Spatio-temporal activation of caspase-8 in myeloid cells upon ischemic stroke

Ischemic stroke (caused by thrombosis, embolism or vasoconstriction) lead to the recruitment and activation of immune cells including resident microglia and infiltrating peripheral macrophages, which contribute to an inflammatory response involved in regulation of the neuronal damage. We showed earlier that upon pro-inflammatory stimuli, the orderly activation of caspase-8 and caspase-3/7 regulates microglia activation through a protein kinase C-δ dependent pathway. Here, we present in vivo evidence for the activation of caspase-8 and caspase-3 in microglia/macrophages in post-mortem tissue from human ischemic stroke subjects. Indeed, CD68-positive microglia/macrophages in the ischemic peri-infarct area exhibited significant expression of the cleaved and active form of caspase-8 and caspase-3. The temporal and spatial activation of caspase-8 was further investigated in a permanent middle cerebral artery occlusion mouse model of ischemic stroke. Increasing levels of active caspase-8 was found in Iba1-positive cells over time in the peri-infarct area, at 6, 24 and 48 h after artery occlusion. Analysis of post-mortem brain tissue from human subject who suffered two stroke events, referred as recent and old stroke, revealed that expression of cleaved caspase-8 and -3 in CD68-positive cells could only be found in the recent stroke area. Analysis of cleaved caspase-8 and -3 expressions in a panel of human stroke cases arranged upon days-after stroke and age-matched controls suggested that the expression of these caspases correlated with the time of onset of stroke. Collectively, these data illustrate the temporal and spatial activation of caspase-8 and -3 in microglia/macrophages occurring upon ischemic stroke and suggest that the expression of these caspases could be used in neuropathological diagnostic wor

Deletion of caspase-8 in mouse myeloid cells blocks microglia pro-inflammatory activation and confers protection in MPTP neurodegeneration model

Increasing evidence involves sustained pro-inflammatory microglia activation in the pathogenesis of different neurodegenerative diseases, particularly Parkinson's disease (PD). We recently uncovered a completely novel and unexpected role for caspase-8 and its downstream substrates caspase-3/7 in the control of microglia activation and associated neurotoxicity to dopaminergic cells. To demonstrate the genetic evidence, mice bearing a floxed allele of CASP8 were crossed onto a transgenic line expressing Cre under the control of Lysozyme 2 gene. Analysis of caspase-8 gene deletion in brain microglia demonstrated a high efficiency in activated but not in resident microglia. Mice were challenged with lipopolysaccharide, a potent inducer of microglia activation, or with MPTP, which promotes specific dopaminergic cell damage and consequent reactive microgliosis. In neither of these models, CASP8 deletion appeared to affect the overall number of microglia expressing the pan specific microglia marker, Iba1. In contrast, CD16/CD32 expression, a microglial pro-inflammatory marker, was found to be negatively affected upon CASP8 deletion. Expression of additional proinflammatory markers were also found to be reduced in response to lipopolysaccharide. Of importance, reduced pro-inflammatory microglia activation was accompanied by a significant protection of the nigro-striatal dopaminergic system in the MPTP mouse model of PD.España Ministerio de Economía y Competitividad SAF2012-39029España Andalucía Junta de Andalucia P10-CTS-649

Innovating carbon-capture biotechnologies through ecosystem-inspired solutions

Rising atmospheric carbon concentrations affect global health, the economy, and overall quality of life. We are fast approaching climate tipping points that must be addressed, not only by reducing emissions but also through new innovation and action toward carbon capture for sequestration and utilization (CCSU). In this perspective, we delineate next-generation biotechnologies for CCSU supported by engineering design principles derived from ecological processes inspired by three major biomes (plant-soil, deep biosphere, and marine). These are to interface with existing industrial infrastructure and, in some cases, tap into the carbon sink potential of nature. To develop ecosystem-inspired biotechnology, it is important to identify accessible control points of CO2 and CH4 within a given system as well as value-chain opportunities that drive innovation. In essence, we must supplement natural biogeochemical carbon sinks with new bioengineering solutions

Microplastics; occurrence, levels and implications for environment and human health related to food. Scientific opinion of the Scientific Steering Committee of the Norwegian Scientific Committee for Food and Environment

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Microplastics; occurrence, levels and implications for environment and human health related to food. Opinion of the Steering Committee of the Norwegian Scientific Committee for Food and Environment

Report from the Norwegian Scientific Committee for Food Safety (VKM) 2019:16. Microplastics; occurrence, levels and implications for environment and human health related to food. Opinion of the Steering Committee of the Norwegian Scientific Committee for Food and Environment. Source at https://www.vkm.no/. The steering committee of VKM has self-initiated a mandate for an opinion on microplastics based on recently published international and/or national reports complemented with literature from December 2016 to February 2019. The mandate requested a summary of the state of knowledge on the presence of microplastics in the environment and the implications for the ecosystem, terrestrial and aquatic organisms, food production and human health. An overview of main national and international ongoing initiatives was also requested, and highlighting of data gaps where specific Norwegian data was needed

Food and chemical substances relevant for monitoring. Report from the Scientific Steering Committee of the Norwegian Scientific Committee for Food and Environment.

