This paper's aim is threefold. First, I wish to show that there is an analogy in section nine that arises out of the interaction of the interlocutors; this analogy is, or has, a certain comic adequatic to the traditional (e.g. Aquinas's) arguments about proofs for the existence of God. Second, Philo's seemingly inconsequential example of the strange necessity of products of 9 in section nine is a perfected analogy of the broken arguments actually given in that section, destroying Philo's earlier (...) arguments. Finally, I raise the question of the designer's intent in creating such a humourous piece. (shrink)

This paper's aim is threefold. First, I wish to show that there is an analogy in section nine that arises out of the interaction of the interlocutors; this analogy is, or has, a certain comic adequatic to the traditional arguments about proofs for the existence of God. Second, Philo's seemingly inconsequential example of the strange necessity of products of 9 in section nine is a perfected analogy of the broken arguments actually given in that section, destroying Philo's earlier arguments. Finally, (...) I raise the question of the designer's intent in creating such a humourous piece. (shrink)

Plato’s dialogues are self-defined as works of mimetic art, and the ancients clearly consider mimesis as working naturally before reason and beneath it. Such aview connects with two contemporary ideas—Rene Girard’s idea of the mimetic basis of culture and neurophysiological research into mirror neurons. Individualityarises out of, and can collapse back into our mimetic origin. This para-rational notion of mimesis as that in which and by which all our knowledge is framed requires we not only concern ourselves with Socrates’s arguments (...) and distinctions, but also see how the dramatic interaction of the characters is working (or not) on/in the characters, and consider how watching the interaction, hearing the parables and myths, and thinking through the arguments and interactions is meant to effect us. That Plato creates mimeses means he aims at passional conversion not merely argumentative worth, since mimesis aims to (and does) work on the passions. (shrink)

On some occasions of self-reference there can be two equally viable forms available to speakers: individual self-reference and collective self-reference. This means that selection of one or the other in talk-in-interaction can — akin to the selection of terms for reference to non-present persons — be guided by such considerations as recipient design and action formation. As a strategy for investigating the selection of self-reference terms, this article examines repairs to self-reference that change the form of reference from individual to (...) collective and vice versa. We first identify two repair operations found in the domain of self-reference: aggregation and extraction and then we track the use of both operations across a range of positions in the repair initiation opportunity space. Finally we consider some of the interactional uses of aggregation and extraction repairs in resolving sources of troubles associated with speaker epistemic authority and responsibility for described actions. (shrink)

Systems involving many interacting variables are at the heart of the natural and social sciences. Causal language is pervasive in the analysis of such systems, especially when insight into their behavior is translated into policy decisions. This is exemplified by economics, but to an increasing extent also by biology, due to the advent of sophisticated tools to identify the genetic basis of many diseases. It is argued here that a regularity notion of causality can only be meaningfully defined for systems (...) with linear interactions among their variables. For the vastly more important class of nonlinear systems, no such notion is likely to exist. This thesis is developed with examples of dynamical systems taken mostly from mathematical biology. It is discussed with particular reference to the problem of causal inference in complex genetic systems, systems for which often only statistical characterizations exist. (shrink)

Research has indicated that microRNAs (miRNAs), a special class of non-coding RNAs (ncRNAs), can perform important roles in different biological and pathological processes. miRNAs’ functions are realized by regulating their respective target genes (targets). It is thus critical to identify and analyze miRNA-target interactions for a better understanding and delineation of miRNAs’ functions. However, conventional knowledge discovery and acquisition methods have many limitations. Fortunately, semantic technologies that are based on domain ontologies can render great assistance in this regard. In (...) our previous investigations, we developed a miRNA domain-specific application ontology, Ontology for MIcroRNA Target (OMIT), to provide the community with common data elements and data exchange standards in the miRNA research. This paper describes (1) our continuing efforts in the OMIT ontology development and (2) the application of the OMIT to enable a semantic approach for knowledge capture of miRNA-target interactions. (shrink)

