Understanding and managing the morphology of branches incising into sand-clay deposits in the Dutch Rhine Delta

In the Rhine-Meuse delta in the south-western part of the Netherlands, the morphology of the river branches is highly dependent on the erodibility of the subsoil. Erosion processes that were initiated after closure of the Haringvliet estuary branch by a dam (in 1970), caused a strong incision of several connecting branches. Due to the geological evolution of this area the lithology of the subsoil shows large variations in highly erodible sand and poorly erodible peat and clay layers. This study shows how the geological information can be used to create 3D maps of the erodibility of the sub-soil, and how this information can be used to schematize the sub-soil in computational models for morphological simulations. Local incisement of sand patches between areas with poorly erodible bed causes deep scour holes, hence increasing the risk on river-bank instability (flow slides) and damage to constructions such as groynes, quays, tunnels, and pipelines. Various types of mathematical models, ranging from 1D (SOBEK) to quasi-3D (Delft3D) have been applied to study the future development of the river bed and possible management options. The results of these approaches demonstrate that models require inclusion of a layer-bookkeeping approach for sub-soil schematization, non-uniform sediment fractions (sand-mud), tidal and river-discharge boundary conditions, and capacity-reduction transport modeling. For risk-reducing river management it has been shown how the development of the river bed can be addressed on a large scale and small scale. For instance, the use of sediment feeding and fixation of bed can be proposed for large-scale management, while monitoring and interventions at initiation of erosion can be proposed as response to small-scale developments that exceed predefined intervention levels

Cellular senescence in renal ageing and disease

Item does not contain fulltextThe senescence programme is implicated in diverse biological processes, including embryogenesis, tissue regeneration and repair, tumorigenesis, and ageing. Although in vivo studies of senescence are in their infancy, evidence suggesting that senescent cells are a heterogeneous cell type is accumulating: senescence can be induced by different stressors, and senescent cells have varying degrees of genomic and epigenomic instability and different cell origins, contributing to their diversity. Two main classes of senescent cells have been identified: acute and chronic senescent cells. Acute senescent cells are generated during coordinated, beneficial biological processes characterized by a defined senescence trigger, transient senescent-cell signalling functions, and eventual senescent-cell clearance. In contrast, chronic senescent cells arise more slowly from cumulative, diverse stresses and are inefficiently eliminated, leading to their accumulation and deleterious effects through a secretory phenotype. Senescent cells have been identified in many tissues and organs, including the kidney. Here, we discuss the emerging roles of senescent cells in renal development, homeostasis, and pathology. We also address how senotherapy, or targeting of senescent cells, might be used to improve renal function with normal ageing, disease, or therapy-induced damage

Understanding and managing the morphology of Rhine Delta branches incising into sand-clay deposits

In the Rhine-Meuse delta in the south-western part of the Netherlands, the morphology of the river branches is highly dependent on the erodibility of the subsoil. Erosion processes that were initiated after closure of the Haringvliet estuary branch by a dam (in 1970), caused a strong incision of several connecting branches. Due to the geological evolution of this area the lithology of the subsoil shows large variations in highly erodible sand and poorly erodible peat and clay layers. In this study is shown how the geological information can be used to create 3D maps of the erodibility of the sub-soil, and how this information can be used to schematize the sub-soil in computational models for morphological simulations. Local incisement of sand patches between areas with poorly erodible bed causes deep scour holes, hence increasing the risk on river-bank instability (flow slides) and damage to constructions such as groynes, quays, tunnels, and pipelines. Different types of mathematical models, ranging from 1D (SOBEK) to quasi-3D (Delft3D) have been applied to study the future development of the river bed and possible management options. The results of these approaches demonstrate that models require inclusion of a bookkeeping-layer approach for sub-soil schematization, non-uniform sediment fractions (sand-mud), tidal and river-discharge boundary conditions, and capacity-reduction transport modeling. For risk-reducing river management it has been shown how the development of the river bed can be addressed on a large scale and small scale. For instance, the use of sediment feeding and fixation of bed can be proposed for large-scale management, while monitoring and interventions at initiation of erosion can be proposed as response to small-scale developments that exceed predefined intervention levels.Hydraulic EngineeringCivil Engineering and Geoscience

River scale model of an training dam using lightweight granulates

Replacing existing river groynes with longitudinal training dams is considered as a promising flood mitigation measure in the main Dutch rivers, which can also serve to guarantee navigability during low flows and to create conditions favourable for ecological development. Whereas the bed response in the streamwise uniform part of a river trained by a longitudinal dam can be readily predicted, the bed response at the transition zones is unclear. In the present study, we investigate the local morphological effects resulting at the intake section of a longitudinal training dam, where the flow is distributed over the main channel and a side channel in between the dam and the river shore. A sediment recirculating model with a nearly undistorted geometry with respect to the prototype was setup. Lightweight polystyrene granulates were used as a surrogate for sediment, to properly scale the Shields parameter without compromising Froude scaling, and reach dynamical similarity. A laser scanner allowed collecting high-resolution bed elevation data. Results obtained under typical low flow and high flow conditions show a general deepening of the bed in the area adjacent to the training dam, in response to narrowing of the main channel. Scour at an upstream river groyne embedded in the model showed a scour hole which was deeper than realistic. Throughout the entire domain, bedforms developed featuring geometrical properties that reproduced the prototype conditions appropriately. Based on a comparison with characteristics from the River Waal, regarded as the prototype without a longitudinal dam, lightweight sediments were considered to be a proper choice for this study, in which bedload is the main sediment transport mode. The main conclusion regards the absence of significant morphodynamic developments at the intake section, both during the high flow experiment and during the low flow experiment, which can be attributed to the alignment of the dam with the local streamlines

