Light and circadian regulation of clock components aids flexible responses to environmental signals

The circadian clock measures time across a 24h period, increasing fitness by phasing biological processes to the most appropriate time of day. The interlocking feedback loop mechanism of the clock is conserved across species; however, the number of loops varies. Mathematical and computational analyses have suggested that loop complexity affects the overall flexibility of the oscillator, including its responses to entrainment signals. We used a discriminating experimental assay, at the transition between different photoperiods, in order to test this proposal in a minimal circadian network (in Ostreococcus tauri) and a more complex network (in Arabidopsis thaliana). Transcriptional and translational reporters in O.tauri primarily tracked dawn or dusk, whereas in A.thaliana, a wider range of responses were observed, consistent with its more flexible clock. Model analysis supported the requirement for this diversity of responses among the components of the more complex network. However, these and earlier data showed that the O.tauri network retains surprising flexibility, despite its simple circuit. We found that models constructed from experimental data can show flexibility either from multiple loops and/or from multiple light inputs. Our results suggest that O.tauri has adopted the latter strategy, possibly as a consequence of genomic reduction

Work in Progress: A meta-literature review of Moral Foundations Theory as applied in game studies

This paper outlines an in-progress systematic review of extant research in game studies that has incorporated Moral Foundations Theory (MFT), or relevant extensions of that theory to media entertainment, such as the Moral Intuition and Media Entertainment/Model of Intuitive Morality and Exemplars (MIME). Due to the interdisciplinary nature of these theoretical perspectives as well as game studies broadly, systematic review is critical to helping us collectively understand and collate the research in this area. The systematic review is done in two parts, one as a deep description of the characteristics of included studies, and one as a statistical analysis (as well as a qualitative assessment) of the quality of those included studies. At this stage, an initial set of 24-26 articles focused on gaming and MFT/MIME have been uncovered via systematic database searching, and both study characteristic and study quality coding sheets in progress (shared, within)

Cannabinoid CB1 receptor inhibition blunts adolescent-typical increased binge alcohol and sucrose consumption in male C57BL/6J mice

Increased binge alcohol consumption has been reported among adolescents as compared to adults in both humans and rodent models, and has been associated with serious long-term health consequences. However, the neurochemical mechanism for age differences in binge drinking between adolescents and adults has not been established. The present study was designed to evaluate the mechanistic role of the cannabinoid CB1 receptor in adolescent and adult binge drinking. Binge consumption was established in adolescent and adult male C57BL/6J mice by providing access to 20% alcohol or 1% sucrose for 4h every other day. Pretreatment with the CB1 antagonist/inverse agonist AM-251 (0, 1, 3, and 10mg/kg) in a Latin square design dose-dependently reduced adolescent alcohol consumption to adult levels without altering adult intake. AM-251 (3mg/kg) also reduced adolescent but not adult sucrose consumption. Adolescent reductions in alcohol and sucrose were not associated with alterations in open-field locomotor activity or thigmotaxis. These findings point to age differences in CB1 receptor activity as a functional mediator of adolescent-typical increased binge drinking as compared to adults. Developmental alterations in endocannabinoid signaling in the adolescent brain may therefore be responsible for the drinking phenotype seen in this age group

Light and circadian regulation of clock components aids flexible responses to environmental signals

PublishedJournal ArticleResearch Support, Non-U.S. Gov'tThe circadian clock measures time across a 24 h period, increasing fitness by phasing biological processes to the most appropriate time of day. The interlocking feedback loop mechanism of the clock is conserved across species; however, the number of loops varies. Mathematical and computational analyses have suggested that loop complexity affects the overall flexibility of the oscillator, including its responses to entrainment signals. We used a discriminating experimental assay, at the transition between different photoperiods, in order to test this proposal in a minimal circadian network (in Ostreococcus tauri) and a more complex network (in Arabidopsis thaliana). Transcriptional and translational reporters in O. tauri primarily tracked dawn or dusk, whereas in A. thaliana, a wider range of responses were observed, consistent with its more flexible clock. Model analysis supported the requirement for this diversity of responses among the components of the more complex network. However, these and earlier data showed that the O. tauri network retains surprising flexibility, despite its simple circuit. We found that models constructed from experimental data can show flexibility either from multiple loops and/or from multiple light inputs. Our results suggest that O. tauri has adopted the latter strategy, possibly as a consequence of genomic reduction.This research was supported by EU FP7 collaborative project TiMet (award 245143), BBSRC and EPSRC awards BB/F005237/1, BB/D019621/1 and BB/J009423 (to A.J.M. and others) and EPSRC award EP/I017445/1 (to O.E.A. and others). C.T.'s work was supported by the Human Frontiers Science Program and the Swedish Research Council (award 2010-5219)

