Browse Articles

Select earthquake forecasting models demonstrate consistency with prospective decadal observations in California

Abstract Earthquake forecasting systems are now operationalized by agencies in several countries, providing situational awareness to at-risk communities. To ensure that forecasts follow the best science available, the underlying models require rigorous testing against prospective data and benchmarking. Between August 2007 and August 2018, 27 forecasting models, including the types used for operational earthquake forecasting, were prospectively operated as part of a multi-institutional project by the Collaboratory for the Study of Earthquake Predictability, generating 51,625 next-day M w  ≥ 3.95 seismicity forecasts for California. Here, we comprehensively evaluate their predictive skills against 597 M w  ≥ 3.95 earthquakes using community-vetted statistical methods. We show that approximately 95%, two-thirds, and 95% of the models produced forecasts consistent with the number, locations, and magnitudes of observed earthquakes, respectively. Individually, select versions of well-established, operational-type models demonstrated sustained consistency with prospective observations. We provide detailed recommendations, software tools, and benchmarking data to support the development of operational earthquake forecasting systems worldwide.

Nuclear exosome targeting complexes modulate cohesin binding and enhancer-promoter interactions in 3D

Abstract Three-dimensional long-range contacts between enhancers and promoters are thought to be largely determined by loop extrusion driven by the cohesin complex and insulator factors. However, recent evidence also suggests a role for noncoding RNAs, such as enhancer-associated RNAs and promoter upstream transcripts, in shaping enhancer-promoter connectivity. While the nuclear RNA exosome, together with targeting complexes, poly(A) tail exosome targeting connection and nuclear exosome targeting complex, controls the decay of noncoding RNAs, it remains unclear whether these complexes regulate three-dimensional chromatin contacts. Chromatin recruitment maps of the nuclear exosome targeting complex subunit ZCCHC8, the poly(A) tail exosome targeting connection subunit ZFC3H1, and the RNA helicase MTR4 in human cells reveal that these factors associate with sites of enhancer–promoter interactions. Depletion of these factors leads to the accumulation of ncRNAs, notably enhancer-associated RNAs and promoter upstream transcripts, and increases cohesin occupancy at these sites. Chromatin conformation capture analysis reveals that MTR4 modulates long-range enhancer-promoter contacts. Upon loss of MTR4, enhancer-promoter contacts increase while intraloop contacts decrease, suggesting that MTR4 facilitates loop extrusion. These data highlight a key interplay between cohesin-mediated enhancer-promoter interactions and the regulation of noncoding RNAs by nuclear RNA exosome targeting complexes that is consistent with a role for RNA in genome folding.

Explainable AI: learning from the learners

Surviving Pediatric Cardiogenic Shock: Clinical Approach, Improving Outcomes, and Future Directions: A Scientific Statement From the American Heart Association

Pediatric heart failure–related cardiogenic shock carries high morbidity and mortality but is understudied. Improving outcomes in pediatric cardiogenic shock hinges on timely diagnosis and appropriate triage, medical management tailored to the cause and phenotype of cardiogenic shock, and optimal timing of escalation to appropriate mechanical circulatory support. This scientific statement provides a diagnostic framework for the bedside clinician, in addition to proposing a pediatric cardiogenic shock definition and severity staging aligned with systems previously validated in other studies. It outlines the initial approach to diagnosis and stabilization of a child with suspected cardiogenic shock and offers guidance on optimal noninvasive and invasive monitoring strategies to determine clinical trajectory because a significant proportion of children with cardiogenic shock will continue to deteriorate in the first 24 hours. Last, it identifies future directions for the field, including educational interventions for the frontline clinicians seeing these patients, studying the role of a multidisciplinary shock team, evaluating the prognostic and clinical relevance of known and novel biomarkers, and leveraging all these to develop clinical decision tools or algorithms to guide nuanced management of these patients.

Decomposition and separation of vibration waves from blasting demolition of tall buildings and their component characteristics

Macroscopic assembly of supramolecular coacervates for underwater adhesion

Archaic ancestry inference in imputed ancient human genomes

Abstract When modern humans expanded from Africa into Eurasia, they interbred with archaic hominins such as Neanderthals and Denisovans. This introgression shaped human evolution, yet most insights have been gained from present-day genomes, leaving little known about how archaic variants evolved after interbreeding. Ancient genomes offer a direct view of this process, but low coverage and poor quality have limited their use. Recent advances in genotype imputation offer a way to overcome these challenges by reconstructing missing information from reference panels and recovering evolutionary signals from low-coverage data. Here, we show that imputation enables accurate detection and quantification of archaic introgression in ancient genomes, improves local archaic ancestry inference, and that regions of archaic ancestry are imputed with especially high accuracy. We further demonstrate that imputed genomes can reconstruct the trajectories of introgressed haplotypes, distinguish populations across time and geography, and identify both known and additional candidates for adaptive introgression.

