The effect of chronic marginal vitamin C deficiency on the α-tocopherol content of the organs and plasma of guinea-pigs

Summary Chronic marginal vitamin C deficiency lasting 270 days induced hypertriglyceridaemia, an abrupt fall of ascorbic acid in all organs and a significant decrease of -tocopherol in the liver and the lungs in guinea-pigs.     

β-Methyl carboline,a benzodiazepine inverse agonist,attenuates the effect of triazolam on the circadian rhythm of locomotor activity

Summary The benzodiazepine triazolam, the benzodiazepine inverse agonist, -methyl carboline (-CCM) or both, were administered to adult male hamsters under conditions of constant light. When given alone, triazolam induced phase advances in the circadian activity rhythm of about 90 min, while -CCM when given alone, had no effect on phase of the activity rhythm. However, when triazolam and -CCM were given at the same time, the magnitude of the phase advances induced by triazolam were attenuated to about 30 min. These data, in conjunction with previous results, provide pharmacological evidence for a GABAergic system involved in the regulation of a central circadian pacemaker.     

The effect ofβ-adrenergic stimulation and blockade on the efflux of PGE1-like material from the isolated perfused rabbit heart

Summary Prostaglandin (PG) release was measured from the isolated perfused rabbit heart. The effects of -adrenergic stimulation and blockade suggest that PG synthesis is regulated in part by adrenergic mechanisms.     

On the action ofβ-melanocyte stimulating hormone (β-MSH) on spontaneous electric discharge of the transparent knife fish,G. eigenmannia

Résumé L'hormone mélanophorétique-MSH, à des concentrations de 0.1 à 0.2µg/ml dans l'eau de l'aquarium, produit une diminution de la fréquence des modifications spontanées de l'amplitude des décharges électriques du poissonG. eigenmannia. Ces résultats sont en accord avec les observations antérieures montrant divers effets de-MSH sur l'activité électrique du système nerveux central chez les mammifères.     

Perfusion studies employing α-C14 acetate to study the synergistic effect of cortisone and insulin on lipogenesis

Zusammenfassung Der vorliegende Aufsatz berichtet über Beobachtungen eines synergistischen Effektes von Insulin und Cortison bei der Fetts?uresynthese in der durchstr?mten Rattenleber. Dabei wurde Natrium-α¹⁴-C-acetat als Tracer verwendet und um Acetat bei der Biosynthese von Cholesterin und Fetts?uren aus dem Zweierbruchstück zu vertreten. Nach Lyophilisation der Leber, Extraktion und Fraktionierung der Lipide wurde gefunden, dass ins Cholesterin der mit Cortison behandelten Leber mehr radioaktiver Kohlenstoff eingetreten war, bei der Behandlung mit Insulin dagegen mehr in die Fetts?uren und schliesslich in dieselben doppelt soviel als ins Cholesterin bei Behandlung mit Insulin und Cortison zusammen. Der Anstieg nach Anwendung von Insulin allein dürfte auf Spuren von Nebennierenrindenhormonen zurückzuführen sein, welche noch in Leber und Blut vorhanden waren. Demnach darf angenommen werden, dass Cortison und Insulin, wenn sie gleichzeitig zur Wirkung kommen, von grossem Einfluss auf die Verwendbarkeit der Zweierbruchstücke sind. Der Anstieg der Cholesterinsynthese nach Behandlung mit Cortison ist durchaus bedeutungsvoll im Hinblick auf neuere Beobachtungen über Hypercholesterin?mien, welche w?hrend Cortisontherapie auftreten.      

Purification and characterization of aβ-glucosidase (linamarase) from the haemolymph ofZygaena trifolii Esper, 1783 (Insecta,Lepidoptera)

Summary A -glucosidase (linamarase) was purified 52-fold with a recovery of 27% from the haemolymph of the larvae ofZygaena trifolii, ESPER, 1783 (Lepidoptera, Zygaenidae). The final enzyme preparation was found to be nearly homogeneous on both disc polyacrylamide gel electrophoresis and SDS-polyacrylamide gel electrophoresis. The molecular weight of the enzyme was determined to be about 130 kDa; it consisted of two subunits of about 66 kDa. The enzyme showed an optimum between pH 4.5 and 5 with linamarin and a broad optimum between pH 3.5 and 6.5 for p-nitrophenyl--D-glucoside; the temperature optimum was 40°C. The -glucosidase showed a high specificity for its endogenous substrates linamarin and lotaustralin. Among the other natural and artificial substrates tested, only prunasin and p-nitrophenyl--D-glucoside were hydrolyzed by the enzyme, whereas linustatin, salicin, cellobiose and trehalose were not. The enzyme is strongly inhibited by -glucosylpiperidine.     

