Tityus discrepans scorpion venom activates platelets through GPVI and a novel Src-dependent signaling pathway

In humans and other mammals, Tityus discrepans (Td) scorpion envenomation produces a variety of systemic effects including respiratory distress, a generalized inflammatory reaction, modulation of blood pressure, fibrin formation, and platelet activation. For many of these effects, the venom components and underlying mechanisms are not known. In the present study, we demonstrate that Td venom (TdV) stimulates integrin αIIbβ3-dependent aggregation of washed human and mouse platelets downstream of Src kinase activation. The pattern of increase in tyrosine phosphorylation induced by TdV in human platelets is similar to that induced by the collagen receptor GPVI, and includes FcR γ-chain, Syk, and PLC γ 2. Confirmation of GPVI activation by TdV was achieved by expression of human GPVI in chicken DT40 B cells and use of a reporter assay. To our surprise, TdV was able to activate mouse platelets deficient in the GPVI-FcR γ-chain complex through a pathway that was also dependent on Src kinases. TdV therefore activates platelets through GPVI and a second, as yet unidentified Src kinase-dependent pathway.

Ibrutinib inhibits platelet integrin αIIbβ3 outside-in signaling and thrombus stability but not adhesion to collagen

OBJECTIVE: Ibrutinib is an irreversible Bruton tyrosine kinase inhibitor approved for treatment of Waldenstrom macroglobulinemia, chronic lymphocytic leukemia, and mantle cell lymphoma that increases the risk of bleeding among patients. Platelets from ibrutinib-treated patients exhibit deficiencies in collagen-evoked signaling in suspension; however, the significance of this observation and how it relates to bleeding risk is unclear, as platelets encounter immobile collagen in vivo. We sought to clarify the effects of ibrutinib on platelet function to better understand the mechanism underlying bleeding risk. APPROACH AND RESULTS: By comparing signaling in suspension and during adhesion to immobilized ligands, we found that the collagen signaling deficiency caused by ibrutinib is milder during adhesion to immobilized collagen. We also found that platelets in whole blood treated with ibrutinib adhered to collagen under arterial shear but formed unstable thrombi, suggesting that the collagen signaling deficiency caused by ibrutinib may not be the predominant cause of bleeding in vivo. However, clot retraction and signaling evoked by platelet adhesion to immobilized fibrinogen were also inhibited by ibrutinib, indicating that integrin αIIbβ3 outside-in signaling is also effected in addition to GPVI signaling. When ibrutinib was combined with the P2Y12 inhibitor, cangrelor, thrombus formation under arterial shear was inhibited additively. CONCLUSIONS: These findings suggest that (1) ibrutinib causes GPVI and integrin αIIbβ3 platelet signaling deficiencies that result in formation of unstable thrombi and may contribute toward bleeding observed in vivo and (2) combining ibrutinib with P2Y12 antagonists, which also inhibit thrombus stability, may have a detrimental effect on hemostasis.

L'effet de compensation morale ou comment les 'bonnes actions' peuvent aboutir à une situation indésirable

Des recherches récentes arguent qu’une « bonne action » pourrait contribuer à « désinhiber » l’individu en lui permettant d’entreprendre des actions « moins souhaitables » par la suite. Cet effet de compensation morale reste un domaine peu étudié, en dépit des conséquences potentielles considérables sur l’efficacité des politiques publiques. L’objectif de notre contribution est de définir et de caractériser cet effet tout en soulignant les risques d’effets pervers associés. Nous utilisons à cet effet des études et des exemples tirés de divers domaines, comme la consommation alimentaire ou les comportements prosociaux, et identifions des pistes de recherche visant à mieux comprendre les conséquences directes et indirectes de cet effet, tout en mentionnant quelques stratégies envisageables afin d’atténuer ce biais.

Self-licensing and financial rewards: is morality for sale?

