Proceedings of the National Academy of Sciences, Volume 122, Issue 16, April 2025.

Regional high-resolution climate projections are crucial for many applications, such as agriculture, hydrology, and natural hazard risk assessment. Dynamical downscaling, the state-of-the-art method to produce localized future climate information, involves running a regional climate model (RCM) driven by an Earth System Model (ESM), but it is too computationally expensive to apply to large climate

Natural faults are typically nonplanar and exhibit multiple bends, which deviate from the general fault orientation at different angles. However, while such deviations are considered a key factor controlling earthquake propagation and, hence, its intensity and magnitude, direct experimental evidence of how bends affect earthquake ruptures is nearly nonexistent. Here, we present direct experimental

The distribution of sugars is crucial for plant energy, signaling, and defense mechanisms. Sugar Transport Proteins (STPs) are Sugar Porters (SPs) that mediate proton-driven cellular uptake of glucose. Some STPs also transport fructose, while others remain highly selective for only glucose. What determines this selectivity, allowing STPs to distinguish between compounds with highly similar chemical

This work treats resonant collisions between five identical ultracold bosons in the framework of the adiabatic hyperspherical representation. The five-body recombination rate coefficient is quantified using a semiclassical description in conjunction with an analysis of the lowest five-body hyperspherical adiabatic potential curves in a scattering length regime with no universal weakly bound tetramers

Clownfishes (Amphiprioninae) are a fascinating example of a marine radiation. From a central Pacific ancestor, they quickly colonized the coral reefs of the Indo-Pacific and diversified independently on each side of the Indo-Australian Archipelago. Their association with sea anemones has been proposed to be a key innovation that enabled the clownfish radiation. However, this intuition has little empirical

Plasmid conjugation is a contact-dependent horizontal gene transfer mechanism that significantly contributes to the dissemination of antibiotic resistance among bacteria. While the molecular mechanisms of conjugation have been extensively studied, our understanding of plasmid transfer dynamics within spatially structured bacterial communities and the influence of community architecture on plasmid dissemination

Neural collapse (NC) reveals that the last layer of the network can capture data representations, leading to similar outputs for examples within the same class, while outputs for examples from different classes form a simplex equiangular tight frame (ETF) structure. This phenomenon has garnered significant attention due to its implications on the intrinsic properties of neural networks. Interestingly

Biogeographic regions arise due to constraints on species ranges, fostering lineage divergence as a result. Yet, convergent evolution means that evolutionary distinct lineages can share similar characteristics when subjected to similar environmental conditions. The ecological convergence of distinct regions has been demonstrated in terrestrial communities, but it remains uncertain if marine systems

Hedgehog (Hh) signaling plays fundamental roles in embryonic development while its abnormal activation in adults is associated with cancer. Hh targeting drugs have gained FDA approval but resistance emerged quickly, underlining the need for novel types of Hh inhibitors. Hh signaling is initiated by the Hh ligand, generated from the autoprocessing of Hh precursor. However, the catalytic role of a highly

DNA topoisomerase 1 (TOP1) is essential for transcription, replication, and repair. Its function relies on two catalytic steps, DNA breakage and rejoining. Inhibitors of the second step prevent DNA rejoining and lead to persistent DNA breaks, acting as topoisomerase poisons, used as anticancer drugs. However, reliable inhibitors of the first step are not available. Here, we provide genetic and molecular

Understanding the effects of solid boundaries on turbulent fluctuations remains a long-standing challenge. Available data on mean-square fluctuations in these flows show apparent contradiction with classical scaling. We had earlier proposed an alternative model based on the principle of bounded dissipation. Despite its putative success, a conclusive outcome requires much higher Reynolds numbers than

Transport of electrons and ions at carbon surfaces immersed in electrolytes is instrumental for a wide variety of membrane processes as well as energy storage in batteries and supercapacitors. Ion transport in a nanoporous electrode strongly depends on its electronic conductance and on the interfacial capacitance with the electrolyte. In this study, we use in-plane impedance spectroscopy to disentangle

Bacterial RNA polymerase (RNAP) is a multisubunit enzyme that copies DNA into RNA in a process known as transcription. Bacteria use σ factors to recruit RNAP to promoter regions of genes that need to be transcribed, with 60% bacteria containing at least one specialized σ factor, σ 54 . σ 54 recruits RNAP to promoters of genes associated with stress responses and forms a stable closed complex that does

