To reveal the connections between the 2024 moment magnitude ( M w ) 7.5 Noto earthquake in Japan and the seismicity swarms that preceded it, we investigated its rupture process through near-source waveform analysis and source imaging techniques, combining seismic and geodetic datasets. We found notable complexity in the initial rupture stages. A strong fault asperity, which remained unbroken in preceding

Single-molecule techniques are ideally poised to characterize complex dynamics but are typically limited to investigating a small number of different samples. However, a large sequence or chemical space often needs to be explored to derive a comprehensive understanding of complex biological processes. Here we describe multiplexed single-molecule characterization at the library scale (MUSCLE), a method

Samarium diiodide (SmI 2 ) is a privileged, single-electron reductant deployed in diverse synthetic settings. However, generalizable methods for catalytic turnover remain elusive because of the well-known challenge associated with cleaving strong Sm III –O bonds. Prior efforts have focused on the use of highly reactive oxophiles to enable catalyst turnover. However, such approaches give rise to complex

Clathrin-mediated endocytosis has characteristic features in neuronal dendrites and presynapses, but how membrane proteins are internalized along the axon shaft remains unclear. We focused on clathrin-coated structures and endocytosis along the axon initial segment (AIS) and their relationship to the periodic actin-spectrin scaffold that lines the axonal plasma membrane. A combination of super-resolution

Impaired cerebral glucose metabolism is a pathologic feature of Alzheimer’s disease (AD), with recent proteomic studies highlighting disrupted glial metabolism in AD. We report that inhibition of indoleamine-2,3-dioxygenase 1 (IDO1), which metabolizes tryptophan to kynurenine (KYN), rescues hippocampal memory function in mouse preclinical models of AD by restoring astrocyte metabolism. Activation of

Spindle bipolarization, the process of a microtubule mass transforming into a bipolar spindle, is a prerequisite for accurate chromosome segregation. In contrast to mitotic cells, the process and mechanism of spindle bipolarization in human oocytes remains unclear. Using high-resolution imaging in more than 1800 human oocytes, we revealed a typical state of multipolar intermediates that form during

Ever since the Cass Review was released in April—an evaluation by the United Kingdom’s National Health Service that has led to a ban on pubertysuppressing medication for transgender and gender diverse (TGD) youth—there has been criticism of the assessment and its recommendations, and concern about how it could be leveraged to more broadly affect public health care. In response, physicians, researchers

Meeting the Paris Agreement’s climate targets necessitates better knowledge about which climate policies work in reducing emissions at the necessary scale. We provide a global, systematic ex post evaluation to identify policy combinations that have led to large emission reductions out of 1500 climate policies implemented between 1998 and 2022 across 41 countries from six continents. Our approach integrates

Wind energy is helping to decarbonize the electrical grid, but wind blades are not recyclable, and current end-of-life management strategies are not sustainable. To address the material recyclability challenges in sustainable energy infrastructure, we introduce scalable biomass-derivable polyester covalent adaptable networks and corresponding fiber-reinforced composites for recyclable wind blade fabrication

Polymer adhesives play an important role in many medical, consumer, and industrial products. Polymers of α-lipoic acid (αLA) have the potential to fulfill the need for versatile and environmentally friendly adhesives, but their performance is plagued by spontaneous depolymerization. We report a family of stabilized αLA polymer adhesives that can be tailored for a variety of medical or nonmedical uses

We present an algorithm to estimate the excited states of a quantum system by variational Monte Carlo, which has no free parameters and requires no orthogonalization of the states, instead transforming the problem into that of finding the ground state of an expanded system. Arbitrary observables can be calculated, including off-diagonal expectations, such as the transition dipole moment. The method

Effective fisheries management requires accurate estimates of stock biomass and trends; yet, assumptions in stock assessment models generate high levels of uncertainty and error. For 230 fisheries worldwide, we contrasted stock biomass estimates at the time of assessment with updated hindcast estimates modeled for the same year in later assessments to evaluate systematic over- or underestimation. For

