The recent sociobiology debate has raised fundamental and previously unresolved conceptual problems. Evolutionary Instability - Logical and Material Aspects of a Unified Theory of Biosocial Evolution - offers ap- proaches for their solution. The scientific applications comprise the dynamics and evolutionary instability of hierarchically organized systems, especially systems of interacting behavioural phenotypes in animals and man. The technical apparatus is thoroughly explained in intuitive terms within the text, and illustrated by numerous familiar examples and graphical representations, supplemented by (...) an informal summary and discussion. The analyses offer new theoretical perspectives to such diverse fields as philosophy of science, evolutionary biology, general system theory and sociology. (shrink)

Genetic mosaicism has long been linked to aging, and several hypotheses have been proposed to explain the potential connections between mosaicism and susceptibility to cancer. It has been proposed that mosaicism may disrupt tissue homeostasis by affecting intercellular communications and releasing microenvironmental constraints within tissues. The underlying mechanisms driving these tissue‐level influences remain unidentified, however. Here, we present an evolutionary perspective on the interplay between mosaicism and cancer, suggesting that the tissue‐level impacts of genetic mosaicism can be attributed to Indirect (...) Genetic Effects (IGEs). IGEs can increase the level of cellular stochasticity and phenotypic instability among adjacent cells, thereby elevating the risk of cancer development within the tissue. Moreover, as cells experience phenotypic changes in response to challenging microenvironmental conditions, these changes can initiate a cascade of nongenetic alterations, referred to as Indirect non‐Genetic Effects (InGEs), which in turn catalyze IGEs among surrounding cells. We argue that incorporating both InGEs and IGEs into our understanding of the process of oncogenic transformation could trigger a major paradigm shift in cancer research with far‐reaching implications for practical applications. (shrink)

Despite its widespread existence, the adaptive role of aneuploidy (the abnormal state of having an unequal number of different chromosomes) has been a subject of debate. Cellular aneuploidy has been associated with enhanced resistance to stress, whereas on the organismal level it is detrimental to multicellular species. Certain aneuploid karyotypes are deleterious for specific environments, but karyotype diversity in a population potentiates adaptive evolution. To reconcile these paradoxical observations, this review distinguishes the role of aneuploidy in cellular versus organismal evolution. (...) Further, it proposes a population genetics perspective to examine the behavior of aneuploidy on a populational versus individual level. By altering the copy number of a significant portion of the genome, aneuploidy introduces large phenotypic leaps that enable small cell populations to explore a wide phenotypic landscape, from which adaptive traits can be selected. The production of chromosome number variation can be further increased by stress‐ or mutation‐induced chromosomal instability, fueling rapid cellular adaptation. (shrink)

DNA mismatch repair is an important pathway of mutation avoidance. It also contributes to the cytotoxic effects of some kinds of DNA damage, and cells defective in mismatch repair are resistant, or tolerant, to the presence of some normally cytotoxic base analogues in their DNA. The absence of a particular mismatch binding function from some mammalian cells confers resistance to the base analogues O6‐methylguanine and 6‐thioguanine in DNA. Cells also acquire a spontaneous mutator phenotype as a consequence of this defect. (...) Impaired mismatch binding can cause an instability in DNA microsatellite regions that comprise repeated dinucleotides. Microsatellite DNA instability is common in familial and sporadic colon carcinomas as well as in a number of other tumours. Several independent lines of investigation have identified defects in mismatch repair proteins that are causally related to these cancers. (shrink)

Phenotypic plasticity is a crucial feature of aggressive cancer, providing the means for cancer progression. Stochastic changes in tumor cell transcriptional programs increase the chances of survival under any condition. I hypothesize that unstable chromatin permits stochastic transitions between transcriptional programs in aggressive cancers and supports non‐genetic heterogeneity of tumor cells as a basis for their adaptability. I present a mechanistic model for unstable chromatin which includes destabilized nucleosomes, mobile chromatin fibers and random enhancer‐promoter contacts, resulting in stochastic transcription. (...) I suggest potential markers for “unsettled” chromatin in tumors associated with poor prognosis. Although many of the characteristics of unstable chromatin have been described, they were mostly used to explain changes in the transcription of individual genes. I discuss approaches to evaluate the role of unstable chromatin in non‐genetic tumor cell heterogeneity and suggest using the degree of chromatin instability and transcriptional noise in tumor cells to predict cancer aggressiveness. (shrink)

Genomic instability is a hallmark of cancer. Cancer cells that exhibit abnormal chromosomes are characteristic of most advanced tumours, despite the potential threat represented by accumulated genetic damage. Carcinogenesis involves a loss of key components of the genetic and signalling molecular networks; hence some authors have suggested that this is part of a trend of cancer cells to behave as simple, minimal replicators. In this study, we explore this conjecture and suggest that, in the case of cancer, genomic (...) class='Hi'>instability has an upper limit that is associated with a minimal cancer cell network. Such a network would include (for a given microenvironment) the basic molecular components that allow cells to replicate and respond to selective pressures. However, it would also exhibit internal fragilities that could be exploited by appropriate therapies targeting the DNA repair machinery. The implications of this hypothesis are discussed. (shrink)