Adolescent C57BL/6J Mice Show Elevated Alcohol Intake, but Reduced Taste Aversion, as Compared to Adult Mice: A Potential Behavioral Mechanism for Binge Drinking: ELEVATED ALCOHOL INTAKE IN ADOLESCENCE

Binge alcohol drinking during adolescence is a serious health problem which may increase future risk of an alcohol use disorder. Although there are several different procedures by which to preclinically model binge-like alcohol intake, limited-access procedures offer the advantage of achieving high voluntary alcohol intake and pharmacologically relevant blood alcohol concentrations (BACs). Therefore, in the current study, developmental differences in binge-like alcohol drinking using a limited-access cycling procedure were examined. In addition, as alcohol drinking has been negatively correlated with sensitivity to the aversive properties of alcohol, we examined developmental differences in sensitivity to an alcohol-induced conditioned taste aversion (CTA)

CaMKII α -GluA1 Activity Underlies Vulnerability to Adolescent Binge Alcohol Drinking

Binge drinking during adolescence is associated with increased risk for developing alcohol use disorders (AUDs); however, the neural mechanisms underlying this liability are unclear. In this study, we sought to determine if binge-drinking alters expression or phosphorylation of two molecular mechanisms of neuroplasticity, calcium/calmodulin dependent kinase II alpha (CaMKIIα) and the GluA1 subunit of AMPA receptors (AMPAR) in addiction-associated brain regions. We also asked if activation of CaMKIIα-dependent AMPAR activity escalates binge-like drinking

Lived Experiences of Gaming and Gambling Related Harm and Implications for Healthcare Services

Children and young people (CYP) are high consumers of loot boxes, raising concerns about the impact of a convergence of gaming and gambling- related harms and their potential negative developmental outcomes in adulthood. Especially, given evidence that practitioners and parents/carers are lacking awareness of the risks of converging gaming-gambling environments. Addressing these risks necessitates understanding the experiences of gaming and gambling- related harm within healthcare systems. This study aimed to gain insights from individuals with previous lived experience of gaming and/or gambling-related harm in the context of CYP and healthcare systems. A qualitative design was adopted using two semi-structured online focus groups, involving five participants with previous lived experience of gaming and/or gambling-related harm. Focus groups explored their experiences of healthcare services and barriers to support in the journey through harm and recovery. Thematic analysis of the data revealed five key themes: i) Escapism; ii) Identity; iii) Preventative Education; iv) Safer Environments; v) Health-based Narratives. Results suggested a convergence of gaming and gambling-related harm in terms of patterns of experiences of escapism and internalising harm with identity, highlighting the need for safer environments and preventative approaches to protect CYP against novel risks of harm through healthcare systems. The results suggest that preventative approaches need to understand the virtual worlds of CYP and the importance of digital resilience. Implications for practitioners, services, policy makers, and regulators seeking to protect CYP from the risks of gaming and gambling-related harm are discussed

Alcohol Alters the Activation of ERK1/2, a Functional Regulator of Binge Alcohol Drinking in Adult C57BL/6J Mice

Binge alcohol drinking is a particularly risky pattern of alcohol consumption that often precedes alcohol dependence and addiction. The transition from binge alcohol drinking to alcohol addiction likely involves mechanisms of synaptic plasticity and learning in the brain. The mitogen-activated protein kinase (MAPK) signaling cascades have been shown to be involved in learning and memory, as well as the response to drugs of abuse, but their role in binge alcohol drinking remains unclear. The present experiments were designed to determine the effects of acute alcohol on extracellular signaling related kinases (ERK1/2) expression and activity, and to determine whether ERK1/2 activity functionally regulates binge-like alcohol drinking