硫黄で増殖したAcidthiobacillus caldus GO-1株による還元型硫黄化合物の酸化機構

The oxidation of reduced sulfur compounds was studied by using resting cells of sulfur-grown Acidithiobacillus caldus strain GO-1. The optimum pHs for the oxidation of thiosulfate, tetrathionate, sulfur, sulfite and sulfide were 2, 3, 3-6, 7 and 7, respectively. The highest oxidation rate was observed with sulfite. The oxidation rates of the reduced sulfur compounds were measured in the absence or presence of inhibitors and uncouplers. 2, 4-dinitrophenol (DNP) and carbonyl cyanide-m-chlorophenylhydrazone (CCCP) strongly inhibited the oxidations of sulfur and sulfite. N-Ethylmaleimide (NEM) strongly inhibited the oxidation of tetrathionate and sulfur. 2-heptyl-4-hydroxy-quinoline-N-oxide(HQNO) inhibited the oxidation of sulfur and sulfite. The results suggested that tetrathionate was oxidized in the periplasmic space, and sulfur and sulfite were oxidized in the cytoplasm. Pyridine ferrohemochromes prepared from the membrane of strain GO-1 cell revealed the involvement of cytochromes b and c. Ubiquinol oxidase activity was detected in strain GO-1 cell, but cytochrome c oxidase measured by using mammalian cytochrome c as an electron donor was not detected in the cell. On the basis of the results a model for the metabolism of the reduced sulfur compounds by At. caldus strain GO-1 was proposed.硫黄で増殖したAcidithiobacilluscaldusGO-1株の休止菌体を用いて，還元型硫黄化合物の酸化機構を検討した．GO-１株は，チオ硫酸，テトラチオン酸，元素硫黄，亜硫酸及び硫化物の酸化活性を持っており，その最適pHは，それぞれ２，３，３-６，７及び７であった．これらの酸化活性の中で，亜硫酸の酸化速度が最も高かった．阻害剤やアンカップラーを用いて，還元型硫黄化合物の酸化への影響を調べた結果，DNPとCCCPによる元素硫黄及び亜硫酸酸化活性の強い阻害，NEMによるテトラチオン酸及び硫黄酸化活性の強い阻害，およびHQNOによる元素硫黄及び亜硫酸酸化活性の阻害が観察された．これらの結果は，テトラチオン酸がペリプラズマで，硫黄及び亜流酸が細胞質で，それぞれ酸化されることを示唆した．細胞膜からピリジンフェロヘモクロームを調製して，シトクロームの構成成分を検討した結果，ヘムb及びcが検出された．また，末端酸化酵素の活性を検討した結果，ユビキノール酸化酵素の活性は検出されたが，哺乳類のシトクロームを用いて測定したシトクロームc酸化酵素の活性は検出されなかった．これらの結果に基づいて，At.caldusGO-１株の還元型硫黄化合物の酸化機構を考察した

Gadolinium modulates gentamicin uptake via an endocytosis-independent pathway in HK-2 human renal proximal tubular cell line

The aim of this study was to characterize the uptake mechanism of gentamicin, an aminoglycoside antibiotic, in human renal proximal tubular cell line HK-2. Sodium-dependent uptake of D-[H-3]glucose and L-[H-3]alanine was observed in HK-2 cells, indicating that the cells employed in this study retain functional characteristics of the renal proximal tubular cells. On the other hand, mRNA and protein expression of megalin, an endocytic receptor which is responsible for the internalization of gentamicin into the renal proximal tubular cells, was very faint in HK-2 cells. Various aminoglycoside antibiotics including amikacin and kanamycin inhibited the uptake of [H-3]gentamicin. Colchicine and cytochalasin D, general endocytosis inhibitors, had no significant effect on [H-3]gentamicin uptake in HK-2 cells, which was in contrast to the results observed in OK cells, a renal proximal tubular cell line expressing megalin. Furthermore, unlike OK cells, [H-3]gentamicin uptake in HK-2 cells was not inhibited by N-WASP181-200, a cationic 20-amino acid peptide. Ruthenium red, a nonspecific cation channel blocker, decreased the uptake of [H-3]gentamicin in HK-2 cells. In contrast, the trivalent cation gadolinium biphasically modulated [H-3]gentamicin uptake with a maximum increase at 0.3 mM gadolinium. The enhanced effect of gadolinium on [H-3]gentamicin uptake was independent of gadolinium-induced increase in intracellular calcium concentration. These findings indicate that gentamicin is primarily taken up via an endocytosis-independent pathway in HK-2 cells with very low expression of megalin, and that the uptake of gentamicin is modulated by gadolinium

