TRAF4 functions as an intermediate of GITR-induced NF-κB activation

Members of the tumor necrosis factor receptor (TNFR) family regulate the activation, differentiation, and function of many cell types, including cells of the immune system. TNFR-associated factors (TRAFs) function as adapter molecules controlling signaling pathways triggered by TNFR family members, such as activation of nuclear factor B (NF-B). Despite intensive research, the function of TRAF4 in signaling pathways triggered by TNFR-related proteins remains enigmatic. Intriguingly, our functional studies indicated that TRAF4 augments NF-B activation triggered by glucocorticoid-induced TNFR (GITR), a receptor expressed on T cells, B cells, and macrophages. Further analyses revealed that TRAF4-mediated NF-B activation downstream of GITR depends on a previously mapped TRAF-binding site in the cytoplasmic domain of the receptor and is inhibited by the cytoplasmic protein A20. GITR is thought to inhibit the suppressive function of regulatory T cells (T_reg cells) and to promote activation of T cells. Taken together, our studies provide the first indications that TRAF4 elaborates GITR signaling and suggest that TRAF4 can modulate the suppressive functions of T_reg cells.Received 20 September 2004; received after revision 8 October 2004; accepted 18 October 2004     

Methylmalonic acid — an endogenous toxin?

Methylmalonic acid was previously considered as major neurotoxin in methylmalonic acidurias. In contrast, recent studies support the notion that other metabolites deriving from propionyl-coenzyme A, inducing synergistic inhibition of mitochondrial energy metabolism, are more important than methylmalonic acid to understand the neuropathogenesis of this disease. However, it is not yet known whether methylmalonic acid is involved in the induction of other organ manifestations in this disease, such as chronic renal failure.Received 21 October 2004; received after revision 29 December 2004; accepted 4 January 2005     

Elektronenmikroskopische Untersuchungen an Bianconekalken des Südtessins

Summary The Biancone limestone (Uppermost Jurassic-? Barremian) from southern Ticino, and the small organisms (Nannoconi incertae sedis) of which it mainly consists, have been examined in the electron microscope.The applied technique of preparing the limestone for investigation is described.Furthermore, a few remarks are made concerning the stratigraphic value of Nannoconus.

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Die Arbeit wurde unterstützt durch den Schweizerischen Nationalfonds.     

Über die Bindung von Kallidin an Heparin

Summary Kallidin gives, with heparin, a non-dialysable complex, which can be precipitated with alcohol. In this binding, kallidin is pharmacologically active, but may be split off by the substance 48/80.     

Cytologische Beobachtungen an Rindererythrocyten mit Hämoglobin-Antikörpern

Summary A commercial crystallised beef-haemoglobin preparation, freed from membranes, produced in rabbits an immune-serum which gave a specific precipitation reaction with haemoglobin and did not agglutinate the trypsin-treated erythrocytes. The haemoglobin is not a structural element of the erythrocyte membrane but it is absorbed to these secondarily during their preparation.     

Untersuchungen an Ionenaustauschmodellen zum Verständnis der Physiologie biogener Amine. Austauschgleichgewichte zwischen Natrium und Aminen an schwefelsäure-und karboxylgruppen-tragenden Ionenaustauschern

Summary The influence of an inorganic cation (sodium) was studied upon the distribution of physiologically or pharmacologically important amines on two different acid ion exchangers. When cation and amine are added in equivalent amounts to an exchange system of corresponding capacity, the distribution pattern of the amine shows differences which are characteristic of the active groups (SO₃H, COOH) of the relevant exchanger. Such reactions are thought to be of importance in biological activities of polyelectrolytes.     

Untersuchung antileukämischer Substanzen an der Hühnerleukose

Summary In leukosis of chickens caused by administration of 1-m-Tolylsemicarbazide (Maretin-Bayer) Butzolidin caused a reduction of the number of leucocytes to normal values. This action might be attributed to a cytostatic effect of Butazolidin.     

Modulation of an ‘equilibrium enzyme’: Ecological evidence

Summary The activity of D-lactate dehydrogenase in the foot of the snail,Helix pomatia, is closely correlated with time of year and mean daily temperature, and increases strikingly after the animals have been exposed to a nitrogen atmosphere for 24 h.I thank U. Platzer for technical assistance and D. Frank for help with the statistics. The investigation was supported by the Fonds zur Förderung der wissenschaftlichen Forschung in Österreich, project No. 1257 and 2919.     

Untersuchungen an Ionenaustauschmodellen zum Verständnis der Physiologie biogener Amine

Summary A synthetic ion exchanger containingR-PO(OH)₂ as active groups was shown to retain histamine and other basic substances selectively and, in most cases, with marked preference over the other cations (Na⁺, H⁺) present in the system. The results are taken to indicate that similar exchange reactions may occur on biogenic polyelectrolytes bearing similar active groups.     

