Many targets of the Wnt/β-catenin signaling pathway are regulated by TCF transcription factors, which play important roles in animal development, stem cell biology, and oncogenesis. TCFs can regulate Wnt targets through a “transcriptional switch,” repressing gene expression in unstimulated cells and promoting transcription upon Wnt signaling. However, it is not clear whether this switch mechanism is a general feature of Wnt gene regulation or limited to a subset of Wnt targets. Co-repressors of the TLE family are known to contribute to (...) the repression of Wnt targets in the absence of signaling, but how they are inactivated or displaced by Wnt signaling is poorly understood. In this mini-review, we discuss several recent reports that address the prevalence and molecular mechanisms of the Wnt transcription switch, including the finding of Wnt-dependent ubiquitination/inactivation of TLEs. Together, these findings highlight the growing complexity of the regulation of gene expression by the Wnt pathway. Wnt targets are regulated by a “switch” where TLE co-repressors are displaced from TCFs by β-catenin, leading to activation of transcription. Recent reports challenge this view and suggest that additional processes, including exchange of specific TCF proteins and Wnt-dependent ubiquitination of TLEs, play important roles in the Wnt transcriptional switch. (shrink)

This collection addresses a post-WWII shift in the hierarchy of scientific explanations, where the highest goal moves from reductionism towards some ...

Context: The majority of contemporary enactivist work is influenced by the philosophical biology of Hans Jonas. Jonas credits all living organisms with experience that involves particular “existential” structures: nascent forms of concern for self-preservation and desire for objects and outcomes that promote well-being. We argue that Jonas’s attitude towards living systems involves a problematic anthropomorphism that threatens to place enactivism at odds with cognitive science, and undermine its legitimate aims to become a new paradigm for scientific investigation and understanding of (...) the mind. Problem: Enactivism needs to address the tension between its Jonasian influences and its aspirations to become a new paradigm for cognitive science. By relying on Jonasian phenomenology, contemporary enactivism obscures alternative ways in which phenomenology can be more smoothly integrated with cognitive science. Method: We outline the historical relationship between enactivism and phenomenology, and explain why anthropomorphism is problematic for a research program that aspires to become a new paradigm for cognitive science. We examine the roots of Jonas’s existential interpretation of biological facts, and describe how and why Jonas himself understood his project as founded on an anthropomorphic assumption that is incompatible with a crucial methodological assumption of scientific enquiry: the prohibition of unexplained natural purposes. We describe the way in which phenomenology can be integrated into Maturana’s autopoietic theory, and use this as an example of how an alternative, non-anthropomorphic science of the biological roots of cognition might proceed. Results: Our analysis reveals a crucial tension between Jonas’s influence on enactivism and enactivism’s paradigmatic aspirations. This suggests the possibility of, and need to investigate, other ways of integrating phenomenology with cognitive science that do not succumb to this tension. Implications: In light of this, enactivists should either eliminate the Jonasian inference from properties of our human experience to properties of the experience of all living organisms, or articulate an alternative conception of scientific enquiry that can tolerate the anthropomorphism this inference entails. The Maturanian view we present in the article’s final section constitutes a possible framework within which enactivist tools and concepts can be used to understand cognition and phenomenology, and that does not involve a problematic anthropomorphism. Constructivist content: Any constructivist approach that aims for integration with current scientific practice must either avoid the type of anthropomorphic inference on which Jonas bases his work, or specify a new conception of scientific enquiry that renders anthropomorphism unproblematic. (shrink)

The present paper is primarily concerned with the application of the transformative approach within the Western philosophical context. My aim is to show how the idea of a transformation is present in Platonic thought based on John Taber’s work on transformative philosophy. According to Taber, transformative thinkers tell us that the unreflecting mind lives in a dream and, if it is to know the truly real, one “must awaken from the dream, enliven slumbering faculties, make a transition to a new (...) state of awareness.” I will use the Platonic dialogue to illustrate how some of the main features of transformative philosophy developed by Taber are exhibited there, if only to emphasize the transformative aspect of Platonic philosophy, although not dismiss the systematic reading of Platonic texts. (shrink)

For the theorists of crisis, the revolutionary state comes into existence through violence, and due to its inability to provide an authoritative katechon (restrainer) against internal and external violence, it perpetuates violence until it self-destructs. Writing during extreme economic depression and growing social and political violence, the crisis theorists––Joseph de Maistre, Juan Donoso Cortés, and Carl Schmitt––each sought to blame the chaos of their time upon the Janus-faced postrevolutionary ideals of liberalism and socialism by urging a return to pre-revolutionary moral (...) and religious values. They are united by three counterrevolutionary principles, all of which are purported to remedy revolutionary violence: traditional constitutional fidelity, the philosophy of the decision, and opposition to bourgeois liberalism. This essay is followed by the first complete English translation and publication of Donoso’s letter of October 24, 1851, which contains Donoso’s only reference to the “discussing class,” a political entity later popularized by Schmitt in his 1922 work Political Theology. (shrink)

The one great quality of Socratic gift is that thinking as an activity continues but not repetitively but every time thinking takes place, it takes place a new. Thinking is the one activity that cannot be repeated like prayers and other pieties. All philosophical thinking is new thinking; it has to be new in order to be thinking. Philosophy had to become the handmaid of sociology and could not be allowed to remain surrogate sociology. When this happened new concepts or (...) new conceptualizations became the need of the hour: in the place of the age-old hierarchic social stratification a novel concept of materialism had to be inducted - after all matter is what matters. And in India morally entangled sociology was holding down the rich human resources of the sub-continent and a development-oriented ideology had to convert this moral society into a legal society: An unlegislated, unlegislatable society is condemned to be unstable andcollapsible; in its place a stable, legislatable society had to be created. With this felt-need Dr. Ambedkar came into the Indian political arena and gave a modernist rethinking to the outmoded Indian social structure: His hallmark was think to change. (shrink)

