Melatonin as a mitochondria-targeted antioxidant: one of evolution’s best ideas

Melatonin is an ancient antioxidant. After its initial development in bacteria, it has been retained throughout evolution such that it may be or may have been present in every species that have existed. Even though it has been maintained throughout evolution during the diversification of species, melatonin’s chemical structure has never changed; thus, the melatonin present in currently living humans is identical to that present in cyanobacteria that have existed on Earth for billions of years. Melatonin in the systemic circulation of mammals quickly disappears from the blood presumably due to its uptake by cells, particularly when they are under high oxidative stress conditions. The measurement of the subcellular distribution of melatonin has shown that the concentration of this indole in the mitochondria greatly exceeds that in the blood. Melatonin presumably enters mitochondria through oligopeptide transporters, PEPT1, and PEPT2. Thus, melatonin is specifically targeted to the mitochondria where it seems to function as an apex antioxidant. In addition to being taken up from the circulation, melatonin may be produced in the mitochondria as well. During evolution, mitochondria likely originated when melatonin-forming bacteria were engulfed as food by ancestral prokaryotes. Over time, engulfed bacteria evolved into mitochondria; this is known as the endosymbiotic theory of the origin of mitochondria. When they did so, the mitochondria retained the ability to synthesize melatonin. Thus, melatonin is not only taken up by mitochondria but these organelles, in addition to many other functions, also probably produce melatonin as well. Melatonin’s high concentrations and multiple actions as an antioxidant provide potent antioxidant protection to these organelles which are exposed to abundant free radicals.     

Jean-François Pilˆatre de Rozier

A translation of Kant's early paper, ‘Die Frage, ob die Erde veralte, physikalisch erwogen’ (‘The question, whether the Earth is ageing, considered physically’) is presented, and the main features of his position on this question in 1754 are summarized. In that year, Kant believed that the Earth was ageing, and that it was about 6000 years old. The paper allows us to understand the approximate outline of Kant's general ‘theory of the Earth’, and the relation of this theory to the cosmogony that he propounded in 1755. His ideas on the processes of erosion, and the formation of rivers, deltas and sandbanks, are noteworthy, and provide a contribution to the eighteenth-century literature on the denudation dilemma. Kant's general theory of erosion and deposition was, it seems, based to a significant extent on his knowledge of the geographical features of the Königsberg district. The general teleological position underpinning his philosophy may be discerned in this early paper, and he may be thought of as having been trying to orientate himself in space and time, so to speak, before undertaking his major reconstructions in philosophy.     

Putting the Earth System in a numerical box? The evolution from climate modeling toward global change

Since the 1980s, climate modeling has undergone major transformations. The most prominent of these are the proliferation of coupled models and the integration within models of a growing number of environments and feedbacks. Climate modelers now increasingly define their object in terms of an “Earth System” instead of a “climate system”. In addition to this proliferation of coupled models, the carbon cycle and its feedback on various environments, from the atmosphere to the ocean and to vegetation cover, has become a prominent component of climate modeling. These transformations derive from the IPCC’s overall methodology, and are closely bound up with both a heightened awareness of the risks of climate change, as well as an issue of crucial political importance: the question of socio-economic/climate integration. In this article I follow, from a roughly chronological point of view, the major steps of this evolution and its links with the evolution of the political agenda. What can we say about this seemingly irreversible tendency to incorporate everything into models and to take account of everything that influences the Earth’s climate? Could we correlate it to the strong tendency toward globalization? How is the notion of climate itself affected? These are the main questions of the paper.     

Revertant mosaicism in genodermatoses

Inherited monogenic skin disorders include blistering disorders, inflammatory disorders, and disorders of differentiation or development. In most cases, the skin is broadly involved throughout the affected individual’s lifetime, but rarely, appearance of normal skin clones has been described. In these cases of revertant mosaicism, cells undergo spontaneous correction to ameliorate the effects of genetic mutation. While targeted reversion of genetic mutation would have tremendous therapeutic value, the mechanisms of reversion in the skin are poorly understood. In this review, we provide an overview of genodermatoses that demonstrate widespread reversion and their corrective mechanisms, as well as the current research aimed to understand this “natural gene therapy”.     

