Attentional focus is an area that has garnered considerable attention in the sport psychology and motor performance literature. This is unsurprising given that attentional focus has been directly linked to performance outcomes and is susceptible to coaching input. While research has amassed supporting benefits of an external focus of attention on motor performance using verbal instruction, other studies have challenged the notion that an EFA is more beneficial than an internal focus of attention for sport-related performance. Further, it is unclear (...) what type of instructions may serve to direct an athlete to an EFA and, in particular, if coaching can utilize imagery to orient an athlete toward an EFA. In the present exploratory study, we evaluate the effectiveness of instruction to improve free-throw shooting performance with an emphasis on an EFA brought about by implementing techniques borrowed from the imagery literature. This was tested relative to an alternate approach with an IFA induced through an emphasis on technique, devised to more closely resemble input typical of coach-to-athlete instruction. Twenty-five male and female university basketball players completed both conditions in a fully counterbalanced within-subject design. Results confirmed that participants in the EFA imagery condition had greater shooting accuracy than in the IFA technique condition. The study provides initial evidence that EFA coaching can borrow from imagery techniques, though future research should elucidate the underlying mechanisms of the effect. (shrink)

This volume centers on debates about how far moral judgments bind across traditions and epochs. Nowadays such debates appear especially volatile, both in popular culture and intellectual discourse: although there is increasing agreement that the moral and political criteria invoked in human rights documents possess cross-cultural force, many modern and postmodern developments erode confidence in moral appeals that go beyond a local consensus or apply outside a particular community. Often the point of departure for discussion is the Enlightenment paradigm of (...) a common morality, in which it is assumed that certain unchanging beliefs inhere in the structure of human reason. Whereas some thinkers continue to defend this paradigm, others modify it in diverse ways without abandoning entirely the attempt to address a universal audience, and still others jettison virtually all of its distinguishing features. Exhibiting a range of positions Western participants take in these debates, this volume seeks to advance the substance of the debates themselves without prejudging the outcome. Rival assessments of the Enlightenment paradigm are offered from various philosophical and theological points of view. In addition to the editors, the contributors include Robert Merrihew Adams, Annette C. Baier, Alan Donagan, Margaret A. Farley, Alan Gewirth, David Little, Richard Rorty, Jeffrey Stout, and Lee H. Yearley. (shrink)

ONE OF THE MOST prominent theorists of anarcho-capitalism is Hans- Hermann Hoppe. In what is perhaps his most famous result, the argumentation ethic for libertarianism, he purports to establish an a priori defense of the justice of a social order based exclusively on pri- vate property. Hoppe claims that all participants in a debate must presuppose the libertarian principle that every person owns himself, since the principle underlies the very concept of argumentation. Some libertarians (e.g., Rothbard 1988) have celebrated Hoppe’s (...) argument as the final nail in the coffin for collectivism of any type; following Hoppe, they believe that to deny the libertarian ethic is not only wrong, but also internally contradictory. On the other hand, a number of other prominent libertarians characterized Hoppe’s initial statement of his case as “one muddle after another” (Steele 1988, p. 47) or “a tissue of bald assertions” (Yeager 1988, p. 45). (shrink)

The prelims comprise: Introduction A (re)Defmition of what Human Gene Therapy is About Neurological Gene Therapy Ethics and Gene Therapy Acknowledgments Notes.

Children's competence to refuse or consent to medical treatment or surgery tends to be discussed in terms of the child's ability or maturity. This paper argues that the social context also powerfully influences the child's capacity to consent. Inner attributes and external influences are discussed using an analogy of the genes and the stars.

Gene therapy approaches have great promise in the treatment of neurodegenerative disorders and malignant brain tumors. Neuwelt et al. review available viral-mediated gene therapy methods and their blood-brain-barrier (BBB) disruption delivery technique, briefly mentioning nonviral mediated gene therapy methods. This commentary discussed the BBB disruption delivery technique, viral and nonviral mediated gene therapy approaches to Parkinson's disease, and the potential use of antisense oligo to suppress malignant brain tumors.

