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Background: Activation of the transcription factor NF-κB and expression of pro-inflammatory mediators have been considered as major events of acute pancreatitis (AP). Karyopherin alpha 2 (KPNA2), a member of the importin α family, reportedly modulates p65 subcellular localization.Aim: This study aimed to investigate the expression and possible functions of KPNA2 in the AP cell and animal model, focusing on its association with NF-κB activation.Methods: An AP cell model was established with the cerulein-stimulated AR42J and isolated rat pancreatic acinar cells. The AP rat model was induced by the intraperitoneal injection of cerulein. The secretion of TNF-α, IL-6, and LDH was detected by ELISA kits and the production of NO using nitric oxide kit. Expression of KPNA2 was measured by RT-PCR and Western blot. Expression levels of IKKα, phosphorylation of p65, and total p65 were detected by Western blot. Co-localization of KPNA2 with p65 was observed by immunofluorescence assay. To determine the biological functions of KPNA2 in cerulein-induced inflammatory response, RNA interference was employed to knockdown KPNA2 expression in AR42J and isolated pancreatic acini cells.Results: Cerulein stimulated KPNA2 expression and IL-6, TNF-α, NO, and LDH production in rat pancreatic acinar cells. Cerulein triggered the phosphorylation and nuclear translocation of NF-κB p65 subunit, indicating the NF-κB activation. The co-localization and nuclear accumulation of KPNA2 and p65 were detected in cerulein-treated cells. Knocking down KPNA2 hindered cerulein-induced nuclear transportation of p65 and alleviated the subsequent inflammatory response in rat pancreatic acinar cells. Additionally, KPNA2 expression was significantly up-regulated in cerulein-induced AP rat model.Conclusions: KPNA2-facilitated p65 nuclear translocation promotes NF-κB activation and inflammation in acute pancreatitis. [ABSTRACT FROM AUTHOR]

Objective: Activation of the transcription factor κB (NF-κB) and secretion of pro-inflammatory mediators are major events in acute pancreatitis (AP). Recently, O-linked- N-acetylglucosamine ( O-GlcNAc) modification, one type of posttranslational modifications, reportedly attunes NF-κB function. However, the expression of O-GlcNAc transferase (OGT), the enzyme responsible for O-GlcNAcylation of proteins, in AP, and the possible contribution of OGT-mediated O-GlcNAcylation to the NF-κB inflammatory activation in pancreatic acinar cells and to the AP progression have not been understood. This study focused on the effects and mechanisms of OGT-mediated O-GlcNAcylation during AP. Methods: An AP cell model was established with the caerulein-stimulated AR42 J rat pancreatic acinar cells. The secretion of pro-inflammatory cytokines TNF-α was detected by ELISA kits, and the production of NO was determined using the colorimetric Griess reaction. Expression of OGT was measured by RT-PCR and Western blot. Expression levels of RL2, phosphorylation of p65, total p65, IKKα were detected by Western blot. The NF-κB activity was evaluated by luciferase reporter gene assay. To determine the biological functions of OGT in caerulein-induced inflammatory response, RNA interference and PUGNAc, the inhibitor of O-GlcNAcase (OGA) was employed to regulate OGT expression in AR42 J cells. Results: Caerulein significantly up-regulated the expression of OGT, and increased the global protein O-GlcNAcylation level in AR42 J cells. Reduction of OGT by small interfering RNA (siRNA) inhibited caerulein-triggered inflammation, assessed by the production of pro-inflammatory mediators (TNF-α and NO). We also demonstrated that O-GlcNAcylation directly modified the NF-κB p65 subunit and its upstream activating kinases IKKα in AR42 J cells. Lowering O-GlcNAcylation by OGT knockdown attenuated p65 activating phosphorylation, nuclear translocation, NF-κB transcriptional activity and levels of NF-κB transcriptional targets TNF-α and NO; on the contrary, elevating O-GlcNAc through PUGNAc increased IKKα and p65 O-GlcNAcylation accompanied by increased p65 phosphorylation, activity and levels of TNF-α and NO in caerulein-treated cells. Conclusions: Our results demonstrate for the first time that OGT-mediated O-GlcNAcylation promotes NF-κB signaling activation and inflammation in pancreatic acinar cells, which might promote the progression of AP. [ABSTRACT FROM AUTHOR]

