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A group of scientists who are experts at spotting fraudulent research outline five essential steps to combat industrialized scientific misconduct. [ABSTRACT FROM AUTHOR]

Researchers have questions about how so many authors have racked up a large number of citations so quickly, although some of those authors are honest overachievers. [ABSTRACT FROM AUTHOR]

It began with concerns about the orbits used to explain the motion of electrons in atoms — but quantum theory ended up upending reality itself. [ABSTRACT FROM AUTHOR]

Two-year collaboration aims to create tools to help counter the tide of flawed research. [ABSTRACT FROM AUTHOR]

The open-access title's bold publishing model has brought long-bubbling conflicts to the fore. [ABSTRACT FROM AUTHOR]

A trove of data is providing insights into the main reasons studies are pulled from the arXiv preprint platform. [ABSTRACT FROM AUTHOR]

Model microbes such as Escherichia coli hog scientists’ attention, leaving most known bacteria with few publications devoted to them. [ABSTRACT FROM AUTHOR]

Two studies show that the light emitted by nanocrystals embedded with luminescent ions can be used to sense forces with high spatial resolution — even when those forces are inside a microscopic living worm.Light-emitting nanoparticles used to measure forces remotely. [ABSTRACT FROM AUTHOR]

Energy-storage devices called capacitors deliver power rapidly, but the amount of energy they can absorb is limited. Deliberately disordered electric dipoles in 'antiferroelectric' capacitor materials could solve this problem. Antiferroelectric materials engineered for use in capacitors. [ABSTRACT FROM AUTHOR]

Developers have tricks to stop artificial intelligence from making things up, but large language models are still struggling to tell the truth, the whole truth and nothing but the truth. [ABSTRACT FROM AUTHOR]

The enzyme nitrogenase ‘fixes’ nitrogen gas to form bioavailable ammonia, a vital process for life. Two studies solve a long-standing mystery: how a small protein saves nitrogenase from destruction by oxygen.Details of how the FeSII protein protects the nitrogenase enzyme. [ABSTRACT FROM AUTHOR]

US technology company Meta has produced an AI model that can directly translate speech in one language to speech in another. Two scientists discuss the technical feats and ethical questions that underpin this advance in machine translation.Two perspectives on speech-to-speech machine translation. [ABSTRACT FROM AUTHOR]

Mathematical modelling suggests that it is theoretically possible to reduce risk of common diseases using heritable genome editing. Scientists argue that the technology involves considerable risk and uncertain benefits. Pitfalls of heritable genome editing undermine theoretical benefits. [ABSTRACT FROM AUTHOR]

Inflammatory diseases are often chronic and recurrent, and current treatments do not typically remove underlying disease drivers 1 . T cells participate in a wide range of inflammatory diseases such as psoriasis 2 , Crohn's disease 3 , oesophagitis 4 and multiple sclerosis 5,6 , and clonally expanded antigen-specific T cells may contribute to disease chronicity and recurrence, in part by forming persistent pathogenic memory. Chronic rhinosinusitis and asthma are inflammatory airway diseases that often present as comorbidities 7 . Chronic rhinosinusitis affects more than 10% of the general population 8 . Among these patients, 20-25% would develop nasal polyps, which often require repeated surgical resections owing to a high incidence of recurrence 9 . Whereas abundant T cells infiltrate the nasal polyps tissue 10,11 , T cell subsets that drive the disease pathology and promote recurrence are not fully understood. By comparing T cell repertoires in nasal polyp tissues obtained from consecutive surgeries, here we report that persistent CD8 + T cell clones carrying effector memory-like features colonize the mucosal tissue during disease recurrence, and these cells characteristically express the tryptase Granzyme K (GZMK). We find that GZMK cleaves many complement components, including C2, C3, C4 and C5, that collectively contribute to the activation of the complement cascade. GZMK-expressing CD8 + T cells participate in organized tertiary lymphoid structures, and tissue GZMK levels predict the disease severity and comorbidities better than well-established biomarkers such as eosinophilia and tissue interleukin-5. Using a mouse asthma model, we further show that GZMK-expressing CD8 + T cells exacerbate the disease in a manner dependent on the proteolytic activity of GZMK and complements. Genetic ablation or pharmacological inhibition of GZMK after the disease onset markedly alleviates tissue pathology and restores lung function. Our work identifies a pathogenic CD8 + memory T cell subset that promotes tissue inflammation and recurrent airway diseases by the effector molecule GZMK and suggests GZMK as a potential therapeutic target., Competing Interests: Competing interests: H.Q. is a cofounder of Emergent Biomed Solutions, Ltd., (© 2025. The Author(s).)

