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PubMed2004

'Wonderment and dread': representations of DNA in ethical disputes about forensic DNA databases.

The national DNA Database of England & Wales is the largest forensic DNA database in the world. Since 1995 it has quickly developed to hold the genetic profiles of over two million people. This collection of tissue samples, taken without consent from a sizeable collection of the population, has engendered a number of ethical commentaries on its legitimacy as a proportionate response to crime. This paper examines the ways in which the ethical discourses, which surround the uses of the National DNA Database, drew upon and deployed a number of distinct representations of DNA. It is argued that key ideas about DNA have become central to everyday assertions about the benefits and dangers of this forensic technology.

Biological Specimen Banks↗
PubMed1985

Determinants of dietary self-selection in experimental animals.

During the past 10 yr, renewed interest has been expressed in the mechanisms controlling the intake of specific dietary components. In particular, this interest has focused on research examining the role of the central nervous system in regulating intake of the three macronutrients protein, fat, and carbohydrate. Several hypotheses relating specific neurotransmitter systems to nutrient selection have developed from this research. However, conflicting data make the acceptance of any one hypothesis about diet selection untenable. As an attempt to reconcile some of the conflicting data, the present paper describes a variety of factors which can influence patterns of nutrient choice. The effects of diet composition, the experimental environment, the animals' background, and nutritional history on diet selection are examined.

Age Factors↗
PubMed2004

Pharmacotherapy, pharmacogenomics, and the future of alcohol dependence treatment, part 1.

PURPOSE: The neurobiological basis of alcohol dependence, established pharmacotherapies for alcohol dependence, pharmacotherapies under investigation, and obstacles to treatment are discussed. SUMMARY: Alcohol binds to hydrophobic pockets of proteins, changing their three-dimensional structure and their function. Proteins that are particularly sensitive to alcohol include ion channels, neurotransmitter receptors, and enzymes involved in signal transduction. Established pharmacologic treatments, notably disulfiram and naltrexone, combined with behavioral therapies, may reduce the amount of drinking, the risk of relapse, the number of days of drinking, and craving in some alcohol-dependent individuals. For many patients, however, these treatments are not effective. Recent advances in molecular and behavior genetics are guiding the development of new drugs; these efforts seek to identify pharmacologic pathways relevant to alcohol dependence and to more effectively match treatments to individuals according to their genetic characteristics. Efficacy and safety concerns for acamprosate have been satisfied; the drug was recently released for marketing in the United States. Medications such as sertraline, ondansetron, topiramate, and aripiprazole represent novel lines of research and are currently being tested for use in the treatment of alcoholism. Even with more efficacious medications, however, a transformation must occur in how alcoholism treatment is viewed, not only by the public but also by clinicians. CONCLUSION: In addition to existing drug treatments for alcohol dependence, many other medications are under investigation, particularly for specific types of alcoholism. Pharmacogenomics is expected to play an important role in this research effort.

Acamprosate↗
PubMed1983

Egg-laying defective mutants of the nematode Caenorhabditis elegans.

We have isolated 145 fertile mutants of C. elegans that are defective in egg laying and have characterized 59 of them genetically, behaviorally and pharmacologically. These 59 mutants define 40 new genes called egl. for egg-laying abnormal. Most of the other mutants are defective in previously identified genes. The egl mutants differ with respect to the severity of their egg-laying defects and the presence of behavioral or morphological pleiotropies. We have defined four distinct categories of mutants based on their responses to the pharmacological agents serotonin and imipramine, which stimulate egg laying by wild-type hermaphrodites. These drugs test the functioning of the vulva, the vulval and uterine muscles and the hermaphrodite-specific neurons (HSNs), which innervate the vulval muscles. Mutants representing 14 egl genes fail to respond to serotonin and to imipramine and are likely to be defective in the functioning of the vulva or the vulval and uterine muscles. Four mutants (representing four different genes) lay eggs in response to serotonin but not to imipramine and appear to be egg-laying defective because of defects in the HSNs; three of these four were selected specifically for these drug responses. Mutants representing seven egl genes lay eggs in response to serotonin and to imipramine. One egl mutant responds to imipramine but not to serotonin. The remaining egl mutants show variable or intermediate responses to the drugs. Two of the HSN-defective mutants, egl-1 and her-1(n695), lack HSN cell bodies and are likely to be expressing the normally male-specific program of HSN cell death. Whereas egl-1 animals appear to be defective specifically in HSN development, her-1(n695) animals exhibit multiple morphological pleiotropies, displaying partial transformation of the sexual phenotype of many cells and tissues. At least two of the egl mutants appear to be defective in the processing of environmental signals that modulate egg laying and may define new components of the neural circuitry that control egg laying.

