经典100 | NCS： 2025-05-27 期

『Abstract』Heterotrophic bacteria and archaea (“heteroprokaryotes”) drive global carbon cycling, but how to quantitatively organize their functional complexity remains unclear. We generated a global-scale understanding of marine heteroprokaryotic functional biogeography by synthesizing genetic sequencing data with a mechanistic marine ecosystem model. We incorporated heteroprokaryotic diversity into the trait-based model along two axes: substrate lability and growth strategy. Using genetic sequences along three ocean transects, we compiled 21 heteroprokaryotic guilds and estimated their degree of optimization for rapid growth (copiotrophy). Data and model consistency indicated that gradients in grazing and substrate lability predominantly set biogeographical patterns, and we identified deep-ocean “slow copiotrophs” whose ecological interactions control the surface accumulation of dissolved organic carbon.

『Abstract』Antagonistic activities of the 53BP1 axis and the tumor suppressor BRCA1-BARD1 determine whether DNA double-strand breaks (DSBs) are repaired by end joining or homologous recombination. We show that the CTC1-STN1-TEN1 (CST) complex, a central 53BP1 axis component, suppresses DNA end resection by EXO1 and the BLM-DNA2 helicase-nuclease complex but acts by distinct mechanisms in restricting these entities. Whereas BRCA1-BARD1 alleviates the CST-imposed EXO1 blockade, it has little effect on BLM-DNA2 restriction. CST mutants impaired for DNA binding or BLM–EXO1 interaction exhibit a hyper-resection phenotype and render BRCA1-deficient cells resistant to poly(ADP–ribose) polymerase (PARP) inhibitors. Our findings mechanistically define the crucial role of CST in DNA DSB repair pathway choice and have implications for understanding cancer therapy resistance stemming from dysfunction of the 53BP1 axis.

『Abstract』Null space theory predicts that neurons generate spikes not only to produce behavior but also to prevent the undesirable effect of other neurons on behavior. In this work, we show that this competitive cancellation is essential for understanding computation in the cerebellum. In marmosets, we identified a vector for each Purkinje cell (P cell) along which its spikes displaced the eyes. Two spikes in two different P cells produced superposition of their vectors. In the resulting population activity, the spikes were canceled if their contributions were perpendicular to the intended movement. Mossy fibers provided a copy of the motor commands and the goal of the movement. Molecular layer interneurons transformed these inputs so that the P cell population predicted when the movement had reached the goal and should be stopped.

『Abstract』Intrinsically disordered regions (IDRs) in proteins play essential roles in cellular function. A growing body of work has shown that IDRs often interact with partners in a manner that does not depend on the precise order of amino acids but is instead driven by complementary chemical interactions, leading to disordered bound-state complexes. However, these chemically specific dynamic interactions are difficult to predict. In this study, we repurposed the chemical physics developed originally for molecular simulations to predict this chemical specificity between IDRs and partner proteins using protein sequence as the only input. Our approach—FINCHES—enables the direct prediction of phase diagrams, the identification of chemically specific interaction hotspots on IDRs, the decomposition of chemically distinct domains in IDRs, and a route to develop and test mechanistic hypotheses regarding IDR function in molecular recognition.

『Abstract』Coherently controlling the motion of single atoms in optical tweezers would enable new applications in quantum information science. To demonstrate this, we first prepared atoms in their motional ground state using a species-agnostic cooling mechanism that converts motional excitations into erasures, errors with a known location. This cooling mechanism fundamentally outperforms idealized traditional sideband cooling, which we experimentally demonstrated. By coherently manipulating the resultant pure motional state, we performed mid-circuit readout and mid-circuit erasure detection through local shelving into motional superposition states. We lastly entangled the motion of two atoms in separate tweezers and generated hyperentanglement by preparing a simultaneous Bell state of motional and optical qubits, unlocking a large class of quantum operations with neutral atoms.

『Abstract』Transforming laboratory-scale perovskite solar cells to large-scale production will require uniform crystallization of the perovskite film. We designed a method to aid the crystallization process by generating well-defined three-dimensional (3D) laminar airflow over square meter–sized perovskite films using a customized 3D-printed structure. The resultant perovskite solar modules with areas of 0.7906 square meters had a certified power conversion efficiency of 15.0% and achieved compliance with three sets of solar cell standards. Our metrics for a 1-year operational study from a 0.5–megawatt peak power perovskite solar farm indicate a 29% higher energy yield per kilowatt of installed capacity compared with that of silicon modules at the same facility that primarily resulted from their temperature-dependent operational characteristics.

『Abstract』Following fertilization, the preimplantation embryo undergoes successive rounds of cell division and must accurately propagate the genetic material to ensure successful development. However, early mammalian embryos lack efficient spindle assembly mechanisms, and it remains unclear how error-free chromosome segregation is achieved. In this work, we imaged early mouse embryos and identified a network of nuclear actin cables that organize prophase chromosomes at the nuclear periphery. Following nuclear envelope breakdown, the network contracts and gathers chromosomes toward the cell center. Network contraction was driven by filament disassembly in a myosin II–independent manner. Additionally, we identified a network of branched actin filaments that attenuates metaphase spindle elongation. We also visualized nuclear actin in human embryos, suggesting a conserved role for actin in ensuring mitotic fidelity during early mammalian development.

