Foley's Threshold View of Belief and The Safety Condition on Knowledge

This paper introduces a new argument against Richard Foley's threshold view of belief. Foley's view is based on the Lockean Thesis (LT) and the Rational Threshold Thesis (RTT). The former thesis is the claim that it is epistemically rational to believe a proposition if and only if it is epistemically rational to have a degree of confidence in that proposition sufficient for belief. The latter thesis is the claim that it is epistemically rational to believe a proposition if and only if it is epistemically rational to have a degree of confidence in that proposition that meets or exceeds a specified threshold. The argument introduced here shows that the views derived from the joint endorsement of the LT and the RTT violate the safety condition on knowledge in way that threatens the LT and/or the RTT.     

The phenotypic consequences of MECP2 mutations extend beyond Rett syndrome

Although MECP2 was initially identified as the causative gene in classic Rett syndrome (RTT), the gene has now been implicated in several phenotypes that extend well beyond the clinically defined disorder. MECP2 mutations have been found in people with various disorders, including neonatal onset encephalopathy, X-linked recessive mental retardation (MRX), classic and atypical RTT, autism, and Angelman syndrome, as well as mildly affected females and normal carrier females. To make matters more complex, in approximately 20% of classic sporadic RTT cases and more than 50% of affected sister pairs, no mutation in MECP2 has been found. X-chromosome inactivation patterns can clearly affect the phenotypic expression in females, while the effect of the type and position of the mutation is more apparent in the broader phenotype than in RTT. Both males and females are at risk, although an excess of paternally derived mutations are found in most cases of classic RTT. Thus, because of the range of disparate phenotypes, the gene may account for a relatively large portion of mental retardation in the population.     

药物成瘾诱导相关大脑核团功能和行为改变的DNA甲基化机制

药物成瘾会导致相关神经环路的结构和功能长期改变.大量新的研究证据表明,在DNA序列不变的情况下,药物成瘾可通过影响不同亚型DNA甲基转移酶(DNMTs)的表达,使脑内多个相关核团发生DNA甲基化以及基因表达的改变,进而导致神经元功能的可塑性变化.因此,DNA甲基化被视作导致成瘾行为长期存在的可能机制之一.结合近几年来的重要发现,本文将重点讨论相关脑区的DNA甲基化在成瘾行为发生发展过程中的作用,以及成瘾药物影响DNA甲基化水平的可能机制,并试图提出可深入的研究展望.     

Leveraging epigenetics to examine differences in developmental trajectories of social attention: A proof-of-principle study of DNA methylation in infants with older siblings with autism

Preliminary evidence suggests that changes in DNA methylation, a widely studied epigenetic mechanism, contribute to the etiology of Autism Spectrum Disorder (ASD). However, data is primarily derived from post-mortem brain samples or peripheral tissue from adults. Deep-phenotyped longitudinal infant cohorts are essential to understand how epigenetic modifications relate to early developmental trajectories and emergence of ASD symptoms. We present a proof-of-principle study designed to evaluate the potential of prospective epigenetic studies of infant siblings of children with ASD.Illumina genome-wide 450 K DNA methylation data from buccal swabs was generated for 63 male infants at multiple time-points from 8 months to 2 years of age (total N = 107 samples). 11 of those infants received a diagnosis of ASD at 3 years. We conducted a series of analyses to characterize DNA methylation signatures associated with categorical outcome and neurocognitive measures from parent-report questionnaire, eye-tracking and electro-encephalography.Effects observed across the entire genome (epigenome-wide association analyses) suggest that collecting DNA methylation samples within infant-sibling designs allows for the detection of meaningful signals with smaller sample sizes than previously estimated. Mapping networks of co-methylated probes associated with neural correlates of social attention implicated enrichment of pathways involved in brain development. Longitudinal modelling found covariation between phenotypic traits and DNA methylation levels in the proximity of genes previously associated with cognitive development, although larger samples and more complete datasets are needed to obtain generalizable results.In conclusion, assessment of DNA methylation profiles at multiple time-points in infant-sibling designs is a promising avenue to comprehend developmental origins and mechanisms of ASD.     

The measurement of role taking in young adults

Sociometry is presented as an alternative way of measuring role taking, specifically, an alternative to an often used projective measure, the Role-Taking Task (RTT). Study 1 assesses role taking in 161 college students. In this study, a sociometric measure, the Peer Role-Taking Questionnaire (PRTQ) was shown to correlate with class year, group status, social choice, and friendship. In contrast, the RTT correlated weakly with grade point average and some personality test measures. In Study 2, the PRTQ, and not the RIT, was associated with interaction skills in a sample of 39 college nursing students. The PRTQ and RTT did not correlate with each other in either study. The validity and reliability of these two role-taking measures are discussed. It is suggested that researchers need to examine the adequacy of the role-taking measures they use.     

