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PubMed2000

Masking and unmasking the sexual abuse of children: perceptions of violence against children in "the Badlands" of Ontario, 1916-1930.

This article explores the legal and social understandings of incest in early-twentieth-century Canada, examining the way in which sexual abuse was identified in sensational court cases but ideologically masked in social consciousness. First, the legal treatment of incest is examined through court cases, with special focus on one case that animated a grand jury report on a rural area where incest and violence supposedly flourished. Second, the grand jury's legal, medical, and social assumptions about incest, reflecting eugenic priorities as well as class and gender prejudices, are surveyed. Third, the actual use of the grand jury report in subsequent cases is probed. The report became a generalized explanation for all kinds of familial violence placing blame for violence on poor, degenerate, and immoral parents but ignoring the structural problems of power and patriachy.

Canada↗
PubMedDate not supplied

Perceived environments as physical activity correlates and moderators of intervention in five studies.

PURPOSE: Few studies have explored how relationships of perceived environment and physical activity vary across different activity domains and populations. This question was explored in five physical activity intervention trials funded by the National Institutes of Health Behavior Change Consortium. DESIGN: Observational. SETTINGS: San Francisco peninsula, California (N = 94); Eugene, Oregon (N = 122); Atlanta, Georgia (N = 256); Kingston, Rhode Island (N = 109); Memphis, Tennessee (N = 64). SUBJECTS: Ethnically diverse community adults ages 18 to 85 years. MEASURES: The Neighborhood Environment Walkability Scale and CHAMPS physical activity questionnaire. Response rate among those invited to complete these measures was 90%. RESULTS: Cross-sectional pooled signal detection analysis indicated that people who reported living in neighborhoods with more attractive scenery and ease of walking were more likely to meet national physical activity recommendations (67%) compared with those without these neighborhood attributes (36%; chi2 = 13.04, p = .0003). Within-site multiple regression identified two additional variables--seeing others when walking and encountering loose dogs that make it difficult to walk--as correlates across multiple sites and activity domains (i.e., minutes of weekly moderate or more vigorous activity, walking for errands, walking leisurely) (incremental R2 = 2.0-7.5; p < .05). Analyses of covariance suggested that traffic safety might be particularly important in facilitating or impeding physical activity in response to a formal intervention (for traffic-arm assignment interactions, F = 3.8-7.0, p < or = .05). CONCLUSIONS: Relationships between perceived environments and physical activity may differ depending upon population groups and activity domains and merit investigation by using stronger prospective designs.

Adolescent↗
PubMed2003

Karl Kleist (1879-1960)- a pioneer of neuropsychiatry.

Karl Kleist (1879-1960) was instrumental in pioneering German neuropsychiatry and neuropsychology, including the description of frontal, constructional, limb-kinetic (innervatory) and psychomotor apraxias, frontal akinesia and aspontaneity, as well as object and form blindness. Besides isolating episodic twilight states, involutional paranoia and symptomatic (especially influenza) psychoses, he was particularly involved in applying Wernicke's syndromatic and Kraepelin's prognostic and aetiological principles to classify "neurogenous" psychoses by refuting the assumption of mixed entities whenever possible. Thus, has phasophrenias denoted manic-depressive illness, unipolar affective disorders and marginal, i.e., atypical psychoses. The rather benign cycloid psychoses form the most prominent examples of the latter. Schizophrenias, on the other hand, were limited to poor long-term catamnestic outcomes. Kleist conceptualized the core group of schizophrenic illness as psychic system diseases-hence the origin of the term "systematic schizophrenias" within the Wernicke-Kleist-Leonhard School. Kleist was mainly influenced by Wernicke and his psychic reflex arc, but Ernst Mach's empiriocriticism, Theodor Meynert's cerebral connectionism, and associationism also shaped his outlook. Kleist's localization of cerebral functions by lesion analyses was indeed the best available at the time and continues to reveal insights to the interested reader. From his Frankfurt School, which may have been the last of a completely unified neuropsychiatry, came sound representatives of psychiatry, neurology and neurosurgery. His technical mastery and achievements seem indisputable, but his balancing acts during the Third Reich may today be questioned. Despite joining the National Socialist German Workers' Party (NSDAP) and the local Court of Genealogical Health (Erbgesundheitsgericht), Kleist was, however, one of the few German physicians who continued to treat Jewish patients, to employ Jewish colleagues and to voice evident criticism of the policies of "eugenics" and "euthanasia". This paper attempts to illuminate Kleist's biography and life's work in the relevant historical context.

