Abstract
The year 2022 saw record breaking temperatures in Europe during both summer and fall. Similar to the recent 2018 drought, close to 30% (3.0 million km
2
) of the European continent was under ...severe summer drought. In 2022, the drought was located in central and southeastern Europe, contrasting the Northern-centered 2018 drought. We show, using multiple sets of observations, a reduction of net biospheric carbon uptake in summer (56-62 TgC) over the drought area. Specific sites in France even showed a widespread summertime carbon release by forests, additional to wildfires. Partial compensation (32%) for the decreased carbon uptake due to drought was offered by a warm autumn with prolonged biospheric carbon uptake. The severity of this second drought event in 5 years suggests drought-induced reduced carbon uptake to no longer be exceptional, and important to factor into Europe’s developing plans for net-zero greenhouse gas emissions that rely on carbon uptake by forests.
When SUCNR1/GPR91-expressing macrophages are activated by inflammatory signals, they change their metabolism and accumulate succinate. In this study, we show that during this activation, macrophages ...release succinate into the extracellular milieu. They simultaneously up-regulate GPR91, which functions as an autocrine and paracrine sensor for extracellular succinate to enhance IL-1β production. GPR91-deficient mice lack this metabolic sensor and show reduced macrophage activation and production of IL-1β during antigen-induced arthritis. Succinate is abundant in synovial fluids from rheumatoid arthritis (RA) patients, and these fluids elicit IL-1β release from macrophages in a GPR91-dependent manner. Together, we reveal a GPR91/succinate-dependent feed-forward loop of macrophage activation and propose GPR91 antagonists as novel therapeutic principles to treat RA.
The evidence of regional authoritarian clustering across different world regions goes together with the finding that after the end of the bipolar world regional patterns of interaction became more ...important. Especially in the 2000s a process of revitalisation of regional organisations and even the creation of new regional organisations took place. Interestingly, these newly founded organisations consist predominantly of authoritarian regimes. Due to the emergence and resilience of authoritarianism in the world, the question arises: To what extent do regional organisations (ROs) play a role in this phenomenon? We argue that authoritarian protagonists which we call authoritarian gravity centres (AGCs) constitute a force of attraction for countries in geopolitical proximity - and use ROs as a transmission belt and a learning room for disseminating autocratic elements. In a cross-regional comparison, based on extensive field work, we provide empirical analysis on two AGCs (Saudi Arabia and Venezuela) within their respective ROs Gulf Cooperation Council (GCC), Bolivarian Alliance for the Peoples of Our America (ALBA-TCP) and tackle the questions of why and how autocracies decide to move forward multilaterally within the RO.
Plant protection products (PPPs) consist of one or more active substances and several co-formulants. Active substances provide the functionality of the PPP and are consequently evaluated according to ...standard test methods set by legal data requirements before approval, whereas co-formulants' toxicity is not as comprehensively assessed. However, in some cases mixture effects of active substances and co-formulants might result in increased or different forms of toxicity. In a proof-of-concept study we hence built on previously published results of Zahn et al. (201838) on the mixture toxicity of Priori Xtra
and Adexar
to specifically investigate the influence of co-formulants on the toxicity of these commonly used fungicides. Products, their respective active substances in combination as well as some co-formulants were applied to human hepatoma cell line (HepaRG) in several dilutions. Cell viability analysis, mRNA expression, abundance of xenobiotic metabolizing enzymes and intracellular concentrations of active substances determined by LC-MS/MS analyses demonstrated that the toxicity of the PPPs is influenced by the presence of co-formulants
. PPPs were more cytotoxic than the mix of their active substances. Gene expression profiles of cells treated with the PPPs were similar to those treated with their respective mixture combinations with marked differences. Co-formulants can cause gene expression changes on their own. LC-MS/MS analyses revealed higher intracellular concentrations of active substances in cells treated with PPPs compared to those treated with the respective active substances' mix. Proteomic data showed co-formulants can induce ABC transporters and CYP enzymes. Co-formulants can contribute to the observed increased toxicity of PPPs compared to their active substances in combination due to kinetic interactions, necessitating a more comprehensive evaluation approach.
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