The heme‐containing cytochromes P‐450 are a ubiquitous family of monooxygenase isozymes responsible for the oxidative metabolism of a wide variety of endogenous as well as exogenous compounds. Many of the compounds metabolized by this enzyme system are effectively detoxified and converted to derivatives more easily eliminated from the organism. However, some compounds can be activated to reactive species capable of eliciting a cascade of toxic lesions, including cancer. Since its discovery nearly 30 years ago, the cytochrome P‐450 enzyme system has (...) received a great deal of attention, particularly in the areas of their mechanisms of metabolism, range of substrate specificity, the purification and characterization of the multiple isozymes and, more recently, the regulation of expression of specific forms. This review will discuss current notions concerning the expression of at least one cytochrome P‐450 isozyme and future directions that should lead to a more complete understanding of cytochrome P‐450 gene expression in general, particularly as it impacts upon biochemical pharmacology. (shrink)

The physical properties of human beings and other organisms as well as their social behavioral traits are manifestations of both genetic inheritance and environment. Recent behavioral research has indicated that certain characteristics or behaviors—such as schizophrenia, divorce, and homosexuality—are highly heritable and are not governed exclusively by social environment. A balanced view of human behavior includes the effects of social learning as well as of genetically determined behavior. A new paradigm promotes enhanced understanding and acceptance of human diversity, be it (...) cultural, racial, or sexual, and has the potential to unite scientists and theologians by creating common grounds of understanding. (shrink)

Abstract:Gene editors such as CRISPR could be used to create stronger, faster, or more resilient nonhuman animals. This is of keen interest to people who breed, train, race, and profit off the millions of animals used in sport that contribute billions of dollars to legal and illegal economies across the globe. People have tried for millennia to perfect sport animals; CRISPR proposes to do in one generation what might have taken decades previously. Moreover, gene editing may facilitate enhancing (...) animals’ capacities beyond their typical limits. This paper describes the state of animal use and engineering for sport, examines the moral status of animals, and analyzes current and future ethical issues at the intersection of animal use, gene editing, and sports. We argue that animal sport enthusiasts and animal welfarists alike should be concerned about the inevitable use of CRISPR in sport animals. Though in principle CRISPR could be used to improve sport animals’ well-being, we think it is unlikely in practice to do so. (shrink)

Clinical gene transfer research has both a unique history and a complex and layered system of research oversight, featuring a unique review body, the Recombinant DNA Advisory Committee. This paper briefly describes the process of decision-making about clinical GTR, considers whether the questions, problems, and issues raised in clinical GTR are unique, and concludes by examining whether the RAC's oversight is a useful model that should be reproduced for other similar areas of clinical research.Clinical GTR is governed by the (...) same oversight system as most clinical trials, with a significant addition: the RAC. Like other research with human subjects, GTR, if it is affiliated with a federally funded institution, must be approved by an institutional review board whose activities are governed by the common rule, that is, the federal regulations for protection of human subjects in research. Like other research intended to produce a drug, device, or biologic to be marketed in the United States, GTR is also overseen by the Food and Drug Administration. (shrink)

The prelims comprise: Germline Gene Therapy Genetic Enhancements The Genome and the Normative Status of Human Nature Conclusion Notes.

The incredible achievements of modern scientific theories lead most of us to embrace scientific realism: the view that our best theories offer us at least roughly accurate descriptions of otherwise inaccessible parts of the world like genes, atoms, and the big bang. In Exceeding Our Grasp, Stanford argues that careful attention to the history of scientific investigation invites a challenge to this view that is not well represented in contemporary debates about the nature of the scientific enterprise. The historical record (...) of scientific inquiry, Stanford suggests, is characterized by what he calls the problem of unconceived alternatives. Past scientists have routinely failed even to conceive of alternatives to their own theories and lines of theoretical investigation, alternatives that were both well-confirmed by the evidence available at the time and sufficiently serious as to be ultimately accepted by later scientific communities. Stanford supports this claim with a detailed investigation of the mid-to-late 19th century theories of inheritance and generation proposed in turn by Charles Darwin, Francis Galton, and August Weismann. He goes on to argue that this historical pattern strongly suggests that there are equally well-confirmed and scientifically serious alternatives to our own best theories that remain currently unconceived. Moreover, this challenge is more serious than those rooted in either the so-called pessimistic induction or the underdetermination of theories by evidence, in part because existing realist responses to these latter challenges offer no relief from the problem of unconceived alternatives itself. Stanford concludes by investigating what positive account of the spectacularly successful edifice of modern theoretical science remains open to us if we accept that our best scientific theories are powerful conceptual tools for accomplishing our practical goals, but abandon the view that the descriptions of the world around us that they offer are therefore even probably or approximately true. (shrink)

