The 50 most-cited articles in Science, 2022

Copper is an essential cofactor for all organisms, and yet it becomes toxic if concentrations exceed a threshold maintained by evolutionarily conserved homeostatic mechanisms. How excess copper induces cell death, however, is unknown. Here, we show in human cells that copper-dependent, regulated cell death is distinct from known death mechanisms and is dependent on mitochondrial respiration. We show that copper-dependent death occurs by means of direct binding of copper to lipoylated components of the tricarboxylic acid (TCA) cycle. This results in lipoylated protein aggregation and subsequent iron-sulfur cluster protein loss, which leads to proteotoxic stress and ultimately cell death. These findings may explain the need for ancient copper homeostatic mechanisms.

Since its initial release in 2000, the human reference genome has covered only the euchromatic fraction of the genome, leaving important heterochromatic regions unfinished. Addressing the remaining 8% of the genome, the Telomere-to-Telomere (T2T) Consortium presents a complete 3.055 billion-base pair sequence of a human genome, T2T-CHM13, that includes gapless assemblies for all chromosomes except Y, corrects errors in the prior references, and introduces nearly 200 million base pairs of sequence containing 1956 gene predictions, 99 of which are predicted to be protein coding. The completed regions include all centromeric satellite arrays, recent segmental duplications, and the short arms of all five acrocentric chromosomes, unlocking these complex regions of the genome to variational and functional studies.

Over the past several years, the term PFAS (per- and polyfluoroalkyl substances) has grown to be emblematic of environmental contamination, garnering public, scientific, and regulatory concern. PFAS are synthesized by two processes, direct fluorination (e.g., electrochemical fluorination) and oligomerization (e.g., fluorotelomerization). More than a megatonne of PFAS is produced yearly, and thousands of PFAS wind up in end-use products. Atmospheric and aqueous fugitive releases during manufacturing, use, and disposal have resulted in the global distribution of these compounds. Volatile PFAS facilitate long-range transport, commonly followed by complex transformation schemes to recalcitrant terminal PFAS, which do not degrade under environmental conditions and thus migrate through the environment and accumulate in biota through multiple pathways. Efforts to remediate PFAS-contaminated matrices still are in their infancy, with much current research targeting drinking water.

Abstract While deep learning has revolutionized protein structure prediction, almost all experimentally characterized de novo protein designs have been generated using physically based approaches such as Rosetta. Here we describe a deep learning based protein sequence design method, ProteinMPNN, with outstanding performance in both in silico and experimental tests. The amino acid sequence at different positions can be coupled between single or multiple chains, enabling application to a wide range of current protein design challenges. On native protein backbones, ProteinMPNN has a sequence recovery of 52.4%, compared to 32.9% for Rosetta. Incorporation of noise during training improves sequence recovery on protein structure models, and produces sequences which more robustly encode their structures as assessed using structure prediction algorithms. We demonstrate the broad utility and high accuracy of ProteinMPNN using X-ray crystallography, cryoEM and functional studies by rescuing previously failed designs, made using Rosetta or AlphaFold, of protein monomers, cyclic homo-oligomers,…

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system of unknown etiology. We tested the hypothesis that MS is caused by Epstein-Barr virus (EBV) in a cohort comprising more than 10 million young adults on active duty in the US military, 955 of whom were diagnosed with MS during their period of service. Risk of MS increased 32-fold after infection with EBV but was not increased after infection with other viruses, including the similarly transmitted cytomegalovirus. Serum levels of neurofilament light chain, a biomarker of neuroaxonal degeneration, increased only after EBV seroconversion. These findings cannot be explained by any known risk factor for MS and suggest EBV as the leading cause of MS.

Climate tipping points occur when change in a part of the climate system becomes self-perpetuating beyond a warming threshold, leading to substantial Earth system impacts. Synthesizing paleoclimate, observational, and model-based studies, we provide a revised shortlist of global "core" tipping elements and regional "impact" tipping elements and their temperature thresholds. Current global warming of ~1.1°C above preindustrial temperatures already lies within the lower end of some tipping point uncertainty ranges. Several tipping points may be triggered in the Paris Agreement range of 1.5 to <2°C global warming, with many more likely at the 2 to 3°C of warming expected on current policy trajectories. This strengthens the evidence base for urgent action to mitigate climate change and to develop improved tipping point risk assessment, early warning capability, and adaptation strategies.