Abstract This paper performs a multi-model comparison to assess strategies for adaptation to climate change impacts in hydropower generation in Brazil under two Representative Concentration Pathways. The approach used allows for evaluating the interactions between climate change mitigation and adaptation strategies under low and high impact scenarios through 2050. Climate change impact projections of sixteen General Circulation Models indicate that a global high emissions trajectory scenario would likely yield more severe impacts on hydropower generation than a mitigation scenario. Adaptation modeling suggests that climate change impacts can be compensated by a wide range of alternatives, whose optimality will depend on the level of mitigation effort pursued. Our results show that climate change impacts would lead to even higher emissions in the absence of climate change mitigation policies. On the other hand, mitigation strategies to pursue lower emissions are maintained under climate change impacts, meaning that mitigation strategies are robust when faced with adaptation challenges. Mitigation efforts could yield a more diverse and less carbon intensive mix of technological options for adaptation. When analyzing investment costs to adapt to climate change impacts, in some cases mitigation can lead to a lower total investment level. Highlights • Climate change impacts on hydropower are assessed for sixteen models and two scenarios. • Interactions between climate change mitigation and adaptation are analyzed. • Adaptation/mitigation strategies from six different energy models are compared. • Adaptation and mitigation investment costs are assessed and compared. [ABSTRACT FROM AUTHOR]

Globally, 15.5 million km of land are currently identified as protected areas, which provide society with many ecosystem services including climate-change mitigation. Combining a global database of protected areas, a reconstruction of global land-use history, and a global biogeochemistry model, we estimate that protected areas currently sequester 0.5 Pg C annually, which is about one fifth of the carbon sequestered by all land ecosystems annually. Using an integrated earth systems model to generate climate and land-use scenarios for the twenty-first century, we project that rapid climate change, similar to high-end projections in IPCC's Fifth Assessment Report, would cause the annual carbon sequestration rate in protected areas to drop to about 0.3 Pg C by 2100. For the scenario with both rapid climate change and extensive land-use change driven by population and economic pressures, 5.6 million km of protected areas would be converted to other uses, and carbon sequestration in the remaining protected areas would drop to near zero by 2100. [ABSTRACT FROM AUTHOR]

Climate change, growing populations, and increasing wealth are increasing demand for food, energy, and water. Additionally, water stress is expected to increase in the future in areas with high rates of seasonality of precipitation, due to increased variability in precipitation. One approach to limiting the impact of climate change on food system productions is through the intensive and extensive expansion of irrigated agriculture. This study develops a hydro-economic model to assess future agriculture production possibilities and the role of irrigation water in the Pacific Slope region of Guatemala, one of the most productive agricultural regions in the country. A range of future scenarios are presented to account for uncertainty around irrigation infrastructure expansion, future crop prices, incentives for production of biomass for bioenergy, and water availability and irrigation demand due to climate change. We find that current surface water irrigation infrastructure increases agricultural output by value in the region by about 5.3% compared to a fully rainfed system. Additionally, we show that with expanded irrigation infrastructure, agricultural output could increase by between 3.4% and 18.4% relative to current levels under current climate conditions, but the value of agricultural production could increase under climate change with projected output from current and expanded irrigation infrastructure resulting in an increase of 1.2–24.8% relative to current irrigation levels. We also present evidence that the marginal benefit from increased irrigation access to smallholder farmers is nearly equal to that received by large-scale industrial agricultural producers. • We defelop a spatially and temporally explicit hydro-economic model to assess alternative irrigation expansion scenarios. • We find that climate change has the potential to shift the location and timing of benefits received from irrigation. • The marginal benefits from irrigation expansion received by small farms are larger than that received by industrial farms. • Climate change has the potential to change the spatial and temporal distribution of irrigation water availability. [ABSTRACT FROM AUTHOR]

We discuss a strategy for investigating the impacts of climate change on Earth's physical, biological and human resources and links to their socio-economic consequences. As examples, we consider effects on agriculture and human health. Progress requires a careful understanding of the chain of physical changes-global and regional temperature, precipitation, ocean acidification, polar ice melting. We relate those changes to other physical and biological variables that help people understand risks to factors relevant to their daily lives-crop yield, food prices, premature death, flooding or drought events, land use change. Finally, we investigate how societies may adapt, or not, to these changes and how the combination of measures to adapt or to live with losses will affect the economy. Valuation and assessment of market impacts can play an important role, but we must recognize the limits of efforts to value impacts where deep uncertainty does not allow a description of the causal chain of effects that can be described, much less assigned a likelihood. A mixed approach of valuing impacts, evaluating physical and biological effects, and working to better describe uncertainties in the earth system can contribute to the social dialogue needed to achieve consensus on the level and type of mitigation and adaptation actions. [ABSTRACT FROM AUTHOR]