Mammals have a very complex, tightly controlled, and developmentally regulated process of dosage compensation. One form of the process equalizes expression of the X‐linked genes, present as a single copy in males (XY) and as two copies in females (XX), by inactivation of one of the two X‐chromosomes in females. The second form of the process leads to balanced expression between the X‐linked and autosomal genes by transcriptional upregulation of the active X in males and females. However, not all X‐linked (...) genes are absolutely balanced. This review is focused on the recent advances in studying the dosage compensation phenomenon in mammals. (shrink)

The apolipoprotein E gene plays an important role in the pathogenesis of Alzheimer's disease , and amyloid plaque comprised mostly of the amyloid-beta peptide ) is one of the major hallmarks of AD. However, the relationship between these two important molecules is poorly understood. We examined how A treatment affects APOE expression in cultured cells and tested the role of the transcription factor NF-B in APOE gene regulation. To delineate NF-B's role, we have characterized a 1098 nucleotide segment containing the (...) 5'-flanking region of the human APOE gene . Sequence analysis of this region suggests the presence of two potential NF-B elements. To demonstrate promoter activity, the region was cloned upstream of a promoterless luciferase gene. This segment was able to drive expression of luciferase in transient transfections of human fetal glial cells. Promoter activity was stimulated twofold by A treatment. Pretreatment with double-stranded DNA decoy oligonucleotides against NF-B reduced A stimulation. Deletion and mutagenetic analyses demonstrated that the distal NF-B element was functional and showed a strong DNA-protein complex band in gel shift analysis, similar to that from control NF-B consensus element. An anti-inflammatory and anti-NF-B drug, sodium salicylate, significantly blocked A-induced APOE promoter function. Our data provide evidence that upregulation of APOE by A in astroglial cells is mediated by an NF-B-element present in the 5'-flanking region of the APOE gene. (shrink)

Sex chromosomes are advantageous to mammals, allowing them to adopt a genetic rather than environmental sex determination system. However, sex chromosome evolution also carries a burden, because it results in an imbalance in gene dosage between females (XX) and males (XY). This imbalance is resolved by X dosage compensation, which comprises both X chromosome inactivation and X chromosome upregulation. X dosage compensation has been well characterized in the soma, but not in the germ line. Germ cells face a special challenge, (...) because genome wide reprogramming erases epigenetic marks responsible for maintaining the X dosage compensated state. Here we explain how evolution has influenced the gene content and germ line specialization of the mammalian sex chromosomes. We discuss new research uncovering unusual X dosage compensation states in germ cells, which we postulate influence sexual dimorphisms in germ line development and cause infertility in individuals with sex chromosome aneuploidy. (shrink)

The sex chromosomes of many species differ in dosage but the total gene expression output is similar, a phenomenon referred to as dosage compensation. Previously, diverse mechanisms were postulated to account for compensation in distantly related taxa. However, two recent papers present evidence that dosage compensation in Drosophila, mammals and nematodes share the property that there is an approximately two‐fold upregulation of the single active X chromosome in each case.1,2 The results suggest that a common mechanism might operate in these (...) different cases. BioEssays 28: 565–568, 2006. © 2006 Wiley Periodicals, Inc. (shrink)

This article addresses the issue of properly assenting children with psychotic disorders to participate in clinical research. Due to the protective concerns with such a vulnerable population, additional precautions are necessary to ensure that youth with psychotic disorders assent to research with an appropriate level of understanding regarding study procedures. Current literature suggests that positive/negative symptoms and minor cognitive deficits do not interfere with the ability to comprehend study-related information for adults with psychosis if the study information is presented through (...) an educative process. Similarly, youth benefit from repeated presentation of procedures and periodic assessment of their comprehension. An integrated educative process is proposed that emphasizes the importance of an interactive consent through repetition and participant/investigator feedback. (shrink)

