Dicationic dithiocarbamate carbapenems with anti-MRSA activity.

A new class of 1 beta-methylcarbapenems bearing a doubly quaternarized 1,4-diazabicyclooctane (DABCO) substituted dithiocarbamate moiety at the C-2 side chain was prepared, and the biological profiles of the compounds, including in vitro and in vivo anti-MRSA activity and DHP-I susceptibility, were evaluated to identify a carbapenem derivative that was superior to BO-3482 (1). As a result, we discovered a 1 beta-methyl-2-[4-(4-carbamoylmethyl-1,4-diazabicyclo[2,2,2]octanediium-1-yl)methyl-1,2,3,6-tetrahydropyridinylthiocarbonylthio]carbapenem, 14a showing greater than 2-fold better anti-MRSA activity in a mouse infection model and 3-fold better DHP-I susceptibility as compared with BO-3482 (1).     

Synthesis, characterization and redox reactivity of l-tartrato bridged dinuclear manganese complex with 2,2′-bipyridine

A new l-tartrato manganese(III) complex was synthesized and characterized as the dinuclear dimanganese(III) structure with a stereospefically formed [Λ-Λ] absolute configuration around Mn(III) ions. The thermal and photo decomposition gave the first example of dihydrogen gas evolution besides CO and CO₂ gas associated with cis-[Mn^II(ox)(bpy)(H₂O)₂]. A proposed redox reaction proceeds from Mn(III) to Mn(II) via intermediate Mn(IV) and Mn(II) with CO anion radical species followed by oxidation of tartrate ligands.     

Albino (al) is a tetrahydrobiopterin (BH4)-deficient mutant of the silkworm Bombyx mori

Albino (al) is a lethal mutant of Bombyx mori that exhibits a colourless cuticle after the first ecdysis and dies without feeding on mulberry. Previous studies have indicated that sclerotisation was insufficient because of defective phenylalanine and tyrosine metabolism in albino larvae. However, the genetic mechanism underlying the albino phenotype has not been determined. Dopamine plays a central role in insect cuticle colouration and sclerotisation. The pathway for dopamine biosynthesis from phenylalanine involves phenylalanine hydroxylase (PAH; EC 1.14.16.1) and tyrosine hydroxylase (TH; EC 1.14.16.2). Tetrahydrobiopterin (BH4) is an essential cofactor of aromatic amino acid hydroxylases, including PAH and TH. Thus, BH4 is indispensable for cuticle colouration and sclerotisation. Here we report on identifying mutations in the gene that encodes for the Bombyx homolog of 6-pyruvoyl-tetrahydropterin synthase (PTS) which is involved in the biosynthesis of BH4, in 2 strains with different al alleles. In strain a60 (al), a transposable element was inserted in exon 2 of BmPTS. In strain a61 (al²), an 11-bp deletion was identified in the exon 2 region of BmPTS. After oral administration of BH4 to the al² larvae, the survival rate was effectively increased and the larval integument was pigmented. These results indicated that BmPTS was responsible for the albino mutants of B. mori. We conclude that (i) a mutation in BmPTS leads to an insufficient supply of BH4 and results in defective dopamine biosynthesis and (ii) lack of dopamine results in cuticle colouration and sclerotisation failure. Lemon (lem) is a BH4-deficient mutant. It has been reported that de novo synthesis of zygotic BH4 was indispensable for viability of the embryo in eggs laid by lem (lem/lem^l) females. We found that lem/lem, al²/al² larvae produced by lem (lem/lem) females were viable during the first instar stage, suggesting that al²/al² embryo could synthesis BH4 by using maternally transmitted BmPTS.     

Evaluation of pest control efficiencies for different banker plant systems with a simple predator–prey model

The banker plant system has been introduced for the biological control of various pest species in Japanese greenhouses. With the banker plant system, non-crop plants infested with a host insect (a non-commercial crop pest) are placed in the greenhouse to provide alternative resources for the parasitoids or predators. We want to evaluate the effectiveness for controlling pests on the crop in a quantitative way by immigrating predators from the banker plant. Therefore, we developed a simple model for the interaction of the pest and predator in the crop and included the banker plant only as a source for predators. For three different pest-predator systems we parameterised the model and used these models to predict under what conditions biological control in a banker plant system is successful. We defined successful as keeping the pest below the economic injury level of the crop estimated from damage analysis. Because the crop is mostly grown during a period that lasts less than a year our analysis should not only focus on the equilibrium dynamics. In contrast, it should also focus on the transient dynamics. Our main analytical result, from the equilibrium analysis, is that for successful control the maximum lifetime consumption of immigrating predators should exceed the daily prey growth at half the value of the maximum consumption rate. For practical purpose this translates into the fact that the immigration of predators at a low initial pest density is crucial for successful control.     

