Social regulation of human gene expression

ABSTRACT— The relationship between genes and social behavior has historically been construed as a one-way street, with genes in control. Recent analyses have challenged this view, by discovering broad alterations in the expression of human genes as a function of differing socio-environmental conditions. The emerging field of social genomics has begun to identity the types of genes subject to social regulation, the biological signaling pathways mediating those effects, and the genetic polymorphisms that moderate socioenvironmental influences on human gene expression.     

论中医的辨证论治与肿瘤的分子靶向治疗

辨证论治是中医认识和治疗疾病的基本原则,“同病异治”和“异病同治”是辨证论治的精神实质。恶性肿瘤的分子靶向治疗在很多方面都贯彻了“辨证论治”观念,将所辨的证候落实到受体、基因和各种调控系统上。尽管两者理论基础完全不同,但都强调以患者为中心的综合治疗和个体化治疗理念,对建立正确的临床思维非常重要。     

Writing and reading skills as assessed by teachers in 7-year olds: A behavioral genetic approach

A behavioral genetic analysis of general writing ability was conducted using teacher assessments based on UK National Curriculum criteria for a sample of 3296 same-sex pairs of 7-year-old twins. Writing was highly heritable within the normal range (0.66) and at the low extreme (0.70). Environmental influences were almost all non-shared, with shared environmental estimates negligible (0.07 normal range, 0.06 low extreme). Bivariate genetic analyses of teacher assessments of writing and reading indicated that 69% of the genetic influences on writing were in common with those on reading, and that the two skills shared all of their shared environmental influences. In contrast, non-shared environmental factors are largely specific, with 86% independent of those on reading.     

Psychological Follow-up of Presymptomatic Genetic Testing for Spinocerebellar Ataxia Type 2 (SCA2) in Cuba

Presymptomatic testing for spinocerebellar ataxia type 2 (SCA2) in Cuba started five years ago. We have now investigated the psychological impact of test results on 150 individuals at 50% risk for SCA2. In a prospective study, psychological instruments were used to evaluate depression, anxiety and family functioning (1) before testing and (2) one year after disclosure of the test result. One year after, anxiety and depression levels decreased both in carriers and non-carriers, but anxiety decreased significantly more in carriers. Pathological levels of anxiety were seen mostly in members of dysfunctional families, but decreased more in them than in other consultands. Presymptomatic testing thus seems to have been especially beneficial for these testees, possibly due to a greater gain from the psychosocial support received. It would be pertinent to evaluate now the impact of other psychosocial variables and perform longer-term longitudinal studies.     

Decision-Making About Reproductive Choices Among Individuals At-Risk for Huntington's Disease

We explored how individuals at-risk for HD who have or have not been tested make reproductive decisions and what factors are involved. We interviewed 21 individuals (8 with and 4 without the mutation, and 9 un-tested) in-depth for 2 hours each. At-risk individuals faced a difficult series of dilemmas of whether to: get pregnant and deliver, have fetal testing, have pre-implantation genetic diagnosis, adopt, or have no children. These individuals weighed competing desires and concerns: their own desires vs. those of spouses vs. broader moral concerns (e.g., to end the disease; and/or follow dictates against abortion) vs. perceptions of the interests of current or future offspring. Quandaries arose of how much and to whom to feel responsible. Some changed their perspectives over time (e.g., first “gambling,” then being more cautious). These data have critical implications for genetic counselors and other health care workers and future research, particularly as more genetic tests become available.     

Etiologic Subtypes of Attention-Deficit/Hyperactivity Disorder: Brain Imaging, Molecular Genetic and Environmental Factors and the Dopamine Hypothesis

Multiple theories of Attention-Deficit/Hyper- activity Disorder (ADHD) have been proposed, but one that has stood the test of time is the dopamine deficit theory. We review the narrow literature from recent brain imaging and molecular genetic studies that has improved our understanding of the role of dopamine in manifestation of symptoms of ADHD, performance deficits on neuropsychological tasks, and response to stimulant medication that constitutes the most common treatment of this disorder. First, we consider evidence of the presence of dopamine deficits based on the recent literature that (1) confirms abnormalities in dopamine-modulated frontal-striatal circuits, reflected by size (smaller-than-average components) and function (hypoactivation); (2) clarifies the agonist effects of stimulant medication on dopaminergic mechanisms at the synaptic and circuit level of analysis; and (3) challenges the most-widely accepted ADHD-related neural abnormality in the dopamine system (higher-than-normal dopamine transporter [DAT] density). Second, we discuss possible genetic etiologies of dopamine deficits based on recent molecular genetic literature, including (1) multiple replications that confirm the association of ADHD with candidate genes related to the dopamine receptor D4 (DRD4) and the DAT; (2) replication of differences in performance of neuropsychological tasks as a function of the DRD4 genotype; and (3) multiple genome-wide linkage scans that demonstrate the limitations of this method when applied to complex disorders but implicate additional genes that may contribute to the genetic basis of ADHD. Third, we review possible environmental etiologies of dopamine deficits based on recent studies of (1) toxic substances that may affect the dopamine system in early development and contribute substantially to the etiology of ADHD; (2) fetal adaptations in dopamine systems in response to stress that may alter early development with lasting effects, as proposed by the developmental origins of health and disease hypothesis; and (3) gene-environment interactions that may moderate selective damage or adaptation of dopamine neurons. Based on these reviews, we identify critical issues about etiologic subtypes of ADHD that may involve dopamine, discuss methods that could be used to address these issues, and review old and new theories that may direct research in this area in the future.     

Improving Service Evaluation in Clinical Genetics: Identifying Effects of Genetic Diseases on Individuals and Families

Outcome measurement in clinical genetics is challenging. Outcome attributes used currently have been developed by service providers or adapted from measures used in other areas of healthcare. Many of the ‘patients’ in clinical genetics are healthy but at risk of developing or transmitting a condition. Usually no pharmacological or surgical treatment is offered, although information-giving is an objective of most consultations. We argue that services should be evaluated on the basis of how well they alleviate the effects of disease, from a patient perspective. This paper describes a qualitative study using seven focus groups with health professionals, patients and patient representatives. Social and emotional effects of genetics diseases were identified. Some differences emerged between the effects identified by health professionals and those identified by patients. These findings will be used to inform the evaluation of existing outcome measures and develop robust measures of outcome for clinical genetics services.     

The molarity of molecular theory and the molecularity of molar theory.

Dinsmoor (2001) rejects shock-frequency reduction as a reinforcer for avoidance behavior, and considers this to be an invalidation of so-called molar avoidance theory. This is a narrow view of operant avoidance theory, for which shock-frequency reduction is by no means the only reinforcer.     

浅谈分子生物学与临床医学研究的结合

随着分子生物学理论和技术从基础研究渗透到临床各个学科,对临床诊断和治疗水平的提高起到了积极的推动作用。但在实际工作中还存在着发展不平衡以及认识与理解上的误区。就分子生物学与临床医学研究的相结合的现状、存在问题及相应对策,以及今后我国临床医学分子生物学研究的发展前景进行了较广泛深入的讨论。     

皮亚杰的方法论：体系、优势与启示

皮亚杰的方法论体系包括：(1）发生学的理念;(2)“适应”和“运演”的理论解释工具;(3)获取资料的临床访谈法．他以这样的方法论体系而建立起来的理论具有：理性性、解释性、整体性等特征。皮亚杰方法论对我们当前的心理学研究具有启示意义。当前的一些研究在很大程度上,恪守着“实证”与“量化”的规范;却忽视研究主体的理性建构作用。