Table Of Contents Page, PNAS Volume 122, Number 21

Enhancing the reliability and reproducibility of optical microscopy by reducing specimen irradiance continues to be an important biotechnology target. As irradiance levels are reduced, however, the particle nature of light is heightened, giving rise to ...

Fluorescent diamond nanocrystals can host spin qubit sensors capable of probing the physical properties of biological systems with nanoscale spatial resolution. Sub-100 nm diamond nanosensors can readily be delivered into intact cells and even living ...

In large, natural ecosystems, many (≳1) phenotypically relevant mutants can emerge over the characteristic turnover time of the population. When this is the case, there can be ‘eco-evolutionary feedback’ between the dynamical processes that underlie ...

Vinculin forms a catch bond with the cytoskeletal polymer actin, displaying an increased bond lifetime upon force application. Notably, this behavior depends on the direction of the applied force, which has significant implications for cellular ...

Potassium (K⁺) channels are widely distributed in many types of organisms. They combine high efficiency (~100 pS) and K⁺/Na⁺ selectivity by a conserved selectivity filter (SF). Molecular Dynamics (MD) simulations can provide detailed, atomistic mechanisms ...

The most efficient lipid nanoparticles (LNPs) for gene therapeutics rely on specific lipids that protect the oligonucleotide cargo and aid cellular uptake and subsequent endosomal escape. Yet, the efficacy of current state-of-the-art LNP formulations ...

Nonenzymatic RNA copying is thought to have been responsible for the replication of genetic information during the origin of life. However, chemical copying with the canonical nucleotides (A, U, G, and C) strongly favors the incorporation of G and C and ...

Autonomous vehicles (AVs) will soon cruise our roads as a global undertaking. Beyond completing driving tasks, AVs are expected to incorporate ethical considerations into their operation. However, a critical challenge remains. When multiple road users are ...

The incident ultraviolet (UV) irradiance on the surface of Mars is strongly sterilizing and plays a critical role in atmospheric and near-surface photochemistry. The Rover Environmental Monitoring Station (REMS) instrument, which includes the first UV ...

Predicting gray swan weather extremes, which are possible but so rare that they are absent from the training dataset, is a major concern for AI weather models and long-term climate emulators. An important open question is whether AI models can extrapolate ...

We explore how and when Hells Canyon, North America’s deepest river gorge (~2,400 m deep), formed, addressing these fundamental questions first posed by W. Lindgren [The Gold Belt of the Blue Mountains of Oregon (1901)]. Existing hypotheses about the ...

Flamingos feature one of the most sophisticated filter-feeding systems among birds, characterized by upside-down feeding, comb-like lamellae, and a piston-like tongue. However, the hydrodynamic functions of their L-shaped chattering beak, S-curved neck, ...

The minimum separation between reconnecting vortices in fluids and superfluids obeys a universal scaling law with respect to time. The prereconnection and the postreconnection prefactors of this scaling law are different, a property related to ...

Gradients of extracellular signals organize cells in tissues. Although there are several models for how gradients can pattern cell behavior, it is not clear how cells react to gradients when the population is undergoing 3D morphogenesis, in which cell–...

Global climate change has triggered an urgent need for predicting the reorganization of Earth’s biodiversity. For dioecious species (those with separate sexes), it is unclear how commonly unique climate sensitivities of females and males could influence ...

Nonenzymatic RNA copying is thought to have been responsible for the replication of genetic information during the origin of life. However, chemical copying with the canonical nucleotides (A, U, G, and C) strongly favors the incorporation of G and C and ...

Cell-membrane proteins are critical mediators of signal transduction, playing essential roles in disease occurrence and progression. The emerging LYTACs (Lysosome-targeting chimeras) technology combines drug-targeting strategies with lysosomal degradation,...

Enhancing the reliability and reproducibility of optical microscopy by reducing specimen irradiance continues to be an important biotechnology target. As irradiance levels are reduced, however, the particle nature of light is heightened, giving rise to ...

The prolyl isomerase Pin1 catalyzes the cis–trans isomerization of proline peptide bonds, a noncovalent posttranslational modification that influences cellular and molecular processes, including protein–protein interactions. Pin1 is a two-domain enzyme ...

Ubiquitin-specific protease 7 (USP7) is a deubiquitinating enzyme that plays a crucial role in cellular processes, including the maintenance of genome stability and regulation of antiviral and immune responses. Its dysfunction is linked to various cancers ...

