Atmospheric and Oceanic Sciences

Abstract ATPases associated with diverse cellular activities (AAA+ -ATPases) catalyse a wide range of remodelling events in all phyla. AAA+ -ATPases of the MoxR-like family typically co-operate with von Willebrand factor type A (VWA) domain containing proteins to facilitate target remodelling and metal ion insertion, but their mechanism of action is poorly understood. We studied the bacterial AAA+ -ATPase NorQ in complex with its VWA domain partner protein NorD, which are essential for nitric oxide reductase (NOR) activity. Our cryo-EM structures and biochemical analyses show that NorQ and NorD engage through two key interfaces: (i) a finger-like extension protruding from the VWA domain that penetrates the central pore of the NorQ hexamer, and (ii) the NorD C- terminus, which contacts the post-sensor 1 loop of NorQ. Our data reveal that NorQ activity remodels a linker region in NorD essential for metal insertion. Together, these findings support a model in which the NorQ complex exerts a twisting and stretching force on the NorD linker, thereby enabling metal insertion into its target NOR.

The nascent polypeptide-associated complex (NAC) co-translationally screens all nascent proteins and regulates their access to signal recognition particle (SRP) to ensure the fidelity of protein targeting to the endoplasmic reticulum (ER). However, the mechanism by which NAC prevents the mistargeting of nascent mitochondrial proteins remains unclear. Here, we identify a molecular switch in NAC that allows its central barrel domain to adopt a stabilized conformation on ribosomes exposing a mitochondrial targeting sequence (MTS). Mutations of the MTS on the nascent chain or in the NAC switch region increase NAC barrel dynamics and reduce its binding to the ribosome. This impairs the ability of NAC to prevent mistargeting by SRP and causes ER stress in human cells. Our work reveals how NAC detects nascent mitochondrial proteins early in translation and prevents their promiscuous access to SRP, elucidating the structural basis that underlies this role and providing mechanistic insights into protein targeting fidelity with broader implications for cellular proteostasis. How ribosome-bound NAC distinguishes mitochondrial precursors from ER clients has remained unclear. Here, authors reveal a molecular switch in NAC that limits SRP access to nascent mitochondrial precursors and prevents their mistargeting to the ER.

The rapid proliferation of Artificial Intelligence applications necessitates scalable solutions that perform efficiently under real-world constraints. Heterogeneous accelerators combining specialized analog and digital units offer localized, energy-efficient neural network computations. However, achieving optimal performance on these platforms requires balancing energy efficiency and model accuracy through optimized neural network layer mapping. To this end, we introduce Mixed-Precision Supernetwork, a unified framework for training mixed-precision supernetworks that seamlessly integrate quantized layers with analog noise-sensitive layers. Mixed-Precision Supernetwork incorporates a mapping-aware adaptation strategy, dynamically optimizing layer assignments while refining the neural network via hardware-aware architecture search. This dual innovation establishes Mixed-Precision Supernetwork as a groundbreaking approach for deploying deep learning models efficiently on heterogeneous accelerators. On average, Mixed-Precision Supernetwork produces mappings ~ 2.2 × faster and achieves a ~ 3.4% increase in model accuracy over a fully analog approach, while improving energy-efficiency by mapping up to 80% of the model’s weights to analog hardware while maintaining full-precision accuracy. Deploying deep learning models efficiently on heterogeneous hardware remains challenging. Here, authors present a mixed-precision supernetwork that jointly optimizes model mapping and adaptation, enabling faster search, higher accuracy, and improved energy efficiency on analog-digital accelerators.

Elevated temperatures enhance plant root growth. We find that cell elongation significantly contributes to this response. While mutations in the auxin transcriptional pathway impair warmth-induced cell elongation, exogenous auxin inhibits this growth. Intriguingly, warmth increases auxin levels and the nuclear accumulation of TIR1/AFB2/AFB3, alongside Aux/IAA stabilisation. This apparent paradox is explained by the concurrent increase in nuclear AFB1, which stabilises Aux/IAAs and promotes cell elongation. Notably, despite enhancing Aux/IAA stability, warmth also promotes ARF transcriptional activity. ARF7/19 are essential for warmth-induced cell growth and its inhibition by exogenous auxin. Warmth directly modulates ARF7/19 by reducing oligomerisation and cytoplasmic condensation, thereby enhancing their nuclear accumulation. This mechanism effectively repurposes the auxin pathway to regulate root cell growth in response to temperature. While auxin typically inhibits root cell growth, elevated temperatures reconfigure the auxin transcriptional pathway to promote elongation. This study reveals how plants reprogram core hormonal signalling to adjust their internal biology to rising temperatures.

