Antitumor studies. Part 1: Design, synthesis, antitumor activity, and AutoDock study of 2-deoxo-2-phenyl-5-deazaflavins and 2-deoxo-2-phenylflavin-5-oxides as a new class of antitumor agents

Novel 2-deoxo-2-phenyl-5-deazaflavins and 2-deoxo-2-phenylflavin-5-oxides were prepared as a new class of antitumor agents and showed significant antitumor activities against NCI-H 460, HCT 116, A 431, CCRF-HSB-2, and KB cell lines. In vivo investigation, 2-deoxo-10-methyl-2-phenyl-5-deazaflavin exhibited the effective antitumor activity against A 431 human adenocarcinoma cells transplanted subcutaneously into nude mouse. Furthermore, AutoDock study has been done by binding of the flavin analogs into PTK pp60(c-src), where a good correlation between their IC50 and AutoDock binding free energy was exhibited. In particular, 2-deoxo-2-phenylflavin-5-oxides exhibited the highest potential binding affinity within the binding pocket of PTK

Association of melanocortin 1 receptor gene (MC1R) polymorphisms with skin reflectance and freckles in Japanese.

Most studies on the genetic basis of human skin pigmentation have focused on people of European ancestry and only a few studies have focused on Asian populations. We investigated the association of skin reflectance and freckling with genetic variants of melanocortin 1 receptor (MC1R) gene in Japanese. DNA samples were obtained from a total of 653 Japanese individuals (ages 19-40 years) residing in Okinawa; skin reflectance was measured using a spectrophotometer and freckling status was determined for each individual. Lightness index (L*) and freckling status were not correlated with age, body mass index or ancestry (Ryukyuan or Main Islanders of Japan). Among the 10 nonsynonymous variants that were identified by direct sequencing of the coding region of MC1R, two variants--R163Q and V92M--with the derived allele frequencies of 78.6 and 5.5%, respectively, were most common. Multiple regression analysis showed that the 163Q allele and the presence of nonsynonymous rare variants (allele frequencies <5%) were significantly associated with an increase in sex-standardized skin lightness (L* of CIELAB (CIE 1976 (L*a*b*) color space)) of the inner upper arm. Relative to the 92V allele, the 92M allele was significantly associated with increased odds of freckling. This is the first study to show an association between the 163Q allele and skin reflectance values; this association indicated that light-toned skin may have been subjected to positive selection in East Asian people

Research on feeding standard of beef cattle and feedstuff database in the Indochinese peninsula

application/pdfAt Khon Kaen in northeastern Thailand, energy metabolism in cattle was studied by a respiration trial system using a ventilated flow-through method with a face mask built with technical and financial support of Japan International Research Center for Agricultural Sciences (JIRCAS). Energy values of locally available feed resources have also been obtained from digestion and respiration trials. JIRCAS also had already completed a new ventilated head-hood apparatus for energy balance trials and started the data accumulation concerning the energy value of Pangola grass (Digitaria eriantha) with Brahman beef steers. As for the energy balance measurement technique, JIRCAS supports the establishment of feeding standard by measuring the energy requirement of domestic animals under the tropical environment and energy value of locally available feed resources in the Indochinese peninsula.2008年帯広農村開発教育国際セミナーシンポジウム「農業と地球環境問題に関する持続的開発のための教育」報告書boo

Structural basis for the adaptation and function of chlorophyll f in photosystem I

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Turbulent Convection Under the Influence of Rotation: Sustaining a Strong Differential Rotation

The intense turbulence present in the solar convection zone is a major challenge to both theory and simulation as one tries to understand the origins of the striking differential rotation profile with radius and latitude that has been revealed by helioseismology. The differential rotation must be an essential element in the operation of the solar magnetic dynamo and its cycles of activity, yet there are many aspects of the interplay between convection, rotation and magnetic fields that are still unclear. We have here carried out a series of 3--D numerical simulations of turbulent convection within deep spherical shells using our anelastic spherical harmonic (ASH) code on massively parallel supercomputers. These studies of the global dynamics of the solar convection zone concentrate on how the differential rotation and meridional circulation are established. We have analyzed the transport of angular momentum in establishing such differential rotation, and clarified the roles played by Reynolds stresses and the meridional circulation in this process. We have found that the Reynolds stresses are crucial in transporting angular momentum toward the equator. The effects of baroclinicity (thermal wind) have been found to have a modest role in the resulting mean zonal flows. The simulations have produced differential rotation profiles within the bulk of the convection zone that make reasonable contact with ones inferred from helioseismic inversions, namely possessing a fast equator, an angular velocity difference of about 30% from equator to pole, and some constancy along radial lines at mid-latitudes.Comment: 25 pages, 14 very low resolution figures, shortened abstract, published by ApJ. High resolution/complete version can be found at http://lcd-www.colorado.edu/sabrun/index_cv.html then Scientific Publication

