Melatonin,mitochondria, and the skin

The skin being a protective barrier between external and internal (body) environments has the sensory and adaptive capacity to maintain local and global body homeostasis in response to noxious factors. An important part of the skin response to stress is its ability for melatonin synthesis and subsequent metabolism through the indolic and kynuric pathways. Indeed, melatonin and its metabolites have emerged as indispensable for physiological skin functions and for effective protection of a cutaneous homeostasis from hostile environmental factors. Moreover, they attenuate the pathological processes including carcinogenesis and other hyperproliferative/inflammatory conditions. Interestingly, mitochondria appear to be a central hub of melatonin metabolism in the skin cells. Furthermore, substantial evidence has accumulated on the protective role of the melatonin against ultraviolet radiation and the attendant mitochondrial dysfunction. Melatonin and its metabolites appear to have a modulatory impact on mitochondrion redox and bioenergetic homeostasis, as well as the anti-apoptotic effects. Of note, some metabolites exhibit even greater impact than melatonin alone. Herein, we emphasize that melatonin–mitochondria axis would control integumental functions designed to protect local and perhaps global homeostasis. Given the phylogenetic origin and primordial actions of melatonin, we propose that the melatonin-related mitochondrial functions represent an evolutionary conserved mechanism involved in cellular adaptive response to skin injury and repair.     

Melatonin,mitochondria, and the metabolic syndrome

A number of risk factors for cardiovascular disease including hyperinsulinemia, glucose intolerance, dyslipidemia, obesity, and elevated blood pressure are collectively known as metabolic syndrome (MS). Since mitochondrial activity is modulated by the availability of energy in cells, the disruption of key regulators of metabolism in MS not only affects the activity of mitochondria but also their dynamics and turnover. Therefore, a link of MS with mitochondrial dysfunction has been suspected since long. As a chronobiotic/cytoprotective agent, melatonin has a special place in prevention and treatment of MS. Melatonin levels are reduced in diseases associated with insulin resistance like MS. Melatonin improves sleep efficiency and has antioxidant and anti-inflammatory properties, partly for its role as a metabolic regulator and mitochondrial protector. We discuss in the present review the several cytoprotective melatonin actions that attenuate inflammatory responses in MS. The clinical data that support the potential therapeutical value of melatonin in human MS are reviewed.     

Melatonin,mitochondria, and the cancer cell

The long-recognized fact that oxidative stress within mitochondria is a hallmark of mitochondrial dysfunction has stimulated the development of mitochondria-targeted antioxidant therapies. Melatonin should be included among the pharmacological agents able to modulate mitochondrial functions in cancer, given that a number of relevant melatonin-dependent effects are triggered by targeting mitochondrial functions. Indeed, melatonin may modulate the mitochondrial respiratory chain, thus antagonizing the cancer highly glycolytic bioenergetic pathway of cancer cells. Modulation of the mitochondrial respiratory chain, together with Ca²⁺ release and mitochondrial apoptotic effectors, may enhance the spontaneous or drug-induced apoptotic processes. Given that melatonin may efficiently counteract the Warburg effect while stimulating mitochondrial differentiation and mitochondrial-based apoptosis, it is argued that the pineal neurohormone could represent a promising new perspective in cancer treatment strategy.     

Kuhn, Popper, and the Superconducting Supercollider

The demise of the Superconducting Supercollider (SSC) is often explained in terms of the strain that it placed on the federal budget of the United States, and change in national security interests with the end of the Cold War. Recent work by Steve Fuller provides a framework to re-examine this episode in epistemological terms using the work of Kuhn and Popper. Using this framework, it is tempting to explain the demise as resulting from the overly Kuhnian character of its proponents, who supposedly argued for its construction by appealing to the importance of testing the predictions of a specific paradigm (i.e. the Standard Model). On this reading, the SSC case appears as an example of how Kuhn’s paradigm-driven view of science was invoked to keep science closed and autonomous from society. I argue that the SSC episode should not be viewed as giving support to the displacement of Kuhn’s view of science for Popper’s, and that such a displacement is detrimental to the project of integrating discussion on science into the public sphere. Drawing upon Rouse and Wimsatt, I argue that understanding paradigms as practices blunts some criticisms against Kuhn’s model, and that his model should play an important epistemological role in the aforementioned project.     

