Variation in life-history traits of male Japanese fluvial sculpin Cottus pollux in relation to nest abundance along a stream course

Life-history theory predicts the occurrence of variation in the life-history traits of fish populations under different environmental conditions; however, most studies have focused on such variation between geographically separated populations. We compared breeding characteristics and life-history traits of the Japanese fluvial sculpin (Cottus pollux), a bottom-dwelling nest-holding fish, between two adjacent sites sub-divided by a weir along a stream course in central Japan. Males in the area with a lower abundance of nest sites reached sexual maturity at an earlier age and had a shorter life span than males in the area with sufficient nest abundance. Size-dependent male reproduction was found only in areas with a shortage of nest sites, supporting the assumption of competitive exclusion among males for nests. Females matured at the same age in both sites with no differences in age-specific growth rates and mortality. Our results provide evidence for life-history variation in age and size at maturity and age-specific mortality schedule of males in nest-holding fishes in a single stream population via different sexual selection regimes related to differences in nest abundance between sites.     

Distinct tRNA modifications in the thermo-acidophilic archaeon, Thermoplasma acidophilum

Thermoplasma acidophilum is a thermo-acidophilic archaeon. We purified tRNA^Leu (UAG) from T. acidophilum using a solid-phase DNA probe method and determined the RNA sequence after determining via nucleoside analysis and m⁷G-specific aniline cleavage because it has been reported that T. acidophilum tRNA contains m⁷G, which is generally not found in archaeal tRNAs. RNA sequencing and liquid chromatography–mass spectrometry revealed that the m⁷G modification exists at a novel position 49. Furthermore, we found several distinct modifications, which have not previously been found in archaeal tRNA, such as 4-thiouridine9, archaeosine13 and 5-carbamoylmethyuridine34. The related tRNA modification enzymes and their genes are discussed.     

Structure-based design,synthesis, and evaluation of imidazo[1,2-b]pyridazine and imidazo[1,2-a]pyridine derivatives as novel dual c-Met and VEGFR2 kinase inhibitors

To identify compounds with potent antitumor efficacy for various human cancers, we aimed to synthesize compounds that could inhibit c-mesenchymal epithelial transition factor (c-Met) and vascular endothelial growth factor receptor 2 (VEGFR2) kinases. We designed para-substituted inhibitors by using co-crystal structural information from c-Met and VEGFR2 in complex with known inhibitors. This led to the identification of compounds 3a and 3b, which were capable of suppressing both c-Met and VEGFR2 kinase activities. Further optimization resulted in pyrazolone and pyridone derivatives, which could form intramolecular hydrogen bonds to enforce a rigid conformation, thereby producing potent inhibition. One compound of particular note was the imidazo[1,2-a]pyridine derivative (26) bearing a 6-methylpyridone ring, which strongly inhibited both c-Met and VEGFR2 enzyme activities (IC₅₀ = 1.9, 2.2 nM), as well as proliferation of c-Met-addicted MKN45 cells and VEGF-stimulated human umbilical vein endothelial cells (IC₅₀ = 5.0, 1.8 nM). Compound 26 exhibited dose-dependent antitumor efficacy in vivo in MKN45 (treated/control ratio [T/C] = 4%, po, 5 mg/kg, once-daily) and COLO205 (T/C = 13%, po, 15 mg/kg, once-daily) mouse xenograft models.     

Absorption,Translocation and Metabolism of Nicotinamide in Some Plants

The seedlings of rice, eggplant and tomato at the 5th leaf stage of growth readily absorbed exogenous ¹⁴C-nicotinamide through the root and the foliage in water culture. Within the 24 hr period after the bigining of cultivation, the radioactivity gradually translocated from the part treated with ¹⁴C-nicotinamide to the whole plant body. This compound was rapidly metabolised in the plants to at least six metabolites, in which three compounds were identified as nicotinic acid, NAD and NADP. ¹⁴C-Nicotinic acid was also taken up quickly through the root of rice and its metabolism showed a similar pattern to that of ¹⁴C-nicotinamide. The incorporation of radioactivity into NAD and NADP from ¹⁴C-nicotinamide added to cultivating solution at a concentration of 0.21 ppm was decreased to 10~20% by the simultaneous addition of unlabeled nicotinic acid at a concentration about 1000 times higher than that of the labeled one. It was concluded that the biosynthesis of these pyridine nucleotides from nicotinamide was chiefly via nicotinic acid. The formation of ¹⁴C-nicotinamide in the ¹⁴C-nicotinic acid metabolism suggested a breakdown of NAD. Three unknown compounds observed in both the metabolisms described above were not intermediates in the pyridine nucleotide biosynthesis.     

Studies on the Mode of Action of Polyoxins

(1) Chitin-UDP acetylglucosaminyltransferase (E.C. 2.4.1.16., chitin synthetase) in the cell-free system from phytopathogenic fungus Piricularia oryzae, and effects of various polyoxins and related compounds on the enzyme activity were studied. Polyoxins A~M, polyoxin A derivatives, polyoxin C derivatives, 5′-amino-5′-deoxyuridine, uridine and thymidine inhibited equally the incorporation of N-acetylglucosamine (GlcNAc) from UDP-N-acetylglucosamine (UDP-GlcNAc) into chitin.