Microscopy and crystallography are two essential experimental methodologies for advancing modern science. They complement one another, with microscopy typically relying on lenses to image the local structures of samples, and crystallography using diffraction to determine the global atomic structure of crystals. Over the past two decades, computational microscopy, encompassing coherent diffractive imaging (CDI) and ptychography, has advanced rapidly, unifying microscopy and crystallography to overcome their limitations. Here, I review the innovative developments in CDI and ptychography, which achieve exceptional imaging capabilities across nine orders of magnitude in length scales, from resolving atomic structures in materials at sub-ångstrom resolution to quantitative phase imaging of centimetre-sized tissues, using the same principle and similar computational algorithms. These methods have been applied to determine the 3D atomic structures of crystal defects and amorphous materials, visualize oxygen vacancies in high-temperature superconductors and capture ultrafast dynamics. They have also been used for nanoscale imaging of magnetic, quantum and energy materials, nanomaterials, integrated circuits and biological specimens. By harnessing fourth-generation synchrotron radiation, X-ray-free electron lasers, high-harmonic generation, electron microscopes, optical microscopes, cutting-edge detectors and deep learning, CDI and ptychography are poised to make even greater contributions to multidisciplinary sciences in the years to come., Competing Interests: Competing interests: The author declares no competing interests., (© 2025. Springer Nature Limited.)

Our understanding of type 2 immunity has undergone a substantial transformation in recent years, revealing previously unknown functions. Beyond its canonical role in defence against parasitic helminth infections, type 2 immunity safeguards the host through additional mechanisms, including the suppression of excessive type 1 immune responses, regulation of tissue repair and maintenance of adipose tissue homeostasis. However, unlike type 1 immune responses, type 2 immunity is perceived as a potential promoter of tumorigenesis. Emerging evidence challenges this perspective, painting a more nuanced picture in which type 2 immunity might protect against or even actively suppress tumour growth and progression. In this Review, we explore discoveries that highlight the potential of type 2 immunity in reshaping the landscape of cancer immunotherapies., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. Springer Nature Limited.)

Many human diseases are the result of early developmental defects. As most paediatric diseases and disorders are rare, children are critically underrepresented in research. Functional genomics studies primarily rely on adult tissues and lack critical cell states in specific developmental windows. In parallel, little is known about the conservation of developmental programmes across non-human primate (NHP) species, with implications for human evolution. Here we introduce the developmental Genotype-Tissue Expression (dGTEx) projects, which span humans and NHPs and aim to integrate gene expression, regulation and genetics data across development and species. The dGTEx cohort will consist of 74 tissue sites across 120 human donors from birth to adulthood, and developmentally matched NHP age groups, with additional prenatal and adult animals, with 126 rhesus macaques (Macaca mulatta) and 72 common marmosets (Callithrix jacchus). The data will comprise whole-genome sequencing, extensive bulk, single-cell and spatial gene expression profiles, and chromatin accessibility data across tissues and development. Through community engagement and donor diversity, the human dGTEx study seeks to address disparities in genomic research. Thus, dGTEx will provide a reference human and NHP dataset and tissue bank, enabling research into developmental changes in expression and gene regulation, childhood disorders and the effect of genetic variation on development., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. Springer Nature Limited.)

