Is the histidine triad nucleotide-binding protein 1 (HINT1) gene a candidate for schizophrenia?

Background: The histidine triad nucleotide-binding protein 1, HINT1, hydrolyzes adenosine 5'monophosphoramidate substrates such as AMP-morpholidate. The human HINT1 gene is located on chromosome 5q31.2, a region implicated in linkage studies of schizophrenia. HINT1 had been shown to have different expression in postmortem brains between schizophrenia patients and unaffected controls. It was also found to be associated with the dysregulation of postsynaptic dopamine transmission, thus suggesting a potential role in several neuropsychiatric diseases.

AKT1 Is Associated with Schizophrenia Across Multiple Symptom Dimensions in the Irish Study of High Density Schizophrenia Families

Background: The phosphatidylinositol 3-kinase (PI3K)-AKT signal transduction pathway is critical to cell growth and survival. In vitro functional studies indicate that the candidate schizophrenia susceptibility gene DTNBP1 influences AKT signaling to promote neuronal viability. The AKT1 gene has also been implicated in schizophrenia by association studies and decreased protein expression in the brains of schizophrenic patients. 
 Methods: The association of DTNBP1 in the Irish Study of High Density Schizophrenia Families (ISHDSF) prompted our investigation of AKT1 for association with disease in this sample. Eight single nucleotide polymorphisms spanning AKT1 were analyzed for association with schizophrenia across four definitions of affection and according to Operational Criteria Checklist of Psychotic Illness (OPCRIT) symptom scales. We examined expression of AKT1 messenger RNA from postmortem brain tissue of schizophrenic, bipolar, and control individuals. 
 Results: No single marker showed significant association, but the risk haplotype previously found over-transmitted to Caucasian schizophrenic patients was significantly under-transmitted in the ISHDSF (.01 < p < .05), across all OPCRIT symptom dimensions. Exploratory haplotype analysis confirmed association with schizophrenia toward the 5’ end of AKT1 (.008 < p < .049, uncorrected). We found significantly decreased RNA levels in prefrontal cortex of schizophrenic individuals, consistent with reduced AKT1 protein levels reported in schizophrenic brain. 
 Conclusions: The replication of association of AKT1 gene variants in a further Caucasian family sample adds support for involvement of AKT signaling in schizophrenia, perhaps encompassing a broader clinical phenotype that includes mood dysregulation. We show that AKT signaling might be compromised in schizophrenic and bipolar patients via reduced RNA expression of specific AKT isoforms.

Genome-wide association study identifies five new schizophrenia loci

We examined the role of common genetic variation in schizophrenia in a genome-wide association study of substantial size: a stage 1 discovery sample of 21,856 individuals of European ancestry and a stage 2 replication sample of 29,839 independent subjects. The combined stage 1 and 2 analysis yielded genome-wide significant associations with schizophrenia for seven loci, five of which are new (1p21.3, 2q32.3, 8p23.2, 8q21.3 and 10q24.32-q24.33) and two of which have been previously implicated (6p21.32-p22.1 and 18q21.2). The strongest new finding (P = 1.6 x 10(-11)) was with rs1625579 within an intron of a putative primary transcript for MIR137 (microRNA 137), a known regulator of neuronal development. Four other schizophrenia loci achieving genome-wide significance contain predicted targets of MIR137, suggesting MIR137-mediated dysregulation as a previously unknown etiologic mechanism in schizophrenia. In a joint analysis with a bipolar disorder sample (16,374 affected individuals and 14,044 controls), three loci reached genome-wide significance: CACNA1C (rs4765905, P = 7.0 x 10(-9)), ANK3 (rs10994359, P = 2.5 x 10(-8)) and the ITIH3-ITIH4 region (rs2239547, P = 7.8 x 10(-9)).

The good our field can hope to do, the harm it should avoid

This paper tries to achieve a balanced view of the ethical issues raised by emotion-oriented technology as it is, rather than as it might be imagined. A high proportion of applications seem ethically neutral. Uses in entertainment and allied areas do no great harm or good. Empowering professions may do either, but regulatory systems already exist. Ethically positive aspirations involve mitigating problems that already exist by supporting humans in emotion-related judgments, by replacing technology that treats people in dehumanized and/or demeaning ways, and by improving access for groups who struggle with existing interfaces. Emotion-oriented computing may also contribute to revaluing human faculties other than pure intellect. Many potential negatives apply to technology as a whole. Concerns specifically related to emotion involve creating a lie, by simulate emotions that the systems do not have, or promoting mechanistic conceptions of emotion. Intermediate issues arise where more general problems could be exacerbated-helping systems to sway human choices or encouraging humans to choose virtual worlds rather than reality. "SIIF" systems (semi-intelligent information filters) are particularly problematic. These use simplified rules to make judgments about people that are complex, and have potentially serious consequences. The picture is one of balances to recognize and negotiate, not uniform good or evil. © 2010-2012 IEEE.

Cross-Cultural Patterns in Dynamic Ratings of Positive and Negative Natural Emotional Behaviour

Background: Studies of cross-cultural variations in the perception of emotion have typically compared rates of recognition of static posed stimulus photographs. That research has provided evidence for universality in the recognition of a range of emotions but also for some systematic cross-cultural variation in the interpretation of emotional expression. However, questions remain about how widely such findings can be generalised to real life emotional situations. The present study provides the first evidence that the previously reported interplay between universal and cultural influences extends to ratings of natural, dynamic emotional stimuli.

