Stimulation of mitogenesis by the epidermal growth factor (EGF) operates through a pathway involving the receptor, the small G‐protein Ras and protein kinases of the MAP kinase cascade. It is proposed that two of the critical steps of that pathway utilize localization of components to the plasma membrane where Ras is located: recruitment of the nucleotide exchange protein Sos to the phosphorylated EGF receptor via a complex with the SH2/SH3‐containing protein Grb2 and recruitment of the protein kinase Raf to activated (...) Ras. Moreover, it is then proposed that Raf associates with the cytoskeleton at the membrane as it is being activated. Other signaling elements, including class I receptor kinases, nonreceptor tyrosine kinases and tyrosine phosphatases, are known to function at specific cellular sites. These observations have led us to propose that localization of signaling components, and particularly sites at membrane‐microfilament interfaces, play critical roles in cellular regulation. (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)

MUC1 and MUC4 are the two membrane mucins that have been best characterized. Although they have superficially similar structures and have both been shown to provide steric protection of epithelial surfaces, recent studies have also implicated them in cellular signaling. They act by substantially different mechanisms, MUC4 as a receptor ligand and MUC1 as a docking protein for signaling molecules. MUC4 is a novel intramembrane ligand for the receptor tyrosine kinase ErbB2/HER2/Neu, triggering a specific phosphorylation of the ErbB2 in the (...) absence of other ErbB ligands and potentiating phosphorylation and signaling through the ErbB2/ErbB3 heterodimeric receptor complex formed in the presence of neuregulin. In contrast, MUC1 has a highly conserved cytoplasmic tail, which binds β‐catenin, a key component of adherens junctions and a regulator of transcription, in a process that is tightly regulated by MUC1 phosphorylation. The specific localization of these membrane mucins to the apical surfaces of epithelial cells suggests that their signaling functions may be important as sensor mechanisms in response to invasion or damage of epithelia. BioEssays 25:66–71, 2003. © 2002 Wiley Periodicals, Inc. (shrink)

En utilisant de première main les sources juives et les textes de la tradition hébraïque, ce livre affirme la différence fondamentale entre le messianisme et ce qui y est souvent assimilé, le millénarisme, la fin du monde, la téléologie, la théodicée et l’eschatologie. Cette distinction préliminaire, philosophiquement articulée, permet de mieux penser le lien entre le temps et la loi, c’est-à-dire finalement entre le politique et le religieux, et d’en dégager quelques significations majeures. En particulier, la sécularisation est ici envisagée (...) sous deux rapports opposés et complémentaires, l’advenir du nouveau et le retour du même, la réparation et la répétition. Le livre éclaire par ailleurs la notion de loi du talion au regard de la rédemption messianique et propose une réflexion sur la relation qu’entretiennent la temporalité et la loi. Il se conclut sur une affirmation : la réalisation messianique ne peut finalement s’inscrire que dans l’éphémère et le messianisme ne peut s’entendre que dans l’instant et non dans la durée, dans l’imprévisibilité et non dans la linéarité. (shrink)

Comment expliquer, dans une perspective psychologique, pourquoi certaines personnes se tournent vers le religieux aujourd’hui? Quels sont les motifs d’attraction pour le religieux? Cette question est particulièrement importante dans le contexte actuel de la sécularisation et du marché du religieux. Des résultats solides soutiennent la présence de vulnérabilités psychologiques préalables à l’attraction pour le religieux. Outre ces besoins compensatoires, nous émettons l’hypothèse que la religiosité moderne est caractérisée par des motivations qui reflètent la réalisation de soi et le développement optimal (...) de la personne . Dans le présent article, sept études sont rapportées. Parmi des populations spécifiques , plusieurs mesures ont été examinées dans le cadre de ces deux paradigmes . Les comparaisons aux scores obtenus par la population tout-venant sur les mêmes mesures suggèrent la coexistence de ces deux types de motifs. En outre, les différences quantitatives observées entre les populations étudiées semblent pouvoir être interprétées en termes de correspondance entre la demande et l’offre. (shrink)