Letter to the Editor [ABSTRACT FROM AUTHOR]

In the aftermath of deadly blazes in Los Angeles, researchers also suggest ways to make homes more resilient. Research also suggests how to make homes more resilient in the aftermath of California's deadly blazes. [ABSTRACT FROM AUTHOR]

Bursts of electromagnetic radiation that share similarities with birdsong have long been observed close to Earth. A detection farther out in space confirms a key part of the theory of their origin, but also poses questions.Electron-hole detection for distant chorus waves. [ABSTRACT FROM AUTHOR]

Machine-learning system can process words spoken in 101 languages, spitting out voice-synthesized translations in 36 target languages. [ABSTRACT FROM AUTHOR]

Research in mice points towards a mechanism that avoids 'catastrophic forgetting'. [ABSTRACT FROM AUTHOR]

Electrochemical reactions for organic synthesis typically require intricate, specialized equipment, slowing progress in this field. Minuscule electric generators now enable faster reaction discovery and development.High-throughput electrochemistry driven by microelectronic devices. [ABSTRACT FROM AUTHOR]

Three researchers talk about life in companies and the key to unlocking opportunities. [ABSTRACT FROM AUTHOR]

Letter to the Editor [ABSTRACT FROM AUTHOR]

In a year that will see many AI achievements and battles, let's not forget that not all AI research makes the front pages. [ABSTRACT FROM AUTHOR]

The Nobel prizewinner used quantum and molecular mechanics to model the dynamics of complex chemical systems. [ABSTRACT FROM AUTHOR]

Behavioural experiments in shell-dwelling cichlid fish reveal evolutionary adaptations in parents and offspring that control the timing of emergence from the nest. Parents and offspring have synchronised schedule for nest emergence. [ABSTRACT FROM AUTHOR]

Letter to the Editor [ABSTRACT FROM AUTHOR]

Letter to the Editor [ABSTRACT FROM AUTHOR]

Cutting-edge simulations reveal a new potential mechanism by which Pluto trapped its biggest satellite, Charon. A new potential mechanism by which Pluto trapped Charon. [ABSTRACT FROM AUTHOR]

In a few decades, gene-editing technologies could reduce the likelihood of common human diseases. Societies must use this time to prepare for their arrival. [ABSTRACT FROM AUTHOR]

Inborn errors of immunity (IEIs) are genetic disorders that underlie susceptibility to infection, autoimmunity, autoinflammation, allergy and/or malignancy1. Incomplete penetrance is common among IEIs despite their monogenic basis2. Here we investigate the contribution of autosomal random monoallelic expression (aRMAE), a somatic commitment to the expression of one allele3,4, to phenotypic variability observed in families with IEIs. Using a clonal primary T cell system to assess aRMAE status of genes in healthy individuals, we find that 4.30% of IEI genes and 5.20% of all genes undergo aRMAE. Perturbing H3K27me3 and DNA methylation alters allele expression commitment, in support of two proposed mechanisms5,6 for the regulation of aRMAE. We tested peripheral blood mononuclear cells from individuals with IEIs with shared genetic lesions but discordant clinical phenotypes for aRMAE. Among two relatives who were heterozygous for a mutation in PLCG2 (delEx19), an antibody deficiency phenotype corresponds to selective mutant allele expression in B cells. By contrast, among relatives who were heterozygous for a mutation in JAK1 (c.2099G>A; p.S700N), the unaffected carrier T cells predominantly expressed the wild-type JAK1 allele, whereas the affected carrier T cells exhibited biallelic expression. Allelic expression bias was also documented in phenotypically discordant family members with mutations in STAT1 and CARD11. This study highlights the importance of considering both the genotype and the 'transcriptotype' in analyses of the penetrance and expressivity of monogenic disorders. Somatically determined preferential allelic expression of select genes that when mutated cause inborn errors of immunity corresponds with disease phenotypes, suggesting that the penetrance and expressivity of monogenic disorders is also dependent on the 'transcriptotype'. [ABSTRACT FROM AUTHOR]