『Abstract』A stellar common envelope occurs in a binary system when the atmosphere of an evolving star expands to encompass an orbiting companion object. Such systems are predicted to evolve rapidly, ejecting the stellar envelope and leaving the companion in a tighter orbit around a stripped star. We used radio timing to identify a pulsar, PSR J1928+1815, with a spin period of 10.55 ms in a compact binary system with an orbital period of 3.60 hours. The companion star has 1.0 to 1.6 solar masses, eclipses the pulsar for about 17% of the orbit, and is undetected at other wavelengths, so it is most likely a stripped helium star. We interpret this system as having recently undergone a common envelope phase, producing a compact binary.

『Abstract』The emergence of multi-tonne herbivores is a recurrent aspect of the Cenozoic mammalian radiation. Several of these giants have vanished within the past 130,000 years, but the timing and macroevolutionary drivers behind this pattern of rise and collapse remain unclear for some megaherbivore lineages. Using trait modeling that combines total-evidence evolutionary trees and a comprehensive size dataset, we show that sloth body mass evolved with major lifestyle shifts and that most terrestrial lineages reached their largest sizes through slower evolutionary rates compared with extant arboreal forms. Size disparity increased during the late Cenozoic climatic cooling, but paleoclimatic changes do not explain the rapid extinction of ground sloths that started approximately 15,000 years ago. Their abrupt demise suggests human-driven factors in the decline and extinction of ground sloths.

『Abstract』In temperate regions experiencing rapid ocean warming, kelp forests are being replaced by chemically rich turf algae. However, the extent to which these turf algae alter the surrounding chemical environment or affect the rebound potential of kelp forests (through chemically mediated interactions) remains unknown. Here, we used underwater visual surveys, comprehensive chemical profiling, and laboratory experiments to reveal that turf algae release bioactive compounds into the water that fundamentally alter the reef “chemical landscape” and directly suppress kelp recruitment. Therefore, our study reveals that chemical ecology is critical in shaping modern kelp forest ecosystems and their resilience. Further, it demonstrates that reversing climate-driven state shifts will require not only curbing global carbon emissions but also implementing targeted local interventions that break harmful ecological feedback loops and foster recovery.

『Abstract』Hydrogen-like light muonic ions, in which one negative muon replaces all of the electrons, are extremely sensitive probes of nuclear structure. Using pulsed laser spectroscopy, we have measured three 2 S -2 P transitions in the muonic helium-3 (μ He ) ion, an ion formed by a negative muon and bare helium-3 nucleus. This allowed us to extract the Lamb shift, the 2 P fine structure splitting, and the 2 S -hyperfine splitting in μ He . Comparing these measurements with theory, we determined the root-mean-square charge radius of the helion ( He nucleus) to be r h = 1.97007(94) fm, in good agreement with the value from elastic electron scattering but a factor 15 more accurate. Our results represent benchmarks for few-nucleon theories and open the way for precision quantum electrodynamics tests in He atoms and ions.

『Abstract』Accurate spectroscopic measurements of calculable systems provide a powerful method for testing the Standard Model and extracting fundamental constants. Recently, spectroscopic measurements of finite nuclear size effects in normal and muonic hydrogen resulted in unexpectedly large adjustments of the proton charge radius and the Rydberg constant. We measured the 2 S →2 S transition frequency in a Fermi gas of He with an order of magnitude higher accuracy than determined previously. Together with a previous measurement in a He Bose-Einstein condensate, a squared charge radius difference r h – r α = 1.0757(12) exp (9) theo fm was determined between the helion and alpha particle. This measurement provides a stringent benchmark for nuclear structure calculations.

『Abstract』Several bacterial pathogens have transitioned from tick-borne to louse-borne transmission, which often involves genome reduction and increasing virulence. However, the timing of such transitions remains unclear. We sequenced four ancient Borrelia recurrentis genomes, the agent of louse-borne relapsing fever, dating from 2300 to 600 years ago. We estimated the divergence from its closest tick-borne relative to 6000 to 4000 years ago, which suggests an emergence coinciding with human lifestyle changes such as the advent of wool-based textiles. Pan-genome analysis indicated that much of the evolution characteristic of B. recurrentis had occurred by ~2300 years ago, though further gene turnover, particularly in plasmid partitioning, persisted until ~1000 years ago. Our findings provide a direct genomic chronology of the evolution of this specialized vector-borne pathogen.

『Abstract』Interfacial polymerization has been an industrial standard for preparing desalination membranes. Extending the same concept to molecular separation of organic solvents would be a key enabler for the decarbonization of the chemical and petrochemical industries through energy-efficient crude or biocrude oil fractionation. Here, we report a molecular engineering approach based on acid-catalyzed interfacial polymerization for efficient hydrocarbon separation. The design strategies include (i) changing the linkage from amide to imine and (ii) subsequent introduction of shape-persistent units such as triptycene and spirobifluorene. The prepared polyimine membranes exhibit ultrahigh microporosity and enhanced swelling and plasticization resistance compared with conventional polyamide counterparts. These membranes, which feature fast and selective transport of hydrocarbons, including multicomponent and industrially relevant mixtures, outperform commercial and state-of-the-art benchmark membranes.

