A ‘fertilization membrane’ in the ascidianHerdmania momus and its relation to self- and cross-fertilization

Zusammenfassung Im Ei der AscidieHerdmania momus hebt sich nach der Besamung die Befruchtungsmembran von der äusseren Haut ab. Die Korrelationen, die bestehen zwischen Membranabhebung und Befruchtung, sowie ihrem Unterbleiben und der Sterilität, stützen wiederum die Chorionblocktheorie der Autosterilität.     

Genetically determined epithelial dysfunction and its consequences for microflora–host interactions

The intestinal epithelium forms a highly active functional interface between the relatively sterile internal body surfaces and the enormously complex and diverse microbiota that are contained within the lumen. Genetic models that allow for manipulation of genes specifically in the intestinal epithelium have provided an avenue to understand the diverse set of pathways whereby intestinal epithelial cells (IECs) direct the immune state of the mucosa associated with homeostasis versus either productive or non-productive inflammation as occurs during enteropathogen invasion or inflammatory bowel disease (IBD), respectively. These pathways include the unfolded protein response (UPR) induced by stress in the endoplasmic reticulum (ER), autophagy, a self-cannibalistic pathway important for intracellular bacterial killing and proper Paneth cell function as well as the interrelated functions of NOD2/NF-κB signaling which also regulate autophagy induction. Multiple genes controlling these IEC pathways have been shown to be genetic risk factors for human IBD. This highlights the importance of these pathways not only for proper IEC function but also suggesting that IECs may be one of the cellular originators of organ-specific and systemic inflammation as in IBD.     

The ‘brown spots’ (bsp) character ofDrosophila melanogaster and its relation to copulation

Riassunto Le autori dimostrano che la manifestazione del fenotipo nelle femmine omozigoti per il caratterebsp è provocata dalla copulazione. L'accoppiamento con maschi di ceppi nonbsp e con maschi sterili (X/Y^Le, X/O, X/X;tra/tra) determina pure la comparsa delle macchie nelle femminebsp, dimostrando che il fenomeno è indipendente dalla presenza degli spermatozoi nello sperma. Esiste una relazione fra frequenza della manifestazione ed età della femmina al momento dell'accoppiamento.     

‘Cystine monosulfoxide’ and related compounds

Zusammenfassung Die früher als «Cystinmonosulfoxyd» beschriebene Verbindung (Thiosulfinat II) verhält sich wie eine äquimolekulare Mischung von Cystin (I) und dem entsprechenden Thiosulfonat (III). Oxydation von Cystin mit Perameisensäure führt, besonders in Gegenwart von HCl, über die Zwischenprodukte Thiosulfonat (III) und Sulfinsäure (VI) zu Cysteinsäure (VII).     

‘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.     

‘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.     

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     

‘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.     

‘Land-marks of the universe’: John Herschel against the background of positional astronomy

John Herschel (1792–1871) was the leading British natural philosopher of the nineteenth century, widely known and regarded for his work in philosophy, optics and chemistry as well as his important research and popular publications on astronomy. To date, however, there exists no extended treatment of his astronomical career. This paper, part of a larger study exploring Herschel's contributions to astronomy, examines his work in the context of positional astronomy, the dominant form of astronomical practice throughout his lifetime. Herschel, who did not himself practice positional astronomy and who was known for his non-meridional observations of specific stellar objects, was nonetheless a strong advocate for positional astronomy—but for very different reasons than the terrestrial applications to which it was most often put. For Herschel, the star catalogues of positional astronomy were the necessary observational foundation upon which information about the stars as physical objects could be constructed. Positional astronomy practiced in the great national observatories was not about navigation or timekeeping; it was a way to standardize stellar observations and make them useful data for constructing theories of the stars themselves. For Herschel, the seeds of the new astronomy emerged from the practices of the old.     

