GSK621 activates AMPK signaling to inhibit LPS-induced TNFα production

International Nuclear Information System (INIS)

Wu, Yong-hong; Li, Quan; Li, Ping; Liu, Bei

2016-01-01

LPS stimulation in macrophages/monocytes induces TNFα production. We here tested the potential effect of GSK621, a novel AMP-activated protein kinase (AMPK) activator, against the process. In RAW264.7 macrophages, murine bone marrow-derived macrophages (BMDMs), and chronic obstructive pulmonary disease (COPD) patients' monocytes, GSK621 significantly inhibited LPS-induced TNFα protein secretion and mRNA synthesis. Inhibition of AMPK, through AMPKα shRNA knockdown or dominant negative mutation (T172A), almost abolished GSK621's suppression on TNFα in RAW264.7 cells. Reversely, forced-expression of a constitutively-active AMPKα (T172D) mimicked GSK621 actions and reduced LPS-induced TNFα production. Molecularly, GSK621 suppressed LPS-induced reactive oxygen species (ROS) production and nuclear factor kappa B (NFκB) activation. In vivo, GSK621 oral administration inhibited LPS-induced TNFα production and endotoxin shock in mice. In summary, GSK621 activates AMPK signaling to inhibit LPS-induced TNFα production in macrophages/monocytes. - Highlights: • GSK621 inhibits LPS-induced TNFα production/expression in RAW264.7 cells and BMDMs. • GSK621 inhibits LPS-induced TNFα production/expression in COPD patients' PBMCs. • GSK621's inhibition on TNFα production by LPS requires AMPK activation. • GSK621 inhibits LPS-induced ROS production and NFκB activation, dependent on AMPK. • GSK621 oral administration inhibits LPS-induced TNFα production and endotoxin shock in mice.

Role of mutual punishment in the snowdrift game

Science.gov (United States)

Yang, Han-Xin; Wang, Zhen

2015-09-01

The effects of punishment on cooperation have drawn increasing attention. In this paper, we propose a new mechanism of punishment, in which an individual will punish each neighbor if their strategies are different, and vice versa. We incorporate the mutual punishment into the snowdrift game. Results for well-mixed and structured populations have shown that, for no punishment or small values of punishment fine, the fraction of cooperators continuously decreases with the temptation to defect. However, for large values of punishment fine, there exists an abrupt transition point, at which the fraction of cooperators suddenly drops from 1 to 0. Compared to no punishment, mutual punishment promotes cooperation when the temptation to defect is small but inhibits cooperation when the temptation to defect is large. For weak (strong) temptation to defect, the cooperation level increases (decreases) with the punishment fine. For moderate temptation to defect, there exists an optimal value of the punishment fine that leads to the highest cooperation level.

Manganese (II) induces chemical hypoxia by inhibiting HIF-prolyl hydroxylase: Implication in manganese-induced pulmonary inflammation

International Nuclear Information System (INIS)

Han, Jeongoh; Lee, Jong-Suk; Choi, Daekyu; Lee, Youna; Hong, Sungchae; Choi, Jungyun; Han, Songyi; Ko, Yujin; Kim, Jung-Ae; Mi Kim, Young; Jung, Yunjin

2009-01-01

Manganese (II), a transition metal, causes pulmonary inflammation upon environmental or occupational inhalation in excess. We investigated a potential molecular mechanism underlying manganese-induced pulmonary inflammation. Manganese (II) delayed HIF-1α protein disappearance, which occurred by inhibiting HIF-prolyl hydroxylase (HPH), the key enzyme for HIF-1α hydroxylation and subsequent von Hippel-Lindau(VHL)-dependent HIF-1α degradation. HPH inhibition by manganese (II) was neutralized significantly by elevated dose of iron. Consistent with this, the induction of cellular HIF-1α protein by manganese (II) was abolished by pretreatment with iron. Manganese (II) induced the HIF-1 target gene involved in pulmonary inflammation, vascular endothelial growth factor (VEGF), in lung carcinoma cell lines. The induction of VEGF was dependent on HIF-1. Manganese-induced VEGF promoted tube formation of HUVEC. Taken together, these data suggest that HIF-1 may be a potential mediator of manganese-induced pulmonary inflammation

Reward and punishment.

Science.gov (United States)

Sigmund, K; Hauert, C; Nowak, M A

2001-09-11

Minigames capturing the essence of Public Goods experiments show that even in the absence of rationality assumptions, both punishment and reward will fail to bring about prosocial behavior. This result holds in particular for the well-known Ultimatum Game, which emerges as a special case. But reputation can induce fairness and cooperation in populations adapting through learning or imitation. Indeed, the inclusion of reputation effects in the corresponding dynamical models leads to the evolution of economically productive behavior, with agents contributing to the public good and either punishing those who do not or rewarding those who do. Reward and punishment correspond to two types of bifurcation with intriguing complementarity. The analysis suggests that reputation is essential for fostering social behavior among selfish agents, and that it is considerably more effective with punishment than with reward.

Glycopyrrolate abolishes the exercise-induced increase in cerebral perfusion in humans

DEFF Research Database (Denmark)

Seifert, Thomas; Fisher, James P; Young, Colin N

2010-01-01

Brain blood vessels contain muscarinic receptors that are important for cerebral blood flow (CBF) regulation, but whether a cholinergic receptor mechanism is involved in the exercise-induced increase in cerebral perfusion or affects cerebral metabolism remains unknown. We evaluated CBF and cerebral......(mean) during ergometer cycling (n = 8). Separate, randomized and counterbalanced trials were performed in control (no drug) conditions and following muscarinic cholinergic receptor blockade by glycopyrrolate. Glycopyrrolate increased resting heart rate from approximately 60 to approximately 110 beats min(-1...... abolished by glycopyrrolate (P important for the exercise-induced increase in cerebral perfusion without affecting the cerebral metabolic rate for oxygen....

The role of the pediatrician in abolishing corporal punishment in schools. Committee on School Health, American Academy of Pediatrics.

Science.gov (United States)

Poole, S R; Ushkow, M C; Nader, P R; Bradford, B J; Asbury, J R; Worthington, D C; Sanabria, K E; Carruth, T

1991-07-01

Corporal punishment in school is allowed in 30 states in the United States. The American Academy of Pediatrics, together with numerous other child-advocacy groups, has reaffirmed its position that corporal punishment in schools should be prohibited by state statute in all states. This article provides background information and recommendations regarding the potential role for pediatricians in attaining this goal.

A critical role of lateral hypothalamus in context-induced relapse to alcohol seeking after punishment-imposed abstinence.

Science.gov (United States)

Marchant, Nathan J; Rabei, Rana; Kaganovsky, Konstantin; Caprioli, Daniele; Bossert, Jennifer M; Bonci, Antonello; Shaham, Yavin

2014-05-28

In human alcoholics, abstinence is often self-imposed, despite alcohol availability, because of the negative consequences of excessive use. During abstinence, relapse is often triggered by exposure to contexts associated with alcohol use. We recently developed a rat model that captures some features of this human condition: exposure to the alcohol self-administration environment (context A), after punishment-imposed suppression of alcohol self-administration in a different environment (context B), provoked renewal of alcohol seeking in alcohol-preferring P rats. The mechanisms underlying context-induced renewal of alcohol seeking after punishment-imposed abstinence are unknown. Here, we studied the role of the lateral hypothalamus (LH) and its forebrain projections in this effect. We first determined the effect of context-induced renewal of alcohol seeking on Fos (a neuronal activity marker) expression in LH. We next determined the effect of LH reversible inactivation by GABAA + GABAB receptor agonists (muscimol + baclofen) on this effect. Finally, we determined neuronal activation in brain areas projecting to LH during context-induced renewal tests by measuring double labeling of the retrograde tracer cholera toxin subunit B (CTb; injected in LH) with Fos. Context-induced renewal of alcohol seeking after punishment-imposed abstinence was associated with increased Fos expression in LH. Additionally, renewal was blocked by muscimol + baclofen injections into LH. Finally, double-labeling analysis of CTb + Fos showed that context-induced renewal of alcohol seeking after punishment-imposed abstinence was associated with selective activation of accumbens shell neurons projecting to LH. The results demonstrate an important role of LH in renewal of alcohol seeking after punishment-imposed abstinence and suggest a role of accumbens shell projections to LH in this form of relapse. Copyright © 2014 the authors 0270-6474/14/347447-11$15.00/0.

Lansoprazole induces apoptosis of breast cancer cells through inhibition of intracellular proton extrusion

Energy Technology Data Exchange (ETDEWEB)

Zhang, Shangrong; Wang, Yifan; Li, Shu Jie, E-mail: shujieli@nankai.edu.cn

2014-06-13

Highlights: • Lansoprazole (LPZ) induces cell apoptosis in breast cancer cells. • LPZ markedly inhibits intracellular proton extrusion. • LPZ induces an increase in intracellular ATP level, lysosomal alkalinization and ROS accumulation. - Abstract: The increased glycolysis and proton secretion in tumors is proposed to contribute to the proliferation and invasion of cancer cells during the process of tumorigenesis and metastasis. Here, treatment of human breast cancer cells with proton pump inhibitor (PPI) lansoprazole (LPZ) induces cell apoptosis in a dose-dependent manner. In the implantation of the MDA-MB-231 xenografts in nude mice, administration of LPZ significantly inhibits tumorigenesis and induces large-scale apopotosis of tumor cells. LPZ markedly inhibits intracellular proton extrusion, induces an increase in intracellular ATP level, lysosomal alkalinization and accumulation of reactive oxygen species (ROS) in breast cancer cells. The ROS scavenger N-acetyl-L-cysteine (NAC) and diphenyleneiodonium (DPI), a specific pharmacological inhibitor of NADPH oxidases (NOX), significantly abolish LPZ-induced ROS accumulation in breast cancer cells. Our results suggested that LPZ may be used as a new therapeutic drug for breast tumor.

Lansoprazole induces apoptosis of breast cancer cells through inhibition of intracellular proton extrusion

International Nuclear Information System (INIS)

Zhang, Shangrong; Wang, Yifan; Li, Shu Jie

2014-01-01

Highlights: • Lansoprazole (LPZ) induces cell apoptosis in breast cancer cells. • LPZ markedly inhibits intracellular proton extrusion. • LPZ induces an increase in intracellular ATP level, lysosomal alkalinization and ROS accumulation. - Abstract: The increased glycolysis and proton secretion in tumors is proposed to contribute to the proliferation and invasion of cancer cells during the process of tumorigenesis and metastasis. Here, treatment of human breast cancer cells with proton pump inhibitor (PPI) lansoprazole (LPZ) induces cell apoptosis in a dose-dependent manner. In the implantation of the MDA-MB-231 xenografts in nude mice, administration of LPZ significantly inhibits tumorigenesis and induces large-scale apopotosis of tumor cells. LPZ markedly inhibits intracellular proton extrusion, induces an increase in intracellular ATP level, lysosomal alkalinization and accumulation of reactive oxygen species (ROS) in breast cancer cells. The ROS scavenger N-acetyl-L-cysteine (NAC) and diphenyleneiodonium (DPI), a specific pharmacological inhibitor of NADPH oxidases (NOX), significantly abolish LPZ-induced ROS accumulation in breast cancer cells. Our results suggested that LPZ may be used as a new therapeutic drug for breast tumor

Punishment-induced fear modifies the daily course of yawning in rats.

Science.gov (United States)

Moyaho, Alejandro; Valencia, Jaime

2010-01-01

A challenge in the study of yawning behavior is understanding the way external factors may modify it. This study investigated whether response-dependent punishment or random punishment decreased yawning by the application of buzzer noise paired with electric shocks in a high-yawning strain of Sprague-Dawley male rats. Yawn rate increased daily in response to the experimental cage, and also to the buzzer noise. Two alternate periods of no punishment and punishment were followed by a final period of buzzer noise occurring alone. Punishment did not diminish yawning significantly in either condition although the yawn rate increased in the following period of no punishment and in the buzzer-noise period, relative to the period of yawn-dependent punishment. Yawn rate increased in the buzzer-noise period relative to the first period of no punishment and first period of random punishment. These findings indicate that there are constraints that impede the suppression of yawning using punishment, and that yawning is a delayed response to fear produced by response-dependent punishment. Copyright 2010 S. Karger AG, Basel.

Aspirin Inhibits Platelet-Derived Sphingosine-1-Phosphate Induced Endothelial Cell Migration.

Science.gov (United States)

Polzin, Amin; Knoop, Betül; Böhm, Andreas; Dannenberg, Lisa; Zurek, Mark; Zeus, Tobias; Kelm, Malte; Levkau, Bodo; Rauch, Bernhard H

2018-01-01

Aspirin plays a crucial role in the prevention of cardiovascular diseases. We previously described that aspirin has effects beyond inhibition of platelet aggregation, as it inhibited thrombin-mediated release of sphingosine-1-phosphate (S1P) from human platelets. S1P is a bioactive lipid with important functions on inflammation and apoptosis. In endothelial cells (EC), S1P is a key regulator of cell migration. In this study, we aimed to analyze the effects of aspirin on platelet-induced EC migration. Human umbilical EC migration was measured by Boyden chamber assay. EC migration was induced by platelet supernatants of thrombin receptor-activating peptide-1 (AP1) stimulated platelets. To investigate the S1P receptor subtype that promotes EC migration, specific inhibitors of S1P receptor subtypes were applied. S1P induced EC migration in a concentration-dependent manner. EC migration induced by AP1-stimulated platelet supernatants was reduced by aspirin. S1P1 receptor inhibition almost completely abolished EC migration induced by activated platelets. The inhibition of S1P2 or S1P3 receptor had no effect. Aspirin inhibits EC migration induced by activated platelets that is in part due to S1P and mediated by the endothelial S1P1 receptor. The clinical significance of this novel mechanism of aspirin action has to be investigated in future studies. © 2017 S. Karger AG, Basel.

Metformin inhibits 17β-estradiol-induced epithelial-to-mesenchymal transition via βKlotho-related ERK1/2 signaling and AMPKα signaling in endometrial adenocarcinoma cells.

Science.gov (United States)

Liu, Zhao; Qi, Shasha; Zhao, Xingbo; Li, Mingjiang; Ding, Sentai; Lu, Jiaju; Zhang, Hui

2016-04-19

The potential role of metformin in treating endometrial cancer remains to be explored. The current study investigated the role of metformin in 17β-estradiol-induced epithelial-mesenchymal transition (EMT) in endometrial adenocarcinoma cells. We found that 17β-estradiol promoted proliferation and migration, attenuated apoptosis in both estrogen receptor (ER) positive and ER negative endometrial adenocarcinoma cells (Ishikawa and KLE cells, respectively). Metformin abolished 17β-estradiol-induced cell proliferation and reversed 17β-estradiol-induced EMT in Ishikawa cells. In addition, metformin increased the expression of βKlotho, a fibroblast growth factors (FGFs) coreceptor, and decreased ERK1/2 phosphorylation in both Ishikawa and KLE cells. Decreased expression of βKlotho was noted in human endometrial adenocarcinomas, and plasmid-driven expression of βKlotho in Ishikawa cells abolished 17β-estradiol-induced EMT via inhibiting ERK1/2 signaling. βKlotho expression and metformin show synergetic effects on the proliferation and the EMT in Ishikawa cells. Furthermore, we demonstrated that the anti-EMT effects of metformin could be partly abolished by introducing Compound C, a specific AMPKα signaling inhibitor. In conclusion, metformin abolishes 17β-estradiol-induced cell proliferation and EMT in endometrial adenocarcinoma cells by upregulating βKlotho expression, inhibiting ERK1/2 signaling, and activating AMPKα signaling. Our study provides novel mechanistic insight into the anti-tumor effects of metformin.

The Effects of Four-Hour Delay of PUnishment under Two Conditions of Verbal Instruction

Science.gov (United States)

Verna, Gary B.

1977-01-01

The effects of 4-hour delay of punishment (withdrawal of reward) on response inhibition was studied with 24 fourth-grade children. Results showed that verbal expression of the punishment contingency allows the 10-year-old child to profit from 4-hour delayed punishment as much as immediate punishment. (Author/JMB)

β3-Adrenoceptor activation relieves oxidative inhibition of the cardiac Na+-K+ pump in hyperglycemia induced by insulin receptor blockade.

Science.gov (United States)

Karimi Galougahi, Keyvan; Liu, Chia-Chi; Garcia, Alvaro; Fry, Natasha A; Hamilton, Elisha J; Figtree, Gemma A; Rasmussen, Helge H

2015-09-01

Dysregulated nitric oxide (NO)- and superoxide (O2 (·-))-dependent signaling contributes to the pathobiology of diabetes-induced cardiovascular complications. We examined if stimulation of β3-adrenergic receptors (β3-ARs), coupled to endothelial NO synthase (eNOS) activation, relieves oxidative inhibition of eNOS and the Na(+)-K(+) pump induced by hyperglycemia. Hyperglycemia was established in male New Zealand White rabbits by infusion of the insulin receptor antagonist S961 for 7 days. Hyperglycemia increased tissue and blood indexes of oxidative stress. It induced glutathionylation of the Na(+)-K(+) pump β1-subunit in cardiac myocytes, an oxidative modification causing pump inhibition, and reduced the electrogenic pump current in voltage-clamped myocytes. Hyperglycemia also increased glutathionylation of eNOS, which causes its uncoupling, and increased coimmunoprecipitation of cytosolic p47(phox) and membranous p22(phox) NADPH oxidase subunits, consistent with NADPH oxidase activation. Blocking translocation of p47(phox) to p22(phox) with the gp91ds-tat peptide in cardiac myocytes ex vivo abolished the hyperglycemia-induced increase in glutathionylation of the Na(+)-K(+) pump β1-subunit and decrease in pump current. In vivo treatment with the β3-AR agonist CL316243 for 3 days eliminated the increase in indexes of oxidative stress, decreased coimmunoprecipitation of p22(phox) with p47(phox), abolished the hyperglycemia-induced increase in glutathionylation of eNOS and the Na(+)-K(+) pump β1-subunit, and abolished the decrease in pump current. CL316243 also increased coimmunoprecipitation of glutaredoxin-1 with the Na(+)-K(+) pump β1-subunit, which may reflect facilitation of deglutathionylation. In vivo β3-AR activation relieves oxidative inhibition of key cardiac myocyte proteins in hyperglycemia and may be effective in targeting the deleterious cardiac effects of diabetes. Copyright © 2015 the American Physiological Society.

Fenspiride inhibits histamine-induced responses in a lung epithelial cell line.

Science.gov (United States)

Quartulli, F; Pinelli, E; Broué-Chabbert, A; Gossart, S; Girard, V; Pipy, B

1998-05-08

Using the human lung epithelial WI26VA4 cell line, we investigated the capacity of fenspiride, an anti-inflammatory drug with anti-bronchoconstrictor properties, to interfere with histamine-induced intracellular Ca2+ increase and eicosanoid formation. Histamine and a histamine H1 receptor agonist elicited a rapid and transient intracellular Ca2+ increase (0-60 s) in fluo 3-loaded WI26VA4 cells. This response was antagonized by the histamine H1 receptor antagonist, diphenhydramine, the histamine H2 receptor antagonist, cimetidine, having no effect. Fenspiride (10(-7)-10(-5) M) inhibited the histamine H1 receptor-induced Ca2+ increase. In addition, histamine induced a biphasic increase in arachidonic acid release. The initial rise (0-30 s), a rapid and transient arachidonic acid release, was responsible for the histamine-induced intracellular Ca2+ increase. In the second phase release (15-60 min), a sustained arachidonic acid release appeared to be associated with the formation of cyclooxygenase and lipoxygenase metabolites. Fenspiride (10(-5) M) abolished both phases of histamine-induced arachidonic acid release. These results suggest that anti-inflammatory and antibronchoconstrictor properties of fenspiride may result from the inhibition of these effects of histamine.

Inhibition of the ERK phosphorylation plays a role in terbinafine-induced p21 up-regulation and DNA synthesis inhibition in human vascular endothelial cells

International Nuclear Information System (INIS)

Ho, P.-Y.; Hsu, S.-P.; Liang, Y.-C.; Kuo, M.-L.; Ho, Y.-S.; Lee, W.-S.

2008-01-01

Previously, we showed that terbinafine (TB) induces cell-cycle arrest in cultured human umbilical vein endothelial cells (HUVEC) through an up-regulation of the p21 protein. The aim of this study is to delineate the molecular mechanisms underlying TB-induced increase of p21 protein. RT-PCR analysis demonstrated that the mRNA levels of p21 and p53 were increased in the TB-treated HUVEC. The p21 promoter activity was also increased by TB treatment. Transfection of HUVEC with p53 dominant negative (DN) abolished the TB-induced increases of p21 promoter activity and protein level, suggesting that the TB-induced increase of p21 is p53-dependent. Western blot analysis demonstrated that TB decreased the levels of phosphorylated extracellular signal-regulated kinase (ERK). Over-expression of mitogen-activated protein kinase (MEK)-1, the immediate upstream activator kinase of ERK, abolished the TB-induced increases of p21 and p53 protein and decrease of thymidine incorporation. The ERK inhibitor (PD98059) enhanced the TB-induced inhibition of thymidine incorporation into HUVEC. Taken together, these data suggest that the decrease of ERK activity plays a role in the TB-induced up-regulation of p21 in HUVEC. On the other hand, pretreatment of the cells with geranylgeraniol (GGOH), farnesol (FOH), or Ras inhibitor peptide did not affect the TB-induced decrease of thymidine incorporation. Taken together, our results suggest that TB might cause a decrease of MEK, which in turn up-regulates p53 through the inhibition of ERK phosphorylation, and finally causes an increase of p21 expression and cell-cycle arrest

Impaired learning of punishments in Parkinson's disease with and without impulse control disorder.

Science.gov (United States)

Leplow, Bernd; Sepke, Maria; Schönfeld, Robby; Pohl, Johannes; Oelsner, Henriette; Latzko, Lea; Ebersbach, Georg

2017-02-01

To document specific learning mechanisms in patients with Parkinson's disease (PD) with and without impulse control disorder (ICD). Thirty-two PD patients receiving dopamine replacement therapy (DRT) were investigated. Sixteen were diagnosed with ICD (ICD + ) and 16 PD patients matched for levodopa equivalence dosage, and DRT duration and severity of disease did not show impulsive behavior (non-ICD). Short-term learning of inhibitory control was assessed by an experimental procedure which was intended to mimic everyday life. Correct inhibition especially, had to be learned without reward (passive avoidance), and the failure to inhibit a response was punished (punishment learning). Results were compared to 16 healthy controls (HC) matched for age and sex. In ICD + patients within-session learning of non-rewarded inhibition was at chance levels. Whereas healthy controls rapidly developed behavioral inhibition, non-ICD patients were also significantly impaired compared to HC, but gradually developed some degree of control. Both patient groups showed significantly decreased learning if the failure to withhold a response was punished. PD patients receiving DRT show impaired ability to acquire both punishment learning and passive avoidance learning, irrespective of whether or not ICD was developed. In ICD + PD patients, behavioral inhibition is nearly absent. Results demonstrate that by means of subtle learning paradigms it is possible to identify PD-DRT patients who show subtle alterations of punishment learning. This may be a behavioral measure for the identification of PD patients who are prone to develop ICD if DRT is continued.

Invisible wounds: corporal punishment in British schools as a form of ritual.

Science.gov (United States)

Benthall, J

1991-01-01

This article examines a presumed historical association between corporal punishment and the British "ruling class," taking as data the elaborate forms of beating practiced at a well-known English fee-paying boarding school in the 1950s and here documented in detail. Analogies with other forms of ritual studied by anthropologists are considered, as well as the psychosexual dynamics of beating for both officiants and victims. The paper argues that ritual corporal punishment must be seen in retrospect as a clear case of child abuse that is both physical and sexual. Such rituals of authority, though virtually abolished in Britain, may well exist in a different form in present day residential institutions for children in some Third World countries that have borrowed from now outdated European practices.

Similarity increases altruistic punishment in humans.

Science.gov (United States)

Mussweiler, Thomas; Ockenfels, Axel

2013-11-26

Humans are attracted to similar others. As a consequence, social networks are homogeneous in sociodemographic, intrapersonal, and other characteristics--a principle called homophily. Despite abundant evidence showing the importance of interpersonal similarity and homophily for human relationships, their behavioral correlates and cognitive foundations are poorly understood. Here, we show that perceived similarity substantially increases altruistic punishment, a key mechanism underlying human cooperation. We induced (dis)similarity perception by manipulating basic cognitive mechanisms in an economic cooperation game that included a punishment phase. We found that similarity-focused participants were more willing to punish others' uncooperative behavior. This influence of similarity is not explained by group identity, which has the opposite effect on altruistic punishment. Our findings demonstrate that pure similarity promotes reciprocity in ways known to encourage cooperation. At the same time, the increased willingness to punish norm violations among similarity-focused participants provides a rationale for why similar people are more likely to build stable social relationships. Finally, our findings show that altruistic punishment is differentially involved in encouraging cooperation under pure similarity vs. in-group conditions.

Catalase inhibits ionizing radiation-induced apoptosis in hematopoietic stem and progenitor cells.

Science.gov (United States)

Xiao, Xia; Luo, Hongmei; Vanek, Kenneth N; LaRue, Amanda C; Schulte, Bradley A; Wang, Gavin Y

2015-06-01

Hematologic toxicity is a major cause of mortality in radiation emergency scenarios and a primary side effect concern in patients undergoing chemo-radiotherapy. Therefore, there is a critical need for the development of novel and more effective approaches to manage this side effect. Catalase is a potent antioxidant enzyme that coverts hydrogen peroxide into hydrogen and water. In this study, we evaluated the efficacy of catalase as a protectant against ionizing radiation (IR)-induced toxicity in hematopoietic stem and progenitor cells (HSPCs). The results revealed that catalase treatment markedly inhibits IR-induced apoptosis in murine hematopoietic stem cells and hematopoietic progenitor cells. Subsequent colony-forming cell and cobble-stone area-forming cell assays showed that catalase-treated HSPCs can not only survive irradiation-induced apoptosis but also have higher clonogenic capacity, compared with vehicle-treated cells. Moreover, transplantation of catalase-treated irradiated HSPCs results in high levels of multi-lineage and long-term engraftments, whereas vehicle-treated irradiated HSPCs exhibit very limited hematopoiesis reconstituting capacity. Mechanistically, catalase treatment attenuates IR-induced DNA double-strand breaks and inhibits reactive oxygen species. Unexpectedly, we found that the radioprotective effect of catalase is associated with activation of the signal transducer and activator of transcription 3 (STAT3) signaling pathway and pharmacological inhibition of STAT3 abolishes the protective activity of catalase, suggesting that catalase may protect HSPCs against IR-induced toxicity via promoting STAT3 activation. Collectively, these results demonstrate a previously unrecognized mechanism by which catalase inhibits IR-induced DNA damage and apoptosis in HSPCs.

"Can I Really Teach without My Magic Cane?" Teachers' Responses to the Banning of Corporal Punishment

Science.gov (United States)

Malak, Md. Saiful; Sharma, Umesh; Deppeler, Joanne M.

2015-01-01

This paper reports on how teachers are responding to students' inappropriate behaviours in public primary schools in Bangladesh. Data in this study were collected after the adoption of a recent government policy that has abolished corporal punishment in primary schools. Semi-structured, one-on-one interviews were conducted with 22 teachers from…

The role of the lateral habenula in punishment.

Science.gov (United States)

Jean-Richard Dit Bressel, Philip; McNally, Gavan P

2014-01-01

The lateral habenula (LHb) is a small epithalamic structure that projects via the fasciculus retroflexus to the midbrain. The LHb is known to modulate midbrain dopamine (DA) neurons, including inhibition of ventral tegmental area (VTA) neurons via glutamatergic excitation of the GABAergic rostromedial tegmental nucleus (RMTg). A variety of lines of evidence show activity in LHb and the LHb-RMTg pathway is correlated with, and is sufficient to support, punishment learning. However, it is not immediately clear whether LHb is necessary for punishment. Here we used a within-subjects punishment task to assess the role of LHb in the acquisition and expression of punishment as well as in aversive choice. Rats that pressed two individually presented levers for pellet rewards rapidly suppressed responding to one lever if it also caused footshock deliveries (punished lever) but continued pressing a second lever that did not cause footshock (unpunished lever). Infusions of an AMPA receptor antagonist (NBQX) into LHb had no effect on the acquisition or expression of this punishment, or on aversive choice, but did increase locomotion. Infusion of the sodium channel blocker bupivacaine likewise had no effect on expression of punishment. However, infusion of the calcium channel blocker mibefradil did affect expression of punishment by significantly decreasing the latency with which rats responded on the punished lever and significantly increasing unpunished lever-pressing. Taken together, these findings indicate that the LHb plays a limited role in punishment, influencing only latency to respond. This role is linked to calcium channel permeability and not AMPA receptor or sodium channel permeability.

Executive functions, parental punishment, and aggression: Direct and moderated relations.

Science.gov (United States)

Fatima, Shameem; Sharif, Imran

2017-12-01

The main focus of the current study was to assess whether executive functions (EFs) moderate the effect of parental punishment on adolescent aggression. The sample were 370 participants (53% girls, 47% boys) enrolled at secondary and higher secondary levels and ranged in age between 13-19 years (M = 15.5, SD = 1.3). Participants were assessed on a self-report measure of aggression and two punishment measures, in addition to a demographic sheet. Then, they were individually assessed on four tests taken from the Delis-Kaplan Executive Functions System (D-KEFS) namely Trial Making Test (TMT), Design Fluency Test (DFT), Color Word Interference Test (CWIT), and Card Sorting Test (CST) to assess cognitive flexibility, nonverbal fluency, inhibition, and problem-solving ability, respectively. Correlation coefficients indicated that all four executive functioning measures and the two punishment measures were significantly correlated with aggression. Moderation analysis indicated that all EFs moderated the relationship between physical punishment and aggression, and only inhibition and problem-solving ability, but not cognitive flexibility and nonverbal fluency, moderated the relations between symbolic punishment and aggression. The findings support the hypothesis that EFs are protective personal factors that promote healthy adolescent adjustment in the presence of challenging environmental factors.

A double-edged sword: Benefits and pitfalls of heterogeneous punishment in evolutionary inspection games

Science.gov (United States)

Perc, Matjaž; Szolnoki, Attila

2015-06-01

As a simple model for criminal behavior, the traditional two-strategy inspection game yields counterintuitive results that fail to describe empirical data. The latter shows that crime is often recurrent, and that crime rates do not respond linearly to mitigation attempts. A more apt model entails ordinary people who neither commit nor sanction crime as the third strategy besides the criminals and punishers. Since ordinary people free-ride on the sanctioning efforts of punishers, they may introduce cyclic dominance that enables the coexistence of all three competing strategies. In this setup ordinary individuals become the biggest impediment to crime abatement. We therefore also consider heterogeneous punisher strategies, which seek to reduce their investment into fighting crime in order to attain a more competitive payoff. We show that this diversity of punishment leads to an explosion of complexity in the system, where the benefits and pitfalls of criminal behavior are revealed in the most unexpected ways. Due to the raise and fall of different alliances no less than six consecutive phase transitions occur in dependence on solely the temptation to succumb to criminal behavior, leading the population from ordinary people-dominated across punisher-dominated to crime-dominated phases, yet always failing to abolish crime completely.

A double-edged sword: Benefits and pitfalls of heterogeneous punishment in evolutionary inspection games.

Science.gov (United States)

Perc, Matjaž; Szolnoki, Attila

2015-06-05

As a simple model for criminal behavior, the traditional two-strategy inspection game yields counterintuitive results that fail to describe empirical data. The latter shows that crime is often recurrent, and that crime rates do not respond linearly to mitigation attempts. A more apt model entails ordinary people who neither commit nor sanction crime as the third strategy besides the criminals and punishers. Since ordinary people free-ride on the sanctioning efforts of punishers, they may introduce cyclic dominance that enables the coexistence of all three competing strategies. In this setup ordinary individuals become the biggest impediment to crime abatement. We therefore also consider heterogeneous punisher strategies, which seek to reduce their investment into fighting crime in order to attain a more competitive payoff. We show that this diversity of punishment leads to an explosion of complexity in the system, where the benefits and pitfalls of criminal behavior are revealed in the most unexpected ways. Due to the raise and fall of different alliances no less than six consecutive phase transitions occur in dependence on solely the temptation to succumb to criminal behavior, leading the population from ordinary people-dominated across punisher-dominated to crime-dominated phases, yet always failing to abolish crime completely.

Agmatine abolishes restraint stress-induced depressive-like behavior and hippocampal antioxidant imbalance in mice.

Science.gov (United States)

Freitas, Andiara E; Bettio, Luis E B; Neis, Vivian B; Santos, Danúbia B; Ribeiro, Camille M; Rosa, Priscila B; Farina, Marcelo; Rodrigues, Ana Lúcia S

2014-04-03

Agmatine has been recently emerged as a novel candidate to assist the conventional pharmacotherapy of depression. The acute restraint stress (ARS) is an unavoidable stress situation that may cause depressive-like behavior in rodents. In this study, we investigated the potential antidepressant-like effect of agmatine (10mg/kg, administered acutely by oral route) in the forced swimming test (FST) in non-stressed mice, as well as its ability to abolish the depressive-like behavior and hippocampal antioxidant imbalance induced by ARS. Agmatine reduced the immobility time in the mouse FST (1-100mg/kg) in non-stressed mice. ARS caused an increase in the immobility time in the FST, indicative of a depressive-like behavior, as well as hippocampal lipid peroxidation, and an increase in the activity of hippocampal superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GR) activities, reduced catalase (CAT) activity and increased SOD/CAT ratio, an index of pro-oxidative conditions. Agmatine was effective to abolish the depressive-like behavior induced by ARS and to prevent the ARS-induced lipid peroxidation and changes in SOD, GR and CAT activities and in SOD/CAT activity ratio. Hippocampal levels of reduced glutathione (GSH) were not altered by any experimental condition. In conclusion, the present study shows that agmatine was able to abrogate the ARS-induced depressive-like behavior and the associated redox hippocampal imbalance observed in stressed restraint mice, suggesting that its antidepressant-like effect may be dependent on its ability to maintain the pro-/anti-oxidative homeostasis in the hippocampus. Copyright © 2013 Elsevier Inc. All rights reserved.

Renewal after the punishment of free operant behavior.

Science.gov (United States)

Bouton, Mark E; Schepers, Scott T

2015-01-01

Three experiments examined the role of context in punishment learning. In Experiment 1, rats were trained to lever press for food in Context A and then punished for responding in Context B (by presenting response-contingent footshock). Punishment led to complete suppression of the response. However, when responding was tested (in extinction) in Contexts A and B, a strong renewal of responding occurred in Context A. In Experiment 2, renewal also occurred when initial reinforcement occurred in Context A, punishment occurred in Context B, and testing occurred in a new context (Context C). In both experiments, behavioral suppression and renewal were not observed in groups that received noncontingent (yoked) footshocks in Context B. In Experiment 3, 2 responses (lever press and chain pull) were separately reinforced in Contexts A and B and then punished in the opposite context. Although the procedure equated the contexts on their association with reinforcement and punishment, renewal of each response was observed when it was tested in its nonpunished context. The contexts also influenced response choice. Overall, the results suggest that punishment is specific to the context in which it is learned, and establish that its context-specificity does not depend on a simple association between the context and shock. Like extinction, punishment may involve learning to inhibit a specific response in a specific context. Implications for theories of punishment and for understanding the cessation of problematic operant behavior (e.g., drug abuse) are discussed. PsycINFO Database Record (c) 2015 APA, all rights reserved.

Transcriptional up-regulation of antioxidant genes by PPARδ inhibits angiotensin II-induced premature senescence in vascular smooth muscle cells

International Nuclear Information System (INIS)

Kim, Hyo Jung; Ham, Sun Ah; Paek, Kyung Shin; Hwang, Jung Seok; Jung, Si Young; Kim, Min Young; Jin, Hanna; Kang, Eun Sil; Woo, Im Sun; Kim, Hye Jung; Lee, Jae Heun; Chang, Ki Churl; Han, Chang Woo; Seo, Han Geuk

2011-01-01

Research highlights: → Activation of PPARδ by GW501516 significantly inhibited Ang II-induced premature senescence in hVSMCs. → Agonist-activated PPARδ suppressed generation of Ang II-triggered ROS with a concomitant reduction in DNA damage. → GW501516 up-regulated expression of antioxidant genes, such as GPx1, Trx1, Mn-SOD and HO-1. → Knock-down of these antioxidant genes abolished the effects of GW501516 on ROS production and premature senescence. -- Abstract: This study evaluated peroxisome proliferator-activated receptor (PPAR) δ as a potential target for therapeutic intervention in Ang II-induced senescence in human vascular smooth muscle cells (hVSMCs). Activation of PPARδ by GW501516, a specific agonist of PPARδ, significantly inhibited the Ang II-induced premature senescence of hVSMCs. Agonist-activated PPARδ suppressed the generation of Ang II-triggered reactive oxygen species (ROS) with a concomitant reduction in DNA damage. Notably, GW501516 up-regulated the expression of antioxidant genes, such as glutathione peroxidase 1, thioredoxin 1, manganese superoxide dismutase and heme oxygenase 1. siRNA-mediated down-regulation of these antioxidant genes almost completely abolished the effects of GW501516 on ROS production and premature senescence in hVSMCs treated with Ang II. Taken together, the enhanced transcription of antioxidant genes is responsible for the PPARδ-mediated inhibition of premature senescence through sequestration of ROS in hVSMCs treated with Ang II.

When Punishment Pays

Science.gov (United States)

Roberts, Gilbert

2013-01-01

Explaining cooperation in groups remains a key problem because reciprocity breaks down between more than two. Punishing individuals who contribute little provides a potential answer but changes the dilemma to why pay the costs of punishing which, like cooperation itself, provides a public good. Nevertheless, people are observed to punish others in behavioural economic games, posing a problem for existing theory which highlights the difficulty in explaining the spread and persistence of punishment. Here, I consider the apparent mismatch between theory and evidence and show by means of instructive analysis and simulation how much of the experimental evidence for punishment comes from scenarios in which punishers may expect to obtain a net benefit from punishing free-riders. In repeated games within groups, punishment works by imposing costs on defectors so that it pays them to switch to cooperating. Both punishers and non-punishers then benefit from the resulting increase in cooperation, hence investing in punishment can constitute a social dilemma. However, I show the conditions in which the benefits of increased cooperation are so great that they more than offset the costs of punishing, thereby removing the temptation to free-ride on others' investments and making punishment explicable in terms of direct self-interest. Crucially, this is because of the leveraging effect imposed in typical studies whereby people can pay a small cost to inflict a heavy loss on a punished individual. In contrast to previous models suggesting punishment is disadvantaged when rare, I show it can invade until it comes into a producer-scrounger equilibrium with non-punishers. I conclude that adding punishment to an iterated public goods game can solve the problem of achieving cooperation by removing the social dilemma. PMID:23483907

Effects of reward and punishment on brain activations associated with inhibitory control in cigarette smokers.

Science.gov (United States)

Luijten, Maartje; O'Connor, David A; Rossiter, Sarah; Franken, Ingmar H A; Hester, Robert

2013-11-01

Susceptibility to use of addictive substances may result, in part, from a greater preference for an immediate small reward relative to a larger delayed reward or relative insensitivity to punishment. This functional magnetic resonance imaging (fMRI) study examined the neural basis of inhibiting an immediately rewarding stimulus to obtain a larger delayed reward in smokers. We also investigated whether punishment could modulate inhibitory control. The Monetary Incentive Go/NoGo (MI-Go/NoGo) task was administered that provided three types of reward outcomes contingent upon inhibitory control performance over rewarding stimuli: inhibition failure was either followed by no monetary reward (neutral condition), a small monetary reward with immediate feedback (reward condition) or immediate monetary punishment (punishment condition). In the reward and punishment conditions, successful inhibitory control resulted in larger delayed rewards. Community sample of smokers in the Melbourne (Australia) area. Nineteen smokers were compared with 17 demographically matched non-smoking controls. Accuracy, reaction times and brain activation associated with the MI-Go/NoGo task. Smokers showed hyperactivation in the right insula (P rewarding stimulus to obtain a larger delayed reward, and during inhibition of neutral stimuli. Group differences in brain activity were not significant in the punishment condition in the right insula and dorsolateral prefrontal cortex, most probably as a result of increased activation in non-smoking controls. Compared with non-smokers, smokers showed increased neural activation when resisting immediately rewarding stimuli and may be less sensitive to punishment as a strategy to increase control over rewarding stimuli. © 2013 Society for the Study of Addiction.

Outsourcing punishment to God: beliefs in divine control reduce earthly punishment

Science.gov (United States)

Laurin, Kristin; Shariff, Azim F.; Henrich, Joseph; Kay, Aaron C.

2012-01-01

The sanctioning of norm-transgressors is a necessary—though often costly—task for maintaining a well-functioning society. Prior to effective and reliable secular institutions for punishment, large-scale societies depended on individuals engaging in ‘altruistic punishment’—bearing the costs of punishment individually, for the benefit of society. Evolutionary approaches to religion suggest that beliefs in powerful, moralizing Gods, who can distribute rewards and punishments, emerged as a way to augment earthly punishment in large societies that could not effectively monitor norm violations. In five studies, we investigate whether such beliefs in God can replace people's motivation to engage in altruistic punishment, and their support for state-sponsored punishment. Results show that, although religiosity generally predicts higher levels of punishment, the specific belief in powerful, intervening Gods reduces altruistic punishment and support for state-sponsored punishment. Moreover, these effects are specifically owing to differences in people's perceptions that humans are responsible for punishing wrongdoers. PMID:22628465

Hydrogen sulfide inhibits high glucose-induced NADPH oxidase 4 expression and matrix increase by recruiting inducible nitric oxide synthase in kidney proximal tubular epithelial cells.

Science.gov (United States)

Lee, Hak Joo; Lee, Doug Yoon; Mariappan, Meenalakshmi M; Feliers, Denis; Ghosh-Choudhury, Goutam; Abboud, Hanna E; Gorin, Yves; Kasinath, Balakuntalam S

2017-04-07

High-glucose increases NADPH oxidase 4 (NOX4) expression, reactive oxygen species generation, and matrix protein synthesis by inhibiting AMP-activated protein kinase (AMPK) in renal cells. Because hydrogen sulfide (H 2 S) inhibits high glucose-induced matrix protein increase by activating AMPK in renal cells, we examined whether H 2 S inhibits high glucose-induced expression of NOX4 and matrix protein and whether H 2 S and NO pathways are integrated. High glucose increased NOX4 expression and activity at 24 h in renal proximal tubular epithelial cells, which was inhibited by sodium hydrosulfide (NaHS), a source of H 2 S. High glucose decreased AMPK phosphorylation and activity, which was restored by NaHS. Compound C, an AMPK inhibitor, prevented NaHS inhibition of high glucose-induced NOX4 expression. NaHS inhibition of high glucose-induced NOX4 expression was abrogated by N (ω)-nitro-l-arginine methyl ester, an inhibitor of NOS. NaHS unexpectedly augmented the expression of inducible NOS (iNOS) but not endothelial NOS. iNOS siRNA and 1400W, a selective iNOS inhibitor, abolished the ameliorative effects of NaHS on high glucose-induced NOX4 expression, reactive oxygen species generation, and, matrix laminin expression. Thus, H 2 S recruits iNOS to generate NO to inhibit high glucose-induced NOX4 expression, oxidative stress, and matrix protein accumulation in renal epithelial cells; the two gasotransmitters H 2 S and NO and their interaction may serve as therapeutic targets in diabetic kidney disease. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Creative Punishment.

Science.gov (United States)

Sweeney, John

1988-01-01

Punishment given in a caring, supportive environment can assist children to learn some tasks more quickly, when used in conjunction with programmed positive reinforcement. The manner in which a punishment is implemented impacts its effectiveness. Two experiments are presented in which teachers used creative punishment to produce classroom behavior…

Punishment.

Science.gov (United States)

Goodwin, Geoffrey P; Gromet, Dena M

2014-09-01

Retributivism is a deontological theory of punishment that calls for the deserved punishment of a guilty offender in proportion with his moral blameworthiness for a past offense. It is often referred to as punishment based on 'just deserts', and it contrasts with consequentialist theories that ground punishment in its potentially beneficial future consequences. Rich philosophical debate surrounds the appropriateness of retributivism. From a psychological perspective, the key question concerns whether retributivism underlies ordinary individuals' desire for the legal punishment of wrongdoers. Past research in social psychology has answered this question in the affirmative. However, much of this existing evidence requires a new look, because it is premised on a fundamental ambiguity. We review alternative evidence for the existence of retributive motives from lesser-known correlational studies, and from studies of the punishment of companies and animals. We also explore the links between retributivism and restorative justice-an alternative justice approach that focuses on repairing the harms caused by an offense. Although often cast as diametrically opposed to one another, retributive and restorative justice in fact share more in common than is often supposed. Both are premised on notions of deservingness, and their goals can be achieved by the same action (i.e., retributive punishment can restore victims). In all areas of the research we review, more work is needed to better understand: retributivism directed at human offenders, the commonalities and discontinuities between retributive and restorative justice, and how the notion of desert structures moral life and thought more generally. WIREs Cogn Sci 2014, 5:561-572. doi: 10.1002/wcs.1301 For further resources related to this article, please visit the WIREs website. The authors have declared no conflicts of interest for this article. © 2014 John Wiley & Sons, Ltd.

Depressive-like behavior induced by tumor necrosis factor-α is abolished by agmatine administration.

Science.gov (United States)

Neis, Vivian Binder; Manosso, Luana Meller; Moretti, Morgana; Freitas, Andiara E; Daufenbach, Juliana; Rodrigues, Ana Lúcia S

2014-03-15

Agmatine, an endogenous cationic amine, has been shown to exert antidepressant-like effects. This study investigated the ability of agmatine administered orally to abolish the depressive-like behavior induced by the administration of the pro-inflammatory cytokine, tumor necrosis factor (TNF-α) in mice. In control animals, agmatine (0.001, 0.01, 0.1, and 1 mg/kg) reduced the immobility time in the tail suspension test (TST). Acute administration of TNF-α (0.001 fg/mouse, i.c.v.) increased immobility time in the TST, indicative of a depressive-like behavior, and agmatine (0.0001, 0.1, and 1 mg/kg) prevented this effect. Additionally, we examined the effects of the combined administration of sub-effective doses of agmatine with antidepressants, the NMDA receptor antagonist MK-801 and the neuronal nitric oxide synthase inhibitor 7-nitroindazole (7-NI) in mice exposed to either TNF-α or saline. In control mice, administration of a sub-effective dose of agmatine (0.0001 mg/kg) combined with sub-effective doses of either fluoxetine (5 mg/kg, p.o.), imipramine (0.1 mg/kg, p.o.), bupropion (1 mg/kg, p.o.), MK-801 (0.001 mg/kg, p.o.) or 7-NI (25 mg/kg, i.p.) produced a synergistic antidepressant-like effect in the TST. All these administrations prevented the increased immobility time induced by TNF-α. The effect of agmatine in the TNF-α model of depression appears to be associated, at least partially, with an activation of the monoaminergic systems and inhibition of NMDA receptors and nitric oxide synthesis, although converging signal transduction pathways that may underlie the effect of agmatine should be further investigated. This set of results indicates that agmatine may constitute a new therapeutic alternative for the treatment of depression associated with inflammation. Copyright © 2014 Elsevier B.V. All rights reserved.

Second-Order Free-Riding on Antisocial Punishment Restores the Effectiveness of Prosocial Punishment

Science.gov (United States)

Szolnoki, Attila; Perc, Matjaž

2017-10-01

Economic experiments have shown that punishment can increase public goods game contributions over time. However, the effectiveness of punishment is challenged by second-order free-riding and antisocial punishment. The latter implies that noncooperators punish cooperators, while the former implies unwillingness to shoulder the cost of punishment. Here, we extend the theory of cooperation in the spatial public goods game by considering four competing strategies, which are traditional cooperators and defectors, as well as cooperators who punish defectors and defectors who punish cooperators. We show that if the synergistic effects are high enough to sustain cooperation based on network reciprocity alone, antisocial punishment does not deter public cooperation. Conversely, if synergistic effects are low and punishment is actively needed to sustain cooperation, antisocial punishment does is viable, but only if the cost-to-fine ratio is low. If the costs are relatively high, cooperation again dominates as a result of spatial pattern formation. Counterintuitively, defectors who do not punish cooperators, and are thus effectively second-order free-riding on antisocial punishment, form an active layer around punishing cooperators, which protects them against defectors that punish cooperators. A stable three-strategy phase that is sustained by the spontaneous emergence of cyclic dominance is also possible via the same route. The microscopic mechanism behind the reported evolutionary outcomes can be explained by the comparison of invasion rates that determine the stability of subsystem solutions. Our results reveal an unlikely evolutionary escape from adverse effects of antisocial punishment, and they provide a rationale for why second-order free-riding is not always an impediment to the evolutionary stability of punishment.

Second-Order Free-Riding on Antisocial Punishment Restores the Effectiveness of Prosocial Punishment

Directory of Open Access Journals (Sweden)

Attila Szolnoki

2017-10-01

Full Text Available Economic experiments have shown that punishment can increase public goods game contributions over time. However, the effectiveness of punishment is challenged by second-order free-riding and antisocial punishment. The latter implies that noncooperators punish cooperators, while the former implies unwillingness to shoulder the cost of punishment. Here, we extend the theory of cooperation in the spatial public goods game by considering four competing strategies, which are traditional cooperators and defectors, as well as cooperators who punish defectors and defectors who punish cooperators. We show that if the synergistic effects are high enough to sustain cooperation based on network reciprocity alone, antisocial punishment does not deter public cooperation. Conversely, if synergistic effects are low and punishment is actively needed to sustain cooperation, antisocial punishment does is viable, but only if the cost-to-fine ratio is low. If the costs are relatively high, cooperation again dominates as a result of spatial pattern formation. Counterintuitively, defectors who do not punish cooperators, and are thus effectively second-order free-riding on antisocial punishment, form an active layer around punishing cooperators, which protects them against defectors that punish cooperators. A stable three-strategy phase that is sustained by the spontaneous emergence of cyclic dominance is also possible via the same route. The microscopic mechanism behind the reported evolutionary outcomes can be explained by the comparison of invasion rates that determine the stability of subsystem solutions. Our results reveal an unlikely evolutionary escape from adverse effects of antisocial punishment, and they provide a rationale for why second-order free-riding is not always an impediment to the evolutionary stability of punishment.

Caffeine Inhibits Fluid Secretion by Interlobular Ducts From Guinea Pig Pancreas.

Science.gov (United States)

Mochimaru, Yuka; Yamamoto, Akiko; Nakakuki, Miyuki; Yamaguchi, Makoto; Taniguchi, Ituka; Ishiguro, Hiroshi

2017-04-01

Caffeine is contained in coffee, tea, and numerous beverages and foods. We examined the direct effects of caffeine on the physiological function of pancreatic duct cells by using interlobular duct segments isolated from guinea pig pancreas. The rate of fluid secretion was continuously measured by monitoring the luminal volume of isolated duct segments. Changes in intracellular Ca concentration ([Ca]i) were estimated by microfluorometry in ducts loaded with Fura-2. Both secretin-stimulated and acetylcholine (ACh)-stimulated fluid secretions were substantially and reversibly inhibited by relatively low concentrations of caffeine as low as 0.03 mM relevant to blood levels after ingestion of caffeine-containing beverages. Caffeine inhibited ACh-induced elevation of [Ca]i and secretin-induced fluctuation of [Ca]i. Caffeine abolished thapsigargin-induced intracellular Ca release but did not affect the entry of extracellular Ca. Caffeine (0.05 mM) abolished ethanol (1 mM)-induced fluid hypersecretion in secretin-stimulated pancreatic duct. Low concentrations of caffeine directly inhibit pancreatic ductal fluid secretion stimulated by secretin or ACh and also ethanol-induced fluid hypersecretion. The inhibition by caffeine seems to be mediated by the blockade of intracellular Ca mobilization. Daily intake of caffeine may reduce the volume of pancreatic juice secretion.

High strength-of-ties and low mobility enable the evolution of third-party punishment

Science.gov (United States)

Roos, Patrick; Gelfand, Michele; Nau, Dana; Carr, Ryan

2014-01-01

As punishment can be essential to cooperation and norm maintenance but costly to the punisher, many evolutionary game-theoretic studies have explored how direct punishment can evolve in populations. Compared to direct punishment, in which an agent acts to punish another for an interaction in which both parties were involved, the evolution of third-party punishment (3PP) is even more puzzling, because the punishing agent itself was not involved in the original interaction. Despite significant empirical studies of 3PP, little is known about the conditions under which it can evolve. We find that punishment reputation is not, by itself, sufficient for the evolution of 3PP. Drawing on research streams in sociology and psychology, we implement a structured population model and show that high strength-of-ties and low mobility are critical for the evolution of responsible 3PP. Only in such settings of high social-structural constraint are punishers able to induce self-interested agents toward cooperation, making responsible 3PP ultimately beneficial to individuals as well as the collective. Our results illuminate the conditions under which 3PP is evolutionarily adaptive in populations. Responsible 3PP can evolve and induce cooperation in cases where other mechanisms alone fail to do so. PMID:24335985

Temporal characteristics of the influence of punishment on perceptual decision making in the human brain.

Science.gov (United States)

Blank, Helen; Biele, Guido; Heekeren, Hauke R; Philiastides, Marios G

2013-02-27

Perceptual decision making is the process by which information from sensory systems is combined and used to influence our behavior. In addition to the sensory input, this process can be affected by other factors, such as reward and punishment for correct and incorrect responses. To investigate the temporal dynamics of how monetary punishment influences perceptual decision making in humans, we collected electroencephalography (EEG) data during a perceptual categorization task whereby the punishment level for incorrect responses was parametrically manipulated across blocks of trials. Behaviorally, we observed improved accuracy for high relative to low punishment levels. Using multivariate linear discriminant analysis of the EEG, we identified multiple punishment-induced discriminating components with spatially distinct scalp topographies. Compared with components related to sensory evidence, components discriminating punishment levels appeared later in the trial, suggesting that punishment affects primarily late postsensory, decision-related processing. Crucially, the amplitude of these punishment components across participants was predictive of the size of the behavioral improvements induced by punishment. Finally, trial-by-trial changes in prestimulus oscillatory activity in the alpha and gamma bands were good predictors of the amplitude of these components. We discuss these findings in the context of increased motivation/attention, resulting from increases in punishment, which in turn yields improved decision-related processing.

When Do Punishment Institutions Work?

OpenAIRE

Patrick Aquino; Robert S. Gazzale; Sarah Jacobson

2015-01-01

While peer punishment sometimes motivates increased cooperation, it sometimes reduces cooperation. We use a lab experiment to study why punishment sometimes fails. We begin with a gift exchange game with punishment as it has typically been implemented therein since punishment has often backfired in this game. We modify two features of punishment that could increase its efficacy: punishment's strength and its timing (whether the punisher publicly pre-commits to punishment or acts after the pun...

Anxiolytic Effect of Exogenous Ketone Supplementation Is Abolished by Adenosine A1 Receptor Inhibition in Wistar Albino Glaxo/Rijswijk Rats.

Science.gov (United States)

Kovács, Zsolt; D'Agostino, Dominic P; Ari, Csilla

2018-01-01

Anxiety disorders are one of the most common mental health problems worldwide, but the exact pathophysiology remains largely unknown. It has been demonstrated previously that administration of exogenous ketone supplement KSMCT (ketone salt/KS + medium chain triglyceride/MCT oil) by intragastric gavage for 7 days decreased the anxiety level in genetically absence epileptic Wistar Albino Glaxo/Rijswijk (WAG/Rij) rats. To investigate the potential role of the adenosinergic system in the pathomechanism of anxiety we tested whether the inhibition of adenosine A 1 receptors (A 1 Rs) influence the anxiolytic effect of the exogenous ketone supplement. As A 1 Rs may mediate such an effect, in the present study we used a specific A 1 R antagonist, DPCPX (1,3-dipropyl-8-cyclopentylxanthine) to test whether it modulates the anxiolytic effect of sub-chronically (7 days) applied KSMCT in the previously tested animal model by using elevated plus maze (EPM) test. We administered KSMCT (2.5 g/kg/day) alone by intragastric gavage and in combination with intraperitoneally (i.p.) injected of DPCPX in two doses (lower: 0.15 mg/kg, higher: 0.25 mg/kg). Control groups represented i.p saline and water gavage with or without i.p. DPCPX administration (2.5 g/kg/day). After treatments, the level of blood glucose and beta-hydroxybutyrate (βHB), as well as body weight were recorded. KSMCT alone significantly increased the time spent in the open arms and decreased the time spent in the closed arms, supporting our previous results. Injection of lower dose of DPCPX decreased, while higher dose of DPCPX abolished the effect of KSMCT administration on EPM. Blood βHB levels were significantly increased after administration of KSMCT, while DPCPX did not change the KSMCT induced increase in blood βHB levels. These results demonstrate that A 1 R inhibition modified (decreased) the anti-anxiety effect of KSMCT administration implying that the adenosinergic system, likely via A 1 Rs, may modulate the

Anxiolytic Effect of Exogenous Ketone Supplementation Is Abolished by Adenosine A1 Receptor Inhibition in Wistar Albino Glaxo/Rijswijk Rats

Directory of Open Access Journals (Sweden)

Zsolt Kovács

2018-02-01

Full Text Available Anxiety disorders are one of the most common mental health problems worldwide, but the exact pathophysiology remains largely unknown. It has been demonstrated previously that administration of exogenous ketone supplement KSMCT (ketone salt/KS + medium chain triglyceride/MCT oil by intragastric gavage for 7 days decreased the anxiety level in genetically absence epileptic Wistar Albino Glaxo/Rijswijk (WAG/Rij rats. To investigate the potential role of the adenosinergic system in the pathomechanism of anxiety we tested whether the inhibition of adenosine A1 receptors (A1Rs influence the anxiolytic effect of the exogenous ketone supplement. As A1Rs may mediate such an effect, in the present study we used a specific A1R antagonist, DPCPX (1,3-dipropyl-8-cyclopentylxanthine to test whether it modulates the anxiolytic effect of sub-chronically (7 days applied KSMCT in the previously tested animal model by using elevated plus maze (EPM test. We administered KSMCT (2.5 g/kg/day alone by intragastric gavage and in combination with intraperitoneally (i.p. injected of DPCPX in two doses (lower: 0.15 mg/kg, higher: 0.25 mg/kg. Control groups represented i.p saline and water gavage with or without i.p. DPCPX administration (2.5 g/kg/day. After treatments, the level of blood glucose and beta-hydroxybutyrate (βHB, as well as body weight were recorded. KSMCT alone significantly increased the time spent in the open arms and decreased the time spent in the closed arms, supporting our previous results. Injection of lower dose of DPCPX decreased, while higher dose of DPCPX abolished the effect of KSMCT administration on EPM. Blood βHB levels were significantly increased after administration of KSMCT, while DPCPX did not change the KSMCT induced increase in blood βHB levels. These results demonstrate that A1R inhibition modified (decreased the anti-anxiety effect of KSMCT administration implying that the adenosinergic system, likely via A1Rs, may modulate the

MFGE8 inhibits inflammasome-induced IL-1β production and limits postischemic cerebral injury.

