Authority dependence and judgments of utilitarian harm

Three studies tested the conditions under which people judge utilitarian harm to be authority dependent (i.e., whether its right or wrongness depends on the ruling of an authority). In Study 1, participants judged the right or wrongness of physical abuse when used as an interrogation method anticipated to yield useful information for preventing future terrorist attacks. The ruling of the military authority towards the harm was manipulated (prohibited vs. prescribed) and found to significantly influence judgments of the right or wrongness of inflicting harm. Study 2 established a boundary condition with regards to the influence of authority, which was eliminated when the utility of the harm was definitely obtained rather than forecasted. Finally, Study 3 replicated the findings of Studies 1-2 in a completely different context—an expert committee’s ruling about the harming of chimpanzees for biomedical research. These results are discussed as they inform ongoing debates regarding the role of authority in moderating judgments of complex and simple harm. 2013 Elsevier B.V. © All rights reserved.

Moral asymmetries in judgments of agency withstand ludicrous causal deviance

Americans have been shown to attribute greater intentionality to immoral than to amoral actions in cases of causal deviance, that is, cases where a goal is satisfied in a way that deviates from initially planned means (e.g., a gunman wants to hit a target and his hand slips, but the bullet ricochets off a rock into the target). However, past research has yet to assess whether this asymmetry persists in cases of extreme causal deviance. Here, we manipulated the level of mild to extreme causal deviance of an immoral versus amoral act. The asymmetry in attributions of intentionality was observed at all but the
most extreme level of causal deviance, and, as we hypothesized, was mediated by attributions of Blame/credit and judgments of action performance. These findings are discussed as they support a multiple-concepts interpretation of the asymmetry, wherein blame renders a naïve concept of intentional action (the outcome matches the intention) more salient than a composite concept (the outcome matches the intention and was brought about by planned means), and in terms of their implications for cross-cultural research on judgments of agency.

Journal of Cantigny Operations, 28 May 1918

A "journal of Cantigny operations" starting at 12:15 a.m. May 28th through May 30th. The final entry reads: "May 30th: Colonel Holbrook reports that the Germans started another Counter Attack about 3:30A.M. that the first wave got through our barrage, but did not reach our lines and that the second wave was destroyed by our barrage."

Standardization of cytokine flow cytometry assays

Affiliation: Faculté de médecine, Université de Montréal & CANVAC

Experiències d'innovació docent en el context de l'EEES: estan preparats els nostres estudiants per al canvi cultural?

L’adaptació a l’EEES comporta un canvi cultural per a les universitats de l’estat espanyol. Desde la perspectiva de la gestió del canvi organitzatiu, marc teòric en el que es sustenta aquest estudi, aquest canvi es pot categoritzar com una reorientació segons la classificació de Nadler i Tushman (1995), donat que es tracta d’un canvi profund, discontinu i radical que s’anticipa als canvis i necessitats de l’entorn. Aquest tipus de canvis requereixen d’una introducció gradual, donat que la seva magnitud qüestiona la identitat i cultura de l’organització, generant moltes resistències. Des d’aquesta literatura es recomana fer un diagnòstic de les forces que afecten al canvi per tal de garantir el seu èxit. En aquest sentit, l’objectiu del present estudi és la identificació de les forces inhibidores del canvi cultural en la URV a partir d’una anàlisi introspectiva de les experiència d’innovació docent en l’assignatura de Pràctiques Integrades I. La metodologia utilitzada per aquest estudi ha estat la introspecció personal subjectiva (Brown & Reid , 1997; Patterson et al., 1998; Holbrook, 2005). L’experiència consistia en l’avaluació de certes competències de saber, saber fer, i saber ser i estar, a través de diferents mètodes d’avaluació docent. Les dades de satisfacció dels estudiants amb la metodologia de l’assignatura es van recollir mitjançant un informe d’opinió anònim i no estructurat que se’ls demanava entregar l’últim dia de classe. Opinions més generals sobre el canvi a l’EEES es van recollir a l’inici de l’assignatura a través d’una sessió de focus group amb cada un dels grups d’activitat de l’assignatura. Son múltiples els estudis que afirmen la conveniència de posar en pràctica noves metodologies i formes d’innovació docent que situïn a l’alumne com a eix central de l’aprenentatge i que avaluïn els seus aprenentatges en funció de l’adquisició de competències (Apodaca, 2006, Bautista et al. 2007, Margalef i Canabal, 2007, Brown i Glasner, 2003). No obstant, els resultats del nostre estudi posen en evidència que una de les principals forces inhibidores per a la gestió del canvi en el sistema docent universitari son les actituds dels alumnes, i en especial les d’aquells alumnes que combinen simultàniament estudis amb l’activitat laboral. Com a resultat de l’anàlisi, es proposen mesures per neutralitzar o eliminar les resistències identificades i es duu a terme una reflexió sobre com s’està duent a terme la gestió del canvi en la universitat

