Plant cell culture systems have become an attractive and sustainable approach to produce high‐value and commercially significant metabolites under controlled conditions. Strategies involving elicitor supplementation into plant cell culture media are employed to mimic natural conditions for increasing the metabolite yield. Studies on nanoparticles (NPs) that have investigated elicitation of specialized metabolism have shown the potential of NPs to be a substitute for biotic elicitors such as phytohormones and microbial extracts. Customizable physicochemical characteristics allow the design of monodispersed‐, (...) stimulus‐responsive‐, and hormone‐carrying‐NPs of precise geometries to enhance their elicitation capabilities based on target metabolite/plant cell culture type. We contextualize advances in NP‐mediated elicitation, especially stimulation of specialized metabolic pathways, the underlying mechanisms, impacts on gene regulation, and NP‐associated cytotoxicity. The novelty of the concept lies in unleashing the potential of designer NPs to enhance yield, harness metabolites, and transform nanoelicitation from exploratory investigations to a commercially viable strategy. (shrink)

This paper examines potential ethical and legal issues arising during the research, develop- ment and clinical use of a proposed strategy in personalized medicine (PM): using human induced pluripotent stem cell (iPSC)-derived tissue cultures as predictive models of individ- ual patients to inform treatment decisions. We focus on epilepsy treatment as a likely early application of this strategy, for which early-stage stage research is underway. In relation to the research process, we examine issues associated with biological samples; data; health; (...) vulnerable populations; neural organoids; and what level of accuracy justifies using the iPSC-derived neural tissue system. In relation to clinical use, we examine potential uses in pre-natal screening, and effects on clinical decision-making. Although our focus is providing recommendations for researchers developing work in this area, we identify the novel issue of deciding on an acceptable accuracy level for the system. We also emphasize an issue thus far neglected in the ethics of PM: PM tends to represent treatment decisions as though they should be directed solely by biomedical information, but this in itself could be detri- mental to best personalizing treatment decisions in the clinic. (shrink)

The PIWI-interacting RNA pathway, one of the major eukaryotic small RNA silencing pathways, is a genome surveillance system that silences selfish genes in animal gonads. piRNAs guide PIWI protein to target genes through Watson–Crick RNA–RNA base-parings. Loss of piRNA function causes genome instability, inducing failure in gametogenesis and infertility. Studies using fruit flies and mice as key experimental models have resulted in tremendous progress in understanding the mechanism underlying the piRNA pathway. Recent work using cultured silkworm germline cells (...) has also expanded our knowledge of piRNA biogenesis in particular, since these silkworm cells are the only cells of germline origin that can be cultured. In this review, we describe elucidation of the piRNA pathway using cultured silkworm cells as an experimental model by focusing on recent work in biochemistry and structural biology. Earlier studies that made important contributions to the field are also described. PIWI-interacting RNAs are germline-enriched small RNAs that silence transposons to maintain genome integrity. Recently, cultured silkworm germline cells such as BmN4 made great contributions to understand the mechanism underlying piRNA biogenesis in particular. In this review, we highlight the recent progress in biochemical and structural biology. (shrink)

The demonstration that pluripotent stem cells could be generated by somatic cell reprogramming led to wonder if these so-called induced pluripotent stem (iPS) cells would extend our investigation capabilities in the cancer research field. The first iPS cells derived from cancer cells have now revealed the benefits and potential pitfalls of this new model. iPS cells appear to be an innovative approach to decipher the steps of cell transformation as well as to screen the activity and toxicity of (...) anticancer drugs. A better understanding of the impact of reprogramming on cancer cell-specific features as well as improvements in culture conditions to integrate the role of the microenvironment in their behavior may strengthen the epistemic interest of iPS cells as model systems in oncology. (shrink)

Recent developments in 3D cultures exploiting the self‐organization ability of pluripotent stem cells have enabled the generation of powerful in vitro systems termed brain organoids. These 3D tissues recapitulate many aspects of human brain development and disorders occurring in vivo. When combined with improved differentiation methods, these in vitro systems allow the generation of more complex “assembloids,” which are able to reveal cell diversities, microcircuits, and cell–cell interactions within their 3D organization. Here, the ways in which human (...) brain organoids have contributed to demystifying the complexities of brain development and modeling of developmental disorders is reviewed and discussed. Furthermore, challenging questions that are yet to be addressed by emerging brain organoid research are discussed. (shrink)

In the development of the immune response, the dendritic cell subset of leukocytes plays a key role in enhancing immunogenicity. Dendritic cells can pick up antigens in the tissues and move to lymphoid organs, through which T cells continually recirculate. It is proposed that dendritic cells at these sites express functions which have beenidentified in tissue culture models. These involve efficient binding to antigen‐specific T lymphocytes, as well as the induction of the lymphokines and growth factor receptors required for (...) immunity. The dendritic cell system, apparently under the control of cytokines, is a sentinel designed to signal T cells that a significant antigen burden is present, and to generate the activated T lymphoblasts that interact with many other cell types to bring about an immune response. (shrink)

Microfilament interactions with the plasma membranes of animal cells appear to vary with cell type and localization. In the erythrocyte, actin oligomers are associated with the membrane via spectrin and ankyrin. The ends of stress fibers in cultured cells, such as fibroblasts, are attached to the plasma membrane at focal adhesion sites and may involve the protein vinculin as a linking protein. In intestinal brush border microvilli a 110,000 dalton protein links the microfilament bundles to sites on the (...) microvillus. A transmembrane complex containing actin stably associated with a cell surface glycoprotein can be isolated from ascites tumor cell microvilli and can be obtained still associated with microfilaments by gentle extraction and gradient centrifugation of the microvilli. These varied interaction mechanisms are believed to be needed to satisfy the different structural and dynamic requirements of the particular systems. (shrink)

The use of socially learned information (culture) is central to human adaptations. We investigate the hypothesis that the process of cultural evolution has played an active, leading role in the evolution of genes. Culture normally evolves more rapidly than genes, creating novel environments that expose genes to new selective pressures. Many human genes that have been shown to be under recent or current selection are changing as a result of new environments created by cultural innovations. Some changed in response to (...) the development of agricultural subsistence systems in the Early and Middle Holocene. Alleles coding for adaptations to diets rich in plant starch (e.g., amylase copy number) and to epidemic diseases evolved as human populations expanded (e.g., sickle cell and G6PD defi- ciency alleles that provide protection against malaria). Large-scale scans using patterns of linkage disequilibrium to detect recent selection suggest that many more genes evolved in response to agriculture. Genetic change in response to the novel social environment of contemporary modern societies is also likely to be occurring. The functional effects of most of the alleles under selection during the last 10,000 years are currently unknown. Also unknown is the role of paleoenvironmental change in regulating the tempo of hominin evolution. Although the full extent of culture-driven gene-culture coevolution is thus far unknown for the deeper history of the human lineage, theory and some evidence suggest that such effects were profound. Genomic methods promise to have a major impact on our understanding of gene-culture coevolution over the span of hominin evolutionary history. (shrink)