Evolutionary feedbacks occur when evolution in one generation alters the environment experienced by subsequent generations and are an expected result of indirect genetic effects (IGEs). Hypotheses abound for the role of evolutionary feedbacks in climate change, agriculture, community dynamics, population persistence, social interactions, the genetic basis of evolution, and more, but evolutionary feedbacks

Although cochlear implants (CI) are the standard of care for profound sensorineural hearing loss they are technically constrained by the tendency of electrical current to spread within the fluid-filled chambers of the cochlea. This limits the resolution of individual electrodes and patients’ perceptions of complex sounds. Infrared irradiation has been proposed as an alternative to electrical stimulation

Synapses have undergone significant diversification and adaptation, contributing to the complexity of the central nervous system. Understanding their molecular architecture is essential for deciphering the brain’s functional evolution. While nicotinic acetylcholine receptors (nAchRs) are widely distributed across metazoan brains, their associated protein networks remain poorly characterized. Using

Pattern formation in spin systems with continuous-rotational symmetry (CRS) provides a powerful platform to study emergent complex magnetic phases and topological defects in condensed-matter physics. However, its understanding and correlation with unconventional magnetic order along with high-resolution nanoscale imaging are challenging. Here, we employ scanning nitrogen vacancy (NV) magnetometry to

Nonsense mutations are associated with numerous and diverse pathologies, yet effective treatment strategies remain elusive. A promising approach to combat these conditions involves the use of aminoglycosides, particularly in combination with stop-codon read-through enhancers, for developing drugs that can rescue the production of full-length proteins. Using X-ray crystallography and single-particle

Disease and behavior subtype identification is of significant interest in biomedical research. However, in many settings, subtype discovery is limited by a lack of robust statistical clustering methods appropriate for binary data. Here, we introduce LACE-UP [latent class analysis ensembled with UMAP (uniform manifold approximation and projection) and PCA (principal components analysis)], an ensemble

UDP-glucuronic acid (UDP-GlcUA) is a nucleotide sugar essential for various biological processes in many organisms, and its excess within the cell can disrupt cellular functions. In Cryptococcus , mutations in the UXS1 gene which encodes an enzyme responsible for converting UDP-GlcUA into UDP-xylose, result in excessive accumulation of UDP-GlcUA and confer resistance to the antifungal drug 5-fluorocytosine

Chronic inflammatory skin disorders are characterized by keratinocyte hyperproliferation and hyperactivation as well as immune cell infiltration. We investigated whether immune cell–derived acetylcholine (ACh) is a modulator of skin inflammation in mice. Here, we identify skin epithelial B cells as a key source of ACh that damps down inflammation. We used imiquimod (IMQ) to induce inflammatory skin

Protein domains of low sequence complexity are unable to fold into stable, three-dimensional structures. In test tube studies, these unusual polypeptide regions can self-associate in a manner causing phase separation from aqueous solution. This form of protein:protein interaction has been implicated in numerous examples of dynamic morphological organization within eukaryotic cells. In several cases

Glutamate-mediated neuronal hyperexcitation plays a causative role in eliciting seizures and promoting epileptogenesis. Recent data suggest that altered autophagy can contribute to the occurrence of epilepsy. We examined the role of autophagy in neuronal physiology by generating knockout mice conditionally lacking the essential autophagy protein ATG5 in glutamatergic neurons. We demonstrate that conditional

Meiotic drivers are selfish genetic elements that bias their own transmission during meiosis or gamete formation. Due to the fundamental differences between male and female meiosis in animals and plants, meiotic drivers operate through distinct mechanisms in the two sexes: In females, they exploit the asymmetry of meiosis to ensure their inclusion in the egg, whereas in males, they eliminate competing

Argonaute (AGO) proteins bind to small RNAs to induce RNA interference (RNAi), a conserved gene regulatory mechanism in animal, plant, and fungal kingdoms. Small RNAs of the fungal plant pathogen Botrytis cinerea were previously shown to translocate into plant cells and to bind to the host AGO, which induced cross-kingdom RNAi to promote infection. However, the role of pathogen AGOs during host infection

The occurrence of coinfections, where hosts are simultaneously infected by multiple pathogens, is widespread in nature and has significant negative impacts on global health. In humans, over one-sixth of the world’s population is affected by coinfections, contributing to several diseases. However, despite the broad ecological relevance and impact on global health, most biomedical research has focused

The tilt illusion—a bias in the perceived orientation of a center stimulus induced by an oriented surround—illustrates how context shapes visual perception. Although extensively studied for decades, we still lack a comprehensive account of the illusion that connects its behavioral and neural characteristics. Here, we demonstrate that the tilt illusion originates from dynamic changes in neural coding