We estimate that 208,000 deep brain stimulation (DBS) devices have been implanted to address neurological and neuropsychiatric disorders worldwide. DBS Think Tank presenters pooled data and determined that DBS expanded in its scope and has been applied to multiple brain disorders in an effort to modulate neural circuitry. The DBS Think Tank was founded in 2012 providing a space where clinicians, engineers, researchers from industry and academia discuss current and emerging DBS technologies and logistical and ethical issues facing the field. (...) The emphasis is on cutting edge research and collaboration aimed to advance the DBS field. The Eighth Annual DBS Think Tank was held virtually on September 1 and 2, 2020 (Zoom Video Communications) due to restrictions related to the COVID-19 pandemic. The meeting focused on advances in: (1) optogenetics as a tool for comprehending neurobiology of diseases and on optogenetically-inspired DBS, (2) cutting edge of emerging DBS technologies, (3) ethical issues affecting DBS research and access to care, (4) neuromodulatory approaches for depression, (5) advancing novel hardware, software and imaging methodologies, (6) use of neurophysiological signals in adaptive neurostimulation, and (7) use of more advanced technologies to improve DBS clinical outcomes. There were 178 attendees who participated in a DBS Think Tank survey, which revealed the expansion of DBS into several indications such as obesity, post-traumatic stress disorder, addiction and Alzheimer’s disease. This proceedings summarizes the advances discussed at the Eighth Annual DBS Think Tank. (shrink)

The neuregulin gene encodes a series of polypeptide growth factors that can influence the growth state of target vertebrate cells in culture. Recently, three studies have explored the in vivo function of the neuregulin signaling system in mice by disrupting the genes encoding the neuregulin ligand(1) and two of its receptors, ErbB2(2) and ErbB4(3). Each of the genes is essential for development, and aberrations in cardiac and neural development are particularly prominent in mutant embryos. The observed defects, together with the (...) localization of expression of the neuregulin signaling components within these tissues, highlight a paracrine mechanism for neuregulin‐mediated intercellular communication. (shrink)

Why are some autocrats able to personalize power within their regimes while others are not? Past studies have focused on the balance of power between the autocrat and his or her supporting coalition of peer or subordinate elites, but we find that often the crucial relationship is between the autocrat and the “old guard”—retired leaders, party elders, and other elites of the outgoing generation. Using an original data set of authoritarian leadership transitions, we argue that when members of the old (...) guard retain oversight capacity over their incoming successor, he or she is less likely to overturn power-sharing arrangements and consolidate individual power. We illustrate this argument with a case study of three leadership transitions in China between 1989 and 2012. This study’s findings advance our understanding of elite politics and intergenerational conflict in authoritarian regimes. (shrink)

— Quand le messie viendra t-il?… — Va lui demander. Traité talmudique Sanhédrin, 98a. Pourquoi parler du messianisme aujourd’hui? Cette notion de messianisme, souvent incomprise et dont la signification est surdéterminée ou connotée, semble de prime abord se référer à l’antique tradition juive, avant d’être reprise par les monothéismes. Mais on la retrouve finalement dans de nombreux discours politiques, journalistiques, sociologiques, ou encore dans les théories millénari...

Le Procès de Kafka est généralement interprété comme une œuvre mettant en scène une victime du système bureaucratique autoritaire : Joseph K., innocent, est condamné à tort par un jugement hâtif, par un semblant de justice, par la faute d’avocats incompétents ou d’une calomnie injustifiée. Personne ne semble remettre en question l’innocence de Joseph K. Et si le procès de Joseph K. n’était pas une procédure infligée à un innocent, mais une occasion pour un coupable se racheter? C’est ce que (...) K. ne verra pas. Si l’innocence n’est qu’une fausse question durant le déroulement du Procès, nous sommes alors contraints d’interroger le rapport entre le coupable et sa faute, entre la peine et son châtiment, pour le dire encore autrement : entre l’individu et la loi. Au regard du droit hébraïque, nous verrons que la question que soulève le Procès n’est pas celle de l’injustice, mais celle de la culpabilité. (shrink)

