penA gene sequences. Some regions in the transpeptidase-encoding domain in this penA gene were similar to those in the penA genes of Neisseria perflava (N. sicca), Neisseria cinerea, Neisseria flavescens, and Neisseria meningitidis. These results showed that a mosaic-like structure in the penA gene conferred reductions in the levels of susceptibility of N. gonorrhoeae to cephems and penicillin in a manner similar to that found for N. meningitidis and Streptococcus pneumoniae.

The study demonstrates that with endurance-training changes in cardiac ANS modulation partly contribute to a decrease in HR at rest and during postexercise recovery period, and that adaptation of the cardiac autonomic control occurs sooner in immediate postexercise periods than at rest.

Staphylococcus aureus is a major causative agent for biofilm-associated infections. Inside biofilms, S. aureus cells are embedded in an extracellular matrix (ECM) composed of polysaccharide-intercellular adhesins (PIA), proteins, and/or extracellular DNA (eDNA). However, the importance of each component and the relationship among them in biofilms of diverse strains are largely unclear. Here, we characterised biofilms formed by 47 S. aureus clinical isolates. In most (42/47) of the strains, biofilm formation was augmented by glucose supplementation. Sodium chloride (NaCl)-triggered biofilm formation was more prevalent in methicillin-sensitive S. aureus (15/24) than in methicillin-resistant strain (1/23). DNase I most effectively inhibited and disrupted massive biofilms, and Proteinase K was also effective. Anti-biofilm effects of Dispersin B, which cleaves PIA, were restricted to PIA-dependent biofilms formed by specific strains and showed significant negative correlations with those of Proteinase K, suggesting independent roles of PIA and proteins in each biofilm. ECM profiling demonstrated that eDNA was present in all strains, although its level differed among strains and culture conditions. These results indicate that eDNA is the most common component in S. aureus biofilms, whereas PIA is important for a small number of isolates. Therefore, eDNA can be a primary target for developing eradication strategies against S. aureus biofilms.

We present a Giant Molecular Cloud (GMC) catalog toward M33, containing 71 GMCs in total, based on wide field and high sensitivity CO(J = 3−2) observations with a spatial resolution of 100 pc using the ASTE 10 m telescope. Employing archival optical data, we identify 75 young stellar groups (YSGs) from the excess of the surface stellar density, and estimate their ages by comparing with stellar evolution models. A spatial comparison among the GMCs, YSGs, and Hii regions enable us to classify GMCs into four categories: Type A showing no sign of massive star formation (SF), Type B being associated only with Hii regions, Type C with both Hii regions and < 10 Myr-old YSGs and Type-D with both Hii regions and 10-30 Myr YSGs. Out of 65 GMCs (discarding those at the edges of the observed fields), 1 (1%), 13 (20%), 29 (45%), and 22 (34%) are Types A, B, C, and D, respectively. We interpret these categories as stages in a GMC evolutionary sequence. Assuming that the timescale for each evolutionary stage is proportional to the number of GMCs, the lifetime of a GMC with a mass > 10 5 M is estimated to be 20-40 Myr. In addition, we find that the dense gas fraction as traced by the CO(J = 3 − 2)/CO(J = 1 − 0) ratio is enhanced around SF regions. This confirms a scenario where dense gas is preferentially formed around previously generated stars, and will be the fuel for the next stellar generation. In this way, massive SF gradually propagates in a GMC until gas is exhausted.

Abstract. Oridonin, a diterpenoid isolated from Rabdosia rubescences, could induce apoptosis through the generation of reactive oxygen species (ROS) in human hepatoma HepG2 cells. p53, a specific inhibitor of pifithrin α (PFT α), markedly inhibited ROS generation and apoptosis, showing that p53 was responsible for the cytotoxity of oridonin through mediation by ROS. Moreover, the ROS activated the p38 kinase, which in turn promoted the activation of p53, as verified by evidence showing that the ROS scavenger N-acetyl-cysteine (NAC) not only blocked the phosphorylation of p38 but also partially inhibited the activation of p53, and the p38 inhibitor SB203580 reduced the activation of p53 as well. Mitochondria were either the sources or the targets of ROS. This study showed that oridonin stimulated mitochondrial transmembrane permeabilization in a ROS-dependent manner because NAC almost thoroughly reversed the drop of mitochondrial transmembrane potential (Δψm) and the release of cytochrome c from the mitochondrial inter-membrane space into cytosol. Furthermore, as a result of mitochondrial permeability transition, procaspases-9 and -3 were cleaved into 37-and 17-kDa proteolytic products, respectively, which acted as executors of oridonin-induced apoptosis.

The cross-sectional area (CSA) of large-conductance arteries increases in response to endurance training in humans. To determine whether training-induced changes in arterial structure are systemic in nature or, rather, are confined to the arteries supplying exercising muscles, we studied 10 young men who performed one-legged cycle training [80% of one-legged peak O2 uptake (VO2 peak)), 40 min/day, 4 days/wk] for 6 wk and detraining for another 6 wk. There were no significant differences in baseline one-legged VO2 peak) and CSA of the common femoral artery and vein (via B-mode ultrasound) between experimental and control legs. In the experimental leg, one-legged VO2 peak) increased 16% [from 3.0 +/- 0.1 to 3.4 +/- 0.1 (SE) l/min], arterial CSA increased 16% (from 84 +/- 3 to 97 +/- 5 mm2), and venous CSA increased 46% (from 56 +/- 5 to 82 +/- 5 mm2) after endurance training. These changes returned to baseline during detraining. There were no changes in one-legged VO2 peak) and arterial CSA in the control leg, whereas femoral venous CSA in the control leg significantly increased 24% (from 54 +/- 5 to 67 +/- 4 mm2) during training. Changes in femoral arterial and venous CSA in the experimental leg were positively and significantly related to corresponding changes in one-legged VO2 peak) (r = 0.86 and 0.76, respectively), whereas there were no such relations in the control leg (r = 0.10 and 0.17). When stepwise regression analysis was performed, a primary determinant of change in VO2 peak) was change in femoral arterial CSA, explaining approximately 70% of the variability. These results support the hypothesis that the regional increase in blood flow, rather than systemic factors, is associated with the training-induced arterial expansion. Femoral arterial expansion may contribute, at least in part, to improvement in efficiency of blood transport from the heart to exercising muscles and may facilitate achievement of aerobic work capacity.

Abstract. Natural products regulate cell growth in response to oncogene activation that induces cell cycle arrest and apoptosis in tumor cell lines. We investigated the mechanisms of caspase activation in human malignant melanoma, A375-S2 cells, by the natural product shikonin, which was isolated from the plant Lithospermum erythrorhizon SIEB. et ZUCC. Shikonin inhibited cell growth in a time-and dose-dependent manner, which might be mediated through up-regulation of p53 and down-regulation of cyclin-dependent protein kinase 4. Caspase activation was detected in shikonin-induced cell apoptosis, which involved in a post-mitochondrial caspase-9-dependent pathway. Decreased Bcl-2 protein levels and increased Bax protein levels were positively correlated with elevated expression of p53 protein. Apoptosis-inducing factor, another apoptotic protein of mitochondria, partially contributed to shikonin-induced release of cytochrome c. Taken together, shikonin-induced DNA damage activates p53 and caspase-9 pathways.