Alzheimer's disease (AD) is the most common cause of dementia, and there is currently no cure. The “β‐amyloid cascade hypothesis” of AD is the basis of current understanding of AD pathogenesis and drug discovery. However, no AD models have fully validated this hypothesis. We recently developed a human stem cell culture model of AD by cultivating genetically modified human neural stem cells in a three‐dimensional (3D) cell culture system. These cells were able to recapitulate key events of (...) AD pathology including β‐amyloid plaques and neurofibrillary tangles. In this review, we will discuss the progress and current limitations of AD mouse models and human stem cell models as well as explore the breakthroughs of 3D cell culture systems. We will also share our perspective on the potential of dish models of neurodegenerative diseases for studying pathogenic cascades and therapeutic drug discovery. (shrink)

This book offers the first comparative account of the changes and stabilities of public perceptions of science within the US, France, China, Japan, and across Europe over the past few decades. The contributors address the influence of cultural factors; the question of science and religion and its influence on particular developments (e.g. stem cell research); and the demarcation of science from non-science as well as issues including the incommensurability versus cognitive polyphasia and the cognitive (in)tolerance of different systems of (...) knowledge. (shrink)

The differentiation of mammalian neurons during development is a highly complex process involving regulation and coordination of gene expression at multiple steps. The P19 mouse embryonal carcinoma cell line is a suitable model system with which to analyze regulation of neuronal differentiation. These multipotential cells can be maintained and propagated in tissue culture in an undifferentiated state. Exposure of aggregated P19 cells to retinoic acid results in the differentiation of cells with many fundamental phenotypes of mammalian neurons. Undifferentiated (...) P19 cells are amenable to genetic manipulations such as transfection and establishment of stable clonal cell lines expressing introduced genes. Proteins that play a key role in the neuronal differentiation of P19 cells are beginning to be identified. These include retinoic acid receptors, the epidermal growth factor receptor and the transcription factors Oct‐3 and Brn‐2. The biological and technical advantages of this system should facilitate deeper analysis of the activities of proteins that play a role in neuronal differentiation. (shrink)

Steady direct current (dc) electric fields exist in many biological systems over many hours. At these times cells are dividing, differentiating, moving to final locations and extending motile processes. Each of these events may be influenced by physiological electric fields in tissue culture and when electric fields are disrupted in vivo, major developmental abnormalities arise. The likelihood of physiological electric fields playing a role in cell behaviours and some potential mechanisms are outlined.

Two welcome extensions of evolutionary thinking have come to prominence over the last thirty years: the so-called ’extended evolutionary synthesis’ (EES) and debate about biological kinds and individuals. These two agendas have, however, remained orthogonal to one another. The EES has mostly restricted itself to widening the explanations of adaptation offered by the preceding ’modern evolutionary synthesis’ by including additional mechanisms of inheritance and variation; while discussion of biological kinds has turned toward philosophical questions of essential vs. contingent properties of (...) life forms and realist vs. epistemological approaches to categorization and classification. Here we attempt to broaden the explanatory scope of evolutionary theory by linking these two agendas. We expand on the mechanistic orientation of the EES, using new understandings of networked systems of components in order to engage the distinct intellectual challenge of the origination of “historical kinds”. With this phrase we designate a subset of natural kinds that acquires, through evolutionary processes, a quasi-independent lineage-history. Such kinds emerge in both biology and culture, and we enlarge the limited number of historical kinds that have thus far been recognized in evolutionary biology in a series of paradigmatic exemplars, from genes and cell types to rituals and music. For each exemplar we discern specific mechanisms by which it arose and persists; comparing these, we suggest a general unity in the ways in which diverse historical kinds originate. (shrink)

From a classical perspective, multinational companies operate based on market determinants, but recent economic discussions emphasize the central role of the human cognitive system in the decision-making process, thereby giving birth to interdisciplinary fields such as behavioral economics and neuroeconomics. While neuroeconomics is still considered an emerging field, hitherto scant studies have investigated the reflection of cultural experiences on the nervous system. Moreover, the interpretation of cultural diversity in the decision-making process, especially from a neuroeconomic perspective, has not (...) been explored. In response, this study, aperspective research in nature, endeavors to research the neural responses to cultural diversity by contextualizing the neuroeconomic discussion within an MNC framework as one of the best multicultural settings. This study demonstrates that the internationalization process of MNCs is established on the cultural identity and integration of the executive. Through a neuroscientific lens, our findings prove that culture is a fundamental determinant of the cognitive makeup; therefore, cultural diversity in MNCs influences their decision-making process. Moreover, the performance of MNCs is driven by cultural harmonization at the executive level. Finally, the study reveals that the novel field of neuroeconomics is instrumental in identifying cultural intuitions on brain cells and the implications on economic decisions even at a corporate level. The main contribution of this study is the initiation of a multidisciplinary merge of the sociocultural and economic as well as neuroscientific fields, as a research center for MNCs’ decision-making processes. (shrink)

This article reviews recent findings that bear on the mechanism(s) of tumor‐specific Lyt‐1+2− T cell‐mediated tumor eradication in vivo A tumor‐immune Lyt‐1+2− T cell subset has been identified which is distinct from T cells mediating in vitro cytotoxicity (Lyt‐1+2+/1−2+). The Lyt‐1+2− cells have a crucial role in rejecting tumor cells when adoptively transferred into T cell‐deprived B cell mice. This indicates that Lyt‐1+2− T cells do not necessarily require recruitment of the host's cytotoxic T cell (...) precursors for implementation of in vivo immunity. Instead, this T cell subset exerts its anti‐tumor effect in collaboration with macrophages as shown with an in vivo tumor cell culture system utilizing a diffusion chamber. A pathway of Lyt‐1+2− T cell‐macrophage interaction leading to tumor cell killing is discussed in terms of its probable relevance to the eradication of tumor cell masses consisting of tumor cells expressing quantitatively and/or qualitatively different tumor antigens. (shrink)

