Approximate analysis of variance of spatially autocorrelated regional data

The classical method for analysis of variance of data divided in geographic regions is impaired if the data are spatially autocorrelated within regions, because the condition of independence of the observations is not met. Positive autocorrelation reduces within-group variability, thus artificially increasing the relative amount of among-group variance. Negative autocorrelation may produce the opposite effect. This difficulty can be viewed as a loss of an unknown number of degrees of freedom. Such problems can be found in population genetics, in ecology and in other branches of biology, as well as in economics, epidemiology, geography, geology, marketing, political science, and sociology. A computer-intensive method has been developed to overcome this problem in certain cases. It is based on the computation of pooled within-group sums of squares for sampled permutations of internally connected areas on a map. The paper presents the theory, the algorithms, and results obtained using this method. A computer program, written in PASCAL, is available.This work was supported by NSERC grant no. A7738 to Pierre Legendre and by grant BSR 8614384 from the National Science Foundation to Robert R. Sokal. This is contribution No. 366 of the Groupe d'Ecologie des Eaux Douces, Université de Montréal, and contribution No. 727 in Ecology and Evolution from the State University of New York at Stony Brook.     

Bone marrow-derived mesenchymal cells and MMP13 contribute to experimental choroidal neovascularization

In this study, we evaluate the potential involvement of collagenase-3 (MMP13), a matrix metalloproteinase (MMP) family member, in the exudative form of age-related macular degeneration characterized by a neovascularisation into the choroid. RT-PCR analysis revealed that human neovascular membranes issued from patients with AMD expressed high levels of Mmp13. The contribution of MMP13 in choroidal neovascularization (CNV) formation was explored by using a murine model of laser-induced CNV and applying it to wild-type mice (WT) and Mmp13-deficient mice (Mmp13 ^?/? mice). Angiogenic and inflammatory reactions were explored by immunohistochemistry. The implication of bone marrow (BM)-derived cells was determined by BM engraftment into irradiated mice and by injecting mesenchymal stem cells (MSC) isolated from WT BM. The deficiency of Mmp13 impaired CNV formation which was fully restored by WT BM engraftment and partially rescued by several injections of WT MSC. The present study sheds light on a novel function of MMP13 during BM-dependent choroidal vascularization and provides evidence for a role for MSC in the pathogenesis of CNV.     

Increased survival time of leukemic mice following treatment with phytohemagglutinin

Résumé Des souris ayant subi un traitement journalier au PHA, entrepris 4 jours avant l'implantation de cellules leucémiques L1210 on survécu plus longtemps que celles qui furent traitées au sel. Le traitement journalier entrepris 24 h après l'inoculation de cellules leucémiques n'a pas eu d'effet sur la durée de survie. Par le traitement au PHA combiné à la 6-mercaptopurine, la durée de vie fut plus longue que par celui que l'on obtint avec d'autres agents employés isolément. Un mécanisme proposé pour l'effet antileucémique de PHA est discuté.

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This work was supported in part by Contract No. NIH-70-2001 from the Cancer Chemotherapy National Service Center, National Cancer Institute and by a grant from the Life Insurance Medical Research fund No. G-68-11.     

Evidence of en bloc duplication in vertebrate genomes

It has been 30 years since it was first proposed that the vertebrate genome evolved through several rounds of genome-wide duplications (polyploidizations). Despite rapid advances in genetics, including sequencing of the complete genomes of several divergent species, this hypothesis has not been tested rigorously and is still a matter of debate. If polyploidizations occurred during chordate evolution, there should be a network of paralogous regions in the present-day jawed vertebrate (Gnathostomata) genomes. Here we present an investigation of the major histocompatibility complex (MHC) paralogous regions, which we accomplished by characterizing the corresponding region in amphioxus by identifying nine anchor genes and sequencing both the anchor genes and the regions that flank them (a total of 400 kb). Phylogenetic analysis of 31 genes (including the anchor genes) in these regions shows that duplications occurred after the divergence of cephalochordates and vertebrates but before the Gnathostomata radiation. The distribution of human and amphioxus orthologs in their respective genomes and the relationship between these distributions support the en bloc duplication events. Our analysis represents the first step towards demonstrating that the human ancestral genome has undergone polyploidization. Moreover, reconstruction of the pre-duplicated region indicates that one of the duplicated regions retains the ancestral organization.     

The European dimension for the mouse genome mutagenesis program

The European Mouse Mutagenesis Consortium is the European initiative contributing to the international effort on functional annotation of the mouse genome. Its objectives are to establish and integrate mutagenesis platforms, gene expression resources, phenotyping units, storage and distribution centers and bioinformatics resources. The combined efforts will accelerate our understanding of gene function and of human health and disease.