Transcription factor binding sites (TFBSs) on the DNA are generally accepted as the key nodes of gene control. However, the multitudes of TFBSs identified in genome‐wide studies, some of them seemingly unconstrained in evolution, have prompted the view that in many cases TF binding may serve no biological function. Yet, insights from transcriptional biochemistry, population genetics and functional genomics suggest that rather than segregating into ‘functional’ or ‘non‐functional’, TFBS inputs to their target genes may be generally cumulative, with varying degrees (...) of potency and redundancy. As TFBS redundancy can be diminished by mutations and environmental stress, some of the apparently ‘spurious’ sites may turn out to be important for maintaining adequate transcriptional regulation under these conditions. This has significant implications for interpreting the phenotypic effects of TFBS mutations, particularly in the context of genome‐wide association studies for complex traits. (shrink)

Complex diseases involve both a genetic component and a response to environmental factors or lifestyle changes. Recently, genome-wide association studies (GWAS) have succeeded in identifying hundreds of polymorphisms that are statistically associated with complex diseases. However, the association is usually weak and none of the associated allelic forms is either necessary or sufficient for the disease occurrence. We argue that this promotes a network view, centred on functional redundancy. We adapted reliability theory to the concerned sub-network, modelled as (...) a parallel array of functional modules. In our model, as long as one module remains active, the function correlated with the respective disease is ensured and disease does not occur. Genetic factors reduce the initial number of available modules while environment, contingent surroundings, personal history, epigenetics, and some intrinsic stochasticity influence their persistence time. This model reproduces age-specific incidence curves and explains the influence of environmental changes. It offers a new paradigm, according to which disease occurs due to a lack of functional elements, depending on many idiosyncratic factors. Genetic risk assessed from GWAS is only a statistical notion with no direct interpretation at the individual level. However, genomic profiling could be useful at population level in devising models to guide decisions in health care policy. (shrink)

There is increasing evidence for the wide‐spread existence of functionally redundant genetic pathways in developmental processes. However, both their significance and manner of evolution are still matters of debate. I will argue here that redundancy of gene actions may, in fact, be a necessary requirement for the development and evolution of complex life forms. One can view development as a process that transmits information from the egg to the adult organism. Transmission of information is, however, always an error‐prone (...) process, which can only be safeguarded by including redundancies in the message. Molecular examples for well analysed redundant processes indicate that redundancies may best be understood within a conceptual framework of overlaps between different gene functions. (shrink)

Over the past decade, there has been an extensive debate about whether researchers have an obligation to disclose genetic research findings, including primary and secondary findings. There appears to be an emerging (but disputed) view that researchers have some obligation to disclose some genetic findings to some research participants. The contours of this obligation, however, remain unclear. -/- As this paper will explore, much of this confusion is definitional or conceptual in nature. The extent of a researcher’s obligation (...) to return secondary and other research findings is often limited by reference to terms and concepts like “incidental,” “analytic validity,” “clinical validity,” “clinical relevance,” “clinical utility,” “clinical significance,” “actionability,” and “desirability.” These terms are used in different ways by different writers to describe obligations in different sorts of cases. -/- Underneath this definitional confusion is a general notion, supported by much of the literature, that findings only need to be disclosed when they surpass certain presumably objective or measureable thresholds, such as medical importance or scientific reproducibility. The problem is that there is significant variability in the way that these terms and concepts are used in the literature and, as such, in defining the scope of an obligation to return findings that surpasses the relevant thresholds. -/- The goal of this paper is to analyze the definitional muddle underlying the debate about returning genetic research findings, with the hope of answering a few questions. First, what is the range of definitions being used in this debate? Based on an extensive literature review, Part 1 will lay out a range of articulated definitions for each relevant term, with the goal of categorizing them into a handful of distinct types. Part 2 explains the definitional redundancy and confusion in the current literature, and, drawing from the terminological patterns identified in Part 1, outlines more cohesive building blocks to inform the development of future disclosure frameworks.Our minimum goal in articulating these conceptual building blocks is to promote clearer articulations of, and distinctions between, future disclosure frameworks. More ambitiously, we suggest which definitions and conceptualizations we consider most appropriate to use in future disclosure frameworks. Here, we seek to balance benefits to participants through the disclosure of important information with the minimization of undue burdens on individual researchers and the research enterprise more generally. -/- Our analysis builds upon the central philosophical distinction between concepts and conceptions. The basic idea is that the “concept” of X refers to the general (and relatively uncontroversial) structure/shape of X, while various “conceptions” of X are more particular, filled out, and controversial elaborations of the concept. In other words, “concepts” of X will be formal representations of X, while “conceptions” of X will be substantive interpretations of the key elements and relationships operating within that formal framework. (Implicit in this distinction is an important point about the nature of disagreement – namely, that in order for two or more parties to “disagree” about X as opposed to simply talk past one another, there must be at least enough shared agreement about X to know that the parties are referring to the same thing. A concept of X provides this point of common agreement, while competing conceptions of X mark the areas where disagreement arises.) In this paper, we will employ this distinction in a fundamental way to clarify exactly where the primary disagreements arise in the debate over disclosing genetic research findings. -/- We propose that, underlying all the seeming confusion and disagreement, there are three central and widely agreed upon concepts at work in this debate—validity, value, and volition. The first two concepts concern the nature of the information itself. An obligation to disclose only exists when findings are valid and have value but there are competing conceptions of how to determine or define validity and valuableness. The third concept—volition—pertains not to the information but rather to the person to whom it will be disclosed. Does that person want or not want the information, and what is the best way of determining this? Here, too, competing conceptions arise. Our key point, though, is that almost all of the ethical disagreement arises because of competing conceptions of these three concepts. Understanding and appreciating this key point can help to refocus the substantive debate by providing some common ground to start from in determining how best to interpret these shared concepts. This refocusing can, ideally, produce more productive debate and facilitate some progress in resolving it. (shrink)

