The distribution of lead in human deciduous teeth

Résumé Douze dents de lait d'enfants citadins, dont deux ayant une intoxication saturnine reconnue, ont été examinées par un microanalyseur à sonde électronique. On a retrouvé du plomb dans toutes les dents, avant tout à la périférie des zones hypominéralisées; mais pas à la surface de l'émail. Les résultats suggèrent que le plomb est incorporé dans la dent pendant la formation de la matrice et sa minéralisation, ainsi que durant la formation de la racine et du dépot de dentine secondaire.     

An evaluation of five algorithms for generating an initial configuration for SINDSCAL

Five different methods for obtaining a rational initial estimate of the stimulus space in the INDSCAL model were compared using the SINDSCAL program for fitting INDSCAL. The effect of the number of stimuli, the number of subjects, the dimensionality, and the amount of error on the quality and efficiency of the final SINDSCAL solution were investigated in a Monte Carlo study. We found that the quality of the final solution was not affected by the choice of the initialization method, suggesting that SINDSCAL finds a global optimum regardless of the initialization method used. The most efficient procedures were the methods proposed by by de Leeuw and Pruzansky (1978) and by Flury and Gautschi (1986) for the simultaneous diagonalization of several positive definite symmetric matrices, and a method based on linearly constraining the stimulus space using the CANDELINC approach developed by Carroll, Pruzansky, and Kruskal (1980).Geert De Soete is supported as Bevoegdverklaard Navorser of the Belgian Nationaal Fonds voor Wetenschappelijk Onderzoek. The authors gratefully acknowledge the helpful comments and suggestions of the reviewers.     

An alternating combinatorial optimization approach to fitting the INDCLUS and generalized INDCLUS models

This paper presents a general approach for fitting the ADCLUS (Shepard and Arabie 1979; Arabie, Carroll, DeSarbo, and Wind 1981), INDCLUS (Carroll and Arabie 1983), and potentially a special case of the GENNCLUS (DeSarbo 1982) models. The proposed approach, based largely on a separability property observed for the least squares loss function being optimized, offers increased efficiency and other advantages over existing approaches like MAPCLUS (Arabie and Carroll 1980) for fitting the ADCLUS model, and the INDCLUS method for fitting the INDCLUS model. The new procedure (called SINDCLUS) is applied to three sets of empirical data to demonstrate the effectiveness of the SINDCLUS methodology. Finally, some potentially useful extensions are discussed.     

FOXA1 is a key determinant of estrogen receptor function and endocrine response

Estrogen receptor-α (ER) is the key feature of most breast cancers and binding of ER to the genome correlates with expression of the Forkhead protein FOXA1 (also called HNF3α). Here we show that FOXA1 is a key determinant that can influence differential interactions between ER and chromatin. Almost all ER-chromatin interactions and gene expression changes depended on the presence of FOXA1 and FOXA1 influenced genome-wide chromatin accessibility. Furthermore, we found that CTCF was an upstream negative regulator of FOXA1-chromatin interactions. In estrogen-responsive breast cancer cells, the dependency on FOXA1 for tamoxifen-ER activity was absolute; in tamoxifen-resistant cells, ER binding was independent of ligand but depended on FOXA1. Expression of FOXA1 in non-breast cancer cells can alter ER binding and function. As such, FOXA1 is a major determinant of estrogen-ER activity and endocrine response in breast cancer cells.     

Ancestry and pharmacogenomics of relapse in acute lymphoblastic leukemia

Although five-year survival rates for childhood acute lymphoblastic leukemia (ALL) are now over 80% in most industrialized countries, not all children have benefited equally from this progress. Ethnic differences in survival after childhood ALL have been reported in many clinical studies, with poorer survival observed among African Americans or those with Hispanic ethnicity when compared with European Americans or Asians. The causes of ethnic differences remain uncertain, although both genetic and non-genetic factors are likely important. Interrogating genome-wide germline SNP genotypes in an unselected large cohort of children with ALL, we observed that the component of genomic variation that co-segregated with Native American ancestry was associated with risk of relapse (P = 0.0029) even after adjusting for known prognostic factors (P = 0.017). Ancestry-related differences in relapse risk were abrogated by the addition of a single extra phase of chemotherapy, indicating that modifications to therapy can mitigate the ancestry-related risk of relapse.     

Hox genes in brachiopods and priapulids and protostome evolution.