In halide perovskite solar cells the formation of secondary-phase excess lead iodide (PbI 2 ) has some positive effects on power conversion efficiency (PCE) but can be detrimental to device stability and lead to large hysteresis effects in voltage sweeps. We converted PbI 2 into an inactive (PbI 2 ) 2 RbCl compound by RbCl doping, which effectively stabilizes the perovskite phase. We obtained a certified PCE of 25.6% for FAPbI 3 (FA, formamidinium) perovskite solar cells on the basis of this strategy. Devices retained 96% of their original PCE values after 1000 hours of shelf storage and 80% after 500 hours of thermal stability testing at 85°C.

Fibrosis affects millions of people with cardiac disease. We developed a therapeutic approach to generate transient antifibrotic chimeric antigen receptor (CAR) T cells in vivo by delivering modified messenger RNA (mRNA) in T cell–targeted lipid nanoparticles (LNPs). The efficacy of these in vivo–reprogrammed CAR T cells was evaluated by injecting CD5-targeted LNPs into a mouse model of heart failure. Efficient delivery of modified mRNA encoding the CAR to T lymphocytes was observed, which produced transient, effective CAR T cells in vivo. Antifibrotic CAR T cells exhibited trogocytosis and retained the target antigen as they accumulated in the spleen. Treatment with modified mRNA-targeted LNPs reduced fibrosis and restored cardiac function after injury. In vivo generation of CAR T cells may hold promise as a therapeutic platform to treat various diseases.

Survival improves when cancer is detected early. However, ~50% of cancers are at an advanced stage when diagnosed. Early detection of cancer or precancerous change allows early intervention to try to slow or prevent cancer development and lethality. To achieve early detection of all cancers, numerous challenges must be overcome. It is vital to better understand who is at greatest risk of developing cancer. We also need to elucidate the biology and trajectory of precancer and early cancer to identify consequential disease that requires intervention. Insights must be translated into sensitive and specific early detection technologies and be appropriately evaluated to support practical clinical implementation. Interdisciplinary collaboration is key; advances in technology and biological understanding highlight that it is time to accelerate early detection research and transform cancer survival.

Grasslands store approximately one third of the global terrestrial carbon stocks and can act as an important soil carbon sink. Recent studies show that plant diversity increases soil organic carbon (SOC) storage by elevating carbon inputs to belowground biomass and promoting microbial necromass contribution to SOC storage. Climate change affects grassland SOC storage by modifying the processes of plant carbon inputs and microbial catabolism and anabolism. Improved grazing management and biodiversity restoration can provide low-cost and/or high-carbon-gain options for natural climate solutions in global grasslands. The achievable SOC sequestration potential in global grasslands is 2.3 to 7.3 billion tons of carbon dioxide equivalents per year (CO 2 e year −1 ) for biodiversity restoration, 148 to 699 megatons of CO 2 e year −1 for improved grazing management, and 147 megatons of CO 2 e year −1 for sown legumes in pasturelands.

Improvements to perovskite solar cells (PSCs) have focused on increasing their power conversion efficiency (PCE) and operational stability and maintaining high performance upon scale-up to module sizes. We report that replacing the commonly used mesoporous–titanium dioxide electron transport layer (ETL) with a thin layer of polyacrylic acid–stabilized tin(IV) oxide quantum dots (paa-QD-SnO 2 ) on the compact–titanium dioxide enhanced light capture and largely suppressed nonradiative recombination at the ETL–perovskite interface. The use of paa-QD-SnO 2 as electron-selective contact enabled PSCs (0.08 square centimeters) with a PCE of 25.7% (certified 25.4%) and high operational stability and facilitated the scale-up of the PSCs to larger areas. PCEs of 23.3, 21.7, and 20.6% were achieved for PSCs with active areas of 1, 20, and 64 square centimeters, respectively.

Despite their crucial role in health and disease, our knowledge of immune cells within human tissues remains limited. We surveyed the immune compartment of 16 tissues from 12 adult donors by single-cell RNA sequencing and VDJ sequencing generating a dataset of ~360,000 cells. To systematically resolve immune cell heterogeneity across tissues, we developed CellTypist, a machine learning tool for rapid and precise cell type annotation. Using this approach, combined with detailed curation, we determined the tissue distribution of finely phenotyped immune cell types, revealing hitherto unappreciated tissue-specific features and clonal architecture of T and B cells. Our multitissue approach lays the foundation for identifying highly resolved immune cell types by leveraging a common reference dataset, tissue-integrated expression analysis, and antigen receptor sequencing.

