Spatio-temporal abundance of flushing leaves shapes host selection in the willow leaf beetle, Plagiodera versicolora

In the willow leaf beetle, Plagiodera versicolora (Laicharting) (Coleoptera: Chrysomelidae), food resources available for adults are severely restricted by leaf toughness, which increases with age. Nevertheless, females require their own food almost all their life in order to produce eggs. In this paper, we have focused our attention on the spatio-temporal abundance of flushing leaves and have examined its effect on host-plant selection by adults among four co-occurring willow species ( Salix chaenomeloides , Salix eriocarpa , Salix integra , and Salix serissaefolia ) (Salicaceae) by field observations and experiments at two spatial scales. Among the various factors associated with this, the amount of new leaf production contributed maximally to variation in adult abundance. By conducting two experiments, we confirmed that the adults preferentially flew towards willow trees with abundant flushing leaves. Furthermore, we detected substantial seasonal changes in new leaf abundance and realized fecundity in the field, and a strong positive correlation was observed between them. Availability of adult food resources limited the reproductive performance of adults, particularly in mid-summer when only S. serissaefolia produced a few new leaves. These results supported the substantial effect of new leaf abundance on adult abundance in the field. Thus, we concluded that adult feeding is a critical factor that shapes the host-plant selection of P. versicolora and determines its seasonal occurrence through the dispersal and settlement of adults.     

Modelling the population dynamics of the toxic dinoflagellate Alexandrium Tamarense in Hiroshima Bay, Japan

In the present study, a numerical model that simulates speciescompetition between the toxic dinoflagellate Alexandrium tamarenseand the non-toxic diatom Skeletonema costatum was constructedusing data from a number of experiments and field observations.In the model, not only vertical migration of swimming cellsbut also the encystment and excystment processes of A. tamarensewere taken into consideration. Sinking of S. costatum cellswas also considered. Both zooplankton and oysters, which areintensively cultured in this bay, feed on the phytoplanktonbut the contribution of grazing to the decrease in the celldensities of both species was small. The model predicts thatwhile sinking is one of the major processes that reduce thecell density of S. costatum, encystment of A. tamarense is acrucial process that determines the cessation of blooms of thisdinoflagellate. Advection and diffusion are also important physicalprocesses that affect, in positive and negative ways, the fluctuationof cell densities.     

Potassium bromate treatment predominantly causes large deletions, but not GC>TA transversion in human cells

Potassium bromate (KBrO(3)) is strongly carcinogenic in rodents and mutagenic in bacteria and mammalian cells in vitro. The proposed genotoxic mechanism for KBrO(3) is oxidative DNA damage. KBrO(3) can generate high yields of 8-hydroxydeoxyguanosine (8OHdG) DNA adducts, which cause GC>TA transversions in cell-free systems. In this study, we investigated the in vitro genotoxicity of KBrO(3) in human lymphoblastoid TK6 cells using the comet (COM) assay, the micronucleus (MN) test, and the thymidine kinase (TK) gene mutation assay. After a 4h treatment, the alkaline and neutral COM assay demonstrated that KBrO(3) directly yielded DNA damages including DNA double strand breaks (DSBs). KBrO(3) also induced MN and TK mutations concentration-dependently. At the highest concentration (5mM), KBrO(3) induced MN and TK mutation frequencies that were over 30 times the background level. Molecular analysis revealed that 90% of the induced mutations were large deletions that involved loss of heterozygosity (LOH) at the TK locus. Ionizing-irradiation exhibited similar mutational spectrum in our system. These results indicate that the major genotoxicity of KBrO(3) may be due to DSBs that lead to large deletions rather than to 8OHdG adducts that lead to GC>TA transversions, as is commonly believed. To better understand the genotoxic mechanism of KBrO(3), we analyzed gene expression profiles of TK6 cells using Affymetrix Genechip. Some genes involved in stress, apoptosis, and DNA repair were up-regulated by the treatment of KBrO(3). However, we could not observe the similarity of gene expression profile in the treatment of KBrO(3) to ionizing-irradiation as well as oxidative damage inducers.     

