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Genetic architecture of a light-temperature coincidence detector
Abstract Light and temperature variations are inescapable in nature. These signals provide daily and seasonal information, guiding life history determinations across many taxa. Here we show that signals from the PHOTOTROPIN2 (PHOT2) blue photoreceptor combine with low temperature information to control flowering. Plants lacking PHOT2 flower later than controls when grown in low ambient temperature. This phenotype requires blue light, is blocked by removal of NON-PHOTOTROPIC HYPOCOTYL 3 (NPH3), and is recapitulated by removing the transcription factor CAMTA2. PHOT2 and CAMTA2 show non-additive genetic interactions in phenotype and gene expression. Network-based co-expression analysis indicates system-level control of key growth modules by PHOT2 and CAMTA2. CAMTA2 is required for low temperature up-regulation of EHB1 , a known NPH3-interacting protein, providing a potential mechanism of temperature information input to the PHOT-NPH3 blue light signaling system. Together these data describe the genetic architecture of environmental signal integration in this blue light-low temperature coincidence detection module.
Quantitative 1H-NMR spectroscopy identifies metabolites and lipoprotein subclasses associated with intermediate phenotypes of chronic diseases in the Japanese Nagahama Study
Comparison of the ABC/2 formula with computer-assisted volumetry of ischemic cerebellar stroke
Introduction Current guidelines suggest surgical decompression for ischemic cerebellar stroke in case of significant mass effect. Recent research has aimed to identify a possible threshold for mass effect. However, a computer-assisted volumetry in acute setting is time consuming and impracticable, wherefore the aim of this study was to assess the accuracy and clinical applicability of the ABC/2 method in case of ischemic cerebellar stroke. Materials and methods Imaging data of 125 patients, including preoperative CT or MRI scans were used for volumetric analysis. The ABC/2 formula using scans in axial and coronal planes. BrainLab® Elements software was used for computer assisted volumetry by defining the region of interest allowing automated volumetric calculation. Measurements were conducted independently by blinded clinicians. Pearson correlation and Bland-Altmann test were used for statistical analysis. Results Among the 125 cerebellar infarctions analyzed, there was no statistical difference of mean infarct volume measurement between the ABC/2 formula and computer-assisted volumetry (16.6mL vs. 15.91mL; range 0.8-67.7mL; p = 0.76). The Spearman correlation test indicated a strong correlation between the two methods (r = 0.985, 95% CI: 0.979–0.990, p < 0.0001). Discrepancies were most notable in smaller infarction volumes (<10 mL), prompting a subgroup analysis. For infarct volume less than 10mL, the ratio of volumetric differences ranged from 47% to 60%, with absolute volume differences from −3–3 mL whereas the ratio ranged from −20% to 29%, with absolute volume differences from −6–8 mL in cases with infarct volume greater equal 10mL. Conclusion ABC/2 formula shows a good correlation with computer-assisted volumetry. Consequently, it could serve as a fast and practical tool for estimating cerebellar infarct volume and aiding decision-making in clinical practice. However, the limitations and variability of the ABC/2 method, particularly for smaller infarcts, must be considered.
Replay in the human visual cortex during brief task pauses is linked to implicit learning of successor representations
Humans can implicitly learn about multistep sequential relationships between events in the environment from their statistical co-occurrence. Theoretical work has suggested that neural replay is a candidate mechanism that aids such learning. Here, we used functional MRI (fMRI) to test whether replay is related to implicit learning of higher-order sequential relationships. Human participants viewed sequences of images that followed probabilistic transitions determined by ring-like graph structures. Behavioral modeling of response times revealed that participants acquired multistep transition knowledge in a manner consistent with gradual updating of an internal successor representation (SR) model. Yet, half of participants did not report being aware of any sequential task structure, and most participants failed to provide meaningful transition probability ratings in a posttask test. Analyses of temporal dynamics of multivariate fMRI patterns during brief 10 s pauses from the ongoing statistical learning task indicated backward sequential replay of multistep sequences in visual cortical areas. Variations in model parameters between participants that captured response time patterns related to strength of neural replay. No corresponding relations between replay and measures of explicit awareness were found. These findings indicate that implicit learning of higher-order relationships establishes an internal SR-based map of the task and is accompanied by cortical on-task replay.
