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Abstract Background Malaria remains one of the most devastating diseases globally, and the control of mosquitoes as the vector is mainly dependent on chemical insecticides. Elevated temperatures associated with future warmer climates could affect mosquitoes' metabolic enzyme expression and increase insecticide resistance, making vector control difficult. Understanding how mosquito rearing temperatures influence their susceptibility to insecticide and expression of metabolic enzymes could aid in the development of novel tools and strategies to control mosquitoes in a future warmer climate. This study evaluated the effects of temperature on the susceptibility of Anopheles gambiae sensu lato (s.l.) mosquitoes to pyrethroids and their expression of metabolic enzymes. Methods Anopheles gambiae s.l. eggs obtained from laboratory-established colonies were reared under eight temperature regimes (25, 28, 30, 32, 34, 36, 38, and 40 °C). Upon adult emergence, 3- to 5-day-old female non-blood-fed mosquitoes were used for susceptibility tests following the World Health Organization (WHO) bioassay protocol. Batches of 20–25 mosquitoes from each temperature regime (25–34 °C) were exposed to two pyrethroid insecticides (0.75% permethrin and 0.05% deltamethrin). In addition, the levels of four metabolic enzymes (α-esterase, β-esterase, glutathione S-transferase [GST], and mixed-function oxidase [MFO]) were examined in mosquitoes that were not exposed and those that were exposed to pyrethroids. Results Mortality in An. gambiae s.l. mosquitoes exposed to deltamethrin and permethrin decreased at temperatures above 28 °C. In addition, mosquitoes reared at higher temperatures were more resistant and had more elevated enzyme levels than those raised at low temperatures. Overall, mosquitoes that survived after being exposed to pyrethroids had higher levels of metabolic enzymes than those that were not exposed to pyrethroids. Conclusions This study provides evidence that elevated temperatures decreased An. gambiae s.l. mosquitoes' susceptibility to pyrethroids and increased the expression of metabolic enzymes. This evidence suggests that elevated temperatures projected in a future warmer climate could increase mosquitoes' resistance to insecticides and complicate malaria vector control measures. This study therefore provides vital information, and suggests useful areas of future research, on the effects of temperature variability on mosquitoes that could guide vector control measures in a future warmer climate. Graphical Abstract

Abstract Background Malaria remains one of the most devastating diseases globally, and the control of mosquitoes as the vector is mainly dependent on chemical insecticides. Elevated temperatures associated with future warmer climates could affect mosquitoes' metabolic enzyme expression and increase insecticide resistance, making vector control difficult. Understanding how mosquito rearing temperatures influence their susceptibility to insecticide and expression of metabolic enzymes could aid in the development of novel tools and strategies to control mosquitoes in a future warmer climate. This study evaluated the effects of temperature on the susceptibility of Anopheles gambiae sensu lato (s.l.) mosquitoes to pyrethroids and their expression of metabolic enzymes. Methods Anopheles gambiae s.l. eggs obtained from laboratory-established colonies were reared under eight temperature regimes (25, 28, 30, 32, 34, 36, 38, and 40 °C). Upon adult emergence, 3- to 5-day-old female non-blood-fed mosquitoes were used for susceptibility tests following the World Health Organization (WHO) bioassay protocol. Batches of 20–25 mosquitoes from each temperature regime (25–34 °C) were exposed to two pyrethroid insecticides (0.75% permethrin and 0.05% deltamethrin). In addition, the levels of four metabolic enzymes (α-esterase, β-esterase, glutathione S-transferase [GST], and mixed-function oxidase [MFO]) were examined in mosquitoes that were not exposed and those that were exposed to pyrethroids. Results Mortality in An. gambiae s.l. mosquitoes exposed to deltamethrin and permethrin decreased at temperatures above 28 °C. In addition, mosquitoes reared at higher temperatures were more resistant and had more elevated enzyme levels than those raised at low temperatures. Overall, mosquitoes that survived after being exposed to pyrethroids had higher levels of metabolic enzymes than those that were not exposed to pyrethroids. Conclusions This study provides evidence that elevated temperatures decreased An. gambiae s.l. mosquitoes' susceptibility to pyrethroids and increased the expression of metabolic enzymes. This evidence suggests that elevated temperatures projected in a future warmer climate could increase mosquitoes' resistance to insecticides and complicate malaria vector control measures. This study therefore provides vital information, and suggests useful areas of future research, on the effects of temperature variability on mosquitoes that could guide vector control measures in a future warmer climate. Graphical Abstract