The growth factor progranulin (PGRN) regulates cell division, survival, and migration. PGRN is an extracellular glycoprotein bearing multiple copies of the cysteine‐rich granulin motif. With PGRN family members in plants and slime mold, it represents one of the most ancient of the extracellular regulatory proteins still extant in modern animals. PRGN has multiple biological roles. It contributes to the regulation of early embryogenesis, to adult tissue repair and inflammation. Elevated PGRN levels often occur in cancers, and PGRN immunotherapy inhibits the (...) growth of hepatic cancer xenografts in mice. Recent studies have demonstrated roles for PGRN in neurobiology. An autosomal dominant mutation in GRN, the gene for PGRN, leads to neuronal atrophy in the frontal and temporal lobes, resulting in the disease frontotemporal lobar dementia. In this review we will discuss current knowledge of the multifaceted biology of PGRN. (shrink)

The computational genomics community has come increasingly to rely on the methodology of creating annotations of scientific literature using terms from controlled structured vocabularies such as the Gene Ontology (GO). We here address the question of what such annotations signify and of how they are created by working biologists. Our goal is to promote a better understanding of how the results of experiments are captured in annotations in the hope that this will lead to better representations of biological reality (...) through both the annotation process and ontology development, and in more informed use of the GO resources by experimental scientists. (shrink)

We discuss the impact of horizontal gene transfer (HGT) on phylogenetic reconstruction and taxonomy. We review the power of HGT as a creative force in assembling new metabolic pathways, and we discuss the impact that HGT has on phylogenetic reconstruction. On one hand, shared derived characters are created through transferred genes that persist in the recipient lineage, either because they were adaptive in the recipient lineage or because they resulted in a functional replacement. On the other hand, taxonomic patterns (...) in microbial phylogenies might also be created through biased gene transfer. The agreement between different molecular phylogenies has encouraged interpretation of the consensus signal as reflecting organismal history or as the tree of cell divisions; however, to date the extent to which the consensus reflects shared organismal ancestry and to which it reflects highways of gene sharing and biased gene transfer remains an open question. Preferential patterns of gene exchange act as a homogenizing force in creating and maintaining microbial groups, generating taxonomic patterns that are indistinguishable to those created by shared ancestry. To understand the evolution of higher bacterial taxonomic units, concepts usually applied in population genetics need to be applied. (shrink)

Behavioural phenotypes have been explained by genetic and environmental factors (E) and their interaction. Here we suggest a rethinking of the E factor. Passively incurred environmental influences (E pass) and actively copied information and behaviour (E act) may be distinguished at shared and non-shared level. We argue that E act underlies mutation and selection and is the base of gene-independent heritability.

In lieu of an abstract, here is a brief excerpt of the content:Reviewed by:Mimesis: Culture, Art, SocietyGene FendtMimesis: Culture, Art, Society, by Gunter Gebauer and Christoph Wulf; translated by Don Reneau; 400 pp. Berkeley: University of California Press, 1995, $45.00 cloth, $18.00 paper.The purpose of this book is to develop “a historical reconstruction of important phases in the development of mimesis” (p. 1) from a brief discussion of its pre-Platonic Greek significance through contemporary thinkers. It is, then, not strictly a (...) philosophical text, as are most of the texts and authors the book takes up. It is, however, a significant effort in the history of ideas, and as such it is shot through with traces of the traditional tropes, shaping power, ideology, and even social relations of that discipline, particularly as it is practiced in the venerable school of German scholarship. That is, the structure, tone, and argument of the book are shaped mimetically. This book’s problematic is, then, not simply historical, as Republic’s problem with the poets is not simply philosophical. Rather, both books partake of mimesis, even while each one aims to criticize or set forth the concept’s historical development.Let this stand as notice of a deep philosophical problem with the method of historical criticism. In fairness we should note that the authors are not unconscious of their difficulty here: “The fact that mimesis cannot be represented without the use of mimetic processes poses the fundamental problem of theory formation in reference to our object. What is the relation between the representational and the represented world? Is the representation of representation structurally equivalent to simple representation?” (p. 21). The authors hope to moot the power of those questions, if not the questions themselves, by attending “first of all to representations of mimesis found in texts best selected for that purpose and only afterward begin to offer considerations of a more generalizing nature” (p. 21). Their reasoning and choice of texts here is the traditional trope of the discipline: a mimema. Among other things, this methodos requires that the authors treat Girard as developing a “literary critical examination of [mimesis in] nineteenth and twentieth century novels” (p. 359n1) and a “new ordering of nineteenth century social relations” (p. 235), rather than, as he claims, a comprehensive anthropological thesis. At least, this method requires treating the former as essential, and the latter as less justifiable, for if Girard’s anthropological thesis about mimesis were justifiable a history of the idea of mimesis would be merely a heresiology. This problem can be restated mutatis mutandis for such thinkers as Plato and Augustine, whose theses—if they have theses—about mimesis are deeply anthropological.Two further questions arise early on and remain at the end. If, as the authors hold (and show), “the concept of mimesis necessarily loses its intellectual centrality with the rise of rational thought,” so much so that “the field of art, which comes to be regarded in the process as autonomous, undergoes a complete and fundamental restructuring” (p. 3), must we not begin to [End Page 199] suspect—as recent philosophers like Derrida attempt to show—that there is a dialectical relationship between the intentional, truth-functional relations of modern rational thought and the mimetic, unformalizable and “ambivalent” (pp. 2–3) processes of mimesis? Rather than conclude that “the question what is mimesis? is one which demonstratively leads to error” (p. 309), does it not begin to seem that intentional representation, as most visible in science, and mimetic assimilations, as most obviously effective in art, are together the necessary dialectical elements of culture, art and science? While it seems that the rise of rational scientific thought pushes mimesis to the social fringes of the arts, isn’t scientific activity and writing still just as much subject, and just as much a product, of the power of mimesis as art? Similarly art is just as bound as science to “probability” or “the convincing impossibility,” to recall Aristotle. This idea is not entirely foreign to the book; it appears subliminally as a plausible explication of the work of theorists like Benjamin and Adorno (pp. 267–93).The third difficulty is a question about selection. As in Auerbach’s renowned precursor, Wulf... (shrink)

