Roles for CEP170 in cilia function and dynein-2 assembly

Primary cilia are essential eukaryotic organelles required for signalling and secretion. Dynein-2 is a microtubule-motor protein complex and is required for ciliogenesis via its role in facilitating retrograde intraflagellar transport (IFT) from the cilia tip to the cell body. Dynein-2 must be assembled and loaded onto IFT trains for entry into cilia for this process to occur, but how dynein-2 is assembled and how it is recycled back into a cilium remain poorly understood. Here, we identify centrosomal protein of 170 kDa (CEP170) as a dynein-2-interacting protein in mammalian cells. We show that loss of CEP170 perturbs intraflagellar transport and hedgehog signalling, and alters the stability of dynein-2 holoenzyme complex. Together, our data indicate a role for CEP170 in supporting cilia function and dynein-2 assembly

Exposure to violence is not associated with accuracy in forecasting conflict outcomes

Exposure to harsh or unpredictable environments can impair social and cognitive functioning. However, people may also develop enhanced abilities for solving challenges relevant in those environments (‘hidden talents’). In the current study, we explored the associations between people’s ability to accurately forecast conflict outcomes and their past and current experiences with violence. To do so, we used dynamic, real-world videos with known outcomes, rather than static, artificial stimuli (e.g., vignettes) with unknown outcomes, as previous research has done. We conducted a preregistered study in the Netherlands that included a final sample of 127 participants: 63 from a community sample and 64 college students. We found no support for our core hypothesis that people who experienced more violence are more accurate in forecasting conflict outcomes. Thus, we did not find support for hidden talents, contributing to an evidence base that was already mixed and inconclusive. We did find support for our auxiliary hypothesis that college students would wear ‘rose-colored glasses’, underestimating the number of conflicts that would escalate into fights. Contrary to our other two auxiliary hypotheses, the community sample did not overestimate the number of conflicts that would escalate into fights, and people who have experienced more violence were not more likely to predict that conflicts will escalate into fights. These findings have implications for the literature on hostile attribution bias, which shows that people with more exposure to violence more likely interpret the ambiguous actions of others as hostile. Whereas this pattern is often attributed to negativity bias in people with more exposure to violence, it might also reflect rose-colored glasses on people living safer lives

The development of instruments to measure the work disability assessment behaviour of insurance physicians

<p>Abstract</p> <p>Background</p> <p>Variation in assessments is a universal given, and work disability assessments by insurance physicians are no exception. Little is known about the considerations and views of insurance physicians that may partly explain such variation. On the basis of the Attitude - Social norm - self Efficacy (ASE) model, we have developed measurement instruments for assessment behaviour and its determinants.</p> <p>Methods</p> <p>Based on theory and interviews with insurance physicians the questionnaire included blocks of items concerning background variables, intentions, attitudes, social norms, self-efficacy, knowledge, barriers and behaviour of the insurance physicians in relation to work disability assessment issues. The responses of 231 insurance physicians were suitable for further analysis. Factor analysis and reliability analysis were used to form scale variables and homogeneity analysis was used to form dimension variables. Thus, we included 169 of the 177 original items.</p> <p>Results</p> <p>Factor analysis and reliability analysis yielded 29 scales with sufficient reliability. Homogeneity analysis yielded 19 dimensions. Scales and dimensions fitted with the concepts of the ASE model. We slightly modified the ASE model by dividing behaviour into two blocks: behaviour that reflects the assessment process and behaviour that reflects assessment behaviour.</p> <p>The picture that emerged from the descriptive results was of a group of physicians who were motivated in their job and positive about the Dutch social security system in general. However, only half of them had a positive opinion about the Dutch Work and Income (Capacity for Work) Act (WIA). They also reported serious barriers, the most common of which was work pressure. Finally, 73% of the insurance physicians described the majority of their cases as 'difficult'.</p> <p>Conclusions</p> <p>The scales and dimensions developed appear to be valid and offer a promising basis for future research. The results suggest that the underlying ASE model, in modified form, is suitable for describing the assessment behaviour of insurance physicians and the determinants of this behaviour. The next step in this line of research should be to validate the model using structural equation modelling. Finally, the predictive value should be tested in relation to outcome measurements of work disability assessments.</p

