Further Insight into the Two Functions of Telomeres: Determining the Role of Tankyrase1 in Telomere Length Regulation and Tin2 in Telomere Protection

Tankyrase1 is a multifunctional poly(ADP-ribose) polymerase that can localize to telomeres through its interaction with the shelterin component TRF1. Tankyrase1 poly(ADP-ribosyl)ates TRF1 in vitro, and its nuclear overexpression leads to loss of TRF1 and telomere elongation, suggesting that tankyrase1 is a positive regulator of telomere length. In agreement with this proposal, we showed that tankyrase1 RNA interference results in telomere shortening proportional to the level of knockdown, while a tankyrase1-resistant form of TRF1 enforced normal telomere length control. Thus, in human cells, tankyrase1 appears to act upstream of TRF1, promoting telomere elongation through the removal of TRF1. This pathway appears absent from mouse cells. We demonstrated that murine TRF1, which lacks the tankyrase1-binding motif, is not a substrate for tankyrase1 poly(ADP-ribosyl)sylation in vitro. Furthermore, overexpression of tankyrase1 in mouse nuclei did not remove TRF1 from telomeres and had no detectable effect on other components of mouse shelterin. We propose that the tankyrase1-controlled telomere extension is a human-specific elaboration that allows additional control over telomere length in telomerase positive cells. TIN2 interacts with the double-stranded telomeric DNA-binding proteins TRF1 and TRF2 independently or simultaneously, acting as a bridge linking TRF1 and TRF2 to TPP1 and POT1, the single-stranded telomeric DNA-binding protein. To gain further insight into the function of the TRF2-TIN2 complex, we created a TRF2 mutant that no longer associates with TIN2. Employing protein overlay assays, we established that TIN2 binds TRF2 within its hinge domain from residues 352 to 367. Deletion of this region led to the production of a TRF2 TIN2-binding mutant, TRF2ΔT, which abrogated TRF2-TIN2 binding in protein overlay assays and in immunoprecipitation analysis. Expression of TRF2ΔT in MEFs that contain a conditionally null allele of TRF2 resulted in substantial loss of TIN2 from telomeres, the formation of telomere dysfunction induced foci (TIFs), and the appearance of multiple telomeric signals and telomere loss at chromatid ends. We show that the ATM signaling pathway is activated in response to the telomere dysfunction induced by loss of TIN2 from the TRF2 complex, suggesting that TIN2 assists TRF2 in suppressing ATM activation at telomeres

Developing optical efficiency through optimized coating structure: biomimetic inspiration from white beetles

Copyright © 2009 Optical Society of America. This paper was published in Applied Optics and is made available as an electronic reprint with the permission of OSA. The paper can be found at the following URL on the OSA website: http://www.opticsinfobase.org/ao/abstract.cfm?uri=ao-48-17-3243 . Systematic or multiple reproduction or distribution to multiple locations via electronic or other means is prohibited and is subject to penalties under law.The recent discovery of brilliant whiteness in ultrathin beetle scales indicated the availability of significant whiteness, brightness, and opacity from limited sample thickness. This is achieved in the beetle through optimization of the packing density of scattering centers in its elytral scales. Here, we directly test and apply this idea to whiteness and brightness in the production and appearance of mineral coatings on paper by varying the scattering center parameters that underpin its optical properties. Through biomimetic design principles, we find that desirably high optical scattering from mineral coatings can be achieved. Commercially, by using appropriately designed coating formulations, this leads to the prospect of equal optical performance using less scattering material

BASINS/HSPF: Model use, calibration, and validation

ABSTRACT. This article presents recommendations by model developers and the authors about calibration and validation procedures for the Hydrological Simulatio

The potential of flood forecasting using a variable-resolution global Digital Terrain Model and flood extents from Synthetic Aperture Radar images

A basic data requirement of a river flood inundation model is a Digital Terrain Model (DTM) of the reach being studied. The scale at which modeling is required determines the accuracy required of the DTM. For modeling floods in urban areas, a high resolution DTM such as that produced by airborne LiDAR (Light Detection And Ranging) is most useful, and large parts of many developed countries have now been mapped using LiDAR. In remoter areas, it is possible to model flooding on a larger scale using a lower resolution DTM, and in the near future the DTM of choice is likely to be that derived from the TanDEM-X Digital Elevation Model (DEM). A variable-resolution global DTM obtained by combining existing high and low resolution data sets would be useful for modeling flood water dynamics globally, at high resolution wherever possible and at lower resolution over larger rivers in remote areas. A further important data resource used in flood modeling is the flood extent, commonly derived from Synthetic Aperture Radar (SAR) images. Flood extents become more useful if they are intersected with the DTM, when water level observations (WLOs) at the flood boundary can be estimated at various points along the river reach. To illustrate the utility of such a global DTM, two examples of recent research involving WLOs at opposite ends of the spatial scale are discussed. The first requires high resolution spatial data, and involves the assimilation of WLOs from a real sequence of high resolution SAR images into a flood model to update the model state with observations over time, and to estimate river discharge and model parameters, including river bathymetry and friction. The results indicate the feasibility of such an Earth Observation-based flood forecasting system. The second example is at a larger scale, and uses SAR-derived WLOs to improve the lower-resolution TanDEM-X DEM in the area covered by the flood extents. The resulting reduction in random height error is significant

