Progressive supranuclear palsy is a movement disorder with prominent tau neuropathology. Brain diseases with abnormal tau deposits are called tauopathies, the most common of which is Alzheimer's disease. Environmental causes of tauopathies include repetitive head trauma associated with some sports. To identify common genetic variation contributing to risk for tauopathies, we carried out a genome-wide association study of 1,114 individuals with PSP and 3,247 controls followed by a second stage in which we genotyped 1,051 cases and 3,560 controls for the (...) stage 1 SNPs that yielded P ≤ 10-3. We found significant previously unidentified signals associated with PSP risk at STX6, EIF2AK3 and MOBP. We confirmed two independent variants in MAPT affecting risk for PSP, one of which influences MAPT brain expression. The genes implicated encode proteins for vesicle-membrane fusion at the Golgi-endosomal interface, for the endoplasmic reticulum unfolded protein response and for a myelin structural component. © 2011 Nature America, Inc. All rights reserved. (shrink)

Our understanding of how evolution acts on biological networks remains patchy, as is our knowledge of how that action is best identified, modelled and understood. Starting with network structure and the evolution of protein–protein interaction networks, we briefly survey the ways in which network evolution is being addressed in the fields of systems biology, development and ecology. The approaches highlighted demonstrate a movement away from a focus on network topology towards a more integrated view, placing biological properties centre‐stage. We argue (...) that there remains great potential in a closer synergy between evolutionary biology and biological network analysis, although that may require the development of novel approaches and even different analogies for biological networks themselves. (shrink)

Despite an expansive literature on communication in medicine, the role of language is dealt with mostly indirectly. Recently, narrative medicine has emerged as a strategy to improve doctor-patient communication and integrate patient perspectives. However, even in this field which is predicated on language use, scholars have not specifically reflected on how language functions in medicine. In this theoretical paper, the authors consider how different models of language use, which have been proposed in the philosophical literature, might be applied to communication (...) in medicine. In particular, the authors contrast the traditional, indexical thesis of language with new models that focus on interpretation instead of standardization. The authors demonstrate how paying close attention to the role of language in medicine provides a philosophical foundation for supporting recent changes in doctor-patient communication. In particular, interpretive models are at the foundation of new approaches such as narrative medicine, that emphasize listening to patient stories, rather than merely collecting information. Ultimately, debates regarding the role of language which have largely resided in non-medical literatures, have important implications for describing communication in medicine. In particular, interpretive models of language use provide an important rationale for facilitating a more robust dialogue between doctors and patients. (shrink)

In this article Kobayashi Toshiaki discusses the importance in all periods of Karatani’s oeuvre of the notion of an “exterior” that necessarily falls beyond the bounds of a system, together with the notion of “singularity” as that which cannot be contained within a “universal.” The existential dread vis-à-vis the uncanny other that Karatani in his early works of literary criticism had initially found to be the underlying tone in Sōseki’s works remained with Karatani himself throughout his career and is what (...) had drawn him closer to philosophy. This sense of the “exterior” to—or other than—the normality of consciousness and the meaningfulness of the world is then extended and applied as the “exterior to systems” in his analyses of logical, mathematical, and linguistic systems, in his reading of Marx’s discussion of capitalist economics, and most recently in his analysis of commodity exchange between communities. (shrink)

In recent decades, the individual has become more and more central in both national and world cultural accounts of the operation of society. This continues a long historical process, intensified by the consolidation of a more global polity and the weakening of the primordial sovereignty of the national state. Increasingly, society is culturally rooted in the natural, historical, and spiritual worlds through the individual, rather than through corporate entities or groups. The shift has produced a proliferation and specification of individual (...) roles, accounting for what individuals do in society. It has also produced an expansion in recognized individual personhood, accounting for who individuals are in the extrasocial cosmos and fueling elaborated personal tastes and preferences. Where it has been contested, the shift to the individual has also produced a rise in specializing identities. These offer accounts of individuals' distinctive linkages to the cosmos, and they serve to bolster individual claims to standard roles and personhood. Over time, specializing identities tend to get absorbed into roles and personhood. And in turn, expanded roles and personhood provide further bases for specializing identity claims. Because many theorists mischaracterize the relationship of specializing identities to roles and personhood, the literature often overemphasizes the anomic character of the identity explosion and the closeness of the coupling between social roles and identity claims. On the contrary, specializing identities tend to be edited to remain within general rules of individual personhood and to be disconnected from the obligations involved in institutionalized roles. (shrink)