Attenuation of obesity-induced adipose tissue inflammation in C3H/HeJ mice carrying a Toll-like receptor 4 mutation

Obese adipose tissue is characterized by increased infiltration of macrophages, suggesting that they might represent an important source of inflammation. We have provided in vitro evidence that saturated fatty acids, which are released from hypertrophied adipocytes via the macrophage-induced adipocyte lipolysis, serve as a naturally occurring ligand for Toll-like receptor 4 (TLR4) to induce the inflammatory changes in macrophages. Here we show the attenuation of adipose tissue inflammation in C3H/HeJ mice carrying a functional mutation in the TLR4 gene relative to control C3H/HeN mice during a 16-week high-fat diet. We also find that adiponectin mRNA expression is significantly reduced by co-culture of hypertrophied 3T3-L1 adipocytes and C3H/HeN peritoneal macrophages, which is reversed, when co-cultured with C3H/HeJ peritoneal macrophages. This study provides in vivo evidence that TLR4 plays a role in obesity-related adipose tissue inflammation and thus helps to identify the therapeutic targets that may reduce obesity-induced inflammation and the metabolic syndrome.     

Valproic acid affects membrane trafficking and cell-wall integrity in fission yeast

Valproic acid (VPA) is widely used to treat epilepsy and manic-depressive illness. Although VPA has been reported to exert a variety of biochemical effects, the exact mechanisms underlying its therapeutic effects remain elusive. To gain further insights into the molecular mechanisms of VPA action, a genetic screen for fission yeast mutants that show hypersensitivity to VPA was performed. One of the genes that we identified was vps45+, which encodes a member of the Sec1/Munc18 family that is implicated in membrane trafficking. Notably, several mutations affecting membrane trafficking also resulted in hypersensitivity to VPA. These include ypt3+ and ryh1+, both encoding a Rab family protein, and apm1+, encoding the mu1 subunit of the adaptor protein complex AP-1. More importantly, VPA caused vacuolar fragmentation and inhibited the glycosylation and the secretion of acid phosphatase in wild-type cells, suggesting that VPA affects membrane trafficking. Interestingly, the cell-wall-damaging agents such as micafungin or the inhibition of calcineurin dramatically enhanced the sensitivity of wild-type cells to VPA. Consistently, VPA treatment of wild-type cells enhanced their sensitivity to the cell-wall-digesting enzymes. Altogether, our results suggest that VPA affects membrane trafficking, which leads to the enhanced sensitivity to cell-wall damage in fission yeast.     

A study on the social structure and dispersal patterns of hamadryas baboons living in a commensal group at Taif,Saudi Arabia

Three levels of hamadryas social structure—the one male unit (OMU), the band, and the troop—have been observed at all sites studied, but a fourth—the clan—has been observed at only one site, Erer-Gota, Ethiopia, during a longitudinal check of the dispersion of identified individuals. The clan is important since it appears to provide the basis for male philopatry, although comparative data is needed from other sites to confirm this. We studied a huge commensal group of hamadryas baboons (over 600 animals) in Saudi Arabia. We put ear tags on baboons between 1998 and 2004 and analyzed social structure, relying on the interactions of these tagged animals by focusing especially on their dispersal patterns from OMUs. OMU membership tended to be looser than that of the Ethiopian hamadryas. Females tended to shift between OMUs on an individual basis in our study group, whereas the collapse of an OMU was a major occasion of adult female transfer in Ethiopia. We found neither stable bands (a “band” in our study group was defined as a regional assemblage of OMUs) nor clans that lasted for several years. Some OMUs moved and transferred into neighboring areas over both the short and long term. Further, some post-adolescent males appeared to move out of the study area. The ratio of adult females in an OMU in our study group was larger than for any other documented study site, and this may be the reason for enhanced female transfer between OMUs. A large proportion of the adolescent females showed no clear membership to OMUs, and no “initial units” (commonly observed in Ethiopia) were discernible. The ease with which young males acquired adult females at the study site must have disrupted the formation of a clan, a “male-bonded society.”     