Science.gov (United States)

Deroide, Nicolas; Li, Xuan; Lerouet, Dominique; Van Vré, Emily; Baker, Lauren; Harrison, James; Poittevin, Marine; Masters, Leanne; Nih, Lina; Margaill, Isabelle; Iwakura, Yoichiro; Ryffel, Bernhard; Pocard, Marc; Tedgui, Alain; Kubis, Nathalie; Mallat, Ziad

2013-03-01

Milk fat globule-EGF 8 (MFGE8) plays important, nonredundant roles in several biological processes, including apoptotic cell clearance, angiogenesis, and adaptive immunity. Several recent studies have reported a potential role for MFGE8 in regulation of the innate immune response; however, the precise mechanisms underlying this role are poorly understood. Here, we show that MFGE8 is an endogenous inhibitor of inflammasome-induced IL-1β production. MFGE8 inhibited necrotic cell-induced and ATP-dependent IL-1β production by macrophages through mediation of integrin β(3) and P2X7 receptor interactions in primed cells. Itgb3 deficiency in macrophages abrogated the inhibitory effect of MFGE8 on ATP-induced IL-1β production. In a setting of postischemic cerebral injury in mice, MFGE8 deficiency was associated with enhanced IL-1β production and larger infarct size; the latter was abolished after treatment with IL-1 receptor antagonist. MFGE8 supplementation significantly dampened caspase-1 activation and IL-1β production and reduced infarct size in wild-type mice, but did not limit cerebral necrosis in Il1b-, Itgb3-, or P2rx7-deficient animals. In conclusion, we demonstrated that MFGE8 regulates innate immunity through inhibition of inflammasome-induced IL-1β production.

Differential vulnerability to the punishment of cocaine related behaviours: effects of locus of punishment, cocaine taking history and alternative reinforcer availability.

Science.gov (United States)

Pelloux, Yann; Murray, Jennifer E; Everitt, Barry J

2015-01-01

The availability of alternative reinforcement has been shown to reduce drug use, but it remains unclear whether it facilitates a reduction or cessation of drug seeking or taking. We compared the effects of punishment of cocaine seeking or taking behaviour after brief or extended cocaine-taking histories when behavioural reallocation was facilitated or not by making available an alternative ingestive reinforcer (sucrose). In the first experiment, punishment of either seeking or taking responses was introduced immediately after training on the seeking-taking chained schedule. In the second experiment, punishment of cocaine seeking was introduced after 12 additional days of either 1 or 6 h daily access to cocaine self-administration. In both experiments, beginning 1 week before the introduction of punishment, a subset of rats had concurrent nose poke access to sucrose while seeking or taking cocaine. The presence of an alternative source of reinforcement markedly facilitated behavioural reallocation from punished cocaine taking after acquisition. It also facilitated punishment-induced suppression of cocaine seeking after an extensive cocaine self-administration history likely by prompting goal-directed motivational control over drug use. However, a significant proportion of rats were deemed compulsive-maintaining drug use after an extensive cocaine history despite the presence of abstinence-promoting positive and negative incentives. Making available an alternative reinforcer facilitates disengagement from punished cocaine use through at least two different processes but remains ineffective in a subpopulation of vulnerable animals, which continued to seek cocaine despite the aversive consequence of punishment and the presence of the alternative positive reinforcer.

IGF-1 protects against Aβ25-35-induced neuronal cell death via inhibition of PUMA expression and Bax activation.

Science.gov (United States)

Hou, Xunyao; Jin, Yan; Chen, Jian; Hong, Yan; Luo, Dingzhen; Yin, Qingqing; Liu, Xueping

2017-01-10

Amyloid-β-peptide (Aβ) is considered to be the toxic species in AD and causes cell death in the affected areas of patient's brain. Insulin-like growth factor 1 (IGF-1) has been reported to attenuate Aβ toxicity in neuronal cells. However, the molecular mechanisms involved in the neuroprotective function of IGF-1 remain largely unknown. In the present study, we for the first time demonstrated that IGF-1 protects against Aβ-induced neurotoxicity via inhibition of PUMA expression and Bax activation. We found that IGF-1 could activate Akt, which in turn inhibited Aβ-induced FOXO3a nuclear translocation and thus decreased the binding ability of FOXO3a to PUMA promoter, leading to decreased PUMA expression. In addition, IGF-1 inhibited the translocation of Bax to the mitochondria induced by Aβ. Notably, addition of wortmannin, a specific inhibitor of PI3K, significantly abolished the neuroprotective effect of IGF-1, suggesting that IGF-1 exerts its anti-apoptotic effect depend on PI3K activity. Our findings may provide new insights into molecular mechanisms mediated by IGF-1 in cell survival against Aβ-induced apoptosis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Reward and punishment

OpenAIRE

Sigmund, Karl; Hauert, Christoph; Nowak, Martin A.

2001-01-01

Minigames capturing the essence of Public Goods experiments show that even in the absence of rationality assumptions, both punishment and reward will fail to bring about prosocial behavior. This result holds in particular for the well-known Ultimatum Game, which emerges as a special case. But reputation can induce fairness and cooperation in populations adapting through learning or imitation. Indeed, the inclusion of reputation effects in the corresponding dynamical models leads to the evolut...

Examining Punishment and Discipline: Defending the Use of Punishment by Coaches

Science.gov (United States)

Seifried, Chad

2008-01-01

Confusion, uncertainty, and debate often surround the terms "discipline" and "punishment" because scholars fail to publicize that they possess distinctive meanings. This article differentiates punishment from discipline and attempts to present some rationale supporting its use, especially corporal punishment, in a sport setting from a coaching…

Experiences of punishment by parents during childhood: A retrospective study

Directory of Open Access Journals (Sweden)

Isaković Olivera

2014-01-01

Full Text Available The study described perceived differences in the choice of child rearing practices aimed at correcting children’s inappropriate behaviors as remembered by the participants at young adulthood. The sample consisted of 207 students of under-graduate studies of the University of Novi Sad. The most of the participants does not have children and they grew up in complete families. On the Dimensions of Discipline Inventory (A (DDI-A, Straus, Fauchier, 2007, the participants estimated the experience and methods of disciplining which were used by their parents during their childhood. The participants describe uniform discipline behaviors of their parents regarding the estimated discipline techniques. These behaviors are dominated by the punishing ones, and the differences between fathers and mothers are visible in a stronger tendency to describe fathers as the ones who use corporal punishment, abolish privileges and give restorative tasks. The described discipline techniques for both fathers and mothers remain stable and similar, regardless of the socio-demographic characteristics of the families as family completeness, work experience and level of education of the parents, as well as estimated economic status of the family.

[4-t-butylphenyl]-N-(4-imidazol-1-yl phenyl)sulfonamide (ISCK03) inhibits SCF/c-kit signaling in 501mel human melanoma cells and abolishes melanin production in mice and brownish guinea pigs.

Science.gov (United States)

Na, Yong Joo; Baek, Heung Su; Ahn, Soo Mi; Shin, Hyun Jung; Chang, Ih-Seop; Hwang, Jae Sung

2007-09-01

It is well known that c-kit is related to pigmentation as well as to the oncology target protein. The objective of this study was to discover a skin-whitening agent that regulates c-kit activity. We have developed a high-throughput screening system using recombinant human c-kit protein. Approximately 10,000 synthetic compounds were screened for their effect on c-kit activity. Phenyl-imidazole sulfonamide derivatives showed inhibitory activity on c-kit phosphorylation in vitro. The effects of one derivative, [4-t-butylphenyl]-N-(4-imidazol-1-yl phenyl)sulfonamide (ISCK03), on stem-cell factor (SCF)/c-kit cellular signaling in 501mel human melanoma cells were examined further. Pretreatment of 501mel cells with ISCK03 inhibited SCF-induced c-kit phosphorylation dose dependently. ISCK03 also inhibited p44/42 ERK mitogen-activated protein kinase (MAPK) phosphorylation, which is known to be involved in SCF/c-kit downstream signaling. However ISCK03 did not inhibit hepatocyte growth factor (HGF)-induced phosphorylation of p44/42 ERK proteins. To determine the in vivo potency of ISCK03, it was orally administered to depilated C57BL/6 mice. Interestingly, oral administration of ISCK03 induced the dose-dependent depigmentation of newly regrown hair, and this was reversed with cessation of ISCK03 treatment. Finally, to investigate whether the inhibitory effect of ISCK03 on SCF/c-kit signaling abolished UV-induced pigmentation, ISCK03 was applied to UV-induced pigmented spots on brownish guinea pig skin. The topical application of ISCK03 promoted the depigmentation of UV-induced hyperpigmented spots. Fontana-Masson staining analysis showed epidermal melanin was diminished in spots treated with ISCK03. These results indicate that phenyl-imidazole sulfonamide derivatives are potent c-kit inhibitors and might be used as skin-whitening agents.

PPARγ activation abolishes LDL-induced proliferation of human aortic smooth muscle cells via SOD-mediated down-regulation of superoxide

International Nuclear Information System (INIS)

Heo, Kyung-Sun; Kim, Dong-Uk; Ryoo, Sungwoo; Nam, Miyoung; Baek, Seung Tae; Kim, Lila; Park, Song-Kyu; Myung, Chang-Seon; Hoe, Kwang-Lae

2007-01-01

Native LDL would be a mitogenic and chemotactic stimulus of VSMC proliferation and differentiation in the atherosclerotic lesion where endothelial disruption occurred. In previous studies, our group investigated the molecular mechanisms by which LDL induces IL-8 production and by which PPARα activation abolishes LDL effects in human aortic SMCs (hAoSMCs). Herein is the first report of PPARγ activation by troglitazone (TG) exerting its inhibitory effects on LDL-induced cell proliferation via generation not of H 2 O 2 , but of O2?-, and the subsequent activation of Erk1/2 in hAoSMCs. Moreover, in this study TG abolished the LDL-accelerated G 1 -S progression to control levels via down-regulation of active cyclinD1/CDK4 and cyclinE/CDK2 complexes and up-regulation of p21 Cip1 expression. TG exerted its anti-proliferative effects through the up-regulation of basal superoxide dismutase (SOD) expression. This data suggests that the regulation of O2?- is located at the crossroads between LDL signaling and cell proliferation

Choosy moral punishers.

Directory of Open Access Journals (Sweden)

Christine Clavien

Full Text Available The punishment of social misconduct is a powerful mechanism for stabilizing high levels of cooperation among unrelated individuals. It is regularly assumed that humans have a universal disposition to punish social norm violators, which is sometimes labelled "universal structure of human morality" or "pure aversion to social betrayal". Here we present evidence that, contrary to this hypothesis, the propensity to punish a moral norm violator varies among participants with different career trajectories. In anonymous real-life conditions, future teachers punished a talented but immoral young violinist: they voted against her in an important music competition when they had been informed of her previous blatant misconduct toward fellow violin students. In contrast, future police officers and high school students did not punish. This variation among socio-professional categories indicates that the punishment of norm violators is not entirely explained by an aversion to social betrayal. We suggest that context specificity plays an important role in normative behaviour; people seem inclined to enforce social norms only in situations that are familiar, relevant for their social category, and possibly strategically advantageous.

Punishment induced behavioural and neurophysiological variability reveals dopamine-dependent selection of kinematic movement parameters

Science.gov (United States)

Galea, Joseph M.; Ruge, Diane; Buijink, Arthur; Bestmann, Sven; Rothwell, John C.

2013-01-01

Action selection describes the high-level process which selects between competing movements. In animals, behavioural variability is critical for the motor exploration required to select the action which optimizes reward and minimizes cost/punishment, and is guided by dopamine (DA). The aim of this study was to test in humans whether low-level movement parameters are affected by punishment and reward in ways similar to high-level action selection. Moreover, we addressed the proposed dependence of behavioural and neurophysiological variability on DA, and whether this may underpin the exploration of kinematic parameters. Participants performed an out-and-back index finger movement and were instructed that monetary reward and punishment were based on its maximal acceleration (MA). In fact, the feedback was not contingent on the participant’s behaviour but pre-determined. Blocks highly-biased towards punishment were associated with increased MA variability relative to blocks with either reward or without feedback. This increase in behavioural variability was positively correlated with neurophysiological variability, as measured by changes in cortico-spinal excitability with transcranial magnetic stimulation over the primary motor cortex. Following the administration of a DA-antagonist, the variability associated with punishment diminished and the correlation between behavioural and neurophysiological variability no longer existed. Similar changes in variability were not observed when participants executed a pre-determined MA, nor did DA influence resting neurophysiological variability. Thus, under conditions of punishment, DA-dependent processes influence the selection of low-level movement parameters. We propose that the enhanced behavioural variability reflects the exploration of kinematic parameters for less punishing, or conversely more rewarding, outcomes. PMID:23447607

Probability differently modulating the effects of reward and punishment on visuomotor adaptation.

Science.gov (United States)

Song, Yanlong; Smiley-Oyen, Ann L

2017-12-01

Recent human motor learning studies revealed that punishment seemingly accelerated motor learning but reward enhanced consolidation of motor memory. It is not evident how intrinsic properties of reward and punishment modulate the potentially dissociable effects of reward and punishment on motor learning and motor memory. It is also not clear what causes the dissociation of the effects of reward and punishment. By manipulating probability of distribution, a critical property of reward and punishment, the present study demonstrated that probability had distinct modulation on the effects of reward and punishment in adapting to a sudden visual rotation and consolidation of the adaptation memory. Specifically, two probabilities of monetary reward and punishment distribution, 50 and 100%, were applied during young adult participants adapting to a sudden visual rotation. Punishment and reward showed distinct effects on motor adaptation and motor memory. The group that received punishments in 100% of the adaptation trials adapted significantly faster than the other three groups, but the group that received rewards in 100% of the adaptation trials showed marked savings in re-adapting to the same rotation. In addition, the group that received punishments in 50% of the adaptation trials that were randomly selected also had savings in re-adapting to the same rotation. Sensitivity to sensory prediction error or difference in explicit process induced by reward and punishment may likely contribute to the distinct effects of reward and punishment.

Punishment does not promote cooperation under exploration dynamics when anti-social punishment is possible.

Science.gov (United States)

P Hauser, Oliver; A Nowak, Martin; G Rand, David

2014-11-07

It has been argued that punishment promotes the evolution of cooperation when mutation rates are high (i.e. when agents engage in 'exploration dynamics'). Mutations maintain a steady supply of agents that punish free-riders, and thus free-riders are at a disadvantage. Recent experiments, however, have demonstrated that free-riders sometimes also pay to punish cooperators. Inspired by these empirical results, theoretical work has explored evolutionary dynamics where mutants are rare, and found that punishment does not promote the evolution of cooperation when this 'anti-social punishment' is allowed. Here we extend previous theory by studying the effect of anti-social punishment on the evolution of cooperation across higher mutation rates, and by studying voluntary as well as compulsory Public Goods Games. We find that for intermediate and high mutation rates, adding punishment does not promote cooperation in either compulsory or voluntary public goods games if anti-social punishment is possible. This is because mutations generate agents that punish cooperators just as frequently as agents that punish defectors, and these two effects cancel each other out. These results raise questions about the effectiveness of punishment for promoting cooperation when mutations are common, and highlight how decisions about which strategies to include in the strategy set can have profound effects on the resulting dynamics. Copyright © 2014 Elsevier Ltd. All rights reserved.

STAT6 silencing induces hepatocellular carcinoma-derived cell apoptosis and growth inhibition by decreasing the RANKL expression.

Science.gov (United States)

Qing, Tian; Yamin, Zhang; Guijie, Wang; Yan, Jin; Zhongyang, Shen

2017-08-01

Signal transducer and activator of transcription-6 (STAT6) is highly expressed in various human cancers and considered a regulator of multiple biological processes in cancers, including cell apoptosis. Evidence has indicated that STAT6 predicts a worse prognosis in hepatocellular carcinoma (HCC) patients. The objective of this study was to investigate the effects and mechanism of STAT6 in human HCC cells. We found that STAT6 silencing significantly inhibited HepG2 and Hep3B cell survival and proliferation. We observed that depletion of STAT6 increased HepG2 and Hep3B cell apoptosis by using a histone DNA ELISA detection kit. STAT6 silencing induced expression of apoptosis-associated genes Bax and caspase-3/7 and inhibited anti-apoptosis gene Bcl-2 levels. We also observed that STAT6 silencing downregulated the expression of receptor activator of NF-κB ligand (RANKL). Our results demonstrated that treatment with pcDNA3.1-RANKL abolished STAT6 depletion-induced HepG2 and Hep3B cell apoptosis and growth inhibition. Based on these findings, we believe that RANKL plays a major role in STAT6-induced HCC cell apoptosis. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Neural components of altruistic punishment

Directory of Open Access Journals (Sweden)

Emily eDu

2015-02-01

Full Text Available Altruistic punishment, which occurs when an individual incurs a cost to punish in response to unfairness or a norm violation, may play a role in perpetuating cooperation. The neural correlates underlying costly punishment have only recently begun to be explored. Here we review the current state of research on the neural basis of altruism from the perspectives of costly punishment, emphasizing the importance of characterizing elementary neural processes underlying a decision to punish. In particular, we emphasize three cognitive processes that contribute to the decision to altruistically punish in most scenarios: inequity aversion, cost-benefit calculation, and social reference frame to distinguish self from others. Overall, we argue for the importance of understanding the neural correlates of altruistic punishment with respect to the core computations necessary to achieve a decision to punish.

Using research to change public policy: reflections on 20 years of effort to eliminate corporal punishment in schools.

Science.gov (United States)

Hyman, I A

1996-10-01

In the past 20 years, over half of the states have abolished corporal punishment in schools. Without the use of ethically questionable, experimental studies in which students were randomly assigned to paddlings, advocacy researchers were able to integrate the literature and experimental research on reward, punishment, and motivation, and conduct enough studies to provide sufficient data for policy changes. Further, every popular school discipline training program promotes well-proven positive and preventive techniques and punishments that do not inflict physical pain. Research on alternatives, naturalistic evidence from schools that eliminated corporal punishment, and survey research prove that schools do not need to use corporal punishment. The movement to eliminate parental spanking is at a stage similar to the beginning of the school corporal punishment debate in 1976. Even though some studies may show that moderate parental spanking may do no short-term harm, there is little scientific evidence that it is necessary. There are no data to indicate that schools which eliminated corporal punishment became any worse. The same demographic factors and political polarizations that have kept about half of American school children from the protections against paddling afforded students in almost all other Western democracies also impede the movement to eliminate parental spanking. Since we know that corporal punishment too often leads to excesses, and since we have a multitude of effective positive approaches, what is the worst thing that would happen if all Americans stopped hitting children in any setting? The same children who are hit for misbehavior would continue that misbehavior and other ineffective punishments would be used. Most parents and teachers would discover what behavioral scientists already know. A combination of reward, positive motivational techniques and appropriate, nonphysical punishments would prevent most misbehavior. Other factors being equal, in

Caffeine Abolishes the Ultraviolet-Induced REV3 Translesion Replication Pathway in Mouse Cells

Directory of Open Access Journals (Sweden)

Kouichi Yamada

2011-11-01

Full Text Available When a replicative DNA polymerase stalls upon encountering a photoproduct on the template strand, it is relieved by other low-processivity polymerase(s, which insert nucleotide(s opposite the lesion. Using an alkaline sucrose density gradient sedimentation technique, we previously classified this process termed UV-induced translesion replication (UV-TLS into two types. In human cancer cells or xeroderma pigmentosum variant (XP-V cells, UV-TLS was inhibited by caffeine or proteasome inhibitors. However, in normal human cells, the process was insensitive to these reagents. Reportedly, in yeast or mammalian cells, REV3 protein (a catalytic subunit of DNA polymerase ζ is predominantly involved in the former type of TLS. Here, we studied UV-TLS in fibroblasts derived from the Rev3-knockout mouse embryo (Rev3KO-MEF. In the wild-type MEF, UV-TLS was slow (similar to that of human cancer cells or XP-V cells, and was abolished by caffeine or MG-262. In 2 cell lines of Rev3KO-MEF (Rev3−/− p53−/−, UV-TLS was not observed. In p53KO-MEF, which is a strict control for Rev3KO-MEF, the UV-TLS response was similar to that of the wild-type. Introduction of the Rev3 expression plasmid into Rev3KO-MEF restored the UV-TLS response in selected stable transformants. In some transformants, viability to UV was the same as that in the wild-type, and the death rate was increased by caffeine. Our findings indicate that REV3 is predominantly involved in UV-TLS in mouse cells, and that the REV3 translesion pathway is suppressed by caffeine or proteasome inhibitors.

Human cooperation based on punishment reputation.

Science.gov (United States)

dos Santos, Miguel; Rankin, Daniel J; Wedekind, Claus

2013-08-01

The threat of punishment usually promotes cooperation. However, punishing itself is costly, rare in nonhuman animals, and humans who punish often finish with low payoffs in economic experiments. The evolution of punishment has therefore been unclear. Recent theoretical developments suggest that punishment has evolved in the context of reputation games. We tested this idea in a simple helping game with observers and with punishment and punishment reputation (experimentally controlling for other possible reputational effects). We show that punishers fully compensate their costs as they receive help more often. The more likely defection is punished within a group, the higher the level of within-group cooperation. These beneficial effects perish if the punishment reputation is removed. We conclude that reputation is key to the evolution of punishment. © 2013 The Author(s). Evolution © 2013 The Society for the Study of Evolution.

Atractylenolide I restores HO-1 expression and inhibits Ox-LDL-induced VSMCs proliferation, migration and inflammatory responses in vitro

Energy Technology Data Exchange (ETDEWEB)

Li, Weifeng, E-mail: liwf@mail.xjtu.edu.cn; Zhi, Wenbing; Liu, Fang; He, Zehong; Wang, Xiuei; Niu, Xiaofeng, E-mail: niuxf@mail.xjtu.edu.cn

2017-04-01

Pathogenesis of atherosclerosis is characterized by the proliferation and migration of vascular smooth muscle cells (VSMCs) and inflammatory lesions. The aim of this study is to elucidate the effect of atractylenolide I (AO-I) on smooth muscle cell inflammation, proliferation and migration induced by oxidized modified low density lipoprotein (Ox-LDL). Here, We found that atractylenolide I inhibited Ox-LDL-induced VSMCs proliferation and migration in a dose-dependent manner, and decreased the production of inflammatory cytokines and the expression of monocyte chemoattractant protein-1 (MCP-1) in VSMCs. The study also identified that AO-I prominently inhibited p38-MAPK and NF-κB activation. More importantly, the specific heme oxygenase-1 (HO-1) inhibitor zinc protoporphyrin (ZnPP) IX partially abolished the beneficial effects of atractylenolide I on Ox-LDL-induced VSMCs. Furthermore, atractylenolide I blocked the foam cell formation in macrophages induced by Ox-LDL. In summary, inhibitory roles of AO-I in VSMCs proliferation and migration, lipid peroxidation and subsequent inflammatory responses might contribute to the anti-atherosclerotic property of AO-I. - Highlights: • AO-I inhibited Ox-LDL-induced VSMCs proliferation and migration. • AO-I alleviated inflammatory response via inhibiting TNF-α, IL-6 and NO production. • AO-I restored HO-1 expression and down-regulated PCNA expression. • MCP-1 overexpression is potentially regulated by NF-κB and p38 MAPK pathway. • AO-I possesses strong anti-lipid peroxidation effect.

Cooperation under punishment: Imperfect information destroys it and centralizing punishment does not help

OpenAIRE

Sven Fischer; Kristoffel Grechenig; Nicolas Meier

2013-01-01

We run several experiments which allow us to compare cooperation under perfect and imperfect information and under a centralized and decentralized punishment regime. We find that (1) centralization by itself does not improve cooperation and welfare compared to an informal, peer-to-peer punishment regime and (2) centralized punishment is equally sensitive to noise as decentralized punishment, that is, it leads to significantly lower cooperation and welfare (total pro ts). Our results shed crit...

PLC-dependent intracellular Ca2+ release was associated with C6-ceramide-induced inhibition of Na+ current in rat granule cells.

Science.gov (United States)

Liu, Zheng; Fei, Xiao-Wei; Fang, Yan-Jia; Shi, Wen-Jie; Zhang, Yu-Qiu; Mei, Yan-Ai

2008-09-01

In this report, the effects of C(6)-ceramide on the voltage-gated inward Na(+) currents (I(Na)), two types of main K(+) current [outward rectifier delayed K(+) current (I(K)) and outward transient K(+) current (I(A))], and cell death in cultured rat cerebellar granule cells were investigated. At concentrations of 0.01-100 microM, ceramide produced a dose-dependent and reversible inhibition of I(Na) without alteration of the steady-state activation and inactivation properties. Treatment with C(2)-ceramide caused a similar inhibitory effect on I(Na). However, dihydro-C(6)-ceramide failed to modulate I(Na). The effect of C(6)-ceramide on I(Na) was abolished by intracellular infusion of the Ca(2+)-chelating agent, 1,2-bis (2-aminophenoxy) ethane-N, N, N9, N9-tetraacetic acid, but was mimicked by application of caffeine. Blocking the release of Ca(2+) from the sarcoplasmic reticulum with ryanodine receptor blocker induced a gradual increase in I(Na) amplitude and eliminated the effect of ceramide on I(Na). In contrast, the blocker of the inositol 1,4,5-trisphosphate-sensitive Ca(2+) receptor did not affect the action of C(6)-ceramide. Intracellular application of GTPgammaS also induced a gradual decrease in I(Na) amplitude, while GDPbetaS eliminated the effect of C(6)-ceramide on I(Na). Furthermore, the C(6)-ceramide effect on I(Na) was abolished after application of the phospholipase C (PLC) blockers and was greatly reduced by the calmodulin inhibitors. Fluorescence staining showed that C(6)-ceramide decreased cell viability and blocking I(Na) by tetrodotoxin did not mimic the effect of C(6)-ceramide, and inhibiting intracellular Ca(2+) release by dantrolene could not decrease the C(6)-ceramide-induced cell death. We therefore suggest that increased PLC-dependent Ca(2+) release through the ryanodine-sensitive Ca(2+) receptor may be responsible for the C(6)-ceramide-induced inhibition of I(Na), which does not seem to be associated with C(6)-ceramide-induced granule

Corporal punishment.

Science.gov (United States)

Bauman, L J; Friedman, S B

1998-04-01

Pediatricians differ on the optimal ways to discipline children. The major controversy surrounds the use of corporal punishment. In an effort to resolve this controversy, the American Academy of Pediatrics (AAP) cosponsored a conference entitled "The Short and Long-Term Consequences of Corporal Punishment" in February 1996. This article reviews scientific literature on corporal punishment and summarizes the proceedings from the conference. The authors conclude that, although the research data are inadequate to resolve the controversy, there are areas of consensus. Practitioners should assess the spanking practices of the parent they see and counsel parents to avoid those that are, by AAP consensus, dangerous, ineffective, or abusive.

Should we punish a remorseful offender? Punishment within a ...

African Journals Online (AJOL)

A theory of symbolic restoration depends on an expressivist account of punishment, like Joel Feinberg's. Expressivism gives us an insight into the importance of the feeling of moral condemnation and it is this feeling that gives rise to the longing for punishment and remorse. Because of moral condemnation after a crime we ...

Technetium-99 conjugated with methylene diphosphonate inhibits receptor activator of nuclear factor-κB ligand-induced osteoclastogenesis.

Science.gov (United States)

Gong, Wei; Dou, Huan; Liu, Xianqin; Sun, Lingyun; Hou, Yayi

2012-10-01

1. In the present study, we investigated the effects of technetium-99 conjugated with methylene diphosphonate ((99)Tc-MDP), an agent used in radionuclide therapy, on receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis and explored the underlying mechanisms. 2. The murine macrophage cell line RAW264.7 and bone marrow-derived-macrophages from C57BL/6 mice (BMM) were used as models for osteoclastogenesis in vitro. The expression of some key factors in RANKL (50 ng/mL)-induced osteoclastogenesis in RAW264.7 cells was investigated by flow cytometry and real-time reverse transcription-polymerase chain reaction (RT-PCR). To detect multinucleated osteoclast formation, RAW264.7 cells were induced with RANKL for 4 days, whereas BMM were induced by 50 ng/mL RANKL and 20 ng/mL macrophage colony-stimulating factor for 7 days, before being stained with tartrate-resistant acid phosphatase. 3. Osteoclastogenesis was evaluated using the osteoclast markers CD51, matrix metalloproteinase (MMP)-9 and cathepsin K. At 0.01 μg/mL, (99)Tc-MDP significantly inhibited RANKL-induced osteoclastogenesis without any cytotoxicity. In addition, (99)Tc-MDP abolished the appearance of multinucleated osteoclasts. 4. Real-time RT-PCR analysis of transcription factor expression revealed that (99)Tc-MDP inhibited the expression of c-Fos and nuclear factor of activated T cells. In addition, (99)Tc-MDP inhibited the expression of the inflammatory factors interleukin (IL)-6, tumour necrosis factor-α and IL-1β. Finally, (99)Tc-MDP inhibited the activation of mitogen-activated protein kinases in RAW264.7 cells following RANKL stimulation. 5. In conclusion, (99)Tc-MDP possesses anti-osteoclastogenic activity against RANKL-induced osteoclast formation. © 2012 The Authors Clinical and Experimental Pharmacology and Physiology © 2012 Wiley Publishing Asia Pty Ltd.

Inhibition of PKMzeta in nucleus accumbens core abolishes long-term drug reward memory.

Science.gov (United States)

Li, Yan-qin; Xue, Yan-xue; He, Ying-ying; Li, Fang-qiong; Xue, Li-fen; Xu, Chun-mei; Sacktor, Todd Charlton; Shaham, Yavin; Lu, Lin

2011-04-06

During abstinence, memories of drug-associated cues persist for many months, and exposure to these cues often provokes relapse to drug use. The mechanisms underlying the maintenance of these memories are unknown. A constitutively active atypical protein kinase C (PKC) isozyme, protein kinase M ζ (PKMζ), is required for maintenance of spatial memory, conditioned taste aversion, and other memory forms. We used conditioned place preference (CPP) and conditioned place aversion (CPA) procedures to study the role of nucleus accumbens PKMζ in the maintenance of drug reward and aversion memories in rats. Morphine CPP training (10 mg/kg, 4 pairings) increased PKMζ levels in accumbens core but not shell. Injections of the PKMζ inhibitor ζ inhibitory peptide (ZIP) into accumbens core but not shell after CPP training blocked morphine CPP expression for up to 14 d after injections. This effect was mimicked by the PKC inhibitor chelerythrine, which inhibits PKMζ, but not by the conventional and novel PKC inhibitor staurosporine, which does not effectively inhibit PKMζ. ZIP injections into accumbens core after training also blocked the expression of cocaine (10 mg/kg) and high-fat food CPP but had no effect on CPA induced by naloxone-precipitated morphine withdrawal. Accumbens core injections of Tat-GluR2(3Y), which inhibits GluR2-dependent AMPA receptor endocytosis, prevented the impairment in morphine CPP induced by local ZIP injections, indicating that the persistent effect of PKMζ is on GluR2-containing AMPA receptors. Results indicate that PKMζ activity in accumbens core is a critical cellular substrate for the maintenance of memories of relapse-provoking reward cues during prolonged abstinence periods.

Punishment goals of crime victims.

Science.gov (United States)

Orth, Uli

2003-04-01

Research on subjective punishment goals has focused on the perspective of third-party observers of criminal offenses and neglected the perspective of victims. This study investigates punishment goals among 174 adult crime victims (rape and nonsexual assault) for each participant's real criminal case. Scales measuring support for punishment goals are constructed by factor analysis of an 18-item list. Results show that 5 highly supported goals can be distinguished: retaliation, recognition of victim status, confirmation of societal values, victim security, and societal security. Analysis of relations between punishment goal scales and personal variables, situational variables, and demanded punishment severity corroborates the view that the punishment goals revealed can be classified according to the two independent dichotomies of moral versus instrumental goals, and micro versus macro goals.

Punishment in a complementarity game

Science.gov (United States)

Li, W.; Cai, X.; Wang, Q. A.

2006-05-01

We study the effects arisen from the punishment in an evolutionary complementarity game. Each round one member of population “buyers” deals with a randomly chosen member of population “sellers”. When the buyer's offer is greater than the seller's, a deal is done and both players are rewarded by gaining some points. Otherwise the transaction is not successful and both will lose certain points as punishment. Our simulations indicate that the resulting equilibrium of the game with punishment embedded is remarkably time-delayed compared to the counterpart of the non-punishment game. However, the median fee and the success rate of deals at the equilibrium remain nearly unchanged in various cases of games with different degrees of punishment, whether severe or not. Symmetry, between the two populations, and the equilibrium value can still be maintained when the members of both of them are punished fairly in any failed transaction. If they are done in a different manner, namely, the members of one population are subject to very severe punishment whereas their opponents receive less or no punishment at all, the latter in most cases will be better off.

More 'altruistic' punishment in larger societies.

Science.gov (United States)

Marlowe, Frank W; Berbesque, J Colette

2008-03-07

If individuals will cooperate with cooperators, and punish non-cooperators even at a cost to themselves, then this strong reciprocity could minimize the cheating that undermines cooperation. Based upon numerous economic experiments, some have proposed that human cooperation is explained by strong reciprocity and norm enforcement. Second-party punishment is when you punish someone who defected on you; third-party punishment is when you punish someone who defected on someone else. Third-party punishment is an effective way to enforce the norms of strong reciprocity and promote cooperation. Here we present new results that expand on a previous report from a large cross-cultural project. This project has already shown that there is considerable cross-cultural variation in punishment and cooperation. Here we test the hypothesis that population size (and complexity) predicts the level of third-party punishment. Our results show that people in larger, more complex societies engage in significantly more third-party punishment than people in small-scale societies.

The cAMP signaling system inhibits the repair of {gamma}-ray-induced DNA damage by promoting Epac1-mediated proteasomal degradation of XRCC1 protein in human lung cancer cells

Energy Technology Data Exchange (ETDEWEB)

Cho, Eun-Ah [Department of Biochemistry and Molecular Biology, Cancer Research Center, Seoul National University College of Medicine, Seoul 110-799 (Korea, Republic of); Juhnn, Yong-Sung, E-mail: juhnn@snu.ac.kr [Department of Biochemistry and Molecular Biology, Cancer Research Center, Seoul National University College of Medicine, Seoul 110-799 (Korea, Republic of)

2012-06-01

Highlights: Black-Right-Pointing-Pointer cAMP signaling system inhibits repair of {gamma}-ray-induced DNA damage. Black-Right-Pointing-Pointer cAMP signaling system inhibits DNA damage repair by decreasing XRCC1 expression. Black-Right-Pointing-Pointer cAMP signaling system decreases XRCC1 expression by promoting its proteasomal degradation. Black-Right-Pointing-Pointer The promotion of XRCC1 degradation by cAMP signaling system is mediated by Epac1. -- Abstract: Cyclic AMP is involved in the regulation of metabolism, gene expression, cellular growth and proliferation. Recently, the cAMP signaling system was found to modulate DNA-damaging agent-induced apoptosis by regulating the expression of Bcl-2 family proteins and inhibitors of apoptosis. Thus, we hypothesized that the cAMP signaling may modulate DNA repair activity, and we investigated the effects of the cAMP signaling system on {gamma}-ray-induced DNA damage repair in lung cancer cells. Transient expression of a constitutively active mutant of stimulatory G protein (G{alpha}sQL) or treatment with forskolin, an adenylyl cyclase activator, augmented radiation-induced DNA damage and inhibited repair of the damage in H1299 lung cancer cells. Expression of G{alpha}sQL or treatment with forskolin or isoproterenol inhibited the radiation-induced expression of the XRCC1 protein, and exogenous expression of XRCC1 abolished the DNA repair-inhibiting effect of forskolin. Forskolin treatment promoted the ubiquitin and proteasome-dependent degradation of the XRCC1 protein, resulting in a significant decrease in the half-life of the protein after {gamma}-ray irradiation. The effect of forskolin on XRCC1 expression was not inhibited by PKA inhibitor, but 8-pCPT-2 Prime -O-Me-cAMP, an Epac-selective cAMP analog, increased ubiquitination of XRCC1 protein and decreased XRCC1 expression. Knockdown of Epac1 abolished the effect of 8-pCPT-2 Prime -O-Me-cAMP and restored XRCC1 protein level following {gamma}-ray irradiation. From

Paeoniflorin Suppressed High Glucose-Induced Retinal Microglia MMP-9 Expression and Inflammatory Response via Inhibition of TLR4/NF-κB Pathway Through Upregulation of SOCS3 in Diabetic Retinopathy.

Science.gov (United States)

Zhu, Su-Hua; Liu, Bing-Qian; Hao, Mao-Juan; Fan, Yi-Xin; Qian, Cheng; Teng, Peng; Zhou, Xiao-Wei; Hu, Liang; Liu, Wen-Tao; Yuan, Zhi-Lan; Li, Qing-Ping

2017-10-01

Diabetic retinopathy (DR) is a serious-threatening complication of diabetes and urgently needed to be treated. Evidence has accumulated indicating that microglia inflammation within the retina plays a critical role in DR. Microglial matrix metalloproteinase 9 (MMP-9) has an important role in the destruction of the integrity of the blood-retinal barrier (BRB) associated with the development of DR. MMP-9 was also considered important for regulating inflammatory responses. Paeoniflorin, a monoterpene glucoside, has a potent immunomodulatory effect on microglia. We hypothesized that paeoniflorin could significantly suppress microglial MMP-9 activation induced by high glucose and further relieve DR. BV2 cells were used to investigate the effects and mechanism of paeoniflorin. The activation of MMP-9 was measured by gelatin zymography. Cell signaling was measured by western blot assay and immunofluorescence assay. High glucose increased the activation of MMP-9 in BV2 cells, which was abolished by HMGB1, TLR4, p38 MAPK, and NF-κB inhibition. Phosphorylation of p38 MAPK induced by high glucose was decreased by TLR4 inhibition in BV2 cells. Paeoniflorin induced suppressor of cytokine signaling 3 (SOCS3) expression and reduced MMP-9 activation in BV2 cells. The effect of paeoniflorin on SOCS3 was abolished by the TLR4 inhibitor. In streptozotocin (STZ)-induced diabetes mice, paeoniflorin induced SOCS3 expression and reduced MMP-9 activation. Paeoniflorin suppressed STZ-induced IBA-1 and IL-1β expression and decreased STZ-induced high blood glucose level. In conclusion, paeoniflorin suppressed high glucose-induced retinal microglia MMP-9 expression and inflammatory response via inhibition of the TLR4/NF-κB pathway through upregulation of SOCS3 in diabetic retinopathy.

miR-339-5p inhibits alcohol-induced brain inflammation through regulating NF-κB pathway

International Nuclear Information System (INIS)

Zhang, Yu; Wei, Guangkuan; Di, Zhiyong; Zhao, Qingjie

2014-01-01

Graphical abstract: - Highlights: • Alcohol upregulates miR-339-5p expression. • miR-339-5p inhibits the NF-kB pathway. • miR-339-5p interacts with and blocks activity of IKK-beat and IKK-epsilon. • miR-339-5p modulates IL-1β, IL-6 and TNF-α. - Abstract: Alcohol-induced neuroinflammation is mediated by the innate immunesystem. Pro-inflammatory responses to alcohol are modulated by miRNAs. The miRNA miR-339-5p has previously been found to be upregulated in alcohol-induced neuroinflammation. However, little has been elucidated on the regulatory functions of this miRNA in alcohol-induced neuroinflammation. We investigated the function of miR-339-5p in alcohol exposed brain tissue and isolated microglial cells using ex vivo and in vitro techniques. Our results show that alcohol induces transcription of miR 339-5p, IL-6, IL-1β and TNF-α in mouse brain tissue and isolated microglial cells by activating NF-κB. Alcohol activation of NF-κB allows for nuclear translocation of the NF-κB subunit p65 and expression of pro-inflammatory mediators. miR-339-5p inhibited expression of these pro-inflammatory factors through the NF-κB pathway by abolishing IKK-β and IKK-ε activity

miR-339-5p inhibits alcohol-induced brain inflammation through regulating NF-κB pathway

Energy Technology Data Exchange (ETDEWEB)

Zhang, Yu [Department of Neurology, The First Affiliated School of Harbin Medical University, Harbin 150001 (China); Wei, Guangkuan [Department of Neurology, Heilongjiang Provincial Hospital, Harbin 150036 (China); Di, Zhiyong [Department of Laboratory, Heilongjiang Provincial Hospital, Harbin 150036 (China); Zhao, Qingjie, E-mail: zhaoqingjie2013@163.com [Department of Neurology, The First Affiliated School of Harbin Medical University, Harbin 150001 (China)

2014-09-26

Graphical abstract: - Highlights: • Alcohol upregulates miR-339-5p expression. • miR-339-5p inhibits the NF-kB pathway. • miR-339-5p interacts with and blocks activity of IKK-beat and IKK-epsilon. • miR-339-5p modulates IL-1β, IL-6 and TNF-α. - Abstract: Alcohol-induced neuroinflammation is mediated by the innate immunesystem. Pro-inflammatory responses to alcohol are modulated by miRNAs. The miRNA miR-339-5p has previously been found to be upregulated in alcohol-induced neuroinflammation. However, little has been elucidated on the regulatory functions of this miRNA in alcohol-induced neuroinflammation. We investigated the function of miR-339-5p in alcohol exposed brain tissue and isolated microglial cells using ex vivo and in vitro techniques. Our results show that alcohol induces transcription of miR 339-5p, IL-6, IL-1β and TNF-α in mouse brain tissue and isolated microglial cells by activating NF-κB. Alcohol activation of NF-κB allows for nuclear translocation of the NF-κB subunit p65 and expression of pro-inflammatory mediators. miR-339-5p inhibited expression of these pro-inflammatory factors through the NF-κB pathway by abolishing IKK-β and IKK-ε activity.

Ginsenoside Rb1 Attenuates Agonist-Induced Contractile Response via Inhibition of Store-Operated Calcium Entry in Pulmonary Arteries of Normal and Pulmonary Hypertensive Rats

Directory of Open Access Journals (Sweden)

Rui-Xing Wang

2015-03-01

Full Text Available Background: Pulmonary hypertension (PH is characterized by sustained vasoconstriction, enhanced vasoreactivity and vascular remodeling, which leads to right heart failure and death. Despite several treatments are available, many forms of PH are still incurable. Ginsenoside Rb1, a principle active ingredient of Panax ginseng, exhibits multiple pharmacological effects on cardiovascular system, and suppresses monocrotaline (MCT-induced right heart hypertrophy. However, its effect on the pulmonary vascular functions related to PH is unknown. Methods: We examined the vasorelaxing effects of ginsenoside Rb1 on endothelin-1 (ET-1 induced contraction of pulmonary arteries (PAs and store-operated Ca2+ entry (SOCE in pulmonary arterial smooth muscle cells (PASMCs from chronic hypoxia (CH and MCT-induced PH. Results: Ginsenoside Rb1 elicited concentration-dependent relaxation of ET-1-induced PA contraction. The vasorelaxing effect was unaffected by nifedipine, but abolished by the SOCE blocker Gd3+. Ginsenoside Rb1 suppressed cyclopiazonic acid (CPA-induced PA contraction, and CPA-activated cation entry and Ca2+ transient in PASMCs. ET-1 and CPA-induced contraction, and CPA-activated cation entry and Ca2+ transients were enhanced in PA and PASMCs of CH and MCT-treated rats; the enhanced responses were abolished by ginsenoside Rb1. Conclusion: Ginsenoside Rb1 attenuates ET-1-induced contractile response via inhibition of SOCE, and it can effectively antagonize the enhanced pulmonary vasoreactivity in PH.

Strict or graduated punishment? Effect of punishment strictness on the evolution of cooperation in continuous public goods games.

Directory of Open Access Journals (Sweden)

Hajime Shimao

Full Text Available Whether costly punishment encourages cooperation is one of the principal questions in studies on the evolution of cooperation and social sciences. In society, punishment helps deter people from flouting rules in institutions. Specifically, graduated punishment is a design principle for long-enduring common-pool resource institutions. In this study, we investigate whether graduated punishment can promote a higher cooperation level when each individual plays the public goods game and has the opportunity to punish others whose cooperation levels fall below the punisher's threshold. We then examine how spatial structure affects evolutionary dynamics when each individual dies inversely proportional to the game score resulting from the social interaction and another player is randomly chosen from the population to produce offspring to fill the empty site created after a player's death. Our evolutionary simulation outcomes demonstrate that stricter punishment promotes increased cooperation more than graduated punishment in a spatially structured population, whereas graduated punishment increases cooperation more than strict punishment when players interact with randomly chosen opponents from the population. The mathematical analysis also supports the results.

Moral punishment in everyday life

NARCIS (Netherlands)

Hofmann, W.; Brandt, M.J.; Wisneski, D.C.; Rockenbach, B.; Skitka, L.J.

2018-01-01

The present research investigated event-related, contextual, demographic, and dispositional predictors of the desire to punish perpetrators of immoral deeds in daily life, as well as connections among the desire to punish, moral emotions, and momentary well-being. The desire to punish was reliably

Punishing second-order free riders before first-order free riders: The effect of pool punishment priority on cooperation

OpenAIRE

Ozono, Hiroki; Kamijo, Yoshio; Shimizu, Kazumi

2017-01-01

Second-order free riders, who do not owe punishment cost to first-order free riders in public goods games, lead to low cooperation. Previous studies suggest that for stable cooperation, it is critical to have a pool punishment system with second-order punishment, which gathers resources from group members and punishes second-order free riders as well as first-order free riders. In this study, we focus on the priority of punishment. We hypothesize that the pool punishment system that prioritiz...

The social costs of punishment

NARCIS (Netherlands)

van den Berg, Pieter; Molleman, Lucas; Weissing, Franz J.

Lab experiments on punishment are of limited relevance for understanding cooperative behavior in the real world. In real interactions, punishment is not cheap, but the costs of punishment are of a different nature than in experiments. They do not correspond to direct payments or payoff deductions,

Reward and Punishment in Minigames

OpenAIRE

Sigmund, K.; Hauert, C.; Nowak, M.A.

2001-01-01

Minigames capturing the essence of Public Goods experiments show that even in the absence of rationality assumptions, both punishment and reward will fail to bring about prosocial behavior. This result holds in particular for the well-known Ultimatum Game, which emerges as a special case. But reputation can induce fairness and cooperation in populations adapting through learning or imitation. Indeed, the inclusion of reputation effects in the corresponding dynamical models leads to the evolut...

Moral Punishment in Everyday Life.

Science.gov (United States)

Hofmann, Wilhelm; Brandt, Mark J; Wisneski, Daniel C; Rockenbach, Bettina; Skitka, Linda J

2018-05-01

The present research investigated event-related, contextual, demographic, and dispositional predictors of the desire to punish perpetrators of immoral deeds in daily life, as well as connections among the desire to punish, moral emotions, and momentary well-being. The desire to punish was reliably predicted by linear gradients of social closeness to both the perpetrator (negative relationship) and the victim (positive relationship). Older rather than younger adults, conservatives rather than people with other political orientations, and individuals high rather than low in moral identity desired to punish perpetrators more harshly. The desire to punish was related to state anger, disgust, and embarrassment, and these were linked to lower momentary well-being. However, the negative effect of these emotions on well-being was partially compensated by a positive indirect pathway via heightened feelings of moral self-worth. Implications of the present field data for moral punishment research and the connection between morality and well-being are discussed.

Inhibition of breast cancer resistance protein (ABCG2 in human myeloid dendritic cells induces potent tolerogenic functions during LPS stimulation.

Directory of Open Access Journals (Sweden)

Jun-O Jin

Full Text Available Breast cancer resistance protein (ABCG2, a member of the ATP-binding cassette transporters has been identified as a major determinant of multidrug resistance (MDR in cancer cells, but ABC transporter inhibition has limited therapeutic value in vivo. In this research, we demonstrated that inhibition of efflux transporters ABCG2 induced the generation of tolerogenic DCs from human peripheral blood myeloid DCs (mDCs. ABCG2 expression was present in mDCs and was further increased by LPS stimulation. Treatment of CD1c+ mDCs with an ABCG2 inhibitor, Ko143, during LPS stimulation caused increased production of IL-10 and decreased production of pro-inflammatory cytokines and decreased expression of CD83 and CD86. Moreover, inhibition of ABCG2 in monocyte-derived DCs (MDDCs abrogated the up-regulation of co-stimulatory molecules and production of pro-inflammatory cytokines in these cells in response to LPS. Furthermore, CD1c+ mDCs stimulated with LPS plus Ko143 inhibited the proliferation of allogeneic and superantigen-specific syngenic CD4+ T cells and promoted expansion of CD25+FOXP3+ regulatory T (Treg cells in an IL-10-dependent fashion. These tolerogenic effects of ABCG2 inhibition could be abolished by ERK inhibition. Thus, we demonstrated that inhibition of ABCG2 in LPS-stimulated mDCs can potently induce tolerogenic potentials in these cells, providing crucial new information that could lead to development of better strategies to combat MDR cancer.

Normal endometrial stromal cells regulate 17β-estradiol-induced epithelial-mesenchymal transition via slug and E-cadherin in endometrial adenocarcinoma cells in vitro.

Science.gov (United States)

Zhang, Hui; Li, Hongyan; Qi, Shasha; Liu, Zhao; Fu, Yibing; Li, Mingjiang; Zhao, Xingbo

2017-01-01

Stroma-tumor communication participates in the pathogenesis of endometrial carcinomas. In previous studies, we found that normal stromal cells inhibited the growth of endometrial carcinoma cells. Here, we investigated the role of normal stromal cells in the epithelial-mesenchymal transition (EMT) of endometrial carcinoma cells and explored the possible mechanism implied. We found that conditioned medium (CM) by normal endometrial stromal cells (NSC) reduced cell growth and induced cell apoptosis in Ishikawa cells. CM by NSC inhibited 17β-estradiol-induced cell growth and apoptosis decrease in Ishikawa cells. Moreover, CM by NSC inhibited the migration and invasion, and 17β-estradiol-induced migration and invasion in Ishikawa cells. Meanwhile, CM by NSC decreased Slug expression and 17β-estradiol-induced Slug expression, increased E-cadherin expression and abolished 17β-estradiol-induced E-cadherin reduction in Ishikawa cells. In conclusion, normal stromal factors can inhibit 17β-estradiol-induced cell proliferation and apoptosis inhibition, and abolished 17β-estradiol-induced EMT in endometrial cancer cell via regulating E-cadherin and Slug expression.

Stop Saying That It Is Wrong! Psychophysiological, Cognitive, and Metacognitive Markers of Children's Sensitivity to Punishment.

Science.gov (United States)

Gonzalez-Gadea, Maria Luz; Scheres, Anouk; Tobon, Carlos Andres; Damm, Juliane; Baez, Sandra; Huepe, David; Marino, Julian; Marder, Sandra; Manes, Facundo; Abrevaya, Sofia; Ibanez, Agustin

2015-01-01

Neurodevelopmental evidence suggests that children's main decision-making strategy is to avoid options likely to induce punishment. However, the cognitive and affective factors contributing to children's avoidance to high punishment frequency remain unknown. The present study explored psychophysiological, cognitive, and metacognitive processes associated with sensitivity to punishment frequency. We evaluated 54 participants (between 8 and 15 years old) with a modified Iowa Gambling Task for children (IGT-C) which included options with varying long-term profit and punishment frequencies. Skin conductance responses (SCRs) were recorded during this task. Additionally, we assessed IGT-C metacognitive knowledge, fluid intelligence, and executive functions. Participants exhibited behavioral avoidance and high anticipatory SCRs to options with high frequency of punishment. Moreover, age, IGT-C metacognitive knowledge, and inhibitory control were associated with individual differences in sensitivity to punishment frequency. Our results suggest that children's preference for infrequently punished decisions is partially explained by psychophysiological signals as well as task complexity and development of cognitive control.

The punishment's purpose

Directory of Open Access Journals (Sweden)

Gheorghe DIACONU

2012-12-01

Full Text Available The repressive reaction involves, as any human action, a certain finality. As the punishment's essence is the suffering, then, in the course of time it has been arisen the question regarding the goal for which the society utilizes the suffering and for what the society punishes. According to the classic penal doctrine that bases on the idea of retribution, the repressive reaction was limited to a simple revenge and it didn't existed any concern in order to influence the doer's future behaviour. In the positivist conception, the punishment's purpose was to shelter the society against the offender's new attacks. Going up to an extreme point with this idea, the positivists equated the punishment with the curative treatment at which the patients in the hospitals were submitted and which it was adequate to each category of offender. For the positivists, the penal sanction, it was meant to combat the organic or the psychological anomalies or the dysfunctions of the social environment that have influenced the offender and that determined him to commit antisocial deeds. In the modern vision, the punishment cannot have a goal on its own and that is to answer to bad with bad because it doesn't come from an abstract desire for revenge, but from a concrete necessity of hindering the repetition of the antisocial deeds and of defending the fundamental social values.

Corporal Punishment and the Schools.

Science.gov (United States)

Bauer, Gordon B.; And Others

1990-01-01

In order to understand and evaluate the continued prevalence of corporal punishment in school systems, this article reviews the following topics: (1) historical issues; (2) current demographics and correlates; (3) the effectiveness of corporal punishment in school settings; (4) myths; (5) alternatives to corporal punishment; and (6) social policy.…

Strict or Graduated Punishment? Effect of Punishment Strictness on the Evolution of Cooperation in Continuous Public Goods Games

Science.gov (United States)

Shimao, Hajime; Nakamaru, Mayuko

2013-01-01

Whether costly punishment encourages cooperation is one of the principal questions in studies on the evolution of cooperation and social sciences. In society, punishment helps deter people from flouting rules in institutions. Specifically, graduated punishment is a design principle for long-enduring common-pool resource institutions. In this study, we investigate whether graduated punishment can promote a higher cooperation level when each individual plays the public goods game and has the opportunity to punish others whose cooperation levels fall below the punisher’s threshold. We then examine how spatial structure affects evolutionary dynamics when each individual dies inversely proportional to the game score resulting from the social interaction and another player is randomly chosen from the population to produce offspring to fill the empty site created after a player’s death. Our evolutionary simulation outcomes demonstrate that stricter punishment promotes increased cooperation more than graduated punishment in a spatially structured population, whereas graduated punishment increases cooperation more than strict punishment when players interact with randomly chosen opponents from the population. The mathematical analysis also supports the results. PMID:23555826

Synapsin determines memory strength after punishment- and relief-learning.

Science.gov (United States)

Niewalda, Thomas; Michels, Birgit; Jungnickel, Roswitha; Diegelmann, Sören; Kleber, Jörg; Kähne, Thilo; Gerber, Bertram

2015-05-13

Adverse life events can induce two kinds of memory with opposite valence, dependent on timing: "negative" memories for stimuli preceding them and "positive" memories for stimuli experienced at the moment of "relief." Such punishment memory and relief memory are found in insects, rats, and man. For example, fruit flies (Drosophila melanogaster) avoid an odor after odor-shock training ("forward conditioning" of the odor), whereas after shock-odor training ("backward conditioning" of the odor) they approach it. Do these timing-dependent associative processes share molecular determinants? We focus on the role of Synapsin, a conserved presynaptic phosphoprotein regulating the balance between the reserve pool and the readily releasable pool of synaptic vesicles. We find that a lack of Synapsin leaves task-relevant sensory and motor faculties unaffected. In contrast, both punishment memory and relief memory scores are reduced. These defects reflect a true lessening of associative memory strength, as distortions in nonassociative processing (e.g., susceptibility to handling, adaptation, habituation, sensitization), discrimination ability, and changes in the time course of coincidence detection can be ruled out as alternative explanations. Reductions in punishment- and relief-memory strength are also observed upon an RNAi-mediated knock-down of Synapsin, and are rescued both by acutely restoring Synapsin and by locally restoring it in the mushroom bodies of mutant flies. Thus, both punishment memory and relief memory require the Synapsin protein and in this sense share genetic and molecular determinants. We note that corresponding molecular commonalities between punishment memory and relief memory in humans would constrain pharmacological attempts to selectively interfere with excessive associative punishment memories, e.g., after traumatic experiences. Copyright © 2015 Niewalda et al.

Synapsin Determines Memory Strength after Punishment- and Relief-Learning

Science.gov (United States)

Niewalda, Thomas; Michels, Birgit; Jungnickel, Roswitha; Diegelmann, Sören; Kleber, Jörg; Kähne, Thilo

2015-01-01

Adverse life events can induce two kinds of memory with opposite valence, dependent on timing: “negative” memories for stimuli preceding them and “positive” memories for stimuli experienced at the moment of “relief.” Such punishment memory and relief memory are found in insects, rats, and man. For example, fruit flies (Drosophila melanogaster) avoid an odor after odor-shock training (“forward conditioning” of the odor), whereas after shock-odor training (“backward conditioning” of the odor) they approach it. Do these timing-dependent associative processes share molecular determinants? We focus on the role of Synapsin, a conserved presynaptic phosphoprotein regulating the balance between the reserve pool and the readily releasable pool of synaptic vesicles. We find that a lack of Synapsin leaves task-relevant sensory and motor faculties unaffected. In contrast, both punishment memory and relief memory scores are reduced. These defects reflect a true lessening of associative memory strength, as distortions in nonassociative processing (e.g., susceptibility to handling, adaptation, habituation, sensitization), discrimination ability, and changes in the time course of coincidence detection can be ruled out as alternative explanations. Reductions in punishment- and relief-memory strength are also observed upon an RNAi-mediated knock-down of Synapsin, and are rescued both by acutely restoring Synapsin and by locally restoring it in the mushroom bodies of mutant flies. Thus, both punishment memory and relief memory require the Synapsin protein and in this sense share genetic and molecular determinants. We note that corresponding molecular commonalities between punishment memory and relief memory in humans would constrain pharmacological attempts to selectively interfere with excessive associative punishment memories, e.g., after traumatic experiences. PMID:25972175

More ‘altruistic’ punishment in larger societies

Science.gov (United States)

Marlowe, Frank W; Berbesque, J. Colette; Barr, Abigail; Barrett, Clark; Bolyanatz, Alexander; Cardenas, Juan Camilo; Ensminger, Jean; Gurven, Michael; Gwako, Edwins; Henrich, Joseph; Henrich, Natalie; Lesorogol, Carolyn; McElreath, Richard; Tracer, David

2007-01-01

If individuals will cooperate with cooperators, and punish non-cooperators even at a cost to themselves, then this strong reciprocity could minimize the cheating that undermines cooperation. Based upon numerous economic experiments, some have proposed that human cooperation is explained by strong reciprocity and norm enforcement. Second-party punishment is when you punish someone who defected on you; third-party punishment is when you punish someone who defected on someone else. Third-party punishment is an effective way to enforce the norms of strong reciprocity and promote cooperation. Here we present new results that expand on a previous report from a large cross-cultural project. This project has already shown that there is considerable cross-cultural variation in punishment and cooperation. Here we test the hypothesis that population size (and complexity) predicts the level of third-party punishment. Our results show that people in larger, more complex societies engage in significantly more third-party punishment than people in small-scale societies. PMID:18089534

Hate and punishment.

