The tetrapeptide sequence of IL-18 and IL-1ß regulates their recruitment and activation by inflammatory caspases.

Inflammasomes are multiprotein signaling complexes that activate the innate immune system. Canonical inflammasomes recruit and activate caspase-1, which then cleaves and activates IL-1ß and IL-18, as well as gasdermin D (GSDMD) to induce pyroptosis. In contrast, non-canonical inflammasomes, caspases-4/-5 (CASP4/5) in humans and caspase-11 (CASP11) in mice, are known to cleave GSDMD, but their role in direct processing of other substrates besides GSDMD has remained unknown. Here, we show that CASP4/5 but not CASP11 can directly cleave and activate IL-18. However, CASP4/5/11 can all cleave IL-1ß to generate a 27-kDa fragment that deactivates IL-1ß signaling. Mechanistically, we demonstrate that the sequence identity of the tetrapeptide sequence adjacent to the caspase cleavage site regulates IL-18 and IL-1ß recruitment and activation. Altogether, we have identified new substrates of the non-canonical inflammasomes and reveal key mechanistic details regulating inflammation that may aid in developing new therapeutics for immune-related disorders.

Identity, gender, and the role of age of acquisition in face processing

Two experiments examined the effects of age of acquisition (AoA) and the gender of stimulus faces on familiarity decisions (Experiment 1) and gender decisions (Experiment 2) to the same set of famous and unfamiliar faces presented as whole faces, internal features or external features. In Experiment 1, familiarity decisions were faster to whole faces than to internal or external features. Famous faces with early AoA were recognized faster than later acquired faces, though the effect was only reliable for famous male faces, and for whole faces and internal features rather than for external features. In Experiment 2, gender decisions were made more rapidly to whole faces than to internal or external features. Classification was faster to famous than to unfamiliar faces when the faces were presented as internal features or external features, but not when they were presented as whole faces. More gender classification errors were made to famous than to un familiar male faces, but there was no effect of familiarity on the accuracy of responses to female faces. A o A had no effect on gender classification of whole faces or external features. Classification from internal features was faster for early than for late acquired male faces, but faster for late than for early female faces. In the light of the anomalous results for female faces, responses to male faces were analysed separately. The results for the male faces form the focus of the discussion (AU)

Dos experimentos examinaron los efectos de la edad de adquisición(AoA) y el género de rostros utilizados como estímulos en tareas de decisión de familiaridad (Experimento 1) y decisión de género (Experimento 2) con el mismo set de rostros famosos y rostros desconocidos presentados completos y sólo con sus características internas o externas. En el experimento 1, las decisiones de familiaridad fueron más rápidas para los rostros completos que para las características internas o externas de los rostros. Los rostros famosos con edad de adquisición temprana fueron reconocidos más rápidamente que aquellos con edad de adquisición tardía, aunque el efecto fue sólo significativo para rostros masculinos famosos, y para rostros completos y características internas que para características externas. En el experimento 2, las decisiones de género se llevaron a cabo más rápidamente para rostros completos que para características internas y externas. La clasificación fue más rápida para rostros famosos que para rostros desconocidos cuando éstos fueron presentados con sus características internas o externas, pero no cuando fueron presentados completos. Se registraron más errores de clasificación para los rostros masculinos famosos que para los desconocidos, pero no hubo efecto de familiaridad en la precisión de las respuestas para los rostros femeninos. La AoA no mostró efecto en la clasificación de género para rostros completos o características externas. La clasificación de características internas fue más rápida para los rostros aprendidos a temprana edad que para aquellos aprendidos a una edad tardía, pero más rápida para rostros femeninos aprendidos a una edad tardía que para aquellos aprendidos a temprana edad. Debido a que los resultados para los rostros femeninos fueron anómalos, las respuestas correspondientes a los rostros masculinos fueron analizadas por separado. Los resultados delos rostros masculinos forman el centro de la discusión (AU)