Loi recently proposed a libertarian right to direct to consumer genetic testing — independent of autonomy or utility—reflecting Cohen’s work on self-ownership and Hohfeld’s model of jural relations. Cohen’s model of libertarianism dealt principally with self-ownership of the physical body. Although Loi adequately accounts for the physical properties of DNA, DNA is also an informational substrate, highly conserved within families. Information about the genome of relatives of the person undergoing testing may be extrapolated without requiring direct engagement with their (...) personal physical copy of the genome, triggering rights and interests of relatives that may differ from the rights and interests of others, that is, individual consumers, testing providers and regulators. Loi argued that regulatory interference with exercise of the right required justification, whereas prima facie exercise of the right did not. Justification of regulatory interference could include ‘conflict with other people’s rights’, ‘aggressive’ use of the genome and ‘harming others’. Harms potentially experienced by relatives as a result of the individual’s exercise of a right to test include breach of genetic privacy, violation of their right to determine when, and if, they undertake genetic testing and discrimination. Such harms may justify regulatory intervention, in the event they are recognised; motives driving ‘aggressive’ use of the genome may also be relevant. Each of the above criteria requires clarification, as potential redundancies and tensions exist between them, with different implications affecting different groups of rights holders. (shrink)

Due to the huge amount of data being generating from different sources, the analyzing and extracting of useful information from these data becomes a very complex task. The difficulty of dealing with big data optimization problems comes from many factors such as the high number of features, and the existing of lost data. The feature selection process becomes an important step in many data mining and machine learning algorithms to reduce the dimensionality of the optimization problems and increase the performance (...) of the classification or clustering algorithms. In this paper, a set of hybrid and efficient genetic algorithms are proposed to solve feature selection problem, when the handled data has a large feature size. The proposed algorithms use a new gene-weighted mechanism that can adaptively classify the features into strong relative features, weak or redundant features, and unstable features during the evolution of the algorithm. Based on this classification, the proposed algorithm gives the strong features high priority and the weak features less priority when generating new candidate solutions. In the same time, the proposed algorithm tries to more concentrate on unstable features that sometimes appear and sometimes disappear from the best solutions of the population. The performance of proposed algorithms is investigated by using different datasets and feature selection algorithms. The results show that our proposed algorithms can outperform the other feature selection algorithms and effectively enhance the classification performance over the tested datasets. (shrink)

