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
FcεRI
granulocyte/macrophage progenitors, and a newly identified SatM progenitor downstream of Ly6C
FcεRI
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.
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.
Thrombocytopenia, a common adverse effect of linezolid, often occurs in patients lacking typical risk factors. In this study, we investigated the key risk factors for linezolid-induced ...thrombocytopenia using two real-world clinical databases and explored its underlying mechanism through in vitro and in vivo experiments. In a retrospective analysis of 150 linezolid-treated patients, multivariate analysis identified coadministration of lansoprazole, a proton pump inhibitor, as a significant independent risk factor for thrombocytopenia (odds ratio: 2.33, p = 0.034). Additionally, analysis of the Food and Drug Administration Adverse Event Reporting System database revealed a reporting odds ratio of thrombocytopenia for lansoprazole of 1.64 (95% CI: 1.25–2.16). In vitro studies showed that the uptake of PNU-142586, a major linezolid metabolite, was significantly higher in human organic anion transporter 3-expressing HEK293 (HEK-hOAT3) cells compared to HEK-pBK cells. The apparent IC50 value of lansoprazole against hOAT3-mediated transport of PNU-142586 was 0.59 ± 0.38 µM. In a pharmacokinetic study using rats, coadministration of linezolid with lansoprazole intravenously resulted in approximately a 1.7-fold increase in the area under the plasma concentration-time curve of PNU-142586, but not linezolid and PNU-142300. Moreover, PNU-142586, but not linezolid, exhibited concentration-dependent cytotoxicity in a human megakaryocytic cell line. These findings suggest that linezolid-induced thrombocytopenia should be due to delayed elimination of PNU-142586. Furthermore, delayed elimination of PNU-142586 due to renal failure and hOAT3-mediated transport inhibition by lansoprazole should exacerbate linezolid-induced thrombocytopenia.
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•PNU-142586 is transported by human organic anion transporter 3 (hOAT3).•Elimination of PNU-142586 is delayed by hOAT3 inhibition.•PNU-142586 has cytotoxic effects on platelets.•Delayed elimination of PNU-142586 exacerbates linezolid-induced thrombocytopenia.
Molecules related to the insulin signaling pathway are widely conserved in the animal kingdom and are responsible for the regulation of various biological functions including growth, metabolism, and ...reproduction. Information on insulin-like peptides (ILPs) is, however, limited to insulin-like androgenic factor (IAG) in crustaceans. To date, in the kuruma prawn
Marsupenaeus japonicus
, only Maj-IAG, which is thought to be a crustacean androgen, and ovarian-specific Maj-ILP1 are the only members of the insulin family that have been reported. In this study, we identified two additional ILPs, Maj-ILP2 and Maj-gonadulin (Maj-GON), from the transcriptome data of
M. japonicus
.
Maj-ILP2
gene expression was observed in the brain ganglia of both sexes and testis, while
Maj-GON
gene expression was limited to the testis. A more detailed tissue expression analysis of three male-dominant ILPs showed clear site-specific gene expression patterns in the gonads:
Maj-ILP2
in the testis,
Maj-GON
in the vas deferens, and
Maj-IAG
in the androgenic gland attaching to the seminal vesicle. The results of this study show that, in addition to Maj-IAG, a crustacean androgen, there are two more ILP molecular species in the male gonad of
M. japonicus
, and suggest that they may serve as signaling molecules involved in the regulation of some male-specific functions.
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
, 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 EC
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, EC
values in MF and 20E treatments showed high consistency in the transitions between zoea to mysis (EC
values for survival; MF: 1.25 and 20E: 0.22 μM), and mysis to post-larvae (EC
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
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.
The greasyback shrimp
Metapenaeus ensis
is widely distributed along the coast of India and the West Pacific where it is an important fisheries species. We have examined seasonal changes in ovarian ...development, spermatogenesis, and mating of
Me. ensis
in histological studies and by external observations on specimens collected in Ise Bay, its northernmost habitat. Ovaries were found to be previtellogenic from February to May, with the first signs of development being the accumulation of yolk in oocytes in late May. Ovarian shadow ratios were high during the period late July to mid-September. The formation of cortical rods in the peripheries of oocytes and germinal vesicle breakdown were observed in ovaries from late June to September. Male shrimps had sperm in the testes during the period early June to early October, and female shrimps had spermatophores in spermatheca after early July. In late July, some post-spawn female shrimps had exogenous vitellogenic oocytes in their ovaries, indicating that ovarian development had been repeated in preparation for the next spawning. Ovarian shadow ratios, which were positively correlated with gonadosomatic indices and ovarian development, seem to be a useful marker to determine ovarian development. Our results indicate that mating in
Me. ensis
started in early July and that the spawning season ranged from July to September with more than two cycles of spawning in Ise Bay.
Delineation of the pathway for BATF2-mediated upregulation of DUSP2
Abstract
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.
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.
Recent research on decapod crustaceans revealed the presence of multiple vitellogenin genes within a single species. Characterizing their expression dynamics and regulatory mechanisms is helpful for ...the sustainability of commercially relevant decapods through a greater comprehension of vitellogenesis. However, it is unclear whether multiple vitellogenin genes exist in the kuruma prawn
Marsupenaeus japonicus
, an essential species in several Asian countries. This study determined the full-length cDNA sequence of the new vitellogenin (Maj-Vg2) using transcriptome analysis and cDNA cloning. The deduced Maj-Vg2 consisted of 2,554 amino acids and shared only 53.8% identity with Maj-Vg1, the known vitellogenin of this species. The Maj-Vg1 gene (
Maj-Vg1
) was expressed in both the hepatopancreas and ovary, whereas the Maj-Vg2 gene (
Maj-Vg2
) was expressed only in the hepatopancreas.
Maj-Vg2
expression in the hepatopancreas was low during the previtellogenic stage and increased during the early and late yolk globule stages
.
When eyestalks were ablated from immature prawns,
Maj-Vg2
expression in the hepatopancreas increased significantly, like
Maj-Vg1
expression in the ovary, suggesting possible regulation by hormones from the eyestalk ganglia. These results suggested that
Maj-Vg2
and
Maj-Vg1
are involved in vitellogenesis in this species
.
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