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Editorial Expression of Concern: Cytokinesis failure generating tetraploids promotes tumorigenesis in p53-null cells
Challenges in global climate models to represent cloud response to aerosols: insights from volcanic eruptions
Abstract Aerosol-cloud interactions (ACI) remain a major source of climate uncertainty due to missing large-scale observational constraints. Such a constraint, with global cloud representativeness, has recently been developed based on the Holuhraun-2014 volcanic eruption from machine learning with satellite observations. Here, we confront this large-scale observational constraint against six diverse global climate models to advance our understanding of ACI simulation uncertainty. We show that marine liquid cloud optical depth responses to aerosols are reasonably well simulated, although through compensating errors. However, all models largely underestimate cloud cover responses to aerosols, with five of them outside the 90% confidence level. This persistent bias remains despite tuning five distinct cloud schemes and testing various key cloud processes. Such bias in cloud cover response is a major driver of simulation uncertainty in ACI cooling and needs to be addressed urgently to improve climate projections and estimations of climate sensitivity.
Circulating causal protein networks linked to future risk of myocardial infarction
Abstract Variations in blood protein levels have been linked to numerous complex diseases, including cardiovascular conditions. These associations highlight the intricate interplay between local and systemic factors in cardiovascular disease development, emphasizing the need for a comprehensive, systems-level understanding of its etiology. To address this, we develop a causal network inference framework using data from one of the largest serum proteomics studies to date, comprising measurements of 7523 serum proteins in the prospective, population-based Age, Gene/Environment Susceptibility-Reykjavik Study (AGES) cohort of 5376 older adults. Using cis -acting protein quantitative trait loci (pQTLs) as instrumental variables within a causal inference framework designed to mitigate hidden confounding, we identify 185 high-confidence causal serum protein subnetworks collectively interacting with 5611 targets. Several subnetworks, many forming hierarchical frameworks of directional relationships, are significantly associated with multiple cardiometabolic traits and with future risk of myocardial infarction and its long-term complication, heart failure.
Varying relationships between experienced income segregation and travel behaviour across neighbourhood social and urban contexts
Abstract Income segregation is a barrier to social inclusivity and equity. It is affected by individuals’ travel behaviour and socioeconomic status and may be intensified by localised living models emphasising conducting daily activities within immediate neighbourhoods. However, how the relationship between experienced income segregation and travel behaviour varies across neighbourhood social and urban contexts remains unclear. Here, we quantify experienced income segregation using a dataset of 1.2 billion mobility records from the contiguous United States and examine its relationships with travel distance and diversity across neighbourhoods with different social and urban contexts. We find that longer travel distances and more diverse destinations are associated with less experienced segregation for least affluent neighbourhoods, especially in less urbanised areas. Our findings underscore the need for urban planning and transport interventions to increase mobility and social integration opportunities for residents from socially disadvantaged neighbourhoods. They also highlight the potential adverse social consequences of localised living models.
Performance-limiting metastable intragrain impurity nanoclusters in metal halide perovskites
High temperature evaporative cooler utilizing boiling suppression at water’s boiling point
Oxyanions stabilized low-coordinated nickel species for efficient and durable nucleophilic electrooxidation
Dietary carotenoids and risk of dyslipidemia among adult participants of Tehran Lipid and Glucose Study
Author Correction: Diversity-oriented synthesis yields novel multistage antimalarial inhibitors
Tariff familiarity sustains household water conservation
Deciphering drought tolerance in cotton genotypes through integrated morpho-physiological and biochemical markers at flowering stage
Deuteration promotes circularly polarized light emission by suppression of vibration
Abstract Circularly polarized light (CPL) is critical for advancing photonic technologies such as spin-based optical communication, quantum computing and displays. Developing these technologies necessitates CPL emitters with large dissymmetry factor ( g ) and high quantum yield ( Φ ). However, there is an inherent trade-off between these two parameters. Here we integrate molecular deuteration into chiral thermally activated delayed fluorescence (TADF) emitters, leading to marked improvements in both g and Φ . Circularly polarized organic light-emitting diodes incorporating deuterated chiral TADF molecules as either emitters or host exhibit high performance, achieving maximum external quantum efficiency close to 40% and demonstrating up to over twofold enhanced electroluminescence g compared to hydrogenated counterparts. Such advancements are attributed to suppression of vibrations by deuteration. Our deuteration strategy sets a foundation for designing organic chiral emitters with large g and high Φ , paving the way for high-performance CPL in display technologies.
