The distribution of Dishevelled in convergently extending mesoderm

Convergent extension (CE) is a conserved morphogenetic movement that drives axial lengthening of the primary body axis and depends on the planar cell polarity (PCP) pathway. In Drosophila epithelia, a polarised subcellular accumulation of PCP core components, such as Dishevelled (Dvl) protein, is associated with PCP function. Dvl has long been thought to accumulate in the mediolateral protrusions in Xenopus chordamesoderm cells undergoing CE. Here we present a quantitative analysis of Dvl intracellular localisation in Xenopus chordamesoderm cells. We find that, surprisingly, accumulations previously observed at mediolateral protrusions of chordamesodermal cells are not protrusion-specific but reflect yolk-free cytoplasm and are quantitatively matched by the distribution of the cytoplasm-filling lineage marker dextran. However, separating cell cortex-associated from bulk Dvl signal reveals a statistical enrichment of Dvl in notochord–somite boundary-(NSB)-directed protrusions, which is dependent upon NSB proximity. Dvl puncta were also observed, but only upon elevated overexpression. These puncta showed no statistically significant spatial bias, in contrast to the strongly posteriorly-enriched GFP-Dvl puncta previously reported in zebrafish. We propose that Dvl distribution is more subtle and dynamic than previously appreciated and that in vertebrate mesoderm it reflects processes other than protrusion as such

Increases in invasive melanoma in England, 1979-2006, by anatomical site

BACKGROUND: National melanoma incidence trends with details of anatomical site have not been previously described for England. OBJECTIVES: To describe site-specific trends in cutaneous melanoma for England as a whole during the last three decades. METHODS: Anonymized data, 1979–2006, were obtained from national cancer registrations of all patients in England up to age 89 years with incident primary invasive cutaneous melanomas (n = 124 055). Sex-specific age-standardized incidence rates and average annual percentage change in rates were calculated for each broad anatomical site. RESULTS: Overall incidence rates of cutaneous melanoma in England, 1979–2006, were 81 and 100 per million, in males and females, respectively. Site-specific rates were consistently highest on the lower limbs in females followed by the trunk in males. Greatest annual increases occurred on the trunk in both sexes over 45 years (males 9·9%, females 6·8%), then upper limbs (males 8·7%, females 6·8%). Incidence trends in males relative to females varied little across sites apart from a more rapid rise in head/neck melanomas in males than in females after the 1980s. CONCLUSIONS: Invasive melanoma rates continue to rise in England, particularly on the trunk and arms, and in males on the head/neck. The steeper increases in melanoma rates among males are consistent with their greater sun exposure and poorer compliance with sun protection measures than females

Dynamic inundation simulation of storm water interaction between sewer system and overland flows

Copyright © 2002 Taylor & FrancisThis is the Author's Accepted Manuscript of an article published in the Journal of the Chinese Institute of Engineers (2002), available online at: http://www.tandfonline.com/10.1080/02533839.2002.9670691An improved urban inundation model, coupling a 2D non‐inertia overland flow model with a storm water management model, is adopted to simulate inundation in urban areas. The model computes, not only the overland runoff and the water overflow through manholes where surface runoff exceeds the capacity of storm sewers, but also the bidirectional flow interactions between sewers and overland runoff. The model was verified by a typhoon event in Nov. 2000, which resulted in serious inundation in the Mucha area of Taipei City. The result shows that the present model indeed improves simulation accuracy over the earlier model, and can be used to provide a more reliable flood mitigation design

A new model for predicting relative nonwetting phase permeability from soil water retention curves

Relative permeability of the nonwetting phase in a multiphase flow in porous media is a function of phase saturation. Specific expressions of this function are commonly determined by combining soil water retention curves with relative nonwetting phase permeability models. Experimental evidence suggests that the relative permeability of the nonwetting phase can be significantly overestimated by the existing relative permeability models. A new model for the prediction of relative nonwetting phase permeability from soil water retention curves is proposed in this paper. A closed form expression can be obtained in combination with soil water retention curves. The model is mathematically simple and can easily and efficiently be implemented in numerical models of multiphase flow processes in porous media. The predicting capability of the proposed model is contrasted with well-supported models by comparing the measured and predicted relative air permeability data for 11 soils, representing a wide range of soil textures, from sand to silty clay loam. In most of the cases the proposed model improves the agreement between the predicted relative air permeability and the measured data. Copyright 2011 by the American Geophysical Union.published_or_final_versio