Science.gov (United States)

Kauppinen, Antti

2015-06-01

According to legal expressivism, neither crime nor punishment consists merely in intentionally imposing some kind of harm on another. Crime and punishment also have an expressive aspect. They are what they are in part because they enact attitudes toward others--in the case of crime, some kind of disrespect, at least, and in the case of punishment, society's condemnation or reprobation. Punishment is justified, at least in part, because (and when) it uniquely expresses fitting condemnation or other retributive attitude. What makes retributive attitudes fitting is that they protect the victim's status as inviolable. Hate or bias crimes dramatize the expressive aspect of crime, as they are often designed to send a message to the victim's group and society at large. Treating the enactment of contempt and denigration toward a historically underprivileged group as an aggravating factor in sentencing may be an appropriate way to counter this message, as it reaffirms and indeed realizes the fundamental equality and inviolability of all members of a democratic community. © The Author(s) 2014.

Effects of Pharmacological Inhibition and Genetic Deficiency of Plasminogen Activator Inhibitor-1 in Radiation-Induced Intestinal Injury

International Nuclear Information System (INIS)

Abderrahmani, Rym; Francois, Agnes; Buard, Valerie; Benderitter, Marc; Sabourin, Jean-Christophe; Crandall, David L.; Milliat, Fabien

2009-01-01

Purpose: To investigate effects of plasminogen activator inhibitor 1 (PAI-1) genetic deficiency and pharmacological PAI-1 inhibition with PAI-039 in a mouse model of radiation-induced enteropathy. Methods and Materials: Wild-type (Wt) and PAI-1 -/- knockout mice received a single dose of 19 Gy to an exteriorized localized intestinal segment. Sham and irradiated Wt mice were treated orally with 1 mg/g of PAI-039. Histological modifications were quantified using a radiation injury score. Moreover, intestinal gene expression was monitored by real-time PCR. Results: At 3 days after irradiation, PAI-039 abolished the radiation-induced increase in the plasma active form of PAI-1 and limited the radiation-induced gene expression of transforming growth factor β1 (TGF-β1), CTGF, PAI-1, and COL1A2. Moreover, PAI-039 conferred temporary protection against early lethality. PAI-039 treatment limited the radiation-induced increase of CTGF and PAI-1 at 2 weeks after irradiation but had no effect at 6 weeks. Radiation injuries were less severe in PAI-1 -/- mice than in Wt mice, and despite the beneficial effect, 3 days after irradiation, PAI-039 had no effects on microscopic radiation injuries compared to untreated Wt mice. Conclusions: A genetic deficiency of PAI-1 is associated with amelioration of late radiation enteropathy. Pharmacological inhibition of PAI-1 by PAI-039 positively impacts the early, acute phase increase in plasma PAI-1 and the associated radiation-induced gene expression of inflammatory/extracellular matrix proteins. Since PAI-039 has been shown to inhibit the active form of PAI-1, as opposed to the complete loss of PAI-1 in the knockout animals, these data suggest that a PAI-1 inhibitor could be beneficial in treating radiation-induced tissue injury in acute settings where PAI-1 is elevated.

Fenoterol inhibits LPS-induced AMPK activation and inflammatory cytokine production through β-arrestin-2 in THP-1 cell line

International Nuclear Information System (INIS)

Wang, Wei; Zhang, Yuan; Xu, Ming; Zhang, You-Yi; He, Bei

2015-01-01

The AMP-activated protein kinase (AMPK) pathway is involved in regulating inflammation in several cell lines. We reported that fenoterol, a β 2 -adrenergic receptor (β 2 -AR) agonist, had anti-inflammatory effects in THP-1 cells, a monocytic cell line. Whether the fenoterol anti-inflammatory effect involves the AMPK pathway is unknown. In this study, we explored the mechanism of β 2 -AR stimulation with fenoterol in a lipopolysaccharide (LPS)-induced inflammatory cytokine secretion in THP-1 cells. We studied whether fenoterol and β-arrestin-2 or AMPKα1 subunit knockdown could affect LPS-induced AMPK activation, nuclear factor-kappa B (NF-κB) activation and inflammatory cytokine secretion. LPS-induced AMPK activation and interleukin 1β (IL-1β) release were reduced with fenoterol pretreatment of THP-1 cells. SiRNA knockdown of β-arrestin-2 abolished the fenoterol inhibition of LPS-induced AMPK activation and interleukin 1β (IL-1β) release, thus β-arrestin-2 mediated the anti-inflammatory effects of fenoterol on LPS-treated THP-1 cells. In addition, siRNA knockdown of AMPKα1 significantly attenuated the LPS-induced NF-κB activation and IL-1β release, so AMPKα1 was a key signaling molecule involved in LPS-induced inflammatory cytokine production. These results suggested the β 2 -AR agonist fenoterol inhibited LPS-induced AMPK activation and IL-1β release via β-arrestin-2 in THP-1 cells. The exploration of these mechanisms may help optimize therapeutic agents targeting these pathways in inflammatory diseases. - Highlights: • β 2 -AR agonist fenoterol exerts its protective effect on LPS-treated THP-1 cells. • Fenoterol inhibits LPS-induced AMPK activation and IL-1β production. • β-arrestin2 mediates fenoterol-inhibited AMPK activation and IL-1β release. • AMPKα1 is involved in LPS-induced NF-κB activation and IL-1β production

Fenoterol inhibits LPS-induced AMPK activation and inflammatory cytokine production through β-arrestin-2 in THP-1 cell line

Energy Technology Data Exchange (ETDEWEB)

Wang, Wei [Department of Respiratory Medicine, Peking University Third Hospital, Beijing (China); Department of Infectious Diseases, Peking University Third Hospital, Beijing (China); Zhang, Yuan [Department of Respiratory Medicine, Peking University Third Hospital, Beijing (China); Xu, Ming; Zhang, You-Yi [Department of Institute of Vascular Medicine and Beijing Key Laboratory of Cardiovascular Receptors Research, Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Peking University Third Hospital, Beijing (China); He, Bei, E-mail: puh3_hb@bjmu.edu.cn [Department of Respiratory Medicine, Peking University Third Hospital, Beijing (China)

2015-06-26

The AMP-activated protein kinase (AMPK) pathway is involved in regulating inflammation in several cell lines. We reported that fenoterol, a β{sub 2}-adrenergic receptor (β{sub 2}-AR) agonist, had anti-inflammatory effects in THP-1 cells, a monocytic cell line. Whether the fenoterol anti-inflammatory effect involves the AMPK pathway is unknown. In this study, we explored the mechanism of β{sub 2}-AR stimulation with fenoterol in a lipopolysaccharide (LPS)-induced inflammatory cytokine secretion in THP-1 cells. We studied whether fenoterol and β-arrestin-2 or AMPKα1 subunit knockdown could affect LPS-induced AMPK activation, nuclear factor-kappa B (NF-κB) activation and inflammatory cytokine secretion. LPS-induced AMPK activation and interleukin 1β (IL-1β) release were reduced with fenoterol pretreatment of THP-1 cells. SiRNA knockdown of β-arrestin-2 abolished the fenoterol inhibition of LPS-induced AMPK activation and interleukin 1β (IL-1β) release, thus β-arrestin-2 mediated the anti-inflammatory effects of fenoterol on LPS-treated THP-1 cells. In addition, siRNA knockdown of AMPKα1 significantly attenuated the LPS-induced NF-κB activation and IL-1β release, so AMPKα1 was a key signaling molecule involved in LPS-induced inflammatory cytokine production. These results suggested the β{sub 2}-AR agonist fenoterol inhibited LPS-induced AMPK activation and IL-1β release via β-arrestin-2 in THP-1 cells. The exploration of these mechanisms may help optimize therapeutic agents targeting these pathways in inflammatory diseases. - Highlights: • β{sub 2}-AR agonist fenoterol exerts its protective effect on LPS-treated THP-1 cells. • Fenoterol inhibits LPS-induced AMPK activation and IL-1β production. • β-arrestin2 mediates fenoterol-inhibited AMPK activation and IL-1β release. • AMPKα1 is involved in LPS-induced NF-κB activation and IL-1β production.

Paddling, Punishing and Force

Science.gov (United States)

Hyman, Irwin A.; And Others

1977-01-01

Discusses the extent and use of corporal punishment in public schools, the results of research on the effectiveness of corporal punishment as a deterrent to misbehavior, and the use and effect of alternative measures of classroom management. (BF)

Patient and impatient punishers of free-riders.

Science.gov (United States)

Espín, Antonio M; Brañas-Garza, Pablo; Herrmann, Benedikt; Gamella, Juan F

2012-12-22

Costly punishment of cheaters who contribute little or nothing to a cooperating group has been extensively studied, as an effective means to enforce cooperation. The prevailing view is that individuals use punishment to retaliate against transgressions of moral standards such as fairness or equity. However, there is much debate regarding the psychological underpinnings of costly punishment. Some authors suggest that costly punishment must be a product of humans' capacity for reasoning, self-control and long-term planning, whereas others argue that it is the result of an impulsive, present-oriented emotional drive. Here, we explore the inter-temporal preferences of punishers in a multilateral cooperation game and show that both interpretations might be right, as we can identify two different types of punishment: punishment of free-riders by cooperators, which is predicted by patience (future orientation); and free-riders' punishment of other free-riders, which is predicted by impatience (present orientation). Therefore, the picture is more complex as punishment by free-riders probably comes not from a reaction against a moral transgression, but instead from a competitive, spiteful drive. Thus, punishment grounded on morals may be related to lasting or delayed psychological incentives, whereas punishment triggered by competitive desires may be linked to short-run aspirations. These results indicate that the individual's time horizon is relevant for the type of social behaviour she opts for. Integrating such differences in inter-temporal preferences and the social behaviour of agents might help to achieve a better understanding of how human cooperation and punishment behaviour has evolved.

Stop Saying That It Is Wrong! Psychophysiological, Cognitive, and Metacognitive Markers of Children’s Sensitivity to Punishment

Science.gov (United States)

Gonzalez-Gadea, Maria Luz; Scheres, Anouk; Tobon, Carlos Andres; Damm, Juliane; Baez, Sandra; Huepe, David; Marino, Julian; Marder, Sandra; Manes, Facundo; Abrevaya, Sofia; Ibanez, Agustin

2015-01-01

Neurodevelopmental evidence suggests that children’s main decision-making strategy is to avoid options likely to induce punishment. However, the cognitive and affective factors contributing to children’s avoidance to high punishment frequency remain unknown. The present study explored psychophysiological, cognitive, and metacognitive processes associated with sensitivity to punishment frequency. We evaluated 54 participants (between 8 and 15 years old) with a modified Iowa Gambling Task for children (IGT-C) which included options with varying long-term profit and punishment frequencies. Skin conductance responses (SCRs) were recorded during this task. Additionally, we assessed IGT-C metacognitive knowledge, fluid intelligence, and executive functions. Participants exhibited behavioral avoidance and high anticipatory SCRs to options with high frequency of punishment. Moreover, age, IGT-C metacognitive knowledge, and inhibitory control were associated with individual differences in sensitivity to punishment frequency. Our results suggest that children’s preference for infrequently punished decisions is partially explained by psychophysiological signals as well as task complexity and development of cognitive control. PMID:26218584

Punishment – and Beyond

Directory of Open Access Journals (Sweden)

Bruno S. Frey

2011-06-01

Full Text Available This paper argues that the “Economics of Crime” concentrates too much on punishment as a means of preventing crime, which is unwise for several reasons. There are important instances in which punishment simply cannot reduce crime. Several feasible alternatives to punishment exist, such as offering positive incentives or handing out awards for law abiding behavior. These alternative approaches tend to create a positive sum environment. When people appreciate living in a society that is to a large extent law abiding, they are more motivated to observe the law.

[Violence in families and its prevention. Also a plea for abolishing the parental right to inflict physical punishment. A report of the "Violence Commission" of the federal government].

Science.gov (United States)

Remschmidt, H; Schmidt, M H; Strunk, P

1990-01-01

Violence in families is rather frequent. Different forms of violent acts can be distinguished: violence between partners, violence between parents and children, violence among siblings, and violence against elder family members. This report gives an overview--with the emphasis on violence in families--of the work of the "Violence Commission" of the Federal Government. This commission worked out proposals for intervention in the case of intrafamiliar violence as well as for prevention. Two proposals of the commission are explained in detail: (1) Rejection of violence and prohibition of corporal punishment in education and (2) punishability of conjugal violation.

TGF-β prevents phosphate-induced osteogenesis through inhibition of BMP and Wnt/β-catenin pathways.

Directory of Open Access Journals (Sweden)

Fátima Guerrero

Full Text Available BACKGROUND: Transforming growth factor-β (TGF-β is a key cytokine during differentiation of mesenchymal stem cells (MSC into vascular smooth muscle cells (VSMC. High phosphate induces a phenotypic transformation of vascular smooth muscle cells (VSMC into osteogenic-like cells. This study was aimed to evaluate signaling pathways involved during VSMC differentiation of MSC in presence or not of high phosphate. RESULTS: Our results showed that TGF-β induced nuclear translocation of Smad3 as well as the expression of vascular smooth muscle markers, such as smooth muscle alpha actin, SM22α, myocardin, and smooth muscle-myosin heavy chain. The addition of high phosphate to MSC promoted nuclear translocation of Smad1/5/8 and the activation of canonical Wnt/β-catenin in addition to an increase in BMP-2 expression, calcium deposition and alkaline phosphatase activity. The administration of TGF-β to MSC treated with high phosphate abolished all these effects by inhibiting canonical Wnt, BMP and TGF-β pathways. A similar outcome was observed in high phosphate-treated cells after the inhibition of canonical Wnt signaling with Dkk-1. Conversely, addition of both Wnt/β-catenin activators CHIR98014 and lithium chloride enhanced the effect of high phosphate on BMP-2, calcium deposition and alkaline phosphatase activity. CONCLUSIONS: Full VSMC differentiation induced by TGF-β may not be achieved when extracellular phosphate levels are high. Moreover, TGF-β prevents high phosphate-induced osteogenesis by decreasing the nuclear translocation of Smad 1/5/8 and avoiding the activation of Wnt/β-catenin pathway.

Punishing adolescents

DEFF Research Database (Denmark)

Ryberg, Jesper

2014-01-01

Should an adolescent offender be punished more leniently than an adult offender? Many theorists believe the answer to be in the affirmative. According to the diminished culpability model, adolescents are less mature than adults and, therefore, less responsible for their wrongdoings and should...... consequently be punished less harshly. This article concerns the first part of the model: the relation between immaturity and diminished responsibility. It is argued that this relation faces three normative challenges which do not allow for easy answers and which are still widely ignored in the comprehensive...

Corporal punishment.

Science.gov (United States)

Zolotor, Adam J

2014-10-01

Corporal punishment is used for discipline in most homes in the United States. It is also associated with a long list of adverse developmental, behavioral, and health-related consequences. Primary care providers, as trusted sources for parenting information, have an opportunity to engage parents in discussions about discipline as early as infancy. These discussions should focus on building parents' skills in the use of other behavioral techniques, limiting (or eliminating) the use of corporal punishment and identifying additional resources as needed. Copyright © 2014 Elsevier Inc. All rights reserved.

Defectors, not norm violators, are punished by third-parties.

Science.gov (United States)

Bone, Jonathan; Silva, Antonio S; Raihani, Nichola J

2014-07-01

Punishment of defectors and cooperators is prevalent when their behaviour deviates from the social norm. Why atypical behaviour is more likely to be punished than typical behaviour remains unclear. One possible proximate explanation is that individuals simply dislike norm violators. However, an alternative possibility exists: individuals may be more likely to punish atypical behaviour, because the cost of punishment generally increases with the number of individuals that are punished. We used a public goods game with third-party punishment to test whether punishment of defectors was reduced when defecting was typical, as predicted if punishment is responsive to norm violation. The cost of punishment was fixed, regardless of the number of players punished, meaning that it was not more costly to punish typical, relative to atypical, behaviour. Under these conditions, atypical behaviour was not punished more often than typical behaviour. In fact, most punishment was targeted at defectors, irrespective of whether defecting was typical or atypical. We suggest that the reduced punishment of defectors when they are common might often be explained in terms of the costs to the punisher, rather than responses to norm violators.

Importance of punishment frequency in the Iowa gambling task: an fMRI study.

Science.gov (United States)

Ma, Shuangye; Zang, Yufeng; Cheung, Vinci; Chan, Chetwyn C H

2015-12-01

It has been widely found that in the Iowa Gambling Task (IGT; Bechara et al. Cognition, 50(1), 7-15 1994) normal subjects would gradually learn to prefer obtaining rewards for long-term benefits than seeking immediate rewards to maximize the overall profit. The current study aimed to gain an understanding of how punishment frequency in the IGT would be processed and its association with subjects' reward preferences. In this study, we employed the clinical version of the IGT, in which response options are not only different in the long-term outcome, but also associated with different punishment frequencies. Event-related functional Magnetic Resonance Imaging (fMRI) was used to capture the subjects' brain activity when performing the IGT. A total of 24 male subjects (mean age = 21.7 years, SD = 1.8 years), who were university students, participated in the experiment. It is found that subjects learned to select more from the decks that were advantageous in the long-term, but they were more sensitive to the effect of long-term outcome under the condition of high punishment frequency. The corresponding brain activation showed that the Anterior Cingulate Cortex (ACC) had significantly higher activation during the disadvantageous choices than the advantageous choices. Such activity difference between the two conditions of long-term outcome was more prominent with high punishment frequency than low punishment frequency; and this brain activity difference was significantly correlated with the behavioral performance under the condition of high punishment frequency. The results suggested that only in the context with high punishment frequency, there would be increased neural activity in ACC when subjects intended to select from the disadvantageous choices so that these choices would be inhibited and advantageous choices would be selected.

Physical Punishment, Childhood Abuse and Psychiatric Disorders

Science.gov (United States)

Afifi, Tracie O.; Brownridge, Douglas A.; Cox, Brian J.; Sareen, Jitender

2006-01-01

Objectives: Physical punishment, as a means of disciplining children, may be considered a mild form of childhood adversity. Although many outcomes of physical punishment have been investigated, little attention has been given to the impact of physical punishment on later adult psychopathology. Also, it has been stated that physical punishment by a…

Less crime, more punishment.

Science.gov (United States)

Cooney, Mark; Burt, Callie Harbin

2008-09-01

Recasting Durkheim's "community of saints" thesis, the authors argue that the severity of punishment is predicted in part by the prevalence of the deviant behavior of which the deviant stands accused. Although there is some curvilinearity at low levels of prevalence, the relationship is generally negative. Thus, all else equal, where a particular crime is frequent, any punishment applied to it is likely to be mild; conversely, where a crime is infrequent, its punishment ought to be severe. Using hierarchical regression models, the authors support this hypothesis with 1988 homicide conviction and imprisonment decisions in 32 U.S. counties.

Shame, Guilt, and Punishment

DEFF Research Database (Denmark)

Rodogno, Raffaele

2009-01-01

The emotions of shame and guilt have recently appeared in debates concerning legal punishment, in particular in the context of so called shaming and guilting penalties. The bulk of the discussion, however, has focussed on the justification of such penalties. The focus of this article is broader...... than that. My aim is to offer an analysis of the concept of legal punishment that sheds light on the possible connections between punishing practices such as shaming and guilting penalties, on the one hand, and emotions such as guilt, shame, and perhaps humiliation, on the other. I contend...

Genistein inhibits phorbol ester-induced NF-κB transcriptional activity and COX-2 expression by blocking the phosphorylation of p65/RelA in human mammary epithelial cells

Energy Technology Data Exchange (ETDEWEB)

Chung, Myung-Hoon; Kim, Do-Hee [Research Institute for Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul (Korea, Republic of); Na, Hye-Kyung [Department of Food and Nutrition, Sungshin Women' s University, Seoul (Korea, Republic of); Kim, Jung-Hwan; Kim, Ha-Na [Research Institute for Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul (Korea, Republic of); Haegeman, Guy [LEGEST, University of Gent (Belgium); Surh, Young-Joon, E-mail: surh@snu.ac.kr [Research Institute for Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul (Korea, Republic of); Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul (Korea, Republic of); Cancer Research Institute, Seoul National University, Seoul (Korea, Republic of)

2014-10-15

Genistein, an isoflavone present in soy products, has chemopreventive effects on mammary carcinogenesis. In the present study, we have investigated the effects of genistein on phorbol ester-induced expression of cyclooxygenase-2 (COX-2) that plays an important role in the pathophysiology of inflammation-associated carcinogenesis. Pretreatment of cultured human breast epithelial (MCF10A) cells with genistein reduced COX-2 expression induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). There are multiple lines of evidence supporting that the induction of COX-2 is regulated by the eukaryotic transcription factor NF-κB. Genistein failed to inhibit TPA-induced nuclear translocation and DNA binding of NF-κB as well as degradation of IκB. However, genistein abrogated the TPA-induced transcriptional activity of NF-κB as determined by the luciferase reporter gene assay. Genistein inhibited phosphorylation of the p65 subunit of NF-κB and its interaction with cAMP regulatory element-binding protein-binding protein (CBP)/p300 and TATA-binding protein (TBP). TPA-induced NF-κB phosphorylation was abolished by pharmacological inhibition of extracellular signal-regulated kinase (ERK). Likewise, pharmacologic inhibition or dominant negative mutation of ERK suppressed phosphorylation of p65. The above findings, taken together, suggest that genistein inhibits TPA-induced COX-2 expression in MCF10A cells by blocking ERK-mediated phosphorylation of p65 and its subsequent interaction with CBP and TBP.

Domestic Non-Compliance with an EU Norm: A Case Study of the Capital Punishment System in Japan

Directory of Open Access Journals (Sweden)

Mika Obara

2013-02-01

Full Text Available There is a worldwide declining trend in the number of countries that have retained capital punishment since the end of World War II, and the international society has created a series of benchmarks for modern democracies represented by the acquis communautaire by the European Union (EU, and relevant covenants by the United Nations (UN. Despite their efforts to urge Japan to abolish capital punishment, the Japanese government does not try to match it up and is rather running backwards in the international trend retaining inhuman and degrading practices. This paper examines the Japanese institutional and cultural context, and clarifies where the governmental resistance to the anti-death penalty norm stems from. It will critically investigate which institutional frameworks have been constraining anti-death penalty activists from getting involved in Japanese policymaking; and the extent to which cultural factors have been hindering their activities from gaining roots in Japan. Critical assessment of which specific approaches can help EU institutions and other European activist groups influence Japan more effectively concludes this paper.

God's punishment and public goods : A test of the supernatural punishment hypothesis in 186 world cultures.

Science.gov (United States)

Johnson, Dominic D P

2005-12-01

Cooperation towards public goods relies on credible threats of punishment to deter cheats. However, punishing is costly, so it remains unclear who incurred the costs of enforcement in our evolutionary past. Theoretical work suggests that human cooperation may be promoted if people believe in supernatural punishment for moral transgressions. This theory is supported by new work in cognitive psychology and by anecdotal ethnographic evidence, but formal quantitative tests remain to be done. Using data from 186 societies around the globe, I test whether the likelihood of supernatural punishment-indexed by the importance of moralizing "high gods"-is associated with cooperation.

COUNTER-PUNISHMENT, COMMUNICATION AND COOPERATION AMONG PARTNERS

Directory of Open Access Journals (Sweden)

Giulia eAndrighetto

2016-04-01

Full Text Available We study how communication affects cooperation in an experimental public goods environment with punishment and counter-punishment opportunities. Participants interacted over thirty rounds in fixed groups with fixed identifiers that allowed them to trace other group members’ behavior over time. The two dimensions of communication we study are asking for a specific contribution level and having to express oneself when choosing to counter-punish. We conduct four experimental treatments, all involving a contribution stage, a punishment stage and a counter-punishment stage in each round. In the first treatment communication is not possible at any of the stages. The second treatment allows participants to ask for a contribution level at the punishment stage and in the third treatment participants are required to send a message if they decide to counter-punishment. The fourth combines the two communication channels of the second and third treatments. We find that the three treatments involving communication at any of the two relevant stages lead to significantly higher contributions than the baseline treatment. We find no difference between the three treatments with communication. We also relate our results to previous results from treatments without counter-punishment opportunities and do not find that the presence of counter-punishment leads to lower cooperation level. The overall pattern of results shows that given fixed identifiers the key factor is the presence of communication. Whenever communication is possible contributions and earnings are higher than when it is not, regardless of counter-punishment opportunities.

CRISPR Epigenome Editing of AKAP150 in DRG Neurons Abolishes Degenerative IVD-Induced Neuronal Activation.

Science.gov (United States)

Stover, Joshua D; Farhang, Niloofar; Berrett, Kristofer C; Gertz, Jason; Lawrence, Brandon; Bowles, Robby D

2017-09-06

Back pain is a major contributor to disability and has significant socioeconomic impacts worldwide. The degenerative intervertebral disc (IVD) has been hypothesized to contribute to back pain, but a better understanding of the interactions between the degenerative IVD and nociceptive neurons innervating the disc and treatment strategies that directly target these interactions is needed to improve our understanding and treatment of back pain. We investigated degenerative IVD-induced changes to dorsal root ganglion (DRG) neuron activity and utilized CRISPR epigenome editing as a neuromodulation strategy. By exposing DRG neurons to degenerative IVD-conditioned media under both normal and pathological IVD pH levels, we demonstrate that degenerative IVDs trigger interleukin (IL)-6-induced increases in neuron activity to thermal stimuli, which is directly mediated by AKAP and enhanced by acidic pH. Utilizing this novel information on AKAP-mediated increases in nociceptive neuron activity, we developed lentiviral CRISPR epigenome editing vectors that modulate endogenous expression of AKAP150 by targeted promoter histone methylation. When delivered to DRG neurons, these epigenome-modifying vectors abolished degenerative IVD-induced DRG-elevated neuron activity while preserving non-pathologic neuron activity. This work elucidates the potential for CRISPR epigenome editing as a targeted gene-based pain neuromodulation strategy. Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

Corporal Punishment: Legalities, Realities, and Implications.

Science.gov (United States)

Hinchey, Patricia H.

2003-01-01

Presents a quiz that will help readers determine the reliability of their own perceptions relating to corporal punishment in schools. Discusses U.S. Courts and corporal punishment, worldwide and nationwide legality, and the realities of corporal punishment in the United States. Discusses implications for what teachers can do to address corporal…

Commitment to Cooperation and Peer Punishment: Its Evolution

Directory of Open Access Journals (Sweden)

Tatsuya Sasaki

2015-11-01

Full Text Available Theoretical and empirical studies have generally weighed the effect of peer punishment and pool punishment for sanctioning free riders separately. However, these sanctioning mechanisms often pose a puzzling tradeoff between efficiency and stability in detecting and punishing free riders. Here, we combine the key aspects of these qualitatively different mechanisms in terms of evolutionary game theory. Based on the dilemmatic donation game, we introduce a strategy of commitment to both cooperation and peer punishment. To make the commitment credible, we assume that those willing to commit have to make a certain deposit. The deposit will be refunded as long as the committers faithfully cooperate in the donation game and punish free riders and non-committers. It turns out that the deposit-based commitment offers both the efficiency of peer punishment and the stability of pool punishment and that the replicator dynamics lead to transitions of different systems: pool punishment to commitment to peer punishment.

Exit, punishment and rewards in commons dilemmas: an experimental study.

Directory of Open Access Journals (Sweden)

Giangiacomo Bravo

Full Text Available Commons dilemmas are interaction situations where a common good is provided or exploited by a group of individuals so that optimal collective outcomes clash with private interests. Although in these situations, social norms and institutions exist that might help individuals to cooperate, little is known about the interaction effects between positive and negative incentives and exit options by individuals. We performed a modified public good game experiment to examine the effect of exit, rewards and punishment, as well as the interplay between exit and rewards and punishment. We found that punishment had a stronger effect than rewards on cooperation if considered by itself, whereas rewards had a stronger effect when combined with voluntary participation. This can be explained in terms of the 'framing effect', i.e., as the combination of exit and rewards might induce people to attach higher expected payoffs to cooperative strategies and expect better behaviour from others.

Criminal Law and the Internal Logic of Punishment

DEFF Research Database (Denmark)

Krause-Jensen, Katrine; Rodogno, Raffaele

2015-01-01

We argue that punishment has an essentially retributive core that carries its own retributive type of logic or reasons. In particular, we show that punishment is something that we understand as in principle always being assessable in terms of deservingness and that this is ultimately......, that is, that the latter involves punishment. For one, purely instrumentalist justificatory accounts of punishment will not work as they fail properly to consider the retributive core of punishment. Next, we consider what follows from the fact that by inflicting punishment, the state takes it upon itself...

Caring Cooperators and Powerful Punishers: Differential Effects of Induced Care and Power Motivation on Different Types of Economic Decision Making.

Science.gov (United States)

Chierchia, G; Lesemann, F H Parianen; Snower, D; Vogel, M; Singer, T

2017-09-11

Standard economic theory postulates that decisions are driven by stable context-insensitive preferences, while motivation psychology suggests they are driven by distinct context-sensitive motives with distinct evolutionary goals and characteristic psycho-physiological and behavioral patterns. To link these fields and test how distinct motives could differentially predict different types of economic decisions, we experimentally induced participants with either a Care or a Power motive, before having them take part in a suite of classic game theoretical paradigms involving monetary exchange. We show that the Care induction alone raised scores on a latent factor of cooperation-related behaviors, relative to a control condition, while, relative to Care, Power raised scores on a punishment-related factor. These findings argue against context-insensitive stable preferences and theories of strong reciprocity and in favor of a motive-based approach to economic decision making: Care and Power motivation have a dissociable fingerprint in shaping either cooperative or punishment behaviors.

Improving control over the impulse for reward: sensitivity of harmful alcohol drinkers to delayed reward but not immediate punishment.

Science.gov (United States)

Rossiter, Sarah; Thompson, Julian; Hester, Robert

2012-09-01

Cognitive control dysfunction has been identified in dependent alcohol users and implicated in the transition from abuse to dependence, although evidence of dyscontrol in chronic but non-dependent 'harmful' alcohol abusers is mixed. The current study examined harmful alcohol users response inhibition over rewarding stimuli in the presence of monetary reward and punishment, to determine whether changes in sensitivity to these factors, noted in imaging studies of dependent users, influences impulse control. Harmful (n=30) and non-hazardous (n=55) alcohol users were administered a Monetary Incentive Go/No-go task that required participants to inhibit a prepotent motor response associated with reward. Harmful alcohol users showed a significantly poorer ability to withhold their impulse for a rewarding stimulus in the presence of immediate monetary punishment for failure, while retaining equivalent response inhibition performance under neutral conditions (associated with neither monetary loss or gain), and significantly better performance under delayed reward conditions. The results of the present study suggest that non-dependent alcohol abusers have altered sensitivity to reward and punishment that influences their impulse control for reward, in the absence of gross dyscontrol that is consistent with past findings in which such performance contingencies were not used. The ability of delayed monetary reward, but not punishment, to increase sustained impulse control in this sample has implications for the mechanism that might underlie the transition from alcohol abuse to dependence, as well as intervention strategies aimed at preventing this transition. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

A TLR4/MD2 fusion protein inhibits LPS-induced pro-inflammatory signaling in hepatic stellate cells

International Nuclear Information System (INIS)

Schnabl, Bernd; Brandl, Katharina; Fink, Marina; Gross, Philipp; Taura, Kojiro; Gaebele, Erwin; Hellerbrand, Claus; Falk, Werner

2008-01-01

Activated hepatic stellate cells (HSCs) play a key role in hepatic fibrogenesis. In injured liver they are the main extracellular matrix protein producing cell type and further perpetuate hepatic injury by secretion of pro-inflammatory mediators. Since LPS-mediated signaling through toll-like receptor 4 (TLR4) has been identified as key fibrogenic signal in HSCs we aimed to test TLR4 as potential target of therapy via ligand-binding soluble receptors. Incubation of human HSCs with a fusion protein between the extracellular domain of TLR4 and MD2 which binds LPS inhibited LPS-induced NFκB and JNK activation. TLR4/MD2 abolished LPS-induced secretion of IL-6, IL-8, MCP1, and RANTES in HSCs. In addition, TLR4/MD2 fused to human IgG-Fc neutralized LPS activity. Since TLR4 mutant mice are resistant to liver fibrosis, the TLR4/MD2 soluble receptor might represent a new therapeutic molecule for liver fibrogenesis in vivo

Reflexive intergroup bias in third-party punishment.

Science.gov (United States)

Yudkin, Daniel A; Rothmund, Tobias; Twardawski, Mathias; Thalla, Natasha; Van Bavel, Jay J

2016-11-01

Humans show a rare tendency to punish norm-violators who have not harmed them directly-a behavior known as third-party punishment. Research has found that third-party punishment is subject to intergroup bias, whereby people punish members of the out-group more severely than the in-group. Although the prevalence of this behavior is well-documented, the psychological processes underlying it remain largely unexplored. Some work suggests that it stems from people's inherent predisposition to form alliances with in-group members and aggress against out-group members. This implies that people will show reflexive intergroup bias in third-party punishment, favoring in-group over out-group members especially when their capacity for deliberation is impaired. Here we test this hypothesis directly, examining whether intergroup bias in third-party punishment emerges from reflexive, as opposed to deliberative, components of moral cognition. In 3 experiments, utilizing a simulated economic game, we varied participants' group relationship to a transgressor, measured or manipulated the extent to which they relied on reflexive or deliberative judgment, and observed people's punishment decisions. Across group-membership manipulations (American football teams, nationalities, and baseball teams) and 2 assessments of reflexive judgment (response time and cognitive load), reflexive judgment heightened intergroup bias, suggesting that such bias in punishment is inherent to human moral cognition. We discuss the implications of these studies for theories of punishment, cooperation, social behavior, and legal practice. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Costly third-party punishment in young children.

Science.gov (United States)

McAuliffe, Katherine; Jordan, Jillian J; Warneken, Felix

2015-01-01

Human adults engage in costly third-party punishment of unfair behavior, but the developmental origins of this behavior are unknown. Here we investigate costly third-party punishment in 5- and 6-year-old children. Participants were asked to accept (enact) or reject (punish) proposed allocations of resources between a pair of absent, anonymous children. In addition, we manipulated whether subjects had to pay a cost to punish proposed allocations. Experiment 1 showed that 6-year-olds (but not 5-year-olds) punished unfair proposals more than fair proposals. However, children punished less when doing so was personally costly. Thus, while sensitive to cost, they were willing to sacrifice resources to intervene against unfairness. Experiment 2 showed that 6-year-olds were less sensitive to unequal allocations when they resulted from selfishness than generosity. These findings show that costly third-party punishment of unfair behavior is present in young children, suggesting that from early in development children show a sophisticated capacity to promote fair behavior. Copyright © 2014 Elsevier B.V. All rights reserved.

Human punishment is not primarily motivated by inequality.

Science.gov (United States)

Marczyk, Jesse

2017-01-01

Previous theorizing about punishment has suggested that humans desire to punish inequality per se. However, the research supporting such an interpretation contains important methodological confounds. The main objective of the current experiment was to remove those confounds in order to test whether generating inequality per se is punished. Participants were recruited from an online market to take part in a wealth-alteration game with an ostensible second player. The participants were given an option to deduct from the other player's payment as punishment for their behavior during the game. The results suggest that human punishment does not appear to be motivated by inequality per se, as inequality that was generated without inflicting costs on others was not reliably punished. Instead, punishment seems to respond primarily to the infliction of costs, with inequality only becoming relevant as a secondary input for punishment decisions. The theoretical significance of this finding is discussed in the context of its possible adaptive value.

Human punishment is not primarily motivated by inequality

Science.gov (United States)

Marczyk, Jesse

2017-01-01

Previous theorizing about punishment has suggested that humans desire to punish inequality per se. However, the research supporting such an interpretation contains important methodological confounds. The main objective of the current experiment was to remove those confounds in order to test whether generating inequality per se is punished. Participants were recruited from an online market to take part in a wealth-alteration game with an ostensible second player. The participants were given an option to deduct from the other player’s payment as punishment for their behavior during the game. The results suggest that human punishment does not appear to be motivated by inequality per se, as inequality that was generated without inflicting costs on others was not reliably punished. Instead, punishment seems to respond primarily to the infliction of costs, with inequality only becoming relevant as a secondary input for punishment decisions. The theoretical significance of this finding is discussed in the context of its possible adaptive value. PMID:28187166

Human punishment is not primarily motivated by inequality.

Directory of Open Access Journals (Sweden)

Jesse Marczyk

Full Text Available Previous theorizing about punishment has suggested that humans desire to punish inequality per se. However, the research supporting such an interpretation contains important methodological confounds. The main objective of the current experiment was to remove those confounds in order to test whether generating inequality per se is punished. Participants were recruited from an online market to take part in a wealth-alteration game with an ostensible second player. The participants were given an option to deduct from the other player's payment as punishment for their behavior during the game. The results suggest that human punishment does not appear to be motivated by inequality per se, as inequality that was generated without inflicting costs on others was not reliably punished. Instead, punishment seems to respond primarily to the infliction of costs, with inequality only becoming relevant as a secondary input for punishment decisions. The theoretical significance of this finding is discussed in the context of its possible adaptive value.

Patient and impatient punishers of free-riders

OpenAIRE

ESPIN Antonio; BRAÑAS-GARZA Pablo; HERRMANN BENEDIKT; GAMELLA Juan

2012-01-01

Costly punishment of cheaters who contribute little or nothing to a cooperating group has been extensively studied, as an effective means to enforce cooperation. The prevailing view is that individuals use punishment to retaliate against transgressions of moral standards such as fairness or equity. However, there is much debate regarding the psychological underpinnings of costly punishment. Some authors suggest that costly punishment must be a product of humans' capacity for reasoning, self-c...

Individual mobility promotes punishment in evolutionary public goods games.

Science.gov (United States)

Cong, Rui; Zhao, Qianchuan; Li, Kun; Wang, Long

2017-10-25

In explaining the pressing issue in biology and social sciences how cooperation emerges in a population of self-interested individuals, researchers recently pay intensive attentions to the role altruistic punishment plays. However, as higher-order cooperators, survival of punishers is puzzling due to their extra cost in regulating norm violators. Previous works have highlighted the importance of individual mobility in promoting cooperation. Yet its effect on punishers remains to be explored. In this work we incorporate this feature into modeling the behavior of punishers, who are endowed with a choice between leaving current place or staying and punishing defectors. Results indicate that optimal mobility level of punishers is closely related to the cost of punishing. For considerably large cost, there exists medium tendency of migration which favors the survival of punishers. This holds for both the direct competition between punishers and defectors and the case where cooperators are involved, and can also be observed when various types of punishers with different mobility tendencies fight against defectors simultaneously. For cheap punishment, mobility does not provide with punishers more advantage even when they are initially rare. We hope our work provide more insight into understanding the role individual mobility plays in promoting public cooperation.

Direct and indirect punishment among strangers in the field.

Science.gov (United States)

Balafoutas, Loukas; Nikiforakis, Nikos; Rockenbach, Bettina

2014-11-11

Many interactions in modern human societies are among strangers. Explaining cooperation in such interactions is challenging. The two most prominent explanations critically depend on individuals' willingness to punish defectors: In models of direct punishment, individuals punish antisocial behavior at a personal cost, whereas in models of indirect reciprocity, they punish indirectly by withholding rewards. We investigate these competing explanations in a field experiment with real-life interactions among strangers. We find clear evidence of both direct and indirect punishment. Direct punishment is not rewarded by strangers and, in line with models of indirect reciprocity, is crowded out by indirect punishment opportunities. The existence of direct and indirect punishment in daily life indicates the importance of both means for understanding the evolution of cooperation.

Emotion expression in human punishment behavior.

Science.gov (United States)

Xiao, Erte; Houser, Daniel

2005-05-17

Evolutionary theory reveals that punishment is effective in promoting cooperation and maintaining social norms. Although it is accepted that emotions are connected to punishment decisions, there remains substantial debate over why humans use costly punishment. Here we show experimentally that constraints on emotion expression can increase the use of costly punishment. We report data from ultimatum games, where a proposer offers a division of a sum of money and a responder decides whether to accept the split, or reject and leave both players with nothing. Compared with the treatment in which expressing emotions directly to proposers is prohibited, rejection of unfair offers is significantly less frequent when responders can convey their feelings to the proposer concurrently with their decisions. These data support the view that costly punishment might itself be used to express negative emotions and suggest that future studies will benefit by recognizing that human demand for emotion expression can have significant behavioral consequences in social environments, including families, courts, companies, and markets.

Inhibition of ethylene production by putrescine alleviates aluminium-induced root inhibition in wheat plants.

Science.gov (United States)

Yu, Yan; Jin, Chongwei; Sun, Chengliang; Wang, Jinghong; Ye, Yiquan; Zhou, Weiwei; Lu, Lingli; Lin, Xianyong

2016-01-08

Inhibition of root elongation is one of the most distinct symptoms of aluminium (Al) toxicity. Although putrescine (Put) has been identified as an important signaling molecule involved in Al tolerance, it is yet unknown how Put mitigates Al-induced root inhibition. Here, the possible mechanism was investigated by using two wheat genotypes differing in Al resistance: Al-tolerant Xi Aimai-1 and Al-sensitive Yangmai-5. Aluminium caused more root inhibition in Yangmai-5 and increased ethylene production at the root apices compared to Xi Aimai-1, whereas the effects were significantly reversed by ethylene biosynthesis inhibitors. The simultaneous exposure of wheat seedlings to Al and ethylene donor, ethephon, or ethylene biosynthesis precursor, 1-aminocyclopropane-1-carboxylic acid (ACC), increased ethylene production and aggravated root inhibition, which was more pronounced in Xi Aimai-1. In contrast, Put treatment decreased ethylene production and alleviated Al-induced root inhibition in both genotypes, and the effects were more conspicuous in Yangmai-5. Furthermore, our results indicated that Al-induced ethylene production was mediated by ACC synthase (ACS) and ACC oxidase, and that Put decreased ethylene production by inhibiting ACS. Altogether, these findings indicate that ethylene is involved in Al-induced root inhibition and this process could be alleviated by Put through inhibiting ACS activity.

Attitudes towards corporal punishment and reporting of abuse.

Science.gov (United States)

Tirosh, Emanuel; Offer Shechter, Shlomit; Cohen, Ayala; Jaffe, Michael

2003-08-01

To assess physicians' attitudes towards corporal punishment in childhood and their subsequent actions regarding the reporting of child abuse. 107 physicians (95 pediatricians and 12 family practitioners) who work in hospitals and community clinics in northern Israel were interviewed. Of the participants, 16% were new immigrants. A structured interview was conducted by one of two pediatric residents. Attitudes towards corporal punishment were not influenced by the physicians' sex or specialty. Corporal punishment was approved by 58% of the physicians. A significant difference in attitudes towards corporal punishment between immigrants and Israeli born physicians was found (p=.004). Family practitioners and especially senior ones were found significantly less tolerant towards corporal punishment than pediatricians (p=.04). While reporting behavior was not found to be associated with parental status and the past experience of the physicians with child abuse, a significant effect of attitudes towards corporal punishment on reporting behavior was found (p=.01). (1) Corporal punishment is still perceived as an acceptable disciplinary act by a significant proportion of physicians responsible for the health care of children in our area. (2) Attitudes towards corporal punishment are different between immigrants and native born Israeli trained doctors and, unexpectedly, pediatricians were more tolerant of corporal punishment than family practitioners.

Licoricidin inhibits the growth of SW480 human colorectal adenocarcinoma cells in vitro and in vivo by inducing cycle arrest, apoptosis and autophagy

Energy Technology Data Exchange (ETDEWEB)

Ji, Shuai [State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Beijing 100191 (China); Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, School of Pharmacy, Xuzhou Medical University, 209 Tongshan Road, Xuzhou 221004 (China); Tang, Shunan; Li, Kai; Li, Ziwei; Liang, Wenfei; Qiao, Xue; Wang, Qi [State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Beijing 100191 (China); Yu, Siwang, E-mail: swang_yu@bjmu.edu.cn [State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Beijing 100191 (China); Ye, Min, E-mail: yemin@bjmu.edu.cn [State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Beijing 100191 (China)

2017-07-01

Licorice (Glycyrrhiza uralensis Fisch.) possesses significant anti-cancer activities, but the active ingredients and underlying mechanisms have not been revealed. By screening the cytotoxic activities of 122 licorice compounds against SW480 human colorectal adenocarcinoma cells, we found that licoricidin (LCD) inhibited SW480 cell viability with an IC{sub 50} value of 7.2 μM. Further studies indicated that LCD significantly induced G1/S cell cycle arrest and apoptosis in SW480 cells, accompanied by inhibition of cyclins/CDK1 expression and activation of caspase-dependent pro-apoptotic signaling. Meanwhile, LCD promoted autophagy in SW480 cells, and activated AMPK signaling and inhibited Akt/mTOR pathway. Overexpression of a dominant-negative AMPKα2 abolished LCD-induced inhibition of Akt/mTOR, autophagic and pro-apoptotic signaling pathways, and significantly reversed loss of cell viability, suggesting activation of AMPK is essential for the anti-cancer activity of LCD. In vivo anti-tumor experiments indicated that LCD (20 mg/kg, i.p.) significantly inhibited the growth of SW480 xenografts in nude mice with an inhibitory rate of 43.5%. In addition, we obtained the glycosylated product LCDG by microbial transformation, and found that glycosylation slightly enhanced the in vivo anti-cancer activities of LCD. This study indicates that LCD could inhibit SW480 cells by inducing cycle arrest, apoptosis and autophagy, and is a potential chemopreventive or chemotherapeutic agent against colorectal cancer. - Highlights: • Molecular mechanisms for cytotoxic activity of licoricidin (LCD) were investigated. • LCD promoted autophagy of SW480 cells through AMPK and Akt/mTOR signaling pathways. • Both LCD and its glucoside showed in vivo anti-colorectal cancer activities.

The opposing effects of calmodulin, adenosine 5 prime -triphosphate, and pertussis toxin on phorbol ester induced inhibition of atrial natriuretic factor stimulated guanylate cyclase in SK-NEP-1 cells

Energy Technology Data Exchange (ETDEWEB)

Sekiya, M.; Frohlich, E.D.; Cole, F.E. (Alton Ochsner Medical Foundation, New Orleans, LA (USA))

1991-01-01

In the present study, we investigated the effects of calmodulin, adenosine 5{prime}-triphosphate (ATP) and pertussis toxin (PT) on phorbol ester (PMA) induced inhibition of ANF-stimulated cyclic GMP formation in cells from the human renal cell line, SK-NEP-1. PMA inhibited ANF-stimulated guanylate cyclase activity in particulate membranes by about 65%. Calmodulin reversed this inhibition in a dose dependent manner. ATP potentiated Mg++ but not Mn++ supported guanylate cyclase activity. In PMA treated membranes, ATP potentiating effects were abolished. PMA also inhibited ANF-stimulated cGMP accumulation, but pretreatment with PT prevented this PMA inhibition. PT did not affect basal or ANF-stimulated cGMP accumulation. In conclusion, these results demonstrated that PMA inhibited ANF stimulation of particulate guanylate cyclase in opposition to the activating effects of calmodulin or ATP in SK-NEP-1 cells. The protein kinase C inhibitory effects appeared to be mediated via a PT-sensitive G protein.

Glutamine deficiency induces DNA alkylation damage and sensitizes cancer cells to alkylating agents through inhibition of ALKBH enzymes.

Directory of Open Access Journals (Sweden)

Thai Q Tran

2017-11-01

Full Text Available Driven by oncogenic signaling, glutamine addiction exhibited by cancer cells often leads to severe glutamine depletion in solid tumors. Despite this nutritional environment that tumor cells often experience, the effect of glutamine deficiency on cellular responses to DNA damage and chemotherapeutic treatment remains unclear. Here, we show that glutamine deficiency, through the reduction of alpha-ketoglutarate, inhibits the AlkB homolog (ALKBH enzymes activity and induces DNA alkylation damage. As a result, glutamine deprivation or glutaminase inhibitor treatment triggers DNA damage accumulation independent of cell death. In addition, low glutamine-induced DNA damage is abolished in ALKBH deficient cells. Importantly, we show that glutaminase inhibitors, 6-Diazo-5-oxo-L-norleucine (DON or CB-839, hypersensitize cancer cells to alkylating agents both in vitro and in vivo. Together, the crosstalk between glutamine metabolism and the DNA repair pathway identified in this study highlights a potential role of metabolic stress in genomic instability and therapeutic response in cancer.

Glutamine deficiency induces DNA alkylation damage and sensitizes cancer cells to alkylating agents through inhibition of ALKBH enzymes.

Science.gov (United States)

Tran, Thai Q; Ishak Gabra, Mari B; Lowman, Xazmin H; Yang, Ying; Reid, Michael A; Pan, Min; O'Connor, Timothy R; Kong, Mei

2017-11-01

Driven by oncogenic signaling, glutamine addiction exhibited by cancer cells often leads to severe glutamine depletion in solid tumors. Despite this nutritional environment that tumor cells often experience, the effect of glutamine deficiency on cellular responses to DNA damage and chemotherapeutic treatment remains unclear. Here, we show that glutamine deficiency, through the reduction of alpha-ketoglutarate, inhibits the AlkB homolog (ALKBH) enzymes activity and induces DNA alkylation damage. As a result, glutamine deprivation or glutaminase inhibitor treatment triggers DNA damage accumulation independent of cell death. In addition, low glutamine-induced DNA damage is abolished in ALKBH deficient cells. Importantly, we show that glutaminase inhibitors, 6-Diazo-5-oxo-L-norleucine (DON) or CB-839, hypersensitize cancer cells to alkylating agents both in vitro and in vivo. Together, the crosstalk between glutamine metabolism and the DNA repair pathway identified in this study highlights a potential role of metabolic stress in genomic instability and therapeutic response in cancer.

Butylated Hydroxyanisole Blocks the Occurrence of Tumor Associated Macrophages in Tobacco Smoke Carcinogen-Induced Lung Tumorigenesis

International Nuclear Information System (INIS)

Zhang, Yan; Choksi, Swati; Liu, Zheng-Gang

2013-01-01

Tumor-associated macrophages (TAMs) promote tumorigenesis because of their proangiogenic and immune-suppressive functions. Here, we report that butylated hydroxyanisole (BHA) blocks occurrence of tumor associated macrophages (TAMs) in tobacco smoke carcinogen-induced lung tumorigenesis. Continuous administration of butylated hydroxyanisole (BHA), a ROS inhibitor, before or after NNK treatment significantly blocked tumor development, although less effectively when BHA is administered after NNK treatment. Strikingly, BHA abolished the occurrence of F4/80 + macrophages with similar efficiency no matter whether it was administered before or after NNK treatment. Detection of cells from bronchioalveolar lavage fluid (BALF) confirmed that BHA markedly inhibited the accumulation of macrophages while slightly reducing the number of lymphocytes that were induced by NNK. Immunohistological staining showed that BHA specifically abolished the occurrence of CD206 + TAMs when it was administered before or after NNK treatment. Western blot analysis of TAMs markers, arginase I and Ym-1, showed that BHA blocked NNK-induced TAMs accumulation. Our study clearly demonstrated that inhibiting the occurrence of TAMs by BHA contributes to the inhibition of tobacco smoke carcinogen-induced tumorigenesis, suggesting ROS inhibitors may serve as a therapeutic target for treating smoke-induced lung cancer

Differential, but not opponent, effects of L -DOPA and citalopram on action learning with reward and punishment.

Science.gov (United States)

Guitart-Masip, Marc; Economides, Marcos; Huys, Quentin J M; Frank, Michael J; Chowdhury, Rumana; Duzel, Emrah; Dayan, Peter; Dolan, Raymond J

2014-03-01

Decision-making involves two fundamental axes of control namely valence, spanning reward and punishment, and action, spanning invigoration and inhibition. We recently exploited a go/no-go task whose contingencies explicitly decouple valence and action to show that these axes are inextricably coupled during learning. This results in a disadvantage in learning to go to avoid punishment and in learning to no-go to obtain a reward. The neuromodulators dopamine and serotonin are likely to play a role in these asymmetries: Dopamine signals anticipation of future rewards and is also involved in an invigoration of motor responses leading to reward, but it also arbitrates between different forms of control. Conversely, serotonin is implicated in motor inhibition and punishment processing. To investigate the role of dopamine and serotonin in the interaction between action and valence during learning.Methods We combined computational modeling with pharmacological manipulation in 90 healthy human volunteers, using levodopa and citalopram to affect dopamine and serotonin, respectively. We found that, after administration of levodopa,action learning was less affected by outcome valence when compared with the placebo and citalopram groups. This highlights in this context a predominant effect of levodopa in controlling the balance between different forms of control.Citalopram had distinct effects, increasing participants'tendency to perform active responses independent of outcome valence, consistent with a role in decreasing motor inhibition. Our findings highlight the rich complexities of the roles played by dopamine and serotonin during instrumental learning.

Corporal Punishment is a Necessary Evil: Parents’ Perceptions On The Use Of Corporal Punishment In School

OpenAIRE

Gomba, Clifford

2015-01-01

Corporal punishment in Zimbabwe is a “hot potato” that is bringing challenges both on the legal and cultural fronts. My interest in doing this study stems from the Supreme Court ruling that ruled the use of corporal punishment is unconstitutional. After the ruling, it became imperative to understand the views of different people pertaining to the use of corporal punishment, especially in schools because that is where it is prevalent. For this study I sought to discover and understand the pers...

Race, punishment, and the Michael Vick experience.

Science.gov (United States)

Piquero, Alex R; Piquero, Nicole Leeper; Gertz, Marc; Baker, Thomas; Batton, Jason; Barnes, J C

2011-01-01

Objective. The relationship between race and crime has been contentious, focusing primarily on offending and incarceration patterns among minorities. There has been some limited work on public perceptions of criminal punishment, and findings show that while minorities believe in the role and rule of law, they simultaneously perceive the justice system as acting in a biased and/or unfair manner. Two limitations have stalled this literature. First, research has focused mainly on criminal punishments to the neglect of noncriminal punishments. Second, most studies have not examined whether race remains salient after considering other demographic variables or discrimination and legitimacy attitudes.Methods. Using data from 400 adults, we examine how race affects perceptions of criminal punishment and subsequent reinstatement into the National Football League in the case of Michael Vick, a star professional quarterback who pled guilty to charges of operating an illegal dog-fighting ring.Results. Findings show that whites are more likely to view Vick's punishment as too soft and that he should not be reinstated, while nonwhites had the opposite views. Race remained significant after controlling for other variables believed to be related to punishment perceptions.Conclusion. Attitudes toward both criminal punishment and NFL reinstatement vary across race such that there exists important divides in how individuals perceive the system meting out punishment and subsequently reintegrating offenders back into society. These results underscore that white and nonwhites perceive the law and its administration differently.

Punishment models of addictive behavior

NARCIS (Netherlands)

Vanderschuren, L.J.M.J.|info:eu-repo/dai/nl/126514917; Minnaard, A.M.|info:eu-repo/dai/nl/413292533; Smeets, J.A.S.|info:eu-repo/dai/nl/413578577; Lesscher, H.M.B.|info:eu-repo/dai/nl/258637196

2017-01-01

Substance addiction is a chronic relapsing brain disorder, characterized by loss of control over substance use. In recent years, there has been a lively interest in animal models of loss of control over substance use, using punishment paradigms. We provide an overview of punishment models of

Predicting Filipino Mothers' and Fathers' Reported Use of Corporal Punishment From Education, Authoritarian Attitudes, and Endorsement of Corporal Punishment.

Science.gov (United States)

Jocson, Rosanne M; Alampay, Liane Peña; Lansford, Jennifer E

2012-03-09

The relations of education, authoritarian childrearing attitudes, and endorsement of corporal punishment to Filipino parents' reported use of corporal punishment were examined using two waves of data. Structured interviews using self-report questionnaires were conducted with 117 mothers and 98 fathers from 120 families when their children were 8 years old, and when their children were 9 years old. Path analyses showed that, among mothers, higher education predicted lower authoritarian attitudes, which in turn predicted lower reports of corporal punishment use. Among fathers, higher education predicted lower endorsement of corporal punishment, which in turn predicted lower reports of its use. Results suggest that education has an indirect relation to use of corporal punishment through parenting cognitions, and highlight distinctions in Filipino mothers' and fathers' parenting roles.

Inhibitory heterotrimeric GTP-binding proteins inhibit hydrogen peroxide-induced apoptosis by up-regulation of Bcl-2 via NF-κB in H1299 human lung cancer cells

International Nuclear Information System (INIS)

Seo, Mi Ran; Nam, Hyo-Jung; Kim, So-Young; Juhnn, Yong-Sung

2009-01-01

Inhibitory heterotrimeric GTP-binding proteins (Gi proteins) mediate a variety of signaling pathways by coupling receptors and effectors to regulate cellular proliferation, differentiation, and apoptosis. However, the role of Gi proteins in the modulation of hydrogen peroxide-induced apoptosis is not clearly understood. Thus, we investigated the effect of Gi proteins on hydrogen peroxide-induced apoptosis and the underlying mechanisms in H1299 human lung cancer cells. The stable expression of constitutively active alpha subunits of Gi1 (Gαi1QL), Gi2, or Gi3 inhibited hydrogen peroxide-induced apoptosis. The expression of Gαi1QL up-regulated Bcl-2 expression, and the knockdown of Bcl-2 with siRNA abolished the anti-apoptotic effect of Gαi1QL. Gαi1 induced the transcription of Bcl-2 by activation of NF-κB, which resulted from an increase in NF-κB p50 protein. We conclude that Gαi1 inhibits hydrogen peroxide-induced apoptosis of H1299 lung cancer cells by up-regulating the transcription of Bcl-2 through a p50-mediated NF-κB activation.