Le caractère institutionnel du messie et sa capacité à instaurer une suspension de la Loi en font une figure étonnamment proche du souverain. Cette possibilité de changer l’état de la Loi que détient le souverain est également celle du messie : comme le souverain, il possède la capacité d’instituer un nouveau rapport à la Loi au sein de la temporalité messianique, en rétablissant ou suspendant les lois alors en vigueur. La Loi, religieuse dans le cas du messianisme juif, juridique dans (...) le cas de l’état d’exception, serait donc susceptible d’un changement significatif d’état. L’examen de cette proximité entre les deux figures nous oblige alors à renouer avec le caractère éminemment politique que possède le messianisme originaire, capable d’accorder une véritable structure conceptuelle à la question de la souveraineté. La politique révolutionnaire et prolétarienne dont parle Benjamin pourrait alors apparaître comme étant l’équivalent profane de la rédemption messianique. (shrink)

O‐glycosylation is the post‐translational process whereby carbohydrate is added to hydroxylated amino acids of proteins. The major O‐glycosylation pathway in animal cells is involved in the synthesis of oligosaccharides linked by N‐acetylgalactosamine to serine or threonine residues in ‘mucin‐type’ proteins or their analogs. In this review, we discuss the evidence for the cellular localization of the biosynthetic steps in this pathway and propose a simplified, consensus version. We also propose variations of the simple pathway to account for its heterogeneity and (...) variability in different cell types and differentiation states. (shrink)

When designing public policies, decision makers often rely on their own behavioral preferences. Pepper & Nettle's theory suggests that these preferences are unlikely to be appropriate when applied to a different environment. This theory has profound implications for the design and ethics of public policies.

The belief in immanent justice is the expectation that the universe is designed to ensure that evil is punished and virtue rewarded. What makes this belief so ‘natural’? Here, we suggest that this intuition of immanent justice derives from our evolved sense of fairness. In cases where a misdeed is followed by a misfortune, our sense of fairness construes the misfortune as a way to compensate for the misdeed. To test this hypothesis, we designed a set of studies in which (...) we show that people who do not believe in immanent justice are nonetheless implicitly influenced by intuitions of immanent justice. Strikingly, this effect disappears when the misfortune is disproportionate compared to the misdeed: In this case, justice is not restored and participants lose the intuition of immanent justice. Following recent theories of religion, we suggest that this intuition contributes to the cultural success of beliefs in immanent justice. (shrink)

This paper investigates the relationship that people with high functioning autism have with organizational temporality by considering this operationalization within the framework of humanistic management. To do so, it proposes an analysis based on seven propositions. Autism is a disorder that is still poorly understood and often linked to social depictions that are as unfounded as they are repulsive. It remains an unexplored area of study in the field of management sciences. Existing scholarship has established that people with autism have (...) great difficulty finding and retaining employment. While it is well known that they have weak social skills, their difficulties in relation to time have only been studied in medical research, even though organizational temporality substantially shapes the functioning of teams. The operationalization of autistic temporality as a particular temporality within humanistic management allows for the development of a new conceptual framework based on a consideration of neuro-atypia. This paper begins with a presentation of the theoretical background. It then develops the theoretical model. Implications, limitations and directions for further studies are discussed before concluding. (shrink)