Background: Fish entrainment through turbine intakes is one of the major issues for operators of hydropower facilities because it causes injury and/or mortality and adversely affects population abundance. Entrainment reduction strategies have been developed based on the behavior of downstream migrating fishes, particularly diadromous species. However, knowledge of the behavior of migratory fishes has very limited application for reducing the entrainment of resident fishes, including several species that represent important recreational and aboriginal fishery resources in reservoirs. In this study, we used fine-scale acoustic telemetry and state-space modeling to investigate behavioral attributes associated with entrainment risk of resident adult bull trout (Salvelinus confluentus) in a large hydropower reservoir in British Columbia, Canada. Results: We found that adult bull trout resided longer in the vicinity of the powerhouse and moved closer to the turbine intakes in the fall and particularly in the winter. Bull trout were more likely to engage in exploratory behavior (characteristic of foraging or reduced activity) during periods when their body temperature was lower or higher than 6°C. We also detected diel changes in behavioral attributes, with bull trout distance to intakes and probability of exploratory behavior slightly increasing at night. Conclusions: We hypothesize that the exploratory behavior in the forebay is associated with foraging for kokanee (nonanadromous form of Oncorhynchus nerka), which have been shown to congregate near the dams of hydropower reservoirs in the winter. Our study findings should be applicable to bull trout populations residing in other reservoirs and indicate that entrainment mitigation (for example, use of deterrent devices) should be focused on the fall and winter. This work also provides a framework for combining acoustic telemetry and state-space models to understand and categorize movement behavior of fish in reservoirs and, more generally, in any environment with fluctuating water levels.

Background: Fish entrainment through turbine intakes is one of the major issues for operators of hydropower facilities because it causes injury and/or mortality and adversely affects population abundance. Entrainment reduction strategies have been developed based on the behavior of downstream migrating fishes, particularly diadromous species. However, knowledge of the behavior of migratory fishes has very limited application for reducing the entrainment of resident fishes, including several species that represent important recreational and aboriginal fishery resources in reservoirs. In this study, we used fine-scale acoustic telemetry and state-space modeling to investigate behavioral attributes associated with entrainment risk of resident adult bull trout (Salvelinus confluentus) in a large hydropower reservoir in British Columbia, Canada. Results: We found that adult bull trout resided longer in the vicinity of the powerhouse and moved closer to the turbine intakes in the fall and particularly in the winter. Bull trout were more likely to engage in exploratory behavior (characteristic of foraging or reduced activity) during periods when their body temperature was lower or higher than 6°C. We also detected diel changes in behavioral attributes, with bull trout distance to intakes and probability of exploratory behavior slightly increasing at night. Conclusions: We hypothesize that the exploratory behavior in the forebay is associated with foraging for kokanee (nonanadromous form of Oncorhynchus nerka), which have been shown to congregate near the dams of hydropower reservoirs in the winter. Our study findings should be applicable to bull trout populations residing in other reservoirs and indicate that entrainment mitigation (for example, use of deterrent devices) should be focused on the fall and winter. This work also provides a framework for combining acoustic telemetry and state-space models to understand and categorize movement behavior of fish in reservoirs and, more generally, in any environment with fluctuating water levels.

The latest information from Hiroshima and Nagasaki on radiation-induced cancer in man includes new DS86 dose assignments and extension of the Life-Span Study Sample cohort through 1985. The implications of these new doses and updated data for the assessment of cancer risk at low to moderate doses have been evaluated. Results from the fitting of three dose-response models (linear, quadratic, linear-quadratic) to the data at doses less than 1.5 Gy are reported. Based on statistical analyses of the authors' results, comments are made concerning the possible shapes of dose-response curves for human cancer.

The latest information from Hiroshima and Nagasaki on radiation-induced cancer in man includes new DS86 dose assignments and extension of the Life-Span Study Sample cohort through 1985. The implications of these new doses and updated data for the assessment of cancer risk at low to moderate doses have been evaluated. Results from the fitting of three dose-response models (linear, quadratic, linear-quadratic) to the data at doses less than 1.5 Gy are reported. Based on statistical analyses of the authors' results, comments are made concerning the possible shapes of dose-response curves for human cancer.

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.