HPTE-Induced Embryonic Thymocyte Death and Alteration of Differentiation Is Not Rescued by ERα or GPER Inhibition but Is Exacerbated by Concurrent TCR Signaling.

Organochlorine pesticides, such as DDT, methoxychlor, and their metabolites, have been characterized as endocrine disrupting chemicals (EDCs); suggesting that their modes of action involve interaction with or abrogation of endogenous endocrine function. This study examined whether embryonic thymocyte death and alteration of differentiation induced by the primary metabolite of methoxychlor, HPTE, rely upon estrogen receptor binding and concurrent T cell receptor signaling. Estrogen receptor inhibition of ERα or GPER did not rescue embryonic thymocyte death induced by HPTE or the model estrogen diethylstilbestrol (DES). Moreover, adverse effects induced by HPTE or DES were worsened by concurrent TCR and CD2 differentiation signaling, compared with EDC exposure post-signaling. Together, these data suggest that HPTE- and DES-induced adverse effects on embryonic thymocytes do not rely solely on ER alpha or GPER but may require both. These results also provide evidence of a potential collaborative signaling mechanism between TCR and estrogen receptors to mediate adverse effects on embryonic thymocytes, as well as highlight a window of sensitivity that modulates EDC exposure severity.

Toward a cognitive view of trait mindfulness: distinct cognitive skills predict its observing and nonreactivity facets.

Dispositional variations in mindfulness and its facets have garnered considerable recent interest in the clinical and personality literatures. Theoretically, high mindful individuals have been characterized as more attuned to momentary sensations and perceptions and/or better able to execute behavior in a controlled manner, yet data of this relatively cognitive type have not been reported. In addition, perceptual attunement and executive control are distinct skills that may underlie, or at least correlate with, distinct facets of mindfulness. In 3 studies involving college students (N = 297), support for the latter idea was found. Individuals high in the observing (but not nonreactivity) facet of mindfulness demonstrated superior perceptual abilities in visual working memory (Study 1) and temporal order (Study 2) tasks. On the other hand, individuals high in the nonreactivity (but not observing) facet of mindfulness exhibited greater cognitive control flexibility (Study 3). Implications for understanding the cognitive basis of mindfulness facets are discussed.

The big chill: interpersonal coldness and emotion-labeling skills.

Interpersonally cold (relative to warm) individuals may be less skilled in inferring the emotional states of others, a factor that should contribute to their poorer social relationships. Systematic support for this hypothesis was obtained in 4 studies (total N = 434 undergraduates) involving diverse emotion- and affect-decoding tasks. Specifically, relatively cold individuals exhibited lower accuracy in decoding emotional facial expressions (Study 1), in labeling the emotions of others from audio and video clips (Study 2), in predicting the emotions of others from social scenario descriptions (Study 3), and in the normative accuracy of their word evaluations (Study 4). Altogether, the results demonstrate that cold individuals appear broadly deficient in linking emotion and affect to relevant environmental stimuli. Implications of the findings for understanding the nature and correlates of interpersonal coldness are discussed.

Counting to ten milliseconds: low-anger, but not high-anger, individuals pause following negative evaluations.

Low-anger individuals are less reactive, both emotionally and behaviourally, to a large variety of situational primes to anger and aggression. Why this is so, from an affective processing perspective, has been largely conjectural. Four studies (total N=270) sought to link individual differences in anger to tendencies exhibited in basic affective processing tasks. On the basis of motivational factors and considerations, it was hypothesised that negative evaluations would differentially activate a psychological alarm system at low levels of anger, resulting in a pause that should be evident in the speed of making subsequent evaluations. Just such a pattern was evident in all studies. By contrast, high-anger individuals did not pause following their negative evaluations. In relation to this affective processing tendency, at least, dramatically different effects were observed among low- versus high-anger individuals. Implications for the personality-processing literature, theories of trait anger, and fast-acting regulatory processes are discussed.

Neuroticism and responsiveness to error feedback: adaptive self-regulation versus affective reactivity.

Responsiveness to negative feedback has been seen as functional by those who emphasize the value of reflecting on such feedback in self-regulating problematic behaviors. On the other hand, the very same responsiveness has been viewed as dysfunctional by its link to punishment sensitivity and reactivity. The present 4 studies, involving 203 undergraduate participants, sought to reconcile such discrepant views in the context of the trait of neuroticism. In cognitive tasks, individuals were given error feedback when they made mistakes. It was found that greater tendencies to slow down following error feedback were associated with higher levels of accuracy at low levels of neuroticism but lower levels of accuracy at high levels of neuroticism. Individual differences in neuroticism thus appear crucial in understanding whether behavioral alterations following negative feedback reflect proactive versus reactive mechanisms and processes. Implications for understanding the processing basis of neuroticism and adaptive self-regulation are discussed.

Neuroticism and Affective Priming: Evidence for a Neuroticism-Linked Negative Schema.

