DING proteins: numerous functions, elusive genes, a potential for health

DING proteins, named after their conserved N-terminus, form an overlooked protein family whose members were generally discovered through serendipity. It is characterized by an unusually high sequence conservation, even between distantly related species, and by an outstanding diversity of activities and ligands. They all share a demonstrated capacity to bind phosphate with high affinity or at least a predicted phosphate-binding site. However, DING protein genes are conspicuously absent from databases. The many novel family members identified in recent years have confirmed that DING proteins are ubiquitous not only in animals and plants but probably also in prokaryotes. At the functional level, there is increasing evidence that they participate in many health-related processes such as cancers as well as bacterial (Pseudomonas) and viral (HIV) infections, by mechanisms that are now beginning to be understood. They thus represent potent targets for the development of novel therapeutic approaches, especially against HIV. The few genomic sequences that are now available are starting to give some clues on why DING protein genes and mRNAs are well conserved and difficult to clone. This could open a new era of research, of both fundamental and applied importance.     

Macrophage skewing by Phd2 haplodeficiency prevents ischaemia by inducing arteriogenesis

PHD2 serves as an oxygen sensor that rescues blood supply by regulating vessel formation and shape in case of oxygen shortage. However, it is unknown whether PHD2 can influence arteriogenesis. Here we studied the role of PHD2 in collateral artery growth by using hindlimb ischaemia as a model, a process that compensates for the lack of blood flow in case of major arterial occlusion. We show that Phd2 (also known as Egln1) haplodeficient (Phd2(+/-)) mice displayed preformed collateral arteries that preserved limb perfusion and prevented tissue necrosis in ischaemia. Improved arteriogenesis in Phd2(+/-) mice was due to an expansion of tissue-resident, M2-like macrophages and their increased release of arteriogenic factors, leading to enhanced smooth muscle cell (SMC) recruitment and growth. Both chronic and acute deletion of one Phd2 allele in macrophages was sufficient to skew their polarization towards a pro-arteriogenic phenotype. Mechanistically, collateral vessel preconditioning relied on the activation of canonical NF-κB pathway in Phd2(+/-) macrophages. These results unravel how PHD2 regulates arteriogenesis and artery homeostasis by controlling a specific differentiation state in macrophages and suggest new treatment options for ischaemic disorders.     

An extremely primitive star in the Galactic halo

The early Universe had a chemical composition consisting of hydrogen, helium and traces of lithium; almost all other elements were subsequently created in stars and supernovae. The mass fraction of elements more massive than helium, Z, is known as 'metallicity'. A number of very metal-poor stars has been found, some of which have a low iron abundance but are rich in carbon, nitrogen and oxygen. For theoretical reasons and because of an observed absence of stars with Z?相似文献   

Optimal Quantization of the Support of a Continuous Multivariate Distribution based on Mutual Information

Based on the notion of mutual information between the components of a random vector, we construct, for data reduction reasons, an optimal quantization of the support of its probability measure. More precisely, we propose a simultaneous discretization of the whole set of the components of the random vector which takes into account, as much as possible, the stochastic dependence between them. Examples are presented.     

The generation of random ultrametric matrices representing dendrograms

Many methods and algorithms to generate random trees of many kinds have been proposed in the literature. No procedure exists however for the generation of dendrograms with randomized fusion levels. Randomized dendrograms can be obtained by randomizing the associated cophenetic matrix. Two algorithms are described. The first one generates completely random dendrograms, i.e., trees with a random topology, random fusion level values, and random assignment of the labels. The second algorithm uses a double-permutation procedure to randomize a given dendrogram; it proceeds by randomization of the fixed fusion levels, instead of using random fusion level values. A proof is presented that the double-permutation procedure is a Uniform Random Generation Algorithmsensu Furnas (1984), and a complete example is given. This work was supported by NSERC Grant No. A7738 to P. Legendre and by a NSERC scholarship to F.-J. Lapointe.     

The hexose content of theα-chains of bone collagen

Résumé Les 3 chaînes du collagène de l'os de poulet ont été isolées en combinant les techniques de filtration sur gel et d'électrophorèse en veine libre. Des substances donnant une réaction d'anthrone positive, avec spectre d'absorption caractéristique des hexoses, ont été mises en évidence dans ces 3 chaînes. En utilisant le glucose comme standard, la détermination des hexoses fournit une valeur de 12 moles d'hexoses par molécule de collagène.