Chromatin architecture is critical in determining nuclear mechanics. Most studies focus on the mechanical rigidity conferred by chromatin condensation from densely packed heterochromatin, but less is known on how transient chromatin decompaction impinge on nucleus stiffness. Here, we used an array of vertically aligned nanopillars to study nuclear deformability in situ after chromatin decompaction

The distinction between “reinforcement” and “cloaking” has been overlooked in optimization-based design of devices intended to conceal a defect in an elastic medium. In the former, a so-called “cloak” is severely biased toward one or a few specific elastic disturbances, whereas in the latter, an “unbiased cloak” is effective under any elastic disturbance. We propose a two-stage approach for optimization-based

Recent research has identified several effective strategies for reducing Americans’ animosity toward supporters of opposing political parties. However, whether these strategies can durably reduce partisan animosity in a scalable manner and in everyday life remains unclear. We bridge the gap between prior research and useful application by assessing whether exposure to multiple, scalable treatments

What mechanisms underlie linguistic generalization in large language models (LLMs)? This question has attracted considerable attention, with most studies analyzing the extent to which the language skills of LLMs resemble rules. As of yet, it is not known whether linguistic generalization in LLMs could equally well be explained as the result of analogy. A key shortcoming of prior research is its focus

Wnt signaling orchestrates gene expression in a plethora of processes during development and adult cell homeostasis via the action of nuclear β-catenin. Yet, little is known about how β-catenin generates context-specific transcriptional outcomes. Understanding this will reveal how aberrant Wnt/β-catenin signaling causes neoplasia specifically of the colorectal epithelium. We have previously identified

RAS is the most frequently mutated oncogene in cancer. RAS proteins show high sequence similarities in their G-domains but are significantly different in their C-terminal hypervariable regions (HVR). These regions interact with the cell membrane via lipid anchors that result from posttranslational modifications (PTM) of cysteine residues. KRAS4b is unique as it has only one cysteine that undergoes

Predicting the exact many-body quantum dynamics of polarons in materials with strong carrier–phonon interactions presents a fundamental challenge, often necessitating one to adopt approximations that sacrifice the ability to predict the transition from nonequilibrium relaxation to thermodynamic equilibrium. Here, we exploit a recent breakthrough that generalizes the concept of memory beyond its conventional

Establishing a dominance hierarchy in social organisms is important for access to resources. Stress has been proposed as a major factor influencing an animal’s likely position in a social hierarchy. Although individual differences in vulnerability to stress are increasingly recognized, how social hierarchy affects vulnerability remains relatively understudied. Here, we examined how the social dominance

The potassium channel TWIK-2 is crucial for ATP-induced activation of the NLRP3 inflammasome in macrophages. The channel is a member of the two-pore domain potassium (K2P) channel superfamily and an emerging therapeutic target to mitigate severe inflammatory injury involving NLRP3 activation. We report the cryo-EM structure of human TWIK-2. In comparison to other K2P channels, the structure reveals

Many phenotypic traits, such as fermentation activity, have been shown to be instable due to stochastic gene expression and environmental influence. While previous studies only have obtained understanding at the level of the microbial community, the fate of extraordinary traits of an individual through generations of reproduction has yet to be adequately investigated. This work uses the lactic acid

Nitrogen is one of the most limiting nutrients to forest productivity worldwide. Recently, it has been established that diverse ecosystems source a substantial fraction of their water from weathered bedrock, leading to questions about whether root-driven nitrogen cycling extends into weathered bedrock as well. In this study, we specifically examined nitrogen dynamics using specialized instrumentation

The aminoacyl-tRNA synthetases (AaRSs) are an ancient family of structurally diverse enzymes that are divided into two major classes. The functionalities of most AaRSs are inextricably linked to their oligomeric states. While GluRSs were previously classified as monomers, the current investigation reveals that the form expressed in Pseudomonas aeruginosa is a rotationally pseudosymmetrical homodimer

Crystallization by amorphous calcium carbonate (ACC) particle attachment (CPA) is a prevalent biomineralization mechanism among calcifying organisms. A narrow, controlled size distribution of ACC nanoparticles is essential for macroscopic crystal formation via CPA. Using in situ synchrotron small-angle X-ray scattering, we demonstrate that synthetic magnesium-stabilized ACC (Mg-ACC) nanoparticles form

