All-polarization-maintaining Er-doped dual comb fiber laser using single-wall carbon nanotubes.

We demonstrated a bi-directional, Er-doped dual comb fiber laser consisting of all-polarization-maintaining fiber devices. Polyimide films in which single-wall carbon nanotubes (SWNTs) were dispersed were used as the in-line saturable absorber. In order to avoid synchronization of the two combs and associated damage to the SWNT film, a two-branch configuration with two SWNT films was employed. Soliton pulses with almost the same optical spectra were generated stably in each direction, and dual comb beats were observed simply by overlapping the two outputs. The repetition frequency was 28 MHz, and the frequency difference was 105-140 Hz. Thanks to the small frequency difference, dual comb beats corresponding to the whole optical spectrum were observed without any overlapping. Fourier transform spectroscopy using the developed dual comb source was examined, and the characteristics of an optical filter were successfully obtained.

Effects of Wolbachia/Cardinium Infection on the Mitochondrial Phylogeny of Oligonychus castaneae (Acari: Tetranychidae).

A wide range of invertebrates harbor intracellular endosymbiotic bacteria. Within these endosymbionts, Wolbachia and Cardinium, have been attracting particular attention because these bacteria frequently affect the genetic structure and genetic diversity of their hosts. They cause various reproductive alterations such as cytoplasmic incompatibility, parthenogenesis induction, male-killing, and feminization. Through these alterations, they also affect the maternally inherited organelles of their hosts. Mitochondrial DNA (mtDNA) can be used for molecular phylogenetic analysis of invertebrates. However, in Wolbachia- or Cardinium-infected invertebrates, phylogenetic trees based on mtDNA are often inconsistent with those based on nuclear DNA. In the present study, we determined the Wolbachia/Cardinium infection status of 45 populations of the mite, Oligonychus castaneae Ehara & Gotoh (Acari: Tetranychidae), collected throughout Japan. Then, we compared phylogenetic trees of O. castaneae based on both the cytochrome c oxidase subunit I (COI) gene of mtDNA and the 28S rRNA gene of nuclear DNA to clarify the effects of Wolbachia and/or Cardinium infection. We found 106 Wolbachia-infected individuals and 250 Cardinium-infected individuals in a total of 450 individuals, indicating an infection rate of 79%. No double-infected individuals were observed. In the 28S tree, almost all populations formed a single group. In the COI tree, O. castaneae formed four separate groups that more closely followed Wolbachia/Cardinium infection than geographic distribution. These results strongly suggest that the endosymbionts affected mitochondrial variation of O. castaneae.

Effects of peripheral administration of a Neuromedin U receptor 2-selective agonist on food intake and body weight in obese mice.

BACKGROUND: Neuromedin U (NMU) is a neuropeptide with various physiological functions, including regulation of smooth-muscle contraction, blood pressure, stress responses and feeding behaviors. NMU activates two distinct receptors, NMUR1 and NMUR2, which are predominantly expressed in peripheral tissues and the central nervous system (CNS), respectively. It is reported that the NMU signaling system regulates food intake (FI) and body weight (BW) via NMUR2, suggesting that an NMUR2 agonist exhibiting anorectic effects would be a potential therapy for obesity. METHODS: Antiobesity effects of NMUR2 activation were assessed using a recently developed, novel NMUR2-selective agonist, NMU-7005 (a polyethylene glycolated octapeptide). Here we assessed cumulative FI and BW loss after peripheral administration of NMU-7005 in NMUR2 knockout and diet-induced obese mice. To gain mechanistic insights, we performed immunohistochemical analysis of c-Fos-like protein expression in the brain. RESULTS: We found that NMU-7005 was a NMUR2-selective agonist with little activity toward NMUR1. The anorectic effect of NMU-7005 was completely abrogated in NMUR2 knockout mice. Repeated subcutaneous administration of NMU-7005 showed a potent antiobesity effect with FI inhibition (P<0.025) in diet-induced obese mice. NMU-7005 in combination with the glucagon-like peptide-1 receptor (GLP-1R) agonist liraglutide showed an additive antiobesity effect, suggesting that NMUR2-mediated anorectic action is different from that of GLP-1R agonists. NMU-7005 also elicited a minimal conditioned taste-aversive effect, while the effect of liraglutide was significant. As c-Fos expression was upregulated in the hypothalamus and the medulla oblongata in NMU-7005-administered mice, the pharmacological effects of NMU-7005 appeared to be mediated via activation of the CNS. CONCLUSION: Our results demonstrated that a novel NMUR2-selective agonist, NMU-7005, is a beneficial tool for the elucidation of NMUR2-mediated physiological functions, which is a promising therapeutic strategy for treating obesity.