『Abstract』Deep learning has advanced the design of static protein structures, but the controlled conformational changes that are hallmarks of natural signaling proteins have remained inaccessible to de novo design. Here, we describe a general deep learning–guided approach for de novo design of dynamic changes between intradomain geometries of proteins, similar to switch mechanisms prevalent in nature, with atomic-level precision. We solve four structures that validate the designed conformations, demonstrate modulation of the conformational landscape by orthosteric ligands and allosteric mutations, and show that physics-based simulations are in agreement with deep-learning predictions and experimental data. Our approach demonstrates that new modes of motion can now be realized through de novo design and provides a framework for constructing biology-inspired, tunable, and controllable protein signaling behavior de novo.

『Abstract』Environmental thermal challenges trigger the brain to coordinate both autonomic and behavioural responses to maintain optimal body temperature . It is unknown how temperature information is precisely stored and retrieved in the brain and how it is converted into a physiological response. Here we investigated whether memories could control whole-body metabolism by training mice to remember a thermal challenge. Mice were conditioned to associate a context with a specific temperature by combining thermoregulatory Pavlovian conditioning with engram-labelling technology, optogenetics and chemogenetics. We report that if mice are returned to an environment in which they previously experienced a 4 °C cold challenge, they increase their metabolic rates regardless of the actual environmental temperature. Furthermore, we show that mice have increased hypothalamic activity when they are exposed to the cold, and that a specific network emerges between the hippocampus and the hypothalamus during the recall of a cold memory. Both natural retrieval and artificial reactivation of cold-sensitive memory engrams in the hippocampus mimic the physiological responses that are seen during a cold challenge. These ensembles are necessary for cold-memory retrieval. These findings show that retrieval of a cold memory causes whole-body autonomic and behavioural responses that enable mice to maintain thermal homeostasis.

『Abstract』The pressures humanity has been placing on the environment have put Earth’s stability at risk. The planetary boundaries framework serves as a method to define a ‘safe operating space for humanity’ and has so far been applied mostly to highlight the currently prevailing unsustainable environmental conditions. The ability to evaluate trends over time, however, can help us explore the consequences of alternative policy decisions and identify pathways for living within planetary boundaries . Here we use the Integrated Model to Assess the Global Environment to project control variables for eight out of nine planetary boundaries under alternative scenarios to 2050, both with and without strong environmental policy measures. The results show that, with current trends and policies, the situation is projected to worsen to 2050 for all planetary boundaries, except for ozone depletion. Targeted interventions, such as implementing the Paris climate agreement, a shift to a healthier diet, improved food, and water- and nutrient-use efficiency, can effectively reduce the degree of transgression of the planetary boundaries, steering humanity towards a more sustainable trajectory (that is, if they can be implemented based on social and institutional feasibility considerations). However, even in this scenario, several planetary boundaries, including climate change, biogeochemical flows and biodiversity, will remain transgressed in 2050, partly as result of inertia. This means that more-effective policy measures will be needed to ensure we are living well within the planetary boundaries.

『Abstract』Liver regeneration after hepatectomy follows accurate coordination with the body’s specific requirements . However, the molecular mechanisms, factors and particular hepatocyte population influencing its efficiency remain unclear. Here we report on a unique regeneration mechanism involving unconventional RPB5 prefoldin interactor 1 (URI1), which exclusively colocalizes with, binds to and activates glutamine synthase (GS) in pericentral hepatocytes. Genetic GS or URI1 depletion in mouse pericentral hepatocytes increases circulating glutamate levels, accelerating liver regeneration after two-third hepatectomy. Conversely, mouse hepatocytic URI1 overexpression hinders liver restoration, which can be reversed by elevating glutamate through supplementation or genetic GS depletion. Glutamate metabolically reprograms bone-marrow-derived macrophages, stabilizing HIF1α, which transcriptionally activates WNT3 to promote YAP1-dependent hepatocyte proliferation, boosting liver regeneration. GS regulation by URI1 is a mechanism that maintains optimal glutamate levels, probably to spatiotemporally fine-tune liver growth in accordance with the body’s homeostasis and nutrient supply. Accordingly, in acute and chronic injury models, including in cirrhotic mice with low glutamate levels and in early mortality after liver resection, as well as in mice undergoing 90% hepatectomy, glutamate addition enhances hepatocyte proliferation and survival. Furthermore, URI1 and GS expression co-localize in human hepatocytes and correlate with WNT3 in immune cells across liver disease stages. Glutamate supplementation may therefore support liver regeneration, benefiting patients awaiting transplants or recovering from hepatectomy.