Estudio prospectivo para la facultad de odontología de la universidad cooperativa de Colombia, sede Villavicencio, 2020

Las tendencias para las Instituciones de Educación Superior, se enmarcan en ambientes cada vez menos predecibles y cambiantes. La anticipación con miras a determinar los diferentes escenarios a los que se pueda ver enfrentada este tipo de organizaciones, facilita la comprensión de los futuros posibles. Por tanto, el propósito de esta investigación se fundamenta en la realización de un estudio que permita la construcción de los escenarios de futuro para la Facultad de Odontología de la Universidad Cooperativa de Colombia, Sede Villavicencio, con un horizonte de tiempo al año 2020. Para esto se desarrolló la metodología basada en los planteamientos de la Prospectiva estratégica de Godet (1997), a través de tres (3) etapas: el Análisis estructural prospectivo, el Sistema de matrices de impacto cruzado y la propuesta del Escenario apuesta. Finalmente, el estudio presenta recomendaciones a los directivos de la Facultad de Odontología, relacionadas con la construcción del Escenario apuesta, catalogándose como herramienta para el direccionamiento estratégico y toma de decisiones.

A functional proteomic method for the enrichment of peripheral membrane proteins reveals the collagen binding protein Hsp47 is exposed on the surface of activated human platelets

Platelets are small blood cells vital for hemostasis. Following vascular damage, platelets adhere to collagens and activate, forming a thrombus that plugs the wound and prevents blood loss. Stimulation of the platelet collagen receptor glycoprotein VI (GPVI) allows recruitment of proteins to receptor-proximal signaling complexes on the inner-leaflet of the plasma membrane. These proteins are often present at low concentrations; therefore, signaling-complex characterization using mass spectrometry is limited due to high sample complexity. We describe a method that facilitates detection of signaling proteins concentrated on membranes. Peripheral membrane proteins (reversibly associated with membranes) were eluted from human platelets with alkaline sodium carbonate. Liquid-phase isoelectric focusing and gel electrophoresis were used to identify proteins that changed in levels on membranes from GPVI-stimulated platelets. Immunoblot analysis verified protein recruitment to platelet membranes and subsequent protein phosphorylation was preserved. Hsp47, a collagen binding protein, was among the proteins identified and found to be exposed on the surface of GPVI-activated platelets. Inhibition of Hsp47 abolished platelet aggregation in response to collagen, while only partially reducing aggregation in response to other platelet agonists. We propose that Hsp47 may therefore play a role in hemostasis and thrombosis.

Future innovations in anti-platelet therapies

Platelets have long been recognized to be of central importance in haemostasis, but their participation in pathological conditions such as thrombosis, atherosclerosis and inflammation is now also well established. The platelet has therefore become a key target in therapies to combat cardiovascular disease. Anti-platelet therapies are used widely, but current approaches lack efficacy in a proportion of patients, and are associated with side effects including problem bleeding. In the last decade, substantial progress has been made in understanding the regulation of platelet function, including the characterization of new ligands, platelet-specific receptors and cell signalling pathways. It is anticipated this progress will impact positively on the future innovations towards more effective and safer anti-platelet agents. In this review, the mechanisms of platelet regulation and current anti-platelet therapies are introduced, and strong, and some more speculative, potential candidate target molecules for future anti-platelet drug development are discussed.