Production of Nucleic Acid-Related Substances by Fermentation Processes

The effects of manganese ion (Mn²⁺) and adenine on the accumulation of 5′ inosinic acid (IMP) by Brevibacterium ammoniagenes KY 13102, were examined. Adenine regulated the accumulation of IMP in the presence of limiting amounts of Mn²⁺ and the accumulation of hypoxanthine (Hx) in the presence of excessive amounts of the ion. Manganese ion markedly affected IMP accumulations, cell growth and cellular morphology. These biological changes caused by Mn²⁺ are related to changes in the syntheses of macromolecules. The cells cultivated under limitation of Mn²⁺ showed abnormally elongated and irregular forms irrespective of adenine levels and had smaller nucleotide pools than those of the cells in the presence of excessive Mn²⁺. The Mn²⁺ limited cells showed ability to accumulate IMP directly in the cell suspension but the Mn²⁺ excessive cells did not accumulated IMP but Hx. These results indicated that adenine and Mn²⁺ affected the IMP accumulation independently each other and adenine acted as a feedback regulator on de novo synthesis of purine nucleotide and limitation of Mn²⁺ caused morphological changes, resulting in changes of permeability of the cells. The fatty acid contents of the Mn²⁺ limited cells were higher than those of the Mn²⁺ excessive cells and the ratio of unsaturated fatty acid to saturated one was higher in the former cells.     

Xtr, a plural tudor domain-containing protein, is involved in the translational regulation of maternal mRNA during oocyte maturation in Xenopus laevis

Xtr in the fertilized eggs of Xenopus has been demonstrated to be a member of a messenger ribonucleoprotein (mRNP) complex that plays a crucial role in karyokinesis during cleavage. Since the Xtr is also present both in oocytes and spermatocytes and its amount increases immediately after spematogenic cells enter into the meiotic phase, this protein was also predicted to act during meiotic progression. Taking advantage of Xenopus oocytes' large size to microinject anti-Xtr antibody into them for inhibition of Xtr function, we examined the role of Xtr in meiotic progression of oocytes. Microinjection of anti-Xtr antibody into immature oocytes followed by reinitiation of oocyte maturation did not affect germinal vesicle break down and the oscillation of Cdc2/cyclin B activity during meiotic progression but caused abnormal spindle formation and chromosomal alignment at meiotic metaphase I and II. Immunoprecipitation of Xtr showed the association of Xtr with FRGY2 and mRNAs such as RCC1 and XL-INCENP mRNAs, which are involved in the progression of karyokinesis. When anti-Xtr antibody was injected into oocytes, translation of XL-INCENP mRNA, which is known to be repressed in immature oocytes and induced after reinitiation of oocyte maturation, was inhibited even if the oocytes were treated with progesterone. A similar translational regulation was observed in oocytes injected with a reporter mRNA, which was composed of an enhanced green fluorescent protein open reading frame followed by the 3' untranslational region (3'UTR) of XL-INCENP mRNA. These results indicate that Xtr regulates the translation of XL-INCENP mRNA through its 3'UTR during meiotic progression of oocyte.     

Effect of post-learning sleep versus wakefulness on advantageous decision-making: A preliminary study

This study evaluates the effect of sleep on learning-based decision-making. Twenty-four healthy volunteers were allocated randomly to two groups: a sleep group and a wake group. A modified Iowa gambling task was administered before and after a 12-h period in which the sleep group slept about 8 h and the other group remained awake. The two groups’ advantageous decision-making during the initial learning phase did not differ, but the advantageous choices of the sleep group improved more than that of the wake group after the 12-h period, suggesting that sleep may have facilitated and/or retained advantageous decision-making.

     

Identification of genes encoding photoconvertible (Class I) water-soluble chlorophyll-binding proteins from Chenopodium ficifolium

Photoconvertible water-soluble chlorophyll-binding proteins, called Class I WSCPs, have been detected in Chenopodiaceae, Amaranthaceae and Polygonaceae plant species. To date, Chenopodium album WSCP (CaWSCP) is the only cloned gene encoding a Class I WSCP. In this study, we identified two cDNAs encoding Chenopodium ficifolium Class I WSCPs, CfWSCP1, and CfWSCP2. Sequence analyses revealed that the open reading frames of CfWSCP1 and CfWSCP2 were 585 and 588 bp, respectively. Furthermore, both CfWSCPs contain cystein2 and cystein30, which are essential for the chlorophyll-binding ability of CaWSCP. Recombinant CfWSCP1 and CfWSCP2, expressed in Escherichia coli as hexa-histidine fusion proteins (CfWSCP1-His and CfWSCP2-His), formed inclusion bodies; however, we were able to solubilize these using a buffer containing 8 M urea and then refold them by dialysis. The refolded CfWSCP1-His and CfWSCP2-His could bind chlorophylls and exhibited photoconvertibility, confirming that the cloned CfWSCPs are further examples of Class I WSCPs.