Preview: /Review: Andrea J. Pitts and Mark William Westmoreland, eds. Beyond Bergson: Examining Race and Colonialism Through the Writings of Henri Bergson, 255 pages./ Among Bergson’s contributions to philosophical and empirical investigations; such as those centered on freedom, memory, and evolution; exists in the form of his last book, The Two Sources of Morality and Religion. It is interesting because, as many readers of Bergson have remarked, it does not seem to fit well, primarily in method, with his other endeavors (...) in the pursuit of philosophical exploration and elaboration. Having been mentored by a philosopher who holds this position, I have long shied away from the text that represents Bergson’s last concerted philosophical effort of inquiry. Meanwhile, having been intrigued by the possibility of a more just world and compelled by a desire to serve such an end, I was interested in envisioning what a Bergsonian philosophy of social justice, revolution, or morality would contain. Early on in my readings of Bergson, I felt the seeming applicability of Bergson’s method of intuition to moral and social questions. Over the years, I have devoted significant time to thinking through durational investigations of intensity to problems of social justice. While I have made some inroads to accomplishing this goal, I feel the journey has just begun for me. It was in this context that I was excited at the prospect of this book, and it is this book that has helped me to appreciate some of the ways that Bergson’s philosophy could be adapted to thinking through moral and social questions. To be clear, much work has been done in the way of expounding political or moral philosophies in which Bergson’s thought might be interpreted as a prelude. My reluctance to embrace Two Sources has been a self-imposed hindrance to my engaging in those extra-Bergsonian works for fear of running against the current of Bergson’s earlier texts. My reticence is intended to be taken as neither a slight of Bergson’s Two Sources nor a discounting of those who find inspiration in that work. (shrink)

Ethical decisions related to computer technology and computer use are subject to three primary influences: (1) the individual's own personal code (2) any informal code of ethical behavior that exists in the work place, and (3) exposure to formal codes of ethics. The relative importance of these codes, as well as factors influencing these codes, was explored in a nationwide survey of information system (IS) professionals. The implications of the findings are important to educators and employers in the development of (...) acceptable ethical standards. (shrink)

Rich with historical and cultural value, these works are published unaltered from the original University of Minnesota Press editions.

A scholarly edition of The Clarendon Edition of the Works of John Locke: Some Thoughts Concerning Education by John W. Yolton and Jean S. Yolton. The edition presents an authoritative text, together with an introduction, commentary notes, and scholarly apparatus.

John Yolton seeks to allow readers of Locke to have accessible in one volume sections from a wide range of Locke's books, structured so that some of the interconnections of his thought can be seen and traced. Although Locke did not write from a system of philosophy, he did have in mind an overall division of human knowledge. The readings begin with Locke's essay on Hermeneutics and the portions of his Essay Concerning Human Understanding on how to read a (...) text. The reset of the selections are organized around Locke's division of human knowledge into natural science, ethics, and the theory of signs. Yolton's introduction and commentary explicate Locke's doctrines and provide the reader with the general background knowledge of other seventeenth-century writers and their works necessary to an understanding of Locke and his time. (shrink)

One of the central problems in the philosophy of psychology is an updated version of the old mind-body problem: how levels of theories in the behavioral and brain sciences relate to one another. Many contemporary philosophers of mind believe that cognitive-psychological theories are not reducible to neurological theories. However, this antireductionism has not spawned a revival of dualism. Instead, most nonreductive physicalists prefer the idea of a one-way dependence of the mental on the physical.In Psychoneural Reduction, John Bickle presents (...) a new type of reductionism, one that is stronger than one-way dependency yet sidesteps the arguments that sank classical reductionism. Although he makes some concessions to classical antireductionism, he argues for a relationship between psychology and neurobiology that shares some of the key aims, features, and consequences of classical reductionism. Parts of Bickle's "new wave" reductionism have emerged piecemeal over the past two decades; this is his first comprehensive statement and defense of it to appear. (shrink)

School principals world-wide report high levels of strain and attrition resulting in a shortage of qualified principals. It is thus, crucial to identify psychosocial risk factors that reflect principals’ occupational wellbeing. For this purpose, we used the Copenhagen Psychosocial Questionnaire (COPSOQ-II), a widely used self-report measure covering multiple psychosocial factors identified by leading occupational stress theories. We evaluated the COPSOQ-II regarding factor structure and longitudinal, discriminant, and convergent validity using latent structural equation modeling in a large sample of Australian school (...) principals (N = 2,049). Results reveal that confirmatory factor analysis produced marginally acceptable model fit. A novel approach we call set exploratory structural equation modeling (ESEM-set), where cross-loadings were only allowed within a priori defined sets of factors, fit well, and was more parsimonious than a full ESEM. Further multitrait-multimethod models based on the set-ESEM confirm the importance of a principal’s psychosocial risk factors; Stressors and depression were related to demands and ill-being, while confidence and autonomy were related to wellbeing. We also show that working in the private sector was beneficial for showing a low psychosocial risk, while other demographics have little effects. Finally, we identify five latent risk profiles (high risk to no risk) of school principals based on all psychosocial factors. Overall the research presented here closes the theory application gap of a strong multi-dimensional measure of psychosocial risk-factors. (shrink)

