Background
IgG4-related disease (IgG4-RD) is a systemic inflammatory disease, which includes type 1 autoimmune pancreatitis (AIP). Interleukin-35 (IL-35) exhibits immunosuppressive effects in several ...autoimmune diseases. However, the expression of IL-35 had not been reported so far in type 1 AIP. We evaluated the association between IL-35 and several cytokines, which mediate the function of Tregs in type 1 AIP.
Methods
Plasma was collected from patients with type 1 AIP, alcoholic chronic pancreatitis (ACP), and healthy controls (HC) and assayed for cytokine expression. Total mRNA separated from peripheral blood was isolated from naïve Tregs (nTregs) and effector Tregs (eTregs).
EBI3
and
IL-12p35
gene expressions were tested in these cells by quantitative PCR. In addition, expression of IL-35 subunits in the pancreatic tissues of patients with type 1 AIP and ACP was analyzed by immunohistochemistry.
Results
IL-35 was significantly elevated in type 1 AIP (
n
= 32) plasma compared with ACP (
n
= 16) and HC (
n
= 22), but IL-27 was not. We also detected many cells expressing both EBI3 and IL-12p35 in type 1 AIP tissues. Moreover, in peripheral blood lymphocyte, the percentage of nTregs and eTregs of CD4
+
T cells in patients with type 1 AIP (
n
= 14) compared with HC (
n
= 15) was significantly decreased and increased, respectively. There were no significant differences of gene expression in patients with type 1 AIP and HC.
Conclusions
This study identified elevated expression of plasma IL-35 and tissue IL-35 subunits in patients with type 1 AIP. This might lead to inflammation suppression via activated eTregs. IL-35 might be associated with this anti-inflammatory role, especially against the Th2 response through several cytokines and the differentiation of Tregs in type 1 AIP.
Significance Selection of actions that allow the seeking of rewards and avoidance of uncomfortable environments is a fundamental animal behavior. Here, we report an in vivo method, in which the ...activities of PKA and ERK were optically recorded by microendoscopy of Förster resonance energy transfer responses of biosensors in distinct D1 and D2 dopamine receptor-expressing neurons of the dorsal striatum. The PKA and ERK were coordinately but reciprocally regulated not only by rewarding and aversive stimuli but also between the two parallel projection neurons. Importantly, the cell type-specific regulation of PKA and ERK was causally linked to active and indifferent mating reactions of male mice. The dynamic modulation of PKA and ERK in the striatum underlies the selection of alternative actions.
The selection of reward-seeking and aversive behaviors is controlled by two distinct D1 and D2 receptor-expressing striatal medium spiny neurons, namely the direct pathway MSNs (dMSNs) and the indirect pathway MSNs (iMSNs), but the dynamic modulation of signaling cascades of dMSNs and iMSNs in behaving animals remains largely elusive. We developed an in vivo methodology to monitor Föörster resonance energy transfer (FRET) of the activities of PKA and ERK in either dMSNs or iMSNs by microendoscopy in freely moving mice. PKA and ERK were coordinately but oppositely regulated between dMSNs and iMSNs by rewarding cocaine administration and aversive electric shocks. Notably, the activities of PKA and ERK rapidly shifted when male mice became active or indifferent toward female mice during mating behavior. Importantly, manipulation of PKA cascades by the Designer Receptor recapitulated active and indifferent mating behaviors, indicating a causal linkage of a dynamic activity shift of PKA and ERK between dMSNs and iMSNs in action selection.
A two-stage closed downflow hanging sponge (DHS) reactor was used as a post-treatment to prevent methane being emitted from upflow anaerobic sludge blanket (UASB) effluents containing unrecovered ...dissolved methane. The performance of the closed DHS reactor was evaluated using real municipal sewage at ambient temperatures (10–28 °C) for one year. The first stage of the closed DHS reactor was intended to recover dissolved methane from the UASB effluent and produce a burnable gas with a methane concentration greater than 30%, and its recovery efficiency was 57–88%, although the amount of dissolved methane in the UASB effluent fluctuated in the range of 46–68 % of methane production greatly depending on the temperature. The residual methane was oxidized and the remaining organic carbon was removed in the second closed DHS reactor, and this reactor performed very well, removing more than 99% of the dissolved methane during the experimental period. The rate at which air was supplied to the DHS reactor was found to be one of the most important operating parameters. Microbial community analysis revealed that seasonal changes in the methane-oxidizing bacteria were key to preventing methane emissions.
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•A new way of recovering dissolved methane from anaerobic-treated effluent is proposed.•A closed downflow hanging sponge (DHS) reactor produced burnable gas (>30% methane).•Stable dissolved methane recovery was achieved treating real municipal wastewater for one year.•The two-stage closed DHS system stopped a UASB emitting methane.