Adapting HYDRUS-1D to Simulate Overland Flow and Reactive Transport during Sheet Flow Deviations

Surface runoff is commonly described in numerical models using either the diffusion wave or kinematic wave equations, which assume that surface runoff occurs as sheet flow with a uniform depth and velocity across the slope. In reality, overland water flow and transport processes are rarely uniform. Local soil topography, vegetation, and spatial soil heterogeneity control directions and magnitudes of water fluxes. These spatially varying surface characteristics can generate deviations from sheet flow such as physical nonequilibrium flow and transport processes that occur only on a limited fraction of the soil surface. In this study, we first adapted the HYDRUS-1D model to solve the diffusion wave equation for overland flow at the soil surface. The numerical results obtained by the new model produced an excellent agreement with an analytical solution for the kinematic wave equation. Additional model tests further demonstrated the applicability of the adapted model to simulate the transport and fate of many different solutes (non-adsorbing tracers, nutrients, pesticides, and microbes) that undergo equilibrium and/or kinetic sorption and desorption and first- or zero-order reactions. HYDRUS-1D includes a hierarchical series of models of increasing complexity to account for both uniform and physical nonequilibrium flow and transport, e.g., dual-porosity and dual-permeability models, up to a dual-permeability model with immobile water. This same conceptualization was adapted to simulate physical nonequilibrium overland flow and transport at the soil surface. The developed model improves our ability to describe nonequilibrium overland flow and transport processes and our understanding of factors that cause this behavior

Satellite-supported flood forecasting in river networks: a real case study

Satellite-based (e.g., Synthetic Aperture Radar [SAR]) water level observations (WLOs) of the floodplain can be sequentially assimilated into a hydrodynamic model to decrease forecast uncertainty. This has the potential to keep the forecast on track, so providing an Earth Observation (EO) based flood forecast system. However, the operational applicability of such a system for floods developed over river networks requires further testing. One of the promising techniques for assimilation in this field is the family of ensemble Kalman (EnKF) filters. These filters use a limited-size ensemble representation of the forecast error covariance matrix. This representation tends to develop spurious correlations as the forecast-assimilation cycle proceeds, which is a further complication for dealing with floods in either urban areas or river junctions in rural environments. Here we evaluate the assimilation of WLOs obtained from a sequence of real SAR overpasses (the X-band COSMO-Skymed constellation) in a case study. We show that a direct application of a global Ensemble Transform Kalman Filter (ETKF) suffers from filter divergence caused by spurious correlations. However, a spatially-based filter localization provides a substantial moderation in the development of the forecast error covariance matrix, directly improving the forecast and also making it possible to further benefit from a simultaneous online inflow error estimation and correction. Additionally, we propose and evaluate a novel along-network metric for filter localization, which is physically-meaningful for the flood over a network problem. Using this metric, we further evaluate the simultaneous estimation of channel friction and spatially-variable channel bathymetry, for which the filter seems able to converge simultaneously to sensible values. Results also indicate that friction is a second order effect in flood inundation models applied to gradually varied flow in large rivers. The study is not conclusive regarding whether in an operational situation the simultaneous estimation of friction and bathymetry helps the current forecast. Overall, the results indicate the feasibility of stand-alone EO-based operational flood forecasting

Sister telomeres rendered dysfunctional by persistent cohesion are fused by NHEJ

Telomeres protect chromosome ends from being viewed as double-strand breaks and from eliciting a DNA damage response. Deprotection of chromosome ends occurs when telomeres become critically short because of replicative attrition or inhibition of TRF2. In this study, we report a novel form of deprotection that occurs exclusively after DNA replication in S/G2 phase of the cell cycle. In cells deficient in the telomeric poly(adenosine diphosphate ribose) polymerase tankyrase 1, sister telomere resolution is blocked. Unexpectedly, cohered sister telomeres become deprotected and are inappropriately fused. In contrast to telomeres rendered dysfunctional by TRF2, which engage in chromatid fusions predominantly between chromatids from different chromosomes (Bailey, S.M., M.N. Cornforth, A. Kurimasa, D.J. Chen, and E.H. Goodwin. 2001. Science. 293:2462–2465; Smogorzewska, A., J. Karlseder, H. Holtgreve-Grez, A. Jauch, and T. de Lange. 2002. Curr. Biol. 12:1635–1644), telomeres rendered dysfunctional by tankyrase 1 engage in chromatid fusions almost exclusively between sister chromatids. We show that cohered sister telomeres are fused by DNA ligase IV–mediated nonhomologous end joining. These results demonstrate that the timely removal of sister telomere cohesion is essential for the formation of a protective structure at chromosome ends after DNA replication in S/G2 phase of the cell cycle