Spectrin and calpain: a ‘target’ and a ‘sniper’ in the pathology of neuronal cells

It is well documented that activation of calpain, a calcium-sensitive cysteine protease, marks the pathology of naturally and experimentally occuring neurodegenerative conditions. Calpain-mediated proteolysis of major membrane-skeletal protein, αII-spectrin, results in the appearance of two unique and highly stable breakdown products, which is an early event in neural cell pathology. This review focuses on spectrin degradation by calpain within neurons induced by diverse conditions, emphasizing a current picture of multi-pattern neuronal death and a recent success in the development of spectrin-based biomarkers. The issue is presented in the context of the major structural and functional properties of the two proteins.Received 7 March 2005; received after revision 22 April 2005; accepted 13 May 2005     

‘Holding’ and ‘endorsing’ claims in the course of scientific activities

My principal aims are to show that holding, adopting and endorsing (definitions of which I provide) are distinct cognitive attitudes that may be taken towards claims at different moments of scientific activities, and that none of them are reducible to acceptance (as defined by Jonathan Cohen); to explore in detail the differences between holding and accepting, using the controversies about GMOs to provide illustrations; and to draw some implications pertinent to democratic decision-making concerning public policies about science and technology, and to the responsibilities that scientists thereby incur.     

‘The happy thought of a single man’: On the legendary beginnings of a style of reasoning

In this paper I direct attention to one feature of Hacking’s recent work on styles of reasoning and argue that this feature is of far greater philosophical significance than Hacking’s limited discussion of this suggests. The feature in question is his use of ‘legendary beginnings’ in setting out a given style, viz. the method of introducing a style of reasoning by recounting a popular and quasi-mythical narrative that ties the crystallisation of that style to a particular person in a particular place and at a particular time. Whilst Hacking both deploys and discusses this method, his comments suggest that this is primarily a stylistic device employed for reasons of expedience. In contrast, it is argued here that recounting the legendary origins of a style of reasoning affords a distinctive way of vindicating that style, a vindication from within the style itself.     

Transplantation and ‘cross-transplantation’ of free muscle grafts in the rat

Zusammenfassung Nachweis, dass ein frei transplantierter Rattenmuskel besser regeneriert, wenn er 14 Tage vor der Transplantation denerviert wurde.

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Work performed during an exchange between the Czechoslovak and US Academies of Sciences and supported in part by a grant from the MDAA.     

Entropy measures of signal in the presence of noise: evidence for ‘byte’ versus ‘bit’ processing in the nervous system

Summary A method for detecting signal in the presence of noise in a highly specific was is described. Using action potential interval data from 12 neurons in rat cerebellum, we have demonstrated that the sequential ordering of spike intervals contains both noise and signal. We have identified and quantified the magnitude of relative entropy (uncertainty) for specified sets of interval patterns, ranging in length from 3–5 successive intervals. Some of these sets have exceptionally low entropy and thus seem to be especially meaningful as a set (word) to the brain.     

‘Chromatoid body’ in the spermatogenesis of scorpions

Zusammenfassung Die von früheren Autoren als «Chromatoidkörper» bezeichnete Struktur der Spermatozoiden von Skorpionen,Palamnaeus bengalensis, ist kein wirklicher «Chromatoidkörper», sondern ein Hilfskörper lipoprotonischer Natur ohne jegliche RNA.     

On factors involved in the mechanism of ‘Taste-blindness’

Zusammenfassung Der genetisch kontrollierte, hohe Geschmacksschwellenwert — Geschmacksblindheit — gegenüber Phenylthioharnstoff (PTC) und anderen bitteren, strukturell ähnlichen Anti-Schilddrüsensubstanzen, scheint durch die Qualität und Quantität des löslichen Speichel-Enzym-Systems Tyrosiniodinase bedingt zu sein.PTC-Geschmacksblinde sind «Alles-Esser», PTC-Schmecker hingegen weisen eine erhöhte kulinarische Selektivität auf. Diese Tatsache ist um so interessanter, als der Schwellenwert der beiden Gruppen gegenüber den klassischen Geschmacksqualitäten — süss, salzig, sauer und bitter — derselbe ist.     

‘Identify’ and ‘lock in’: molecular integration during synaptic target recognition

Synaptic target recognition is a complex molecular event. In a differentiating presynaptic terminal, relatively ‘rare’ molecules first detect the cell identity of the synaptic target. Subsequently, many ‘common’ molecules continue the process of synaptogenesis. We present a theoretical framework for understanding synaptic target recognition and discuss the features of its molecular components and their integration, drawing on the rapid progress made in recent studies.     

Histochemistry of the so-called ‘golgi complex’ in the mammalian spermatid

Résumé L'examen histochimique des spermatides du bouc et du buffle montre que le «complexe de Golgi» des auteurs comprend l'idiosome constitué par des protéides et des lipidoprotéides, les bâtonnets et granules constitués par des phospholipides et peut-être des protéides et enfin les vacuoles.     