Animals↗
PubMed2003

Genetic analysis of Caenorhabditis elegans glp-1 mutants suggests receptor interaction or competition.

glp-1 encodes a member of the highly conserved LIN-12/Notch family of receptors that mediates the mitosis/meiosis decision in the C. elegans germline. We have characterized three mutations that represent a new genetic and phenotypic class of glp-1 mutants, glp-1(Pro). The glp-1(Pro) mutants display gain-of-function germline pattern defects, most notably a proximal proliferation (Pro) phenotype. Each of three glp-1(Pro) alleles encodes a single amino acid change in the extracellular part of the receptor: two in the LIN-12/Notch repeats (LNRs) and one between the LNRs and the transmembrane domain. Unlike other previously described gain-of-function mutations that affect this region of LIN-12/Notch family receptors, the genetic behavior of glp-1(Pro) alleles is not consistent with simple hypermorphic activity. Instead, the mutant phenotype is suppressed by wild-type doses of glp-1. Moreover, a trans-heterozygous combination of two highly penetrant glp-1(Pro) mutations is mutually suppressing. These results lend support to a model for a higher-order receptor complex and/or competition among receptor proteins for limiting factors that are required for proper regulation of receptor activity. Double-mutant analysis with suppressors and enhancers of lin-12 and glp-1 further suggests that the functional defect in glp-1(Pro) mutants occurs prior to or at the level of ligand interaction.

Animals↗
PubMed1996

Theoretical developments in the psychology of aging.

This article presents a summary overview of the most distinctive psychological theories of aging since World War II. Theoretical developments are broadly classified into three periods, respectively: The Classical period ('40s-'70s), represented by Developmental Tasks/Activity Theory, Psychosocial Theory of Personality Development, Counterpart Theory, Disengagement/Activity Theory, Personality Theory of Age and Aging, and Cognitive Theory of Personality and Aging; the Modern period ('70s-'90s), which includes theories on Life-span Development and Aging, Reduced Processing Resources, Personality and Aging, Behavioral Genetics and Aging; and the New period ('80s-'90s), represented by Gerotranscendence and Gerodynamics/Branching Theory. The overview ends with an outlook on psychogerontological theorizing.

Aged↗
PubMed2007

Changes in dietary fat and fiber and serum hormone concentrations: nutritional strategies for breast cancer prevention over the life course.

The association between dietary fat intake and breast cancer risk has appeared in a meta-analysis of epidemiologic research, migration studies from countries of low to high risk for breast cancer, and animal experiments. With this background, dietary intervention research aims to reduce fat intake and increase fruit, vegetable, and fiber intake, relying on changes in hormone concentrations as biomarkers for reduction in risk of breast cancer. To date, this dietary intervention research spans the life course and has demonstrated stellar success in some studies but sobering results in others. The purpose of this article is to review the intervention research since a 1999 meta-analysis that reported reduced estradiol levels on a low-fat diet and to explore the lessons learned from intervention research on changes in dietary fat and fiber intake and serum hormone concentrations. Secular trends in obesity and ages at pubertal onset and menarche provide dynamic behavioral, genetic, and developmental challenges to the success of dietary prevention. The goal is to formulate an integrative approach to dietary intervention, taking into consideration ethnic group differences in energy expenditure that modulate weight and hormones influencing breast cancer risk over the life course.

Breast Neoplasms↗
PubMed1983

Comparison of Trembler and Trembler-J mouse phenotypes: varying severity of peripheral hypomyelination.

