SWAP-70 is a guanine-nucleotide-exchange factor that mediates signalling of membrane ruffling

Phosphoinositide-3-OH kinase (PI(3)K), activated through growth factor stimulation, generates a lipid second messenger, phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P3). PtdIns(3,4,5)P3 is instrumental in signalling pathways that trigger cell activation, cytoskeletal rearrangement, survival and other reactions. However, some targets of PtdIns(3,4,5)P3 are yet to be discovered. We demonstrate that SWAP-70, a unique signalling protein, specifically binds PtdIns(3,4,5)P3. On stimulation by growth factors, cytoplasmic SWAP-70, which is dependent on PI(3)K but independent of Ras, moved to cell membrane rearrangements known as ruffles. However, mutant SWAP-70 lacking the ability to bind PtdIns(3,4,5)P3 blocked membrane ruffling induced by epidermal growth factor or platelet-derived growth factor. SWAP-70 shows low homology with Rac-guanine nucleotide exchange factors (GEFs), and catalyses PtdIns(3,4,5)P3-dependent guanine nucleotide exchange to Rac. SWAP-70-deficient fibroblasts showed impaired membrane ruffling after stimulation with epidermal growth factor, and failed to activate Rac fully. We conclude that SWAP-70 is a new type of Rac-GEF which, independently of Ras, transduces signals from tyrosine kinase receptors to Rac.     

The role of sex steroid in two avian song behaviours differing in ontogenetic process

The male Bengalese finch,Lonchura striata, has two types of song behaviour (directed song, DS and undirected song, US). DS and US share a basically identical syllable repertoire, sequence pattern and tempo, but differ in the time course of appearance during the maturational process. In order to examine whether this results from a difference in testosterone (T) dependency, we studied developmental changes in the fecal T level and the amounts of DS and US during the 2–4 month period (N=7). DS appeared between 83 and 94 days of age, 4–16 days after a rise in the fecal T level. In contrast, US appeared earlier and at high frequency even when T was still at a very low level. These results suggest that DS is more dependent on the T level than US, and is not activated until the T level rises during the maturational process.     

Effects of chloroiodoquine and lethal doses in various mouse strains]

Chloroiodoquine has been implied in numerous cases of myeloneuropathy in Japan, while in other countries although equally frequently used, only a few cases have been reported after treatment with this drug. Studies on the effect of chloroiodoquine in mice of various inbred strains or from crossings between sensitive and insensitive strains demonstrated a genetic predisposition of sensitivity to chloroiodoquine.     

The axon reflex sweating produced by potassium and sodium cyanides

Zusammenfassung Subkutane Einspritzung von Kalium- oder Natriumzyanid in die Zehenballen der Katze führt über einen Axonreflex zu merklichem Schwitzen. Dieser Effekt von Kaliumzyanid wird durch Procain und Atropin gehemmt, nicht aber durch Hexamethonium. Auch beim Menschen ruft intrakutan eingeführtes Natriumzyanid eine entsprechende Schweissabsonderung hervor.     

Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses

The innate immune system senses viral infection by recognizing a variety of viral components (including double-stranded (ds)RNA) and triggers antiviral responses. The cytoplasmic helicase proteins RIG-I (retinoic-acid-inducible protein I, also known as Ddx58) and MDA5 (melanoma-differentiation-associated gene 5, also known as Ifih1 or Helicard) have been implicated in viral dsRNA recognition. In vitro studies suggest that both RIG-I and MDA5 detect RNA viruses and polyinosine-polycytidylic acid (poly(I:C)), a synthetic dsRNA analogue. Although a critical role for RIG-I in the recognition of several RNA viruses has been clarified, the functional role of MDA5 and the relationship between these dsRNA detectors in vivo are yet to be determined. Here we use mice deficient in MDA5 (MDA5-/-) to show that MDA5 and RIG-I recognize different types of dsRNAs: MDA5 recognizes poly(I:C), and RIG-I detects in vitro transcribed dsRNAs. RNA viruses are also differentially recognized by RIG-I and MDA5. We find that RIG-I is essential for the production of interferons in response to RNA viruses including paramyxoviruses, influenza virus and Japanese encephalitis virus, whereas MDA5 is critical for picornavirus detection. Furthermore, RIG-I-/- and MDA5-/- mice are highly susceptible to infection with these respective RNA viruses compared to control mice. Together, our data show that RIG-I and MDA5 distinguish different RNA viruses and are critical for host antiviral responses.     

Involvement of thiols in the induction of inward current induced by silver in frog skeletal muscle membrane

Exposure of voltage-clamped frog skeletal muscle fibres to silver caused a maintained inward current which could be carried by Ca²⁺, Mg²⁺ or Na⁺. Inorganic Ca²⁺ channel blockers and dithiothreitol (SH reducing agent) diminished this current, but a Na⁺ channel blocker did not. Thus, silver activates the Ca²⁺ channel by acting on SH groups in a Ca²⁺ channel protein.