Antibody neutralization and escape by HIV-1

Neutralizing antibodies (Nab) are a principal component of an effective human immune response to many pathogens, yet their role in HIV-1 infection is unclear. To gain a better understanding of this role, we examined plasma from patients with acute HIV infection. Here we report the detection of autologous Nab as early as 52 days after detection of HIV-specific antibodies. The viral inhibitory activity of Nab resulted in complete replacement of neutralization-sensitive virus by successive populations of resistant virus. Escape virus contained mutations in the env gene that were unexpectedly sparse, did not map generally to known neutralization epitopes, and involved primarily changes in N-linked glycosylation. This pattern of escape, and the exceptional density of HIV-1 envelope glycosylation generally, led us to postulate an evolving 'glycan shield' mechanism of neutralization escape whereby selected changes in glycan packing prevent Nab binding but not receptor binding. Direct support for this model was obtained by mutational substitution showing that Nab-selected alterations in glycosylation conferred escape from both autologous antibody and epitope-specific monoclonal antibodies. The evolving glycan shield thus represents a new mechanism contributing to HIV-1 persistence in the face of an evolving antibody repertoire.     

CD43, a molecule defective in Wiskott-Aldrich syndrome, binds ICAM-1.

THE protein CD43 (also known as sialophorin, leukosialin, large sialoglycoprotein or gp115) is expressed on the surface of T lymphocytes, monocytes, neutrophils, platelets and some B lymphocytes. Expression of CD43 is deficient and/or defective in the X-chromosome-linked immunodeficiency disorder Wiscott-Aldrich syndrome, suggesting that CD43 might have a role in T-cell activation. We have shown that expression of human CD43 in an HLA-DR-specific murine T-cell hybridoma enhances the antigen-specific response to stimulation by the human lymphoblastoid cell line Daudi, and that Daudi cells bind specifically to purified immobilized CD43. These data indicate that the specific interaction of CD43 with a ligand on the surface of Daudi cells might contribute to T-cell activation. Here we report evidence that intercellular adhesion molecule-1 (ICAM-1, or CD54), is a ligand for CD43.     

Electroencephalography of the olfactory bulb in relation to prespawn homing

Summary remarks It is evident that the bulbar EEG is a complex response which can be influenced by several methodological and stimulant variables. What EEG patterns tell us about actual behavior remains obscure. The bulbar EEG which is evoked by homestream water is not necessarily a reflection of olfactory memory. The evoked bulbar EEG also does not necessarily demonstrate the salmon has distinguished the home-water from another water in terms of migrational orientation. Despite lack of absolute specificity, a correlation between bulbar EEG and actual behavioral performance has been observed even though some non-home waters evoke responses similar to that of the home water. In general it has been found that the home water response can be distinguished from the response to other natural waters. Failure to obtain complete specificity may be due to a variety of variables which have been alluded to earlier in this section. Thus considering that the evoked EEG is a reflection of the integration of a diverse afferent input, further electrical and computer analyses may eventually permit the decoding of the EEG in terms of behavior. However, if the EEG proves to be more a quantitative rather than qualitative reflection of brain activity, relating EEG to behavior will prove to be of limited value. Since afferent responses in the olfactory bulb are influenced by impulses from higher brain centers, studies on centrifugal aspects during olfactory stimulation may be useful in gaining some qualitative understanding of the home water evoked EEG of the olfactory bulb.     

Stabilization of DNA structure by histones against thermal denaturation

Zusammenfassung Durch grösseren Gehalt an Resthiston wird die Stabilität von Desoxyribonucleinsäure gegenüber der thermischen Denaturierung in 0.0025M NaNO₂ erhöht und die Zunahme des ntomaren Extinktionskoeffizienten (P) während der Denaturierung verringert.

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With the aid of a grant from the Schweizerischer Nationalfonds zur Förderung der wissenschaftlichen Forschung and the aid of the Muscular Dystrophy Association of America to Prof.F. Verzár.