『Abstract』Parkinson’s disease is caused by the loss of dopamine neurons, causing motor symptoms. Initial cell therapies using fetal tissues showed promise but had complications and ethical concerns . Pluripotent stem (PS) cells emerged as a promising alternative for developing safe and effective treatments . In this phase I/II trial at Kyoto University Hospital, seven patients (ages 50–69) received bilateral transplantation of dopaminergic progenitors derived from induced PS (iPS) cells. Primary outcomes focused on safety and adverse events, while secondary outcomes assessed motor symptom changes and dopamine production for 24 months. There were no serious adverse events, with 73 mild to moderate events. Patients’ anti-parkinsonian medication doses were maintained unless therapeutic adjustments were required, resulting in increased dyskinesia. Magnetic resonance imaging showed no graft overgrowth. Among six patients subjected to efficacy evaluation, four showed improvements in the Movement Disorder Society Unified Parkinson’s Disease Rating Scale part III OFF score, and five showed improvements in the ON scores. The average changes of all six patients were 9.5 (20.4%) and 4.3 points (35.7%) for the OFF and ON scores, respectively. Hoehn–Yahr stages improved in four patients. Fluorine-18- l -dihydroxyphenylalanine ( F-DOPA) influx rate constant ( K i ) values in the putamen increased by 44.7%, with higher increases in the high-dose group. Other measures showed minimal changes. This trial (jRCT2090220384) demonstrated that allogeneic iPS-cell-derived dopaminergic progenitors survived, produced dopamine and did not form tumours, therefore suggesting safety and potential clinical benefits for Parkinson’s disease.

『Abstract』Reactive oxygen species (ROS) underlie human pathologies including cancer and neurodegeneration . However, the proteins that sense ROS levels and regulate their production through their cysteine residues remain ill defined. Here, using systematic base-editing and computational screens, we identify cysteines in VPS35, a member of the retromer trafficking complex , that phenocopy inhibition of mitochondrial translation when mutated. We find that VPS35 underlies a reactive metabolite-sensing pathway that lowers mitochondrial translation to decrease ROS levels. Intracellular hydrogen peroxide oxidizes cysteine residues in VPS35, resulting in retromer dissociation from endosomal membranes and subsequent plasma membrane remodelling. We demonstrate that plasma membrane localization of the retromer substrate SLC7A1 is required to sustain mitochondrial translation. Furthermore, decreasing VPS35 levels or oxidation of its ROS-sensing cysteines confers resistance to ROS-generating chemotherapies, including cisplatin, in ovarian cancer models. Thus, we identify that intracellular ROS levels are communicated to the plasma membrane through VPS35 to regulate mitochondrial translation, connecting cytosolic ROS sensing to mitochondrial ROS production.

『Abstract』Despite the widespread use of mRNA vaccines against COVID-19, little is known about the metabolism of therapeutic RNAs. Here we use nanopore sequencing to analyse individual therapeutic mRNA molecules, focusing on their poly(A) tails. We show that the Moderna mRNA-1273 vaccine has a poly(A) tail of around 100 nucleotides, followed by an mΨCmΨAG sequence. In cell lines, mRNA-1273 undergoes rapid degradation initiated by mΨCmΨAG removal, followed by CCR4–NOT-mediated deadenylation. However, in medically relevant preclinical models, particularly in macrophages, mRNA-1273 poly(A) tails are extended to up to 200 nucleotides by the TENT5A poly(A) polymerase , which is induced by the vaccine. Re-adenylation, which stabilizes target mRNAs, is consistently observed in synthetic mRNAs that encode proteins targeted to the endoplasmic reticulum, such as ovalbumin or antigens from Zika virus or the malaria parasite . The extent of re-adenylation varies: the BioNTech–Pfizer BNT162b2 vaccine shows less potent re-adenylation than mRNA-1273, which correlates with a smaller proportion of membrane-associated BNT162b2. This highlights the crucial role of spatial accessibility to ER-resident TENT5A in determining re-adenylation efficiency. In vivo, TENT5A is expressed in immune cells that take up mRNA vaccine, and TENT5A deficiency reduces specific immunoglobulin production for mRNA vaccines after immunization in mice. Overall, our findings reveal a principle for enhancing the efficacy of therapeutic mRNAs, paving the way for improvement.

『Abstract』In quantum mechanics, empty space is not void but is characterized by vacuum-field fluctuations, which underlie phenomena such as the Lamb shift , spontaneous emission, and the Casimir effect . Due to their quantitatively small relative contributions in free-space atomic physics, they were traditionally overlooked in solid-state systems. Recently, however, the interplay between electronic correlations and quantum electrodynamical effects in low-dimensional systems has become a rapidly advancing area in condensed matter physics , with substantial implications for quantum materials and device engineering. High-mobility two-dimensional electron gases in the quantum Hall regime offer an ideal platform to investigate how vacuum electromagnetic fields affect strongly correlated electronic states. Here we demonstrate that adjusting the coupling strength between a two-dimensional electron gas and the vacuum fields of a hovering split-ring resonator leads to a significant reduction in exchange splitting at odd-integer filling factors, along with an enhancement of fractional quantum Hall gaps at filling factors 4/3, 5/3 and 7/5. Theoretical analysis indicates that these effects stem from an effective long-range attractive interaction mediated by virtual cavity photons in regions with strong vacuum electric field gradients. Our findings uncover a new mechanism by which cavity vacuum fields can reshape electronic correlations in quantum Hall systems, establishing a new approach for manipulating correlated quantum phases in low-dimensional materials and paving the way for engineering tailored many-body interactions in compact devices.