Ectopic lymphoid aggregates, termed tertiary lymphoid structures (TLSs), are formed in numerous cancer types, and, with few exceptions, their presence is associated with superior prognosis and response to immunotherapy. In spite of their presumed importance, the triggers that lead to TLS formation in cancer tissue and the contribution of these structures to intratumoral immune responses remain incompletely understood. Here, we discuss the present knowledge on TLSs in cancer, focusing on (i) the drivers of TLS formation, (ii) the function and contribution of TLSs to the antitumor immune response, and (iii) the potential of TLSs as therapeutic targets in human cancers.

BACKGROUND: In the Coronavirus Efficacy (COVE) trial, estimated mRNA-1273 vaccine efficacy against coronavirus disease-19 (COVID-19) was 94%. SARS-CoV-2 antibody measurements were assessed as correlates of COVID-19 risk and as correlates of protection. METHODS: Through case-cohort sampling, participants were selected for measurement of four serum antibody markers at Day 1 (first dose), Day 29 (second dose), and Day 57: IgG binding antibodies (bAbs) to Spike, bAbs to Spike receptor-binding domain (RBD), and 50% and 80% inhibitory dilution pseudovirus neutralizing antibody titers calibrated to the WHO International Standard (cID50 and cID80). Participants with no evidence of previous SARS-CoV-2 infection were included. Cox regression assessed in vaccine recipients the association of each Day 29 or 57 serologic marker with COVID-19 through 126 or 100 days of follow-up, respectively, adjusting for risk factors. RESULTS: Day 57 Spike IgG, RBD IgG, cID50, and cID80 neutralization levels were each inversely correlated with risk of COVID-19: hazard ratios 0.66 (95% CI 0.50, 0.88; p=0.005);…

High-entropy nanoparticles have become a rapidly growing area of research in recent years. Because of their multielemental compositions and unique high-entropy mixing states (i.e., solid-solution) that can lead to tunable activity and enhanced stability, these nanoparticles have received notable attention for catalyst design and exploration. However, this strong potential is also accompanied by grand challenges originating from their vast compositional space and complex atomic structure, which hinder comprehensive exploration and fundamental understanding. Through a multidisciplinary view of synthesis, characterization, catalytic applications, high-throughput screening, and data-driven materials discovery, this review is dedicated to discussing the important progress of high-entropy nanoparticles and unveiling the critical needs for their future development for catalysis, energy, and sustainability applications.

Molecular characterization of cell types using single-cell transcriptome sequencing is revolutionizing cell biology and enabling new insights into the physiology of human organs. We created a human reference atlas comprising nearly 500,000 cells from 24 different tissues and organs, many from the same donor. This atlas enabled molecular characterization of more than 400 cell types, their distribution across tissues, and tissue-specific variation in gene expression. Using multiple tissues from a single donor enabled identification of the clonal distribution of T cells between tissues, identification of the tissue-specific mutation rate in B cells, and analysis of the cell cycle state and proliferative potential of shared cell types across tissues. Cell type-specific RNA splicing was discovered and analyzed across tissues within an individual.

Further enhancing the performance and stability of inverted perovskite solar cells (PSCs) is crucial for their commercialization. We report that the functionalization of multication and halide perovskite interfaces with an organometallic compound, ferrocenyl-bis-thiophene-2-carboxylate (FcTc 2 ), simultaneously enhanced the efficiency and stability of inverted PSCs. The resultant devices achieved a power conversion efficiency of 25.0% and maintained >98% of their initial efficiency after continuously operating at the maximum power point for 1500 hours under simulated AM1.5 illumination. Moreover, the FcTc 2 -functionalized devices passed the international standards for mature photovoltaics (IEC61215:2016) and have exhibited high stability under the damp heat test (85°C and 85% relative humidity).

Programming is a powerful and ubiquitous problem-solving tool. Systems that can assist programmers or even generate programs themselves could make programming more productive and accessible. Recent transformer-based neural network models show impressive code generation abilities yet still perform poorly on more complex tasks requiring problem-solving skills, such as competitive programming problems. Here, we introduce AlphaCode, a system for code generation that achieved an average ranking in the top 54.3% in simulated evaluations on recent programming competitions on the Codeforces platform. AlphaCode solves problems by generating millions of diverse programs using specially trained transformer-based networks and then filtering and clustering those programs to a maximum of just 10 submissions. This result marks the first time an artificial intelligence system has performed competitively in programming competitions.