Abstract Agricultural ecosystems play a significant role in global food security and climate mitigation through crop production and soil organic carbon sequestration. It is well-established that potassium fertilization enhances crop yield in potassium-deficient regions; however, the factors driving crop yield responses to potassium remain insufficiently characterized at a large scale. Moreover, despite the significant roles of soil organic carbon in soil health and global carbon cycling, the effect of potassium on soil organic carbon in croplands has been less studied. Herein, we collect data from 1185 observations in agricultural ecosystems to conduct a meta-analysis study. We find that potassium fertilization increases cereal yield and soil organic carbon by 19.3% and 4.4%, respectively. Mean annual precipitation and experimental duration are the most important factors affecting potassium effects on cereal yield and soil organic carbon, respectively. Specifically, potassium effects on cereal yield increase with mean annual precipitation, and the potassium-induced increase in soil organic carbon is significant only after long-term (> 20 years) potassium fertilization. Our findings suggest that, in addition to nitrogen and phosphorus, potassium is also crucial for not only cereal yield but also soil carbon sequestration, which should be fully valued in future soil nutrient management, especially in potassium-deficient regions.

Abstract The ability to accurately measure aberrant DNA methylation levels is integral to the understanding of DNA methylation biology. It is well-established that in cancer, the largest, and thus, most biologically important absolute gains of DNA methylation levels occur at CpG sites with low native levels while the largest losses occur at CpG sites with high native levels. Conventional wisdom assumes that the observed association between the degree of the alterations and the native levels are largely due to the limitations of change within the DNA methylation scale. Here, we present evidence that this association is largely caused by alterations occurring as a global rate of change relative to the native level. We show that DNA methylation alterations can be accurately compared by calculating the rate of change relative to the native level. Most importantly, this approach enables the identification of more biologically significant DNA methylation alterations.

Copy number variation (CNV) plays a fundamental role in modulating plant agronomic traits and tumorigenesis in animals. While frequently linked to replication stress, the mechanisms giving rise to CNVs are not fully elucidated. Here we characterize the mutational consequences associated with losing the conserved TONSOKU (TSK/TONSL) pathway (CAF-1-H3.1-TSK), which is required to resolve impaired DNA replication forks. Using Arabidopsis thaliana, we demonstrate that tsk mutants rapidly accumulate large, heritable tandem duplications within their genomes that are consistent with DNA Polymerase θ (Pol θ) activity. These duplications are associated with late replicating heterochromatin enriched in sources of replication stress. We also show that stochastic developmental phenotypes in tsk plants are the result of the DNA Damage Response (DDR), with phenotype suppression occurring when ATR–WEE1 checkpoint signaling is removed. We thus describe a previously uncharacterized source of large tandem duplications that are relevant to understanding genome stability in diverse eukaryotes, and in disease contexts. Large tandem duplications arise in Arabidopsis genomes in the absence of the DNA repair protein TONSOKU. This is linked to the activity of Pol θ and sites of late-replicating heterochromatin. This genome instability causes developmental defects dependent on the ATR-WEE1 axis of the DNA damage response.

Abstract Cholesteric liquid crystal elastomers (CLCEs) change color under strain, offering attractive prospects for soft robotics and photonic devices. However, the helical structure of CLCEs averages out the exceptional anisotropy and soft elasticity of the nematic phase, leaving little scope for also using the director orientation to program their thermal or mechanical actuation. Here, we develop programmable CLCE hollow fibers with longitudinal, circumferential, or twisted alignments via the integration of dynamic boronic ester bonds and mechanical force/pressure-induced orientation, all while preserving sufficient periodicity for structural color. Upon inflation, these fibers exhibit diverse motions—expansion, contraction, elongation, twisting—with synchronous color adaptation. Accordingly, we derive a membrane balloon model based on the non-ideal neo-classical LCE energy with suitable CLCE director profiles, successfully capturing key mechanical features including non-monotonicity and sub-criticality. This study provides a paradigm for the development of intelligent shape- and color-changing systems in a bespoke and versatile way.