Neuroticism has been hypothesized to systematically relate to semantic memory networks favoring negative affect, but no studies using affective priming tasks have established this link. The present two studies, involving 145 undergraduate participants, sought to provide initial evidence along these lines. Study 1 used a task in which participants were asked to judge their emotions in the past, whereas Study 2 used a perceptual identification task in which participants merely had to identify the word in question. In both studies, neuroticism was positively correlated with negative affective priming, but not positive affective priming. The studies suggest that neuroticism systematically relates to the inter-connectivity of negative affect with semantic memory systems, whether involving the self-concept (Study 1) or not (Study 2). These results are novel and important in understanding individual differences in neuroticism and their affective processing correlates.

When the going gets tough, the differentiated keep going: cybernetic self-determination, daily obstacles, and persistent goal pursuit.

Cybernetic theories of self-regulation contend that an individual's goal system may work best to the extent it is differentiated. The present investigation pioneered an assessment of goal differentiation in relation to an important feature of goals--intrinsic motivation--and quantified the extent to which intrinsic motivation systematically increased from low- to mid- to high-level goals, the resulting individual difference termed cybernetic self-determination. In Study 1 (n = 106), it was found that frustrating daily events precipitated motivations to quit at low, but not high, levels of cybernetic self-determination. In Study 2 (n = 111), it was found that negative feedback was associated with reduced goal persistence at low, but not high, levels of cybernetic self-determination. The findings therefore converge on the idea that individual differences in cybernetic self-determination are consequential in buffering reactions to obstacles in daily life. Implications for personality, motivation, and self-regulation literatures are discussed.

Modulation of P2X4/P2X7/Pannexin-1 sensitivity to extracellular ATP via Ivermectin induces a non-apoptotic and inflammatory form of cancer cell death.

Overexpression of P2X7 receptors correlates with tumor growth and metastasis. Yet, release of ATP is associated with immunogenic cancer cell death as well as inflammatory responses caused by necrotic cell death at sites of trauma or ischemia-reperfusion injury. Using an FDA-approved anti-parasitic agent Ivermectin as a prototype agent to allosterically modulate P2X4 receptors, we can switch the balance between the dual pro-survival and cytotoxic functions of purinergic signaling in breast cancer cells. This is mediated through augmented opening of the P2X4/P2X7-gated Pannexin-1 channels that drives a mixed apoptotic and necrotic mode of cell death associated with activation of caspase-1 and is consistent with pyroptosis. We show that cancer cell death is dependent on ATP release and death signals downstream of P2X7 receptors that can be reversed by inhibition of NADPH oxidases-generated ROS, Ca(2+)/Calmodulin-dependent protein kinase II (CaMKII) or mitochondrial permeability transition pore (MPTP). Ivermectin induces autophagy and release of ATP and HMGB1, key mediators of inflammation. Potentiated P2X4/P2X7 signaling can be further linked to the ATP rich tumor microenvironment providing a mechanistic explanation for the tumor selectivity of purinergic receptors modulation and its potential to be used as a platform for integrated cancer immunotherapy.

Responsiveness to the Negative Affect System as a Function of Emotion Perception: Relations Between Affect and Sociability in Three Daily Diary Studies.

Perceiving emotions clearly and accurately is an important component of emotional intelligence (EI). This skill is thought to predict emotional and social outcomes, but evidence for this point appears somewhat underwhelming in cross-sectional designs. The present work adopted a more contextual approach to understanding the correlates of emotion perception. Because emotion perception involves awareness of affect as it occurs, people higher in this skill might reasonably be expected to be more attuned to variations in their affective states and be responsive to them for this reason. This novel hypothesis was pursued in three daily diary studies (total N = 247), which found systematic evidence for the idea that higher levels of daily negative affect predicted lesser sociability particularly, and somewhat exclusively, among people whose emotion perception skills were high rather than low. The results support a contextual understanding of individual differences in emotion perception and how they operate.

Neuroticism as distancing: perceptual sources of evidence.

Several theories and self-reported sources of data link individual differences in negative affectivity to avoidance motivation. Chronic avoidance motivation, through repeated practice, may result in a relatively cognitive distance-enhancing dynamic whereby events and stimuli are perceived as further away from the self, even when they are not threatening. Such predictions are novel but follow from cybernetic theories of self-regulation. In 5 studies (total N = 463), relations of this type were investigated. Study 1 presented participants with phrases that were ambiguous and found that trait negative affect predicted phrase interpretation in a distance-enhancing temporal direction. Study 2 replicated this effect across a systematic manipulation of event valence. Study 3 asked individuals to estimate the size of words and found that individuals higher in neuroticism generally perceived words to be smaller than did individuals lower in neuroticism. In Study 4, people high (but not low) in neuroticism perceived words to be shrinking faster than they were growing. In Study 5, greater perceptual distancing, in a font size estimation task, predicted more adverse reactions to negative events in daily life. Although normative effects varied across studies, consistent support for a chronic distancing perspective of individual differences in negative affectivity was found.