The adjustment of hydraulic retention time (HRT) and the supplement of titanium(III) nitrilotriacetate (Ti(III)-NTA) as a reducing agent were implemented in an anaerobic downflow hanging sponge (DHS) ...reactor with the aims to (i) improve nitrogen removal performance and to (ii) eliminate N2O emission. A laboratory-scale DHS reactor was operated at 35 °C, under autotrophic denitrification conditions with methane gas (14.2 L d−1) as the main carbon source, NaNO3 and NaNO2 (20 mg N L−1 per compound) as nitrogen sources. The sufficient HRT for simultaneously removing nitrate and nitrite in this reactor was found at 12 h when HRT was reduced from 24 to 6 h. Then at the HRT of 12 h, the addition of Ti(III)-NTA at a final concentration of 25 μM Ti(III) boosted the reactor’s nitrogen removal rates from 1.4 ± 0.6 to 4.1 ± 1.9 g NO3−-N m−3 d−1 and 3.2 ± 2.8 to 6.6 ± 3.3 g NO2−-N m−3 d−1. Furthermore, this study is the first to consider the N2O emission in a continuous reactor applying denitrification coupled to anaerobic methane oxidation (DAMO) process. Produced N2O in this DHS reactor was from 10.6 × 10−4% to 89.0 × 10−4% of removed NOx− without Ti(III)-NTA and from 0.7 × 10−4% to 61.4 × 10−4% of removed NOx− with Ti(III)-NTA. Overall, these findings suggested the advantage of Ti(III)-NTA as an oxygen scavenger for denitrification processes and the potential of the anaerobic DHS reactor for facilitating the DAMO processes and mitigating N2O gas.
•The closed-type DHS reactor emitted only a trace amount of N2O.•Shorten HRT caused an increase in NO2− loading rate to a toxic level.•Ti(III)-NTA solution is an effective oxygen scavenger without any inhibition.•N2O emission was irrelevant to NOx− removal in the DAMO processes.
Forest fragmentation can increase dry deposition of atmospheric ammonia (NH3) volatilized from agricultural areas, and consequently increase spatial variability of Nr deposition within the forest ...(“elevated reactive nitrogen (Nr) deposition”). However, little is known about this effect and its impact on forest production in a deciduous broad-leaved forest in Asian countries. Here, we performed the field observations of atmospheric concentration and deposition of inorganic Nr gases and particles in a Japanese fragmented forest from May 2018 to April 2019. Leaf traits and growth of Japanese oak tree and understory vegetation were also measured. Atmospheric concentration and deposition of dissolved inorganic Nr (DIN) to tree canopies were measured via filter sampling and throughfall methods, respectively. Canopy retention/exchange was also estimated as a part of dry deposition using the canopy budget model. The results demonstrated that annual dry deposition of NH3 to tree canopies (4.4 kgN ha−1 y−1) was dominant in the annual total DIN deposition (7.1 kgN ha−1 y−1) at the forest edge, including the elevated Nr deposition of approximately 2 kgN ha−1 y−1. Additionally, agricultural activities such as fertilization in the area surrounding the forest likely enhanced the potential of canopy retention of NH4+, readily absorbed by tree canopy. The growth rates of tree and understory vegetation (dwarf bamboo) were higher at the edge than that at the interior, emphasizing a need for further investigation to quantify the effect of low Nr deposition (<3–5 kgN ha−1 y−1) on forest production, along with the conventional experimental studies under a high Nr deposition.
•Field observations were conducted in a Japanese cool-temperate fragmented forest.•Canopy retention was estimated using the canopy budget model.•The edge effect of NH3 dry deposition was about 2 kgN ha−1 y−1.•Agricultural activities surrounding the forest enhanced the NH3 canopy retention.•Growth rates of tree and dwarf bamboo may be enhanced due to the edge effect.
Aim: To clarify the mechanism by which pitavastatin reduced cardiovascular (CV) events more effectively than atorvastatin in the TOHO Lipid Intervention Trial Using Pitavastatin (TOHO-LIP), the ...changes in (Δ) non-heparinized serum level of lipoprotein lipase mass (LPL mass) during administration of the respective statins were investigated. Methods: From TOHO-LIP data, 223 hypercholesterolemic patients with any CV risks followed at Toho University Sakura Medical Center were analyzed. The patients were randomized to pitavastatin (2 mg/day) group (n=107) or atorvastatin (10 mg/day) group (n=116), and followed for 240 weeks. In this subgroup study, the primary and secondary end points were the same as those in TOHO-LIP, and 3-point major adverse cardiovascular events (3P-MACE) was added. The relationship between ΔLPL mass during the first year and the incidences of each end point was analyzed. Results: The lipid-lowering effect was not different between the two statins. Cumulative 240-week incidence of each end point was significantly lower in pitavastatin group (primary: 1.9% vs. 10.3%, secondary: 4.7% vs. 18.1%, 3P-MACE: 0.9% vs. 6.9%). Mean LPL mass (64.9 to 69.0 ng/mL) and eGFR (70.1 to 73.6 ml/min/1.73m 2) increased in pitavastatin group, but not in atorvastatin group during the first year. Cox proportional-hazards model revealed that ΔLPL mass (1 ng/mL or 1SD) contributed to almost all end points. Conclusions: Pitavastatin administration reduced CV events more efficaciously than atorvastatin despite similar LDL cholesterol-lowering effect of the two statins. Increased LPL mass during the first year by pitavastatin treatment may be associated with this efficacy.
