Biosynthetic Machinery of Diterpene Pleuromutilin Isolated from Basidiomycete Fungi

The diterpene pleuromutilin is a ribosome‐targeting antibiotic isolated from basidiomycete fungi, such as Clitopilus pseudo‐pinsitus. The functional characterization of all biosynthetic enzymes involved in pleuromutilin biosynthesis is reported and a biosynthetic pathway proposed. In vitro enzymatic reactions and mutational analysis revealed that a labdane‐related diterpene synthase, Ple3, catalyzed two rounds of cyclization from geranylgeranyl diphosphate to premutilin possessing a characteristic 5–6–8‐tricyclic carbon skeleton. Biotransformation experiments utilizing Aspergillus oryzae transformants possessing modification enzyme genes allowed the biosynthetic pathway from premutilin to pleuromutilin to be proposed. The present study sets the stage for the enzymatic synthesis of natural products isolated from basidiomycete fungi, which are a prolific source of structurally diverse and biologically active terpenoids.     

Thermal and mechanical properties of (U,Er)O2

Erbium is considered as a slow burnable poison suitable for use in light water reactors (LWRs). Addition of a small amount of Er₂O₃ to all UO₂ pellets will make it possible to develop super high burnup fuels in Japanese nuclear facilities which are now under the restriction of the upper limit of ²³⁵U enrichment. When utilizing the (U,Er)O₂ fuels, it is very important to understand the thermal and mechanical properties. Here we show the characterization results of (U_1−xEr_x)O₂ (0 ? x ? 0.1). We measured their thermal and mechanical properties and investigated the effect of Er addition on these properties of (U,Er)O₂. All Er completely dissolved in UO₂, and the lattice parameter decreased linearly with the Er content. Both the thermal conductivity and Young’s modulus of (U,Er)O₂ decreased with the Er content. These results would be useful for us in evaluating the performance of the (U,Er)O₂ fuels in LWRs.     

Survey of pesticide residues in baby foods (1999.4-2005.6)

A survey of pesticide residues in 316 baby foods on the Tokyo market from April 1999 to June 2005 was carried out. Fifteen kinds of pesticides, including organophosphorus, organochlorine, carbamate, pyrethroid and others, were detected between at levels Tr (below 0.01 ppm) and 0.55 ppm from 28 samples. The baby foods in which residual pesticides were detected were produced from flour, leaf vegetable and fruits. The pesticides were detected in baby foods produced with minimal processing, such as straining and squeezing. For the baby foods containing pesticides, the amounts of intake of the pesticides were calculated from the recommended servings, and compared with the ADI values. Residual pesticide levels in baby food were between 0.06 and 16.6% of the ADI. Therefore, these foods should be safe in normal usage.     

Raman Spectroscopy of Oral Candida Species: Molecular-Scale Analyses,Chemometrics, and Barcode Identification

Oral candidiasis, a common opportunistic infection of the oral cavity, is mainly caused by the following four Candida species (in decreasing incidence rate): Candida albicans, Candida glabrata, Candida tropicalis, and Candida krusei. This study offers in-depth Raman spectroscopy analyses of these species and proposes procedures for an accurate and rapid identification of oral yeast species. We first obtained average spectra for different Candida species and systematically analyzed them in order to decode structural differences among species at the molecular scale. Then, we searched for a statistical validation through a chemometric method based on principal component analysis (PCA). This method was found only partially capable to mechanistically distinguish among Candida species. We thus proposed a new Raman barcoding approach based on an algorithm that converts spectrally deconvoluted Raman sub-bands into barcodes. Barcode-assisted Raman analyses could enable on-site identification in nearly real-time, thus implementing preventive oral control, enabling prompt selection of the most effective drug, and increasing the probability to interrupt disease transmission.     

Mirror system for a VUV beam line at the Photon Factory

An optical reflection system for conveying synchrotron radiation to experimental stations with a grasshopper monochromator, a constant deviation monochromator, a Seya-Namioka monochromator, and a double crystal monochromator in a typical VUV beam line attached to the Photon Factory ring is described. In particular, a system for precision adjustment of the orientation and location of a mirror in ultra-high vacuum is shown in detail. The experience gained from the first two years of operation is described.     