This paper studies the impact of financially rewarding good deeds on self-licensing. We run a between-subjects experiment comprised of an adapted dictator game preceded by paid and unpaid pro-environmental tasks. We find that prefacing the dictator game with an unpaid good deed seems to establish a 'moral rectitude' which licenses subsequent selfish behaviour, whereas a paid good deed dampens this effect. Interestingly, the nature of the initial task has more of an effect on the binary option (give vs. not give) than on the amount donated.

Smug alert! Exploring self-licensing behaviour in a cheating game

We test experimentally a prediction of the ‘moral credit model’, in which committing a virtuous act creates moral credits that can license immoral behavior in a succeeding decision. We use a basic cheating experiment that was either preceded by a virtuous deed or not in a developing country context. We found that people who previously achieved a good deed cheat more. Gender and origin are also significant explicative variables for cheating.

Do good deeds make bad people?

According to the so-called ‘self-licensing effect’, committing to a virtuous act in a preceding choice may lead to behave less virtuously in the succeeding decision. Consequently, well-intentioned policies can lead to overall counter-productive effects by licensing people to behave badly in related behaviors. On the other side, motivational crowding theory argues that constraining people to adopt a desirable behavior can backfire. We use of a classroom experiment to test whether a regulatory framework to incentivize individuals to adopt pro-environmental behavior generate similar spillovers in terms of licensing effect than a non-regulatory framework. We show that the way the good deed is caused doesn’t seem to influence the licensing effect. Nevertheless, we found that business- and environmental-orientated majors react adversely to the regulatory framework. We show that environmental-orientated students exhibit higher intrinsically motivations than business-orientated ones. Accordingly, we suggest that the licensing effect is more likely to arise when the preceding ‘virtuous’ act is freely chosen (respectively regulatory caused) for non-intrinsically (respectively intrinsically) motivated individuals.

Present bias predicts participation in payments for environmental services: evidence from a behavioral experiment in Uganda

Farmers are necessary agents in global efforts to conserve the environment now that croplands and pastures together constitute the largest terrestrial system on Earth – covering some 48% of ice-free land surface. Whereas standard economic models predict that farmers will participate in conservation programs so long as they are profitable, empirical findings from behavioral economics point to a number of normally unobservable preferences that may influence the decision-making process. This study tests, for the first time, whether heterogeneity in behavioral preferences correlates with decisions to participate in Payments for Environmental Services (PES) programs. We elicit individual trust and time preferences using economic experiments and link resulting measures to household survey data and participation decisions in a Ugandan PES program. We find that farmers who exhibit a preference for proximate gains – present-biased preferences – are 47.7% more likely to participate in the program than those who show time-consistent or future-biased preferences. This result has implications for ongoing and planned PES programs involving farmers, particularly in Africa, by highlighting a potential relationship between payment timing and participation, and further validates the use of behavioral experiments in explaining real-world decisions.

Compensation and Rewards for Environmental Services (CRES) and efficient design of contracts in developing countries. Behavioral insights from a natural field experiment

The use of economic incentives for biodiversity (mostly Compensation and Reward for Environmental Services including Payment for ES) has been widely supported in the past decades and became the main innovative policy tools for biodiversity conservation worldwide. These policy tools are often based on the insight that rational actors perfectly weigh the costs and benefits of adopting certain behaviors and well-crafted economic incentives and disincentives will lead to socially desirable development scenarios. This rationalist mode of thought has provided interesting insights and results, but it also misestimates the context by which ‘real individuals’ come to decisions, and the multitude of factors influencing development sequences. In this study, our goal is to examine how these policies can take advantage of some unintended behavioral reactions that might in return impact, either positively or negatively, general policy performances. We test the effect of income's origin (‘Low effort’ based money vs. ‘High effort’ based money) on spending decisions (Necessity vs. Superior goods) and subsequent pro social preferences (Future pro-environmental behavior) within Madagascar rural areas, using a natural field experiment. Our results show that money obtained under low effort leads to different consumption patterns than money obtained under high efforts: superior goods are more salient in the case of low effort money. In parallel, money obtained under low effort leads to subsequent higher pro social behavior. Compensation and rewards policies for ecosystem services may mobilize knowledge on behavioral biases to improve their design and foster positive spillovers on their development goals.