Self-organization of punishment in structured populations

Science.gov (United States)

Perc, Matjaž; Szolnoki, Attila

2012-04-01

Cooperation is crucial for the remarkable evolutionary success of the human species. Not surprisingly, some individuals are willing to bear additional costs in order to punish defectors. Current models assume that, once set, the fine and cost of punishment do not change over time. Here we show that relaxing this assumption by allowing players to adapt their sanctioning efforts in dependence on the success of cooperation can explain both the spontaneous emergence of punishment and its ability to deter defectors and those unwilling to punish them with globally negligible investments. By means of phase diagrams and the analysis of emerging spatial patterns, we demonstrate that adaptive punishment promotes public cooperation through the invigoration of spatial reciprocity, the prevention of the emergence of cyclic dominance, or the provision of competitive advantages to those that sanction antisocial behavior. The results presented indicate that the process of self-organization significantly elevates the effectiveness of punishment, and they reveal new mechanisms by means of which this fascinating and widespread social behavior could have evolved.

Turkish Primary School Pupils' Views on Punishment

Science.gov (United States)

Aydin, Bahri

2010-01-01

Teachers meet with unwanted behavior when they are acting as facilitators of the learning process and they resort to certain tactics to deal with them. One of these tactics is punishment. This study aimed to identify the views held by Turkish primary school pupils on punishment. According to the results of the study, pupils were punished for…

Corporal Punishment and Youth Externalizing Behavior in Santiago, Chile

Science.gov (United States)

Ma, Julie; Han, Yoonsun; Grogan-Kaylor, Andrew; Delva, Jorge; Castillo, Marcela

2012-01-01

Objectives Corporal punishment is still widely practiced around the globe, despite the large body of child development research that substantiates its short- and long-term consequences. Within this context, this paper examined the relationship between parental use of corporal punishment and youth externalizing behavior with a Chilean sample to add to the growing empirical evidence concerning the potential relationship between increased corporal punishment and undesirable youth outcomes across cultures. Methods Analysis was based on 919 adolescents in Santiago, Chile. Descriptive and multivariate analyses were conducted to examine the extent to which parents’ use of corporal punishment and positive family measures were associated with youth externalizing behavior. Furthermore, the associations between self-reported externalizing behavior and infrequent, as well as frequent, use of corporal punishment were investigated to contribute to understanding how varying levels of parental use of corporal punishment were differently related to youth outcomes. Results Both mother’s and father’s use of corporal punishment were associated with greater youth externalizing behavior. Additionally, increases in positive parenting practices, such as parental warmth and family involvement, were met with decreases in youth externalizing behavior when controlling for youth demographics, family socioeconomic status, and parents’ use of corporal punishment. Finally, both infrequent and frequent use of corporal punishment were positively associated with higher youth problem behaviors, though frequent corporal punishment had a stronger relationship with externalizing behavior than did infrequent corporal punishment. Conclusions Parental use of corporal punishment, even on an occasional basis, is associated with greater externalizing behavior for youth while a warm and involving family environment may protect youth from serious problem behaviors. Therefore, findings of this study add

Peer punishment promotes enforcement of bad social norms.

Science.gov (United States)

Abbink, Klaus; Gangadharan, Lata; Handfield, Toby; Thrasher, John

2017-09-20

Social norms are an important element in explaining how humans achieve very high levels of cooperative activity. It is widely observed that, when norms can be enforced by peer punishment, groups are able to resolve social dilemmas in prosocial, cooperative ways. Here we show that punishment can also encourage participation in destructive behaviours that are harmful to group welfare, and that this phenomenon is mediated by a social norm. In a variation of a public goods game, in which the return to investment is negative for both group and individual, we find that the opportunity to punish led to higher levels of contribution, thereby harming collective payoffs. A second experiment confirmed that, independently of whether punishment is available, a majority of subjects regard the efficient behaviour of non-contribution as socially inappropriate. The results show that simply providing a punishment opportunity does not guarantee that punishment will be used for socially beneficial ends, because the social norms that influence punishment behaviour may themselves be destructive.Punishment by peers can enforce social norms, such as contributing to a public good. Here, Abbink and colleagues show that individuals will enforce norms even when contributions reduce the net benefit of the group, resulting in the maintenance of wasteful contributions.

Mutual punishment promotes cooperation in the spatial public goods game

International Nuclear Information System (INIS)

Yang, Han-Xin; Rong, Zhihai

2015-01-01

Punishment has been proved to be an effective mechanism to sustain cooperation among selfish individuals. In previous studies, punishment is unidirectional: an individual i can punish j but j cannot punish i. In this paper, we propose a mechanism of mutual punishment, in which the two individuals will punish each other if their strategies are different. Because of the symmetry in imposing the punishment, one might expect intuitively the strategy to have little effect on cooperation. Surprisingly, we find that the mutual punishment can promote cooperation in the spatial public goods game. Other pertinent quantities such as the time evolution of cooperator density and the spatial distribution of cooperators and defectors are also investigated

Punishment mechanisms and their effect on cooperation: A simulation study

NARCIS (Netherlands)

Farjam, M.D.; Faillo, M.; Sprinkhuizen-Kuyper, I.G.; Haselager, W.F.G.

2015-01-01

In social dilemmas punishment costs resources, not just from the one who is punished but often also from the punisher and society. Reciprocity on the other side is known to lead to cooperation without the costs of punishment. The questions at hand are whether punishment brings advantages besides its

Tolerance-based punishment in continuous public goods game

Science.gov (United States)

Gao, Jia; Li, Zhi; Cong, Rui; Wang, Long

2012-08-01

Altruistic punishment for defectors is considered as a key motive for the explanation of cooperation. However, there is no clear border between the cooperative and defective behaviors in a continuous strategy game. We propose a model to study the effect of punishment on the evolution of cooperation in continuous public goods game, wherein individuals have the traits to punish the co-players based on social tolerance. We show that a reasonable punishment with a uniform tolerance can spur individuals to make more investments. Additionally, for a fixed punishment cost and a fixed fine, a moderate value of tolerance can result in the best promotion of cooperation. Furthermore, we investigate the coevolutionary dynamics of investment and tolerance. We find that the population splits into two branches: high-tolerance individuals who make high investments and low-tolerance individuals who make low investments. A dynamic equilibrium is achieved between these two types of individuals. Our work extends punishment to continuous cooperative behaviors and the results may enhance the understanding of altruistic punishment in the evolution of human cooperation.

A monoclonal antibody against PDGF B-chain inhibits PDGF-induced DNA synthesis in C3H fibroblasts and prevents binding of PDGF to its receptor.

Science.gov (United States)

Vassbotn, F S; Langeland, N; Hagen, I; Holmsen, H

1990-09-01

A monoclonal antibody (MAb 6D11) against platelet-derived growth factor (PDGF) was studied. We found that the MAb 6D11 in concentrations equimolar to PDGF blocked the [3H]thymidine incorporation in C3H/10T1/2 C18 fibroblasts stimulated by PDGF B-B and PDGF A-B. This inhibition was overcome by high doses of PDGF. The [3H]thymidine incorporation stimulated by other growth factors (aFGF, bFGF and bombesin) was not inhibited by the antibody. The MAb 6D11 blocked receptor binding of PDGF B-B, but not PDGF A-A. These findings suggest that the MAb 6D11 abolishes PDGF-induced DNA synthesis by blocking PDGF receptor binding. In this communication we demonstrate an isoform-specific monoclonal antibody against PDGF.

Peer pressure: Enhancement of cooperation through mutual punishment

Science.gov (United States)

Yang, Han-Xin; Wu, Zhi-Xi; Rong, Zhihai; Lai, Ying-Cheng

2015-02-01

An open problem in evolutionary game dynamics is to understand the effect of peer pressure on cooperation in a quantitative manner. Peer pressure can be modeled by punishment, which has been proved to be an effective mechanism to sustain cooperation among selfish individuals. We investigate a symmetric punishment strategy, in which an individual will punish each neighbor if their strategies are different, and vice versa. Because of the symmetry in imposing the punishment, one might intuitively expect the strategy to have little effect on cooperation. Utilizing the prisoner's dilemma game as a prototypical model of interactions at the individual level, we find, through simulation and theoretical analysis, that proper punishment, when even symmetrically imposed on individuals, can enhance cooperation. Also, we find that the initial density of cooperators plays an important role in the evolution of cooperation driven by mutual punishment.

Attitudes mediate the intergenerational transmission of corporal punishment in China.

Science.gov (United States)

Wang, Fang; Wang, Meifang; Xing, Xiaopei

2018-02-01

This research aimed to examine the intergenerational transmission of corporal punishment and the role of parents' attitudes toward corporal punishment in the transmission processes in Chinese societies. Based on social-cognitive theory, it was hypothesized that parents' attitudes toward corporal punishment would mediate the transmission of corporal punishment. Seven hundred and eighty-five fathers and eight hundred and eleven mothers with elementary school-age children (data collected in winter 2009) were recruited through convenience sampling techniques. The Chinese version of Parent-Child Conflict Tactics Scale (CTSPC) and Attitude toward Physical Punishment Scale (ATPP) were used as the main assessment tools to measure parents' corporal punishment experiences in childhood, current use of corporal punishment and attitudes toward corporal punishment. Findings revealed that the strength of intergenerational transmission of corporal punishment was strong and parents' attitudes toward corporal punishment played a mediating role in the continuity of corporal punishment for both fathers and mothers in China. The findings highlighted the role of attitudes in the intergenerational transmission of corporal punishment within the Chinese cultural context and also suggested the need for intervention programs to focus on modification of maladaptive attitudes toward what is appropriate and effective discipline. Copyright © 2017 Elsevier Ltd. All rights reserved.

A New Definition of Punishment

Science.gov (United States)

Hall, Philip S.

2013-01-01

Punishment is a procedure in which responses are followed by either the removal of positive reinforcement or the presentation of an aversive stimulus (Skinner, 1953) that results in a decrease in the frequency and/or intensity of the response (Azrin & Holtz, 1966). By definition, punishment seeks to stop unacceptable, unwanted, and bothersome…

STAT1 is essential for the inhibition of hepatitis C virus replication by interferon-λ but not by interferon-α.

Science.gov (United States)

Yamauchi, Shota; Takeuchi, Kenji; Chihara, Kazuyasu; Honjoh, Chisato; Kato, Yuji; Yoshiki, Hatsumi; Hotta, Hak; Sada, Kiyonao

2016-12-08

Interferon-α (IFN-α) and IFN-λ are structurally distinct cytokines that bind to different receptors, but induce expression of similar sets of genes through Janus kinase (JAK)-signal transducers and activators of transcription (STAT) pathways. The difference between IFN-α and IFN-λ signaling remains poorly understood. Here, using the CRISPR/Cas9 system, we examine the role of STAT1 and STAT2 in the inhibition of hepatitis C virus (HCV) replication by IFN-α and IFN-λ. Treatment with IFN-α increases expression of IFN-stimulated genes (ISGs) such as double-stranded RNA-activated protein kinase (PKR) and decreases viral RNA and protein levels in HCV-infected Huh-7.5 human hepatoma cells. These responses are only partially attenuated by knockout of STAT1 but are abolished by knockout of STAT2. In contrast, the inhibition of HCV replication by IFN-λ is abolished by knockout of STAT1 or STAT2. Microarray analysis reveals that IFN-α but not IFN-λ can induce expression of the majority of ISGs in STAT1 knockout cells. These findings suggest that IFN-α can inhibit HCV replication through a STAT2-dependent but STAT1-independent pathway, whereas IFN-λ induces ISG expression and inhibits HCV replication exclusively through a STAT1- and STAT2-dependent pathway.

No evidence for punishment in communally nursing female house mice (Mus musculus domesticus).

Science.gov (United States)

Ferrari, Manuela; König, Barbara

2017-01-01

Punishment is claimed as an important mechanism to stabilise costly cooperation in humans, but its importance in social animals has been questioned recently due to both conceptual considerations and a lack of empirical evidence (only few published studies). We empirically tested whether there is evidence for punishment in communally nursing house mice (Mus musculus domesticus, direct descendants of "wild" animals). Communally breeding females pool their litters and raise all offspring together, indiscriminately caring for own and other offspring. Such a situation resembles a public good and provides scope for exploitation if females vary in their relative contributions to the joint nest (offspring number). We allowed two females to communally breed and conducted removal experiments both in the presence and absence of pups. We aimed to test whether reduced investment by one of the females (induced through separation from the partner and their combined offspring for 4 or 12 hours) leads to increased aggression by the other female after the reunion. We found no evidence for punishment, on the contrary, females increased socio-positive behaviours. The costs of losing a partner in a communally breeding species might be too high and hinder the evolution of punishment. Our findings add to a growing list of examples questioning the role of punishment in cooperating non-human animals and emphasise the importance of empirical testing of its assumptions and predictions.

Exploring the Motivations for Punishment: Framing and Country-Level Effects.

Science.gov (United States)

Bone, Jonathan E; McAuliffe, Katherine; Raihani, Nichola J

2016-01-01

Identifying the motives underpinning punishment is crucial for understanding its evolved function. In principle, punishment of distributional inequality could be motivated by the desire to reciprocate losses ('revenge') or by the desire to reduce payoff asymmetries between the punisher and the target ('inequality aversion'). By separating these two possible motivations, recent work suggests that punishment is more likely to be motivated by disadvantageous inequality aversion than by a desire for revenge. Nevertheless, these findings have not consistently replicated across different studies. Here, we suggest that considering country of origin-previously overlooked as a possible source of variation in responses-is important for understanding when and why individuals punish one another. We conducted a two-player stealing game with punishment, using data from 2,400 subjects recruited from the USA and India. US-based subjects punished in response to losses and disadvantageous inequality, but seldom invested in antisocial punishment (defined here as punishment of non-stealing partners). India-based subjects, on the other hand, punished at higher levels than US-based subjects and, so long as they did not experience disadvantageous inequality, punished stealing and non-stealing partners indiscriminately. Nevertheless, as in the USA, when stealing resulted in disadvantageous inequality, India-based subjects punished stealing partners more than non-stealing partners. These results are consistent with the hypothesis that variation in punitive behavior varies across societies, and support the idea that punishment might sometimes function to improve relative status, rather than to enforce cooperation.

Corporal Punishment and Child Adjustment

Science.gov (United States)

Aucoin, Katherine J.; Frick, Paul J.; Bodin, S. Doug

2006-01-01

The association between corporal punishment and children's emotional and behavioral functioning was studied in a sample of 98 non-referred children with a mean age of 12.35 (SD=1.72) recruited from two school systems in the southeastern United States. Children were divided into those who had experienced no corporal punishment over approximately a…

Genipin inhibits TNF-α-induced vascular smooth muscle cell proliferation and migration via induction of HO-1.

Directory of Open Access Journals (Sweden)

Fengrong Jiang

Full Text Available Vascular smooth muscle cell (VSMC proliferation and migration triggered by inflammatory stimuli contributes importantly to the pathogenesis of atherosclerosis and restenosis. On the other hand, genipin, an aglycon of geniposide, exhibits diverse pharmacological functions such as antitumor and anti-inflammatory effects. The protective effects of genipin on the cardiovascular system have also been reported. However, the molecular mechanism involved remains unknown. This study aimed to elucidate the precise function of genipin in VSMCs, focusing particularly on the role of heme oxygenase-1 (HO-1, a potent anti-inflammatory enzyme. We found that pretreatment of genipin induced HO-1 mRNA and protein levels, as well as its activity in VSMCs. Genipin inhibited TNF-α-induced VSMC proliferation and migration in a dose-dependent manner. At the molecular level, genipin prevented ERK/MAPK and Akt phosphorylation while left p38 MAPK and JNK unchanged. Genipin also blocked the increase of ROS generation induced by TNF-α. More importantly, the specific HO-1 siRNA partially abolished the beneficial effects of genipin on VSMCs. These results suggest that genipin may serve as a novel drug in the treatment of these pathologies by inducing HO-1 expression/activity and subsequently decreasing VSMC proliferation and migration.

Inhibition of radiation-induced EGFR nuclear import by C225 (Cetuximab) suppresses DNA-PK activity

International Nuclear Information System (INIS)

Dittmann, Klaus; Mayer, Claus; Rodemann, Hans-Peter

2005-01-01

Background and purpose: Inhibition of EGFR-function can induce radiosensitization in tumor cells. Purpose of our investigation was to identify the possible molecular mechanism of radiosensitization following treatment with anti-EGFR-antibody C225 (Cetuximab). Materials and methods: The effect of C225 on radiation response was determined in human cell lines of bronchial carcinoma (A549) and breast adenoma cells (MDA MB 231). The molecular effects of C225 on EGFR-function after irradiation were analyzed applying western blotting, immune-precipitation and kinase assays. Effects on DNA-repair were detected by quantification of γ-H2AX positive foci 24 h after irradiation. Results: The EGFR specific antibody C225 induced radiosensitization in A549 and also in MDA MB 231 cells. Radiosensitization in A549 was associated with blockage of radiation-induced EGFR transport into the nucleus, and immobilized the complex of EGFR with DNA-dependent protein kinase (DNA-PK) in the cytoplasm. As a consequence radiation-induced DNA-PK activation was abolished, a process that is essential for DNA-repair after radiation exposure. Likewise C225 treatment increased the residual amount of γ-H2AX-positive foci 24 h after irradiation in A549 and in MDA MB 231 cells. Conclusions: Our results suggest that irradiation induced DNA-PK activation-essential for DNA repair-may be hampered specifically by use of the anti-EGFR-antibody C225. This process is associated with radiosensitization

Wrath of God: religious primes and punishment.

Science.gov (United States)

McKay, Ryan; Efferson, Charles; Whitehouse, Harvey; Fehr, Ernst

2011-06-22

Recent evidence indicates that priming participants with religious concepts promotes prosocial sharing behaviour. In the present study, we investigated whether religious priming also promotes the costly punishment of unfair behaviour. A total of 304 participants played a punishment game. Before the punishment stage began, participants were subliminally primed with religion primes, secular punishment primes or control primes. We found that religious primes strongly increased the costly punishment of unfair behaviours for a subset of our participants--those who had previously donated to a religious organization. We discuss two proximate mechanisms potentially underpinning this effect. The first is a 'supernatural watcher' mechanism, whereby religious participants punish unfair behaviours when primed because they sense that not doing so will enrage or disappoint an observing supernatural agent. The second is a 'behavioural priming' mechanism, whereby religious primes activate cultural norms pertaining to fairness and its enforcement and occasion behaviour consistent with those norms. We conclude that our results are consistent with dual inheritance proposals about religion and cooperation, whereby religions harness the byproducts of genetically inherited cognitive mechanisms in ways that enhance the survival prospects of their adherents.

Oxidative inhibition of the vascular Na+-K+ pump via NADPH oxidase-dependent β1-subunit glutathionylation: implications for angiotensin II-induced vascular dysfunction.

Science.gov (United States)

Liu, Chia-Chi; Karimi Galougahi, Keyvan; Weisbrod, Robert M; Hansen, Thomas; Ravaie, Ramtin; Nunez, Andrea; Liu, Yi B; Fry, Natasha; Garcia, Alvaro; Hamilton, Elisha J; Sweadner, Kathleen J; Cohen, Richard A; Figtree, Gemma A

2013-12-01

Glutathionylation of the Na(+)-K(+) pump's β1-subunit is a key molecular mechanism of physiological and pathophysiological pump inhibition in cardiac myocytes. Its contribution to Na(+)-K(+) pump regulation in other tissues is unknown, and cannot be assumed given the dependence on specific β-subunit isoform expression and receptor-coupled pathways. As Na(+)-K(+) pump activity is an important determinant of vascular tone through effects on [Ca(2+)]i, we have examined the role of oxidative regulation of the Na(+)-K(+) pump in mediating angiotensin II (Ang II)-induced increases in vascular reactivity. β1-subunit glutathione adducts were present at baseline and increased by exposure to Ang II in rabbit aortic rings, primary rabbit aortic vascular smooth muscle cells (VSMCs), and human arterial segments. In VSMCs, Ang II-induced glutathionylation was associated with marked reduction in Na(+)-K(+)ATPase activity, an effect that was abolished by the NADPH oxidase inhibitory peptide, tat-gp91ds. In aortic segments, Ang II-induced glutathionylation was associated with decreased K(+)-induced vasorelaxation, a validated index of pump activity. Ang II-induced oxidative inhibition of Na(+)-K(+) ATPase and decrease in K(+)-induced relaxation were reversed by preincubation of VSMCs and rings with recombinant FXYD3 protein that is known to facilitate deglutathionylation of β1-subunit. Knock-out of FXYD1 dramatically decreased K(+)-induced relaxation in a mouse model. Attenuation of Ang II signaling in vivo by captopril (8 mg/kg/day for 7 days) decreased superoxide-sensitive DHE levels in the media of rabbit aorta, decreased β1-subunit glutathionylation, and enhanced K(+)-induced vasorelaxation. Ang II inhibits the Na(+)-K(+) pump in VSMCs via NADPH oxidase-dependent glutathionylation of the pump's β1-subunit, and this newly identified signaling pathway may contribute to altered vascular tone. FXYD proteins reduce oxidative inhibition of the Na(+)-K(+) pump and may have an

Shame, Guilt, and Punishment

DEFF Research Database (Denmark)

Rodogno, Raffaele

2009-01-01

that this analysis enhances our understanding of the various theories of punishment that populate this part of criminal law theory and thereby sharpens the critical tools needed to assess them. My general conclusion is that, in different ways, all of the theories we encounter in this area can benefit from paying...... renewed attention to the nature of the connection between the states act of punishing and its expected or perceived emotional effect on the individual. Udgivelsesdato: 2009...

Promote or hinder? The role of punishment in the emergence of cooperation.

Science.gov (United States)

Gao, Shiping; Wu, Te; Nie, Suli; Wang, Long

2015-12-07

Investigation of anti-social punishment has shaken the positive role of punishment in the evolution of cooperation. However, punishment is ubiquitous in nature, and the centralized, apposed to decentralized, punishment is more favored by certain modern societies in particular. To explore the underlying principle of such phenomenon, we study the evolution of cooperation in the context of pro- and anti-social punishments subject to two distinct patterns: costly centralized and decentralized punishments. The results suggest that the pattern of punishment has a great effect on the role of punishment in the evolution of cooperation. In the absence of anti-social punishment, the costly centralized punishment is more effective in promoting the emergence of cooperation. Anti-social punishment can subvert the positive role of punishment when anti- and pro-social punishments are in the same pattern. However, driven by centralized pro-social punishment, cooperation can be more advantageous than defection even in the presence of decentralized anti-social punishment. Copyright © 2015 Elsevier Ltd. All rights reserved.

Fisetin, a dietary flavonoid, induces apoptosis of cancer cells by inhibiting HSF1 activity through blocking its binding to the hsp70 promoter.

Science.gov (United States)

Kim, Joo Ae; Lee, Somyoung; Kim, Da-Eun; Kim, Moonil; Kwon, Byoung-Mog; Han, Dong Cho

2015-06-01

Heat shock factor 1 (HSF1) is a transcription factor for heat shock proteins (HSPs) expression that enhances the survival of cancer cells exposed to various stresses. HSF1 knockout suppresses carcinogen-induced cancer induction in mice. Therefore, HSF1 is a promising therapeutic and chemopreventive target. We performed cell-based screening with a natural compound collection and identified fisetin, a dietary flavonoid, as a HSF1 inhibitor. Fisetin abolished heat shock-induced luciferase activity with an IC50 of 14 μM in HCT-116 cancer cells. The treatment of HCT-116 with fisetin inhibited proliferation with a GI50 of 23 μM. When the cells were exposed to heat shock in the presence of fisetin, the induction of HSF1 target proteins, such as HSP70, HSP27 and BAG3 (Bcl-2-associated athanogene domain 3), were inhibited. HSP70/BAG3 complexes protect cancer cells from apoptosis by stabilizing anti-apoptotic Bcl-2 family proteins. The downregulation of HSP70/BAG3 by fisetin significantly reduced the amounts of Bcl-2, Bcl-xL and Mcl-1 proteins, subsequently inducing apoptotic cell death. Chromatin immunoprecipitation assays showed that fisetin inhibited HSF1 activity by blocking the binding of HSF1 to the hsp70 promoter. Intraperitoneal treatment of nude mice with fisetin at 30mg/kg resulted in a 35.7% (P < 0.001) inhibition of tumor growth. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Altruism in multiplayer snowdrift games with threshold and punishment

Science.gov (United States)

Zhang, Chunyan; Liu, Zhongxin; Sun, Qinglin; Chen, Zengqiang

2015-09-01

The puzzle of cooperation attracts broader concerns of the scientific community nowadays. Here we adopt an extra mechanism of punishment in the framework of a threshold multiple-player snowdrift game employed as the scenario for the cooperation problem. Two scenarios are considered: defectors will suffer punishment regardless of the game results, and defectors will incur punishment only when the game fails. We show by analysis that given this assumption, punishing free riders can significantly influence the evolution outcomes, and the results are driven by the specific components of the punishing rule. Particularly, punishing defectors always, not only when the game fails, can be more effective for maintaining public cooperation in multi-player systems. Intriguingly larger thresholds of the game provide a more favorable scenario for the coexistence of the cooperators and defectors under a broad value range of parameters. Further, cooperators are best supported by the large punishment on defectors, and then dominate and stabilize in the population, under the premise that defectors always incur punishment regardless of whether the game ends successfully or not.

Beyond revenge: neural and genetic bases of altruistic punishment.

Science.gov (United States)

Strobel, Alexander; Zimmermann, Jan; Schmitz, Anja; Reuter, Martin; Lis, Stefanie; Windmann, Sabine; Kirsch, Peter

2011-01-01

It is still debated how altruistic punishment as one form of strong reciprocity has established during evolution and which motives may underlie such behavior. Recent neuroscientific evidence on the activation of brain reward regions during altruistic punishment in two-person one-shot exchange games suggests satisfaction through the punishment of norm violations as one underlying motive. In order to address this issue in more detail, we used fMRI during a one-shot economic exchange game that warrants strong reciprocity by introducing a third party punishment condition wherein revenge is unlikely to play a role. We report here that indeed, reward regions such as the nucleus accumbens showed punishment-related activation. Moreover, we provide preliminary evidence that genetic variation of dopamine turnover impacts similarly on punishment-related nucleus accumbens activation during both first person and third party punishment. The overall pattern of results suggests a common cognitive-affective-motivational network as the driving force for altruistic punishment, with only quantitative differences between first person and third party perspectives. Copyright © 2010 Elsevier Inc. All rights reserved.

Predictors of Parental Use of Corporal Punishment in Ukraine.

Science.gov (United States)

Grogan-Kaylor, Andrew; Burlaka, Viktor; Ma, Julie; Lee, Shawna; Castillo, Berenice; Churakova, Iuliia

2018-05-01

Despite a great deal of evidence that corporal punishment is harmful, corporal punishment is still very prevalent worldwide. We examine predictors of different types of corporal punishment among Ukrainian mothers in 12 communities across Ukraine. Findings suggest that maternal spirituality, maternal coping styles, family communication, and some demographic characteristics are predictive of mothers' use of corporal punishment.

A novel assessment of nefazodone-induced hERG inhibition by electrophysiological and stereochemical method

Energy Technology Data Exchange (ETDEWEB)

Shin, Dae-Seop; Park, Myoung Joo [Drug Discovery Platform Technology Research Group, Korea Research Institute of Chemical Technology, Daejeon (Korea, Republic of); Lee, Hyang-Ae [Korea Institute of Toxicology, Korea Research Institute of Chemical Technology, Daejeon (Korea, Republic of); Lee, Joo Yun; Chung, Hee-Chung; Yoo, Dae Seok; Chae, Chong Hak [Drug Discovery Platform Technology Research Group, Korea Research Institute of Chemical Technology, Daejeon (Korea, Republic of); Park, Sang-Joon [College of Veterinary Medicine, Kyungpook National University, Daegu (Korea, Republic of); Kim, Ki-Suk [Korea Institute of Toxicology, Korea Research Institute of Chemical Technology, Daejeon (Korea, Republic of); Bae, Myung Ae, E-mail: mbae@krict.re.kr [Drug Discovery Platform Technology Research Group, Korea Research Institute of Chemical Technology, Daejeon (Korea, Republic of)

2014-02-01

Nefazodone was used widely as an antidepressant until it was withdrawn from the U.S. market in 2004 due to hepatotoxicity. We have investigated methods to predict various toxic effects of drug candidates to reduce the failure rate of drug discovery. An electrophysiological method was used to assess the cardiotoxicity of drug candidates. Small molecules, including withdrawn drugs, were evaluated using a patch-clamp method to establish a database of hERG inhibition. Nefazodone inhibited hERG channel activity in our system. However, nefazodone-induced hERG inhibition indicated only a theoretical risk of cardiotoxicity. Nefazodone inhibited the hERG channel in a concentration-dependent manner with an IC{sub 50} of 45.3 nM in HEK-293 cells. Nefazodone accelerated both the recovery from inactivation and its onset. Nefazodone also accelerated steady-state inactivation, although it did not modify the voltage-dependent character. Alanine mutants of hERG S6 and pore region residues were used to identify the nefazodone-binding site on hERG. The hERG S6 point mutants Y652A and F656A largely abolished the inhibition by nefazodone. The pore region mutant S624A mildly reduced the inhibition by nefazodone but T623A had little effect. A docking study showed that the aromatic rings of nefazodone interact with Y652 and F656 via π–π interactions, while an amine interacted with the S624 residue in the pore region. In conclusion, Y652 and F656 in the S6 domain play critical roles in nefazodone binding. - Highlights: • Nefazodone inhibits hERG channels with an IC{sub 50} of 45.3 nM in HEK-293 cells. • Nefazodone blocks hERG channels by binding to the open channels. • Y652 and F656 are important for binding of nefazodone. • The aromatic rings of nefazodone interact with Y652 and F656 via π–π interactions.

m-Trifluoromethyl-diphenyl Diselenide Regulates Prefrontal Cortical MOR and KOR Protein Levels and Abolishes the Phenotype Induced by Repeated Forced Swim Stress in Mice.

Science.gov (United States)

Rosa, Suzan Gonçalves; Pesarico, Ana Paula; Martini, Franciele; Nogueira, Cristina Wayne

2018-04-05

The present study aimed to investigate the m-trifluoromethyl-diphenyl diselenide [(m-CF 3 -PhSe) 2 ] effects on prefrontal cortical MOR and KOR protein levels and phenotype induced by repeated forced swim stress (FSS) in mice. Adult Swiss mice were subjected to repeated FSS sessions, and after that, they performed the spontaneous locomotor/exploratory activity, tail suspension, and splash tests. (m-CF 3 -PhSe) 2 (0.1 to 5 mg/kg) was administered to mice 30 min before the first FSS session and 30 min before the subsequent repeated FSS. (m-CF 3 -PhSe) 2 abolished the phenotype induced by repeated FSS in mice. In addition, a single FSS session increased μ but reduced δ-opioid receptor contents, without changing the κ content. Mice subjected to repeated FSS had an increase in the μ content when compared to those of naïve group or subjected to single FSS. Repeated FSS induced an increase of δ-opioid receptor content compared to those mice subjected to single FSS. However, the δ-opioid receptor contents were lower than those found in the naïve group. The mice subjected to repeated FSS showed an increase in the κ-opioid receptor content when compared to that of the naïve mice. (m-CF 3 -PhSe) 2 regulated the protein contents of μ and κ receptors in mice subjected to repeated FSS. These findings demonstrate that (m-CF 3 -PhSe) 2 was effective to abolish the phenotype induced by FSS, which was accompanied by changes in the contents of cortical μ- and κ-opioid receptors.

Targeted inhibition of disheveled PDZ domain via NSC668036 depresses fibrotic process

Energy Technology Data Exchange (ETDEWEB)

Wang, Cong, E-mail: wangcongweihai@126.com [Immunology and Reproduction Biology Laboratory, Medical School, Nanjing University, Nanjing, Hankou Road 22, Jiangsu 210093 (China); Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, Jiangsu 210093 (China); State Key Laboratory of Analytical Chemistry for Life Science, Nanjing University, Nanjing, Jiangsu 210093 (China); Dai, Jinghong, E-mail: daijinghongnew@163.com [Department of Respiratory Medicine, Nanjing Drum Tower Hospital Affiliated to Medical School of Nanjing University (China); Sun, Zhaorui, E-mail: lanseyunduan@163.com [Immunology and Reproduction Biology Laboratory, Medical School, Nanjing University, Nanjing, Hankou Road 22, Jiangsu 210093 (China); Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, Jiangsu 210093 (China); State Key Laboratory of Analytical Chemistry for Life Science, Nanjing University, Nanjing, Jiangsu 210093 (China); Department of Emergency, Jinling Hospital, Medical School, Nanjing University, Nanjing, Jiangsu 210093 (China); Shi, Chaowen, E-mail: willscw@live.cn [Immunology and Reproduction Biology Laboratory, Medical School, Nanjing University, Nanjing, Hankou Road 22, Jiangsu 210093 (China); Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, Jiangsu 210093 (China); State Key Laboratory of Analytical Chemistry for Life Science, Nanjing University, Nanjing, Jiangsu 210093 (China); Cao, Honghui, E-mail: caohonghui92@gmail.com [Immunology and Reproduction Biology Laboratory, Medical School, Nanjing University, Nanjing, Hankou Road 22, Jiangsu 210093 (China); Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, Jiangsu 210093 (China); State Key Laboratory of Analytical Chemistry for Life Science, Nanjing University, Nanjing, Jiangsu 210093 (China); and others

2015-02-01

In this study, we determined the effects of transforming growth factor-beta (TGF-β) and Wnt/β-catenin signaling on myofibroblast differentiation of NIH/3T3 fibroblasts in vitro and evaluated the therapeutic efficacy of NSC668036 in bleomycin-induced pulmonary fibrosis murine model. In vitro study, NSC668036, a small organic inhibitor of the PDZ domain in Dvl, suppressed β-catenin-driven gene transcription and abolished TGF-β1-induced migration, expression of collagen I and α-smooth muscle actin (α-SMA) in fibroblasts. In vivo study, we found that NSC668036 significantly suppressed accumulation of collagen I, α-SMA, and TGF-β1 but increased the expression of CK19, Occludin and E-cadherin that can inhibit pulmonary fibrogenesis. Because fibrotic lung exhibit aberrant activation of Wnt/β-catenin signaling, these data collectively suggest that inhibition of Wnt/β-catenin signaling at the Dvl level may be an effective approach to the treatment of fibrotic lung diseases. - Highlights: • NSC668036 inhibited the proliferation and migration of NIH/3T3 fibroblasts. • NSC668036 suppressed the Wnt/β-catenin signaling pathway. • TGF-β-induced stimulation of profibrotic responses were inhibited by NSC668036. • NSC668036 can inhibit the development of bleomycin-induced pulmonary fibrosis.

The academic plagiarism and its punishments - a review

Directory of Open Access Journals (Sweden)

Roberto G. S. Berlinck

2011-06-01

Full Text Available Currently there is an increase in the occurrence of plagiarism in varied types of academic texts. Therefore, in agreement with the Brazilian Coordination of Improvement of Higher Education Personnel (CAPES policies, Brazilian higher education institutions should establish guidelines for the detection and inhibition of academic plagiarism. However, the notion of plagiarism is extremely complex, since the ability of textual construction acquired during education is also developed using others' words. Thus, it is necessary to better know the concept of plagiarism and its implications, as well as the consequences of plagiarism and the punishments that may result from it. Consequently, rules and policies to be established will be better founded in order to address the problem of plagiarism in academic texts in a comprehensive and consistent way, not only to inhibit plagiarism but also to promote education on how is possible to create texts in an original fashion.

Group Cooperation without Group Selection: Modest Punishment Can Recruit Much Cooperation.

Science.gov (United States)

Krasnow, Max M; Delton, Andrew W; Cosmides, Leda; Tooby, John

2015-01-01

Humans everywhere cooperate in groups to achieve benefits not attainable by individuals. Individual effort is often not automatically tied to a proportionate share of group benefits. This decoupling allows for free-riding, a strategy that (absent countermeasures) outcompetes cooperation. Empirically and formally, punishment potentially solves the evolutionary puzzle of group cooperation. Nevertheless, standard analyses appear to show that punishment alone is insufficient, because second-order free riders (those who cooperate but do not punish) can be shown to outcompete punishers. Consequently, many have concluded that other processes, such as cultural or genetic group selection, are required. Here, we present a series of agent-based simulations that show that group cooperation sustained by punishment easily evolves by individual selection when you introduce into standard models more biologically plausible assumptions about the social ecology and psychology of ancestral humans. We relax three unrealistic assumptions of past models. First, past models assume all punishers must punish every act of free riding in their group. We instead allow punishment to be probabilistic, meaning punishers can evolve to only punish some free riders some of the time. This drastically lowers the cost of punishment as group size increases. Second, most models unrealistically do not allow punishment to recruit labor; punishment merely reduces the punished agent's fitness. We instead realistically allow punished free riders to cooperate in the future to avoid punishment. Third, past models usually restrict agents to interact in a single group their entire lives. We instead introduce realistic social ecologies in which agents participate in multiple, partially overlapping groups. Because of this, punitive tendencies are more expressed and therefore more exposed to natural selection. These three moves toward greater model realism reveal that punishment and cooperation easily evolve by

Group Cooperation without Group Selection: Modest Punishment Can Recruit Much Cooperation.

Directory of Open Access Journals (Sweden)

Max M Krasnow

Full Text Available Humans everywhere cooperate in groups to achieve benefits not attainable by individuals. Individual effort is often not automatically tied to a proportionate share of group benefits. This decoupling allows for free-riding, a strategy that (absent countermeasures outcompetes cooperation. Empirically and formally, punishment potentially solves the evolutionary puzzle of group cooperation. Nevertheless, standard analyses appear to show that punishment alone is insufficient, because second-order free riders (those who cooperate but do not punish can be shown to outcompete punishers. Consequently, many have concluded that other processes, such as cultural or genetic group selection, are required. Here, we present a series of agent-based simulations that show that group cooperation sustained by punishment easily evolves by individual selection when you introduce into standard models more biologically plausible assumptions about the social ecology and psychology of ancestral humans. We relax three unrealistic assumptions of past models. First, past models assume all punishers must punish every act of free riding in their group. We instead allow punishment to be probabilistic, meaning punishers can evolve to only punish some free riders some of the time. This drastically lowers the cost of punishment as group size increases. Second, most models unrealistically do not allow punishment to recruit labor; punishment merely reduces the punished agent's fitness. We instead realistically allow punished free riders to cooperate in the future to avoid punishment. Third, past models usually restrict agents to interact in a single group their entire lives. We instead introduce realistic social ecologies in which agents participate in multiple, partially overlapping groups. Because of this, punitive tendencies are more expressed and therefore more exposed to natural selection. These three moves toward greater model realism reveal that punishment and cooperation

Fasitibant chloride, a kinin B2 receptor antagonist, and dexamethasone interact to inhibit carrageenan-induced inflammatory arthritis in rats

Science.gov (United States)

Valenti, Claudio; Giuliani, Sandro; Cialdai, Cecilia; Tramontana, Manuela; Maggi, Carlo Alberto

2012-01-01

BACKGROUND AND PURPOSE Bradykinin, through the kinin B2 receptor, is involved in inflammatory processes related to arthropathies. B2 receptor antagonists inhibited carrageenan-induced arthritis in rats in synergy with anti-inflammatory steroids. The mechanism(s) underlying this drug interaction was investigated. EXPERIMENTAL APPROACH Drugs inhibiting inflammatory mediators released by carrageenan were injected, alone or in combination, into the knee joint of pentobarbital anaesthetized rats 30 min before intra-articular administration of carrageenan. Their effects on the carrageenan-induced inflammatory responses (joint pain, oedema and neutrophil recruitment) and release of inflammatory mediators (prostaglandins, IL-1β, IL-6 and the chemokine GRO/CINC-1), were assessed after 6 h. KEY RESULTS The combination of fasitibant chloride (MEN16132) and dexamethasone was more effective than each drug administered alone in inhibiting knee joint inflammation and release of inflammatory mediators. Fasitibant chloride, MK571, atenolol, des-Arg9-[Leu8]-bradykinin (B2 receptor, leukotriene, catecholamine and B1 receptor antagonists, respectively) and dexketoprofen (COX inhibitor), reduced joint pain and, except for the latter, also diminished joint oedema. A combination of drugs inhibiting joint pain (fasitibant chloride, des-Arg9-[Leu8]-bradykinin, dexketoprofen, MK571 and atenolol) and oedema (fasitibant chloride, des-Arg9-[Leu8]-bradykinin, MK571 and atenolol) abolished the respective inflammatory response, producing inhibition comparable with that achieved with the combination of fasitibant chloride and dexamethasone. MK571 alone was able to block neutrophil recruitment. CONCLUSIONS AND IMPLICATIONS Bradykinin-mediated inflammatory responses to intra-articular carrageenan were not controlled by steroids, which were not capable of preventing bradykinin effects either by direct activation of the B2 receptor, or through the indirect effects mediated by release of eicosanoids

The Dark Side of Altruistic Third-Party Punishment

Science.gov (United States)

Leibbrandt, Andreas; Lopez-Perez, Raul

2011-01-01

This article experimentally studies punishment from unaffected third parties in ten different games. The authors show that third-party punishment exhibits several features that are arguably undesirable. First, third parties punish strongly a decider if she chooses a socially efficient or a Pareto efficient allocation and becomes the richest party…

Leptin Inhibits the Proliferation of Vascular Smooth Muscle Cells Induced by Angiotensin II through Nitric Oxide-Dependent Mechanisms

Directory of Open Access Journals (Sweden)

Amaia Rodríguez

2010-01-01

Full Text Available Objective. This study was designed to investigate whether leptin modifies angiotensin (Ang II-induced proliferation of aortic vascular smooth muscle cells (VSMCs from 10-week-old male Wistar and spontaneously hypertensive rats (SHR, and the possible role of nitric oxide (NO. Methods. NO and NO synthase (NOS activity were assessed by the Griess and 3H-arginine/citrulline conversion assays, respectively. Inducible NOS (iNOS and NADPH oxidase subutnit Nox2 expression was determined by Western-blot. The proliferative responses to Ang II were evaluated through enzymatic methods. Results. Leptin inhibited the Ang II-induced proliferative response of VSMCs from control rats. This inhibitory effect of leptin was abolished by NOS inhibitor, NMMA, and iNOS selective inhibitor, L-NIL, and was not observed in leptin receptor-deficient fa/fa rats. SHR showed increased serum leptin concentrations and lipid peroxidation. Despite a similar leptin-induced iNOS up-regulation, VSMCs from SHR showed an impaired NOS activity and NO production induced by leptin, and an increased basal Nox2 expression. The inhibitory effect of leptin on Ang II-induced VSMC proliferation was attenuated. Conclusion. Leptin blocks the proliferative response to Ang II through NO-dependent mechanisms. The attenuation of this inhibitory effect of leptin in spontaneous hypertension appears to be due to a reduced NO bioavailability in VSMCs.

Law & psychiatry: punishing juveniles who kill.

Science.gov (United States)

Appelbaum, Paul S

2012-10-01

Punishment of juvenile murderers forces policy makers to weigh the developmental immaturity of adolescents against the heinousness of their crimes. The U.S. Supreme Court has progressively limited the severity of punishments that can be imposed on juveniles, holding that their impulsivity, susceptibility to peer pressure, and more fluid character render them less culpable for their actions. Having eliminated the death penalty as a punishment, the Court recently struck down mandatory life sentences without prospect of parole. The decision is interesting for its emphasis on rehabilitation, opening the door to further restrictions on punitive sentences for juveniles-and perhaps for adults too.

Corporal punishment in schools: myths, problems and alternatives.

Science.gov (United States)

Dubanoski, R A; Inaba, M; Gerkewicz, K

1983-01-01

In many countries, corporal punishment of school children continues to be an officially or unofficially sanctioned form of institutional child abuse. Continuing support for the use of corporal punishment is related to the following factors: (1) widely held beliefs regarding the effectiveness of corporal punishment, (2) an unawareness of problems resulting from the use of physical punishment, and (3) a lack of knowledge about effective disciplinary alternatives. The purpose of this paper is threefold: One is to show that many of the beliefs are myths, e.g., corporal punishment is not needed to build character. The second purpose is to show that physical punishment can lead to more problems than it appears to solve, e.g., the punitive teacher is avoided, and thus, is not a positive factor in the child's education and development. The third purpose is to discuss two types of alternatives to punishment, the social learning approach and communication skills training. These positive methods of discipline not only enhance classroom behavior, but also facilitate learning. In an atmosphere free of abusing and demeaning acts and in a classroom characterized by positive mutual regard, teachers can maximize their effectiveness as teachers and students can maximize their effectiveness as learners.

Corporal punishment in South African schools : a neglected ...

African Journals Online (AJOL)

The South African education system historically has used corporal punishment to maintain discipline. Criticism of its effects led, in 1996, to the banning of this form of punishment. But this legislative intervention did not end the use of corporal punishment in schools. This article offers an explanation for the ongoing use of ...

The effect of monetary punishment on error evaluation in a Go/No-go task.

Science.gov (United States)

Maruo, Yuya; Sommer, Werner; Masaki, Hiroaki

2017-10-01

Little is known about the effects of the motivational significance of errors in Go/No-go tasks. We investigated the impact of monetary punishment on the error-related negativity (ERN) and error positivity (Pe) for both overt errors and partial errors, that is, no-go trials without overt responses but with covert muscle activities. We compared high and low punishment conditions where errors were penalized with 50 or 5 yen, respectively, and a control condition without monetary consequences for errors. Because we hypothesized that the partial-error ERN might overlap with the no-go N2, we compared ERPs between correct rejections (i.e., successful no-go trials) and partial errors in no-go trials. We also expected that Pe amplitudes should increase with the severity of the penalty for errors. Mean error rates were significantly lower in the high punishment than in the control condition. Monetary punishment did not influence the overt-error ERN and partial-error ERN in no-go trials. The ERN in no-go trials did not differ between partial errors and overt errors; in addition, ERPs for correct rejections in no-go trials without partial errors were of the same size as in go-trial. Therefore the overt-error ERN and the partial-error ERN may share similar error monitoring processes. Monetary punishment increased Pe amplitudes for overt errors, suggesting enhanced error evaluation processes. For partial errors an early Pe was observed, presumably representing inhibition processes. Interestingly, even partial errors elicited the Pe, suggesting that covert erroneous activities could be detected in Go/No-go tasks. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Amphiregulin mediates hCG-induced StAR expression and progesterone production in human granulosa cells.

Science.gov (United States)

Fang, Lanlan; Yu, Yiping; Zhang, Ruizhe; He, Jingyan; Sun, Ying-Pu

2016-04-26

Progesterone plays critical roles in maintaining a successful pregnancy at the early embryonic stage. Human chorionic gonadotropin (hCG) rapidly induces amphiregulin (AREG) expression. However, it remains unknown whether AREG mediates hCG-induced progesterone production. Thus, the objective of this study was to investigate the role of AREG in hCG-induced progesterone production and the underlying molecular mechanism in human granulosa cells; primary cells were used as the experimental model. We demonstrated that the inhibition of EGFR and the knockdown of AREG abolished hCG-induced steroidogenic acute regulatory protein (StAR) expression and progesterone production. Importantly, follicular fluid AREG levels were positively correlated with progesterone levels in the follicular fluid and serum. Treatment with AREG increased StAR expression and progesterone production, and these stimulatory effects were abolished by EGFR inhibition. Moreover, activation of ERK1/2, but not PI3K/Akt, signaling was required for the AREG-induced up-regulation of StAR expression and progesterone production. Our results demonstrate that AREG mediates hCG-induced StAR expression and progesterone production in human granulosa cells, providing novel evidence for the role of AREG in the regulation of steroidogenesis.

Self-Punishment Promotes Forgiveness in the Direct and Indirect Reciprocity Contexts.

Science.gov (United States)

Zhu, Ruida; Shen, Xueyi; Tang, Honghong; Ye, Peixia; Wang, Huagen; Mai, Xiaoqin; Liu, Chao

2017-06-01

Most previous studies regarding self-punishment have focused on the correlation between moral emotion and self-punishment. Only a few studies have attempted to understand self-punishment from the perspective of seeking forgiveness, and no study has yet directly tested whether wrongdoers' self-punishment promotes others to forgive the wrongdoers. In three studies, the participants judged the wrongdoers' self-punishment behaviors following an unfair allocation and reported the extent to which they forgave the wrongdoers. The results demonstrated that self-punishment did promote forgiveness in both the direct (Studies 1 and 2) and indirect reciprocity (Study 3) contexts. Consistent with costly signaling theory, the costlier the self-punishment was, the stronger the effect it had on forgiveness. Moreover, communicative self-punishment had a better effect than silent self-punishment when the cost was relatively high in the direct-reciprocity studies. These findings can guide us regarding how to address a damaged relationship via self-punishment when compensation is not feasible or acceptable.

Smad7 induces tumorigenicity by blocking TGF-beta-induced growth inhibition and apoptosis.

Science.gov (United States)

Halder, Sunil K; Beauchamp, R Daniel; Datta, Pran K

2005-07-01

Smad proteins play a key role in the intracellular signaling of the transforming growth factor beta (TGF-beta) superfamily of extracellular polypeptides that initiate signaling to regulate a wide variety of biological processes. The inhibitory Smad, Smad7, has been shown to function as intracellular antagonists of TGF-beta family signaling and is upregulated in several cancers. To determine the effect of Smad7-mediated blockade of TGF-beta signaling, we have stably expressed Smad7 in a TGF-beta-sensitive, well-differentiated, and non-tumorigenic cell line, FET, that was derived from human colon adenocarcinoma. Smad7 inhibits TGF-beta-induced transcriptional responses by blocking complex formation between Smad 2/3 and Smad4. While Smad7 has no effect on TGF-beta-induced activation of p38 MAPK and ERK, it blocks the phosphorylation of Akt by TGF-beta and enhances TGF-beta-induced phosphorylation of c-Jun. FET cells expressing Smad7 show anchorage-independent growth and enhance tumorigenicity in athymic nude mice. Smad7 blocks TGF-beta-induced growth inhibition by preventing TGF-beta-induced G1 arrest. Smad7 inhibits TGF-beta-mediated downregulation of c-Myc, CDK4, and Cyclin D1, and suppresses the expression of p21(Cip1). As a result, Smad7 inhibits TGF-beta-mediated downregulation of Rb phosphorylation. Furthermore, Smad7 inhibits the apoptosis of these cells. Together, Smad7 may increase the tumorigenicity of FET cells by blocking TGF-beta-induced growth inhibition and by inhibiting apoptosis. Thus, this study provides a mechanism by which a portion of human colorectal tumors may become refractory to tumor-suppressive actions of TGF-beta that might result in increased tumorigenicity.

Research on Corporal Punishment Effectiveness: Contributions and Limitations.

Science.gov (United States)

Hapkiewicz, Walter G.

A review of research literature on corporal punishment reveals that the incidence of corporal punishment has increased over the last twenty years and that it is widely used in some local school districts. Because it is limited by ethical problems, research cannot answer many questions about the direct and indirect effects of corporal punishment.…

Punishing the enemies of all mankind

NARCIS (Netherlands)

Smeulers, A.L.

2008-01-01

How do we and how should we punish perpetrators of international crimes such as war crimes, crimes against humanity, and genocide? Is it fair to hold individuals responsible for their role in manifestations of this type of collective violence? Do the punishments issued by international criminal

Rationality alters the rank between peer punishment and social exclusion

Science.gov (United States)

Sui, Xiukai; Wu, Bin; Wang, Long

2018-02-01

Peer punishment and social exclusion are two ways to punish free-riders. Previous work usually focuses on how their presence, either peer punishment or social exclusion, shapes the evolution of cooperation. Little attention has been given to which of these two strategies is favored by natural selection when they are both present. Here we investigate how rationality alters the ranking of these two strategies. Under weak rationality, for compulsory public goods games, peer punishment has an evolutionary advantage over social exclusion if the efficiency of punishment or the cost of exclusion is high. Furthermore, this rank is preserved for voluntary public goods games where loners are involved. Under strong rationality, however, peer punishment cannot prevail over social exclusion for both compulsory and voluntary public goods games. This indicates that rationality greatly alters the rank between peer punishment and social exclusion. Moreover, we find that this ranking is sensitive to the rationality. Our work thus gives an insight into how different types of punishment evolve.

Are the effects of benzodiazepines on discrimination and punishment dissociable?

Science.gov (United States)

Hodges, H; Green, S

1987-01-01

Studies have shown that benzodiazepines (BZs) both disrupt discrimination and increase resistance to punishment. Using a delayed response task, we provide evidence that effects of BZs on discrimination cannot be fully explained by deficits in either short or long term memory, or by intolerance for delay of reward. A schedule with rewarded, nonrewarded (Time out: TO) and conflict components was used to investigate effects in rats of compounds active at the BZ receptor on successive discrimination and punished responding in parallel. The GABA transaminase inhibitor ethanolamine-O-sulphate exerted additive effects with chlordiazepoxide (CDP) on punished but not TO responding. Both GABA and CDP injected into the amygdala selectively increased conflict rates, but with peripheral treatment CDP also increased TO rates. Two inverse BZ agonists, CGS 8216 and FG 7142 antagonzied the anti-conflict effects of GABA and CDP, given within the amygdala or peripherally, but the increase in TO rates induced by systemic CDP was counteracted only by peripheral treatments. These compounds also reduced rates of conflict responding below baseline, consistent with anxiogenic activity. Effects of the BZ antagonist Ro 15-1788 were broadly similar to those of the inverse agonists, except that it did not antagonise the anti-conflict action of intra-amygdaloid GABA, nor significantly reduce punished responding at the single dose used. We conclude from these results that the anti-conflict effects of BZs are mediated by a GABAergic amygdaloid mechanism, but that the same mechanism is not involved in BZ effects on discrimination.

Constitutional Liberty and the Progression of Punishment

OpenAIRE

Smith, Robert; Robinson, Zoe

2018-01-01

102 Cornell L. Rev. 413 (2017) The Eighth Amendment’s prohibition on cruel and unusual punishment has long been interpreted by scholars and judges to provide very limited protections for criminal defendants. This understanding of the Eighth Amendment claims that the prohibition is operationalized mostly to prevent torturous methods of punishment or halt the isolated use of a punishment practice that has fallen into long-term disuse. This Article challenges these assumptions. It argues that wh...

I dare you to punish me-vendettas in games of cooperation.

Directory of Open Access Journals (Sweden)

Katrin Fehl

Full Text Available Everybody has heard of neighbours, who have been fighting over some minor topic for years. The fight goes back and forth, giving the neighbours a hard time. These kind of reciprocal punishments are known as vendettas and they are a cross-cultural phenomenon. In evolutionary biology, punishment is seen as a mechanism for maintaining cooperative behaviour. However, this notion of punishment excludes vendettas. Vendettas pose a special kind of evolutionary problem: they incur high costs on individuals, i.e. costs of punishing and costs of being punished, without any benefits. Theoretically speaking, punishment should be rare in dyadic relationships and vendettas would not evolve under natural selection. In contrast, punishment is assumed to be more efficient in group environments which then can pave the way for vendettas. Accordingly, we found that under the experimental conditions of a prisoner's dilemma game, human participants punished only rarely and vendettas are scarce. In contrast, we found that participants retaliated frequently in the group environment of a public goods game. They even engaged in cost-intense vendettas (i.e. continuous retaliation, especially when the first punishment was unjustified or ambiguous. Here, punishment was mainly targeted at defectors in the beginning, but provocations led to mushrooming of counter-punishments. Despite the counter-punishing behaviour, participants were able to enhance cooperation levels in the public goods game. Few participants even seemed to anticipate the outbreak of costly vendettas and delayed their punishment to the last possible moment. Overall, our results highlight the importance of different social environments while studying punishment as a cooperation-enhancing mechanism.

I dare you to punish me-vendettas in games of cooperation.

Science.gov (United States)

Fehl, Katrin; Sommerfeld, Ralf D; Semmann, Dirk; Krambeck, Hans-Jürgen; Milinski, Manfred

2012-01-01

Everybody has heard of neighbours, who have been fighting over some minor topic for years. The fight goes back and forth, giving the neighbours a hard time. These kind of reciprocal punishments are known as vendettas and they are a cross-cultural phenomenon. In evolutionary biology, punishment is seen as a mechanism for maintaining cooperative behaviour. However, this notion of punishment excludes vendettas. Vendettas pose a special kind of evolutionary problem: they incur high costs on individuals, i.e. costs of punishing and costs of being punished, without any benefits. Theoretically speaking, punishment should be rare in dyadic relationships and vendettas would not evolve under natural selection. In contrast, punishment is assumed to be more efficient in group environments which then can pave the way for vendettas. Accordingly, we found that under the experimental conditions of a prisoner's dilemma game, human participants punished only rarely and vendettas are scarce. In contrast, we found that participants retaliated frequently in the group environment of a public goods game. They even engaged in cost-intense vendettas (i.e. continuous retaliation), especially when the first punishment was unjustified or ambiguous. Here, punishment was mainly targeted at defectors in the beginning, but provocations led to mushrooming of counter-punishments. Despite the counter-punishing behaviour, participants were able to enhance cooperation levels in the public goods game. Few participants even seemed to anticipate the outbreak of costly vendettas and delayed their punishment to the last possible moment. Overall, our results highlight the importance of different social environments while studying punishment as a cooperation-enhancing mechanism.

I Dare You to Punish Me—Vendettas in Games of Cooperation

Science.gov (United States)

Fehl, Katrin; Sommerfeld, Ralf D.; Semmann, Dirk; Krambeck, Hans-Jürgen; Milinski, Manfred

2012-01-01

Everybody has heard of neighbours, who have been fighting over some minor topic for years. The fight goes back and forth, giving the neighbours a hard time. These kind of reciprocal punishments are known as vendettas and they are a cross-cultural phenomenon. In evolutionary biology, punishment is seen as a mechanism for maintaining cooperative behaviour. However, this notion of punishment excludes vendettas. Vendettas pose a special kind of evolutionary problem: they incur high costs on individuals, i.e. costs of punishing and costs of being punished, without any benefits. Theoretically speaking, punishment should be rare in dyadic relationships and vendettas would not evolve under natural selection. In contrast, punishment is assumed to be more efficient in group environments which then can pave the way for vendettas. Accordingly, we found that under the experimental conditions of a prisoner’s dilemma game, human participants punished only rarely and vendettas are scarce. In contrast, we found that participants retaliated frequently in the group environment of a public goods game. They even engaged in cost-intense vendettas (i.e. continuous retaliation), especially when the first punishment was unjustified or ambiguous. Here, punishment was mainly targeted at defectors in the beginning, but provocations led to mushrooming of counter-punishments. Despite the counter-punishing behaviour, participants were able to enhance cooperation levels in the public goods game. Few participants even seemed to anticipate the outbreak of costly vendettas and delayed their punishment to the last possible moment. Overall, our results highlight the importance of different social environments while studying punishment as a cooperation-enhancing mechanism. PMID:23028776

AS1411-Induced Growth Inhibition of Glioma Cells by Up-Regulation of p53 and Down-Regulation of Bcl-2 and Akt1 via Nucleolin.