Platelets release novel thiol isomerase enzymes which are recruited to the cell surface following activation

The thiol isomerase enzymes protein disulphide isomerase (PDI) and endoplasmic reticulum protein 5 (ERp5) are released by resting and activated platelets. These re-associate with the cell surface where they modulate a range of platelet responses including adhesion, secretion and aggregation. Recent studies suggest the existence of yet uncharacterised platelet thiol isomerase proteins. This study aimed to identify which other thiol isomerase enzymes are present in human platelets. Through the use of immunoblotting, flow cytometry, cell-surface biotinylation and gene array analysis, we report the presence of five additional thiol isomerases in human and mouse platelets and megakaryocytes, namely; ERp57, ERp72, ERp44, ERp29 and TMX3. ERp72, ERp57, ERp44 and ERp29 are released by platelets and relocate to the cell surface following platelet activation. The transmembrane thiol isomerase TMX3 was also detected on the platelet surface but does not increase following activation. Extracellular PDI is also implicated in the regulation of coagulation by the modulation of tissue factor activity. ERp57 was identified within platelet-derived microparticle fractions, suggesting that ERp57 may also be involved in the regulation of coagulation as well as platelet function. These data collectively implicate the expanding family of platelet-surface thiol isomerases in the regulation of haemostasis.

Platelet endothelial cell adhesion molecule-1 regulates collagen-stimulated platelet function by modulating the association of phosphatidylinositol 3-kinase with Grb-2-associated binding protein-1 and linker for activation of T cells

Background: Platelet activation by collagen depends on signals transduced by the glycoprotein (GP)VI–Fc receptor (FcR)-chain collagen receptor complex, which involves recruitment of phosphatidylinositol 3-kinase (PI3K) to phosphorylated tyrosines in the linker for activation of T cells (LAT). An interaction between the p85 regulatory subunit of PI3K and the scaffolding molecule Grb-2-associated binding protein-1 (Gab1), which is regulated by binding of the Src homology 2 domain-containing protein tyrosine phosphatase-2 (SHP-2) to Gab1, has been shown in other cell types to sustain PI3K activity to elicit cellular responses. Platelet endothelial cell adhesion molecule-1 (PECAM-1) functions as a negative regulator of platelet reactivity and thrombosis, at least in part by inhibiting GPVI–FcR-chain signaling via recruitment of SHP-2 to phosphorylated immunoreceptor tyrosine-based inhibitory motifs in PECAM-1. Objective: To investigate the possibility that PECAM-1 regulates the formation of the Gab1–p85 signaling complexes, and the potential effect of such interactions on GPVI-mediated platelet activation in platelets. Methods: The ability of PECAM-1 signaling to modulate the LAT signalosome was investigated with immunoblotting assays on human platelets and knockout mouse platelets. Results: PECAM-1-associated SHP-2 in collagen-stimulated platelets binds to p85, which results in diminished levels of association with both Gab1 and LAT and reduced collagen-stimulated PI3K signaling. We therefore propose that PECAM-1-mediated inhibition of GPVI-dependent platelet responses result, at least in part, from recruitment of SHP-2–p85 complexes to tyrosine-phosphorylated PECAM-1, which diminishes the association of PI3K with activatory signaling molecules, such as Gab1 and LAT.

