A neural cocktail-party processor

Sensory segmentation is an outstanding unsolved problem of theoretical, practical and technical importance. The basic idea of a solution is described in the form of a model. The response of neurons within the sensory field is temporally unstable. Segmentation is expressed by synchronization within segments and desynchronization between segments. Correlations are generated by an autonomous pattern formation process. Neuronal coupling is the result both of peripheral evidence (similarity of local quality) and of central evidence (common membership in a stored pattern). The model is consistent with known anatomy and physiology. However, a new physiological function, synaptic modulation, has to be postulated. The present paper restricts explicit treatment to the peripheral evidence represented by amplitude modulations globally present in all components of a sound spectrum. Generalization to arbitrary sensory qualities will be the subject of a later paper. The model is an application and illustration of the Correlation Theory of brain function.This work has been supported by Grant I/37-821 of the Stiftung Volkswagenwerk.     

Biosynthesis and maturation of arylsulfatase B in normal and mutant cultured human fibroblasts

The biosynthesis of arylsulfatase B in normal and mutant human skin fibroblasts was studied by metabolic labeling with radioactive amino acids, monosaccharides, or 32Pi and by specific immunoprecipitation followed by polyacrylamide gel electrophoresis and fluorography. Three major polypeptides with apparent molecular weights of 47,000, 40,000, and 31,000 were found intracellularly and one of 64,000 in the medium. Pulse-chase labeling and uptake experiments showed that arylsulfatase B synthesized and secreted as a 64,000 precursor was intracellularly processed within less than 24 h via short lived intermediates to two different forms. Form I (chains of 47,000 and 11,500) was labeled earlier and was about twice as stable as form II (chains of 40,000 and 31,000). The secreted 64,000 precursor and the 40,000 chain of form II contained oligosaccharides resistant to endo-beta-N-acetylglucosaminidase H. In the other chains mainly cleavable and phosphorylated oligosaccharides were found. Arylsulfatase B activity was associated with the 64,000 precursor and with form I, but not with form II. Fibroblasts of four patients with the severe form of mucopolysaccharidosis type VI, which were deficient in arylsulfatase B activity, synthesized and secreted the 64,000 precursor at a normal rate. This precursor, however, had little if any catalytic activity and one of its mature forms (I) was rapidly degraded.     

Elucidation of the antigenic determinant in lipotropin for two monoclonal antibodies

Two monoclonal antibodies were found to give enhanced affinity for β-lipotropin when mixed, as evidenced by competitive radioimmunoassay. Both monoclonals were found to react with a pentapeptide Ala-Glu-Leu-Glu-Tyr, which is a sequence of high local hydrophilicity within the N-terminal section of β-lipotropin.     

Chronic caffeine consumption potentiates the hypotensive action of circulating adenosine

Mean arterial blood pressure was correlated with arterial plasma adenosine levels during intravenous adenosine infusion in unanesthetized, unrestrained rats. Elevation of plasma adenosine to 5 to 6 microM (normal range 1.6 to 4.6 microM) depressed mean arterial pressure by 20 to 30 percent: this was blocked by a single caffeine injection (15 mg/kg). In contrast, caffeine consumption for 3 weeks, followed by a 1-day washout, markedly potentiated responses to adenosine, plasma levels in the 2 to 4 microM range causing 30 to 40 percent reductions in mean arterial pressure. These observations suggest that chronic occupancy of cardiovascular adenosine receptors by caffeine can enhance tissue responsiveness to adenosine, and that endogenous adenosine might act as a circulating hormone.     

Identification and characterization of gp TFA-1, a guinea pig T cell surface antigen associated with T cell function

Monoclonal antibodies (Ab) were produced that specifically recognized guinea pig T cells. FACS analysis revealed that Ab 188 bound to the majority of peripheral T lymphocytes of strain 2 and strain 13 guinea pigs and to a minor population of thymocytes. It failed to react with the Ia-bearing guinea pig B cell leukemia line EN-L2C, with macrophages, bone marrow cells, erythrocytes, or thrombocytes. Treatment of T cells with Ab 188 and complement prevented T cell activation. Culturing primed T cells with antigen- or mitogen-pulsed syngeneic or with allogeneic macrophages in the continuous presence of Ab 188 produced a marked, dose-dependent inhibition of T cell proliferation. The antigen defined by Ab 188 was therefore designated guinea pig T lymphocyte function-associated antigen-1, gp TFA-1. The magnitude of inhibition by Ab 188 varied between 65 and 85% whereas three other antibodies to guinea pig T cells had no inhibitory effect on T cell proliferation. Time course experiments revealed that gp TFA-1 is critically involved in an early phase of T cell activation. Maximal inhibition was achieved only if the antibody was present from the beginning of the cell culture; the addition of antibody after 24 hr of culture no longer had an inhibitory effect. Ab 188 did not induce T cell mitogenesis. Two-dimensional analysis (one-dimensional, IEF; two-dimensional, SDS-PAGE) of immunoprecipitates obtained from NP40 lysates of [35S]methionine-labeled T cell blasts indicated that a molecule was specifically precipitated that consisted of two noncovalently associated polypeptide chains with apparent m.w. of 43,000 and 38,000. Both subunits displayed extensive charge heterogeneity focusing at an average isoelectric point of 5.0 and 6.5, respectively. The gp TFA-1 molecule exhibits striking similarities in its functional and structural properties to recently described clonotypically expressed T cell glycoproteins, which were shown to be involved in antigen recognition by T cells in the murine and human systems.     