Murine Dishevelled 3 Functions in Redundant Pathways with Dishevelled 1 and 2 in Normal Cardiac Outflow Tract, Cochlea, and Neural Tube Development

Dishevelled (Dvl) proteins are important signaling components of both the canonical β-catenin/Wnt pathway, which controls cell proliferation and patterning, and the planar cell polarity (PCP) pathway, which coordinates cell polarity within a sheet of cells and also directs convergent extension cell (CE) movements that produce narrowing and elongation of the tissue. Three mammalian Dvl genes have been identified and the developmental roles of Dvl1 and Dvl2 were previously determined. Here, we identify the functions of Dvl3 in development and provide evidence of functional redundancy among the three murine Dvls. Dvl3−/− mice died perinatally with cardiac outflow tract abnormalities, including double outlet right ventricle and persistent truncus arteriosis. These mutants also displayed a misorientated stereocilia in the organ of Corti, a phenotype that was enhanced with the additional loss of a single allele of the PCP component Vangl2/Ltap (LtapLp/+). Although neurulation appeared normal in both Dvl3−/− and LtapLp/+ mutants, Dvl3+/−;LtapLp/+ combined mutants displayed incomplete neural tube closure. Importantly, we show that many of the roles of Dvl3 are also shared by Dvl1 and Dvl2. More severe phenotypes were observed in Dvl3 mutants with the deficiency of another Dvl, and increasing Dvl dosage genetically with Dvl transgenes demonstrated the ability of Dvls to compensate for each other to enable normal development. Interestingly, global canonical Wnt signaling appeared largely unaffected in the double Dvl mutants, suggesting that low Dvl levels are sufficient for functional canonical Wnt signals. In summary, we demonstrate that Dvl3 is required for cardiac outflow tract development and describe its importance in the PCP pathway during neurulation and cochlea development. Finally, we establish several developmental processes in which the three Dvls are functionally redundant

Extreme multi-basin flooding linked with extra-tropical cyclones

© 2017 The Author(s). Published by IOP Publishing Ltd. Fluvial floods are typically investigated as 'events' at the single basin-scale, hence flood management authorities may underestimate the threat of flooding across multiple basins driven by large-scale and nearly concurrent atmospheric event(s). We pilot a national-scale statistical analysis of the spatio-temporal characteristics of extreme multi-basin flooding (MBF) episodes, using peak river flow data for 260 basins in Great Britain (1975-2014), a sentinel region for storms impacting northwest and central Europe. During the most widespread MBF episode, 108 basins (∼46% of the study area) recorded annual maximum (AMAX) discharge within a 16 day window. Such episodes are associated with persistent cyclonic and westerly atmospheric circulations, atmospheric rivers, and precipitation falling onto previously saturated ground, leading to hydrological response time

Deficiency in origin licensing proteins impairs cilia formation: implications for the aetiology of meier-gorlin syndrome

Mutations in ORC1, ORC4, ORC6, CDT1, and CDC6, which encode proteins required for DNA replication origin licensing, cause Meier-Gorlin syndrome (MGS), a disorder conferring microcephaly, primordial dwarfism, underdeveloped ears, and skeletal abnormalities. Mutations in ATR, which also functions during replication, can cause Seckel syndrome, a clinically related disorder. These findings suggest that impaired DNA replication could underlie the developmental defects characteristic of these disorders. Here, we show that although origin licensing capacity is impaired in all patient cells with mutations in origin licensing component proteins, this does not correlate with the rate of progression through S phase. Thus, the replicative capacity in MGS patient cells does not correlate with clinical manifestation. However, ORC1-deficient cells from MGS patients and siRNA-mediated depletion of origin licensing proteins also have impaired centrosome and centriole copy number. As a novel and unexpected finding, we show that they also display a striking defect in the rate of formation of primary cilia. We demonstrate that this impacts sonic hedgehog signalling in ORC1-deficient primary fibroblasts. Additionally, reduced growth factor-dependent signaling via primary cilia affects the kinetics of cell cycle progression following cell cycle exit and re-entry, highlighting an unexpected mechanism whereby origin licensing components can influence cell cycle progression. Finally, using a cell-based model, we show that defects in cilia function impair chondroinduction. Our findings raise the possibility that a reduced efficiency in forming cilia could contribute to the clinical features of MGS, particularly the bone development abnormalities, and could provide a new dimension for considering developmental impacts of licensing deficiency