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Physiological functions of juvenile hormone (JH) and molting hormone have been demonstrated in insects. JH, molting hormone and their mimics (insect growth regulators, IGRs) show endocrine-disrupting effects not only on target pest insects but also on other arthropod species such as crustaceans. However, little is known about the endocrine-disrupting effects of IGRs on benthic crustaceans. In this study, laboratory experiments were conducted to investigate effects of representative innate JH in crustaceans (methyl farnesoate, MF) and molting hormone (20-hydroxyecdysone, 20E, active form of ecdysteroid) on larval stages of the kuruma prawn Marsupenaeus japonicus, which is a decapod crustacean living in warm seawater. Larval development of kuruma prawn progresses in the order of nauplius, zoea, mysis, and then post-larvae with molting and metamorphosis, but it is unknown whether both MF and 20E have crucial roles in metamorphosis and molting of this species. Treatments of either MF or 20E on shrimp larvae were attempted at each developmental stage and those effects were validated. In terms of EC50 values between mortality and metamorphosis, there were apparent differences in the transition from nauplius to zoea (MF: 7.67 and 0.12 μM; 20E: 3.84 and 0.06 μM in survival and metamorphic rates, respectively). In contrast, EC50 values in MF and 20E treatments showed high consistency in the transitions between zoea to mysis (EC50 values for survival; MF: 1.25 and 20E: 0.22 μM), and mysis to post-larvae (EC50 values for survival; MF: 0.65 and 20E: 0.46 μM). These data suggest that nauplius has strong resistance against exposure to MF and 20E. Moreover, both chemicals induced high mortality triggered by the disruption of molting associated with metamorphosis. To our knowledge, this is the first experimental evidence that investigates in vivo physiological functions of MF and 20E in the larval stages of kuruma prawn, shedding light on not only ecotoxicological impacts of IGRs released into nature, but also endocrine mechanisms underlying larval development with metamorphosis in benthic decapod crustaceans.

Schlafen-8 (Slfn8) is a member of the Schlafen family of proteins, which harbor helicase domains and are induced by LPS and interferons. It has been reported that the Schlafen family are involved in various cellular functions, including proliferation, differentiation and regulation of virus replication. Slfn8 has been implicated in T-cell differentiation in the thymus. However, the roles of Slfn8 in the immune system remains unclear. In this study, we generated Slfn8 knockout mice (Slfn8−/−) and investigated the immunological role of Slfn8 using the T-cell-mediated autoimmune model experimental autoimmune encephalomyelitis (EAE). We found that the clinical score was reduced in Slfn8−/− mice. IL-6 and IL-17A cytokine production, which are associated with EAE onset and progression, were decreased in the lymph nodes of Slfn8−/− mice. Immune cell populations in Slfn8−/− mice, including macrophages, neutrophils, T cells and B cells, did not reveal significant differences compared with wild-type mice. In vitro activation of Slfn8−/− T cells in response to TCR stimulation also did not reveal significant differences. To confirm the involvement of non-hematopoietic cells, we isolated CD45− CD31+ endothelial cells and CD45−CD31− gp38+ fibroblastic reticular cells by FACS sorting. We showed that the levels of IL-6 and Slfn8 mRNA in CD45− CD31+ endothelial cells were increased after EAE induction. In contrast, the level of IL-6 mRNA after EAE induction was markedly decreased in CD31+ endothelial cells from Slfn8−/− mice. These results indicate that Slfn8 may play a role in EAE by regulating inflammation in endothelial cells.

This article investigates the shadow value of resilience in complex natural lands acting as wild pollinator habitats. We capture the linkage between pollination services in crop production and habitat conditions in the surrounding natural land with a bioeconomic model. Our case study is buckwheat, which is produced in the hilly and mountainous region of central Japan and is greatly dependent on diverse fauna for pollination services. We model the mechanism of regime shifts in ecosystems consisting of buckwheat fields and the surrounding natural land with a threshold estimation model. We then find that the forest around the crop fields, which serves as a habitat for wild pollinators, is a determinant of an ecological threshold that causes regime shifts. We calculate the shadow value of resilience provided by forest habitat around a unit of buckwheat field to be $9,796, implying that the total value of resilience in complex natural land amounts to half of the stock price of buckwheat land. This overlooked value gives us useful insights on the sustainable use of ecosystems, including both pollinator‐mediated crop fields and habitats for pollinators.