Germany↗
PubMedDate not supplied

Hospice care or assisted suicide: a false dichotomy.

In this paper, the author argues that making assisted suicide available is not a contradictory position to espousing hospice care. He draws on historical and political examples to explain the ethical basis for this assertion. By defining the issue at stake as one of personal autonomy (the loss or gain thereof), the author challenges the argument that making assisted suicide available leads to a slippery slope towards euthanasia, eugenics, or genocide. He asserts that narrowing choices by preventing people from seeking assistance in suicide is more likely to lead us down the slippery slope towards coercive medical and state intervention in our lives.

Attitude to Death↗
PubMed2000

Health implications of modern childhood.

Childhood has undergone many reconstructions since its 'recognition' in the 18th century. The medicalized child is rooted in eugenics, political economy and professional interests and has implication for practice. The modern child is now viewed as a stakeholder in a political sense. Childhood requires recognition in a 'health' sense if it is to survive as a category. Different medical expectations and models of childhood are likely to evolve.

Attitude to Health↗
PubMed2005

Integrating alternative splicing detection into gene prediction.

BACKGROUND: Alternative splicing (AS) is now considered as a major actor in transcriptome/proteome diversity and it cannot be neglected in the annotation process of a new genome. Despite considerable progresses in term of accuracy in computational gene prediction, the ability to reliably predict AS variants when there is local experimental evidence of it remains an open challenge for gene finders. RESULTS: We have used a new integrative approach that allows to incorporate AS detection into ab initio gene prediction. This method relies on the analysis of genomically aligned transcript sequences (ESTs and/or cDNAs), and has been implemented in the dynamic programming algorithm of the graph-based gene finder EuGENE. Given a genomic sequence and a set of aligned transcripts, this new version identifies the set of transcripts carrying evidence of alternative splicing events, and provides, in addition to the classical optimal gene prediction, alternative optimal predictions (among those which are consistent with the AS events detected). This allows for multiple annotations of a single gene in a way such that each predicted variant is supported by a transcript evidence (but not necessarily with a full-length coverage). CONCLUSIONS: This automatic combination of experimental data analysis and ab initio gene finding offers an ideal integration of alternatively spliced gene prediction inside a single annotation pipeline.

Algorithms↗
PubMed2006

A survey of motif discovery methods in an integrated framework.

BACKGROUND: There has been a growing interest in computational discovery of regulatory elements, and a multitude of motif discovery methods have been proposed. Computational motif discovery has been used with some success in simple organisms like yeast. However, as we move to higher organisms with more complex genomes, more sensitive methods are needed. Several recent methods try to integrate additional sources of information, including microarray experiments (gene expression and ChlP-chip). There is also a growing awareness that regulatory elements work in combination, and that this combinatorial behavior must be modeled for successful motif discovery. However, the multitude of methods and approaches makes it difficult to get a good understanding of the current status of the field. RESULTS: This paper presents a survey of methods for motif discovery in DNA, based on a structured and well defined framework that integrates all relevant elements. Existing methods are discussed according to this framework. CONCLUSION: The survey shows that although no single method takes all relevant elements into consideration, a very large number of different models treating the various elements separately have been tried. Very often the choices that have been made are not explicitly stated, making it difficult to compare different implementations. Also, the tests that have been used are often not comparable. Therefore, a stringent framework and improved test methods are needed to evaluate the different approaches in order to conclude which ones are most promising. REVIEWERS: This article was reviewed by Eugene V. Koonin, Philipp Bucher (nominated by Mikhail Gelfand) and Frank Eisenhaber.

Journal Article↗
PubMed2006

Positive selection on the nonhomologous end-joining factor Cernunnos-XLF in the human lineage.

