Construction of 7-Diethylaminocoumarins Promoted by an Electron-Withdrawing Group.

The coumarin skeleton has been a focus of attention for many years, and its fluorescence properties vary depending on the substituents. Fluorescent coumarin derivatives are useful tools for many strategies have been developed for their synthesis. Although 7-diethylaminocoumarin has excellent fluorescence properties, it is unstable. We have developed a facile strategy for the synthesis of 7-diethylaminocoumarin derivatives by increasing the electrophilicity of the ynone moiety to promote nucleophilic addition reactions and cyclization. The reaction tolerates a variety of substitutions at the 4-position.

Synthesis of a Coumarin-Based PPARγ Fluorescence Probe for Competitive Binding Assay.

Peroxisome proliferator-activated receptor γ (PPARγ) is a molecular target of metabolic syndrome and inflammatory disease. PPARγ is an important nuclear receptor and numerous PPARγ ligands were developed to date; thus, efficient assay methods are important. Here, we investigated the incorporation of 7-diethylamino coumarin into the PPARγ agonist rosiglitazone and used the compound in a binding assay for PPARγ. PPARγ-ligand-incorporated 7-methoxycoumarin, 1, showed weak fluorescence intensity in a previous report. We synthesized PPARγ-ligand-incorporating coumarin, 2, in this report, and it enhanced the fluorescence intensity. The PPARγ ligand 2 maintained the rosiglitazone activity. The obtained partial agonist 6 appeared to act through a novel mechanism. The fluorescence intensity of 2 and 6 increased by binding to the ligand binding domain (LBD) of PPARγ and the affinity of reported PPARγ ligands were evaluated using the probe.

Tracking long-distance migration of marine fishes using compound-specific stable isotope analysis of amino acids.

The long-distance migrations by marine fishes are difficult to track by field observation. Here, we propose a new method to track such migrations using stable nitrogen isotopic composition at the base of the food web (δ15 NBase ), which can be estimated by using compound-specific isotope analysis. δ15 NBase exclusively reflects the δ15 N of nitrate in the ocean at a regional scale and is not affected by the trophic position of sampled organisms. In other words, δ15 NBase allows for direct comparison of isotope ratios between proxy organisms of the isoscape and the target migratory animal. We initially constructed a δ15 NBase isoscape in the northern North Pacific by bulk and compound-specific isotope analyses of copepods (n = 360 and 24, respectively), and then we determined retrospective δ15 NBase values of spawning chum salmon (Oncorhynchus keta) from their vertebral centra (10 sections from each of two salmon). We then estimated the migration routes of chum salmon during their skeletal growth by using a state-space model. Our isotope tracking method successfully reproduced a known chum salmon migration route between the Okhotsk and Bering seas, and our findings suggest the presence of a new migration route to the Bering Sea Shelf during a later growth stage.

Response of N2O production rate to ocean acidification in the western North Pacific.

Ocean acidification induced by the increase of anthropogenic CO2 emissions has a profound impact on marine organisms and biogeochemical processes.1 The response of marine microbial activities to ocean acidification might play a crucial role in the future evolution of air-sea fluxes of biogenic gases such as nitrous oxide (N2O), a strong greenhouse gas and the dominant stratospheric ozone-depleting substance.2 Here, we examine the response of N2O production from nitrification to acidification in a series of incubation experiments conducted in subtropical and subarctic western North Pacific. The experiments show that, when pH was reduced, the N2O production rate during nitrification measured at subarctic stations increased significantly whereas nitrification rates remained stable or decreased. Contrary to what was previously thought, these results suggest that the effect of ocean acidification on N2O production during nitrification and nitrification rates are likely uncoupled. Collectively these results suggest that, if seawater pH continues to decline at the same rate, ocean acidification could increase the marine N2O production during nitrification in subarctic North Pacific by 185 to 491% by the end of the century.

Serotonergic modulation of neuronal activity in the nucleus accumbens following repeated methamphetamine administration in rats.

Electrophysiological studies were performed to determine whether serotonergic modulation in the nucleus accumbens (NAcc) was affected after repeated methamphetamine (MAP) administration. NAcc slices (400 µm) from Wistar rats administered MAP (5 mg/kg) or saline once daily for 5 days were prepared 1, 5, or 10 days after the final injection. Population spikes (PS) induced by local stimulation of NAcc were recorded. PS inhibition by serotonin was significantly attenuated in the MAP group at 5 days but did not differ at 1 or 10 days. We next analyzed the effects of serotonin receptor subtype (5-HT1A,2,3,4,6,7)-selective agonists of PS. Differences between saline and MAP groups in 5-HT1A,2,3,4,6 receptor agonist-induced changes of PS were small or not significant. Interestingly, 5-HT7 receptor agonists significantly enhanced PS in the MAP group. Changes in the secondary messenger system related to 5-HT7 receptors were also investigated. Adenylate cyclase activator-induced PS enhancements were significantly larger in the MAP group. However, dibutyryl-cAMP-induced PS enhancement was not significantly different. In conclusion, 5-HT-induced inhibition of PS in NAcc was attenuated 5 days after repeated MAP treatment: the change in the effect of 5-HT was probably due to enhancement of the excitatory modulation via the 5-HT7 receptor with adenylate cyclase signal transduction systems.

Mental, physical, dietary, and nutritional effects on irritable bowel syndrome in young Japanese women.

OBJECTIVE: Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder. The pathogenesis of IBS is multifactorial. The aim of this study was to investigate the prevalence of IBS using the Rome III criteria in young Japanese women and to assess the effects of mental, physical, dietary and nutritional factors on IBS. METHODS: In this cross-sectional study, data obtained from self-administered questionnaires, including age, height, weight, lifestyle, food habits, anxiety and depressive states and IBS-related symptoms, were analyzed in 245 participants. An established semiquantitative questionnaire available for clinical investigation (FFQg) was used to obtain a detailed assessment of food intake and the physical activity levels. RESULTS: The prevalence of IBS was 12.0%. Of the IBS participants, constipation-predominant IBS (25.0%) was more prevalent than the diarrhea-predominant subtype (17.9%). The IBS participants had lower body mass indices, consumed less eggs and milk and were more physically active than the non-IBS participants. In addition, an anxiety state was more common in the IBS participants. Those who hesitated with evacuation of stool and who thought that there is an association between abdominal symptoms, such as constipation and diarrhea, and menstruation were more predominant among the IBS participants. The percentage of individuals who reported often rushing to the toilet within the past year and experiencing borborygmus (rumbling stomach) was greater among the IBS participants. A logistic regression analysis revealed that milk intake was an independent predictor of IBS. CONCLUSION: The prevalence of IBS observed in this study was similar to that reported in previous studies conducted in Japan and other countries. Mental, physical, dietary and nutritional factors have an impact on IBS.