Indirect reciprocity can overcome free-rider problems on costly moral assessment

Indirect reciprocity is one of the major mechanisms of the evolution of cooperation. Because constant monitoring and accurate evaluation in moral assessments tend to be costly, indirect reciprocity can be exploited by cost evaders. A recent study crucially showed that a cooperative state achieved by indirect reciprocators is easily destabilized by cost evaders in the case with no supportive mechanism. Here, we present a simple and widely applicable solution that considers pre-assessment of cost evaders. In the pre-assessment, those who fail to pay for costly assessment systems are assigned a nasty image that leads to them being rejected by discriminators. We demonstrate that considering the pre-assessment can crucially stabilize reciprocal cooperation for a broad range of indirect reciprocity models. In particular for the most leading social norms, we analyse the conditions under which a prosocial state becomes locally stable.     

Optimization of 5,6,7,8-tetrahydropyrido[4,3-d]pyrimidines to generate a highly selective PI3Kδ inhibitor

Chemical optimization of the 5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine (THPP) scaffold was conducted with a focus on cellular potency while maintaining high selectivity against PI3K isoforms. Compound 11f was identified as a potent, highly selective and orally available PI3Kδ inhibitor. In addition, 11f exhibited efficacy in an in vivo antibody production model. The desirable drug-like properties and in vivo efficacy of 11f suggest its potential as a drug candidate for the treatment of autoimmune diseases and leukocyte malignancies.     

Carbon accumulation and vertical accretion in a restored versus historic salt marsh in southern Puget Sound,Washington, United States

Few comparisons exist between vertical accretion (VA) and carbon accumulation rates (CARs) in restored versus historic (i.e. reference) marshes. Here, we compare these processes in a formerly diked, sparsely vegetated, restored salt marsh (Six Gill Slough, SG), whose surface is subsided relative to the tidal frame, to an adjacent, relatively pristine, historic salt marsh (Animal Slough, AS). Six sediment cores were collected at both AS and SG approximately 6 years after restoration. Cores were analyzed for bulk density (BD), % loss of ignition, % organic carbon, and ²¹⁰Pb. We found that sharp changes in BD in surface layers of SG cores were highly reliable markers for the onset of restoration. The mean VA since restoration at SG (0.79 [SD = 0.29] cm/year) was approximately twice that of AS (0.41 [SD = 0.16] cm/year). In comparison, the VA at AS over 50 years was 0.30 (SD = 0.09) cm/year. VA consisted almost entirely of inorganic sediment at SG whereas at AS it was approximately 55%. Mean CARs at SG were somewhat greater than at AS, but the difference was not significant due to high variability (SG: 81–210 g C m^?2 year^?1; AS: 115–168 g C m^?2 year^?1). The mean CAR at AS over the past 50 years was 118 (SD = 23) g C m^?2 year^?1. This study demonstrates that a sparsely vegetated, restored salt marsh can quickly begin to accumulate carbon and that historic and restored marshes can have similar CARs despite highly divergent formation processes.     

Cloning and characterization of ferredoxin and ferredoxin-NADP+ reductase from human malaria parasite

The human malaria parasite (Plasmodium falciparum) possesses a plastid-derived organelle called the apicoplast, which is believed to employ metabolisms crucial for the parasite's survival. We cloned and studied the biochemical properties of plant-type ferredoxin (Fd) and Fd-NADP+ reductase (FNR), a redox system that potentially supplies reducing power to Fd-dependent metabolic pathways in malaria parasite apicoplasts. The recombinant P. falciparum Fd and FNR proteins were produced by synthetic genes with altered codon usages preferred in Escherichia coli. The redox potential of the Fd was shown to be considerably more positive than those of leaf-type and root-type Fds from plants, which is favourable for a presumed direction of electron flow from catabolically generated NADPH to Fd in the apicoplast. The backbone structure of P. falciparum Fd, as solved by X-ray crystallography, closely resembles those of Fds from plants, and the surface-charge distribution shows several acidic regions in common with plant Fds and some basic regions unique to this Fd. P. falciparum FNR was able to transfer electrons selectively to P. falciparum Fd in a reconstituted system of NADPH-dependent cytochrome c reduction. These results indicate that an NADPH-FNR-Fd cascade is operative in the apicoplast of human malaria parasites.     