In this Review, we explore the transformative potential of decentralized clinical trials (DCTs) in addressing the limitations of traditional randomized controlled trials (RCTs). We highlight the merits of DCTs fostering greater inclusivity, efficiency, and adaptability. We emphasize the challenges of RCTs, including limited participant diversity and logistical barriers, geographical constraints, and

At the core of molecular biology lies the intricate interplay between sequence, structure, and function. Single-molecule techniques provide in-depth dynamic insights into structure and function, but laborious assays impede functional screening of large sequence libraries. We introduce high-throughput Single-molecule Parallel Analysis for Rapid eXploration of Sequence space (SPARXS), integrating single-molecule

When it comes to making decisions about artificial intelligence (AI), Eric Schmidt is very clear. In 2023, the former Google CEO told NBC’s Meet the Press , “there’s no way a nonindustry person can understand what is possible. It’s just too new, too hard, there’s not the expertise.” But if, as Schmidt believes, AI will be the next industrial revolution, then the technology is too important to be left

Safe drinking water access is a human right, but data on safely managed drinking water services (SMDWS) is lacking for more than half of the global population. We estimate SMDWS use in 135 low- and middle-income countries (LMICs) at subnational levels with a geospatial modeling approach, combining existing household survey data with available global geospatial datasets. We estimate that only one in

Memory consolidation involves the synchronous reactivation of hippocampal cells active during recent experience in sleep sharp-wave ripples (SWRs). How this increase in firing rates and synchrony after learning is counterbalanced to preserve network stability is not understood. We discovered a network event generated by an intrahippocampal circuit formed by a subset of CA2 pyramidal cells to chole

The entorhinal cortex represents allocentric spatial geometry and egocentric speed and heading information required for spatial navigation. However, it remains unclear whether it contributes to the prediction of an animal’s future location. We discovered grid cells in the medial entorhinal cortex (MEC) that have grid fields representing future locations during goal-directed behavior. These predictive

In the underdoped n-type cuprate Nd 2- x Ce x CuO 4 , long-range antiferromagnetic order reconstructs the Fermi surface, resulting in a putative antiferromagnetic metal with small Fermi pockets. Using angle-resolved photoemission spectroscopy, we observe an anomalous energy gap, an order of magnitude smaller than the antiferromagnetic gap, in a wide portion of the underdoped regime and smoothly connecting

An impact at Chicxulub, Mexico, occurred 66 million years ago, producing a global stratigraphic layer that marks the boundary between the Cretaceous and Paleogene eras. That layer contains elevated concentrations of platinum-group elements, including ruthenium. We measured ruthenium isotopes in samples taken from three Cretaceous-Paleogene boundary sites, five other impacts that occurred between 36

The functions of proteins generally depend on their assembly into complexes. During evolution, some complexes have transitioned from homomers encoded by a single gene to heteromers encoded by duplicate genes. This transition could occur without adaptive evolution through intermolecular compensatory mutations. Here, we experimentally duplicated and evolved a homodimeric enzyme to determine whether and

Memories are dynamic constructs whose properties change with time and experience. The biological mechanisms underpinning these dynamics remain elusive, particularly concerning how shifts in the composition of memory-encoding neuronal ensembles influence the evolution of a memory over time. By targeting developmentally distinct subpopulations of principal neurons, we discovered that memory encoding

“Can machines think?” So asked Alan Turing in his 1950 paper , “Computing Machinery and Intelligence.” Turing quickly noted that, given the difficulty of defining thinking , the question is “too meaningless to deserve discussion.” As is often done in philosophical debates, he proposed replacing it with a different question. Turing imagined an “imitation game,” in which a human judge converses with

In the well-known case of Henrietta Lacks, cells from her tumor were taken without consent and used more than 70 years ago to create the first immortal human cell line (“HeLa” cells). That event led to many scientific breakthroughs and to the debate about the ethics of consent and requirements for compensation. May 2024 saw two decisions by US federal courts—one related to Lacks—that could narrow the

Air sensitivity remains a substantial barrier to the commercialization of sodium (Na)–layered oxides (NLOs). This problem has puzzled the community for decades because of the complexity of interactions between air components and their impact on both bulk and surfaces of NLOs. We show here that water vapor plays a pivotal role in initiating destructive acid and oxidative degradations of NLOs only when