Directory of Open Access Journals (Sweden)

Ye Cheng

Full Text Available AS1411 binds nucleolin (NCL and is the first oligodeoxynucleotide aptamer to reach phase I and II clinical trials for the treatment of several cancers. However, the mechanisms by which AS1411 targets and kills glioma cells and tissues remain unclear. Here we report that AS1411 induces cell apoptosis and cycle arrest, and inhibits cell viability by up-regulation of p53 and down-regulation of Bcl-2 and Akt1 in human glioma cells. NCL was overexpressed in both nucleus and cytoplasm in human glioma U87, U251 and SHG44 cells compared to normal human astrocytes (NHA. AS1411 bound NCL and inhibited the proliferation of glioma cells but not NHA, which was accompanied with up-regulation of p53 and down-regulation of Bcl-2 and Akt1. Moreover, AS1411 treatment resulted in the G2/M cell cycle arrest in glioma cells, which was however abolished by overexpression of NCL. Further, AS1411 induced cell apoptosis, which was prevented by silencing of p53 and overexpression of Bcl-2. In addition, AS1411 inhibited the migration and invasion of glioma cells in an Akt1-dependent manner. Importantly, AS1411 inhibited the growth of glioma xenograft and prolonged the survival time of glioma tumor-bearing mice. These results revealed a promising treatment of glioma by oligodeoxynucleotide aptamer.

Attitudes of Kuwaiti parents toward physical punishment of children.

Science.gov (United States)

Qasem, F S; Mustafa, A A; Kazem, N A; Shah, N M

1998-12-01

The major aim was to describe parental attitudes to physical punishments and examine their sociodemographic correlates. A related aim was to assess the association of parents' own experience of physical punishment with attitudes to punishment of children. A cross-sectional survey was conducted during the second week of December, 1996 in five general clinics covering the major administrative areas of Kuwait: 337 Kuwaiti mothers and fathers with at least one living child were contacted; 95% were successfully interviewed using a structured questionnaire. Eighty-six percent of parents agreed with physical punishment as a means of child disciplining. Agreement with punishment was higher in case of serious misbehaviors such as stealing (63%), sniffing glue and using drugs (77%). Multiple regression results showed that parent's lower level of education and Bedouin ethnicity were positively associated with agreement on physical punishment. Larger percentages of parents who had experienced physical punishments themselves agreed with such punishment to discipline their children, but this was not statistically significant. In recent years education has become widespread for both sexes. An inverse association between educational level and agreement on physical beating suggest that attitudes to this form of child disciplining are changing. Those with a Bedouin ethnic background still adhere more strictly to the traditional forms of child disciplining including physical beating. There is a need for conducting research on the possible negative psychosocial impacts of physical punishment in view of findings from other countries.

Justine effect: punishment of the unduly self-sacrificing cooperative individuals.

Science.gov (United States)

Kuběna, Aleš Antonín; Houdek, Petr; Lindová, Jitka; Příplatová, Lenka; Flegr, Jaroslav

2014-01-01

Allowing players to punish their opponents in Public Goods Game sustains cooperation within a group and thus brings advantage to the cooperative individuals. However, the possibility of punishment of the co-players can result in antisocial punishment, the punishment of those players who contribute the most in the group. To better understand why antisocial punishment exists, it must be determined who are the anti-social punishers and who are their primary targets. For resolving these questions we increased the number of players in a group from usual four to twelve. Each group played six rounds of the standard Public Goods Game and six rounds of the Public Goods Game with punishment. Each player in each round received 20 CZK ($ 1.25). Players (N = 118) were rematched after each round so that they would not take into consideration opponents' past behavior. The amount of the punishment received correlated negatively with the contribution (ρ = -0.665, pboarder of the upper quartile. The antisocial punishment was present in all groups, and in eight out of ten groups the Justine Effect (the positive correlation between the contribution to the public pool and the risk of suffering punishment in the subpopulation of altruistic players) emerged. In our sample, 22.5% subjects, all of them Free riders and low contributors, punished the altruistic players. The results of our experimental game-study revealed the existence of the Justine effect--the positive correlation between the contribution to the public pool by a subpopulation of the most altruistic players, and the amount of punishment these players obtained from free-riders.

Against the Corporal Punishment of Children

Science.gov (United States)

Clark, John

2004-01-01

John Wilson suggests there are six advantages for corporal punishment: cheap and easy to administer, effective deterrent, effective reform, adjustable pain, fair because of similar dislike of pain, no permanent damage. None of these survive close scrutiny. An alternative, deontological argument against corporal punishment is proposed building on…

Relationship of corporal punishment and antisocial behavior by neighborhood.

Science.gov (United States)

Grogan-Kaylor, Andrew

2005-10-01

To examine the relationship of corporal punishment with children's behavior problems while accounting for neighborhood context and while using stronger statistical methods than previous literature in this area, and to examine whether different levels of corporal punishment have different effects in different neighborhood contexts. Longitudinal cohort study. General community. 1943 mother-child pairs from the National Longitudinal Survey of Youth. Internalizing and externalizing behavior problem scales of the Behavior Problems Index. Parental use of corporal punishment was associated with a 0.71 increase (Pcorporal punishment and children's externalizing behavior problems was not dependent on neighborhood context. The research found no discernible relationship between corporal punishment and internalizing behavior problems.

An economic experiment reveals that humans prefer pool punishment to maintain the commons

Science.gov (United States)

Traulsen, Arne; Röhl, Torsten; Milinski, Manfred

2012-01-01

Punishment can stabilize costly cooperation and ensure the success of a common project that is threatened by free-riders. Punishment mechanisms can be classified into pool punishment, where the punishment act is carried out by a paid third party, (e.g. a police system or a sheriff), and peer punishment, where the punishment act is carried out by peers. Which punishment mechanism is preferred when both are concurrently available within a society? In an economic experiment, we show that the majority of subjects choose pool punishment, despite being costly even in the absence of defectors, when second-order free-riders, cooperators that do not punish, are also punished. Pool punishers are mutually enforcing their support for the punishment organization, stably trapping each other. Our experimental results show how organized punishment could have displaced individual punishment in human societies. PMID:22764167

Stimulus variation as a means of enhancing punishment effects.

OpenAIRE

Charlop, M H; Burgio, L D; Iwata, B A; Ivancic, M T

1988-01-01

We compared the effects of varied punishers (presentation of one of three available punishers) with the single presentation of one of the punishers on the occurrence of inappropriate behaviors with three developmentally delayed children. Two children were presented with varied-punisher conditions in which either overcorrection, time-out, or a verbal "no" was presented contingent upon inappropiate behavior. A loud noise was substituted for overcorrection for a third child. Results of the multi...

The evolution of anti-social punishment in optional public goods games

Science.gov (United States)

Rand, David G.; Nowak, Martin A.

2011-01-01

Cooperation, where one individual incurs a cost to help another, is a fundamental building block of the natural world and of human society. It has been suggested that costly punishment can promote the evolution of cooperation, with the threat of punishment deterring free-riders. Recent experiments, however, have revealed the existence of ‘anti-social’ punishment, where non-cooperators punish cooperators. While various theoretical models find that punishment can promote the evolution of cooperation, these models a priori exclude the possibility of anti-social punishment. Here we extend the standard theory of optional public goods games to include the full set of punishment strategies. We find that punishment no longer increases cooperation, and that selection favors substantial levels of anti-social punishment for a wide range of parameters. Furthermore, we conduct behavioral experiments, which lead to results that are consistent with our model predictions. As opposed to an altruistic act that promotes cooperation, punishment is mostly a self-interested tool for protecting oneself against potential competitors. PMID:21847108

The Ethics of Proportionate Punishment

DEFF Research Database (Denmark)

Ryberg, Jesper

The book deals with the question of how severely criminals should be punished for their crimes. It provides a critical investigation of a fundamental principle in penal theory and practice: the principle of proportionality.......The book deals with the question of how severely criminals should be punished for their crimes. It provides a critical investigation of a fundamental principle in penal theory and practice: the principle of proportionality....

Behavioral studies with anxiolytic drugs. IV. Serotonergic involvement in the effects of buspirone on punished behavior of pigeons

International Nuclear Information System (INIS)

Witkin, J.M.; Mansbach, R.S.; Barrett, J.E.; Bolger, G.T.; Skolnick, P.; Weissman, B.

1987-01-01

Interactions of the nonbenzodiazepine anxiolytic, buspirone, with serotonin (5-HT) were studied using behavioral and neurochemical procedures. Punished responding was studied in pigeons as this behavior is a generally acknowledged preclinical predictor of anxiolytic activity and because buspirone increases punished responding of pigeons with greater potency and efficacy than in other species. Keypeck responses were maintained under either fixed-interval or fixed-ratio schedules of food presentation; every 30th response produced a brief electric shock and suppressed responding (punishment). Buspirone (0.1-5.6 mg/kg i.m.) produced dose-related increases in punished responding which reached a maximum at 1 mg/kg. A serotonin agonist, MK-212 (0.01 mg/kg), antagonized whereas the 5-HT antagonist, cyproheptadine (0.01 mg/kg), potentiated the effects of buspirone without having behavioral effects of their own. The characteristics of [ 3 H]-5-HT binding in pigeon brain membranes were similar to results reported in mammalian brain. Neither buspirone, MJ-13805 (gepirone, a related analog), nor MJ-13653 (a buspirone metabolite), significantly affected [ 3 H]-5-HT binding and none of the compounds appreciably inhibited uptake of [ 3 H]-5-HT into pigeon cerebral synaptosomes. Hill coefficients significantly less than unity for all drugs except 5-HT suggested multiple serotonergic binding sites for buspirone and analogs. Buspirone and MJ-13805 (1 nM) inhibited [ 3 H]ketanserin binding (a measure of 5-HT2 binding sites) in pigeon cerebrum with Ki values above 10(-6) M. The number of [ 3 H]ketanserin binding sites was estimated to be 109 fmol/mg of protein in pigeon cerebrum compared to 400 fmol/mg of protein in rat cerebrum

Mechanism of palytoxin-induced [3H]norepinephrine release from a rat pheochromocytoma cell line

International Nuclear Information System (INIS)

Tatsumi, M.; Takahashi, M.; Ohizumi, Y.

1984-01-01

Palytoxin, isolated from the zoanthid Palytoha species, is one of the most potent marine toxins. Palytoxin caused a release of [ 3 H]norepinephrine from clonal rat pheochromocytoma cells in a concentration-dependent manner. This releasing action of palytoxin was markedly inhibited or abolished by Co 2+ or Ca 2+ -free medium, but was not modified by tetrodotoxin. The release of [ 3 H]norepinephrine induced by a low concentration of palytoxin was abolished in sodium-free medium and increased as the external Na+ concentrations were increased, but the release induced by a high concentration was unaffected by varying the concentration of external Na + . The release of [ 3 H]norepinephrine induced by both concentrations of palytoxin increased with increasing Ca 2+ concentrations. Palytoxin caused a concentration-dependent increase in 22 Na and 45 Ca influxes into pheochromocytoma cells. The palytoxin-induced 45 Ca influx was markedly inhibited by Co 2+ , whereas the palytoxin-induced 22 Na influx was not affected by tetrodotoxin. These results suggest that in pheochromocytoma cells the [ 3 H]norepinephrine release induced by lower concentrations of palytoxin is primarily brought about by increasing tetrodotoxin-insensitive Na + permeability across the cell membrane, whereas that induced by higher concentrations is mainly caused by a direct increase in Ca 2+ influx into them

Celastrol inhibits TGF-β1-induced epithelial–mesenchymal transition by inhibiting Snail and regulating E-cadherin expression

Energy Technology Data Exchange (ETDEWEB)

Kang, Hyereen; Lee, Minjae [Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul 138-736 (Korea, Republic of); Jang, Sung-Wuk, E-mail: swjang@amc.seoul.kr [Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul 138-736 (Korea, Republic of); Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul 138-736 (Korea, Republic of)

2013-08-09

Highlights: •We investigated the effects of celastrol on TGF-β1-induced EMT in epithelial cells. •Celastrol regulates TGF-β1-induced morphological changes and E-cadherin expression. •Celastrol inhibits TGF-β1-induced Snail expression. •Celastrol strongly suppresses TGF-β1-induced invasion in MDCK and A549 cells. -- Abstract: The epithelial–mesenchymal transition (EMT) is a pivotal event in the invasive and metastatic potentials of cancer progression. Celastrol inhibits the proliferation of a variety of tumor cells including leukemia, glioma, prostate, and breast cancer; however, the possible role of celastrol in the EMT is unclear. We investigated the effect of celastrol on the EMT. Transforming growth factor-beta 1 (TGF-β1) induced EMT-like morphologic changes and upregulation of Snail expression. The downregulation of E-cadherin expression and upregulation of Snail in Madin–Darby Canine Kidney (MDCK) and A549 cell lines show that TGF-β1-mediated the EMT in epithelial cells; however, celastrol markedly inhibited TGF-β1-induced morphologic changes, Snail upregulation, and E-cadherin expression. Migration and invasion assays revealed that celastrol completely inhibited TGF-β1-mediated cellular migration in both cell lines. These findings indicate that celastrol downregulates Snail expression, thereby inhibiting TGF-β1-induced EMT in MDCK and A549 cells. Thus, our findings provide new evidence that celastrol suppresses lung cancer invasion and migration by inhibiting TGF-β1-induced EMT.

Justine effect: punishment of the unduly self-sacrificing cooperative individuals.

Directory of Open Access Journals (Sweden)

Aleš Antonín Kuběna

Full Text Available Allowing players to punish their opponents in Public Goods Game sustains cooperation within a group and thus brings advantage to the cooperative individuals. However, the possibility of punishment of the co-players can result in antisocial punishment, the punishment of those players who contribute the most in the group. To better understand why antisocial punishment exists, it must be determined who are the anti-social punishers and who are their primary targets.For resolving these questions we increased the number of players in a group from usual four to twelve. Each group played six rounds of the standard Public Goods Game and six rounds of the Public Goods Game with punishment. Each player in each round received 20 CZK ($ 1.25. Players (N = 118 were rematched after each round so that they would not take into consideration opponents' past behavior.The amount of the punishment received correlated negatively with the contribution (ρ = -0.665, p<0.001. However, this correlation was positive for players in the highest contributors-quartile (ρ = 0.254, p<0.001. Therefore, the graph of relation between the contribution given and punishment obtained was U-shaped (R2 = 0.678, p<0.001 with the inflection point near the left boarder of the upper quartile. The antisocial punishment was present in all groups, and in eight out of ten groups the Justine Effect (the positive correlation between the contribution to the public pool and the risk of suffering punishment in the subpopulation of altruistic players emerged. In our sample, 22.5% subjects, all of them Free riders and low contributors, punished the altruistic players.The results of our experimental game-study revealed the existence of the Justine effect--the positive correlation between the contribution to the public pool by a subpopulation of the most altruistic players, and the amount of punishment these players obtained from free-riders.

Alternatives to Using Exercise as Punishment

Science.gov (United States)

Rosenthal, Maura; Pagnano-Richardson, Karen; Burak, Lydia

2010-01-01

Although the National Association for Sport and Physical Education and other governing bodies discourage coaches and teachers from using exercise as punishment, its use is still fairly widespread. In order to better understand why coaches and teachers use exercise as punishment, this article examines some of the findings from a recent study (Burak…

Avoiding Corporal Punishment in School: Issues for School Counselors.

Science.gov (United States)

Forness, Steven R.; Sinclair, Esther

1984-01-01

Focuses on the legal status and societal values that promote the use of corporal punishment in public schools, and on the role of the elementary school counselor in helping teachers deal with punishment. Discusses factors affecting the effectiveness of punishment and suggests alternatives. (JAC)

Trichilia monadelpha Bark Extracts Inhibit Carrageenan-Induced ...

African Journals Online (AJOL)

The present study was undertaken to evaluate the anti-inflammatory properties of aqueous (TWE), alcoholic (TAE) and petroleum ether extract (TPEE) of T. ... The reference anti-inflammatory drugs (diclofenac and dexamethasone) inhibited the chick-carrageenan-induced footpad oedema, with maximal inhibitions of ...

Competitions between prosocial exclusions and punishments in finite populations

Science.gov (United States)

Liu, Linjie; Chen, Xiaojie; Szolnoki, Attila

2017-04-01

Prosocial punishment has been proved to be a powerful mean to promote cooperation. Recent studies have found that social exclusion, which indeed can be regarded as a kind of punishment, can also support cooperation. However, if prosocial punishment and exclusion are both present, it is still unclear which strategy is more advantageous to curb free-riders. Here we first study the direct competition between different types of punishment and exclusion. We find that pool (peer) exclusion can always outperform pool (peer) punishment both in the optional and in the compulsory public goods game, no matter whether second-order sanctioning is considered or not. Furthermore, peer exclusion does better than pool exclusion both in the optional and in the compulsory game, but the situation is reversed in the presence of second-order exclusion. Finally, we extend the competition among all possible sanctioning strategies and find that peer exclusion can outperform all other strategies in the absence of second-order exclusion and punishment, while pool exclusion prevails when second-order sanctioning is possible. Our results demonstrate that exclusion is a more powerful strategy than punishment for the resolution of social dilemmas.

Inhibition by acrolein of light-induced stomatal opening through inhibition of inward-rectifying potassium channels in Arabidopsis thaliana.

Science.gov (United States)

Islam, Md Moshiul; Ye, Wenxiu; Matsushima, Daiki; Khokon, Md Atiqur Rahman; Munemasa, Shintaro; Nakamura, Yoshimasa; Murata, Yoshiyuki

2015-01-01

Acrolein is a reactive α,β-unsaturated aldehyde derived from lipid peroxides, which are produced in plants under a variety of stress. We investigated effects of acrolein on light-induced stomatal opening using Arabidopsis thaliana. Acrolein inhibited light-induced stomatal opening in a dose-dependent manner. Acrolein at 100 μM inhibited plasma membrane inward-rectifying potassium (Kin) channels in guard cells. Acrolein at 100 μM inhibited Kin channel KAT1 expressed in a heterologous system using Xenopus leaves oocytes. These results suggest that acrolein inhibits light-induced stomatal opening through inhibition of Kin channels in guard cells.

Justine Effect: Punishment of the Unduly Self-Sacrificing Cooperative Individuals

Science.gov (United States)

Kuběna, Aleš Antonín; Houdek, Petr; Lindová, Jitka; Příplatová, Lenka; Flegr, Jaroslav

2014-01-01

Background Allowing players to punish their opponents in Public Goods Game sustains cooperation within a group and thus brings advantage to the cooperative individuals. However, the possibility of punishment of the co-players can result in antisocial punishment, the punishment of those players who contribute the most in the group. To better understand why antisocial punishment exists, it must be determined who are the anti-social punishers and who are their primary targets. Methods For resolving these questions we increased the number of players in a group from usual four to twelve. Each group played six rounds of the standard Public Goods Game and six rounds of the Public Goods Game with punishment. Each player in each round received 20 CZK ($ 1.25). Players (N = 118) were rematched after each round so that they would not take into consideration opponents' past behavior. Results The amount of the punishment received correlated negatively with the contribution (ρ = −0.665, ppunishment obtained was U-shaped (R2 = 0.678, ppunishment was present in all groups, and in eight out of ten groups the Justine Effect (the positive correlation between the contribution to the public pool and the risk of suffering punishment in the subpopulation of altruistic players) emerged. In our sample, 22.5% subjects, all of them Free riders and low contributors, punished the altruistic players. Conclusions The results of our experimental game-study revealed the existence of the Justine effect – the positive correlation between the contribution to the public pool by a subpopulation of the most altruistic players, and the amount of punishment these players obtained from free-riders. PMID:24670974

Indirubin-3-Oxime Prevents H2O2-Induced Neuronal Apoptosis via Concurrently Inhibiting GSK3β and the ERK Pathway.

Science.gov (United States)

Yu, Jie; Zheng, Jiacheng; Lin, Jiajia; Jin, Linlu; Yu, Rui; Mak, Shinghung; Hu, Shengquan; Sun, Hongya; Wu, Xiang; Zhang, Zaijun; Lee, Mingyuen; Tsim, Wahkeung; Su, Wei; Zhou, Wenhua; Cui, Wei; Han, Yifan; Wang, Qinwen

2017-05-01

Oxidative stress-induced neuronal apoptosis plays an important role in many neurodegenerative disorders. In this study, we have shown that indirubin-3-oxime, a derivative of indirubin originally designed for leukemia therapy, could prevent hydrogen peroxide (H 2 O 2 )-induced apoptosis in both SH-SY5Y cells and primary cerebellar granule neurons. H 2 O 2 exposure led to the increased activities of glycogen synthase kinase 3β (GSK3β) and extracellular signal-regulated kinase (ERK) in SH-SY5Y cells. Indirubin-3-oxime treatment significantly reversed the altered activity of both the PI3-K/Akt/GSK3β cascade and the ERK pathway induced by H 2 O 2 . In addition, both GSK3β and mitogen-activated protein kinase inhibitors significantly prevented H 2 O 2 -induced neuronal apoptosis. Moreover, specific inhibitors of the phosphoinositide 3-kinase (PI3-K) abolished the neuroprotective effects of indirubin-3-oxime against H 2 O 2 -induced neuronal apoptosis. These results strongly suggest that indirubin-3-oxime prevents H 2 O 2 -induced apoptosis via concurrent inhibiting GSK3β and the ERK pathway in SH-SY5Y cells, providing support for the use of indirubin-3-oxime to treat neurodegenerative disorders caused or exacerbated by oxidative stress.

Rewarding and punishing children of different social behavior

Directory of Open Access Journals (Sweden)

Lalić-Vučetić Nataša

2007-01-01

Full Text Available This paper discusses the actions of rewarding and punishing children of different social behavior. The application of rewarding and punishing demands knowing and fulfilling several conditions which enable their efficiency: the nature of reward and punishment, the way in which pupils receive them, the context in which rewarding and punishing takes place and the characteristics of the subject (age, gender, cognitive capacities, social behavior. It is familiar that teachers prefer pupils who are cooperative, socially responsible, prone to conforming to school rules, kind, friendly and polite, while teacher’s work can often be aggravated on the part of the pupils who are aggressive, asocial, socially irresponsible, disruptive or prone to deviant behavior. In order to accomplish the outcomes which want to be achieved by these procedures, in applying reward and punishment, it is necessary to figure out carefully the criteria of rewarding and punishing and adhere to them consistently, paying attention to the characteristics of social behavior of the pupils. A special chapter is devoted to the consideration of unjust reward and punishment as one of the phenomena present in the experience of a large number of children. The analyzed problems assume adequate preparation of teachers, that is, the knowledge about basic characteristics of upbringing procedures applied in working with pupils, and which will have as a result a more successful social behavior, a more positive attitude towards school and studying.

Controlling young people through treatment and punishment

DEFF Research Database (Denmark)

Bengtsson, Tea Torbenfeldt

2015-01-01

This chapter demonstrates how both treatment and punishment is part of controlling young people involved in crime in the Danish welfare state. Lately there has been an increase in the use of confinement in young offenders institutions and thus a turn towards stricter punishments for crime. However......, treatment aiming at rehabilitation is still an integrated part of the system and the organization of the young offenders institutions. For the young people subjected to control both treatment and punishment are regarded as effective means of risk-control but there are also limitations and unintended results...

The investigation of minoxidil-induced [Ca2+]i rises and non-Ca2+-triggered cell death in PC3 human prostate cancer cells.

Science.gov (United States)

Chen, I-Shu; Chou, Chiang-Ting; Liu, Yuan-Yuarn; Yu, Chia-Cheng; Liang, Wei-Zhe; Kuo, Chun-Chi; Shieh, Pochuen; Kuo, Daih-Huang; Chen, Fu-An; Jan, Chung-Ren

2017-02-01

Minoxidil is clinically used to prevent hair loss. However, its effect on Ca 2+ homeostasis in prostate cancer cells is unclear. This study explored the effect of minoxidil on cytosolic-free Ca 2+ levels ([Ca 2+ ] i ) and cell viability in PC3 human prostate cancer cells. Minoxidil at concentrations between 200 and 800 μM evoked [Ca 2+ ] i rises in a concentration-dependent manner. This Ca 2+ signal was inhibited by 60% by removal of extracellular Ca 2+ . Minoxidil-induced Ca 2+ influx was confirmed by Mn 2+ -induced quench of fura-2 fluorescence. Pre-treatment with the protein kinase C (PKC) inhibitor GF109203X, PKC activator phorbol 12-myristate 13 acetate (PMA), nifedipine and SKF96365 inhibited minoxidil-induced Ca 2+ signal in Ca 2+ containing medium by 60%. Treatment with the endoplasmic reticulum Ca 2+ pump inhibitor 2,5-ditert-butylhydroquinone (BHQ) in Ca 2+ -free medium abolished minoxidil-induced [Ca 2+ ] i rises. Conversely, treatment with minoxidil abolished BHQ-induced [Ca 2+ ] i rises. Inhibition of phospholipase C (PLC) with U73122 abolished minoxidil-evoked [Ca 2+ ] i rises. Overnight treatment with minoxidil killed cells at concentrations of 200-600 μM in a concentration-dependent fashion. Chelation of cytosolic Ca 2+ with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid/AM (BAPTA/AM) did not prevent minoxidil's cytotoxicity. Together, in PC3 cells, minoxidil induced [Ca 2+ ] i rises that involved Ca 2+ entry through PKC-regulated store-operated Ca 2+ channels and PLC-dependent Ca 2+ release from the endoplasmic reticulum. Minoxidil-induced cytotoxicity in a Ca 2+ -independent manner.

Angiotensin II inhibits the Na+-K+ pump via PKC-dependent activation of NADPH oxidase.

Science.gov (United States)

White, Caroline N; Figtree, Gemma A; Liu, Chia-Chi; Garcia, Alvaro; Hamilton, Elisha J; Chia, Karin K M; Rasmussen, Helge H

2009-04-01

The sarcolemmal Na(+)-K(+) pump, pivotal in cardiac myocyte function, is inhibited by angiotensin II (ANG II). Since ANG II activates NADPH oxidase, we tested the hypothesis that NADPH oxidase mediates the pump inhibition. Exposure to 100 nmol/l ANG II increased superoxide-sensitive fluorescence of isolated rabbit ventricular myocytes. The increase was abolished by pegylated superoxide dismutase (SOD), by the NADPH oxidase inhibitor apocynin, and by myristolated inhibitory peptide to epsilon-protein kinase C (epsilonPKC), previously implicated in ANG II-induced Na(+)-K(+) pump inhibition. A role for epsilonPKC was also supported by an ANG II-induced increase in coimmunoprecipitation of epsilonPKC with the receptor for the activated kinase and with the cytosolic p47(phox) subunit of NADPH oxidase. ANG II decreased electrogenic Na(+)-K(+) pump current in voltage-clamped myocytes. The decrease was abolished by SOD, by the gp91ds inhibitory peptide that blocks assembly and activation of NADPH oxidase, and by epsilonPKC inhibitory peptide. Since colocalization should facilitate NADPH oxidase-dependent regulation of the Na(+)-K(+) pump, we examined whether there is physical association between the pump subunits and NADPH oxidase. The alpha(1)-subunit coimmunoprecipitated with caveolin 3 and with membrane-associated p22(phox) and cytosolic p47(phox) NADPH oxidase subunits at baseline. ANG II had no effect on alpha(1)/caveolin 3 or alpha(1)/p22(phox) interaction, but it increased alpha(1)/p47(phox) coimmunoprecipitation. We conclude that ANG II inhibits the Na(+)-K(+) pump via PKC-dependent NADPH oxidase activation.

Crime and punishment: Does it pay to punish?

Science.gov (United States)

Iglesias, J. R.; Semeshenko, V.; Schneider, E. M.; Gordon, M. B.

2012-08-01

Crime is the result of a rational distinctive balance between the benefits and costs of an illegal act. This idea was proposed by Becker more than forty years ago (Becker (1968) [1]). In this paper, we simulate a simple artificial society, in which agents earn fixed wages and can augment (or lose) wealth as a result of a successful (or not) act of crime. The probability of apprehension depends on the gravity of the crime, and the punishment takes the form of imprisonment and fines. We study the costs of the law enforcement system required for keeping crime within acceptable limits, and compare it with the harm produced by crime. A sharp phase transition is observed as a function of the probability of punishment, and this transition exhibits a clear hysteresis effect, suggesting that the cost of reversing a deteriorated situation might be much higher than that of maintaining a relatively low level of delinquency. Besides, we analyze economic consequences that arise from crimes under different scenarios of criminal activity and probabilities of apprehension.

Sustainable institutionalized punishment requires elimination of second-order free-riders

Science.gov (United States)

Perc, Matjaž

2012-03-01

Although empirical and theoretical studies affirm that punishment can elevate collaborative efforts, its emergence and stability remain elusive. By peer-punishment the sanctioning is something an individual elects to do depending on the strategies in its neighborhood. The consequences of unsustainable efforts are therefore local. By pool-punishment, on the other hand, where resources for sanctioning are committed in advance and at large, the notion of sustainability has greater significance. In a population with free-riders, punishers must be strong in numbers to keep the ``punishment pool'' from emptying. Failure to do so renders the concept of institutionalized sanctioning futile. We show that pool-punishment in structured populations is sustainable, but only if second-order free-riders are sanctioned as well, and to a such degree that they cannot prevail. A discontinuous phase transition leads to an outbreak of sustainability when punishers subvert second-order free-riders in the competition against defectors.

Punishment as a means of competition: implications for strong reciprocity theory.

Science.gov (United States)

Paál, Tünde; Bereczkei, Tamás

2015-01-01

Strong negative reciprocity, that is, sanctions imposed on norm violators at the punisher's own expense, has powerful cooperation-enhancing effects in both real-life and experimental game situations. However, it is plausible that punishment may obtain alternative roles depending on social context and the personality characteristics of participants. We examined the occurrence of punishing behavior among 80 subjects in a strongly competitive Public Goods game setting. Despite the punishment condition, the amount of the contributions decreased steadily during the game. The amount of contributions had no significant effect on received and imposed punishments. The results indicate that certain social contexts (in this case, intensive competition) exert modifying effects on the role that punishment takes on. Subjects punished each other in order to achieve a higher rank and a financially better outcome. Punishment primarily functioned as a means of rivalry, instead of as a way of second-order cooperation, as strong reciprocity suggests. These results indicate the need for the possible modification of the social conditions of punishment mechanisms described by the strong reciprocity theory as an evolutionary explanation of human cooperation.

Andrographolide inhibits arrhythmias and is cardioprotective in rabbits.

Science.gov (United States)

Zeng, Mengliu; Jiang, Wanzhen; Tian, Youjia; Hao, Jie; Cao, Zhenzhen; Liu, Zhipei; Fu, Chen; Zhang, Peihua; Ma, Jihua

2017-09-22

Andrographolide has a protective effect on the cardiovascular system. To study its cardic-electrophysiological effects, action potentials and voltage-gated Na + (I Na ), Ca 2+ (I CaL ), and K + (I K1 , I Kr , I to and I Kur ) currents were recorded using whole-cell patch clamp and current clamp techniques. Additionally, the effects of andrographolide on aconitine-induced arrhythmias were assessed on electrocardiograms in vivo . We found that andrographolide shortened action potential duration and reduced maximum upstroke velocity in rabbit left ventricular and left atrial myocytes. Andrographolide attenuated rate-dependence of action potential duration, and reduced or abolished delayed afterdepolarizations and triggered activities induced by isoproterenol (1 μM) and high calcium ([Ca 2+ ] o =3.6 mM) in left ventricular myocytes. Andrographolide also concentration-dependently inhibited I Na and I CaL , but had no effect on I to , I Kur , I K1 , or I Kr in rabbit left ventricular and left atrial myocytes. Andrographolide treatment increased the time and dosage thresholds of aconitine-induced arrhythmias, and reduced arrhythmia incidence and mortality in rabbits. Our results indicate that andrographolide inhibits cellular arrhythmias (delayed afterdepolarizations and triggered activities) and aconitine-induced arrhythmias in vivo , and these effects result from I Na and I CaL inhibition. Andrographolide may be useful as a class I and IV antiarrhythmic therapeutic.

Indirect reciprocity provides a narrow margin of efficiency for costly punishment

Science.gov (United States)

Iwasa, Yoh; Nowak, Martin A.

2008-01-01

Indirect reciprocity1-5 is a key mechanism for the evolution of human cooperation. Our behavior toward other people depends not only on what they have done to us, but also on what they have done to others. Indirect reciprocity works via reputation5-17. The standard model of indirect reciprocity offers a binary choice: people can either cooperate or defect. Cooperation implies a cost for the donor and a benefit for the recipient. Defection has no cost and yields no benefit. Currently there is considerable interest in studying the effect of costly (or altruistic) punishment on human behavior18-25. Punishment implies a cost for the punished person. Costly punishment means that the punisher also pays a cost. It has been suggested that costly punishment between individuals can promote cooperation. Here we study the role of costly punishment in an explicit model of indirect reciprocity. We analyze all social norms, which depend on the action of the donor and the reputation of the recipient. We allow errors in assigning reputation and study gossip as a mechanism for establishing coherence. We characterize all strategies that allow the evolutionary stability of cooperation. Some of those strategies use costly punishment, while others do not. We find that punishment strategies typically reduce the average payoff of the population. Consequently, there is only a small parameter region where costly punishment leads to an efficient equilibrium. In most cases, the population does better by not using costly punishment. The efficient strategy for indirect reciprocity is to withhold help for defectors rather than punish them. PMID:19122640

Punishment Insensitivity in Early Childhood: A Developmental, Dimensional Approach.

Science.gov (United States)

Nichols, Sara R; Briggs-Gowan, Margaret J; Estabrook, Ryne; Burns, James L; Kestler, Jacqueline; Berman, Grace; Henry, David B; Wakschlag, Lauren S

2015-08-01

Impairment in learning from punishment ("punishment insensitivity") is an established feature of severe antisocial behavior in adults and youth but it has not been well studied as a developmental phenomenon. In early childhood, differentiating a normal: abnormal spectrum of punishment insensitivity is key for distinguishing normative misbehavior from atypical manifestations. This study employed a novel measure, the Multidimensional Assessment Profile of Disruptive Behavior (MAP-DB), to examine the distribution, dimensionality, and external validity of punishment insensitivity in a large, demographically diverse community sample of preschoolers (3-5 years) recruited from pediatric clinics (N = 1,855). Caregivers completed surveys from which a seven-item Punishment Insensitivity scale was derived. Findings indicated that Punishment Insensitivity behaviors are relatively common in young children, with at least 50 % of preschoolers exhibiting them sometimes. Item response theory analyses revealed a Punishment Insensitivity spectrum. Items varied along a severity continuum: most items needed to occur "Often" in order to be severe and behaviors that were qualitatively atypical or intense were more severe. Although there were item-level differences across sociodemographic groups, these were small. Construct, convergent, and divergent validity were demonstrated via association to low concern for others and noncompliance, motivational regulation, and a disruptive family context. Incremental clinical utility was demonstrated in relation to impairment. Early childhood punishment insensitivity varies along a severity continuum and is atypical when it predominates. Implications for understanding the phenomenology of emergent disruptive behavior are discussed.

Retrieval-Induced Inhibition in Short-Term Memory.

Science.gov (United States)

Kang, Min-Suk; Choi, Joongrul

2015-07-01

We used a visual illusion called motion repulsion as a model system for investigating competition between two mental representations. Subjects were asked to remember two random-dot-motion displays presented in sequence and then to report the motion directions for each. Remembered motion directions were shifted away from the actual motion directions, an effect similar to the motion repulsion observed during perception. More important, the item retrieved second showed greater repulsion than the item retrieved first. This suggests that earlier retrieval exerted greater inhibition on the other item being held in short-term memory. This retrieval-induced motion repulsion could be explained neither by reduced cognitive resources for maintaining short-term memory nor by continued inhibition between short-term memory representations. These results indicate that retrieval of memory representations inhibits other representations in short-term memory. We discuss mechanisms of retrieval-induced inhibition and their implications for the structure of memory. © The Author(s) 2015.

Individual differences in sensitivity to reward and punishment and neural activity during reward and avoidance learning.

Science.gov (United States)

Kim, Sang Hee; Yoon, HeungSik; Kim, Hackjin; Hamann, Stephan

2015-09-01

In this functional neuroimaging study, we investigated neural activations during the process of learning to gain monetary rewards and to avoid monetary loss, and how these activations are modulated by individual differences in reward and punishment sensitivity. Healthy young volunteers performed a reinforcement learning task where they chose one of two fractal stimuli associated with monetary gain (reward trials) or avoidance of monetary loss (avoidance trials). Trait sensitivity to reward and punishment was assessed using the behavioral inhibition/activation scales (BIS/BAS). Functional neuroimaging results showed activation of the striatum during the anticipation and reception periods of reward trials. During avoidance trials, activation of the dorsal striatum and prefrontal regions was found. As expected, individual differences in reward sensitivity were positively associated with activation in the left and right ventral striatum during reward reception. Individual differences in sensitivity to punishment were negatively associated with activation in the left dorsal striatum during avoidance anticipation and also with activation in the right lateral orbitofrontal cortex during receiving monetary loss. These results suggest that learning to attain reward and learning to avoid loss are dependent on separable sets of neural regions whose activity is modulated by trait sensitivity to reward or punishment. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Neferine reduces cisplatin-induced nephrotoxicity by enhancing autophagy via the AMPK/mTOR signaling pathway.

Science.gov (United States)

Li, Hui; Tang, Yuling; Wen, Long; Kong, Xianglong; Chen, Xuelian; Liu, Ping; Zhou, Zhiguo; Chen, Wenhang; Xiao, Chenggen; Xiao, Ping; Xiao, Xiangcheng

2017-03-11

Cisplatin is one of the most effective chemotherapeutic agents; however, its clinical use is limited by serious side effects of which nephrotoxicity is the most important. Nephrotoxicity induced by cisplatin is closely associated with autophagy reduction and caspase activation. In this study, we investigated whether neferine, an autophagy inducer, had a protective effect against cisplatin-induced nephrotoxicity. In an in vitro cisplatin-induced nephrotoxicity model, we determined that neferine was able to induce autophagy and that pretreatment with neferine not only attenuated cisplatin-induced cell apoptosis but further activated cell autophagy. This pro-survival effect was abolished by the autophagic flux inhibitor chloroquine. Furthermore, neferine pretreatment activated the AMPK/mTOR pathway; however, pharmacological inhibition of AMPK abolished neferine-mediated autophagy and nephroprotection against cisplatin-induced apoptosis. Collectively, our findings suggest for the first time the possible protective mechanism of neferine, which is crucial for its further development as a potential therapeutic agent for cisplatin-induced nephrotoxicity. Copyright © 2017 Elsevier Inc. All rights reserved.

The inhibition of the dorsal paragigantocellular reticular nucleus induces waking and the activation of all adrenergic and noradrenergic neurons: a combined pharmacological and functional neuroanatomical study.

Science.gov (United States)

Clément, Olivier; Valencia Garcia, Sara; Libourel, Paul-Antoine; Arthaud, Sébastien; Fort, Patrice; Luppi, Pierre-Hervé

2014-01-01

GABAergic neurons specifically active during paradoxical sleep (PS) localized in the dorsal paragigantocellular reticular nucleus (DPGi) are known to be responsible for the cessation of activity of the noradrenergic neurons of the locus coeruleus during PS. In the present study, we therefore sought to determine the role of the DPGi in PS onset and maintenance and in the inhibition of the LC noradrenergic neurons during this state. The effect of the inactivation of DPGi neurons on the sleep-waking cycle was examined in rats by microinjection of muscimol, a GABAA agonist, or clonidine, an alpha-2 adrenergic receptor agonist. Combining immunostaining of the different populations of wake-inducing neurons with that of c-FOS, we then determined whether muscimol inhibition of the DPGi specifically induces the activation of the noradrenergic neurons of the LC. Slow wave sleep and PS were abolished during 3 and 5 h after muscimol injection in the DPGi, respectively. The application of clonidine in the DPGi specifically induced a significant decrease in PS quantities and delayed PS appearance compared to NaCl. We further surprisingly found out that more than 75% of the noradrenergic and adrenergic neurons of all adrenergic and noradrenergic cell groups are activated after muscimol treatment in contrast to the other wake active systems significantly less activated. These results suggest that, in addition to its already know inhibition of LC noradrenergic neurons during PS, the DPGi might inhibit the activity of noradrenergic and adrenergic neurons from all groups during PS, but also to a minor extent during SWS and waking.

The inhibition of the dorsal paragigantocellular reticular nucleus induces waking and the activation of all adrenergic and noradrenergic neurons: a combined pharmacological and functional neuroanatomical study.

Directory of Open Access Journals (Sweden)

Olivier Clément

Full Text Available GABAergic neurons specifically active during paradoxical sleep (PS localized in the dorsal paragigantocellular reticular nucleus (DPGi are known to be responsible for the cessation of activity of the noradrenergic neurons of the locus coeruleus during PS. In the present study, we therefore sought to determine the role of the DPGi in PS onset and maintenance and in the inhibition of the LC noradrenergic neurons during this state. The effect of the inactivation of DPGi neurons on the sleep-waking cycle was examined in rats by microinjection of muscimol, a GABAA agonist, or clonidine, an alpha-2 adrenergic receptor agonist. Combining immunostaining of the different populations of wake-inducing neurons with that of c-FOS, we then determined whether muscimol inhibition of the DPGi specifically induces the activation of the noradrenergic neurons of the LC. Slow wave sleep and PS were abolished during 3 and 5 h after muscimol injection in the DPGi, respectively. The application of clonidine in the DPGi specifically induced a significant decrease in PS quantities and delayed PS appearance compared to NaCl. We further surprisingly found out that more than 75% of the noradrenergic and adrenergic neurons of all adrenergic and noradrenergic cell groups are activated after muscimol treatment in contrast to the other wake active systems significantly less activated. These results suggest that, in addition to its already know inhibition of LC noradrenergic neurons during PS, the DPGi might inhibit the activity of noradrenergic and adrenergic neurons from all groups during PS, but also to a minor extent during SWS and waking.

Corporal Punishment in Schools: Theoretical Discussion and Personal Experience

Science.gov (United States)

Alsaif, Omar Abdulaziz

2015-01-01

This paper ponders the lasting effects of corporal punishment on students. The paper first considers the benefits and faults of corporal punishment by comparing the experiences of two generations of students and teachers. Starting with the definition of corporal punishment as applied locally and globally, the paper analyzes the reasons for its…

Kierkegaardian Implications of Punishment, Guilt, and Forgiveness for Education.

Science.gov (United States)

Senyshyn, Yaroslav

1998-01-01

Explores Soren Kierkegaard's notion of punishment, which should interest educators because it provides a way to avoid the pitfalls of unjust punishment by viewing it in conjunction with the implications of guilt and forgiveness. The paper notes the need to question the notion of punishment closely and seek to understand its implications. (SM)

Stimulus Variation as a Means of Enhancing Punishment Effects.

Science.gov (United States)

Charlop, Marjorie H.; And Others

1988-01-01

The study examined effects of varied punishers (overcorrection, time-out, or a verbal "no" compared with the single presentation of one punisher (a loud noise) on occurrence of inappropriate behaviors in three developmentally delayed children (ages 5-6). Both formats produced a decrease in target behaviors, with the varied-punisher format slightly…

Gliclazide directly inhibits arginine-induced glucagon release

DEFF Research Database (Denmark)

Cejvan, Kenan; Coy, David H; Holst, Jens Juul

2002-01-01

Arginine-stimulated insulin and somatostatin release is enhanced by the sulfonylurea gliclazide. In contrast, gliclazide inhibits the glucagon response. The aim of the present study was to investigate whether this inhibition of glucagon release was mediated by a direct suppressive effect of glicl......Arginine-stimulated insulin and somatostatin release is enhanced by the sulfonylurea gliclazide. In contrast, gliclazide inhibits the glucagon response. The aim of the present study was to investigate whether this inhibition of glucagon release was mediated by a direct suppressive effect....... In islet perifusions with DC-41-33, arginine-induced glucagon release was inhibited by 66%. We therefore concluded that gliclazide inhibits glucagon release by a direct action on the pancreatic A cell....

Parental attitudes to corporal punishment of children and the analysis of possible Reasons for applying corporal punishment in the family

OpenAIRE

Jusienė, Roma

2006-01-01

Parental use of corporal punishment is one of the most emotionally charged and attention eliciting topic in child rearing theory and practice, and in social and legal debates as well. The aim of this study is to analyse the parental use of corporal punishment (CP) and attitude to it as related to personal experience of corporal punishment in childhood and to children's psychological adjustment. 110 parents (88 mothers and 22 fathers) who have children aged 4 to 16 years old participated in th...

Reward/Punishment reversal learning in older suicide attempters.

Science.gov (United States)

Dombrovski, Alexandre Y; Clark, Luke; Siegle, Greg J; Butters, Meryl A; Ichikawa, Naho; Sahakian, Barbara J; Szanto, Katalin

2010-06-01

Suicide rates are high in old age, and the contribution of cognitive risk factors remains poorly understood. Suicide may be viewed as an outcome of an altered decision process. The authors hypothesized that impairment in reward/punishment-based learning, a component of affective decision making, is associated with attempted suicide in late-life depression. They expected that suicide attempters would discount past reward/punishment history, focusing excessively on the most recent rewards and punishments. The authors further hypothesized that this impairment could be dissociated from executive abilities, such as forward planning. The authors assessed reward/punishment-based learning using the probabilistic reversal learning task in 65 individuals age 60 and older: suicide attempters, suicide ideators, nonsuicidal depressed elderly, and nondepressed comparison subjects. The authors used a reinforcement learning computational model to decompose reward/punishment processing over time. The Stockings of Cambridge test served as a control measure of executive function. Suicide attempters but not suicide ideators showed impaired probabilistic reversal learning compared to both nonsuicidal depressed elderly and nondepressed comparison subjects, after controlling for effects of education, global cognitive function, and substance use. Model-based analyses revealed that suicide attempters discounted previous history to a higher degree relative to comparison subjects, basing their choice largely on reward/punishment received on the last trial. Groups did not differ in their performance on the Stockings of Cambridge test. Older suicide attempters display impaired reward/punishment-based learning. The authors propose a hypothesis that older suicide attempters make overly present-focused decisions, ignoring past experiences. Modification of this "myopia for the past" may have therapeutic potential.

Anger Management: Aggression and Punishment in the Provision of Public Goods

Directory of Open Access Journals (Sweden)

Laura K. Gee

2017-01-01

Full Text Available The ability to punish free-riders can increase the provision of public goods. However, sometimes, the benefit of increased public good provision is outweighed by the costs of punishments. One reason a group may punish to the point that net welfare is reduced is that punishment can express anger about free-riding. If this is the case, then tools that regulate emotions could decrease the use of punishments while keeping welfare high, possibly depending on pre-existing levels of aggression. In this lab experiment, we find that adopting an objective attitude (objective, through a form of emotion regulation called cognitive reappraisal, decreases the use of punishments and makes a statistically insignificant improvement to both net earnings and self-reported emotions compared to a control condition (natural. Although the interaction between the emotion regulation treatment and level of aggression is not significant, only low aggression types reduce their punishments; the results are of the same direction, but statistically insignificant for high aggression types. Overall, our findings suggest that pairing emotion regulation with punishments can decrease the use of punishments without harming monetary and mental welfare.

Punishment as a means of competition: implications for strong reciprocity theory.

Directory of Open Access Journals (Sweden)

Tünde Paál

Full Text Available Strong negative reciprocity, that is, sanctions imposed on norm violators at the punisher's own expense, has powerful cooperation-enhancing effects in both real-life and experimental game situations. However, it is plausible that punishment may obtain alternative roles depending on social context and the personality characteristics of participants. We examined the occurrence of punishing behavior among 80 subjects in a strongly competitive Public Goods game setting. Despite the punishment condition, the amount of the contributions decreased steadily during the game. The amount of contributions had no significant effect on received and imposed punishments. The results indicate that certain social contexts (in this case, intensive competition exert modifying effects on the role that punishment takes on. Subjects punished each other in order to achieve a higher rank and a financially better outcome. Punishment primarily functioned as a means of rivalry, instead of as a way of second-order cooperation, as strong reciprocity suggests. These results indicate the need for the possible modification of the social conditions of punishment mechanisms described by the strong reciprocity theory as an evolutionary explanation of human cooperation.

The empowering effect of punishment on forgiveness

NARCIS (Netherlands)

Strelan, Peter; Di Fiore, Carolyn; van Prooijen, Jan Willem

2017-01-01

We examined the process by which punishment enables forgiveness, testing the proposition that punishment restores a sense of justice to victims, an experience that is empowering. In Study 1 (N = 69), university students received insulting feedback and were given the opportunity (or not) to sanction

changing perceptions of discipline and corporal punishment

African Journals Online (AJOL)

Through a qualitative research methodology of semi-structured inter- views, data ... punishment for classroom discipline in order to achieve the vision of quality education. ... committed to ending corporal punishment of children. Being hit ... are relevant to policymakers and other stakeholders who should take cognisance of.

Inhibition of CLIC4 enhances autophagy and triggers mitochondrial and ER stress-induced apoptosis in human glioma U251 cells under starvation.

Directory of Open Access Journals (Sweden)

Jiateng Zhong

Full Text Available CLIC4/mtCLIC, a chloride intracellular channel protein, localizes to mitochondria, endoplasmic reticulum (ER, nucleus and cytoplasm, and participates in the apoptotic response to stress. Apoptosis and autophagy, the main types of the programmed cell death, seem interconnected under certain stress conditions. However, the role of CLIC4 in autophagy regulation has yet to be determined. In this study, we demonstrate upregulation and nuclear translocation of the CLIC4 protein following starvation in U251 cells. CLIC4 siRNA transfection enhanced autophagy with increased LC3-II protein and puncta accumulation in U251 cells under starvation conditions. In that condition, the interaction of the 14-3-3 epsilon isoform with CLIC4 was abolished and resulted in Beclin 1 overactivation, which further activated autophagy. Moreover, inhibiting the expression of CLIC4 triggered both mitochondrial apoptosis involved in Bax/Bcl-2 and cytochrome c release under starvation and endoplasmic reticulum stress-induced apoptosis with CHOP and caspase-4 upregulation. These results demonstrate that CLIC4 nuclear translocation is an integral part of the cellular response to starvation. Inhibiting the expression of CLIC4 enhances autophagy and contributes to mitochondrial and ER stress-induced apoptosis under starvation.

Building the Leviathan--Voluntary centralisation of punishment power sustains cooperation in humans.

Science.gov (United States)

Gross, Jörg; Méder, Zsombor Z; Okamoto-Barth, Sanae; Riedl, Arno

2016-02-18

The prevalence of cooperation among humans is puzzling because cooperators can be exploited by free riders. Peer punishment has been suggested as a solution to this puzzle, but cumulating evidence questions its robustness in sustaining cooperation. Amongst others, punishment fails when it is not powerful enough, or when it elicits counter-punishment. Existing research, however, has ignored that the distribution of punishment power can be the result of social interactions. We introduce a novel experiment in which individuals can transfer punishment power to others. We find that while decentralised peer punishment fails to overcome free riding, the voluntary transfer of punishment power enables groups to sustain cooperation. This is achieved by non-punishing cooperators empowering those who are willing to punish in the interest of the group. Our results show how voluntary power centralisation can efficiently sustain cooperation, which could explain why hierarchical power structures are widespread among animals and humans.

Mitochondrial ADP/ATP exchange inhibition: a novel off-target mechanism underlying ibipinabant-induced myotoxicity.

Science.gov (United States)

Schirris, Tom J J; Ritschel, Tina; Herma Renkema, G; Willems, Peter H G M; Smeitink, Jan A M; Russel, Frans G M

2015-09-29

Cannabinoid receptor 1 (CB1R) antagonists appear to be promising drugs for the treatment of obesity, however, serious side effects have hampered their clinical application. Rimonabant, the first in class CB1R antagonist, was withdrawn from the market because of psychiatric side effects. This has led to the search for more peripherally restricted CB1R antagonists, one of which is ibipinabant. However, this 3,4-diarylpyrazoline derivative showed muscle toxicity in a pre-clinical dog study with mitochondrial dysfunction. Here, we studied the molecular mechanism by which ibipinabant induces mitochondrial toxicity. We observed a strong cytotoxic potency of ibipinabant in C2C12 myoblasts. Functional characterization of mitochondria revealed increased cellular reactive oxygen species generation and a decreased ATP production capacity, without effects on the catalytic activities of mitochondrial enzyme complexes I-V or the complex specific-driven oxygen consumption. Using in silico off-target prediction modelling, combined with in vitro validation in isolated mitochondria and mitoplasts, we identified adenine nucleotide translocase (ANT)-dependent mitochondrial ADP/ATP exchange as a novel molecular mechanism underlying ibipinabant-induced toxicity. Minor structural modification of ibipinabant could abolish ANT inhibition leading to a decreased cytotoxic potency, as observed with the ibipinabant derivative CB23. Our results will be instrumental in the development of new types of safer CB1R antagonists.

A potential role of reward and punishment in the facilitation of the emotion-cognition dichotomy in the Iowa Gambling Task

Directory of Open Access Journals (Sweden)

Varsha eSingh

2013-12-01

Full Text Available The Iowa Gambling Task (IGT is based on the assumption that a decision maker is equally motivated to seek reward and avoid punishment, and that decision making is governed solely by the intertemporal attribute (i.e., preference for an option that produces an immediate outcome instead of one that yields a delayed outcome is believed to reflect risky decision making and is considered a deficit. It was assumed in the present study that the emotion- and cognition-based processing dichotomy manifests in the IGT as reward and punishment frequency and the intertemporal attribute. It was further proposed that the delineation of emotion- and cognition-based processing is contingent upon reward and punishment as manifested in the frame of the task (variant type and task motivation (instruction type. The effects of IGT variant type (reward vs. punishment and instruction type (task motivation induced by instruction types: reward, punishment, reward and punishment, or no hint on the intertemporal and frequency attributes of IGT decision-making were analyzed. Decision making in the reward variant was equally governed by both attributes, and significantly affected by instruction type, while decision making in the punishment variant was differentially affected by the two attributes and not significantly impacted by instruction type. These results suggest that reward and punishment manifested via task frame as well as the task motivation may facilitate the differentiation of emotion- and cognition-based processing in the IGT.

A potential role of reward and punishment in the facilitation of the emotion-cognition dichotomy in the Iowa Gambling Task.

Science.gov (United States)

Singh, Varsha

2013-01-01

The Iowa Gambling Task (IGT) is based on the assumption that a decision maker is equally motivated to seek reward and avoid punishment, and that decision making is governed solely by the intertemporal attribute (i.e., preference for an option that produces an immediate outcome instead of one that yields a delayed outcome is believed to reflect risky decision making and is considered a deficit). It was assumed in the present study that the emotion- and cognition-based processing dichotomy manifests in the IGT as reward and punishment frequency and the intertemporal attribute. It was further proposed that the delineation of emotion- and cognition-based processing is contingent upon reward and punishment as manifested in the frame of the task (variant type) and task motivation (instruction type). The effects of IGT variant type (reward vs. punishment) and instruction type (task motivation induced by instruction types: reward, punishment, reward and punishment, or no hint) on the intertemporal and frequency attributes of IGT decision-making were analyzed. Decision making in the reward variant was equally governed by both attributes, and significantly affected by instruction type, while decision making in the punishment variant was differentially affected by the two attributes and not significantly impacted by instruction type. These results suggest that reward and punishment manifested via task frame as well as the task motivation may facilitate the differentiation of emotion- and cognition-based processing in the IGT.

[Parental corporal punishment in children with attention-deficit hyperactivity syndrome].

Science.gov (United States)

Błachno, Magda; Szamańska, Urszula; Kołakowski, Artur; Pisula, Agnieszka

2006-01-01

The aim of this study was to assess the frequency and causes of corporal punishment in children with attention-deficit hyperactivity disorder in comparison with the general population and to evaluate methods of prevention applied in The Department of Child Psychiatry in Warsaw. 82 parents of children with ADHD participating in the Parental Training Programme were asked to fill in an anonymous questionnaire concerning corporal punishment. 95% parents abuse their children physically. ADHD in parents and co-occurrence of ADHD symptoms in children influence punishment frequency. Parents with ADHD, in comparison with parents without ADHD use more serious types of physical punishment. After the Parental Training Programme 72% parents used other kinds of punishment. Parental corporal punishment in children with ADHD is not uncommon. The efficacy of psychoeducation in the examined area seems to be very promising.

Naftopidil inhibits 5-hydroxytryptamine-induced bladder contraction in rats.

Science.gov (United States)

Sakai, Takumi; Kasahara, Ken-ichi; Tomita, Ken-ichi; Ikegaki, Ichiro; Kuriyama, Hiroshi

2013-01-30

Naftopidil is an α(1D) and α(1A) subtype-selective α(1)-adrenoceptor antagonist that has been used to treat lower urinary tract symptoms of benign prostatic hyperplasia. In this study, we investigated the effects of naftopidil on 5-hydroxytryptamine (5-HT)-induced rat bladder contraction (10(-8)-10(-4) M). Naftopidil (0.3, 1, and 3 μM) inhibited 5-HT-induced bladder contraction in a concentration-dependent manner. On the other hand, other α(1)-adrenoceptor antagonists, tamsulosin, silodosin or prazosin, did not inhibit 5-HT-induced bladder contraction. The 5-HT-induced bladder contraction was inhibited by both ketanserin and 4-(4-fluoronaphthalen-1-yl)-6-propan-2-ylpyrimidin-2-amine (RS127445), serotonin 5-HT(2A) and 5-HT(2B) receptor antagonists, respectively. In addition, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and α-methyl-5-HT, 5-HT(2A) and 5-HT(2) receptor agonists, respectively, induced bladder contraction. The 5-HT-induced bladder contraction was not inhibited by N-[2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl]-N-pyridin-2-yl-cyclohexanecarboxamide (WAY-100635), [1-[2[(methylsulfonyl)amino]ethyl]-4-piperidinyl]methyl-1-methyl-1H-indole-3-carboxylate (GR113808) or (R)-3-[2-[2-(4-methylpiperidin-1-yl)ethyl]pyrrolidine-1-sulphonyl]phenol (SB269970), 5-HT(1A), 5-HT(4) and 5-HT(7) receptor antagonists, respectively. Naftopidil inhibited both the 5-HT(2A) and 5-HT(2) receptor agonists-induced bladder contractions. Naftopidil binds to the human 5-HT(2A) and 5-HT(2B) receptors with pKi values of 6.55 and 7.82, respectively. These results suggest that naftopidil inhibits 5-HT-induced bladder contraction via blockade of the 5-HT(2A) and 5-HT(2B) receptors in rats. Furthermore, 5-HT-induced bladder contraction was enhanced in bladder strips obtained from bladder outlet obstructed rats, with this contraction inhibited by naftopidil. The beneficial effects of naftopidil on storage symptoms such as urinary frequency and nocturia in patients with benign

Stimulation of the cardiac myocyte Na+-K+ pump due to reversal of its constitutive oxidative inhibition.