Summary Introduction Globally, there have been more than 404 million cases of SARS-CoV-2, with 5.8 million confirmed deaths, as of February 2022. South Africa has experienced four waves of SARS-CoV-2 transmission, with the second, third, and fourth waves being driven by the Beta, Delta, and Omicron variants, respectively. A key question with the emergence of new variants is the extent to which they are able to reinfect those who have had a prior natural infection. Rationale We developed two approaches to monitor routine epidemiological surveillance data to examine whether SARS-CoV-2 reinfection risk has changed through time in South Africa, in the context of the emergence of the Beta (B.1.351), Delta (B.1.617.2), and Omicron (B.1.1.529) variants. We analyze line list data on positive tests for SARS-CoV-2 with specimen receipt dates between 04 March 2020 and 31 January 2022, collected through South Africa’s National Notifiable Medical Conditions Surveillance System. Individuals having sequential positive tests at least 90 days apart were considered to have suspected reinfections. Our…

High–energy density lithium (Li) metal batteries (LMBs) are promising for energy storage applications but suffer from uncontrollable electrolyte degradation and the consequently formed unstable solid-electrolyte interphase (SEI). In this study, we designed self-assembled monolayers (SAMs) with high-density and long-range–ordered polar carboxyl groups linked to an aluminum oxide–coated separator to provide strong dipole moments, thus offering excess electrons to accelerate the degradation dynamics of carbon-fluorine bond cleavage in Li bis(trifluoromethanesulfonyl)imide. Hence, an SEI with enriched lithium fluoride (LiF) nanocrystals is generated, facilitating rapid Li + transfer and suppressing dendritic Li growth. In particular, the SAMs endow the full cells with substantially enhanced cyclability under high cathode loading, limited Li excess, and lean electrolyte conditions. As such, our work extends the long-established SAMs technology into a platform to control electrolyte degradation and SEI formation toward LMBs with ultralong life spans.

A stable perovskite heterojunction was constructed for inverted solar cells through surface sulfidation of lead (Pb)-rich perovskite films. The formed lead-sulfur (Pb-S) bonds upshifted the Fermi level at the perovskite interface and induced an extra back-surface field for electron extraction. The resulting inverted devices exhibited a power conversion efficiency (PCE) >24% with a high open-circuit voltage of 1.19 volts, corresponding to a low voltage loss of 0.36 volts. The strong Pb-S bonds could stabilize perovskite heterojunctions and strengthen underlying perovskite structures that have a similar crystal lattice. Devices with surface sulfidation retained more than 90% of the initial PCE after aging at 85°C for 2200 hours or operating at the maximum power point under continuous illumination for 1000 hours at 55° ± 5°C.

If perovskite solar cells (PSCs) with high power conversion efficiencies (PCEs) are to be commercialized, they must achieve long-term stability, which is usually assessed with accelerated degradation tests. One of the persistent obstacles for PSCs has been successfully passing the damp-heat test (85°C and 85% relative humidity), which is the standard for verifying the stability of commercial photovoltaic (PV) modules. We fabricated damp heat-stable PSCs by tailoring the dimensional fragments of two-dimensional perovskite layers formed at room temperature with oleylammonium iodide molecules; these layers passivate the perovskite surface at the electron-selective contact. The resulting inverted PSCs deliver a 24.3% PCE and retain >95% of their initial value after >1000 hours at damp-heat test conditions, thereby meeting one of the critical industrial stability standards for PV modules.

Abstract The ability to obtain single cell transcriptomes for stable cell types and dynamic cell states is ushering in a new era for biology. We created the Tabula Drosophilae , a single cell atlas of the adult fruit fly which includes 580k cells from 15 individually dissected sexed tissues as well as the entire head and body. Over 100 researchers from the fly community contributed annotations to >250 distinct cell types across all tissues. We provide an in-depth analysis of cell type-related gene signatures and transcription factor markers, as well as sexual dimorphism, across the whole animal. Analysis of common cell types that are shared between tissues, such as blood and muscle cells, allowed the discovery of rare cell types and tissue-specific subtypes. This atlas provides a valuable resource for the entire Drosophila community and serves as a comprehensive reference to study genetic perturbations and disease models at single cell resolution.

Forest restoration is being scaled up globally to deliver critical ecosystem services and biodiversity benefits; however, there is a lack of rigorous comparison of cobenefit delivery across different restoration approaches. Through global synthesis, we used 25,950 matched data pairs from 264 studies in 53 countries to assess how delivery of climate, soil, water, and wood production services, in addition to biodiversity, compares across a range of tree plantations and native forests. Benefits of aboveground carbon storage, water provisioning, and especially soil erosion control and biodiversity are better delivered by native forests, with compositionally simpler, younger plantations in drier regions performing particularly poorly. However, plantations exhibit an advantage in wood production. These results underscore important trade-offs among environmental and production goals that policy-makers must navigate in meeting forest restoration commitments.