In recent years, sequencing technologies have enabled the identification of a wide range of non-coding RNAs (ncRNAs). Unfortunately, annotation and integration of ncRNA data has lagged behind their identification. Given the large quantity of information being obtained in this area, there emerges an urgent need to integrate what is being discovered by a broad range of relevant communities. To this end, the Non-Coding RNA Ontology (NCRO) is being developed to provide a systematically structured and precisely defined controlled vocabulary for the (...) domain of ncRNAs, thereby facilitating the discovery, curation, analysis, exchange, and reasoning of data about structures of ncRNAs, their molecular and cellular functions, and their impacts upon phenotypes. The goal of NCRO is to serve as a common resource for annotations of diverse research in a way that will significantly enhance integrative and comparative analysis of the myriad resources currently housed in disparate sources. It is our belief that the NCRO ontology can perform an important role in the comprehensive unification of ncRNA biology and, indeed, fill a critical gap in both the Open Biological and Biomedical Ontologies (OBO) Library and the National Center for Biomedical Ontology (NCBO) BioPortal. Our initial focus is on the ontological representation of small regulatory ncRNAs, which we see as the first step in providing a resource for the annotation of data about all forms of ncRNAs. (shrink)

Ethical debates around genetic enhancement tend to include an argument that the technology will eventually be fairly accessible once available. That we can fairly distribute genetic enhancement has become a moral defence of genetic enhancement. Two distribution solutions are argued for, the first being equal distribution. Equality of access is generally believed to be the fairest and most just method of distribution. Second, equitable distribution: providing genetic enhancements to reduce social inequalities. In this paper, I make two claims. I first (...) argue that the very assumption that genetic enhancements can be distributed fairly is problematic when considering our understanding of gene–environment interactions, for example, epigenetics. I then argue that arguments that genetic enhancements are permissible because the intended benefits can be distributed fairly as intended are misinformed. My first claim rests on the assertion that genetic enhancements do not enhance traits in a vacuum; genes are dependent on conducive environments for expression. If society cannot guarantee fair environments, then any benefit conferred from being genetically enhanced will be undermined. Thus, any argument that the distribution of genetic enhancements will be fair and that the technology is therefore morally permissible, is mistaken. (shrink)

Major hallmarks of Alzheimer's disease include brain deposition of the amyloid-beta peptide , which is proteolytically cleaved from a large Abeta precursor protein by beta and gamma- secretases. A transmembrane aspartyl protease, beta-APP cleaving enzyme , has been recognized as the beta-secretase. We review the structure and function of the BACE1 protein, and of 4129 bp of the 5'-flanking region sequence of the BACE1 gene and its interaction with various transcription factors involved in cell signaling. The promoter region and (...) 5'-untranslated region contain multiple transcription factor binding sites, such as AP-1, CREB and MEF2. A 91 bp fragment is the shortest region with significant reporter gene activity and constitutes the minimal promoter element for BACE1. The BACE1 promoter contains six unique functional domains and three structural domains of increasing sequence complexity as the "ATG" start codon is approached. Notably, the BACE1 gene promoter contains basal regulatory elements, inducible features and sites for regulation by various important transcription factors. Herein, we also discuss and speculate how the interaction of these transcription factors with the BACE1 promoter can modulate synaptic plasticity, neuronal apoptosis and oxidative stress, which are pertinent to the pathogenesis and progression of AD. (shrink)

Extensive research has demonstrated that rs1360780, a common single nucleotide polymorphism within the FKBP5 gene, interacts with early-life stress in predicting psychopathology. Previous results suggest that carriers of the TT genotype of rs1360780 who were exposed to child abuse show differences in structure and functional activation of emotion-processing brain areas belonging to the salience network. Extending these findings on intermediate phenotypes of psychopathology, we examined if the interaction between rs1360780 and child abuse predicts resting-state functional connectivity (rsFC) between the (...) amygdala and other areas of the salience network. We analyzed data of young European adults from the general population (N = 774; mean age = 18.76 years) who took part in the IMAGEN study. In the absence of main effects of genotype and abuse, a significant interaction effect was observed for rsFC between the right centromedial amygdala and right posterior insula (p <.025, FWE-corrected), which was driven by stronger rsFC in TT allele carriers with a history of abuse. Our results suggest that the TT genotype of rs1360780 may render individuals with a history of abuse more vulnerable to functional changes in communication between brain areas processing emotions and bodily sensations, which could underlie or increase the risk for psychopathology. (shrink)