Second-Order Confirmatory Factor Analysis of the Reactions to Tests Scale with Cross-Validation

The factor structure of the RTT was evaluated by testing a series of confirmatory factor models including a second-order structure. The results indicated that a reduced 20-item RTT scale fit the data better than the 40-item original RTT and that a second-order structure explained the data very well. The models were cross-validated using several strategies. The reduced RTT was found not to cross-validate in terms of overall fit. However, when the parameter estimates were tested across samples, all parameters were found to be invariant except the item residuals. Because the cross-validation results were not conclusive, the need for additional theoretical and empirical research on the cross-validation of covariance models was discussed.     

多巴胺相关基因甲基化、家庭环境与创造力的关系

“遗传与环境”的争论一直是创造力研究的核心问题, 但目前对于环境以及遗传与环境交互作用对创造力影响的分子生物机制还未有研究涉及。近年来, 随着表观遗传学的兴起, 揭示影响心理行为的表观遗传机制现已成为心理学研究的热点。作为环境与基因组之间的纽带, 表观遗传学研究为揭示环境以及遗传与环境交互作用对创造力影响的分子生物机制提供了机遇。本研究以多巴胺相关基因、家庭环境以及两者对于创造力的交互作用为切入点, 对影响创造力的表观遗传机制进行考察, 并在此基础之上, 对环境以及遗传与环境交互作用对创造力影响的分子生物机制进行探索。具体研究内容包括：(1)通过对多巴胺相关基因甲基化模式与创造力关系的系统考察, 筛选出甲基化模式与创造力有关的基因; (2)对筛选出的基因, 进一步考察其甲基化模式在家庭环境及其遗传多态性与家庭环境交互作用对创造力影响中的中介作用。本研究有助于揭示创造力的表观遗传机制, 深化关于遗传与环境对创造力影响的作用机制的理解。     

DNA methylation of NR3c1 in infancy: Associations between maternal caregiving and infant sex

Caregivers play a critical role in scaffolding infant stress reactivity and regulation, but the mechanisms by which this scaffolding occurs is unclear. Animal models strongly suggest that epigenetic processes, such as DNA methylation, are sensitive to caregiving behaviors and, in turn, offspring stress reactivity. We examined the direct effects of caregiving behaviors on DNA methylation in infants and infant stress reactivity. Infants and mothers (N = 128) were assessed during a free play when infants were 5 months old. Maternal responsiveness and appropriate touch were coded. and infant buccal epithelial cells were sampled to assess for DNA methylation of the glucocorticoid receptor gene, NR3c1 exon 1F. Infant cortisol reactivity was assessed in response to the still-face paradigm. Greater levels of maternal responsiveness and appropriate touch were related to less DNA methylation of specific regions in NR3c1 exon 1F, but only for females. There was no association with maternal responsiveness and appropriate touch or DNA methylation of NR3c1 exon 1F on prestress cortisol or cortisol reactivity. Our results are discussed in relation to programming models that implicate maternal care as an important factor in programing infant stress reactivity.     

DNA甲基化与衰老的哲学思考

伴随着分子生物学的发展,人类对于衰老的认识从最初的整体动物水平推进到了细胞水平和分子水平,DNA甲基化与衰老的研究也成为生命科学领域研究的热点之一。DNA甲基化与衰老中体现了微观与宏观的哲学思想,在实际的科研及临床工作中掌握科学的哲学思维方法非常重要。     

Epigenetic programming of the HPA axis: early life decides

Stress during early life can impact the developing brain and increase vulnerability to mood disorders later in life. Here, we argue that epigenetic mechanisms can mediate the gene-environment dialogue in early life and give rise to persistent epigenetic programming of adult physiology eventually resulting in disease. Early life stress in mice leads to epigenetic marking of the arginine vasopressin (AVP) gene underpinning sustained expression and increased hypothalamic-pituitary-adrenal axis activity. This epigenetic memory is laid down in the parvocellular neurons of the paraventricular nucleus and involves Ca(2+)/calmodulin kinase-mediated phosphorylation of the methyl-CpG binding domain protein MeCP2 leading to dissociation from its DNA-binding site and derepression of the AVP gene. The reduced occupancy of MeCP2 during this early stage of life facilitates the development of hypomethylation at the AVP enhancer, which sustains derepression throughout later life and thereby serves to hardwire early life experiences. The sequential order of these events may represent a critical time window for the preventive therapy of severe trauma.     

慢性应激诱导的抑郁大鼠纹状体par-4基因的表达

为研究慢性温和应激诱导的抑郁大鼠纹状体内前列腺凋亡反应蛋白(prostate apoptosis response-4, par-4)的表达, 及甲基化是否参与par-4基因表达的调控, 将10周龄大鼠随机分为实验组和对照组, 实验组接受慢性温和应激, 对照组不接受实验性处理。于大鼠13周龄时, 采用强迫游泳、糖水偏爱测验测定大鼠的抑郁水平, 以实时定量PCR检测纹状体par-4及多巴胺D2受体(Dopamine receptor D2, DRD2) mRNA表达水平, 免疫印迹法检测纹状体par-4蛋白质表达水平, 用亚硫酸盐测序法检测par-4基因启动子区甲基化水平。结果发现, 与对照组大鼠相比, 实验组大鼠漂浮时间延长, 糖水偏爱率降低, 脑纹状体par-4、DRD2 mRNA及par-4蛋白质表达水平均降低, par-4基因启动子区甲基化水平两组差异不显著。提示慢性温和应激诱导大鼠产生了抑郁样行为, 并能抑制纹状体par-4基因的表达, 而基因甲基化可能并不参与其调控机制。     