The origin,diversity, and structure function relationships of insect luciferases

Luciferases are the enzymes that catalyze the reactions that produce light in bioluminescence. Whereas the oxidative mechanism which leads to light emission is similar for most luciferases, these enzymes and their substrates are evolutionarily unrelated. Among all bioluminescent groups, insects constitute one of the most diverse in terms of biochemistry. In the fungus-gnats (Mycetophilidae: Diptera), for example, bioluminescence is generated by two biochemically distinct systems. Despite the diversity, investigations on insect luciferases and biochemistry have been conducted mostly with fireflies. The luciferases from the related phengodid beetles, which can produce green to red bioluminescence using the same chemistry as firefly luciferases, have been recently investigated. Beetle luciferases originated from ancestral acyl-CoA ligases. Present data suggest that conserved motifs among this class of ligases are involved in substrate adenylation. The three-dimensional structure of firefly luciferase was recently solved and mutagenesis studies have been performed identifying putative residues involved in luciferin binding and bioluminescence color determination in several beetle luciferases. The knowledge gained through these studies is helping in the development of useful reporter gene tools for biotechnological and biomedical purposes. Received 4 March 2002; received after revision 13 May 2002; accepted 21 May 2002     

Satellite DNAs in eukaryotes: A non-adaptive mechanism of speciation which originated with sexual reproduction?

Summary Satellite DNAs may have originated during evolution at the same time as sexual reproduction in order to suppress crossingover between the 2 heterogametic sex chromosomes, and may have acquired a function of sterility barriers in hybrid species during evolution. This origin of satellite DNAs appears to be reflected in different stages of speciation: partial and total heterogametic sex hybrid sterility and full hybrid sterility might correspond to subspecies, semispecies and full species.This work was supported by grant No. CT.76.01203.04. from CNR Rome.     

Jean Méry (1645–1722) and his ideas on the foetal blood flow

We present an analysis, and first full English translation, of a paper by Kant entitled ‘Über die Vulcane im Monde’ (1785). Kant became interested in the question of whether the mountains of the Moon were extinct volcanoes. Stimulated by the work of Herschel, Aepinus, and others, he considered the appearance of the Moon's surface and the possibility of lunar vulcanism. From this, he was led to consider the structures of mountain ranges on the Earth, which he decided were non-volcanic in origin, being produced by eruptions of vapours from the interior of the Earth soon after it formed from an original ‘chaos’. Kant developed his ideas in such a way as to yield a characteristic eighteenth-century ‘theory of the Earth’. We argue that the empirical base of his theory was provided by knowledge of the mountain ranges of Bohemia and Moravia. Analogies based on observations of the Moon further assisted in the construction of the theory. But the reasoning ran in two directions: what was seen on the Moon was construed in terms of what Kant knew of the Earth's topography; and the Earth's topography was presumed to be analogous to that of the Moon, for both the Earth and the Moon (and indeed all heavenly bodies) supposedly had essentially similar origins. Kant's ideas of 1785 are related to his earlier writings of 1754, 1755, and 1756, and also to the lectures on physical geography that he presented at Königsberg.     

Stable regularities without governing laws?

Can stable regularities be explained without appealing to governing laws or any other modal notion? In this paper, I consider what I will call a ‘Humean system’—a generic dynamical system without guiding laws—and assess whether it could display stable regularities. First, I present what can be interpreted as an account of the rise of stable regularities, following from Strevens (2003), which has been applied to explain the patterns of complex systems (such as those from meteorology and statistical mechanics). Second, since this account presupposes that the underlying dynamics displays deterministic chaos, I assess whether it can be adapted to cases where the underlying dynamics is not chaotic but truly random—that is, cases where there is no dynamics guiding the time evolution of the system. If this is so, the resulting stable, apparently non-accidental regularities are the fruit of what can be called statistical necessity rather than of a primitive physical necessity.     