Abstract Aging accelerates central nervous system remyelination failure and neurodegeneration. Microglia promote remyelination by phagocytosing myelin debris, but this function is impaired by aging-related CD22 upregulation. However, the molecular mechanisms counteracting premature aging-related microglial dysfunction and remyelination impairment remain unclear. Here, we report that Aurka-Bhlhe41 axis prevents premature aging-like microglial dysfunction and promotes remyelination by restraining progressive CD22 upregulation. We identified that microglia-enriched Bhlhe41 was negatively autoregulated and inhibited by Aurka loss. Bhlhe41- or Aurka -deficient young mice exhibited aging-like microglial morphology, phagocytic deficits, progressive CD22 upregulation, and remyelination impairment in cuprizone-induced demyelination model. Conversely, ectopic Bhlhe41 expression induced hypertrophic microglia, and counteracted phagocytic deficits and CD22 upregulation in Aurka -deficient microglia. CD22 blockade restored phagocytic function and remyelination in Bhlhe41 -deficient mice. Notably, a conserved pattern of CD22 upregulation was observed in human PCDH9 high microglia subsets with BHLHE41 downregulation. These findings offer insights into potential therapeutic strategies to combat aging-related neurodegeneration and central nervous system functional decline.

Weak seed dormancy (SD) is prone to pre-harvest sprouting (PHS), which reduces cereal yield and quality. Here, through map-based analysis, we identify TaCNGC-2A, encoding a cyclic nucleotide-gated channel protein, as a negative regulator of wheat SD. Knocking out of TaCNGC-2A enhances SD and PHS resistance, with no yield penalty. Two transcription factors, TaMYB-5B and TaMYB-5D, directly bind to the T/A mutation site of TaCNGC-2A promoter to synergistically repress its expression. The calmodulin TaCaM-3A interacts with TaCNGC-2A to jointly modulate SD and PHS resistance through influencing calcium and multiple hormonal signaling pathways. Knocking out of TaCaM-3A not only enhances SD and PHS resistance, but also increases grain weight and per-plant yield. Finally, we identify allele combinations of TaCNGC-2A and other known dormancy genes associated with strong SD. This study uncovers a regulatory mechanism underlying SD and PHS resistance and provides gene targets for breeding wheat varieties with PHS resistance. Pre-harvest sprouting (PHS) causes severe yield and quality loss in cereal crops worldwide. Here, the authors report a cyclic nucleotide-gated channel/Ca2 + -permeable channel encoding protein negatively regulate PHS and its involvement in modulating of calcium and hormonal signaling pathways in wheat.

Abstract Photon-recoil–based actuation enables maneuvering of micro- and nanoscale objects without beam steering or tight focusing, mitigating system complexity and photodamage. Recent light-driven microdrones achieved full control in two dimensions using multiple laser fields; however, for many applications, sacrificing degrees of freedom allows substantial miniaturization and improved propulsion efficiency. Here, we demonstrate sub-micrometer nanorobots actuated by a plasmonic directional antenna that simultaneously provides propulsion force and orientation control. The nanorobots reach propulsion speeds up to 50 μm/s, with their motion direction intrinsically locked perpendicular to the linear polarization axis. Circularly polarized light pulses lift the resulting twofold orientational degeneracy through spin–momentum transfer. Using opto-thermophoretic forces, nanorobots efficiently capture, transport, reversibly assemble, and release bacteria. By sequencing linear and circular polarization states, they execute complex, high-precision trajectories to systematically sweep defined regions, functioning as light-driven robotic cleaners. This work expands the capabilities of nanorobots for biological manipulation and high-speed, localized sensing.

Plants use the plant hormone auxin to incorporate environmental cues into their growth and development to shape the final form. Temperature is an important modulator of all aspects of plant function and growth. In this work, we uncover temperature-regulated accumulation and solubility of members of the AUXIN RESPONSE FACTOR transcription factor family. We determine that ARF7 and ARF19 proteins rapidly hyperaccumulate in response to elevated temperature. Furthermore, we find that diffuse concentrations of ARF protein increase under elevated temperature, consistent with increased solubility. Temperature-driven ARF hyperaccumulation is not fully dependent on the well-established temperature response pathways. We find that natural variation in thermoregulated ARF accumulation is correlated with thermomorphogenesis, suggesting that this is a dial switch in plant temperature response. Regulated ARF thermoaccumulation provides a layer of complexity in shaping and plant growth and form, allowing plants to respond rapidly and persistently to elevated temperatures by modulating levels of nuclear ARF protein accumulation. Elevated temperature is shown to rapidly increase the abundance and solubility of key auxin regulators, ARF7 and ARF19. Natural variation in this thermoregulated accumulation correlates with plant growth responses, suggesting a tunable mechanism for temperature adaptation.