8-oxoguanine (8-oxoGua) is one of the most frequent forms of oxidative DNA base lesions, repaired by 8-oxoguanine DNA glycosylase 1 (OGG1) via base excision repair (BER) pathway to maintain genome fidelity. The human allelic variant hOGG1 S326C , prevalent in Caucasians and Asians, has been regarded as a susceptibility factor for various diseases, yet its pathogenic mechanism remains elusive. In this

Mitochondria are central metabolic organelles that control cell fate and the development of mitochondrial diseases. Traditionally, phase separation directly regulates cell functions by driving RNA, proteins, or other molecules to concentrate into lipid droplets. Recent studies show that phase separation regulates cell functions and diseases through the regulation of subcellular organelles, particularly

Proceedings of the National Academy of Sciences, Volume 122, Issue 18, May 2025.

Bloch wavefunctions in crystals experience localization within the bulk when disorder is introduced, a phenomenon commonly known as Anderson localization. This effect is considered universal, being applicable to all types of waves, quantum or classical. However, the interaction between disorder and topology—a concept that has profoundly transformed many branches of physics—necessitates revisiting the

Single-cell organisms and various cell types use a range of motility modes when following a chemical gradient, but it is unclear which mode is best suited for different gradients. Here, we model directional decision-making in chemotactic amoeboid cells as a stimulus-dependent actin recruitment contest. Pseudopods extending from the cell body compete for a finite actin pool to push the cell in their

Circadian regulation of the cell cycle progression generates a diurnal supply of newborn cells to replace those lost in organs and tissues. In this study, we analyzed circadian time-dependent changes in cell types within the mouse tongue epithelium. Using single-cell RNA sequencing, we observed circadian time-dependent changes in the populations of stem/progenitor cells and the differentiated cells

Spreading depolarizations (SDs) have been identified in various brain pathologies. SDs increase the cerebral energy demand and, concomitantly, oxygen consumption, which indicates enhanced synthesis of adenosine triphosphate (ATP) by oxidative phosphorylation. Therefore, SDs are considered particularly detrimental during reduced supply of oxygen and glucose. However, measurements of intracellular neuronal

The protein midnolin (MIDN) augments proteasome activity in lymphocytes and dramatically facilitates the survival and proliferation of B-lymphoid malignancies. MIDN binds both to proteasomes and to substrates, but the mode of interaction with the proteasome is unknown, and the mechanism by which MIDN facilitates substrate degradation in a ubiquitin-independent manner is incompletely understood. Here

Diverse genetic strategies are being pursued to control mosquito-borne infectious diseases. These strategies often rely on the release of nonbiting males to either reduce the target mosquito population or render them resistant to pathogens. Male-only releases are important as any contaminating females can bite and potentially transmit pathogens. Despite significant efforts, it remains a major bottleneck

Despite the promise of vastly expanding the druggable genome, rational design of RNA-targeting ligands remains challenging as it requires the rapid identification of hits and visualization of the resulting cocomplexes for guiding optimization. Here, we leveraged high-throughput screening, medicinal chemistry, and structural biology to identify a de novo splicing inhibitor against a large and highly

Cancer cells frequently reprogram one-carbon metabolic pathways to fulfill their vigorous demands of biosynthesis and antioxidant defense for survival and proliferation. Dysfunction of oncogenes or tumor suppressor genes is critically involved in this process, but the precise mechanisms by which cancer cells actively trigger one-carbon metabolic alterations remain incompletely elucidated. Here, by

Vascular development is a precisely controlled process, yet how it is spatiotemporally orchestrated remains enigmatic. We previously identified DEAD-box RNA helicase 24 (DDX24) as a pathogenic gene for multiorgan vascular anomalies. Here, we show that DDX24 is expressed in the endothelium during embryonic angiogenesis in zebrafish. DDX24 deficiency causes intersegmental vessel hyperbranching in the

The latitudinal diversity gradient (LDG) is the most notable global biodiversity pattern, but its underlying mechanisms remain unresolved. The evolutionary speed hypothesis (ESH) posits that molecular rates play a crucial role in shaping the LDG, suggesting that higher temperatures accelerate molecular rates, thereby facilitating rapid speciation and accumulation of biodiversity in the tropics. However

Proton transport plays a fundamental role in many biological and chemical systems. In life, proton transport is crucial for biochemical and physiological functions. It is usually accepted that the main mechanism of proton transfer is a result of hopping between neighboring water molecules and amino acid side chains. It was recently suggested that the proton transfer can be simultaneously coupled with