Exogenous gangliosides, neuronal plasticity and repair, and the neurotrophins

Gangliosides, a heterogeneous family of glycosphingolipids abundant in the brain, have been shown to affect neuronal plasticity during development, adulthood and aging. This review will examine old and recent evidence that exogenous gangliosides and in particular GM1, the prototype member of this family, exhibit multimodal neurotrophic effects. Since these compounds are a potential therapeutic tool for the treatment of various forms of acute or chronic neurodegenerative diseases, understanding the dynamic interplay of gangliosides and neuronal cells is essential in the effort to cure neurological disorders. Focus will be given to the novel and provocative hypothesis that gangliosides' neuroprotective properties may derive from their ability to mimic endogenous neurotrophic factors.     

Measurement,coordination, and the relativized a priori

The problem of measurement is a central issue in the epistemology and methodology of the physical sciences. In recent literature on scientific representation, large emphasis has been put on the “constitutive role” played by measurement procedures as forms of representation. Despite its importance, this issue hardly finds any mention in writings on constitutive principles, viz. in Michael Friedman׳s account of relativized a priori principles. This issue, instead, was at the heart of Reichenbach׳s analysis of coordinating principles that has inspired Friedman׳s interpretation. This paper suggests that these procedures should have a part in an account of constitutive principles of science, and that they could be interpreted following the intuition originally present (but ultimately not fully developed) in Reichenbach׳s early work.     

Aristotle, Copernicus, Bruno: centrality, the principle of movement and the extension of the Universe

This paper¹ studies the different conceptions of both centrality and the principle or starting point of motion in the Universe held by Aristotle and later on by Copernicanism until Kepler and Bruno. According to Aristotle, the true centre of the Universe is the sphere of the fixed stars. This is also the starting point of motion. From this point of view, the diurnal motion is the fundamental one. Our analysis gives pride of place to De caelo II, 10, a chapter of Aristotle’s text which curiously allows an ‘Alpetragian’ reading of the transmission of motion.In Copernicus and the Copernicans, natural centrality is identified with the geometrical centre and, therefore, the Sun is acknowledged as the body through which the Deity acts on the world and it also plays the role of the principle and starting point of cosmic motion. This motion, however, is no longer diurnal motion, but the annual periodical motion of the planets. Within this context, we pose the question of to what extent it is possible to think that, before Kepler, there is a tacit attribution of a dynamic or motive role to the Sun by Copernicus, Rheticus, and Digges.For Bruno, since the Universe is infinite and homogeneous and the relationship of the Deity with it is one of indifferent presence everywhere, the Universe has no absolute centre, for any point is a centre. By the same token, there is no place that enjoys the prerogative of being—as being the seat of God—the motionless principle and starting point of motion.     

Thermoscopes, thermometers, and the foundations of measurement

Psychologists debate whether mental attributes can be quantified or whether they admit only qualitative comparisons of more and less. Their disagreement is not merely terminological, for it bears upon the permissibility of various statistical techniques. This article contributes to the discussion in two stages. First it explains how temperature, which was originally a qualitative concept, came to occupy its position as an unquestionably quantitative concept (§§1–4). Specifically, it lays out the circumstances in which thermometers, which register quantitative (or cardinal) differences, became distinguishable from thermoscopes, which register merely qualitative (or ordinal) differences. I argue that this distinction became possible thanks to the work of Joseph Black, ca. 1760. Second, the article contends that the model implicit in temperature’s quantitative status offers a better way for thinking about the quantitative status of mental attributes than models from measurement theory (§§5–6).     

Cosmology,particles, and the unity of science

During the last three decades, there has been a growing realization among physicists and cosmologists that the relation between particle physics and cosmology may constitute yet another successful example of the unity of science. However, there are important conceptual problems in the unification of the two disciplines, e.g. in connection with the cosmological constant and the conjecture of inflation. The present article will outline some of these problems, and argue that the victory for the unity of science in the context of cosmology and particle physics is still far from obvious.     

Effects of the metals,Be, Fe,Cu and Al,on the mobility of immunoglobulin receptors

Summary Cap formation in mouse spleen cells induced by antiimmunoglobulin was inhibited by the metals Be, Fe, Cu and Al. Be was especially strong as an inhibitor of cap formation. It is suggested that these metals might change the mobility of the membrane and have some biological effects on the cross association of antigen receptors when B lymphocytes are attached by them.