『Abstract』The mammalian nucleus is compartmentalized by diverse subnuclear structures. These subnuclear structures, marked by nuclear bodies and histone modifications, are often cell-type specific and affect gene regulation and 3D genome organization . Understanding their relationships rests on identifying the molecular constituents of subnuclear structures and mapping their associations with specific genomic loci and transcriptional levels in individual cells, all in complex tissues. Here, we introduce two-layer DNA seqFISH+, which enables simultaneous mapping of 100,049 genomic loci, together with the nascent transcriptome for 17,856 genes and subnuclear structures in single cells. These data enable imaging-based chromatin profiling of diverse subnuclear markers and can capture their changes at genomic scales ranging from 100–200 kilobases to approximately 1 megabase, depending on the marker and DNA locus. By using multi-omics datasets in the adult mouse cerebellum, we showed that repressive chromatin regions are more variable by cell type than are active regions across the genome. We also discovered that RNA polymerase II-enriched foci were locally associated with long, cell-type-specific genes (bigger than 200 kilobases) in a manner distinct from that of nuclear speckles. Furthermore, our analysis revealed that cell-type-specific regions of heterochromatin marked by histone H3 trimethylated at lysine 27 (H3K27me3) and histone H4 trimethylated at lysine 20 (H4K20me3) are enriched at specific genes and gene clusters, respectively, and shape radial chromosomal positioning and inter-chromosomal interactions in neurons and glial cells. Together, our results provide a single-cell high-resolution multi-omics view of subnuclear structures, associated genomic loci and their effects on gene regulation, directly within complex tissues.

『Abstract』Bar structures are present in about half of local disk galaxies and play pivotal roles in secular galaxy evolution. Bars impose a non-axisymmetric perturbation on the rotating disk and transport gas inwards to feed the central starburst and, possibly, the activity of the nuclear supermassive black hole . They are believed to be long-lived structures and are now identified at redshift z > 2 (refs. ). However, little is known about the onset and effects of bars in the early cosmic epoch because the spectroscopy of distant bars at sufficient resolution is prohibitively expensive. Here we report on a kinematic study of a galactic bar at redshift 2.467, 2.6 billion years after the Big Bang. We observed the carbon monoxide and atomic carbon emission lines of the dusty star-forming galaxy J0107a and found the bar of J0107a has gas distribution and motion in a pattern identical to local bars . At the same time, the bar drives large-scale non-circular motions that dominate over disk rotation, funnelling molecular gas into its centre at a rate of approximately 600 solar masses per year. Our results show that bar-driven dynamical processes and secular evolution were already at play 11.1 billion years ago, powering active star formation amid the gas-rich and far-infrared luminous growth phase in a massive disk galaxy.

『Abstract』Acute myocardial infarction is a leading cause of morbidity and mortality worldwide . Clinical studies have shown that the severity of cardiac injury after myocardial infarction exhibits a circadian pattern, with larger infarcts and poorer outcomes in patients experiencing morning-onset events . However, the molecular mechanisms underlying these diurnal variations remain unclear. Here we show that the core circadian transcription factor BMAL1 regulates circadian-dependent myocardial injury by forming a transcriptionally active heterodimer with a non-canonical partner—hypoxia-inducible factor 2 alpha (HIF2A) —in a diurnal manner. To substantiate this finding, we determined the cryo-EM structure of the BMAL1–HIF2A–DNA complex, revealing structural rearrangements within BMAL1 that enable cross-talk between circadian rhythms and hypoxia signalling. BMAL1 modulates the circadian hypoxic response by enhancing the transcriptional activity of HIF2A and stabilizing the HIF2A protein. We further identified amphiregulin (AREG) as a rhythmic target of the BMAL1–HIF2A complex, critical for regulating daytime variations of myocardial injury. Pharmacologically targeting the BMAL1–HIF2A–AREG pathway provides cardioprotection, with maximum efficacy when aligned with the pathway’s circadian phase. These findings identify a mechanism governing circadian variations of myocardial injury and highlight the therapeutic potential of clock-based pharmacological interventions for treating ischaemic heart disease.

