Proceedings of the National Academy of Sciences, Volume 122, Issue 22, June 2025. SignificanceHow membraneless organelles like nucleolus assemble within cells is not well understood. Recent experiments suggest that transcription of ribosomal RNA actively drives nucleolar assembly. Our proposed model of active transcription-templated ...

Proceedings of the National Academy of Sciences, Volume 122, Issue 22, June 2025. SignificanceTogether with tunneling and entanglement, coherence belongs among the hallmarks of quantum mechanics and among the prerequisites for building quantum devices. In attochemistry, the loss of electronic coherence induced by nuclear motion ...

Proceedings of the National Academy of Sciences, Volume 122, Issue 22, June 2025. SignificanceBispecific T cell engagers (TcEs) are immunotherapeutic drugs that trigger the destruction of cancer cells by linking T cells to cancer cells through specific surface molecules (antigens). We designed a series of TcEs with varying distances ...

Proceedings of the National Academy of Sciences, Volume 122, Issue 22, June 2025. SignificanceUnderstanding differences in outcomes between social groups—such as wage gaps between men and women—remains a central challenge in social science. While researchers have long studied how observable factors contribute to these differences, ...

Proceedings of the National Academy of Sciences, Volume 122, Issue 22, June 2025. SignificanceThe tessellated material is poised to become a fascinating subject in materials science, following the initial exploration of quasicrystals. Specifically, supramolecular tessellation at the molecular level has primarily been observed in ...

Proceedings of the National Academy of Sciences, Volume 122, Issue 22, June 2025. SignificanceThe human pathogen and marine microbeVibrio choleraehas been shown to activate extracellular DNA uptake and transformation when in contact with chitin, the most abundant structural biomaterial in the oceans and a primary source of nutrition ...

Proceedings of the National Academy of Sciences, Volume 122, Issue 22, June 2025. SignificanceGastric cancer is the fifth most common cause of human cancer deaths, but the genetic underpinnings are poorly understood. Harnessing the genetic homogeneity of purebred dogs, we identify 18 loci governing gastric cancer susceptibility in a ...

Proceedings of the National Academy of Sciences, Volume 122, Issue 22, June 2025. SignificanceClassically, granites are separated into two broad categories—“I-type” vs. “S-type”—representing different igneous vs. (meta)sedimentary rock sources for melting. Their geochemistry differs for diverse geochemical systems. Himalayan granites ...

Proceedings of the National Academy of Sciences, Volume 122, Issue 22, June 2025. SignificanceTo fight infections and cancer, T cells must selectively recognize low levels of foreign peptides from pathogens or cancer cells, but the mechanisms that enable these properties remain unclear. Using computational modeling and experiments, we ...

Proceedings of the National Academy of Sciences, Volume 122, Issue 22, June 2025. SignificanceThe protection of key developmental processes from the immune system, while allowing the immune system to defend against pathogens, is central for the survival and reproduction of nearly all multicellular organisms. The rice immune receptor ...

Proceedings of the National Academy of Sciences, Volume 122, Issue 22, June 2025. SignificanceWe demonstrate that external (sensory and motor processing) and internal cognition (mind wandering) are dynamically interdependent. Easier external tasks require fewer executive resources, leaving more cognitive resources for internal mind ...

Proceedings of the National Academy of Sciences, Volume 122, Issue 22, June 2025. SignificanceHomeostatic plasticity maintains normal brain functions by constraining various network features of neural circuits, yet how this is realized on the cellular level remains unknown. Synaptic and intrinsic forms of homeostatic plasticity adjust ...

Proceedings of the National Academy of Sciences, Volume 122, Issue 22, June 2025. SignificanceFerroptosis is an iron-dependent cell death mechanism that results from increased oxidation of cell membrane lipids. We conducted a CRISPR-based positive selection screen in clear cell ovarian cancer cells treated with a nanoparticle drug to ...

Proceedings of the National Academy of Sciences, Volume 122, Issue 22, June 2025. SignificanceIn 2021, antimicrobial-resistant bacteria were responsible for 1.14 million deaths and associated with 4.71 million deaths globally. Patients who experience sepsis often face a higher risk of reinfections and hospital readmissions. To combat ...

Proceedings of the National Academy of Sciences, Volume 122, Issue 22, June 2025. SignificanceIn the secretory pathway, the pH within organelles is gradually acidified, starting at 7.1 to 7.2 in the endoplasmic reticulum, decreasing to 6.0 to 6.7 in the Golgi apparatus/trans-Golgi network (Golgi/TGN), and reaching 4.5 to 5.0 in ...

Proceedings of the National Academy of Sciences, Volume 122, Issue 22, June 2025. SignificanceSorting cells with target metabolic functions from a mutant pool exhibiting substantial genetic diversity is often the rate-limiting step in synthetic biology. Here, we developed a label-free, high-throughput Raman-activated cell sorting ...