High-fidelity geometric quantum gates exceeding 99.9% in germanium quantum dots
An innovative process for lead upgrade from Kaldo smelting slag of lead ores: characterization and flotation
The interaction between candidate SNPs and social factors significantly influences the prevalence of alcohol use disorder in Chinese young male adults
Alcohol use disorder (AUD) is a growing public health issue which has caused global concern. Previous evidence has identified several genes significantly associated with alcohol-related traits. However, it remains unclear whether these associations are robust across different ethnic groups and whether they may be moderated by some specific social factors. The current study aimed to investigate the associations between candidate SNPs and AUD and to examine whether the associations could be moderated by socioeconomic status and social environment among a cohort of young Chinese males. A cross-sectional survey using convenient sampling was conducted in 2017 in four communities of Guangzhou, China. The current cohort consists of 320 male drinkers aged 18–31 years. Logistic regression was employed to explore the influence of candidate SNPs on AUD. And then, moderation regression model was constructed to investigate the potential moderation effects of multiple social factors measured by attitudes towards alcohol (ATA), personal income level, work-related stress, peer drinking behaviors, and childhood traumas. Of the ten candidate SNPs incorporated in the current study, four (ALDH2 rs671, COMT rs165774, OPRK1 rs6473797, and GABRA2 rs279858) were significantly associated with AUD. Moderation analyses revealed that the protective effect of the minor allele of ALDH2 rs671 was moderated by ATA; the effect of COMT rs165774 was moderated by personal income level; and childhood trauma moderated the association between OPRK1 rs6473797 and AUD. Additionally, COMT rs165774 moderated the relationship between work-related stress and AUD risk. This study closely aligned with previous research conducted in Chinese populations and highlighted the importance of considering both genetic and environmental factors in AUD research.
Underappreciated role of canopy nitrogen deposition for forest productivity
Atmospheric nitrogen (N) deposition is generally expected to stimulate plant carbon (C) sequestration and promote tree growth, thereby mitigating atmospheric CO 2 accumulation. Yet, the magnitude of N deposition contribution to forest productivity remains contentious. While correlative studies suggest substantial plant growth enhancement, controlled fertilization experiments typically demonstrate a limited impact. This discrepancy may arise from whether or not to consider canopy N uptake processes. Here, we conducted a 10-y field experiment comparing canopy addition of N (CAN) with understory addition of N (UAN) at the rate of 0, 25, and 50 kg N ha –1 y –1 in a temperate deciduous forest in central China. We show that CAN significantly enhanced net primary productivity by 37.0% over control, driven by enhanced leaf litterfall, wood and fine root production, whereas UAN effects were marginal (8%). 15 N isotopic tracing revealed that CAN, through enhanced plant N uptake and increased ecosystem N retention, yielded a 3.5-fold higher C sequestration efficiency (∆C/∆N) of 54.5 ± 7.7 kg C kg –1 N, than UAN (12.2 ± 3.4 kg C kg –1 N) resulted from greater N loss through leaching. Physiological measurements indicated CAN enhanced leaf photosynthetic rates, modified leaf morphology, and extended leaf lifespan via delayed senescence. These findings provide robust empirical evidence that canopy N uptake is crucial for maximizing N-induced forest productivity, thereby holding significant implications for refining global C models and urging modelers to incorporate canopy processes for more accurate projections of future C sinks and climate change mitigation strategies.