Isolation and characterization of a collagen-binding glycoprotein from chondrocyte membranes

A collagen-binding glycoprotein was isolated from purified chick chondrocyte surface membranes by affinity chromatography on type II collagen-Sepharose. The purified glycoprotein has an apparent mol. wt. of 31,000 and binds to native chick collagen types I, II, III, V and M. Although it contains 30% carbohydrates, the majority of which is fucose, it is hydrophobic and soluble only in detergents. The integral membrane protein character of the 31-K protein became apparent from its ability to insert into lecithin vesicles. Liposome-inserted 31-K protein binds 125I-labelled type II collagen in the presence of 0.5 M NaCl, while detergent-solubilized 31-K protein is dissociated from type II collagen by 0.05-0.1 M NaCl. Electron microscopic studies employing the rotary shadowing technique indicate that 31-K protein particles bind to the ends of collagen molecules. We propose that this glycoprotein serves as anchorage site for extracellular collagen to the chondrocyte membrane and thus may be involved in cell-matrix interactions in cartilage.     

Lymphoid cell subclasses in rejecting renal allograft in the rat

We have quantitated the frequency of lymphoid cell subsets in rejecting renal allografts and in the spleen of the allograft recipient during drug-unmodified rejection in the rat. The number of inflammatory (white) cells in the graft was approximately similar to the number of white cells responding to the allograft in the recipient spleen. The inflammatory population of the graft consisted of lymphoid cells and mononuclear phagocytes, with increasing numbers of macrophages toward the end of rejection. Analysis of allograft cellular dispersates with monoclonal antibodies directed to the lymphoid cell subsets demonstrated that although the majority of allograft-infiltrating lymphocytes were T cells, a sizable B-cell proliferation and immunoglobulin synthesis was associated with the inflammatory response of rejection. Within the T-cell subset, the T suppressor/killer cells predominated in the graft whereas the predominant lymphoid cell subset responding to the allograft in the recipient spleen was the T helper cell.     

Maternal effects and temperature-sensitive period of mutations affecting embryogenesis in Caenorhabditis elegans

We have used standard tests to investigate the nature of gene expression of a new set of temperature-sensitive mutants defining 30 emb genes (essential for embryogenesis) in the nematode Caenorhabditis elegans. The mode of gene expression as determined by progeny tests for parental effects divides the genes into four classes. For 18 genes maternal gene expression is necessary and sufficient for normal embryogenesis; for 2 genes zygotic expression is necessary and sufficient; for 7 genes either maternal or zygotic expression is sufficient; for 3 genes both maternal and zygotic expression are necessary. One mutant displayed partial paternal sufficiency. The results of temperature-shift experiments define two “execution stages,” corresponding to the limits of the temperature-sensitive period (TSP), and indicate the nature and the time of action or synthesis of the gene products. Most of the maternally expressed genes have very early execution stages indicating translation before fertilization, but some are temperature sensitive late in embryogenesis. Early execution stages for 2 zygotically necessary genes demonstrate that the zygotic genome can be active in the earliest stages of embryogenesis. All taken together, the mode of gene expression, TSP, and arrest stage (terminal phenotype) allow us to classify functionally and begin to order the genes essential for embryogenesis. The results indicate a preeminent role for maternal genes and gene products in embryogenesis, in agreement with the results of others.     

Stoffwechsel-Regulation aerober Zellsuspensionen vonSaccharomyces carlsbergensis nach Glucosezugabe

Zusammenfassung Wird eine ausgehungerte aerobe Zellsuspension vonSaccharomyces carlsbergensis mit Glucose gefüttert, dann ist eine deutliche Stimulierung des O₂-Verbrauchs zu registrieren. Mit Hilfe verschiedener Meßmethoden wurde der Verlauf dieser nicht-linearen O₂-Abnahme analysiert und mit den gleichzeitig auftretenden Konzentrationsänderungen einiger glykolytischer Metabolite korreliert.Dabei zeigt sich, daß ca. 20–60 Sekunden nach Glucosezugabe die Rate des O₂-Verbrauchs abnimmt und gleichzeitig eine deutliche Äthanol-Synthese einsetzt, obgleich der O₂-Partialdruck zu diesem Zeitpunkt noch etwa halbmaximal ist.

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Metabolite-regulation of aerobic cell-suspension ofSaccharomyces carlsbergensis after feeding with glucose. I. Shift from respiration to aerobic fermentation

Summary After feeding with glucose, an aerobic starved cell-suspension ofSaccharomyces carlsbergensis shows an increasing of oxygen consumption. This stimulation is not linear during the transition from high to low oxygen-level.For this aerobic phase the regulated fluxes of some metabolites are analyzed. It could be shown that with highest oxygen consumption an ethanol synthesis is starting.

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Herrn Prof. Dr.A. Betz danke ich an dieser Stelle für viele wertvolle Hinweise zur Interpretation der hier beschriebenen Ergebnisse. Die gewissenhafte technische Assistenz erfolgte durch FrauR. Hinrichs. Die Durchführung dieser Arbeit wurde durch Sachbeihilfen der Stiftung Volkswagenwerk und der Deutschen Forschungsgemeinschaft ermöglicht.