Reflecting ‘Popular Culture’: The Introduction,Diffusion, and Construction of the Reflecting Telescope in the Netherlands

The eighteenth century was an era in which science came to play a major role in the cultural ideal of the city elite. The phenomenon of the ‘gentleman-scientist’ arose: a layman without a scientific education who for a variety of often socially desirable reasons devoted himself to scientific endeavours. Scientific instruments were the tools for this interest. This article describes the introduction, diffusion, and construction in the Netherlands of one of the most prominent eighteenth-century instruments: the reflecting telescope. The reception of this instrument casts new light on the usually almost invisible network of gentleman-scientists and instrument-makers in this region. The specific economic and political factors of the Netherlands led to a totally different development of this instrument compared with the ‘motherland’ England. Whereas in Great Britain the reflecting telescope was a great success well into the nineteenth century, in the Netherlands it became a symbol of technical inability and stagnation.     

Freiberg and the Frontier: Louis Janin,German Engineering,and ‘Civilisation’ in the American West

Mining companies after the Gold Rush depended heavily on foreign expertise, and yet historians of mining have glorified ‘German engineering’ in America. The application of German technology in America was fraught with difficulties, and most advances were micro- rather than macro-innovations, such as Philip Deidesheimer's famous square-set timbering on the Comstock Lode. The problem began at German mining schools, such as the Freiberg Mining Academy, where Americans like Louis and Henry Janin, while they acquired advanced training and adopted an engineering ethos, struggled to learn about Mexican and American mining. Having complemented their course of study to remedy this deficiency, the brothers returned to the US intending to modernize mining on the frontier. Louis attempted the ‘Freiberg Process’ of amalgamation on the Comstock Lode, but locally developed methods proved more feasible, and the experiment failed. He came to apply his training rather toward the micro-level problem of how to reprocess amalgamation waste heaps.     

Striated inclusions and defective mitochondria in the restricted form of the ‘amycelial’ mutant ofNeurospora crassa

Summary The cytoplasm of the restrictive form of the amycelial mutant ofNeurospora crassa, growing on sucrosemedium, contains paracrystalline, microfilamentous inclusions and mitochondria with internal membranous whorls lacking in acetate-grown cultures.The support of the Fonds national suisse de la recherche scientifique is gratefully acknowledged.     

Blood ‘Contamination’ of liver homogenates and the liver cathepsines

Zusammenfassung Es wurde die Blutmenge in der Rattenleber sowie die Kathepsinaktivität der Leberhomogenate und des Blutes bestimmt. Unter den beschriebenen Bedingungen war die Kathepsinaktivität der Leberhomogenate nicht durch Blutkontamination beeinflusst.     

Alexis Fontaine's ‘Fluxio-differential method’ and the origins of the calculus of several variables

Alexis Fontaine des Bertins (1704–1771) was the first French mathematician to introduce what we would now regard as results in the calculus of several variables. One example is Fontaine's theorem nF = (?F/?x)x + (?F/?y)y of 1737 for homogeneous expressions F of degree n in x and y. Many years later Fontaine indicated this particular result to have been ‘a continuation of the method of solution’ introduced by him in 1734 to solve the problem of the tautochrones. It is tempting to disregard this announcement, since the method applied to the tautochrones was a method of variations and not manifestly an exercise in the calculus of several variables. Do we have just another case of a mathematician's confusion about the origins of his earlier work? In this paper I describe Fontaine's possible intentions in his remarks.     

‘Soup’ vs. ‘Sparks’: Alexander Forbes and the Synaptic Transmission Controversy

During the twentieth century, a controversy raged over the role of electrical forces and chemical substances in synaptic transmission. Although the story of the ‘main’ participants is well documented, the story of ‘lesser’ known participants is seldom told. For example, Alexander Forbes, who was a prominent member of the axonologists, played an active role in the controversy and yet is seldom mentioned in standard accounts of the controversy. During the 1930s, Forbes incorporated chemical substances into his theory of synaptic transmission, advocating a complementarity model for the role of electrical forces and chemical substances. By focusing on Forbes and the axonologists, the controversy is simply more than a debate over ‘soup’ vs. ‘sparks’ but also involves the relative roles of electrical forces and chemical substances in synaptic transmission. The implications of this case study for the nature of scientific controversies are also discussed.     

The ‘nec plus ultra’ of precision measurement: Geodesy and the forgotten purpose of the Metre Convention

Geodesy—the determination of the size and shape of the earth—has often been the science operating at the frontier of precision in the measurement of length. Its contribution to the technologies and standards of length measurement has, however, been underestimated in the literature. That, instead, places emphasis on the on the creation and international acceptance of the metric system as a whole. By new research into the standards-in-use of the community of geodesists, I rediscover the original purpose of the Metre Convention of 1875, and show for the first time the significant influence of geodesy on the standardisation of length measurement thereafter. I emphasise the role of the coherence of the web of measurement in the context of change and improvement in standards.     

Quantitative investigation of the P and N loss in the rat liver when using various media in the ‘freeze-substitution’ technique

Résumé Les auteurs ont examiné les possibilités de diminution du contenu en azote et phosphore et de la masse sèche au cours de la congelation-dissolution des tissus. La diminution la plus marquée a été observée après l'usage de méthanol. Tandis qu'avec l'acétone elle est insignifiante.