『Abstract』Precision measurements using low-energy antiprotons, exclusively available at the antimatter factory (AMF) of CERN , offer stringent tests of charge–parity–time (CPT) invariance, which is a fundamental symmetry in the Standard Model of particle physics . These tests have been realized, for example, in antiprotonic helium and antihydrogen . In our cryogenic Penning-trap experiments , we measure the magnetic moments and charge-to-mass ratios of protons and antiprotons and now provide the most precise test of CPT invariance in the baryon sector . Our experiments are limited by magnetic field fluctuations imposed by the decelerators in the AMF; therefore, we are advancing the relocation of antiprotons to dedicated precision laboratories. Here we present the successful transport of a trapped proton cloud from the AMF using BASE-STEP —a transportable, superconducting, autonomous and open Penning-trap system that can distribute antiprotons into other experiments. We transferred the trapped protons from our experimental area at the AMF onto a truck and transported them across the Meyrin site of CERN, demonstrating autonomous operation without external power for 4 h and loss-free proton relocation. We thereby confirm the feasibility of transferring particles into low-noise laboratories in the vicinity of the AMF and of using a power generator on the truck to reach laboratories throughout Europe. This marks the potential start of a new era in precision antimatter research, enabling low-noise measurements of antiprotons, the charged antimatter ions (Too complex for web display.), and other accelerator-produced ions, such as hydrogen-like lead or uranium ions.

『Abstract』Anthropogenic biodiversity decline threatens the functioning of ecosystems and the many benefits they provide to humanity . As well as causing species losses in directly affected locations, human influence might also reduce biodiversity in relatively unmodified vegetation if far-reaching anthropogenic effects trigger local extinctions and hinder recolonization. Here we show that local plant diversity is globally negatively related to the level of anthropogenic activity in the surrounding region. Impoverishment of natural vegetation was evident only when we considered community completeness: the proportion of all suitable species in the region that are present at a site. To estimate community completeness, we compared the number of recorded species with the dark diversity—ecologically suitable species that are absent from a site but present in the surrounding region . In the sampled regions with a minimal human footprint index, an average of 35% of suitable plant species were present locally, compared with less than 20% in highly affected regions. Besides having the potential to uncover overlooked threats to biodiversity, dark diversity also provides guidance for nature conservation. Species in the dark diversity remain regionally present, and their local populations might be restored through measures that improve connectivity between natural vegetation fragments and reduce threats to population persistence.

『Abstract』Imposing incommensurable periodicity on the periodic atomic lattice can lead to complex structural phases consisting of locally periodic structure bounded by topological defects . Twisted trilayer graphene (TTG) is an ideal material platform to study the interplay between different atomic periodicities, which can be tuned by twist angles between the layers, leading to moire-of-moire lattices . Interlayer and intralayer interactions between two interfaces in TTG transform this moire-of-moire lattice into an intricate network of domain structures at small twist angles, which can harbour exotic electronic behaviours . Here we report a complete structural phase diagram of TTG with atomic-scale lattice reconstruction. Using transmission electron microscopy (TEM) combined with a new interatomic potential simulation , we show several large-scale moire lattices, including triangular, kagome and a corner-shared hexagram-shaped domain pattern. Each domain is bounded by a 2D network of domain-wall lattices. In the limit of small twist angles, two competing structural orders—rhombohedral and Bernal stackings—with a slight energy difference cause unconventional lattice reconstruction with spontaneous symmetry breaking (SSB) and nematic instability, highlighting the importance of long-range interlayer interactions across entire van der Waals layers. The diverse tessellation of distinct domains, whose topological network can be tuned by the adjustment of the twist angles, establishes TTG as a platform for exploring the interplay between emerging quantum properties and controllable nontrivial lattices.

『Abstract』The shortage of donors is a major challenge for transplantation; however, organs from genetically modified pigs can serve as ideal supplements . Until now, porcine hearts and kidneys have been successively transplanted into humans . In this study, heterotopic auxiliary transplantation was used to donate a six-gene-edited pig liver to a brain-dead recipient. The graft function, haemodynamics, and immune and inflammatory responses of the recipient were monitored over the subsequent 10 days. Two hours after portal vein reperfusion of the xenograft, goldish bile was produced, increasing to 66.5 ml by postoperative day 10. Porcine liver-derived albumin also increased after surgery. Alanine aminotransferase levels remained in the normal range, while aspartate aminotransferase levels increased on postoperative day 1 and then rapidly declined. Blood flow velocity in the porcine hepatic artery and portal and hepatic veins remained at an acceptable level. Although platelet numbers decreased early after surgery, they ultimately returned to normal levels. Histological analyses showed that the porcine liver regenerated capably with no signs of rejection. T cell activity was inhibited by anti-thymocyte globulin administration, and B cell activation increased 3 days after surgery and was then inhibited by rituximab. There were no significant peri-operative changes in immunoglobulin G or immunoglobulin M levels. C-reactive protein and procalcitonin levels were initially elevated and then quickly declined. The xenograft remained functional until study completion.