Electrolytes and the associated interphases constitute the critical components to support the emerging battery chemistries that promise tantalizing energy but involve drastic phase and structure complications. Designing better electrolytes and interphases holds the key to the success of these batteries. As the only component that interfaces with every other component in the device, an electrolyte must satisfy multiple criteria simultaneously. These include transporting ions while insulating electrons between the electrodes and maintaining stability against electrodes of extreme chemical natures: the strongly oxidative cathode and the strongly reductive anode. In most advanced batteries, the two electrodes operate at potentials far beyond the thermodynamic stability limits of electrolytes, so the stability therein has to be realized kinetically through an interphase formed from the sacrificial reactions between electrolyte and electrodes.

High-entropy alloys are solid solutions of multiple principal elements that are capable of reaching composition and property regimes inaccessible for dilute materials. Discovering those with valuable properties, however, too often relies on serendipity, because thermodynamic alloy design rules alone often fail in high-dimensional composition spaces. We propose an active learning strategy to accelerate the design of high-entropy Invar alloys in a practically infinite compositional space based on very sparse data. Our approach works as a closed-loop, integrating machine learning with density-functional theory, thermodynamic calculations, and experiments. After processing and characterizing 17 new alloys out of millions of possible compositions, we identified two high-entropy Invar alloys with extremely low thermal expansion coefficients around 2 × 10 −6 per degree kelvin at 300 kelvin. We believe this to be a suitable pathway for the fast and automated discovery of high-entropy alloys with optimal thermal, magnetic, and electrical properties.

Considerable research effort has been made worldwide to decipher the immune response triggered upon severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, identify the drivers of severe and fatal COVID-19, and understand what leads to the prolongation of symptoms after disease resolution. We review the results of almost 2 years of COVID-19 immunology research and discuss definitive findings and remaining questions regarding our understanding of COVID-19 pathophysiology. We discuss emerging understanding of differences in immune responses seen in those with and without Long Covid syndrome, also known as post-acute sequelae of SARS-CoV-2. We hope that the knowledge gained from this COVID-19 research will be applied in studies of inflammatory processes involved in critical and chronic illnesses, which remain a major unmet need.

The high-entropy concept provides extended, optimized space of a composition, resulting in unusual transport phenomena and excellent thermoelectric performance. By tuning electron and phonon localization, we enhanced the figure-of-merit value to 2.7 at 750 kelvin in germanium telluride-based high-entropy materials and realized a high experimental conversion efficiency of 13.3% at a temperature difference of 506 kelvin with the fabricated segmented module. By increasing the entropy, the increased crystal symmetry delocalized the distribution of electrons in the distorted rhombohedral structure, resulting in band convergence and improved electrical properties. By contrast, the localized phonons from the entropy-induced disorder dampened the propagation of transverse phonons, which was the origin of the increased anharmonicity and largely depressed lattice thermal conductivity. We provide a paradigm for tuning electron and phonon localization by entropy manipulation, but we have also demonstrated a route for improving the performance of high-entropy thermoelectric materials.

Land degradation reduces soil functioning and, consequently, the services that soil provides. Soil hydrological functions are critical to combat soil degradation and promote soil restoration. Soil microorganisms affect soil hydrology, but the role of soil microbiota in forming and sustaining soil is not well explored. Case studies indicate the potential of soil microorganisms as game-changers in restoring soil functions. We review the state of the art of microorganism use in land restoration technology, the groups of microorganisms with the greatest potential for soil restoration, knowledge of the effect of microorganisms on soil physical properties, and proposed strategies for the long-term restoration of degraded lands. We also emphasize the need to advance the emerging research field of biophysical landscape interactions to support soil-plant ecosystem restoration practices.

Memristive devices, which combine a resistor with memory functions such that voltage pulses can change their resistance (and hence their memory state) in a nonvolatile manner, are beginning to be implemented in integrated circuits for memory applications. However, memristive devices could have applications in many other technologies, such as non-von Neumann in-memory computing in crossbar arrays, random number generation for data security, and radio-frequency switches for mobile communications. Progress toward the integration of memristive devices in commercial solid-state electronic circuits and other potential applications will depend on performance and reliability challenges that still need to be addressed, as described here.

The human immune system displays substantial variation between individuals, leading to differences in susceptibility to autoimmune disease. We present single-cell RNA sequencing (scRNA-seq) data from 1,267,758 peripheral blood mononuclear cells from 982 healthy human subjects. For 14 cell types, we identified 26,597 independent cis-expression quantitative trait loci (eQTLs) and 990 trans-eQTLs, with most showing cell type-specific effects on gene expression. We subsequently show how eQTLs have dynamic allelic effects in B cells that are transitioning from naïve to memory states and demonstrate how commonly segregating alleles lead to interindividual variation in immune function. Finally, using a Mendelian randomization approach, we identify the causal route by which 305 risk loci contribute to autoimmune disease at the cellular level. This work brings together genetic epidemiology with scRNA-seq to uncover drivers of interindividual variation in the immune system.