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein binds the receptor angiotensin converting enzyme 2 (ACE2) and drives virus-host membrane fusion through refolding of its S2 domain. Whereas the S1 domain contains high sequence variability, the S2 domain is conserved and is a promising pan-betacoronavirus vaccine target. We applied cryo–electron tomography to capture intermediates

Metal oxide films are essential in most electronic devices, yet they are typically deposited at elevated temperatures by using slow, vacuum-based processes. We printed native oxide films over large areas at ambient conditions by moving a molten metal meniscus across a target substrate. The oxide gently separates from the metal through fluid instabilities that occur in the meniscus, leading to uniform

Quantum many-body scars are notable as nonthermal, low-entanglement states that exist at high energies. Here, we use attractively interacting dysprosium gases to create scar states that are stable enough to be driven into a strongly nonlinear regime while retaining their character. We measure how the kinetic and total energies evolve after quenching the confining potential. Although the bare interactions

Spontaneous activity refines neural connectivity prior to the onset of sensory experience, but it remains unclear how such activity instructs axonal connectivity with subcellular precision. We simultaneously measured spontaneous retinal waves and the activity of individual retinocollicular axons and tracked morphological changes in axonal arbors across hours in vivo in neonatal mice. We demonstrate

Whereas [4 + 2] cycloadditions are among the most powerful tools in the chemist’s synthetic arsenal, controlling reactivity and selectivity of [6 + 4] cycloadditions has proven to be extremely challenging. Such transformations, especially if compatible with simple hydrocarbon-based substrates, could ultimately provide a general approach to highly valuable and otherwise difficult to access 10-membered

Discussions around global equity and justice in science typically emphasize the lack of diversity in the editorial boards of scientific journals, inequities in authorship, “parachute research,” dominance of the English language, or scientific awards garnered predominantly by Global North scientists. These inequities are pervasive and must be redressed. But there is a bigger problem. The legacy of colonialism

Antiviral therapies with reduced frequencies of administration and high barriers to resistance remain a major goal. For HIV, theories have proposed that viral-deletion variants, which conditionally replicate with a basic reproductive ratio [R 0 ] > 1 (termed “therapeutic interfering particles” or “TIPs”), could parasitize wild-type virus to constitute single-administration, escape-resistant antiviral

Prymnesium parvum are harmful haptophyte algae that cause massive environmental fish kills. Their polyketide polyether toxins, the prymnesins, are among the largest nonpolymeric compounds in nature and have biosynthetic origins that have remained enigmatic for more than 40 years. In this work, we report the “PKZILLAs,” massive P. parvum polyketide synthase (PKS) genes that have evaded previous detection

The short-term impact of famines on death and disease is well documented, but estimating their potential long-term impact is difficult. We used the setting of the man-made Ukrainian Holodomor famine of 1932–1933 to examine the relation between prenatal famine and adult type 2 diabetes mellitus (T2DM). This ecological study included 128,225 T2DM cases diagnosed from 2000 to 2008 among 10,186,016 male

Flexible integration spurs diverse applications in metal-organic frameworks (MOFs). However, current configurations suffer from the trade-off between MOF loadings and mechanical compliance. We report a wrinkled configuration of MOF thin films. We established an interfacial synthesis confined and controlled by a polymer topcoat and achieved multiple Turing motifs in the wrinkled thin films. These films

Materials with multifunctionality affect society enormously. However, the inability to surmount multiple functionality trade-offs limits the discovery of next-generation multifunctional materials. Departing from conventional alloying design philosophy, we present a hierarchical nanostructure (HNS) strategy to simultaneously break multiple performance trade-offs in a material. Using a praseodymium-cobalt

Despite recent studies implicating liquid-like biomolecular condensates in diverse cellular processes, many biomolecular condensates exist in a solid-like state, and their function and regulation are less understood. We show that the tumor suppressor Merlin, an upstream regulator of the Hippo pathway, localizes to both cell junctions and medial apical cortex in Drosophila epithelia, with the latter

