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Abstract: The proinflammatory cytokine tumor necrosis factor (TNF) binds two distinct plasma membrane receptors, TNFR1 and TNFR2. We have produced different receptor mutants fused with enhanced green fluorescent protein to study their membrane dynamics by fluorescence correlation spectroscopy (FCS). TNFR1 mutants show diffusion constants of approximately 1.2×10−9 cm2/s and a broad distribution of diffusion times, which is hardly affected by ligand binding. However, cholesterol depletion enhances their diffusion, suggesting a constitutive affinity to cholesterol rich membrane microdomains. In contrast, TNFR2 and mutants thereof diffuse rather fast (D̄ =3.1×10−9 cm2/s) with a marked reduction after 30min of TNF treatment (D̄ =0.9×10−9 cm2/s). This reduction cannot be explained by the formation of higher ordered receptor clusters, since the fluorescence intensity of TNF treated receptors indicate the presence of a few receptor molecules per complex only. Together, these data point to a topological segregation of the two TNF receptors in different microcompartments of the plasma membrane independent of the cytoplasmic signaling domains of the receptors. [Copyright &y& Elsevier]

• A study by experts analysed ChatGPT's safety-related advice in nine domains. • Misuse concerns raised for ChatGPT in providing safety-related information. • Populations with lower literacy and education are at higher risk of consuming unreliable content. • Incomplete safety research limits ChatGPT's safety advice. • ChatGPT currently appears not to favour contents based on their factuality or reliability. ChatGPT is a highly advanced AI language model that has gained widespread popularity. It is trained to understand and generate human language and is used in various applications, including automated customer service, chatbots, and content generation. While it has the potential to offer many benefits, there are also concerns about its potential for misuse, particularly in relation to providing inappropriate or harmful safety-related information. To explore ChatGPT's (specifically version 3.5) capabilities in providing safety-related advice, a multidisciplinary consortium of experts was formed to analyse nine cases across different safety domains: using mobile phones while driving, supervising children around water, crowd management guidelines, precautions to prevent falls in older people, air pollution when exercising, intervening when a colleague is distressed, managing job demands to prevent burnout, protecting personal data in fitness apps, and fatigue when operating heavy machinery. The experts concluded that there is potential for significant risks when using ChatGPT as a source of information and advice for safety-related issues. ChatGPT provided incorrect or potentially harmful statements and emphasised individual responsibility, potentially leading to ecological fallacy. The study highlights the need for caution when using ChatGPT for safety-related information and expert verification, as well as the need for ethical considerations and safeguards to ensure users understand the limitations and receive appropriate advice, especially in low- and middle-income countries. The results of this investigation serve as a reminder that while AI technology continues to advance, caution must be exercised to ensure that its applications do not pose a threat to public safety. [ABSTRACT FROM AUTHOR]

Abstract: Ciliary neurotrophic factor (CNTF) signals via a receptor complex consisting of the specific CNTF receptor (CNTFR) and two promiscuous signal transducers, gp130 and leukemia inhibitory factor receptor (LIFR). Whereas earlier studies suggested that the signaling complex is a hexamer, more recent analyses strongly support a tetrameric structure. However, all studies so far analyzed the stoichiometry of the CNTF receptor complex in vitro and not in the context of living cells. We generated and expressed in mammalian cells acyl carrier protein-tagged versions of both CNTF and CNTFR. After labeling CNTF and CNTFR with different dyes we analyzed their diffusion behavior at the cell surface. Fluorescence (cross) correlation spectroscopy (FCS/FCCS) measurements reveal that CNTFR diffuses with a diffusion constant of about 2×10−9 cm2 s−1 independent of whether CNTF is bound or not. FCS and FCCS measurements detect the formation of receptor complexes containing at least two CNTFs and CNTFRs. In addition, we measured Förster-type fluorescence resonance energy transfer between two differently labeled CNTFs within a receptor complex indicating a distance of 5–7 nm between the two. These findings are not consistent with a tetrameric structure of the CNTFR complex suggesting that either hexamers and or even higher-order structures (e.g. an octamer containing two tetramers) are formed. [Copyright &y& Elsevier]