2-Arylimino-5,6-dihydro-4H-1,3-thiazines as a new class of cannabinoid receptor agonists. Part 2: orally bioavailable compounds

Structure-activity relationships and efforts to optimize the pharmacokinetic profile of a class of 2-arylimino-5,6-dihydro-4H-1,3-thiazines as cannabinoid receptor agonists are described. Among the compounds examined, compound 14 showed potent affinity and high selectivity for CB2, and compound 23 showed potent affinities against CB1 and CB2. These compounds displayed oral bioavailability.     

RNAi gene silencing using cerasome as a viral-size siRNA-carrier free from fusion and cross-linking

Surface-rigidified cerasomes (ceramic-coated liposomes) are neither fused nor cross-linked when bound to siRNA (short duplex RNA) but not to plasmid DNA (long duplex DNA) which induces cross-linking. Non-ceramic reference liposomes are easily fused by the siRNA. The cerasome can thus be used as a viral-size siRNA-carrier in a wide range of concentration for RNAi silencing of exogenous and endogenous genes.     

Osteoblastic differentiation improved by bezafibrate-induced mitochondrial biogenesis in deciduous tooth-derived pulp stem cells from a child with Leigh syndrome

Leigh syndrome is a highly heterogeneous condition caused by pathological mutations in either nuclear or mitochondrial DNA regions encoding molecules involved in mitochondrial oxidative phosphorylation, in which many organs including the brain can be affected. Among these organs, a high incidence of poor bone health has been recognized in primary mitochondrial diseases including Leigh syndrome. However, the direct association between mitochondrial dysfunction and poor bone health has not been fully elucidated. Mitochondrial biosynthesis is a potential therapeutic target for this syndrome, as it can ameliorate the impairment of oxidative phosphorylation without altering these gene mutations. A recent study has shown the impaired osteogenesis in the dental pulp stem cells derived from the deciduous teeth of a child with Leigh syndrome, harboring the heteroplasmic mutation G13513A in the mitochondrial DNA region encoding the ND5 subunit of the respiratory chain complex I. The present study aimed to investigate whether mitochondrial biogenesis could be a therapeutic target for improving osteogenesis, using the same stem cells in a patient-specific cellular model. For this purpose, bezafibrate was used because it has been reported to induce mitochondrial biogenesis as well as to improve bone metabolism and osteoporosis. Bezafibrate clearly improved the differentiation of patient-derived stem cells into osteoblasts and the mineralization of differentiated osteoblasts. The mRNA expression of peroxisome proliferator-activated receptor-gamma coactivator-1α, ATP production, and mitochondrial Ca²⁺ levels were all significantly increased by bezafibrate in the patient-derived cells. In addition, the increased amount and morphological shift from the fragmentary to network shape associated with DRP1 downregulation were also observed in the bezafibrate-treated patient-derived cells. These results suggest that mitochondrial biogenesis may be a potential therapeutic target for improving osteogenesis in patients with Leigh syndrome, and bezafibrate may be one of the candidate treatment agents.     

TGF-β mediated FGF10 signaling in cranial neural crest cells controls development of myogenic progenitor cells through tissue-tissue interactions during tongue morphogenesis

Skeletal muscles are formed from two cell lineages, myogenic and fibroblastic. Mesoderm-derived myogenic progenitors form muscle cells whereas fibroblastic cells give rise to the supportive connective tissue of skeletal muscles, such as the tendons and perimysium. It remains unknown how myogenic and fibroblastic cell-cell interactions affect cell fate determination and the organization of skeletal muscle. In the present study, we investigated the functional significance of cell-cell interactions in regulating skeletal muscle development. Our study shows that cranial neural crest (CNC) cells give rise to the fibroblastic cells of the tongue skeletal muscle in mice. Loss of Tgfbr2 in CNC cells (Wnt1-Cre;Tgfbr2^flox/flox) results in microglossia with reduced Scleraxis and Fgf10 expression as well as decreased myogenic cell proliferation, reduced cell number and disorganized tongue muscles. Furthermore, TGF-β2 beads induced the expression of Scleraxis in tongue explant cultures. The addition of FGF10 rescued the muscle cell number in Wnt1-Cre;Tgfbr2^flox/flox mice. Thus, TGF-β induced FGF10 signaling has a critical function in regulating tissue-tissue interaction during tongue skeletal muscle development.