A major obstacel to the study of mammalian development, and to the practical application of knowledge gained from it in the clinic during therapeutic in vitro fertilisation and embryo transfer (IVF‐ET), is the propensity of embryos to become retarded or arrested during their culture in vitro. The precise developmental cell cycle in which embryos arrest or delay is characteristic for the species and coincides with the earliest period of embryonic gene expression. Much evidence reviewed here implicates free oxygen radicals (...) (FORs) in the process of arrest. Thus, studies on the development of mouse preimplantation embryos in vitro have shown that (i) FORs are elevated in vitro, but not in vivo, at the time at which embryos become arrested or delayed, (ii) systems for removing reactive oxygen species to limit the formation of hydroxy radicals are present, although they have not yet been assessed quantitatively and may differ qualitatively from those in adult cells, (iii) metabolic and possibly genetic adaptations to oxidative damage are evident, (iv) published procedures for overcoming in vitro arrest are explicable in terms of FOR‐mediated damage or responses and (v) the arrest or delay of most embryos in vitro can be reduced or prevented experimentally by addition of metal chelators to limit hydroxy radical formation and lipid hydroperoxidation. (shrink)

During the formation of the brain, neuronal cell migration and neurite extension are controlled by extracellular guidance cues. Here, I discuss experiments showing that the messenger nitric oxide (NO) is an additional regulator of cell motility. NO is a membrane permeant molecule, which activates soluble guanylyl cyclase (sGC) and leads to the formation of cyclic GMP (cGMP) in target cells. The analysis of specific cells types in invertebrate models such as molluscs, insects and the medicinal leech provides insight (...) how NO and cyclic nucleotides affect the wiring of nervous systems by regulating cell and growth‐cone motility. Inhibition of the NOS and sGC enzymes combined with rescue experiments show that NO signalling orchestrates neurite outgrowth and filopodial dynamics, cell migration of enteric neurons, glial migration and axonogenesis of pioneer fibers. Cultured insect embryos are accessible model systems in which cellular mechanisms of NO‐induced cytoskeletal reorganizations can be analyzed in natural settings. Finally, I will outline some indications that NO may also regulate cell motility in the developing and regenerating vertebrate nervous system. BioEssays 27:495–505, 2005. © 2005 Wiley Periodicals, Inc. (shrink)

I argue that it is time for many feminists to rethink their attitudes towards evolutionary biology, not because feminists have been wrong to be deeply sceptical about many of its claims, both explicit and implicit, but because biology itself has changed. A new appreciation for the importance of development in biology has become mainstream and a new ontology, associated with developmental systems theory, has been introduced over the last two decades. This turn challenges some of the features of evolutionary biology (...) that have most troubled feminists. DST undermines the idea of biologicales sence and challenges both nature / nurture and nature/ culture distinctions. Freed from these conceptual constraints, evolutionary biology no longer poses the problems that have justified feminist scepticism. Indeed, feminists have already found useful applications for DST and I argue that they should expand their use of DST to support more radical and wide-ranging political theories. Si les féministes n’ont pas eu tort d’être profondément sceptiques face aux nombreuses revendications de la biologie, leur attitude face à cette science doit être remise en question car la biologie s’est transformée au courant des dernières décennies. La «théorie des systèmes de développement» est une théorie qui s’est considérablement développée et qui a pris beaucoup d’ampleur. Cette théorie n’accepte pas le concept d’essence biologique ce qui pose un défi important à la distinction nature/ culture. Une des conséquences de cet apport théorique est que le scepticisme des féministes face à la biologie de l’évolution n’est plus justifié car la biologie ne comporte plus les contraintes essentialistes qui s’avéraient contentieuses. En effet, certaines féministes ont déjà trouvé des applications utiles pour la TDS et nous avançons que les féministes doivent maintenant élargir l’utilisation de la TDS car la porté de celle-ci pourrait être significative dans d’autres domaines tel celui de la théorie politique. (shrink)

We consider the evidence that RA†, the vitamin A metabolite, is involved in three fundamental aspects of the development of the CNS: (1) the stimulation of axon outgrowth in particular neuronal sub‐types; (2) the migration of the neural crest; and (3) the specification of rostrocaudal position in the developing CNS (forebrain, midbrain, hindbrain, spinal cord). The evidence we discuss involves RA‐induction of neurites in cell cultures and explants of neural tissue; the teratological effects of RA on the embryo's nervous (...) system; the observation that RA can be detected endogenously in the spinal cord; and the fact that the receptors and binding proteins for RA are expressed in precise domains and neuronal cell types within the nervous system. (shrink)

One of the great challenges of the modern world is the control and management of complexity. After the infinitely large and the infinitely small, we once again find ourselves confronting an unfathomable infinite?the infinitely complex. With its capability for simulation, the computer has become a macroscope. It helps us understand complexity and act on it more effectively to build and manage the large systems of which we are the cells?companies, cities, economies, societies, ecosystems. Thanks to this macroscope, a new vision (...) of the world is emerging, based on a unified approach to the self-organization and evolution of complex systems. On the basis of this comprehensive vision, it becomes possible to describe the origin of a new form of life on Earth, a planetary macro-organism made up of human beings and machines, networks, and nations?a still-embryonic macro-organism that is trying to live in symbiosis with the planetary ecosystem. This new vision of the world brings together two complementary modes of analysis and action: the analytic method and the systemic approach. It can be called the unified theory of the self-organization and dynamics of complex systems. More concisely, one can propose the term symbionomics to describe the range of phenomena covered by this unified theory. Symbionomics can be defined as the study of the emergence of complex systems through self-organization, self-selection, coevolution, and symbiosis. Symbiotic relationships form through coevolution with other organisms or organizations, and collective properties emerge. This information is transmitted to succeeding generations through the memorization of structures and reproductive and evolutionary mechanisms by means of chemical or electronic coding or by the culture. A complex organization is born. From a symbionomic perspective, it is then possible to trace the essential phases of the emergence of a new form of life on Earth, a macrolife, of which humanity, this time, is not the evolutionary end point, but the starting point and catalyst. (shrink)

Several general anesthetics produce their sedative effect by activating endogenous sleep pathways. We propose that general anesthesia is a two‐step process targeting sleep circuits at low doses, and synaptic release mechanisms across the entire brain at the higher doses required for surgery. Our hypothesis synthesizes data from a variety of model systems, some which require sleep (e.g. rodents and adult flies) and others that probably do not sleep (e.g. adult nematodes and cultured cell lines). Non‐sleeping systems can be (...) made insensitive (or hypersensitive) to some anesthetics by modifying a single pre‐synaptic protein, syntaxin1A. This suggests that the synaptic release machinery, centered on the highly conserved SNARE complex, is an important target of general anesthetics in all animals. A careful consideration of SNARE architecture uncovers a potential mechanism for general anesthesia, which may be the primary target in animals that do not sleep, but a secondary target in animals that sleep. (shrink)

