Independent stratum formation on the avian sex chromosomes reveals inter-chromosomal gene conversion and predominance of purifying selection on the w chromosome

We used a comparative approach spanning three species and 90 million years to study the evolutionary history of the avian sex chromosomes. Using whole transcriptomes, we assembled the largest cross-species dataset of W-linked coding content to date. Our results show that recombination suppression in large portions of the avian sex chromosomes has evolved independently, and that long-term sex chromosome divergence is consistent with repeated and independent inversions spreading progressively to restrict recombination. In contrast, over short-term periods we observe heterogeneous and locus-specific divergence. We also uncover four instances of gene conversion between both highly diverged and recently evolved gametologs, suggesting a complex mosaic of recombination suppression across the sex chromosomes. Lastly, evidence from 16 gametologs reveal that the W chromosome is evolving with a significant contribution of purifying selection, consistent with previous findings that W-linked genes play an important role in encoding sex-specific fitness

Real-world memory and executive processes in cannabis users and non-users

The relationships between executive processes, associative learning and different aspects of real world memory functioning were explored in a sample of cannabis users and nonusers. Measures of executive component processes, associative learning, everyday memory, prospective memory, and cognitive failures were administered. Relative to nonusers, cannabis users were found to be impaired in several aspects of real world memory functioning. No other group differences were apparent. The absence of cannabis related deficits in those executive component processes and aspects of learning that are believed to support real world memory processes is surprising given that cannabis related deficits were obtained in real world memory. The present results are discussed within the context of neuroimaging evidence which suggests that cannabis users may exhibit different patterns of neural activation when performing executive tasks while not always exhibiting deficits on these tasks

Everyday memory deficits in ecstasy-polydrug users

Rationale/Objectives: Recent research suggests that not only does the use of recreational drugs impact working memory functioning, but more “everyday” aspects of memory (e.g. remembering to do something in the future) are also affected. Methods: Forty-three ecstasy-polydrug users and 51 non-ecstasy users were recruited from a university population. Each participant completed the Cognitive Failures Questionnaire (CFQ) and Everyday Memory Questionnaire (EMQ). Of these, 28 ecstasy-polydrug users and 35 non-ecstasy users completed the Prospective Memory Questionnaire (PMQ). In addition, an objective measure of cognitive failures (the CFQ-for-others) was completed by friends of participants. Results: There was a main effect of ecstasy-polydrug use on CFQ, EMQ, CFQ-for-others, Long-Term (LT) PM and internally cued PM scores. These were slightly attenuated following control for working memory capacity. Correlations were found between the different indicators of everyday memory and various measures of illicit drug use. Cannabis featured prominently in this respect. In addition, all ecstasy-related deficits were reduced to below statistical significance following control for cannabis use. Conclusions: The present study provides further support for cannabis related deficits in aspects of everyday memory functioning. Ecstasy may also be associated with cognitive slips, but not to the same extent as cannabis

Sleep Impairment in Ecstasy/Polydrug and Cannabis-Only Users

The present study investigated aspects of sleep quality in ecstasy and cannabis users. Two-hundred and twenty seven participants (117 ecstasy/polydrug users, 53 cannabis users and 57 drug naive participants) took part. The participants completed measures of daytime sleepiness, and indicators of sleep quality. The results demonstrated that ecstasy/polydrug users viewed themselves as being more evening types and having poorer sleep quality than cannabis users and drug naive participants. They were also more likely to have missed a night's sleep. The reported differences in sleep type may reflect ecstasy-related serotonergic dysfunction resulting in problems with shifting circadian rhythms