Motile cells migrate directionally in the electric field (EF) in a process known as galvanotaxis, an important phenomenon in wound healing and development. We previously reported that individual fish keratocyte cells migrate to the cathode in EFs, that ...

NOD-like receptors (NLRs) are a highly conserved family of cytosolic pattern recognition receptors that drive innate immune responses against pathogens, pathogen-associated molecular patterns, damage-associated molecular patterns, and homeostatic ...

Gradients of extracellular signals organize cells in tissues. Although there are several models for how gradients can pattern cell behavior, it is not clear how cells react to gradients when the population is undergoing 3D morphogenesis, in which cell–...

Flamingos feature one of the most sophisticated filter-feeding systems among birds, characterized by upside-down feeding, comb-like lamellae, and a piston-like tongue. However, the hydrodynamic functions of their L-shaped chattering beak, S-curved neck, ...

Overexploitation has depleted fish stocks during the past century; nonetheless, its genomic consequences remain poorly understood for most species. Characterizing the spatiotemporal patterns of these consequences may provide baseline estimates of past ...

The incident ultraviolet (UV) irradiance on the surface of Mars is strongly sterilizing and plays a critical role in atmospheric and near-surface photochemistry. The Rover Environmental Monitoring Station (REMS) instrument, which includes the first UV ...

Mutation rates vary across the tree of life by many orders of magnitude, with fewer mutations occurring each generation in species that reproduce quickly and maintain large effective population sizes. A compelling explanation is that large effective ...

The maintenance of biodiversity crucially depends on the evolutionary potential of populations to adapt to environmental change. Accelerating climate change and extreme temperature events urge us to better understand and forecast evolutionary responses. ...

We employ fine-scale population genetic analyses to reveal dynamics among interacting forces that act at synonymous sites and introns among closely related Drosophila species. Synonymous codon usage bias has proven to be well suited for population genetic ...

Since the discovery of spliceosomal introns in eukaryotic genomes, the proximate molecular and evolutionary processes that generate new introns have remained a critical mystery. Specialized transposable elements (TEs), introners, are thought to be one of ...

Coevolution is a ubiquitous driver of diversification in both mutualistic and antagonistic interactions between species. In mutualisms, coevolution can result in trait complementarity between partners that facilitates their persistence. Despite its ...

Measures of general cognitive ability (GCA) are highly stable from adolescence onward, particularly at the level of genetic influences. In contrast, measurement of GCA in early life (before 3 y old) is less reliable and less is known about the stability ...

Acute knockout of the rod photoreceptor transcription factor Nrl delays retinal degeneration in multiple mouse models of blindness, but the downstream transcriptomic changes that mediate these therapeutic effects are unknown. Here, we show that acute Nrl ...

A major focus of human genetics is to map severe disease mutations. Increasingly, that goal is understood as requiring huge numbers of people to be sequenced from every broadly defined genetic ancestry group, so as not to miss “ancestry-specific variants.”...

Calcineurin is a highly conserved phosphatase that plays a central role in sensing calcium and governing transcriptional, posttranscriptional, and posttranslational signaling networks. Calcineurin is a heterodimer consisting of a catalytic A subunit and a ...

Concussions can cause debilitating symptoms despite no evidence of structural changes on diagnostic imaging. The cellular events occurring in the brain parenchyma following concussion, especially repetitive concussion, are not well elucidated. We ...

We demonstrate that exposure to the AB5 subtilase cytotoxin (SubAB) induces the unfolded protein response (UPR) in human peripheral blood mononuclear cells, concomitant with a proinflammatory response across distinct cell subsets. Notably, SubAB ...

MHC class II glycoproteins (MHC-II) bind peptides derived from exogenous antigens and dendritic cells (DCs) present these peptide MHC-II (pMHC-II) complexes to antigen-specific CD4 T cells during immune responses. The turnover of surface pMHC-II on ...

Calreticulin (CALR) is primarily an endoplasmic reticulum chaperone protein that also plays a key role in facilitating programmed cell removal (PrCR) by acting as an “eat-me” signal for macrophages, directing their recognition and engulfment of dying, ...

Broad immune responses are needed to mitigate viral evolution and escape. To induce antibodies against conserved receptor-binding domain (RBD) regions of SARS-like betacoronavirus (sarbecovirus) spike proteins that recognize SARS-CoV-2 variants of concern ...

Platform technologies are fundamentally reshaping the pharmaceutical industry, offering unprecedented potential for innovation across multiple therapeutic areas. However, traditional valuation models, focused on single-asset metrics, struggle to capture ...