The authors find East Asians to be holistic, attending to the entire field and assigning causality to it, making relatively little use of categories and formal logic, and relying on "dialectical" reasoning, whereas Westerners, are more analytic, paying attention primarily to the object and the categories to which it belongs and using rules, including formal logic, to understand its behavior. The 2 types of cognitive processes are embedded in different naive metaphysical systems and tacit epistemologies. The authors speculate that the (...) origin of these differences is traceable to markedly different social systems. The theory and the evidence presented call into question long-held assumptions about basic cognitive processes and even about the appropriateness of the process–content distinction. (shrink)

DNA repair is important in such phenomena as carcinogenesis and aging. While much is known about DNA repair in single‐cell systems such as bacteria, yeast, and cultured mammalian cells, it is necessary to examine DNA repair in a developmental context in order to completely understand its processes in complex metazoa such as man. We present data to support the notion that proliferating cells from organ systems, tumors, and embryos have a greater DNA repair capacity than terminally differentiated, nonproliferating (...) cells. Differential expression of repair genes and accessibility of chromatin to repair enzymes are considered as determinants in the developmental regulation of DNA repair. (shrink)

The c‐ros, c‐met and c‐neu genes encode receptor‐type tyrosine kinases and were originally identified because of their oncogenic potential. However, recent progress in the analysis of these receptors and their respective ligands indicate that they do not mediate exclusively mitogenic signals. Rather, they can induce cell movement, differentiation or morphogenesis of epithelial cells in culture. Interestingly, the discussed receptors are expressed in embryonal epithelia, whereas direct and indirect evidence shows that the corresponding ligands are produced in mesenchymal cells. In (...) development, signals given by mesenchymal cells are major driving forces for differentiation and morphogenesis of epithelia; embryonal epithelia are generally unable to differentiate without the appropriate mesenchymal factors. The observed activities of these receptor/ligand systems in cultured cells and their expression patterns indicate that they regulate epithelial differentiation and morphogenesis also during embryogenesis and suggest thus a molecular basis for mesenchymal epithelial interactions. (shrink)

The emergence of a new tissue economy raises issues for the governance of risk and concepts of the body and self. This article explores the development of autologous cell therapies as a form of tissue engineering and considers how and why autologous applications are seen as less risky and more socially and politically acceptable. In a careful analysis of contemporary debates around the need for new international policies to regulate these technologies, we critically assess the discursive strategies employed to (...) support ideas of the body as a natural entity. Central to these debates are assumptions that autologous applications do not threaten the moral or corporeal integrity of the individual and that they are ‘an ethics-free zone’. Analysis reveals that concepts such as intercorporeality need to be refined if they are to assist our understanding of these cell-based therapies. We consider the biopolitics of Autologous Chondrocyte Implantation (ACI) in order to show the linkages between the culturing of cells, regulation and the reproduction of the self. (shrink)

Antes da Filosofia, a Sabedoria era a que continha o "saber" humano haurido da experiéncia vivida. E, portanto, Sabedoria expressava mais ou menos o que hoje concebemos como Cultura. Ora, a Filosofia construiu-se mediante a operacionalização de uma passagem: do contexto da Cultura (a qual se expressava mediante um sistema simbolico próprio do mito, da religião e da literatura heróica) para o contexto da Ciencia (a qual se expressou, na dependència do antigo, através de um novo sistema simbólico conceitual, pelo (...) exercicio de uma determinada competência). Do contexto de uma Sabedoria experimental, organizada no tempo da experiência da vida, construiu-se uma habilidade de tipo próprio: a de elaborar considerações sábias ou a de formular máximas mediante observações precisas. Tales representa, nos primórdios da descoberta do pensamento racional, orientando-a, não tanto para o governo da vida ou do viver, mas para o governo da Natureza, pela observação dos seus fenómenos. É sobre a instauração desta nova atitude (inferida do exercicio prático e não de discurso teórico feito por Tales) que se detém este artigo. Ele versa, num primeiro momento, sobre a sua figura de Sábio; sobre a sua necessidade de viajar, como forma de estudo e de instrução; sobre o seu envolvimento com a Geometria (uma ciência de feição especulativa, mas de carácter empírico); enfim, sobre a sua habilidade teórica e prática (mediante relatos de Platão e de Aristóteles). Num segundo momento, e finalmente, aborda a sua explicação racional da "physis". /// Avant la Philosophie, la sagesse détenait le "savoir" humain extrait de l'expérience vécue. La sagesse s'approchait done de ce que nous comprenons aujourd'hui comme culture. La Philosophic est le fruit du passage du contexte de la Culture (celle qui s'exprimait par un système symbolique propre au mythe, à la religion, à la littérature héroïque) à celui de la Science (qui s'est exprimée, pour la dépendance du système ancien, par le biais d'un nouveau système symbolique conceptuel moyennant l'exercice d'une compétence détérminée). C'est à partir de la Sagesse experimentale, organisée pendant l'expérience de la vie, que s'est construite une capacité propre: celle qui consiste à élaborer des considérations sages ou à formuler des maximes moyennant des observations précises. Aux origines de la découverte de la pensée rationnelle, Thalès fut un jalon dans ce mouvement de la sagesse: il a marqué le début d'une nouvelle activité du sage, par l'exercice spécifique de la recherche ou de l'élévation rationnelle, en l'orientant, non seulement pour la conduite de la vic (ou du vivre), mais encore pour la connaissance de la nature, grace à l'observation de ses phénomenes. Le thème de cet article aborde l'instauration de cette nouvelle attitude (induite de l'exercice pratique et non du discours théorique fait par Thalès). II traite, en un premier moment, de Thalès comme Savant; de ses voyages comme forme d'etude et d'instruction, de son introduction à la Géométrie (une science de nature spéculative mais de caractère empirique); enfin, de son habileté théorique et pratique (en utilisant des récits de Platon et d'Aristote). En un second moment, il traite de son explication rationnelle de la "Physis". /// Before Philosophy, Wisdom included much of human "knowledge" learned through the experience of life. Wisdom was thus approximately what we nowadays call Culture. Philosophy was built up by way of a passage: from the context of Culture (wheh espresses itself by means of a symbolic system peculiar to myth, religion and epic literature) to the context of Science (which although still dependent from the ancient tradition expresses itself through a new conceptual symbolic system by means of the exercise of a specific competence). Out of the context of an experimental Wisdom, a specific skill developed organized on the basis of experience of life: to elaborate wise considerations, or to formulate propositions based upon precise observations. In the early days of the discovery of rational thought, Thales represents a landmark in his sapiential movement: the inauguration of a new activity of Scholars, through the specific exercise either of research or of rational speculation, directed mainly not to the rule of life, but to the rule of Nature through the observations of its phenomena. This paper deals with the instauration of this new activity (inferred from Thales 1 practice and not from his theoretical discourse). First, Thales personality of a Scholar is analysed: his need to travel as a way of study and instruction; his interest for Geometry (a science of speculative kind, but of empirical character); his theoretical and practical skill (according to the reports of both Plato and Aristotle). In a second part, Thales' rational explanation of "physis" is examined. (shrink)