The U.S. oversight system for genetically engineered organisms was evaluated to develop hypotheses and derive lessons for oversight of other emerging technologies, such as nanotechnology. Evaluation was based upon quantitative expert elicitation, semi-standardized interviews, and historical literature analysis. Through an interdisciplinary policy analysis approach, blending legal, ethical, risk analysis, and policy sciences viewpoints, criteria were used to identify strengths and weaknesses of GEOs oversight and explore correlations among its attributes and outcomes. From the three sources of data, hypotheses and broader (...) conclusions for oversight were developed. Our analysis suggests several lessons for oversight of emerging technologies: the importance of reducing complexity and uncertainty in oversight for minimizing financial burdens on small product developers; consolidating multi-agency jurisdictions to avoid gaps and redundancies in safety reviews; consumer benefits for advancing acceptance of GEO products; rigorous and independent pre- and post-market assessment for environmental safety; early public input and transparency for ensuring public confidence; and the positive role of public input in system development, informed consent, capacity, compliance, incentives, and data requirements and stringency in promoting health and environmental safety outcomes, as well as the equitable distribution of health impacts. Our integrated approach is instructive for more comprehensive analyses of oversight systems, developing hypotheses for how features of oversight systems affect outcomes, and formulating policy options for oversight of future technological products, especially nanotechnology products. (shrink)

Evolutionary genetics is concerned with natural selection and neutral drift, to the virtual exclusion of almost everything else. In its current focus on DNA variation, it reduces phenotypes to symbols. Varying phenotypes, however, are the units of evolution, and, if we want a comprehensive theory of evolution, we need to consider both the internal and external evolutionary forces that shape the development of phenotypes. Genetic systems are redundant, modular and subject to a variety of genomic mechanisms of “turnover” (transposition, (...) gene conversion, unequal crossingover, slippage and so on). As such the construction and spread of novel combinations of modules by turnover, in particular within gene promoters, contributes significantly to the evolution of phenotypes. Furthermore, redundancy, turnover and modularity lead to ever more complex networks of genetic interactions and ever more functions for a given module. The significant interaction between genomic turnover and natural selection leads to a molecular coevolution between interacting modules and hence facilitates the establishment of biological novelties. BioEssays 22:1153–1159, 2000. © 2000 John Wiley & Sons, Inc. (shrink)

Advances in developmental genetics and evo-devo in the last several decades have enabled the growth of novel developmental approaches to the classic theme of homology. These approaches depart from the more standard phylogenetic view by contending that homology between morphological characters depends on developmental-genetic individuation and explanation. This article provides a systematic re-examination of the relationship between developmental and phylogenetic homology in light of current evidence from developmental and evolutionary genetics and genomics. I present a qualitative model of the (...) processes that cause de-coupling of morphological and molecular evolution by developmental system drift (DSD), and hypothesize that DSD is a widespread and regular stochastic process that is predictable from parameters such as population size, pleiotropy, and regulatory redundancy. These theoretical findings support an integrative approach in which models of DSD aid in determining when developmental-genetic explanations of homology apply and when other explanations such as stabilizing selection are needed. I argue that a phylogenetic monism about the definition and criteria of homology supports the integration of different explanations into a theory of homology better than pluralism does. (shrink)

Reinforcement learning is very effective for robot learning. Because it does not need priori knowledge and has higher capability of reactive and adaptive behaviors. In our previous works, we proposed new reinforcement learning algorithm: “Q-learning with Dynamic Structuring of Exploration Space Based on Genetic Algorithm (QDSEGA)”. It is designed for complicated systems with large action-state space like a robot with many redundant degrees of freedom. And we applied it to 50 link manipulator and effective behavior is acquired. However optimality (...) and fault tolerance of the proposed algorithm were not considered and to demonstrate effectiveness of the proposed algorithm other applications are necessary. Acquiring of locomotion patterns by a multi-legged robot is a very interesting problem. As it has many redundant degrees of freedom, application of usual reinforcement learning is difficult and an optimal locomotion has not been acquired using previous reinforcement learning algorithm. And the redundancy of the robot is effective to the fault tolerance and various locomotion patterns can be acquired for adapting the faults of the legs. In this paper, we applied QDSEGA to acquiring of locomotion pattern by the multi-legged robot and considered the optimality and fault tolerance. Effective behavior has been obtained by using our proposed algorithm. (shrink)

Reinforcement learning has recently received much attention as a learning method for complicated systems, e.g., robot systems. It does not need prior knowledge and has higher capability of reactive and adaptive behaviors. However increase in dimensionality of the action-state space makes it diffcult to accomplish learning. The applicability of the existing reinforcement learning algorithms are effective for simple tasks with relatively small action-state space. In this paper, we propose a new reinforcement learning algorithm: “Q-learning with Dynamic Structuring of Exploration Space (...) Based on Genetic Algorithm ”. The algorithm is applicable to systems with high dimensional action and interior state spaces, for example a robot with many redundant degrees of freedom. To demonstrate the effectiveness of the proposed algorithm simulations of obstacle avoidance by a 50 links manipulator have been carried out. It is shown that effective behavior can be learned by using the proposed algorithm. (shrink)