Degradation of 1,1,1-trichloro-2,2-bis (4-chlorophenyl) ethane (DDT) by brown-rot fungi

Twelve species of brown-rot fungi (BRF) have been investigated for their ability to degrade 1,1,1-trichloro-2,2-bis (4-chlorophenyl) ethane (DDT). In potato dextrose broth (PDB) medium, Gloeophyllum trabeum, Fomitopsis pinicola and Daedalea dickinsii showed a high ability to degrade DDT. 1,1-Dichloro-2,2-bis (4-chlorophenyl) ethane (DDD), 1,1-dichloro-2,2-bis (4-chlorophenyl) ethylene (DDE) and 4,4-dichlorobenzophenone (DBP) were detected as metabolic products of DDT degradation by G. trabeum in PDB medium. The DDT degradation pathway in G. trabeum is proposed, which differs from the proposed pathways in bacteria and other fungi, particularly in the transformation of DDE to DDD. On the other hand, DBP was not detected as a metabolic product of DDT degradation in FeSO(4)-deficient cultures of G. trabeum, whereas DDE and DDD were detected, indicating the involvement of an iron-dependent reaction. Only DBP was detected from DDT, DDE and DDD degradation via a chemical Fenton reaction under conditions similar to those in G. trabeum cultures. These compounds may be directly transformed to DBP via a Fenton reaction.     

Synthesis of 5-Hydroxy-3′,4′,7-trimethoxyflavone and Related Compounds and Elucidation of Their Reversal Effects on BCRP/ABCG2-Mediated Anticancer Drug Resistance

3′,4′,7-Trimethoxyflavone (TMF) has been reported to show a potent reversal effect on drug resistance mediated by breast cancer resistance protein (BCRP)/ATP-binding cassette subfamily G member 2 (ABCG2). In this study, we designed and synthesized five derivatives with either a hydroxy group or a fluorine atom at C-5 and several kinds of capping moiety at the C-7 hydroxy group, on the same 3′,4′-dimethoxy-substituted flavone skeleton. We subsequently evaluated the efficacies of these compounds against BCRP-expressing human leukaemia K562/BCRP cells. Reversal of drug resistance was expressed as the concentration of compound causing a twofold reduction in drug sensitivity (RI₅₀). Of the synthesized compounds, the reversal effect of 5-hydroxy-3′,4′,7-trimethoxyflavone (HTMF, RI₅₀ 7.2 nm ) towards 7-ethyl-10-hydroxycamptothecin (SN-38) was stronger than that of TMF (RI₅₀ 18 nm ). Fluoro-substituted 5-fluoro-3′,4′,7-trimethoxyflavone (FTMF, RI₅₀ 25 nm ) and monoglycosylated 7-(β-glucosyloxy)-5-hydroxy-3′,4′-dimethoxyflavone (GOHDMF, 91 nm ) also exhibited reversal effects, whereas the di- and triglycoside derivatives did not. TMF, HTMF and FTMF at 0.01–10 μm upregulated the K562/BCRP cellular accumulation of Hoechst 33342 nuclear staining dye. In addition, western blotting revealed that treatment of K562/BCRP cells with 0.1 μm TMF, HTMF or FTMT suppressed the expression of BCRP. HTMF showed the strongest inhibition of BCRP-mediated efflux and suppression of BCRP expression of the three effective synthesized flavones.     

Sorption and desorption behavior of hydrogen isotopes from tungsten deposits caused by deuterium gas or deuterium plasma exposure

To understand the behavior of hydrogen isotopes in deposits formed on plasma-facing wall is an important issue for development of a fusion reactor. In this study, sorption/desorption behaviors of hydrogen isotopes when tungsten deposits were exposed to deuterium gas or deuterium plasma at 300 °C were investigated. Samples of tungsten deposits were produced by the sputtering method using hydrogen plasma. After deuterium gas exposure or deuterium plasma exposure, the desorption behavior of hydrogen isotopes from the deposit was observed by the thermal desorption spectroscopy method. It was found that not a small amount of deuterium is retained in tungsten deposit by not only the plasma exposure but also the gas exposure while the amount of hydrogen incorporated in the deposit during sputter-deposition process is reduced. The amount of deuterium retained in the deposit by the plasma exposure was larger than that by the gas exposure in the experimental conditions in this work. The amount of hydrogen left after deuterium plasma exposure was larger than that after deuterium gas exposure.     

Local Lattice Distortion and Photo-Induced Phase Transition in Transition-Metal Compounds with Orbital Degeneracy

Transition-metal compounds with spin, charge, and orbital degrees of freedom tend to have frustrated electronic states coupled with local lattice distortions and to show drastic response against external stimuli such as optical excitation. By means of photoemission spectroscopy, we have studied the electronic states of transition-metal compounds with corner-sharing and edge-sharing MX ₆ octahedra (M=transition metal, X=O, S, Se, Br) such as prerovskite-type Pr_0.55(Ca_1−y Sr _y )_0.45MnO₃ and Cs₂Au₂Br₆, spinel-type CuIr₂S₄, and quasi-one-dimensional Ta₂NiSe₅. In the perovskite compounds with corner-sharing octahedra, the charge-orbital states are stabilized by Jahn–Teller or breathing-type lattice distortions and can be destroyed by optical excitations. On the other hand, the charge-orbital states in the edge-sharing systems are stabilized by dimer formation and tend to be robust against optical excitations. Based on the photoemission results, we will discuss effects of local lattice distortions on the excitonic states obtained by optical excitations as well as those in ground states.