A chromatin-informed transcriptional regulatory framework to stratify patients and guide therapy selection in triple-negative breast cancer

Surfaceome CRISPR activation screening uncovers ligands regulating tumor sensitivity to NK cell killing

Leaf development regulates state transition capacity in trees

Abstract State transitions (ST) balance excitation energy between photosystem I and II. This process has been extensively studied in Arabidopsis but the regulation and physiological significance of ST in other angiosperms remain largely unknown. Here, we investigate ST in hybrid aspen and other tree species using physiological, biochemical, ultrastructural, and genetic approaches. We discover a pronounced canopy gradient in greenhouse-grown aspens, with young, upper leaves exhibiting substantially higher fluorescence-derived state-transition capacity (qT) than lower, older leaves. Seasonal monitoring of field-grown trees reveals a conserved developmental decline in qT across species. Reduced qT correlates with increased grana stacking and lower LHCII/PSII ratios, but not with LHCII phosphorylation, suggesting developmental remodeling of thylakoid architecture may influence the functional reorganization of PSII antenna connectivity during state transitions. Using the serine/threonine protein kinase (STN7) knockout mutant characterized outside Arabidopsis , we show that aspens lacking ST exhibit altered PSI/PSII ratios, reduced PSII operating efficiency in young leaves, and slower growth under greenhouse conditions with naturally variable light conditions but not under constant-light climate room condition. These findings indicate that ST is important for performance under dynamic light conditions, particularly in young leaves, and reveal a previously unrecognized developmental control of photosynthetic regulation.

MBNL depletion drives stem cell fusion and immature myonuclear states in myotonic dystrophy type 1

Abstract Myotonic dystrophy type 1 is caused by the expression of expanded CTG repeats in the DMPK gene and the resulting loss of function of MBNL protein. Affected skeletal muscle displays abundant centrally located nuclei despite limited immune-cell–associated fibre necrosis, complicating interpretation of muscle damage and remodelling mechanisms. Here we show that muscle stem cells are activated and fuse with existing muscle fibres in myotonic dystrophy type 1. Single-nucleus transcriptomics in patient’s muscle identifies increased activated muscle stem cells and distinct myonuclear populations exhibiting transitional transcriptional states, including muscle stem cell associated markers and elevated DMPK expression. Myofibre-specific MBNL knockdown mouse models demonstrate that muscle stem cell fusion contributes to central nucleation, whereas their deletion does not improve myotonia or muscle strength. Together, these findings indicate that loss of MBNL function in muscle drives myonuclear accretion through stem cell-mediated fusion, giving rise to myonuclei with immature states in myotonic dystrophy type 1.

Longer-lived mammals exhibit greater evolutionary conservatism and epigenetic modification at cancer-associated loci

Regional diversity of cranial skeletal stem cells governs bone morphogenetic protein-2 mediated bone regeneration

Abstract Skeletal stem cells (SSCs), originally identified in 2015, are increasingly understood to exhibit significant heterogeneity throughout the body. Cranial SSCs provide a unique model to investigate this diversity because cranial bones arise from both neural crest and mesoderm, unlike mesoderm-derived long bones. Here, we show that cranial SSCs possess anatomically defined transcriptomic and functional heterogeneity. Through comprehensive in vitro and in vivo functional assays combined with targeted gene expression analyses by qPCR, we demonstrate that cranial SSCs exhibit region-specific transcriptional signatures and lineage biases that influence their osteogenic and chondrogenic capacities. Temporal analysis further reveals that SSCs progressively outnumber progenitor cells with age, suggesting that the SSC-to-progenitor ratio may serve as an indicator of skeletal developmental and regenerative potential. Finally, we demonstrate that SSC heterogeneity critically influences bone regeneration in response to Bone Morphogenetic Protein-2 in vitro and in vivo, supporting the need for region-specific optimization of BMP-2-based regenerative therapies.