Monocytes and macrophages comprise a variety of subsets with diverse functions. It is thought that these cells play a crucial role in homeostasis of peripheral organs, key immunological processes and development of various diseases. Among these diseases, fibrosis is a life-threatening disease of unknown aetiology. Its pathogenesis is poorly understood, and there are few effective therapies. The development of fibrosis is associated with activation of monocytes and macrophages. However, the specific subtypes of monocytes and macrophages that are involved in fibrosis have not yet been identified. Here we show that Ceacam1+Msr1+Ly6C-F4/80-Mac1+ monocytes, which we term segregated-nucleus-containing atypical monocytes (SatM), share granulocyte characteristics, are regulated by CCAAT/enhancer binding protein β (C/EBPβ), and are critical for fibrosis. Cebpb deficiency results in a complete lack of SatM. Furthermore, the development of bleomycin-induced fibrosis, but not inflammation, was prevented in chimaeric mice with Cebpb-/- haematopoietic cells. Adoptive transfer of SatM into Cebpb-/- mice resulted in fibrosis. Notably, SatM are derived from Ly6C-FceRI+ granulocyte/macrophage progenitors, and a newly identified SatM progenitor downstream of Ly6C-FceRI+ granulocyte/macrophage progenitors, but not from macrophage/dendritic-cell progenitors. Our results show that SatM are critical for fibrosis and that C/EBPβ licenses differentiation of SatM from their committed progenitor.

This study investigates the dynamic linkage between crop diversity and agro-ecosystem resilience. The analysis estimates a panel data of rice farming in Japan using a time-varying transition probability Markov switching model, capturing (i) the alternate regimes of agro-ecosystems, (ii) the controlling factors affecting the regime shifts of agro-ecosystems, and (iii) the nonmonotonic response of agricultural production under alternate regimes. Results show that the effect of crop diversity on agro-ecosystem productivity differs depending on its regimes. Crop diversity increases productivity during normal periods, a normal regime, while it decreases the productivity during periods exposed to disturbances such as extreme weather events and disease and insect damage, an adverse regime. Further, we find that crop diversity enhances the agro-ecosystem resilience. Thus, it increases the likelihood of the agro-ecosystem remaining in a normal regime and staving off an adverse regime. The crop diversity loss has gradually increased in agro-ecosystems without sufficient understanding about the linkage between crop diversity and agro-ecosystem resilience. Our findings suggest the possibility that the agro-ecosystem resilience would be a key driver of sustainable agriculture under increasing uncertainties. This study gives useful insights on this issue by empirically demonstrating the effects of crop diversity on the agro-ecosystem resilience.

Interleukin 34 (IL-34) constitutes a cytokine that shares a common receptor, colony-stimulating factor-1 receptor (CSF-1R), with CSF-1. We recently identified a novel type of monocytic cell termed follicular dendritic cell-induced monocytic cells (FDMCs), whose differentiation depended on CSF-1R signaling through the IL-34 produced from a follicular dendritic cell line, FL-Y. Here, we report the functional mechanisms of the IL-34–mediated CSF-1R signaling underlying FDMC differentiation. CRIPSR/Cas9-mediated knockout of the Il34 gene confirmed that the ability of FL-Y cells to induce FDMCs completely depends on the IL-34 expressed by FL-Y cells. Transwell culture experiments revealed that FDMC differentiation requires a signal from a membrane-anchored form of IL-34 on the FL-Y cell surface, but not from a secreted form, in a direct interaction between FDMC precursor cells and FL-Y cells. Furthermore, flow cytometric analysis using an anti–IL-34 antibody indicated that IL-34 was also expressed on the FL-Y cell surface. Thus, we explored proteins interacting with IL-34 in FL-Y cells. Mass spectrometry analysis and pulldown assay identified that IL-34 was associated with the molecular chaperone 78-kDa glucose-regulated protein (GRP78) in the plasma membrane fraction of FL-Y cells. Consistent with this finding, GRP78-heterozygous FL-Y cells expressed a lower level of IL-34 protein on their cell surface and exhibited a reduced competency to induce FDMC differentiation compared with the original FL-Y cells. These results indicated a novel GRP78-dependent localization and specific function of IL-34 in FL-Y cells related to monocytic cell differentiation.

