Multicomponent Analysis of Junctional Movements Regulated by Myosin II Isoforms at the Epithelial Zonula Adherens

The zonula adherens (ZA) of epithelial cells is a site of cell-cell adhesion where cellular forces are exerted and resisted. Increasing evidence indicates that E-cadherin adhesion molecules at the ZA serve to sense force applied on the junctions and coordinate cytoskeletal responses to those forces. Efforts to understand the role that cadherins play in mechanotransduction have been limited by the lack of assays to measure the impact of forces on the ZA. In this study we used 4D imaging of GFP-tagged E-cadherin to analyse the movement of the ZA. Junctions in confluent epithelial monolayers displayed prominent movements oriented orthogonal (perpendicular) to the ZA itself. Two components were identified in these movements: a relatively slow unidirectional (translational) component that could be readily fitted by least-squares regression analysis, upon which were superimposed more rapid oscillatory movements. Myosin IIB was a dominant factor responsible for driving the unilateral translational movements. In contrast, frequency spectrum analysis revealed that depletion of Myosin IIA increased the power of the oscillatory movements. This implies that Myosin IIA may serve to dampen oscillatory movements of the ZA. This extends our recent analysis of Myosin II at the ZA to demonstrate that Myosin IIA and Myosin IIB make distinct contributions to junctional movement at the ZA

Evidence of gene-environment interaction for two genes on chromosome 4 and environmental tobacco smoke in controlling the risk of nonsyndromic cleft palate

Nonsyndromic cleft palate (CP) is one of the most common human birth defects and both genetic and environmental risk factors contribute to its etiology. We conducted a genome-wide association study (GWAS) using 550 CP case-parent trios ascertained in an international consortium. Stratified analysis among trios with different ancestries was performed to test for GxE interactions with common maternal exposures using conditional logistic regression models. While no single nucleotide polymorphism (SNP) achieved genome-wide significance when considered alone, markers in SLC2A9 and the neighboring WDR1 on chromosome 4p16.1 gave suggestive evidence of gene-environment interaction with environmental tobacco smoke (ETS) among 259 Asian trios when the models included a term for GxE interaction. Multiple SNPs in these two genes were associated with increased risk of nonsyndromic CP if the mother was exposed to ETS during the peri-conceptual period (3 months prior to conception through the first trimester). When maternal ETS was considered, fifteen of 135 SNPs mapping to SLC2A9 and 9 of 59 SNPs in WDR1 gave P values approaching genome-wide significance (10-6<P<10-4) in a test for GxETS interaction. SNPs rs3733585 and rs12508991 in SLC2A9 yielded P = 2.26×10-7 in a test for GxETS interaction. SNPs rs6820756 and rs7699512 in WDR1 also yielded P = 1.79×10-7 and P = 1.98×10-7 in a 1 df test for GxE interaction. Although further replication studies are critical to confirming these findings, these results illustrate how genetic associations for nonsyndromic CP can be missed if potential GxE interaction is not taken into account, and this study suggest SLC2A9 and WDR1 should be considered as candidate genes for CP. © 2014 Wu et al

Multi-ancestry genome-wide association study of 21,000 cases and 95,000 controls identifies new risk loci for atopic dermatitis

Genetic association studies have identified 21 loci associated with atopic dermatitis risk predominantly in populations of European ancestry. To identify further susceptibility loci for this common, complex skin disease, we performed a meta-analysis of >15 million genetic variants in 21,399 cases and 95,464 controls from populations of European, African, Japanese and Latino ancestry, followed by replication in 32,059 cases and 228,628 controls from 18 studies. We identified ten new risk loci, bringing the total number of known atopic dermatitis risk loci to 31 (with new secondary signals at four of these loci). Notably, the new loci include candidate genes with roles in the regulation of innate host defenses and T cell function, underscoring the important contribution of (auto)immune mechanisms to atopic dermatitis pathogenesis

Formation of an Hesperian-aged sedimentary basin containing phyllosilicates in Coprates Catena, Mars

The extensive light-toned deposits in canyons and troughs in Valles Marineris provide evidence of formation through water-related processes. As such, these deposits offer a window to past conditions on Mars. We study a small outcrop of light-toned deposits in a closed trough in Coprates Catena, a chain of collapse pits to the south-east of the main Valles Marineris system. A well-exposed sequence of deposits on the base of the north wall of the trough offers a 220 m section for geochemical and morphologic analysis. Using CRISM data we identify the presence of both phyllosilicates and sulfates and/or opaline silica in the light toned deposits, which vary in relative strength with elevation. We observe a trend in the dominant mineralogical signal, with Al phyllosilicates occurring near the base of the deposits, both below and above a band of Fe/Mg phyllosilicates, before a transition to more sulfate- or opaline silica-rich material near the top of the section. This trend likely reflects a change in the chemistry of the water in which the deposits formed. Using a HiRISE Digital Elevation Model, we find that the layers in the light-toned deposits on both sides of the trough dip gently towards the center of the trough, with a dip direction that aligns with the strike of the trough, suggesting that the light-toned deposits formed after the trough. Our general morphologic and mineralogical observations fit well with significant amounts of water in the trough. The deposits are too small to be dated using crater counting techniques, however, our crater analysis suggests that the plains in which the trough formed are probably Late Hesperian in age. If the chemistry of the light-toned deposits reflects the primary depositional mineralogy, then this and other small troughs in Coprates Catena might provide evidence of limited phyllosilicate formation in this region towards the end of the Hesperian era on Mars

Numerical Modelling of Self-Channeling Granular Flows and of Their Levee-Channel Deposits

International audienc

Numerical Modelling of Self-Channeling Granular Flows and of Their Levee-Channel Deposits

International audienc

Numerical Modelling of Self-Channeling Granular Flows and of Their Levee-Channel Deposits

International audienc