Aggression is a prevalent behavior in the animal kingdom that is used to settle competition for limited resources. Given the high risk associated with fighting, the central nervous system has evolved ...an active mechanism to modulate its expression. Lesioning the lateral septum (LS) is known to cause “septal rage,” a phenotype characterized by a dramatic increase in the frequency of attacks. To understand the circuit mechanism of LS-mediated modulation of aggression, we examined the influence of LS input on the cells in and around the ventrolateral part of the ventromedial hypothalamus (VMHvl)—a region required for male mouse aggression. We found that the inputs from the LS inhibited the attack-excited cells but surprisingly increased the overall activity of attack-inhibited cells. Furthermore, optogenetic activation of the projection from LS cells to the VMHvl terminated ongoing attacks immediately but had little effect on mounting. Thus, LS projection to the ventromedial hypothalamic area represents an effective pathway for suppressing male aggression.
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•Inhibiting LS increases aggression, whereas its activation suppresses ongoing attack•Activating the LS-VMHvl projection inhibits attack but not mounting behaviors•LS sends monosynaptic GABAergic inputs to the VMHvl glutamatergic cells•The LS-VMHvl pathway inhibits attack-excited cells but activates attack-inhibited cells
Lesioning the lateral septum (LS) causes exaggerated aggression. Wong et al. find that LS sends direct inhibition to the ventromedial hypothalamus, ventrolateral part, a region essential for male mouse aggression. This input can effectively suppress ongoing aggression by shifting the activity balance between attack-inhibited and attack-excited cells.
Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis with insulin resistance, oxidative stress, lipotoxicity, adipokine secretion by fat cells, endotoxins ...(lipopolysaccharides) released by gut microbiota, and endoplasmic reticulum stress. Together, these factors promote NAFLD progression from steatosis to nonalcoholic steatohepatitis (NASH), fibrosis, and eventually end-stage liver diseases in a proportion of cases. Hepatic fibrosis and carcinogenesis often progress together, sharing inflammatory pathways. However, NASH can lead to hepatocarcinogenesis with minimal inflammation or fibrosis. In such instances, insulin resistance, oxidative stress, and lipotoxicity can directly lead to liver carcinogenesis through genetic and epigenetic alterations. Transforming growth factor (TGF)-β signaling is implicated in hepatic fibrogenesis and carcinogenesis. TGF-β type I receptor (TβRI) and activated-Ras/c-Jun-N-terminal kinase (JNK) differentially phosphorylate the mediator Smad3 to create two phospho-isoforms: C-terminally phosphorylated Smad3 (pSmad3C) and linker-phosphorylated Smad3 (pSmad3L). TβRI/pSmad3C signaling terminates cell proliferation, while constitutive Ras activation and JNK-mediated pSmad3L promote hepatocyte proliferation and carcinogenesis. The pSmad3L signaling pathway also antagonizes cytostatic pSmad3C signaling. This review addresses TGF-β/Smad signaling in hepatic carcinogenesis complicating NASH. We also discuss Smad phospho-isoforms as biomarkers predicting HCC in NASH patients with or without cirrhosis.
Microbial systems are widely used to treat different types of wastewater from domestic, agricultural, and industrial sources. Community composition is an important factor in determining the ...successful performance of microbial treatment systems; however, a variety of uncultured and unknown lineages exist in sludge that requires identification and characterization. The present study examined the archaeal community composition in methanogenic, denitrifying, and nitrogen-/phosphate-removing wastewater treatment sludge by Archaea-specific 16S rRNA gene sequencing analysis using Illumina sequencing technology. Phylotypes belonging to Euryarchaeota, including methanogens, were most abundant in all samples except for nitrogen-/phosphate-removing wastewater treatment sludge. High levels of Deep Sea Hydrothermal Vent Group 6 (DHVEG-6), WSA2, Terrestrial Miscellaneous Euryarchaeotal Group, and Miscellaneous Crenarchaeotic Group were also detected. Interestingly, DHVEG-6 was dominant in nitrogen-/phosphate-removing wastewater treatment sludge, indicating that unclear lineages of Archaea still exist in the anaerobic wastewater treatment sludges. These results reveal a previously unknown diversity of Archaea in sludge that can potentially be exploited for the development of more efficient wastewater treatment strategies.
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