The interactions between genetic and environmental risk factors contribute to the aetiology of complex human diseases. Genome‐wide association studies (GWAS) have revealed that most of the genetic variants associated with complex diseases are located in the non‐coding part of the genome, preferentially within enhancers. Enhancers are distal cis‐regulatory elements composed of clusters of transcription factors binding sites that positively regulate the expression of their target genes. The generation of genome‐wide maps for histone marks (e.g., H3K27ac), chromatin accessibility and (...) transcription factor and coactivator (e.g., p300) binding profiles have enabled the identification of enhancers across many human cell types and tissues. Nonetheless, the functional and pathological consequences of the majority of disease‐associated genetic variants located within enhancers seem to be rather minor under normal conditions, thus questioning their medical relevance. Here we propose that, due to the prevalence of enhancer redundancy, the pathological effects of many disease‐associated non‐coding genetic variants might be preferentially (or even only) manifested under environmental stress. (shrink)

We respond to a number of objections raised by John Harris in this journal to our argument that we should pursue genetic and other biological means of morally enhancing human beings (moral bioenhancement). We claim that human beings now have at their disposal means of wiping out life on Earth and that traditional methods of moral education are probably insufficient to achieve the moral enhancement required to ensure that this will not happen. Hence, we argue, moral bioenhancement should be (...) sought and applied. We argue that cognitive enhancement and technological progress raise acute problems because it is easier to harm than to benefit. We address objections to this argument. We also respond to objections that moral bioenhancement: (1) interferes with freedom; (2) cannot be made to target immoral dispositions precisely; (3) is redundant, since cognitive enhancement by itself suffices. (shrink)

Each year, over 200 million people are infected with the malaria parasite, nearly half a million of whom succumb to the disease. Emerging genetic technologies could, in theory, eliminate the burden of malaria throughout the world by intentionally eradicating the mosquitoes that transmit the disease. In this paper, we offer an ethical examination of the intentional eradication of Anopheles gambiae, the main malaria vector of sub-Saharan Africa. In our evaluation, we focus on two main considerations: the benefit of alleviating (...) the malaria burden, and the loss of value that would accompany the eradication of the species. We outline a typology of the different ways in which species are valued or could be valuable, then use that typology to appraise the value of the species in question. We argue that Anopheles gambiae has minor (and redundant) instrumental value, little final subjective value and no objective final value. (shrink)

Accurate and reliable prediction of Perfobond Rib Shear Strength Connector is considered as a major issue in the structural engineering sector. Besides, selecting the most significant variables that have a major influence on PRSC in every important step for attaining economic and more accurate predictive models, this study investigates the capacity of deep learning neural network for shear strength prediction of PRSC. The proposed DLNN model is validated against support vector regression, artificial neural network, and M5 tree model. In the (...) second scenario, a comparable AI model hybridized with genetic algorithm as a robust bioinspired optimization approach for optimizing the related predictors for the PRSC is proposed. Hybridizing AI models with GA as a selector tool is an attempt to acquire the best accuracy of predictions with the fewest possible related parameters. In accordance with quantitative analysis, it can be observed that the GA-DLNN models required only 7 input parameters and yielded the best prediction accuracy with highest correlation coefficient and lowest value root mean square error. However, the other comparable models such as GA-M5Tree, GA-ANN, and GA-SVR required 10 input parameters to obtain a relatively acceptable level of accuracy. Employing GA as a feature parameter selection technique improves the precision of almost all hybrid models by optimally removing redundant variables which decrease the efficiency of the model. (shrink)

Gene targeting has allowed the dissection of complex biological processes at the genetic level. Our understanding of the nuances of skeletal muscle development has been greatly increased by the analysis of mice carrying targeted null mutations in the Myf‐5, MyoD and myogenin genes, encoding members of the myogenic regulatory factor (MRF) family. These experiments have elucidated the hierarchical relationships existing between the MRFs, and established that functional redundancy is a feature of the MRF regulatory network. Either MyoD or (...) Myf‐5 is sufficient for the formation or survival of skeletal myoblasts. Myogenin acts later in development and plays an essential in vivo role in the terminal differentiation of myotubes. (shrink)