We have achieved a residue‐level resolution of genetic interaction mapping – a technique that measures how the function of one gene is affected by the alteration of a second gene – by analyzing point mutations. Here, we describe how to interpret point mutant genetic interactions, and outline key applications for the approach, including interrogation of protein interaction interfaces and active sites, and examination of post‐translational modifications. Genetic interaction analysis has proven effective for characterizing cellular processes; however, to (...) date, systematic high‐throughput genetic interaction screens have relied on gene deletions or knockdowns, which limits the resolution of gene function analysis and poses problems for multifunctional genes. Our point mutant approach addresses these issues, and further provides a tool for in vivo structure‐function analysis that complements traditional biophysical methods. We also discuss the potential for genetic interaction mapping of point mutations in human cells and its application to personalized medicine. (shrink)

Although the field of psychiatry has witnessed the proliferation of studies on Gene x Environment (GxE) interactions, still limited is the knowledge we possess of GxE interactions regarding developmental disorders. In this perspective paper, we discuss why GxE interaction studies are needed to broaden our knowledge of developmental disorders. We also discuss the different roles of hazardous versus self-generated environmental factors and how these types of factors may differentially engage with an individual’s genetic background in predicting a (...) resulting phenotype. Then, we present exemplar studies that highlight the role of GxE in predicting atypical developmental trajectories as well as provide insight regarding treatment outcomes. Supported by these examples, we explicate the need to move beyond merely examining statistical interactions between genes and the environment, and to investigate specific genetic susceptibility and environmental contexts that drive developmental disorders. We propose that further parsing of genetic and environmental components is required to fully understand the unique contribution of each factor to the etiology of developmental disorders. Finally, with a greater appreciation of the complexities of GxE interaction, this discussion will converge upon the potential implications for clinical and translational research. (shrink)

The work in progress reported by Wright & Liley shows great promise, primarily because of their experimental and simulation paradigms. However, their tentative conclusion that macroscopic neocortex may be considered (approximately) a linear near-equilibrium system is premature and does not correspond to tentative conclusions drawn from other studies of neocortex.

Examining the interconnections between genes and culture is crucial for a more complete understanding of psychological processes. Genetic predispositions may predict different outcomes depending on one's cultural context, and culture may predict different outcomes depending on genetic predispositions - that is, genes and culture interact. Less is understood, however, about how genes and culture interact, or the psychological mechanisms through which gene–culture interactions occur. In this Element, Joni Y. Sasaki and Heewon Kwon review key findings and theories in (...) gene–culture interaction research. They then go on to discuss current issues and future directions in gene–culture research that may illuminate the path toward an explanatory framework. (shrink)

Conceptual developments have defined concrete questions about the timing and precise location of cellular pattern formation. Plants in general, and the trichomes of Arabidopsis in particular, are remarkably suited for research on these problems. Genetic analysis requires the quantitative characterizations of the developmental processes by which patterning occurs. Larkin et al.(1) have provided measures of the non‐random distances between trichomes. They have also obtained evidence about the cell lineages leading to trichome development, and this evidence constrains the possible role of (...) intracellular programs. Continued genetic analysis may call for the identification of mutations that are expressed only during development and whose effects are corrected before the phenotype matures. (shrink)

The scope of the thermodynamic theory of nonlinear irreversible processes is widened to include the nonlinear stability analysis of system motion. The emphasis is shifted from the analysis of instantaneous energy flows to that of the average work performed by periodic nonlinear processes. The principle of virtual work separates dissipative and conservative forces. The vanishing of the work of conservative forces determines the natural period of oscillation. Stability is then determined by the variations of the dissipative forces (...) with amplitude of oscillation. If the work is a minimum, under certain conditions, the motion is stable. Reduction to linear analysis shows the coincidence with the impedance analysis of electrical circuit theory. The theory is applied to the analysis of temporal interactions of nonlinear irreversible processes in the particular cases of synchronization and hysteresis. Characteristic nonequilibrium phenomena of directional energy transfers, self-excitation, system passivity, wave modulation, and “beat” phenomena are observed. Possible relationships with biological processes are discussed. (shrink)