Methodology/Principal Findings: Participants from Northern Ireland, Serbia, Guatemala and Peru used a computer based tool to continuously rate the strength of positive and negative emotion being displayed in twelve short video sequences by people from the United Kingdom engaged in emotional conversations. Generalized additive mixed models were developed to assess the differences in perception of emotion between countries and sexes. Our results indicate that the temporal pattern of ratings is similar across cultures for a range of emotions and social contexts. However, there are systematic differences in intensity ratings between the countries, with participants from Northern Ireland making the most extreme ratings in the majority of the clips.

Conclusions/Significance: The results indicate that there is strong agreement across cultures in the valence and patterns of ratings of natural emotional situations but that participants from different cultures show systematic variation in the intensity with which they rate emotion. Results are discussed in terms of both ‘in-group advantage’ and ‘display rules’ approaches. This study indicates that examples of natural spontaneous emotional behaviour can be used to study cross-cultural variations in the perception of emotion.

Evidence for Alteration of EZH2, BMI1, and KDM6A and Epigenetic Reprogramming in Human Papillomavirus Type 16 E6/E7-Expressing Keratinocytes

A number of epigenetic alterations occur in both the virus and host cellular genomes during human papillomavirus (HPV)-associated carcinogenesis, and investigations of such alterations, including changes in chromatin proteins and histone modifications, have the potential to lead to therapeutic epigenetic reversion. We report here that transformed HPV16 E6/E7-expressing primary human foreskin keratinocytes (HFKs) (E6/E7 cells) demonstrate increased expression of the PRC2 methyltransferase EZH2 at both the mRNA and protein levels but do not exhibit the expected increase in trimethylated H3K27 (H3K27me3) compared to normal keratinocytes. In contrast, these cells show a reduction in global H3K27me3 levels in vitro, as well as upregulation of the KDM6A demethylase. We further show for the first time that transformation with the HPV16 E6 and E7 oncogenes also results in an increase in phosphorylated EZH2 serine 21 (P-EZH2-Ser21), mediated by active Akt, and in a downregulation of the PRC1 protein BMI1 in these cells. High-grade squamous cervical intraepithelial lesions also showed a loss of H3K27me3 in the presence of increased expression of EZH2. Correlating with the loss of H3K27me3, E6/E7 cells exhibited derepression of specific EZH2-, KMD6A-, and BMI1-targeted HOX genes. These results suggest that the observed reduction in H3K27me3 may be due to a combination of reduced activities/levels of specific polycomb proteins and increases in demethylases. The dysregulation of multiple chromatin proteins resulting in the loss of global H3K27me3 and the transcriptional reprogramming in HPV16 E6/E7-infected cells could provide an epigenetic signature associated with risk and/or progression of HPV16-associated cancers, as well as the potential for epigenetic reversion in the future.

Tracking the Links to Social Functioning: Asperger Syndrome and Gaze Patterns

The application of Eye Tracking (ET) to the study of social functioning in Asperger Syndrome (AS) provides a unique perspective into social attention and cognition in this atypical neurodevelopmental group. Research in this area has shown how ET can capture social attention atypicalities within this group, such as diminished fixations to the eye region when viewing still images and movie clips; increased fixation to the mouth region; reduced face gaze. Issues exist, however, within the literature, where the type (static/dynamic) and the content (ecological validity) of stimuli used appear to affect the nature of the gaze patterns reported. Objectives: Our research aims were: using the same group of adolescents with AS, to compare their viewing patterns to age and IQ matched typically developing (TD) adolescents using stimuli considered to represent a hierarchy of ecological validity, building from static facial images; through a non-verbal movie clip; through verbal footage from real-life conversation; to eye tracking during real-life conversation. Methods: Eleven participants with AS were compared to 11 TD adolescents, matched for age and IQ. In Study 1, participants were shown 2 sets of static facial images (emotion faces, still images taken from the dynamic clips). In Study 2, three dynamic clips were presented (1 non-verbal movie clip, 2 verbal footage from real-life conversation). Study 3 was an exploratory study of eye tracking during a real-life conversation. Eye movements were recorded via a HiSpeeed (240Hz) SMI eye tracker fitted with chin and forehead rests. Various methods of analysis were used, including a paradigm for temporal analysis of the eye movement data. Results: Results from these studies confirmed that the atypical nature of social attention in AS was successfully captured by this paradigm. While results differed across stimulus sets,
collectively they demonstrated how individuals with AS failed to focus on the most socially relevant aspects of the various stimuli presented. There was also evidence that the eye movements of the AS group were atypically affected by the presence of motion and verbal information. Discriminant Function Analysis demonstrated that the ecological validity of stimuli was an important factor in identifying atypicalities associated with AS, with more accurate classifications of AS and TD groups occurring for more naturalistic stimuli (dynamic rather than static). Graphical analysis of temporal sequences of eye movements revealed the atypical manner in which AS participants followed interactions within the dynamic stimuli. Taken together with data on the order of gaze patterns, more subtle atypicalities were detected in the gaze behaviour of AS individuals towards more socially pertinent regions of the dynamic stimuli. Conclusions: These results have potentially important implications for our understanding of deficits in Asperger Syndrome, as they show that, with more naturalistic stimuli, subtle differences in social attention can be detected that