The use of atoms, molecules, and free electrons in quantum amplifiers has greatly advanced precision measurements, paving the way for the development of extremely-low-noise quantum devices such as masers and lasers. Here, we investigate the signal amplification of interacting spins and observe the amplification of magnetic fields using mixtures of interacting alkali-metal and noble gases. In contrast

Developmental time (or time to maturity) strongly correlates with an animal’s maximum lifespan, with late-maturing individuals often living longer. However, the genetic mechanisms underlying this phenomenon remain largely unknown. This may be because most previously identified longevity genes regulate growth rate rather than developmental time. To address this gap, we genetically manipulated prothoracicotropic

Rare earth oxyphosphates represent a large family of compounds with the general formula (RE 2 O 3 ) x (REPO 4 ), where RE refers to lanthanides and yttrium. At least four known stoichiometries have been established, each with distinct structures. These compounds have potential applications as refractory coatings, catalysts, and magnetic materials. We modeled the stability of RE 3 PO 7 [RE 3 (PO 4 )O

It is common to say that people feel entitled to rewards—they think they have earned or deserve them—based on their effort and achievement. However, effort and achievement draw on different principles to justify reward. They can also conflict over when people should feel entitled to rewards. These observations raise the question: In everyday settings, do people feel entitled to rewards because of their

DNA damage repair (DDR) is essential for cancer cell survival and treatment resistance, making it a critical target for tumor therapy. The eukaryotic AAA+ adenosine triphosphatase valosin-containing protein (VCP), which is transported from the cytoplasm into the nucleus, plays a critical role in the DDR process. However, the nuclear translocation and molecular mechanism of VCP for DDR remain elusive

The detection and identification of polycyclic aromatic hydrocarbons (PAHs) and their modified derivatives in contaminated soil is challenging due to the chemical and microbial complexity of soil organic matter. To address these challenges, we developed an innovative analytical approach that combines Surface-enhanced Raman spectroscopy with a Raman spectral library constructed in silico using density

Regulating multistimulus responses in artificial systems remains a challenge in smart material development. We present a versatile chemical switching system that precisely controls the self-assembly of metal–organic cages via temperature and solvent changes. The key component, cyclo[2](1,3-(4,6-dimethyl)benzene) (4-pyridine)[6](1,3-(4,6-dimethyl)benzene) ( CP2 ), was generated as three atropisomers

Despite the rapid proliferation of AI tools, we know little about how people who use them are perceived by others. Drawing on theories of attribution and impression management, we propose that people believe they will be evaluated negatively by others for using AI tools and that this belief is justified. We examine these predictions in four preregistered experiments (N = 4,439) and find that people

Liquid manipulation is ubiquitous in nature and engineering, enabling controllable and efficient liquid delivery. Conventional understanding of liquid manipulation relies on inhomogeneous chemical modifications or single-scale structure design. Here, we present how water is directionally navigated and spontaneously reallocated at high efficiency via the cross-scale topology on Tillandsia capitata leaves

Resistance to chemotherapeutics is one major challenge to clinical effectiveness of cancer treatment and is primarily interpreted by various biochemical mechanisms. This study establishes an inverse correlation between tumor cell contractility and chemosensitivity. In both clinical biopsies and cancer cell lines, high/low actomyosin-mediated contractile force attenuates/enhances the vulnerability to

During meiosis, the correct pairing, synapsis, and recombination of homologous chromosome pairs is critical for fertility of sexual eukaryotes. These processes are challenged in polyploids, which possess additional copies of each chromosome. Polyploidy thus provides a unique context to study how evolution can modify meiotic programs in response to challenges. We previously observed that in newly formed

Yellow fever vaccination provides long-lasting protection and is a unique model for studying the immune response to an acute RNA virus infection in humans. To elucidate the early innate immune events preceding the rapid generation of protective immunity, we performed transcriptome analysis of human blood dendritic cell (DC) and monocyte subpopulations before and 3, 7, 14, and 28 d after vaccination

Heterotrimeric Gα:Gβγ G proteins function as molecular switches downstream of G protein–coupled receptors (GPCRs). They alternate between a heterotrimeric GDP-bound OFF-state and a GTP-bound ON-state in which Gα GTP is separated from the Gβγ dimer. Consequently, pharmacological tools to securely prevent the OFF-ON transition are of utmost importance to investigate their molecular switch function, specific