Comprehensive molecular exploration identified promoter DNA methylation of the CRBP1 gene as a determinant of radiation sensitivity in rectal cancer.

BACKGROUND: Neoadjuvant chemoradiotherapy (NCRT) for advanced rectal cancer (RC) is a well-evidenced therapy; however, some RC patients have no therapeutic response. Patient selection for NCRT so that non-responsive patients are excluded has been subjective. To date, no molecular markers indicating radiation sensitivity have been reported. METHODS: We irradiated six colorectal cancer (CRC) cell lines and identified HCT116 cells as radiation-sensitive and HCT15 and DLD-1 cells as radiation resistant. Using a microarray, we selected candidate radiation sensitivity marker genes by choosing genes whose expression was consistent with a radiation-resistant or sensitive cell phenotype. RESULTS: Among candidate genes, cellular retinol binding protein 1 (CRBP1) was of particular interest because it was not only induced in HCT116 cells by tentative 10 Gy radiation treatments, but also its expression was increased in HCT116-derived radiation-resistant cells vs parental cells. Forced expression of CRBP1 decreased the viability of both HCT15 and DLD-1 cells in response to radiation therapy. We also confirmed that CRBP1 was epigenetically silenced by hypermethylation of its promoter DNA, and that the quantitative methylation value of CRBP1 significantly correlated with histological response in RC patients with NCRT (P=0.031). CONCLUSIONS: Our study identified CRBP1 as a radiation-sensitive predictor in RC.

Development of a high power supercontinuum source in the 1.7 µm wavelength region for highly penetrative ultrahigh-resolution optical coherence tomography.

We developed a high power supercontinuum source at a center wavelength of 1.7 µm to demonstrate highly penetrative ultrahigh-resolution optical coherence tomography (UHR-OCT). A single-wall carbon nanotube dispersed in polyimide film was used as a transparent saturable absorber in the cavity configuration and a high-repetition-rate ultrashort-pulse fiber laser was realized. The developed SC source had an output power of 60 mW, a bandwidth of 242 nm full-width at half maximum, and a repetition rate of 110 MHz. The average power and repetition rate were approximately twice as large as those of our previous SC source [20]. Using the developed SC source, UHR-OCT imaging was demonstrated. A sensitivity of 105 dB and an axial resolution of 3.2 µm in biological tissue were achieved. We compared the UHR-OCT images of some biological tissue samples measured with the developed SC source, the previous one, and one operating in the 1.3 µm wavelength region. We confirmed that the developed SC source had improved sensitivity and penetration depth for low-water-absorption samples.

Power scaling of dispersion-managed Er-doped ultrashort pulse fiber laser with single wall carbon nanotubes.

A high-power, passively mode-locked, Er-doped fiber laser with a single wall carbon nanotube polyimide film was demonstrated in dispersion-managed dissipative-soliton mode-locking operation. The average maximum power of 285 mW and a pulse energy of 8.1 nJ are the highest values yet achieved for single-pulse operation in a nanotube fiber laser. A high-power ultrashort pulse of 680 fs was generated by dispersion compensation at a repetition rate of 34.9 MHz. Passive mode-locking was numerically analyzed, and the dynamics and output properties are discussed.

Dispersion-managed, high-power, Er-doped ultrashort-pulse fiber laser using carbon-nanotube polyimide film.

We investigated a dispersion-managed, passively mode-locked, ultrashort-pulse, Er-doped fiber laser using a polyimide film containing dispersed single-wall carbon nanotubes (SWNTs) and examined the dependence on net cavity dispersion and output coupling ratio using normal-dispersion fibers and a variable output coupler. For the dissipative soliton mode-locking condition, we achieved a pulse energy of 3.5 nJ and an average power of 114 mW, the highest values yet reported for an SWNT fiber laser under single-pulse operation.

Ultralow-repetition-rate, high-energy, polarization-maintaining, Er-doped, ultrashort-pulse fiber laser using single-wall-carbon-nanotube saturable absorber.

