Alveolar macrophages and Toll-like receptor 4 mediate ventilated lung ischemia reperfusion injury in mice.

BackgroundIschemia-reperfusion (I-R) injury is a sterile inflammatory process that is commonly associated with diverse clinical situations such as hemorrhage followed by resuscitation, transient embolic events, and organ transplantation. I-R injury can induce lung dysfunction whether the I-R occurs in the lung or in a remote organ. Recently, evidence has emerged that receptors and pathways of the innate immune system are involved in recognizing sterile inflammation and overlap considerably with those involved in the recognition of and response to pathogens.MethodsThe authors used a mouse surgical model of transient unilateral left pulmonary artery occlusion without bronchial involvement to create ventilated lung I-R injury. In addition, they mimicked nutritional I-R injury in vitro by transiently depriving cells of all nutrients.ResultsCompared with sham-operated mice, mice subjected to ventilated lung I-R injury had up-regulated lung expression of inflammatory mediator messenger RNA for interleukin-1β, interleukin-6, and chemokine (C-X-C motif) ligand-1 and -2, paralleled by histologic evidence of lung neutrophil recruitment and increased plasma concentrations of interleukin-1β, interleukin-6, and high-mobility group protein B1 proteins. This inflammatory response to I-R required toll-like receptor-4 (TLR4). In addition, the authors demonstrated in vitro cooperativity and cross-talk between human macrophages and endothelial cells, resulting in augmented inflammatory responses to I-R. Remarkably, the authors found that selective depletion of alveolar macrophages rendered mice resistant to ventilated lung I-R injury.ConclusionsThe data reveal that alveolar macrophages and the pattern recognition receptor toll-like receptor-4 are involved in the generation of the early inflammatory response to lung I-R injury

Limited carbon and biodiversity co-benefits for tropical forest mammals and birds

The conservation of tropical forest carbon stocks offers the opportunity to curb climate change by reducing greenhouse gas emissions from deforestation and simultaneously conserve biodiversity. However, there has been considerable debate about the extent to which carbon stock conservation will provide benefits to biodiversity in part because whether forests that contain high carbon density in their aboveground biomass also contain high animal diversity is unknown. Here, we empirically examined medium to large bodied ground-dwelling mammal and bird (hereafter "wildlife") diversity and carbon stock levels within the tropics using camera trap and vegetation data from a pantropical network of sites. Specifically, we tested whether tropical forests that stored more carbon contained higher wildlife species richness, taxonomic diversity, and trait diversity. We found that carbon stocks were not a significant predictor for any of these three measures of diversity, which suggests that benefits for wildlife diversity will not be maximized unless wildlife diversity is explicitly taken into account; prioritizing carbon stocks alone will not necessarily meet biodiversity conservation goals. We recommend conservation planning that considers both objectives because there is the potential for more wildlife diversity and carbon stock conservation to be achieved for the same total budget if both objectives are pursued in tandem rather than independently. Tropical forests with low elevation variability and low tree density supported significantly higher wildlife diversity. These tropical forest characteristics may provide more affordable proxies of wildlife diversity for future multi-objective conservation planning when fine scale data on wildlife are lacking

Development of inclusive education in England: Impact on children with special educational needs and disabilities

This is an accepted manuscript of a book chapter published by Springer Routledge in the Handbook on Promoting Social Justice in Education, available online: https://doi.org/10.1007/978-3-319-74078-2_151-1 The accepted version of the publication may differ from the final published version. Please refer to the publisher's terms and conditions for re-use.This chapter considers a historical account of the development of inclusion in England and the changes made to the education of children with SEND since the 1940s. The chapter details the development of inclusive education, the complexity of defining inclusion, and what inclusion has come to mean in current practice. This historical account is considered alongside the development and dominance of the standards agenda. In considering inclusion in this manner, the original intentions of its agenda are questioned against the practical implementation of inclusive education in current practice. The chapter concludes by proposing that significant progress has not been made with inclusion because it has not been possible to accommodate it within the competing political agendas replete in England’s education system

The Dynamic Duo: Niche/Stem Cell Interdependency

Most tissues in our bodies undergo constant cellular turnover. This process requires a dynamic balance between cell production and elimination. Stem cells have been shown in many of these tissues to be the major source of new cells. However, despite the tremendous advances made, it still remains unclear how stem cell behavior and activity are regulated in vivo. Furthermore, we lack basic understanding for the mechanisms that coordinate niche/stem cell interactions to maintain normal tissue homeostasis. Our lab has established a novel imaging approach in live mice using the skin as a model system to investigate these fundamental processes in both physiological and pathological settings such as cancer, with the goal of understanding how tissues successfully orchestrate tissue regeneration throughout the lifetime of an organism

A Customized Bayesian Algorithm to Optimize Enzyme-Catalyzed Reactions

Design of experiments (DoE) plays an important role in optimizing the catalytic performance of chemical reactions. The most commonly used DoE relies on the response surface methodology (RSM) to model the variable space of experimental conditions with the fewest number of experiments. However, the RSM leads to an exponential increase in the number of required experiments as the number of variables increases. Herein we describe a Bayesian optimization algorithm (BOA) to optimize the continuous parameters (e.g., temperature, reaction time, reactant and enzyme concentrations, etc.) of enzyme-catalyzed reactions with the aim of maximizing performance. Compared to existing Bayesian optimization methods, we propose an improved algorithm that leads to better results under limited resources and time for experiments. To validate the versatility of the BOA, we benchmarked its performance with biocatalytic C–C bond formation and amination for the optimization of the turnover number. Gratifyingly, up to 80% improvement compared to RSM and up to 360% improvement vs previous Bayesian optimization algorithms were obtained. Importantly, this strategy enabled simultaneous optimization of both the enzyme’s activity and selectivity for cross-benzoin condensation.ISSN:2168-048