(2) Competition between the above inhibitors and UDP-GlcNAc was observed by kinetic studies. The Km for UDP-GlcNAc was determined to be 3.3 × 10^?3 m and the Ki values for polyoxins A~M, except polyoxin C, were found to be in the range of 3.3 × 10^?5 m to 3.4 × 10^?6 m. For polyoxin C, 5′-amino-5′-deoxyuridine and uridine, the Ki values of 2.7 × 10^?3 m, 8.0 × 10^?3 m and 3.0 × 10^?3 m were given, respectively. The inhibitor constants for other related compounds were also calculated.

(3) The values of binding affinity, ?ΔG, for formation of substrate- or inhibitor-enzyme complexes were calculated from the Km or Ki values. In addition, partial binding affinities, ?Δg, for certain moieties or groups of polyoxins were estimated from the ?ΔG. For instance, the ?ΔG values for UDP-GlcNAc and polyoxin L were 5.7 kcal/mole and 9.2 kcal/mole, respectively. And the ?Δg values for the nucleoside moiety (part I), the carbamylpolyoxamic acid moiety (part II) and the carboxyl group at C5′ position of polyoxin L were 5.2, 3.5 and 0.7 kcal/mole, respectively.

(4) From the results obtained, the mechanism of action and relation between chemical structure and competitive inhibition of chitin synthetase were discussed.

     

Antitumor Lipopolysaccharide from Heptoseless Mutant of Proteus mirabilis

Studies on lipopolysaccharide (LPS) from the cells of Proteus mirabilis RMS-203 were focused upon reduction of lethal toxicity and of pyrogenicity by biological and chemical modification. A heptoseless mutant, strain N-434, was isolated by the use of phage resistancy as a tool. LPS from that heptoseless mutant was completely deficient in neutral sugars and mainly composed of 2-keto-deoxy-octonic acid (KDO), glucosamine and fatty acids. It revealed almost the same antitumor activity as LPS of the wild type but it was less toxic and less pyrogenic.

Hydroxylaminolysis and reduction with LiAlH₄ resulted in removal of fatty acids from LPS accompanied with decrease in lethal toxicity and antitumor acitivity but not in pyrogenicity.

Lipid A fractions showed almost the same antitumor activity as intact LPS but less lethality and less pyrogenicity.     

Further Study on the Relation of Polyoxin Structure to Chitin Synthetase Inhibition

As a part of studies on the mechanism of action of antibiotics polyoxins, effects of various N-aminoacyl derivatives of polyoxin C and other polyoxins on chitin-UDP acetylglucosaminyl-transferase (EC 2.4.1.16, chitin synthetase) prepared from phytopathogenic fungus Piricularia oryzae were investigated. It was found that they inhibited the enzyme in competition with the substrate UDP-N-acetylglucosamine, Inhibitor constants, Ki, for these polyoxins were determined and the values of binding affinity, ?ΔG_bind of the inhibitors to the enzyme were calculated from the Ki values. In addition, by using these ?ΔG_bind values the values of partial binding affinity, ?Δg for the several atoms and atomic groups or the several moieties contained in the polyoxin J molecule were estimated. From the results obtained, it was concluded that the carbamoylpolyoxamic acid moiety of polyoxins helps to stabilize the polyoxin-enzyme complex through the contributions of its oxygen atom at C?1″, amino group at C?2″, hydroxyl groups at C?3″ and C?4″, aliphatic carbon chain and terminal carbamoyloxy group.

The results obtained by the kinetic investigation using various nucleotides and nucleotide sugars suggested that there was a specific binding site on the enzyme corresponding to the uridine moiety of UDP-N-acetylglucosamine, and that the pyrimidine nucleoside moiety of polyoxins was also bound to this site.     

Permanent Genetic Resources added to Molecular Ecology Resources Database 1 August 2012 – 30 September 2012

This article documents the addition of 83 microsatellite marker loci and 96 pairs of single‐nucleotide polymorphism (SNP) sequencing primers to the Molecular Ecology Resources Database. Loci were developed for the following species: Bembidion lampros, Inimicus japonicus, Lymnaea stagnalis, Panopea abbreviata, Pentadesma butyracea, Sycoscapter hirticola and Thanatephorus cucumeris (anamorph: Rhizoctonia solani). These loci were cross‐tested on the following species: Pentadesma grandifolia and Pentadesma reyndersii. This article also documents the addition of 96 sequencing primer pairs and 88 allele‐specific primers or probes for Plutella xylostella.     

Relationship between G1287A of the NET Gene Polymorphisms and Brain Volume in Major Depressive Disorder: A Voxel-Based MRI Study

Background

Earlier studies implicated norepinephrine transporter (NET) gene (SLC6A2) polymorphisms in the etiology of major depressive disorder (MDD). Recently, two single nucleotide SLC6A2 polymorphisms, G1287A in exon 9 and T-182C in the promoter region, were found to be associated with MDD in different populations. We investigated the relationship between the brain volume and these two polymorphisms of the SLC6A2 in MDD patients.

Methods

We obtained 3D high-resolution T1-weighted images of 30 first-episode MDD patients and 48 age- and sex-matched healthy subjects (HS). All were divided into 4 groups based on polymorphism of either the G1287A or the T-182C genotype. VBM analysis examined the effects of diagnosis, genotype, and genotype-diagnosis interactions.

Results

Diagnosis effects on the brain morphology were found in the left superior temporal cortex. No significant genotype effects were found in the T-182C and the G1287A. A significant genotype (G1287A)–diagnosis interaction was found in the left dorsolateral prefrontal cortex. No significant genotype (T-182C)–diagnosis interaction effects were observed in any brain region.

Conclusions

In MDD patients there seems to be a relationship between the volume of the dorsolateral prefrontal cortex and polymorphism of the SLC6A2 G1287A gene.