30 research outputs found

    A biochemical and genetic discovery pipeline identifies PLCδ4b as a non-receptor activator of heterotrimeric G proteins

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    Recent evidence has revealed that heterotrimeric G proteins can be activated by cytoplasmic proteins that share an evolutionarily conserved sequence called the Gα-binding-and-activating (GBA) motif. This mechanism alternative to canonical activation by GPCRs plays important roles in cell function and its dysregulation is linked to disease such as cancer. Here we describe a discovery pipeline that uses biochemical and genetic approaches to validate GBA candidates identified by sequence similarity. First, putative GBA motifs discovered in bioinformatics searches were synthesized on peptide arrays and probed in batch for Gαi3 binding. Then, cDNAs encoding proteins with Gαi3-binding sequences were expressed in a genetically-modified yeast strain that reports mammalian G protein activity in the absence of GPCRs. The resulting GBA motif candidates were characterized by comparison of their biochemical, structural, and signaling properties with those of all previously described GBA motifs in mammals (GIV/Girdin, DAPLE, Calnuc, and NUCB2). We found that the phospholipase C δ4 (PLCδ4) GBA motif binds G proteins with high affinity, has guanine-nucleotide exchange factor activity in vitro, and activates G-protein signaling in cells, as indicated by bioluminescence resonance energy transfer (BRET)-based biosensors of G-protein activity. Interestingly, the PLCδ4 isoform b, which lacks the domains required for PLC activity, bound and activated G proteins more efficiently than the full-length isoform a, suggesting that PLCδ4b functions as a G-protein regulator rather than as a PLC. In summary, we have identified PLCδ4 as a non-receptor activator of G proteins, and established an experimental pipeline to discover and characterize GBA motif-containing proteins

    Working with offenders and those with problem behaviours: a primer

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    The presentation will equip participants with information pertaining to their work with clients with offence histories and/or problem behaviours. Problem behaviours are defined as those activities in which people engage that might result in offending behaviour (e.g., arson, problem gambling, threats, stalking, sexual offending, aggression and violence). The underpinning ethical principles for dealing with such clients will be reviewed. Information will be provided regarding some foundation issues relevant to this population: demographic factors, lifestyle factors, mental health features, substance misuse, and education. A framework will be presented that allows for an understanding of why [most] people offend: The General Personality and Social Psychological Perspective on Criminal Conduct. Flowing from the framework, the Risk Need Responsivity model will be used to help differentiate forensic counselling work from more general counselling and the roles will be explained based on the type of work in which the counsellor is employed to engage. The presentation will conclude with information about dealing with clients who exhibit challenging behaviour for the counsellor. The presentation will include brief case studies to help illustrate the points being made and time will be allocated for questions and discussion

    Validity of assessing people experiencing mental illness who have offended using the camberwell assessment of need-forensic and health of the nation outcome scales-secure

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    Evidence-based practices for forensic mental health services have been slow to develop, and there is a lack of measures that assess the mental health and criminogenic needs of people experiencing mental illness who have offended. The present study aimed to investigate the interrelationship between a clinician-rated forensic mental health needs assessment (health of the nation outcomes scales-secure (honos-s)), a forensic mental health needs assessment that considers both clinician and patient perspectives (camberwell assessment of need-forensic (canfor)), and measures of general and violent recidivism (level service-case management inventory (ls-cmi) and hcr-20 violence risk assessment scheme (hcr-20)). Needs were assessed for 72 forensic patients aged between 20 and 62 years of age, located in a secure forensic mental health facility. The findings revealed significant positive correlations between the honos-s, canfor, and hcr-20. Only the canfor was positively correlated with the ls-cmi, and uniquely contributed variance to the hcr-20. Patients and nurses differed in the total number of needs and met needs they identified as present. The findings suggest that the collaborative approach of the canfor might be more appropriate for measuring outcomes in the treatment of individuals experiencing mental illness who have offended