Morphological and histochemical demonstration of a glycocalyx on the cell surface ofChattonella antiqua,a ‘naked flagellate’

Summary Electron microscopy demonstrated the presence of glycocalyx on the cell surface ofChattonella antiqua, which was previously believed to be naked. Histochemical analysis of this structure indicates that the glycocalyx consists of at least two different types of acidic complex carbohydrates, sulfated and nonsulfated, together with a neural carbohydrate-protein complex with 1,2-glycol groups and -D-mannosyl and -D-glucosyl residues.     

A molecular pin to study the dynamics of β-barrel formation in pore-forming toxins on erythrocytes: a sliding model

γ-Hemolysins are pore-forming toxins which develop from water-soluble monomers by combining two different ‘albeit homologous’ proteins. They form oligomeric pores in both cell and model membranes by undergoing a still poorly understood conformational rearrangement in the stem region. The stem is formed by three β-strands, folded onto the core of the soluble protein and completely extended in the pore. We propose a new model to explain such a process. Seven double-cysteine mutants were developed by inserting one cysteine on the stretch that links the β-hairpin to the core of the protein and another on different positions along the β-strands. The membrane bound protein was blocked in a non-lytic state by S–S bond formation. Six mutants were oxidized as inactive intermediates, but became active after adding DTT. These results demonstrate that the stem extension can be temporarily frozen and that the β-barrel formation occurs by β-strand concerted step-by-step sliding. Received 22 October 2007; received after revision 15 November 2007; accepted 19 November 2007     

Dopamine-β-hydroxylase,adrenaline, noradrenaline and dopamine in the venous blood of adrenal gland of man: A comparison with levels in the periphery of the circulation

Summary In 10 human subjects plasma dopamine--hydroxylase activity was found in the adrenal vein blood to be as high as in the periphery of the circulation. Adrenaline concentration in the adrenal vein blood was in the mean 170 times, noradrenaline concentration 11 times and dopamine concentration little higher than levels in the periphery.This study was supported by the Deutsche Forschungsgemeinschaft.     

The effect of cyclic cytidine 3′,5′-monophosphate (cCMP) on the in vitro development,hatching and attachment of the mouse blastocyst

Summary The in vitro development and attachment of hatched mouse blastocysts on the untreated substratum was enhanced by 10 M dibutyryl cCMP (dbcCMP). The result suggests that cCMP has an effect on embryonic development and on the blastocyst attachment process.25 November1986     

Into the ‘regions of physical and metaphysical chaos’: Maxwell’s scientific metaphysics and natural philosophy of action (agency,determinacy and necessity from theology,moral philosophy and history to mathematics,theory and experiment)

Maxwell’s writings exhibit an enduring preoccupation with the role of metaphysics in the advancement of science, especially the progress of physics. I examine the question of the distinction and the proper relation between physics and metaphysics and the way in which the question relies on key notions that bring together much of Maxwell’s natural philosophy, theoretical and experimental. Previous discussions of his attention to metaphysics have been confined to specific issues and polemics such as conceptions of matter and the problem of free will. I suggest a unifying pattern based on a generalized philosophical perspective and varying expressions, although never a systematic or articulated philosophical doctrine, but at least a theme of action and active powers, natural and human, intellectual and material, with sources and grounds in theology, moral philosophy and historical argument. While science was developing in the direction of professional specialization and alongside the rise of materialism, Maxwell held on to conservative intellectual outlook, but one that included a rich scientific life and held science as part of a rich intellectual, cultural and material life. His philosophical outlook integrated his science with and captured the new Victorian culture of construction and work, political, economic, artistic and engineering.     

