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BackgroundAlcohol abuse is a risk factor for bone damage and fracture‐related complications. Through precise β‐catenin signaling, canonical Wnt signaling plays a key role in fracture repair by promoting the differentiation of new bone and cartilage cells. In this study, we examined the effects of alcohol on the Wnt pathway in injured bone using a murine model of alcohol‐induced impaired fracture healing.MethodsMale C57Bl/6 or T cell factor (TCF)‐transgenic mice were administered 3 daily intraperitoneal doses of alcohol or saline. One hour following the final injection, mice were subjected to a stabilized, mid‐shaft tibial fracture. Injured and contralateral tibias were harvested at 6, 9, or 14 days post‐fracture for the analysis of biomechanical strength, callus tissue composition, and Wnt/β‐catenin signaling.ResultsAcute alcohol treatment was associated with a significant decrease in fracture callus volume, diameter, and biomechanical strength at day 14 post‐fracture. Histology revealed an alcohol‐related reduction in cartilage and bone formation at the fracture site, and that alcohol inhibited normal cartilage maturation. Acute alcohol exposure caused a significant 2.3‐fold increase in total β‐catenin protein at day 6 and a significant decrease of 53 and 56% at days 9 and 14, respectively. lacZ staining in β‐galactosidase‐expressing TCF‐transgenic mice revealed spatial and quantitative differences in Wnt‐specific transcriptional activation at day 6 in the alcohol group. Days 9 and 14 post‐fracture showed that acute alcohol exposure decreased Wnt transcriptional activation, which correlates with the modulation of total β‐catenin protein levels observed at these time points.ConclusionsAcute alcohol exposure resulted in significant impairment of fracture callus tissue formation, perturbation of the key Wnt pathway protein β‐catenin, and disruption of normal Wnt‐mediated transcription. These data suggest that the canonical Wnt pathway is a target for alcohol in bone and may partially explain why impaired fracture healing is observed in alcohol‐abusing individuals.

BackgroundAlcohol abuse is a risk factor for bone damage and fracture‐related complications. Through precise β‐catenin signaling, canonical Wnt signaling plays a key role in fracture repair by promoting the differentiation of new bone and cartilage cells. In this study, we examined the effects of alcohol on the Wnt pathway in injured bone using a murine model of alcohol‐induced impaired fracture healing.MethodsMale C57Bl/6 or T cell factor (TCF)‐transgenic mice were administered 3 daily intraperitoneal doses of alcohol or saline. One hour following the final injection, mice were subjected to a stabilized, mid‐shaft tibial fracture. Injured and contralateral tibias were harvested at 6, 9, or 14 days post‐fracture for the analysis of biomechanical strength, callus tissue composition, and Wnt/β‐catenin signaling.ResultsAcute alcohol treatment was associated with a significant decrease in fracture callus volume, diameter, and biomechanical strength at day 14 post‐fracture. Histology revealed an alcohol‐related reduction in cartilage and bone formation at the fracture site, and that alcohol inhibited normal cartilage maturation. Acute alcohol exposure caused a significant 2.3‐fold increase in total β‐catenin protein at day 6 and a significant decrease of 53 and 56% at days 9 and 14, respectively. lacZ staining in β‐galactosidase‐expressing TCF‐transgenic mice revealed spatial and quantitative differences in Wnt‐specific transcriptional activation at day 6 in the alcohol group. Days 9 and 14 post‐fracture showed that acute alcohol exposure decreased Wnt transcriptional activation, which correlates with the modulation of total β‐catenin protein levels observed at these time points.ConclusionsAcute alcohol exposure resulted in significant impairment of fracture callus tissue formation, perturbation of the key Wnt pathway protein β‐catenin, and disruption of normal Wnt‐mediated transcription. These data suggest that the canonical Wnt pathway is a target for alcohol in bone and may partially explain why impaired fracture healing is observed in alcohol‐abusing individuals.

New transparent optodes for life-time based microscopic imaging of O₂ were developed by spin-coating a μm-thin layer of a highly luminescent cyclometalated iridium(III) coumarin complex in polystyrene onto glass cover slips. Compared to similar thin-film O₂ optodes based on a ruthenium(II) polypyridyl complex or a platinum(II) porphyrin, the new planar sensors have i) higher brightness allowing for much shorter exposure times and thus higher time resolution, ii) more homogeneous and smaller pixel to pixel variation over the sensor area resulting in less noisy O₂ images, and iii) a lower temperature dependency simplifying calibration procedures. We used the new optodes for microscopic imaging of the spatio-temporal O₂ dynamics at the base of heterotrophic biofilms in combination with confocal imaging of bacterial biomass and biofilm structure. This allowed us to directly link biomass distribution to O₂ distribution under both steady state and non-steady state conditions. We demonstrate that the O₂ dynamics in biofilms is governed by a complex interaction between biomass distribution, mass transfer and flow that cannot be directly inferred from structural information on biomass distribution alone.

New transparent optodes for life-time based microscopic imaging of O₂ were developed by spin-coating a μm-thin layer of a highly luminescent cyclometalated iridium(III) coumarin complex in polystyrene onto glass cover slips. Compared to similar thin-film O₂ optodes based on a ruthenium(II) polypyridyl complex or a platinum(II) porphyrin, the new planar sensors have i) higher brightness allowing for much shorter exposure times and thus higher time resolution, ii) more homogeneous and smaller pixel to pixel variation over the sensor area resulting in less noisy O₂ images, and iii) a lower temperature dependency simplifying calibration procedures. We used the new optodes for microscopic imaging of the spatio-temporal O₂ dynamics at the base of heterotrophic biofilms in combination with confocal imaging of bacterial biomass and biofilm structure. This allowed us to directly link biomass distribution to O₂ distribution under both steady state and non-steady state conditions. We demonstrate that the O₂ dynamics in biofilms is governed by a complex interaction between biomass distribution, mass transfer and flow that cannot be directly inferred from structural information on biomass distribution alone.

Public policy requires public support, which in turn implies a need to enable the public not just to understand policy but also to be engaged in its development. Where complex science and technology issues are involved in policy making, this takes time, so it is important to identify emerging issues of this type and prepare engagement plans. In our horizon scanning exercise, we used a modified Delphi technique. A wide group of people with interests in the science and policy interface (drawn from policy makers, policy adviser, practitioners, the private sector and academics) elicited a long list of emergent policy issues in which science and technology would feature strongly and which would also necessitate public engagement as policies are developed. This was then refined to a short list of top priorities for policy makers. Thirty issues were identified within broad areas of business and technology; energy and environment; government, politics and education; health, healthcare, population and aging; information, communication, infrastructure and transport; and public safety and national security.

Public policy requires public support, which in turn implies a need to enable the public not just to understand policy but also to be engaged in its development. Where complex science and technology issues are involved in policy making, this takes time, so it is important to identify emerging issues of this type and prepare engagement plans. In our horizon scanning exercise, we used a modified Delphi technique. A wide group of people with interests in the science and policy interface (drawn from policy makers, policy adviser, practitioners, the private sector and academics) elicited a long list of emergent policy issues in which science and technology would feature strongly and which would also necessitate public engagement as policies are developed. This was then refined to a short list of top priorities for policy makers. Thirty issues were identified within broad areas of business and technology; energy and environment; government, politics and education; health, healthcare, population and aging; information, communication, infrastructure and transport; and public safety and national security.