The exhausted CD8 + T (T EX ) cells consist of distinct subsets including Tcf1 + stem-like, Tcf1 – Cx3cr1 + intermediate (T EX -int) and Tcf1 – Cx3cr1 – terminally exhausted cells; yet, epigenetic determinants of T EX subset differentiation remain incompletely understood. Using chronic viral infection, we show that histone deacetylase 1 (Hdac1) was specifically required for the formation of antigen-specific

Phase separation is an important mechanism to generate certain biomolecular condensates and organize the cell interior. Condensate formation and function remain incompletely understood due to difficulties in visualizing the condensate interior at high resolution. Here, we analyzed the structure of biochemically reconstituted chromatin condensates through cryoelectron tomography. We found that traditional

A key unresolved question in microbial ecology is how the extraordinary diversity of microbiomes emerges from the interactions among their many functionally distinct populations. This process is driven in part by the cross-feeding networks that help to structure these systems, in which consumers use resources to fuel their metabolism, creating by-products which can be used by others in the community

Natural and synthetic multicomponent gels display emergent properties, which implies that they are more than just the sum of their components. This warrants the investigation of the role played by interspecies interactions in shaping gel architecture and rheology. Here, using computer simulations, we investigate the effect of changing the strength of the interactions between two species forming a fibrous

Cell division is a fundamental biological process that allows a single mother cell to produce two daughter cells. In walled bacteria, different modes of cell division have been reported that are notably associated with distinctive cell shapes. In all cases, division involves a step of septation, corresponding to the growth of a new dividing cell wall, followed by splitting of the two daughter cells

Within Earth’s climate system, the ocean, cryosphere, and vegetation exhibit hysteresis behavior such that their state depends on their past and not merely on their current boundary conditions. The atmosphere’s fast mixing time scales were thought to inhibit the necessary memory effect for such multistability. Here, we show that moisture accumulation within the atmospheric column generates hysteresis

Past research finds that sleep duration is reliably linked with health yet sleep durations differ substantially between countries. We investigated whether countries with shorter sleep durations have worse health. Study 1 analyzed national sleep durations from 14 past investigations ( k = 353) and found that they were not associated with national health. Study 2 collected sleep duration and health data

Social touch is crucial for human well-being, as a lack of tactile interactions increases anxiety, loneliness, and need for social support. To address the detrimental effects of social isolation, we build on cutting-edge research on social touch and movement sonification to investigate whether social tactile gestures could be recognized through sounds, a sensory channel giving access to remote information

Genes and the environment jointly shape individual traits, but the influence of indirect genetic effects (IGEs), arising from the genetic composition of interacting conspecific individuals, is often ignored or underemphasized. Moreover, because of practical challenges in characterizing IGEs, empirical research has fallen behind theoretical advancement. The fire ant Solenopsis invicta offers a uniquely

Infiltrating neutrophils are key effector cells in inflammatory bowel disease (IBD) while providing antimicrobial defense and tissue restitution in the intestine. The complexity of neutrophil functions in local environments underscores our limited understanding of how their adaptation in tissues influences disease progression. Here, we demonstrate that neutrophils recruited in murine colitis and infection

PARK7/DJ-1, a redox-sensitive protein implicated in neurodegeneration, cancer, and inflammation, exhibits increased secretion under stress. We previously demonstrated that, as a leaderless protein, PARK7 relies on an unconventional autophagy pathway for stress-induced secretion. The current study delves deeper into the mechanisms governing PARK7 secretion under oxidative stress triggered by the neurotoxin

Diverse single-stranded RNA viruses employ different host cellular organelles or membrane systems to compartmentalize their replication intermediates and proviral factors, ensuring robust replication. Replication of Bamboo mosaic virus (BaMV), an Alphaflexiviridae family, is tightly associated with chloroplasts and dynamic cytosolic viral replication complex (VRC) clusters. BaMV VRC clusters comprise

Genetically encoded biosensors with changes in fluorescence lifetime (as opposed to fluorescence intensity) can quantify small molecules in complex contexts, even in vivo. However, lifetime-readout sensors are poorly understood at a molecular level, complicating their development. Although there are many sensors that have fluorescence-intensity changes, there are currently only a few with fluorescence-lifetime

Sensory enteroendocrine cells in the intestinal epithelium detect and relay information about the luminal environment to other cells within and outside the gut. Serotonergic enterochromaffin (EC) cells are a subset of enteroendocrine cells that detect noxious stimuli within the gut lumen, such as chemical irritants and microbial byproducts, and transduce this information to sensory nerve fibers to