Spontaneous rescue behavior enhances the well-being and survival of social animals, yet the neural mechanisms underlying the recognition and response to conspecifics in need remain unclear. Here, we report that observer mice experience distress when encountering anesthetized conspecifics, prompting spontaneous rescue-like behavior toward the unconscious mice. This behavior facilitates the earlier awakening

Predicting human displacements is crucial for addressing various societal challenges, including urban design, traffic congestion, epidemic management, and migration dynamics. While predictive models like deep learning and Markov models offer insights into individual mobility, they often struggle with out-of-routine behaviors. Our study introduces an approach that dynamically integrates individual and

Helicobacter pylori has evolved distinct flagellar motility to colonize the human stomach. Rotation of the H. pylori flagella is driven by one of the largest known bacterial flagellar motors. In addition to the core motor components found in Escherichia coli and Salmonella enterica , the flagellar motor in H. pylori possesses many accessories that enable the bacteria to penetrate the gastric mucus

Many GPCRs initiate a second phase of G protein-mediated signaling from endosomes. This inherently requires the GPCR to increase cognate G protein activity on the endosome surface. G s -coupled GPCRs are thought to achieve this by internalizing and mediating a second round of allosteric coupling to G proteins on the endosome membrane. Here, we provide evidence that the μ-opioid receptor (MOR), a G

Horizontal transfer of nuclear DNA between cells of host and cancer is a potential source of adaptive variation in cancer cells. An understanding of the frequency and significance of this process in naturally occurring tumors is, however, lacking. We screened for this phenomenon in the transmissible cancers of dogs and Tasmanian devils and found an instance in the canine transmissible venereal tumor

Generic equilibria are derived for turbulent relaxing plasmas via an entropy-maximization procedure that accounts for the short-time conservation of certain collisionless invariants. The conservation of these collisionless invariants endows the system with a partial “memory” of its prior conditions but is imperfect on long time scales due to the development of a turbulent cascade to small scales, which

Observations of the hot rocky exoplanet 55 Cancri e report significant but unexplained variability in brightness across visible and infrared bands, e.g., on subweekly timescales, its mid-infrared brightness temperature fluctuates by approximately 1,400 K (with hundreds of Kelvin uncertainty). We propose a magma temperature–cloud feedback as a potential explanation that relies on the planet’s atmosphere

RNAs are critical regulators of gene expression, and their functions are often mediated by complex secondary and tertiary structures. Structured regions in RNA can selectively interact with small molecules—via well-defined ligand-binding pockets—to modulate the regulatory repertoire of an RNA. The broad potential to modulate biological function intentionally via RNA–ligand interactions remains unrealized

Cystic fibrosis (CF) is a lethal genetic disorder caused by variants in CF transmembrane conductance regulator (CFTR). Many variants are treatable with correctors, which enhance the folding and trafficking of CFTR. However, approximately 3% of persons with CF harbor poorly responsive variants. Here, we used affinity purification mass spectrometry proteomics to profile the protein homeostasis (proteostasis)

A combination of ultrafast, long-range, and low-loss excitation energy transfer from the photoreceptor location to a functionally active site is essential for cost-effective polymeric semiconductors. Delocalized electronic wavefunctions along π-conjugated polymer (CP) backbone can enable efficient intrachain transport, while interchain transport is generally thought slow and lossy due to weak chain–chain

Local wounding in plants triggers signals that travel locally within the wounded leaf or systemically through the vasculature to distant leaves. Our understanding of the mechanisms of initiation and propagation of this ubiquitous class of signals remains incomplete. Here, we develop a unifying framework based on poroelastic dynamics to study two coupled biophysical processes—propagation of pressure

Inflammation plays an essential role in eliminating microbial pathogens and repairing tissues, while sustained inflammation accelerates kidney damage and disease progression. Therefore, understanding the mechanisms of the inflammatory response is vital for developing therapies for inflammatory kidney diseases like acute kidney injury (AKI), which currently lacks effective treatment. Here, we identified

The physical limit in determining the atomic structure of biological molecules is radiation damage. In electron cryomicroscopy, there have been numerous attempts to reduce the effects of radiation damage by cooling the specimen beyond liquid-nitrogen temperatures, yet all failed to realize the potential improvement for single-particle structure determination. We have identified the physical causes