Accurate goal-directed behaviour requires the sense of touch to be integrated with information about body position and ongoing motion1,2. Behaviours such as chewing, swallowing and speech critically depend on precise tactile events on a rapidly moving tongue3, but neural circuits for dynamic touch-guided tongue control are unknown. Here, using high-speed videography, we examined three-dimensional lingual kinematics as mice drank from a water spout that unexpectedly changed position during licking, requiring re-aiming in response to subtle contact events on the left, centre or right surface of the tongue. Mice integrated information about both precise touch events and tongue position to re-aim ensuing licks. Touch-guided re-aiming was unaffected by photoinactivation of tongue sensory, premotor and motor cortices, but was impaired by photoinactivation of the lateral superior colliculus (latSC). Electrophysiological recordings identified latSC neurons with mechanosensory receptive fields for precise touch events that were anchored in tongue-centred, head-centred or conjunctive reference frames. Notably, latSC neurons also encoded tongue position before contact, information that is important for tongue-to-head-based coordinate transformations underlying accurate touch-guided aiming. Viral tracing revealed tongue sensory inputs to the latSC from the lingual trigeminal nucleus, and optical microstimulation in the latSC revealed a topographic map for aiming licks. These findings demonstrate that touch-guided tongue control relies on a collicular mechanosensorimotor map, analogous to collicular visuomotor maps associated with visually guided orienting across many species. Touch-guided tongue control in mice relies on a collicular mechanosensorimotor map, analogous to collicular visuomotor maps associated with visually guided orienting across many species. [ABSTRACT FROM AUTHOR]

With the convergence of notable advances in molecular and spatial profiling methods and new computational approaches taking advantage of artificial intelligence and machine learning, the construction of cell atlases is progressing from data collection to atlas integration and beyond. Here, we explore five ways in which cell atlases, including the Human Cell Atlas, are already revealing valuable biological insights, and how they are poised to provide even greater benefits in the coming years. In particular, we discuss cell atlases as censuses of cells; as 3D maps of cells in the body, across modalities and scales; as maps connecting genotype causes to phenotype effects; as 4D maps of development; and, ultimately, as foundation models of biology unifying all of these aspects and helping to transform medicine. This Perspective explores five ways in which cell atlases are revealing valuable biological insights, and how they are poised to provide considerable benefits in the coming years. [ABSTRACT FROM AUTHOR]

Roman writers found the relative empowerment of Celtic women remarkable1. In southern Britain, the Late Iron Age Durotriges tribe often buried women with substantial grave goods2. Here we analyse 57 ancient genomes from Durotrigian burial sites and find an extended kin group centred around a single maternal lineage, with unrelated (presumably inward migrating) burials being predominantly male. Such a matrilocal pattern is undescribed in European prehistory, but when we compare mitochondrial haplotype variation among European archaeological sites spanning six millennia, British Iron Age cemeteries stand out as having marked reductions in diversity driven by the presence of dominant matrilines. Patterns of haplotype sharing reveal that British Iron Age populations form fine-grained geographical clusters with southern links extending across the channel to the continent. Indeed, whereas most of Britain shows majority genomic continuity from the Early Bronze Age to the Iron Age, this is markedly reduced in a southern coastal core region with persistent cross-channel cultural exchange3. This southern core has evidence of population influx in the Middle Bronze Age but also during the Iron Age. This is asynchronous with the rest of the island and points towards a staged, geographically granular absorption of continental influence, possibly including the acquisition of Celtic languages. An analysis of ancient mitochondrial and nuclear DNA shows evidence of matrilocal communities in Iron Age Britain. [ABSTRACT FROM AUTHOR]

Dielectric-based energy storage capacitors characterized with fast charging and discharging speed and reliability1, 2, 3–4 play a vital role in cutting-edge electrical and electronic equipment. In pursuit of capacitor miniaturization and integration, dielectrics must offer high energy density and efficiency5. Antiferroelectrics with antiparallel dipole configurations have been of significant interest for high-performance energy storage due to their negligible remanent polarization and high maximum polarization in the field-induced ferroelectric state6, 7–8. However, the low antiferroelectric–ferroelectric phase-transition field and accompanying large hysteresis loss deteriorate energy density and reliability. Here, guided by phase-field simulations, we propose a new strategy to frustrate antipolar ordering in antiferroelectrics by incorporating non-polar or polar components. Our experiments demonstrate that this approach effectively tunes the antiferroelectric–ferroelectric phase-transition fields and simultaneously reduces hysteresis loss. In PbZrO3-based films, we hence realized a record high energy density among all antiferroelectrics of 189 J cm−3 along with a high efficiency of 81% at an electric field of 5.51 MV cm−1, which rivals the most state-of-the-art energy storage dielectrics9, 10, 11–12. Atomic-scale characterization by scanning transmission electron microscopy directly revealed that the dispersed non-polar regions frustrate the long-range antipolar ordering, which contributes to the improved performance. This strategy presents new opportunities to manipulate polarization profiles and enhance energy storage performances in antiferroelectrics. This study reports that incorporating non-polar nanodomains into antiferroelectrics greatly enhanced the energy density and efficiency. [ABSTRACT FROM AUTHOR]