Because the term ‘epigenetics’ has been used in a wide array of inquires within the life-sciences, it has come to bear a significant number of meanings. And just as biologists cannot come to an univocal understanding on what epigenetics connotes, the effect that its study has had in challenging contemporary neo-Darwinian, genecentred paradigms is also unclear. Some scientists and philosophers go as far as to say epigenetics has eroded dichotomies central to modern western thought, such as nature and nurture, or (...) genotype and phenotype – but the matter ignites a great deal of controversy. What seems unquestionable, however, is that the notion that genetic material is a ‘programme’ that simply manifests itself in an external correlative, thus accounting for the development of a living organism, seems to have – at the very least – shifted. Rather than attempting to pinpoint the implications of epigenetics in contemporary biology, this article focuses on the ‘literary’ dimension of scientific debate: instability of meaning, metaphorical shifts, a redrawing of margins and limits. Furthermore, it will be argued that metaphor does not merely have a pedagogical value in the field but rather works proactively throughout the genesis, development and morphology of science and theory. By outlining a ‘literary’ dimension in discussions around genetics one can identify what Squier refers to as ‘the epistemological value of the imprecise’, which in the case of epigenetics seems to have jeopardized not only the boundaries between genes and their external correlatives, but even challenged the frontiers of traditional disciplinary discourse. (shrink)

Cancers have a formidable capacity to develop resistance to a large and diverse array of chemical, biologic, and physical anti‐neoplastic agents. This can be largely traced to the instability of the tumor cell genome, and the resultant ability of tumor cell populations to generate phenotypic variants rapidly. It is therefore argued that anti‐cancer strategies should be directed at eliminating those genetically stable normal diploid cells that are required for the progressive growth of tumors. Micro‐vascular endothelial cells comprising the (...) tumor vasculature represent such a normal cell target. Moreover, specificity for tumor associated vasculature by anti‐cancer agents may be achieved by virtue of the fact that many of the endothelial cells that comprise these blood vessels are in an immature, cycling, and ‘activated’ state, in contrast to the endothelial cells associated with normal tissue and organ blood vessels. (shrink)

Tumor‐cell diversification mechanisms insure that malignant neoplasms contain diversified tumor‐cell subpopulations. Because of the instability of tumor cell phenotypes, some malignant cells will evolve with the most favorable properties for their progression to highly metastatic cells. The rates of cellular phenotypic diversification vary greatly among different tumors, and they are probably modulated, in part, by genetic and chromosome defects and by epigenetic events that may vary widely depending upon the nature of the tumor cells and their microenvironments. As (...) tumor diversification and selection proceed, the most malignant cell subpopulations may eventually become dominant and gradually lose their microenvironmental responsiveness. Tumor‐cell diversification mechanisms may be similar or identical to normal, developmentally regulated diversification mechanisms that are used during embryonic cell diversification and differentiation. (shrink)

Recent studies indicate that mammalian chromosomes contain discretecis‐acting loci that control replication timing, mitotic condensation, and stability of entire chromosomes. Disruption of the large non‐coding RNA gene ASAR6 results in late replication, an under‐condensed appearance during mitosis, and structural instability of human chromosome 6. Similarly, disruption of the mouse Xist gene in adult somatic cells results in a late replication and instability phenotype on the X chromosome. ASAR6 shares many characteristics with Xist, including random mono‐allelic expression and asynchronous (...) replication timing. Additional “chromosome engineering” studies indicate that certain chromosome rearrangements affecting many different chromosomes display this abnormal replication and instability phenotype. These observations suggest that all mammalian chromosomes contain “inactivation/stability centers” that control proper replication, condensation, and stability of individual chromosomes. Therefore, mammalian chromosomes contain four types ofcis‐acting elements, origins, telomeres, centromeres, and “inactivation/stability centers”, all functioning to ensure proper replication, condensation, segregation, and stability of individual chromosomes. (shrink)

We address the controversy in the literature concerning the definition of holobionts and the apparent constraints on their evolution using concepts from community population genetics. The genetics of holobionts, consisting of a host and diverse microbial symbionts, has been neglected in many discussions of the topic, and, where it has been discussed, a gene-centric, species-centric view, based in genomic conflict, has been predominant. Because coevolution takes place between traits or genes in two or more species and not, strictly speaking, between (...) species, it may affect some traits but not others in either host or symbiont. Moreover, when interacting species pairs are embedded in a larger community, indirect ecological effects can alter the expected pairwise dynamics. Mode of symbiont transmission and the degree of host inbreeding both affect the extent of microbial mixing across host lineages and thereby the degree to which selection on one trait of either partner affects other aspects of a holobiont phenotype. We discuss several potential defining criteria for holobionts using community genetics and population genetics models, suggesting their application and limitations. Using community genetics models, we show how conflict between genomes can be self-limiting, while cooperation and mutualism tend to be self-accelerating. It is likely that this bias in the evolutionary dynamics of interaction between hosts and symbionts is an important feature of holobionts. This bias in the evolutionary dynamic could contribute to explaining the absence of cheaters from natural mutualisms, although cheaters are predicted by gene-centered conflict theory to cause the evolutionary instability of mutualisms. Additionally, it may help explain the more frequent origin of mutualisms from parasitic than from free-living systems, an evolutionary trajectory opposite to that predicted by genome conflict theory. (shrink)