The platelet-surface thiol isomerase enzyme ERp57 modulates platelet function

Background: Thiol isomerases are a family of endoplasmic reticulum enzymes which orchestrate redox-based modifications of protein disulphide bonds. Previous studies have identified important roles for the thiol isomerases PDI and ERp5 in the regulation of normal platelet function. Objectives: Recently, we demonstrated the presence of a further five thiol isomerases at the platelet surface. In this report we aim to report the role of one of these enzymes - ERp57 in the regulation of platelet function. Methods/Results: Using enzyme activity function blocking antibodies, we demonstrate a role for ERp57 in platelet aggregation, dense granule secretion, fibrinogen binding, calcium mobilisation and thrombus formation under arterial conditions. In addition to the effects of ERp57 on isolated platelets, we observe the presence of ERp57 in the developing thrombus in vivo. Furthermore the inhibition of ERp57 function was found to reduce laser-injury induced arterial thrombus formation in a murine model of thrombosis. Conclusions: These data suggest that ERp57 is important for normal platelet function and opens up the possibility that the regulation of platelet function by a range of cell surface thiol isomerases may represent a broad paradigm for the regulation of haemostasis and thrombosis.

Staphylococcal extracellular adherence protein induces platelet activation by stimulation of thiol isomerases

OBJECTIVE: Staphylococcus aureus can induce platelet aggregation. The rapidity and degree of this correlates with the severity of disseminated intravascular coagulation, and depends on platelet peptidoglycans. Surface-located thiol isomerases play an important role in platelet activation. The staphylococcal extracellular adherence protein (Eap) functions as an adhesin for host plasma proteins. Therefore we tested the effect of Eap on platelets. METHODS AND RESULTS: We found a strong stimulation of the platelet-surface thiol isomerases protein disulfide isomerase, endoplasmic reticulum stress proteins 57 and 72 by Eap. Eap induced thiol isomerase-dependent glycoprotein IIb/IIIa activation, granule secretion, and platelet aggregation. Treatment of platelets with thiol blockers, bacitracin, and anti-protein disulfide isomerase antibody inhibited Eap-induced platelet activation. The effect of Eap on platelets and protein disulfide isomerase activity was completely blocked by glycosaminoglycans. Inhibition by the hydrophobic probe bis(1-anilinonaphthalene 8-sulfonate) suggested the involvement of hydrophobic sites in protein disulfide isomerase and platelet activation by Eap. CONCLUSIONS: In the present study, we found an additional and yet unknown mechanism of platelet activation by a bacterial adhesin, involving stimulation of thiol isomerases. The thiol isomerase stimulatory and prothrombotic features of a microbial secreted protein are probably not restricted to S aureus and Eap. Because many microorganisms are coated with amyloidogenic proteins, it is likely that the observed mechanism is a more general one.

Platelet protein disulfide isomerase is required for thrombus formation but not essential for hemostasis in mice

Protein disulfide isomerase (PDI) derived from intravascular cells is required for thrombus formation. However, it remains unclear whether platelet PDI contributes to the process. Using platelet-specific PDI-deficient mice, we demonstrate that PDI-null platelets have defects in aggregation and ATP secretion induced by thrombin, collagen, and ADP. Such defects were rescued by exogenously-added wild-type but not mutant PDI, indicating that the isomerase activity of platelet surface PDI is critical for the regulatory effect. PDI-deficient platelets expressed increased levels of intracellular ERp57 and ERp72. Platelet PDI regulated αIIbβ3 integrin activation but not P-selectin exposure, Ca2+ mobilization, β3-talin interaction, and platelet spreading on immobilized fibrinogen. Inhibition of ERp57 further diminished αIIbβ3 integrin activation, aggregation and ATP secretion of activated PDI-deficient platelets, suggesting distinct roles of PDI and ERp57 in platelet functions. We found that platelet PDI is important for thrombus formation on collagen-coated surfaces under arteriolar shear. Intravital microscopy demonstrates that platelet PDI is important for platelet accumulation but not initial adhesion and fibrin generation following laser-induced arteriolar injury. Tail bleeding time and blood loss in platelet-specific PDI-deficient mice were not significantly increased. Our results provide important evidence that platelet PDI is essential for thrombus formation but not for hemostasis in mice.