Uterine adaptations driven by the steroid hormones estrogen and progesterone are pivotal for embryo implantation and, ultimately, for a successful pregnancy. Here, we show in mice that genetic ablation of the membrane lipid flippase Atp11a causes severe deficits in this hormonal response and profound defects in the morphological organization and transcriptional profile of the uterine epithelial compartment

40 Hz sensory stimulation (“flicker”) has emerged as a new technique to potentially mitigate pathology and improve cognition in mouse models of Alzheimer’s disease (AD) pathology. However, it remains unknown how 40 Hz flicker affects neural codes essential for memory. Accordingly, we investigate the effects of 40 Hz flicker on neural representations of experience in the hippocampus of the 5XFAD mouse

We developed a two-tiered strategy aiming to identify gut bacteria functionally linked to the development of multiple sclerosis (MS). First, we compared gut microbial profiles in a cohort of 81 monozygotic twins discordant for MS. This approach allowed to minimize confounding effects by genetic and early environmental factors and identified over 50 differently abundant taxa with the majority of increased

The resilience of an ecological community informs us how it will respond to future environmental disturbances. However, the concept is rarely tested in the context of predicting biodiversity change, particularly at broad spatial and taxonomic scales. Here, we show that measures of instability derived from the resilience of the current state of community compositions greatly improve the predictability

Mitigating climate change and social injustice are critical, interwoven challenges. Climate change is driven by grossly unequal contributions to elevated greenhouse gas emissions among individuals, socioeconomic groups, and nations. Yet, its deleterious impacts disproportionately affect poor and less powerful nations, and the poor and the less powerful within each nation. This climate injustice prompts

Twice during the Neoproterozoic Era, Earth experienced runaway ice-albedo catastrophes that resulted in multimillion year, low-latitude glaciations: the Sturtian and Marinoan snowball Earths. In the snowball climate state, CO 2 consumption through silicate weathering collapses, and atmospheric CO 2 accumulates via volcanic outgassing until a sufficiently strong greenhouse causes deglaciation. The duration

Prosody, the musical facet of speech, is pivotal in human communication, and its structure and meaning remain subjects of ongoing research. In this study, we introduce a data-driven model for English prosody, based on large-scale analysis of spontaneous conversations. As a first step, we identify approximately 200 discernible prosodic patterns—which we view as building blocks of the prosodic vocabulary—and

The molecular framework for protometabolism—chemical reactions in a prebiotic environment preceding modern metabolism—has remained unknown in evolutionary biology. Mono-, di-, and tricarboxylic acids that comprise contemporary metabolism, such as the Krebs cycle, are of particular prebiotic relevance and are theorized to predate life on Earth. Researchers have struggled to unravel the molecular origins

Air quality is associated with adverse health outcomes and mortality risk. While most research has focused on the association between air quality estimates and these outcomes, little is known about the presence of air quality monitoring sites across the United States or the place-level characteristics associated with such placements. We classify counties without a monitoring station as air quality

Rapid social–ecological intensification is a recurrent feature of human history. It occurred in different forms and contexts; its outcomes may have been sustainable or transient. Until recently, such intensifications usually accompanied state formation: Consolidation of political power was often coupled with exponential increase in human exploitation of the environment of a given area. Here, we study

United States (US) croplands are ideal recipient environments for solar photovoltaic (PV) energy because they are flat and have a high solar resource. Perceived threats of solar to agriculture have led some stakeholders to suggest that croplands be exclusively used to produce food. However, 12 million hectares of US croplands, an area about the size of New York State, are already dedicated to corn

Biological invasions are profoundly altering Earth’s ecosystems, but generalities about the effects of nonnative species on the diversity and productivity of native communities have been elusive. This lack of generality may reflect the limited spatial and temporal extents of most previous studies. Using >5 million tree measurements across eastern US forests from 1995 to 2023, we quantified temporal

The nature of solid phases and cross-over of order–disorder phase transitions from two-dimensional (2D) layers to three-dimensional (3D) bulk in confined atomic systems remain largely unexplained. To this end, we consider noble gases and aluminum confined between graphene sheets at different pressures and temperatures. Using crystal structure search methods and molecular dynamics based on machine-learned

Rab32 is a small GTPase and molecular switch implicated in vesicular trafficking. Rab32 is also an A-Kinase Anchoring Protein (AKAP), which anchors cAMP-dependent Protein Kinase (PKA) to specific subcellular locations and specifies PKA phosphorylation of nearby substrates. Surprisingly, we found that a form of Rab32 deficient in PKA binding (Rab32 L188P) relocalized away from the Golgi apparatus and