『Abstract』Fibrosis, the replacement of healthy tissue with collagen-rich matrix, can occur following injury in almost every organ . Mouse lungs follow a stereotyped sequence of fibrogenesis-to-resolution after bleomycin injury , and we reasoned that profiling post-injury histological stages could uncover pro-fibrotic versus anti-fibrotic features with functional value for human fibrosis. Here we quantified spatiotemporally resolved matrix transformations for integration with multi-omic data. First, we charted stepwise trajectories of matrix aberration versus resolution, derived from a high-dimensional set of histological fibre features, that denoted a reversible transition in uniform-to-disordered histological architecture. Single-cell sequencing along these trajectories identified temporally enriched ‘ECM-secreting’ ( Csmd1 -expressing) and ‘pro-resolving’ ( Cd248 -expressing) fibroblasts at the respective post-injury stages. Visium-based spatial analysis further suggested divergent matrix architectures and spatial–transcriptional neighbourhoods by fibroblast subtype, identifying distinct fibrotic versus non-fibrotic biomolecular milieu. Critically, pro-resolving fibroblast instillation helped to ameliorate fibrosis in vivo. Furthermore, the fibroblast neighbourhood-associated factors SERPINE2 and PI16 functionally modulated human lung fibrosis ex vivo. Spatial phenotyping of idiopathic pulmonary fibrosis at protein level additionally uncovered analogous fibroblast subtypes and neighbourhoods in human disease. Collectively, these findings establish an atlas of pro- and anti-fibrotic factors that underlie lung matrix architecture and implicate fibroblast-associated biological features in modulating fibrotic progression versus resolution.

『Abstract』A chain of quantum dots (QDs) in semiconductor–superconductor hybrid systems can form an artificial Kitaev chain hosting Majorana bound states (MBSs) . These zero-energy states are expected to be localized on the edges of the chain , at the outermost QDs. The remaining QDs, comprising the bulk, are predicted to host an excitation gap that protects the MBSs at the edges from local on-site perturbations. Here we demonstrate this connection between the bulk and edges in a minimal system, by engineering a three-site Kitaev chain in a two-dimensional electron gas. Through direct tunnelling spectroscopy on each site, we show that the appearance of stable zero-bias conductance peaks at the outer QDs is correlated with the presence of an excitation gap in the middle QD. Furthermore, we show that this gap can be controlled by applying a superconducting phase difference between the two hybrid segments and that the MBSs are robust only when the excitation gap is present. We find a close agreement between experiments and the original Kitaev model, thus confirming key predictions for MBSs in a three-site chain.

『Abstract』The structural evolution of molecular hydrogen H 2 under multi-megabar compression and its relation to atomic metallic hydrogen is a key unsolved problem in condensed-matter physics. Although dozens of crystal structures have been proposed by theory , only one, the simple hexagonal-close-packed ( hcp ) structure of only spherical disordered H 2 , has been previously confirmed in experiments . Through advancing nano-focused synchrotron X-ray probes, here we report the observation of the transition from hcp H 2 to a post- hcp structure with a six-fold larger supercell at pressures above 212 GPa, indicating the change of spherical H 2 to various ordered configurations. Theoretical calculations based on our XRD results found a time-averaged structure model in the space group \(P\bar{6}2c\) with alternating layers of spherically disordered H 2 and new graphene-like layers consisting of H 2 trimers (H 6 ) formed by the association of three H 2 molecules. This supercell has not been reported by any previous theoretical study for the post- hcp phase, but is close to a number of theoretical models with mixed-layer structures. The evidence of a structural transition beyond hcp establishes the trend of H 2 molecular association towards polymerization at extreme pressures, giving clues about the nature of the molecular-to-atomic transition of metallic hydrogen. Considering the spectroscopic behaviours that show strong vibrational and bending peaks of H 2 up to 400 GPa, it would be prudent to speculate the continuation of hydrogen molecular polymerization up to its metallization.

『Abstract』The in vivo responses of dorsal raphe nucleus serotonin neurons to emotionally salient stimuli are a puzzle . Existing theories centring on reward , surprise , salience and uncertainty individually account for some aspects of serotonergic activity but not others. Merging ideas from reinforcement learning theory with recent insights into the filtering properties of the dorsal raphe nucleus , here we find a unifying perspective in a prospective code for value. This biological code for near-future reward explains why serotonin neurons are activated by both rewards and punishments , and why these neurons are more strongly activated by surprising rewards but have no such surprise preference for punishments —observations that previous theories have failed to reconcile. Finally, our model quantitatively predicts in vivo population activity better than previous theories. By reconciling previous theories and establishing a precise connection with reinforcement learning, our work represents an important step towards understanding the role of serotonin in learning and behaviour.

『Abstract』Depicting spatial distributions of disease-relevant cells is crucial for understanding disease pathology . Here we present genetically informed spatial mapping of cells for complex traits (gsMap), a method that integrates spatial transcriptomics data with summary statistics from genome-wide association studies to map cells to human complex traits, including diseases, in a spatially resolved manner. Using embryonic spatial transcriptomics datasets covering 25 organs, we benchmarked gsMap through simulation and by corroborating known trait-associated cells or regions in various organs. Applying gsMap to brain spatial transcriptomics data, we reveal that the spatial distribution of glutamatergic neurons associated with schizophrenia more closely resembles that for cognitive traits than that for mood traits such as depression. The schizophrenia-associated glutamatergic neurons were distributed near the dorsal hippocampus, with upregulated expression of calcium signalling and regulation genes, whereas depression-associated glutamatergic neurons were distributed near the deep medial prefrontal cortex, with upregulated expression of neuroplasticity and psychiatric drug target genes. Our study provides a method for spatially resolved mapping of trait-associated cells and demonstrates the gain of biological insights (such as the spatial distribution of trait-relevant cells and related signature genes) through these maps.