BACKGROUND: Cernunnos-XLF is a nonhomologous end-joining factor that is mutated in patients with a rare immunodeficiency with microcephaly. Several other microcephaly-associated genes such as ASPM and microcephalin experienced recent adaptive evolution apparently linked to brain size expansion in humans. In this study we investigated whether Cernunnos-XLF experienced similar positive selection during human evolution. RESULTS: We obtained or reconstructed full-length coding sequences of chimpanzee, rhesus macaque, canine, and bovine Cernunnos-XLF orthologs from sequence databases and sequence trace archives. Comparison of coding sequences revealed an excess of nonsynonymous substitutions consistent with positive selection on Cernunnos-XLF in the human lineage. The hotspots of adaptive evolution are concentrated around a specific structural domain, whose analogue in the structurally similar XRCC4 protein is involved in binding of another nonhomologous end-joining factor, DNA ligase IV. CONCLUSION: Cernunnos-XLF is a microcephaly-associated locus newly identified to be under adaptive evolution in humans, and possibly played a role in human brain expansion. We speculate that Cernunnos-XLF may have contributed to the increased number of brain cells in humans by efficient double strand break repair, which helps to prevent frequent apoptosis of neuronal progenitors and aids mitotic cell cycle progression. REVIEWERS: This article was reviewed by Chris Ponting and Richard Emes (nominated by Chris Ponting), Kateryna Makova, Gáspár Jékely and Eugene V. Koonin.

Journal Article↗
PubMed2006

Genome increase as a clock for the origin and evolution of life.

BACKGROUND: The size of non-redundant functional genome can be an indicator of biological complexity of living organisms. Several positive feedback mechanisms including gene cooperation and duplication with subsequent specialization may result in the exponential growth of biological complexity in macro-evolution. RESULTS: I propose a hypothesis that biological complexity increased exponentially during evolution. Regression of the logarithm of functional non-redundant genome size versus time of origin in major groups of organisms showed a 7.8-fold increase per 1 billion years, and hence the increase of complexity can be viewed as a clock of macro-evolution. A strong version of the exponential hypothesis is that the rate of complexity increase in early (pre-prokaryotic) evolution of life was at most the same (or even slower) than observed in the evolution of prokaryotes and eukaryotes. CONCLUSION: The increase of functional non-redundant genome size in macro-evolution was consistent with the exponential hypothesis. If the strong exponential hypothesis is true, then the origin of life should be dated 10 billion years ago. Thus, the possibility of panspermia as a source of life on earth should be discussed on equal basis with alternative hypotheses of de-novo life origin. Panspermia may be proven if bacteria similar to terrestrial ones are found on other planets or satellites in the solar system. REVIEWERS: This article was reviewed by Eugene V. Koonin, Chris Adami and Arcady Mushegian.

Journal Article↗
PubMed2006

Variation in fiberoptic bead-based oligonucleotide microarrays: dispersion characteristics among hybridization and biological replicate samples.

BACKGROUND: Gene expression microarray technology continues to evolve and its use has expanded into all areas of biology. However, the high dimensionality of the data makes analysis a difficult challenge. Evaluating measurements and estimating the significance of the observed differences among samples remain important issues that must be addressed for each technology platform. In this work we use a consecutive sampling method to characterize the dispersion patterns of data generated from Illumina fiberoptic bead-based oligonucleotide arrays. RESULTS: To describe general properties of the dispersion we used a linear function SD = a + bY(mean), approximating the standard deviation across arrays (Y(mean) is the mean expression of a given consecutive sample). First we examined three levels of variability: 1) same cell culture, same reverse transcription, duplicate hybridizations; 2) same cell culture, reverse transcription replicates; 3) parallel cultures. Each higher level is expected to introduce a new source of variability. We observed minor differences in the constant term: the mean values are 3.5, 3.1 and 3.5, respectively. However, the mean coefficient b increased from 0.045 to 0.147 and 0.133. We compared the coefficients derived from the consecutive sampling to those obtained from the standard deviation of individual gene expressions and found them in good agreement. In the second experiment samples we detected 11 genes with systematically different expressions between the experiment samples treated with glucose oxidase and controls and corroborated the selection using the Mann-Whitney and other tests. We also compared the consecutive sampling and coincidence method to t-test: the average percentage of consistency was above 80 for the former and below 50 for the latter. CONCLUSION: Our results indicate that the consecutive sampling method and standard deviation function provide a convenient description of the overall dispersion of Illumina arrays. We observed that the constant term of the standard deviation function is at average approximately the same for duplicate hybridization as for the assays with additional sources of variability. Furthermore, among the genes affected by glucose oxidase treatment we identified 6 genes in oxidative stress pathways and 5 genes involved in DNA repair. Finally, we noted that the consecutive sampling and coincidence test provide, under given conditions, more consistent results than the t-test. REVIEWERS: This article was reviewed by Alexander Karpikov (nominated by Mark Gerstein), Jordan King and Eugene V. Koonin.

