The larval arms of echinoid plutei are used for locomotion and feeding. They are composed of internal calcite skeletal rods covered by an ectoderm layer bearing a ciliary band. Skeletogenesis includes an autonomous molecular differentiation program in primary mesenchyme cells (PMCs), initiated when PMCs leave the vegetal plate for the blastocoel, and a patterning of the differentiated skeletal units that requires molecular cues from the overlaying ectoderm. The arms represent a larval feature that arose in the echinoid lineage during the (...) Paleozoic and offers a subject for the study of gene co-option in the evolution of novel larval features. We isolated new molecular markers in two closely related but differently developing species, Heliocidaris tuberculata and Heliocidaris erythrogramma. We report the expression of a larval arm-associated ectoderm gene tetraspanin, as well as two new PMC markers, advillin and carbonic anhydrase. Tetraspanin localizes to the animal half of blastula stage H. tuberculata and then undergoes a restriction into the putative oral ectoderm and future location of the postoral arms, where it continues to be expressed at the leading edge of both the postoral and anterolateral arms. In H. erythrogramma, its expression initiates in the animal half of blastulae and expands over the entire ectoderm from gastrulation onward. Advillin and carbonic anhydrase are upregulated in the PMCs postgastrulation and localized to the leading edge of the growing larval arms of H. tuberculata but do not exhibit coordinated expression in H. erythrogramma larvae. The tight spatiotemporal regulation of these genes in H. tuberculata along with other ontogenetic and phylogenetic evidence suggest that pluteus arms are novel larval organs, distinguishable from the processes of skeletogenesis per se. The dissociation of expression control in H. erythrogramma suggest that coordinate gene expression in H. tuberculata evolved as part of the evolution of pluteus arms, and is not required for larval or adult development. (shrink)

The Health Protection Agency has recently attempted to create a postmortem tissue archive to determine the prevalence of abnormal prion protein. The success of this archive was prevented because the Health Protection Agency could not convince coroners to support the study’s methodology and participate on that basis. The findings of this paper detail and support the view that the Coroners’ Society of England and Wales’s refusal to participate was misguided and failed to appreciate that coroners have a moral obligation to (...) protect public health. Measures to assist coroners in fulfilling this role are proposed. (shrink)

Psychiatric disorders present distinct clinical challenges which are partly attributable to their multifactorial aetiology and the absence of laboratory tests that can be used to confirm diagnosis or predict risk. Psychiatric disorders are highly heritable, but also polygenic, with genetic risk conferred by interactions between thousands of variants of small effect that can be summarized in a polygenic risk score. We discuss four areas in which the use of polygenic risk scores in psychiatric research and clinical contexts could have ethical (...) implications. First, there is concern that clinical use of polygenic risk scores may exacerbate existing health inequities. Second, research findings regarding polygenic risk could be misinterpreted in stigmatising or discriminatory ways. Third, there are concerns associated with testing minors as well as eugenics concerns elicited by prenatal polygenic risk testing. Fourth, potential challenges that could arise with the feedback and interpretation of high polygenic risk for a psychiatric disorder would require consideration. While there would be extensive overlap with the challenges of feeding back genetic findings in general, the potential clinical use of polygenic risk scoring warrants discussion in its own right, given the recency of this possibility. To this end, we discuss how lay interpretations of risk and genetic information could intersect. Consideration of these factors would be necessary for ensuring effective and constructive communication and interpretation of polygenic risk information which, in turn, could have implications for the uptake of any therapeutic recommendations. Recent advances in polygenic risk scoring have major implications for its clinical potential, however, care should be taken to ensure that communication of polygenic risk does not feed into problematic assumptions regarding mental disorders or support reductive interpretations. (shrink)

