Table Of Contents Page, PNAS Volume 122, Number 23

DNA–RNA hybrid strand displacement underpins the function of many natural and engineered systems. Understanding and controlling factors affecting DNA–RNA strand displacement reactions is necessary to enable control of processes such as CRISPR-Cas9 gene ...

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 ...

Interaction of cells and the surrounding lumen drives the formation of tubular system that plays the transport and exchange functions within an organism. The physical and biological mechanisms of lumen expansion have been explored. However, how cells ...

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 ...

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 ...

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 ...

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 ...

Using high-precision ice core measurements of CO₂, δ¹³C–CO₂, CH₄, and N₂O, this study provides carbon isotope constraints on a sizeable, centennial-scale CO₂ jump at the onset of Marine Isotope Stage 9 (MIS 9). The very end of the Heinrich stadial (HS) ...

Empirical slip-rate- and state-dependent friction laws and linear fracture mechanics constitute popular approaches to explaining earthquakes. However, the physics underlying friction laws remain elusive and fracture mechanics does not specify fault ...

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 ...

Seismic low-velocity layers (LVLs), frequently attributed to hydrous-silicate melts, are detected globally but exhibit lateral discontinuities. Geophysical and laboratory studies of water content in the mantle transition zone (MTZ) and upper mantle ...

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 ...

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 ...

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 ...

Soft magnetic miniature devices are crucial for applications in minimally invasive medicine, soft electronics, and robotics. While substantial progress has been made, current magnetic programming techniques are inherently tied to template-based and ...

Shape-shifting structures can transform and recover their shapes in response to external stimuli, but they often lack programmable, clock-like control over spatiotemporal deformation and motion, especially after stimuli are removed. Achieving autonomous, ...

Accurate identification of sleep stages and disorders is crucial for maintaining health, preventing chronic conditions, and improving diagnosis and treatment. Direct respiratory measurements, as key biomarkers, are missing in traditional wrist- or finger-...

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 ...

The influence of seasonal variations in temperature and precipitation on subsurface biogeochemical processes remains poorly understood. In the Lavey-les-Bains thermal system in the Swiss Alps, annual variations in electrical conductivity are observed to ...

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 ...

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 ...

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 ...

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. ...

Despite living in an era where the mere concept of truth is increasingly contested, the cognitive processes underlying the processing of information we believe or disbelieve remain largely unexplored. In this fMRI study, we investigated how belief ...

Several cross-country examinations have found larger gender differences in Western countries. More recently, it has been argued, from an evolutionary standpoint, that equality may paradoxically increase gender differences, because it provides more freedom ...

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 ...

Inequality in outcomes may emerge through a reinforcement process in which stochastic variation in values is determined by prior values but may also originate in preexisting differences in unobserved factors. A common approach toward differentiating ...

Scientific inquiry about the transmissibility of infectious diseases is largely based on the basic reproduction number ($R_0$) and its derivations. This paper describes a mechanism overlooked in most conventional analyses, in which a disease can endogenously “...

The number of acutely food insecure people worldwide has doubled since 2017, increasing demand for early warning systems (EWS) that can predict food emergencies. Advances in computational methods, and the growing availability of near-real time remote ...

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, ...

Molecular mechanisms underlying the green insect camouflage have puzzled researchers for over a century. Here, we isolated and identified a green water-soluble protein from the integument of bush-cricket Tettigonia cantans. De novo sequencing and cloning ...

DNA–RNA hybrid strand displacement underpins the function of many natural and engineered systems. Understanding and controlling factors affecting DNA–RNA strand displacement reactions is necessary to enable control of processes such as CRISPR-Cas9 gene ...

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 ...

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 ...

Characterizing the conformational ensemble of biomolecular systems is key to understand their functions. Cryoelectron microscopy (cryo-EM) captures two-dimensional snapshots of biomolecular ensembles, giving in principle access to thermodynamics. However, ...

The focus of aging research has shifted from increasing lifespan to enhancing healthspan to reduce the time spent living with disability. Despite significant efforts to develop biomarkers of aging, few studies have focused on biomarkers of healthspan. We ...

The protein α-syn adopts a wide variety of conformations including an intrinsically disordered monomeric form and an α-helical-rich membrane-associated form that is thought to play an important role in cellular membrane processes. However, despite the ...

Collective cell migration is a key driver of tissue morphogenesis and cancer invasion. Here, we identified the tumor suppressor Ras association domain-containing protein 8 (RASSF8) as a WAVE interactor required for border cell migration. RASSF8 ...