Aus bekannten Versuchsergebnissen und Naturbeobachtungen lÄsst sich ein Mechanismus der ontogenetischen Evolution und Involution ableiten, der mit den unten stehenden vier GrundsÄtzen gekennzeichnet werden kann. Es wird dabei als anerkannt vorausgesetzt, dass die Entwicklung der Lebewesen auf genotypischen Potenzen beruht, die nach Einwirkung bestimmter Umweltreize bestimmte phÄnotypische Effekte bewirken. Es wird als “phylogenetischer Auslesefaktor” einer genotypischen Potenz derjenige Faktor der Äusseren oder inneren Umwelt bezeichnet, an den in der Phylogenese die Anpassung erfolgt ist. Der phylogenetische Auslesefaktor einer genotypischen Potenz wird (...) in der Ontogenese als genaktivierender Manifestationsreiz für den entsprechenden phÄnotypischen Effekt rekapituliert. Nach dem Ende des genaktivierenden Manifestationsreizes nimmt der von diesem Reiz abhÄngige Aktivierungszustand der genotypischen Potenz in charakteristischer Weise ab, und entsprechend bildet sich der von diesem Genaktivierungszustand abhÄngige phÄnotypische Effekt zurück; infolgedessen wird der phÄnotypische Effekt je nach der verschiedenen ReizabhÄngigkeit des Genaktivierungszustandes manifest als reizabhÄngige Modifikation, als vorübergehend reizunabhÄngige Dauermodifikation oder als fortgepflanzte vorübergehend reizunabhÄngige Dauermodifikation. Bei der ontogenetischen Evolution ist im Bereich der inneren Umwelt der phÄnotypische Effekt einer Entwicklungsstufe als rekapitulierter phylogenetischer Auslesefaktor der genotypischen Potenz der nÄchsten Entwicklungsstufe auch der genaktivierende Manifestationsreiz für den phÄnotypischen Effekt der nÄchsten Entwicklungsstufe . Bei Beendigung der ontogenetischen Evolution mit PhÄn x ist im Bereich der inneren Umwelt PhÄn x−1 der phylogenetische Auslesefaktor für Gen x−1 und wird als der genaktivierende Manifestationsreiz für PhÄn x rekapituliert. Mit der Manifestation von PhÄn x verschwindet PhÄn x−1 und damit auch der von ihm ausgehende genaktivierende Manifestationsreiz für PhÄn x ; infolgedessen beginnt die ontogenetische Involution von PhÄn x nach Massgabe der StabilitÄt des Aktivierungsgrades von Gen x−1.The development of living individuals is due to genotypical potencies, which lead to certain phenotypical effects after the influence of certain stimuli of the environment. The factor of the exogenous or endogenous environment to which adaptation has occurred during the phylogenesis is defined as the phylogenetical selectionfactor.A mechanism of ontogenetical evolution and involution is deduced from known experimental results and observations. This mechanism can be characterized by the following four main principles. The phylogenetical selectionfactor of a genotypical potency is recapitulated during ontogenesis as the gene-activating stimulus for the manifestation of the corresponding phenotypical effect. After the cessation of the gene-activating stimulus the activation of the genotypical potency declines in a characteristic manner. And according to it the phenotypical effect being dependent on this condition of gene-activation is involuted. This means that a phenotypical effect is manifest as stimulus dependent modification, as a temporary stimulus independent modification or as a temporary stimulus independent modification which is transmitted from generation to generation. During the ontogenetical evolution the phenotypical effect in a certain step of the development in the sphere of the endogenous environment is the manifestation stimulus activating the gene for the phenotypical effect of the following developmental step , since Phene n or Substrate n is the recapitulated selectionfactor for the genotypical potency of this step . When the ontogenetical evolution ends with the appearance of Phene n , Phene x−1 is the phylogenetical selectionfactor for Gene x−1 in the endogenous environment and is recapitulated as the gene-activating stimulus for the manifestation of Phene x . By the manifestation of Phene x Phene x−1 vanishes and thus the manifestationstimulus for Phene x . Consequently the ontogenetical involution of Phene x begins according to the degree of instability of the activated condition of Gene x−1. (shrink)

Despite the extensive literature describing the somatic genetic alterations in cancer cells, the precise origins of cancer cells remain controversial. In this article, I suggest that the etiology of cancer and the generation of genetic instability in cancer cells should be considered in the light of recent findings on both the stochastic nature of gene expression and its regulation at tissue level. By postulating that gene expression is intrinsically probabilistic and that stabilization of gene expression arises by cellular interactions (...) in “morphogenetic fields”, development and cellular differentiation can be rethought in an evolutionary perspective. In particular, this article proposes that disruptions of cellular interactions are the initial source of abnormal gene expression in cancer cells. Consequently, cancer phenotypes such as genetic and epigenetic instabilities, and also the presence of cells with stem cell‐like properties, may result from inaccurate and aberrant patterns of gene expression generated by microenvironmental alterations. Finally, the therapeutic implications of this view are discussed. BioEssays 27:1277–1285, 2005. © 2005 Wiley Periodicals, Inc. (shrink)

The validity of the fruit‐fly as a model of human disease has been confirmed in a striking way by Green and colleagues.1 They show that the mutations causing a necrotic disease phenotype in Drosophila, precisely mirror those resulting in a group of well‐studied but perplexing diseases in the human. These diseases, ranging from thrombosis to dementia, arise from mutations causing a conformational instability of serpin protease inhibitors. The findings provide clues as to the unusual severity and variable onset of (...) such conformational diseases and demonstrate the potential of Drosophila as a model for their future study. BioEssays 26:1–5, 2004. © 2003 Wiley Periodicals, Inc. (shrink)

