A receptor for the immunosuppressant FK506 is a cis-trans peptidyl-prolyl isomerase

The structurally novel macrolide FK506 (refs 1,2) has recently been demonstrated to have potent immunosuppressive activity at concentrations several hundredfold lower than cyclosporin A (CsA). Cyclosporin A, a cyclic peptide, has found widespread clinical use in the prevention of graft rejection following bone marrow and organ transplantation. The mechanisms of immunosuppression mediated by FK506 and CsA appear to be remarkably similar, suggesting that these unrelated structures act on a common receptor or on similar molecular targets, perhaps the CsA receptor, cyclophilin, which has recently been shown by Fischer et al. and Takahashi et al. to have cis-trans peptidyl-prolyl isomerase activity. We have prepared an FK506 affinity matrix and purified a binding protein for FK506 from bovine thymus and from human spleen. This FK506-binding protein (FKBP) has a relative molecular mass (Mr) of approximately 14,000(14K), a pI of 8.8-8.9, and does not cross-react with antisera against cyclophilin. The first 40 N-terminal residues of the bovine and 16 residues of the human FKBP were determined; the 16-residue fragments are identical to each other and unrelated to any known sequences. This protein catalyses the cis-trans isomerization of the proline amide in a tetrapeptide substrate and FK506 inhibits the action of this new isomerase. The FKBP and cyclophilin appear to be members of an emerging class of novel proteins that regulate T cell activation and other metabolic processes, perhaps by the recognition (and possibly the isomerization) of proline-containing epitopes in target proteins.     

Isolation of a hypothalamic peptide with TRF (thyreotrophin releasing factor) activityin vitro

Zusammenfassung Die elektrophoretisch isolierte Fraktion des hypothalamischen Extraktes, die die adenohypophysären sauren Phosphatasenin vitro und die Sekretion des TSH aktiviert, wurde mittels Gel-Filtration an einer Sephadex G-25 Säule weiter gereinigt. Elektrochromatographische Analyse der gereinigten Fraktion zeigte, dass sie in nativem Zustand Ninhydrin-negativ ist und dass nach der sauren Hydrolyse folgende Aminosäuren aus ihr entstehen: Lysin, Serin, Glycin, Alanin, Asparagin, Glutamsäure, Valin, Isoleucin und Leucin. Dieselbe Fraktion erhöht die Sekretion des TSH aus Rattenhypophysein vitro. Die Fraktion enthält also wahrscheinlich den hypothalamischen Peptid, der die Sekretion des TSH aus der Hypophyse stimuliert (thyreotrophin releasing factor, TRF).     

Die Dünnschichtchromatographie von Gibberellinen

Summary Thin-layer chromatography on silica gel is described as a new method for the separation and identification of the gibberellins A₁, A₃, A₄, A₅, A₇, A₈, and A₉.     

Photolyse von N-Nitroso-22,26-iminocholestanen: Eine neue Synthese von Spirosolan-Alkaloiden

Summary Photolysis of N-nitroso-22,26-imino-5-cholestane-3,16-diols in acidic solution leads to the corresponding spirosolane alkaloids soladulcidine, solasodine and tomatidine, respectively.

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Photochemische Reaktionen, 5. Mitteilung. — 3. und 4. Mitteilung vgl.². Die vorliegende Arbeit ist zugleich 62. Mitteilung der ReiheSolanum-Alkaloide.     

Isolierung von 4α-methyl-5α-stigmasta-7,24(28)-dien-3β-ol ausSolanum tuberosum sowie über die Identität dieser Verbindung mitα 1-Sitosterin

Summary The sterol fraction from leaves of the potato plant,Solanum tuberosum, was found to contain a minor constituent, the structure of which has been established as 4-methyl-5-stigmasta-7,24(28)-diene-3-ol (I). This sterol is most probably identical with ₁-sitosterol and has the same constitution as citrostadienol, differing only in the configuration of the ^{24 (28)}-double bond.

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Sterine und Triterpenoide. III. Mitteilung. — II. Mitteilung s. 3.     

Chemolithoautotrophic metabolism of anaerobic extremely thermophilic archaebacteria

Several types of extremely thermophilic archaebacteria have recently been isolated from solfataric water holes, hot springs and hot sea floors. It has been shown that some of them can live using sulphur respiration of reduced carbon substrates as a source of energy, a type of metabolism previously described for the eubacterium Desulfuromonas. We report here that several extremely thermophilic archaebacteria can live with carbon dioxide as their sole carbon source, obtaining energy from the oxidation of hydrogen by sulphur, producing hydrogen sulphide. They are thus capable of a new type of anaerobic, purely chemolithoautotrophic metabolism, a possible primaeval mode of life.     

Heterogeneity of membrane phospholipid mobility in endothelial cells depends on cell substrate

Cellular growth control and differentiation have been shown to be dependent on both cell-cell and cell-substrate contacts. Interactions of cells with extracellular material are critical events during embryonic development and maintenance of tissue function. Plasma membrane receptors have been described for components of the extracellular matrix such as fibronectin, laminin and various collagen types. Transmembrane signalling has been shown to be influenced by the lateral mobilities of the plasma membrane constituents. The interaction of cells with their extracellular matrix could thus have a significant effect on the mobility properties of the plasma membrane components. Here we have studied the dynamic properties of fluorescent membrane phospholipids in bovine endothelial cells using fluorescence recovery after photo-bleaching measurements. At this molecular level we find that the phospholipid lateral diffusion coefficient is dependent on the substrate upon which cells are allowed to adhere (collagen, fibronectin or a natural basement membrane) and on the topography of the cell (basal versus apical plasma membrane).     

A human IFNGR1 small deletion hotspot associated with dominant susceptibility to mycobacterial infection

The immunogenetic basis of severe infections caused by bacille Calmette-Guérin vaccine and environmental mycobacteria in humans remains largely unknown. We describe 18 patients from several generations of 12 unrelated families who were heterozygous for 1 to 5 overlapping IFNGR1 frameshift small deletions and a wild-type IFNGR1 allele. There were 12 independent mutation events at a single mutation site, defining a small deletion hotspot. Neighbouring sequence analysis favours a small deletion model of slipped mispairing events during replication. The mutant alleles encode cell-surface IFNgamma receptors that lack the intra-cytoplasmic domain, which, through a combination of impaired recycling, abrogated signalling and normal binding to IFNgamma exert a dominant-negative effect. We thus report a hotspot for human IFNGR1 small deletions that confer dominant susceptibility to infections caused by poorly virulent mycobacteria.     

纤维及工艺对高膨松性非织造布性能的影响

采用双组分热熔聚酯纤维粘合法制得高膨松性非织造布，讨论了所用纤维性能及加工工艺参数对非织造布力学性能的影响，并探讨了利用双组分热熔纤维粘合法生产非织造的工艺参数的选择，结果表明对于皮层熔点低的双组分纤维其加工温度范围较宽，而对皮层熔点高的双组分纤维最佳加工温度约比其多１５℃。