Journal Article↗
PubMed2006

A system for studying evolution of life-like virtual organisms.

BACKGROUND: Fitness landscapes, the dependences of fitness on the genotype, are of critical importance for the evolution of living beings. Unfortunately, fitness landscapes that are relevant to the evolution of complex biological functions are very poorly known. As a result, the existing theory of evolution is mostly based on postulated fitness landscapes, which diminishes its usefulness. Attempts to deduce fitness landscapes from models of actual biological processes led, so far, to only limited success. RESULTS: We present a model system for studying the evolution of biological function, which makes it possible to attribute fitness to genotypes in a natural way. The system mimics a very simple cell and takes into account the basic properties of gene regulation and enzyme kinetics. A virtual cell contains only two small molecules, an organic nutrient A and an energy carrier X, and proteins of five types--two transcription factors, two enzymes, and a membrane transporter. The metabolism of the cell consists of importing A from the environment and utilizing it in order to produce X and an unspecified end product. The genome may carry an arbitrary number of genes, each one encoding a protein of one of the five types. Both major mutations that affect whole genes and minor mutations that affect individual characteristics of genes are possible. Fitness is determined by the ability of the cell to maintain homeostasis when its environment changes. The system has been implemented as a computer program, and several numerical experiments have been performed on it. Evolution of the virtual cells usually involves a rapid initial increase of fitness, which eventually slows down, until a fitness plateau is reached. The origin of a wide variety of genetic networks is routinely observed in independent experiments performed under the same conditions. These networks can have different, including very high, levels of complexity and often include large numbers of non-essential genes. CONCLUSION: The described system displays a rich repertoire of biologically sensible behaviors and, thus, can be useful for investigating a number of unresolved issues in evolutionary biology, including evolution of complexity, modularity and redundancy, as well as for studying the general properties of genotype-to-fitness maps. REVIEWERS: This article was reviewed by Drs. Eugene Koonin, Shamil Sunyaev and Arcady Mushegian.

Journal Article↗
PubMed2006

Refuting phylogenetic relationships.

BACKGROUND: Phylogenetic methods are philosophically grounded, and so can be philosophically biased in ways that limit explanatory power. This constitutes an important methodologic dimension not often taken into account. Here we address this dimension in the context of concatenation approaches to phylogeny. RESULTS: We discuss some of the limits of a methodology restricted to verificationism, the philosophy on which gene concatenation practices generally rely. As an alternative, we describe a software which identifies and focuses on impossible or refuted relationships, through a simple analysis of bootstrap bipartitions, followed by multivariate statistical analyses. We show how refuting phylogenetic relationships could in principle facilitate systematics. We also apply our method to the study of two complex phylogenies: the phylogeny of the archaea and the phylogeny of the core of genes shared by all life forms. While many groups are rejected, our results left open a possible proximity of N. equitans and the Methanopyrales, of the Archaea and the Cyanobacteria, and as well the possible grouping of the Methanobacteriales/Methanoccocales and Thermosplasmatales, of the Spirochaetes and the Actinobacteria and of the Proteobacteria and firmicutes. CONCLUSION: It is sometimes easier (and preferable) to decide which species do not group together than which ones do. When possible topologies are limited, identifying local relationships that are rejected may be a useful alternative to classical concatenation approaches aiming to find a globally resolved tree on the basis of weak phylogenetic markers. REVIEWERS: This article was reviewed by Mark Ragan, Eugene V Koonin and J Peter Gogarten.

