Beyond shared signals: The role of downward gaze in the stereotypical representation of sad facial expressions

According to the influential shared signal hypothesis, perceived gaze direction influences the recognition of emotion from the face, for example, gaze averted sideways facilitates the recognition of sad expressions because both gaze and expression signal avoidance. Importantly, this approach assumes that gaze direction is an independent cue that influences emotion recognition. But could gaze direction also impact emotion recognition because it is part of the stereotypical representation of the expression itself? In Experiment 1, we measured gaze aversion in participants engaged in a facial expression posing task. In Experiment 2, we examined the use of gaze aversion when constructing facial expressions on a computerized avatar. Results from both experiments demonstrated that downward gaze plays a central role in the representation of sad expressions. In Experiment 3, we manipulated gaze direction in perceived facial expressions and found that sadness was the only expression yielding a recognition advantage for downward, but not sideways gaze. Finally, in Experiment 4 we independently manipulated gaze aversion and eyelid closure, thereby demonstrating that downward gaze enhances sadness recognition irrespective of eyelid position. Together, these findings indicate that (1) gaze and expression are not independent cues and (2) the specific type of averted gaze is critical. In consequence, several premises of the shared signal hypothesis may need revision. (PsycINFO Database Record (c) 2019 APA, all rights reserved

Cyclodextrin-mediated Crystallization of Acid β-glucosidase in Complex with Amphiphilic Bicyclic Nojirimycin Analogues

Cyclodextrin-based host-guest chemistry has been exploited to facilitate co-crystallization of recombinant human acid β-glucosidase (β-glucocerebrosidase, GlcCerase) with amphiphilic bicyclic nojirimycin analogues of the sp2-iminosugar type. Attempts to co-crystallize GlcCerase with 5-N,6-O-[N′-(n-octyl)iminomethylidene]nojirimycin (NOI-NJ) or with 5-N,6-S-[N′-(n-octyl)iminomethylidene]-6-thionojirimycin (6S-NOI-NJ), two potent inhibitors of the enzyme with promising pharmacological chaperone activity for several Gaucher disease-associated mutations, were unsuccessful probably due to the formation of aggregates that increase the heterogeneity of the sample and affect nucleation and growth of crystals. Cyclomaltoheptaose (β-cyclodextrin, βCD) efficiently captures NOI-NJ and 6S-NOI-NJ in aqueous media to form inclusion complexes in which the lipophilic tail is accommodated in the hydrophobic cavity of the cyclooligosaccharide. The dissociation constant of the complex of the amphiphilic sp2-iminosugars with βCD is two orders of magnitude higher than that of the corresponding complex with GlcCerase, allowing the efficient transfer of the inhibitor from the βCD cavity to the GlcCerase active site. Enzyme-inhibitor complexes suitable for X-ray analysis were thus grown in the presence of βCD. In contrast to what was previously observed for the complex of GlcCerase with the more basic derivative, 6-amino-6-deoxy-5-N,6-N-[N′-(n-octyl)iminomethylidene]nojirimycin (6N-NOI-NJ), the β-anomers of both NOI-NJ and 6S-NOI-NJ were seen in the active site, even though the α-anomer was exclusively detected both in aqueous solution and in the corresponding βCD:sp2-iminosugar complexes. Our results further suggest that cyclodextrin derivatives might serve as suitable delivery systems of amphiphilic glycosidase inhibitors in a biomedical context.Ministerio de Ciencia e Innovación CTQ2007-61180/PPQ, SAF2010-15670, CTQ2010-15848Junta de Andalucía P08-FQM-03711Fondo Europeo de Desarrollo Regional 03122, ISSG-CT-2007-03719

Context Modulation of Facial Emotion Perception Differed by Individual Difference

Background: Certain facial configurations are believed to be associated with distinct affective meanings (i.e. basic facial expressions), and such associations are common across cultures (i.e. universality of facial expressions). However, recently, many studies suggest that various types of contextual information, rather than facial configuration itself, are important factor for facial emotion perception. Methodology/Principal Findings: To examine systematically how contextual information influences individuals ’ facial emotion perception, the present study estimated direct observers ’ perceptual thresholds for detecting negative facial expressions via a forced-choice psychophysical procedure using faces embedded in various emotional contexts. We additionally measured the individual differences in affective information-processing tendency (BIS/BAS) as a possible factor that may determine the extent to which contextual information on facial emotion perception is used. It was found that contextual information influenced observers ’ perceptual thresholds for facial emotion. Importantly, individuals ’ affectiveinformation tendencies modulated the extent to which they incorporated context information into their facial emotion perceptions. Conclusions/Significance: The findings of this study suggest that facial emotion perception not only depends on facial configuration, but the context in which the face appears as well. This contextual influence appeared differently wit