Structural basis for the adaptation and function of chlorophyll f in photosystem I

Chlorophylls (Chl) play pivotal roles in energy capture, transfer and charge separation in photosynthesis. Among Chls functioning in oxygenic photosynthesis, Chl f is the most red-shifted type first found in a cyanobacterium Halomicronema hongdechloris. The location and function of Chl f in photosystems are not clear. Here we analyzed the high-resolution structures of photosystem I (PSI) core from H. hongdechloris grown under white or far-red light by cryo-electron microscopy. The structure showed that, far-red PSI binds 83 Chl a and 7 Chl f, and Chl f are associated at the periphery of PSI but not in the electron transfer chain. The appearance of Chl f is well correlated with the expression of PSI genes induced under far-red light. These results indicate that Chl f functions to harvest the far-red light and enhance uphill energy transfer, and changes in the gene sequences are essential for the binding of Chl f

The effect of anaerobic digestion in biogas plants on survival of pathogenic bacteria

application/pdfThe paper deals with the hygienic advantages of sanitation to treat dairy manure in full-scale biogas plants. Slurry samples were collected from two thermophilic biogas plants (55ºC) and two mesophilic biogas plants (38ºC) in Hokkaido, Japan. The detectable number of Coli-aerogenes group and Enterococcus in the slurries after anaerobic digestion could not be found in both thermophilic biogas plants. In both mesophilic biogas plants, however, the viable numbers of Coli-aerogenes group and Enterococcus were detected in the slurries even after anaerobic digestion. The mean decimation reduction time (T90) values of Coli-aerogenes group and Enterococcus in the slurries during mesophilic digestion were 13.3 d and 16.7 d, respectively.2009年帯広農村開発教育国際セミナーシンポジウム「農畜産物生産と地球環境に関する持続的開発のための教育」報告書boo

Responsiveness of eyes with polypoidal choroidal vasculopathy with choroidal hyperpermeability to intravitreal ranibizumab

Abstract Background To determine the role played by vascular endothelial growth factor (VEGF) in polypoidal choroidal vasculopathy (PCV) based on an interventional immunology theory. Methods Eyes with PCV were divided in a masked fashion into those with choroidal hyperpermeability (HP group) and those with normal choroidal permeability (NP group) based on the indocyanine green angiograms. The inter-rater agreement rate was evaluated using Fleiss’ kappa. Patients were treated by intravitreal ranibizumab (IVB). The central choroidal thickness and central foveal thickness (CFT) at the baseline and 7 days after the treatment were measured by optical coherence tomography. Results Among the 57 consecutive eyes diagnosed with PCV, 42 eyes of 42 patients met the inclusion criteria (21 eyes/HP group vs 21 eyes /NP group). Central choroidal thickness in HP group was significantly thicker than that in the NP group (P &lt; .001, Mann–Whitney U test). The inter-rater agreement was high with a Fleiss’ kappa = 0.95, P &lt; .0001. The percentage reduction in the CFT in HP group (14.0%) was significantly less than that in NP group (20.4%; P = .013, Mann–Whitney U test). Conclusions Eyes with PCV that are associated with choroidal hyper-permeability may not be strongly associated with VEGF-related pathology, and may not respond favorably to anti-VEGF monotherapy. </jats:sec

Kynurenic acid may underlie sex-specific immune responses to COVID-19

Coronavirus disease 2019 (COVID-19) has poorer clinical outcomes in males than in females, and immune responses underlie these sex-related differences. Because immune responses are, in part, regulated by metabolites, we examined the serum metabolomes of COVID-19 patients. In male patients, kynurenic acid (KA) and a high KA–to–kynurenine (K) ratio (KA:K) positively correlated with age and with inflammatory cytokines and chemokines and negatively correlated with T cell responses. Males that clinically deteriorated had a higher KA:K than those that stabilized. KA inhibits glutamate release, and glutamate abundance was lower in patients that clinically deteriorated and correlated with immune responses. Analysis of data from the Genotype-Tissue Expression (GTEx) project revealed that the expression of the gene encoding the enzyme that produces KA, kynurenine aminotransferase, correlated with cytokine abundance and activation of immune responses in older males. This study reveals that KA has a sex-specific link to immune responses and clinical outcomes in COVID-19, suggesting a positive feedback between metabolites and immune responses in males