Journal Article↗
PubMed2006

A computational analysis of the three isoforms of glutamate dehydrogenase reveals structural features of the isoform EC 1.4.1.4 supporting a key role in ammonium assimilation by plants.

BACKGROUND: There are three isoforms of glutamate dehydrogenase. The isoform EC 1.4.1.4 (GDH4) catalyses glutamate synthesis from 2-oxoglutarate and ammonium, using NAD(P)H. Ammonium assimilation is critical for plant growth. Although GDH4 from animals and prokaryotes are well characterized, there are few data concerning plant GDH4, even from those whose genomes are well annotated. RESULTS: A large set of the three GDH isoforms was built resulting in 116 non-redundant full polypeptide sequences. A computational analysis was made to gain more information concerning the structure-function relationship of GDH4 from plants (Eukaryota, Viridiplantae). The tested plant GDH4 sequences were the two ones known to date, those of Chlorella sorokiniana. This analysis revealed several structural features specific of plant GDH4: (i) the lack of a structure called "antenna"; (ii) the NAD(P)-binding motif GAGNVA; and (iii) a second putative coenzyme-binding motif GVLTGKG together with four residues involved in the binding of the reduced form of NADP. CONCLUSION: A number of structural features specific of plant GDH4 have been found. The results reinforce the probable key role of GDH4 in ammonium assimilation by plants. REVIEWERS: This article was reviewed by Tina Bakolitsa (nominated by Eugene Koonin), Martin Jambon (nominated by Laura Landweber), Sandor Pangor and Franck Eisenhaber.

Journal Article↗
PubMed2006

Phylogenetic inference from homologous sequence data: minimum topological assumption, strict mutational compatibility consensus tree as the ultimate solution.

BACKGROUND: For the purposes of phylogenetic inference from molecular data sets many different methods are currently offered as alternatives for researchers in phylogenetic systematics. The vast majority of these methods are based on specific topological assumptions relating to the resultant genealogical tree. Each of these has been shown to perform effectively in special conditions and for specific data sets while yielding less reliable results in other instances. Moreover, the majority of the methods include information from homoplastic characters in spite of a universally accepted agreement in their ineffectiveness for phylogenetic inference, which may often lead to inaccuracy and inconsistency. As an alternative to such methods, a strict mutational compatibility consensus tree building method as a universally applicable and reliable method is reported. RESULTS: The analysis of a data set from a previously published experimental phylogeny demonstrates the accuracy of the strict mutational compatibility consensus tree building method and illustrates its potential for obtaining unambiguous and precise results with full resolution. CONCLUSION: The universal applicability of a simplified compatibility method in its algorithmic form for phylogenetic inference is described. Firstly, dismissal of topological assumptions creates a general potential for agreement of inferred with true phylogeny. Second, exclusion of irregular characters from analysis repeatably enables construction of consistent phylogeny. Third, a direct calculation of bootstrap proportion values for individual nodes of the resulting tree is possible rather than their empirical estimation. Finally, guidance is given for empirical assessment of the sample size necessary for full genealogical resolution and significant bootstrap proportions. REVIEWERS: This article was reviewed by Yuri I. Wolf (nominated by Eugene Koonin), Arcady Mushegian and Martijn Huynen.

Journal Article↗
PubMed1997

Opportunities for psychiatry from genetic findings.

BACKGROUND: The opportunities for psychiatry deriving from available or likely genetic advances are reviewed. METHOD: Clinical implications are considered in the context of both the misconceptions and benefits associated with relevant genetic findings. RESULTS: Misconceptions include that: heritability estimates have a 'true' fixed value; a high heritability means that environmental interventions will be ineffective; a high heritability within groups means that differences between groups will also be due to genes; genetic effects are determinative; 'genetic' means single abnormal genes; genes associated with disease must be bad and justify eugenic measures; gene therapy will be widely applicable; and genetic screening of the general population will be useful. The benefits include demonstrations that: both genes and environment have an ubiquitous influence; some prevailing diagnostic assumptions are mistaken; genes influence development; the effects of nature and nurture are not separate; and environmental effects tend to be person-specific. The potential value of molecular genetics lies in elucidation of causal processes as they apply to both brain systems and nature-nurture interplay; improving diagnosis and genetic counselling; and the development of improved pharmacological interventions. CONCLUSION: Advances in genetics will make a major impact on clinical psychiatry, and should bring practical benefits for both prevention and treatment.