The great majority of phenotypic characteristics are complex traits, complicating the identification of the genes underlying their expression. However, both methodological and theoretical progress in genome‐wide association studies have resulted in a much better understanding of the underlying genetics of many phenotypic traits, including externally visible characteristics (EVCs) such as eye and hair color. Consequently, it has become possible to predict EVCs from human samples lacking phenotypic information. Predicting EVCs from genetic evidence is clearly appealing for forensic (...) applications involving the personal identification of human remains. Now, a recent paper has reported the genetic determination of eye and hair color in samples up to 800 years old. The ability to predict EVCs from ancient human remains opens up promising perspectives for ancient DNA research, as this could allow studies to directly address archaeological and evolutionary questions related to the temporal and geographical origins of the genetic variants underlying phenotypes. (shrink)

This article briefly outlines some of the key problems with the way in which the moral realm has traditionally been understood and analysed. I propose two alternative views of what is morally interesting and applicable to nursing practice and I indicate that instability has its upsides. I begin with a moral tale – a 'Good Samaritan' story – which raises fairly usual questions about the nature of morality but also the more philosophically fundamental question about the relationship between subjectivity (...) and moral agency. I then consider this relationship from the perspectives of two twentieth century philosophers: Emmanuel Levinas and Michel Foucault. Levinas' basic point is that the experience of ethical subjectivity is made possible through others: the demand to respond to the existence of others is the basic social structure that precedes individual freedom. If Levinas posits intersubjectivity as a fundamental or primitive feature of the moral realm, Foucault poses an even more basic question: how have moral subjects and relations of obligation been constituted? The aim of ethical inquiry, for Foucault, is to describe the network of discourses, institutions, relations, and practices through which certain kinds of subjects are constituted and constitute themselves, e.g. as a kind of person who can act morally. Finally, I consider some recent research in philosophy of nursing which illustrates how Levinasian and/or Foucauldian perspectives can deepen understanding of nurses' moral practices, specifically, the work of Norwegian public health nurses, Canadian pediatric nurses, and Irish midwives. I suggest that in spite of the instability of morality in general and the particular ethical challenges that face nurses, there are grounds for hope and possible strategies for living in unstable times. (shrink)

Autism Spectrum Disorder (ASD) is extremely heterogeneous clinically and genetically. There is a pressing need for a better understanding of the heterogeneity of ASD based on scientifically rigorous approaches centered on systematic evaluation of the clinical and research utility of both phenotype and genotype markers. This paper presents a holistic PheWAS-inspired method to identify meaningful associations between ASD phenotypes and genotypes. We generate two types of phenotype-phenotype (p-p) graphs: a direct graph that utilizes only phenotype data, and an indirect graph (...) that incorporates genotype as well as phenotype data. We introduce a novel methodology for fusing the direct and indirect p-p networks in which the genotype data is incorporated into the phenotype data in varying degrees. The hypothesis is that the heterogeneity of ASD can be distinguished by clustering the p-p graph. The obtained graphs are clustered using network-oriented clustering techniques, and results are evaluated. The most promising clusterings are subsequently analyzed for biological and domain-based relevance. Clusters obtained delineated different aspects of ASD, including differentiating ASD-specific symptoms, cognitive, adaptive, language and communication functions, and behavioral problems. Some of the important genes associated with the clusters have previous known associations to ASD. We found that clusters based on integrated genetic and phenotype data were more effective at identifying relevant genes than clusters constructed from phenotype information alone. These genes included five with suggestive evidence of ASD association and one known to be a strong candidate. (shrink)

Phenotypic Evolution explicitly recognizes organisms as complex genetic-epigenetic systems developing in response to changing internal and external environments. As a key to a better understanding of how phenotypes evolve, the authors have developed a framework that centers on the concept of the Developmental Reaction Norm. This encompasses their views: (1) that organisms are better considered as integrated units than as disconnected parts (allometry and phenotypic integration); (2) that an understanding of ontogeny is vital for evaluating evolution of adult (...) forms (ontogenetic trajectories, epigenetics, and constraints); and (3) that environmental heterogeneity is ubiquitous and must be acknowledged for its pervasive role in phenotypic expression. (shrink)

Phenotypic plasticity integrates the insights of ecological genetics, developmental biology, and evolutionary theory. Plasticity research asks foundational questions about how living organisms are capable of variation in their genetic makeup and in their responses to environmental factors. For instance, how do novel adaptive phenotypes originate? How do organisms detect and respond to stressful environments? What is the balance between genetic or natural constraints (such as gravity) and natural selection? The author begins by defining phenotypic plasticity and detailing its (...) history, including important experiments and methods of statistical and graphical analysis. He then provides extended examples of the molecular basis of plasticity, the plasticity of development, the ecology of plastic responses, and the role of costs and constraints in the evolution of plasticity. A brief epilogue looks at how plasticity studies shed light on the nature/nurture debate in the popular media. (shrink)

The paper describes the context and the origin of a particular debate that concerns the evolution of phenotypic plasticity. In 1965, British biologist A. D. Bradshaw proposed a widely cited model intended to explain the evolution of norms of reaction, based on his studies of plant populations. Bradshaw’s model went beyond the notion of the “adaptive norm of reaction” discussed before him by Dobzhansky and Schmalhausen by suggesting that “plasticity” the ability of a phenotype to be modified by the (...) environment should be genetically determined. To prove Bradshaw’s hypothesis, it became necessary for some authors to identify the pressures exerted by natural selection on phenotypic plasticity in particular traits, and thus to model its evolution. In this paper, I contrast two different views, based on quantitative genetic models, proposed in the mid-1980s: Russell Lande and Sara Via’s conception of phenotypic plasticity, which assumes that the evolution of plasticity is linked to the evolution of the plastic trait itself, and Samuel Scheiner and Richard Lyman’s view, which assumes that the evolution of plasticity is independent from the evolution of the trait. I show how the origin of this specific debate, and different assumptions about the evolution of phenotypic plasticity, depended on Bradshaw’s definition of plasticity and the context of quantitative genetics. (shrink)

In other works, I’ve proposed a solution to the semantic paradoxes which, at the technical level, basically relies on failure of contraction. I’ve also suggested that, at the philosophical level, contraction fails because of the instability of certain states of affairs. In this paper, I try to make good on that suggestion.

