EPA,not DHA,prevents fibrosis in pressure overload-induced heart failure: potential role of free fatty acid receptor 4

Heart failure with preserved ejection fraction (HFpEF) is half of all HF, but standard HF therapies are ineffective. Diastolic dysfunction, often secondary to interstitial fibrosis, is common in HFpEF. Previously, we found that supra-physiologic levels of ω3-PUFAs produced by 12 weeks of ω3-dietary supplementation prevented fibrosis and contractile dysfunction following pressure overload [transverse aortic constriction (TAC)], a model that resembles aspects of remodeling in HFpEF. This raised several questions regarding ω3-concentration-dependent cardioprotection, the specific role of EPA and DHA, and the relationship between prevention of fibrosis and contractile dysfunction. To achieve more clinically relevant ω3-levels and test individual ω3-PUFAs, we shortened the ω3-diet regimen and used EPA- and DHA-specific diets to examine remodeling following TAC. The shorter diet regimen produced ω3-PUFA levels closer to Western clinics. Further, EPA, but not DHA, prevented fibrosis following TAC. However, neither ω3-PUFA prevented contractile dysfunction, perhaps due to reduced uptake of ω3-PUFA. Interestingly, EPA did not accumulate in cardiac fibroblasts. However, FFA receptor 4, a G protein-coupled receptor for ω3-PUFAs, was sufficient and required to block transforming growth factor β1-fibrotic signaling in cultured cardiac fibroblasts, suggesting a novel mechanism for EPA. In summary, EPA-mediated prevention of fibrosis could represent a novel therapy for HFpEF.     

Indoor environmental study and post occupancy evaluation in an office environment

1. 1. The objective of this paper is to investigate the indoor environment from the viewpoint of interaction between physical environment and the human responses. The field survey has been conducted over 1 year.

2. 2. A continuous measurement has been carried out for 1 week and distribution of variables have been measured for 1 day.

3. 3. The attitude of workers was investigated by a questionnaire.

4. 4. As the result, average luminance represented more than 1000 lx in the new building, in contrast with less tha 300 lx in the existing building.

5. 5. There was a significant difference of the occupants' response to the light environment between the two buildings.

6. 6. Measured thermal conditions are on the edge of the ASHRAE comfort envelope in summer, and in the neighborhood of the lower dry limit of the envelope in spring.

7. 7. The occupants' evaluations were remarkably changed before and after the moving. The office environment is better than that of the factory.

Side reaction in peptide synthesis. Formation of oxazolidone derivatives

2-Oxazolidone derivatives formed through an intramolecular reaction in the process of alkaline treatment of urethane-type N-protected peptides of which the N-terminal residues were Ser or Thr having unprotected hydroxyl groups. In oder to avoid this side reaction, the esters of these peptides could be cleaved by enzymatic hydrolyses instead of saponification.     

建立以TK基因为标记将外源基因导入臭曲霉（Asper—gillus...

A new system for selection of transformed Aspergillus foetidus was reported. In this system, TK- A. foetidus which were constructed by homologous recombination of mutated TK gene of vaccinia virus with TK gene of A. foetidus were screened by adding BUdR in agar plates. Conditions for screen of TK+ A. foetidus strain, transformation of A. foetidus and selection of transformed TK- A. foetidus have been studied. By using this system, several transformed A. foetidus which contained HBsAg gene derived bf a promoter H8 cloned from genomic DNA of A. foetidus were isolated. It was demonstrated that HBsAg gene was integrated into the chromosome DNA of A. foetidus by Southern blot after many passages of spores. ELISA showed that HBsAg was positive in the growth medium (p/n = 20). The 22 nm particles which were very similar to the HBsAg particles in human serum were found in the growth medium by immunoelectromicroscope. Western blot also gave the specific bands. All these data showed that HBsAg gene was expressed in A. foetidus and the products were secreted into the growth medium. The selection system using TK gene as marker could generally be used to study the expression of foreign gene in A. foetidus.     

Enhanced catalytic efficiency and enantioselectivity of epoxide hydrolase from Agrobacterium radiobacter AD1 by iterative saturation mutagenesis for (R)-epichlorohydrin synthesis

Applied Microbiology and Biotechnology - Enantioselective hydrolysis of epoxides by epoxide hydrolase (EH) is one of the most attractive approaches for the synthesis of chiral epoxides. So far,...     

Nickel chloride inhibits the DNA repair of UV-treated but not methyl methanesulfonate-treated chinese hamster ovary cells

Nickel, a human carcinogen, has been shown to enhance the cytotoxicity, mutagenicity, and sister-chromatid exchanges (SCE) induced by ultraviolet (UV) light but not by methyl methanesulfonate (MMS). To verify that the cocytotoxicity and cogenotoxicity of nickel are correlated with its inhibition on DNA repair, the effects of nickel on the DNA repair induced by UV and by MMS have been investigated. Our analyses of DNA repair of single-strand breaks by alkaline elution and alkaline sucrose sedimentation indicate that nickel inhibited the DNA repair in UV-treated, but not in MMS-treated cells. Therefore, the inhibition of DNA repair seems to play an important role in the cocytotoxicity and comutagenicity of nickel. However, the inhibition of DNA repair seems not to play a decisive role in enhancing SCE, because we have previously shown that arsenite inhibits the UV-induced DNA repair, but has no enhancing effect on the UV-induced SCE. Our results also show that nickel had obvious inhibitory effects on DNA ligation and postreplication repair, but had no apparent effect on nucleotide excision and DNA polymerization in the UV repair. The results of the DNA ligation inhibition by nickel in UV but not in MMS repair suggest that different ligases are used in the DNA repair of UV- and MMS-induced damages.