Inhibition of prandial and waterspray-induced rat grooming by 8-OH-DPAT

The effects of 8-OH-DPAT treatment on rat grooming behaviour, elicited either prandially or in response to spraying with water were investigated. Dose (≤0.1 mg/kg s.c.) response studies employed momentary time sampling over 30 or 60 min with behaviour being scored in one of 6 or 7 (depending on food availability) mutually exclusive categories (feeding, active, scratching, face-grooming, body grooming, genital-grooming and resting) at 15 s intervals. In non-deprived rats, tested with wet mash available, feeding and activity frequencies were increased, but resting and total grooming were inhibited by 8-OH-DPAT. Face-, body- and genital-grooming occurred at higher levels than scratching, but all categories were reduced with reductions in scratching occurring at a lower dose (0.01 mg/kg). Misting rats with a fine water spray selectively increased body grooming and decreased activity without altering feeding, while 8-OH-DPAT increased feeding and reduced face-, body- and genital-grooming, without affecting already low levels of scratching. In misted rats, tested without food, 8-OH-DPAT reduced face-, body- and genital-grooming and increased resting. These results confirm i) that the water spray technique is a useful method for increasing grooming and ii) that 8-OH-DPAT has a suppressant effect on grooming independent of response competition from enhanced feeding

The nature of ecstasy-group related deficits in associative learning

Rationale/objectives: Research has revealed associative learning deficits among users of ecstasy; the present study explored the component processes underlying these deficits. Methods: Thirty-five ecstasy users and 62 non-ecstasy users completed a computer-based, verbal paired-associates learning task. Participants attempted to learn eight sequentially presented word pairs. After all eight had been presented, the first member of each pair was displayed and participants attempted to recall the second. Eight trials were administered. Correct responses on each trial, forgetting at various levels of learning, perseveration errors and the rate at which the associations were learned (trials to completion) were all recorded. Results: MANOVA revealed that ecstasy users performed worse overall and subsequent ANOVAs showed that users performed significantly worse on virtually all measures. Regression analysis revealed that over half of the ecstasy-group related variance in trials to completion was attributable to group differences in initial learning and forgetting. In relation to forgetting, it appears that cannabis use may be an important determinant. In relation to rate of learning (trials to completion) and initial learning, both ecstasy and cannabis may be implicated. Conclusions: There appears to be abundant evidence of associative learning deficits among ecstasy users. However, it appears that a range of illicit drugs including cannabis and ecstasy may contribute to these deficits

Differences in prefrontal blood oxygenation during an acute multitasking stressor in ecstasy polydrug users

Background: Cognitive deficits are well documented in ecstasy (MDMA) users with such deficits being taken as evidence of dysregulation of the 5HT system. More recently neuroimaging has been used to corroborate these deficits. The present study aimed to assess multitasking performance in ecstasy polydrug users, polydrug users and drug naïve individuals. It was predicted that ecstasy polydrug users would perform worse than nonusers on the behavioural measure and this would be supported by difference in cortical blood oxygenation. Methods: Twenty ecstasy-polydrug users, 17 polydrug users and 19 drug naïve individuals took part. On day 1 drug use history was taken and questionnaire measures were completed. On day 2, participants completed a 20 minute multitasking stressor while brain blood oxygenation was measured using functional near infrared spectroscopy (fNIRS). Results: There were no significant differences between the 3 groups on the subscales of the multitasking stressor. In addition, there were no significant differences on self-report measures of perceived workload (NASA – TLX). In terms of mood, ecstasy users were significantly less calm and less relaxed compared to drug-naïve controls. There were also significant differences at 3 voxels on the fNIRS indicating decreased blood oxygenation in ecstasy users compared to drug naïve controls at V2 (left DLPFC), V14 and V16 (right DLPFC), and compared to polydrug controls at V14. Conclusions: The results of the present study provide support for changes in brain activation during performance of demanding tasks in ecstasy polydrug users, which could be related to cerebral vasoconstriction

Electrophysiological Evidence of Atypical Processing Underlying Mental Set Shifting in Ecstasy Polydrug and Polydrug Users