Evaporation or freezing of water-rich fluids with dilute concentrations of dissolved salts can produce brines, as observed in closed basins on Earth1 and detected by remote sensing on icy bodies in the outer Solar System2,3. The mineralogical evolution of these brines is well understood in regard to terrestrial environments4, but poorly constrained for extraterrestrial systems owing to a lack of direct sampling. Here we report the occurrence of salt minerals in samples of the asteroid (101955) Bennu returned by the OSIRIS-REx mission5. These include sodium-bearing phosphates and sodium-rich carbonates, sulfates, chlorides and fluorides formed during evaporation of a late-stage brine that existed early in the history of Bennu's parent body. Discovery of diverse salts would not be possible without mission sample return and careful curation and storage, because these decompose with prolonged exposure to Earth's atmosphere. Similar brines probably still occur in the interior of icy bodies Ceres and Enceladus, as indicated by spectra or measurement of sodium carbonate on the surface or in plumes2,3. Samples from the asteroid (101955) Bennu, returned by the OSIRIS-REx mission, include sodium-bearing phosphates and sodium-rich carbonates, sulfates, chlorides and fluorides formed during evaporation of a late-stage brine. [ABSTRACT FROM AUTHOR]

Electrons in topological flat bands can form new topological states driven by correlation effects. The pentalayer rhombohedral graphene/hexagonal boron nitride (hBN) moiré superlattice was shown to host fractional quantum anomalous Hall effect (FQAHE) at approximately 400 mK (ref. 1), triggering discussions around the underlying mechanism and role of moiré effects2, 3, 4, 5–6. In particular, new electron crystal states with non-trivial topology have been proposed3,4,7, 8, 9, 10, 11, 12, 13, 14–15. Here we report electrical transport measurements in rhombohedral pentalayer and tetralayer graphene/hBN moiré superlattices at electronic temperatures down to below 40 mK. We observed two more fractional quantum anomalous Hall (FQAH) states and smaller Rxx values in pentalayer devices than those previously reported. In the new tetralayer device, we observed FQAHE at moiré filling factors v = 3/5 and 2/3. With a small current at the base temperature, we observed a new extended quantum anomalous Hall (EQAH) state and magnetic hysteresis, where Rxy = h/e2 and vanishing Rxx spans a wide range of v from 0.5 to 1.3. At increased temperature or current, EQAH states disappear and partially transition into the FQAH liquid16, 17–18. Furthermore, we observed displacement field-induced quantum phase transitions from the EQAH states to the Fermi liquid, FQAH liquid and the likely composite Fermi liquid. Our observations established a new topological phase of electrons with quantized Hall resistance at zero magnetic field and enriched the emergent quantum phenomena in materials with topological flat bands. New topological states have been observed in rhombohedral graphene/hBN moiré superlattices, including fractional and extended quantum anomalous Hall effects, at ultra-low temperatures, demonstrating the rich quantum phenomena emerging from correlated electrons in topological flat bands. [ABSTRACT FROM AUTHOR]

