An H+-ATPase in opposite plasma membrane domains in kidney epithelial cell subpopulations

Vectorial solute transport by epithelia requires the polarized insertion of transport proteins into apical or basolateral plasmalemmal domains. In the specialized intercalated cells of the kidney collecting duct, the selective placement of an apical plasma membrane proton-pumping ATPase (H+-ATPase) and of a basolateral membrane anion-exchange protein results in transepithelial proton secretion. It is currently believed that amino-acid sequences of membrane proteins contain critical signalling regions involved in sorting these proteins to specific membrane domains. Recently, it was proposed that intercalated cells can reverse their direction of proton secretion under different acid-base conditions by redirecting proton pumps from apical to basolateral membranes, and anion exchangers from basolateral to apical membranes. But others have found that antibodies raised against the red cell anion-exchange protein (Band 3) only labelled intercalated cells at the basolateral plasma membrane, providing evidence against the model of polarity reversal. In this report, we have examined directly the distribution of proton pumps in kidney intercalated cells using specific polyclonal antibodies against subunits of a bovine kidney medullary H+-ATPase. We find that some cortical collecting duct intercalated cells have apical plasma membrane proton pumps, whereas others have basolateral pumps. This is the first direct demonstration of neighbouring epithelial cells maintaining opposite polarities of a transport protein. Thus, either subtle structural differences exist between proton pumps located at opposite poles of the cell, or factors other than protein sequence determine the polarity of H+-ATPase insertion.     

Identification of genes involved in Drosophila melanogaster geotaxis,a complex behavioral trait

Identifying the genes involved in polygenic traits has been difficult. In the 1950s and 1960s, laboratory selection experiments for extreme geotaxic behavior in fruit flies established for the first time that a complex behavioral trait has a genetic basis. But the specific genes responsible for the behavior have never been identified using this classical model. To identify the individual genes involved in geotaxic response, we used cDNA microarrays to identify candidate genes and assessed fly lines mutant in these genes for behavioral confirmation. We have thus determined the identities of several genes that contribute to the complex, polygenic behavior of geotaxis.     

Effects of lithium chloride on peripheral acetylcholine release and brain acetylcholine levels in the guinea-pig

Summary Lithium chloride administered acutely or chronically to guinea-pigs had no effect on brain level of acetylcholine or on peripheral release of acetylcholine from longitudinal muscle of the ileum. The results suggest differences between in vitro and in vivo action of lithium.To whom correspondence should be addressed.     

Rapid developmental switch in the mechanisms driving early cortical columnar networks

The immature cerebral cortex self-organizes into local neuronal clusters long before it is activated by patterned sensory inputs. In the cortical anlage of newborn mammals, neurons coassemble through electrical or chemical synapses either spontaneously or by activation of transmitter-gated receptors. The neuronal network and the cellular mechanisms underlying this cortical self-organization process during early development are not completely understood. Here we show in an intact in vitro preparation of the immature mouse cerebral cortex that neurons are functionally coupled in local clusters by means of propagating network oscillations in the beta frequency range. In the newborn mouse, this activity requires an intact subplate and is strongly synchronized within a cortical column by gap junctions. With the developmental disappearance of the subplate at the end of the first postnatal week, activation of NMDA (N-methyl-D-aspartate) receptors in the immature cortical network is essential to generate this columnar activity pattern. Our findings show that during a brief developmental period the cortical network switches from a subplate-driven, gap-junction-coupled syncytium to a synaptic network acting through NMDA receptors to generate synchronized oscillatory activity, which may function as an early functional template for the development of the cortical columnar architecture.     

HIV-specific cytotoxic T lymphocytes in seropositive individuals

Virus-specific cytotoxic T lymphocytes (CTL) which kill virus-infected cells are thought to be a major host defence against viral infections. Here we report the existence of human immunodeficiency virus (HIV)-specific CTL in persons infected with this virus, the aetiological agent of AIDS (acquired immunodeficiency syndrome). Recombinant HIV-vaccinia viruses were used to express HIV antigens in B-cell lines established from subjects seropositive for HIV and seronegative controls. Circulating lymphocytes capable of killing HIV env-expressing autologous B cells were detected in eight of eight seropositive subjects; in addition, at least three seropositive subjects demonstrated gag-specific cytotoxic responses. No HIV-specific cytotoxicity was observed in seronegative subjects. Selective inhibition of the env-specific cytotoxicity by a CD3-specific monoclonal antibody indicates that the effectors are T cells. This demonstration of a cytotoxic T-cell immune response to HIV in infected individuals should prove useful in investigating the immunopathogenesis of HIV infection further and in evaluating AIDS vaccine strategies.     

Oscillation and noise determine signal transduction in shark multimodal sensory cells

Oscillating membrane potentials that generate rhythmic impulse patterns are considered to be of particular significance for neuronal information processing. In contrast, noise is usually seen as a disturbance which limits the accuracy of information transfer. We show here, however, that noise in combination with intrinsic oscillations can provide neurons with particular encoding properties, a discovery we made when recording from single electro-sensory afferents of a fish. The temporal sequence of the impulse trains indicates oscillations that operate near the spike-triggering threshold. The oscillation frequency determines the basic rhythm of impulse generation, but whether or not an impulse is actually triggered essentially depends on superimposed noise. The probability of impulse generation can be altered considerably by minor modifications of oscillation baseline and amplitude, which may underlie the exquisite sensitivity of these receptors to thermal and electrical stimuli. Additionally, thermal, but not electrical, stimuli alter the oscillation frequency, allowing dual sensory messages to be conveyed in a single spike train. These findings demonstrate novel properties of sensory transduction which may be relevant for neuronal signalling in general.     

Disputanda Differenzierung der Wirkung von Desinfizienzienin vitro,von W. Schuler

Ohne Zusammenfassung     

Activities of cystathionase,cysteine sulphinic acid decarboxylase and serine dehydrase in the liver of tumour-bearing rats

Résumé Dans le foie de rats porteurs de tumeurs (épithéliome de Guérin et sarcome de l'estomac), les activités de la cystathionase, de la décarboxylase de l'acide cysteine sulfinique et de la sérine déhydrase sont considérablement diminuées: cette diminution est de l'ordre de 50%, 15 jours après implantation de ces tumeurs. Si à ce moment le sarcome (qui ne provoque pas de métastases) est chirurgicalement extirpé, on observe une restauration des activités enzymatiques qui, après 15 jours, est totale pour la cystathionase et très significative pour la décarboxylase.

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Equipe de Recherche C.N.R.S. No. 43.