Human skin forms a protective barrier against the external environment and is our first line of defense against toxic, solar, and pathogenic insults. Our skin also defines our outward appearance, protects our internal tissues and organs, acts as a sensory interface, and prevents dehydration. Crucial to the skin's barrier function is the colonizing microbiota, which provides protection against pathogens, tunes immune responses, and fortifies the epithelium. Here we highlight recent advances in our understanding of how the microbiota mediates multiple facets of skin barrier function. We discuss recent insights into pathological host-microbiota interactions and implications for disorders of the skin and distant organs. Finally, we examine how microbiota-based mechanisms can be targeted to prevent or manage skin disorders and impaired wound healing.

Mixed plastics waste represents an abundant and largely untapped feedstock for the production of valuable products. The chemical diversity and complexity of these materials, however, present major barriers to realizing this opportunity. In this work, we show that metal-catalyzed autoxidation depolymerizes comingled polymers into a mixture of oxygenated small molecules that are advantaged substrates for biological conversion. We engineer a robust soil bacterium, Pseudomonas putida , to funnel these oxygenated compounds into a single exemplary chemical product, either β-ketoadipate or polyhydroxyalkanoates. This hybrid process establishes a strategy for the selective conversion of mixed plastics waste into useful chemical products.

Ultracompact sources of circularly polarized light are important for classical and quantum optical information processing. Conventional approaches for generating chiral emission are restricted to excitation power ranges and fail to provide high-quality radiation with perfect polarization conversion. We used the physics of chiral quasi-bound states in the continuum to demonstrate the efficient and controllable emission of circularly polarized light from resonant metasurfaces. Exploiting intrinsic chirality and giant field enhancement, we revealed how to simultaneously modify and control spectra, radiation patterns, and spin angular momentum of photoluminescence and lasing without any spin injection. The superior characteristics of chiral emission and lasing promise multiple applications in nanophotonics and quantum optics.

The newly reported Omicron variant is poised to replace Delta as the most prevalent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant across the world. Cryo–electron microscopy (cryo-EM) structural analysis of the Omicron variant spike protein in complex with human angiotensin-converting enzyme 2 (ACE2) reveals new salt bridges and hydrogen bonds formed by mutated residues arginine-493, serine-496, and arginine-498 in the receptor binding domain with ACE2. These interactions appear to compensate for other Omicron mutations such as the substitution of asparagine for lysine at position 417 (K417N) that are known to reduce ACE2 binding affinity, resulting in similar biochemical ACE2 binding affinities for the Delta and Omicron variants. Neutralization assays show that pseudoviruses that display the Omicron spike protein exhibit increased antibody evasion. The increase in antibody evasion and the retention of strong interactions at the ACE2 interface thus represent important molecular features that likely contribute to the rapid spread of the Omicron variant.

Intrinsically stretchable bioelectronic devices based on soft and conducting organic materials have been regarded as the ideal interface for seamless and biocompatible integration with the human body. A remaining challenge is to combine high mechanical robustness with good electrical conduction, especially when patterned at small feature sizes. We develop a molecular engineering strategy based on a topological supramolecular network, which allows for the decoupling of competing effects from multiple molecular building blocks to meet complex requirements. We obtained simultaneously high conductivity and crack-onset strain in a physiological environment, with direct photopatternability down to the cellular scale. We further collected stable electromyography signals on soft and malleable octopus and performed localized neuromodulation down to single-nucleus precision for controlling organ-specific activities through the delicate brainstem.

Abstract Existing human genome assemblies have almost entirely excluded highly repetitive sequences within and near centromeres, limiting our understanding of their sequence, evolution, and essential role in chromosome segregation. Here, we present an extensive study of newly assembled peri/centromeric sequences representing 6.2% (189.9 Mb) of the first complete, telomere-to-telomere human genome assembly (T2T-CHM13). We discovered novel patterns of peri/centromeric repeat organization, variation, and evolution at both large and small length scales. We also found that inner kinetochore proteins tend to overlap the most recently duplicated subregions within centromeres. Finally, we compared chromosome X centromeres across a diverse panel of individuals and uncovered structural, epigenetic, and sequence variation at single-base resolution across these regions. In total, this work provides an unprecedented atlas of human centromeres to guide future studies of their complex and critical functions as well as their unique evolutionary dynamics. One-sentence summary Deep characterization…

Continuous imaging of internal organs over days could provide crucial information about health and diseases and enable insights into developmental biology. We report a bioadhesive ultrasound (BAUS) device that consists of a thin and rigid ultrasound probe robustly adhered to the skin via a couplant made of a soft, tough, antidehydrating, and bioadhesive hydrogel-elastomer hybrid. The BAUS device provides 48 hours of continuous imaging of diverse internal organs, including blood vessels, muscle, heart, gastrointestinal tract, diaphragm, and lung. The BAUS device could enable diagnostic and monitoring tools for various diseases.

