The problem of coincidences

Summary This paper deals with the origin, history and various appearances of the problem of coincidences (matches, rencontres) in the theory of probability.     

Synthesis and structural characterization of lanthanide coordination polymers constructed from a 13-membered macrocycle

The lanthanide coordination polymers bearing a 13-membered macrocycle, [(13-EDTA-pnOH)H2] were synthesized. The products [Ln(13-EDTA-pnOH)(H2O)2·NO3]n (Ln = Eu(1), Tb(2), Dy(3)) have been obtained by MS, IR and element analyses. The solid-state structure of 1 was established by single-crystal X-ray analysis. The coordination geometry around the central metal atom in complex 1 is a nine-coor-dinated, tricapped-trigonal prism having six donor atoms (two amine nitrogen atoms, two amide oxygen atoms and two carboxymethyl oxygen atoms) from one ligand, one oxygen atom from a neighboring ligand, and two more oxygen atoms from two water molecules. The europium atoms are linked by―Eu―O―C―O―Eu―bridges to form an infinite chain.     

Common variants at CD40 and other loci confer risk of rheumatoid arthritis

To identify rheumatoid arthritis risk loci in European populations, we conducted a meta-analysis of two published genome-wide association (GWA) studies totaling 3,393 cases and 12,462 controls. We genotyped 31 top-ranked SNPs not previously associated with rheumatoid arthritis in an independent replication of 3,929 autoantibody-positive rheumatoid arthritis cases and 5,807 matched controls from eight separate collections. We identified a common variant at the CD40 gene locus (rs4810485, P = 0.0032 replication, P = 8.2 x 10(-9) overall, OR = 0.87). Along with other associations near TRAF1 (refs. 2,3) and TNFAIP3 (refs. 4,5), this implies a central role for the CD40 signaling pathway in rheumatoid arthritis pathogenesis. We also identified association at the CCL21 gene locus (rs2812378, P = 0.00097 replication, P = 2.8 x 10(-7) overall), a gene involved in lymphocyte trafficking. Finally, we identified evidence of association at four additional gene loci: MMEL1-TNFRSF14 (rs3890745, P = 0.0035 replication, P = 1.1 x 10(-7) overall), CDK6 (rs42041, P = 0.010 replication, P = 4.0 x 10(-6) overall), PRKCQ (rs4750316, P = 0.0078 replication, P = 4.4 x 10(-6) overall), and KIF5A-PIP4K2C (rs1678542, P = 0.0026 replication, P = 8.8 x 10(-8) overall).     

Potentiation of sympathetic effects by a new diphenylpropylamine derivative

Résumé Par le composé 1, 1-bis-(4-amino-phényl)-propyl-(3)-amine (TK174), de même que par la cocaïne, les actions de la noradrénaline sont considérablement augmentées tandis que celles de la tyramine sont bloquées. Les autres effets pharmacodynamiques de la cocaïne ne sont pas produits par TK 174.

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A detailed report will be published in the journal Drug Research (Arzneimittelforschung).     

The effect of vasoactive agents on nutritive collateral circulation in rat muscles

Summary The relationship between the collateral and control nutritive blood flow (⁸⁶Rb) of the triceps muscle was not influenced by vasoactive agents (phenylephrine, angiotensin II, vasopressin) in the rat. Isolevine caused vasodilation only in the control muscle.     

Impaired proximal tubular transport functions in anaesthetized splanchnicotomized dogs

Summary The maximal tubular transport of inorganic phosphate,d-glucose and para-aminohippuric acid, respectively, was depressed on the denervated side in unilaterally splanchnicotomized, anaesthetized dogs. It is concluded that renal sympathetic activity might in general regulate proximal tubular transport functions.The authors are indebted to Mrs V. Vajda, Mr A. Karai, Mrs K. Kéry, Mrs B. Asztalos, Mr S. Szécsi and Mr J. Vártok for their valuable technical assistance.     

Severe impairment of interleukin-1 and Toll-like receptor signalling in mice lacking IRAK-4

Toll-like receptors (TLRs), which recognize pathogen-associated molecular patterns, and members of the pro-inflammatory interleukin-1 receptor (IL-1R) family, share homologies in their cytoplasmic domains called Toll/IL-1R/plant R gene homology (TIR) domains. Intracellular signalling mechanisms mediated by TIRs are similar, with MyD88 (refs 5-8) and TRAF6 (refs 9, 10) having critical roles. Signal transduction between MyD88 and TRAF6 is known to involve the serine-threonine kinase IL-1 receptor-associated kinase 1 (IRAK-1) and two homologous proteins, IRAK-2 (ref. 12) and IRAK-M. However, the physiological functions of the IRAK molecules remain unclear, and gene-targeting studies have shown that IRAK-1 is only partially required for IL-1R and TLR signalling. Here we show by gene-targeting that IRAK-4, an IRAK molecule closely related to the Drosophila Pelle protein, is indispensable for the responses of animals and cultured cells to IL-1 and ligands that stimulate various TLRs. IRAK-4-deficient animals are completely resistant to a lethal dose of lipopolysaccharide (LPS). In addition, animals lacking IRAK-4 are severely impaired in their responses to viral and bacterial challenges. Our results indicate that IRAK-4 has an essential role in innate immunity.     

Immune suppression by neutrophils and granulocytic myeloid-derived suppressor cells: similarities and differences

Neutrophils are essential effector cells in the host defense against invading pathogens. Recently, novel neutrophil functions have emerged in addition to their classical anti-microbial role. One of these functions is the suppression of T cell responses. In this respect, neutrophils share similarities with granulocytic myeloid-derived suppressor cells (G-MDSCs). In this review, we will discuss the similarities and differences between neutrophils and G-MDSCs. Various types of G-MDSCs have been described, ranging from immature to mature cells shaping the immune response by different immune suppressive mechanisms. However, all types of G-MDSCs share distinct features of neutrophils, such as surface markers and morphology. We propose that G-MDSCs are heterogeneous and represent novel phenotypes of neutrophils, capable of suppressing the immune response. In this review, we will attempt to clarify the differences and similarities between neutrophils and G-MDSCs and attempt to facilitate further research.