The delta sleep inducing peptide (DSIP). Comparative properties of the original and synthetic nonapeptide

Summary Both the original and the synthetic nonapeptide Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu enhance, in recipient rabbits, spindle and delta EEG activity as in orthodox slow wave sleep.Acknowledgment. This work was supported by grants from the Swiss National Foundation for Scientific Research (No. 3.871.72, 3.527.75,3.443.074, 3.780.076), Fonds für Lehre und Forschung der Universität Basel, Merck Sharp and Dohme (USA), Ciba-Stiftung Basel, Hoffmann La Roche Ltd Basel, Sandoz Ltd Basel. We received valuable help from Dr S. Roncari, Dr B. Wilson and Dr C. D. Bennett for chemical research, and from Prof. A. Cerletti, Dr H. J. Tobler and Mr J. J. Regez (Division of Application and Research Development, Sandoz Ltd) for data processing.     

Immunosuppressive and specific antimitotic effects of ovalicin

Zusammenfassung Ovalicin, isoliert aus dem Kulturfiltrat vonPseudeurotium ovalis, hemmt die Bildung von Antikörpern schon nach einmaliger Applikation. Es kommt zur Ausbildung einer partiellen immunologischen Toleranz. Die Abstossungszeit von homologen Hauttransplantaten wird bei Mäusen durch eine einmalige Ovalicinbehandlung signifikant verlängert. Die Substanz hemmt den Anstieg des Milzgewichtes bei Mäusen, die mit Schaferythrozyten immunisiert und/oder mit lebenden Leukämie-L-1210-Zellen geimpft wurden; letzteres gilt auch für den isologen Wirt (L-1210-Zellen in DBA/2-Mäusen). Die Hemmung des Milzgewichtanstieges durch Ovalicin geht parallel mit einer Reduktion des Mitoseindex in der Milz von immunologisch stimulierten Tieren; die Mitosenzahl im Darmepithel wird hingegen nicht beeinflusst.     

Staining of the reducing material in the tubero-hypophysial system of the rat with osmium tetroxide

Zusammenfassung Im Perikaryon der kleinen Neuronen des Nucleus arcuatus und periventricularis des Rattenhypothalamus kann man nach Fixation mit Glutardialdehyd und nach Oxydation durch Osmiumtetroxyd reduzierendes Material darstellen. Die gleichen reduzierenden Substanzen gibt es auch in der Eminentia mediana, wo sie perivasculär teilweise in Form kleiner Granula angehäuft sind oder eine bandartige Anordnung zeigen.

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Aided by a grant from the Sigrid Jusélius Stiftelse.     

Levels of cytochromes in heart,liver, kidney and brain in the developing rat

Zusammenfassung Der Gehalt an Cytochromen (c+c ₁,aa ₃ undb) in Herz, Leber, Gehirn und Niere der Ratte wurde bestimmt. Ihre Vermehrung nach der Geburt erwies sich in den Geweben als relativ individuell. Die Vermehrung des ausserhalb der Mitochondrien synthetisierten Cytochromenc ging den übrigen, von der intramitochondrialen Proteinsynthese unabhängigen Cytochromen voraus.     

Species-dependent stereospecific serum protein binding of the oral anticoagulant drug phenprocoumon

Summary 13 mammalian species are classified into 3 clearcut groups with respect to the stereospecific serum proteinbinding of phenprocoumon: 2 groups showing opposed stereospecific binding characteristics and a 3rd group exhibiting no stereospecific binding. Structural differences in the albumin molecule account for these stereospecific differences in serum protein-binding.This research was supported by a grant from the Deutsche Forschungsgemeinschaft (Ja/185/6).     