Comprehending the origin of marine invertebrate larvae remains a key domain of research for evolutionary biologists, including the repeated origin of direct developmental modes in echinoids. In order to address the latter question, we surveyed existing evidence on relationships of homology between the ectoderm territories of two closely related sea urchin species in the genus Heliocidaris that differ in their developmental mode. Additionally, we explored a recently articulated idea about homology called ‘organizational homology’ (Muller 2003. In: Muller GB, Newman SA, (...) editors. Origination of organismal form: beyond the gene in developmental and evolutionary biology. Cambridge, MA: A Bradford Book, The MIT Press. p 51–69. ) in the context of this specific empirical case study. Applying the perspective of organizational homology to our experimental system of congeneric echinoids has led us to a new hypothesis concerning the ectoderm evolution in these species. The extravestibular ectoderm of the direct developer Heliocidaris erythrogramma is a novel developmental territory that arose as a fusion of the oral and aboral ectoderm territories found in indirect developing echinoids such as Heliocidaris tuberculata. This hypothesis instantiates a theoretical principle concerning the origin of developmental modules, ‘integration’, which has been neglected because the opposite theoretical principle, ‘parcellation’, is more readily observable in events such as gene duplication and divergence (Wagner 1996. Am Zool 36:36–43). J. Exp. Zool. (Mol. Dev. Evol.) 306B:18– 34, 2006. (shrink)

The origin of marine invertebrate larvae has been an area of controversy in developmental evolution for over a century. Here, we address the question of whether a pelagic “larval” or benthic “adult” morphology originated first in metazoan lineages by testing the hypothesis that particular gene co-option patterns will be associated with the origin of feeding, indirect developing larval forms. Empirical evidence bearing on this hypothesis is derivable from gene expression studies of the sea urchin larval gut of two closely related (...) but differently developing congenerics, Heliocidaris tuberculata (feeding indirect-developing larva) and H. erythrogramma (nonfeeding direct developer), given two subsidiary hypotheses. (1) If larval gut gene expression in H. tuberculata was co-opted from an ancestral adult expression pattern, then the gut expression pattern will remain in adult H. erythrogramma despite its direct development. (2) Genes expressed in the larval gut of H. tuberculata will not have a coordinated expression pattern in H. erythrogramma larvae due to loss of a functional gut. Five structural genes expressed in the invaginating archenteron of H. tuberculata during gastrulation exhibit substantially different expression patterns in H. erythrogramma with only one remaining endoderm specific. Expression of these genes in the adult of H. erythrogramma and larval gut of H. tuberculata, but not in H. erythrogramma larval endoderm, supports the hypothesis that they first played roles in the formation of adult structures and were subsequently recruited into larval ontogeny during the origin and evolution of feeding planktotrophic deuterostome larvae. (shrink)

Neuroscientists are searching for the engram within the conceptual framework established by John Locke's theory of mind. This framework was elaborated before the development of information theory, before the development of information processing machines and the science of computation, before the discovery that molecules carry hereditary information, before the discovery of the codon code and the molecular machinery for editing the messages written in this code and translating it into transcription factors that mark abstract features of organic structure such as (...) anterior and distal. The search for the engram needs to abandon Locke's conceptual framework and work within a framework informed by these developments. The engram is the medium by which information extracted from past experience is transmitted to the computations that inform future behavior. The information-conveying symbols in the engram are rapidly generated in the course of computations, which implies that they are molecules. (shrink)

ABSTRACTFacial stimuli are widely used in behavioural and brain science research to investigate emotional facial processing. However, some studies have demonstrated that dynamic expressions elicit stronger emotional responses compared to static images. To address the need for more ecologically valid and powerful facial emotional stimuli, we created Dynamic FACES, a database of morphed videos from younger, middle-aged, and older adults displaying naturalistic emotional facial expressions. To assess adult age differences in emotion identification of dynamic stimuli and to provide normative ratings (...) for this modified set of stimuli, healthy adults categorised for each video the emotional expression displayed, rated the expression distinctiveness, estimated the age of the face model, and rated the naturalness of the expression. We found few age differences in emotion identification when using dynamic stimuli. On... (shrink)