The 26S proteasome typically degrades proteins marked by ubiquitin chains. However, a distinct, ubiquitin-independent degradation pathway for nuclear proteins exists, mediated by the adaptor protein midnolin, yet its molecular mechanism remains poorly understood. Here, we present nine cryo-electron microscopy structures of the human 26S proteasome in complex with midnolin, which collectively delineate a near-complete catalytic cycle. Our structures reveal that midnolin binds to the proteasome via the RPN1 subunit by its C-terminal helix. Unexpectedly, its ubiquitin-like domain interacts with the RPN11 deubiquitinase in a non-catalytic role. This interaction positions the adjacent Catch domain, which is responsible for substrate binding, directly above the proteasomal entrance, potentially facilitating substrate entry into the proteasome. Furthermore, we observe four consecutive spiral staircase conformations of the AAA+ ATPase hexamer during substrate translocation. These findings provide insights into the mechanisms underlying ubiquitin-independent nuclear protein degradation and may help develop strategies for targeting nuclear proteins via direct proteasomal degradation. Proteasomes typically degrades ubiquitin-tagged proteins, but midnolin enables a distinct ubiquitin-independent pathway. Here, the authors present cryo-EM structures of the midnolin-proteasome complex, revealing how midnolin directly captures and feeds untagged nuclear proteins into the proteasome.

CDK4/6 inhibitors (CDK4/6i) have shown striking clinical potential in hormone receptor-positive breast cancers (BC) and endometrial cancers (EC), whereas resistance hinders their clinical utilization. The role of epigenetic alterations in CDK4/6i resistance remains poorly elucidated. Herein, through a comprehensive analysis of transcriptomic and chromatin profiles in 16 EC tissues and cell-based resistance models, we delineate the super-enhancer (SE) landscape and identify aldehyde dehydrogenase 1 family member A1 (ALDH1A1) as a SE-driven gene closely associated with CDK4/6i resistance. ALDH1A1 inhibition increases susceptibility to CDK4/6i in multiple EC and BC models. Mechanistically, we demonstrate that ALDH1A1 promotes vitamin A (vitA) metabolism and induces the accumulation of its downstream metabolite, retinoic acid (RA), in resistant cells. In return, the elevated RA potentiates the interaction between retinoic acid receptor alpha (RARα) and estrogen receptor alpha (ERα) in the nucleus and facilitates RARα/ERα-occupied SE-driven transcriptional activation of ALDH1A1, establishing a positive feedback loop that promotes CDK4/6i resistance. These findings highlight the crucial role of vitA metabolism in the epigenetic transcriptional program associated with CDK4/6i resistance, suggesting that avoiding high vitA intake or inhibiting the ALDH1A1-RA axis may be effective strategies to overcome this challenge. CDK4/6 inhibitors response is limited by frequent resistance in hormone receptor– positive cancers. Here, the authors show that a super enhancer driven increase in aldehyde dehydrogenase creates a vitamin A/retinoic acid feedback loop that promotes resistance in breast and endometrial cancer.

Rooftop photovoltaics are widely recognized for the carbon mitigation benefits, yet uncertainties persist regarding their future dynamics and broader impacts on water and land. Here we develop a city-level integrated framework to quantify rooftop photovoltaics potential across 349 Chinese cities, and evaluate evolving carbon-water-land tradeoffs under shared socioeconomic and representative concentration pathways. By 2050, projections across 15 combined scenarios indicate China’s rooftop photovoltaic areas will increase by 9.2 to 34.8 percent relative to 2020 levels. Installed capacity ranges from 7.19 to 9.05 terawatts in 2050, expanding rapidly in eastern coastal cities. Under a moderate socioeconomic and climate scenario, the national carbon mitigation benefits peak during 2035 to 2040, accumulating 2.04 to 2.18 gigatons of carbon dioxide equivalent by 2050. In contrast, the water and land saving benefits continue to rise, reaching 16.5 to 17.4 cubic kilometers and 281 to 297 thousand square kilometers by 2050. These findings underscore the critical need for multidimensional planning to optimize future sustainable photovoltaics deployment. This study maps China’s rooftop PV potential across 349 cities through 2050. It reveals diverging trajectories where carbon mitigation peaks in 2035–2040, yet water and land savings rise continuously, highlighting PV system’s evolving systemic value.