Loss-of-function mutations in TYROBP (DAP12) result in a presenile dementia with bone cysts

Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL; MIM 221770), also known as Nasu-Hakola disease, is a recessively inherited disease characterized by a combination of psychotic symptoms rapidly progressing to presenile dementia and bone cysts restricted to wrists and ankles. PLOSL has a global distribution, although most of the patients have been diagnosed in Finland and Japan, with an estimated population prevalence of 2x10-6 (ref. 2) in the Finns. We have previously identified a shared 153-kb ancestor haplotype in all Finnish disease alleles between markers D19S1175 and D19S608 on chromosome 19q13.1 (refs 5,6). Here we characterize the molecular defect in PLOSL by identifying one large deletion in all Finnish PLOSL alleles and another mutation in a Japanese patient, both representing loss-of-function mutations, in the gene encoding TYRO protein tyrosine kinase binding protein (TYROBP; formerly DAP12). TYROBP is a transmembrane protein that has been recognized as a key activating signal transduction element in natural killer (NK) cells. On the plasma membrane of NK cells, TYROBP associates with activating receptors recognizing major histocompatibility complex (MHC) class I molecules. No abnormalities in NK cell function were detected in PLOSL patients homozygous for a null allele of TYROBP.     

Solid-state NMR determination of the secondary structure of Samia cynthia ricini silk

Silks are fibrous proteins that form heterogeneous, semi-crystalline solids. Silk proteins have a variety of physical properties reflecting their range of functions. Spider dragline silk, for example, has high tensile strength and elasticity, whereas other silks are better suited to making housing, egg sacs or the capture spiral of spiders' webs. The differing physical properties arise from variation in the protein's primary and secondary structure, and their packing in the solid phase. The high mechanical performance of spider dragline silk, for example, is probably due to a beta-sheet conformation of poly-alanine domains, embedded as small crystallites within the fibre. Only limited structural information can be obtained from diffraction of silks, so further characterization requires spectroscopic studies such as NMR. However, the classical approach to NMR structure determination fails because the high molecular weight, repetitive primary structure and structural heterogeneity of solid silk means that signals from individual amino-acid residues cannot be resolved. Here we adapt a recently developed solid-state NMR technique to determine torsion angle pairs (phi, psi) in the protein backbone, and we study the distribution of conformations in silk from the Eri silkworm, Samia cynthia ricini. Although the most probable conformation in native fibres is an anti-parallel beta-sheet, film produced from liquid directly extracted from the silk glands appears to be primarily alpha-helical.     

Observation of five-fold local symmetry in liquid lead

The local point symmetry of the short-range order in simple monatomic liquids remains a fundamental open question in condensed-matter science. For more than 40 years it has been conjectured that liquids with centrosymmetric interactions may be composed of icosahedral building blocks. But these proposed mobile, randomly orientated structures have remained experimentally inaccessible owing to the unavoidable averaging involved in scattering experiments, which can therefore determine only the isotropic radial distribution function. Here we overcome this limitation by capturing liquid fragments at a solid-liquid interface, and observing the scattering of totally internally reflected (evanescent) X-rays, which are sensitive only to the liquid structure at the interface. Using this method, we observe five-fold local symmetry in liquid lead adjacent to a silicon wall, and obtain an experimental portrait of the icosahedral fragments that are predicted to occur in all close-packed monatomic liquids. By shedding new light on local bond order in disordered structures such as liquids and glasses, these results should lead to a better microscopic understanding of melting, freezing and supercooling.     

Card9 controls a non-TLR signalling pathway for innate anti-fungal immunity

Fungal infections are increasing worldwide due to the marked rise in immunodeficiencies including AIDS; however, immune responses to fungi are poorly understood. Dectin-1 is the major mammalian pattern recognition receptor for the fungal component zymosan. Dectin-1 represents the prototype of innate non-Toll-like receptors (TLRs) containing immunoreceptor tyrosine-based activation motifs (ITAMs) related to those of adaptive antigen receptors. Here we identify Card9 as a key transducer of Dectin-1 signalling. Although being dispensable for TLR/MyD88-induced responses, Card9 controls Dectin-1-mediated myeloid cell activation, cytokine production and innate anti-fungal immunity. Card9 couples to Bcl10 and regulates Bcl10-Malt1-mediated NF-kappaB activation induced by zymosan. Yet, Card9 is dispensable for antigen receptor signalling that uses Carma1 as a link to Bcl10-Malt1. Thus, our results define a novel innate immune pathway and indicate that evolutionarily distinct ITAM receptors in innate and adaptive immune cells use diverse adaptor proteins to engage selectively the conserved Bcl10-Malt1 module.