Atomism and ‘subtlety’ in Francis Bacon's philosophy

Francis Bacon's reflections on atomism have generally been misunderstood because they have never been systematically studied in relation to the speculative chemical philosophy which he developed in the interval between about 1592 and his death in 1626. This philosophy, in many respects unknown to historians until quite recently, was the only body of positive science which Bacon ever accepted. The speculative philosophy was, on the whole, chemical and non-mechanical, and consequently not consistent with atomist doctrines. In fact, Bacon never at any time accepted the principal atomist tenets. It is therefore necessary to explain why he was interested in atomism at all. Of the several reasons for his interest one (hitherto unrecognised) is especially important—namely, his belief that the speculative and atomic philosophies had affinities. In particular, he believed that of all the ancient philosophies atomism alone approached the ideals associated with the key notion of ‘subtlety’—ideals represented in their highest form (as he imagined) in the speculative philosophy.     

The ‘Darwin-Marx correspondence’: a correction and revision

The logical links between the Judaeo-Christian doctrine of creation and the practice of natural philosophy on the one hand, and the rejection of belief in demonic agency on the other, were made explicit in the seventeenth century by, among others, Balthasar Bekker (1634–98), whose ideas I argue to have been not without influence. In section 1, I present the accounts of three historians of the opposition to belief in witchcraft and of the decline of the witch-persecution, Hugh Trevor-Roper, Keith Thomas, and Brian Easlea. In section 2, I maintain that Bekker has been underestimated both by Trevor-Roper and by Easlea. In section 3, I investigate more generally some of the connections between the new natural philosophy and belief in supernatural interventions, cast doubt on the view that rejection of belief in witchcraft and the devil requires rejection of belief in creation, and thus supplement or qualify the accounts of Trevor-Roper, Thomas, and Easlea of why belief in witchcraft faded away.     

Time-Symmetrised Quantum Theory,Counterfactuals and ‘Advanced Action’

Recent authors have raised objections to the counterfactual interpretation of the Aharonov–Bergmann–Lebowitz (ABL) rule of time-symmetrised quantum theory (TSQT). I distinguish between two different readings of the ABL rule, counterfactual and non-counterfactual, and confirm that TSQT advocate L. Vaidman is employing the counterfactual reading to which these authors object. Vaidman has responded to the objections by proposing a new kind of time-symmetrised counterfactual, which he has defined in two different ways. It is argued that neither definition succeeds in overcoming the objections, except in a limited special case previously noted by Cohen and Hiley. In addition, a connection is made between TSQT and Price’s concept of ‘advanced action’, which further supports the special case discussed.     

‘Classical’ and ‘new’ diabetogens—comparison of their effects on isolated rat pancreatic islets in vitro

This study compares functional and morphological alterations caused by application of alloxan, streptozotocin, xanthine oxidase/hypoxanthine (generation of reactive oxygen species), or S-nitroso-N-acetyl-D,L-penicillamine (SNAP, liberation of nitric oxide) to isolated rat pancreatic islets in vitro. In perifusion experiments, membrane leakage—detected by non-stimulated insulin release—was found after application of all drugs, but showed a substance-specific time pattern. Twenty-four hours after application of the classical diabetogens (alloxan or streptozotocin), potassium chloride- and glucose-stimulated insulin secretion were markedly reduced, while a persistent reduction was observed neither after exposure to xanthine oxidase/hypoxanthine, nor to SNAP. Morphological analysis of the islets revealed that nearly all β-cells were destroyed following alloxan or streptozotocin treatment, while the majority of β-cells were configured regularly after application of xanthine oxidase/hypoxanthine or SNAP. Necrotic cells found after xanthine oxidase/hypoxanthine usually differed in morphology from those observed after application of the classical diabetogens. While the former cells were characterised by swollen nuclei, the latter had shrunken nuclei with irregular condensed chromatin. Apoptosis was found only following nitric oxide exposure. Due to these differences, it seems unlikely that alloxan, streptozotocin, xanthine oxidase/hypoxanthine, and nitric oxide have a common major feature in their toxic action. Received 16 September 1999; received after revision 15 November 1999; accepted 26 November 1999