Isoleucine Accumulation by Regulatory Mutants of Serratia marcescens: Lack of Both Feedback Inhibition and Repression

Double mutants of Serratia marcescens resistant to isoleucine hydroxamate and alpha-aminobutyric acid accumulated large amounts of isoleucine in a salts-sugar medium and lacked both feedback inhibition and repression of the isoleucine biosynthesis.     

Augmented production of platelet-activating factor in human polymorphonuclear leukocytes by ketone bodies

The production of platelet-activating factor (PAF) in A23187-stimulated human polymorphonuclear leukocytes was markedly increased in the presence of 5 mM acetoacetate and beta-hydroxybutyrate. Such an augmentation was observed even at 500 microM but not at 50 microM. The augmented production of PAF by acetoacetate was also observed in the presence of autologous serum and was most prominent in the case of opsonized zymosan-stimulation rather than A23187-stimulation. These observations suggest that increased levels of acetoacetate and beta-hydroxybutyrate in blood may lead to the augmented production of PAF, which would amplify the various PAF-mediated biological reactions.     

Distribution,Elimination, and Renal Effects of Single Oral Doses of Europium in Rats

Single doses of europium (III) chloride hexahydrate were orally administered to several groups of rats. Cumulative urine samples were taken at 0–24 h, and blood samples were drawn after 24-h administration. The europium concentration was determined in these samples by inductively coupled plasma atomic emission spectroscopy. The volume, creatinine, ß-2-microglobulin, and N-acetyl-ß-d-glucosaminidase were measured in the urine samples to evaluate possible europium-induced renal effects. The blood samples showed low europium distribution, with an average of 77.5 μg/L for all groups. Although the urinary concentration and excretion showed dose-dependent increases, the percentage of europium excreted showed a dose-dependent decrease, with an average of 0.31% in all groups. The administration of europium resulted in a significant decrease of creatinine and a significant increase of urinary volume, N-acetyl-ß-d-glucosaminidase, and ß-2-microglobulin. Rare earth elements, including europium, are believed to form colloidal conjugates that deposit in the reticuloendothelial system and glomeruli. This specific reaction may contribute to low europium bioavailability and renal function disturbances. Despite low bioavailability, the high performance of the analytical method for determination of europium makes the blood and urine sampling suitable tools for monitoring of exposure to this element. The results presented in this study will be of great importance in future studies on the health impacts of rare earth elements.     

Variation in Spatial Cohesiveness in a Group of Japanese Macaques (<Emphasis Type="Italic">Macaca fuscata</Emphasis>)

The spatial cohesiveness of a group is an important element that characterizes the social structure of group-living species. Moreover, remaining cohesive is crucial if individuals are to coordinate their activities and reach collective decisions. We measured interindividual spacing in a group of wild Japanese macaques (Macaca fuscata) to assess the spatial cohesiveness of a social group quantitatively. We used simultaneous focal animal sampling, with 2 observers recording individuals’ locations with a global positioning system (GPS) during 3 seasons. Interindividual distances differed among seasons; they were short in autumn (mean ± SD: 25.6 ± 20.1 m), intermediate in winter (mean ± SD: 46.3 ± 35.7 m), and long in summer (mean ± SD: 62.3 ± 47.1 m). Measurements taken in summer revealed extremely wide spacing (maximum: 1225 m), suggesting subgrouping. Distances also varied with activity during each season; they were short during resting and grooming, intermediate during foraging, and long during moving. Group cohesion was also influenced by food distribution. More group members were ≤20 m of the focal individual during foraging on clumped food than foraging on scattered food in each season, and the group foraged on clumped food most frequently in autumn. Individuals were also likely to aggregate at resting/grooming sites and clumped food patches and to disperse when moving within a day. These results demonstrate that Japanese macaques show considerable variation in spatial cohesiveness both within short time periods, e.g., 1 d, and among seasons, and that they adjust group cohesiveness flexibly depending on the food conditions and foraging tactics.     

Pyrazolo[1,5-a]pyrimidines, triazolo[1,5-a]pyrimidines and their tricyclic derivatives as corticotropin-releasing factor 1 (CRF₁) receptor antagonists

To identify structurally novel CRF1 receptor antagonists, a series of bicyclic core antagonists, pyrazolo[1,5-a]pyrimidines, triazolo[1,5-a]pyrimidines, imidazo[1,2-a]pyrimidines and pyrazolo[1,5-a][1,3,5]triazines were designed, synthesized and evaluated as CRF1 receptor antagonists. Compounds 2-27 showed binding affinity (IC(50)=4.2-418 nM) and antagonist activity (EC(50)=4.0-889 nM). Compound 5 was found to show oral efficacy in an Elevated Plus Maze test in rats. Further chemical modification of them led us to discovery of the tricyclic core antagonists pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidines. The discovery process of these compounds is presented, as is the study of the structure-activity relationship.     

Change of positive selection pressure on HIV-1 envelope gene inferred by early and recent samples

HIV-1 infection has been on the rise in Japan recently, and the main transmission route has changed from blood transmission in the 1980s to homo- and/or hetero-sexual transmission in the 2000s. The lack of early viral samples with clinical information made it difficult to investigate the possible virological changes over time. In this study, we sequenced 142 full-length env genes collected from 16 Japanese subjects infected with HIV-1 in the 1980s and in the 2000s. We examined the diversity change in sequences and potential adaptive evolution of the virus to the host population. We used a codon-based likelihood method under the branch-site and clade models to detect positive selection operating on the virus. The clade model was extended to account for different positive selection pressures in different viral populations. The result showed that the selection pressure was weaker in the 2000s than in the 1980s, indicating that it might have become easier for the HIV to infect a new host and to develop into AIDS now than 20 years ago and that the HIV may be becoming more virulent in the Japanese population. The study provides useful information on the surveillance of HIV infection and highlights the utility of the extended clade models in analysis of virus populations which may be under different selection pressures.     

Optimal Leaf-to-Root Ratio and Leaf Nitrogen Content Determined by Light and Nitrogen Availabilities

Plants exhibit higher leaf-to-root ratios (L/R) and lower leaf nitrogen content (N _area) in low-light than in high-light environments, but an ecological significance of this trait has not been explained from a whole-plant perspective. This study aimed to theoretically and experimentally demonstrate whether these observed L/R and N _area are explained as optimal biomass allocation that maximize whole-plant relative growth rate (RGR). We developed a model which predicts optimal L/R and N _area in response to nitrogen and light availability. In the model, net assimilation rate (NAR) was determined by light-photosynthesis curve, light availability measured during experiments, and leaf temperature affecting the photosynthesis and leaf dark respiration rate in high and low-light environments. Two pioneer trees, Morus bombycis and Acer buergerianum, were grown in various light and nitrogen availabilities in an experimental garden and used for parameterizing and testing the model predictions. They were grouped into four treatment groups (relative photosynthetic photon flux density, RPPFD 100% or 10%×nitrogen-rich or nitrogen-poor conditions) and grown in an experimental garden for 60 to 100 days. The model predicted that optimal L/R is higher and N _area is lower in low-light than high-light environments when compared in the same soil nitrogen availability. Observed L/R and N _area of the two pioneer trees were close to the predicted optimums. From the model predictions and pot experiments, we conclude that the pioneer trees, M. bombycis and A. buergerianum, regulated L/R and N _area to maximize RGR in response to nitrogen and light availability.