A bidentate Polycomb Repressive-Deubiquitinase complex is required for efficient activity on nucleosomes

Attachment of ubiquitin to lysine 119 of Histone 2A (H2AK119Ub) is an epigenetic mark characteristic of repressed developmental genes, which is removed by the Polycomb Repressive-Deubiquitinase (PR-DUB) complex. Here we report the crystal structure of the Drosophila PR-DUB, revealing that the deubiquitinase Calypso and its activating partner ASX form a 2:2 complex. The bidentate Calypso–ASX complex is generated by dimerisation of two activated Calypso proteins through their coiled-coil regions. Disrupting the Calypso dimer interface does not affect inherent catalytic activity, but inhibits removal of H2AK119Ub as a consequence of impaired recruitment to nucleosomes. Mutating the equivalent surface on the human counterpart, BAP1, also compromises activity on nucleosomes. Together, this suggests that high local concentrations drive assembly of bidentate PR-DUB complexes on chromatin—providing a mechanistic basis for enhanced PR-DUB activity at specific genomic foci, and the impact of distinct classes of PR-DUB mutations in tumorigenesis

Human responses to Covid-19: The role of optimism bias, perceived severity, and anxiety

During the Covid-19 pandemic, the governments are trying to contain the spread with non-pharmaceutical interventions (NPIs), such as social distancing rules, restrictions, and lockdowns. In an effort to identify factors that may influence population adherence to NPIs, we examined the role of optimism bias, anxiety, and perceived severity of the situation in relation to engagement in protective behavioral changes and satisfaction with governments' response to this pandemic. We conducted an online survey in 935 participants (Mage = 34.29; 68.88% females) that was disseminated in April and May 2020 in the Netherlands, Germany, Greece, and USA. Individuals with high optimism bias engaged less in behavioral changes, whereas individuals with high levels of anxiety and high perceived severity engaged more in behavioral changes. Individuals with high optimism bias and high levels of anxiety were less satisfied with the governments' response, albeit for different reasons. Individuals who reported low perceived severity and low government satisfaction engaged the least in behavioral changes, whereas participants who reported high perceived severity and low government satisfaction engaged the most in behavioral changes. This study contributes to a better understanding of the psychological factors that influence people's responses to NPIs.</p

Human responses to Covid-19: The role of optimism bias, perceived severity, and anxiety

During the Covid-19 pandemic, the governments are trying to contain the spread with non-pharmaceutical interventions (NPIs), such as social distancing rules, restrictions, and lockdowns. In an effort to identify factors that may influence population adherence to NPIs, we examined the role of optimism bias, anxiety, and perceived severity of the situation in relation to engagement in protective behavioral changes and satisfaction with governments' response to this pandemic. We conducted an online survey in 935 participants (Mage = 34.29; 68.88% females) that was disseminated in April and May 2020 in the Netherlands, Germany, Greece, and USA. Individuals with high optimism bias engaged less in behavioral changes, whereas individuals with high levels of anxiety and high perceived severity engaged more in behavioral changes. Individuals with high optimism bias and high levels of anxiety were less satisfied with the governments' response, albeit for different reasons. Individuals who reported low perceived severity and low government satisfaction engaged the least in behavioral changes, whereas participants who reported high perceived severity and low government satisfaction engaged the most in behavioral changes. This study contributes to a better understanding of the psychological factors that influence people's responses to NPIs.Ethics & Philosophy of Technolog

Roles for CEP170 in cilia function and dynein-2 assembly

Primary cilia are essential eukaryotic organelles required for signalling and secretion. Dynein-2 is a microtubule-motor protein complex and is required for ciliogenesis via its role in facilitating retrograde intraflagellar transport from the cilia tip to the cell body. Dynein-2 must be assembled and loaded onto IFT-trains for entry into cilia for this process to occur but how dynein-2 is assembled and how it is recycled back into a cilium remain poorly understood. Here, we identify Centrosomal Protein of 170 kDa (CEP170) as a dynein-2 interacting protein. We show that loss of CEP170 perturbs intraflagellar transport, Hedgehog signalling, and alters the stability of dynein-2 holoenzyme complex. Together, our data indicate a role for CEP170 in supporting cilia function and dynein-2 assembly.</p