Proceedings of the National Academy of Sciences, Volume 122, Issue 22, June 2025.

Many remarkable phenotypes have repeatedly occurred across vast evolutionary distances. When convergent traits emerge on the tree of life, they are sometimes driven by the same underlying gene families, while other times, many different gene families are involved. Conversely, a gene family may be repeatedly recruited for a single trait or many different traits. To understand the general rules governing

What is the neural substrate that enables the cerebral cortex to control a single mystacial vibrissa and orchestrate its movement? To answer this question, we injected rabies virus into the intrinsic muscle that protracts the rat C3 vibrissa and used retrograde transneuronal transport to identify the cortical neurons that influence the muscle. A surprisingly diverse set of cortical areas is the origin

Historically, endocrine cells were perceived to coordinate their output in a uniform manner. Recently however, single-cell technologies have uncovered heterogeneity within these populations, indicating that individual cells may operate as independently regulated units. Using high-resolution tools such as single-molecule fluorescent in situ hybridization (sm-FISH) and single-cell RNA sequencing (scRNA-seq)

Biomass burning can affect climate via the emission of aerosols and their subsequent impact on radiation, cloud microphysics, and surface and atmospheric albedo. Biomass burning emissions (BBEs) over the boreal region have strongly increased during the last decade and are expected to continue increasing as the climate warms. Climate models simulate aerosol processes, yet historical and future Coupled

Hundreds of human mutations are linked to autism and related disorders, yet the functions of many of these mutated genes during vertebrate neurodevelopment are unclear. We generated 27 zebrafish mutants with presumptive protein-truncating mutations or specific missense variants corresponding to autism-risk alleles in 17 human genes. We observed baseline and stimulus-driven behavioral changes at larval

The globus pallidus externa (GPe) is a heterogeneous nucleus of the basal ganglia, with intricate connections to other basal ganglia nuclei, as well as direct connections to the cortex. The anatomic, molecular, and electrophysiologic properties of cortex-projecting pallidocortical neurons are not well characterized. Here, we show that pallidocortical neurons project to diverse motor and nonmotor cortical

Recent approvals of polymeric adenosine diphosphate ribose (poly(ADP-ribose) polymerase inhibitors (PARPi) for BRCA-mutant metastatic castration resistant prostate cancer necessitate an understanding of the factors that shape sensitivity and resistance. Reversion mutations that restore homologous recombination (HR) repair are detected in ~50 to 80% of BRCA-mutant patients who respond but subsequently

Familial advanced sleep phase (FASP) is a heritable human sleep trait characterized by early sleep onset and offset times. We have identified five variants in five different families in the human voltage-gated calcium channel subunit alpha1 D ( CACNA1D ) that cosegregate with FASP. The variants in CACNA1D lead to altered channel dynamics in vitro. A mouse model of the E427K variant has a normal circadian

We employed cryogenic X-ray Raman spectroscopy to investigate the early-stage decomposition of the high explosive molecule hexanitrohexaazaisowurtzitane (CL-20). By systematically varying the radiation dose under cryogenic conditions, we induced the decomposition of the molecule using ionizing radiation and observed the evolution of spectral features at the carbon, nitrogen, and oxygen K edges. Through

Genomic diversity in pathogen populations is foundational for evolution and adaptation. Understanding population-level diversity is also essential for tracking sources and revealing detailed pathways of transmission and spread. For bacteria, culturing, isolating, and sequencing the large number of individual colonies required to adequately sample diversity can be prohibitively time-consuming and expensive

One key component of study design in population genetics is the “geographic breadth” of a sample (i.e., how broad a region across which individuals are sampled). How the geographic breadth of a sample impacts observations of rare, deleterious variants is unclear, even though such variants are of particular interest for biomedical and evolutionary applications. Here, in order to gain insight into the

Regnase-1 is a ribonuclease that regulates inflammation in immune cells by degrading cytokine mRNA. Regnase-1 was identified as one of the frequently mutated genes in the inflamed colorectal epithelium of patients with ulcerative colitis; however, its significance in intestinal epithelial cells during the tumorigenic process remains unknown. Therefore, we developed an Apc Min/+ mouse model lacking

Due to increasing anthropogenic impacts, many species survive only in small and isolated populations. Active conservation management to reduce extinction risk includes increasing habitat connectivity, translocations from captive populations, or intensive surveillance of highly protected closed populations. Advances in sequencing technology mean that it is now possible to consider the genomic impacts

The rapidly expanding lithium-ion battery (LIB) market has heightened the demand for efficient diagnostics for in-use cells and the reliable grading of used cells. Various purpose-built analysis tools and statistical algorithms have been developed, but often rely on redundant instrumentation and computationally intensive procedures. Here, we propose using the variance of the capacity difference between