Social context influences recognition of bodily expressions

Previous studies have shown that recognition of facial expressions is influenced by the affective information provided by the surrounding scene. The goal of this study was to investigate whether similar effects could be obtained for bodily expressions. Images of emotional body postures were briefly presented as part of social scenes showing either neutral or emotional group actions. In Experiment 1, fearful and happy bodies were presented in fearful, happy, neutral and scrambled contexts. In Experiment 2, we compared happy with angry body expressions. In Experiment 3 and 4, we blurred the facial expressions of all people in the scene. This way, we were able to ascribe possible scene effects to the presence of body expressions visible in the scene and we were able to measure the contribution of facial expressions to the body expression recognition. In all experiments, we observed an effect of social scene context. Bodily expressions were better recognized when the actions in the scenes expressed an emotion congruent with the bodily expression of the target figure. The specific influence of facial expressions in the scene was dependent on the emotional expression but did not necessarily increase the congruency effect. Taken together, the results show that the social context influences our recognition of a person’s bodily expression

Characterization of gene-activated human acid-β-glucosidase: Crystal structure, glycan composition, and internalization into macrophages

Gaucher disease, the most common lysosomal storage disease, can be treated with enzyme replacement therapy (ERT), in which defective acid-β-glucosidase (GlcCerase) is supplemented by a recombinant, active enzyme. The X-ray structures of recombinant GlcCerase produced in Chinese hamster ovary cells (imiglucerase, Cerezyme®) and in transgenic carrot cells (prGCD) have been previously solved. We now describe the structure and characteristics of a novel form of GlcCerase under investigation for the treatment of Gaucher disease, Gene-ActivatedTM human GlcCerase (velaglucerase alfa). In contrast to imiglucerase and prGCD, velaglucerase alfa contains the native human enzyme sequence. All three GlcCerases consist of three domains, with the active site located in domain III. The distances between the carboxylic oxygens of the catalytic residues, E340 and E235, are consistent with distances proposed for acid–base hydrolysis. Kinetic parameters (Km and Vmax) of velaglucerase alfa and imiglucerase, as well as their specific activities, are similar. However, analysis of glycosylation patterns shows that velaglucerase alfa displays distinctly different structures from imiglucerase and prGCD. The predominant glycan on velaglucerase alfa is a high-mannose type, with nine mannose units, while imiglucerase contains a chitobiose tri-mannosyl core glycan with fucosylation. These differences in glycosylation affect cellular internalization; the rate of velaglucerase alfa internalization into human macrophages is at least 2-fold greater than that of imiglucerase

Darwin's Duchenne: Eye constriction during infant joy and distress

Darwin proposed that smiles with eye constriction (Duchenne smiles) index strong positive emotion in infants, while cry-faces with eye constriction index strong negative emotion. Research has supported Darwin's proposal with respect to smiling, but there has been little parallel research on cry-faces (open-mouth expressions with lateral lip stretching). To investigate the possibility that eye constriction indexes the affective intensity of positive and negative emotions, we first conducted the Face-to-Face/Still-Face (FFSF) procedure at 6 months. In the FFSF, three minutes of naturalistic infant-parent play interaction (which elicits more smiles than cry-faces) are followed by two minutes in which the parent holds an unresponsive still-face (which elicits more cry-faces than smiles). Consistent with Darwin's proposal, eye constriction was associated with stronger smiling and with stronger cry-faces. In addition, the proportion of smiles with eye constriction was higher during the positive-emotion eliciting play episode than during the still-face. In parallel, the proportion of cry-faces with eye constriction was higher during the negative-emotion eliciting still-face than during play. These results are consonant with the hypothesis that eye constriction indexes the affective intensity of both positive and negative facial configurations. A preponderance of eye constriction during cry-faces was observed in a second elicitor of intense negative emotion, vaccination injections, at both 6 and 12 months of age. The results support the existence of a Duchenne distress expression that parallels the more well-known Duchenne smile. This suggests that eye constriction-the Duchenne marker-has a systematic association with early facial expressions of intense negative and positive emotion. © 2013 Mattson et al

DNA methylation landscapes of 1538 breast cancers reveal a replication-linked clock, epigenomic instability and cis-regulation.

DNA methylation is aberrant in cancer, but the dynamics, regulatory role and clinical implications of such epigenetic changes are still poorly understood. Here, reduced representation bisulfite sequencing (RRBS) profiles of 1538 breast tumors and 244 normal breast tissues from the METABRIC cohort are reported, facilitating detailed analysis of DNA methylation within a rich context of genomic, transcriptional, and clinical data. Tumor methylation from immune and stromal signatures are deconvoluted leading to the discovery of a tumor replication-linked clock with genome-wide methylation loss in non-CpG island sites. Unexpectedly, methylation in most tumor CpG islands follows two replication-independent processes of gain (MG) or loss (ML) that we term epigenomic instability. Epigenomic instability is correlated with tumor grade and stage, TP53 mutations and poorer prognosis. After controlling for these global trans-acting trends, as well as for X-linked dosage compensation effects, cis-specific methylation and expression correlations are uncovered at hundreds of promoters and over a thousand distal elements. Some of these targeted known tumor suppressors and oncogenes. In conclusion, this study demonstrates that global epigenetic instability can erode cancer methylomes and expose them to localized methylation aberrations in-cis resulting in transcriptional changes seen in tumors