Rawls’ The Law of Peoples is vulnerable to the criticism of instability, which is exemplified by his oversight of the aggressive state. In order to address this criticism in keeping with Rawls’ overall project, I argue that the grounds for intervention in the Society of Peoples ought to be extended from merely human rights violations to also include the imposition of unjust inequalities by one state upon another. I also argue that Rawls’ conception of public reason is too narrow, (...) and must be expanded to include participation of all reasonable citizens, not merely representatives of the peoples with membership in the Society of Peoples. In refuting objections to each of these alterations, I establish that this two-part revision is a successful route to be taken in addressing the concern of instability while also remaining in keeping with – and perhaps making more Rawlsian – Rawls’ overall project. My solution does this by further advancing liberalism, reflecting a commitment to pluralism and the social contract tradition, and more resolutely recognizing a possible divergence in moral capacities between representatives and citizens. (shrink)

Some claim that digital phenotyping will revolutionize understanding of human psychology and experience and significantly promote human wellbeing. This paper investigates the nature of digital phenotyping in relation to its alleged promise. Unlike most of the literature to date on philosophy and digital phenotyping, which has focused on its ethical aspects, this paper focuses on its epistemic and methodological aspects. The paper advances a tetra-taxonomy involving four scenario types in which knowledge may be acquired from human “digitypes” by digital phenotyping. (...) These scenarios comprise two causal relations and a correlative and constitutive relation that can exist between information generated by digital systems/devices on the one hand and psychological or behavioral phenomena on the other. The paper describes several modes of inference involved in deriving knowledge within these scenarios. After this epistemic mapping, the paper analyzes the possible knowledge potential and limitations of digital phenotyping. It finds that digital phenotyping holds promise of delivering insight into conditions and states as well producing potentially new psychological categories. It also argues that care must be taken that digital phenotyping does not make unwarranted conclusions and is aware of potentially distorting effects in digital sensing and measurement. If digital phenotyping is to truly revolutionize knowledge of human life, it must deliver on a range of fronts, including making accurate forecasts and diagnoses of states and behaviors, providing causal explanations of these phenomena, and revealing important constituents of human conditions, psychology, and experience. (shrink)

A new voice in the nature-nurture debate can be heard at the interface between evolution and development. Phenotypic integration is a major growth area in research.

Hyperplasia and hypertrophy are elements of phenotypic plasticity adjusting organ size and function. Because they are costly, we assume that they are beneficial. In this review, the authors discuss examples of tissue and organ systems that respond with plastic changes to osmotic stress to raise awareness that we do not always have sufficient experimental evidence to conclude that such processes provide fitness advantages. Changes in hydranth architecture in the hydroid Cordylophora caspia or variations in size in the anal papillae (...) of insect larvae upon changes in medium salinity may be adaptive or not. The restructuring of salt glands in ducklings upon salt‐loading is an example of phenotypic plasticity which indeed seems beneficial. As the genomes of model species are recently sequenced and the animals are easy to rear, these species are suitable study objects to investigate the biological significance of phenotypic plasticity and to study potential epigenetic and other mechanisms underlying phenotypic changes. (shrink)

A growing body of empirical literature challenges philosophers’ reliance on intuitions as evidence based on the fact that intuitions vary according to factors such as cultural and educational background, and socio-economic status. Our research extends this challenge, investigating Lehrer’s appeal to the Truetemp Case as evidence against reliabilism. We found that intuitions in response to this case vary according to whether, and which, other thought experiments are considered first. Our results show that compared to subjects who receive the Truetemp Case (...) first, subjects first presented with a clear case of knowledge are less willing to attribute knowledge in the Truetemp Case, and subjects first presented with a clear case of nonknowledge are more willing to attribute knowledge in the Truetemp Case. We contend that this instability undermines the supposed evidential status of these intuitions, such that philosophers who deal in intuitions can no longer rest comfortably in their armchairs. (shrink)

During the period 1860-1880, a number of physicists and mathematicians, including Maxwell, Stewart, Cournot and Boussinesq, used theories formulated in terms of physics to argue that the mind, the soul or a vital principle could have an impact on the body. This paper shows that what was primarily at stake for these authors was a concern about the irreducibility of life and the mind to physics, and that their theories can be regarded primarily as reactions to the law of conservation (...) of energy, which was used among others by Helmholtz and Du Bois-Reymond as an argument against the possibility of vital and mental causes in physiology. In light of this development, Maxwell, Stewart, Cournot and Boussinesq showed that it was still possible to argue for the irreducibility of life and the mind to physics, through an appeal to instability or indeterminism in physics: if the body is an unstable or physically indeterministic system, an immaterial principle can act through triggering or directing motions in the body, without violating the laws of physics. (shrink)