Causality↗
PubMed1999

"To see oursels as others see us". Aubrey Lewis's insight.

BACKGROUND: This paper takes as its starting point the paper by Aubrey Lewis entitled "The psychopathology of insight" published in 1934, unreferenced. AIMS: To attempt to explore the historical antecedents and consequences of this work. METHOD: Speculative review. RESULTS: Lewis's approach to phenomenology, contemporaneous movements in psychology and Lewis's own life and times--notably the eugenics legislation in Nazi Germany--probably shaped his conclusions. Modern concepts of insight, which emphasise neuropsychology as well as social psychology, were anticipated in Lewis's writings. CONCLUSIONS: The concept of insight has stimulated research into difficult theoretical and practical areas such as self-awareness and treatment compliance, respectively. Concern over a patient's capacity for insight has the potential to humanise psychiatry.

Cognition Disorders↗
PubMed1993

Prevalence of myotonic dystrophy in Guipúzcoa (Basque Country, Spain).

Prevalence figures for inherited neuromuscular disorders are important both for health care planning purposes and for evaluating the need for DNA diagnostic services for eugenic approaches. We screened for the prevalence of myotonic dystrophy (MyD) through extensive inquiry of neurologic and primary health services of Guipúzcoa (Basque Country, northern Spain) between 1989 and 1991. Typical adult-onset and neonatal cases and relatives at risk; suffering from a partial syndrome, were included. In the latter, molecular typing was performed with DNA probes close to the MyD gene to demonstrate the MyD gene carrier status. The high prevalence detected (26.5 cases per 100,000 population) could be explained by methodological factors, but intrinsic factors, such as a possible founder genetic effect or the quick growth of the Guipúzcoa population since the last century may contribute to one of the highest MyD prevalence in the world. In the future, the methodological basis for epidemiologic surveys of MyD must combine molecular technology with more-extensive family inquiries.

Humans↗
PubMed1997

Flight and size constraints: hovering performance of large hummingbirds under maximal loading.

As the smallest birds, hummingbirds are the only birds capable of prolonged hovering. This suggests that hovering locomotion scales unfavourably with size. Is the hovering performance of larger hummingbird species more constrained by size than that of smaller ones? Maximal load-lifting capacities of the two largest species of hummingbirds found in the United States, the blue-throated (Lampornis clemenciae, 8.4 g) and magnificent (Eugenes fulgens, 7.4 g) hummingbird, as well as the two other local small species, the black-chinned (Archilochus alexandri, 3.0 g) and rufus (Selasphorus rufus, 3.3 g) hummingbird, were determined under conditions of short-burst performance. The power reserves of hummingbirds are substantial relative to normal hovering performance. The two large species lifted maximal loads close to twice their body mass for a very brief duration of over 0.4 s. The small species lifted maximal loads approximately equal to their own mass with a longer duration of over 0.6 s. For the two large species under maximal loading, estimates of burst muscle mass-specific mechanical power output assuming perfect elastic energy storage averaged 309 W kg-1, compared with 75 W kg-1 during free hovering without loading. For the two small species, these values were 228 W kg-1 and 88 W kg-1, respectively. The differences in aerodynamic force production and power output between the large and small size classes occur despite their similar wing stroke velocity. This indicates that, during burst performance in these hummingbirds, the larger ones had a higher load-lifting capacity and generated more muscle power. In spite of the twofold difference in body mass, both large and small hummingbirds have evolved to become potent aerial competitors in order to exploit their common food resource, nectar. Both size classes have evolved to cope with the multi-dimensional effects of size constraining their aerodynamics, muscle mechanics, metabolism and ecology.

Animals↗