Trogocytosis of CARs depends on transmembrane domains
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A combination of measures limits demand for critical materials in Sweden’s electric car transition
Electrification of passenger cars will result in an increased demand for critical raw materials. Here we estimate the quantities of nickel, manganese, cobalt, lithium, and graphite that could be required for a transition to electric cars in Sweden and how different measures can limit material demand. We find notable reduction potentials for shorter battery range—enabled by improved charging infrastructure, increased vehicle energy efficiency, and reduced travel demand compared to a reference scenario. The reduction potentials for downsizing and more lightweight cars, and car sharing are more modest. The combined impact of these measures would be 50–75% reduction in cumulative demand and 72–87% reduction in in-use stock in 2050, depending on the material and battery chemistry pathway. Generally, the reduction potentials are larger than the potential contributions from recycling, suggesting that these complementary measures may be more effective in reducing material demand.
SETD1B-mediated broad H3K4me3 controls proper temporal patterns of gene expression critical for spermatid development
Epigenetic programming governs cell fate determination during development through intricately controlling sequential gene activation and repression. Although H3K4me3 is widely recognized as a hallmark of gene activation, its role in modulating transcription output and timing within a continuously developing system remains poorly understood. In this study, we provide a detailed characterization of the epigenomic landscapes in developing male germ cells. We identified thousands of spermatid-specific broad H3K4me3 domains regulated by the SETD1B-RFX2 axis, representing a previously underappreciated form of H3K4me3. These domains, overlapping with H3K27ac-marked enhancers and promoters, play critical roles in orchestrating robust transcription and accurate temporal control of gene expression. Mechanistically, these broad H3K4me3 compete effectively with regular H3K4me3 for transcriptional machinery, thereby ensuring robust levels and precise timing of master gene expression in mouse spermiogenesis. Disruption of this mechanism compromises the accuracy of transcription dosage and timing, ultimately impairing spermiogenesis. Additionally, we unveil remarkable changes in the distribution of heterochromatin marks, including H3K27me3 and H3K9me2, during the mitosis-to-meiosis transition and completion of meiotic recombination, which closely correlates with gene silencing. This work underscores the highly orchestrated epigenetic regulation in spermatogenesis, highlighting the previously unrecognized role of Setd1b in the formation of broad H3K4me3 domains and transcriptional control, and provides an invaluable resource for future studies toward the elucidation of spermatogenesis.
The closing longevity gap between battery electric vehicles and internal combustion vehicles in Great Britain
Electric vehicles are increasingly being adopted in Great Britain and other parts of the world, driven by the perception that they offer a cost-effective alternative to internal combustion engine vehicles while reducing emissions. However, a key element that underpins this perception is the longevity of electric vehicles, which remains relatively under researched. Here we show that although early battery electric vehicles (BEVs) exhibited lower reliability than internal combustion engine vehicles, rapid technological advancements have allowed newer BEVs to achieve comparable lifespans, even under more intensive use. Longevity is also found to be impacted by engine size, location and make of vehicle. We provide parameter estimates for life mileage that can be used to update life cycle assessment and total cost of ownership studies of different vehicle powertrains. Our results also shed light on BEV diffusion patterns, fleet replacement strategies and end-of-life treatment planning, including the increasingly important debate around BEV battery recycling and second-life options.
A systematic review and meta-analyses of the temporal stability and convergent validity of risk preference measures
Understanding whether risk preference represents a stable, coherent trait is central to efforts aimed at explaining, predicting and preventing risk-related behaviours. We help characterize the nature of the construct by adopting a systematic review and individual participant data meta-analytic approach to summarize the temporal stability of 358 risk preference measures (33 panels, 57 samples, 579,114 respondents). Our findings reveal noteworthy heterogeneity across and within measure categories (propensity, frequency and behaviour), domains (for example, investment, occupational and alcohol consumption) and sample characteristics (for example, age). Specifically, while self-reported propensity and frequency measures of risk preference show a higher degree of stability than behavioural measures, these patterns are moderated by domain and age. Crucially, an analysis of convergent validity reveals a low agreement across measures, questioning the idea that they capture the same underlying phenomena. Our results raise concerns about the coherence and measurement of the risk preference construct.
The contribution of genetic determinants of blood gene expression and splicing to molecular phenotypes and health outcomes
The biological mechanisms through which most nonprotein-coding genetic variants affect disease risk are unknown. To investigate gene-regulatory mechanisms, we mapped blood gene expression and splicing quantitative trait loci (QTLs) through bulk RNA sequencing in 4,732 participants and integrated protein, metabolite and lipid data from the same individuals. We identified cis-QTLs for the expression of 17,233 genes and 29,514 splicing events (in 6,853 genes). Colocalization analyses revealed 3,430 proteomic and metabolomic traits with a shared association signal with either gene expression or splicing. We quantified the relative contribution of the genetic effects at loci with shared etiology, observing 222 molecular phenotypes significantly mediated by gene expression or splicing. We uncovered gene-regulatory mechanisms at disease loci with therapeutic implications, such as WARS1 in hypertension, IL7R in dermatitis and IFNAR2 in COVID-19. Our study provides an open-access resource on the shared genetic etiology across transcriptional phenotypes, molecular traits and health outcomes in humans (https://IntervalRNA.org.uk).
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