Growing evidence has revealed that the transcription factor basic leucine zipper transcription factor ATF-like 2 (BATF2) has unique transcriptional activities, including regulating cytokines via TLR signals in macrophages, which affect mortality due to infection and cancer. On the basis of genome-wide analyses using the chromatin immunoprecipitation-sequencing technique, we found that dual-specificity phosphatase 2 (Dusp2) had a significantly lower acetyl-histone status in Batf2−/− bone marrow-derived macrophages (BMDMs) compared with wild-type (WT) BMDMs. The phosphatase DUSP2 has been reported to play a critical role in inflammatory responses. Therefore, we evaluated the BATF2 transcriptional activities on the Dusp2 promoter. We found that the DUSP2 and IL-12 p40 expression levels were significantly lower in Batf2−/− BMDMs than in WT controls following their stimulation with TLR7 ligands. Further in vitro studies revealed that phospho-STAT3 was up-regulated and NF-κB p50/p65 were down-regulated in Batf2−/− BMDMs compared with their levels in WT controls. Additionally, Th1 immunity was impaired in Batf2−/− mice following their stimulation with TLR7 ligands. We also found that BATF2 interacts with NF-κB p65 and promotes DUSP2 expression through the NF-κB-binding site in the Dusp2 promoter at −203 to −121. Collectively, our findings suggest that BATF2 activates DUSP2 gene expression and up-regulates NF-κB activity via phospho-STAT3 dephosphorylation.

The therapeutic activity of checkpoint blockers and toll-like receptor (TLR) agonists, which show some efficacy against malignancies, appears to at least partially result from the secretion of type-I IFNs. Thus, we hypothesized that type-I IFN-inducible transcription factors, such as basic leucine zipper transcription factor ATF-like 2 (Batf2), might play a role in tumor immunity. Here, we investigated the role of Batf2, especially its positive transcriptional activities, and evaluated its antitumor effect. This study shows that Batf2 has an antitumor effect through the up-regulation of IL-12 p40 in tumor-associated macrophages, which eventually induces the activation of CD8+ T cells and their accumulation within the tumor. Batf2 may be an important target in anticancer treatment with immune checkpoint blockers and TLR agonists.

Significance The therapeutic activity of checkpoint blockers and toll-like receptor (TLR) agonists, which show some efficacy against malignancies, appears to at least partially result from the secretion of type-I IFNs. Thus, we hypothesized that type-I IFN-inducible transcription factors, such as basic leucine zipper transcription factor ATF-like 2 ( Batf2 ), might play a role in tumor immunity. Here, we investigated the role of Batf2 , especially its positive transcriptional activities, and evaluated its antitumor effect. This study shows that Batf2 has an antitumor effect through the up-regulation of IL-12 p40 in tumor-associated macrophages, which eventually induces the activation of CD8 + T cells and their accumulation within the tumor. Batf2 may be an important target in anticancer treatment with immune checkpoint blockers and TLR agonists.

The Fukushima Daiichi accident raises various kinds of social unease in Japan. Especially, unease for radioactive contamination around the Fukushima Daiichi plant is serious. Also, around the other nuclear power plants, local residents would feel unease for a similar accident in the future. Although the government and the electric power companies have already implemented or plan to implement several measures to mitigate such unease, it is difficult to progress their policies effectively because the effect of each measure is not quantitatively clarified. The purpose of our research is to evaluate these effects by analyzing fluctuations in local property values and local residents economic welfare, which are monetary indexes reflecting the social unease, to construct information that is useful to plan an optimal package of mitigation measures in each nuclear power plant site from the viewpoint of cost-benefit analysis. In this paper, we explain the immediate plans of this research and its academic and political contributions.

Under the scheme of the Kyoto Protocol, there are plans for the efficient reduction of carbon dioxide emissions. In the electric power sector, nuclear power generation, which emits no carbon dioxide in the process of generating electricity, has come under scrutiny. However, this energy produces a new environmental issue: the disposal of radioactive waste. First, we derive shadow prices of carbon dioxide and low-level waste as marginal abatement costs in the case of the electric power sector in Japan, employing a directional output distance function. It is found that the shadow prices are US$39 per tonne for carbon dioxide and US$1531 per liter for low-level waste. Secondly, we calculate the indirect Morishima elasticity between carbon dioxide and low-level waste in order to identify their substitutability, and it is found that the substitution of low-level waste for carbon dioxide is easier than the reverse. This result suggests that, with the amount of generated electricity fixed, carbon dioxide can be substituted more easily by low-level waste when the relative price of carbon dioxide increases, for example, as a result of implementation of a carbon dioxide tax or an emissions trading system.