The aberrations of a gene can influence it and the functions of its neighbour genes in gene interaction network, leading to the development of carcinogenesis of normal cells. In consideration of gene interaction network as a complex network, previous studies have made efforts on the driver attribute filling of genes via network properties of nodes and network propagation of mutations. However, there are still obstacles from problems of small size of cancer samples and the existence of drivers (...) without property of network neighbours, limiting the discovery of cancer driver genes. To address these obstacles, we propose an efficient modularity subspace based concept learning model. Our model can overcome the curse of dimensionality due to small samples via dimension reduction in the task of attribute concept learning and explore the features of genes through modularity subspace beyond the network neighbours. The evaluation analysis also demonstrates the superiority of our model in the task of driver attribute filling on two gene interaction networks. Generally, our model shows a promising prospect in the application of interaction network analysis of tumorigenesis. (shrink)

The presence of gene–environment statistical interaction and correlation in biological development has led both practitioners and philosophers of science to question the legitimacy of heritability estimates. The paper offers a novel approach to assess the impact of GxE and rGE on the way genetic and environmental causation can be partitioned. A probabilistic framework is developed, based on a quantitative genetic model that incorporates GxE and rGE, offering a rigorous way of interpreting heritability estimates. Specifically, given an estimate of heritability (...) and the variance components associated with estimates of GxE and rGE, I arrive at a probabilistic account of the relative effect of genes and environment. (shrink)

More than a simple expository history, A Thousand Years of Nonlinear History sketches the outlines of a renewed materialist philosophy of history in the tradition of Fernand Braudel, Gilles Deleuze, and F lix Guattari, while also engaging the critical new understanding of material processes derived from the sciences of dynamics.Following in the wake of his groundbreaking War in the Age of Intelligent Machines, Manuel De Landa presents a radical synthesis of historical development over the last one thousand years. More (...) than a simple expository history, A Thousand Years of Nonlinear History sketches the outlines of a renewed materialist philosophy of history in the tradition of Fernand Braudel, Gilles Deleuze, and F lix Guattari, while also engaging the critical new understanding of material processes derived from the sciences of dynamics. Working against prevailing attitudes that see history as an arena of texts, discourses, ideologies, and metaphors, De Landa traces the concrete movements and interplays of matter and energy through human populations in the last millennium. De Landa attacks three domains that have given shape to human societies: economics, biology, and linguistics. In every case, what one sees is the self-directed processes of matter and energy interacting with the whim and will of human history itself to form a panoramic vision of the West free of rigid teleology and naive notions of progress, and even more important, free of any deterministic source of its urban, institutional, and technological forms. Rather, the source of all concrete forms in the West's history are shown to derive from internal morphogenetic capabilities that lie within the flow of matter-energy itself. (shrink)

I provide a history of research on G×E in this article, showing that there have actually been two distinct concepts of G×E since the very origins of this research. R. A. Fisher introduced what I call the biometric concept of G×E, or G×EB, while Lancelot Hogben introduced what I call the developmental concept of G×E, or G×ED. Much of the subsequent history of research on G×E has largely consisted in the separate legacies of these separate concepts, along with the (sometimes (...) acrimonious) disputes that have arisen time and again when employers of each have argued over the appropriate way to conceptualize the phenomenon. With this history in place, I then consider more recent attempts to distinguish between different concepts of G×E, paying particular attention to the commonly made distinction between “statistical interaction” and “interactionism,” and also Michael Rutter’s distinction between “statistical interaction” and “the biological concept of interaction.” I argue that the history of the separate legacies of G×EB and G×ED better supports Rutter’s analysis of the situation, and that this analysis best paves the way for an integrative relationship between the various scientists investigating the place of G×E in the etiology of complex traits. (shrink)

Les scolastiques indiennes: Genèses, développements, interactions. Edited by Émilie Aussant and Gérard Colas. Études thématiques, vol. 32. Paris: École française d’Extrême-orient, 2020. Pp. 322. €40.

Somatic complementation by fusion of two mutant cells and mixing of their cytoplasms occurs when the genetic defect of one fusion partner is cured by the functional gene product provided by the other. We have found that complementation of mutational defects in the network mediating stimulus‐induced commitment and sporulation of Physarum polycephalum may reflect time‐dependent changes in the signaling state of its molecular building blocks. Network perturbation by fusion of mutant plasmodial cells in different states of activation, and the (...) time‐resolved analysis of somatic complementation effects can be used to systematically probe network structure and dynamics. Time‐resolved somatic complementation quantitatively detects regulatory interactions between the functional modules of a network, independent of their biochemical composition or subcellular localization, and without being limited to direct physical interactions. BioEssays 25:950–960, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