Degeneracy is a poorly understood process, essential to natural selection. In the 18th and 19th centuries, the concept of degeneracy was commandeered by the colonial imagination. A rigid understanding of species, race, and culture grew to dominate the normative thinking that persisted well into the burgeoning new industrial age. A 20th-century reconfiguration of the concept by George Gamow highlighted a form of intraorganismic variation that is still underexplored. Degeneracy exists in a population of variants where structurally different components perform a (...) similar, but not necessarily identical, function with respect to context. The presence of degeneracy increases a system’s complexity and robustness against perturbations. The loss of a genetic component in biological systems, for example, can be compensated by redundant elements , or by degenerate elements . A historical survey of the use of the term “degeneracy” reveals how and why the processes it once designated, and the mechanisms it now represents, have largely escaped the purview of contemporary science. Despite confusion and general oversight, degeneracy has been characterized by select researchers at the molecular, genetic, and neuronal levels. The concept is a potent analytical tool to understand selection, variation, and transmission. (shrink)

The development of vertebrate and invertebrate nervous systems requires the production of thousands to millions of uniquely specified neurons from progenitor neural stem cells. A central question focuses on the elucidation of the developmental mechanisms that function within neural stem cell lineages to impart unique identities to neurons. A recent report(1) details the roles that two genes, pdm‐1 and pdm‐2, play within an identified neural stem cell lineage in the Drosophila embryonic central nervous system. The results show that pdm‐1 and (...) pdm‐2 are coexpressed in an identified neural precursor and function redundantly to specify the fate of this cell. As such this report offers an initial view of the genetic programs that create neural diversity. (shrink)

The dauer larva is a specialized third‐larval stage of Caenorhabditis elegans that is long‐lived and resistant to environmental insult. The dauer larva is formed in response to a high external concentration of a constitu‐tively secreted pheromone. Response to the dauer‐inducing pheromone of C. elegans is a promising genetic model for metazoan chemosensory transduction. More than 20 genes have been identified that are required for normal pheromone response. The functions of these genes include production of the pheromone, exposure of sensory (...) neuron endings to the environment, structural and functional integrity of those sensory endings, and the capacity of sensory neurons to make appropriate output. Genetic evidence suggests that two partially redundant sensory pathways act in concert to control dauer formation. At least two classes of chemosensory neurons, ADF and ASI, are implicated in the pheromone response. On the basis of on these findings, a speculative model for the pheromone response is proposed. In this model, the neurons ADF and ASI are pheromone sensors that repress dauer formation in the absence of pheromone and dere‐press dauer formation in response to pheromone. It is currently unclear whether or not the two genetically defined sensory pathways both act in ADF and ASI. (shrink)

This article argues for a shift in evolutionary metaphor-from fitness and the elimination of the less fit to fragility and passage through fragile periods of change. Childhood, for example, can be viewed as state of protected weakness, allowing time for more neural development, learning, and play. Similarly, evolutionary change can be released precisely when competitive pressure is relaxed. The fragility of evolution in time extends to several biological domains. The genetic system exhibits a surprising fluidity, whether from mobile (...) class='Hi'>genetic elements or hypermutation due to stress. Through gene duplication, organisms build up redundancy, which can more readily diverge into novelty. With endo-symbiosis one organism becomes incorporated into another, merging genomes, membranes, and metabolisms. As a result novel structures and genetic restructuring occur, making for profound evolutionary change. In a sexual life cycle, gametes within a species group fuse and amplify subtle variation. Hybridization, or unions between atypical sexual partners, can cause instant speciation and an instability that leads to more evolution. With development organisms go through rapid morphological change and sensitive transition phases. Importantly, dissociation of developmental modules in both temporal and spatial ways allow for evolutionary novelty to emerge. Several lines of evidence lead to the hypothesis that the organism's inner matrix can respond to stresses and help shape a fluid genome. In a second article, three more biological domains will be examined, in which organisms and environment more obviously interpenetrate: the remarkably plastic neural/behavioral system, novel synergisms between organisms, and the multiple, complex dynamics of ecosystems-all of which help to generate life's outstanding diversity. Last, the protection of fragile human populations will be discussed. (shrink)

