Melatonin transport into mitochondria

Melatonin is a well-known, nighttime-produced indole found in bacteria, eukaryotic unicellulars, animals or vascular plants. In vertebrates, melatonin is the major product of the pineal gland, which accounts for its increase in serum during the dark phase, but it is also produced by many other organs and cell types. Such a wide distribution is consistent with its multiple and well-described functions which include from the circadian regulation and adaptation to seasonal variations to immunomodulatory and oncostatic actions in different types of tumors. The discovery of its antioxidant properties in the early 1990s opened a new field of potential protective functions in multiple tissues. A special mention should be made regarding the nervous system, where the indole is considered a major neuroprotector. Furthermore, mitochondria appear as one of the most important targets for the indole’s protective actions. Melatonin’s mechanisms of action vary from the direct molecular interaction with free radicals (free radical scavenger) to the binding to membrane (MLT1A and MLT1B) or nuclear receptors (RZR/RORα). Receptor binding has been associated with some, but not all of the indole functions reported to date. Recently, two new mechanisms of cellular uptake involving the facilitative glucose transporters GLUT/SLC2A and the proton-driven oligopeptide transporter PEPT1/2 have been reported. Here we discuss the potential importance that these newly discovered transport systems could have in determining the actions of melatonin, particularly in the mitochondria. We also argue the relative importance of passive diffusion vs active transport in different parts of the cell.     

The invention of atmosphere

The word “atmosphere” was a neologism Willebrord Snellius created for his Latin translation of Simon Stevin's cosmographical writings. Astronomers and mathematical practitioners, such as Snellius and Christoph Scheiner, applying the techniques of Ibn Mu‘ādh and Witelo, were the first to use the term in their calculations of the height of vapors that cause twilight. Their understandings of the atmosphere diverged from Aristotelian divisions of the aerial region. From the early years of the seventeenth century, the term was often associated with atomism or corpuscular matter theory. The concept of the atmosphere changed dramatically with the advent of pneumatic experiments in the middle of the seventeenth century. Pierre Gassendi, Walter Charleton, and Robert Boyle transformed the atmosphere of the mathematicians giving it the characteristics of weight, specific gravity, and fluidity, while disputes about its extent and border remained unresolved.     

Managing the Technological Edge: The UNESCO International Computation Centre and the Limits to the Transfer of Computer Technology, 1946-61

The spread of the modern computer is assumed to have been a smooth process of technology transfer. This view relies on an assessment of the open circulation of knowledge ensured by the US and British governments in the early post-war years. This article presents new historical evidence that question this view. At the centre of the article lies the ill-fated establishment of the UNESCO International Computation Centre. The project was initially conceived in 1946 to provide advanced computation capabilities to scientists of all nations. It soon became a prize sought by Western European countries like the Netherlands and Italy seeking to speed up their own national research programs. Nonetheless, as the article explains, the US government's limitations on the research function of the future centre resulted in the withdrawal of European support for the project. These limitations illustrate the extent to which US foreign science policy could operate as (stealth) industrial policy to secure a competitive technological advantage and the prospects of US manufacturers in a future European market.     

Adaptation in the innate immune system and heterologous innate immunity

The innate immune system recognizes deviation from homeostasis caused by infectious or non-infectious assaults. The threshold for its activation seems to be established by a calibration process that includes sensing of microbial molecular patterns from commensal bacteria and of endogenous signals. It is becoming increasingly clear that adaptive features, a hallmark of the adaptive immune system, can also be identified in the innate immune system. Such adaptations can result in the manifestation of a primed state of immune and tissue cells with a decreased activation threshold. This keeps the system poised to react quickly. Moreover, the fact that the innate immune system recognizes a wide variety of danger signals via pattern recognition receptors that often activate the same signaling pathways allows for heterologous innate immune stimulation. This implies that, for example, the innate immune response to an infection can be modified by co-infections or other innate stimuli. This “design feature” of the innate immune system has many implications for our understanding of individual susceptibility to diseases or responsiveness to therapies and vaccinations. In this article, adaptive features of the innate immune system as well as heterologous innate immunity and their implications are discussed.