10 research outputs found
Genome sequence analysis of new plum pox virus isolates from Japan
Objective To find mutations that may have recently occurred in Plum pox virus (PPV), we collected six PPV-infected plum/peach trees from the western part of Japan and one from the eastern part. After sequencing the full-length PPV genomic RNAs, we compared the amino acid sequences with representative isolates of each PPV strain. Results All new isolates were found to belong to the PPV-D strain: the six isolates collected from western Japan were identified as the West-Japan strain while the one collected from eastern Japan as the East-Japan strain. Amino acid sequence analysis of these seven isolates suggested that the 1407th and 1529th amino acid residues are characteristic of the West-Japan and the East-Japan strains, respectively. Comparing them with the corresponding amino acid residues of the 47 non-Japanese PPV-D isolates revealed that these amino acid residues are undoubtedly unique. A further examination of the relevant amino acid residues of the other 210 PPV-D isolates collected in Japan generated a new hypothesis regarding the invasion route from overseas and the subsequent diffusion route within Japan: a PPV-D strain might have invaded the western part of Japan from overseas and spread throughout Japan
Diol Dehydratase-Reactivase Is Essential for Recycling of Coenzyme B<sub>12</sub> in Diol Dehydratase
Holoenzymes of adenosylcobalamin-dependent
diol and glycerol dehydratases
undergo mechanism-based inactivation by glycerol and O<sub>2</sub> inactivation in the absence of substrate, which accompanies irreversible
cleavage of the coenzyme Co–C bond. The inactivated holodiol
dehydratase and the inactive enzyme·cyanocobalamin complex were
(re)Âactivated by incubation with NADH, ATP, and Mg<sup>2+</sup> (or
Mn<sup>2+</sup>) in crude extracts of <i>Klebsiella oxytoca</i>, suggesting the presence of a reactivating system in the extract.
The reducing system with NADH could be replaced by FMNH<sub>2</sub>. When inactivated holoenzyme or the enzyme·cyanocobalamin complex,
a model of inactivated holoenzyme, was incubated with purified recombinant
diol dehydratase-reactivase (DD-R) and an ATP:cobÂ(I)Âalamin adenosyltransferase
in the presence of FMNH<sub>2</sub>, ATP, and Mg<sup>2+</sup>, diol
dehydratase activity was restored. Among the three adenosyltransferases
(PduO, EutT, and CobA) of this bacterium, PduO and CobA were much
more efficient for the reactivation than EutT, although PduO showed
the lowest adenosyltransfease activity toward free cobÂ(I)Âalamin. These
results suggest that (1) diol dehydratase activity is maintained through
coenzyme recycling by a reactivating system for diol dehydratase composed
of DD-R, PduO adenosyltransferase, and a reducing system, (2) the
releasing factor DD-R is essential for the recycling of adenosycobalamin,
a tightly bound, prosthetic group-type coenzyme, and (3) PduO is a
specific adenosylating enzyme for the DD reactivation, whereas CobA
and EutT exert their effects through free synthesized coenzyme. Although
FMNH<sub>2</sub> was mainly used as a reductant in this study, a natural
reducing system might consist of PduS cobalamin reductase and NADH
Comparison of gemcitabine-based chemotherapies for advanced biliary tract cancers by renal function: an exploratory analysis of JCOG1113
Abstract JCOG1113 is a randomized phase III trial in patients with advanced biliary tract cancers (BTCs) (UMIN000001685), and gemcitabine plus S-1 (GS) was not inferior to gemcitabine plus cisplatin (GC). However, poor renal function often results in high toxicity of S-1. Therefore, we examined whether GS can be recommended for patients with low creatinine clearance (CCr). Renal function was classified by CCr as calculated by the Cockcroft-Gault formula: high CCr (CCr ≥ 80 ml/min) and low CCr (80 > CCr ≥ 50 ml/min). Of 354 patients, 87 patients on GC and 91 on GS were included in the low CCr group, while there were 88 patients on GC and 88 patients on GS in the high CCr group. The HR of overall survival for GS compared with GC was 0.687 (95% CI 0.504–0.937) in the low CCr group. Although the total number of incidences of all Grade 3–4 non-haematological adverse reactions was higher (36.0% vs. 11.8%, p = 0.0002), the number of patients who discontinued treatment was not different (14.1% vs. 16.9%, p = 0.679) for GS compared with GC in the low CCr group. This study suggests that GS should be selected for the treatment of advanced BTC patients with reduced renal function