Palmitoylation by DHHC3 is critical for the function, expression, and stability of integrin α6β4

The laminin-binding integrin α6β4 plays key roles in both normal epithelial and endothelial cells and during tumor cell progression, metastasis, and angiogenesis. Previous cysteine mutagenesis studies have suggested that palmitoylation of α6β4 protein supports a few integrin-dependent functions and molecular associations. Here we took another approach and obtained strikingly different results. We used overexpression and RNAi knockdown in multiple cell types to identify protein acyl transferase DHHC3 as the enzyme responsible for integrin β4 and α6 palmitoylation. Ablation of DHHC3 markedly diminished integrin-dependent cellular cable formation on Matrigel, integrin signaling through Src, and β4 phosphorylation on key diagnostic amino acids (S1356 and 1424). However, unexpectedly, and in sharp contrast to prior α6β4 mutagenesis results, knockdown of DHHC3 accelerated the degradation of α6β4, likely due to an increase in endosomal exposure to cathepsin D. When proteolytic degradation was inhibited (by Pepstatin A), rescued α6β4 accumulated intracellularly, but was unable to reach the cell surface. DHHC3 ablation effects were strongly selective for α6β4. Cell-surface levels of ~10 other proteins (including α3β1) were not diminished, and the appearance of hundreds of other palmitoylated proteins was not altered. Results obtained here demonstrate a new substrate for the DHHC3 enzyme and provide novel opportunities for modulating α6β4 expression, distribution, and function.     

Nicolas Béguelin and his search for a crucial experiment on the nature of light (1772)

In the second half of the eighteenth century a lively debate was going on in Germany about the nature of light. One important contribution to this discussion, namely a paper by Nicolas Béguelin, is studied in this article. In his essay, Béguelin compared the Newtonian emission theory of light and the wave theory of Leonhard Euler. Whereas others opted for one of the two theories by invoking arguments or authorities, Béguelin made a systematic search for experiments which he hoped would settle the dispute. Two of these experiments were most original. The first, which Béguelin himself performed, concerned light rays grazing a glass surface. For several reasons it did not have the impact it deserved. The second one was a thought experiment which was meant to illustrate a major tenet of the wave theory, that is, the analogy between light and sound. An analysis is given of these two experiments, and it is shown that neither of them brought the debate to an end.     

A selective concentration-dependent dysrhythmogenic and antidysrhythmic action of prostaglandins E2, F2α and I2 (prostacyclin) on isolated rat hearts

Summary Prostaglandins (PGs) E₂, F₂, and I₂ were examined for their effects on the electrical and mechanical activities of isolated rat, rabbit and guinea-pig hearts. All PGs produced dysrhythmias in rat hearts at low concentrations only, while higher concentrations were antiarrhythmic. Guinea-pig hearts were less responsive while rabbit hearts were completely resistant.We thank the Manitoba Heart Foundation for financial support and Dr J. Pike (Upjohn, Kalamazoo, MI, USA) for gifts of prostaglandins. Dr M. Karmazyn is a Fellow of the Canadian Heart Foundation.     

Effects of physalaemin, a vaso-active peptide from amphibian skin, on the excitability of an identifiable molluscan giant neurone of Achatina fulica Férussac.

We examined effects of several vasoactive peptides (substance P, physalaemin, neurotensin, bradykinin, angiotensin etc.) on the excitability of molluscan giant neurones identified in the subesophageal ganglia of Achatina fulica Férussac. Of these peptides, only physalaemin showed a remarkable excitatory effect on a giant tonically autoactive neurone.     

Influence of sex,developmental time and food onβ-N-acetylglucosaminidase activity in the rice weevilSitophilus oryzae L.

Summary The effects of some biological parameters on -N-acetylglucosaminidase activity have been investigated inS. oryzae. There is no significant influence of sex and developmental time on the enzyme activity level, which appears in contrast to be greatly influenced by food (wheat or sorghum). Sorghum contains competitive inhibitors which are almost completely removed after dialysis. Fasting relieves this inhibition very quickly, suggesting that inhibitors act directly at the gut level.     

A dialyzable factor from plasma responsible for the “viscous metamorphosis” of the blood platelets. Its role in clot retraction and haemostasis

Zusammenfassung Die visköse Metamorphose der Blutplättchen ist ein von der Fibrinbildung unabhängiger Prozess, der durch Thrombin und einen thermostabilen, dialysierbaren Faktor aus Plasma oder Serum ausgelöst wird. Das unter diesen Bedingungen aus den zerfallenden Plättchen austretende Material kontrahiert sich spontan. Dies erklärt die Gerinnselretraktion, bei der dem Fibrin folglich eine völlig passive Rolle zukommt.

---

---

Supported by grants from the Swiss National Foundation for Scientific Research and the F. Hoffmann-La Roche Foundation.