Maintenance olaparib after platinum-based chemotherapy for advanced/metastatic endometrial cancer: GINECO randomized phase IIb UTOLA trial
Sex steroid hormones drive dimorphic responses in GDF15-deficient mouse models of cardiometabolic diseases
Flexible and scalable participatory syndromic and virological surveillance for respiratory infections: Our experiences in The Netherlands
Background During the COVID-19 pandemic participatory digital surveillance of symptoms (syndromic surveillance) re-established itself as a worthy addition to the surveillance pyramid, as they are scalable, flexible and function independent from the health care system or health care seeking behaviour. A limitation of syndromic surveillance however is the inability of pathogen identification. We describe our experiences regarding integrating self-swabs with centralized testing into a participatory syndromic surveillance system in the Netherlands (Infectieradar). Methods In the 2022/2023 winter season Infectieradar was extended to include nose- and throat swabs. Participants received test-kits including SARS-CoV-2 antigen tests for home use as well as nose- and throat swabs. All SARS-CoV-2 positive participants and a random sample of symptomatic SARS-CoV-2 self-test negative participants were asked to return a nose- and throat swab by regular post. Self-test negative swabs were tested by multiplex-PCR on 22 pathogens, including SARS-CoV-2. Self-test SARS-CoV-2 positive samples with a Ct-value < 30 were sequenced for variant analysis. Results Over 17,000 participants were included in the study, which involved relatively older persons and relatively more women compared to the general Dutch population. We collected 1,475 (median: 37 per week) swabs from participants with positive and 4,096 swabs (median: 136 per week) from participants with negative SARS-CoV-2 antigen self-tests (74% of those who requested to send in a swab). Of the swabs following a negative self-test, 47.7% tested positive in the multiplex-PCR, with rhinovirus/enterovirus being the most frequently detected pathogen (24.5%). Self-test SARS-CoV-2 positivity was laboratory-confirmed in 96.1% of swabs and showed parallel variant distributions as the national SARS-CoV-2 variant surveillance. Conclusion This large-scale, centralized participatory surveillance system provides a comprehensive approach for performing syndromic and virological surveillance in the general population, including respiratory pathogen detection by self-test or multiplex-PCR. Despite the non-representative sample it was possible to monitor the variant distribution. Given the continuous collection of samples among those who don’t seek care, the system provides valuable insights into circulating respiratory pathogens and is part of an answer on how to study the transmission, competition, virulence and evolution of circulating pathogens in interpandemic periods.
Definition of the components required for selective packaging of coronavirus genomic RNA
Most cytoplasmic RNA viruses have evolved mechanisms to identify their genomic RNA (gRNA) as the sole RNA species to be packaged into assembled virions. Coronaviruses exhibit highly selective packaging of their gRNA, in spite of the presence of a large excess of subgenomic viral and host RNA in infected cells. Failure to accomplish this selectivity does not impair virion assembly but renders the virus vulnerable to host innate immunity. In the prototype coronavirus mouse hepatitis virus (MHV) packaging selectivity is brought about by a packaging signal (PS), an RNA structure found exclusively in gRNA and absent from subgenomic RNAs. However, it is not well resolved how virion structural proteins participate in the recognition of the PS. Previous studies with virions have shown that the nucleocapsid (N) protein carboxy-terminal RNA-binding domain (CTD) and the carboxy-terminal tail (domain N3) both have roles in PS recognition. Separately, work with a virus-like particle system has implicated the viral membrane (M) protein as the main factor in this process. Here, we pinpoint key amino acids in the CTD and domain N3 that govern selective gRNA packaging into virions, and we provide genetic evidence that the M protein endodomain also plays a required role. We show that the N protein CTD is the primary determinant of PS recognition, and we localize residues in the CTD structure that are critical for specific and nonspecific RNA binding.
