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Aims The ability to suppress soil nitrification through the release of nitrification inhibitors from plant roots is termed ‘biological nitrification inhibition’ (BNI). Here, we aimed at the quantification and characterization of the BNI function in sorghum that includes inhibitor production, their chemical identity, functionality and factors regulating their release. Methods Sorghum was grown in solution culture and root exudate was collected using aerated NH4Cl solutions. A bioluminescence assay using recombinant Nitrosomonas europaea was employed to determine the BNI activity. Activity-guided chromatographic fractionation was used to isolate biological nitrification inhibitors (BNIs). The chemical structure was analyzed using NMR and mass spectrometry; pH-stat systems were deployed to analyze the role of rhizosphere pH on BNIs release. Results Sorghum roots released two categories of BNIs: hydrophilic- and hydrophobic-BNIs. The release rates for hydrophilic- and hydrophobic- BNIs ranged from 10 to 25 ATU g−1 root dwt. d−1. Addition of hydrophilic BNIs (10 ATU g−1 soil) significantly inhibited soil nitrification (40 % inhibition) during a 30-d incubation test. Two BNI compounds isolated are: sakuranetin (ED80 0.6 μM; isolated from hydrophilic-BNIs fraction) and sorgoleone (ED80 13.0 μM; isolated from hydrophobic-BNIs fraction), which inhibited Nitrosomonas by blocking AMO and HAO enzymatic pathways. The BNIs release required the presence of NH4+ in the root environment and the stimulatory effect of NH4+ lasted 24 h. Unlike the hydrophobic-BNIs, the release of hydrophilic-BNIs declined at a rhizosphere pH >5.0; nearly 80 % of hydrophilic-BNI release was suppressed at pH ≥7.0. The released hydrophilic-BNIs were functionally stable within a pH range of 5.0 to 9.0. Sakuranetin showed a stronger inhibitory activity (ED50 0.2 μM) than methyl 3-(4-hydroxyphenyl) propionate (MHPP) (ED50 100 μM) (isolated from hydrophilic-BNIs fraction) in the in vitro culture-bioassay, but the activity was non-functional and ineffective in the soil-assay. Conclusions There is an urgent need to identify sorghum genetic stocks with high potential to release functional-BNIs for suppressing nitrification and to improve nitrogen use efficiency in sorghum-based production systems.

Nitrification, a key process in the global nitrogen cycle that generates nitrate through microbial activity, may enhance losses of fertilizer nitrogen by leaching and denitrification. Certain plants can suppress soil-nitrification by releasing inhibitors from roots, a phenomenon termed biological nitrification inhibition (BNI). Here, we report the discovery of an effective nitrification inhibitor in the root-exudates of the tropical forage grass Brachiaria humidicola (Rendle) Schweick. Named \"brachialactone,\" this inhibitor is a recently discovered cyclic diterpene with a unique 5-8-5-membered ring system and a γ-lactone ring. It contributed 60-90% of the inhibitory activity released from the roots of this tropical grass. Unlike nitrapyrin (a synthetic nitrification inhibitor), which affects only the ammonia monooxygenase (AMO) pathway, brachialactone appears to block both AMO and hydroxylamine oxidoreductase enzymatic pathways in NITROSOMONAS: Release of this inhibitor is a regulated plant function, triggered and sustained by the availability of ammonium (NH[Formula: see text]) in the root environment. Brachialactone release is restricted to those roots that are directly exposed to NH[Formula: see text]. Within 3 years of establishment, Brachiaria pastures have suppressed soil nitrifier populations (determined as amoA genes; ammonia-oxidizing bacteria and ammonia-oxidizing archaea), along with nitrification and nitrous oxide emissions. These findings provide direct evidence for the existence and active regulation of a nitrification inhibitor (or inhibitors) release from tropical pasture root systems. Exploiting the BNI function could become a powerful strategy toward the development of low-nitrifying agronomic systems, benefiting both agriculture and the environment.

Background: Global hypomethylation has been suggested to cause genomic instability and lead to an increased risk of cancer. We examined the association between the global methylation level of peripheral blood leukocyte DNA and breast cancer among Japanese women. Methods: We conducted a hospital-based case–control study of 384 patients aged 20–74 years with newly diagnosed, histologically confirmed invasive breast cancer, and 384 matched controls from medical checkup examinees in Nagano, Japan. Global methylation levels in leukocyte DNA were measured by LUminometric Methylation Assay. Odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between global hypomethylation and breast cancer were estimated using a logistic regression model. Results: Compared with women in the highest tertile of global methylation level, ORs for the second and lowest tertiles were 1.87 (95% CI=1.20–2.91) and 2.86 (95% CI=1.85–4.44), respectively. Global methylation levels were significantly lower in cases than controls, regardless of the hormone receptor status of the cancer (all P values for trend <0.05). Interpretation: These findings suggest that the global methylation level of peripheral blood leukocyte DNA is low in patients with breast cancer and may be a potential biomarker for breast cancer risk.