All-inorganic perovskites prepared by substituting the organic cations (for example, methylammonium and formamidinium) with inorganic cations (for example, Cs+) are effective concepts to enhance the long-term photostability and thermal stability of perovskite solar cells (PSCs)1,2. Hence, inorganic perovskite tandem solar cells (IPTSCs) are promising candidates for breaking the efficiency bottleneck and addressing the stability issue, too3,4. However, challenges remain in fabricating two-terminal (2T) IPTSCs due to the inferior film formation and deep trap states induced by tin cations5, 6–7. Here a ligand evolution (LE) strategy with p-toluenesulfonyl hydrazide (PTSH) is used to regulate film formation and eliminate deep traps in inorganic narrow-bandgap (NBG) perovskites, enabling the successful development of 2T IPTSCs. Accordingly, the 1.31 eV CsPb0.4Sn0.6I3:LE device delivers a record efficiency of 17.41%. Combined with the 1.92 eV CsPbI2Br top cell, 2T IPTSCs exhibit a champion efficiency of 22.57% (certified, 21.92%). Moreover, IPTSCs are engineered to deliver remarkable durability under maximum power point (MPP) tracking, maintaining 80% of their initial efficiency at 65 °C for 1,510 h and at 85 °C for 800 h. We elucidate that LE deliberately leverages multiple roles for inorganic NBG perovskite growth and anticipate that our study provides an insightful guideline for developing high-efficiency and stable IPTSCs. Inorganic perovskite tandem solar cells using ligand evolution strategy achieve record efficiencies and durability, maintaining 80% of their initial efficiency under light/heat stresses, guiding the development of high-efficiency, stable inorganic perovskite tandem solar cells. [ABSTRACT FROM AUTHOR]

Increasing soil salinity causes significant crop losses globally; therefore, understanding plant responses to salt (sodium) stress is of high importance. Plants avoid sodium toxicity through subcellular compartmentation by intricate processes involving a high level of elemental interdependence. Current technologies to visualize sodium, in particular, together with other elements, are either indirect or lack in resolution. Here we used the newly developed cryo nanoscale secondary ion mass spectrometry ion microprobe1, which allows high-resolution elemental imaging of cryo-preserved samples and reveals the subcellular distributions of key macronutrients and micronutrients in root meristem cells of Arabidopsis and rice. We found an unexpected, concentration-dependent change in sodium distribution, switching from sodium accumulation in the cell walls at low external sodium concentrations to vacuolar accumulation at stressful concentrations. We conclude that, in root meristems, a key function of the NHX family sodium/proton antiporter SALT OVERLY SENSITIVE 1 (also known as Na+/H+ exchanger 7; SOS1/NHX7) is to sequester sodium into vacuoles, rather than extrusion of sodium into the extracellular space. This is corroborated by the use of new genomic, complementing fluorescently tagged SOS1 variants. We show that, in addition to the plasma membrane, SOS1 strongly accumulates at late endosome/prevacuoles as well as vacuoles, supporting a role of SOS1 in vacuolar sodium sequestration. This study demonstrates that cryo nanoscale secondary ion mass spectrometry (CryoNanoSIMS) enables direct multi-elemental imaging at subcellular resolution of macro- and micronutrients or trace elements in plants and may provide insights into the in vivo roles of many transporters. [ABSTRACT FROM AUTHOR]

The amount of methane released to the atmosphere from the Nord Stream subsea pipeline leaks remains uncertain, as reflected in a wide range of estimates1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17–18. A lack of information regarding the temporal variation in atmospheric emissions has made it challenging to reconcile pipeline volumetric (bottom-up) estimates1, 2, 3, 4, 5, 6, 7–8 with measurement-based (top-down) estimates8, 9, 10, 11, 12, 13, 14, 15, 16, 17–18. Here we simulate pipeline rupture emission rates and integrate these with methane dissolution and sea-surface outgassing estimates9,10 to model the evolution of atmospheric emissions from the leaks. We verify our modelled atmospheric emissions by comparing them with top-down point-in-time emission-rate estimates and cumulative emission estimates derived from airborne11, satellite8,12, 13–14 and tall tower data. We obtain consistency between our modelled atmospheric emissions and top-down estimates and find that 465 ± 20 thousand metric tons of methane were emitted to the atmosphere. Although, to our knowledge, this represents the largest recorded amount of methane released from a single transient event, it is equivalent to 0.1% of anthropogenic methane emissions for 2022. The impact of the leaks on the global atmospheric methane budget brings into focus the numerous other anthropogenic methane sources that require mitigation globally. Our analysis demonstrates that diverse, complementary measurement approaches are needed to quantify methane emissions in support of the Global Methane Pledge19. Modelling of the evolution of atmospheric methane emissions from the 2022 Nord Stream subsea pipeline leaks shows that the event emitted the largest recorded amount of methane from a single transient event. [ABSTRACT FROM AUTHOR]