Trembler (Tr) is an autosomal dominant mutation which produces hypomyelination and demyelination in the mouse peripheral nervous system. This paper compares the genetic, behavioral, and pathological aspects of trembler-J, (TrJ) to those of the original Tr mutation. We found that TrJ was tightly linked on chromosome 11 to vestigial tail, vt, as is Tr. Most TrJ/? animals were more mildly affected behaviorally and pathologically than Tr/? animals. Tr/? animals were rather uniformly affected. In contrast, with matings of mildly affected TrJ/? (putative TrJ/+) animals to each other, and not with matings of putative TrJ/+ X +/+, some offspring, putative homozygotes, TrJ/TrJ, were more severely affected behaviorally and had more extreme peripheral hypomyelination than any Tr/? animals. In spite of their differences, Tr/?, putative TrJ/+, and putative TrJ/TrJ animals shared a failure or marked delay of Schwann cells to progress from the stage of axonal ensheathment in a 1:1 relationship to myelination. We conclude that Tr and TrJ are probably allelic, and that despite their phenotypic differences, their actions are fundamentally similar. While Tr is a dominant, we believe that TrJ behaves as a semidominant, which in homozygotes, TrJ/TrJ, produces the most severe heritable peripheral myelin deficiency hitherto described.

Alleles↗
PubMed2005

Neuropsychiatric consequences of traumatic brain injury: a review of recent findings.

PURPOSE OF REVIEW: Behavioral and psychiatric disturbances are the more frequent consequences of traumatic brain injury and major determinants of the quality of life of patients. This review was designed to familiarize the reader with the more recent work published in this field. RECENT FINDINGS: We have now a more consistent view of the epidemiology of post-traumatic brain injury psychiatric disorders both in adult and pediatric populations. Mood disorders, anxiety disorders and substance use disorders are the more prevalent psychiatric diagnoses among traumatic brain injury patients. The phenomenological characteristics and clinical correlates of major depression, post-traumatic stress disorder, alcohol use disorders, and post-traumatic brain injury attention deficit hyperactivity disorder have been studied in more detail. Newer structural, metabolic and functional neuroimaging techniques help to clarify the pathogenesis of these disorders. In turn, this knowledge may lead to the implementation of more efficient therapeutic interventions. Unfortunately, controlled treatment studies have been the exception in the field, and treatment decisions usually lack adequate empirical support. SUMMARY: Recent advances in the basic neuroscience of traumatic brain injury as well as in behavioral genetics, social science and neuroimaging techniques should contribute to a better understanding of the pathophysiology of the psychiatric disorders occurring after the injury. There is a great need for randomized, double-blind, placebo-controlled trials to establish the most effective treatments for these disorders.

Journal Article↗
PubMed1999

Epigenetic interactions among three dTph1 transposons in two homologous chromosomes activate a new excision-repair mechanism in petunia.

Unstable anthocyanin3 (an3) alleles of petunia with insertions of the Activator/Dissociation-like transposon dTph1 fall into two classes that differ in their genetic behavior. Excision of the (single) dTph1 insertion from class 1 an3 alleles results in the formation of a footprint, similar to the "classical" mechanism observed for excisions of maize and snapdragon transposons. By contrast, dTph1 excision and gap repair in class 2 an3 alleles occurs via a newly discovered mechanism that does not generate a footprint at the empty donor site. This novel mechanism depends on the presence of two additional dTph1 elements: one located in cis, 30 bp upstream of the an3 translation start in the same an3 allele, and a homologous copy, which is located in trans in the homologous an3 allele. Absence of the latter dTph1 element causes a heritable suppression of dTph1 excision-repair from the homologous an3 allele by the novel mechanism, which to some extent resembles paramutation. Thus, an epigenetic interaction among three dTph1 copies activates a novel recombination mechanism that eliminates a transposon insertion.

Alleles↗
PubMedDate not supplied

Life with (or without) father: the benefits of living with two biological parents depend on the father's antisocial behavior.

The salutary effects of being raised by two married, biological parents depend on the quality of care parents can provide. Using data from an epidemiological sample of 1,116 5-year-old twin pairs and their parents, this study found that the less time fathers lived with their children, the more conduct problems their children had, but only if the fathers engaged in low levels of antisocial behavior. In contrast, when fathers engaged in high levels of antisocial behavior, the more time they lived with their children, the more conduct problems their children had. Behavioral genetic analyses showed that children who resided with antisocial fathers received a "double whammy" of genetic and environmental risk for conduct problems. Marriage may not be the answer to the problems faced by some children living in single-parent families unless their fathers can become reliable sources of emotional and economic support.

Adolescent↗
PubMed2002

Parent-offspring resemblance for reading performance at 7, 12 and 16 years of age in the Colorado Adoption Project.