The genetic code appeared on Earth at the origin of life, and the codes of culture arrived almost four billion years later. For a long time it has been assumed that these are the only codes that exist in Nature, and if that were true we would have to conclude that codes are extraordinary exceptions that appeared only at the beginning and at the end of the history of life. In reality, various other organic codes have been discovered in the (...) past few decades and it is likely that more will come to light in the future. The existence of many organic codes in Nature is therefore an experimental fact, but also more than that. It is one of those facts that have extraordinary implications. In this book it is shown that the genetic code was a precondition for the origin of the first cells, the signal transduction codes divided the first cells into three primary kingdoms (Archaea, Bacteria and Eukarya), the splicing codes were instrumental to the origin of the eukaryotic nucleus, the histone code provided a new regulation system in eukaryotic genomes, and the cytoskeleton codes allowed the Eukarya to perform internal movements, including those of mitosis and meiosis. It is shown, furthermore, that organic codes had a key role in multicellular life, in particular in the origin of animals, the origin of mind and the origin of language. The great events of macroevolution, in other words, were associated with the appearance of new organic codes, and we can easily understand why. The reason is that a new code brings into existence something that has never existed before because it creates arbitrary associations, relationships that are not determined by physical necessity. Another outstanding implication is the fact that codes involve meaning and we need therefore to introduce in biology, with the standard methods of science, not only the concept of biological information but also that of biological meaning. The research on biological codes, in conclusion, is bringing to light new mechanisms in evolution and new fundamental concepts in science. This research is the field of Code Biology, the study of all codes of life, from the genetic code to the codes of culture, from the origin of life to the origin of man. (shrink)

Our purpose in this essay is to introduce new concepts in a wide and recursive view of the systemic consequences of the following biological facts that I and we have presented that can be resumed as: that as living systems we human beings are molecular autopoietic system; that living systems live only as long as they find themselves in a medium that provides them with all the conditions that make the realization of their living possible, that is, in the (...) continuous conservation of their relation of adaptation to the circumstances in which they find themselves; that as a living system exists only in a relation of adaptation with the medium that operates as its ecological niche, its reproduction necessarily occurs as a process of systemic duplication or multiplication of the ecological organism-niche unity that it integrates; that the worlds of doings that we generate as languaging beings in our conversations, explanations, reflections and theories are part of our ecological niche; and that we human beings as living beings that exist in languaging, are biological–cultural beings in which our cultural and our biological manners of existences can be distinguished but cannot be separated. Of the systemic consequences of these biological facts that we consider in this essay, we wish to mention two as the principal: that the diversification of manners of living produced in biological evolution is the result of differential survival in a changing medium through the conservation of adaptation, and not through competitive survival of the best; and that we in our living as languaging human beings are the epistemological fundament of all that we do and know as such. (shrink)

Embryos, cells, genes, and organisms : reflections on the history of evolutionary developmental biology / Manfred D. Laubichler and Jane Maienschein The organismic systems approach : streamlining the naturalistic agenda / Werner Callebaut, Gerd B. Müller, and Stuart A. Newman Complex traits : genetics, development, and evolution / H. Frederik Nijhout Functional and developmental constraints on life-cycle evolution : an attempt on the architecture of constraints / Gerhard Schlosser Legacies of adaptive development / Roger Sansom Evo-devo meets the mind : (...) toward a developmental evolutionary psychology / Paul E. Griffiths Reproducing entrenchments to scaffold culture : the central role of development in cultural evolution / William C. Wimsatt and James R. Griesemer. (shrink)

English summary: Nietzsche's work does not fit into readily defined categories or disciplinary fields. Rejecting definitive truths and assumptions, he nourished his philosophical explorations with constant experimentation, reading widely on texts as varied as Greek philosophy, Darwinian evolution, thermodynamic cosmology, and the history of religion. Through this multiplication of perspectives, Nietzsche developed a philosophy of culture that sought to raise mankind up beyond the possibilities of Judeo-Christian values. Although his philosophy would later be misappropriated for National Socialism, other much nobler (...) readers, such as Heidegger and Foucault, would find value in his works. French description: L'oeuvre de Nietzsche ne se presente pas comme un systeme qui permettrait une categorisation simple dans un champ disciplinaire existant. Professeur de philologie classique a l'Universite de Bale, Nietzsche a renonce a sa chaire universitaire pour devenir un philosophe itinerant et un esprit libre. C'est l'epoque ou il rompt avec ses anciens mentors: Arthur Schopenhauer, son maitre en philosophie, et Richard Wagner, ce mystagogue dans les secrets de l'art et de la vie dont il avait salue le projet culturel dans La Naissance de la tragedie (1872). Nietzsche se mefiera dorenavant de toutes les convictions et de toutes les verites definitives. Sa philosophie sera une constante experimentation, nourrie d'innombrables lectures qui forment quasiment un panorama de l'histoire de la culture humaine: des Grecs a la theorie de l'evolution darwinienne, de la cosmologie thermodynamique a l'anthropologie evolutionniste, en passant par l'histoire du christianisme et des religions extra europeennes. On assiste chez Nietzsche a une multiplication indefinie des perspectives, au fil d'ecrits aphoristiques qui ne livrent jamais leur dernier mot. Une problematique essentielle se dessine cependant a travers ces multiples experimentations: c'est celle d'une philosophie de la culture, qui aspire a elever l'homme - tant au sens d'un elevage zoologique que d'une elevation de valeur - pour en faire un etre plus epanoui et plus puissant qu'il ne l'a ete jusqu'a present sous l'emprise des valeurs judeo chretiennes. Nietzsche propose ainsi une veritable transvaluation de toutes les valeurs, qui se veut tout autre chose qu'un retour a la barbarie des origines. L'auteur d'Ainsi parlait Zarathoustra a conscience, ce faisant, de s'affirmer comme un philosophe dangereux. Mais il pense que la creation est fondamentalement indissociable de la destruction, voyant dans cette idee le secret du dionysiaque et donc de la tragedie grecque. Les posterites de l'oeuvre de Nietzsche confirment son caractere a la fois dangereux et fecond. On ne saurait passer sous silence l'appropriation nazie, qui oblige a s'interroger sur ce qui, chez Nietzsche, pouvait preter le flanc a un tel detournement. Mais pour autant, il serait injuste de reduire Nietzsche a cette tragique caricature, alors qu'il a trouve en Heidegger, Deleuze ou encore Foucault des lecteurs bien plus dignes de lui. (shrink)