    The development of an adolescent measure of EI

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    The purpose of this paper was to evaluate the reliability and validity of a modified adolescent version of the Swinburne University Emotional Intelligence Test (Adolescent SUEIT). Study 1 identified qualitative changes and rewording of items necessary to make the SUEIT more ‘adolescent friendly’. In Study 2 the adolescent modified version of the SUEIT was administered to a larger sample of adolescents (N = 1002) to gather information on internal reliability, and to perform validity testing via exploratory factor analysis. The sub-scale reliability of the Adolescent SUEIT was found to be moderate to high, and a four-factor model was most representative of the adolescent sample. It was also noted that the more basic emotional intelligence (EI) abilities were positively related to age; females reported higher levels of emotional perception; and mean scores for the adolescent sample were below the norm for an adult population. With the amount of EI research with adolescents increasing, it is important to have valid and reliable tests available for research into important social and educational outcomes for adolescents. This initial evidence suggests the Adolescent SUEIT is a reliable and valid tool, and should be used to further understand the role of EI in adolescence, and how EI relates to important life criteria

    'It's not really stalking if you know the person': measuring community attitudes that normalize, justify and minimise stalking

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    It has been hypothesised that attitudes minimising, justifying and normalising stalking exist in the community, influencing whether or not stalking is recognised, and potentially affecting the responses of police and others to whom victims turn for support. This study investigates the nature of these attitudes as measured using the Stalking Related Attitudes Questionnaire (SRAQ). Two hundred and forty-four community members and 280 police officers in Victoria, Australia (total sample 61% male, mean age=43.3, SD = 13.3) completed the SRAQ. Full information factor analysis identified three underlying stalking-related attitudes: "stalking isn't serious", "stalking is romantic" and "victims are to blame". Males endorsed all to a greater extent than females, whereas police and community only differed in that police believed stalking to be more serious. Stronger stereotype endorsement was related to judgements of not guilty in a fictional stalking case. These results indicate that attitudes and beliefs that downplay, excuse and normalise stalking behaviour can be measured, and have some influence on recognition of stalking behaviour

    Gender and Ethnicity in Juvenile Risk Assessment

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    Systematized risk assessment and management in juveniles is still in its infancy, and the bulk of the validation literature focuses on males as they account for a significant proportion of crime. In recent years there has been growing recognition that female arrest rates and convictions are steadily increasing and that there is a need to ensure that risk assessment tools that have been validated with males are appropriate for females, who may have different criminal trajectories. The applicability of violence risk assessment tools for ethnically diverse populations has not been extensively examined, but the limited literature suggests that there may be differences in scores for risk and protective factors across ethnic groups. To address this subject, a review of the literature on the predictive validity of current juvenile risk assessment tools was performed. This summary produced equivocal findings and a requirement for further investigation comprising cohorts with greater diversity

    Are youth violence risk instruments interchangeable? Evaluating instrument convergence in a sample of incarcerated adolescent offenders

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    In light of the growing number of youth violence instruments at a clinician’s disposal, this study sought to investigate the interchangeability of two widely validated adolescent violence risk instruments. The concurrent and incremental validity of the Structured Assessment of Violence Risk in Youth (SAVRY) and the Youth Level of Service/Case Management Inventory (YLS/CMI) were evaluated in a young Australian custodial population. A significant degree of dimensional construct overlap between instruments was discovered. Both measures were similarly found to be moderately predictive of general and violent recidivism. Findings indicate that the instruments are potentially substitutable when used to evaluate future violence in these settings. Clinical implications for risk assessment practice are discussed

    The role of protective factors and the relationship with recidivism for high-risk young people in detention

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    This study sought to ascertain the prevalence of protective factors and association with client risk level and future offending in a sample of 177 Australian youth in detention. The Protective Domain on the Structured Assessment of Violence Risk in Youth (SAVRY) instrument was utilized to identify protective items in the cohort. The mean number of protective factors for the entire sample was low (under two) with higher risk clients averaging less than one current protective item. Although the number of protective factors engendered criminal desistance, this effect did not extend to the highest risk young offenders. Clients who re-offended were significantly less likely to present with five out of the six SAVRY protective items. In addition, pro-social involvement and school engagement had the strongest associations with non re-offense. Clinical implications for client risk management are discussed
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