Phenotype, whether conventional or extended, is defined as a reflectionof an underlying genotype. Adaptation and the natural selection thatfollows from it depends upon a progressively harmonious fit betweenphenotype and environment. There is in Richard Dawkins' notion ofthe extended phenotype a paradox that seems to undercut conventionalviews of adaptation, natural selection and adaptation. In a nutshell, ifthe phenotype includes an organism's environment, how then can theorganism adapt to itself? The paradox is resolvable through aphysiological, as opposed to a genetic, theory of (...) natural selection andadaptation. (shrink)

Territory loss and uninhabitability characterize the current environmental background conditions of the international state system. Such conditions present pressing moral questions about our obligations to protect those who are displaced by anthropogenic climate change. By virtue of our participation in the territorial state system, understood as a social practice, we have principled grounds to address some of the consequences of the uninhabitability conditions brought on by climate change. By assuming territorial instability and employing a practice-based method of justification we (...) can identify a fundamental, basic right protected under the state system – the right to a livable locality – which grounds a moral obligation to protect against climate change-induced displacement. Assuming territorial instability and uninhabitability compels us to recognize that the causes generating climate-displacement are not merely natural but rather deeply political and that displacement is a foreseeable failure that results because of the state system’s organizational structure. (shrink)

Co-creating knowledge takes a new approach to human phenotypic morality as a biologically based, human lineage specific trait. Authors from very different backgrounds first review research on the nature and origins of morality using the social brain network, and studies of individuals who cannot “know good” or think morally because of brain dysfunction. They find these models helpful but insufficient, and turn to paleoanthropology, cognitive science, and neuroscience to understand human moral capacity and its origins long ago, in the (...) genus Homo. An unusual narrative capturing “morality in action” takes the reader back 900,000 years, and then the authors analyze the essential features of moral thinking and behavior as expressed by early and later species on our lineage. In what has primarily been the province of philosophers to date, the authors’ morality model is presented for further scientific testing. (shrink)

Predicting the phenotype of an organism from its genotype is a central question in genetics. Most importantly, we would like to find out if the perturbation of a single gene may be the cause of a disease. However, our current ability to predict the phenotypic effects of perturbations of individual genes is limited. Network models of genes are one tool for tackling this problem. In a recent study, (Lee et al.) it has been shown that network models covering the (...) majority of genes of an organism can be used for accurately predicting phenotypic effects of gene perturbations in multicellular organisms. BioEssays 30:707–710, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

John Rawls’s most mature notion of political order is “stability for the right reasons.” Stability for the right reasons is the kind of political order that Rawls hoped a well-ordered society could ideally achieve. In this paper, I demonstrate through the tools of modern game theory, the instability of “stability for the right reasons.” Specifically, I will show that a well-ordered society can completely destabilize by the introduction of an arbitrarily small number of non- compliers whenever individuals fail to (...) achieve full common knowledge ever so slightly. (shrink)

The analysis of genetic and epigenetic mechanisms of the genotype–phenotypic connection has, so far, only been possible in a handful of genetic model systems. Recent technological advances, including next‐generation sequencing methods such as RNA‐seq, ChIP‐seq and RAD‐seq, and genome‐editing approaches including CRISPR‐Cas, now permit to address these fundamental questions of biology also in organisms that have been studied in their natural habitats. We provide an overview of the benefits and drawbacks of these novel techniques and experimental approaches that can (...) now be applied to ecological and evolutionary vertebrate models such as sticklebacks and cichlid fish. We can anticipate that these new methods will increase the understanding of the genetic and epigenetic factors influencing adaptations and phenotypic variation in ecological settings. These new arrows in the methodological quiver of ecologist will drastically increase the understanding of the genetic basis of adaptive traits – leading to a further closing of the genotype–phenotype gap. -/- . (shrink)

In a now classic paper published in 1991, Alberch introduced the concept of genotype–phenotype (G!P) mapping to provide a framework for a more sophisticated discussion of the integration between genetics and developmental biology that was then available. The advent of evo-devo first and of the genomic era later would seem to have superseded talk of transitions in phenotypic space and the like, central to Alberch’s approach. On the contrary, this paper shows that recent empirical and theoretical advances have only (...) sharpened the need for a different conceptual treat- ment of how phenotypes are produced. Old-fashioned metaphors like genetic blueprint and genetic programme are not only woefully inadequate but positively misleading about the nature of G!P, and are being replaced by an algorithmic approach emerging from the study of a variety of actual G!P maps. These include RNA folding, protein function and the study of evolvable soft- ware. Some generalities are emerging from these disparate fields of analysis, and I suggest that the concept of ‘developmental encoding’ (as opposed to the classical one of genetic encoding) provides a promising computational–theoretical underpinning to coherently integrate ideas on evolvability, modularity and robustness and foster a fruitful framing of the G!P mapping problem. (shrink)

Recent evidence shows that dynamic instability is the dominant mechanism for the assembly of pure tubulin in vitro and for the great majority of microtubules in the mitotic spindle and the interphase cytoplasmic microtubule complex. The basic concepts of this model provide a framework for future characterization of the molecular basis of spatial and temporal regulation of microtubule dynamics in the cell and the function of microtubule dynamics in motile processes such as chromosome movement.