This study examines several nuclear power plant sites in Japan by hedonic house rent analysis. As a result, for some plants, the neighboring houses are negatively evaluated by the residents, that is, their economic welfare get worse by living near the plants, whereas there are no or positive evaluations for the other plants. Meta analysis is carried out to examine social factors causing these differences – such as plant's attributes (operation years and past accidents) and host community's attributes (population density, change in employment and industrial structure, financial condition and change in social infrastructures).

The subject of this paper is to estimate consumers' welfare loss when the BSE testing age criterion for cattle is revised from all months to older than 21 months, by analyzing the change in meat demand due to this revision. However this analysis is different from ordinary revealed preference methods in that the demand data after this policy change are stated, while the data before this change are revealed as usual. This is because this paper focuses on a policy change which is not substantially executed yet. Using this demand data I estimated the generalized corner solution model of Phaneuf et al. (2000) for an incomplete demand system model. When I simulated each monitor's welfare loss based on the model estimation result, the expected compensating variation per household per month was 214 yen at the sample mean and 55 yen at the sample median.

Kumamoto Area is so rich in groundwater that it is possible to supply all their residential water for a population of about 900, 000 from groundwater. Such plentiful supply of groundwater is coursed by geological features and land use in Kumamoto Area. However, in this area, groundwater level has been getting lower in recent years and we are anxious about a water shortage in the future. Now, some policies for maintenance of groundwater recharge function have been investigated.The main theme of this paper is economical evaluation for maintenance of groundwater recharge function. To do this, we estimated WTP for maintenance of this function by using CVM. In the economical evaluation process, I carried out questionnaire survey for residents in Kumamoto City because they will pay the cost of the policy based on the beneficiary payment principle. Consequently, the total WTP was estimated about 3, 260, 400, 000 yen per year by using medium of WTP.

We develop a new and less burdensome methodology called the high-and-low choice method to elicit and analyse ambiguity in public risk perception. We apply this method to the cancer mortality risk due to low-dose radiation exposure around the Fukushima Daiichi nuclear power plant, a real uncertain problem caused by the accident that is the second severest one after the Chernobyl case. The empirical results shed new light on Slovic fs (1987) seminal work; considering radiation as an unknown risk made public perceptions for the mortality rate more ambiguous, and the dread image led people to perceive larger and more ambiguous risks. In addition, those who accessed popular information media (television, newspaper, internet, social network services, and conversations with neighbours) tended to have more negative and ambiguous perceptions.

With the use of a mouse FDC line, FL-Y, we have been analyzing roles for FDCs in controlling B cell fate in GCs. Beside these regulatory functions, we fortuitously found that FL-Y cells induced a new type of CD11b+ monocytic cells (F4/80+, Gr-1−, Ly6C−, I-A/E−/lo, CD11c−, CD115+, CXCR4+, CCR2+, CX3CR1−) when cultured with a Lin−c-kit+ population from mouse spleen cells. The developed CD11b+ cells shared a similar gene-expression profile to mononuclear phagocytes and were designated as FDMCs. Here, we describe characteristic immunological functions and the induction mechanism of FDMCs. Proliferation of anti-CD40 antibody-stimulated B cells was markedly accelerated in the presence of FDMCs. In addition, the FDMC-activated B cells efficiently acquired GC B cell-associated markers (Fas and GL-7). We observed an increase of FDMC-like cells in mice after immunization. On the other hand, FL-Y cells were found to produce CSF-1 as well as IL-34, both of which are known to induce development of macrophages and monocytes by binding to the common receptor, CSF-1R, expressed on the progenitors. However, we show that FL-Y-derived IL-34, but not CSF-1, was selectively responsible for FDMC generation using neutralizing antibodies and RNAi. We also confirmed that FDMC generation was strictly dependent on CSF-1R. To our knowledge, a CSF-1R-mediated differentiation process that is intrinsically specific for IL-34 has not been reported. Our results provide new insights into understanding the diversity of IL-34 and CSF-1 signaling pathways through CSF-1R.