Body mass index and colorectal cancer risk : A Mendelian randomization study

Traditional observational studies have reported a positive association between higher body mass index (BMI) and the risk of colorectal cancer (CRC). However, evidence from other approaches to pursue the causal relationship between BMI and CRC is sparse. A two-sample Mendelian randomization (MR) study was undertaken using 68 single nucleotide polymorphisms (SNPs) from the Japanese genome-wide association study (GWAS) and 654 SNPs from the GWAS catalogue for BMI as sets of instrumental variables. For the analysis of SNP-BMI associations, we undertook a meta-analysis with 36 303 participants in the Japanese Consortium of Genetic Epidemiology studies (J-CGE), comprising normal populations. For the analysis of SNP-CRC associations, we utilized 7636 CRC cases and 37 141 controls from five studies in Japan, and undertook a meta-analysis. Mendelian randomization analysis of inverse-variance weighted method indicated that a one-unit (kg/m2) increase in genetically predicted BMI was associated with an odds ratio of 1.13 (95% confidence interval, 1.06-1.20; P value <.001) for CRC using the set of 68 SNPs, and an odds ratio of 1.07 (1.03-1.11, 0.001) for CRC using the set of 654 SNPs. Sensitivity analyses robustly showed increased odds ratios for CRC for every one-unit increase in genetically predicted BMI. Our MR analyses strongly support the evidence that higher BMI influences the risk of CRC. Although Asians are generally leaner than Europeans and North Americans, avoiding higher BMI seems to be important for the prevention of CRC in Asian populations

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Wave flume testing of an oscillating-body wave energy converter with a tuned inerter

In this study, the effectiveness of an oscillating-body WEC with a tuned inerter (TI) proposed by the authors is shown through wave flume testing. The TI mechanism consisting of a tuning spring, a rotational inertial mass, and a viscous damping component is able to increase energy absorption capability by taking advantage of the resonance effect of the rotational mass. This mechanism has been recently introduced for civil structures subjected to external loadings such as earthquakes and winds to decay vibration response immediately. The authors applied this mechanism to oscillating-body WECs and showed that the proposed WEC increased the power generation performance and broadened the effective frequency range without increasing the mass of the buoy itself through numerical simulation studies. To verify the validity of the proposed WEC experimentally, a small-scale prototype of the proposed device is designed and wave flume testing is carried out with various regular wave inputs of different frequencies. The results show that the WEC with the properly adjusted TI mechanism demonstrates better power generation performance compared to the conventional WEC over a wide range of wave frequencies

Greater Progression of Age-Related Aortic Stiffening in Adults with Poor Trunk Flexibility: A 5-Year Longitudinal Study

Purpose: Having a low level of physical fitness, especially cardiorespiratory fitness, appears to accelerate age-related aortic stiffening. Whereas, some studies have reported that trunk flexibility is a component of physical fitness, it is also negatively associated with arterial stiffening independent of cardiorespiratory fitness in cross-sectional studies. However, no long-term longitudinal study has determined whether poor trunk flexibility accelerates the progression of age-related aortic stiffening. We examined trunk flexibility and aortic stiffness progression in a 5-year longitudinal study.Methods and Results: A total of 305 apparently healthy men and women participated in this study (49.6 ± 9.5 years of age). Trunk flexibility was measured using a sit-and-reach test. Aortic stiffness was assessed using carotid-femoral pulse wave velocity (cfPWV) at baseline and after 5 years. Analysis of covariance (ANCOVA) was used to assess the association of the annual rate of cfPWV across flexibility levels (low, middle, high). There were no significant differences in baseline cfPWV among the three groups (835 ± 164, 853 ± 140, 855 ± 2.68 cm/s; P = 0.577). Annual ΔcfPWV was significantly higher in the low-flexibility group than in the high-flexibility group (P = 0.009). ANCOVA revealed an inverse relationship between flexibility level and annual ΔcfPWV (14.41 ± 2.73, 9.79 ± 2.59, 2.62 ± 2.68 cm/s/year; P for trend = 0.011). Multiple regression analysis revealed that baseline sit and reach (β = −0.12, −0.70 to −0.01) was independently correlated with ΔcfPWV following adjustment for baseline peak oxygen uptake, age, sex, body fat, heart rate, and cfPWV. The 5-year change in cfPWV was not significantly correlated with 5-year change in sit-and-reach performance (P = 0.859).Conclusion: Poor trunk flexibility is associated with greater progression of age-related aortic stiffening in healthy adults. However, we failed to confirm a significant association between 5-year change in aortic stiffness and 5-year change in trunk flexibility. The association between increased age-related increase in aortic stiffness and deterioration in flexibility due to age may require observation for more than 5 years