While niche construction theory locates animal artefacts in their constructors’ environment, hence treating them as capable of exerting selective pressure on both the constructors and their descendants, the extended phenotype concept assimilates artefacts with their constructors’ genes. Analogous contrasts apply in the case of endoparasite and brood parasite genes influencing host behaviour. The explanatory power of these competing approaches are assessed by re-examining the core chapters of Richard Dawkins’ _The Extended Phenotype_. Because animal artefacts have multiple evolutionary consequences for their (...) constructors, the extra-body effects of a gene seemingly include feedback effects on multiple other genes, a result which is more consistent with niche construction theory than with selfish gene theory. In the case of endoparasite genes influencing host behaviour, Dawkins’ argument leaves out what appears to be the key explanatory component, namely the role of the host’s own bodily systems in making it possible for such genes to exist. For action at a distance, it is unclear whether the key genes have extended effects because they sit in the body of the manipulating organism, or alternatively do not have such effects because they sit in the body of its victim. It is argued that niche construction theory offers a superior explanation in all three cases, regardless of whether the extended phenotype concept is interpreted in selfish gene or selfish organism terms. (shrink)

The paper takes a detailed look at a surprising new aspect of the dynamics of rigid bodies. Far from the usual consideration of rigid body theory as a merely technical chapter of classical physics, I demonstrate here that there are solutions to the conservation equations of mechanics that imply the spontaneous, unpredictable splitting of a rigid body in free rotation, something that has direct implications for the problem of causality. The paper also shows that the instability revealed in indeterminist (...) splitting processes does not depend solely on the bodies’ inertial properties but also on the number of dimensions of the physical space they inhabit. The paper concludes with a conjecture on the behavior of rigid bodies in four-dimensional space. (shrink)

(1995). Instability and uneasiness in Hume's theories of belief and justification. British Journal for the History of Philosophy: Vol. 3, No. 2, pp. 301-327.

In the framework of population dynamics, we start from the logistic equation describing the evolution of one species with limited food supply. A split device allows us to consider the population as two sub-populations x and y evolving analogously. The dynamical system has a one-parameter family of equilibria which is structurally unstable. Then small perturbations of the system (describing functional or ethological differentiations between the sub-species) lead in general to a new system involving a fast and a slow dynamics with (...) a finite number of equilibria. In simple situations where the differentiation is clearly either an advantage or an inconvenience for one of the subspecies, the stable equilibrium amounts to extinction of the disadvantaged subspecies (elementary Darwinism). Oppositely more complex differentiations (involving both advantages and inconveniences) often lead to stable equilibria with well-defined non zero proportions of the sub-populations (preservation of the biodiversity). Other examples are concerned with symbiosis-like differentiations, leading to preservation, whereas the opposite case (mutual nuisances) has an unstable equilibrium and lead to extinction of one or the other subspecies according to the initial conditions. The case of a scission into three subspecies is more rich in consequences. In certain cases, predator-prey relations lead to auto-organization phenomena with stable diversity-preserving diversity. Cases of instability are also possible, leading to orbits tending towards a poly-cycle.This implies some kind of pseudo-extinction: this amounts to “pseudo-periodic-like” orbits with “pseudo-periods” larger and larger, tending to infinity; each pseudo-period contains parts where one of the sub-populations practically vanish. Other non-linear perturbations lead to stable orbits. (shrink)

Phenotypic integration refers to the study of complex patterns of covariation among functionally related traits in a given organism. It has been investigated throughout the 20th century, but has only recently risen to the forefront of evolutionary ecological research. In this essay, I identify the reasons for this late flourishing of studies on integration, and discuss some of the major areas of current endeavour: the interplay of adaptation and constraints, the genetic and molecular bases of integration, the role of (...) phenotypic plasticity, macroevolutionary studies of integration, and statistical and conceptual issues in the study of the evolution of complex phenotypes. I then conclude with a brief discussion of what I see as the major future directions of research on phenotypic integration and how they relate to our more general quest for the understanding of phenotypic evolution within the neo-Darwinian framework. I suggest that studying integration provides a particularly stimulating and truly interdisciplinary convergence of researchers from fields as disparate as molecular genetics, developmental biology, evolutionary ecology, palaeontology and even philosophy of science. (shrink)

According to "skepticism about the external world", one cannot know whether there are any things that have these two characteristics: they exist, or occur, at, or come from, some place, and they might have existed even had no one been conscious of them. In attempting to show that one cannot know whether or not there are any such things, the skeptic appeals to the alleged fact that one cannot rule out various possibilities, e.g., the possibility that one is dreaming. But, (...) if one cannot rule out these possibilities, then how can one even have any grounds for believing that there are such things? I show how certain attempts to explain how one can have such grounds cannot succeed, and I offer an alternative that does succeed. This alternative depends upon a certain analysis of the notion of sensory experience. After providing that analysis, and showing how, by appeal to it, we can explain not only how it is possible to have grounds for believing that there are external things, but how it is possible to know that there are, I explain why it is that philosophers have failed to appreciate the possibility of providing such an explanation. In offering this explanation, I also explain why it is that skepticism about the external world, as well as various other philosophical doctrines, is subject to what I call "instability". (shrink)

The narrative of the digital phenotype as a transformative vector in healthcare is nearly identical to the concept of “data drivenness” in other fields such as law enforcement. We examine the role of a prescription drug monitoring program in California—a computerized law enforcement surveillance program enabled by a landmark Supreme Court case that upheld “broad police powers”—in the interprofessional conflict between physicians and law enforcement over the jurisdiction of drug use. We bring together interview passages, clinical artifacts, and academic and (...) gray literature to investigate the power relations between police, physicians, and patients to show that prescribing data appear to the physician as evidence of problematic patient behavior by the patients, and to law enforcement as evidence of physician misconduct. In turn, physicians have adopted a disciplinary approach to patients, using quasi-legalistic documents to litigate patient behavior. We conclude that police powers have been used to pave data infrastructure through a contested jurisdiction, and law enforcement have used that infrastructure to enroll physicians into the work of disciplining patients. (shrink)