Comparison of cutaneous hyperemia in cattle elicited by larvae ofBoophilus microplus and by prostaglandins and other mediators

Summary Blood flow has been measured in bovine skin following the injection of tick antigens and a number of pharmacological mediators; including histamine, prostaglandins and slow reacting substance of anaphylaxis. The greates increase in blood flow (20 times normal) was recorded with tick antigens and with prostaglandin F2. This mediator may therefore influence blood flow during immune reactions to ticks and during the rapid ingestion of blood by the ticks.Acknowledgments. This work was supported by the Australian Meat Research Committee. We would like to thank J. M. Gough for her technical assistance.     

Thomas Harriot’s optics,between experiment and imagination: the case of Mr Bulkeley’s glass

Some time in the late 1590s, the Welsh amateur mathematician John Bulkeley wrote to Thomas Harriot asking his opinion about the properties of a truly gargantuan (but totally imaginary) plano-spherical convex lens, 48 feet in diameter. While Bulkeley’s original letter is lost, Harriot devoted several pages to the optical properties of “Mr Bulkeley his Glasse” in his optical papers (now in British Library MS Add. 6789), paying particular attention to the place of its burning point. Harriot’s calculational methods in these papers are almost unique in Harriot’s optical remains, in that he uses both the sine law of refraction and interpolation from Witelo’s refraction tables in order to analyze the passage of light through the glass. For this and other reasons, it is very likely that Harriot wrote his papers on Bulkeley’s glass very shortly after his discovery of the law and while still working closely with Witelo’s great Optics; the papers represent, perhaps, his very first application of the law. His and Bulkeley’s interest in this giant glass conform to a long English tradition of curiosity about the optical and burning properties of large glasses, which grew more intense in late sixteenth-century England. In particular, Thomas Digges’s bold and widely known assertions about his father’s glasses that could see things several miles distant and could burn objects a half-mile or further away may have attracted Harriot and Bulkeley’s skeptical attention; for Harriot’s analysis of the burning distance and the intensity of Bulkeley’s fantastic lens, it shows that Digges’s claims could never have been true about any real lens (and this, I propose, was what Bulkeley had asked about in his original letter to Harriot). There was also a deeper, mathematical relevance to the problem that may have caught Harriot’s attention. His most recent source on refraction—Giambattista della Porta’s De refractione of 1593—identified a mathematical flaw in Witelo’s cursory suggestion about the optics of a lens (the only place that lenses appear, however fleetingly, in the writings of the thirteenth-century Perspectivist authors). In his early notes on optics, in a copy of Witelo’s optics, Harriot highlighted Witelo’s remarks on the lens and della Porta’s criticism (which he found unsatisfactory). The most significant problem with Witelo’s theorem would disappear as the radius of curvature of the lens approached infinity. Bulkeley’s gigantic glass, then, may have provided Harriot an opportunity to test out Witelo’s claims about a plano-spherical glass, at a time when he was still intensely concerned with the problems and methods of the Perspectivist school.     

Von Neumann’s impossibility proof: Mathematics in the service of rhetorics

According to what has become a standard history of quantum mechanics, in 1932 von Neumann persuaded the physics community that hidden variables are impossible as a matter of principle, after which leading proponents of the Copenhagen interpretation put the situation to good use by arguing that the completeness of quantum mechanics was undeniable. This state of affairs lasted, so the story continues, until Bell in 1966 exposed von Neumann’s proof as obviously wrong. The realization that von Neumann’s proof was fallacious then rehabilitated hidden variables and made serious foundational research possible again. It is often added in recent accounts that von Neumann’s error had been spotted almost immediately by Grete Hermann, but that her discovery was of no effect due to the dominant Copenhagen Zeitgeist.We shall attempt to tell a story that is more historically accurate and less ideologically charged. Most importantly, von Neumann never claimed to have shown the impossibility of hidden variables tout court, but argued that hidden-variable theories must possess a structure that deviates fundamentally from that of quantum mechanics. Both Hermann and Bell appear to have missed this point; moreover, both raised unjustified technical objections to the proof. Von Neumann’s argument was basically that hidden-variables schemes must violate the “quantum principle” that physical quantities are to be represented by operators in a Hilbert space. As a consequence, hidden-variables schemes, though possible in principle, necessarily exhibit a certain kind of contextuality.As we shall illustrate, early reactions to Bohm’s theory are in agreement with this account. Leading physicists pointed out that Bohm’s theory has the strange feature that pre-existing particle properties do not generally reveal themselves in measurements, in accordance with von Neumann’s result. They did not conclude that the “impossible was done” and that von Neumann had been shown wrong.     