Theoretical minimal RNA rings are candidate primordial genes evolved for non‐redundant coding of the genetic code's 22 coding signals (one codon per biogenic amino acid, a start and a stop codon) over the shortest possible length: 29520 22‐nucleotide‐long RNA rings solve this min‐max constraint. Numerous RNA ring properties are reminiscent of natural genes. Here we present analyses showing that all RNA rings lack dinucleotide CG (a mutable, chemically instable dinucleotide coding for Arginine), bearing a resemblance to known CG‐depleted genomes. (...) CG in “incomplete” RNA rings (not coding for all coding signals, with only 3–12 nucleotides) gradually decreases towards CG absence in complete, 22‐nucleotide‐long RNA rings. Presumably, feedback loops during RNA ring growth during evolution (when amino acid assignment fixed the genetic code) assigned Arg to codons lacking CG (AGR) to avoid CG. Hence, as a chemical property of base pairs, CG mutability restructured the genetic code, thereby establishing itself as genetically encoded biological information. (shrink)

During evolution, the genomes of eukaryotic cells have undergone major restructuring to meet the new regulatory challenges associated with compartmentalization of the genetic material in the nucleus and the organelles acquired by endosymbiosis (mitochondria and plastids). Restructuring involved the loss of dispensable or redundant genes and the massive translocation of genes from the ancestral organelles to the nucleus. Genomics and bioinformatic data suggest that the process of DNA transfer from organelles to the nucleus still continues, providing raw material for (...) evolutionary tinkering in the nuclear genome. Recent reconstruction of these events in the laboratory has provided a unique tool to observe genome evolution in real time and to study the molecular mechanisms by which plastid genes are converted into functional nuclear genes. Here, we summarize current knowledge about plastid‐to‐nuclear gene transfer in the context of genome evolution and discuss new insights gained from experiments that recapitulate endosymbiotic gene transfer in the laboratory. BioEssays 30:556–566, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

Sociological, economic and evolutionary paradigms of human agency have often seen social agents either as the rational controllers of their fate or as marionettes on the strings of historical, functional or adaptive necessity. They found it therefore difficult to account for the variability, intentionality and creativity of human behaviour and for its frequently redundant or harmful results. This paper argues that human agency is a product of evolution, but that genetic variation and inheritance can only provide a limited explanation (...) of its complex nature. The primary evolutionary problem which human agents face while they are alive is not to adapt to stable environments, but to respond flexibly and creatively to a contingent, uncertain world. Variation and selection therefore take two connected but distinct forms, one external, genetic, and inherited across generations, the other internal and cognitive, and operating during the lifetime of individuals. An examination of this lived part of evolution provides a better understanding of key properties of agency. (shrink)

The recent ability to inactivate specific genes in mice has significantly accelerated our understanding of molecular, cellular, and even behavioral aspects of normal and disease processes. However, this ability has also demonstrated the extreme complexity of genetic determination in mammals, in particular, that genes in the same family or pathway can be functionally redundant and that a given gene often has multiple roles. Thus, inactivation of a gene often does not indicate its complete spectrum of functions. To circumvent this (...) problem, many new tools and novel applications of classic techniques have been developed to place spatial and temporal restrictions on the genomic alterations. These approaches include chimera and mosaic studies, organ transplantation, complementation assays, dominant negative mutants, conditional gene knockouts, and lineage-specific gene rescue. Not only has this opened up more sophisticated ways to make genomic alterations, but it has provided the opportunity to create animal models for sporadic human genetic diseases. BioEssays 20:200–208, 1998. © 1998 John Wiley & Sons, Inc. (shrink)

Barbieri introduced and developed the concept of organic codes. The most basic of them is the genetic code, a set of correspondence rules between otherwise unrelated sequences: strings of nucleotides on the one hand, polypeptidic chains on the other hand. Barbieri noticed that it implies ‘coding by convention’ as arbitrary as the semantic relations a language establishes between words and outer objects. Moreover, the major transitions in life evolution originated in new organic codes similarly involving conventional rules. Independently, dealing (...) with heredity as communication over time and relying on information theory, we asserted that the conservation of genomes over the ages demands that error-correcting codes make them resilient to casual errors. Moreover, the better conservation of very old parts of the genome demands that they result from combining successively established nested codes such that the older an information, the more numerous component codes protect it. Barbieri’s concept of organic code and that of genomic error-correcting code may seem unrelated. We show however that organic codes actually entail error-correcting properties. Error-correcting, in general, results from constraints being imposed on a set of sequences. Mathematical equalities are conveniently used in communication engineering for expressing constraints but error correction only needs that constraints exist. Biological sequences are similarly endowed with error-correcting ability by physical-chemical or linguistic constraints, thus defining ‘soft codes’. These constraints are moreover presumably efficient for correcting errors. Insofar as biological sequences are subjected to constraints, organic codes necessarily involve soft codes, and their successive onset results in the nested structure we hypothesized. Organic codes are generated and maintained by means of molecular ‘semantic feedback loops’. Each of these loops involves genes which code for proteins, the enzymatic action of which controls a function needed for the protein assembly. Taken together, thus, they control the assembly of their own structure as instructed by the genome and, once closed, these loops ensure their own conservation. However, the semantic feedback loops do not prevent the genome lengthening. It increases both the redundancy of the genome and the information quantity it bears, thus improving the genome reliability and the specificity of the enzymes, which enables further evolution. (shrink)