Chad A Witt, Ramsey R Hachem Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, Washington University School of Medicine, Saint Louis, MO, USA: The role of donor-specific antibodies to human leukocyte antigens and the burden of antibody-mediated rejection in lung transplantation remain enigmatic. Over the past several years, evidence has been emerging that humoral immunity plays an important role in the development of both acute and chronic lung allograft dysfunction. Multiple case reports and case series have identified (...) lung allograft recipients with clinical findings consistent with acute AMR. However, there is currently no widely accepted definition for AMR in lung transplantation, and this has been a significant barrier to furthering our understanding of this form of rejection. Nonetheless, the development of DSA after transplantation has consistently been identified as an independent risk factor for persistent and high-grade acute cellular rejection and CLAD. This has raised the possibility that chronic AMR may be a distinct phenotype of CLAD although evidence supporting this paradigm is still lacking. Additionally, antibodies to lung-restricted self-antigens have been associated with primary graft dysfunction early and the development of CLAD late after transplantation, and emerging evidence underscores significant interactions between autoimmunity and alloimmunity after transplantation. There is currently an active International Society for Heart and Lung Transplantation working group that is developing an operational definition for AMR in lung transplantation. This will be critical to improve our understanding of this form of rejection and conduct clinical trials to identify optimal treatment strategies. This review will summarize the literature on DSA and AMR in lung transplantation and discuss the impact of antibodies to self-antigens on lung allograft dysfunction. Keywords: antibody-mediated rejection, donor-specific antibodies, lung transplantation. (shrink)

This paper examines the identity of Asian swamp buffalo (Bubalus bubalis) from different value orientations. Buffalo were introduced into Northern (Top End) Australia in the early nineteenth century. A team of transdisciplinary researchers, including an ethicist, has been engaged in field research on feral buffalo in Arnhem Land over the past three years. Using historical documents, literature review, field observations, interviews with key informants, and interaction with the Indigenous land owners, an understanding of the diverse views on the scientific, cultural, (...) and economic significance of buffalo was obtained. While the diverse stakeholders in buffalo exploitation and management have historically delivered divergent value orientations on the nature of the human–buffalo relationship, we argue that over time there is the possibility of values and ethical convergence. Such convergence is possible via transdisciplinary and transcultural agreement on the value stances that constitute the construction of the being or identity of buffalo in the face of the overwhelming need to manage population density and gross numbers. (shrink)

_Sonoran Desert, Stuart Hameroff and Alwyn Scott awoke from their_ _siestas to take margaritas in the shade of a ramada. On a nearby_ _table, a tape recorder had accidentally been left on and the following_ _is an unedited transcript of their conversation._.

“Tell me," Wittgenstein once asked a friend, "why do people always say, it was natural for man to assume that the sun went round the earth rather than that the earth was rotating?" His friend replied, "Well, obviously because it just looks as though the Sun is going round the Earth." Wittgenstein replied, "Well, what would it have looked like if it had looked as though the Earth was rotating?” What would it have looked like if we looked at all (...) sciences from the viewpoint of Wittgenstein’s philosophy? Wittgenstein is undoubtedly one of the most influential philosophers of the twentieth century. His complex body of work has been analysed by numerous scholars, from mathematicians and physicists, to philosophers, linguists, and beyond. This volume brings together some of his central perspectives as applied to the modern sciences and studies the influence they may have on the thought processes underlying science and on the world view it engenders. The contributions stem from leading scholars in philosophy, mathematics, physics, economics, psychology and human sciences; all of them have written in an accessible style that demands little specialist knowledge, whilst clearly portraying and discussing the deep issues at hand. (shrink)

Papers presented at a symposium on philosophy and medicine at the Institute for the Medical Humanities at the University of Texas Medical Branch in 1974 were published in the inaugural volume of this series.

Objectives: To assess French district nurses’ opinions towards euthanasia and to study factors associated with these opinions, with emphasis on attitudes towards terminal patients.Design and setting: An anonymous telephone survey carried out in 2005 among a national random sample of French district nurses.Participants: District nurses currently delivering home care who have at least 1 year of professional experience. Of 803 district nurses contacted, 602 agreed to participate .Main outcome measures: Opinion towards the legalisation of euthanasia , attitudes towards terminal patients (...) .Results: Overall, 65% of the 602 nurses favoured legalising euthanasia. Regarding associated factors, this proportion was higher among those who discuss end-of-life issues with terminal patients , who consider competent patients should always be told their prognosis and who value the role of advance directives and surrogates in end-of-life decision-making for incompetent patients . Women and older nurses were less likely to favour legalising euthanasia, as were those who believed in a god who masters their destiny.Conclusions: French nurses are more in favour of legalising euthanasia than French physicians; these two populations contrast greatly in the factors associated with this support. Further research is needed to investigate how and to what extent such attitudes may affect nursing practice and emotional well-being in the specific context of end-of-life home care. (shrink)