Epithelial–mesenchymal transition (EMT) has a major role in cancer progression, as well as normal organ development and human pathology such as organ fibrosis and wound healing. Here, we performed a gene expression array specialized in EMT of colorectal cancer (CRC). From a comprehensive gene expression analysis using epithelial- and mesenchymal-like CRC cell lines, and following the ontology (GO) analysis, SIX1 gene was identified to be an EMT-related gene in CRC. Using SW480 cells stably transfected with a SIX1 expression construct and their control counterparts, we demonstrated that SIX1 overexpression represses CDH1 expression and promotes EMT in CRC. SIX1 -induced CDH1 repression and EMT in CRC cells were correlated at least in part with posttranscriptional ZEB1 activation and miR-200 -family transcriptional repression. In primary tumors of CRC, in accord with the functional findings, aberrant expression of SIX1 in cancer cells was observed at the disruption of the basement membrane and at the tumor invasive front, where tumor cells underwent EMT in vivo . Taken together, SIX1 overexpression is suggested to occur in carcinogenesis, and contribute to repression of CDH1 expression and promotion of EMT partly through repression of miR-200 -family expression and activation of ZEB1 in CRC.

BACKGROUND In Japan, endoscopic mucosal resection (EMR) is accepted as a treatment option for cases of early gastric cancer (EGC) where the probability of lymph node metastasis is low. The results of EMR for EGC at the National Cancer Center Hospital, Tokyo, over a 11 year period are presented. METHODS EMR was applied to patients with early cancers up to 30 mm in diameter that were of a well or moderately histologically differentiated type, and were superficially elevated and/or depressed (types I, IIa, and IIc) but without ulceration or definite signs of submucosal invasion. The resected specimens were carefully examined by serial sections at 2 mm intervals, and if histopathology revealed submucosal invasion and/or vessel involvement or if the resection margin was not clear, surgery was recommended. RESULTS Four hundred and seventy nine cancers in 445 patients were treated by EMR from 1987 to 1998 but submucosal invasion was found on subsequent pathological examination in 74 tumours. Sixty nine percent of intramucosal cancers (278/405) were resected with a clear margin. Of 127 cancers without “complete resection”, 14 underwent an additional operation and nine were treated endoscopically; the remainder had intensive follow up. Local recurrence in the stomach occurred in 17 lesions followed conservatively, in one lesion treated endoscopically, and in five lesions with complete resection. All tumours were diagnosed by follow up endoscopy and subsequently treated by surgery. There were no gastric cancer related deaths during a median follow up period of 38 months (3–120 months). Bleeding and perforation (5%) were two major complications of EMR but there were no treatment related deaths. CONCLUSION In our experience, EMR allows us to perform less invasive treatment without sacrificing the possibility of cure.

Sedentary time (ST) is associated with mortality independent of moderate-to-vigorous physical activity in patients with COPD. The proper processing methods for the measurement data and factors related to ST are still unknown. We investigated several conditions for determining the proper processing of ST accelerometric data and created a reference equation for ST using ST-related factors. In Study 1, we evaluated the minimum required number of days to obtain repeatability at different measurement times and assessed the effects of rainy days or weekend days on ST in patients with COPD. In Study 2, we detected the ST-related factors among 28 parameters and created a reference equation for ST using the detected factors. In Study 1, 38 patients with stable COPD were analyzed. The minimum number of days required for repeatability was 3 for 8-h wearing and 2 for 10-h wearing. The ST was significantly prolonged on rainy days, but not on weekends. In Study 2, 216 patients with stable COPD were analyzed. BMI, FEV1%pred, 6MWD, and mMRC were detected as ST-related factors, and a reference equation could be created using these four factors. The equation was validated for patients whose ST was ≥ 6 h. By using properly processed measurement data of ST, we created a reference equation for assessing ST that is expected to be useful for providing individual guidance on the shortening of ST to patients with COPD.