Magnetic effects of lanthanide bonding Lanthanide coordination compounds have attracted attention for their persistent magnetic properties near liquid nitrogen temperature, well above alternative molecular magnets. Gould et al . report that introducing metal-metal bonding can enhance coercivity. Reduction of iodide-bridged terbium or dysprosium dimers resulted in a single electron bond between the metals, which enforced alignment of the other valence electrons. The resultant coercive fields exceeded 14 tesla below 50 and 60 kelvin for the terbium and dysprosium compounds, respectively. —JSY

Realizing solution-processed heterostructures is a long-enduring challenge in halide perovskites because of solvent incompatibilities that disrupt the underlying layer. By leveraging the solvent dielectric constant and Gutmann donor number, we could grow phase-pure two-dimensional (2D) halide perovskite stacks of the desired composition, thickness, and bandgap onto 3D perovskites without dissolving the underlying substrate. Characterization reveals a 3D–2D transition region of 20 nanometers mainly determined by the roughness of the bottom 3D layer. Thickness dependence of the 2D perovskite layer reveals the anticipated trends for n-i-p and p-i-n architectures, which is consistent with band alignment and carrier transport limits for 2D perovskites. We measured a photovoltaic efficiency of 24.5%, with exceptional stability of T 99 (time required to preserve 99% of initial photovoltaic efficiency) of >2000 hours, implying that the 3D/2D bilayer inherits the intrinsic durability of 2D perovskite without compromising efficiency.

Tropical deforestation continues at alarming rates with profound impacts on ecosystems, climate, and livelihoods, prompting renewed commitments to halt its continuation. Although it is well established that agriculture is a dominant driver of deforestation, rates and mechanisms remain disputed and often lack a clear evidence base. We synthesize the best available pantropical evidence to provide clarity on how agriculture drives deforestation. Although most (90 to 99%) deforestation across the tropics 2011 to 2015 was driven by agriculture, only 45 to 65% of deforested land became productive agriculture within a few years. Therefore, ending deforestation likely requires combining measures to create deforestation-free supply chains with landscape governance interventions. We highlight key remaining evidence gaps including deforestation trends, commodity-specific land-use dynamics, and data from tropical dry forests and forests across Africa.

Elucidating the wiring diagram of the human cell is a central goal of the postgenomic era. We combined genome engineering, confocal live-cell imaging, mass spectrometry, and data science to systematically map the localization and interactions of human proteins. Our approach provides a data-driven description of the molecular and spatial networks that organize the proteome. Unsupervised clustering of these networks delineates functional communities that facilitate biological discovery. We found that remarkably precise functional information can be derived from protein localization patterns, which often contain enough information to identify molecular interactions, and that RNA binding proteins form a specific subgroup defined by unique interaction and localization properties. Paired with a fully interactive website (opencell.czbiohub.org), our work constitutes a resource for the quantitative cartography of human cellular organization.

organic-inorganic lead halide perovskites (OLHPs) was conventionally believed to hardly affect their optoelectronic properties. However, more recent developments have unraveled the critical role of the A cation in the regulation of the physicochemical and optoelectronic properties of OLHPs. We review the important breakthroughs enabled by the versatility of the A cation and highlight potential opportunities and unanswered questions related to the A cation in OLHPs.

Advances in solid-state batteries have primarily been driven by the discovery of superionic conducting structural frameworks that function as solid electrolytes. We demonstrate the ability of high-entropy metal cation mixes to improve ionic conductivity in a compound, which leads to less reliance on specific chemistries and enhanced synthesizability. The local distortions introduced into high-entropy materials give rise to an overlapping distribution of site energies for the alkali ions so that they can percolate with low activation energy. Experiments verify that high entropy leads to orders-of-magnitude higher ionic conductivities in lithium (Li)-sodium (Na) superionic conductor (Li-NASICON), sodium NASICON (Na-NASICON), and Li-garnet structures, even at fixed alkali content. We provide insight into selecting the optimal distortion and designing high-entropy superionic conductors across the vast compositional space.