Scientists now agree that common diseases arise through interactions of genetic and environmental factors, but there is less agreement about how scientific research should account for these interactions. This paper examines the politics of quantification in gene–environment interaction research. Drawing on interviews and observations with GEI researchers who study common, complex diseases, we describe quantification as an unfolding moral economy of science, in which researchers collectively enact competing “virtues.” Dominant virtues include molecular precision, in which behavioral and (...) social risk factors are moved into the body, and “harmonization,” in which scientists create large data sets and common interests in multisited consortia. We describe the negotiations and trade-offs scientists enact in order to produce credible knowledge and the forms of discipline that shape researchers, their practices, and objects of study. We describe how prevailing techniques of quantification are premised on the shrinking of the environment in the interest of producing harmonized data and harmonious scientists, leading some scientists to argue that social, economic, and political influences on disease patterns are sidelined in postgenomic research. We consider how a variety of GEI researchers navigate quantification’s productive and limiting effects on the science of etiological complexity. (shrink)

The glucocorticoid receptor belongs to an important class of transcription factors that alter the expression of target genes in response to a specific hormone signal. The glucocorticoid receptor can function at least at three levels: (1) recruitment of the general transcription machinery; (2) modulation of transcription factor action, independent of DNA binding, through direct protein‐protein interactions; and (3) modulation of chromatin structure to allow the assembly of other gene regulatory proteins and/or the general transcription machinery on the DNA. (...) This review will focus on the multifaceted nature of protein‐protein interactions involving the glucocorticoid receptor and basal transcription factors, coactivators and other transcription factors, occurring at these different levels of regulation. (shrink)

Amyloid-beta peptide plaque in the brain is the primary diagnostic criterion of Alzheimer's disease . The physiological role of Abeta are poorly understood. We have previously determined an Abeta interacting domain in the promoters of AD-associated genes . This AbetaID interacts in a DNA sequence-specific manner with Abeta. We now demonstrate novel Abeta activity as a possible transcription factor. Herein, we detected Abeta-chromatin interaction in cell culture by ChIP assay. We observed that human neuroblastoma cells treated with FITC conjugated Abeta1-40 (...) localized Abeta to the nucleus in the presence of H2O2-mediated oxidative stress. Furthermore, primary rat fetal cerebrocortical cultures were transfected with APP and BACE1 promoter-luciferase fusions, and rat PC12 cultures were transfected with polymorphic APP promoter-CAT fusion clones. Transfected cells were treated with different Abeta peptides and/or H2O2. Abeta treatment of cell cultures produced a DNA sequence-specific response in cells transfected with polymorphic APP clones. Our results suggest the Abeta peptide may regulate its own production through feedback on its precursor protein and BACE1, leading to amyloidogenesis in AD. (shrink)

After more than 15 years of study, the 1/f noise or complex-systems approach to cognitive science has delivered promises of progress, colorful verbiage, and statistical analyses of phenomena whose relevance for cognition remains unclear. What the complex-systems approach has arguably failed to deliver are concrete insights about how people perceive, think, decide, and act. Without formal models that implement the proposed abstract concepts, the complex-systems approach to cognitive science runs the danger of becoming a philosophical exercise in futility. The complex-systems (...) approach can be informative and innovative, but only if it is implemented as a formal model that allows concrete prediction, falsification, and comparison against more traditional approaches. (shrink)

The nuclear envelope shapes the functional organization of the nucleus. Increasing evidence indicates that one of its main components, the nuclear lamina, dynamically interacts with the genome, including the promoter region of specific genes. This seems to occur in a manner that accords developmental significance to these interactions. This essay addresses key issues raised by recent data on the association of nuclear lamins with the genome. We discuss how lamins interact with large chromatin domains and with spatially restricted regions (...) on gene promoters. We address the relationship between these interactions, chromatin modifications and gene expression outcomes. Lamin‐genome contacts are redistributed after cell division and during stem cell differentiation, with evidence of lineage specificity. Thus, we also speculate on a developmental role of lamin interactions with specific genes. Finally, we highlight how concepts arising from this recent work lay the foundations of future challenges and investigations. (shrink)