Primitive actimoterigian fishes can synthesize ascorbic acid

Amphibians and reptiles evolved with the capacity to synthesize ascorbic acid. Some higher vertebrates, like bats, guinea pigs, primates, and humans have lost the microsomal enzyme gulonolactone oxidase, and in cases of ascorbic acid deficiency suffer from symptoms of scurvy. The question of whether the capacity to synthesize ascorbate is also present in lower vertebrates could throw light on the evolution of this pathway. In order to find out whether ascorbic acid synthesis took place in two primitive Actinopterigian fish, the paddlefish (Polydon spathula) and the white sturgeon (Acipenser transmontanus) were fed with a scorbutogenic diet or diet(s) supplemented with a graded level of ascorbic acid. We found no growth depression nor external symptoms of scurvy, which would be pronounced in modern bony fishes (Teleostei) under similar conditions. The tissue level of ascorbate in both these primitive species indicated that vitamin C in intestine and liver is not depleted when fed a scorbutogenic diet. Gulonolactone oxidase activity was found in the kineys of the Actinopterigian fishes. Thus, I question the accepted evolutionary pathway for ascorbic acid biosynthesis in lower vertebrates and suggest that the modern bony fishes,Teleostei, lost their ability to express the gulonolactone oxidase genes after they had separated during the Silurian from their common ancestor with the coelacanths (Latimeria) and Dipnoi.     

Narratives of Charles Darwin Down Under

Despite the fact that Charles Darwin spent several months in Australia in the final year of his Beagle voyage that circumnavigated the globe, most studies that deal with Darwin's life or his discovery of evolution spend little time discussing his Australian period, if it is mentioned at all. His time there is largely deemed to have produced little of significance in comparison to his visits to other places such as the Galápagos Islands, which has long been mythologized as providing the key sources of observable data that ultimately led Darwin to develop his evolutionary speculations. In recent years, however, Darwin's period in Australia has received more attention, most notably a series of studies detailing the observations and connections Darwin made while in New South Wales, Tasmania, and King George Sound. While much of this literature has provided an important corrective to previous Darwin scholarship that had largely ignored Darwin's period in Australia, it has also worked to perpetuate a romantic and heroic view of scientific discovery by suggesting that Darwin's key “evolutionary revelation” was made not in the Galápagos Islands but in the Blue Mountains, a claim that has been recently made in print and online. This paper therefore examines the historical literature on Darwin Down Under, focussing in particular on this recent romantic turn that seeks to situate Australia as the key site of inspiration for Darwin's theory of evolution.     

Deoxyribozymes: useful DNA catalysts in vitro and in vivo

Deoxyribozymes (DNA enzymes; DNAzymes) are catalytic DNA sequences. Using the technique of in vitro selection, individual deoxyribozymes have been identified that catalyze RNA cleavage, RNA ligation, and a growing range of other chemical reactions. DNA enzymes have been used in vitro for applications such as biochemical RNA manipulation and analytical assays for metal ions, small organic compounds, oligonucleotides, and proteins. Deoxyribozymes have also been utilized as in vivo therapeutic agents to destroy specific mRNA targets. Although many conceptual and practical challenges remain to be addressed, deoxyribozymes have substantial promise to contribute meaningfully for applications both in vitro and in vivo.     