Neurobiology and neuroimmunology of Tourette’s syndrome: an update

Tourettes syndrome is a childhood-onset neuropsychiatric disorder characterized by the presence of both multiple motor and vocal tics. While the pathogenesis at a molecular and cellular level remains unknown, structural and functional neuroimaging studies point to the involvement of the basal ganglia and related cortico-striato-thalamo-cortical circuits as the neuroanatomical site for Tourettes syndrome. Moreover, Tourettes syndrome has a strong genetic component, and considerable progress has been made in understanding the mode of transmission and in identifying potential genomic loci. Summaries of recent findings in these areas will be reviewed, followed by a critical overview of findings both supporting and challenging the proposed autoimmune hypothesis of Tourettes syndrome. We conclude that Tourettes syndrome is a heterogeneous disorder, and that immune factors may indeed be involved in some patients.Received 12 August 2003; received after revision 8 October 2003; accepted 31 October 2003     

极小(C_4,K_4;7)-平面图

若平面图G没有与H1同构的子图,且G没有与H2同构的子图,则G称为(H1,H2)-平面图.(H1,H2;n)-平面图表示n阶的(H1,H2)-平面图。若G是(H1,H2;n)-平面图,去掉G的任意一条边,都不再是(H1,H2;n)-平面图,则G称为极小(H1,H2;n)-平面图.本文给出了所有的极小(C4,K4;7)-平面图,有助于证明PR(C4,K8)。     

Casein,a prohormone with an immunomodulating role for the newborn?

Summary Maternal colostrum and milk, the earliest food of the newborn, should not only be considered as supplying nutrients, but also as agents providing protection against aggressions from the new environment. Indeed by enzymatic digestion of the main milk proteins, the caseins, biologically active peptides are released; they may be implicated in the stimulation of the newborn's immune system. From this point of view a strategic active zone has been characterized in -casein. A possible role of casein as a prohormone for the newborn is suggested.     

γ-Glutamyl-transpeptidase in lymphatic tissues ofMastomys natalensis during an infection withAcanthocheilonema viteae

Summary DuringAcanthocheilonema viteae infection, the specific activity of -glutamyltranspeptidase (-GT) increased in peritoneal exudate cells and bone marrow and decreased in lymphnodes ofMastomys natalensis throughout the course of infection. However, though there was an increase in specific activity of -GT in thymus and spleen during the prepatent phase ofA. viteae infection, the level either returned to normal or decreased during the latent phase of infection. A close correlation was observed between the host's immune status duringA. viteae infection and the level of -GT in lymphoid tissues.Communication No. 4535 from Central Drug Research Institute, Lucknow.     

Die normale Zusammensetzung des Plasmaproteinfilmes an der Oberfläche von Kaninchenerythrocyten

Summary A plasma protein film is adsorbed at the surface of the red cells of rabbit. The percentage composition of this plasma protein film is different from the protein composition of plasma.-Globulin, lipoprotein and prealbumin are increased, albumin is decreased at the surface of the red cells.     

Genetisch bedingte Tumoren und der Gehalt an freien Aminosäuren beiNicotiana

Summary The amphidiploid hybrid ofNicotiana glauca ×N. langsdorffi, producing tumors spontaneously, contains essentially more of the following free amino acids than the inital species: cystine, histamine, oxyproline, alanine, kynurenine, tryptophane, and a non-identified ninhydrine positive substance. It is supposed that the abnormally high content of free amino acids is connected with the spontaneous formation of tumors.

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Mit Unterstützung durch die Deutsche Forschungsgemeinschaft.     

Does an inhibitor of mitochondrial adenylate kinase also affect oxidative phosphorylation?

Summary Adenylate kinase activity of intact mitochondria is strongly inhibited by Ap₅A, i.e.p ¹,p ⁵-Di (adenosine-5-) pentaphosphate, whereas oxidative phosphorylation is not affected. Therefore, Ap₅A is a useful tool to distinguish between oxidative and non oxidative ATP generating reactions.Acknowledgment. The generous support of Prof. Dr.Walther Lamprecht is gratefully acknowledged. J. L. thanks the Stipendienfonds des Verbandes der Chemische Industrie for a scholarship.     

Elektronenmikroskopische Beobachtungen an den Hülsenarteriolen in der Milz des Hundes

Summary The endothelial cells of sheathed arterioles of dog spleen were found to contain an abundance of intracytoplasmic filaments about 80 Å in diameter. The endothelium is surrounded by a fenestrated clastin skeleton. The sheath cells show signs of phagocytosis. A possible vasomotor function of the endothelial cells is discussed.