Dynamic construction of a durable epitaxial catalytic layer for industrial alkaline water splitting
Numerical simulation of velocity gradient scattering waves in visco-acoustic smooth media based on F-K domain integration method
Correction: No evidence for parallel evolution of cursorial limb adaptations among Neogene South American native ungulates (SANUs)
Reduced gas accretion onto galaxies due to effects of external giant radio lobes
Suppression effects of giant radio lobes from supermassive black holes on gas accretion onto galaxies in the surrounding regions are quantified using cosmological magneto-hydrodynamic simulations. With an appropriate amount of radio jet energy injected into the intergalactic medium following the formation peak of supermassive black holes at redshift two, we find that galaxies in the greater neighborhood of the jet-launching massive galaxies subsequently experience a significant reduction in the amount of accreted gas. The distribution of the resulting magnetic field in the intergalactic medium is highly inhomogeneous, due to the highly biased nature of the most massive supermassive black holes. In regions with magnetic field strength B > 10 − 2 μ G, the baryon fraction is on average reduced by 17%, 14%, and 12%, respectively, for halos of mass in the range of [ 10 11 , 10 12 ) M ⊙ , [ 10 12 , 10 13 ) M ⊙ , and [ 10 13 , 10 14 ) M ⊙ . A proper inclusion of this new, external, global, preventive feedback mechanism from active galactic nuclei (AGN) in the next generation of cosmological simulation may be necessary.
Evaluation of the protective effect of Benfotiamine against neurotoxic effects, depression and oxidative stress induced by noise exposure
Research on risk decision-making generation method for water conservancy project based on multimodal knowledge graph and large language model
Traditional knowledge graphs of water conservancy project risks have supported risk decision-making. However, they are constrained by limited data modalities and low accuracy in information extraction. A multimodal water conservancy project risk knowledge graph is proposed in this study, along with a synergistic strategy involving multimodal large language models Risk decision-making generation is facilitated through a multi-agent agentic retrieval-augmented generation framework. To enhance visual recognition, a DenseNet-based image classification model is improved by incorporating single-head self-attention and coordinate attention mechanisms. For textual data, risk entities such as locations, components, and events are extracted using a BERT-BiLSTM-CRF architecture. These extracted entities serve as the foundation for constructing the multimodal knowledge graph. To support generation, a multi-agent agentic retrieval-augmented generation mechanism is introduced. This mechanism enhances the reliability and interpretability of risk decision-making outputs. In experiments, the enhanced DenseNet model outperforms the original baseline in both precision and recall for image recognition tasks. In risk decision-making tasks, the proposed approach—combining a multimodal knowledge graph with a multi-agent agentic retrieval-augmented generation method—achieves strong performance on BERTScore and ROUGE-L metrics. This work presents a novel perspective for leveraging multimodal knowledge graphs in water conservancy project risk management.
FliO is an evolutionarily conserved yet diversified core component of the bacterial flagellar type III secretion system
The bacterial flagellum is a complex nanomachine essential for motility, environmental sensing, and host colonization. While many of its core components have been well characterized, the relevance of proteins such as FliO, which are inconsistently annotated and poorly conserved at the sequence level, has remained ambiguous in their evolutionary and functional status. Here, we present a comprehensive phylogenomic and structural analysis of FliO across >30,000 representative genomes spanning >100 bacterial phyla. Additionally, during this analysis, we found that approximately 40% of bacterial genomes contain flagellar genes—significantly fewer than previously reported. Using a custom pipeline combining low-threshold Hidden Markov models searches, operon context analysis, and structural information, we demonstrate that FliO is present in ~95% of genomes encoding the core flagellar components FliP, FliQ, and FliR. This suggests that FliO is a nearly ubiquitous and ancestral core component of the flagellar type III secretion system (fT3SS). FliO exhibits considerable structural diversity, including lineage-specific acquisitions of LysM and AMIN domains. We identify FliO homologs not only in canonical flagellar systems but also in some virulence-associated T3SS and even some nonflagellated organisms, suggesting functional repurposing and highlighting its functional plasticity. Functional studies in Campylobacter jejuni reveal that FliO and its AMIN domain are critical for efficient amphitrichous flagellation, membrane stability of the export gate component FlhB, and colonization of the host. These findings establish FliO as a core, yet evolutionarily dynamic, component of flagella and provide insights into the evolution and diversification of bacterial secretion systems.