In the course of an immune response, antibodies undergo affinity maturation in order to increase their efficiency in neutralizing foreign invaders. Affinity maturation occurs by the introduction of multiple point mutations in the variable region gene that encodes the antigen binding site. This somatic hypermutation is restricted to immunoglobulin genes and occurs at very high rates. The precise molecular basis of this process remains obscure. However, recent studies using a variety of in vivo and in vitro systems have revealed (...) important regulatory regions, base motifs that are preferred targets of mutation and evidence that transcription may play an active role in hypermutation. BioEssays 20:227–234, 1998. © 1998 John Wiley & Sons, Inc. (shrink)

One of the unique insights provided by the growing number of fully sequenced genomes is the pervasiveness of gene duplication and gene loss. Indeed, several metrics now suggest that rates of gene birth and death per gene are only 10–40% lower than nucleotide substitutions per site, and that per nucleotide, the consequent lineage‐specific expansion and contraction of gene families may play at least as large a role in adaptation as changes in orthologous sequences. While (...) class='Hi'>gene family evolution is pervasive, it may be especially important in our own evolution since it appears that the “revolving door” of gene duplication and loss has undergone multiple accelerations in the lineage leading to humans. In this paper, we review current understanding of gene family evolution including: methods for inferring copy number change, evidence for adaptive expansion and adaptive contraction of gene families, the origins of new families and deaths of previously established ones, and finally we conclude with a perspective on challenges and promising directions for future research. (shrink)

Source preference in which equally distributed risks may be valued differently has been receiving increasing attention. Using subjects recruited in Berkeley, Fox and Tversky demonstrate a familiarity bias in source preference—betting on a less than even-chance event based on San Francisco temperature is valued more than betting on a better than even-chance event based on Istanbul temperature. Neophobia is associated with the amygdala which is GABA-rich and is known to be modulated by benzodiazepines as anxiolytic agents that enhance the activity (...) of the GABAA receptor in processing anxiety and fear. This leads to our hypothesis that familiarity bias in decision making may be explained by polymorphic variations in this receptor mediated by anxiety regulation in the amygdala. In two companion studies involving Beijing-based subjects, we examine 10 single nucleotide polymorphisms of GABRB2 and find 7 SNPs each showing negative association between familiarity bias—preference for betting on parity of Beijing temperature over Tokyo temperature—and having at least one minor allele. In an imaging genetics study of a subsample of subjects based on the SNP with the most balanced allelic distribution, we find that subjects’ familiarity bias in terms of risk aversion towards bets on the parity of the temperature of 20 Chinese cities is negatively associated with their post-scanning familiarity ratings of the cities only for those with no minor allele in this SNP. Moreover, familiarity bias is positively associated with activation in the right amygdala along with the brain’s attention networks. Overall, our findings help discriminate between ambiguity aversion and familiarity bias in source preference and supports our gene–brain–behavior hypothesis of GABAergic modulation of amygdala activation in response to familiarity towards the source of uncertainty. (shrink)