An ultralow-repetition-rate, all-polarization-maintaining (PM), Er-doped, ultrashort-pulse fiber laser was demonstrated using a single-wall-carbon-nanotube polyimide film. Using a ring cavity configuration, output pulses with pulse energy of 0.7-2.6 nJ were obtained at an ultralow repetition rate of 943-154 kHz for a fiber length of 0.1-1.3 km. A novel θ (theta) cavity configuration was proposed, which enabled us to reduce the required fiber length by half. A repetition rate of 132 kHz was achieved using this configuration with 909 m of PM fiber.

Wideband spectral compression of wavelength-tunable ultrashort soliton pulse using comb-profile fiber.

We demonstrated spectral compression of ultrashort soliton pulses in a wide wavelength region based on an adiabatic soliton spectral compression technique using a comb-profile fiber. The comb-profile fiber was carefully designed using numerical analysis and fabricated using a conventional single-mode fiber and a dispersion-shifted fiber. The spectral width of a 200 fs soliton pulse was compressed from 12 to 15 nm to 0.54-0.71 nm in the wavelength region 1620-1850 nm, giving a spectral compression factor of up to 19.8-25.9. Owing to the soliton effect, the side lobe level was suppressed to -19.2 to -9.7 dB.

Polarization-maintaining, high-energy, wavelength-tunable, Er-doped ultrashort pulse fiber laser using carbon-nanotube polyimide film.

A high-energy, wavelength-tunable, all-polarization-maintaining Er-doped ultrashort fiber laser was demonstrated using a polyimide film dispersed with single-wall carbon nanotubes. A variable output coupler and wavelength filter were used in the cavity configuration, and high-power operation was demonstrated. The maximum average power was 12.6 mW and pulse energy was 585 pJ for stable single-pulse operation with an output coupling ratio as high as 98.3%. Wide wavelength-tunable operation at 1532-1562 nm was also demonstrated by controlling the wavelength filter. The RF amplitude noise characteristics were examined in terms of their dependence on output coupling ratio and oscillation wavelength.

All-polarization-maintaining Er-doped ultrashort-pulse fiber laser using carbon nanotube saturable absorber.

We present an all-polarization-maintaining Er-doped ultrashort-pulse fiber laser using a single-wall carbon nanotube polyimide nanocomposite saturable absorber. The maximum average power for single-pulse operation is 4.8 mW, and the repetition frequency is 41.3 MHz. Self-start and stable mode-locking operation is achieved. The RF amplitude noise is also examined and it is confirmed that the noise figure is as low as that of a solid-state laser. Using a polarization-maintaining anomalous dispersive fiber, a 314 fs output pulse is compressed to 107 fs via higher-order soliton compression. The peak power of the compressed pulse is up to 1.1 kW.

Filter cigarette smoking and lung cancer risk; a hospital-based case--control study in Japan.

Recent changes in the histology of lung cancer, namely a relative increase of adenocarcinoma compared to squamous cell carcinoma, might be due to a temporal shift from nonfilter to filter cigarettes. To investigate the association between type of cigarette and lung cancer by histological type, we conducted a case-control study in Japan, comprising 356 histologically confirmed lung cancer cases and 162 controls of male current smokers, who provided complete smoking histories. Overall, logistic regression analysis after controlling for age and prefecture revealed decreased risk, as shown by adjusted odds ratios, for both squamous cell carcinoma and adenocarcinoma among lifelong filter-exclusive smokers as compared to nonfilter or mixed smokers. This decrease was greater for squamous cell carcinoma than for adenocarcinoma. Among men under 54 years, filter-exclusive smokers displayed increased risk of adenocarcinoma, but decreased risk of squamous cell carcinoma. The recent shift in histology from squamous cell carcinoma to adenocarcinoma, particularly among younger smokers, might be due to changes in cigarette type. However, among subjects aged 65 years or more, no differences in histological type appeared related to type of cigarette smoked, implying that other factors are associated with increases in adenocarcinoma among older Japanese population.

Real-time, ultrahigh-resolution, optical coherence tomography with an all-fiber, femtosecond fiber laser continuum at 1.5 microm.