We use data from the 2002 International Social Survey Programme, with roughly 42,000 individuals nested within twenty-nine countries, to examine the determinants of happiness in a comparative perspective. We hypothesize that social democratic welfare states redistribute happiness among policytargeted demographic groups in these countries. The redistributive properties of the social democratic welfare states generate an alternate form of \"happiness inequality\" in which winners and losers are defined by marital status, presence of children, and income. We apply multilevel modeling and focus on public social expenditures (as percentage of GDP) as proxy measures of state intervention at the macro level, and happiness as the specific measure of welfare outcome at the micro level. We find that aggregate happiness is not greater in the social democratic welfare states, but happiness closely reflects the redistribution of resources in these countries. Happiness is redistributed from low-risk to high-risk individuals. For example, women with small children are significantly happier, but single persons are significantly less happy in the welfare states. This suggests that the pro-family ideology of the social democratic welfare states protects families from social risk and improves their well-being at the cost of single persons. Further, we find that the happiness gap between high-versus low-income earners is considerably smaller in the social democratic welfare states, suggesting that happiness is redistributed from the privileged to the less privileged.

The first tunable fibre ring laser in the 1700 nm wavelength region has been developed. To achieve this fibre laser, a Tm3+–Tb3+-doped fibre is used as the active fibre, along with a tunable bandpass filter. A fibre ring laser that consisted of a 1.2/1.7 μm band wavelength division multiplexing coupler, a tunable bandpass filter, an active fibre and one 1.21 μm pump laser diode has been realised. A wide tuning wavelength band of 130.4 nm (from 1635.6 to 1766.0 nm) was achieved with a launched pump power of over ∼ 30 mW. The lasing threshold pump power at 1716 nm was ∼ 9 mW.

Background Whether proton pump inhibitors (PPIs) relieve heartburn or precordial pain after endoscopic resection (ER) for esophageal squamous cell carcinoma (ESCC) remains unclear. The aim of this study was to investigate the efficacy of PPI therapy for these symptoms after ER for ESCC. Methods We conducted a multicenter prospective randomized controlled trial among 15 hospitals in Japan. In total, 229 patients with cT1a ESCC were randomly assigned to receive PPI therapy for 5 weeks after ER (the PPI group, n  = 115) or follow-up without PPI therapy (the non-PPI group, n  = 114). The primary end point was the incidence of gastroesophageal reflux disease (GERD)-like symptoms after ER from a self-reported questionnaire (Frequency Scale for Symptoms of GERD). Secondary end points were ulcer healing rate at 5 weeks, incidence of pain, improvement rate of symptoms in those who started PPI therapy because of GERD-like symptoms in the non-PPI group, and adverse events. Results No significant difference was observed in the incidence of GERD-like symptoms after ER between the non-PPI and PPI groups (30 % vs 34 %, respectively). No significant differences were observed in the ulcer healing rate at 5 weeks (84 % vs 85 %) and incidence of pain within 1 week (36 % vs 45 %). In nine of ten patients (90 %) who started PPI therapy because of GERD-like symptoms in the non-PPI group, PPI administration relieved GERD-like symptoms. No adverse events related to PPI administration were observed. Conclusion PPI therapy is not efficacious in reducing symptoms and did not promote healing of ulcers in patients undergoing ER for ESCC.

To improve physical activity (PA) in patients with chronic obstructive pulmonary disease (COPD), providing a target PA value based on the individual patient's condition may be a useful interventional strategy. However, to determine the target value, a predictive PA value for each patient is required. What is the reference equation consisting of PA-related factors to determine the predictive PA value for each patient with COPD? In this prospective cross-sectional observational study, we measured the PA with a triaxial accelerometer and several other factors including demographic factors, pulmonary function, dyspnea, exercise capacity, muscle strength, nutrition, and indicators of several comorbidities in stable Japanese outpatients with COPD aged ≥40 years old and detected PA-related factors by a multiple regression analysis and stepwise method. We created reference equations for four indices of PA using multiple linear regression equations. Two hundred and twenty-seven patients were registered. The equations of duration at ≥2.0 metabolic equivalents (METs) and step count consisted of 4 factors: 6-minute walk distance, modified Medical Research Council dyspnea scale, anxiety score of the Hospital Anxiety and Depression Scale, and the forced expiratory volume in 1 second % of predicted value. Those of duration at ≥3.0 METs and total activity at ≥3.0 METs consisted of 5 factors: the above 4 factors and age or brain natriuretic peptide. There was no fixed bias or proportional bias between the measured and predictive values in patients with non-high measured PA values. We determined reference equations for four indicators of PA using PA-related factors in Japanese patients with COPD. The predictive values calculated using the equations could be useful for deciding target PA values for each patient. UMIN-CTR; No.: UMIN000025459; URL: https://www.umin.ac.jp/ctr/index.htm.