Multicomponent reactions—those where three or more substrates combine into a product—have been highly useful in rapidly building chemical building blocks of increased complexity1, but achieving this enzymatically has remained rare2, 3, 4–5. This limitation primarily arises because an enzyme's active site is not typically set up to address multiple substrates, especially in cases involving multiple radical intermediates6. Recently, chemical catalytic radical sorting has emerged as an enabling strategy for a variety of useful reactions7,8. However, making such processes enantioselective is highly challenging owing to the inherent difficulty in the stereochemical control of radicals9. Here we repurpose a thiamine-dependent enzyme10,11 through directed evolution and combine it with photoredox catalysis to achieve a photobiocatalytic enantioselective three-component radical cross-coupling. This approach combines three readily available starting materials—aldehydes, α-bromo-carbonyls and alkenes—to give access to enantioenriched ketone products. Mechanistic investigations provide insights into how this dual photocatalyst–enzyme system precisely directs the three distinct radicals involved in the transformation, unlocking enzyme reactivity. Our approach has achieved exceptional stereoselectivity, with 24 out of 33 examples achieving ≥97% enantiomeric excess. Enantioselective three-component radical cross-coupling is achieved using a thiamine-dependent enzyme and photoredox catalysis, giving access to ketone products with exceptional stereoselectivity. [ABSTRACT FROM AUTHOR]

Reproduction, development and homeostasis depend on motile cilia, whose rhythmic beating is powered by a microtubule-based molecular machine called the axoneme. Although an atomic model of the axoneme is available for the alga Chlamydomonas reinhardtii1, structures of mammalian axonemes are incomplete1, 2, 3, 4–5. Furthermore, we do not fully understand how molecular structures of axonemes vary across motile-ciliated cell types in the body. Here we use cryoelectron microscopy, cryoelectron tomography and proteomics to resolve the 96-nm modular repeat of axonemal doublet microtubules (DMTs) from both sperm flagella and epithelial cilia of the oviduct, brain ventricles and respiratory tract. We find that sperm DMTs are the most specialized, with epithelial cilia having only minor differences across tissues. We build a model of the mammalian sperm DMT, defining the positions and interactions of 181 proteins including 34 newly identified proteins. We elucidate the composition of radial spoke 3 and uncover binding sites of kinases associated with regeneration of ATP and regulation of ciliary motility. We discover a sperm-specific, axoneme-tethered T-complex protein ring complex (TRiC) chaperone that may contribute to construction or maintenance of the long flagella of mammalian sperm. We resolve axonemal dyneins in their prestroke states, illuminating conformational changes that occur during ciliary movement. Our results illustrate how elements of chemical and mechanical regulation are embedded within the axoneme, providing valuable resources for understanding the aetiology of ciliopathy and infertility, and exemplifying the discovery power of modern structural biology. Cryoelectron microscopy, cryoelectron tomography and proteomics are used to resolve the 96-nm modular repeat of axonemal doublet microtubules from both sperm flagella and epithelial cilia of the oviduct, brain ventricles and respiratory tract. [ABSTRACT FROM AUTHOR]