Children's biobehavioral reactivity to challenge predicts DNA methylation in adolescence and emerging adulthood

A growing body of research has documented associations between adverse childhood environments and DNA methylation, highlighting epigenetic processes as potential mechanisms through which early external contexts influence health across the life course. The present study tested a complementary hypothesis: indicators of children's early internal, biological, and behavioral responses to stressful challenges may also be linked to stable patterns of DNA methylation later in life. Children's autonomic nervous system reactivity, temperament, and mental health symptoms were prospectively assessed from infancy through early childhood, and principal components analysis (PCA) was applied to derive composites of biological and behavioral reactivity. Buccal epithelial cells were collected from participants at 15 and 18 years of age. Findings revealed an association between early life biobehavioral inhibition/disinhibition and DNA methylation across many genes. Notably, reactive, inhibited children were found to have decreased DNA methylation of the DLX5 and IGF2 genes at both time points, as compared to non‐reactive, disinhibited children. Results of the present study are provisional but suggest that the gene's profile of DNA methylation may constitute a biomarker of normative or potentially pathological differences in reactivity. Overall, findings provide a foundation for future research to explore relations among epigenetic processes and differences in both individual‐level biobehavioral risk and qualities of the early, external childhood environment.     

反社会行为的遗传基础:基因多态性和DNA甲基化

反社会行为是受遗传与环境共同影响的不良行为。分子遗传学和神经生物学的研究发现,基因以基因多态性和DNA甲基化的方式影响脑结构、功能及脑内神经递质的产生和释放,进而影响反社会行为的发生发展。本文从基因多态性和DNA甲基化两方面整理了5-HTT、MAOA、OXTR等8个候选基因与反社会行为的关联。并提出未来研究需进一步探讨基因、脑和神经递质对反社会行为的联合作用。同时,扩展多基因位点、基因多态性与DNA甲基化、积极环境与基因交互作用对反社会行为影响的研究,以全面探索反社会行为发生的遗传基础,进而更加有效的预防反社会行为。     

反社会行为的遗传基础:基因多态性和DNA甲基化

反社会行为是受遗传与环境共同影响的不良行为。分子遗传学和神经生物学的研究发现,基因以基因多态性和DNA甲基化的方式影响脑结构、功能及脑内神经递质的产生和释放,进而影响反社会行为的发生发展。本文从基因多态性和DNA甲基化两方面整理了5-HTT、MAOA、OXTR等8个候选基因与反社会行为的关联。并提出未来研究需进一步探讨基因、脑和神经递质对反社会行为的联合作用。同时,扩展多基因位点、基因多态性与DNA甲基化、积极环境与基因交互作用对反社会行为影响的研究,以全面探索反社会行为发生的遗传基础,进而更加有效的预防反社会行为。     

Dyadic processes of relational turbulence theory

This study tested dyadic processes of relational turbulence theory (RTT) in heterosexual marriages. We tested propositions 1, 2, and 5 of RTT, which propose that uncertainty about the marriage biases cognitive appraisals, and that interference from a partner heightens negative emotions, both of which culminate in relational turbulence for spouses. Guided by these propositions, husbands' and wives' (N = 510; 255 marital dyads) dyadic cognitive and emotional processes were estimated using the actor-partner interdependence mediation model. Consistent with theoretical propositions, we found evidence for actor-actor indirect effects; for both husbands and wives (a) the effect of spouses' relationship uncertainty on their own relational turbulence was mediated by their own biased cognitive appraisals, and (b) the effect of spouses' experienced interference on their own relational turbulence was mediated by their own anger from communicating in the marriage. However, controlling for actor-actor indirect effects, partner-defined processes (i.e., actor-partner and partner-actor indirect effects) uniquely explained husbands' and wives' relational turbulence.     

Mood as a Result of Temperament Profile: Predictions from the Regulative Theory of Temperament

The paper examines the relationship between three dimensions of mood and temperament traits according to the Regulative Theory of Temperament (RTT). The theory emphasises the role of temperament in meeting environmental requirements and implies that temperamental traits influence mood. The results showed that subjective level of energy was linked most strongly to activity (undertaking behaviours providing intense stimuli). It is questioned whether energy should be considered as a result or a cause of high activity. The best predictor of tense arousal and hedonic tone proved to be emotional reactivity. The former mood dimension was positively related to emotional reactivity, whereas the latter was negatively linked to this trait. The results are consistent with previous investigations on neuroticism and extraversion and widen the knowledge on temperamental predictors of mood by showing associations between briskness and all three mood dimensions. Moreover, the results showed that advantageous mood profile was associated with advantageous temperamental structure which corroborates the relevance of RTT.