Physical arguments stemming from the theory of black-hole thermodynamics are used to put constraints on the dynamics of closed-string tachyon condensation in Scherk–Schwarz compactifications. A geometrical interpretation of the tachyon condensation involves an effective capping of a noncontractible cycle, thus removing the very topology that supports the tachyons. A semiclassical regime is identified in which the matching between the tachyon condensation and the black-hole instability flow is possible. We formulate a generalized correspondence principle and illustrate it in several different (...) circumstances: an Euclidean interpretation of the transition from strings to black holes across the Hagedorn temperature and instabilities in the brane-antibrane system. (shrink)

This chapter contains section titled: Introduction: What is Phenotypic Plasticity? Developmental Conversion and Developmental Sensitivity: Two Forms of Phenotypic Plasticity Environmental Heterogeneity, Cues, and Plasticity Phenotypic Plasticity and Developmental Buffering The Future of Phenotypic Plasticity Research Acknowledgments References Further Reading.

Political theories of modus vivendi start from an assumption of deep and permanent disagreement about conceptions of the good and conceptions of justice. In response to this disagreement, modus vivendi provides an account of legitimacy as a result of a minimally restricted bargaining process. This account of legitimacy faces three major criticisms. Firstly, that the political arrangement will be unstable, secondly that a modus vivendi will institutionalise injustice, and thirdly, that it will institutionalise the status quo. I concede the objection (...) that a modus vivendi is unstable in order to address the more serious objections that it institutionalises injustice or the status quo. Through its acceptance of instability, modus vivendi theory is no more likely than liberal theory to institutionalise injustice. Far from the conservatism it is often associated with, modus vivendi permits radical political doctrines and radical political action in a way that is precluded by mainstream liberal theory. (shrink)

Selection operates at many levels. Robert Brandon has distinguished the question of the level of selection from the unit of selection, arguing that the phenotype is commonly the target of selection, whatever the unit of selection might be. He uses "screening off" as a criterion for distinguishing the level of selection. Cave animals show a common morphological pattern which includes hypertrophy of some structures and reduction or loss of others. In a study of a cave dwelling crustacean, Gammarus minus, we (...) find evidence for selection for both increased antennal size and reduction of eyes. The genetic structure of the population does not support the view that the phenotype screens off the genotype in explaining the differences in fitness. Nonetheless, the results do indicate that the level of selection is at least at the level of the phenotype in both cases. (shrink)

Mathematical modeling can ground communication and reciprocal enrichment among fields of knowledge whose domains are very different. We propose a new mathematical model applicable in biology, specified into ecology and evolutionary biology, and in cultural transmission studies, considered as a branch of economics. Main inspiration for the model are some biological concepts we call “eco-phenotypic” such as development, plasticity, reaction norm, phenotypic heritability, epigenetics, and niche construction. “Physiology” is a core concept we introduce and translate differently in the (...) biological and cultural domains. The model is ecological in that it aims at describing and studying organisms and populations that perform living, intended as a thermodynamic, matter-energy process concerning resources gathering, usage, and depletion in a spatiotemporal context with given characteristics, as well as with multiplication and space occupation. The model also supports evolution, intended as a dynamics including cumulative change in the features of unique organisms that are connected into breeding populations. The model is then applicable to the economics of cultural transmission in which individuals form their attitudes and patterns of behavior under a complex system of influences derived from their “cultural parents”, other members of the society, and the environment. On the side of biology, an innovative goal is to integrate in a single model all the eco-phenotypic concepts as well as both evolution and ecology. On the side of cultural transmission, eco-phenotypic modeling seems more appropriate in capturing some aspects of cultural systems which are modeled away in the earlier framework based on Mendelian population genetics. (shrink)

Homologous recombination (HR) is required to protect and restart stressed replication forks. Paradoxically, the Mrc1 branch of the S phase checkpoints, which is activated by replicative stress, prevents HR repair at breaks and arrested forks. Indeed, the mechanisms underlying HR can threaten genome integrity if not properly regulated. Thus, understanding how cells avoid genetic instability associated with replicative stress, a hallmark of cancer, is still a challenge. Here I discuss recent results that support a model by which HR responds (...) to replication stress through replicative and repair activities that operate at different stages of the cell cycle (S and G2, respectively) and in distinct subnuclear structures. Remarkably, the replication checkpoint appears to control this scenario by inhibiting the assembly of HR repair centers at stressed forks during S phase, thereby avoiding genetic instability. (shrink)

Skepticism about the epistemic value of intuition in theoretical and philosophical inquiry fueled by the empirical discovery of irrational bias (e.g., the order effect) in people's judgments has recently been challenged by research suggesting that people can introspectively track intuitional instability. The two studies reported here build upon this, the first by demonstrating that people are able to introspectively track instability that was experimentally induced by introducing conflicting expert opinion about certain cases, and the second by demonstrating that (...) it was the presence of instability?not merely the presence of conflicting information?that resulted in changes in the relevant attitudinal states (i.e., confidence and belief strength). The paper closes with the suggestion that perhaps the best explanation for these (and other) findings may be that intuitional instability is not actually ?intuitional.? (shrink)