Science.gov (United States)

Chia, Karin K M; Liu, Chia-Chi; Hamilton, Elisha J; Garcia, Alvaro; Fry, Natasha A; Hannam, William; Figtree, Gemma A; Rasmussen, Helge H

2015-08-15

Protein kinase C can activate NADPH oxidase and induce glutathionylation of the β1-Na(+)-K(+) pump subunit, inhibiting activity of the catalytic α-subunit. To examine if signaling of nitric oxide-induced soluble guanylyl cyclase (sGC)/cGMP/protein kinase G can cause Na(+)-K(+) pump stimulation by counteracting PKC/NADPH oxidase-dependent inhibition, cardiac myocytes were exposed to ANG II to activate NADPH oxidase and inhibit Na(+)-K(+) pump current (Ip). Coexposure to 3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole (YC-1) to stimulate sGC prevented the decrease of Ip. Prevention of the decrease was abolished by inhibition of protein phosphatases (PP) 2A but not by inhibition of PP1, and it was reproduced by an activator of PP2A. Consistent with a reciprocal relationship between β1-Na(+)-K(+) pump subunit glutathionylation and pump activity, YC-1 decreased ANG II-induced β1-subunit glutathionylation. The decrease induced by YC-1 was abolished by a PP2A inhibitor. YC-1 decreased phosphorylation of the cytosolic p47(phox) NADPH oxidase subunit and its coimmunoprecipitation with the membranous p22(phox) subunit, and it decreased O2 (·-)-sensitive dihydroethidium fluorescence of myocytes. Addition of recombinant PP2A to myocyte lysate decreased phosphorylation of p47(phox) indicating the subunit could be a substrate for PP2A. The effects of YC-1 to decrease coimmunoprecipitation of p22(phox) and p47(phox) NADPH oxidase subunits and decrease β1-Na(+)-K(+) pump subunit glutathionylation were reproduced by activation of nitric oxide-dependent receptor signaling. We conclude that sGC activation in cardiac myocytes causes a PP2A-dependent decrease in NADPH oxidase activity and a decrease in β1 pump subunit glutathionylation. This could account for pump stimulation with neurohormonal oxidative stress expected in vivo. Copyright © 2015 the American Physiological Society.

Administrators' Perceptions of Corporal Punishment in Four Tennessee Counties

Science.gov (United States)

Hanger, Brian S.

2009-01-01

Corporal punishment is one of the most litigious issues in education. Proponents of corporal punishment believe it is a necessary and effective way to keep order in the schools. Opponents of corporal punishment feel it is detrimental to the welfare of children and should be prohibited in schools. Many states have banned the use of school corporal…

Irreversible inhibition of RANK expression as a possible mechanism for IL-3 inhibition of RANKL-induced osteoclastogenesis

Energy Technology Data Exchange (ETDEWEB)

Khapli, Shruti M.; Tomar, Geetanjali B.; Barhanpurkar, Amruta P.; Gupta, Navita; Yogesha, S.D.; Pote, Satish T. [National Center for Cell Science, University of Pune Campus, Pune 411 007 (India); Wani, Mohan R., E-mail: mohanwani@nccs.res.in [National Center for Cell Science, University of Pune Campus, Pune 411 007 (India)

2010-09-03

Research highlights: {yields} IL-3 inhibits receptor activator of NF-{kappa}B ligand (RANKL)-induced osteoclastogenesis. {yields} IL-3 inhibits RANKL-induced JNK activation. {yields} IL-3 down-regulates expression of c-Fos and NFATc1 transcription factors. {yields} IL-3 down-regulates RANK expression posttranscriptionally and irreversibly. {yields} IL-3 inhibits in vivo RANK expression. -- Abstract: IL-3, a cytokine secreted by activated T lymphocytes, stimulates the proliferation, differentiation and survival of pluripotent hematopoietic stem cells. In this study, we investigated the mechanism of inhibitory action of IL-3 on osteoclast differentiation. We show here that IL-3 significantly inhibits receptor activator of NF-{kappa}B (RANK) ligand (RANKL)-induced activation of c-Jun N-terminal kinase (JNK). IL-3 down-regulates expression of c-Fos and nuclear factor of activated T cells (NFATc1) transcription factors. In addition, IL-3 down-regulates RANK expression posttranscriptionally in both purified osteoclast precursors and whole bone marrow cells. Furthermore, the inhibitory effect of IL-3 on RANK expression was irreversible. Interestingly, IL-3 inhibits in vivo RANK expression in mice. Thus, we provide the first evidence that IL-3 irreversibly inhibits RANK expression that results in inhibition of important signaling molecules induced by RANKL.

Irreversible inhibition of RANK expression as a possible mechanism for IL-3 inhibition of RANKL-induced osteoclastogenesis

International Nuclear Information System (INIS)

Khapli, Shruti M.; Tomar, Geetanjali B.; Barhanpurkar, Amruta P.; Gupta, Navita; Yogesha, S.D.; Pote, Satish T.; Wani, Mohan R.

2010-01-01

Research highlights: → IL-3 inhibits receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis. → IL-3 inhibits RANKL-induced JNK activation. → IL-3 down-regulates expression of c-Fos and NFATc1 transcription factors. → IL-3 down-regulates RANK expression posttranscriptionally and irreversibly. → IL-3 inhibits in vivo RANK expression. -- Abstract: IL-3, a cytokine secreted by activated T lymphocytes, stimulates the proliferation, differentiation and survival of pluripotent hematopoietic stem cells. In this study, we investigated the mechanism of inhibitory action of IL-3 on osteoclast differentiation. We show here that IL-3 significantly inhibits receptor activator of NF-κB (RANK) ligand (RANKL)-induced activation of c-Jun N-terminal kinase (JNK). IL-3 down-regulates expression of c-Fos and nuclear factor of activated T cells (NFATc1) transcription factors. In addition, IL-3 down-regulates RANK expression posttranscriptionally in both purified osteoclast precursors and whole bone marrow cells. Furthermore, the inhibitory effect of IL-3 on RANK expression was irreversible. Interestingly, IL-3 inhibits in vivo RANK expression in mice. Thus, we provide the first evidence that IL-3 irreversibly inhibits RANK expression that results in inhibition of important signaling molecules induced by RANKL.

Punishments, Rewards, and the Production of Evidence

NARCIS (Netherlands)

Boer, A.

2014-01-01

In legal knowledge acquisition, the threat of punishment remains an important litmus test for categorizing legal rules: something is a real duty if it is backed - directly or indirectly - by a threat of punishment. In practice, no accounts of how enforcement design patterns are superposed on

changing perceptions of discipline and corporal punishment

African Journals Online (AJOL)

punishment and, secondly, their perceptions of their disciplinary techniques since ... research on teachers' (un)changing perceptions with regard to the practice of corporal punishment for classroom discipline in order to achieve the vision of quality ...... teaching and classroom management with the aim of enhancing teacher ...

Autophagy contributes to gefitinib-induced glioma cell growth inhibition

Energy Technology Data Exchange (ETDEWEB)

Chang, Cheng-Yi [Department of Surgery, Fong-Yuan Hospital, Taichung 420, Taiwan (China); Graduate Institute of Pharmaceutical Science and Technology, Central Taiwan University of Science and Technology, Taichung 406, Taiwan (China); Kuan, Yu-Hsiang [Department of Pharmacology, School of Medicine, Chung Shan Medical University, Taichung 402, Taiwan (China); Department of Pharmacy, Chung Shan Medical University Hospital, Taichung 402, Taiwan (China); Ou, Yen-Chuan; Li, Jian-Ri [Division of Urology, Taichung Veterans General Hospital, Taichung 407, Taiwan (China); Wu, Chih-Cheng [Department of Anesthesiology, Taichung Veterans General Hospital, Taichung 407, Taiwan (China); Department of Financial and Computational Mathematics, Providence University, Taichung 433, Taiwan (China); Pan, Pin-Ho [Department of Pediatrics, Tungs’ Taichung MetroHarbor Hospital, Taichung 435, Taiwan (China); Chen, Wen-Ying [Department of Veterinary Medicine, National Chung Hsing University, Taichung 402, Taiwan (China); Huang, Hsuan-Yi [Department of Surgery, Fong-Yuan Hospital, Taichung 420, Taiwan (China); Chen, Chun-Jung, E-mail: cjchen@vghtc.gov.tw [Department of Medical Research, Taichung Veterans General Hospital, Taichung 407, Taiwan (China); Institute of Biomedical Sciences, National Chung Hsing University, Taichung 402, Taiwan (China); Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung 402, Taiwan (China); Center for General Education, Tunghai University, Taichung 407, Taiwan (China); Department of Nursing, HungKuang University, Taichung 433, Taiwan (China)

2014-09-10

Epidermal growth factor receptor tyrosine kinase inhibitors, including gefitinib, have been evaluated in patients with malignant gliomas. However, the molecular mechanisms involved in gefitinib-mediated anticancer effects against glioma are incompletely understood. In the present study, the cytostatic potential of gefitinib was demonstrated by the inhibition of glioma cell growth, long-term clonogenic survival, and xenograft tumor growth. The cytostatic consequences were accompanied by autophagy, as evidenced by monodansylcadaverine staining of acidic vesicle formation, conversion of microtubule-associated protein-1 light chain 3-II (LC3-II), degradation of p62, punctate pattern of GFP-LC3, and conversion of GFP-LC3 to cleaved-GFP. Autophagy inhibitor 3-methyladenosine and chloroquine and genetic silencing of LC3 or Beclin 1 attenuated gefitinib-induced growth inhibition. Gefitinib-induced autophagy was not accompanied by the disruption of the Akt/mammalian target of rapamycin signaling. Instead, the activation of liver kinase-B1/AMP-activated protein kinase (AMPK) signaling correlated well with the induction of autophagy and growth inhibition caused by gefitinib. Silencing of AMPK suppressed gefitinib-induced autophagy and growth inhibition. The crucial role of AMPK activation in inducing glioma autophagy and growth inhibition was further supported by the actions of AMP mimetic AICAR. Gefitinib was shown to be capable of reducing the proliferation of glioma cells, presumably by autophagic mechanisms involving AMPK activation. - Highlights: • Gefitinib causes cytotoxic and cytostatic effect on glioma. • Gefitinib induces autophagy. • Gefitinib causes cytostatic effect through autophagy. • Gefitinib induces autophagy involving AMPK.

Autophagy contributes to gefitinib-induced glioma cell growth inhibition

International Nuclear Information System (INIS)

Chang, Cheng-Yi; Kuan, Yu-Hsiang; Ou, Yen-Chuan; Li, Jian-Ri; Wu, Chih-Cheng; Pan, Pin-Ho; Chen, Wen-Ying; Huang, Hsuan-Yi; Chen, Chun-Jung

2014-01-01

Epidermal growth factor receptor tyrosine kinase inhibitors, including gefitinib, have been evaluated in patients with malignant gliomas. However, the molecular mechanisms involved in gefitinib-mediated anticancer effects against glioma are incompletely understood. In the present study, the cytostatic potential of gefitinib was demonstrated by the inhibition of glioma cell growth, long-term clonogenic survival, and xenograft tumor growth. The cytostatic consequences were accompanied by autophagy, as evidenced by monodansylcadaverine staining of acidic vesicle formation, conversion of microtubule-associated protein-1 light chain 3-II (LC3-II), degradation of p62, punctate pattern of GFP-LC3, and conversion of GFP-LC3 to cleaved-GFP. Autophagy inhibitor 3-methyladenosine and chloroquine and genetic silencing of LC3 or Beclin 1 attenuated gefitinib-induced growth inhibition. Gefitinib-induced autophagy was not accompanied by the disruption of the Akt/mammalian target of rapamycin signaling. Instead, the activation of liver kinase-B1/AMP-activated protein kinase (AMPK) signaling correlated well with the induction of autophagy and growth inhibition caused by gefitinib. Silencing of AMPK suppressed gefitinib-induced autophagy and growth inhibition. The crucial role of AMPK activation in inducing glioma autophagy and growth inhibition was further supported by the actions of AMP mimetic AICAR. Gefitinib was shown to be capable of reducing the proliferation of glioma cells, presumably by autophagic mechanisms involving AMPK activation. - Highlights: • Gefitinib causes cytotoxic and cytostatic effect on glioma. • Gefitinib induces autophagy. • Gefitinib causes cytostatic effect through autophagy. • Gefitinib induces autophagy involving AMPK

Ciprofloxacin blocked enterohepatic circulation of diclofenac and alleviated NSAID-induced enteropathy in rats partly by inhibiting intestinal β-glucuronidase activity

Science.gov (United States)

Zhong, Ze-yu; Sun, Bin-bin; Shu, Nan; Xie, Qiu-shi; Tang, Xian-ge; Ling, Zhao-li; Wang, Fan; Zhao, Kai-jing; Xu, Ping; Zhang, Mian; Li, Ying; Chen, Yang; Liu, Li; Xia, Lun-zhu; Liu, Xiao-dong

2016-01-01

Aim: Diclofenac is a non-steroidal anti-inflammatory drug (NSAID), which may cause serious intestinal adverse reactions (enteropathy). In this study we investigated whether co-administration of ciprofloxacin affected the pharmacokinetics of diclofenac and diclofenac-induced enteropathy in rats. Methods: The pharmacokinetics of diclofenac was assessed in rats after receiving diclofenac (10 mg/kg, ig, or 5 mg/kg, iv), with or without ciprofloxacin (20 mg/kg, ig) co-administered. After receiving 6 oral doses or 15 intravenous doses of diclofenac, the rats were sacrificed, and small intestine was removed to examine diclofenac-induced enteropathy. β-Glucuronidase activity in intestinal content, bovine liver and E coli was evaluated. Results: Following oral or intravenous administration, the pharmacokinetic profile of diclofenac displayed typical enterohepatic circulation, and co-administration of ciprofloxacin abolished the enterohepatic circulation, resulted in significant reduction in the plasma content of diclofenac. In control rats, β-glucuronidase activity in small intestinal content was region-dependent: proximal intestinediclofenac, typical enteropathy was developed with severe enteropathy occurred in distal small intestine. Co-administration of ciprofloxacin significantly alleviated diclofenac-induced enteropathy. Conclusion: Co-administration of ciprofloxacin attenuated enterohepatic circulation of diclofenac and alleviated diclofenac-induced enteropathy in rats, partly via the inhibition of intestinal β-glucuronidase activity. PMID:27180979

Ciprofloxacin blocked enterohepatic circulation of diclofenac and alleviated NSAID-induced enteropathy in rats partly by inhibiting intestinal β-glucuronidase activity.

Science.gov (United States)

Zhong, Ze-Yu; Sun, Bin-Bin; Shu, Nan; Xie, Qiu-Shi; Tang, Xian-Ge; Ling, Zhao-Li; Wang, Fan; Zhao, Kai-Jing; Xu, Ping; Zhang, Mian; Li, Ying; Chen, Yang; Liu, Li; Xia, Lun-Zhu; Liu, Xiao-Dong

2016-07-01

Diclofenac is a non-steroidal anti-inflammatory drug (NSAID), which may cause serious intestinal adverse reactions (enteropathy). In this study we investigated whether co-administration of ciprofloxacin affected the pharmacokinetics of diclofenac and diclofenac-induced enteropathy in rats. The pharmacokinetics of diclofenac was assessed in rats after receiving diclofenac (10 mg/kg, ig, or 5 mg/kg, iv), with or without ciprofloxacin (20 mg/kg, ig) co-administered. After receiving 6 oral doses or 15 intravenous doses of diclofenac, the rats were sacrificed, and small intestine was removed to examine diclofenac-induced enteropathy. β-Glucuronidase activity in intestinal content, bovine liver and E coli was evaluated. Following oral or intravenous administration, the pharmacokinetic profile of diclofenac displayed typical enterohepatic circulation, and co-administration of ciprofloxacin abolished the enterohepatic circulation, resulted in significant reduction in the plasma content of diclofenac. In control rats, β-glucuronidase activity in small intestinal content was region-dependent: proximal intestinediclofenac, typical enteropathy was developed with severe enteropathy occurred in distal small intestine. Co-administration of ciprofloxacin significantly alleviated diclofenac-induced enteropathy. Co-administration of ciprofloxacin attenuated enterohepatic circulation of diclofenac and alleviated diclofenac-induced enteropathy in rats, partly via the inhibition of intestinal β-glucuronidase activity.

Punishing hypocrisy: the roles of hypocrisy and moral emotions in deciding culpability and punishment of criminal and civil moral transgressors.

Science.gov (United States)

Laurent, Sean M; Clark, Brian A M; Walker, Stephannie; Wiseman, Kimberly D

2014-01-01

Three experiments explored how hypocrisy affects attributions of criminal guilt and the desire to punish hypocritical criminals. Study 1 established that via perceived hypocrisy, a hypocritical criminal was seen as more culpable and was punished more than a non-hypocritical criminal who committed an identical crime. Study 2 expanded on this, showing that negative moral emotions (anger and disgust) mediated the relationships between perceived hypocrisy, criminal guilt, and punishment. Study 3 replicated the emotion finding from Study 2 using new scenarios where group agents were clearly aware of the hypocrisy of their actions, yet acted anyway. Again, perceived hypocrisy worked through moral emotions to affect criminal guilt and punishment. The current studies provide empirical support for theories relating hypocrisy and moral transgressions to moral emotions, also informing the literature on the role of moral emotions in moral reasoning and legal decision making.

Punishment Strategies: First Choice or Last Resort

Science.gov (United States)

Lukowiak, Twila; Bridges, Jennifer

2010-01-01

Is it appropriate to implement punishment strategies in the home and school settings when children display disrespectful and inappropriate behaviors? This article depicts the advantages and disadvantages of teachers and parents utilizing an array of punishment strategies including: (a) reprimands, (b) response cost, (c) timeout, and (d) corporal…

Childhood Corporal Punishment and Future Perpetration of Physical Dating Violence.

Science.gov (United States)

Temple, Jeff R; Choi, Hye Jeong; Reuter, Tyson; Wolfe, David; Taylor, Catherine A; Madigan, Sheri; Scott, Lauren E

2018-03-01

To test whether experiencing childhood corporal punishment is linked to later perpetration of dating violence. Young adults (n = 758; 61% female; mean age of 20 years), originally recruited for a longitudinal study as 9th- and 10th-grade Texas high school students, were asked about their childhood experiences with corporal punishment and physical abuse, as well as current experiences with dating violence. A path model was used to determine whether childhood corporal punishment was related to recent perpetration of physical dating violence, while controlling for childhood physical abuse, age, sex, ethnicity, and socioeconomic status. In all, 19% of participants (n = 134) reported physical dating violence perpetration and 68% reported experiencing corporal punishment as children (n = 498). Analysis showed a significant positive association between corporal punishment and physical perpetration of dating violence (OR 1.30, 95% CI 1.07-1.59). Even after controlling for sex, ethnicity, age, parental education, and child physical abuse, childhood corporal punishment was associated significantly with physical dating violence perpetration (aOR 1.29, 95% CI 1.02-1.62). The finding that childhood corporal punishment was associated with perpetration of young adult physical dating violence, even after controlling for several demographic variables and childhood physical abuse, adds to the growing literature demonstrating deleterious outcomes associated with corporal punishment. Copyright © 2017 Elsevier Inc. All rights reserved.

A survey of parental opinions on corporal punishment in schools.

Science.gov (United States)

Kelly, P C; Weir, M R; Fearnow, R G

1985-06-01

Forty-three states permit corporal punishment in schools. This practice continues despite the universal opposition of professional organizations, including the American Academy of Pediatrics. This study determines parental attitudes concerning the use of physical punishment in schools. The surveyed sample is drawn from parents of military dependents who brought their children to this clinic for routine physical examinations. One hundred and twenty-nine of 132 questionnaires were returned for a 98% response rate. Fifty-one percent of the parents supported the use of corporal punishment in schools, 37% disagreed (77% of these strongly), 11% had no opinion, and 1% did not respond to the question. Analysis of the responses displayed a relationship between parental attitudes on the use of corporal punishment and opinion of the positive effects of physical punishment on children's behavior (p less than 0.0001). No relationship was found between position on corporal punishment and the respondent (mother, father, or both), the age of parents, the military rank of the sponsor (the individual whose military service makes the child eligible for military medical care, i.e., father, mother, guardian, etc.), the sex of the children, the marital status of the parents, or the schools attended by the children (public or private). Thirty-four percent of parents believed corporal punishment would improve behavior, and 20% of parents felt that physical punishment would improve their child's academic performance.

Global inhibition of reactive oxygen species (ROS inhibits paclitaxel-induced painful peripheral neuropathy.

Directory of Open Access Journals (Sweden)

Mehmet Fidanboylu

Full Text Available Paclitaxel (Taxol® is a widely used chemotherapeutic agent that has a major dose limiting side-effect of painful peripheral neuropathy. Currently there is no effective therapy for the prevention or treatment of chemotherapy-induced painful peripheral neuropathies. Evidence for mitochondrial dysfunction during paclitaxel-induced pain was previously indicated with the presence of swollen and vacuolated neuronal mitochondria. As mitochondria are a major source of reactive oxygen species (ROS, the aim of this study was to examine whether pharmacological inhibition of ROS could reverse established paclitaxel-induced pain or prevent the development of paclitaxel-induced pain. Using a rat model of paclitaxel-induced pain (intraperitoneal 2 mg/kg paclitaxel on days 0, 2, 4 & 6, the effects of a non-specific ROS scavenger, N-tert-Butyl-α-phenylnitrone (PBN and a superoxide selective scavenger, 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL were compared. Systemic 100 mg/kg PBN administration markedly inhibited established paclitaxel-induced mechanical hypersensitivity to von Frey 8 g and 15 g stimulation and cold hypersensitivity to plantar acetone application. Daily systemic administration of 50 mg/kg PBN (days -1 to 13 completely prevented mechanical hypersensitivity to von Frey 4 g and 8 g stimulation and significantly attenuated mechanical hypersensitivity to von Frey 15 g. Systemic 100 mg/kg TEMPOL had no effect on established paclitaxel-induced mechanical or cold hypersensitivity. High dose (250 mg/kg systemic TEMPOL significantly inhibited mechanical hypersensitivity to von Frey 8 g & 15 g, but to a lesser extent than PBN. Daily systemic administration of 100 mg/kg TEMPOL (day -1 to 12 did not affect the development of paclitaxel-induced mechanical hypersensitivity. These data suggest that ROS play a causal role in the development and maintenance of paclitaxel-induced pain, but such effects cannot be attributed to superoxide radicals

Corporal punishment: mother's disciplinary behavior and child's psychological profile in Alexandria, Egypt.

Science.gov (United States)

Abolfotouh, Mostafa A; El-Bourgy, Mohamed D; Seif El Din, Amira G; Mehanna, Azza A

2009-01-01

Although all professionals oppose abusive physical punishment, nonabusive physical punishment is still controversial. The aim of the present study was (i) to determine parents' behavior regarding the discipline of their children using corporal punishment or other alternative disciplinary methods, (ii) to identify the different associated factors for corporal punishment, and (iii) to determine the association between exposure of the child to corporal punishment and his or her psychosocial well-being. A representative sample of 400 fifth-grade primary school children and their mothers were subjected to a cross-sectional survey. Mothers were subjected to a questionnaire to assess their behavior on corporal punishment and other disciplinary methods. The children were subjected to Coopersmith Self-Esteem Inventory to assess their self-esteem, and a questionnaire to assess their relationship with others. About three-quarter of children (76.3%) were corporally punished, and about half of them (46.2%) were punished on sites other than the extremities or buttocks. In 59.3% of them the frequency of the punishment ranged from once or twice/week to more than once/day, and it left marks in about 20%. Other disciplinary methods used by mothers were yelling/insulting (43.5%), taking away a toy or privilege (39.3%), discussing/explaining (9.5%), and time out (2.8%). The significant predictors of mothers' use of corporal punishment were male gender of the child (p corporal punishment of children and their self-esteem was not statistically significant; however, corporally punished children scored lower on their relationship with others than noncorporally punished ones (Z= 2.60, p Corporal punishment is a widespread disciplinary method in Alexandria. The use of corporal punishment could have adverse effects on the child especially on his or her relationship with others. Planning an awareness-raising educational program for current and expectant parents is recommended, to promote

The advantage of democratic peer punishment in sustaining cooperation within groups

DEFF Research Database (Denmark)

Pfattheicher, Stefan; Boehm, Robert; Kesberg, Rebekka

2018-01-01

(i.e., antisocial punishment) is possible. In the present work, we propose that a system of democratic peer punishment, that is, direct and equal participation of each individual in the punishment decision‐making process with punishment only executed when a majority has voted for its execution, can......In social dilemma situations, individuals benefit from uncooperative behavior while exploiting resources of the collective. One prominent solution to prevent uncooperative behavior and to increase cooperation is to establish a system of costly peer punishment, that is, the possibility for every...

A Cross-Cultural Study of Punishment Beliefs and Decisions.

Science.gov (United States)

Zhang, Yanyan; Chen, Chuansheng; Greenberger, Ellen; Knowles, Eric D

2017-02-01

The current research examined cultural similarities and differences in punishment beliefs and decisions. Participants were European Americans ( N = 50), Chinese Americans ( N = 57), and Chinese in Mainland China ( N = 50). The Functions of Punishment Questionnaire was used to measure participants' beliefs about the retributive or deterrent functions of punishment and a scenario method was used to measure the extent to which punishment decisions were driven by individuals' concerns for retribution or deterrence. The results indicated that, contrary to the hypothesis that the retributive function would be emphasized by individualistic groups and the deterrent function by collectivistic groups, Mainland Chinese participants had a stronger belief in retribution and a weaker belief in deterrence than did European and Chinese Americans. The results also indicated that retribution played a bigger role in punishment decisions for Chinese than for the other two groups, but the importance of the deterrence function in punishment decisions did not differ across the three groups. Finally, the correlation between interdependence orientation and the belief in retribution was positive for Chinese but negative for European Americans. Taken together, the findings provided little evidence that collectivists are more deterrence-oriented and individualists more retribution-oriented.

Jasmonic Acid Enhances Al-Induced Root Growth Inhibition.

Science.gov (United States)

Yang, Zhong-Bao; He, Chunmei; Ma, Yanqi; Herde, Marco; Ding, Zhaojun

2017-02-01

Phytohormones such as ethylene and auxin are involved in the regulation of the aluminum (Al)-induced root growth inhibition. Although jasmonate (JA) has been reported to play a crucial role in the regulation of root growth and development in response to environmental stresses through interplay with ethylene and auxin, its role in the regulation of root growth response to Al stress is not yet known. In an attempt to elucidate the role of JA, we found that exogenous application of JA enhanced the Al-induced root growth inhibition. Furthermore, phenotype analysis with mutants defective in either JA biosynthesis or signaling suggests that JA is involved in the regulation of Al-induced root growth inhibition. The expression of the JA receptor CORONATINE INSENSITIVE1 (COI1) and the key JA signaling regulator MYC2 was up-regulated in response to Al stress in the root tips. This process together with COI1-mediated Al-induced root growth inhibition under Al stress was controlled by ethylene but not auxin. Transcriptomic analysis revealed that many responsive genes under Al stress were regulated by JA signaling. The differential responsive of microtubule organization-related genes between the wild-type and coi1-2 mutant is consistent with the changed depolymerization of cortical microtubules in coi1 under Al stress. In addition, ALMT-mediated malate exudation and thus Al exclusion from roots in response to Al stress was also regulated by COI1-mediated JA signaling. Together, this study suggests that root growth inhibition is regulated by COI1-mediated JA signaling independent from auxin signaling and provides novel insights into the phytohormone-mediated root growth inhibition in response to Al stress. © 2017 American Society of Plant Biologists. All Rights Reserved.

Punishment Learning in U.S. Veterans With Posttraumatic Stress Disorder.

Science.gov (United States)

Sawyer, Alice T; Liverant, Gabrielle I; Jun, Janie J; Lee, Daniel J; Cohen, Andrew L; Dutra, Sunny J; Pizzagalli, Diego A; Sloan, Denise M

2016-08-01

Learning processes have been implicated in the development and course of posttraumatic stress disorder (PTSD); however, little is currently known about punishment-based learning in PTSD. The current study investigated impairments in punishment-based learning in U.S. veterans. We expected that veterans with PTSD would demonstrate greater punishment-based learning compared to a non-PTSD control group. We compared a PTSD group with and without co-occurring depression (n = 27) to a control group (with and without trauma exposure) without PTSD or depression (n = 29). Participants completed a computerized probabilistic punishment-based learning task. Compared to the non-PTSD control group, veterans with PTSD showed significantly greater punishment-based learning. Specifically, there was a significant Block × Group interaction, F(1, 54) = 4.12, p = .047, η(2) = .07. Veterans with PTSD demonstrated greater change in response bias for responding toward a less frequently punished stimulus across blocks. The observed hypersensitivity to punishment in individuals with PTSD may contribute to avoidant responses that are not specific to trauma cues. Copyright © 2016 International Society for Traumatic Stress Studies No claim to original US government works.

Fluoxetine-induced inhibition of synaptosomal [3H]5-HT release: Possible Ca2+-channel inhibition

International Nuclear Information System (INIS)

Stauderman, K.A.; Gandhi, V.C.; Jones, D.J.

1992-01-01

Fluoxetine, a selective 5-Ht uptake inhibitor, inhibited 15 mM K + -induced [ 3 H]5-HT release from rat spinal cord and cortical synaptosomes at concentrations > 0.5 uM. This effect reflected a property shared by another selective 5-HT uptake inhibitor paroxetine but not by less selective uptake inhibitors such as amitriptyline, desipramine, imipramine or nortriptyline. Inhibition of release by fluoxetine was inversely related to both the concentration of K + used to depolarize the synaptosomes and the concentration of external Ca 2+ . Experiments aimed at determining a mechanism of action revealed that fluoxetine did not inhibit voltage-independent release of [ 3 H]5-HT release induced by the Ca 2+ -ionophore A 23187 or Ca 2+ -independent release induced by fenfluramine. Moreover the 5-HT autoreceptor antagonist methiothepin did not reverse the inhibitory actions of fluoxetine on K + -induced release. Further studies examined the effects of fluoxetine on voltage-dependent Ca 2+ channels and Ca 2+ entry

Taurine protects against methotrexate-induced toxicity and inhibits leukocyte death

International Nuclear Information System (INIS)

Cetiner, Mustafa; Sener, Goeksel; Sehirli, A. Ozer; Eksioglu-Demiralp, Emel; Ercan, Feriha; Sirvanci, Serap; Gedik, Nursal; Akpulat, Sertac; Tecimer, Tuelay; Yegen, Berrak C.

2005-01-01

The efficacy of methotrexate (MTX), a widely used cytotoxic chemotherapeutic agent, is often limited by severe side effects and toxic sequelae. Regarding the mechanisms of these side effects, several hypotheses have been put forward, among which oxidative stress is noticeable. The present study was undertaken to determine whether taurine, a potent free radical scavenger, could ameliorate MTX-induced oxidative injury and modulate immune response. Following a single dose of methotrexate (20 mg/kg), either saline or taurine (50 mg/kg) was administered for 5 days. After decapitation of the rats, trunk blood was obtained and the ileum, liver, and kidney were removed to measure malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity, and collagen content, as well as histological examination. Our results showed that MTX administration increased the MDA, MPO activity, and collagen contents and decreased GSH levels in all tissues (P < 0.001), while these alterations were reversed in taurine-treated group (P < 0.05-0.01). Elevated (P < 0.001) TNF-α level observed following MTX treatment was depressed with taurine (P < 0.01). Oxidative burst of neutrophils stimulated by phorbol myristate acetate was reduced in saline-treated MTX group (P < 0.001), while taurine abolished this effect. Similarly, flow cytometric measurements revealed that leukocyte apoptosis and cell death were increased in MTX-treated animals, while taurine reversed these effects (P < 0.05). Reduced cellularity in bone marrow samples of MTX-treated group (P < 0.01) was reversed back to control levels in taurine-treated rats. Severe degeneration of the intestinal mucosa, liver parenchyma, glomerular, and tubular epithelium observed in saline-treated group was improved by taurine treatment. In conclusion, it appears that taurine protects against methotrexate-induced oxidant organ injury and inhibits leukocyte apoptosis and may be of therapeutic potential in alleviating the systemic

Corporal punishment and the growth trajectory of children's antisocial behavior.

Science.gov (United States)

Grogan-Kaylor, Andrew

2005-08-01

Despite considerable research, the relationship between corporal punishment and antisocial behavior is unclear. This analysis examined (a) the functional form of this relationship, (b) the correlation of initial antisocial behavior and changes in antisocial behavior, (c) differences in the relationship of corporal punishment and antisocial behavior by race, and (d) whether this relationship could be accounted for by unmeasured characteristics of children and their families. Data from 6,912 children in the National Longitudinal Survey of Youth were analyzed using hierarchical linear models. Findings suggested that corporal punishment has a relationship with children's initial antisocial behavior and with changes in antisocial behavior. No evidence was found for differences in the effect of corporal punishment across racial groups. The relationship between corporal punishment and antisocial behavior persists even when accounting for unmeasured time invariant characteristics of children and families. The findings suggest that corporal punishment is not a preferable technique for disciplining children.

School corporal punishment in global perspective: prevalence, outcomes, and efforts at intervention.

Science.gov (United States)

Gershoff, Elizabeth T

2017-03-01

School corporal punishment continues to be a legal means of disciplining children in a third of the world's countries. Although much is known about parents' use of corporal punishment, there is less research about school corporal punishment. This article summarizes what is known about the legality and prevalence of school corporal punishment, about the outcomes linked to it, and about interventions to reduce and eliminate school corporal punishment around the world.

To Punish or Not to Punish-That Is the Question.

Science.gov (United States)

Chen, Gila; Einat, Tomer

2017-02-01

Attitudes toward punishment have long been of interest to policymakers, researchers, and criminal justice practitioners. The current study examined the relationship between academic education in criminology and attitudes toward punishment among 477 undergraduate students in three subgroups: police officers, correctional officers, and criminology students who were not employed by the criminal justice system (CJS). Our main findings concluded that (a) punitive attitudes of the correctional officers and police officers at the beginning of their academic studies were harsher than those of the criminology and criminal justice students who were not employed by the CJS, (b) punitive attitudes of the correctional officers at the end of their academic studies were less severe than their first-year counterparts, (c) fear of crime was higher among women than among men, and (d) the strongest predictor of punitive attitudes was a firm belief in the principles of the classical and labeling theories (beyond group). Implications of these results are discussed.

Predicting Filipino Mothers' and Fathers' Reported Use of Corporal Punishment from Education, Authoritarian Attitudes, and Endorsement of Corporal Punishment

Science.gov (United States)

Jocson, Rosanne M.; Alampay, Liane Pena; Lansford, Jennifer E.

2012-01-01

The relations of education, authoritarian child-rearing attitudes, and endorsement of corporal punishment to Filipino parents' reported use of corporal punishment were examined using two waves of data. Structured interviews using self-report questionnaires were conducted with 117 mothers and 98 fathers from 120 families when their children were 8…

Osthole pretreatment alleviates TNBS-induced colitis in mice via both cAMP/PKA-dependent and independent pathways.

Science.gov (United States)

Sun, Wu; Cai, Yun; Zhang, Xin-Xin; Chen, Hao; Lin, Yan-Die; Li, Hao

2017-08-01

Osthole, a natural coumarin found in traditional Chinese medicinal plants, has shown multiple biological activities. In the present study, we investigated the preventive effects of osthole on inflammatory bowel disease (IBD). Colitis was induced in mice by infusing TNBS into the colonic lumen. Before TNBS treatment, the mice received osthole (100 mg·kg -1 ·d -1 , ip) for 3 d. Pretreatment with osthole significantly ameliorated the clinical scores, colon length shortening, colonic histopathological changes and the expression of inflammatory mediators in TNBS-induced colitis. Pretreatment with osthole elevated serum cAMP levels; but treatment with the PKA inhibitor H89 (10 mg·kg -1 ·d -1 , ip) did not abolish the beneficial effects of osthole on TNBS-induced colitis. In mouse peritoneal macrophages, pretreatment with osthole (50 μmol/L) significantly attenuated the LPS-induced elevation of cytokines at the mRNA level; inhibition of PKA completely reversed the inhibitory effects of osthole on IL-1β, IL-6, COX2, and MCP-1 but not on TNFα. In Raw264.7 cells, the p38 inhibitor SB203580 markedly suppressed LPS-induced upregulation of the cytokines, whereas the PKA inhibitors H89 or KT5720 did not abolish the inhibitory effects of SB203580. Moreover, in LPS-stimulated mouse peritoneal macrophages, SB203580 strongly inhibited the restored expression of IL-1β, IL-6, COX2, and MCP-1, which was achieved by abolishing the suppressive effects of osthole with the PKA inhibitors. Western blot analysis showed that osthole significantly suppressed the phosphorylation of p38, which was induced by TNBS in mice or by LPS in Raw264.7 cells. Inhibition of PKA partially reversed the suppressive effects of osthole on p38 phosphorylation in LPS-stimulated cells. Collectively, our results suggest that osthole is effective in the prevention of TNBS-induced colitis by reducing the expression of inflammatory mediators and attenuating p38 phosphorylation via both cAMP/PKA-dependent and

Punishment as a Means of Competition: Implications for Strong Reciprocity Theory

Science.gov (United States)

Paál, Tünde; Bereczkei, Tamás

2015-01-01

Strong negative reciprocity, that is, sanctions imposed on norm violators at the punisher’s own expense, has powerful cooperation-enhancing effects in both real-life and experimental game situations. However, it is plausible that punishment may obtain alternative roles depending on social context and the personality characteristics of participants. We examined the occurrence of punishing behavior among 80 subjects in a strongly competitive Public Goods game setting. Despite the punishment condition, the amount of the contributions decreased steadily during the game. The amount of contributions had no significant effect on received and imposed punishments. The results indicate that certain social contexts (in this case, intensive competition) exert modifying effects on the role that punishment takes on. Subjects punished each other in order to achieve a higher rank and a financially better outcome. Punishment primarily functioned as a means of rivalry, instead of as a way of second-order cooperation, as strong reciprocity suggests. These results indicate the need for the possible modification of the social conditions of punishment mechanisms described by the strong reciprocity theory as an evolutionary explanation of human cooperation. PMID:25811464

The Role of Compassion in Altruistic Helping and Punishment Behavior.

Science.gov (United States)

Weng, Helen Y; Fox, Andrew S; Hessenthaler, Heather C; Stodola, Diane E; Davidson, Richard J

2015-01-01

Compassion, the emotional response of caring for another who is suffering and that results in motivation to relieve suffering, is thought to be an emotional antecedent to altruistic behavior. However, it remains unclear whether compassion enhances altruistic behavior in a uniform way or is specific to sub-types of behavior such as altruistic helping of a victim or altruistic punishment of a transgressor. We investigated the relationship between compassion and subtypes of altruistic behavior using third-party paradigms where participants (1) witnessed an unfair economic exchange between a transgressor and a victim, and (2) had the opportunity to either spend personal funds to either economically (a) help the victim or (b) punish the transgressor. In Study 1, we examined whether individual differences in self-reported empathic concern (the emotional component of compassion) was associated with greater altruistic helping or punishment behavior in two independent samples. For participants who witnessed an unfair transaction, trait empathic concern was associated with greater helping of a victim and had no relationship to punishment. However, in those who decided to punish the transgressor, participants who reported greater empathic concern decided to punish less. In Study 2, we directly enhanced compassion using short-term online compassion meditation training to examine whether altruistic helping and punishment were increased after two weeks of training. Compared to an active reappraisal training control group, the compassion training group gave more to help the victim and did not differ in punishment of the transgressor. Together, these two studies suggest that compassion is related to greater altruistic helping of victims and is not associated with or may mitigate altruistic punishment of transgressors.

The Role of Compassion in Altruistic Helping and Punishment Behavior.

Directory of Open Access Journals (Sweden)

Helen Y Weng

Full Text Available Compassion, the emotional response of caring for another who is suffering and that results in motivation to relieve suffering, is thought to be an emotional antecedent to altruistic behavior. However, it remains unclear whether compassion enhances altruistic behavior in a uniform way or is specific to sub-types of behavior such as altruistic helping of a victim or altruistic punishment of a transgressor. We investigated the relationship between compassion and subtypes of altruistic behavior using third-party paradigms where participants (1 witnessed an unfair economic exchange between a transgressor and a victim, and (2 had the opportunity to either spend personal funds to either economically (a help the victim or (b punish the transgressor. In Study 1, we examined whether individual differences in self-reported empathic concern (the emotional component of compassion was associated with greater altruistic helping or punishment behavior in two independent samples. For participants who witnessed an unfair transaction, trait empathic concern was associated with greater helping of a victim and had no relationship to punishment. However, in those who decided to punish the transgressor, participants who reported greater empathic concern decided to punish less. In Study 2, we directly enhanced compassion using short-term online compassion meditation training to examine whether altruistic helping and punishment were increased after two weeks of training. Compared to an active reappraisal training control group, the compassion training group gave more to help the victim and did not differ in punishment of the transgressor. Together, these two studies suggest that compassion is related to greater altruistic helping of victims and is not associated with or may mitigate altruistic punishment of transgressors.

Prevalence of corporal punishment among students in Washington State schools.

Science.gov (United States)

Grossman, D C; Rauh, M J; Rivara, F P

1995-05-01

To determine the prevalence of corporal punishment in Washington State and the factors associated with its use in Washington elementary and secondary schools. Cross-sectional mail survey performed during the summer of 1992. All elementary and secondary schools in the state of Washington. One thousand eighteen schools (47%) responded to the survey, of which 80% were publicly funded and 63% were located in urban areas. The study sample closely resembled the profile of all schools in the state. Almost 11% of participating schools permitted corporal punishment at the time of the survey and 3.2% reported its actual use during the 1991-1992 school year, resulting in an estimated prevalence of 7.2 incidents per 1000 students per year. Sixteen percent of corporal punishment actions occurred in schools not permitting its use. Ninety percent of public schools relied on district policy regarding corporal punishment. School characteristics associated with the use of corporal punishment included rural location (crude odds ratio, 2.2; 95% confidence interval, 1.5 to 3.4), enrollment of less than 500 students (crude odds ratio, 1.7; 95% confidence interval, 1.1 to 2.7), and kindergarten to eighth-grade or kindergarten to 12th-grade enrollment (crude odds ratio, 2.5; 95% confidence interval, 1.6 to 3.9). The lack of a statewide ban on school corporal punishment at the time of this survey was associated with the continued use of corporal punishment against children in districts that continued to permit it. School policies against corporal punishment were associated with much lower prevalence. Continued efforts are needed to enact and enforce laws in the remaining states that have not yet banned corporal punishment.

Neural reward and punishment sensitivity in cigarette smokers.

Science.gov (United States)

Potts, Geoffrey F; Bloom, Erika L; Evans, David E; Drobes, David J

2014-11-01

Nicotine addiction remains a major public health problem but the neural substrates of addictive behavior remain unknown. One characteristic of smoking behavior is impulsive choice, selecting the immediate reward of smoking despite the potential long-term negative consequences. This suggests that drug users, including cigarette smokers, may be more sensitive to rewards and less sensitive to punishment. We used event-related potentials (ERPs) to test the hypothesis that smokers are more responsive to reward signals and less responsive to punishment, potentially predisposing them to risky behavior. We conducted two experiments, one using a reward prediction design to elicit a Medial Frontal Negativity (MFN) and one using a reward- and punishment-motivated flanker task to elicit an Error Related Negativity (ERN), ERP components thought to index activity in the cortical projection of the dopaminergic reward system. The smokers had a greater MFN response to unpredicted rewards, and non-smokers, but not smokers, had a larger ERN on punishment motivated trials indicating that smokers are more reward sensitive and less punishment sensitive than nonsmokers, overestimating the appetitive value and underestimating aversive outcomes of stimuli and actions. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

[Parent's perspective on child rearing and corporal punishment].

Science.gov (United States)

Donoso, Miguir Terezinha Vieccelli; Ricas, Janete

2009-02-01

To describe parents' current perception of corporal punishment associated to child rearing and its practices. There were studied 31 family members whose children were warded due to child abuse complaints (12) and not warded (19) at a health care unit and a local social service unit in the city of Belo Horizonte (Southeastern Brazil) in 2006. Data was collected through semi-structured interviews and speech analysis was performed grouped by subjects and categories. ANALYSIS OF DISCOURSE: There was limitation of the respondents' speeches based on their production means. There was a diversity of conceptions on child rearing and its practices and corporal punishment was reported by all parents, even among those who expressed strong disapproval of this practice. Speeches were characterized by heterogeneity and polyphony with emphasis on the tradition speech, the religious speech and the popular scientific speech. Respondents did not express concepts of legal interdiction of corporal punishment or its excesses. The culture of corporal punishment of children is changing; tradition approving it has weakened and prohibition has been slowly adopted. Reinforcing legal actions against this practice can contribute to speed up the process to end corporal punishment of children.

Punishment sustains large-scale cooperation in prestate warfare

Science.gov (United States)

Mathew, Sarah; Boyd, Robert

2011-01-01

Understanding cooperation and punishment in small-scale societies is crucial for explaining the origins of human cooperation. We studied warfare among the Turkana, a politically uncentralized, egalitarian, nomadic pastoral society in East Africa. Based on a representative sample of 88 recent raids, we show that the Turkana sustain costly cooperation in combat at a remarkably large scale, at least in part, through punishment of free-riders. Raiding parties comprised several hundred warriors and participants are not kin or day-to-day interactants. Warriors incur substantial risk of death and produce collective benefits. Cowardice and desertions occur, and are punished by community-imposed sanctions, including collective corporal punishment and fines. Furthermore, Turkana norms governing warfare benefit the ethnolinguistic group, a population of a half-million people, at the expense of smaller social groupings. These results challenge current views that punishment is unimportant in small-scale societies and that human cooperation evolved in small groups of kin and familiar individuals. Instead, these results suggest that cooperation at the larger scale of ethnolinguistic units enforced by third-party sanctions could have a deep evolutionary history in the human species. PMID:21670285

Emotions and Actions Associated with Altruistic Helping and Punishment

Directory of Open Access Journals (Sweden)

Omar Tonsi Eldakar

2006-01-01

Full Text Available Evolutionary altruism (defined in terms of fitness effects exists in the context of punishment in addition to helping. We examine the proximate psychological mechanisms that motivate altruistic helping and punishment, including the effects of genetic relatedness, potential for future interactions, and individual differences in propensity to help and punish. A cheater who is a genetic relative provokes a stronger emotional reaction than a cheater who is a stranger, but the behavioral response is modulated to avoid making the transgression public in the case of cheating relatives. Numerous behavioral differences are not accompanied by emotional differences, suggesting that other psychological mechanisms dictate the specific response to emotion-provoking events. Paradoxically, there is a positive correlation between temptation to cheat and propensity to punish others for cheating, leading to a concept of “selfish punishment” that has been substantiated by a computer simulation model. This study demonstrates that fictional scenarios can provide an important methodological tool for studying the psychological basis of helping and punishment.

The Effect of Corporal Punishment on Antisocial Behavior in Children.

Science.gov (United States)

Grogan-Kaylor, Andrew

2004-01-01

This study was conducted to examine the effect of corporal punishment on antisocial behavior of children using stronger statistical controls than earlier literature in this area; to examine whether the effect of corporal punishment on antisocial behavior is nonlinear; and to investigate whether the effects of corporal punishment on antisocial…

Preschoolers' group bias in punishing selfishness in the Ultimatum Game.

Science.gov (United States)

Wu, Zhen; Gao, Xiaohe

2018-02-01

Previous studies have shown that both adults and children tend to favor members of their own group and expect reciprocity of such in-group privilege. If a person is treated unfairly by an in-group member, a conflict arises between the tendency of in-group favoritism and the desire to punish violators of in-group norms. How do children solve the conflict at different points in development? We compared how preschoolers punished in-group and out-group members (marked by color preference) for selfishness in the Ultimatum Game. We found that (a) 3- to 6-year-old Chinese children rejected selfish allocations more often than fair ones, showing a robust preference for fairness; (b) 3- and 4-year-olds showed no group differences in their punishment behavior, suggesting that second-party punishment of selfishness is not biased during early childhood; (c) 5- and 6-year-old girls were more likely to punish selfishness of in-groups than of out-groups, illuminating an early sign of maintaining group-based fairness norms even at a personal cost; and (d) 5- and 6-year-old boys, however, punished in-groups and out-groups equally often and punished out-groups more often than did girls. These age and gender differences in children's punishment imply that socialization may play an important role in showing group bias when enforcing fairness norms. Copyright © 2017 Elsevier Inc. All rights reserved.

Sanctions as honest signals--the evolution of pool punishment by public sanctioning institutions.

Science.gov (United States)

Schoenmakers, Sarah; Hilbe, Christian; Blasius, Bernd; Traulsen, Arne

2014-09-07

In many species, mutual cooperation is stabilized by forms of policing and peer punishment: if cheaters are punished, there is a strong selective pressure to cooperate. Most human societies have complemented, and sometimes even replaced, such peer punishment mechanisms with pool punishment, where punishment is outsourced to central institutions such as the police. Even before free-riding occurs, such institutions require investments, which could serve as costly signals. Here, we show with a game theoretical model that this signaling effect in turn can be crucial for the evolution of punishment institutions: In the absence of such signals, pool punishment is only stable with second-order punishment and can only evolve when individuals have the freedom not to take part in any interaction. With such signals, individuals can opportunistically adjust their behavior, which promotes the evolution of stable pool punishment even in situations where no one can stand aside. Thus, the human propensity to react opportunistically to credible punishment threats is often sufficient to establish stable punishment institutions and to maintain high levels of cooperation. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Evolutionary snowdrift game incorporating costly punishment in structured populations

Science.gov (United States)

Chan, Nat W. H.; Xu, C.; Tey, Siew Kian; Yap, Yee Jiun; Hui, P. M.

2013-01-01

The role of punishment and the effects of a structured population in promoting cooperation are important issues. Within a recent model of snowdrift game (SG) incorporating a costly punishing strategy (P), we study the effects of a population connected through a square lattice. The punishers, who carry basically a cooperative (C) character, are willing to pay a cost α so as to punish a non-cooperative (D) opponent by β. Depending on α, β, the cost-to-benefit ratio r in SG, and the initial conditions, the system evolves into different phases that could be homogeneous or inhomogeneous. The spatial structure imposes geometrical constraint on how one agent is affected by neighboring agents. Results of extensive numerical simulations, both for the steady state and the dynamics, are presented. Possible phases are identified and discussed, and isolated phases in the r-β space are identified as special local structures of strategies that are stable due to the lattice structure. In contrast to a well-mixed population where punishers are suppressed due to the cost of punishment, the altruistic punishing strategy can flourish and prevail for appropriate values of the parameters, implying an enhancement in cooperation by imposing punishments in a structured population. The system could evolve to a phase corresponding to the coexistence of C, D, and P strategies at some particular payoff parameters, and such a phase is absent in a well-mixed population. The pair approximation, a commonly used analytic approach, is extended from a two-strategy system to a three-strategy system. We show that the pair approximation can, at best, capture the numerical results only qualitatively. Due to the improper way of including spatial correlation imposed by the lattice structure, the approximation does not give the frequencies of C, D, and P accurately and fails to give the homogeneous AllD and AllP phases.

Parsing the Behavioral and Brain Mechanisms of Third-Party Punishment.

Science.gov (United States)

Ginther, Matthew R; Bonnie, Richard J; Hoffman, Morris B; Shen, Francis X; Simons, Kenneth W; Jones, Owen D; Marois, René

2016-09-07

The evolved capacity for third-party punishment is considered crucial to the emergence and maintenance of elaborate human social organization and is central to the modern provision of fairness and justice within society. Although it is well established that the mental state of the offender and the severity of the harm he caused are the two primary predictors of punishment decisions, the precise cognitive and brain mechanisms by which these distinct components are evaluated and integrated into a punishment decision are poorly understood. Using fMRI, here we implement a novel experimental design to functionally dissociate the mechanisms underlying evaluation, integration, and decision that were conflated in previous studies of third-party punishment. Behaviorally, the punishment decision is primarily defined by a superadditive interaction between harm and mental state, with subjects weighing the interaction factor more than the single factors of harm and mental state. On a neural level, evaluation of harms engaged brain areas associated with affective and somatosensory processing, whereas mental state evaluation primarily recruited circuitry involved in mentalization. Harm and mental state evaluations are integrated in medial prefrontal and posterior cingulate structures, with the amygdala acting as a pivotal hub of the interaction between harm and mental state. This integrated information is used by the right dorsolateral prefrontal cortex at the time of the decision to assign an appropriate punishment through a distributed coding system. Together, these findings provide a blueprint of the brain mechanisms by which neutral third parties render punishment decisions. Punishment undergirds large-scale cooperation and helps dispense criminal justice. Yet it is currently unknown precisely how people assess the mental states of offenders, evaluate the harms they caused, and integrate those two components into a single punishment decision. Using a new design, we isolated

Delta-like Ligand-4-Notch Signaling Inhibition Regulates Pancreatic Islet Function and Insulin Secretion

Directory of Open Access Journals (Sweden)

Fabienne Billiard

2018-01-01

Full Text Available Although Notch signaling has been proposed as a therapeutic target for type-2 diabetes, liver steatosis, and atherosclerosis, its direct effect on pancreatic islets remains unknown. Here, we demonstrated a function of Dll4-Notch signaling inhibition on the biology of insulin-producing cells. We confirmed enhanced expression of key Notch signaling genes in purified pancreatic islets from diabetic NOD mice and showed that treatment with anti-Dll4 antibody specifically abolished Notch signaling pathway activation. Furthermore, we showed that Notch inhibition could drive proliferation of β-islet cells and confer protection from the development of STZ-induced diabetes. Importantly, inhibition of the Dll4 pathway in WT mice increased insulin secretion by inducing the differentiation of pancreatic β-islet cell progenitors, as well as the proliferation of insulin-secreting cells. These findings reveal a direct effect of Dll4-blockade on pancreatic islets that, in conjunction with its immunomodulatory effects, could be used for unmet medical needs hallmarked by inefficient insulin action.

Chk1 inhibition activates p53 through p38 MAPK in tetraploid cancer cells.

Science.gov (United States)

Vitale, Ilio; Senovilla, Laura; Galluzzi, Lorenzo; Criollo, Alfredo; Vivet, Sonia; Castedo, Maria; Kroemer, Guido

2008-07-01

We have previously shown that tetraploid cancer cells succumb through a p53-dependent apoptotic pathway when checkpoint kinase 1 (Chk1) is depleted by small interfering RNAs (siRNAs) or inhibited with 7-hydroxystaurosporine (UCN-01). Here, we demonstrate that Chk1 inhibition results in the activating phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK). Depletion of p38 MAPK by transfection with a siRNA targeting the alpha isoform of p38 MAPK (p38alpha MAPK) abolishes the phosphorylation of p53 on serines 15 and 46 that is induced by Chk1 knockdown. The siRNA-mediated downregulation and pharmacological inhibition of p38alpha MAPK (with SB 203580) also reduces cell death induced by Chk1 knockdown or UCN-01. These results underscore the role of p38 MAPK as a pro-apoptotic kinase in the p53-dependant pathway for the therapeutic elimination of polyploidy cells.

Fisetin induces Sirt1 expression while inhibiting early adipogenesis in 3T3-L1 cells.

Science.gov (United States)

Kim, Sang Chon; Kim, Yoo Hoon; Son, Sung Wook; Moon, Eun-Yi; Pyo, Suhkneung; Um, Sung Hee

2015-11-27

Fisetin (3,7,3',4'-tetrahydroxyflavone) is a naturally found flavonol in many fruits and vegetables and is known to have anti-aging, anti-cancer and anti-viral effects. However, the effects of fisetin on early adipocyte differentiation and the epigenetic regulator controlling adipogenic transcription factors remain unclear. Here, we show that fisetin inhibits lipid accumulation and suppresses the expression of PPARγ in 3T3-L1 cells. Fisetin suppressed early stages of preadipocyte differentiation, and induced expression of Sirt1. Depletion of Sirt1 abolished the inhibitory effects of fisetin on intracellular lipid accumulation and on PPARγ expression. Mechanistically, fisetin facilitated Sirt1-mediated deacetylation of PPARγ and FoxO1, and enhanced the association of Sirt1 with the PPARγ promoter, leading to suppression of PPARγ transcriptional activity, thereby repressing adipogenesis. Lowering Sirt1 levels reversed the effects of fisetin on deacetylation of PPARγ and increased PPARγ transactivation. Collectively, our results suggest the effects of fisetin in increasing Sirt1 expression and in epigenetic control of early adipogenesis. Copyright © 2015 Elsevier Inc. All rights reserved.

Freedom deprivation punishment in Serbia during 1804-1860

Directory of Open Access Journals (Sweden)

Mirković Zoran

2013-01-01

Full Text Available This text is on freedom deprivation punishment in Serbia during the first half of 19th century, i.e. since the beginning of the First Serbian uprising in 1804 and till passing the Criminal law in 1860. Author first emphasises that the freedom deprivation punishment doesn't have long tradition, although in medieval Serbia and under Turkish rule existed imprisonment in dungeon, but it was foremost some form of custody before a trial, and subsequently as keeping a prisoner after the verdict until its effectuation. It wasn't a freedom deprivation punishment in modern sense. During 1804 - 1813 there was so called 'haps' i.e. apprehension, though Uprising authorities built also 'real' prisons for punishment purpose. Imprisonment of culprits was a condition for compulsory labour, which could be very useful utilized under given circumstances. Since the beginning 1820-ties when first Serbian courts were established, beside 'haps' appears also imprisonment in heavy shackles. However there was no substantial difference between apprehension and imprisonment. In this time the sentence to imprisonment was combined with the punishment with beating (or sometimes with the flogging at the end of imprisonment. The Regulation of County courts from January 26th 1840 mentions several forms of freedom deprivation punishment, but in praxis freedom deprivation was reduced on either 'eternal' imprisonment or time-sentenced imprisonment. Since the beginning of 1840-ties freedom deprivation was more frequently used as punishment and its implementation was continually spreading. For heaviest crimes was instead death penalty and running gauntlet sentenced freedom deprivation, either from courts or from supreme authority in the amnesty process. Imprisonment was effectuated either at police reformatories (for shorter penalties or at the penitentiary institutions (for longer imprisonment. By the end of 1830-ties an issue of imprisonment of female perpetrators emerged, together

Transcription regulator TRIP-Br2 mediates ER stress-induced brown adipocytes dysfunction.