A long tradition of research in WEIRD (Western, Educated, Industrialized, Rich, Democratic) countries has investigated how people weigh individual welfare versus group welfare in their moral judgments. Relatively less research has investigated the generalizability of results across non-WEIRD populations. In the current study, we ask participants across nine diverse cultures (Bali, Costa Rica, France, Guatemala, Japan, Madagascar, Mongolia, Serbia, and the USA) to make a series of moral judgments regarding both third-party sacrifice for group welfare and first-person sacrifice for group (...) welfare. In addition to finding some amount of cross-cultural variation on most of our questions, we also find two cross-culturally consistent judgments: (1) when indi- viduals are in equivalent situations, overall welfare should be maximized, and (2) harm to individuals should be taken into account, and some types of individual harm can trump overall group welfare. We end by discussing the specific pattern of variable and consistent features in the context of evolutionary theories of the evolution of morality. (shrink)

Neonatal behavioral data support the argument that multiple relations exist between vision and touch. Looking at an object triggers the motion of a neonate's arm and hand towards it. A textured surface that is seen can be recognized tactilely, but not a volumetric shaped object in cross-modal transfer tasks. These data are supported by adult neuroimaging data.

We designed a new protocol requiring French adult participants to group a large number of Munsell colour chips into three or four groups. On one, relativist, view, participants would be expected to rely on their colour lexicon in such a task. In this framework, the resulting groups should be more similar to French colour categories than to other languages categories. On another, universalist, view, participants would be expected to rely on universal features of perception. In this second framework, the resulting (...) groups should match colour categories of three and four basic terms languages. In this work, we first collected data to build an accurate map of French colour terms categories. We went on testing how native French speakers spontaneously sorted a set of randomly presented coloured chips and, in line with the relativist prediction, we found that the resulting colour groups were more similar to French colour categories than to three and four basic terms languages. However, the same results were obtained in a verbal interference condition, suggesting that participants rely on language specific and nevertheless perceptual, colour categories. Collectively, these results suggest that the universalist/relativist dichotomy is a too narrow one. (shrink)

We designed a new protocol requiring French adult participants to group a large number of Munsell colour chips into three or four groups. On one, relativist, view, participants would be expected to rely on their colour lexicon in such a task. In this [ramework, the resulting groups should be more similar to French colour categories than to other languages categories. On another, universalist, view, participants would be expected to rely on universal features of perception. In this second framework, the resulting (...) groups should match colour categories of three and four basic terms languages. In this work, we first collected data to build an accurate map of French colour terms categories (Experiment 1). We went on testing how native French speakers spontaneously sorted a set of randomly presented coloured chips and, in line with the relativist prediction, we found that the resulting colour groups were more similar to French colour categories than to three and four basic terms languages (Experiment 2). However, the same results were obtained in a verbal interference condition (Experiment 3), suggesting that participants rely on language specific and nevertheless perceptual, colour categories. Collectively, these results suggest that the universalist/relativist dichotomy is a too narrow one. (shrink)

Investigating the bases of inter-individual differences in risk-taking is necessary to refine our cognitive and neural models of decision-making and to ultimately counter risky behaviours in real-life policy settings. However, recent evidence suggests that behavioural tasks fare poorly compared to standard questionnaires to measure individual differences in risk-taking. Crucially, using model-based measures of risk taking does not seem to improve reliability. Here we put forward two possible - not mutually exclusive - explanations for these results and suggest future avenues of (...) research to improve the assessment of inter-individual differences in risk-taking by combining repeated online testing and mechanistic computational models. (shrink)

The book presents the most relevant theories of truth (correspondence, semantic, deflational, pragmaticist, coherentist, constructivist, evidential), with the emphasis of analytical approaches. The author develops a version of the realist correspondence concept of truth while distinguishing various criteria of truth. He is skeptical in regard of any, complete or certain truth but he does not accept epistemic skepticism either, but argues for a moderate realism where objective orientation towards truth suffices as catching (ever) more truth than falsity.