BackgroundResearch on prevalence of cognitive frailty phenotypes in community-dwelling older adults in different countries is important to estimate their prevalence and to determine the influence of cognitive reserve and mental health in order to prevent frailty. The aims of this study were to estimate the prevalence of reversible and potentially reversible cognitive frailty in a Portuguese sample of old adults and explore the associations between these phenotypes and demographic, comorbidity, social support, cognitive reserve and mental health factors.MethodsWe assessed frailty in (...) 250 community-dwelling older adults aged 60 years or over without dementia, neurological or psychiatric disorders. Subjective cognitive decline and Mild cognitive impairment were diagnosed according to standard criteria. The questionnaires Charlson Index, Medical Outcomes Study Social Support, Cognitive Reserve Index and General Health were used for assessing comorbidity, social support, cognitive reserve and mental health, respectively.ResultsPrevalence of R-CF was 14%, and that of PR-CF, 15.2%. Cognitive frailty profiles differed significantly in relation to education, comorbidity, mental health, and cognitive reserve, but not in age or sex. Multivariate logistic regression showed that age, sex, comorbidity, social support, mental health, and cognitive reserve together predicted R-CF and PR-CF with significant OR for mental health and cognitive reserve.DiscussionCognitive reserve and mental health are important factors predicting R-CF and PR-CF. We recommend assessing these factors for early detection of cognitive frailty and promoting psychological well-being and lifestyles that increase cognitive reserve in adults. (shrink)

Societies with a higher level of income inequality tend to have lower levels of intergenerational income mobility. Known as the Great Gatsby Curve, this negative relationship in part derives from greater intergenerational economic heritance among the poor. Societies with higher rates of relative poverty will have a higher level of income inequality, but they will also tend to have lower intergenerational mobility due to the reduced capacity of low-income persons to become upwardly mobile. Reviewing relevant research in psychology, we describe (...) how poverty is associated with decreased psychological resources that compromise the competitiveness of low-income persons for superior attainment in the educational system and for greater productivity in the labor market. Economic deprivation in itself thus leads to a “vicious circle” of disadvantage that diminishes intergenerational mobility even without the existence of any culture of poverty or monopolistic institutions in the economy. (shrink)

The reinforcement/extinction disorder hypothesis (Sagvolden et al.) is an important counterweight to the executive dysfunction model of attention-deficit/hyperactivity disorder (ADHD). However, like that model, it conceptualises ADHD as pathophysiologically homogeneous, resulting from a common core dysfunction. Recent studies reporting neuropsychological heterogeneity suggest that this common core dysfunction may be the scientific equivalent of a red herring.

A response to Lee Basham's 'The Need for Accountable Witnesses: A Reply to Dentith'.

This essay illustrates what the Chinese family-based and harmony-oriented model of medical decision making is like as well as how it differs from the modern Western individual-based and autonomy-oriented model in health care practice. The essay discloses the roots of the Chinese model in the Confucian account of the family and the Confucian view of harmony. By responding to a series of questions posed to the Chinese model by modern Western scholars in terms of the basic individualist concerns and values (...) embedded in the modern Western model, we conclude that the Chinese people have justifiable reasons to continue to apply the Chinese model to their contemporary health care and medical practice. (shrink)

This reply to an ongoing debate between conspiracy theory researchers from different disciplines exposes the conceptual confusions that underlie some of the disagreements in conspiracy theory research. Reconciling these conceptual confusions is important because conspiracy theories are a multidisciplinary topic and a profound understanding of them requires integrative insights from different fields. Specifically, we distinguish research focussing on conspiracy *theories* (and theorizing) from research of conspiracy *belief* (and mindset, theorists) and explain how particularism with regards to conspiracy theories does not (...) mean we cannot define a problematic subclass of conspiracy beliefs, while avoiding the problems of generalism. We hope this reply helps conspiracy theory researchers recognize the differences between studying conspiracy theories and conspiracy beliefs and appreciate the possibilities for fruitful, integrative, and interdisciplinary research. (shrink)

Violations and biases relative to normative principles of rationality tend to occur when the structure of task environments is novel or the decision goals are in conflict. The two blades of bounded rationality, the structure of task environments and the computational capacities of the actor, can sharpen the conceptual distinctions between the sources of the normative and descriptive gap.

Intentional change when viewed as making a risky or intertemporal choice with evolutionary relevance helps us understand its successes and its failures. To promote future-oriented ecological rationality requires establishing a linkage between nongenetic, cultural, and symbolic selections and genetic adaptations. Coupled with biophilic instinct, intentional conservation is more likely to prevail against evolved desires of environmental exploitation.

We agree with Ainslie's general approach to intertemporal choices and self-control. However, we argue that a concept of “will” is superfluous in explaining tradeoffs between SS (smaller and sooner) and LL (larger and later) rewards in a framework of temporal goal setting and goal aggregation. We provide an alternative framework of reference point-dependent tradeoffs between SS and LL options.