A familial case of visceral toxocariasis due to consumption of raw bovine liver

We present 3 adult cases of visceral toxocariasis from the same family, who each consumed thin slices of raw bovine liver weekly, and developed eosinophilia and multiple small lesions in their livers and lungs. Serological examinations using the larval excretory–secretory product of Toxocara canis strongly indicated infection with Toxocara species larvae. The patients responded well to treatment with albendazole. Ingestion of raw liver from paratenic animals is considered to be a common transmission route of human toxocariasis, especially in adults.     

Expression of novel extracellular sulfatases Sulf-1 and Sulf-2 in normal and osteoarthritic articular cartilage

Introduction  

Changes in sulfation of cartilage glycosaminoglycans as mediated by sulfatases can regulate growth factor signaling. The aim of this study was to analyze expression patterns of recently identified extracellular sulfatases Sulf-1 and Sulf-2 in articular cartilage and chondrocytes.     

Fragment-based discovery of hepatitis C virus NS5b RNA polymerase inhibitors

Non-nucleoside inhibitors of HCV NS5b RNA polymerase were discovered by a fragment-based lead discovery approach, beginning with crystallographic fragment screening. The NS5b binding affinity and biochemical activity of fragment hits and inhibitors was determined by surface plasmon resonance (Biacore) and an enzyme inhibition assay, respectively. Crystallographic fragment screening hits with 1–10 mM binding affinity (K_D) were iteratively optimized to give leads with 200 nM biochemical activity and low μM cellular activity in a Replicon assay.     

Molecular basis for peroxisomal localization of tetrameric carbonyl reductase

Pig heart peroxisomal carbonyl reductase (PerCR) belongs to the short-chain dehydrogenase/reductase family, and its sequence comprises a C-terminal SRL tripeptide, which is a variant of the type 1 peroxisomal targeting signal (PTS1) Ser-Lys-Leu. PerCR is imported into peroxisomes of HeLa cells when the cells are transfected with vectors expressing the enzyme. However, PerCR does not show specific targeting when introduced into the cells with a protein transfection reagent. To understand the structural basis for peroxisomal localization of PerCR, we determined the crystal structure of PerCR. Our data revealed that the C-terminal PTS1 of each subunit of PerCR was involved in intersubunit interactions and was buried in the interior of the tetrameric molecule. These findings indicate that the PTS1 receptor Pex5p in the cytosol recognizes the monomeric form of PerCR whose C-terminal PTS1 is exposed, and that this PerCR is targeted into the peroxisome, thereby forming a tetramer.     

RNA-binding protein hoip accelerates polyQ-induced neurodegeneration in Drosophila

Abnormal polyglutamine (polyQ) expansion in the N-terminal domain of the human androgen receptor (hAR) is known to cause spinobulbar muscular atrophy (SBMA), a hereditary human neurodegenerative disorder. To explore the molecular mechanisms of neurodegeneration in SBMA, we genetically screened modulators of neurodegeneration in a Drosophila SBMA experimental model system. We identified hoip as an accelerator of polyQ-induced neurodegeneration. We found that hoip forms a complex with 18s rRNA together nop56 and nop5 proteins, whose human homologs are known to form a snoRNP complex involved in ribosomal RNA processing. Significantly, the levels of mutant polyQ-hAR were up-regulated in a mutant line overexpressing hoip. Consistently, severe neurodegeneration phenotype (rough eye) was also observed in both nop56 and nop5 overexpression mutant lines. These findings suggest that the process of neurodegeneration induced by abnormal polyQ expansion in the hAR may be regulated by the activity of snoRNP complex.     

Food conditions, competitive regime, and female social relationships in Japanese macaques: within-population variation on Yakushima

Feeding conditions, competitive regime, and female social relationships of Japanese macaques (Macaca fuscata) on Yakushima were compared between the two habitats at two different altitudes (coniferous forest, 1,000–1,200 m and coastal forest, 0–200 m). Fruit availability was higher in the coastal forest. There was no consistent difference in the frequency of agonistic interactions within a group during feeding between the two habitats. The coastal forest evoked stronger inter-group contest competition compared to the coniferous forest as evidenced by a higher inter-group encounter rate and a higher proportion of aggressive encounters to non-aggressive ones. Birth rate was higher in larger groups compared to smaller ones in the coastal forest, but did not differ in the coniferous forest. In spite of these differences in competitive regime, no variation in female social relationships was observed, such as direction and concentration on particular individuals in grooming, linearity in dominance rank, counter-attack, and support of juvenile kin during agonistic interactions. The present results indicate that the female social relationships of Japanese macaques are robust and do not change according to changes in the current environment.     

Tonically immobilized selfish prey can survive by sacrificing others

Death-feigning, also called tonic immobility, is found in a number of animal species across vertebrate and invertebrate taxa. To date, five hypotheses have been proposed for the adaptive significance of tonic immobility. These are that tonic immobility is effective for prey because (i) avoiding dead prey is safer for predators, (ii) immobility plays a role in physical defence, (iii) immobility plays a role in concealment and/or background matching, (iv) predators lose interest in unmoving prey, and (v) the characteristic immobilization posture signals a bad taste to predators. The fourth and fifth hypotheses have been considered suitable explanations for tonic immobility of the red flour beetle against its predator, the jumping spider. In the present study, we used chemical analyses of secretions by the red flour beetles under attack by the jumping spider to reject the fifth hypothesis for this system. More importantly, we tested a selfish-prey hypothesis for the adaptive significance of death-feigning as an anti-predator strategy, in which individuals adopting tonic immobility survive by sacrificing neighbours. Findings showed that survival rates of feigners were higher when in the presence of non-feigners or prey of a different species, compared to when alone, thus confirming our selfish-prey hypothesis. In summary, our results suggest that immobility following a spider attack is selfish; death-feigning prey increase their probability of survival at the expense of more mobile neighbours.     

Genetic mouse models to investigate cell cycle regulation

Early studies on cell cycle regulation were based on experiments in model systems (Yeast, Xenopus, Starfish, Drosophila) and have shaped the way we understand many events that control the cell cycle. Although these model systems are of great value, the last decade was highlighted by studies done in human cells and using in vivo mouse models. Mouse models are irreplaceable tools for understanding the genetics, development, and survival strategies of mammals. New developments in generating targeting vectors and mutant mice have improved our approaches to study cell cycle regulation and cancer. Here we summarize the most recent advances of mouse model approaches in dissecting the mechanisms of cell cycle regulation and the relevance to human disease. W. Li and S. Kotoshiba contributed equally.