RNA conformational diversity has fundamental biological roles1, 2, 3, 4–5, but direct visualization of its full conformational space in solution has not been possible using traditional biophysical techniques. Using solution atomic force microscopy, a deep neural network and statistical analyses, we show that the ribonuclease P (RNase P) RNA adopts heterogeneous conformations consisting of a conformationally invariant core and highly flexible peripheral structural elements that sample a broad conformational space, with amplitudes as large as 20–60 Å in a multitude of directions, with very low net energy cost. Increasing Mg2+ drives compaction and enhances enzymatic activity, probably by narrowing the conformational space. Moreover, analyses of the correlations and anticorrelations between spatial flexibility and sequence conservation suggest that the functional roles of both the structure and dynamics of key regions are embedded in the primary sequence. These findings reveal the structure–dynamics basis for the embodiment of both enzymatic precision and substrate promiscuity in the RNA component of the RNase P. Mapping the conformational space of the RNase P RNA demonstrates a new general approach to studying RNA structure and dynamics. Using a deep neural network and statistical analyses of atomic force microscopy images of individual RNA molecules enables the mapping of RNA conformational space in solution. [ABSTRACT FROM AUTHOR]

Recently acquired memories are reactivated in the hippocampus during sleep, an initial step for their consolidation1, 2–3. This process is concomitant with the hippocampal reactivation of previous memories4, 5–6, posing the problem of how to prevent interference between older and recent, initially labile, memory traces. Theoretical work has suggested that consolidating multiple memories while minimizing interference can be achieved by randomly interleaving their reactivation7, 8, 9–10. An alternative is that a temporal microstructure of sleep can promote the reactivation of different types of memories during specific substates. Here, to test these two hypotheses, we developed a method to simultaneously record large hippocampal ensembles and monitor sleep dynamics through pupillometry in naturally sleeping mice. Oscillatory pupil fluctuations revealed a previously unknown microstructure of non-REM sleep-associated memory processes. We found that memory replay of recent experiences dominated in sharp-wave ripples during contracted pupil substates of non-REM sleep, whereas replay of previous memories preferentially occurred during dilated pupil substates. Selective closed-loop disruption of sharp-wave ripples during contracted pupil non-REM sleep impaired the recall of recent memories, whereas the same manipulation during dilated pupil substates had no behavioural effect. Stronger extrinsic excitatory inputs characterized the contracted pupil substate, whereas higher recruitment of local inhibition was prominent during dilated pupil substates. Thus, the microstructure of non-REM sleep organizes memory replay, with previous versus new memories being temporally segregated in different substates and supported by local and input-driven mechanisms, respectively. Our results suggest that the brain can multiplex distinct cognitive processes during sleep to facilitate continuous learning without interference. The temporal microstructure of the brain can multiplex distinct cognitive processes during sleep to support continuous learning. [ABSTRACT FROM AUTHOR]

Quantum materials governed by emergent topological fermions have become a cornerstone of physics. Dirac fermions in graphene form the basis for moiré quantum matter and Dirac fermions in magnetic topological insulators enabled the discovery of the quantum anomalous Hall (QAH) effect1, 2–3. By contrast, there are few materials whose electromagnetic response is dominated by emergent Weyl fermions4, 5–6. Nearly all known Weyl materials are overwhelmingly metallic and are largely governed by irrelevant, conventional electrons. Here we theoretically predict and experimentally observe a semimetallic Weyl ferromagnet in van der Waals (Cr,Bi)2Te3. In transport, we find a record bulk anomalous Hall angle of greater than 0.5 along with non-metallic conductivity, a regime that is strongly distinct from conventional ferromagnets. Together with symmetry analysis, our data suggest a semimetallic Fermi surface composed of two Weyl points, with a giant separation of more than 75% of the linear dimension of the bulk Brillouin zone, and no other electronic states. Using state-of-the-art crystal-synthesis techniques, we widely tune the electronic structure, allowing us to annihilate the Weyl state and visualize a unique topological phase diagram exhibiting broad Chern insulating, Weyl semimetallic and magnetic semiconducting regions. Our observation of a semimetallic Weyl ferromagnet offers an avenue towards new correlated states and nonlinear phenomena, as well as zero-magnetic-field Weyl spintronic and optical devices. Van der Waals (Cr,Bi)2Te3, synthesized by non-equilibrium molecular beam epitaxy, is characterized by magnetotransport measurements and shown to be a semimetallic Weyl ferromagnet, with Fermi surface composed of two Weyl points and no irrelevant electronic states. [ABSTRACT FROM AUTHOR]