Room-temperature ferroelectrically switchable quantum geometry in few-layer WTe2 for complementary in-memory computing

Population-scale disease-associated tandem repeat analysis reveals locus and ancestry-specific insights

Glycoprotein-induced phase separation drives unconventional secretion of galectin-3

Abstract The mechanism of unconventional protein secretion remains an unresolved issue. Here, we describe an unconventional protein secretion pathway for galectin-3 that is mediated by phase separation and condensation. Using four lysosomal damage models, we observed a rapid, pronounced release of galectin-3 in large, non-exosomal particles. This secretion is driven by glycoprotein-induced galectin-3 phase separation and is independent of pyroptosis and secretory autophagy. During phase separation, the S-face of galectin-3 carbohydrate recognition domain binds glycoproteins that triggers galectin-3 N-terminal tail release and condensation. These condensates then recruit ALG-2 via the exposed N-terminal tail. ALG-2 directs the condensates to the endoplasmic reticulum–late endosome interface. After translocation into late endosomes, galectin-3 condensates are secreted into the extracellular milieu by SNARE-dependent vesicular transport. This mechanism of exporting phase-separated protein condensates may serve as a clean-up response to membrane damage.

Retraction Note: Proteogenomics of diffuse gliomas reveal molecular subtypes associated with specific therapeutic targets and immune-evasion mechanisms

Strategic timing for the decarbonization contributions by China’s photovoltaic manufacturers in global energy transition

Abstract Photovoltaic (PV) technology is central to clean electricity and the Sustainable Development Goals. However, China’s PV manufacturing industry, which accounts for nearly two-thirds of global capacity, is often criticized for its high carbon emissions. Existing studies typically assign emission responsibility to manufacturers while attributing decarbonization benefits to power generation, overlooking upstream producers’ contributions. Here we propose a Producer Decarbonization Contribution framework to quantify these long-overlooked contributions at national and global scales. We show that China’s PV manufacturers contribute 31.4%-73.8% of total PV decarbonization in China and 27.9%-45.4% globally. We further identify a strategic timing, defined as the point at which the PV’s decarbonization contributions reach their maximum, occurring around 2035 in China under the Announced Pledges Scenario and 2030 globally under the Net Zero Emissions Scenario proposed by the International Energy Agency. These findings suggest maintaining supportive policies for China before 2035, while adopting more stringent measures globally after 2030 to avoid overproduction. The proposed framework that enables adaptive industrial policy design can be extended to other renewable energy technologies.

Dilute electrolytes for suppressing metal anode corrosion during calendar aging and cycling in aqueous zinc batteries

Abstract While numerous improvements in cycling stability have been demonstrated for next-generation battery chemistries with metallic anodes, their calendar aging (e.g., capacity loss during idle periods of rest) performance painfully lags behind and remains a critical bottleneck hindering their practical deployment. In contrast to their commercial counterparts, metallic anodes exhibit substantial capacity loss during calendar aging. Despite several recent studies exploring the underlying reasons for calendar aging, few solutions have been proposed to mitigate this key issue. Here, we design a low concentration electrolyte (0.1 M ZnSO 4 ) that can reduce calendar aging losses in Zn metal chemistries by more than an order of magnitude (<1.5% capacity fade after 24 hours of aging) while still maintaining improved cycling stability (>3300 cycles at 4 C) with an average Coulombic efficiency of 99.8%. We find that solvated water molecules (rather than unsolvated water molecules) drive Zn corrosion, motivating our effort to minimize these reactive solvated water molecules through a holistic approach centered around concentration reduction, aided by isotopic solvent substitution and targeted additives. This strategy could be applicable to other battery chemistries and provides an approach that can address both calendar aging and cycling stability, both of which are necessary for practical applications.

Enhanced spin-to-charge conversion in epitaxial La0.67Sr0.33MnO3/NdNiO3 bilayers at the nickelate metal-insulator phase transition

Abstract Phase transition materials such as NdNiO 3 (NNO) when coupled with low damping ferromagnets such as La 0.67 Sr 0.33 MnO 3 (LSMO) hold the promise for developing new multi-functional material systems harnessing the interplay of charge, spin, and orbital degrees of freedom. In this study, we probe the evolution of spin-to-charge conversion in epitaxial all-oxide LSMO (12 nm)/NNO (4, 8, and 16 nm) bilayers. Using spin pumping ferromagnetic resonance, we track the spin-to-charge conversion within the NNO layer through the paramagnetic metal to antiferromagnetic insulator transition and observe a pronounced enhancement of the inverse spin Hall effect signal at the onset of this phase transition. We attribute this enhancement to the electronic and magnetic disorder in NNO at the first-order phase transition, thereby providing insights into the mechanism of spin transport through the phase transition. The tunability of spin-to-charge conversion in this low damping bilayer system offers a pathway for developing reconfigurable, energy-efficient spintronic devices.