Identity, gender, and the role of age of acquisition in face processing

Dos experimentos examinaron los efectos de la edad de adquisición (AoA) y el género de rostros utilizados como estímulos en tareas de decisión de familiaridad (Experimento 1) y decisión de género (Experimento 2) con el mismo set de rostros famosos y rostros desconocidos presentados completos y sólo con sus características internas o externas. En el experimento 1, las decisiones de familiaridad fueron más rápidas para los rostros completos que para las características internas o externas de los rostros. Los rostros famosos con edad de adquisición temprana fueron reconocidos más rápidamente que aquellos con edad de adquisición tardía, aunque el efecto fue sólo significativo para rostros masculinos famosos, y para rostros completos y características internas que para características externas. En el experimento 2, las decisiones de género se llevaron a cabo más rápidamente para rostros completos que para características internas y externas. La clasificación fue más rápida para rostros famosos que para rostros desconocidos cuando éstos fueron presentados con sus características internas o externas, pero no cuando fueron presentados completos. Se registraron más errores de clasificación para los rostros masculinos famosos que para los desconocidos, pero no hubo efecto de familiaridad en la precisión de las respuestas para los rostros femeninos. La AoA no mostró efecto en la clasificación de género para rostros completos o características externas. La clasificación de características internas fue más rápida para los rostros aprendidos a temprana edad que para aquellos aprendidos a una edad tardía, pero más rápida para rostros femeninos aprendidos a una edad tardía que para aquellos aprendidos a temprana edad. Debido a que los resultados para los rostros femeninos fueron anómalos, las respuestas correspondientes a los rostros masculinos fueron analizadas por separado. Los resultados de los rostros masculinos forman el centro de la discusión (AU)

Two experiments examined the effects of age of acquisition (AoA) and the gender of stimulus faces on familiarity decisions (Experiment 1) and gender decisions (Experiment 2) to the same set of famous and unfamiliar faces presented as whole faces, internal features or external features. In Experiment 1, familiarity decisions were faster to whole faces than to internal or external features. Famous faces with early AoA were recognized faster than later acquired faces, though the effect was only reliable for famous male faces, and for whole faces and internal features rather than for external features. In Experiment 2, gender decisions were made more rapidly to whole faces than to internal or external features. Classification was faster to famous than to unfamiliar faces when the faces were presented as internal features or external features, but not when they were presented as whole faces. More gender classification errors were made to famous than to un familiar male faces, but there was no effect of familiarity on the accuracy of responses to female faces. AoA had no effect on gender classification of whole faces or external features. Classification from internal features was faster for early than for late acquired male faces, but faster for late than for early female faces. In the light of the anomalous results for female faces, responses to male faces were analysed separately. The results for the male faces form the focus of the discussion (AU)

Mechanisms of identity and gender decisions to faces: who rocked in 1986?

Two experiments are reported in which participants made familiarity decisions (Is this face familiar or not?) or gender decisions (Is this face male or female?) to the same sets of faces presented as whole faces or as internal features only. The experimental items on which the analysis was performed were famous and unfamiliar male faces that differed on rated masculinity. The famous faces also differed on age of acquisition (AoA). The experimental male faces were combined with an equal number of famous and unfamiliar female faces for presentation to participants. In experiment 1 we found faster and more accurate familiarity decisions to whole male faces than to internal features; also an interaction between AoA and masculinity such that familiarity decisions were both faster and more accurate to high- than to low-masculinity faces when those faces were late-acquired, but not when they were early-acquired. In experiment 2 we found the same benefit for whole faces over internal features and the same interaction between AoA and masculinity in gender decisions. The similarity between the effects of AoA and masculinity in familiarity and gender decisions is more readily accounted for by models of face processing which posit a close relationship between gender and identity processing than by models which maintain that those aspects of face perception are dealt with by quite separate processing streams. We propose that gender decisions, like familiarity decisions, are semantic judgments (rather than judgments based on the analysis of the surface features of faces), and that the shared basis of the two forms of decision explains why they show similar influences of AoA and masculinity.