Comment devient-on philosophe? Par quel sursaut un Aristoclès se fait-il Platon, jusqu'à s'imposer dans la liste des " auteurs philo " Il faut enquêter, non pas sur la vie privée, mais sur la vie intime : rumination intellectuelle, ton sur lequel on parle, motivations amoureuses... Ce qui fait un philosophe, c'est un immense travail sur soi, et la rencontre d'autres philosophes, vivants, de leurs problématiques. Mémoire sémantique + obsession métaphysique, voilà le code génétique du philosophe. Il débute par un attentat (...) religieux, puisqu'il commence sa carrière en niant tel ou tel sacré. Bien sûr, il vaut mieux être mâle, communiquer par les livres adopter la langue dominante, écrire quand on est célibataire. Comment gagner sa vie? Pas forcément en étant enseignant, comme c'est le cas aujourd'hui. Le profil du philosophe nous le révèle orphelin, vivant à l'étranger, souvent laid, jamais fou, et serial thinker, prêt à changer de philosophie pourvu qu'il reste, lui, à menacer le monde donnera ou donnera pas du sens à notre vie? Le philosophe est l'être inquiet qui pense inquiéter l'Être par deux trois mots bien aiguisés. (shrink)

How (Not) to Be Secular is what Jamie Smith calls "your hitchhiker's guide to the present" -- it is both a reading guide to Charles Taylor's monumental work A Secular Age and philosophical guidance on how we might learn to live in our times. Taylor's landmark book A Secular Age (2007) provides a monumental, incisive analysis of what it means to live in the post-Christian present -- a pluralist world of competing beliefs and growing unbelief. Jamie Smith's book is a (...) compact field guide to Taylor's insightful study of the secular, making that very significant but daunting work accessible to a wide array of readers. Even more, though, Smith's How (Not) to Be Secular is a practical philosophical guidebook, a kind of how-to manual on how to live in our secular age. It ultimately offers us an adventure in self-understanding and maps out a way to get our bearings in today's secular culture, no matter who "we" are -- whether believers or skeptics, devout or doubting, self-assured or puzzled and confused. This is a book for any thinking person to chew on. (shrink)

Extraterrestrial Altruism examines a basic assumption of the Search for Extraterrestrial Intelligence (SETI): that extraterrestrials will be transmitting messages to us for our benefit. This question of whether extraterrestrials will be altruistic has become increasingly important in recent years as SETI scientists have begun contemplating transmissions from Earth to make contact. Technological civilizations that transmit signals for the benefit of others, but with no immediate gain for themselves, certainly seem to be altruistic. But does this make biological sense? Should we (...) expect altruism to evolve throughout the cosmos, or is this only wishful thinking? Is it dangerous to send messages to other worlds, as Stephen Hawking has suggested, or might humankind benefit from an exchange with intelligence elsewhere in the galaxy? Would extraterrestrial societies be based on different ethical principles, or would we see commonalities with Earthly notions of morality? Extraterrestrial Altruism explores these and related questions about the motivations of civilizations beyond Earth, providing new insights that are critical for SETI. Chapters are authored by leading scholars from diverse disciplines—anthropology, astronomy, biology, chemistry, computer science, cosmology, engineering, history of science, law, philosophy, psychology, public policy, and sociology. The book is carefully edited by Douglas Vakoch, Director of Interstellar Message Composition at the SETI Institute and professor of clinical psychology at the California Institute of Integral Studies. The Foreword is by Frank Drake. This interdisciplinary book will benefit everybody trying to understand whether evolution and ethics are unique to Earth, or whether they are built into the fabric of the universe. (shrink)

While there are numerous doubts, controversies and lack of consensus on alternative definitions of human death, it is argued that it is more ethical to allow people to choose either cessation of cardio-respiratory function or loss of entire brain function as the definition of death based on their own views. This paper presents the law of organ transplantation in Japan, which allows people to decide whether brain death can be used to determine their death in agreement with their family. Arguably, (...) Japan could become a unique example of individual choice in the definition of death if the law is revised to allow individuals choose definition of death independently of their family. It suggests that such an approach is one of the reasonable policy options a country can adopt for legislation on issues related to the definition of death. (shrink)