Fever in the monkey produced by the direct action of pyrogen on the hypothalamus

Zusammenfassung Eine dosisabhängige Steigerung der Körpertemperatur wurde erzielt, wenn Pyrogen-Substanzen aus verschiedenen gram-negativen Bakterienstämmen stereotaktisch in den Hypothalamus nicht narkotisierter Affen injiziert wurden.

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Supported in part by USA Office of Naval Research Contract No. N00014-67-A-0026-0003 and National Science Foundation Grant No. GB 7906. We are indebted toP. Curzon for his valuable technical assistance, and to Dr.R. L. Somerville for preparing the pyrogens.

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Post-Doctoral Fellow supported by NIH Health Sciences Advancement Award No. PHS 5-S04-FR-0615.

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NIH Pre-Doctoral Fellow in Neurobiology.     

Redox regulation of protein tyrosine phosphatase 1B involves a sulphenyl-amide intermediate

The second messenger hydrogen peroxide is required for optimal activation of numerous signal transduction pathways, particularly those mediated by protein tyrosine kinases. One mechanism by which hydrogen peroxide regulates cellular processes is the transient inhibition of protein tyrosine phosphatases through the reversible oxidization of their catalytic cysteine, which suppresses protein dephosphorylation. Here we describe a structural analysis of the redox-dependent regulation of protein tyrosine phosphatase 1B (PTP1B), which is reversibly inhibited by oxidation after cells are stimulated with insulin and epidermal growth factor. The sulphenic acid intermediate produced in response to PTP1B oxidation is rapidly converted into a previously unknown sulphenyl-amide species, in which the sulphur atom of the catalytic cysteine is covalently linked to the main chain nitrogen of an adjacent residue. Oxidation of PTP1B to the sulphenyl-amide form is accompanied by large conformational changes in the catalytic site that inhibit substrate binding. We propose that this unusual protein modification both protects the active-site cysteine residue of PTP1B from irreversible oxidation to sulphonic acid and permits redox regulation of the enzyme by promoting its reversible reduction by thiols.     

Crackling noise

Crackling noise arises when a system responds to changing external conditions through discrete, impulsive events spanning a broad range of sizes. A wide variety of physical systems exhibiting crackling noise have been studied, from earthquakes on faults to paper crumpling. Because these systems exhibit regular behaviour over a huge range of sizes, their behaviour is likely to be independent of microscopic and macroscopic details, and progress can be made by the use of simple models. The fact that these models and real systems can share the same behaviour on many scales is called universality. We illustrate these ideas by using results for our model of crackling noise in magnets, explaining the use of the renormalization group and scaling collapses, and we highlight some continuing challenges in this still-evolving field.     

Human pro alpha 1(I) collagen gene structure reveals evolutionary conservation of a pattern of introns and exons

The collagens represent an interesting example of a structurally related but genetically distinct family of proteins. Type I, the most abundant of the vertebrate collagens, comprises two pro alpha 1(I) chains and one pro alpha 2(I) chain, each containing terminal propeptides and a central domain of 338 (Gly, X, Y) repeats. The structure of the chicken pro alpha 2(I) gene shows an intriguing relationship between exon organization and the arrangement of (Gly, X, Y) repeats (see ref. 2 for review). This has led to the suggestion that the collagens evolved from a common ancestral unit of 54 base pairs (bp). Here we present the structure of the entire human pro alpha 1(I) gene and compare this with the chicken pro alpha 2(I). The exon arrangement of the two genes is remarkably similar, although the human pro alpha 1(I) is more compact because of the shorter length of its introns. The data strongly support the notion that the type I genes have evolved from an ancestral multi-exon unit, and that once the gene was translated, a strong evolutionary pressure caused it to maintain this elaborate structure.     

Ethanol preference in rats with a prior history of acetaldehyde self-administration

Peripherally self-injected acetaldehyde in interaction with environmental and nutritional variables significantly enhances alcohol drinking in rats and suggests an involvement of acetaldehyde in voluntary alcohol intake.     

The effect of protein-energy malnutrition on appositional bone growth in the rat

Summary During protein-energy malnutrition appositional bone growth in the seventh caudal vertebra of the rat slows and finally ceases. During rehabilitation appositional growth begins agains and attains a rate in excess of that of the controls. This may account for alterations in skeletal proportions resulting from manutrition.Supported in part by National Research Council of Canada grant A4692.