Requirements for leukocyte transmigration via the transmembrane chemokine CX3CL1

The surface-expressed transmembrane CX3C chemokine ligand 1 (CX3CL1/fractalkine) induces firm adhesion of leukocytes expressing its receptor CX3CR1. After shedding by the disintegrins and metalloproteinases (ADAM) 10 and 17, CX3CL1 also acts as soluble leukocyte chemoattractant. Here, we demonstrate that transmembrane CX3CL1 expressed on both endothelial and epithelial cells induces leukocyte transmigration. To investigate the underlying mechanism, we generated CX3CR1 variants lacking the intracellular aspartate-arginine-tyrosine (DRY) motif or the intracellular C-terminus which led to a defect in intracellular calcium response and impaired ligand uptake, respectively. While both variants effectively mediated firm cell adhesion, they failed to induce transmigration and rather mediated retention of leukocytes on the CX3CL1-expressing cell layer. Targeting of ADAM10 led to increased adhesion but reduced transmigration in response to transmembrane CX3CL1, while transmigration towards soluble CX3CL1 was not affected. Thus, transmembrane CX3CL1 mediates leukocyte transmigration via the DRY motif and C-terminus of CX3CR1 and the activity of ADAM10.     

Variations in cardiac noradrenaline content during sodium loading in hypertension prone and resistant rats

Summary The cardiac catecholamine content of Sabra rats and their 2 genetically derived substrains, hypertension prone and resistant rats, was studied by high pressure liquid chromatography and electrochemical detection. Both in the control period and after sodium and DOCA administration the cardiac noradrenaline level is higher in hypertension resistant rats than in Sabra rats, and also higher than in hypertension prone rats. This finding suggests that a reduction of the cardiac sympathetic nervous tone is involved in the genetic resistance to sodium.     

Redundant and unique roles of coronin proteins in <Emphasis Type="Italic">Dictyostelium</Emphasis>

Dictyostelium discoideum harbors a short (CRN12) and a long coronin (CRN7) composed of one and two beta-propellers, respectively. They are primarily present in the cell cortex and cells lacking CRN12 (corA ⁻) or CRN7 (corB ⁻) have defects in actin driven processes. We compared the characteristics of a mutant cell line (corA ⁻ /corB ⁻) lacking CRN12 and CRN7 with the single mutants focusing on cytokinesis, phagocytosis, chemotaxis and development. Cytokinesis, uptake of small particles, and developmental defects were not enhanced in the corA ⁻ /corB ⁻ strain as compared to the single mutants, whereas motility and phagocytosis of yeast particles were more severely impaired. It appears that although both proteins affect the same processes they do not act in a redundant manner. Rather, they often act antagonistically, which is in accordance with their proposed roles in the actin cytoskeleton where CRN12 acts in actin disassembly whereas CRN7 stabilizes actin filaments and protects them from disassembly.     

HCN2 channels in local inhibitory interneurons constrain LTP in the hippocampal direct perforant path

Neuronal hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are known to modulate spontaneous activity, resting membrane potential, input resistance, afterpotential, rebound activity, and dendritic integration. To evaluate the role of HCN2 for hippocampal synaptic plasticity, we recorded long-term potentiation (LTP) in the direct perforant path (PP) to CA1 pyramidal cells. LTP was enhanced in mice carrying a global deletion of the channel (HCN2^−/−) but not in a pyramidal neuron-restricted knockout. This precludes an influence of HCN2 located in postsynaptic pyramidal neurons. Additionally, the selective HCN blocker zatebradine reduced the activity of oriens-lacunosum moleculare interneurons in wild-type but not HCN2^−/− mice and decreased the frequency of spontaneous inhibitory currents in postsynaptic CA1 pyramidal cells. Finally, we found amplified LTP in the PP of mice carrying an interneuron-specific deletion of HCN2. We conclude that HCN2 channels in inhibitory interneurons modulate synaptic plasticity in the PP by facilitating the GABAergic output onto pyramidal neurons.     

The visualization of the granulated mitochondrial inner body through treatment of isolated mitochondria with xylene

Zusammenfassung Die Autoren stellen mit einer speziellen Technik Präparate von aus Rattenleber isolierten Mitochondrien her, die mit Xylol nachbehandelt werden. Dadurch wird der Innenkörper der Mitochondrien einer eingehenden elektronenmikroskopischen Untersuchung zugänglich. Der Innenkörper besteht aus einzelnen Granula, die einen Durchmesser von 300 Å haben. Die Anordnung der Granula ergibt eine charakteristische Querstreifung des Innenkörpers.

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This work is a part of an investigation supported by a grant from The Swedish Cancer Society.

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Research Fellow aided by the Stiftung für biologisch-medizinische Stipendien, Basle (Switzerland). Present address: Institute of Anatomy, University of Basle.     

Applications of a generalized data-management language in medicine: Some recent experience at Stanford university

Zusammenfassung Um den Zugang zum Computer auch für den Nichtfachmann möglichst einfach und effektiv zu gestalten, müssen neue Programmiertechniken entwickelt werden. Ein Teil dieser Neuentwicklungen beschäftigt sich mit dem Aufbau und dem Gebrauch von Computer-Dateien. Zu diesem Zwecke wurde DIRAC an der Stanford-University entwickelt und getestet. Diese Sprache ist die erste einer ganzen Familie von Prototypen, welche eingesetzt werden, um die organisatorischen Probleme der Speicherung und Wiederauffindung wissenschaftlicher Information zu lösen. Die Sprache ist so konstruiert, dass die Benützer via einen Fernschreiber, der weit von der Computer-Zentrale entfernt aufgestellt sein kann, mit Hilfe einfacher Schlüsselwörter ihren Zwecken angepasste Kartotheken aufbauen können («create»), die einmal gespeicherte Information ergänzen, zerstören oder modifizieren können («up date»), die Kartothek nach fast beliebigen Kriterien abfragen und gesuchte Informationen heraussortieren können («query») sowie den Inhalt der ganzen Kartothek herausdrucken und einfach statistisch bearbeiten lassen können («status»). Ein kurzer Überblick über den Sprachaufbau von DIRAC und Beispiele für den Gebrauch von DIRAC durch verschiedene medizinische Abteilungen der Stanford-University sind beschrieben.