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Colorectal cancer (CRC) has a high mortality rate among cancers worldwide. To reduce this mortality rate, chemotherapy (5-fluorouracil, oxaliplatin, and irinotecan) or targeted therapy (bevacizumab, cetuximab, and panitumumab) has been used to treat CRC. However, due to various side effects and poor responses to CRC treatment, novel therapeutic targets for drug development are needed. In this study, we identified the overexpression of EHMT1 in CRC using RNA sequencing (RNA-seq) data derived from TCGA, and we observed that knocking down EHMT1 expression suppressed cell growth by inducing cell apoptosis in CRC cell lines. In Gene Ontology (GO) term analysis using RNA-seq data, apoptosis-related terms were enriched after EHMT1 knockdown. Moreover, we identified the CHOP gene as a direct target of EHMT1 using a ChIP (chromatin immunoprecipitation) assay with an anti-histone 3 lysine 9 dimethylation (H3K9me2) antibody. Finally, after cotransfection with siEHMT1 and siCHOP, we again confirmed that CHOP-mediated cell apoptosis was induced by EHMT1 knockdown. Our findings reveal that EHMT1 plays a key role in regulating CRC cell apoptosis, suggesting that EHMT1 may be a therapeutic target for the development of cancer inhibitors.

The human microbiome plays an essential role in the human immune system, food digestion, and protection from harmful bacteria by colonizing the human intestine. Recently, although the human microbiome affects colorectal cancer (CRC) treatment, the mode of action between the microbiome and CRC remains unclear. This study showed that propionate suppressed CRC growth by promoting the proteasomal degradation of euchromatic histone-lysine N-methyltransferase 2 (EHMT2) through HECT domain E3 ubiquitin protein ligase 2 (HECTD2) upregulation. In addition, EHMT2 downregulation reduced the H3K9me2 level on the promoter region of tumor necrosis factor α-induced protein 1 (TNFAIP1) as a novel direct target of EHMT2. Subsequently, TNFAIP1 upregulation induced the apoptosis of CRC cells. Furthermore, using Bacteroides thetaiotaomicron culture medium, we confirmed EHMT2 downregulation via upregulation of HECTD2 and TNFAIP1 upregulation. Finally, we observed the synergistic effect of propionate and an EHMT2 inhibitor (BIX01294) in 3D spheroid culture models. Thus, we suggest the anticancer effects of propionate and EHMT2 as therapeutic targets for colon cancer treatment and may provide the possibility for the synergistic effects of an EHMT2 inhibitor and microbiome in CRC treatment.

This study experimentally investigates how repeatedly‐induced exogenous happiness and anger affect the dynamics of cooperation and punishment in a public good game with repeated trials, wherein costly punishment is available and stranger matching is used. The study finds that induced happiness may harm cooperation when the reactions of the punished are also considered. Indeed, contributions in the happiness treatment decay with each round, while those in the anger treatment are stable. The main reason for this is found to be that the antisocial‐punished cooperators in the happiness treatment reduce their contributions, while those in the anger treatment do not.

Microbial fuel cell (MFC) is one of renewable biofuel production technology that directly converts biomass to electricity. Cellulosic biomass is particularly attractive renewable resources for its low cost and abundance and neutral carbon balance. However, methanogenesis remains as a major factor limiting MFC performance. The current study reports that saponin addition at 0.05% w/v dose to anolyte in MFCs inhibited methanogenesis and improves power generation and cellulose fermentation. Mediator-less two chamber H-type MFCs were prepared using rumen fluid as anode inocula at 20% v/v of anolyte to convert finely ground pine tree (Avicel) at 2%, w/v to electricity. Saponin was added to the anode of MFC at 0.005% or 0.05% v/v dosage for treatment. MFC power and current across an external resistor were measured daily for 10d. On d10, collected gases from anode compartment were measured for total gas volume and analyzed for gas composition on gas chromatography. Supplementation of saponin to MFC at 0.005% did not have any effects on electricity generation or biogas production and composition. Saponin at 0.05% dose reduced 10% of methane production and increased 40% of CO2 production and 6.4% of total gas production for 10d MFC operation. Voltage across resistor prior to treatment addition (d0) was 164.75 ± 9.07 mV. In control group, voltage across resistor did not change (P = 0.9153) with time course and mean was 167.8 ± 8.20 mV ranged from 157 to 174.5 mV during 10d operation. In 0.05% Saponin group, voltage across resistor increased (P 0.0001) after d2 and mean was 187.3 ± 4.30 mV ranged between 161.5 and 204.0 mV and the 10d mean of voltage across resistor in 0.05% Saponin was greater (P 0.0001) than in control group. 0.05% Saponin also had greater voltage across resistor at d5 (P = 0.0030) and d6 (P = 0.0246) than control. End point potential increased (P 0.0001) in 0.05% Saponin after d2. 0.05% Saponin had greater (P 0.0001) in 0.05% Saponin. Power density increased (P 0.0001) after d2 in 0.05% Saponin. 0.05% Saponin MFCs had greater (P 0.0001) overall mean of 10d operation. The current study provides strong background for potential use of saponin and saponin containing natural resources for methanogenesis inhibitor and cellulolysis enhancer in MFC and also cellulolysis reactors.