Sweet taste preferences and experiences predict prosocial inferences, personalities, and behaviors.

It is striking that prosocial people are considered "sweet" (e.g., "she's a sweetie") because they are unlikely to differentially taste this way. These metaphors aid communication, but theories of conceptual metaphor and embodiment led us to hypothesize that they can be used to derive novel insights about personality processes. Five studies converged on this idea. Study 1 revealed that people believed strangers who liked sweet foods (e.g., candy) were also higher in agreeableness. Studies 2 and 3 showed that individual differences in the preference for sweet foods predicted prosocial personalities, prosocial intentions, and prosocial behaviors. Studies 4 and 5 used experimental designs and showed that momentarily savoring a sweet food (vs. a nonsweet food or no food) increased participants' self-reports of agreeableness and helping behavior. The results reveal that an embodied metaphor approach provides a complementary but unique perspective to traditional trait views of personality.

The regulatory benefits of high levels of affect perception accuracy: a process analysis of reactions to stressors in daily life.

Individuals attuned to affective signals from the environment may possess an advantage in the emotion-regulation realm. In two studies (total n = 151), individual differences in affective perception accuracy were assessed in an objective, performance-based manner. Subsequently, the same individuals completed daily diary protocols in which daily stressor levels were reported as well as problematic states shown to be stress-reactive in previous studies. In both studies, individual differences in affect perception accuracy interacted with daily stressor levels to predict the problematic outcomes. Daily stressors precipitated problematic reactions--whether depressive feelings (study 1) or somatic symptoms (study 2)--at low levels of affect perception accuracy, but did not do so at high levels of affect perception accuracy. The findings support a regulatory view of such perceptual abilities. Implications for understanding emotion regulation processes, emotional intelligence, and individual differences in reactivity are discussed.

You never think about my feelings: interpersonal dominance as a predictor of emotion decoding accuracy.

Dominance and submission constitute fundamentally different social interaction strategies that may be enacted most effectively to the extent that the emotions of others are relatively ignored (dominance) versus noticed (submission). On the basis of such considerations, we hypothesized a systematic relationship between chronic tendencies toward high versus low levels of interpersonal dominance and emotion decoding accuracy in objective tasks. In two studies (total N = 232), interpersonally dominant individuals exhibited poorer levels of emotion recognition in response to audio and video clips (Study 1) and facial expressions of emotion (Study 2). The results provide a novel perspective on interpersonal dominance, suggest its strategic nature (Study 2), and are discussed in relation to Fiske's (1993) social-cognitive theory of power.

Integrating trait and social-cognitive views of personality: neuroticism, implicit stress priming, and neuroticism-outcome relationships.

The trait perspective of personality emphasizes the broad role of traits in outcome prediction, whereas the social-cognitive perspective emphasizes the importance of if-then intrapsychic associations. Three studies (N = 188) were conducted to reconcile these alternative views of personality in the context of stress-related behaviors. Implicit priming tasks were used to quantify the extent to which stress primes activated thoughts of aggression (Studies 1 and 2) or eating (Study 3), and trait levels of neuroticism were also assessed. Neuroticism did not consistently predict stress-related implicit associations, consistent with the independence of these predictors. Of more importance, such implicit associations predicted problematic outcomes (e.g., physical aggression), but only to the extent that relevant individuals were also high in neuroticism. The results highlight an interface of trait and social-cognitive views of personality and do so in the context of understanding stress-reactivity processes, a topic of importance to multiple literatures.

Extraversion and reward-related processing: probing incentive motivation in affective priming tasks.

Based on an incentive motivation theory of extraversion (Depue & Collins, 1999), it was hypothesized that extraverts (relative to introverts) would exhibit stronger positive priming effects in affective priming tasks, whether involving words or pictures. This hypothesis was systematically supported in four studies involving 229 undergraduates. In each of the four studies, and in a subsequent combined analysis, extraversion was positively predictive of positive affective priming effects, but was not predictive of negative affective priming effects. The results bridge an important gap in the literature between biological and trait models of incentive motivation and do so in a way that should be informative to subsequent efforts to understand the processing basis of extraversion as well as incentive motivation.

Personality dominance and preferential use of the vertical dimension of space: evidence from spatial attention paradigms.

Previous research has shown that dominant individuals frequently think in terms of dominance hierarchies, which typically invoke vertical metaphor (e.g., "upper" vs. "lower" class). Accordingly, we predicted that in spatial attention paradigms, such individuals would systematically favor the vertical dimension of space more than individuals low in dominance. This prediction was supported by two studies (total N= 96), which provided three tests involving two different spatial attention paradigms. In all cases, analyses controlling for speed of response to horizontal spatial probes revealed that more dominant individuals were faster than less dominant individuals to respond to probes along the vertical dimension of space. Such data support the metaphor-representation perspective, according to which people think in metaphoric terms, even in on-line processing tasks. These results have implications for understanding dominance and also indicate that conceptual metaphor is relevant to understanding the cognitive-processing basis of personality.