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Adoptive transfer of T regulatory cells (Treg) has been successfully exploited in the context of graft-versus-host disease, transplantation, and autoimmune disease. For the majority of applications, clinical administration of Treg requires laborious expansion and typically involves open handling for culture feeds and repetitive sampling. Here we show results from our approach to translate manual Treg manufacturing to the fully closed automated CliniMACS Prodigy® system reducing contamination risk, hands-on time, and quality variation from human intervention. Polyclonal Treg were isolated from total nucleated cells obtained through leukapheresis of healthy donors by CD8 cell depletion and subsequent CD25 enrichment. Treg were expanded with the CliniMACS Prodigy® device using clinical-grade cell culture medium, rapamycin, IL-2, and αCD3/αCD28 beads for 13-14 days. We successfully integrated expansion bead removal and final formulation into the automated procedure, finalizing the process with a ready to use product for bedside transfusion. Automated Treg expansion was conducted in parallel to an established manual manufacturing process using G-Rex cell culture flasks. We could prove similar expansion kinetics leading to a cell yield of up to 2.12 × 10 cells with the CliniMACS Prodigy® and comparable product phenotype of >90% CD4 CD25 CD127 FOXP3 cells that had similar immunosuppressive function. Efficiency of expansion bead depletion was comparable to the CliniMACS® Plus system and the final ready-to-infuse product had phenotype stability and high vitality after overnight storage. We anticipate this newly developed closed system expansion approach to be a starting point for the development of enhanced throughput clinical scale Treg manufacture, and for safe automated generation of antigen-specific Treg grafted with a chimeric antigen receptor (CAR Treg).

This paper explores whether efficacy beliefs can alter the relationship between worry about climate change and personal energy-saving behaviors, controlling for climate change beliefs and socio-demographics. For this purpose, we used data from 23 countries that participated in the European Social Survey Round 8 (N = 44 387). Worry about climate change, personal efficacy, personal outcome expectancy, and collective outcome expectancy were each associated with personal energy-saving behaviors concerning either energy curtailment or energy efficiency. The results further show that outcome expectancies moderate the association between worry about climate change and both types of energy behaviors. Worry was more strongly related to energy curtailment behaviors among those with high levels of personal and collective outcome expectancy. A similar pattern was found for energy efficiency behaviors, which were more strongly predicted by worry about climate change when combined with high levels of collective outcome expectancy. These findings are relevant for climate change communication, especially informational campaigns aiming to lower overall household energy use.

This study examines what individuals expect will be the most important impacts of climate change on their respective countries, and how these expectations relate to individual risk judgments. Open-ended responses from representative samples in four European countries (each n > 1000), were sorted into six categories: expectations of climate change leading to changes in attitudes and goals, human activities, emissions and pollution, environmental changes, impacts on humans, or few or no impacts. The results showed that the most frequently mentioned climate change impacts were related to environmental changes. Although most results were consistent across the UK, Norway, Germany, and France, some differences were identified. For example, respondents in the UK and Norway more frequently mentioned changes in human actions and activities among the most important climate change impacts. We also found differences between demographic groups; men, those in the oldest age groups, and those placing themselves further right on the political spectrum were more likely to expect few or no consequences of climate change on their country. Additional analyses examined relationships between the six impact categories and two different measures of individual risk judgments. Those expecting climate change to lead to changes in attitudes and goals, environmental changes, or impacts on humans reported higher levels of worry about climate change and expected more negative effects on their country. Climate change worry, but not the evaluation of how positive or negative effects will be on one’s country, was further related to the number of consequences mentioned in response to the open-ended question and the specificity conveyed.

Efficient cellular fusion of mononuclear precursors is the prerequisite for the generation of fully functional multinucleated bone-resorbing osteoclasts. However, the exact molecular factors and mechanisms controlling osteoclast fusion remain incompletely understood. Here we identify RANKL-mediated activation of caspase-8 as early key event during osteoclast fusion. Single cell RNA sequencing-based analyses suggested that activation of parts of the apoptotic machinery accompanied the differentiation of osteoclast precursors into mature multinucleated osteoclasts. A subsequent characterization of osteoclast precursors confirmed that RANKL-mediated activation of caspase-8 promoted the non-apoptotic cleavage and activation of downstream effector caspases that translocated to the plasma membrane where they triggered activation of the phospholipid scramblase Xkr8. Xkr8-mediated exposure of phosphatidylserine, in turn, aided cellular fusion of osteoclast precursors and thereby allowed generation of functional multinucleated osteoclast syncytia and initiation of bone resorption. Pharmacological blockage or genetic deletion of caspase-8 accordingly interfered with fusion of osteoclasts and bone resorption resulting in increased bone mass in mice carrying a conditional deletion of caspase-8 in mononuclear osteoclast precursors. These data identify a novel pathway controlling osteoclast biology and bone turnover with the potential to serve as target for therapeutic intervention during diseases characterized by pathologic osteoclast-mediated bone loss.

This study examines what individuals expect will be the most important impacts of climate change on their respective countries, and how these expectations relate to individual risk judgments. Open-ended responses from representative samples in four European countries (each n > 1000), were sorted into six categories: expectations of climate change leading to changes in attitudes and goals, human activities, emissions and pollution, environmental changes, impacts on humans, or few or no impacts. The results showed that the most frequently mentioned climate change impacts were related to environmental changes. Although most results were consistent across the UK, Norway, Germany, and France, some differences were identified. For example, respondents in the UK and Norway more frequently mentioned changes in human actions and activities among the most important climate change impacts. We also found differences between demographic groups; men, those in the oldest age groups, and those placing themselves further right on the political spectrum were more likely to expect few or no consequences of climate change on their country. Additional analyses examined relationships between the six impact categories and two different measures of individual risk judgments. Those expecting climate change to lead to changes in attitudes and goals, environmental changes, or impacts on humans reported higher levels of worry about climate change and expected more negative effects on their country. Climate change worry, but not the evaluation of how positive or negative effects will be on one's country, was further related to the number of consequences mentioned in response to the open-ended question and the specificity conveyed.

Based on national survey data from Norway, this study assesses if exposure to the IPCC special report on global warming of 1.5 °C can be associated with support for climate protests and mitigation policies. Respondents were asked if they had heard about the report (closed-ended question) and what they had learned from or about the report (open-ended question). Analyses of the closed-ended question showed that those who had heard about the report were also more likely to express their support for, as well as to plan on engaging in, protest for increased action by the government against climate change. A similar pattern was observed with respect to support for policy changes that can assist in mitigating climate change. Complementary analyses of the open-ended question revealed that evaluative statements formed the largest category of responses. This category included both references to the seriousness of the evolving climate crisis and comments questioning the credibility of the presented information, with the former being the most frequent response. The findings from this study are discussed in the context of public engagement with climate change, with a particular scope on the potential impacts of making the insights from scientific reports known to the general public.