3D simulation of remodeling at the level of the cell and its deregulation in disuse

A load-adaptive bone remodeling theory is used to simulate remodeling at the level of the cell in threedimensional models. It was found that the theory can successfully explain the formation of hemi-osteons in trabecular bone and full osteons in cortical bone and their deregulation after disuse. Introduction: Osteoporosis can occur as the result of mechanical disuse. In recent studies, we developed a remodeling theory that explains bone remodeling at the level of the cell as the result of changes in local mechanical loading that is sensed by osteocytes which then regulate osteoblast and osteoclast activity. Using two-dimensional computer simulation modeling, we demonstrated that this theory can explain the coupling between osteoclast and osteoblast cells, the formation of trabeculae and cortical osteons, and their adaptation to changes in mechanical loading. The goal of the present study was to extend the modeling to three dimensions and to investigate if it can explain the three-dimensional direction of resorption and the coupling of formation as well as the effects of disuse at the level of the cell. Methods: Finite element analysis is used to calculate the local mechanical strains resulting from external loads acting on the bone structure that either represents a single trabeculae or a cortical osteon. Osteocytes within the bone are modeled to sense mechanical loading and emit a signal. This signal inhibits attachment of osteoclasts, which are explicitly represented using a cell simulation model, and stimulates bone formation by osteoblasts. Osteon development was simulated starting from an initial resorption cavity, first for normal and second for 25% reduced loading conditions. Results: In the cortical volume, cylindrical osteons aligned to the principal loading direction developed. In the modeled trabecula, osteoclasts moved along the surface, creating hemi-osteons. In both situations, a clear coupling between osteoclast and osteoblast activity was found. Reducing the load resulted in increased osteon diameter in cortical bone and perforation of the trabecula. Discussion: The model successfully captured typical bone remodeling characteristics at the level of the cell as a result of the strain-induced osteocyte signaling theory. Changes in remodeling after simulation of disuse concur with observations reported in the literature

The structure of the lantibiotic lacticin 481 produced by Lactococcus lactis: Location of the thioether bridges

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Rare mutations in XRCC2 increase the risk of breast cancer

Item does not contain fulltextAn exome-sequencing study of families with multiple breast-cancer-affected individuals identified two families with XRCC2 mutations, one with a protein-truncating mutation and one with a probably deleterious missense mutation. We performed a population-based case-control mutation-screening study that identified six probably pathogenic coding variants in 1,308 cases with early-onset breast cancer and no variants in 1,120 controls (the severity grading was p < 0.02). We also performed additional mutation screening in 689 multiple-case families. We identified ten breast-cancer-affected families with protein-truncating or probably deleterious rare missense variants in XRCC2. Our identification of XRCC2 as a breast cancer susceptibility gene thus increases the proportion of breast cancers that are associated with homologous recombination-DNA-repair dysfunction and Fanconi anemia and could therefore benefit from specific targeted treatments such as PARP (poly ADP ribose polymerase) inhibitors. This study demonstrates the power of massively parallel sequencing for discovering susceptibility genes for common, complex diseases

Rare mutations in XRCC2 increase the risk of breast cancer

Item does not contain fulltextAn exome-sequencing study of families with multiple breast-cancer-affected individuals identified two families with XRCC2 mutations, one with a protein-truncating mutation and one with a probably deleterious missense mutation. We performed a population-based case-control mutation-screening study that identified six probably pathogenic coding variants in 1,308 cases with early-onset breast cancer and no variants in 1,120 controls (the severity grading was p < 0.02). We also performed additional mutation screening in 689 multiple-case families. We identified ten breast-cancer-affected families with protein-truncating or probably deleterious rare missense variants in XRCC2. Our identification of XRCC2 as a breast cancer susceptibility gene thus increases the proportion of breast cancers that are associated with homologous recombination-DNA-repair dysfunction and Fanconi anemia and could therefore benefit from specific targeted treatments such as PARP (poly ADP ribose polymerase) inhibitors. This study demonstrates the power of massively parallel sequencing for discovering susceptibility genes for common, complex diseases