The one great quality of Socratic gift is that thinking as an activity continues but not repetitively but every time thinking takes place, it takes place a new. Thinking is the one activity that cannot be repeated like prayers and other pieties. All philosophical thinking is new thinking; it has to be new in order to be thinking. Philosophy had to become the handmaid of sociology and could not be allowed to remain surrogate sociology. When this happened new concepts or (...) new conceptualizations became the need of the hour: in the place of the age-old hierarchic social stratification a novel concept of materialism had to be inducted - after all matter is what matters. And in India morally entangled sociology was holding down the rich human resources of the sub-continent and a development-oriented ideology had to convert this moral society into a legal society: An unlegislated, unlegislatable society is condemned to be unstable andcollapsible; in its place a stable, legislatable society had to be created. With this felt-need Dr. Ambedkar came into the Indian political arena and gave a modernist rethinking to the outmoded Indian social structure: His hallmark was think to change. (shrink)

The one great quality of Socratic gift is that thinking as an activity continues but not repetitively but every time thinking takes place, it takes place a new. Thinking is the one activity that cannot be repeated like prayers and other pieties. All philosophical thinking is new thinking; it has to be new in order to be thinking. Philosophy had to become the handmaid of sociology and could not be allowed to remain surrogate sociology. When this happened new concepts or (...) new conceptualizations became the need of the hour: in the place of the age-old hierarchic social stratification a novel concept of materialism had to be inducted - after all matter is what matters. And in India morally entangled sociology was holding down the rich human resources of the sub-continent and a development-oriented ideology had to convert this moral society into a legal society: An unlegislated, unlegislatable society is condemned to be unstable andcollapsible; in its place a stable, legislatable society had to be created. With this felt-need Dr. Ambedkar came into the Indian political arena and gave a modernist rethinking to the outmoded Indian social structure: His hallmark was think to change. (shrink)

On Vedanta philosophy based on Śaṅkarācārya's commentary on Bhagavadgītā, Brahmasūtra, and Upanishads.

Since 1900, debates about the justification of punishment have also been debates about the cause of crime. In the early twentieth century, the rehabilitative ideal of punishment viewed mental illness and dysfunction in individuals as the cause of crime. Starting in the 1970s, retributivism identified the immorality of human agents as the source of crime, which dovetailed well with the “tough-on-crime” political milieu of the 1980s and 1990s that produced mass incarceration. After surveying these historical trends, Wirts argues for a (...) social critical view that crime is best understood as a product of an unjust society, not faulty human beings. This view should take the lessons learned by the critiques of rehabilitation, however, and resist the tendency to reduce human beings to recipients of social services. (shrink)

Donald Davidson has made enormous contributions to the philosophy of action, epistemology, semantics and philosophy of mind and today is recognized as one of the most important analytical philosophers of the late twentieth century. _Donald Davidson: Truth, Meaning and Knowledge_ addresses * Davidson's writings on epistemology and theory of language with their implications of ontology and philosophy of mind * the central issue of whether truth is the ultimate goal of enquiry, challenged by contributions from Richard Rorty and Paul Horwich (...) * Davidson's approach to semantics and applied linguistics as addressed by Kirk Ludwig, Gabriel Segal, Peter Pagin, Stephen Neale, Herman Cappelen and Ernie Lepore and Reinaldo Elugardo * Davidson's advances in the philosophy of mind in relation to the views of Williard V. Quine, John McDowell and Peter F. Strawson, in essays by Roger Gibson and Anita Avramides. (shrink)

The topic of professionalism has dominated the content of major academic medicine publications during the past decade and continues to do so. The message of this current wave of professionalism is that medical educators need to be more attentive to the moral sensibilities of trainees, to their interpersonal and affective dimensions, and to their social conscience, all to the end of skilled, humanistic physicians. Urgent calls to address professionalism from such groups as the Association of American Medical Colleges, the American (...) Board of Internal Medicine, and the Accreditation Council for Graduate Medical Education, among others. In fact, at the 2004 annual meeting of the AAMC six separate presentations addressed professionalism with such titles as "Evaluating Humanism and Professionalism," Professionalism: Expectation, Education, Evaluation," or "Toward Assessing Professional Behaviors of Medical Students through Peer Observations". Professionalism, then, has become part of the current academic medicine parlance, used by administrators, clinical faculty, residency programs, and professional organizations with an expectation of shared meanings and goals. All of these stakeholders focus on what has become a consistent list of attributes deemed to be the essence of professionalism, which usually include variations on altruism, duty, excellence, honor and integrity, accountability, and respect. In fact, most of the scholarly work to date has been listing, describing, decrying, and measuring/evaluating it. In this collection of essays, we don’t argue with these attributes. Instead, we ask questions of the discourse from which they arise, how the specialized language of academic medicine disciplines has defined, organized, contained, and made seemingly immutable a group of attitudes, values, and behaviors subsumed under the label "professional" or "professionalism." This collection aims to be a critical text, one that questions the profession’s beliefs about the nature of its work and how such beliefs are enacted in medical education, particularly as they fuel the professionalism discourse. In addition, we will scrutinize how the discourse is enacted in both the formal and hidden curriculum, and in the larger medical environment. (shrink)