Visually perceived depth from single-dot circular trajectories
Abstract This study investigates the perception of three-dimensional depth elicited by a single dot traversing an oblique projection of circular motion within the frontal plane. We show that this minimal motion stimulus evokes vivid depth experiences comparable to those from two-dot relative motion, demonstrating that speed variations of a single element alone enable 3D space perception. In addition, perspective projection which is an important depth-cue for other stimuli, for example resulting in linear perspective and texture gradients in stills, do not contribute much compared to parallel projection for our stimuli. The results also demonstrate a robust view-from-above perceptual bias, indicating that ecological priors influence depth disambiguation. These effects are discussed using Gestalt principles of simplicity and Bayesian models of perception. Together, these findings enrich our understanding of motion-based depth perception and highlight novel mechanisms by which the visual system reconstructs depth from minimal cues.
Author Correction: Evidence for improved DNA repair in the long-lived bowhead whale
Utilizing nanoinducers for precision degradation of bacterial protein to mitigate antibiotic resistance
Evolution, composition and functions of cullin E3 ubiquitin ligases in trypanosomes
Abstract Post-translational modifications (PTMs) modulate protein functions, with ubiquitylation a pre-eminent example, and playing major roles in protein turnover. Ubiquitylation utilises a ligase enzyme cascade for conjugation of ubiquitin to client proteins, of which there are a large number in humans and lesser numbers in unicellular eukaryotes. The Cullin-RING ligases are amongst the most complex ligase subfamily and are present across the eukaryote lineage. We have reconstructed the evolution of cullin-RING E3 ubiquitin ligases across eukaryotes and experimentally determined the composition of six of seven cullin complexes in trypanosomatids. We find considerable diversity within cullins and reconstruct at least four ancestral pan-eukaryotic subfamilies. Furthermore, we identify expansions of cullin client adaptor protein families, novel client adaptors and demonstrate client specificity in trypanosomatids. We also find evidence for increasing complexity within client adaptors, suggesting ongoing expansion of adapter architecture. Finally, we show that turnover of ornithine decarboxylase (TbODC), an important target of the trypanocide eflornithine, is mediated by TbCul-A/CUL-1. These studies highlight lineage-specific aspects of cullin E3 ligases and their contributions towards eukaryotic complexity.
Dysfunctional CD4 T cells in an oncovirus-specific TCR-transgenic in vivo model
Efficacy of fourteen-day once-daily vonoprazan-based quadruple therapy for Helicobacter pylori in high clarithromycin-resistance regions (ONCE-VONO Trial)
Neoadjuvant immunotherapy in mismatch-repair-proficient colon cancers
Abstract Immune checkpoint blockade has led to paradigm shifts in the treatment of various tumour types 1–4 , yet limited efficacy has been observed in patients with metastatic mismatch-repair-proficient (pMMR) colorectal cancer 5 . Here we report clinical results and in-depth analysis of patients with early-stage pMMR colon cancer from the phase II NICHE study (ClinicalTrials.gov: NCT03026140). A total of 31 patients received neoadjuvant treatment of nivolumab plus ipilimumab followed by surgery. The response rate was 26% and included six patients with a major pathological response (10% or less residual viable tumour). One patient with an ongoing clinical complete response did not undergo surgery. Circulating tumour DNA was positive in 26 of 31 patients at baseline, and clearance was observed in 5 of 6 responders before surgery, whereas 19 of 20 non-responders remained circulating tumour DNA positive. Responses were observed despite a low tumour mutational burden in all tumours, whereas chromosomal genomic instability scores were significantly higher in responders than in non-responders. Furthermore, responding tumours had significantly higher baseline expression of proliferation signatures and TCF1, and imaging mass cytometry revealed a higher percentage of Ki-67 + cancer and Ki-67 + CD8 + T cells in responders than in non-responders. These results provide a comprehensive analysis of response to neoadjuvant immune checkpoint blockade in early-stage pMMR colon cancers and identify potential biomarkers for patient selection.