Understanding the early evolution of animal body plans requires knowledge both of metazoan phylogeny and of the genetic and developmental changes involved in the emergence of particular forms. Recent 18S ribosomal RNA phylogenies suggest a three-branched tree for the Bilateria comprising the deuterostomes and two great protostome clades, the lophotrochozoans and ecdysozoans. Here, we show that the complement of Hox genes in critical protostome phyla reflects these phylogenetic relationships and reveals the early evolution of developmental regulatory potential in bilaterians. We have identified Hox genes that are shared by subsets of protostome phyla. These include a diverged pair of posterior (Abdominal-B-like) genes in both a brachiopod and a polychaete annelid, which supports the lophotrochozoan assemblage, and a distinct posterior Hox gene shared by a priapulid, a nematode and the arthropods, which supports the ecdysozoan clade. The ancestors of each of these two major protostome lineages had a minimum of eight to ten Hox genes. The major period of Hox gene expansion and diversification thus occurred before the radiation of each of the three great bilaterian clades.     

Mineral disequilibrium in lavas explained by convective self-mixing in open magma chambers.

Characteristic features of many porphyritic andesite and dacite lavas are that they are rich in crystals and display a range of disequilibrium features, including reversely zoned crystals, resorption surfaces, wide ranges of mineral compositions and minerals which are not in equilibrium with the surrounding rock matrix. These features are often interpreted as evidence of the mixing of magmas of contrasting composition, temperature and origin. Here, however, we propose that such features can also be caused by convection within a magma body with a single composition, that is heated from below and cooled from above. We describe petrological observations of andesite lava erupted at the Soufrière Hills volcano, Montserrat, which indicate a heating event and the intermingling of crystals that have very different thermal histories. We present experimental data on a representative groundmass composition of this lava, which indicate that it is difficult to explain the calcic compositions of plagioclase overgrowth rims and microphenocrysts unless parts of the magma were at temperatures much higher than the inferred average temperature. The concept of convective self-mixing allows us to explain the occurrence of compositions of minerals that apparently cannot coexist under equilibrium conditions.     

Identification of loci associated with schizophrenia by genome-wide association and follow-up

We carried out a genome-wide association study of schizophrenia (479 cases, 2,937 controls) and tested loci with P < 10(-5) in up to 16,726 additional subjects. Of 12 loci followed up, 3 had strong independent support (P < 5 x 10(-4)), and the overall pattern of replication was unlikely to occur by chance (P = 9 x 10(-8)). Meta-analysis provided strongest evidence for association around ZNF804A (P = 1.61 x 10(-7)) and this strengthened when the affected phenotype included bipolar disorder (P = 9.96 x 10(-9)).     

Collagens in the developing and diseased nervous system

Collagens are extracellular proteins characterized by a structure in triple helices. There are 28 collagen types which differ in size, structure and function. Their architectural and functional roles in connective tissues have been widely assessed. In the nervous system, collagens are rare in the vicinity of the neuronal soma, occupying mostly a “marginal” position, such as the meninges, the basement membranes and the sensory end organs. In neural development, however, where various ECM molecules are known to be determinant, recent studies indicate that collagens are no exception, participating in axonal guidance, synaptogenesis and Schwann cell differentiation. Insights on collagens function in the brain have also been derived from neural pathophysiological conditions. This review summarizes the significant advances which underscore the function and importance of collagens in the nervous system. Received 09 September 2008; received after revision 24 October 2008; accepted 28 October 2008     

CLUSCALE ("CLUstering and multidimensional SCAL[E]ing"): A Three-Way Hybrid Model Incorporating Overlapping Clustering and Multidimensional Scaling Structure

Traditional techniques of perceptual mapping hypothesize that stimuli are differentiated in a common perceptual space of quantitative attributes. This paper enhances traditional perceptual mapping techniques such as multidimensional scaling (MDS) which assume only continuously valued dimensions by presenting a model and methodology called CLUSCALE for capturing stimulus differentiation due to perceptions that are qualitative, in addition to quantitative or continuously varying perceptual attributes or dimensions. It provides models and OLS parameter estimation procedures for both a two-way and a three-way version of this general model. Since the two-way version of the model and method has already been discussed by Chaturvedi and Carroll (2000), and a stochastic variant discussed by Navarro and Lee (2003), we shall deal in this paper almost entirely with the three-way version of this model. We recommend the use of the three-way approach over the two-way approach, since the three-way approach both accounts for and takes advantage of the heterogeneity in subjects’ perceptions of stimuli to provide maximal information; i.e., it explicitly deals with individual differences among subjects.