BACKGROUND: The study aimed to conduct the first analysis of CAP parent-offspring resemblance for reading performance in children aged 7, 12 and 16 years, and to assess the etiology of individual differences in reading performance of children at 16 years of age. METHOD: The Reading Recognition subtest of the Peabody Individual Achievement Test was administered to children in the Colorado Adoption Project (CAP) at 7, 12 and 16 years of age, and to their adoptive and nonadoptive parents when the children were 7 years of age. RESULTS: Resulting parent-offspring correlations in adoptive families were not significant at any age, but correlations between scores of nonadoptive control parents and their offspring were significant at all three ages. CONCLUSIONS: Results obtained from behavioral genetic model-fitting analyses of data from parents and their children tested at age 16 are consistent with results of studies of twins and siblings indicating that individual differences in reading performance are due substantially to genetic influences. In contrast, environmental transmission from parents to offspring was negligible, suggesting that environmental influences on individual differences in the reading performance of children are largely independent of parental reading performance.

Adolescent↗
PubMed1994

A longitudinal family study of personality change and stability.

The 19-year stability of personality from late adolescence to early adulthood was examined in a sample of 121 men and women who had participated in an earlier study of articulation and language development (Templin, 1966; Templin & Glaman, 1976). Personality was assessed using the Eysenck Personality Inventory (EPI). At the time of retest, personality data were also collected from the participants' mothers. Modest stability of individual differences in personality was observed, consistent with the literature on longitudinal studies of personality during late adolescence and early adulthood. For the Extraversion and Neuroticism scales, offspring means decreased significantly over the 19-year period such that the offspring means were closer to the mean scores of their mothers when they were followed up in adulthood as compared to their first testing in adolescence. There was, however, no change in mother-offspring resemblance from the initial test to retest. Mother-offspring resemblance appears to be due largely to aspects of personality that were stable from adolescence to early adulthood. Implications of these results are discussed in relation to the findings of previous longitudinal studies of adult personality and recent behavioral genetic evidence regarding personality change and stability.

Adolescent↗
PubMed2005

Behavioural profiles of inbred mouse strains used as transgenic backgrounds. II: cognitive tests.

One of the characteristic manifestations of several neurodegenerative diseases is the progressive decline in cognitive ability. In order to determine the suitability of six mouse strains (129S2/Sv, BALB/c, C3H/He, C57BL/6j, CBA/Ca and DBA/2) as transgenic background strains, we investigated the performance on a variety of tasks designed to identify subtle changes in cognition. In addition, a test of exploratory behaviour was used to probe the level of underlying anxiety in these mouse strains, as anxiety can be a confounding factor on behavioural performance generally. The C3H/He mice exhibited the least anxiogenic behavioural profile spending most time on the open arms of the maze, in contrast to the 129S2/Sv mice which spent the least amount of time in this location and were the quickest to move into a closed arm. The C3H/He mouse strain failed to acquire a visual discrimination task and failed to demonstrate learning on a water maze spatial learning task, in contrast to the CBA/Ca, DBA/2 and C57BL/6j strains which demonstrated a degree of learning in both tasks. No significant strain differences were identified on the object recognition task. These data, taken together, suggest that care must be taken when choosing cognitive tasks to be used with particular mouse strains and that task sensitivity must be considered as a critical element to research protocols with regard to these mouse strains.

Analysis of Variance↗
PubMed2006

Wild mouse open field behavior is embedded within the multidimensional data space spanned by laboratory inbred strains.

The vast majority of studies on mouse behavior are performed on laboratory mouse strains (Mus laboratorius), while studies of wild-mouse behavior are relatively rare. An interesting question is the relationship between the phenotypes of M. laboratorius and the phenotypes of their wild ancestors. It is commonly believed, often in the absence of hard evidence, that the behavior of wild mice exceeds by far, in terms of repertoire richness, magnitude of variables and variability of behavioral measures, the behavior of the classical inbred strains. Having phenotyped the open field behavior (OF) of eight of the commonly used laboratory inbred strains, two wild-derived strains and a group of first-generation-in-captivity local wild mice (Mus musculus domesticus), we show that contrary to common belief, wild-mouse OF behavior is moderate, both in terms of end-point values and in terms of their variability, being embedded within the multidimensional data space spanned by laboratory inbred strains. The implication could be that whereas natural selection favors moderate locomotor behavior in wild mice, the inbreeding process tends to generate in mice, in some of the features, extreme and more variable behavior.

Animals↗