Astrocytes, a type of glia, are abundant and morphologically complex cells. Here, we report astrocyte molecular profiles, diversity, and morphology across the mouse central nervous system (CNS). We identified shared and region-specific astrocytic genes and functions and explored the cellular origins of their regional diversity. We identified gene networks correlated with astrocyte morphology, several of which unexpectedly contained Alzheimer's disease (AD) risk genes. CRISPR/Cas9-mediated reduction of candidate genes reduced astrocyte morphological complexity and resulted in cognitive deficits. The same genes were down-regulated in human AD, in an AD mouse model that displayed reduced astrocyte morphology, and in other human brain disorders. We thus provide comprehensive molecular data on astrocyte diversity and mechanisms across the CNS and on the molecular basis of astrocyte morphology in health and disease.

Abstract Filament assembly of amyloid-β peptides ending at residue 42 (Aβ42) is a central event in Alzheimer’s disease. We report the cryo-EM structures of Aβ42 filaments from brain. Two structurally related S-shaped protofilament folds give rise to two types of filaments. Type I filaments were found mostly in the brains of individuals with sporadic Alzheimer’s disease and Type II filaments in individuals with familial Alzheimer’s disease and other conditions. The structures of Aβ42 filaments from brain differ from those of filaments assembled in vitro . By contrast, in App NL-F knock-in mice, Aβ42 deposits were made of Type II filaments. Knowledge of Aβ42 filament structures from human brain may lead to the development of inhibitors of assembly and improved imaging agents.

CrCoNi-based medium- and high-entropy alloys display outstanding damage tolerance, especially at cryogenic temperatures. In this study, we examined the fracture toughness values of the equiatomic CrCoNi and CrMnFeCoNi alloys at 20 kelvin (K). We found exceptionally high crack-initiation fracture toughnesses of 262 and 459 megapascal-meters ½ (MPa·m ½ ) for CrMnFeCoNi and CrCoNi, respectively; CrCoNi displayed a crack-growth toughness exceeding 540 MPa·m ½ after 2.25 millimeters of stable cracking. Crack-tip deformation structures at 20 K are quite distinct from those at higher temperatures. They involve nucleation and restricted growth of stacking faults, fine nanotwins, and transformed epsilon martensite, with coherent interfaces that can promote both arrest and transmission of dislocations to generate strength and ductility. We believe that these alloys develop fracture resistance through a progressive synergy of deformation mechanisms, dislocation glide, stacking-fault formation, nanotwinning, and phase transformation, which act in concert to prolong strain hardening that…

Understanding animal movement is essential to elucidate how animals interact, survive, and thrive in a changing world. Recent technological advances in data collection and management have transformed our understanding of animal "movement ecology" (the integrated study of organismal movement), creating a big-data discipline that benefits from rapid, cost-effective generation of large amounts of data on movements of animals in the wild. These high-throughput wildlife tracking systems now allow more thorough investigation of variation among individuals and species across space and time, the nature of biological interactions, and behavioral responses to the environment. Movement ecology is rapidly expanding scientific frontiers through large interdisciplinary and collaborative frameworks, providing improved opportunities for conservation and insights into the movements of wild animals, and their causes and consequences.

Human activities have caused global temperatures to increase by 1.25°C, and the current emissions trajectory suggests that we will exceed 1.5°C in less than 10 years. Though the growth rate of global carbon dioxide emissions has slowed and many countries have strengthened their emissions targets, current midcentury net zero goals are insufficient to limit global warming to 1.5°C above preindustrial temperatures. The primary barriers to the achievement of a 1.5°C-compatible pathway are not geophysical but rather reflect inertia in our political and technological systems. Both political and corporate leadership are needed to overcome this inertia, supported by increased societal recognition of the need for system-level and individual lifestyle changes. The available evidence does not yet indicate that the world has seriously committed to achieving the 1.5°C goal.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant of concern evades antibody-mediated immunity that comes from vaccination or infection with earlier variants due to accumulation of numerous spike mutations. To understand the Omicron antigenic shift, we determined cryo-electron microscopy and x-ray crystal structures of the spike protein and the receptor-binding domain bound to the broadly neutralizing sarbecovirus monoclonal antibody (mAb) S309 (the parent mAb of sotrovimab) and to the human ACE2 receptor. We provide a blueprint for understanding the marked reduction of binding of other therapeutic mAbs that leads to dampened neutralizing activity. Remodeling of interactions between the Omicron receptor-binding domain and human ACE2 likely explains the enhanced affinity for the host receptor relative to the ancestral virus.