『Abstract』Parkinson’s disease is a progressive neurodegenerative condition with a considerable health and economic burden . It is characterized by the loss of midbrain dopaminergic neurons and a diminished response to symptomatic medical or surgical therapy as the disease progresses . Cell therapy aims to replenish lost dopaminergic neurons and their striatal projections by intrastriatal grafting. Here, we report the results of an open-label phase I clinical trial (NCT04802733) of an investigational cryopreserved, off-the-shelf dopaminergic neuron progenitor cell product (bemdaneprocel) derived from human embryonic stem (hES) cells and grafted bilaterally into the putamen of patients with Parkinson’s disease. Twelve patients were enrolled sequentially in two cohorts—a low-dose (0.9 million cells, n = 5) and a high-dose (2.7 million cells, n = 7) cohort—and all of the participants received one year of immunosuppression. The trial achieved its primary objectives of safety and tolerability one year after transplantation, with no adverse events related to the cell product. At 18 months after grafting, putaminal Fluoro-DOPA positron emission tomography uptake increased, indicating graft survival. Secondary and exploratory clinical outcomes showed improvement or stability, including improvement in the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part III OFF scores by an average of 23 points in the high-dose cohort. There were no graft-induced dyskinesias. These data demonstrate safety and support future definitive clinical studies.

『Abstract』Ancient DNA from the Mediterranean region has revealed long-range connections and population transformations associated with the spread of food-producing economies . However, in contrast to Europe, genetic data from this key transition in northern Africa are limited, and have only been available from the far western Maghreb (Morocco) . Here we present genome-wide data for nine individuals from the Later Stone Age through the Neolithic period from Algeria and Tunisia. The earliest individuals cluster with pre-Neolithic people of the western Maghreb (around 15,000–7,600 years before present ( bp )), showing that this ‘Maghrebi’ ancestry profile had a substantial geographic and temporal extent. At least one individual from Djebba (Tunisia), dating to around 8,000 years bp , harboured ancestry from European hunter–gatherers, probably reflecting movement in the Early Holocene across the Strait of Sicily. Later Neolithic people from the eastern Maghreb retained largely local forager ancestry, together with smaller contributions from European farmers (by around 7,000 years bp ) and Levantine groups (by around 6,800 years bp ), and were thus far less impacted by external gene flow than were populations in other parts of the Neolithic Mediterranean.

『Abstract』Rapid learning confers significant advantages on animals in ecological environments. Despite the need for speed, animals appear to only slowly learn to associate rewarded actions with predictive cues . This slow learning is thought to be supported by gradual changes to cue representation in the sensory cortex . However, evidence is growing that animals learn more rapidly than classical performance measures suggest , challenging the prevailing model of sensory cortical plasticity. Here we investigated the relationship between learning and sensory cortical representations. We trained mice on an auditory go/no-go task that dissociated the rapid acquisition of task contingencies (learning) from its slower expression (performance) . Optogenetic silencing demonstrated that the auditory cortex drives both rapid learning and slower performance gains but becomes dispensable once mice achieve ‘expert’ performance. Instead of enhanced cue representations , two-photon calcium imaging of auditory cortical neurons throughout learning revealed two higher-order signals that were causal to learning and performance. A reward-prediction signal emerged rapidly within tens of trials, was present after action-related errors early in training, and faded in expert mice. Silencing at the time of this signal impaired rapid learning, suggesting that it serves an associative role. A distinct cell ensemble encoded and controlled licking suppression that drove slower performance improvements. These ensembles were spatially clustered but uncoupled from sensory representations, indicating higher-order functional segregation within auditory cortex. Our results reveal that the sensory cortex manifests higher-order computations that separably drive rapid learning and slower performance improvements, reshaping our understanding of the fundamental role of the sensory cortex.

『Abstract』Close-in companion stars are expected to adversely influence the formation and orbital stability of circumstellar (S-type) planets by tidally truncating protoplanetary discs , impeding mutual accretion of planetesimals and narrowing dynamically stable regions . This explains the observed dearth of S-type planets in tight binary star systems . ν Octantis, whose stellar components have a mean separation of 2.6 au , has long been suspected of hosting a circum-primary planet in a retrograde and exceptionally wide orbit that resides midway between the stars . Strong theoretical grounds against its formation and the absence of observational precedents, however, have challenged the reality of the planet. Here we present new radial velocity measurements that consolidate the planet hypothesis. Stable fits to all radial velocity data require the planetary orbit to be retrograde and practically coplanar. We also report the critical discovery from adaptive optics imaging that the companion star is a white dwarf. Our exploration of credible primordial binary orbital settings shows that the minimum separation between the stars was 1.3 au initially, which overlaps the current planetary orbit and makes any scenarios in which the circum-primary planetary orbit formed coevally with the young stars hardly conceivable. The retrograde planet must have originated from a circumbinary orbit or a second-generation protoplanetary disc, showing the role of binary stellar evolution in the formation and evolution of planetary systems.