Endothelial cells, when cultured on gelled basement membrane matrix exert forces of tension through which they deform the matrix and at the same time they aggregate into clusters. The cells eventually form a network of cord-like structures connecting cell aggregates. In this network, almost all of the matrix has been pulled underneath the cell cords and cell clusters. This phenomenon has been proposed as a possible model for the growth and development of planar vascular systems in (...) vitro. Our hypothesis is that the matrix is reorganized and the cellular networks form as a result of traction forces exerted by the cells on the matrix and the latter's elasticity. We construct and analyze a mathematical model based on this hypothesis and examine conditions necessary for the formation of the pattern. We show cell migration is not necessary for pattern formation and that isotropic, strain-stimulated traction is sufficient to form the observed patterns. (shrink)

Subjective experience is transformed into objective reality for societal members through cultural idea systems that can be represented with theory and data models. A theory model shows relationships and their logical implications that structure a cultural idea system. A data model expresses patterning found in ethnographic observations regarding the behavioral implementation of cultural idea systems. An example of this duality for modeling cultural idea systems is illustrated with Arabic proverbs that structurally link friend and enemy as concepts through a (...) culturally defined computational system. Computational systems also generate new concepts, as will be illustrated through a theory model for the structure of a .. (shrink)

Surprise is treated as an affect in Aristotelian philosophy as well as in Cartesian philosophy. In experimental psychology, surprise is considered to be an emotion. In phenomenology, it is only addressed indirectly (Husserl, Heidegger, Levinas), with the important exception of Ricoeur and Maldiney; it is reduced to a break in cognition by cognitivists (Dennett). Only recently was it broached in linguistics, with a focus on lexico-syntactic categories. As for the expression of surprise, it has been studied in connection with evidentiality (...) in languages that encode surprise morphosyntactically. However, how surprise is encoded in languages that lack an evidential morphosyntactic system has been largely unexplored. This book provides new insights into the dynamics of surprise based on a heuristic hypothesis tested against the investigation of time, language and emotion. It is intended to arouse the interest of a multidisciplinary audience keen on crossing the disciplinary borders of phenomenology, cognitive sciences, and pragmatics. The theoretical approaches adopted in this collection of articles rely on experiments and corpus data. They advance knowledge by building on robust empirical results coming from psychology, microphenomenology, linguistics and physiology. (shrink)

We have been studying cognition and learning in research laboratories in the field of biomedical engineering. Through our combining of ethnography and cognitive-historical analysis in studying these settings we have been led to understand these labs as comprising evolving distributed cognitive systems and as furnishing agentive learning environments. For this paper we develop the theme of 'models-in-action,' a variant of what Knorr Cetina has called 'knowledge-in-action.' Among the epistemically most salient objects in these labs are so called "model systems," which (...) are designs that blend engineering with the study and use of biological systems for purposes of simulative model-based reasoning. We portray the prevalent design-orientation in this engineering specialty and how the prevailing activity of cell-culturing in these labs transitions into a design activity for the bio-medical engineers, leading them to work with 'wet' devices. We discuss how devices, 'wet' and 'dry,' situate model-based understandings and how they participate in model systems in these labs. Models tend to come in clusters or configurations, and the model systems in these labs are epistemically salient junctures of interlocking models. Model systems in these labs evolve thereby consolidating what we want to call a 'fabric of interlocking models,' which functions as point of stability and departure in these labs. We convey a taste of such a 'fabric' for a tissue-engineering lab. We conjecture that through this 'fabric' extended developments in technology and methodology have a 'situated' presence in the workings of these labs. (shrink)

The book will be an invaluable source for cognitive psychologists, neuroscientists, and students interested in this active and exciting area of research. This volume is the third in a series.

Human cerebral organoids (HCOs) are three-dimensional in vitro cell cultures that mimic the developmental process and organization of the developing human brain. In just a few years this technique has produced brain models that are already being used to study diseases of the nervous system and to test treatments and drugs. Currently, HCOs consist of tens of millions of cells and have a size of a few millimeters. The greatest limitation to further development is due to their lack (...) of vascularization. However, recent research has shown that human cerebral organoids can manifest the same electrical activity and connections between brain neurons and EEG patterns as those recorded in preterm babies. All this suggests that, in the future, HCOs may manifest an ability to experience basic sensations such as pain, therefore manifesting sentience, or even rudimentary forms of consciousness. This calls for consideration of whether cerebral organoids should be given a moral status and what limitations should be introduced to regulate research. In this article I focus particularly on the study of the emergence and mechanisms of human consciousness, i.e. one of the most complex scientific problems there are, by means of experiments on HCOs. This type of experiment raises relevant ethical issues and, as I will argue, should probably not be considered morally acceptable. (shrink)

During somitogenesis an oscillatory mechanism termed the “segmentation” clock generates periodic waves of gene expression, which translate into the periodic spatial pattern manifest as somites. The dynamic expression of the clock genes shares the same periodicity as somitogenesis. Notch signaling is believed to play a role in the segmentation clock mechanism. The paper by Hirata et al.(1) identifies a biological clock in cultured cells that is dependent upon the Notch target gene Hes1, and which shows a periodicity similar to (...) that of the segmentation clock. This finding opens the possibility that the same oscillator mechanism might also operate in other tissues or cell types. BioEssays 25:200–203, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