The early gene knockout studies with a neurobiological focus were directed at fairly obvious target genes and added very little to our knowledge of behavioural neuroscience. On the contrary, since the behavioural consequences were often predictable, this helped confirm that the technology was working. However, a substantial number of knockouts of genes expressed in the brain have been without obvious behavioural consequences, supporting the concept of genetic canalisation and redundancy. Others have produced a behavioural deficit for which there (...) is no obvious explanation. Many cells of different tissue types have a capacity for memory, and in the brain, cells of the hippocampus are important for spatial learning and memory. Deleting genes that are expressed in the happpocampus has received considerable attention in this behavioural context. Although the initial studies experienced problems of interpretation, considerable advances have since been made. Knockout mice are now subject to tests of different forms of learning, multicellular hippocampal recordings, and restricted gene deletion specific to cells of component regions. This multi‐level approach is proving more informative. Nevertheless, there is still a need to recognise that behavioural expression is several steps removed from gene expression, and that the relationship between genes and behaviour can be reciprocal. (shrink)

Mice with alterations to specific endogenous genes can be produced by gene targeting in embryonic stem cells. The field has developed rapidly over the past decade, so that large numbers of mice with different gene deficiencies have been generated. Knockout mice provide an ideal opportunity to analyse the function of individual mammalian genes and to model a range of human inherited disorders. This powerful approach has also identified numerous examples of gene redundancy and has highlighted the need to consider (...) metabolic differences between man and mouse in disease modelling. More sophisticated gene‐targeting methods are now being used to introduce subtle gene alterations. In the future, more refined genetic analysis and genome, rather than individual gene, alterations will be achieved by incorporating site‐specific recombination into targeting strategies. Gene targeting could also make a contribution to improved protocols for gene therapy. (shrink)

It is argued that John Bickle’s Ruthless Reductionism is flawed as an account of the practice of neuroscience. Examples from genetics and linguistics suggest, first, that not every mind-brain link or gene-phenotype link qualifies as a reduction or as a complete explanation, and, second, that the higher (psychological) level of analysis is not likely to disappear as neuroscience progresses. The most plausible picture of the evolving sciences of the mind-brain seems a patchwork of multiple connections and partial explanations, linking anatomy, (...) mechanisms and functions across different domains, levels, and grain sizes. Bickle’s claim that only the molecular level provides genuine explanations, and higher level concepts are just heuristics that will soon be redundant, is thus rejected. In addition, it is argued that Bickle’s recasting of philosophy of science as metascience explicating empirical practices, ignores an essential role for philosophy in reflecting upon criteria for reduction and explanation. Many interesting and complex issues remain to be investigated for the philosophy of science, and in particular the nature of interlevel links found in empirical research requires sophisticated philosophical analysis. (shrink)

Information Theory, Evolution and The Origin ofLife: The Origin and Evolution of Life as a Digital Message: How Life Resembles a Computer, Second Edition. Hu- bert P. Yockey, 2005, Cambridge University Press, Cambridge: 400 pages, index; hardcover, US $60.00; ISBN: 0-521-80293-8. The reason that there are principles of biology that cannot be derived from the laws of physics and chemistry lies simply in the fact that the genetic information content of the genome for constructing even the simplest organisms is (...) much larger than the information content of these laws. Yockey in his previous book (1992, 335) In this new book, Information Theory, Evolution and The Origin ofLife, Hubert Yockey points out that the digital, segregated, and linear character of the genetic information system has a fundamental significance. If inheritance would blend and not segregate, Darwinian evolution would not occur. If inheritance would be analog, instead of digital, evolution would be also impossible, because it would be impossible to remove the effect of noise. In this way, life is guided by information, and so information is a central concept in molecular biology. The author presents a picture of how the main concepts of the genetic code were developed. He was able to show that despite Francis Crick's belief that the Central Dogma is only a hypothesis, the Central Dogma of Francis Crick is a mathematical consequence of the redundant nature of the genetic code. The redundancy arises from the fact that the DNA and mRNA alphabet is formed by triplets of 4 nucleotides, and so the number of letters (triplets) is 64, whereas the proteome alphabet has only 20 letters (20 amino acids), and so the translation from the larger alphabet to the smaller one is necessarily redundant. Except for Tryptohan and Methionine, all amino acids are coded by more than one triplet, therefore, it is undecidable which source code letter was actually sent from mRNA. This proof has a corollary telling that there are no such mathematical constraints for protein-protein communication. With this clarification, Yockey contributes to diminishing the widespread confusion related to such a central concept like the Central Dogma. Thus the Central Dogma prohibits the origin of life "proteins first." Proteins can not be generated by "self-organization." Understanding this property of the Central Dogma will have a serious impact on research on the origin of life. (shrink)