This research paper investigates the prevalence of functional limitations among employed adults in the United States and the association between these limitations and medical conditions. The authors administered a survey adapted from the Dutch Functional Abilities List to a nationally representative sample of US adults ages 22 and older, finding that nearly three-quarters of working adults report at

The quantum acoustic framework has recently emerged as a nonperturbative, coherent approach to electron–lattice interactions, uncovering rich physics often obscured by perturbative methods with incoherent scattering events. Here, we model the strongly coupled dynamics of electrons and acoustic lattice vibrations within this framework, representing lattice vibrations as coherent states and electrons

Lineages that have invaded subterranean environments have repeatedly evolved remarkable adaptations to life in darkness. However, observational and experimental studies in additional natural systems are needed to further our understanding of repeated evolution and convergence. In Texas, a radiation of groundwater salamanders (genus Eurycea ), with independent invasions of subterranean karstic environments

The challenge of accurately predicting which genetic alternations lead to the desired phenotype necessitates high-throughput metabolic engineering approaches where numerous hypotheses can be tested simultaneously. We describe the CRISPR-Cas9-based method TUNE YALI that enables high-throughput tuning of gene expression in the common industrial yeast Yarrowia lipolytica . The method is based on replacing

Transcranial direct current stimulation (tDCS) is an easy to use, noninvasive brain stimulation technique that gained prominence for its potential in cognitive rehabilitation. Electroencephalography (EEG), which records electrical brain activity with a high temporal resolution, is well suited to quantify tDCS-induced neuromodulation in humans. However, most studies relying on scalp EEG recordings or

Multiple studies have recently proposed the summer solstice as a universal cue for major plant physiological processes. While this would have strong implications for fundamental plant biology and climate change forecasting, we currently have no clear mechanisms to explain the emergence and importance of solstice as a cue. Here, we analyze temperature accumulation patterns in relation to the summer

The Earth system model CLIMBER-2 has been used in past work to successfully reproduce the glacial/interglacial cycles of the Plio–Pleistocene and the Mid-Pleistocene Transition (MPT) from predominantly 40 to 100 ky timescale oscillatory behavior as a function of declining volcanic outgassing and regolith removal. In this study, we further examine the sensitivity of this previous work to varying prescribed

Industrial activities have increased the supply of iron to the ocean, but the magnitude of anthropogenic input and its ecological consequences are not well-constrained by observations. Across four expeditions to the North Pacific transition zone, we document a repeated supply of isotopically light iron from an atmospheric source in spring, reflecting an estimated 39 ± 9 % anthropogenic contribution

Using high-precision ice core measurements of CO 2 , δ 13 C–CO 2 , CH 4 , and N 2 O, this study provides carbon isotope constraints on a sizeable, centennial-scale CO 2 jump at the onset of Marine Isotope Stage 9 (MIS 9). The very end of the Heinrich stadial (HS) characterizing Termination IV (T-IV, ca. 343 to 333 ka ago) shows a 250-y-long jump in greenhouse gas concentrations, followed by a 1.3 ka

Observational and modeling results show that the frequency and amplitude of extreme climatic events have increased significantly in the context of global warming. However, whether abrupt climate changes intensified during past warm periods remains poorly constrained due to the lack of high-resolution geological records. Here, we report a 512-m predominantly lacustrine sedimentary record from the Weihe

Diverse animals across the tree of life undergo the life-history transition of metamorphosis in response to bacteria. Although immunity has been implicated in this metamorphosis in response to bacteria, no functional connection has yet been demonstrated between immunity and metamorphosis. We investigated a host–microbe interaction involving a marine tubeworm, Hydroides elegans , that undergoes metamorphosis

Jansen’s metaphyseal chondrodysplasia (JMC) is a rare disorder caused by activating mutations in the parathyroid hormone (PTH)/PTH-related peptide (PTHrP) receptor (PTH1R). Patients exhibit short stature, dysmorphic bones, and severe growth plate abnormalities, as well as hypercalcemia, hypercalciuria, hypophosphatemia, and reduced plasma PTH levels. Humanized PTH1R (hPTH1R) mice expressing the H223R-hPTH1R

Oceanic dimethyl sulfide (DMS) is the largest natural source of atmospheric sulfur. DMS is biologically produced in seawater and emitted into the atmosphere, where its oxidation products contribute to aerosol formation with consequences for cloud albedo and the Earth’s radiative budget and climate. Climate model projections of how DMS emissions change with global warming are largely uncertain, even

Biomolecular condensates form by phase separation of biological polymers and have important functions in the cell—functions that are inherently linked to their physical properties at different scales. A notable aspect of such membraneless organelles is that their viscoelastic properties can vary by orders of magnitude, but it has remained unclear how these pronounced differences are rooted in the nanoscale

