DUX4c Is Up-Regulated in FSHD. It Induces the MYF5 Protein and Human Myoblast Proliferation

Facioscapulohumeral muscular dystrophy (FSHD) is a dominant disease linked to contractions of the D4Z4 repeat array in 4q35. We have previously identified a double homeobox gene (DUX4) within each D4Z4 unit that encodes a transcription factor expressed in FSHD but not control myoblasts. DUX4 and its target genes contribute to the global dysregulation of gene expression observed in FSHD. We have now characterized the homologous DUX4c gene mapped 42 kb centromeric of the D4Z4 repeat array. It encodes a 47-kDa protein with a double homeodomain identical to DUX4 but divergent in the carboxyl-terminal region. DUX4c was detected in primary myoblast extracts by Western blot with a specific antiserum, and was induced upon differentiation. The protein was increased about 2-fold in FSHD versus control myotubes but reached 2-10-fold induction in FSHD muscle biopsies. We have shown by Western blot and by a DNA-binding assay that DUX4c over-expression induced the MYF5 myogenic regulator and its DNA-binding activity. DUX4c might stabilize the MYF5 protein as we detected their interaction by co-immunoprecipitation. In keeping with the known role of Myf5 in myoblast accumulation during mouse muscle regeneration DUX4c over-expression activated proliferation of human primary myoblasts and inhibited their differentiation. Altogether, these results suggested that DUX4c could be involved in muscle regeneration and that changes in its expression could contribute to the FSHD pathology

Empirische analyse van de relatie tussen overstromingen en landgebruik

Vergeleken met verzegelde of vegetatie-arme landgebruikstypes leiden bos- en natuursystemen tot vertraagde en verminderde afstroming van water naar de waterlopen. Door in te zetten op behoud en de oordeelkundige aanleg van nieuwe bos- en natuursystemen kunnen deze ecosystemen meer bijdragen aan de vermindering van de frequentie, uitgebreidheid en impact van benedenstroomse overstromingen. Om de hypothese te testen dat de toenemende urbanisatie en verlies aan (semi-)natuurlijke ecosystemen in Vlaanderen een impact hebben op benedenstroomse overstromingen, werden geodata van historische overstromingen en landgebruik (1988-2016) geanalyseerd aan de hand van multivariate regressieanalyse en machine learning technieken. De voorlopige resultaten bevestigen de verwachting dat er een positieve correlatie bestaat tussen de uitgebreidheid van verharding en de ernst van overstromingen.status: publishe

A data-driven analysis, and its limitations, of the spatial flood archive of Flanders, Belgium to assess the impact of soil sealing on flood volume and extent.

Soil sealing increases surface runoff in a watershed and decreases infiltration into the soil. Consequently, urbanization poses a significant challenge for watershed management to mitigate faster runoff accumulation downstream and associated floods. Hydrological models are often employed to assess the impact of land-use dynamics on flood events. Alternatively, data-driven approaches combining time series of land use geodatasets and georeferenced flooded zones also allow to assess the relationship between soil sealing and flood severity. This study presents such data-driven analysis using a spatially explicit archive of flooded areas dating back to 1988 in the Flanders region of Belgium, which is characterized by urban sprawl. This archived data, along with time series of rainfall and land use, were analyzed for three middle-sized river subbasins using two machine learning methods: boosted regression trees and support vector regression. The machine learning methods were found suitable for this type of analysis, since their flexibility allows for spatially explicit models with larger sample sizes. However, the relationship between soil sealing and flood volume and extent could not be conclusively confirmed by our models. This may be due to data limitations, such as the limited number of recorded historical floods, inaccuracies in recorded historical flood polygons and inconsistencies in the land use classifications. It is therefore stressed that continued consistent monitoring of floods and land use changes is required

A data-driven analysis, and its limitations, of the spatial flood archive of Flanders, Belgium to assess the impact of soil sealing on flood volume and extent

Soil sealing increases surface runoff in a watershed and decreases infiltration into the soil. Consequently, urbanization poses a significant challenge for watershed management to mitigate faster runoff accumulation downstream and associated floods. Hydrological models are often employed to assess the impact of land-use dynamics on flood events. Alternatively, data-driven approaches combining time series of land use geodatasets and georeferenced flooded zones also allow to assess the relationship between soil sealing and flood severity. This study presents such data-driven analysis using a spatially explicit archive of flooded areas dating back to 1988 in the Flanders region of Belgium, which is characterized by urban sprawl. This archived data, along with time series of rainfall and land use, were analyzed for three middle-sized river subbasins using two machine learning methods: boosted regression trees and support vector regression. The machine learning methods were found suitable for this type of analysis, since their flexibility allows for spatially explicit models with larger sample sizes. However, the relationship between soil sealing and flood volume and extent could not be conclusively confirmed by our models. This may be due to data limitations, such as the limited number of recorded historical floods, inaccuracies in recorded historical flood polygons and inconsistencies in the land use classifications. It is therefore stressed that continued consistent monitoring of floods and land use changes is required.status: publishe