Spartan deficiency causes accumulation of Topoisomerase 1 cleavage complexes and tumorigenesis

Contains fulltext : 174445.pdf (publisher's version ) (Open Access)Germline mutations in SPRTN cause Ruijs-Aalfs syndrome (RJALS), a disorder characterized by genome instability, progeria and early onset hepatocellular carcinoma. Spartan, the protein encoded by SPRTN, is a nuclear metalloprotease that is involved in the repair of DNA-protein crosslinks (DPCs). Although Sprtn hypomorphic mice recapitulate key progeroid phenotypes of RJALS, whether this model expressing low amounts of Spartan is prone to DPC repair defects and spontaneous tumors is unknown. Here, we showed that the livers of Sprtn hypomorphic mice accumulate DPCs containing Topoisomerase 1 covalently linked to DNA. Furthermore, these mice exhibited DNA damage, aneuploidy and spontaneous tumorigenesis in the liver. Collectively, these findings provide evidence that partial loss of Spartan impairs DPC repair and tumor suppression

Mosaic-variegated aneuploidy syndrome mutation or haploinsufficiency in Cep57 impairs tumor suppression

Item does not contain fulltextA homozygous truncating frameshift mutation in CEP57 (CEP57T/T) has been identified in a subset of mosaic-variegated aneuploidy (MVA) patients; however, the physiological roles of the centrosome-associated protein CEP57 that contribute to disease are unknown. To investigate these, we have generated a mouse model mimicking this disease mutation. Cep57T/T mice died within 24 hours after birth with short, curly tails and severely impaired vertebral ossification. Osteoblasts in lumbosacral vertebrae of Cep57T/T mice were deficient for Fgf2, a Cep57 binding partner implicated in diverse biological processes, including bone formation. Furthermore, a broad spectrum of tissues of Cep57T/T mice had severe aneuploidy at birth, consistent with the MVA patient phenotype. Cep57T/T mouse embryonic fibroblasts and patient-derived skin fibroblasts failed to undergo centrosome maturation in G2 phase, causing premature centriole disjunction, centrosome amplification, aberrant spindle formation, and high rates of chromosome missegregation. Mice heterozygous for the truncating frameshift mutation or a Cep57-null allele were overtly indistinguishable from WT mice despite reduced Cep57 protein levels, yet prone to aneuploidization and cancer, with tumors lacking evidence for loss of heterozygosity. This study identifies Cep57 as a haploinsufficient tumor suppressor with biologically diverse roles in centrosome maturation and Fgf2-mediated bone formation

Scale model of a training dam using lightweight granulates

Longitudinal training dams (LTDs) are a promising alternative for river groynes. Here we summarize findings of a recent study focused on the along river transition from a series of river groynes to an LTD, where the flow divides between the fairway and the side channel between the LTD and the river bank. A scale model is setup using lightweight granulates made of polystyrene to create conditions that are dynamically similar to a prototype situation in the River Waal. The key advantage of using lightweight granulates is that both the Shields number and the Froude number are similar in the model and the prototype. A high flow and a low flow experiment were carried out. The bedforms in the physical model have dimensions that correspond to theoretical dune height predictions, and also the channel incision due to width reduction is in accordance with expectations. The scour holes that develop near the tip of the groynes, however, are too deep, which may relate to improper scaling of the local turbulent vortices, initiated at the groynes. The morphodynamic developments in the flow divergence zone are subtle, and are overwhelmed by the mobile bed response to the presence of groynes. Considering that the physical model over-predicts the erosion caused by groynes, this suggests that the LTD configuration subject to study results in a comparatively stable bed morphology.Rivers, Ports, Waterways and Dredging Engineerin

Naturally occurring p16(Ink4a)-positive cells shorten healthy lifespan

Cellular senescence, a stress-induced irreversible growth arrest often characterized by expression of p16(Ink4a) (encoded by the Ink4a/Arf locus, also known as Cdkn2a) and a distinctive secretory phenotype, prevents the proliferation of preneoplastic cells and has beneficial roles in tissue remodelling during embryogenesis and wound healing. Senescent cells accumulate in various tissues and organs over time, and have been speculated to have a role in ageing. To explore the physiological relevance and consequences of naturally occurring senescent cells, here we use a previously established transgene, INK-ATTAC, to induce apoptosis in p16(Ink4a)-expressing cells of wild-type mice by injection of AP20187 twice a week starting at one year of age. We show that compared to vehicle alone, AP20187 treatment extended median lifespan in both male and female mice of two distinct genetic backgrounds. The clearance of p16(Ink4a)-positive cells delayed tumorigenesis and attenuated age-related deterioration of several organs without apparent side effects, including kidney, heart and fat, where clearance preserved the functionality of glomeruli, cardio-protective KATP channels and adipocytes, respectively. Thus, p16(Ink4a)-positive cells that accumulate during adulthood negatively influence lifespan and promote age-dependent changes in several organs, and their therapeutic removal may be an attractive approach to extend healthy lifespan