Starch-binding domains in the post-genome era

Starch belongs to the most abundant biopolymers on Earth. As a source of energy, starch is degraded by a large number of various amylolytic enzymes. However, only about 10% of them are capable of binding and degrading raw starch. These enzymes usually possess a distinct sequence-structural module, the so-called starchbinding domain (SBD). In general, all carbohydrate-binding modules (CBMs) have been classified into the CBM families. In this sequence-based classification the individual types of SBDs have been placed into seven CBM families: CBM20, CBM21, CBM25, CBM26, CBM34, CBM41 and CBM45. The family CBM20, known also as a classical C-terminal SBD of microbial amylases, is the most thoroughly studied. The three-dimensional structures have already been determined by X-ray crystallography or nuclear magnetic resonance for SBDs from five CBM families (20, 25, 26, 34 and 41), and the structure of the CBM21 has been modelled. Despite differences among the amino acid sequences, the fold of a distorted β-barrel seems to be conserved together with a similar way of substrate binding (mainly stacking interactions between aromatic residues and glucose rings). SBDs have recently been discovered in many non-amylolytic proteins. These may, for example, have regulatory functions in starch metabolism in plants or glycogen metabolism in mammals. SBDs have also found practical uses. Received 25 May 2006; received after revision 26 June 2006; accepted 3 August 2006     

Reviving material theories of induction

John Norton says that philosophers have been led astray for thousands of years by their attempt to treat induction formally. He is correct that such an attempt has caused no end of trouble, but he is wrong about the history. There is a rich tradition of non-formal induction. In fact, material theories of induction prevailed all through antiquity and from the Renaissance to the mid-1800s. Recovering these past systems would not only fill lacunae in Norton’s own theory but would highlight areas where Norton has not freed himself from the straightjacket of formal induction as much as he might think. This essay begins that recovery.     

Becoming a Darwinian: the Micro‐politics of Sir Francis Galton's Scientific Career 1859–65

In 1865 Francis Galton (1822–1911) published ‘Hereditary Talent and Character’, an elaborate attempt to prove the heritability of intelligence on the basis of pedigree data. It was the start of Galton's lifelong commitment to investigating the statistical patterns and physiological mechanisms of hereditary transmission. Most existing attempts to explain Galton's fascination for heredity have argued that he was driven by a commitment to conservative political ideologies to seek means of naturalizing human inequality. However, this paper shows that another factor of at least equal importance has been overlooked by Galton scholars: his determination during the 1860s to be accepted among the ranks of the Darwinian inner circle. By hitching his career to the fortunes of what looked likely to emerge as a new scientific elite, Galton felt that he could bypass the typically slow and uncertain route to achieving scientific distinction. For this essentially strategic reason, between 1860 and 1865 he drifted away from a set of existing scientific concerns that were failing to deliver the approbation that he desired. Earnestly seeking to ingratiate himself with the Darwinian lobby, he then toyed with a variety of potential research projects relevant to Darwinian evolution. Yet Galton consistently failed to stimulate the enthusiasm of the Darwinians. Finally, however, after several months of ruminating, in 1864 he settled on a study of eminent pedigrees as a subject that was both germane and highly useful to the Darwinian enterprise. Galton's willingness to shift the direction of his scientific career during the 1860s underscores the importance of examining the micro‐politics of scientific careers in addition to their broader social and political context. This account also emphasizes the limitations of class‐based explanations even when considering scientists whose work seems so manifestly indicative of ideological motivation.     

A study and critique of the teaching of the history of science and technology. Interim report by the committee on undergraduate education of the history of science society (U.S.A.)

A great deal is known about the technical issues surrounding the introduction of Hugo De Vries's mutation theory and the subsequent development of the modern genetical theory of natural selection. But so far little has been done to relate these events to the wider issues of the time. This article suggests that extra-scientific factors played a significant role, and substantiates this by comparing De Vries's respect for the original Darwinian spirit with Thomas Hunt Morgan's use of the mutation theory as part of an attack on the whole philosophy of Darwinism. In particular, it is argued that Morgan's attitude was dictated by his moral objections to the picture of a world dominated by struggle.