A customized Bayesian algorithm to optimize enzyme-catalyzed reactions

Design of experiments (DoE) plays an important role in optimizing the catalytic performance of chemical reactions. The most commonly-used DoE relies on the response surface methodology (RSM) to model the variable space of experimental condi-tions with a minimal number of experiments. However, the RSM leads to an exponential increase in the number of required experiments to be evaluated as the number of variables increases. Herein we describe a Bayesian optimization algorithm (BOA) to optimize the continuous parameters (e.g. temperature, reaction time, reactant and enzyme concentrations etc.) of enzyme-catalyzed reactions with the aim of maximizing performance. Compared to existing Bayesian optimization methods, we propose an improved algorithm that leads to better results under limited resources and time for experiments. To validate the versatility of BOA for the optimization of the turnover number in enzyme-catalyzed reactions, we benchmarked its per-formance for a biocatalytic C-C bond-forming reaction as well as an amination reaction. Gratifyingly, up to 80% improvement compared to RSM and up to 360% improvement vs. previous Bayesian optimization algorithms was obtained. Importantly, this strategy enabled the simultaneous optimization of both the enzyme’s activity and chemoselectivity for a cross-benzoin condensation

Alveolar Macrophages and Toll-like Receptor 4 Mediate Ventilated Lung Ischemia Reperfusion Injury in Mice

BACKGROUND: Ischemia reperfusion (I/R) injury involves sterile inflammation and is commonly associated with diverse clinical situations such as hemorrhage followed by resuscitation, transient embolic events, and organ transplantation. I/R injury can induce lung dysfunction whether the I/R occurs in the lung itself or in a remote organ. Recently, evidence has emerged that receptors and pathways of the innate immune system are involved in recognizing sterile inflammation and overlap considerably with those involved in recognition and response to pathogens. METHODS: We used a mouse surgical model of transient unilateral left pulmonary artery occlusion without bronchial involvement to create ventilated lung I/R injury. Additionally, we mimicked nutritional I/R injury in vitro by transiently depriving cells of all nutrients. RESULTS: Compared with sham-operated mice, mice subjected to ventilated lung I/R injury had upregulated lung expression of inflammatory mediator messenger RNA for IL-1β, IL-6, and CXCL1 and 2, paralleled by histologic evidence of lung neutrophil recruitment, and increased plasma levels of IL-1β, IL-6 and HMGB1 proteins. This inflammatory response to I/R required toll-like receptor-4. Furthermore, we demonstrated in vitro cooperativity and cross-talk between macrophages and endothelial cells, resulting in augmented inflammatory responses to I/R. Remarkably, we found that selective depletion of alveolar macrophages rendered mice resistant to ventilated lung I/R injury. CONCLUSIONS: Our data reveal that alveolar macrophages and the pattern recognition receptor, toll-like receptor-4 are required for the generation of the early inflammatory response to lung I/R injury

Alveolar macrophages and Toll-like receptor 4 mediate ventilated lung ischemia reperfusion injury in mice.

BackgroundIschemia-reperfusion (I-R) injury is a sterile inflammatory process that is commonly associated with diverse clinical situations such as hemorrhage followed by resuscitation, transient embolic events, and organ transplantation. I-R injury can induce lung dysfunction whether the I-R occurs in the lung or in a remote organ. Recently, evidence has emerged that receptors and pathways of the innate immune system are involved in recognizing sterile inflammation and overlap considerably with those involved in the recognition of and response to pathogens.MethodsThe authors used a mouse surgical model of transient unilateral left pulmonary artery occlusion without bronchial involvement to create ventilated lung I-R injury. In addition, they mimicked nutritional I-R injury in vitro by transiently depriving cells of all nutrients.ResultsCompared with sham-operated mice, mice subjected to ventilated lung I-R injury had up-regulated lung expression of inflammatory mediator messenger RNA for interleukin-1β, interleukin-6, and chemokine (C-X-C motif) ligand-1 and -2, paralleled by histologic evidence of lung neutrophil recruitment and increased plasma concentrations of interleukin-1β, interleukin-6, and high-mobility group protein B1 proteins. This inflammatory response to I-R required toll-like receptor-4 (TLR4). In addition, the authors demonstrated in vitro cooperativity and cross-talk between human macrophages and endothelial cells, resulting in augmented inflammatory responses to I-R. Remarkably, the authors found that selective depletion of alveolar macrophages rendered mice resistant to ventilated lung I-R injury.ConclusionsThe data reveal that alveolar macrophages and the pattern recognition receptor toll-like receptor-4 are involved in the generation of the early inflammatory response to lung I-R injury

Citizens of local jurisdictions enhance plant community preservation through ballot initiatives and voter-driven conservation efforts

Open space areas protected by local communities may augment larger scale preservation efforts and may offer overlooked benefits to biodiversity conservation provided they are in suitable ecological condition. We examine protected areas established by local communities through ballot initiatives, a form of direct democracy, in California, USA. We compare ecological conditions of wooded habitats on local ballot protected sites and on sites protected by a state-level conservation agency. Collectively, we found few differences in ecological conditions on each protected area type. Ballot sites had greater invasive understory cover and larger trees. Community dissimilarity patterns suggested ballot sites protect a complementary set of tree species to those on state lands. Overall, geographic characteristics influenced onsite conditions more than details of how sites were protected. Thus, community-driven conservation efforts contribute to protected area networks by augmenting protection of some species while providing at least some protection to others that might otherwise be missed