Rho/Rac proteins constitute a subgroup of the Ras superfamily of GTP hydrolases. Although originally implicated in the control of cytoskeletal events, it is currently known that these GTPases coordinate diverse cellular functions, including cell polarity, vesicular trafficking, the cell cycle and transcriptomal dynamics. In this review, we will provide an overview on the recent advances in this field regarding the mechanism of regulation and signaling, and the roles in vivo of this important GTPase family. BioEssays 29:356–370, 2007. © 2007 Wiley (...) Periodicals, Inc. (shrink)

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

Metastasis is one of the clinical parameters that has a strong negative influence on the prognosis of cancer patients. In recent years, significant advances have furthered our understanding of this process at the molecular and biological levels. This paper will discuss recent discoveries relating to the earliest, intra‐tumoral stages of metastasis in cancer cells, specifically focusing on: (i) the development of metastatic traits during primary tumorigenesis; (ii) intrinsic and extrinsic cancer cell programs associated with malignant traits; (iii) the intra‐tumoral migration (...) patterns of cancer cells and the dynamic roles played by the Rho/Rac GTPases and epithelial‐mesenchymal transitions in this process; and (iv) the genetic strategies used by metastatic cancer cells to promote intra‐tumoral cell migration and their subsequent escape to peripheral tissues. Finally, the therapeutic and diagnostic relevance of this information will be discussed, as well as potential future developments. (shrink)

Experiments with cell lines have unveiled the implication of the Rho/Rac family of GTPases in cytoskeletal organization, mitogenesis, and cell migration. However, there have not been adequate animal models to investigate the role of these proteins in more physiological settings. This scenario has changed recently in the case of the T‐cell lineage after the generation of animal models for Rho/Rac family members, their regulators, and effectors. These studies have revealed the implication of these GTPases on multiple regulatory layers of T‐cells, (...) including the coordination of cytoskeletal change, activation of kinase cascades, stimulation of calcium fluxes, and the induction of gene expression. These pathways affect the transition of different T‐cell maturation stages, the positive/negative selection of thymocytes, T‐cell responses to antigens, and the homeostasis of peripheral T‐lymphocytes. Moreover, these animals have revealed interesting cross‐talks between Rho/Rac pathways and other signal transduction routes that participate in lymphocyte responses. BioEssays 24:602–612, 2002. © 2002 Wiley Periodicals, Inc. (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)

Some theories of goodness are descriptively rich: they have much to say about what makes things good. Neo-Aristotelian accounts, for instance, detail the various features that make a human being, a dog, a bee good relative to facts about those forms of life. Famously, such theories of relative goodness tend to be comparatively poor: they have little or nothing to say about what makes one kind of being better than another kind. Other theories of goodness—those that take there to be (...) absolute goodness—are comparatively rich: they offer grounds for judging some types of things better than others because they have more absolute goodness. Moorean accounts, for example, can tell us that humans and human experiences are superior to bees and blades of grass. But such theories tend to be descriptively poor: they struggle to tell us in virtue of what this is so. In this essay we motivate and flesh out a view that splits the difference between accounts of goodness as relative and accounts of goodness as absolute. Such a view holds promise only if the mechanics of this kind of metaphysics of goodness can be worked out. Here we present a view on which the paradigm for absolute goodness is God and the paradigm for each kind of relative goodness is a divine idea. (shrink)

This paper analyses the suitability of Effective Altruism as an ethical frame for the practices of Education for Global Citizenship in the University. According to Effective Altruism, altruistic and solidary practices should be based not only on emotional decisions, but also on a rational analysis to achieve the greatest possible impact for the benefit of third parties. Simultaneously, Universities promote Education for Global Citizenship that includes the development of competencies for the application of ethical principles focused on the improvement of (...) the world as defined in the United Nations 2030 Agenda for Sustainable Development. But the breadth of development problems demands decision criteria to select those causes that can have a greater and better impact. Therefore, Effective Altruism enumerates a reasoned repertoire of decision criteria that could facilitate the application of ethical principles among university global citizenship. (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)

In much of the current academic and public discussion, conspiracy theories are portrayed as a negative phenomenon, linked to misinformation, mistrust in experts and institutions, and political propaganda. Rather surprisingly, however, philosophers working on this topic have been reluctant to incorporate a negatively evaluative aspect when either analyzing or engineering the concept conspiracy theory. In this paper, we present empirical data on the nature of the concept conspiracy theory from five studies designed to test the existence, prevalence and exact form (...) of an evaluative dimension to the ordinary concept conspiracy theory. These results reveal that, while there is a descriptive concept of conspiracy theory, the predominant use of conspiracy theory is deeply evaluative, encoding information about epistemic deficiency and often also derogatory and disparaging information. On the basis of these results, we present a new strategy for engineering conspiracy theory to promote theoretical investigations and institutional discussions of this phenomenon. We argue for engineering conspiracy theory to encode an epistemic evaluation, and to introduce a descriptive expression—such as ‘conspiratorial explanation’—to refer to the purely descriptive concept conspiracy theory. (shrink)

El texto aborda uno de los temas de la violencia contemporánea, la violencia política de las mujeres. A partir de los problemas para nombrar la violencia y de los análisis de A. Cavarero sobre el «horrorismo», se centra en dos casos: la muerte de Yoyes y las mujeres bombas suicidas chechenas, mostrando las construcciones sociales y culturales de sexo/género, sus mitos y estereotipos, en cuanto constituyen una de las raíces más profundas y persistentes de la violencia. En definitiva, de lo (...) que se trata es de reflexionar y comprender la vulnerabilidad de la condición humana. (shrink)