Science.gov (United States)

Qiang, Guifen; Whang Kong, Hyerim; Gil, Victoria; Liew, Chong Wee

2017-01-09

In contrast to white adipose tissue, brown adipose tissue (BAT) is known to play critical roles for both basal and inducible energy expenditure. Obesity is associated with reduction of BAT function; however, it is not well understood how obesity promotes BAT dysfunction, especially at the molecular level. Here we show that the transcription regulator TRIP-Br2 mediates ER stress-induced inhibition of lipolysis and thermogenesis in BAT. Using in vitro, ex vivo, and in vivo approaches, we demonstrate that obesity-induced inflammation upregulates brown adipocytes TRIP-Br2 expression via the ER stress pathway and amelioration of ER stress in mice completely abolishes high fat diet-induced upregulation of TRIP-Br2 in BAT. We find that increased TRIP-Br2 significantly inhibits brown adipocytes thermogenesis. Finally, we show that ablation of TRIP-Br2 ameliorates ER stress-induced inhibition on lipolysis, fatty acid oxidation, oxidative metabolism, and thermogenesis in brown adipocytes. Taken together, our current study demonstrates a role for TRIP-Br2 in ER stress-induced BAT dysfunction, and inhibiting TRIP-Br2 could be a potential approach for counteracting obesity-induced BAT dysfunction.

Madecassoside Inhibits Melanin Synthesis by Blocking Ultraviolet-Induced Inflammation

Directory of Open Access Journals (Sweden)

Eunsun Jung

2013-12-01

Full Text Available Madecassoside (MA, a pentacyclic triterpene isolated from Centella asitica (L., is used as a therapeutic agent in wound healing and also as an anti-inflammatory and anti-aging agent. However, the involvement of MA in skin-pigmentation has not been reported. This study was conducted to investigate the effects of MA on ultraviolet (UV-induced melanogenesis and mechanisms in a co-culture system of keratinocytes and melanocytes. MA significantly inhibited UVR-induced melanin synthesis and melanosome transfer in the co-culture system. These effects were further demonstrated by the MA-induced inhibition of protease-activated receptor-2 expression and its signaling pathway, cyclooxygenase-2, prostaglandin E2 and prostaglandin F2 alpha in keratinocytes. The clinical efficacy of MA was confirmed on artificially tanned human skin. MA significantly reduced UV-induced melanin index at 8 weeks after topical application. Overall, the study demonstrated significant benefits of MA use in the inhibition of hyperpigmentation caused by UV irradiation.

Monopolizing sanctioning power under noise eliminates perverse punishment but does not increase cooperation

Directory of Open Access Journals (Sweden)

Sven Fischer

2016-09-01

Full Text Available We run several experiments which allow us to compare cooperation under perfect and imperfect information in a centralized and decentralized punishment regime. Under perfect and extremely noisy information, aggregate behavior does not differ between institutions. Under intermediate noise, punishment escalates in the decentralized peer-to-peer punishment regime which badly affects efficiency while sustaining cooperation for longer. Only decentralized punishment is often directed at cooperators (perverse punishment. We report several, sometimes subtle, differences in punishment behavior, and how contributions react.

Monopolizing Sanctioning Power under Noise Eliminates Perverse Punishment But Does Not Increase Cooperation

Science.gov (United States)

Fischer, Sven; Grechenig, Kristoffel; Meier, Nicolas

2016-01-01

We run several experiments which allow us to compare cooperation under perfect and imperfect information in a centralized and decentralized punishment regime. Under perfect and extremely noisy information, aggregate behavior does not differ between institutions. Under intermediate noise, punishment escalates in the decentralized peer-to-peer punishment regime which badly affects efficiency while sustaining cooperation for longer. Only decentralized punishment is often directed at cooperators (perverse punishment). We report several, sometimes subtle, differences in punishment behavior, and how contributions react. PMID:27746725

Significance of bacterial flora in abdominal irradiation-induced inhibition of lung metastases

International Nuclear Information System (INIS)

Matsumoto, T.; Ando, K.; Koike, S.

1988-01-01

We have previously reported that abdominal irradiation prior to i.v. injection of syngeneic tumor cells reduced metastases in lung. Our report described an investigation of the significance of intestinal organisms in the radiation effect. We found that eliminating intestinal organisms with antibiotics totally abolished the radiation effect. Monoassociation of germ-free mice revealed that the radiation effect was observable only for Enterobacter cloacae, never for Streptococcus faecium, Bifidobacterium adlesentis, or Escherichia coli. After abdominal irradiation of regular mice, E. cloacae multiplied in cecal contents, adhered to mucous membranes, invaded the cecal wall, and translocated to mesenteric lymph nodes. Intravenous administration of E. cloacae in place of abdominal irradiation inhibited metastases. E. cloacae-monoassociated mice developed fewer metastases than germ-free mice, and the reduction was further enhanced by abdominal irradiation. We concluded that abdominal irradiation caused the invasion of E. cloacae from the mucous membrane of the intestine and inhibited formation of lung metastases

Effects of monetary reward and punishment on information checking behaviour.

Science.gov (United States)

Li, Simon Y W; Cox, Anna L; Or, Calvin; Blandford, Ann

2016-03-01

Two experiments were conducted to examine whether checking one's own work can be motivated by monetary reward and punishment. Participants were randomly assigned to one of three conditions: a flat-rate payment for completing the task (Control); payment increased for error-free performance (Reward); payment decreased for error performance (Punishment). Experiment 1 (N = 90) was conducted with liberal arts students, using a general data-entry task. Experiment 2 (N = 90) replicated Experiment 1 with clinical students and a safety-critical 'cover story' for the task. In both studies, Reward and Punishment resulted in significantly fewer errors, more frequent and longer checking, than Control. No such differences were obtained between the Reward and Punishment conditions. It is concluded that error consequences in terms of monetary reward and punishment can result in more accurate task performance and more rigorous checking behaviour than errors without consequences. However, whether punishment is more effective than reward, or vice versa, remains inconclusive. Copyright © 2015 Elsevier Ltd and The Ergonomics Society. All rights reserved.

Building the Leviathan – Voluntary centralisation of punishment power sustains cooperation in humans

Science.gov (United States)

Gross, Jörg; Méder, Zsombor Z.; Okamoto-Barth, Sanae; Riedl, Arno

2016-01-01

The prevalence of cooperation among humans is puzzling because cooperators can be exploited by free riders. Peer punishment has been suggested as a solution to this puzzle, but cumulating evidence questions its robustness in sustaining cooperation. Amongst others, punishment fails when it is not powerful enough, or when it elicits counter-punishment. Existing research, however, has ignored that the distribution of punishment power can be the result of social interactions. We introduce a novel experiment in which individuals can transfer punishment power to others. We find that while decentralised peer punishment fails to overcome free riding, the voluntary transfer of punishment power enables groups to sustain cooperation. This is achieved by non-punishing cooperators empowering those who are willing to punish in the interest of the group. Our results show how voluntary power centralisation can efficiently sustain cooperation, which could explain why hierarchical power structures are widespread among animals and humans. PMID:26888519

Arctigenin inhibits triple-negative breast cancers by targeting CIP2A to reactivate protein phosphatase 2A.

Science.gov (United States)

Huang, Qiuyue; Qin, Shanshan; Yuan, Xiaoning; Zhang, Liang; Ji, Juanli; Liu, Xuewen; Ma, Wenjing; Zhang, Yunfei; Liu, Pengfei; Sun, Zhiting; Zhang, Jingxuan; Liu, Ying

2017-07-01

We have shown that a novel STAT3 inhibitor arctigenin (Atn) induces significant cytotoxicity in triple-negative breast cancer (TNBC) cells. This study further delineated molecular mechanisms where by Atn triggered cytotoxicity in TNBC cells. We found Atn can also inhibit metastasis in TNBC cells through cancerous inhibitor of protein phosphatase 2A (CIP2A) pathway. CIP2A is an endogenous inhibitor of protein phosphatase 2A (PP2A), which can increase the migration and invasion of various cancer cells. PP2A is a tumor suppressor, which is functionally defective in various cancers. Atn-induced metastasis inhibition was associated with reactivation of PP2A, downregulation of CIP2A and Akt phosphorylation. Silencing CIP2A enhanced Atn-induced metastasis inhibition and apoptosis in TNBCs. Furthermore, ectopic expression of CIP2A or inhibition of PP2A in TNBC cells abolished the effects of Atn. In conclusion, we found that enhancement of PP2A activity by inhibition of CIP2A, at least in part, promotes the anti-metastasis effect induced by Atn. Our findings disclose the novel therapeutic mechanism of this targeted agent, and suggest the therapeutic potential and feasibility of developing PP2A enhancers as a novel anticancer strategy.

Acute anal stretch inhibits NMDA-dependent pelvic-urethra reflex potentiation via spinal GABAergic inhibition in anesthetized rats.

Science.gov (United States)

Chen, Sung-Lang; Huang, Yu-Hui; Kao, Yu-Lin; Chen, Gin-Den; Cheng, Chen-Li; Peng, Hsien-Yu; Liao, Jiuan-Miaw; Huang, Pei-Chen; Tsai, Shih-Jei; Lin, Tzer-Bin

2008-10-01

The impact of acute anal stretch on the pelvic-urethra reflex potentiation was examined in urethane-anesthetized rats by recording the external urethra sphincter electromyogram activity evoked by the pelvic afferent stimulation. Test stimulation (1 stimulation/30 s) evoked a baseline reflex activity with a single action potential that was abolished by gallamine (5 mg/kg iv). On the other hand, the repetitive stimulation (1 stimulation/1 s) induced spinal reflex potentiation (SRP) that was attenuated by intrathecal 6-cyano-7-nitroquinoxaline-2,4-dione (a glutamatergic alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionat receptor antagonist, 100 microM, 10 microl) and d-2-amino-5-phosphonovalerate [a glutamatergic N-methyl-D-aspartate (NMDA) antagonist, 100 microM, 10 microl]. Acute anal stretch using a mosquito clamp with a distance of 4 mm exhibited no effect, whereas distances of 8 mm attenuated and 12 mm abolished the repetitive stimulation-induced SRP. Intrathecal NMDA (100 microM, 10 microl) reversed the abolition on SRP caused by anal stretch. On the other hand, pretreated bicuculline [gamma-aminobutyric acid (GABA) A receptor antagonist, 100 microM, 10 microl] but not hydroxysaclofen (GABAB receptor antagonist) counteracted the abolition on the repetitive stimulation-induced SRP caused by the anal stretch. All of the results suggested that anal stretch may be used as an adjunct to assist voiding dysfunction in patients with overactive urethra sphincter and that GABAergic neurotransmission is important in the neural mechanisms underlying external urethra sphincter activity inhibited by anal stretch.

Iptakalim inhibits PDGF-BB-induced human airway smooth muscle cells proliferation and migration

Energy Technology Data Exchange (ETDEWEB)

Liu, Wenrui; Kong, Hui; Zeng, Xiaoning; Wang, Jingjing; Wang, Zailiang; Yan, Xiaopei; Wang, Yanli; Xie, Weiping, E-mail: wpxie@njmu.edu.cn; Wang, Hong, E-mail: hongwang@njmu.edu.cn

2015-08-15

Chronic airway diseases are characterized by airway remodeling which is attributed partly to the proliferation and migration of airway smooth muscle cells (ASMCs). ATP-sensitive potassium (K{sub ATP}) channels have been identified in ASMCs. Mount evidence has suggested that K{sub ATP} channel openers can reduce airway hyperresponsiveness and alleviate airway remodeling. Opening K{sup +} channels triggers K{sup +} efflux, which leading to membrane hyperpolarization, preventing Ca{sup 2+}entry through closing voltage-operated Ca{sup 2+} channels. Intracellular Ca{sup 2+} is the most important regulator of muscle contraction, cell proliferation and migration. K{sup +} efflux decreases Ca{sup 2+} influx, which consequently influences ASMCs proliferation and migration. As a K{sub ATP} channel opener, iptakalim (Ipt) has been reported to restrain the proliferation of pulmonary arterial smooth muscle cells (PASMCs) involved in vascular remodeling, while little is known about its impact on ASMCs. The present study was designed to investigate the effects of Ipt on human ASMCs and the mechanisms underlying. Results obtained from cell counting kit-8 (CCK-8), flow cytometry and 5-ethynyl-2′-deoxyuridine (EdU) incorporation showed that Ipt significantly inhibited platelet-derived growth factor (PDGF)-BB-induced ASMCs proliferation. ASMCs migration induced by PDGF-BB was also suppressed by Ipt in transwell migration and scratch assay. Besides, the phosphorylation of Ca{sup 2+}/calmodulin-dependent kinase II (CaMKII), extracellular regulated protein kinases 1/2 (ERK1/2), protein kinase B (Akt), and cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) were as well alleviated by Ipt administration. Furthermore, we found that the inhibition of Ipt on the PDGF-BB-induced proliferation and migration in human ASMCs was blocked by glibenclamide (Gli), a selective K{sub ATP} channel antagonist. These findings provide a strong evidence to support that Ipt

Optogenetic Inhibition Reveals Distinct Roles for Basolateral Amygdala Activity at Discrete Time Points during Risky Decision Making.

Science.gov (United States)

Orsini, Caitlin A; Hernandez, Caesar M; Singhal, Sarthak; Kelly, Kyle B; Frazier, Charles J; Bizon, Jennifer L; Setlow, Barry

2017-11-29

Decision making is a multifaceted process, consisting of several distinct phases that likely require different cognitive operations. Previous work showed that the basolateral amygdala (BLA) is a critical substrate for decision making involving risk of punishment; however, it is unclear how the BLA is recruited at different stages of the decision process. To this end, the current study used optogenetics to inhibit the BLA during specific task phases in a model of risky decision making (risky decision-making task) in which rats choose between a small, "safe" reward and a large reward accompanied by varying probabilities of footshock punishment. Male Long-Evans rats received intra-BLA microinjections of viral vectors carrying either halorhodopsin (eNpHR3.0-mCherry) or mCherry alone (control) followed by optic fiber implants and were trained in the risky decision-making task. Laser delivery during the task occurred during intertrial interval, deliberation, or reward outcome phases, the latter of which was further divided into the three possible outcomes (small, safe; large, unpunished; large, punished). Inhibition of the BLA selectively during the deliberation phase decreased choice of the large, risky outcome (decreased risky choice). In contrast, BLA inhibition selectively during delivery of the large, punished outcome increased risky choice. Inhibition had no effect during the other phases, nor did laser delivery affect performance in control rats. Collectively, these data indicate that the BLA can either inhibit or promote choice of risky options, depending on the phase of the decision process in which it is active. SIGNIFICANCE STATEMENT To date, most behavioral neuroscience research on neural mechanisms of decision making has used techniques that preclude assessment of distinct phases of the decision process. Here we show that optogenetic inhibition of the BLA has opposite effects on choice behavior in a rat model of risky decision making, depending on the phase

Power Asymmetries and Punishment in a Prisoner's Dilemma with Variable Cooperative Investment.

Science.gov (United States)

Bone, Jonathan E; Wallace, Brian; Bshary, Redouan; Raihani, Nichola J

2016-01-01

In many two-player games, players that invest in punishment finish with lower payoffs than those who abstain from punishing. These results question the effectiveness of punishment at promoting cooperation, especially when retaliation is possible. It has been suggested that these findings may stem from the unrealistic assumption that all players are equal in terms of power. However, a previous empirical study which incorporated power asymmetries into an iterated prisoner's dilemma (IPD) game failed to show that power asymmetries stabilize cooperation when punishment is possible. Instead, players cooperated in response to their partner cooperating, and punishment did not yield any additional increase in tendency to cooperate. Nevertheless, this previous study only allowed an all-or-nothing-rather than a variable-cooperation investment. It is possible that power asymmetries increase the effectiveness of punishment from strong players only when players are able to vary their investment in cooperation. We tested this hypothesis using a modified IPD game which allowed players to vary their investment in cooperation in response to being punished. As in the previous study, punishment from strong players did not increase cooperation under any circumstances. Thus, in two-player games with symmetric strategy sets, punishment does not appear to increase cooperation.

Power Asymmetries and Punishment in a Prisoner's Dilemma with Variable Cooperative Investment.

Directory of Open Access Journals (Sweden)

Jonathan E Bone

Full Text Available In many two-player games, players that invest in punishment finish with lower payoffs than those who abstain from punishing. These results question the effectiveness of punishment at promoting cooperation, especially when retaliation is possible. It has been suggested that these findings may stem from the unrealistic assumption that all players are equal in terms of power. However, a previous empirical study which incorporated power asymmetries into an iterated prisoner's dilemma (IPD game failed to show that power asymmetries stabilize cooperation when punishment is possible. Instead, players cooperated in response to their partner cooperating, and punishment did not yield any additional increase in tendency to cooperate. Nevertheless, this previous study only allowed an all-or-nothing-rather than a variable-cooperation investment. It is possible that power asymmetries increase the effectiveness of punishment from strong players only when players are able to vary their investment in cooperation. We tested this hypothesis using a modified IPD game which allowed players to vary their investment in cooperation in response to being punished. As in the previous study, punishment from strong players did not increase cooperation under any circumstances. Thus, in two-player games with symmetric strategy sets, punishment does not appear to increase cooperation.

Parafibromin inhibits cancer cell growth and causes G1 phase arrest

International Nuclear Information System (INIS)

Zhang Chun; Kong Dong; Tan, M.-H.; Pappas, Donald L.; Wang, P.-F.; Chen, Jindong; Farber, Leslie; Zhang Nian; Koo, H.-M.; Weinreich, Michael; Williams, Bart O.; Teh, B.T.

2006-01-01

The HRPT2 (hereditary hyperparathyroidism type 2) tumor suppressor gene encodes a ubiquitously expressed 531 amino acid protein termed parafibromin. Inactivation of parafibromin predisposes one to the development of HPT-JT syndrome. To date, the role of parafibromin in tumorigenesis is largely unknown. Here, we report that parafibromin is a nuclear protein that possesses anti-proliferative properties. We show that overexpression of parafibromin inhibits colony formation and cellular proliferation, and induces cell cycle arrest in the G1 phase. Moreover, HPT-JT syndrome-derived mutations in HRPT2 behave in a dominant-negative manner by abolishing the ability of parafibromin to suppress cell proliferation. These findings suggest that parafibromin has a critical role in cell growth, and mutations in HRPT2 can directly inhibit this role

Sanctions as honest signals – The evolution of pool punishment by public sanctioning institutions

Science.gov (United States)

Schoenmakers, Sarah; Hilbe, Christian; Blasius, Bernd; Traulsen, Arne

2014-01-01

In many species, mutual cooperation is stabilized by forms of policing and peer punishment: if cheaters are punished, there is a strong selective pressure to cooperate. Most human societies have complemented, and sometimes even replaced, such peer punishment mechanisms with pool punishment, where punishment is outsourced to central institutions such as the police. Even before free-riding occurs, such institutions require investments, which could serve as costly signals. Here, we show with a game theoretical model that this signaling effect in turn can be crucial for the evolution of punishment institutions: In the absence of such signals, pool punishment is only stable with second-order punishment and can only evolve when individuals have the freedom not to take part in any interaction. With such signals, individuals can opportunistically adjust their behavior, which promotes the evolution of stable pool punishment even in situations where no one can stand aside. Thus, the human propensity to react opportunistically to credible punishment threats is often sufficient to establish stable punishment institutions and to maintain high levels of cooperation. PMID:24768866

Outcomes and intentions in children's, adolescents', and adults' second- and third-party punishment behavior.

Science.gov (United States)

Gummerum, Michaela; Chu, Maria T

2014-10-01

Theories of morality maintain that punishment supports the emergence and maintenance of moral behavior. This study investigated developmental differences in the role of outcomes and the violator's intentions in second-party punishment (where punishers are victims of a violation) and third-party punishment (where punishers are unaffected observers of a violation). Four hundred and forty-three adults and 8-, 12-, and 15-year-olds made choices in mini-ultimatum games and newly-developed mini-third-party punishment games, which involved actual incentives rather than hypothetical decisions. Adults integrated outcomes and intentions in their second- and third-party punishment, whereas 8-year-olds consistently based their punishment on the outcome of the violation. Adolescents integrated outcomes and intentions in second- but not third-party punishment. Copyright © 2014 Elsevier B.V. All rights reserved.

On the determinants and consequences of punishment goals : power, distrust, and rule compliance

NARCIS (Netherlands)

Mooijman, M.

2016-01-01

This dissertation focuses on the determinants and consequences of leaders’ punishment goals. I investigate how and why leaders rely on certain punishment goals, and how and why leaders’ reliance on such punishment goals affects punishment effectiveness. Specifically, in this dissertation I

Escherichia coli DinB inhibits replication fork progression without significantly inducing the SOS response.

Science.gov (United States)

Mori, Tetsuya; Nakamura, Tatsuro; Okazaki, Naoto; Furukohri, Asako; Maki, Hisaji; Akiyama, Masahiro Tatsumi

2012-01-01

The SOS response is readily triggered by replication fork stalling caused by DNA damage or a dysfunctional replicative apparatus in Escherichia coli cells. E. coli dinB encodes DinB DNA polymerase and its expression is upregulated during the SOS response. DinB catalyzes translesion DNA synthesis in place of a replicative DNA polymerase III that is stalled at a DNA lesion. We showed previously that DNA replication was suppressed without exogenous DNA damage in cells overproducing DinB. In this report, we confirm that this was due to a dose-dependent inhibition of ongoing replication forks by DinB. Interestingly, the DinB-overproducing cells did not significantly induce the SOS response even though DNA replication was perturbed. RecA protein is activated by forming a nucleoprotein filament with single-stranded DNA, which leads to the onset of the SOS response. In the DinB-overproducing cells, RecA was not activated to induce the SOS response. However, the SOS response was observed after heat-inducible activation in strain recA441 (encoding a temperature-sensitive RecA) and after replication blockage in strain dnaE486 (encoding a temperature-sensitive catalytic subunit of the replicative DNA polymerase III) at a non-permissive temperature when DinB was overproduced in these cells. Furthermore, since catalytically inactive DinB could avoid the SOS response to a DinB-promoted fork block, it is unlikely that overproduced DinB takes control of primer extension and thus limits single-stranded DNA. These observations suggest that DinB possesses a feature that suppresses DNA replication but does not abolish the cell's capacity to induce the SOS response. We conclude that DinB impedes replication fork progression in a way that does not activate RecA, in contrast to obstructive DNA lesions and dysfunctional replication machinery.

Cannabidiol restores intestinal barrier dysfunction and inhibits the apoptotic process induced by Clostridium difficile toxin A in Caco-2 cells.

Science.gov (United States)

Gigli, Stefano; Seguella, Luisa; Pesce, Marcella; Bruzzese, Eugenia; D'Alessandro, Alessandra; Cuomo, Rosario; Steardo, Luca; Sarnelli, Giovanni; Esposito, Giuseppe

2017-12-01

Clostridium difficile toxin A is responsible for colonic damage observed in infected patients. Drugs able to restore Clostridium difficile toxin A-induced toxicity have the potential to improve the recovery of infected patients. Cannabidiol is a non-psychotropic component of Cannabis sativa, which has been demonstrated to protect enterocytes against chemical and/or inflammatory damage and to restore intestinal mucosa integrity. The purpose of this study was to evaluate (a) the anti-apoptotic effect and (b) the mechanisms by which cannabidiol protects mucosal integrity in Caco-2 cells exposed to Clostridium difficile toxin A. Caco-2 cells were exposed to Clostridium difficile toxin A (30 ng/ml), with or without cannabidiol (10 -7 -10 -9  M), in the presence of the specific antagonist AM251 (10 -7  M). Cytotoxicity assay, transepithelial electrical resistence measurements, immunofluorescence analysis and immunoblot analysis were performed in the different experimental conditions. Clostridium difficile toxin A significantly decreased Caco-2 cells' viability and reduced transepithelial electrical resistence values and RhoA guanosine triphosphate (GTP), bax, zonula occludens-1 and occludin protein expression, respectively. All these effects were significantly and concentration-dependently inhibited by cannabidiol, whose effects were completely abolished in the presence of the cannabinoid receptor type 1 (CB1) antagonist, AM251. Cannabidiol improved Clostridium difficile toxin A-induced damage in Caco-2 cells, by inhibiting the apoptotic process and restoring the intestinal barrier integrity, through the involvement of the CB1 receptor.

[A retrospective survey of childhood corporal punishment by school teachers in students].

Science.gov (United States)

Chen, Jing-qi; Wu, Chun-mei; Dunne, Michael P; Ma, Yu-xia; Chen, Bo; Liang, Yi-huai; Cheng, Ya-jie

2006-01-01

To ascertain the prevalence of childhood corporal punishment by teachers in students, to explore the influencing factors and associations between childhood corporal punishment and psychological problems. Five hundred and twenty-eight students from a college and a technical secondary school in Hebei province were surveyed by self-administered questionnaire anonymously in Dec. 2004. The questionnaire used for this survey mainly included (1) general demographic information; (2) 5 forms of childhood corporal punishments, in this study, cases of teachers' corporal punishments were defined as those who answered positively one or more of the 5 questions relating to childhood corporal punishment by school teachers occurring before the age of 16 years; (3) Symptom Checklist-90 (SCL-90); (4) Youth Risk Behaviours. Overall, 57.6% of students reported having been corporally punished at least one time, one of four forms of corporal punishment by teachers before age of 16 years, the four forms corporal punishment were non-contact corporal punishment, e.g., running for punishment, repeat-doing homework many times for punishment, standing for punishment, kneel down for punishment, not allowing to eat, sending outside in winter, etc. (53.4%), hitting/kicking/pushing very hard with open hands/fist/feet/other part of body (16.1%), beating with an object (10.2%), and locking in a small compartment/tying with rope (0.2%). No students reported having been choked, or burned/scalded, or stabbed with a sharp object by the teachers. Males had a significantly higher overall prevalence rate than females (66.4% vs. 46.6%, chi(2) = 21.01, P = 0.000). There was no statistically significant association between a history of childhood corporal punishment and the three other demographic indicators, which included residence region (rural and non-rural area) prior to 16 years of age, parental education level, and whether the respondent lived in a single or multiple children family. Compared with their

76 FR 81910 - Abolishment of Privacy Act System of Records

Science.gov (United States)

2011-12-29

... Program Manager, USDA, Forest Service, Office of Safety and Occupational and Health, 1400 Independence... Management Handbook (FSH) 6209.11. This system is abolished and removed from the inventory of the USDA System... DEPARTMENT OF AGRICULTURE Office of the Secretary Abolishment of Privacy Act System of Records...

Induction of autocrine factor inhibiting cell motility from murine B16-BL6 melanoma cells by alpha-melanocyte stimulating hormone.

Science.gov (United States)

Murata, J; Ayukawa, K; Ogasawara, M; Watanabe, H; Saiki, I

1999-03-15

We have previously reported that neuropeptide alpha-melanocyte stimulating hormone (alpha-MSH) successfully inhibited Matrigel invasion and haptotactic migration of B16-BL6 melanoma cells towards both fibronectin and laminin without affecting their growth. In the present study, we investigated the inhibitory mechanism of tumor cell motility by alpha-MSH. Alpha-MSH significantly blocked the autocrine motility factor (AMF)-enhanced cell motility. However, alpha-MSH did neither prevent the secretion of AMF from B16-BL6 cells nor alter the expression level of AMF receptor (gp78). On the other hand, alpha-MSH induced the secretion of the motility inhibitory factor(s) from B16-BL6 cells in a concentration- and time-dependent manner. The induction of the motility inhibitor(s) was proportional to increasing levels of intracellular cAMP induced by alpha-MSH as well as forskolin, and the activity was abolished by an adenylate cyclase inhibitor, 2',5'-dideoxyadenosine (DDA). The motility-inhibiting activity in conditioned medium (CM) from alpha-MSH-treated B16-BL6 cells was found to have a m.w. below 3 kDa after fractionation. This activity was abolished by boiling but insensitive to trypsin. The treatment of tumor cells with cycloheximide reduced the activity in alpha-MSH-stimulated CM. Our results suggest that alpha-MSH inhibited the motility of B16-BL6 cells through induction of autocrine factor(s).

Unexpected neuronal protection of SU5416 against 1-Methyl-4-phenylpyridinium ion-induced toxicity via inhibiting neuronal nitric oxide synthase.

Directory of Open Access Journals (Sweden)

Wei Cui

Full Text Available SU5416 was originally designed as a potent and selective inhibitor of vascular endothelial growth factor receptor-2 (VEGFR-2 for cancer therapy. In this study, we have found for the first time that SU5416 unexpectedly prevented 1-methyl-4-phenylpyridinium ion (MPP(+-induced neuronal apoptosis in cerebellar granule neurons, and decreased 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP-induced loss of dopaminergic neurons and impairment of swimming behavior in zebrafish in a concentration-dependent manner. However, VEGFR-2 kinase inhibitor II, another specific VEGFR-2 inhibitor, failed to reverse neurotoxicity at the concentration exhibiting anti-angiogenic activity, strongly suggesting that the neuroprotective effect of SU5416 is independent from its anti-angiogenic action. SU5416 potently reversed MPP(+-increased intracellular nitric oxide level with an efficacy similar to 7-nitroindazole, a specific neuronal nitric oxide synthase (nNOS inhibitor. Western blotting analysis showed that SU5416 reduced the elevation of nNOS protein expression induced by MPP(+. Furthermore, SU5416 directly inhibited the enzyme activity of rat cerebellum nNOS with an IC(50 value of 22.7 µM. In addition, knock-down of nNOS expression using short hairpin RNA (shRNA abolished the neuroprotective effects of SU5416 against MPP(+-induced neuronal loss. Our results strongly demonstrate that SU5416 might exert its unexpected neuroprotective effects by concurrently reducing nNOS protein expression and directly inhibiting nNOS enzyme activity. In view of the capability of SU5416 to cross the blood-brain barrier and the safety for human use, our findings further indicate that SU5416 might be a novel drug candidate for neurodegenerative disorders, particularly those associated with NO-mediated neurotoxicity.

Elimination of corporal punishment of children's a human right

Directory of Open Access Journals (Sweden)

Stevanović Ivana

2010-01-01

Full Text Available The authors indicate the necessity of explicit legal prohibition of all corporal punishment of children that represent a violation of the right of the child to respect his/her physical integrity and human dignity. The paper emphasizes why all corporal punishment of children should be prohibited and points out the progress made at the legislative level to the elimination of all corporal punishment of children in some member states of the Council of Europe and the Republic of Serbia.

hERG trafficking inhibition in drug-induced lethal cardiac arrhythmia.

Science.gov (United States)

Nogawa, Hisashi; Kawai, Tomoyuki

2014-10-15

Acquired long QT syndrome induced by non-cardiovascular drugs can cause lethal cardiac arrhythmia called torsades de points and is a significant problem in drug development. The prolongation of QT interval and cardiac action potential duration are mainly due to reduced physiological function of the rapidly activating voltage-dependent potassium channels encoded by human ether-a-go-go-related gene (hERG). Structurally diverse groups of drugs are known to directly inhibit hERG channel conductance. Therefore, the ability of acute hERG inhibition is routinely assessed at the preclinical stages in pharmaceutical testing. Recent findings indicated that chronic treatment with various drugs not only inhibits hERG channels but also decreases hERG channel expression in the plasma membrane of cardiomyocytes, which has become another concern in safety pharmacology. The mechanisms involve the disruption of hERG trafficking to the surface membrane or the acceleration of hERG protein degradation. From this perspective, we present a brief overview of mechanisms of drug-induced trafficking inhibition and pathological regulation. Understanding of drug-induced hERG trafficking inhibition may provide new strategies for predicting drug-induced QT prolongation and lethal cardiac arrhythmia in pharmaceutical drug development. Copyright © 2014 Elsevier B.V. All rights reserved.

Crime and punishment in a roaming cleanerfish.

Science.gov (United States)

Mills, Suzanne C; Côté, Isabelle M

2010-12-07

Cheating is common in cooperative interactions, but its occurrence can be controlled by various means ranging from rewarding cooperators to active punishment of cheaters. Punishment occurs in the mutualism involving the cleanerfish Labroides dimidiatus and its reef fish clients. When L. dimidiatus cheats, by taking scales and mucus rather than ectoparasites, wronged clients either chase or withhold further visits to the dishonest cleaner, which leads to more cooperative future interactions. Punishment of cheating L. dimidiatus may be effective largely because these cleaners are strictly site-attached, increasing the potential for repeated interactions between individual cleaners and clients. Here, we contrast the patterns of cheating and punishment in L. dimidiatus with its close relative, the less site-attached Labroides bicolor. Overall, L. bicolor had larger home ranges, cheated more often and, contrary to our prediction, were punished by cheated clients as frequently as, and not less often than, L. dimidiatus. However, adult L. bicolor, which had the largest home ranges, did not cheat more than younger conspecifics, suggesting that roaming, and hence the frequency of repeated interactions, has little influence on cheating and retaliation in cleaner-client relationships. We suggest that roaming cleaners offer the only option available to many site-attached reef fish seeking a cleaning service. This asymmetry in scope for partner choice encourages dishonesty by the partner with more options (i.e. L. bicolor), but to be cleaned by a cleaner that sometimes cheats may be a better option than not to be cleaned at all.

The Role of the Basolateral Amygdala in Punishment

Science.gov (United States)

Dit-Bressel, Philip Jean-Richard; McNally, Gavan P.

2015-01-01

Aversive stimuli not only support fear conditioning to their environmental antecedents, they also punish behaviors that cause their occurrence. The amygdala, especially the basolateral nucleus (BLA), has been critically implicated in Pavlovian fear learning but its role in punishment remains poorly understood. Here, we used a within-subjects…

Group Membership Modulates the Neural Circuitry Underlying Third Party Punishment.

Science.gov (United States)

Morese, Rosalba; Rabellino, Daniela; Sambataro, Fabio; Perussia, Felice; Valentini, Maria Consuelo; Bara, Bruno G; Bosco, Francesca M

2016-01-01

This research aims to explore the neural correlates involved in altruistic punishment, parochial altruism and anti-social punishment, using the Third-Party Punishment (TPP) game. In particular, this study considered these punishment behaviors in in-group vs. out-group game settings, to compare how people behave with members of their own national group and with members of another national group. The results showed that participants act altruistically to protect in-group members. This study indicates that norm violation in in-group (but not in out-group) settings results in increased activity in the medial prefrontal cortex and temporo-parietal junction, brain regions involved in the mentalizing network, as the third-party attempts to understand or justify in-group members' behavior. Finally, exploratory analysis during anti-social punishment behavior showed brain activation recruitment of the ventromedial prefrontal cortex, an area associated with altered regulation of emotions.

Downregulation of sphingosine 1-phosphate (S1P) receptor 1 by dexamethasone inhibits S1P-induced mesangial cell migration.

Science.gov (United States)

Koch, Alexander; Jäger, Manuel; Völzke, Anja; Grammatikos, Georgios; Zu Heringdorf, Dagmar Meyer; Huwiler, Andrea; Pfeilschifter, Josef

2015-06-01

Sphingosine 1-phosphate (S1P) is generated by sphingosine kinase (SK)-1 and -2 and acts mainly as an extracellular ligand at five specific receptors, denoted S1P1-5. After activation, S1P receptors regulate important processes in the progression of renal diseases, such as mesangial cell migration and survival. Previously, we showed that dexamethasone enhances SK-1 activity and S1P formation, which protected mesangial cells from stress-induced apoptosis. Here we demonstrate that dexamethasone treatment lowered S1P1 mRNA and protein expression levels in rat mesangial cells. This effect was abolished in the presence of the glucocorticoid receptor antagonist RU-486. In addition, in vivo studies showed that dexamethasone downregulated S1P1 expression in glomeruli isolated from mice treated with dexamethasone (10 mg/kg body weight). Functionally, we identified S1P1 as a key player mediating S1P-induced mesangial cell migration. We show that dexamethasone treatment significantly lowered S1P-induced migration of mesangial cells, which was again reversed in the presence of RU-486. In summary, we suggest that dexamethasone inhibits S1P-induced mesangial cell migration via downregulation of S1P1. Overall, these results demonstrate that dexamethasone has functional important effects on sphingolipid metabolism and action in renal mesangial cells.

Reward and punishment enhance motor adaptation in stroke.

Science.gov (United States)

Quattrocchi, Graziella; Greenwood, Richard; Rothwell, John C; Galea, Joseph M; Bestmann, Sven

2017-09-01

The effects of motor learning, such as motor adaptation, in stroke rehabilitation are often transient, thus mandating approaches that enhance the amount of learning and retention. Previously, we showed in young individuals that reward and punishment feedback have dissociable effects on motor adaptation, with punishment improving adaptation and reward enhancing retention. If these findings were able to generalise to patients with stroke, they would provide a way to optimise motor learning in these patients. Therefore, we tested this in 45 patients with chronic stroke allocated in three groups. Patients performed reaching movements with their paretic arm with a robotic manipulandum. After training (day 1), day 2 involved adaptation to a novel force field. During the adaptation phase, patients received performance-based feedback according to the group they were allocated: reward, punishment or no feedback (neutral). On day 3, patients readapted to the force field but all groups now received neutral feedback. All patients adapted, with reward and punishment groups displaying greater adaptation and readaptation than the neutral group, irrespective of demographic, cognitive or functional differences. Remarkably, the reward and punishment groups adapted to similar degree as healthy controls. Finally, the reward group showed greater retention. This study provides, for the first time, evidence that reward and punishment can enhance motor adaptation in patients with stroke. Further research on reinforcement-based motor learning regimes is warranted to translate these promising results into clinical practice and improve motor rehabilitation outcomes in patients with stroke. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Differentiating corporal punishment from physical abuse in the prediction of lifetime aggression.

Science.gov (United States)

King, Alan R; Ratzak, Abrianna; Ballantyne, Sage; Knutson, Shane; Russell, Tiffany D; Pogalz, Colton R; Breen, Cody M

2018-05-01

Corporal punishment and parental physical abuse often co-occur during upbringing, making it difficult to differentiate their selective impacts on psychological functioning. Associations between corporal punishment and a number of lifetime aggression indicators were examined in this study after efforts to control the potential influence of various forms of co-occurring maltreatment (parental physical abuse, childhood sexual abuse, sibling abuse, peer bullying, and observed parental violence). College students (N = 1,136) provided retrospective self-reports regarding their history of aggression and levels of exposure to childhood corporal punishment and maltreatment experiences. Analyses focused on three hypotheses: 1) The odds of experiencing childhood physical abuse would be higher among respondents reporting frequent corporal punishment during upbringing; 2) Corporal punishment scores would predict the criterion aggression indices after control of variance associated with childhood maltreatment; 3) Aggression scores would be higher among respondents classified in the moderate and elevated corporal punishment risk groups. Strong support was found for the first hypothesis since the odds of childhood physical abuse recollections were higher (OR = 65.3) among respondents who experienced frequent (>60 total disciplinary acts) corporal punishment during upbringing. Partial support was found for the second and third hypotheses. Dimensional and categorical corporal punishment scores were associated significantly with half of the criterion measures. These findings support efforts to dissuade reliance on corporal punishment to manage child behavior. © 2018 Wiley Periodicals, Inc.

Crime and Punishment

NARCIS (Netherlands)

Dostoevsky, Fyodor

2005-01-01

Crime and Punishment is the story of a brutal double murder and its aftermath. Raskolnikov, a poor student, kills a pawnbroker and her sister, and then has to face up to the moral consequences of his actions. The novel is compelling and rewarding, full of meaning and symbolism, and raises profound

Moral emotions as determinants of third-party punishment

Directory of Open Access Journals (Sweden)

Rob M. A. Nelissen

2009-12-01

Full Text Available Third-party punishment has recently received attention as an explanation for human altruism. Feelings of anger in response to norm violations are assumed to motivate third-party sanctions, yet there is only sparse and indirect support for this idea. We investigated the impact of both anger and guilt feelings on third-party sanctions. In two studies both emotions were independently manipulated. Results show that anger and guilt independently constitute sufficient but not necessary causes of punishment. Low levels of punishment are observed only when neither emotion is elicited. We discuss the implications of these findings for the functions of altruistic sanctions.

Corporal Punishment and Student Outcomes in Rural Schools

Science.gov (United States)

Han, Seunghee

2014-01-01

This study examined the effects of corporal punishment on student outcomes in rural schools by analyzing 1,067 samples from the School Survey on Crime and Safety 2007-2008. Results of descriptive statistics and multivariate regression analyses indicated that schools with corporal punishment may decrease students' violent behaviors and…

Effects of lesions to the dorsal noradrenergic bundle on counterconditioning of punished barpressing.

Science.gov (United States)

Tsaltas, E; Gray, J A; Preston, G C

1987-01-01

The possible contribution of the dorsal noradrenergic bundle (DB) to the development of a simple form of counterconditioning (an associative mechanism leading to behavioural tolerance for stress) was assessed by comparison of the performance of animals with 6-hydroxydopamine-induced lesions of the DB to that of sham-operated (SH) animals. Animals engaging in barpressing for food reward on a random-interval (RI) 64 sec schedule were presented with a stimulus signalling the concurrent operation of an RI-64 sec schedule of response-contingent shock. In the control condition (punishment), shock and reward never occurred as a result of the same barpress. In the experimental condition (counterconditioning), the frequency of shock and reward were the same as for the punishment condition but the two events always occurred in succession, with food following shock, as a consequence of the same barpress. DB lesions had no effect on the acquisition of rewarded barpressing or on the initial acquisition of the discrimination between the shock-free and shock-containing (signalled) components of the schedule. However, once performance on the discrimination had reached asymptote, DB animals in the punishment control group showed significantly less suppression to the signal than SH animals. The counterconditioning schedule used was effective, leading to significantly reduced response suppression in the SH animals in comparison to the SH group subjected to punishment. The pattern of findings in the DB groups was consistent with a blockade by the lesion of the development of counterconditioning. These results suggest, therefore, that the DB is involved in at least one associative mechanism leading to tolerance for stress.

Effects of punishment in a mobile population playing the prisoner's dilemma game

Science.gov (United States)

Amor, Daniel R.; Fort, Joaquim

2011-12-01

We deal with a system of prisoner's dilemma players undergoing continuous motion in a two-dimensional plane. In contrast to previous work, we introduce altruistic punishment after the game. We find punishing only a few of the cooperator-defector interactions is enough to lead the system to a cooperative state in environments where otherwise defection would take over the population. This happens even with soft nonsocial punishment (where both cooperators and defectors punish other players, a behavior observed in many human populations). For high enough mobilities or temptations to defect, low rates of social punishment can no longer avoid the breakdown of cooperation.

Curcumin-induced histone acetylation inhibition improves stress-induced gastric ulcer disease in rats.

Science.gov (United States)

He, Ping; Zhou, Renmin; Hu, Guorui; Liu, Zhifeng; Jin, Yu; Yang, Guang; Li, Mei; Lin, Qian

2015-03-01

Curcumin is known to possess anti‑inflammatory properties. Despite the fact that curcumin is known to be a strong inhibitor of H+, K+‑ATPase activity, the mechanism underlying the curcumin‑induced inhibition of the transcription of the H+, K+‑ATPase α subunit in gastric mucosal parietal cells remains unclear. The present study investigated the possible mechanism by which curcumin inhibits stomach H+, K+‑ATPase activity during the acute phase of gastric ulcer disease. A rat model of stress‑induced gastric ulcers was produced, in which the anti‑ulcer effects of curcumin were examined. Curcumin‑induced inhibition of the H+, K+‑ATPase promoter via histone acetylation, was verified using a chromatin immunoprecipitation assay. The results showed that curcumin improved stress‑induced gastric ulcer disease in rats, as demonstrated by increased pH values and reduced gastric mucosal hemorrhage and ulcer index. These effects were accompanied by a significant reduction in the level of histone H3 acetylation at the site of the H+, K+‑ATPase promoter and in the expression of the gastric H+,K+‑ATPase α subunit gene and protein. In conclusion, curcumin downregulated the acetylation of histone H3 at the site of the H+, K+‑ATPase promoter gene, thereby inhibiting the transcription and expression of the H+, K+‑ATPase gene. Curcumin was shown to have a preventive and therapeutic effect in gastric ulcer disease.

Diet-induced changes in subcutaneous adipose tissue blood flow in man: effect of beta-adrenoceptor inhibition

DEFF Research Database (Denmark)

Simonsen, L; Bülow, J; Astrup, A

1990-01-01

: the forearm, the thigh and the abdomen. The subjects were given a meal consisting of white bread, jam, honey and apple juice (about 2300 kJ). The meal induced a twofold increase in blood flow in the examined tissues. Propranolol abolished the flow increase in the thigh and the abdomen and reduced...

The Predictors of Parental Use of Corporal Punishment

Science.gov (United States)

Grogan-Kaylor, Andrew; Otis, Melanie D.

2007-01-01

Corporal punishment has been the focus of considerable study over the past decade. Some recent research suggesting that the use of corporal punishment may have significant long-term negative effects on children has prompted increasing exploration and interest in the issue. We used tobit regression analysis and data from the 2000 National…

Resveratrol induces autophagy by directly inhibiting mTOR through ATP competition

Science.gov (United States)

Park, Dohyun; Jeong, Heeyoon; Lee, Mi Nam; Koh, Ara; Kwon, Ohman; Yang, Yong Ryoul; Noh, Jungeun; Suh, Pann-Ghill; Park, Hwangseo; Ryu, Sung Ho

2016-01-01

Resveratrol (RSV) is a natural polyphenol that has a beneficial effect on health, and resveratrol-induced autophagy has been suggested to be a key process in mediating many beneficial effects of resveratrol, such as reduction of inflammation and induction of cancer cell death. Although various resveratrol targets have been suggested, the molecule that mediates resveratrol-induced autophagy remains unknown. Here, we demonstrate that resveratrol induces autophagy by directly inhibiting the mTOR-ULK1 pathway. We found that inhibition of mTOR activity and presence of ULK1 are required for autophagy induction by resveratrol. In line with this mTOR dependency, we found that resveratrol suppresses the viability of MCF7 cells but not of SW620 cells, which are mTOR inhibitor sensitive and insensitive cancer cells, respectively. We also found that resveratrol-induced cancer cell suppression occurred ULK1 dependently. For the mechanism of action of resveratrol on mTOR inhibition, we demonstrate that resveratrol directly inhibits mTOR. We found that resveratrol inhibits mTOR by docking onto the ATP-binding pocket of mTOR (i.e., it competes with ATP). We propose mTOR as a novel direct target of resveratrol, and inhibition of mTOR is necessary for autophagy induction. PMID:26902888

Protestant fundamentalism and attitudes toward corporal punishment of children.

Science.gov (United States)

Grasmick, H G; Bursik, R J; Kimpel, M

1991-01-01

The present research demonstrates what others have suspected: Protestant fundamentalism is closely linked to favorable attitudes toward corporal punishment of children in the home and the school. The relationship persists with controls for socioeconomic and demographic variables. Three explanations of the greater support for corporal punishment among people affiliated with fundamentalist denominations are tested. Greater personal religiosity and adherence to a punitive image of God account for very little of the relationship. Instead, the emphasis on biblical literalness among fundamentalists appears to be a major source of their advocacy of corporal punishment. Given the potential political effectiveness of fundamentalist churches, the policy implications of these findings present a difficult challenge for those who have called for the prohibition of corporal punishment of children as a crucial step toward reducing the level of violence in our society.

Talking about Corporal Punishment: Nine Low-Income African American Mothers' Perspectives

Science.gov (United States)

Ispa, J.M.; Halgunseth, L.C.

2004-01-01

Qualitative interviews conducted over the course of 5 years with nine young low-income African American mothers were analyzed in order to gain understanding of their perspectives on corporal punishment. All used corporal punishment with their children. Results pertain to the vocabulary mothers used to describe corporal punishment (pop, tap, whup,…

The Importance of Emotions for the Effectiveness of Social Punishment

DEFF Research Database (Denmark)

Reuben, Ernesto; Hopfensitz, Astrid

This paper experimentally explores how the enforcement of cooperative behavior in a social dilemma is facilitated through institutional as well as emotional mechanisms. Recent studies emphasize the importance of anger and its role in motivating individuals to punish free riders. However, we find...... that anger also triggers retaliatory behavior by the punished individuals. This makes the enforcement of a cooperative norm more costly. We show that in addition to anger, ‘social’ emotions like guilt need to be present for punishment to be an effective deterrent of uncooperative actions. They play a key...... role by subduing the desire of punished individuals to retaliate and by motivating them to behave more cooperatively in the future...

Cell-induced potentiation of the plasminogen activation system is abolished by a monoclonal antibody that recognizes the NH2-terminal domain of the urokinase receptor

DEFF Research Database (Denmark)

Rønne, E; Behrendt, N; Ellis, V

1991-01-01

We have raised four monoclonal antibodies recognizing different epitopes within the human cell-surface receptor for urokinase-type plasminogen activator (u-PA). One of these antibodies completely abolishes the potentiation of plasmin generation observed upon incubation of the zymogens pro......-u-PA and plasminogen with U937 cells. This antibody, which is also the only one to completely inhibit the binding of DFP-inactivated [125I]-u-PA to U937 cells, is directed against the u-PA binding NH2-terminal domain of u-PAR, a well-defined fragment formed by limited chymotrypsin digestion of purified u......-PAR, demonstrating the functional independence of the u-PA binding domain as well as the critical role of u-PAR in the assembly of the cell-surface plasminogen activation system....

Acting on social exclusion: neural correlates of punishment and forgiveness of excluders.

Science.gov (United States)

Will, Geert-Jan; Crone, Eveline A; Güroğlu, Berna

2015-02-01

This functional magnetic resonance imaging study examined the neural correlates of punishment and forgiveness of initiators of social exclusion (i.e. 'excluders'). Participants divided money in a modified Dictator Game between themselves and people who previously either included or excluded them during a virtual ball-tossing game (Cyberball). Participants selectively punished the excluders by decreasing their outcomes; even when this required participants to give up monetary rewards. Punishment of excluders was associated with increased activation in the pre-supplementary motor area (pre-SMA) and bilateral anterior insula. Costly punishment was accompanied by higher activity in the pre-SMA compared with punishment that resulted in gains or was non-costly. Refraining from punishment (i.e. forgiveness) was associated with self-reported perspective-taking and increased activation in the bilateral temporoparietal junction, dorsomedial prefrontal cortex, dorsal anterior cingulate cortex, and ventrolateral and dorsolateral prefrontal cortex. These findings show that social exclusion can result in punishment as well as forgiveness of excluders and that separable neural networks implicated in social cognition and cognitive control are recruited when people choose either to punish or to forgive those who excluded them. © The Author (2014). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Oridonin attenuates Aβ1-42-induced neuroinflammation and inhibits NF-κB pathway.

Directory of Open Access Journals (Sweden)

Sulei Wang

Full Text Available Neuroinflammation induced by beta-amyloid (Aβ plays a critical role in the pathogenesis of Alzheimer's disease (AD, and inhibiting Aβ-induced neuroinflammation serves as a potential strategy for the treatment of AD. Oridonin (Ori, a compound of Rabdosia rubescens, has been shown to exert anti-inflammatory effects. In this study, we demonstrated that Ori inhibited glial activation and decreased the release of inflammatory cytokines in the hippocampus of Aβ1-42-induced AD mice. In addition, Ori inhibited the NF-κB pathway and Aβ1-42-induced apoptosis. Furthermore, Ori could attenuate memory deficits in Aβ1-42-induced AD mice. In conclusion, our study demonstrated that Ori inhibited the neuroinflammation and attenuated memory deficits induced by Aβ1-42, suggesting that Ori might be a promising candidate for AD treatment.

Change in Corporal Punishment Over Time in a Representative Sample of Canadian Parents.

Science.gov (United States)

Fréchette, Sabrina; Romano, Elisa

2015-08-01

Corporal punishment is a controversial form of discipline. Although its prevalence appears high, legal reforms and public education efforts to limit corporal punishment may be resulting in a decrease in its prevalence and frequency of use. This study drew on Canadian nationally representative data to understand the social change that might be happening and to characterize parents who continue to use corporal punishment. The study relied on cross-sectional data from Cycles 1 (1994) to 8 (2008) of the Canadian National Longitudinal Survey of Children and Youth to examine parental reports of corporal punishment for children ages 2–11 years. Analyses were conducted separately for 2- to 5-, 6- to 9-, and 10- to 11-year-olds, and sociodemographics associated with corporal punishment were examined. A significant decrease in the prevalence and frequency of corporal punishment use was observed across time for all age groups. Child sex, parent age, employment status, family structure, household size, immigration status, ethnicity, and religion significantly distinguished parents who use corporal punishment from those who do not, but there was variability across the age groups. Effect sizes question the relevance of the observed decrease in corporal punishment from an applied perspective. Approximately 25% of Canadian parents still use corporal punishment with children ages 2–11 years; therefore, it remains an issue that merits continued attention. Certain child, parent, and family characteristics seem to characterize parents who use corporal punishment, but other more dynamic variables may be important to consider, such as parental stress and their attitudes toward corporal punishment.

Opinions about Child Corporal Punishment and Influencing Factors

Science.gov (United States)

Bell, Tessa; Romano, Elisa

2012-01-01

The use of corporal punishment has been linked to negative developmental outcomes for children. Despite this finding, Section 43 of the Canadian Criminal Code permits the use of corporal punishment by parents for children 2 to 12 years of age. Therefore, this study's first objective is to investigate opinions toward Section 43 and spanking more…

The Effects of Perceived Anonymity on Altruistic Punishment

Directory of Open Access Journals (Sweden)

Jared Piazza

2008-07-01

Full Text Available Previous studies investigating altruistic punishment have confounded the effects of two independent variables: information transmission (or breach of privacy and personal identification (or breach of anonymity. Here we report findings from a brief study in which participants were asked to respond to a social norm violation (i.e., an anonymous actor had behaved selfishly in an economic game by deciding whether to sacrifice their own endowment to punish this person. A third of the participants were told that their economic decisions would be made known to another player but could not be identified (privacy breach condition, whereas another third were informed that their decision as well as their names would be made known (anonymity breach condition. (The decisions of control participants were completely anonymous and private. Participants also justified their economic decisions and reported their emotional experiences. The results were participants punished most in the privacy and anonymity breach conditions and least in the control condition. These findings have implications for existing evolutionary accounts of altruistic punishment.

Effect of Manilkara hexandra (Roxb.) Dubard against experimentally-induced gastric ulcers.

Science.gov (United States)

Shah, Mamta B; Goswami, S S; Santani, D D

2004-10-01

Effects of the flavonoid rich fraction of the stem bark of Manilkara hexandra (Roxb.) Dubard, have been studied on ethanol, ethanol-indomethacin and pylorus ligated gastric ulcers in experimental animals. Oral administration of the ethyl acetate extract (extract A3) inhibited the formation of gastric lesions induced by ethanol in a dose dependent manner. The protective effect of extract A3 against ethanol induced gastric lesions was not abolished by pretreatment with indomethacin (10 mg kg(-1)). Further, extract A3 inhibited increase in vascular permeability due to ethanol administration. Extent of lipid peroxidation was significantly reduced in animals treated with extract. Extract A3 also inhibited the formation of gastric ulcers induced by pylorus ligation, when administered both orally and intraperitoneally. Moreover, pretreatment with extract A3 increased mucus production and glycoprotein content, which was evident from the rise in mucin activity and TC: PR ratio. Copyright 2004 John Wiley & Sons, Ltd.

Looking Under the Hood of Third-Party Punishment Reveals Design for Personal Benefit.

Science.gov (United States)

Krasnow, Max M; Delton, Andrew W; Cosmides, Leda; Tooby, John

2016-03-01

Third-party intervention, such as when a crowd stops a mugger, is common. Yet it seems irrational because it has real costs but may provide no personal benefits. In a laboratory analogue, the third-party-punishment game, third parties ("punishers") will often spend real money to anonymously punish bad behavior directed at other people. A common explanation is that third-party punishment exists to maintain a cooperative society. We tested a different explanation: Third-party punishment results from a deterrence psychology for defending personal interests. Because humans evolved in small-scale, face-to-face social worlds, the mind infers that mistreatment of a third party predicts later mistreatment of oneself. We showed that when punishers do not have information about how they personally will be treated, they infer that mistreatment of other people predicts mistreatment of themselves, and these inferences predict punishment. But when information about personal mistreatment is available, it drives punishment. This suggests that humans' punitive psychology evolved to defend personal interests. © The Author(s) 2016.

Facial Likability and Smiling Enhance Cooperation, but Have No Direct Effect on Moralistic Punishment.

Science.gov (United States)

Mieth, Laura; Bell, Raoul; Buchner, Axel

2016-09-01

The present study serves to test how positive and negative appearance-based expectations affect cooperation and punishment. Participants played a prisoner's dilemma game with partners who either cooperated or defected. Then they were given a costly punishment option: They could spend money to decrease the payoffs of their partners. Aggregated over trials, participants spent more money for punishing the defection of likable-looking and smiling partners compared to punishing the defection of unlikable-looking and nonsmiling partners, but only because participants were more likely to cooperate with likable-looking and smiling partners, which provided the participants with more opportunities for moralistic punishment. When expressed as a conditional probability, moralistic punishment did not differ as a function of the partners' facial likability. Smiling had no effect on the probability of moralistic punishment, but punishment was milder for smiling in comparison to nonsmiling partners.

The effect of power asymmetries on cooperation and punishment in a prisoner's dilemma game.

Directory of Open Access Journals (Sweden)

Jonathan E Bone

Full Text Available Recent work has suggested that punishment is detrimental because punishment provokes retaliation, not cooperation, resulting in lower overall payoffs. These findings may stem from the unrealistic assumption that all players are equal: in reality individuals are expected to vary in the power with which they can punish defectors. Here, we allowed strong players to interact with weak players in an iterated prisoner's dilemma game with punishment. Defecting players were most likely to switch to cooperation if the partner cooperated: adding punishment yielded no additional benefit and, under some circumstances, increased the chance that the partner would both defect and retaliate against the punisher. Our findings show that, in a two-player game, cooperation begets cooperation and that punishment does not seem to yield any additional benefits. Further work should explore whether strong punishers might prevail in multi-player games.

Who Punishes? Personality Traits Predict Individual Variation in Punitive Sentiment

Directory of Open Access Journals (Sweden)

S. Craig Roberts

2013-01-01

Full Text Available Cross-culturally, participants in public goods games reward participants and punish defectors to a degree beyond that warranted by rational, profit-maximizing considerations. Costly punishment, where individuals impose costs on defectors at a cost to themselves, is thought to promote the maintenance of cooperation. However, despite substantial variation in the extent to which people punish, little is known about why some individuals, and not others, choose to pay these costs. Here, we test whether personality traits might contribute to variation in helping and punishment behavior. We first replicate a previous study using public goods scenarios to investigate effects of sex, relatedness and likelihood of future interaction on willingness to help a group member or to punish a transgressor. As in the previous study, we find that individuals are more willing to help related than unrelated needy others and that women are more likely to express desire to help than men. Desire to help was higher if the probability of future interaction is high, at least among women. In contrast, among these variables, only participant sex predicted some measures of punitive sentiment. Extending the replication, we found that punitive sentiment, but not willingness to help, was predicted by personality traits. Most notably, participants scoring lower on Agreeableness expressed more anger towards and greater desire to punish a transgressor, and were more willing to engage in costly punishment, at least in our scenario. Our results suggest that some personality traits may contribute to underpinning individual variation in social enforcement of cooperation.