John Carroll undertakes a careful philosophical examination of laws of nature, causation, and other related topics. He argues that laws of nature are not susceptible to the sort of philosophical treatment preferred by empiricists. Indeed he shows that emperically pure matters of fact need not even determine what the laws are. Similar, even stronger, conclusions are drawn about causation. Replacing the traditional view of laws and causation requiring some kind of foundational legitimacy, the author argues that these phenomena are (...) inextricably intertwined with everything else. This distinctively clear and detailed discussion of what it is to be a law will be valuable to a broad swathe of philosophers in metaphysics, the philosophy of mind, and the philosophy of science. (shrink)

In his contribution to Human Senses and Perception, R. J. Hirst has made a number of important suggestions about perceptual consciousness, He has emphasised the need to describe ‘what the percipient is or may be conscious of’ from the percipient's own point of view. This mode of description is contrasted with stimulus or neurological description. Perceptual consciousness of one object is distinguished from perceptual consciousness of another object ‘only by or on the evidence of, the person concerned’. The method of (...) obtaining descriptions of perceptual consciousness is either to question a percipient or to reflect on our own experience, The second important point stressed by Hirst is that the end product of perceiving is ‘the conscious experience of external objects’. Such an obvious point is often lost sight of in behavioural, dispositional, or neurophysiological analyses, The third and final suggestion made by Hirst to which I want to call attention is the usefulness of a genetic hypothesis to explain and account for perceptual consciousness. Hirst feels that perceptual consciousness is ‘unanalysable at the conscious level’, meaning that it is ‘a unitary awareness of objects or scenes’ and that the ‘various interacting unconscious activities’ which coexist with awareness ‘cannot be brought forward into consciousness’. The various analytical theories of perception have been designed to break perceptual consciousness into its components. This has resulted in their being false to perceptual consciousness. A genetic explanation of awareness has several advantages, prime among them being its ability to explain the complexity and development of awareness. (shrink)

There are two main groups of essays in this volume. The first centres on Locke's theories of religion and their relation to contemporary scientific thought and the work of Descartes, Leibniz and Hume. The second group explores the relation between biology and physiology, and the science of man.

In recent years there has been a tendency in some quarters to see an affinity between the views of Kierkegaard and Wittgenstein on the subject of religious belief. It seems to me that this is a mistake, that Kierkegaard's views were fundamentally at odds with Wittgenstein's. That this fact is not generally recognized is, I suspect, owing to the obscurity of Kierkegaard's most fundamental assumptions. My aim here is to make those assumptions explicit and to show how they differ from (...) Wittgenstein's. (shrink)

Professor Yolton delves into John Locke 's most important work, the Essay Concerning Human Understanding.

Ted Sider aptly and concisely states the self-visitation paradox thus: 'Suppose I travel back in time and stand in a room with my sitting 10-year-old self. I seem to be both sitting and standing, but how can that be?' (2001, 101). I will explore a relativist resolution of this paradox offered by, or on behalf of, endurantists.1 It maintains that the sitting and the standing are relative to the personal time or proper time of the time traveler and is intended (...) to yield the result that Ted is sitting at a certain initial personal/proper time but is not standing relative to that time. Similarly, it is also supposed to yield that Ted is standing relative to a later personal/proper time, but not sitting relative to that .. (shrink)

Using his intimate knowledge of John Locke's writings, John W. Yolton shows that Locke comprehends 'human understanding' as a subset of a larger understanding ...

This book tells for the first time the long and complex story of the involvement of Locke's suggestion that God could add to matter the power of thought in his Essay Concerning Human Understanding in the growth of French materialism. There is a discussion of the 'affaire de Prades', in which Locke's name was linked with a censored thesis at the Faculty of Theology in Paris. The similarities and differences between English "thinking matter" and the French "matiere pensante" of the (...) philosophes are also discussed. (shrink)

In 1984, John W. Yolton published Perceptual Acquaintance from Descartes to Reid. His most recent book builds on that seminal work and greatly extends its relevance to issues in current philosophical debate. Perception and Reality examines the theories of perception implicit in the work of seventeenth- and eighteenth-century philosophers which centered on the question: How is knowledge of the body possible? That question raises issues of mind-body relation, the way that mentality links with physicality, and the nature of the (...) known world. In contrast to commonsense realism, which suggests that the world is as it appears to be, a more complex theory developed throughout this period. Yolton traces its evolution from Descartes to Kant, via Arnauld, Malebranche, Locke, Berkeley, and Hume. Yolton explains that the new theory postulated two interactive relations between perceivers and the physical world, one physical and causal, the other cognitive. An understanding of this double relation is important for an accurate construction of the history of philosophy. It is also important for contemporary thought because it suggests a way to account for representation (cognitivity) and realism at the same time. (shrink)