The upper Miocene Deurne Member of the Diest Formation revisited : unexpected results from the study of a large temporary outcrop near Antwerp International Airport, Belgium

A 5.50 m thick interval of fossiliferous intensely bioturbated heterogenous glauconiferous sand of the upper Miocene Diest Formation is documented from a very large temporary outcrop just southeast of Antwerp International Airport (northern Belgium), allowing to observe lateral variations over several hundreds of meters and to collect many vertebrate and invertebrate fossils. This paper documents observations on lithology, sedimentary and post-sedimentary structures, and discusses the results of the multi-proxy analyses of the sediment (granulometry, glauconite content, clay mineralogy, Fe content and Fe3+/Fe2+ ratios), the interpretation of the trace fossil assemblage and the sedimentary structures as well as of the large-scale samplings of micro-, meso- and macrofossils. We evidence that the Diest Formation in the Antwerp area consists of two different lithological entities, and that this twofold character can be extrapolated to all previously recorded Deurne Member outcrops. A revised lithostratigraphic scheme for the Diest Formation in the Antwerp area is proposed, with the new Borsbeek member at the base and a redefmed Deurne Member at the top

MRI-based quantification of outflow boundary conditions for computational fluid dynamics of stenosed human carotid arteries

Accurate assessment of wall shear stress (WSS) is vital for studies on the pathogenesis of atherosclerosis. WSS distributions can be obtained by computational fluid dynamics (CFD) using patient-specific geometries and flow measurements. If patient-specific flow measurements are unavailable, in- and outflow have to be estimated, for instance by using Murray's Law. It is currently unknown to what extent this law holds for carotid bifurcations, especially in cases where stenoses are involved. We performed flow measurements in the carotid bifurcation using phase-contrast MRI in patients with varying degrees of stenosis. An empirical relation between outflow and degree of area stenosis was determined and the outflow measurements were compared to estimations based on Murray's Law. Furthermore, the influence of outflow conditions on the WSS distribution was studied. For bifurcations with an area stenosis smaller than 65%, the outflow ratio of the internal carotid artery (ICA) to the common carotid artery (CCA) was 0.62 +/- 0.12 while the outflow ratio of the external carotid artery (ECA) was 0.35 +/- 0.13. If the area stenosis was larger than 65%, the flow to the ICA decreased linearly to zero at 100% area stenosis. The empirical relation fitted the flow data well (R-2=0.69), whereas Murray's Law overestimated the flow to the ICA substantially for larger stenosis, resulting in an overestimation of the WSS. If patient-specific flow measurements of the carotid bifurcation are unavailable, estimation of the outflow ratio by the presented empirical relation will result in a good approximation of calculated WSS using CFD. (C) 2010 Elsevier Ltd. All rights reserved

De novo mutations in the actin genes ACTB and ACTG1 cause Baraitser-Winter syndrome

Brain malformations are individually rare but collectively common causes of developmental disabilities. Many forms of malformation occur sporadically and are associated with reduced reproductive fitness, pointing to a causative role for de novo mutations. Here, we report a study of Baraitser-Winter syndrome, a well-defined disorder characterized by distinct craniofacial features, ocular colobomata and neuronal migration defect. Using whole-exome sequencing of three proband-parent trios, we identified de novo missense changes in the cytoplasmic acting-encoding genes ACTB and ACTG1 in one and two probands, respectively. Sequencing of both genes in 15 additional affected individuals identified disease-causing mutations in all probands, including two recurrent de novo alterations (ACTB, encoding p.Arg196His, and ACTG1, encoding p.Ser155Phe). Our results confirm that trio-based exome sequencing is a powerful approach to discover genes causing sporadic developmental disorders, emphasize the overlapping roles of cytoplasmic actin proteins in development and suggest that Baraitser-Winter syndrome is the predominant phenotype associated with mutation of these two genes. © 2012 Nature America, Inc. All rights reserved

De novo mutations in the actin genes ACTB and ACTG1 cause Baraitser-Winter syndrome

Item does not contain fulltextBrain malformations are individually rare but collectively common causes of developmental disabilities. Many forms of malformation occur sporadically and are associated with reduced reproductive fitness, pointing to a causative role for de novo mutations. Here, we report a study of Baraitser-Winter syndrome, a well-defined disorder characterized by distinct craniofacial features, ocular colobomata and neuronal migration defect. Using whole-exome sequencing of three proband-parent trios, we identified de novo missense changes in the cytoplasmic actin-encoding genes ACTB and ACTG1 in one and two probands, respectively. Sequencing of both genes in 15 additional affected individuals identified disease-causing mutations in all probands, including two recurrent de novo alterations (ACTB, encoding p.Arg196His, and ACTG1, encoding p.Ser155Phe). Our results confirm that trio-based exome sequencing is a powerful approach to discover genes causing sporadic developmental disorders, emphasize the overlapping roles of cytoplasmic actin proteins in development and suggest that Baraitser-Winter syndrome is the predominant phenotype associated with mutation of these two genes