The energetic disorder induced by fluctuating liquid environments acts in opposition to the precise control required for coherence-based sensing. Overcoming fluctuations requires a protected quantum subspace that only weakly interacts with the local environment. We report a ytterbium complex that exhibited an ultranarrow absorption linewidth in solution at room temperature with a full width at half

Defense-associated reverse transcriptase (DRT) systems perform DNA synthesis to protect bacteria against viral infection, but the identities and functions of their DNA products remain largely unknown. Here we show that DRT2 systems encode an unprecedented immune pathway that involves de novo gene synthesis via rolling circle reverse transcription of a non-coding RNA (ncRNA). Programmed template jumping

One of the biggest neurophysiological science news headlines of the 2024 summer reported a critical link between post-traumatic stress disorder (PTSD), suicide, and brain injury from blast events in members of the elite US fighting force, Navy SEALS. Researchers from the Department of Defense/Uniformed Services University Brain Tissue Repository (DOD/USU BTR) had discovered a border of neural damage

Materials often fail prematurely or catastrophically under load while containing voids, posing a challenge to materials manufacturing. We found that a metal (gold) containing spherical voids with a fraction of up to 10% does not fracture prematurely in tension when the voids are shrunk to the submicron or nanometer scale. Instead, the dispersed nanovoids increase the strength and ductility of the material

The upper mantle is critical for our understanding of terrestrial magmatism, crust formation, and element cycling between Earth’s solid interior, hydrosphere, atmosphere, and biosphere. Mantle composition and evolution have been primarily inferred by surface sampling and indirect methods. We recovered a long (1268-meter) section of serpentinized abyssal mantle peridotite interleaved with thin gabbroic

Periods of large igneous province (LIP) magmatism have shaped Earth’s biological and climatic history, causing major climatic shifts and biological reorganizations. The vegetation response to LIP-induced perturbations may affect the efficiency of the carbon-climate regulation system and the post-LIP climate evolution. Using an eco-evolutionary vegetation model, we demonstrate here that the vegetation’s

Endoplasmic Reticulum (ER) stress induces repression of protein synthesis throughout the cell. Attempts to understand how localized stress leads to widespread repression have been limited by difficulties in resolving translation rates at the subcellular level. Here, using live-cell imaging of reporter mRNA translation, we unexpectedly found that during ER stress active translation at mitochondria was

Hematopoietic stem cells (HSCs) are routinely mobilized from the bone marrow (BM) to the blood circulation for clinical transplantation. However, the precise mechanisms by which individual stem cells exit the marrow are not understood. This study identified cell-extrinsic and molecular determinants of a mobilizable pool of blood-forming stem cells. We found that a subset of HSCs displays macrophage-associated

Pure metal nanowires (NWs) are one-dimensional nanomaterials with distinctive properties for various applications. Nevertheless, mass-growth forests have not been developed because of vapor pressure limitations, chemical reduction problems, or both. We succeeded in the mass growth of aluminum (Al) NW forests at desired locations by controlling atomic diffusion within the solid film. Whereas prior attention

Ketamine has been found to have rapid and potent antidepressant activity. However, despite the ubiquitous brain expression of its molecular target, the N -methyl- d -aspartate receptor (NMDAR), it was not clear whether there is a selective, primary site for ketamine’s antidepressant action. We found that ketamine injection in depressive-like mice specifically blocks NMDARs in lateral habenular (LHb)

Bacterial small molecule metabolites such as adenosine-diphosphate- d - glycero -β- d - manno -heptose (ADP-heptose) and their derivatives act as effective innate immune agonists in mammals. We show that functional nucleotide-diphosphate-heptose biosynthetic enzymes (HBEs) are distributed widely in bacteria, archaea, eukaryotes, and viruses. We identified a conserved STT R5 motif as a hallmark of heptose

The chemical composition of the interstellar medium and planetary atmospheres is constantly in flux as atoms and molecules collide and interact with high-energy particles such as electrons, protons, and photons. These transformative processes ultimately lead to the coalescence of molecules and eventually the birth of stars. Our understanding of these chemical ecosystems relies on models that synthesize