alpha-Synuclein stimulates differentiation of osteosarcoma cells: relevance to down-regulation of proteasome activity

Because a limited study previously showed that alpha-synuclein (alpha-syn), the major pathogenic protein for Parkinson disease, was expressed in differentiating brain tumors as well as various peripheral cancers, the main objective of the present study was to determine whether alpha-syn might be involved in the regulation of tumor differentiation. For this purpose, alpha-syn and its non-amyloidogenic homologue beta-syn were stably transfected to human osteosarcoma MG63 cell line. Compared with beta-syn-overexpressing and vector-transfected cells, alpha-syn-overexpressing cells exhibited distinct features of differentiated osteoblastic phenotype, as shown by up-regulation of alkaline phosphatase and osteocalcin as well as inductive matrix mineralization. Further studies revealed that proteasome activity was significantly decreased in alpha-syn-overexpressing cells compared with other cell types, consistent with the fact that proteasome inhibitors stimulate differentiation of various osteoblastic cells. In alpha-syn-overexpressing cells, protein kinase C (PKC) activity was significantly decreased, and reactivation of PKC by phorbol ester significantly restored the proteasome activity and abrogated cellular differentiation. Moreover, activity of lysosome was up-regulated in alpha-syn-overexpressing cells, and treatment of these cells with autophagy-lysosomal inhibitors resulted in a decrease of proteasome activity associated with up-regulation of alpha-syn expression, leading to enhance cellular differentiation. Taken together, these results suggest that the stimulatory effect of alpha-syn on tumor differentiation may be attributed to down-regulation of proteasome, which is further modulated by alterations of various factors, such as protein kinase C signaling pathway and a autophagy-lysosomal degradation system. Thus, the mechanism of alpha-syn regulation of tumor differentiation and neuropathological effects of alpha-syn may considerably overlap with each other.     

Gliadain, a gibberellin-inducible cysteine proteinase occurring in germinating seeds of wheat, Triticum aestivum L., specifically digests gliadin and is regulated by intrinsic cystatins

We cloned a new cysteine proteinase of wheat seed origin, which hydrolyzed the storage protein gliadin almost specifically, and was named gliadain. Gliadain mRNA was expressed 1 day after the start of seed imbibition, and showed a gradual increase thereafter. Gliadain expression was suppressed when uniconazol, a gibberellin synthesis inhibitor, was added to germinating seeds. Histochemical detection with anti-gliadain serum indicated that gliadain was present in the aleurone layer and also that its expression intensity increased in sites nearer the embryo. The enzymological characteristics of gliadain were investigated using recombinant glutathione S-transferase (GST)-progliadain fusion protein produced in Escherichia coli. The GST-progliadain almost specifically digested gliadin into low molecular mass peptides. These results indicate that gliadain is produced via gibberellin-mediated gene activation in aleurone cells and secreted into the endosperm to digest its storage proteins. Enzymologically, the GST-progliadain hydrolyzed benzyloxycarbonyl-Phe-Arg-7-amino-4-methylcoumarin (Z-Phe-Arg-NH(2)-Mec) at K(m) = 9.5 microm, which is equivalent to the K(m) value for hydrolysis of this substrate by cathepsin L. Hydrolysis was inhibited by two wheat cystatins, WC1 and WC4, with IC(50) values of 1.7 x 10(-8) and 5.0 x 10(-8) m, respectively. These values are comparable with those found for GST-progliadain inhibition by E-64 and egg-white cystatin, and are consistent with the possibility that, in germinating wheat seeds, gliadain is under the control of intrinsic cystatins.     

