Influence of the hypoxic cell sensitizer misonidazole on the proliferation of well-oxygenated cells in vitro during prolonged exposure.

Analysis of time-lapse cinematographic film permitted the construction of pedigrees from 88 well oxygenated cells of a mouse osteosarcoma (MOS). These cells have been chronically treated with various concentrations of the hypoxic cell sensitizer misonidazole (MIS) over periods of up to 96 h. At concentrations of 0.5 and 7 mM there is a 2--3 h increase in cell-cycle time. Concentrations of 2 mM show an intermitotic time delay of 7.6--10.3 h. At 4 mM cells divided only once. With increasing drug concentration there was an increase in the number of abnormal mitoses. These results were compared with cloning efficiency (PE) experiments. PE at 0.5 mM is 80%, at 1 mM 40 and at 2 mM is reduced to 4%. Cells treated with 2mM MIS over a period of 28.6 h resume their normal cycle when the drug is washed from the culture. This may indicate that DNA is not a major target for MIS. It is concluded that this hypoxic cell sensitizer is also toxic for MOS cells in well oxygenated conditions

Benchmarking the vertically integrated ice-sheet model IMAU-ICE (version 2.0)

Ice-dynamical processes constitute a large uncertainty in future projections of sea-level rise caused by anthropogenic climate change. Improving our understanding of these processes requires ice-sheet models that perform well at simulating both past and future ice-sheet evolution. Here, we present version 2.0 of the ice-sheet model IMAU-ICE, which uses the depth-integrated viscosity approximation (DIVA) to solve the stress balance. We evaluate its performance in a range of benchmark experiments, including simple analytical solutions and both schematic and realistic model intercomparison exercises. IMAU-ICE has adopted recent developments in the numerical treatment of englacial stress and sub-shelf melt near the grounding line, which result in good performance in experiments concerning grounding-line migration (MISMIP, MISMIP+) and buttressing (ABUMIP). This makes it a model that is robust, versatile, and user-friendly, which will provide a firm basis for (palaeo-)glaciological research in the coming years.publishedVersio

Juiste zorg begint bij de basis: structurele aandacht voor suïcidepreventie in de opleidingen tot hulpverlener in de ggz

Stress and Psychopatholog

Active caspase-3 is removed from cells by release of caspase-3-enriched vesicles

AbstractCleavage of Rho associated Coiled Coil kinase I (ROCK I) by caspase-3 contributes to membrane blebbing. Whether caspase-3 and ROCK I also play a role in the release of membrane vesicles is unknown. Therefore, we transfected a human breast cancer cell line (MCF-7) that is caspase-3 deficient, lacks membrane blebbing, and does not release membrane vesicles, with caspase-3. Cells expressing caspase-3 demonstrate both ROCK I-mediated membrane blebbing, and release of small (400–600nm) membrane vesicles in a ROCK I-independent manner. These membrane vesicles contain caspase-3, and are enriched in caspase-3 activity compared to the releasing cells. Caspase-3-containing vesicles are taken up by untransfected cells but the cells do not show any sign of apoptosis. In conclusion, we show that the release of caspase-3-enriched membrane vesicles and membrane blebbing are two differentially regulated processes. Furthermore, we hypothesize that packaging of caspase-3 into membrane vesicles contributes to cellular homeostasis by the removal of caspase-3, and concurrently, protects the cells' environment from direct exposure to caspase-3 activity

Marine stepping‐stones: Connectivity of Mytilus edulis populations between offshore energy installations

Recent papers have suggested that epifaunal organisms use artificial structures as stepping‐stones to spread to areas that are too distant to reach in a single generation. With thousands of artificial structures present in the North Sea, we test the hypothesis that these structures are connected by water currents and act as an interconnected reef. Population genetic structure of the blue mussel, Mytilus edulis, was expected to follow a pattern predicted by a particle tracking model (PTM). Correlation between population genetic differentiation, based on microsatellite markers, and particle exchange was tested. Specimens of M. edulis were found at each location, although the PTM indicated that locations >85 km offshore were isolated from coastal subpopulations. The fixation coefficient FST correlated with the number of arrivals in the PTM. However, the number of effective migrants per generation as inferred from coalescent simulations did not show a strong correlation with the arriving particles. Isolation by distance analysis showed no increase in isolation with increasing distance and we did not find clear structure among the populations. The marine stepping‐stone effect is obviously important for the distribution of M. edulis in the North Sea and it may influence ecologically comparable species in a similar way. In the absence of artificial shallow hard substrates, M. edulis would be unlikely to survive in offshore North Sea waters

Benchmarking the vertically integrated ice-sheet model IMAU-ICE (version 2.0)

Ice-dynamical processes constitute a large uncertainty in future projections of sea-level rise caused by anthropogenic climate change. Improving our understanding of these processes requires ice-sheet models that perform well at simulating both past and future ice-sheet evolution. Here, we present version 2.0 of the ice-sheet model IMAU-ICE, which uses the depth-integrated viscosity approximation (DIVA) to solve the stress balance. We evaluate its performance in a range of benchmark experiments, including simple analytical solutions and both schematic and realistic model intercomparison exercises. IMAU-ICE has adopted recent developments in the numerical treatment of englacial stress and sub-shelf melt near the grounding line, which result in good performance in experiments concerning grounding-line migration (MISMIP, MISMIP+) and buttressing (ABUMIP). This makes it a model that is robust, versatile, and user-friendly, which will provide a firm basis for (palaeo-)glaciological research in the coming years

Modelling feedbacks between the Northern Hemisphere ice sheets and climate during the last glacial cycle

During the last glacial cycle (LGC), ice sheets covered large parts of Eurasia and North America, which resulted in ∼120 m of sea level change. Ice sheet-climate interactions have considerable influence on temperature and precipitation patterns and therefore need to be included when simulating this time period. Ideally, ice sheet-climate interactions are simulated by a high-resolution Earth system model. While these models are capable of simulating climates at a certain point in time, such as the pre-industrial (PI) or the Last Glacial Maximum (LGM; 21 000 years ago), a full transient glacial cycle is currently computationally unfeasible as it requires a too-large amount of computation time. Nevertheless, ice sheet models require forcing that captures the gradual change in climate over time to calculate the accumulation and melt of ice and its effect on ice sheet extent and volume changes. Here we simulate the LGC using an ice sheet model forced by LGM and PI climates. The gradual change in climate is modelled by transiently interpolating between pre-calculated results from a climate model for the LGM and the PI. To assess the influence of ice sheet-climate interactions, we use two different interpolation methods: the climate matrix method, which includes a temperature-albedo and precipitation-topography feedback, and the glacial index method, which does not. To investigate the sensitivity of the results to the prescribed climate forcing, we use the output of several models that are part of the Paleoclimate Modelling Intercomparison Project Phase III (PMIP3). In these simulations, ice volume is prescribed, and the climate is reconstructed with a general circulation model (GCM). Here we test those models by using their climate to drive an ice sheet model over the LGC. We find that the ice volume differences caused by the climate forcing exceed the differences caused by the interpolation method. Some GCMs produced unrealistic LGM volumes, and only four resulted in reasonable ice sheets, with LGM Northern Hemisphere sea level contribution ranging between 74-113 m with respect to the present day. The glacial index and climate matrix methods result in similar ice volumes at the LGM but yield a different ice evolution with different ice domes during the inception phase of the glacial cycle and different sea level rates during the deglaciation phase. The temperature-albedo feedback is the main cause of differences between the glacial index and climate matrix methods