Disintegrins: integrin selective ligands which activate integrin-coupled signaling and modulate leukocyte functions

Extracellular matrix proteins and cell adhesion receptors (integrins) play essential roles in the regulation of cell adhesion and migration. Interactions of integrins with the extracellular matrix proteins lead to phosphorylation of several intracellular proteins such as focal adhesion kinase, activating different signaling pathways responsible for the regulation of a variety of cell functions, including cytoskeleton mobilization. Once leukocytes are guided to sites of infection, inflammation, or antigen presentation, integrins can participate in the initiation, maintenance, or termination of the immune and inflammatory responses. The modulation of neutrophil activation through integrin-mediated pathways is important in the homeostatic control of the resolution of inflammatory states. In addition, during recirculation, T lymphocyte movement through distinct microenvironments is mediated by integrins, which are critical for cell cycle, differentiation and gene expression. Disintegrins are a family of low-molecular weight, cysteine-rich peptides first identified in snake venom, usually containing an RGD (Arg-Gly-Asp) motif, which confers the ability to selectively bind to integrins, inhibiting integrin-related functions in different cell systems. In this review we show that, depending on the cell type and the microenvironment, disintegrins are able to antagonize the effects of integrins or to act agonistically by activating integrin-mediated signaling. Disintegrins have proven useful as tools to improve the understanding of the molecular events regulated by integrin signaling in leukocytes and prototypes in order to design therapies able to interfere with integrin-mediated effects.

Pain-related diseases and sleep disorders

Pain and sleep share mutual relations under the influence of cognitive and neuroendocrine changes. Sleep is an important homeostatic feature and, when impaired, contributes to the development or worsening of pain-related diseases. The aim of the present review is to provide a panoramic view for the generalist physician on sleep disorders that occur in pain-related diseases within the field of Internal Medicine, such as rheumatic diseases, acute coronary syndrome, digestive diseases, cancer, and headache.

As convenções de desenvolvimento no governo Lula: um ensaio de economia política

Development conventions in Lula's mandates: an essay on political economy. This article analyses the different development proposals put forward during the two Lula Presidential mandates. It is argued that such proposals are structured as "development conventions", which involve different priorities and different solutions to the problem of structural transformation. Their analytical frame is also different as are the interest groups which uphold them. Therefore their epistemology must be placed in the political economy context. It is argued that, notwithstanding the weight gained by a "developmental" convention over the second mandate, a "stability" convention is still hegemonic and commands macroeconomic policies.

Karl Popper versus Theodor Adorno: lições de um confronto histórico

Karl Popper versus Theodor Adorno: Lessons from a historical confrontation. In 1961, during the Congress of the German Society of Sociology, two great theoretical references of the XX century faced in a historical debate about the logic of the social sciences. In addition to methodological issues strict sense, the confrontation became known as a debate between positivism and dialectic. The article first deals with the theoretical trajectories of Popper and Adorno and the relation of their theories with their political and ideological certainties. On one hand, the trajectory of the Popperian epistemology is examined, its contributions and vigorous attacks on Marx in what he called 'poverty of historicism" and false predictive Marxist world, and, on the other hand, the role of Adorno in the Frankfurt School, his criticism of totalitarianism and the defense of a critical emancipatory reason. The article also deals with the confrontation itself, the exposure of Popper's twenty-seven theses that culminate with the situation logic and the method of the economy as exemplary for the social sciences and Adorno's critical perspective of sociology and society as non-separable objects. In conclusion we show how the articulation of theory with the weltanschauung of each author helps to clarify the terms of the debate and how the confrontation contributed unequivocally to the dynamics of scientific progress and for the critical history of the ideas.

Of empty thoughts and blind intuitions Kant's answer to McDowell

This paper examines the relation between intuition and concept in Kant in light of John McDowell's neo-Kantian position that intuitions are concept-laden.2 The focus is on Kant's twofold pronouncement that thoughts without content are empty and that intuitions without concepts are blind. I show that intuitions as singular representations are not instances of passive data intake but the result of synthetic unification of the given manifold of the senses by the power of the imagination under the guidance of the understanding. Against McDowell I argue that the amenability of intuitions to conceptual determination is not due some pre-existing, absolute conceptuality of the real but to the "work of the subject."3 On a more programmatic level, this paper seeks to demonstrate the limitations of a selective appropriation of Kant and the philosophical potential of a more comprehensive and thorough consideration of his work. Section 1 addresses the unique balance in Kant's philosophy between the work on particular problems and the orientation toward a systematic whole. Section 2 outlines McDowell's take on the Kantian distinction between intuition and concept in the context of the Kant readings by Sellars and Strawson. Section 3 exposes McDowell's relapse into the Myth of the Given. Section 4 proposes a reading of Kant's theoretical philosophy as an epistemology of metaphysical cognition. Section 5 details Kant's original account of sensible intuition in the Inaugural-Dissertation of 1770. Section 6 presents the transition from the manifold of the senses to the synthesis in the imagination and the unification through the categories in the Critique of pure reason (1781 and 1787). Section 7 addresses Kant's formalism in epistemology and metaphysics.

Putting the horse before the cart: a pragmatist analysis of knowledge

The definition of knowledge as justified true belief is the best we presently have. However, the canonical tripartite analysis of knowledge does not do justice to it due to a Platonic conception of a priori truth that puts the cart before the horse. Within a pragmatic approach, I argue that by doing away with a priori truth, namely by submitting truth to justification, and by accordingly altering the canonical analysis of knowledge, this is a fruitful definition. So fruitful indeed that it renders the Gettier counterexamples vacuous, allowing positive work in epistemology and related disciplines.