In a widely acclaimed study from 2002, researchers found a case of gene-environment interaction for a gene controlling neuroenzymatic activity (low vs. high), exposure to childhood maltreatment, and antisocial personality disorder (ASPD). Cases of gene-environment interaction are generally characterized as evincing a genetic predisposition; for example, individuals with low neuroenzymatic activity are generally characterized as having a genetic predisposition to ASPD. I first argue that the concept of a genetic predisposition fundamentally misconstrues these cases of gene-environment (...) interaction. This misconstrual will be diagnosed, and then a new concept—interactive predisposition—will be introduced. I then show how this conceptual shift reconfigures old questions and raises new questions for genetic screening. Attempts to screen embryos or fetuses for the gene associated with low neuroenzymatic activity with an eye towards selecting against the low-activity variant fall prey to the myth of pre-environmental prediction; attempts to screen newborns for the gene associated with low neuroenzymatic activity with an eye towards early intervention will have to face the interventionist’s dilemma. (shrink)

Cooperation is rife in the microbial world, yet our best current theories of the evolution of cooperation were developed with multicellular animals in mind. Hamilton’s theory of inclusive fitness is an important case in point: applying the theory in a microbial setting is far from straightforward, as social evolution in microbes has a number of distinctive features that the theory was never intended to capture. In this article, I focus on the conceptual challenges posed by the project of extending Hamilton’s (...) theory to accommodate the effects of gene mobility. I begin by outlining the basics of the theory of inclusive fitness, emphasizing the role that the concept of relatedness is intended to play. I then provide a brief history of this concept, showing how, over the past fifty years, it has departed from the intuitive notion of genealogical kinship to encompass a range of generalized measures of genetic similarity. I proceed to argue that gene mobility forces a further revision of the concept. The reason in short is that, when the genes implicated in producing social behaviour are mobile, we cannot talk of an organism’s genotype simpliciter; we can talk only of an organism’s genotype at a particular stage in its life cycle. We must therefore ask: with respect to which stage(s) in the life cycle should relatedness be evaluated? For instance: is it genetic similarity at the time of social interaction that matters to the evolution of social behaviour, or is it genetic similarity at the time of reproduction? I argue that, strictly speaking, it is neither of these: what really matters to the evolution of social behaviour is diachronic genetic similarity between the producers of fitness benefits at the time they produce them and the recipients of those benefits at the end of their life-cycle. I close by discussing the implications of this result. The main payoff is that it makes room for a possible new mechanism for the evolution of altruism in microbes that does not require correlated interaction among bearers of the genes for altruism. The importance of this mechanism in nature remains an open empirical question. (shrink)

The aim of our commentary is to strengthen Cowan's proposal for an inherent capacity limitation in STM by suggesting a neurobiological mechanism based on competitive networks and nonlinear oscillations that avoids some of the shortcomings of the scheme discussed in the target article (Lisman & Idiart 1995).

Recognition of the plasticity of development — from gene expression to neuroplasticity — is increasingly undermining the traditional distinction between structure and function, or anatomy and behavior. At the same time, dynamic systems theory — a set of tools and concepts drawn from the physical sciences — has emerged as a way of describing what Maurice Merleau-Ponty calls the “dynamic anatomy” of the living organism. This article surveys and synthesizes dynamic systems models of development from biology, neuroscience, and psychology (...) in order to propose an integrated account of growth, learning, and behavior. Key to this account is the concept of self-differentiation or symmetry-breaking. I argue that development can be understood as a cascade of symmetry-breaking events brought about by the ongoing interactions of multiple, nested, nonlinear dynamic systems whose self-organizing behaviors gradually alter their own anatomical conditions. I begin by introducing the concept of symmetry-breaking as a way of understanding anatomical development. I then extend this approach to motor development by arguing that the organism’s behavior grows along with its body, like a new organ. Finally, I argue that the organism’s behavior and its world grow together dialectically, each driving the other to become more complex and asymmetrical through its own increasing asymmetry. Thus development turns out to be a form of cognition or sense-making, and cognition a form of development. (shrink)