Real-time, ultrahigh-resolution optical coherence tomography (OCT) is demonstrated in the 1.4-1.7-microm wavelength region with a stretched-pulse, passively mode-locked, Er-doped fiber laser and highly nonlinear fiber. The fiber laser generates 100-mW, linearly chirped pulses at a 51-MHz repetition rate. The pulses are compressed and then coupled into a normally dispersive highly nonlinear fiber to generate a low-noise supercontinuum with a 180-nm FWHM bandwidth and 38 mW of output power. This light source is stable, compact, and broadband, permitting high-speed, real-time, high-resolution OCT imaging. In vivo high-speed OCT imaging of human skin with approximately 5.5-microm resolution and 99-dB sensitivity is demonstrated.

In vitro and in vivo inhibition of muscle lipid and protein oxidation by carnosine.

Carnosine, a beta-alanyl-L-histidine dipeptide with antioxidant properties is present at high concentrations in skeletal muscle tissue. In this study, we report on the antioxidant activity of carnosine on muscle lipid and protein stability from both in vitro and in vivo experiments. Carnosine inhibited lipid peroxidation and oxidative modification of protein in muscle tissue prepared from rat hind limb homogenates exposed to in vitro Fenton reactant (Fe2+, H2O2)-generated free radicals. The minimum effective concentrations of carnosine for lipid and protein oxidation were 2.5 and 1 mM, respectively. Histidine and beta-alanine, active components of carnosine, showed no individual effect towards inhibiting either lipid or protein oxidation. Skeletal muscle of rats fed a histidine supplemented diet for 13 days exhibited a marked increase in carnosine content with a concomitant reduction in muscle lipid peroxidation and protein carbonyl content in skeletal muscle caused by subjecting rats to a Fe-nitrilotriacetate administration treatment. This significant in vitro result confirms the in vivo antioxidant activity of carnosine for both lipid and protein constituents of muscle under physiological conditions.

Identification of the opener and closer of the pharyngoesophagus in laryngectomees.

BACKGROUND: In esophageal and tracheoesophageal speakers, the neoglottis acts not only as the orifice of the digestive tract but also as the airway and the voice source. The opening and closing mechanism is thought to be essential for these functions. It is not known, however, whether there is any active muscular control of neoglottal opening and closing. Examinations have been carried out to find the physiological background of the opening and closing of the neoglottis. In this paper, we present our findings of the opening and closing mechanism of the neoglottis and discuss them with reviewing the previous studies. SUBJECTS AND METHODS: Subjects were volunteer esophageal speakers. Neoglottal width, EMG of the inferior pharyngeal constrictor (IPC) and that of the geniohyoid muscle (GH) were recorded simultaneously during swallowing and air intake for esophageal speech. RESULTS: At rest, the neoglottis was closed by the mucosal protrusion in the posterior wall of the pharyngoesophagus. During swallowing, the neoglottis was widely opened. Traction of the anterior pharyngeal wall anteriorly by the GH and reciprocal suppression of the IPC activity was thought to be the mechanism of the neoglottal opening in this case. However, such simple reciprocity was not observed during air intake, although transient opening of the neoglottis was commonly observed. The GH showed increased activity at neoglottal opening as it did during swallowing. The IPC was. on the other hand, continuously activated, and no significant suppression was observed. During air intake, the muscle is assumed to play a role in maintaining the shape and tension of the posterior mucosal protrusion which acts as a voice source in subsequent phonation. CONCLUSIONS: The GH and the IPC were found to open and close the neoglottis, respectively. Their activities were not always clearly reciprocal in the various functions of the neoglottis.

Technical advance: an automated device for cryofixation of specimens of electron microscopy using liquid helium.

Metal-contact rapid freezing using liquid helium is theoretically the best method for preserving the fine structure of living cells with high temporal resolution in preparation of tissue samples for electron microscopy. However, this method is not commonly used, because of its technical difficulty and low reproducibility. We have designed and constructed an automatic device which allows simple, rapid and reproducible preparation of high-quality electron microscopic specimens by the non-specialist. We assessed the quality of cryofixation in samples prepared using this device by examining the preservation of cellular ultrastructure in relation to distance from the freezing block, and found that the region within 10 microm of the metal-contact plane was fixed with the highest quality. We applied this device, in combination with freeze-substitution methods and immunocytochemical techniques, to two phenomena involving rapid movement of subcellular components: (1) active movement of subcellular structures in the papillar cells of stigma and (2) light-induced rapid subcellular translocation of phytochrome A. Considering the importance of understanding subcellular processes of living cells for molecular and cell biology, this device will be a useful tool for diverse biological applications in the near future.