Executive functioning deficits are reported in ecstasy users. However research into mental set switching has been equivocal, with behavioural studies suggesting the function is preserved. The current study sought to address the issue of switching deficits in ecstasy users by combining behavioural performance with electrophysiological correlates (EEG). Twenty ecstasy polydrug users, 20 non-ecstasy polydrug users and 20 drug naive controls were recruited. Participants completed questionnaires about their drug use, sleep quality, fluid intelligence and current mood state. Each participant completed a mental set switching task (the number-letter task) whilst EEG measures were recorded. ANOVA revealed no between group differences on performance of the task, however a regression suggested that ecstasy use was a significant predictor for performance, after controlling for cannabis use. Mixed ANOVA revealed a significant effect of group on the P3, with significant differences between both drug groups and naives. There was also an interaction between electrode and group on the P2 component, with ecstasy users differing from both other groups. On the P3 component the results suggest a reduction in positivity at parieto-occipital electrodes for drug users compared to controls. Furthermore a significant increase in negativity in ecstasy users compared to control groups could be observed in several occipito-parietal electrodes at an N2 component as well as observable atypicalities in early processing (P2) displayed by ecstasy users and polydrug controls. The present study provides evidence of atypical processing of attentional shifting in ecstasy and polydrug users. Deficits in this executive function could reflect cognitive inflexibility and paucity of rapid behavioural adjustment, which may be problematic in real world situations. Keywords: Ecstasy; cannabis; executive function; stimulants; cannabis

Inferring regulatory change from gene expression: the confounding effects of tissue scaling

Comparative studies of gene expression are often designed with the aim of identifying regulatory changes associated with phenotypic variation. In recent years, large-scale transcriptome sequencing methods have increasingly been applied to nonmodel organisms to ask important ecological or evolutionary questions. Although experimental design varies, many of these studies have been based on RNA libraries obtained from heterogeneous tissue samples, for example homogenized whole bodies. Comparisons between groups of samples that vary in tissue composition can introduce sufficient variation in RNA abundance to produce patterns of differential expression that are mistakenly interpreted as evidence of regulatory differences. Here, we present a simple model that demonstrates this effect. The model describes the relationship between transcript abundance and tissue composition in a two-tissue system, and how this relationship varies under different scaling relationships. Using a range of biologically realistic variables, including real biological examples, to parameterize the model we highlight the potentially severe influence of tissue scaling on relative transcript abundance. We use these results to identify key aspects of experimental design and analysis that can help to limit the influence of tissue scaling on the inference of regulatory difference from comparative studies of gene expression.SHM is grateful for funding from an Early Career Research Fellowship from the Leverhulme Trust, and JEM acknowledges support from the European Research Council (grant agreements 260233 and 680951)

Inferring regulatory change from gene expression: the confounding effects of tissue scaling

Comparative studies of gene expression are often designed with the aim of identifying regulatory changes associated with phenotypic variation. In recent years, large-scale transcriptome sequencing methods have increasingly been applied to nonmodel organisms to ask important ecological or evolutionary questions. Although experimental design varies, many of these studies have been based on RNA libraries obtained from heterogeneous tissue samples, for example homogenized whole bodies. Comparisons between groups of samples that vary in tissue composition can introduce sufficient variation in RNA abundance to produce patterns of differential expression that are mistakenly interpreted as evidence of regulatory differences. Here, we present a simple model that demonstrates this effect. The model describes the relationship between transcript abundance and tissue composition in a two-tissue system, and how this relationship varies under different scaling relationships. Using a range of biologically realistic variables, including real biological examples, to parameterize the model we highlight the potentially severe influence of tissue scaling on relative transcript abundance. We use these results to identify key aspects of experimental design and analysis that can help to limit the influence of tissue scaling on the inference of regulatory difference from comparative studies of gene expression.SHM is grateful for funding from an Early Career Research Fellowship from the Leverhulme Trust, and JEM acknowledges support from the European Research Council (grant agreements 260233 and 680951)