Osteoarthritis (OA) is one of the most common causes of physical disability among older people and its incidence increases with age. Removal of the senescent cells (SNCs) delays OA pathologies, but little is known about the heterogeneity of SNCs and their ...

Metabolism fuels cell growth and functions. While it is well established that cellular growth rate scales with cell size, how cells alter their metabolism as they change size remains largely unexplored. Here, we conducted a systematic analysis of cell ...

To fertilize an oocyte, mammalian spermatozoa must undergo a maturation step known as capacitation that takes place after ejaculation. Protein kinase A (PKA) plays a fundamental role in capacitation in all mammalian species. Before capacitation, PKA is ...

Interaction of cells and the surrounding lumen drives the formation of tubular system that plays the transport and exchange functions within an organism. The physical and biological mechanisms of lumen expansion have been explored. However, how cells ...

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 ...

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 ...

Prior studies have indicated that the transcription factor Creb5 is expressed in the joint interzone, which contains the progenitors for all synovial joint tissues in both mouse and human embryos. In the absence of Creb5 function, most synovial joint ...

The tightly controlled spatiotemporal expression of developmental genes depends on the concerted action of cis-regulatory elements (CREs) and transcription factors (TFs) to ensure cell fate decisions. Endothelial-to-hematopoietic transition (EHT) is a ...

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 ...

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 ...

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 ...

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, ...

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. ...

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 ...

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, ...

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 ...

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 ...

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 ...

tRNA introns are a universally conserved feature of eukaryotic genomes, but the reason for their conservation has remained obscure. We have previously shown that a defect in the essential tRNA splicing endonuclease of yeast results in transcriptome ...

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) ...

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 ...

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 ...

The dense extracellular matrix (ECM) of stroma-rich solid tumors acts as a significant barrier to effective chemotherapy by hindering drug penetration. In this study, a supramolecular hydrogel was successfully developed, enabling the codelivery and ...

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. ...

The influence of seasonal variations in temperature and precipitation on subsurface biogeochemical processes remains poorly understood. In the Lavey-les-Bains thermal system in the Swiss Alps, annual variations in electrical conductivity are observed to ...

HIV-1 has been observed to enter target cells at both the plasma membrane and endosomes. However, which pathways mediate its entry into primary CD4⁺ T cells, the major targets of this virus, remains unclear. Here, we show that HIV-1 can enter primary CD4⁺ ...

Two-component system (TCS) histidine kinases enable bacterial pathogens to sense environmental signals and regulate adaptive responses during infection. The EnvZ/OmpR TCS, known for its role in osmolarity/pH-dependent regulation of outer membrane porins ...

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 ...

To better understand the potential health threats and underlying visual pathways of long-term light at night (LAN) exposure, we adopted a widely accepted diurnal animal model tree shrew (Tupaia belangeri chinensis), which is a close relative to primates, ...

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 ...

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 ...

Paracetamol has been used for decades to relieve mild-to-moderate pain. Its analgesic effect is mainly attributed to its metabolite, AM404, acting on cannabinoid receptors or TRPV1 channels in central nervous system (CNS) neurons. Here, we show that AM404 ...

Since our first steps in life, we are forming incidental associations between diverse stimuli across various sensory modalities that influence our future choices and facilitate adaptation to environmental fluctuations. Daily behavior is usually governed ...

Understanding how neural populations emerge to give rise to behavior is a major goal in neuroscience. Here, we explore the self-assembly of neural circuits in Hydra, an organism with a simple nervous system but no centralized information processing, to ...

Neuronal activity in the hippocampus creates a cognitive map of space that is essential for navigation. In any given environment, a fraction of hippocampal pyramidal cells (PCs) is active at specific locations (place cells), others are sparsely active ...

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 ...

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-...

Plasma membrane-localized autoinhibited Ca²⁺ pumps are essential for maintaining basal cytosolic Ca²⁺ levels for regulating growth processes and environmental responses. These pumps are known to be activated by calmodulins to maintain Ca²⁺ homeostasis in ...

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 ...

Bioactive gibberellins (GAs) are a class of plant hormones that regulate various aspects of plant growth and development, and several key GA deactivation enzymes have been identified. In rice, non-13-hydroxylated GAs have been shown to be deactivated via ...

The start of seed germination is a major decision point in plant life cycle, which relies on seed stored mRNA. However, the underlying translational mechanism remains less illustrated. Here, we demonstrate that inhibiting translation using translation ...