A proteinase-storing body that prepares for cell death or stresses in the epidermal cells of Arabidopsis.

Plants degrade cellular materials during senescence and under various stresses. We report that the precursors of two stress-inducible cysteine proteinases, RD21 and a vacuolar processing enzyme (VPE), are specifically accumulated in approximately 0.5 microm diameter x approximately 5 microm long bodies in Arabidopsis thaliana. Such bodies have previously been observed in Arabidopsis but their function was not known. They are surrounded with ribosomes and thus are assumed to be directly derived from the endoplasmic reticulum (ER). Therefore, we propose to call them the ER bodies. The ER bodies are observed specifically in the epidermal cells of healthy seedlings. These cells are easily wounded and stressed by the external environment. When the seedlings are stressed with a concentrated salt solution, leading to death of the epidermal cells, the ER bodies start to fuse with each other and with the vacuoles, thereby mediating the delivery of the precursors directly to the vacuoles. This regulated, direct pathway differs from the usual case in which proteinases are transported constitutively from the ER to the Golgi complex and then to vacuoles, with intervention of vesicle-transport machinery, such as a vacuolar-sorting receptor or a syntaxin of the SNARE family. Thus, the ER bodies appear to be a novel proteinase-storing system that assists in cell death under stressed conditions.

The expression of a barley HvNAS1 nicotianamine synthase gene promoter-gus fusion gene in transgenic tobacco is induced by Fe-deficiency in roots.

Nicotianamine (NA) is a precursor for mugineic acid-family phytosiderophores, which are a critical component of the Fe aquisition process in graminaceous plants. In addition, nicotianamine synthase (NAS) is strongly induced in these plants by Fe deficiency. NA is essential for Fe metabolism also in dicots, but NAS is not induced by Fe deficiency. We introduced a barley HvNAS1 promoter-gus fusion gene into tobacco. GUS activity was induced in the roots of these plants by Fe deficiency, and was constitutively expressed at a low level in their leaves.

In vivo evidence that Ids3 from Hordeum vulgare encodes a dioxygenase that converts 2'-deoxymugineic acid to mugineic acid in transgenic rice.

We proposed that an Fe-deficiency-induced gene, Ids3 (Iron deficiency specific clone no. 3), from barley (Hordeum vulgare L.) roots encodes a dioxygenase that catalyzes the hydroxylation step from 2'-deoxymugineic acid (DMA) to mugineic acid (MA). To prove this hypothesis, we introduced the Ids3 gene into rice (Oryza sativa L.), which lacks Ids3 homologues and secretes DMA, but not MA. Transgenic rice plants, carrying either Ids3 cDNA or a barley genomic DNA fragment (20 kb) containing Ids3, were obtained using Agrobacterium-mediated transformation. Ids3 cDNA under the control of the cauliflower mosaic virus 35S promoter was constitutively expressed in both the roots and the leaves of the transgenic rice, regardless of Fe nutrition status. In contrast, in the roots of transformants carrying a barley genomic fragment, transcripts of Ids3 were markedly increased in response to Fe deficiency. Slight expression of Ids3 was also observed in the leaves of the Fe-deficient plants. Western blot analysis confirmed the induction of Ids3 in response to Fe deficiency in the roots of the transformants carrying a genomic fragment. These expression patterns indicate that the 5'-flanking region of Ids3 works as a strong Fe-deficiency-inducible promoter in rice, as well as in barley. Both kinds of transgenic rice secreted MA in addition to DMA under Fe-deficient conditions, but wild-type rice secreted only DMA. This is in vivo evidence that IDS3 is the "MA synthase" that converts DMA to MA.

Molecular properties of apelin: tissue distribution and receptor binding.

We analyzed the tissue distribution of apelin mRNA in rats by a quantitative reverse transcription-polymerase chain reaction and that of immunoreactive apelin (ir-apelin) by an enzyme immunoassay (EIA) using a monoclonal antibody. The expression levels of apelin mRNA and ir-apelin seemed to be consistent among tissues: they were highly expressed in the lung and mammary gland. By the combination of gel filtration and EIA, we found that the molecular forms of apelin differ among respective tissues: apelin molecules with sizes close to apelin-36 (long forms) were major components in the lung, testis, and uterus, but both long and short (whose sizes were close to [