Ex Post Evaluation of Thirty Years of Compact Urban Development in the Netherlands

Despite the wide array of academic research, the impacts of compact urban development are not very well understood. What is lacking are, firstly, the insights into how a region or country would have appeared under policy regimes other than those realised and, secondly, a broad evaluation of relevant land-use, transport, accessibility and related societal and ecological impacts. Here, we report on an initial attempt to establish a methodology and evaluation framework for analysing the effectiveness of Dutch compact urbanisation policies implemented between 1970 and 2000. Our conclusion is that without compact urban development policies, urban sprawl in the Netherlands would have likely been greater, car use would have been higher at the cost of alternative modes, emission and noise levels in residential and natural environments, and the fragmentation of wildlife habitats would have been higher.Technology, Policy and Managemen

Evaluating expert-based habitat suitability information of terrestrial mammals with GPS-tracking data

In our paper "Evaluating expert-based habitat suitability information of terrestrial mammals with GPS-tracking data" (Global Ecology and Biogeography) we use GPS tracking data from 1,498 from 49 different species to evaluate the expert-based habitat suitability data from the International Union for Conservation of Nature (IUCN). Therefore, we used the GPS tracking data to estimate two measures of habitat suitability for each individual animal and habitat type: proportional habitat use (proportion of GPS locations within a habitat type), and selection ratio (habitat use relative to its availability). For each individual we then evaluated whether the GPS-based habitat suitability measures were in agreement with the IUCN data. To that end, we calculated the probability that the ranking of empirical habitat suitability measures was in agreement with IUCN’s classification into suitable, marginal and unsuitable habitat types. Our results showed that IUCN habitat suitability data were in accordance with the GPS data (>95% probability of agreement) for 33 out of 49 species based on proportional habitat use estimates and for 25 out of 49 species based on selection ratios. In addition, 37 and 34 species had a >50% probability of agreement based on proportional habitat use and selection ratios, respectively. These findings indicate that for the majority of species included in this study, it is appropriate to use IUCN habitat suitability data in macroecological studies. Furthermore, our study shows that GPS tracking data can be used to identify and prioritize species and habitat types for re-evaluation of IUCN habitat suitability data. In this dataset we provide the measures of habitat suitability for each individual and each habitat type, calculated using different methods. In addition, we provide data on the body mass and IUCN Red List category of the species, as well as whether the species can be considered a habitat specialist or habitat generalist

Data of "Evaluating expert-based habitat suitability information of terrestrial mammals with GPS-tracking data"

In our paper "Evaluating expert-based habitat suitability information of terrestrial mammals with GPS-tracking data" (Global Ecology and Biogeography) we use GPS tracking data from 1,498 from 49 different species to evaluate the expert-based habitat suitability data from the International Union for Conservation of Nature (IUCN). Therefore, we used the GPS tracking data to estimate two measures of habitat suitability for each individual animal and habitat type: proportional habitat use (proportion of GPS locations within a habitat type), and selection ratio (habitat use relative to its availability). For each individual we then evaluated whether the GPS-based habitat suitability measures were in agreement with the IUCN data. To that end, we calculated the probability that the ranking of empirical habitat suitability measures was in agreement with IUCN’s classification into suitable, marginal and unsuitable habitat types. Our results showed that IUCN habitat suitability data were in accordance with the GPS data (>95% probability of agreement) for 33 out of 49 species based on proportional habitat use estimates and for 25 out of 49 species based on selection ratios. In addition, 37 and 34 species had a >50% probability of agreement based on proportional habitat use and selection ratios, respectively. These findings indicate that for the majority of species included in this study, it is appropriate to use IUCN habitat suitability data in macroecological studies. Furthermore, our study shows that GPS tracking data can be used to identify and prioritize species and habitat types for re-evaluation of IUCN habitat suitability data. In this dataset we provide the measures of habitat suitability for each individual and each habitat type, calculated using different methods. In addition, we provide data on the body mass and IUCN Red List category of the species, as well as whether the species can be considered a habitat specialist or habitat generalist