During somitogenesis an oscillatory mechanism termed the “segmentation” clock generates periodic waves of gene expression, which translate into the periodic spatial pattern manifest as somites. The dynamic expression of the clock genes shares the same periodicity as somitogenesis. Notch signaling is believed to play a role in the segmentation clock mechanism. The paper by Hirata et al.(1) identifies a biological clock in cultured cells that is dependent upon the Notch target gene Hes1, and which shows a periodicity similar to (...) that of the segmentation clock. This finding opens the possibility that the same oscillator mechanism might also operate in other tissues or cell types. BioEssays 25:200–203, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

Growing ecological problems have raised the need for conceptual tools dedicated to studying semiotic processes in cultural-ecological systems. Departing from both ecosemiotics and cultural semiotics, the concept of an ecosemiosphere is proposed to denote the entire complex of semiosis in an ecosystem, including the involvement of human cultural semiosis. More specifically, the ecosemiosphere is a semiotic system comprising all species and their umwelts, alongside the diverse semiotic relations (including humans with their culture) that they have in the given ecosystem, (...) and also the material supporting structures that enable the ecosemiosphere to thrive. Drawing parallels with Juri Lotman’s semiosphere concept, the ecosemiosphere is characterized by its heterogeneity, asymmetry, and boundedness. But unlike Lotman’s concept, the ecosemiosphere is not characterized by an overall boundedness, that is, by the presence of external binary boundaries and the shared identity arising from this unity. The involvement of human culture in the ecosemiosphere manifests in interspecies dialogues and semiotic engagements. We need to scrutinize what affordances and semiotic resources culture could offer to nonhuman species and how culture could, by semiotic means, raise the integrity, stability, and resiliency of the ecosystem. The ecosemiosphere is a grounded semiosphere. (shrink)

1. Tout système juridique est production d’une histoire et d’une culture politiques déterminée, qui lui ont donné une organisation spécifique. Parler des limites de telles organisations peut s’entendre en deux sens, qui interagissent: premièrement, elles peuvent servir à différencier ces systèmes par rapport à d’autres ordres normatifs. Secondement, elles désignent ce que, par sa texture, le droit est hors d’état de réussir. 2. On comprend le concept de système comme une organisation aux structures différenciées de textes, de normes, d’acteurs. Ce (...) qui caractérise un système est son autoréférentialité et ses modes de clôture et ses modes d’ouverture. 3. Concernant la limite dans le second sens, on observera que la normativité comme mode d’action propre au droit le met souvent dans l’incapacité d’assumer pleinement les tâches de régulation qui lui sont confiées. Il s’agit d’une part d’une limite factuelle: celle de la technicité et du volume de ces tâches. D’autre part, la nécessité de plus en plus fréquente de prendre en compte les circonstances individuelles concrètes de l’application entraîne une légistique de diminution de la densité normative et, par conséquent, de déplacer une épistémologie fondée sur la répétition en direction de l’innovation. 4. Ces deux facteurs notamment font du droit un univers qui ne peut plus prétendre à une complétude cohérente: c’est un univers en constante évolution, qui exige pour sa mise en œuvre, de manière continue, l’apport d’informations provenant de son environnement. Ces apports circulent dans les modes d’ouverture du droit—la diminution de la densité normative et le recours à des expertises, des savoirs, des déontologies extérieures. Cependant, en vertu de l’autoréférentialité du droit, ces apports doivent être sélectionnés et juridicisés pour être intégrés dans le système juridique et préserver ainsi sa clôture. Il y a là une double programmation à respecter: la sélection doit d’une part respecter le cadre normatif du droit et de l’autre porter sur un choix correspondant aux attentes sociales qu’il s’agit de convaincre de son bien-fondé. Les limites du droit par rapport à d’autres ordres normatifs est ainsi définie par l’ordre juridique lui-même, dans le respect de cette double programmation. 5. Ce système a des présupposés politiques, culturels et historiques qui empêchent d’élaborer sans autre une essence du droit, valable urbi et orbi: notamment séparation des pouvoirs et liberté d’expression. Il n’est même pas certain qu’il puisse perdurer. En particulier, l’internalisation croissante du droit n’est guère conciliable avec son organisation telle que l’Occident l’a conçue. En outre, de plus en plus le droit devient l’objet d’une normativité supérieure, au nom de laquelle il est lui-même jugé: c’est le phénomène de l’économisation du droit. (shrink)

The gap between Science and the Humanities becomes tangible when they both attempt to address the same problem. One such case is relationship between Life and biological molecules. Traditionally, molecular biology has attempted to explain biological processes in terms of physicochemical characteristics of individual macromolecules. The new science of systems biology largely ignores the molecular characteristics of specific molecules and endeavors to analyze biological processes through the relationship between thousands of molecules. On the face of it, the difference between the (...) molecular and the systems approach to biological research corresponds to the tension between the reductionist and the emergentist view in the philosophy of biology. However, a closer analysis reveals that experimental science and philosophy are concerned with different aspects of the problem and therefore search for different solutions. A main reason for this is the difference in their respective concepts of “question” and “answer”, which is essentially unbridgeable. (shrink)

Evolutionary epistemology has experienced a continuous rise over the last decades. Important new theoretical considerations and novel empirical findings have been integrated into the existing framework. In this paper, I would like to suggest three lines of research that I believe will significantly contribute to further advance EE: ontogenetic considerations, key ideas from cognitive biology, and the framework of the Extended Evolutionary Synthesis. EE, in particular the program of the evolution of epistemological mechanisms, seeks to provide a phylogenetic account of (...) the generation of cognitive processes underlying knowledge creation. Traditionally, EE and EEM have been oriented towards an account of evolutionary theory that mainly drew from the tenets of the Modern Synthesis. The Modern Synthesis largely dismisses ontogenetic processes and considers them irrelevant for evolutionary explanations. If anything, the role of development in evolution is believed to be that of a constraint. There is, however, ample evidence for a tight intertwinement of developmental and evolutionary processes. Organisms employ their cognitive apparatus to interact with the environment in order to achieve a fully functioning perceptual and cognitive nervous system. Also, ontogeny provides generative potentials to enable variations that natural selection can act upon. EEM’s agenda may, therefore, strongly benefit from bringing together ontogenetic and phylogenetic approaches. To grapple with this challenge, an alternative vision of the evolutionary theory termed Extended Evolutionary Synthesis could be used. This extended evolutionary theory explores relationships between the processes of individual development and phenotypic change during evolution and can provide a more suitable framework for EEM to draw from. In recent years, cognitive biology has gained momentum as an independent research field. Cognitive biology builds on the concepts of EEM and understands knowledge as a biogenic phenomenon. Its main objective is also the formulation of substantiated interrelations between cognition and evolution but it focuses on cognitive functionality at all levels of biological organization. It thus employs a “vertical” approach that encompasses nested hierarchies which span from single molecules, cells, and tissues to the organismal level, communities, and societies. In contrast to cognitive biology, EEM is here understood to adopt a “horizontal” approach that focuses on phylogenetic explanations of cognition and knowledge acquisition. Linking EEM with the key ideas of cognitive biology could make EEM’s research program stronger as it can more easily accommodate phylogenetic and ontogenetic questions within a hierarchical, multilevel perspective. This is of particular importance for a more comprehensive account of cognition since living systems are subject to context-dependent causal influences from different organizational levels. In addition to EEM, there is a second program of EE. This program has been labeled evolutionary epistemology of theories and understands the increase in human knowledge, such as scientific theories, as naturalistic accounts of evolution. Both, EEM and EET initially drew from the core concepts of the Modern Synthesis. Several scholars have severely criticized the analogies made between EET and the Neo-Darwinian key processes of evolution. In particular processes of random mutation, the rate of variation, natural selection as the unique driving force, and the adaptationist agenda are believed to reveal disanalogies. In contrast to the Modern Synthesis, the Extended Evolutionary Synthesis not only recognizes developmental processes but also ecological interactions and systems dynamics as well as social and cultural evolutionary reciprocity as important evolutionary processes. Concepts of the Extended Evolutionary Synthesis are therefore expected to be more fruitful for re-conceptualizing parallels between scientific theorizing and biological evolution. (shrink)