Source at https://vkm.no/At request from the Norwegian Food Safety Authority (NFSA), VKM has identified food groups and food items consumed by the Norwegian population that are relevant for monitoring regarding content of one or more undesirable chemical substances (Figure 1). Undesirable chemical substances were defined as chemical substances in food that may constitute a potential health risk. VKM has created a knowledge base (an Excel file) as a tool for planning and prioritising monitoring of foods and undesirable chemical substances. The substance groups included in the knowledge base are flavourings, food additives, metals and metalloids, natural toxins, persistent organic pollutants, process-induced contaminants, substances in food contact materials, substances in food supplements, and trace elements. More than 40 different substances were included

Food and chemical substances relevant for monitoring. Report from the Scientific Steering Committee of the Norwegian Scientific Committee for Food and Environment.

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Food and chemical substances relevant for monitoring - Scientific Opinion of the Scientific Steering Committee of the Norwegian Scientific Committee for Food and Environment

Source at https://vkm.no/</a

Food and chemical substances relevant for monitoring - Scientific Opinion of the Scientific Steering Committee of the Norwegian Scientific Committee for Food and Environment

At request from the Norwegian Food Safety Authority (NFSA), VKM has identified food groups and food items consumed by the Norwegian population that are relevant for monitoring regarding content of one or more undesirable chemical substances (Figure 1). Undesirable chemical substances were defined as chemical substances in food that may constitute a potential health risk.publishedVersionPaid open acces

Genome editing in food and feed production – implications for risk assessment. Scientific Opinion of the Scientific Steering Committee of the Norwegian Scientific Committee for Food and Environment

The Norwegian Scientific Committee for Food and Environment (VKM) initiated this work to examine the extent to which organisms developed by genome-editing technologies pose new challenges in terms of risk assessment. This report considers whether the risk assessment guidance on genetically modified organisms, developed by the European Food Safety Authority (EFSA), can be applied to evaluate potential risks of organisms developed by genome editing. Background Gene technology has allowed for the transfer of genes between organisms and species, and thereby to design altered genotypes with novel traits, i.e. GMOs. A new paradigm started in the early 2000s with the development of genome-editing techniques. Unlike traditional genetic modification techniques resulting in insertion of foreign DNA fragments at random locations in the genome, the new genome-editing techniques additionally open for a few single nucleotide edits or short insertions/deletions at a targeted site in an organism’s genome. These new techniques can be applied to most types of organisms, including plants, animals and microorganisms of commercial interest. An important question is how the novel, genome-edited organisms should be evaluated with respect to risks to health and the environment. The European Court of Justice decided in 2018 to include genome-edited organisms in the GMO definition and hence in the regulatory system already in place. This implies that all products developed by genome-editing techniques must be risk-assessed within the existing regulatory framework for GMOs. The European and Norwegian regulatory frameworks regulate the production, import and placing on the market of food and feed containing, consisting of or produced from GMOs, as well as the release of GMOs into the environment. The assessment draws on guidance documents originally developed by EFSA for risk assessment of GMOs, which were drawn up mainly to address risks regarding insertion of transgenes. The new genome-editing techniques, however, provide a new continuum of organisms ranging from those only containing a minor genetic alteration to organisms containing insertion or deletion of larger genomic regions. Risk assessment of organisms developed by genome editing The present discourse on how new genome-editing techniques should be regulated lacks an analysis of whether risk assessment methodologies for GMOs are adequate for risk assessment of organisms developed through the use of the new genome-editing techniques. Therefore, this report describes the use of genome-editing techniques in food and feed production and discusses challenges in risk assessment with the regulatory framework. Specifically, this report poses the question as to whether the EFSA guidance documents are sufficient for evaluating risks to health and environment posed by genome-edited plants, animals and microorganisms. To address these questions, the report makes use of case examples relevant for Norway. These examples, intended for food and feed, include oilseed rape with a modified fatty acid profile, herbicide-tolerant and pest-resistant crops, sterile salmon, virus-resistant pigs and hornless cattle. The report considers all aspects of the stepwise approach as described in the EFSA guidance documents. Conclusions The inherent flexibility of the EFSA guidance makes it suitable to cover health and environmental risk assessments of a wide range of organisms with various traits and intended uses. Combined with the embedded case-by-case approach the guidance is applicable to genome-edited organisms. The evaluation of the guidance demonstrates that the parts of the health and environmental risk assessment concerned with novel traits (i.e. the phenotype of the organism) may be fully applied to all categories of genome-edited organisms. ............acceptedVersionpublishedVersio