Alzheimer’s disease (AD) and traumatic brain injury (TBI) are currently untreatable neurodegenerative disorders afflicting millions of people worldwide. These conditions are pathologically related, and TBI is one of the greatest risk factors for AD. ...

Liver metastasis remains the predominant cause of mortality in patients with colorectal cancer (CRC). Nevertheless, the mechanisms underlying the initiation of colorectal cancer liver metastasis remain poorly elucidated. During the metastatic process of ...

Insulin receptors are present on cells throughout the body, including the brain. Dysregulation of insulin signaling in neurons and astrocytes has been implicated in altered mood, cognition, and the pathogenesis of Alzheimer’s disease (AD). To define the ...

Failure to anticipate new forms of antibiotic resistance has led to resistance developing rapidly to virtually all antibiotics that have entered clinical use. Many of the most problematic types of resistance originated in the environment, where ancient ...

The natural products actinonin and matlystatin feature an N-hydroxy-2-pentyl-succinamyl (HPS) chemophore that facilitates metal chelation and confers their metalloproteinase inhibitory activity. Actinonin is the most potent natural inhibitor of peptide ...

A major challenge for HIV type 1 (HIV-1) cure is the presence of viral latent reservoirs. The “Shock & Kill” strategy involves the combined use of latency reversal agents (LRA) and antiretroviral treatment (ART) to reactivate HIV-1 latent reservoirs, ...

Zika virus (ZIKV) infection can lead to a variety of clinical outcomes, including severe congenital abnormalities. The phosphatidylserine receptors AXL and TIM-1 are recognized as critical entry factors for ZIKV in vitro. However, it remains unclear ...

Social communication between animals is often mediated by sequences of acoustic signals, sometimes spanning long timescales. How auditory neural circuits respond to extended input sequences to guide behavior is not understood. We address this problem ...

Astrocytes, the most abundant type of glial cell, play a fundamental role in memory. Despite most hippocampal synapses being contacted by an astrocyte, there are no current theories that explain how neurons, synapses, and astrocytes might collectively ...

Many neurodegenerative disorders (NDDs) preferentially affect neurons with long or complex axonal arbors but the cellular and molecular bases for neurite length-dependent vulnerability of neurons to degeneration is largely unknown. Using Drosophila ...

Physical exercise is known to reduce depression, but the underlying brain mechanisms remain unclear. Based on a chronic restraint stress model in mice, we showed that 4-wk treadmill exercise profoundly maintained normal neural activity in the nucleus ...

A recent study has suggested that the stimulus responses of cortical neural populations follow a critical power law. More precisely, the power spectrum of the covariance matrix of neural responses follows a power law with an exponent indicating that the ...

We perceive a stable, continuous world despite drastic changes of retinal images across saccades. However, while persistent objects in daily life appear stable across saccades, stimuli flashed around saccades can be grossly mislocalized. We address this ...

Stathmin-2 (also known as SCG10) is encoded by the STMN2 gene, whose mRNA is one of the most abundantly expressed in human motor neurons. In almost all instances of ALS and other TDP-43 proteinopathies, stathmin-2 encoding mRNAs are cryptically spliced ...

Small-cell lung cancer (SCLC) is the most lethal type of lung cancer, characterized by rapid evolution from chemosensitivity to chemoresistance and limited treatment options. However, the mechanisms underlying this evolution remain poorly understood. Here,...

Our biological clock, located in the suprachiasmatic nucleus (SCN), controls behavioral activity rhythms by producing circadian rhythms in SCN electrical activity. Behavioral studies in humans suggest that the clock is sensitive not only to light but also ...

In response to changing blood pressure, arteries adjust their caliber to control blood flow. This vital autoregulatory property, termed vascular myogenic tone, stabilizes downstream capillary pressure. Here, we reveal that tissue temperature, combined ...

During arbuscular mycorrhiza (AM) symbiosis AM fungi form tree-shaped structures called arbuscules in root cortex cells of host plants. Arbuscules and their host cells are central for reciprocal nutrient exchange between the symbionts. REQUIRED FOR ...

New evidence on the timing of early angiosperm evolution is presented through the discovery of four well-dated tricolpate pollen grains from the Early Cretaceous midlatitudes. Recovered from nearshore marine sediments in the Lusitanian Basin of Portugal, ...

Root development is tightly regulated in plants to optimize nutrient acquisition and interactions with soil microorganisms. In legumes, the Autoregulation of Nodulation (AoN) pathway systemically controls the proliferation of root nodules, which are ...