A simple method to disperse eggs from lepidopteran scalelike egg masses and to observe embryogenesis

Various insect species lay tiny, thin- and soft-shelled eggs in a connected “egg mass”. Especially in several lepidopteran species, the structure of such clustered eggs is covered with complicated scale-like secretion, which has so far prevented analysis of individual embryos. However, few studies on methods to disperse egg clusters of such insects and to compare different methods have been carried out. To overcome these problems, we developed methods to separate egg masses into individual eggs, using two Tortricidae pests, Homona magnanima Diakonoff and Adoxophyes honmai Yasuda (Lepidoptera: Tortricidae). The eggs were successfully separated from each other using potassium hydroxide and sodium hypochlorite. Although the separated eggs no longer continued their embryogenesis, fixation with heptane–paraformaldehyde, permeabilization with heptane–methanol, and staining with several dyes enabled easy observation of embryogenesis. This protocol is expected to be applicable to other insect taxa and will facilitate further morphological and genetic studies in insects that lay egg masses.     

Prevalence and species richness of trematode parasites only partially recovers after the 2011 Tohoku,Japan, earthquake tsunami

Trematode parasites have complex life cycles and use a variety of host species across different trophic levels. Thus, they can be used as indicators of disturbance and recovery of coastal ecosystems. Estuaries on the Pacific coast of northeastern Japan were heavily affected by the 2011 Tohoku earthquake tsunami. To evaluate the effect of the tsunami on the trematode community, we examined trematodes in the mud snail, Batillaria attramentaria, at five study sites (three sites severely exposed to the tsunami and two sites sheltered from the tsunami) in Sendai Bay for 2 years prior to and 8 years after the tsunami. While the trematode prevalence decreased at all study sites, the species richness decreased only at the sites exposed to the tsunami. Although parasitism increased over the study period post-tsunami, the community had not fully recovered 8 years after the event. Trematode community structure has changed every year since the tsunami and has not stabilised. This could be explained by the alteration of first and second intermediate host communities. Our study suggests that it will take more time for the recovery of the trematode community and the associated coastal ecosystem in the Tohoku region.     

Comparison Study of Allelochemicals and Bispyribac-Sodium on the Germination and Growth Response of Echinochloa crus-galli L.

The phytotoxic effects of two allelochemicals (trans-cinnamic acid and syringaldehyde) at different concentrations (1000, 100, 10, and 1 µM) on seed germination, seedling growth, and physiological and biochemical changes of Echinochloa crus-galli L. were tested by comparison to a commercial herbicide ‘Nominee’ (that is, 100 g/L bispyribac-sodium). trans-Cinnamic acid and the herbicide inhibited seed germination completely at 100 µM, whereas for syringaldehyde, complete inhibition required 1000 µM. However, with 100 µM syringaldehyde, the seed germination of the test species was 53% of the control. Allelochemicals and the herbicide delayed seed germination and significantly affected the speed of germination index (S), speed of cumulative germination index (AS), and coefficient of germination rate (CRG). The roots were more affected when nutrients were not added to the growth bioassay. In general, with the increasing concentration of allelochemicals from 100 to 1000 µM, the inhibitory effects increased. Via microscopy analysis, we found leaf blade wilting and necrosis at concentrations above 100 µM in allelochemical-treated plants. Roots of E. crus-galli treated with 1000 µM allelochemicals had black points on root nodes but had no root hairs. The anatomy of roots treated with allelochemicals (1000 µM) showed contraction or reduction of root pith cells as well as fewer and larger vacuoles compared to the control. The allelochemicals also showed remarkable effects on seedling growth, SPAD index, chlorophyll content, and free proline content in a pot culture bioassay, indicating that trans-cinnamic acid and syringaldehyde are potent inhibitors of E. crus-galli growth and can be developed as herbicides for future weed management strategies.