This article argues that the translation of books may be fruitfully understood as constituting a cultural world-system. The working of this system, based on a core-periphery structure, accounts for the uneven flows of translations between language groups as well as for the varying role of translations within language groups. The final part outlines how this general sociological model may be further developed.

Mouse embryo cells, primed to differentiate with the hypomethylating agent 5‐azacytidine (5‐aza‐CR), provide an excellent model system in which cellular differentiation can be studied at the molecular level. An inherent advantage of this system is the availability of clonal populations of cells representative of the non‐differentiated precursor, those whose determinative state is that of a specific lineage, and the end stage, phenotypically mature cell. Analysis of these cultures at the cellular and molecular level will advance our understanding (...) of requirements for and the mechanism of action of growth modulators as well as the necessity for controlled expression of certain proto‐oncogenes. At a more fundamental level, the system can be used to identify, isolate and characterize genes whose expression alters the phenotypic fate of cells. (shrink)

Long ago, I set out to solve a problem, but something happened along the way: I was diverted by an unexpected observation. Thereafter, the direction of my research was guided at each stage by increasing familiarity with the experimental material and what could be done with it. The result was the birth of therapy with cultured keratinocytes. Subsequent developments soon led to the formation of the company Biosurface Technology (later taken over by the Genzyme Corporation), which provided autologous cultures (...) for burn victims in many parts of the world. Further progress by others led to new therapeutic applications of cultured keratinocytes, such as treatment of an ocular disease and gene therapy. Unfortunately, there have developed serious regulatory problems that are a danger to future progress. As described in this brief history, the initial stages of development of cell therapy for the treatment of human disease were possible only because there was no restraint by committees or governmental regulations. BioEssays 30:897–903, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

Continuous culture techniques were developed in the early twentieth century to replace cumbersome studies of cell growth in batch cultures. In contrast to batch cultures, they constituted an open concept, as cells are forced to proliferate by adding new medium while cell suspension is constantly removed. During the 1940s and 1950s new devices have been designed—called “automatic syringe mechanism,” “turbidostat,” “chemostat,” “bactogen,” and “microbial auxanometer”—which allowed increasingly accurate quantitative measurements of bacterial growth. With these devices cell growth (...) came under the external control of the experimenters and thus accessible for developing a mathematical theory of growth kinetics—developed mainly by Jacques Monod, Aron Novick and Leo Szilard in the early 1950s and still in use today. The paper explores the development of continuous culture devices and claims that these devices are simulators for standard cells following specific requirements, in particular involving mathematical constraints in the design and setting of the devices as well as experiments. These requirements have led to contemporary designs of continuous culture techniques realizing a specific event-based flow algorithm able to simulate directed evolution and produce artificial cells and microorganisms. This current development is seen as an alternative approach to today’s synthetic biology. (shrink)

Cognitive deficits were produced in rats by different methods of damaging the brain: chronic ingestion of alcohol, causing widespread damage to diffuse cholinergic and aminergic projection systems; lesions (by local injection of the excitotoxins, ibotenate, quisqualate, and AMPA) of the nuclei of origin of the forebrain cholinergic projection system (FCPS), which innervates the neocortex and hippocampal formation; transient cerebral ischaemia, producing focal damage especially in the CA1 pyramidal cells of the dorsal hippocampus; and lesions (by local injection of the (...) neurotoxin, colchicine) of the granule cells of the dentate gyrus. Following chronic alcohol or lesions of the FCPS, transplants of cholinergically rich fetal brain tissue into the terminal areas (neocortex and/or hippocampus) restored performance almost to control levels, with a time course consistent with growth of the transplants and integration with host tissue; transplants of cholinergically poor fetal tissue (hippocampus) were without effect, as were transplants of cholinergically rich tissue into the region containing the nuclei of origin of the FCPS. Grafts of primary cells enriched in glia and cultured neuroblastoma cells into the terminal areas of the FCPS were equally effective, suggesting that there are multiple mechanisms by which neural transplants can restore cognitive function following diffuse cholinergic damage. In contrast, after ischaemia- or neurotoxin-induced damage to CA1 or dentate granule cells respectively, cholinergically rich fetal transplants into the damaged hippocampal formation were ineffective in restoring performance. After ischaemic damage, however, performance was restored by suspension grafts of CA1 cells but not by transplants containing CA3 pyramidal cells or granule cells; and after colchicine damage it was restored by solid grafts containing granule but not CA1 pyramidal cells. Furthermore, electrophysiological evidence has demonstrated functional, graft type-specific host-graft functional neuronal connectivity. Thus, restoration of cognitive function by neural transplants is possible after damage to either diffuse (cholinergic) or point-to-point (intrahippocampal) forebrain systems, but the transplant must be appropriate to the damage to be repaired. Because the different types of brain damage studied provide analogues of human alcoholic dementia, Alzheimer's disease, and heart attack, these results are encouraging with regard to the eventual application of neural transplant surgery to the treatment of cognitive deficits in humans. (shrink)