Identifying upstream locations which are critical for downstream floods

Soil sealing affects the hydrological processes in a watershed by increasing the surface runoff and decreasing infiltration into the soil. Consequently, urbanization poses a significant challenge for watershed management to mitigate the accumulation of runoff downstream and the associated occurrence and severity of flood events. Hydrological models are often employed to assess the impact of land-use dynamics on flood events and, conversely, the fraction of sealed soil is a common variable in conceptual, lumped or spatially distributed, mechanistic models. However, with the availability of longer time series of observed georeferenced flooded zones (derived from satellite sensors or compiled by ad hoc observations), there is now the opportunity to assess the relationship between soil sealing and flood frequency and severity in a data-driven approach taking the meteorological conditions and landscape configuration into account. An empirical, data-driven analysis was performed in Flanders, a highly urbanized region in Belgium parts of which are prone to flooding, to assess the impact of soil sealing on flood events using a spatially explicit archive of the flooded areas dating back to 1988. Data from this archive, along with time series of rainfall, river discharge and land use data, were collected for three middle-sized river basins, and analyzed using three methods: a linear regression and two machine learning techniques, boosted regression trees and support vector regression. The results of these analyses show that the hypothesis that more soil sealing would lead to more severe floods downstream taking into account rainfall characteristics, is only partially confirmed: there are still data limitations to overcome, which also affect the performance of spatial decision support systems.status: publishe

Data driven assessment of the impact of upstream soil sealing on downstream floods in Flanders, Belgium

Soil sealing affects the hydrological processes in a watershed by increasing the surface runoff and decreasing infiltration into the soil. Consequently, urbanization poses a significant challenge for watershed management to mitigate the accumulation of runoff downstream and the associated occurrence and severity of flood events. Hydrological models are often employed to assess the impact of land-use dynamics on flood events and, conversely, the fraction of sealed soil is a common variable in conceptual, lumped or spatially distributed, mechanistic models. However, with the availability of longer time series of observed georeferenced flooded zones (derived from satellite sensors or compiled by ad hoc observations), there is now the opportunity to assess the relationship between soil sealing and flood frequency and severity in a data-driven approach taking the meteorological conditions and landscape configuration into account. An empirical, data-driven analysis was performed in Flanders, a highly urbanized region in Belgium parts of which are prone to flooding, to assess the impact of soil sealing on flood events using a spatially explicit archive of the flooded areas dating back to 1988. Data from this archive, along with time series of rainfall, river discharge and land use data, were collected for three middle-sized river basins, and analyzed using three methods: a linear regression and two machine learning techniques, boosted regression trees and support vector regression. The results of these analyses show that the hypothesis that more soil sealing would lead to more severe floods downstream taking into account rainfall characteristics, is only partially confirmed: there are still data limitations to overcome, which also affect the performance of spatial decision support systems.status: publishe

Flood insurance value of land use systems and its application in spatial planning

So far science, policy nor the insurance business have devoted targeted attention to the capacity of ecosystems to mitigate the intensity and impact of naturally occurring damaging events. This capacity is rather obvious though for ecosystems capable of storing excess water, hence preventing or mitigating flooding of downstream settlements or ecosystems acting as wind breaks hence reducing storm damage of nearby infrastructure. The damage-preventing and reducing capacity of ecosystems can be interpreted as another ecosystem service expressed in terms of the ecosystems’ insurance value. In an insurance business logic, the presence of ecosystems with a given preventive or ex-ante insurance value can be seen as a complement to the traditional financial insurance system meant to compensate people ex-post for damage to their assets due to natural disasters. Whereas financial insurances cover damages resulting from natural hazards, but do not reduce these hazards, ecosystem insurance has the capacity to reduce the risk, but does not compensate for the damages. With regard to flood control and damage mitigation, investing in the proper ecosystem management upstream can be viewed as a mostly societal ex-ante payment for an ecosystem insurance which could lead to reduced individual financial insurance premiums. In this paper we further develop the concept of ‘insurance value of ecosystems’ and its relationship with the financial insurance logic. We illustrate the applicability for the case of flood risk and damage mitigation in the region of Flanders in Belgium and highlight the role of spatial planning and targeted ecosystem management practices to maximize the insurance value of ecosystems. We argue that such applications require spatially explicit information and decision support tools for addressing the typically off-site effects of ecosystems where it regards their insurance service.status: publishe

The insurance value of ecosystems: concept and applicability

So far science, policy nor the insurance business have devoted targeted attention to the capacity of ecosystems to mitigate the intensity and impact of naturally occurring damaging events. This capacity is rather obvious though for ecosystems capable of storing excess water, hence preventing or mitigating flooding of downstream settlements or ecosystems acting as wind breaks hence reducing storm damage of nearby infrastructure. The damagepreventing and reducing capacity of ecosystems can be interpreted as another ecosystem service expressed in terms of the ecosystems’ insurance value. In an insurance business logic, the presence of ecosystems with a given preventive or exante insurance value can be seen as a complement to the traditional financial insurance system meant to compensate people ex-post for damage to their assets due to natural disasters. Whereas financial insurances cover damages resulting from natural hazards, but do not reduce these hazards, ecosystem insurance has the capacity to reduce the risk, but does not compensate for the damages. With regard to flood control and damage mitigation, investing in the proper ecosystem management upstream can be viewed as a mostly societal ex-ante payment for an ecosystem insurance which could lead to reduced individual financial insurance premiums. In this paper we further develop the concept of ‘insurance value of ecosystems’ and its relationship with the financial insurance logic. We illustrate the applicability for the case of flood risk and damage mitigation in the region of Flanders in Belgium and highlight the role of spatial planning and targeted ecosystem management practices to maximize the insurance value of ecosystems. We argue that such applications require spatially explicit information and decision support tools for addressing the typically off-site effects of ecosystems where it regards their insurance service.status: publishe