Using an ultimatum game experiment where a representative makes a decision on behalf of the group members and equally shares the outcomes with them, we investigate whether the representative’s soci...

Particulate matter (PM) can be categorized by particle size (PM

Dozens of histone methyltransferases have been identified and biochemically characterized, but the pathological roles of their dysfunction in human diseases such as cancer remain largely unclear. Here, we demonstrate the involvement of EHMT1, a histone lysine methyltransferase, in lung cancer. Immunohistochemical analysis indicated that the expression levels of EHMT1 are significantly elevated in human lung carcinomas compared with non‐neoplastic lung tissues. Through gene ontology analysis of RNA‐seq results, we showed that EHMT1 is clearly associated with apoptosis and the cell cycle process. Moreover, FACS analysis and cell growth assays showed that knockdown of EHMT1 induced apoptosis and G1 cell cycle arrest via upregulation of CDKN1A in A549 and H1299 cell lines. Finally, in 3D spheroid culture, compared to control cells, EHMT1 knockdown cells exhibited reduced aggregation of 3D spheroids and clear upregulation of CDKN1A and downregulation of E‐cadherin. Therefore, the results of the present study suggest that EHMT1 plays a critical role in the regulation of cancer cell apoptosis and the cell cycle by modulating CDKN1A expression. Further functional analyses of EHMT1 in the context of human tumorigenesis may aid in the development of novel therapeutic strategies for cancer., Although histone methyltransferases have been previously well characterized, their role in carcinogenesis remains underexplored. In our study, we detected the overexpression of the histone lysine methyltransferase EHMT1 in lung cancer. EHMT1 modulated the gene expression of CDKN1A by regulating H3K9 dimethylation. Knockdown of EHMT1 in lung cancer cell lines upregulated CDKN1A expression and induced both apoptosis and cell cycle arrest. Our findings suggest that EHMT1 may potentially serve as a therapeutic target for the treatment of patients with lung cancer.

Experimental studies regularly show that third-party punishment (TPP) substantially exists in various settings. This study further investigates the robustness of TPP under an environment where context effects are involved. In our experiment, we offer a third party an additional but unattractive risky investment option. We find that, when the dominated investment option irrelevant to prosocial behavior is available, the demand for punishment decreases, whereas the demand for investment increases. These findings support our hypothesis that the seemingly unrelated and dominated investment option may work as a compromise and suggest the fragility of TPP in this setting.

BackgroundBacteroides thetaiotaomicron (BT) is the second most commonly isolated bacterium in the human microbiome after B. fragilis and is involved in the hydrolysis of glycosidic bonds in dietary carbohydrates. Although the human microbiome has recently been shown to affect colorectal cancer (CRC) treatment, the mode of action (MOA) between the microbiome and CRC is still unclear.MethodsTo assess the colon cancer apoptosis, we performed western blot, qRT-PCR and FACS analysis using BT supernatant (Sup), sodium propionate (SP), and EHMT2 specific siRNA. Using RNA-seq analysis and ChIP-seq analysis, we identified HECTD2 (E3 ligase) and TNFAIP1 (EHMT2 target) genes. The antitumor activity of EHMT2 was determined by an in vivo xenograft model.ResultsWe selected propionate derived from BT and showed that it suppressed CRC growth by promoting proteasomal degradation of EHMT2 through HECTD2 upregulation. Moreover, downregulation of EHMT2 reduced the level of H3K9me2 on the promoter region of TNFAIP1, and subsequently, upregulation of TNFAIP1 induced apoptosis of CRC cells. Finally, we performed an in vivo study using BIX01294 to inactivate EHMT2 and observed a reduction in the tumor size of the CRC xenograft models.ConclusionsWe suggest anticancer effects of BT and EHMT2 as therapeutic targets for colon cancer treatment, and we will provide the possibility for synergistic effects of an EHMT2 inhibitor and BT in CRC treatment.*Authors share co-first authorship