Punitive preferences, monetary incentives and tacit coordination in the punishment of defectors promote cooperation in humans

Science.gov (United States)

Diekmann, Andreas; Przepiorka, Wojtek

2015-05-01

Peer-punishment is effective in promoting cooperation, but the costs associated with punishing defectors often exceed the benefits for the group. It has been argued that centralized punishment institutions can overcome the detrimental effects of peer-punishment. However, this argument presupposes the existence of a legitimate authority and leaves an unresolved gap in the transition from peer-punishment to centralized punishment. Here we show that the origins of centralized punishment could lie in individuals’ distinct ability to punish defectors. In our laboratory experiment, we vary the structure of the punishment situation to disentangle the effects of punitive preferences, monetary incentives, and individual punishment costs on the punishment of defectors. We find that actors tacitly coordinate on the strongest group member to punish defectors, even if the strongest individual incurs a net loss from punishment. Such coordination leads to a more effective and more efficient provision of a cooperative environment than we observe in groups of all equals. Our results show that even an arbitrary assignment of an individual to a focal position in the social hierarchy can trigger the endogenous emergence of more centralized forms of punishment.

Baicalein induces cell death in murine T cell lymphoma via inhibition of thioredoxin system.

Science.gov (United States)

Patwardhan, Raghavendra S; Pal, Debojyoti; Checker, Rahul; Sharma, Deepak; Sandur, Santosh K

2017-10-01

We have earlier demonstrated the radioprotective potential of baicalein using murine splenic lymphocytes. Here, we have studied the effect of baicalein on murine T cell lymphoma EL4 cells and investigated the underlying mechanism of action. We observed that baicalein induced a dose dependent cell death in EL4 cells in vitro and significantly reduced the frequency of cancer stem cells. Previously, we have reported that murine and human T cell lymphoma cells have increased oxidative stress tolerance capacity due to active thioredoxin system. Hence, we monitored the effect of baicalein on thioredoxin system in EL4 cells. Docking studies revealed that baicalein could bind to the active site of thioredoxin reductase. Baicalein treatment led to significant reduction in the activity of thioredoxin reductase and nuclear levels of thioredoxin-1 thereby increasing ASK1 levels and caspase-3 activity. Interestingly, CRISPR-Cas9 based knock-out of ASK1 or over-expression of thioredoxin-1 abolished anti-tumor effects of baicalein in EL4 cells. Further, baicalein administration significantly reduced intra-peritoneal tumor burden of EL4 cells in C57BL/6 mice. Thus, our study describes anti-tumor effects of baicalein in EL4 cells via inhibition of thioredoxin system. Copyright © 2017 Elsevier Ltd. All rights reserved.

Punishment in the form of shared cost promotes altruism in the cooperative dilemma games.

Science.gov (United States)

Zhang, Chunyan; Zhu, Yuying; Chen, Zengqiang; Zhang, Jianlei

2017-05-07

One phenomenon or social institution often observed in multi-agent interactions is the altruistic punishment, i.e. the punishment of unfair behavior by others at a personal cost. Inspired by the works focusing on punishment and the intricate mechanism behind it, we theoretically study the strategy evolution in the framework of two-strategy game models with the punishment on defectors, moreover, the cost of punishing will be evenly shared among the cooperators. Theoretical computations suggest that larger punishment on defectors or smaller punishment cost incurred by cooperators will enhance the fixation of altruistic cooperation in the population. Through the replicate dynamics, the group size of the randomly selected individuals from the sufficiently large population will notably affect the strategy evolution in populations nested within a dilemma. By theoretical modeling the concept of shared cost for punishment from one point of view, our findings underscore the importance of punishment with shared cost as a factor in real-life decisions in an evolutionary game context. Copyright © 2017 Elsevier Ltd. All rights reserved.

Dimensions of physical punishment and their associations with children's cognitive performance and school adjustment.

Science.gov (United States)

Font, Sarah A; Cage, Jamie

2018-01-01

This study examined how a range of physical punishment measures, ranging from mild corporal punishment to physical abuse, are associated with cognitive performance, school engagement, and peer isolation over a 3- year span among 658 children initially observed between the ages of 8 and 14. Physical punishment was captured in three groups: mild corporal punishment, harsh corporal punishment, and physical abuse, and both caregiver- and child-reported punishment measures were considered. After accounting for socioeconomic and demographic characteristics, only Ninitial exposure to physical abuse was significantly associated with declines in cognitive performance. However, all forms of physical punishment were associated with declines in school engagement, and harsh corporal punishment was associated with increased peer isolation. Our findings were relatively consistent regardless of whether physical punishment was reported by the child or caregiver. Overall, our findings suggest that the prevention of physical abuse may enhance children's cognitive performance, but that alone may not be sufficient to ensure children are engaged and well-adjusted in school. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cyanidin-3-glucoside inhibits glutamate-induced Zn2+ signaling and neuronal cell death in cultured rat hippocampal neurons by inhibiting Ca2+-induced mitochondrial depolarization and formation of reactive oxygen species.

Science.gov (United States)

Yang, Ji Seon; Perveen, Shazia; Ha, Tae Joung; Kim, Seong Yun; Yoon, Shin Hee

2015-05-05

Cyanidin-3-glucoside (C3G), a member of the anthocyanin family, is a potent natural antioxidant. However, effects of C3G on glutamate-induced [Zn(2+)]i increase and neuronal cell death remain unknown. We studied the effects of C3G on glutamate-induced [Zn(2+)]i increase and cell death in cultured rat hippocampal neurons from embryonic day 17 maternal Sprague-Dawley rats using digital imaging methods for Zn(2+), Ca(2+), reactive oxygen species (ROS), mitochondrial membrane potential and a MTT assay for cell survival. Treatment with glutamate (100 µM) for 7 min induces reproducible [Zn(2+)]i increase at 35 min interval in cultured rat hippocampal neurons. The intracellular Zn(2+)-chelator TPEN markedly blocked glutamate-induced [Zn(2+)]i increase, but the extracellular Zn(2+) chelator CaEDTA did not affect glutamate-induced [Zn(2+)]i increase. C3G inhibited the glutamate-induced [Zn(2+)]i response in a concentration-dependent manner (IC50 of 14.1 ± 1.1 µg/ml). C3G also significantly inhibited glutamate-induced [Ca(2+)]i increase. Two antioxidants such as Trolox and DTT significantly inhibited the glutamate-induced [Zn(2+)]i response, but they did not affect the [Ca(2+)]i responses. C3G blocked glutamate-induced formation of ROS. Trolox and DTT also inhibited the formation of ROS. C3G significantly inhibited glutamate-induced mitochondrial depolarization. However, TPEN, Trolox and DTT did not affect the mitochondrial depolarization. C3G, Trolox and DTT attenuated glutamate-induced neuronal cell death in cultured rat hippocampal neurons, respectively. Taken together, all these results suggest that cyanidin-3-glucoside inhibits glutamate-induced [Zn(2+)]i increase through a release of Zn(2+) from intracellular sources in cultured rat hippocampal neurons by inhibiting Ca(2+)-induced mitochondrial depolarization and formation of ROS, which is involved in neuroprotection against glutamate-induced cell death. Copyright © 2015 Elsevier B.V. All rights reserved.

Fucoxanthin prevents H2O2-induced neuronal apoptosis via concurrently activating the PI3-K/Akt cascade and inhibiting the ERK pathway.

Science.gov (United States)

Yu, Jie; Lin, Jia-Jia; Yu, Rui; He, Shan; Wang, Qin-Wen; Cui, Wei; Zhang, Jin-Rong

2017-01-01

Background : As a natural carotenoid abundant in chloroplasts of edible brown algae, fucoxanthin possesses various health benefits, including anti-oxidative activity in particular. Objective : In the present study, we studied whether fucoxanthin protected against hydrogen peroxide (H 2 O 2 )-induced neuronal apoptosis. Design : The neuroprotective effects of fucoxanthin on H 2 O 2 -induced toxicity were studied in both SH-SY5Y cells and primary cerebellar granule neurons. Results : Fucoxanthin significantly protected against H 2 O 2 -induced neuronal apoptosis and intracellular reactive oxygen species. H 2 O 2 treatment led to the reduced activity of phosphoinositide 3-kinase (PI3-K)/Akt cascade and the increased activity of extracellular signal-regulated kinase (ERK) pathway in SH-SY5Y cells. Moreover, fucoxanthin significantly restored the altered activities of PI3-K/Akt and ERK pathways induced by H 2 O 2 . Both specific inhibitors of glycogen synthase kinase 3β (GSK3β) and mitogen-activated protein kinase kinase (MEK) significantly protected against H 2 O 2 -induced neuronal death. Furthermore, the neuroprotective effects of fucoxanthin against H 2 O 2 -induced neuronal death were abolished by specific PI3-K inhibitors. Conclusions : Our data strongly revealed that fucoxanthin protected against H 2 O 2 -induced neurotoxicity via concurrently activating the PI3-K/Akt cascade and inhibiting the ERK pathway, providing support for the use of fucoxanthin to treat neurodegenerative disorders induced by oxidative stress.

Hyperforin inhibits vesicular uptake of monoamines by dissipating pH gradient across synaptic vesicle membrane.

Science.gov (United States)

Roz, Netta; Rehavi, Moshe

2003-06-13

Extracts of Hypericum perforatum (St. John's wort) have antidepressant properties in depressed patients and exert antidepressant-like action in laboratory animals. The phloroglucinol derivative hyperforin has become a topic of interest, as this Hypericum component is a potent inhibitor of monoamines reuptake. The molecular mechanism by which hyperforin inhibits monoamines uptake is yet unclear. In the present study we try to clarify the mechanism by which hyperforin inhibits the synaptic vesicle transport of monoamines. The pH gradient across the synaptic vesicle membrane, induced by vacuolar type H(+)-ATPase, is the major driving force for vesicular monoamines uptake and storage. We suggest that hyperforin, like the protonophore FCCP, dissipates an existing Delta pH generated by an efflux of inwardly pumped protons. Proton transport was measured by acridine orange fluorescence quenching. Adding Mg-ATP to a medium containing 130 mM KCl and synaptic vesicles caused an immediate decrease in fluorescence of acridine orange and the addition of 1 microM FCCP abolished this effect. H(+)-ATPase dependent proton pumping was inhibited by hyperforin in a dose dependent manner (IC(50) = 1.9 x 10(-7) M). Hyperforin acted similarly to the protonophore FCCP, abolishing the ATP induced fluorescence quenching (IC(50) = 4.3 x 10(-7) M). Hyperforin and FCCP had similar potencies for inhibiting rat brain synaptosomal uptake of [3H]monoamines as well as vesicular monoamine uptake. The efflux of [3H]5HT from synaptic vesicles was sensitive to both drugs, thus 50% of preloaded [3H]5HT was released in the presence of 2.1 x 10(-7) M FCCP and 4 x 10(-7) M hyperforin. The effect of hyperforin on the pH gradient in synaptic vesicle membrane may explain its inhibitory effect on monoamines uptake, but could only partially explain its antidepressant properties.

A look at corporal punishment and some implications of its use.

Science.gov (United States)

Wilson, F C

1982-01-01

The author notes several legal, social, philosophical and educational attitudes common to Canada and the United States which have, for centuries, characterized the uses of corporal punishment with children. Specifically, corporal punishment is viewed as a technique for developing discipline within the school system. Inconsistencies in both Canada and the U.S. are noted regarding court decisions and their application in the classroom. Recent revisions to The Ontario Child Welfare Act are discussed in light of its implications for parents and teachers who physically punish their children or students. Research findings related to corporal punishment and their implications for schools are cited. Negative side-effects of administering punishment are also described. The evidence suggests that corporal punishment besides being an ineffective learning technique, is not the uncomplicated, quick solution many may think it. The author concludes by proposing that because of their important role in the lives of developing children and considering the resources devoted to teacher training, teachers should be held as legally accountable for their use of corporal punishment with children as parents are. As well, he indicates the need for (1) increased teacher training in the areas of child management, classroom management and interactional processes; (2) greater opportunity to devise creative problem-solving strategies; and (3) a re-ordering of priorities at universities, colleges and faculties of education which would benefit not only teachers, but ultimately their students.

'Being hit was normal': teachers' (unchanging perceptions of discipline and corporal punishment

Directory of Open Access Journals (Sweden)

D Sagree Govender

2014-06-01

Full Text Available Global and national concerns that corporal punishment is still being used, openly in certain milieus and surreptitiously in others, suggests that education stakeholders need to take cognisance of teachers' perceptions and experiences that influence their classroom discipline in the context of changing curriculum policies and legislation. This study was guided by research objectives that explored, firstly, teachers perceptions of their past experiences of corporal punishment and, secondly, their perceptions of their disciplinary techniques since the abolition of corporal punishment. Through a qualitative research methodology of semi-structured interviews, data were collected from seven primary school teachers in KwaZulu-Natal. Teachers' perceptions of their experiences and practices of corporal punishment were explored through two dimensions of the Foucauldian concept of bio-power, namely, disciplinary power and governmentality. The findings show that although all teachers experienced corporal punishment negatively when they were pupils, their responses to the abolition of corporal punishment were varied, multiple and complex. Recommendations for further research include exploring the resilience of authoritarian teaching approaches and teacher professional development of learner-centred approaches to curb teacher frustration that contributes to their use of corporal punishment.

The impact of reward and punishment on skill learning depends on task demands.

Science.gov (United States)

Steel, Adam; Silson, Edward H; Stagg, Charlotte J; Baker, Chris I

2016-10-27

Reward and punishment motivate behavior, but it is unclear exactly how they impact skill performance and whether the effect varies across skills. The present study investigated the effect of reward and punishment in both a sequencing skill and a motor skill context. Participants trained on either a sequencing skill (serial reaction time task) or a motor skill (force-tracking task). Skill knowledge was tested immediately after training, and again 1 hour, 24-48 hours, and 30 days after training. We found a dissociation of the effects of reward and punishment on the tasks, primarily reflecting the impact of punishment. While punishment improved serial reaction time task performance, it impaired force-tracking task performance. In contrast to prior literature, neither reward nor punishment benefitted memory retention, arguing against the common assumption that reward ubiquitously benefits skill retention. Collectively, these results suggest that punishment impacts skilled behavior more than reward in a complex, task dependent fashion.

Parental use of corporal punishment in Europe: intersection between public health and policy.

Science.gov (United States)

duRivage, Nathalie; Keyes, Katherine; Leray, Emmanuelle; Pez, Ondine; Bitfoi, Adina; Koç, Ceren; Goelitz, Dietmar; Kuijpers, Rowella; Lesinskiene, Sigita; Mihova, Zlatka; Otten, Roy; Fermanian, Christophe; Kovess-Masfety, Viviane

2015-01-01

Studies have linked the use of corporal punishment of children to the development of mental health disorders. Despite the recommendation of international governing bodies for a complete ban of the practice, there is little European data available on the effects of corporal punishment on mental health and the influence of laws banning corporal punishment. Using data from the School Children Mental Health Europe survey, the objective of this cross-sectional study was to examine the prevalence and legal status of corporal punishment across six European countries and to evaluate the association between parental use of corporal punishment and children's mental health. The study found that odds of having parents who reported using occasional to frequent corporal punishment were 1.7 times higher in countries where its use is legal, controlling for socio-demographic factors. Children with parents who reported using corporal punishment had higher rates of both externalized and internalized mental health disorders.

Parental use of corporal punishment in Europe: intersection between public health and policy.

Directory of Open Access Journals (Sweden)

Nathalie duRivage

Full Text Available Studies have linked the use of corporal punishment of children to the development of mental health disorders. Despite the recommendation of international governing bodies for a complete ban of the practice, there is little European data available on the effects of corporal punishment on mental health and the influence of laws banning corporal punishment. Using data from the School Children Mental Health Europe survey, the objective of this cross-sectional study was to examine the prevalence and legal status of corporal punishment across six European countries and to evaluate the association between parental use of corporal punishment and children's mental health. The study found that odds of having parents who reported using occasional to frequent corporal punishment were 1.7 times higher in countries where its use is legal, controlling for socio-demographic factors. Children with parents who reported using corporal punishment had higher rates of both externalized and internalized mental health disorders.

Parental Use of Corporal Punishment in Europe: Intersection between Public Health and Policy

Science.gov (United States)

duRivage, Nathalie; Keyes, Katherine; Leray, Emmanuelle; Pez, Ondine; Bitfoi, Adina; Koç, Ceren; Goelitz, Dietmar; Kuijpers, Rowella; Lesinskiene, Sigita; Mihova, Zlatka; Otten, Roy; Fermanian, Christophe; Kovess-Masfety, Viviane

2015-01-01

Studies have linked the use of corporal punishment of children to the development of mental health disorders. Despite the recommendation of international governing bodies for a complete ban of the practice, there is little European data available on the effects of corporal punishment on mental health and the influence of laws banning corporal punishment. Using data from the School Children Mental Health Europe survey, the objective of this cross-sectional study was to examine the prevalence and legal status of corporal punishment across six European countries and to evaluate the association between parental use of corporal punishment and children’s mental health. The study found that odds of having parents who reported using occasional to frequent corporal punishment were 1.7 times higher in countries where its use is legal, controlling for socio-demographic factors. Children with parents who reported using corporal punishment had higher rates of both externalized and internalized mental health disorders. PMID:25674788

Symmetric vs. asymmetric punishment regimes for bribery

OpenAIRE

Engel, Christoph; Goerg, Sebastian J.; Yu, Gaoneng

2012-01-01

In major legal orders such as UK, the U.S., Germany, and France, bribers and recipients face equally severe criminal sanctions. In contrast, countries like China, Russia, and Japan treat the briber more mildly. Given these differences between symmetric and asymmetric punishment regimes for bribery, one may wonder which punishment strategy is more effective in curbing corruption. For this purpose, we designed and ran a lab experiment in Bonn (Germany) and Shanghai (China) with exactly the same...

From Blame to Punishment: Disrupting Prefrontal Cortex Activity Reveals Norm Enforcement Mechanisms.

Science.gov (United States)

Buckholtz, Joshua W; Martin, Justin W; Treadway, Michael T; Jan, Katherine; Zald, David H; Jones, Owen; Marois, René

2015-09-23

The social welfare provided by cooperation depends on the enforcement of social norms. Determining blameworthiness and assigning a deserved punishment are two cognitive cornerstones of norm enforcement. Although prior work has implicated the dorsolateral prefrontal cortex (DLPFC) in norm-based judgments, the relative contribution of this region to blameworthiness and punishment decisions remains poorly understood. Here, we used repetitive transcranial magnetic stimulation (rTMS) and fMRI to determine the specific role of DLPFC function in norm-enforcement behavior. DLPFC rTMS reduced punishment for wrongful acts without affecting blameworthiness ratings, and fMRI revealed punishment-selective DLPFC recruitment, suggesting that these two facets of norm-based decision making are neurobiologically dissociable. Finally, we show that DLPFC rTMS affects punishment decision making by altering the integration of information about culpability and harm. Together, these findings reveal a selective, causal role for DLPFC in norm enforcement: representational integration of the distinct information streams used to make punishment decisions. Copyright © 2015 Elsevier Inc. All rights reserved.

Undestanding of the past and present meaning of punishment and penal policies

Directory of Open Access Journals (Sweden)

Marjeta Tesla

2011-06-01

Full Text Available Punishment has a dual meaning: it is necessary because it leads to a change in behavior, but it also causes emotional imbalance between teachers and pupils. There are three basic theories of punishment – retributivism, which requires pu- nishment as a method that will stop the individual from wanting to repeat the offense; utilitarianism, in which the primary goal of punishment is changing the individual, whereas the abolitionism theory searches for alternative forms of resolving disputes and deviant behavior. Zero tolerance means application of the same penalties for minor and major transgressions. Its opposite is inclusion, aimed at enabling people of different abilities to live together in peace and develop positive values. It is hard to imagine upbringing without punishment, despite the fact that the use of sanctions have negative effects. Theore- tically speaking, if punishment is whatever an individual experiences as unpleasantness, then penalty cannot be eliminated in upbringing. Classic penalties can be replaced by measures proposed by opponents of traditional punishment

Inhibition of VDAC1 prevents Ca²⁺-mediated oxidative stress and apoptosis induced by 5-aminolevulinic acid mediated sonodynamic therapy in THP-1 macrophages.

Science.gov (United States)

Chen, Haibo; Gao, Weiwei; Yang, Yang; Guo, Shuyuan; Wang, Huan; Wang, Wei; Zhang, Shuisheng; Zhou, Qi; Xu, Haobo; Yao, Jianting; Tian, Zhen; Li, Bicheng; Cao, Wenwu; Zhang, Zhiguo; Tian, Ye

2014-12-01

Ultrasound combined with endogenous protoporphyrin IX derived from 5-aminolevulinic acid (ALA-SDT) is known to induce apoptosis in multiple cancer cells and macrophages. Persistent retention of macrophages in the plaque has been implicated in the pathophysiology and progression of atherosclerosis. Here we investigated the effects of inhibition of voltage-dependent anion channel 1 (VDAC1) on ALA-SDT-induced THP-1 macrophages apoptosis. Cells were pre-treated with VDAC1 inhibitor 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) disodium salt for 1 h or downregulated VDAC1 expression by small interfering RNA and exposed to ultrasound. Cell viability was assessed by MTT assay, and cell apoptosis along with necrosis was evaluated by Hoechst 33342/propidium iodide staining and flow cytometry. Levels of cytochrome c release was assessed by confocal microscope and Western blot. The levels of full length caspases, caspase activation, and VDAC isoforms were analyzed by Western blot. Intracellular reactive oxygen species generation, mitochondrial membrane permeability, and intracellular Ca(2+) [Ca(2+)]i levels were measured with fluorescent probes. We confirmed that the pharmacological inhibition of VDAC1 by DIDS notably prevented ALA-SDT-induced cell apoptosis in THP-1 macrophages. Additionally, DIDS significantly inhibited intracellular ROS generation and apoptotic biochemical changes such as inner mitochondrial membrane permeabilization, loss of mitochondrial membrane potential, cytochrome c release and activation of caspase-3 and caspase-9. Moreover, ALA-SDT elevated the [Ca(2+)]i levels and it was also notably reduced by DIDS. Furthermore, both of intracellular ROS generation and cell apoptosis were predominately inhibited by Ca(2+) chelating reagent BAPTA-AM. Intriguingly, ALA-treatment markedly augmented VDAC1 protein levels exclusively, and the downregulation of VDAC1 expression by specific siRNA also significantly abolished cell apoptosis. Altogether, these

Monopolizing sanctioning power under noise eliminates perverse punishment but does not increase cooperation

OpenAIRE

Sven Fischer; Kristoffel Grechenig; Nicolas Meier

2016-01-01

We run several experiments which allow us to compare cooperation under perfect and imperfect information in a centralized and decentralized punishment regime. Under perfect and extremely noisy information, aggregate behavior does not differ between institutions. Under intermediate noise, punishment escalates in the decentralized peer-to-peer punishment regime which badly affects efficiency while sustaining cooperation for longer. Only decentralized punishment is often directed at cooperators ...

Serotonergic neurons signal reward and punishment on multiple timescales

Science.gov (United States)

Cohen, Jeremiah Y; Amoroso, Mackenzie W; Uchida, Naoshige

2015-01-01

Serotonin's function in the brain is unclear. One challenge in testing the numerous hypotheses about serotonin's function has been observing the activity of identified serotonergic neurons in animals engaged in behavioral tasks. We recorded the activity of dorsal raphe neurons while mice experienced a task in which rewards and punishments varied across blocks of trials. We ‘tagged’ serotonergic neurons with the light-sensitive protein channelrhodopsin-2 and identified them based on their responses to light. We found three main features of serotonergic neuron activity: (1) a large fraction of serotonergic neurons modulated their tonic firing rates over the course of minutes during reward vs punishment blocks; (2) most were phasically excited by punishments; and (3) a subset was phasically excited by reward-predicting cues. By contrast, dopaminergic neurons did not show firing rate changes across blocks of trials. These results suggest that serotonergic neurons signal information about reward and punishment on multiple timescales. DOI: http://dx.doi.org/10.7554/eLife.06346.001 PMID:25714923

Dissociable roles for the basolateral amygdala and orbitofrontal cortex in decision-making under risk of punishment.

Science.gov (United States)

Orsini, Caitlin A; Trotta, Rose T; Bizon, Jennifer L; Setlow, Barry

2015-01-28

Several neuropsychiatric disorders are associated with abnormal decision-making involving risk of punishment, but the neural basis of this association remains poorly understood. Altered activity in brain systems including the basolateral amygdala (BLA) and orbitofrontal cortex (OFC) can accompany these same disorders, and these structures are implicated in some forms of decision-making. The current study investigated the role of the BLA and OFC in decision-making under risk of explicit punishment. Rats were trained in the risky decision-making task (RDT), in which they chose between two levers, one that delivered a small safe reward, and the other that delivered a large reward accompanied by varying risks of footshock punishment. Following training, they received sham or neurotoxic lesions of BLA or OFC, followed by RDT retesting. BLA lesions increased choice of the large risky reward (greater risk-taking) compared to both prelesion performance and sham controls. When reward magnitudes were equated, both BLA lesion and control groups shifted their choice to the safe (no shock) reward lever, indicating that the lesions did not impair punishment sensitivity. In contrast to BLA lesions, OFC lesions significantly decreased risk-taking compared with sham controls, but did not impair discrimination between different reward magnitudes or alter baseline levels of anxiety. Finally, neither lesion significantly affected food-motivated lever pressing under various fixed ratio schedules, indicating that lesion-induced alterations in risk-taking were not secondary to changes in appetitive motivation. Together, these findings indicate distinct roles for the BLA and OFC in decision-making under risk of explicit punishment. Copyright © 2015 the authors 0270-6474/15/351368-12$15.00/0.

Attributions of guilt and punishment as functions of physical attractiveness and smiling.

Science.gov (United States)

Abel, Millicent H; Watters, Heather

2005-12-01

The authors found an interaction between sex of participant and sex of defendant in the leniency bias toward a smiling defendant. Differences occurred for male participants when levying punishment for a smiling male defendant vs. a smiling female defendant and for a smiling male defendant vs. a nonsmiling male defendant, whereas differences did not occur for female participants. The authors found moderating effects of physical attractiveness and smiling between guilt and punishment. The only significant positive relationship between guilt and punishment occurred for the defendant whom participants rated low in physical attractiveness and who was not smiling. When guilty, the smiling and unattractive defendant received less punishment than did the smiling and attractive defendant. The authors discussed complex relationships between physical attractiveness, smiling, guilt, and punishment.

Physical punishment of children: can we continue to accept the status quo?

Science.gov (United States)

Oates, Kim

2011-08-01

All children require discipline, although physical punishment is just one form of discipline. Parental use of physical punishment is inter-generational. There is now evidence that physical punishment of children is not only less effective than other forms of discipline but can also lead to aggressive behaviour in childhood and adult life. Twenty-nine countries, including New Zealand, have laws against physical punishment in the home. Australian attitudes are slowly changing in favour of less use of physical punishment, but there is a long way to go. As advocates for children, paediatricians should not be content to accept the status quo. © 2011 The Author. Journal of Paediatrics and Child Health © 2011 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

Inhibition of basophil histamine release by gangliosides. Further studies on the significance of cell membrane sialic acid in the histamine release process

DEFF Research Database (Denmark)

Jensen, C; Norn, S; Thastrup, Ole

1987-01-01

with the glucolipid mixture increased the sialic acid content of the cells, and this increase was attributed to an insertion of gangliosides into the cell membrane. The inhibition of histamine release was abolished by increasing the calcium concentration, which substantiates our previous findings that cell membrane......Histamine release from human basophils was inhibited by preincubation of the cells with a glucolipid mixture containing sialic acid-containing gangliosides. This was true for histamine release induced by anti-IgE, Concanavalin A and the calcium ionophore A23187, whereas the release induced by S....... aureus Wood 46 was not affected. It was demonstrated that the inhibitory capacity of the glucolipid mixture could be attributed to the content of gangliosides, since no inhibition was obtained with cerebrosides or with gangliosides from which sialic acid was removed. Preincubation of the cells...

Corporal Punishment and Youth Externalizing Behavior in Santiago, Chile

Science.gov (United States)

Ma, Julie; Han, Yoonsun; Grogan-Kaylor, Andrew; Delva, Jorge; Castillo, Marcela

2012-01-01

Objectives: Corporal punishment is still widely practiced around the globe, despite the large body of child development research that substantiates its short- and long-term consequences. Within this context, this paper examined the relationship between parental use of corporal punishment and youth externalizing behavior with a Chilean sample to…

Religious Beliefs, Sociopolitical Ideology, and Attitudes toward Corporal Punishment

Science.gov (United States)

Ellison, Christopher G.; Bradshaw, Matt

2009-01-01

The use of corporal punishment to discipline children remains a perennial focus of controversy. Several studies published in the 1990s linked support for, and use of, corporal punishment with religious factors, particularly core doctrines of conservative (i.e., evangelical and fundamentalist) Protestantism. This study reexamines the relationships…

The tetrapeptide Arg-Leu-Tyr-Glu inhibits VEGF-induced angiogenesis

International Nuclear Information System (INIS)

Baek, Yi-Yong; Lee, Dong-Keon; So, Ju-Hoon; Kim, Cheol-Hee; Jeoung, Dooil; Lee, Hansoo; Choe, Jongseon; Won, Moo-Ho; Ha, Kwon-Soo; Kwon, Young-Guen; Kim, Young-Myeong

2015-01-01

Kringle 5, derived from plasminogen, is highly capable of inhibiting angiogenesis. Here, we have designed and synthesized 10 tetrapeptides, based on the amino acid properties of the core tetrapeptide Lys-Leu-Tyr-Asp (KLYD) originating from anti-angiogenic kringle 5 of human plasminogen. Of these, Arg-Leu-Tyr-Glu (RLYE) effectively inhibited vascular endothelial growth factor (VEGF)-induced endothelial cell proliferation, migration and tube formation, with an IC 50 of 0.06–0.08 nM, which was about ten-fold lower than that of the control peptide KLYD (0.79 nM), as well as suppressed developmental angiogenesis in a zebrafish model. Furthermore, this peptide effectively inhibited the cellular events that precede angiogenesis, such as ERK and eNOS phosphorylation and nitric oxide production, in endothelial cells stimulated with VEGF. Collectively, these data demonstrate that RLYE is a potent anti-angiogenic peptide that targets the VEGF signaling pathway. - Highlights: • The tetrapeptide RLYE inhibited VEGF-induced angiogenesis in vitro. • RLYE also suppressed neovascularization in a zebrafish model. • Its effect was correlated with inhibition of VEGF-induced ERK and eNOS activation. • RLYE may be used as a therapeutic drug for angiogenesis-related diseases

The tetrapeptide Arg-Leu-Tyr-Glu inhibits VEGF-induced angiogenesis

Energy Technology Data Exchange (ETDEWEB)

Baek, Yi-Yong; Lee, Dong-Keon [Department of Molecular and Cellular Biochemistry, School of Medicine, Kangwon National University, Chuncheon, Gangwon-do, 200-702 (Korea, Republic of); So, Ju-Hoon; Kim, Cheol-Hee [Department of Biology, Chungnam National University, Daejeon, 305-764 (Korea, Republic of); Jeoung, Dooil [Department of Biochemistry, College of Natural Sciences, Kangwon National University, Chuncheon, Gangwon-do, 200-702 (Korea, Republic of); Lee, Hansoo [Department of Life Sciences, College of Natural Sciences, Kangwon National University, Chuncheon, Gangwon-do, 200-702 (Korea, Republic of); Choe, Jongseon [Department of Immunology, School of Medicine, Kangwon National University, Chuncheon, Gangwon-do, 200-702 (Korea, Republic of); Won, Moo-Ho [Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon, Gangwon-do, 200-702 (Korea, Republic of); Ha, Kwon-Soo [Department of Molecular and Cellular Biochemistry, School of Medicine, Kangwon National University, Chuncheon, Gangwon-do, 200-702 (Korea, Republic of); Kwon, Young-Guen [Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, 120-752 (Korea, Republic of); Kim, Young-Myeong, E-mail: ymkim@kangwon.ac.kr [Department of Molecular and Cellular Biochemistry, School of Medicine, Kangwon National University, Chuncheon, Gangwon-do, 200-702 (Korea, Republic of)

2015-08-07

Kringle 5, derived from plasminogen, is highly capable of inhibiting angiogenesis. Here, we have designed and synthesized 10 tetrapeptides, based on the amino acid properties of the core tetrapeptide Lys-Leu-Tyr-Asp (KLYD) originating from anti-angiogenic kringle 5 of human plasminogen. Of these, Arg-Leu-Tyr-Glu (RLYE) effectively inhibited vascular endothelial growth factor (VEGF)-induced endothelial cell proliferation, migration and tube formation, with an IC{sub 50} of 0.06–0.08 nM, which was about ten-fold lower than that of the control peptide KLYD (0.79 nM), as well as suppressed developmental angiogenesis in a zebrafish model. Furthermore, this peptide effectively inhibited the cellular events that precede angiogenesis, such as ERK and eNOS phosphorylation and nitric oxide production, in endothelial cells stimulated with VEGF. Collectively, these data demonstrate that RLYE is a potent anti-angiogenic peptide that targets the VEGF signaling pathway. - Highlights: • The tetrapeptide RLYE inhibited VEGF-induced angiogenesis in vitro. • RLYE also suppressed neovascularization in a zebrafish model. • Its effect was correlated with inhibition of VEGF-induced ERK and eNOS activation. • RLYE may be used as a therapeutic drug for angiogenesis-related diseases.

The Incompatibility of Punishment and Moral Education: A Reply to Peter Hobson.

Science.gov (United States)

Marshall, James D.

1989-01-01

Responds to Peter Hobson's assertions concerning the relationship of punishment and moral education. Draws upon the writings of Michael Foucoult in suggesting that punishment in the legal sense does not fit well with efforts to develop rational autonomy. Suggests that traditional talk of punishment obscures the reality of practice. (KO)

Distinct medial temporal networks encode surprise during motivation by reward versus punishment

Science.gov (United States)

Murty, Vishnu P.; LaBar, Kevin S.; Adcock, R. Alison

2016-01-01

Adaptive motivated behavior requires predictive internal representations of the environment, and surprising events are indications for encoding new representations of the environment. The medial temporal lobe memory system, including the hippocampus and surrounding cortex, encodes surprising events and is influenced by motivational state. Because behavior reflects the goals of an individual, we investigated whether motivational valence (i.e., pursuing rewards versus avoiding punishments) also impacts neural and mnemonic encoding of surprising events. During functional magnetic resonance imaging (fMRI), participants encountered perceptually unexpected events either during the pursuit of rewards or avoidance of punishments. Despite similar levels of motivation across groups, reward and punishment facilitated the processing of surprising events in different medial temporal lobe regions. Whereas during reward motivation, perceptual surprises enhanced activation in the hippocampus, during punishment motivation surprises instead enhanced activation in parahippocampal cortex. Further, we found that reward motivation facilitated hippocampal coupling with ventromedial PFC, whereas punishment motivation facilitated parahippocampal cortical coupling with orbitofrontal cortex. Behaviorally, post-scan testing revealed that reward, but not punishment, motivation resulted in greater memory selectivity for surprising events encountered during goal pursuit. Together these findings demonstrate that neuromodulatory systems engaged by anticipation of reward and punishment target separate components of the medial temporal lobe, modulating medial temporal lobe sensitivity and connectivity. Thus, reward and punishment motivation yield distinct neural contexts for learning, with distinct consequences for how surprises are incorporated into predictive mnemonic models of the environment. PMID:26854903

Distinct medial temporal networks encode surprise during motivation by reward versus punishment.

Science.gov (United States)

Murty, Vishnu P; LaBar, Kevin S; Adcock, R Alison

2016-10-01

Adaptive motivated behavior requires predictive internal representations of the environment, and surprising events are indications for encoding new representations of the environment. The medial temporal lobe memory system, including the hippocampus and surrounding cortex, encodes surprising events and is influenced by motivational state. Because behavior reflects the goals of an individual, we investigated whether motivational valence (i.e., pursuing rewards versus avoiding punishments) also impacts neural and mnemonic encoding of surprising events. During functional magnetic resonance imaging (fMRI), participants encountered perceptually unexpected events either during the pursuit of rewards or avoidance of punishments. Despite similar levels of motivation across groups, reward and punishment facilitated the processing of surprising events in different medial temporal lobe regions. Whereas during reward motivation, perceptual surprises enhanced activation in the hippocampus, during punishment motivation surprises instead enhanced activation in parahippocampal cortex. Further, we found that reward motivation facilitated hippocampal coupling with ventromedial PFC, whereas punishment motivation facilitated parahippocampal cortical coupling with orbitofrontal cortex. Behaviorally, post-scan testing revealed that reward, but not punishment, motivation resulted in greater memory selectivity for surprising events encountered during goal pursuit. Together these findings demonstrate that neuromodulatory systems engaged by anticipation of reward and punishment target separate components of the medial temporal lobe, modulating medial temporal lobe sensitivity and connectivity. Thus, reward and punishment motivation yield distinct neural contexts for learning, with distinct consequences for how surprises are incorporated into predictive mnemonic models of the environment. Copyright © 2016 Elsevier Inc. All rights reserved.

SPRY4-mediated ERK1/2 signaling inhibition abolishes 17β-estradiol-induced cell growth in endometrial adenocarcinoma cell.

Science.gov (United States)

Li, Mingjiang; Zhang, Hui; Zhao, Xingbo; Yan, Lei; Wang, Chong; Li, Chunyan; Li, Changzhong

2014-08-01

Basic fibroblast growth factor (FGF2)-mediated Extracellular signal-regulated kinases1/2 (ERK1/2) signaling is a critical modulator in angiogenesis. SPRY4 has been reported to be a feedback negative regulator of FGFs-induced ERK1/2 signaling. The aim of this study was to explore the role of SPRY4 in endometrial adenocarcinoma cell. The effect of SPRY4 expression on FGF2-mediated ERK1/2 signaling was detected by luciferase assay and Western blot analysis. The growth of Ishikawa cells was detected using colony formation assay and cell number counting experiment. We found that plasmid-driven SPRY4 expression efficiently blocked the activity of FGF2-induced ERK1/2 signaling in Ishikawa cells. SPRY4 expression significantly reduced the proliferation and 17β-estradiol-induced proliferation of Ishikawa cells. SPRY4 may function as a tumor suppressor in endometrial adenocarcinoma.

Corporal punishment-related ocular injuries in Nigerian children

Directory of Open Access Journals (Sweden)

Oluwakemi Adegbehingbe

2007-01-01

Full Text Available Objective: To determine the contribution of corporal punishment to ocular morbidity and visual impairment in Nigerian children. Materials and Methods: A prospective study was conducted of all patients aged 0-15 years seen with ocular injuries over a four year period. Those who sustained ocular injuries during the administration of corporal punishment were further studied. Relevant information was documented using a semistructured questionnaire. Data was analyzed by simple descriptive statistics using SPSS statistical package version 10. Results: A total of 186 children were seen within the study period. Eighty-nine (47.8% had ocular injuries and 27 (30.3% had ocular injuries resulting from corporal punishment. Of the latter group, eighteen were males and nine were females. Their ages ranged from 3-15 years (mean = 8.5 ± 2.4 years. Corporal punishment-associated injuries occurred most commonly as seen in 17 (63% of our study population who were aged 7-12 years. These 27 cases of injuries were sustained in the schools: 13 (48.2%, homes: eight (29.6%, market place: three (11.1%, workshop: two (7.4% and worship houses: one (3.7%. A stick was the object mostly implicated in causing ocular injuries in 13 (48.2% followed by a belt in five (18.5% and a whip in four (14.8%. Severe visual impairment occurred in two (7.4% patients while blindness occurred in three (11.1% patients. Conclusion: Corporal punishment is a major cause of ocular morbidity and blindness in Nigerian children.

The animal in you: animalistic descriptions of a violent crime increase punishment of perpetrator.

Science.gov (United States)

Vasquez, Eduardo A; Loughnan, Steve; Gootjes-Dreesbach, Ellis; Weger, Ulrich

2014-01-01

Criminal acts are sometimes described using animal metaphors. What is the impact of a violent crime being described in an animalistic versus a non-animalistic way on the subsequent retribution toward the perpetrator? In two studies, we experimentally varied animalistic descriptions of a violent crime and examined its effect on the severity of the punishment for the act. In Study 1, we showed that compared to non-animalistic descriptions, animalistic descriptions resulted in significantly harsher punishment for the perpetrator. In Study 2, we replicated this effect and further demonstrated that this harsher sentencing is explained by an increase in perceived risk of recidivism. Our findings suggest that animalistic descriptions of crimes lead to more retaliation against the perpetrator by inducing the perception that he is likely to continue engaging in violence. © 2014 Wiley Periodicals, Inc.

Inhibition of dehydration-induced water intake by glucocorticoids is associated with activation of hypothalamic natriuretic peptide receptor-A in rat.

Directory of Open Access Journals (Sweden)

Chao Liu

Full Text Available Atrial natriuretic peptide (ANP provides a potent defense mechanism against volume overload in mammals. Its primary receptor, natriuretic peptide receptor-A (NPR-A, is localized mostly in the kidney, but also is found in hypothalamic areas involved in body fluid volume regulation. Acute glucocorticoid administration produces potent diuresis and natriuresis, possibly by acting in the renal natriuretic peptide system. However, chronic glucocorticoid administration attenuates renal water and sodium excretion. The precise mechanism underlying this paradoxical phenomenon is unclear. We assume that chronic glucocorticoid administration may activate natriuretic peptide system in hypothalamus, and cause volume depletion by inhibiting dehydration-induced water intake. Volume depletion, in turn, compromises renal water excretion. To test this postulation, we determined the effect of dexamethasone on dehydration-induced water intake and assessed the expression of NPR-A in the hypothalamus. The rats were deprived of water for 24 hours to have dehydrated status. Prior to free access to water, the water-deprived rats were pretreated with dexamethasone or vehicle. Urinary volume and water intake were monitored. We found that dexamethasone pretreatment not only produced potent diuresis, but dramatically inhibited the dehydration-induced water intake. Western blotting analysis showed the expression of NPR-A in the hypothalamus was dramatically upregulated by dexamethasone. Consequently, cyclic guanosine monophosphate (the second messenger for the ANP content in the hypothalamus was remarkably increased. The inhibitory effect of dexamethasone on water intake presented in a time- and dose-dependent manner, which emerged at least after 18-hour dexamethasone pretreatment. This effect was glucocorticoid receptor (GR mediated and was abolished by GR antagonist RU486. These results indicated a possible physiologic role for glucocorticoids in the hypothalamic control of

Effects of Corporal Punishment on Disciplinary Control of Secondary ...

African Journals Online (AJOL)

Administration of corporal punishment in secondary schools tends to be cruel, inhuman and could result in child abuse. Therefore, the purpose of this study was to determine the effects of the use of corporal punishment on the disciplinary control of secondary education students in Calabar Metropolis of Nigeria. The study ...

Corporal Punishment: Does It Hinder the Development of Children?

Science.gov (United States)

Chenoweth, T.; Just, H.

Noting that parents' use of corporal punishment to discipline their children remains a strongly debated issue, this paper examines the impact of corporal punishment on children's development, focusing primarily on its long-term effectiveness. The paper presents the history of spanking in the United States, including public opinion on corporal…

Phase diagrams for the spatial public goods game with pool punishment

Science.gov (United States)

Szolnoki, Attila; Szabó, György; Perc, Matjaž

2011-03-01

The efficiency of institutionalized punishment is studied by evaluating the stationary states in the spatial public goods game comprising unconditional defectors, cooperators, and cooperating pool punishers as the three competing strategies. Fines and costs of pool punishment are considered as the two main parameters determining the stationary distributions of strategies on the square lattice. Each player collects a payoff from five five-person public goods games, and the evolution of strategies is subsequently governed by imitation based on pairwise comparisons at a low level of noise. The impact of pool punishment on the evolution of cooperation in structured populations is significantly different from that reported previously for peer punishment. Representative phase diagrams reveal remarkably rich behavior, depending also on the value of the synergy factor that characterizes the efficiency of investments payed into the common pool. Besides traditional single- and two-strategy stationary states, a rock-paper-scissors type of cyclic dominance can emerge in strikingly different ways.

Dimensions of child punishment in two Central American countries: Guatemala and El Salvador.

Science.gov (United States)

Speizer, Ilene S; Goodwin, Mary M; Samandari, Ghazaleh; Kim, Shin Y; Clyde, Maureen

2008-04-01

Severe physical punishment of children is an important issue in international child health and welfare. This study examines such punishment in Guatemala and El Salvador. Data came from nationally representative surveys of women aged 15-49 and men aged 15-59 residing in Guatemala (2002) and El Salvador (2002-2003). The surveys included questions about punishment experienced during childhood, with response options ranging from verbal scolding to beating. In Guatemala, parents were asked how they disciplined their children; questions allowed them to compare how they were punished in their childhood with how they punished their own children. Bivariate and multivariate analyses are presented. In Guatemala, 35% of women and 46% of men reported being beaten as punishment in childhood; in El Salvador, the figures were 42% and 62%, respectively. In both countries, older participants were relatively more likely than younger participants to have been beaten as children. Witnessing familial violence was associated with an increased risk of being beaten in childhood. In Guatemala, having experienced physical punishment as a child increased the chance that parents would use physical punishment on their own children. Multivariate analyses revealed that women who were beaten in childhood were significantly more likely in both countries to be in a violent relationship. The use of beating to physically punish children is a common problem in Guatemala and El Salvador, with generational and intergenerational effects. Its negative and lingering effects necessitate the introduction of policies and programs to decrease this behavior.

No Punishment Without Guilt: The Case concerning German Prosecution of a Former GDR Border Guard

DEFF Research Database (Denmark)

Rytter, Jens Elo

2003-01-01

Menneskerettigheder, Human Rights, Den Europæiske Menneskerettighedskonvention, European Convention of Human Rights, Straf, Punishment, tilbagevirkende straf, retroactive punishment......Menneskerettigheder, Human Rights, Den Europæiske Menneskerettighedskonvention, European Convention of Human Rights, Straf, Punishment, tilbagevirkende straf, retroactive punishment...

Does dishonesty really invite third-party punishment? Results of a more stringent test.

Science.gov (United States)

Konishi, Naoki; Ohtsubo, Yohsuke

2015-05-01

Many experiments have demonstrated that people are willing to incur cost to punish norm violators even when they are not directly harmed by the violation. Such altruistic third-party punishment is often considered an evolutionary underpinning of large-scale human cooperation. However, some scholars argue that previously demonstrated altruistic third-party punishment against fairness-norm violations may be an experimental artefact. For example, envy-driven retaliatory behaviour (i.e. spite) towards better-off unfair game players may be misidentified as altruistic punishment. Indeed, a recent experiment demonstrated that participants ceased to inflict third-party punishment against an unfair player once a series of key methodological problems were systematically controlled for. Noticing that a previous finding regarding apparently altruistic third-party punishment against honesty-norm violations may have been subject to methodological issues, we used a different and what we consider to be a more sound design to evaluate these findings. Third-party punishment against dishonest players withstood this more stringent test. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

Third-party punishment increases cooperation in children through (misaligned) expectations and conditional cooperation.

Science.gov (United States)

Lergetporer, Philipp; Angerer, Silvia; Glätzle-Rützler, Daniela; Sutter, Matthias

2014-05-13

The human ability to establish cooperation, even in large groups of genetically unrelated strangers, depends upon the enforcement of cooperation norms. Third-party punishment is one important factor to explain high levels of cooperation among humans, although it is still somewhat disputed whether other animal species also use this mechanism for promoting cooperation. We study the effectiveness of third-party punishment to increase children's cooperative behavior in a large-scale cooperation game. Based on an experiment with 1,120 children, aged 7 to 11 y, we find that the threat of third-party punishment more than doubles cooperation rates, despite the fact that children are rarely willing to execute costly punishment. We can show that the higher cooperation levels with third-party punishment are driven by two components. First, cooperation is a rational (expected payoff-maximizing) response to incorrect beliefs about the punishment behavior of third parties. Second, cooperation is a conditionally cooperative reaction to correct beliefs that third party punishment will increase a partner's level of cooperation.

A new perspective on punishments and rewards in marketing channel relationships

OpenAIRE

Chow, M.W.

2007-01-01

How effective are punishments and rewards in influencing dealer performance in marketing channel relationships? Although often used in managerial practice, academic research on the relationship between punishment/reward and dealer performance has been scarce and demonstrates variable results. The aim of this dissertation is to resolve the indistinctness that currently surrounds academic research on the use of punishments and rewards in marketing channel relationships. The three studies in thi...

The role of perspective taking and emotions in punishing identified and unidentified wrongdoers.

Science.gov (United States)

Kogut, Tehila

2011-12-01

We present two studies examining the effect of identifiability on willingness to punish, emphasising that identifiability of the wrongdoer may increase or decrease willingness to punish depending on the punisher's perspective. When taking the wrongdoer's perspective, identifiability increases pity and decreases anger towards the wrongdoer, leading to a lighter punishment. On the other hand, when adopting the injured perspective, identifiability decreases pity and increases anger, resulting in a severe punishment. We show that while deliberation and rational factors affect the decision regardless of identification, the role of emotions in the decision is greater in the identified condition. Possible implications for public and educational policy are discussed.

Blunted cardiovascular reactivity in dysphoria during reward and punishment anticipation.

Science.gov (United States)

Franzen, Jessica; Brinkmann, Kerstin

2015-03-01

Hyposensitivity to reward in depression and dysphoria has been found in behavioral and neuroimaging studies. For punishment responsiveness, some studies showed hyposensitivity to punishment while other studies demonstrated hypersensitivity. Only few studies have addressed the motivational question as to whether depressed individuals mobilize less effort in anticipation of a positive or a negative consequence. The present study aimed at investigating reward and punishment responsiveness in subclinical depression from an effort mobilization perspective. Working on a recognition memory task, one third of the participants could earn small amounts of money, one third could lose small amounts of money, and one third could neither earn nor lose money. Effort mobilization was operationalized as participants' cardiovascular reactivity during task performance. As expected, reactivity of cardiac pre-ejection period and heart rate was higher in both incentive conditions compared to the neutral condition for nondysphorics, while it was blunted across conditions for dysphorics. Moreover, the present study found that dysphorics show an altered behavioral response to punishment. These findings thus show that dysphorics present a reduced motivation to obtain a reward or to avoid a punishment in terms of reduced effort-related cardiac reactivity. Copyright © 2014 Elsevier B.V. All rights reserved.

Impact of Social Punishment on Cooperative Behavior in Complex Networks

Science.gov (United States)

Wang, Zhen; Xia, Cheng-Yi; Meloni, Sandro; Zhou, Chang-Song; Moreno, Yamir

2013-10-01

Social punishment is a mechanism by which cooperative individuals spend part of their resources to penalize defectors. In this paper, we study the evolution of cooperation in 2-person evolutionary games on networks when a mechanism for social punishment is introduced. Specifically, we introduce a new kind of role, punisher, which is aimed at reducing the earnings of defectors by applying to them a social fee. Results from numerical simulations show that different equilibria allowing the three strategies to coexist are possible as well as that social punishment further enhance the robustness of cooperation. Our results are confirmed for different network topologies and two evolutionary games. In addition, we analyze the microscopic mechanisms that give rise to the observed macroscopic behaviors in both homogeneous and heterogeneous networks. Our conclusions might provide additional insights for understanding the roots of cooperation in social systems.

Statins activate GATA-6 and induce differentiated vascular smooth muscle cells

International Nuclear Information System (INIS)

Wada, Hiromichi; Abe, Mitsuru; Ono, Koh; Morimoto, Tatsuya; Kawamura, Teruhisa; Takaya, Tomohide; Satoh, Noriko; Fujita, Masatoshi; Kita, Toru; Shimatsu, Akira; Hasegawa, Koji

2008-01-01

The beneficial effects of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) beyond cholesterol lowering involve their direct actions on vascular smooth muscle cells (VSMCs). However, the effects of statins on phenotypic modulation of VSMCs are unknown. We herein show that simvastatin (Sm) and atorvastatin (At) inhibited DNA synthesis in human aortic VSMCs dose-dependently, while cell toxicity was not observed below the concentration of 1 μM of Sm or 100 nM of At. Stimulating proliferative VSMCs with Sm or At induced the expression of SM-α-actin and SM-MHC, highly specific markers of differentiated phenotype. Sm up-regulated the binding activity of GATA-6 to SM-MHC GATA site and activated the transfected SM-MHC promoter in proliferative VSMCs, while mutating the GATA-6 binding site abolished this activation. Geranylgeranylpyrophosphate (10 μM), an inhibitor of Rho family proteins, abolished the statin-mediated induction of the differentiated phenotype in VSMCs. These findings suggest that statins activate GATA-6 and induce differentiated VSMCs

Statins activate GATA-6 and induce differentiated vascular smooth muscle cells

Energy Technology Data Exchange (ETDEWEB)

Wada, Hiromichi [Division of Translational Research, National Hospital Organization Kyoto Medical Center, 1-1 Mukaihata-cho, Fukakusa, Fushimi-ku, Kyoto 612-8555 (Japan); Abe, Mitsuru; Ono, Koh [Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto (Japan); Morimoto, Tatsuya; Kawamura, Teruhisa; Takaya, Tomohide [Division of Translational Research, National Hospital Organization Kyoto Medical Center, 1-1 Mukaihata-cho, Fukakusa, Fushimi-ku, Kyoto 612-8555 (Japan); Satoh, Noriko [Division of Metabolic Research, National Hospital Organization Kyoto Medical Center, Kyoto (Japan); Fujita, Masatoshi [Department of Human Health Sciences, Graduate School of Medicine, Kyoto University, Kyoto (Japan); Kita, Toru [Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto (Japan); Shimatsu, Akira [Clinical Research Institute, National Hospital Organization Kyoto Medical Center, Kyoto (Japan); Hasegawa, Koji [Division of Translational Research, National Hospital Organization Kyoto Medical Center, 1-1 Mukaihata-cho, Fukakusa, Fushimi-ku, Kyoto 612-8555 (Japan)

2008-10-03

The beneficial effects of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) beyond cholesterol lowering involve their direct actions on vascular smooth muscle cells (VSMCs). However, the effects of statins on phenotypic modulation of VSMCs are unknown. We herein show that simvastatin (Sm) and atorvastatin (At) inhibited DNA synthesis in human aortic VSMCs dose-dependently, while cell toxicity was not observed below the concentration of 1 {mu}M of Sm or 100 nM of At. Stimulating proliferative VSMCs with Sm or At induced the expression of SM-{alpha}-actin and SM-MHC, highly specific markers of differentiated phenotype. Sm up-regulated the binding activity of GATA-6 to SM-MHC GATA site and activated the transfected SM-MHC promoter in proliferative VSMCs, while mutating the GATA-6 binding site abolished this activation. Geranylgeranylpyrophosphate (10 {mu}M), an inhibitor of Rho family proteins, abolished the statin-mediated induction of the differentiated phenotype in VSMCs. These findings suggest that statins activate GATA-6 and induce differentiated VSMCs.

Gendering Corporal Punishment: Beyond the Discourse of Human Rights

Science.gov (United States)

Humphreys, Sara

2008-01-01

In the last few years the Global Initiative to End All Corporal Punishment of Children has been gathering momentum, with a submission to "The United Nations Secretary General's study on violence against children" the most recent addition to the cause. Nevertheless, corporal punishment in schools is still condoned in many countries and…

Collective punishment is more effective than collective reward for promoting cooperation

Science.gov (United States)

Gao, Lei; Wang, Zhen; Pansini, Riccardo; Li, Yao-Tang; Wang, Rui-Wu

2015-12-01

Collective punishment and reward are usually regarded as two potential mechanisms to explain the evolution of cooperation. Both scenarios, however, seem problematic to understand cooperative behavior, because they can raise the second-order free-rider problem and many organisms are not able to discriminate less cooperating individuals. Even though they have been proved to increase cooperation, there has been a debate about which one being more effective. To address this issue, we resort to the N-player evolutionary snowdrift game (NESG), where a collective punishment/reward mechanism is added by allowing some players to display punishment/reward towards all remaining players. By means of numerous simulations and analyses, we find that collective punishment is more effective in promoting cooperation for a relatively high initial frequency of cooperation or for a relatively small group. When the intensity of punishment exceeds a certain threshold, a stable state of full cooperation emerges for both small and large groups. In contrast, such state does not appear for large groups playing a NESG with reward mechanism. In the case of mutualistic interactions, finally, our results show the new payoff with collective punishment/reward can lead to the coexistence of cooperators and defectors when discrimination between these two is not possible.

Inhibition of ribosomal RNA synthesis in yeast by ionizing radiations

Energy Technology Data Exchange (ETDEWEB)

Weber, K; Kiefer, J [Giessen Univ. (Germany, F.R.). Strahlenzentrum

1984-12-01

Synthesis of ribosomal RNA(r-RNA) was measured for 1 h after exposure of Saccharomyces cerevisiae to ..gamma..-rays, X-rays or ..cap alpha.. particles. ..gamma..- or X-ray induced transcription inhibition was always found to decrease exponentially with dose. D/sub 0/ values of 2150 or 1950 Gy were determined in wild-type cells, corresponding to a mean energy of about 60 eV per r-RNA gene. The finding of differential sensitivities of the two high molecular-weight r-RNA species which are cotranscribed from r-DNA is compatible with the existence of a transcription terminating mechanism. Cells from a mutant strain (rad-9), radiation sensitive to colony forming ability, showed an approximately equal sensitivity for transcription inhibition compared to the wild-type (D/sub 0/ (2095) = 2400 Gy). Inactivation of r-RNA synthesis in cells exposed to ..cap alpha..-particles at room-temperature showed a decreased sensitivity with higher particle fluences ('resistant tail'). This phenomenon was drastically reduced if the temperature during irradiation was lowered to 4/sup 0/C and completely abolished when dried cells were used. An inactivation cross-section for ..cap alpha..-particle induced transcription inhibition of about 0.02 ..mu..m/sup 2/ can be derived from the experimental data.

Phosphatidylcholine reverses ethanol-induced increase in transepithelial endotoxin permeability and abolishes transepithelial leukocyte activation

DEFF Research Database (Denmark)

Mitscherling, K.; Volynets, V.; Parlesak, Alexandr

2009-01-01