Association of tyrosine kinase p56lck with CD4 inhibits the induction of growth through the alpha beta T-cell receptor.

The membrane glycoprotein CD4 enhances antigen-mediated activation of T cells restricted by class II molecules of the major histocompatibility complex (MHC). This positive function has been attributed to the protein tyrosine kinase p56lck (ref. 4), which is noncovalently associated with the cytoplasmic portion of CD4, and is activated on CD4 aggregation. Antigen presentation by MHC class II molecules coaggregates CD4 and the T-cell antigen receptor (TCR alpha beta-CD3). Thus, the mutual specificity of CD4 and TCR alpha beta for the MHC-antigen complex results in the juxtaposition of p56lck and TCR alpha beta-CD3. In contrast, anti-CD4 antibodies can abrogate antigen-induced, as well as anti-TCR-induced T-cell activation, indicating that CD4 might also transduce negative signals. The molecular basis for this opposing function remains unclear. Here we show that the CD4-p56lck complex prohibits the induction of activation signals through the TCR-CD3 complex when not specifically included in the signalling process. This negative effect does not require anti-CD4 treatment, indicating that the induction of distinct negative signals is probably not involved. Rather, the results demonstrate that the CD4-p56lck complex provides prerequisite signals for antigen-receptor-induced T-cell growth and thus characterize a molecular mechanism for functional constraints imposed on T-cell activation by the MHC.     

Clustering and clique partitioning: Simulated annealing and tabu search approaches

We study the application of simulated annealing and tabu search to the solution of the clique partitioning problem. We illustrate the effecveness of these techniques by computational results associated not only with randomly generated problems, but also with real-life problems arising from applications concerning the optimal aggregation of binary relations into an equivalence relation. The need for these approaches is emphasized by the example of a special class of instances of the clique partitioning problem for which the most commonly used heuristics perform arbitrarily badly, while tabu search systematically obtains the optimal solution.

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Résumé Nous étudions dans cet article l'application du recuit simulé et de la méthode de recherche tabou dans la résolution du problème de partitionnement de graphes en cliques. Nous illustrons l'efficacité de ces techniques par des résultats numériques associés soit à des problèmes génerés au hasard, soit à des problèmes réels concernant l'agrégation de relations binaires dans une relation d'équivalence. L'intérêt de ces approches est mis en évidence à travers une classe de problèmes pour lesquels les heuristiques les plus connues ont une performance arbitrairement mauvaise, tandis que la méthode de recherche tabou obtient systématiquement des solutions optimales.

     

La pseudohémoglobine et le catabolisme des composés hémiques

Summary (1) Coupled oxidation by atmospheric oxygen of systems containing hæmoglobin and various reducing agents results in the successive formation of oxyhæm, oxohæm, and pseudohæm from the prosthetic group of hæmoglobin.(2) Of the verdoglobins, sulfhæmoglobin is analogous to oxohæm whereas choleglobin and pseudohæmoglobin are pseudohæms and apparently identical.(3) It is at present impossible to decide whether the green intermediate in the physiological formation of bilirubin is sulfhæmoglobin or pseudohæmoglobin.(4) Part of the bilirubin formed in the body is probably derived from catalase, hæmatin, myoglobin and the cytochromes.

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Conférence principale, présentée à la Société suisse de biologie médicale lors de la 127me Assemblée générale de la Société helvétique des sciences naturelles à Genève, le 31 août 1947.     

Operational and Strategic Decisions in Hospitality. Lessons from an Action Research Process

Systemic Practice and Action Research - The aim of this article is to find measures that reduce personnel costs in a catering company through the optimization of routes and tasks for staff to...     

A Brief Crack of Light?

This is a contribution to an inquiry into the historical meaning of Professor Checkland's soft systems thinking. Heidegger's picture of the present postmodern (or high-modern) epoch provides a context for unfolding that historical meaning. The discussion is focused on the possibility that Checkland's thinking could represent one of the "brief cracks" in the solid neo-instrumental way of appearing (whatever-is-the-case) that characterizes our present epoch.     

Biographical Notes

Biography

Biographical Notes     

The early effects of low DDT doses on the nervous system in animal experiments

Zusammenfassung Es wurde bei Verabreichung eines mit 40-0,5 mg DDT/kg Körpergewicht vermischten Futters an Ratten festgestellt, dass 40 und 20 mg DDT die Frequenz und Amplitude, 10 mg nur die Amplitude des spontanen EEG erhöht. Bei Verabreichung von 5 mg waren, bei stroboskoper Belastung, die Veränderungen noch sichtbar. Dosen zwischen 20 und 2,5 mg verminderten die Dauer und Tiefe der auf den Gehirnstamm als Angriffspunkt wirkenden Nembutalnarkose. Dosen von 2 bis 0,5 mg blieben wirkungslos. Die Vermutung wird ausgesprochen, dass sich durch DDT im Gehirnstamm ein Irritationsherd im Zusammenhang mit der Anhäufung von Acetylcholin bildet.     

A mechanistic principle for proton pumping by cytochrome c oxidase

In aerobic organisms, cellular respiration involves electron transfer to oxygen through a series of membrane-bound protein complexes. The process maintains a transmembrane electrochemical proton gradient that is used, for example, in the synthesis of ATP. In mitochondria and many bacteria, the last enzyme complex in the electron transfer chain is cytochrome c oxidase (CytcO), which catalyses the four-electron reduction of O2 to H2O using electrons delivered by a water-soluble donor, cytochrome c. The electron transfer through CytcO, accompanied by proton uptake to form H2O drives the physical movement (pumping) of four protons across the membrane per reduced O2. So far, the molecular mechanism of such proton pumping driven by electron transfer has not been determined in any biological system. Here we show that proton pumping in CytcO is mechanistically coupled to proton transfer to O2 at the catalytic site, rather than to internal electron transfer. This scenario suggests a principle by which redox-driven proton pumps might operate and puts considerable constraints on possible molecular mechanisms by which CytcO translocates protons.     

Advanced optics in a jellyfish eye

Cubozoans, or box jellyfish, differ from all other cnidarians by an active fish-like behaviour and an elaborate sensory apparatus. Each of the four sides of the animal carries a conspicuous sensory club (the rhopalium), which has evolved into a bizarre cluster of different eyes. Two of the eyes on each rhopalium have long been known to resemble eyes of higher animals, but the function and performance of these eyes have remained unknown. Here we show that box-jellyfish lenses contain a finely tuned refractive index gradient producing nearly aberration-free imaging. This demonstrates that even simple animals have been able to evolve the sophisticated visual optics previously known only from a few advanced bilaterian phyla. However, the position of the retina does not coincide with the sharp image, leading to very wide and complex receptive fields in individual photoreceptors. We argue that this may be useful in eyes serving a single visual task. The findings indicate that tailoring of complex receptive fields might have been one of the original driving forces in the evolution of animal lenses.