Background: This study examined the degree of hemolysis during vacuum-assisted venous drainage at different negative pressures to identify an adequate negative pressure that provides effective venous drainage without significant hemolysis in open-heart surgery in children weighing less than 10 kg. Methods: Patients weighing less than 10 kg who underwent surgery for ventricular septal defect or atrial septal defect from 2011 to 2014 were enrolled. We used one of four negative pressures (20, 30, 40, or 60 mm Hg) for each patient. We measured haptoglobin, plasma hemoglobin, aspartate aminotransferase, and lactate dehydrogenase levels in the patients’ blood three times perioperatively and determined the potential correlation between the change in each parameter with the level of negative pressure. Results: Forty-six patients were enrolled in this study (mean age: 7.1 ± 7.0 months, mean body weight: 6.1 ± 1.8 kg). There were no significant differences according to the degree of negative pressure with respect to patient age, body weight, cardiopulmonary bypass (CPB) time, aorta cross-clamping time, blood flow during CPB, or lowest body temperature. All parameters that we measured reflected progression of hemolysis during CPB; however, the degree of change in the parameters did not correlate with negative pressure. Conclusion: In pediatric patients weighing less than 10 kg, the change in the degree of hemolysis did not differ with the amount of negative pressure. We may apply negative pressures up to 60 mm Hg without increasing the risk of hemolysis, with almost same the level of hemolysis using negative pressures of 20, 30, and 40 mm Hg for effective venous drainage and an ideal operative field during open-heart surgery.

In rodents, the preovulatory LH surge is temporally gated, but the timing cue is unknown. Estrogen primes neurons in the anteroventral periventricular nucleus (AVPV) to secrete kisspeptin, which potently activates GnRH neurons to release GnRH, eliciting a surge of LH to induce ovulation. Deletion of the circadian clock gene Bmal1 results in infertility. Previous studies have found that Bmal1 knockout (KO) females do not display an LH surge at any time of day. We sought to determine whether neuroendocrine disruption contributes to the absence of the LH surge. Because Kiss1 expression in the AVPV is critical for regulating ovulation, we hypothesized that this population is disrupted in Bmal1 KO females. However, we found an appropriate rise in AVPV Kiss1 and Fos mRNA at the time of lights out in ovariectomized estrogen-treated animals, despite the absence of a measureable increase in LH. Furthermore, Bmal1 KO females have significantly increased LH response to kiss-10 administration, although the LH response to GnRH was unchanged. We then created Kiss1- and GnRH-specific Bmal1 KO mice to examine whether Bmal1 expression is necessary within either kisspeptin or GnRH neurons. We detected no significant differences in any measured reproductive parameter. Our results indicate that disruption of the hypothalamic regulation of fertility in the Bmal1 KO females is not dependent on endogenous clocks within either the GnRH or kisspeptin neurons.

This study provides new insight on the established issue of elicitation bias in hypothetical choice settings. In particular, using an experiment that elicits real and hypothetical willingness to pay for the protection of otters, we provide evidence that the observed bias is driven by those who are both uncertain about their value and exhibit hypothetical bias in risk attitudes. This finding provides a reason why calibration approaches based on follow-up certainty questions have proven useful, but also suggests a degree of caution in applying the approach. Our results favour combining uncertainty calibration with CVM-X in which hypothetical bias in risk attitudes is also taken account to correct for hypothetical bias in WTP.