Incorporation of polymer chain entanglements within a single network can synergistically improve stiffness and toughness, yet attaining such dense entanglements through vat photopolymerization additive manufacturing [e.g., digital light processing (DLP)] remains elusive. We report a facile strategy that combines light and dark polymerization to allow constituent polymer chains to densely entangle as

The human nucleosome acetyltransferase of histone H4 (NuA4)/Tat-interactive protein, 60 kilodalton (TIP60) coactivator complex, a fusion of the yeast switch/sucrose nonfermentable related 1 (SWR1) and NuA4 complexes, both incorporates the histone variant H2A.Z into nucleosomes and acetylates histones H4, H2A, and H2A.Z to regulate gene expression and maintain genome stability. Our cryo–electron microscopy

Earlier this year, an international group of scientists published a paper in Science Advances on the draft genome of the little bush moa ( Anomalopteryx didiformis ), one of about nine species of extinct flightless birds endemic to Aotearoa (New Zealand). The genome was sequenced from the ancient DNA of a “ poorly provenanced ” fossil bone acquired by the Royal Ontario Museum. It held important clues

The proliferating cell nuclear antigen (PCNA) clamp encircles DNA to hold DNA polymerases (Pols) to DNA for processivity. The Ctf18-RFC PCNA loader, a replication factor C (RFC) variant, is specific to the leading-strand Pol (Polε). We reveal here the underlying mechanism of Ctf18-RFC specificity to Polε using cryo–electron microscopy and biochemical studies. We found that both Ctf18-RFC and Polε contain

X-ray crystallography provides a distinctive view on the three-dimensional structure of crystals. To reconstruct the electron density map, the complex structure factors F = F exp i ϕ of a sufficiently large number of diffracted reflections must be known. In a conventional experiment, only the amplitudes F are obtained, and the phases ϕ are lost. This is the crystallographic phase problem. In this work

Mollusks encompass enormous disparity, including familiar clams and snails alongside less familiar aculiferans (chitons and vermiform aplacophorans) with complex multicomponent skeletons. Paleozoic fossils trace crown mollusks to forms exhibiting a combination of biomineralized shells and sclerites (e.g., scales, spines, and spicules). We describe a shell-less, Cambrian stem mollusk, Shishania aculeata

Despite extensive investigation, the nature and causes of the Mid-Pleistocene Transition remain enigmatic. In this work, we assess its linkage to asynchronous development of bipolar ice sheets by synthesizing Pleistocene mid- to high-latitude proxy records linked to hemispheric ice sheet evolution. Our results indicate substantial growth of the Antarctic Ice Sheets (AISs) at 2.0 to 1.25 million years

Understanding molecular state evolution is central to many disciplines, including molecular dynamics, precision measurement, and molecule-based quantum technology. Details of this evolution are obscured when observing a statistical ensemble of molecules. Here, we report real-time observations of thermal radiation–driven transitions between individual states (“jumps”) of a single molecule. We reversed

Patients with devastating illnesses demonstrate incredible courage in battling their disease. Innovative cell and gene therapies (CGTs), built on decades of research, are changing the lives of those who suffer from conditions ranging from cancer to sickle cell disease to neurologic diseases. Although hailed for their promise and recognized for benefits that will exceed the costs, the high prices of

An ever-present limitation of transmission electron microscopy is the damage caused by high-energy electrons interacting with any sample. By reconsidering the fundamentals of imaging, we demonstrate an event-responsive approach to electron microscopy that delivers more information about the sample for a given beam current. Measuring the time to achieve an electron count threshold rather than waiting

Late-onset Alzheimer’s disease (LOAD) is the most common form of Alzheimer’s disease (AD). However, modeling sporadic LOAD that endogenously captures hallmark neuronal pathologies such as amyloid-β (Aβ) deposition, tau tangles, and neuronal loss remains an unmet need. We demonstrate that neurons generated by microRNA (miRNA)–based direct reprogramming of fibroblasts from individuals affected by autosomal