The release of genetically engineered organisms into the shared environment raises scientific, ethical, and societal issues. Using some form of democratic deliberation to provide the public with a voice on the policies that govern these technologies is important, but there has not been enough attention to how we should connect public deliberation to the existing regulatory process. Drawing on lessons from previous public deliberative efforts by U.S. federal agencies, we identify several practical issues that will need to be addressed if (...) relevant federal agencies are to undertake public deliberative activities to inform decision‐making about gene editing in the wild. We argue that, while agencies may have institutional capacity to undertake public deliberative activities, there may not be sufficient political support for them to do so. Advocates of public deliberation need to make a stronger case to Congress about why federal agencies should be encouraged and supported to conduct public deliberations. (shrink)

This paper responds to the essay reviews by David Haig, Alan Love and Rachel Brown of my recently published book “Homology, Genes and Evolutionary Innovation”. The issues addressed here relate to: the notion of classes and individuals, issues of explanatory value of adaptive and structuralist explanations in evolutionary biology, the role of homology in evolutionary theory, the limits of a pluralist stance vis a vis alternative explanations of homology, as well as the question whether and to what extend the perspective (...) laid out in HGEI can be or should be transferred to other branches of study, like comparative behavioral biology. (shrink)

Throughout evolution, there has been interaction and exchange between RNA pools in the environment, and DNA and RNA pools of eukaryotic organisms. Metagenomic and metatranscriptomic sequencing of invertebrate hosts and their microbiota has revealed a rich evolutionary history of RNA virus shuttling between species. Horizontal transfer adapted the RNA pool for successful future interactions which lead to zoonotic transmission and detrimental RNA viral pandemics like SARS‐CoV2. In eukaryotes, noncoding RNA (ncRNA) is an established mechanism derived from prokaryotes to defend against (...) viral attack through innate immunity and regulation of host‐derived mRNA. Transgenerational inheritance of ncRNA is evidence for feedforward adaptive immunity and epigenetically encoded environmental change across generations, which may explain the ‘‘missing heritability’’ of common disease. Causal graph theory and the Price Equation can model epigenetic inheritance involving dynamic internal and external RNA pools. Experimental designs should include metatranscriptomic analyses to understand how ncRNA responds to rapidly changing environmental conditions, within and between organisms, and across generations. (shrink)

Niche construction is a potentially important concept for the human behavioural sciences but we question how it differs from models of gene-culture coevolution and whether it can be developed in the detailed ways that will be necessary if it is going to make a significant contribution to the human behavioural sciences.

The aim of this paper is to explore in the light of recent scientific discoveries, coupled with a return to biblical orthodoxy, the question of the Fall, and the apparent intergenerational conditions of original sin. This is the human condition – East of Eden. Invoking Darwin's theory of evolution through natural selection from random mutation as a means of repudiating the existence of original sin can no longer be sustained, scientifically; the biology of horizontal gene transfer, transgenerational epigenetics, accelerated (...) evolution and biological plasticity has rendered Darwinism grounded in a Naturalistic methodology an inadequate explanation. If humanity is ‘born this way’ – mired in sin – have we condemned ourselves and our children to this status? How does this affect the relationship between biology and free will, between a form of predestination and decision-making? Therefore, this paper is towards an understanding of the ontology of the original, or first, sin, and is a biblical and scientific exploration of postlapsarian humanity's self-willed state, ‘East of Eden.’. (shrink)

The metabolic organization of both normal and malignant prostate cellular phenotypes involves some unusual and surprising features. In particular, both conditions exhibit ratios of NADH/NAD+ and NADPH/NADP+ charactersitic of high oxidative states despite a chronic shortage of O2 in both conditions. In this paper, we observe that, in prostate cancer cells, the oxidizing power of the fatty acid synthesis (FAS) pathway is so large that redox is stabilized more favorably (more oxidized) than in normal prostate cells. This FAS‐facilitated redox improvement (...) occurs despite the fact that malignant cells are more O2 limited and therefore express more hypoxia inducible factor 1 (HIF1) and express hypoxia‐regulated genes more robustly. This unusual metabolic situation clearly separates direct regulatory effects of redox balance from secondary effects of hypoxia per se. The physiological significance of the FAS pathway is thus the harnessing of its oxidizing power for improving redox balance despite conditions of more extreme hypoxia. Similar hypoxia defense strategies are found in animal species that are unusually tolerant to oxygen lack. Our hypothesis is that the metabolic organization in the “low zinc, low citrate” phenotype reflects an hypoxia‐defense adaptation geared toward redox balance, with prostate cancer cells being relatively more oxidized, even if more hypoxic, than normal prostate cells. Recognition and understanding of these redox balancing and hypoxia defense functions may lead to new intervention strategies by developing new intracellular targets for prostate cancer therapy. BioEssays 24:749–757, 2002. © 2002 Wiley Periodicals, Inc. (shrink)