Ever wonder if it is possible to construct a numeric scale for environmental variables, like one does for the temperature? This paper is an attempt to construct one. There are two main parts: section “Statistical Analysis of Variations” presents a general statistical strategy for environmental factor selection. Section “Nonlinear Analytical Geometric Model of Variations” develops an analytical geometric representation of system variations in response to environmental changes. The model is used to quantify the effects of environmental interactions. The (...) paper treats only one-dimensional case, however, the derivation of the case of multiple independent factors follows immediately. The general method developed in this paper may prove applicable to many different fields, such as extensions beyond classical physics, economics, and other sciences. Section “Conclusion” provides an illustration of applications, examples and implications of the results. (shrink)

Study of electroencephalographic brain activity in behaving animals has guided development of a model for the self-organization of goal-directed behavior. Synthesis of a dynamical representation of brain function is based in the concept of intentionality as the organizing principle of animal and human behavior. The constructions of patterns of brain activity constitute meaning and not information or representations. The three accepted meanings of intention: "aboutness," goal-seeking, and wound healing, can be incorporated into the dynamics of meaningful behavior, centered in the (...) limbic system interacting with the sensory and motor systems. Evidence is noted for the maintenance in cortical neuropil of a felt work of synaptic connections, that have incorporated past experience by changes in learning, and that act as a unified whole in shaping each intentional action at each moment. This constitutes the intentional structure of the brain. Meaning is a focus having a place without edges in this structure. The focus continually moves through it along a chaotic trajectory; the meaning occupies the whole structure. In this view, consciousness is the active state of an intentional structure, and awareness is the subjective aspect of the shifting focus. (shrink)

Quantitative genetics (QG) analyses variation in traits of humans, other animals, or plants in ways that take account of the genealogical relatedness of the individuals whose traits are observed. “Classical” QG, where the analysis of variation does not involve data on measurable genetic or environmental entities or factors, is reformulated in this article using models that are free of hypothetical, idealized versions of such factors, while still allowing for defined degrees of relatedness among kinds of individuals or “varieties.” The (...) class='Hi'>gene - free formulation encompasses situations encountered in human QG as well as in agricultural QG. This formulation is used to describe three standard assumptions involved in classical QG and provide plausible alternatives. Several concerns about the partitioning of trait variation into components and its interpretation, most of which have a long history of debate, are discussed in light of the gene-free formulation and alternative assumptions. That discussion is at a theoretical level, not dependent on empirical data in any particular situation. Additional lines of work to put the gene-free formulation and alternative assumptions into practice and to assess their empirical consequences are noted, but lie beyond the scope of this article. The three standard QG assumptions examined are: (1) partitioning of trait variation into components requires models of hypothetical, idealized genes with simple Mendelian inheritance and direct contributions to the trait; (2) all other things being equal, similarity in traits for relatives is proportional to the fraction shared by the relatives of all the genes that vary in the population (e.g., fraternal or dizygotic twins share half of the variable genes that identical or monozygotic twins share); (3) in analyses of human data, genotype-environment interaction variance (in the classical QG sense) can be discounted. The concerns about the partitioning of trait variation discussed include: the distinction between traits and underlying measurable factors; the possible heterogeneity in factors underlying the development of a trait; the kinds of data needed to estimate key empirical parameters; and interpretations based on contributions of hypothetical genes; as well as, in human studies, the labeling of residual variance as a non-shared environmental effect; and the importance of estimating interaction variance. (shrink)

Graphical AbstractCurrent differentiation therapies for cancer may not be effective because it might not be enough to only use molecules targeting chromatin remodelers. It may also be necessary to stabilize the re-expressed genes to convert malignant cells into benign ones.

In our commentary we ask whether we should ultimately endeavour to find the deep causes of behaviours? Then we discuss two extensions of the proposed framework: (1) Mendelian randomisation and (2) hypothesis-free gene–environment interaction (leveraging heterogeneity in genetic associations). These complementary methods help move us towards second-generation causal knowledge, ultimately understanding mechanistic pathways and identifying more effective intervention targets.

Using the genetic algorithm and fuzzy logic, this study presents a nonlinear approach to the evaluation of biofunctional intelligence. According to the biofunctional model, intelligence may be viewed as a multisource phenomenon resulting in part from the interaction of learning processes and sources of self-regulation. Learning processes are regulated by three sources of control , producing three subprocesses for each learning process. This paper examines the role of five such subprocesses as contributors to intelligence. Fuzzy logic captures the fuzzy (...) nature of human intelligence with GA providing a method for determining and optimizing the contribution of these learning subprocesses. (shrink)