Circuit complexity, defined as the minimum circuit size required for implementing a particular Boolean computation, is a foundational concept in computer science. Determining circuit complexity is believed to be a hard computational problem. Recently, in the context of black holes, circuit complexity has been promoted to a physical property, wherein the growth of complexity is reflected in the time

Plasma membrane-localized autoinhibited Ca 2+ pumps are essential for maintaining basal cytosolic Ca 2+ levels for regulating growth processes and environmental responses. These pumps are known to be activated by calmodulins to maintain Ca 2+ homeostasis in plants and animals. Here, we demonstrate that the evolutionarily conserved copine protein BON1 is critical for maintaining low cytosolic Ca 2+

How brain structure relates to function is a critical and open question in neuroscience. Here, we characterize regional variation in structure–function coupling, capturing the degree to which a cortical region’s structural connections relate to patterns of coordinated neural activity in healthy, term-born neonates ( n = 239). Regional structure–function coupling is heterogeneously patterned across

Bisphenol A (BPA) substitutes are widely used as food contact materials and consumer products, while the effects of pathophysiologically relevant concentrations of BPA substitutes on aging remain unclear. In this study, we used Caenorhabditis elegans ( C. elegans ) to investigate the effects of five BPA substitutes [bisphenol S (BPS), bisphenol B, bisphenol F (BPF), tetramethyl BPF, and 4,4′-(Perfluoropropane-2

Macromolecular organic solids found in primitive meteorites were the main source of carbon delivered to forming planets in the early Solar System. However, the conditions under which this material formed and its subsequent incorporation into growing planetesimals remains a subject of vigorous debate. Here, we show that C isotope variations among these organics in most carbonaceous chondrites are strongly

The sensitivity of coral reefs to climate change is well established. As the oceans warm and acidify, the calcification of coral reefs declines with net calcium carbonate dissolution projected under even moderate emissions trajectories. The impact of this on the global carbon cycle is however yet to be accounted for. Here, we use a synthesis of the sensitivity of coral reef calcification to climate

A universal response of plants to environmental stresses is the activation of plasma membrane (PM) phospholipase C, which hydrolyzes phosphoinositides to produce soluble inositol phosphate and diacylglycerol (DAG). Because of their conical shape, DAG amounts have to be tightly regulated or they can destabilize membranes. We previously showed that upon stress, Synaptotagmin1 (SYT1) transports DAG from

Despite Myc oncoproteins being major causal factors in human cancer, they remain “undruggable.” The MYCN oncogene is one of the most powerful prognostic markers for the childhood cancer neuroblastoma and represents an important target for developing novel therapeutics. Here, we report the finding and characterization of M606, a selective small molecule inhibitor of MYCN, which was identified by screening

We report here transport of full-length epidermal growth factor receptor (EGFR), Insulin Receptor, 7-pass transmembrane receptor Smoothened, and 13-pass Sodium-iodide symporter to extracellular vesicles (EVs) for structural and functional studies. Mass spectrometry confirmed the transported proteins are the most abundant in EV membranes, and the presence of many receptor-interacting proteins in EVs

While symmetry breaking in 2D ferroelectrics is obviously linked to the single-layer structure, layered (van der Waals) ferroelectrics can have a multitude of underlying mechanisms, making their identification nontrivial and often controversial. This complexity is exemplified by tin chalcogenides whose equilibrium structure, the orthorhombic α-phase with space group Pnma , includes an inversion center

Understanding the dynamical behavior of complex systems from their underlying network architectures is a long-standing question in complexity theory. Therefore, many metrics have been devised to extract network features like motifs, centrality, and modularity measures. It has previously been proposed that network symmetries are of particular importance since they are expected to underlie the synchronization

The expansion of commodity agriculture into tropical and subtropical woodlands degrades ecosystem functionality, biodiversity, and the livelihood base of millions of people. Understanding where and how agricultural frontiers emerge is thus important. Yet, existing monitoring approaches typically focus on mapping deforestation and do not capture the shifts in land access and ownership that lay the ground

Through the industrial era, pollutants have been unevenly distributed in the environment, disproportionately impacting disenfranchised communities. Redressing the unequal distribution of environmental pollution is thus a question of environmental justice and public health that requires policy solutions. However, data on pollutants for many locations and time periods are limited because environmental

Proceedings of the National Academy of Sciences, Volume 122, Issue 22, June 2025. SignificanceAlcohol triggers the liver to produce the hormone FGF21, which helps protect against its toxic effects. However, how alcohol induces FGF21 synthesis is incompletely understood. We now show that two byproducts of alcohol metabolism, glycerol-3-...

Proceedings of the National Academy of Sciences, Volume 122, Issue 22, June 2025. SignificanceThe prostaglandin D2 receptor (DP1) functions as a critical regulator of diverse physiological processes, including sleep–wake cycles, allergic responses, and inflammatory cascades. By determining high-resolution cryo-EM structures of DP1 in ...