Society has historically not taken a benign view of genetic disease. The laws permitting sterilization of the mentally re tarded~ and those proscribing consanguineous marriages are but two examples. Indeed as far back as the 5th-10th centuries, B.C.E., consanguineous unions were outlawed (Leviticus XVIII, 6). Case law has traditionally tended toward the conservative. It is reactive rather than directive, exerting its influence only after an individual or group has sustained injury and brought suit. In contrast, state legislatures have not (...) been inhibited in enacting statutes. Many of their products can be characterized as hasty, unnecessary, ill-conceived, and based on the heart rather than the head. Moreover the lack of expert consultation sought has also been remarkable. One state legislature, for example, has advocated immunization for sickle cell anemia! Many others have enacted laws for the screening of inborn errors of metabolism, e.g., phenylketon uria, but have poorly defined the lines of responsibility to secure compliance. A spate of specific disease-related bills has emerged in the u.S. Congress, each seeking recognition and appropriations. Sickle cell anemia, hemophilia, Cooley's anemia and Tay-Sachs disease have been among the front-runners for support. Finally, in 1975, Congress has begun to examine an omnibus bill concerning all forms of genetic disease. The bill, termed the National Genetic Diseases Act is, however, still far from being enacted. (shrink)

The rapidly changing field of genetics affects society through advances in health-care and through implications of genetic research. This study addresses the impacts of new genetic discoveries and technologies on different segments of today's society. The book begins with a chapter on genetic complexity, and subsequent chapters discuss moral and ethical questions arising from today's genetics from the perspectives of health care professionals, the media, the general public, special interest groups and commercial interests.

The role of fixed charges present at the surface of biological membranes is usually described by the Gouy-Chapman-Grahame theory of the electric double-layer where the Grahame equation is applied independently on each side of the membrane and where the capacitive charges are disregarded. In this article, we generalize the Gouy-Chapman-Grahame theory by taking into account both intrinsic charges and capacitive charges, in the density value of the membrane surface charges. In the first part, we show that capacitive charges couple electrostatic (...) potentials present on both sides of the membrane. The intensity of this coupling depends both on the value of the membrane specific capacitance and the transmembrane electric potential difference. In the second part, we suggest some physiological implications of membrane electric double-layers. (shrink)

The Epic of Evolution is a course taught at Northern Arizona University. It engages the task of formulating a new epic myth that is based on the physical, natural, social, and cultural sciences. It aims to serve the need of providing meaning for human living in the vast and complex universe that the sciences now depict for us. It is an interdisciplinary effort in an academic setting that is often divided by specializations; it focuses on values in a climate of (...) relativism; and it concentrates on an enterprise for which there are few textbooks at hand. The course is presented in three segments: the cosmos before humans appeared, the human phenomenon, and scenarios for the future of evolution. (shrink)

Building on the emerging literature on the ethics of social enterprises (SEs), this paper advances the underexplored role of frontline workers (FLWs) as embedded agents at the interface between communities and SEs. Specifically, we uncover the subjectivity of FLWs as they navigate moral ambiguities while performing their professional roles, dealing with rules and regulations within the organizational hierarchy and living as members of local communities. Based on an inductive case study of a microfinance organization in Cameroon, we find that FLWs (...) engage in three rationalization strategies: cautious disengaging, safeguarding self-interest, and justifying relevance. Our findings offer a better understanding of the ethics of SEs by unpacking the subjectivity of FLWs. We highlight a bottom-up account of caring SEs, identify a boundary condition to subjectivity, and present a nuanced view of FLWs in embedded organizations. We also discuss the practical implications for SEs to improve their compassion and cater for the mental wellbeing of FLWs. (shrink)