Grossman and Helpman highlighted a political framework to internalize inefficiency incurred due to unilateral trade policy implementation by sovereign countries. This paper extensively adopts their framework to explore the effects of special interest politics on governments under negotiation to forge international environmental standards to control global emission. Particular attention is given to a case in which negotiation is driven by transferring the abatement technology. Within a specific factor model of international trade, improving the abatement efficiency through technology transfer can give the most mutually beneficial outcome, achieving the lowest level of global pollution compared to other political benchmarks.

We experimentally investigate the effect of an independent and exogenous background risk to initial wealth on subjects’ risk attitudes and explore an appropriate incentive mechanism when identical or similar tasks are repeated in an experiment. Taking a simple chance improving decision model under risk where the winning probabilities are negatively related to the potential gain, we find that such a background risk tends to make risk-averse subjects behave more risk aversely. Furthermore, we find that risk-averse subjects tend to show decreasing absolute risk aversion (DARA), and that a random round payoff mechanism (RRPM) would control the possible wealth effect. This suggests that RRPM would be a better incentive mechanism for an experiment where repetition of a task is used.

While experimental methods have been an effective tool for economic research, there have been controversies on the methodological aspects. The reason why we need to care about it is clear: if the method in an experiment is not valid, the results from that experiment cannot be valid too. Among other things, the methodological issues of financial incentives and repetition, which are norms in experimental economics, have been at the centre of many debates. While there are previous reviews that investigate financial incentives and repetition separately, our view is that the effects of these two factors are interdependent rather than independent. Thus, our review here is more specific and more conditional, that is, we are interested in the answer to the question, 'Do we need to use financial incentives conditional on the use of repetition?' After we discuss the relationship between financial incentives and repetition, we argue, from a review of 44 experimental studies, that using financial incentives would be more necessary to improve the validity of experimental results if an experimenter needs to use repetition. Copyright 2007 The Author Journal compilation © 2007 Blackwell Publishing Ltd.

We have attempted to reduce blood use during the perioperative period to avoid complications associated with blood transfusions in pediatric patients undergoing open-heart surgery. We retrospectively reviewed clinical data of patients who underwent open-heart surgery (age

In many experiments, particularly individual choice experiments, experimenters ask many questions to the subjects and use the random lottery incentive mechanism to give an incentive to the subjects. That is, the experimenter, at the end of the experiment, picks just one of the questions, plays out that question, and pays the subject on the basis of this one question. The idea is that subjects should separate the various questions and reply to each as if it were a separate question—in isolation from all the other questions in the experiment. This procedure is methodologically sound if the subjects behave in accordance with Expected Utility (EU) theory, since this theory says that the best procedure for the subjects is to separate the various questions. However, if there is any doubt as to whether the subjects obey EU theory, and particularly if the experiment is designed to test whether the behaviour of the subjects is in accordance with EU, this incentive mechanism is open to criticism. Indeed many referees use this argument against the research. The response that the subjects may not respect EU, yet still separate the various questions, is obviously open to objection and generally it is not clear whether this response is valid or not. There have been two direct tests of this separation hypothesis (by Starmer and Sugden (1991) and by Cubitt et al. (1998), which suggest that it is valid, but further evidence is required. This paper provides a further, stronger, test of this hypothesis: we confront the two stories—(1) that the subjects answer the various questions separately, and (2) that the subjects respond to the experiment as a whole—using experimental data from an experiment in which the random lottery incentive mechanism was used. Our analysis shows that it would appear that subjects do answer as if they were separating the questions. This should be considered reassuring for those experimenters who use the random lottery incentive mechanism.

In many experiments, experimenters use the random lottery incentive mechanism and ask many questions to each subject. That is, at the end of the experiment, just one of the questions is picked at random, and the subject paid on the basis of their answer to this one question. The idea is that subjects should separate the various questions and reply to each as if it were a separate question. This procedure is methodologically sound if the subjects’ preferences obey Expected Utility (EU) theory (which implies a form of separation), but if they do not, this incentive mechanism is open to criticism. Indeed many referees use this argument against the research: they argue that subjects do not consider questions separately. If the questions are revealed to the subjects one by one, then the appropriate alternative hypothesis is that their behaviour evolves with the questions. Here this hypothesis is tested: that the questions already answered affect the answers to the subsequent questions. The analysis shows that ...