Physics

Funding holdups for PEPFAR put prevention and treatment at risk.

The Agency for Healthcare Research and Quality has grant money, but nobody to hand it out.

The bioactivity of complex organic macrocycles can vary unpredictably with their three-dimensional structural contours. Here, we present a streamlined, programmable and systematic strategy for skeletal remodeling of large organic rings. The central diversification platform (hub) is a readily available macrocyclic olefin or a diene. Six transformations, all but one catalytic, are needed: macrocyclic ring-opening/cross-metathesis for cleaving a ring to generate a diene, cross-metathesis and allylic substitution for one-unit chain homologation, alkene isomerization and ethenolysis for one-unit chain clipping, and macrocyclic ring-closing metathesis for reforming a ring. The methods are practical, mild, efficient, and amenable to iteration. Fourteen analogs of anti-cancer agent epothilone C (the primary model macrocycle) were accessed through a divergent network of reactions that correspond to an average of three steps per analog from the diene hub.

Major questions remain about how H5N1 moves between dairy cows and from farm to farm.

Octopuses use the same system for sensing food or a mate, which has implications for speciation

Covalent protein drugs offer therapeutic potential but are limited by slow target engagement and the absence of high-throughput selection platforms. Rapid covalent binding requires coordinated optimization of affinity, stability, and warhead geometry-an intrinsically multidimensional challenge. We develop a yeast display platform coupled with chemoselective modification that enables selection of fast-acting covalent proteins without increasing intrinsic warhead reactivity. Using this system, we engineered a covalent programmed death-ligand 1 (PD-L1) antagonistic nanobody with rapid crosslinking kinetics (<i>k</i>_obs = 0.18 min^-1, t_1/2 = 3.8 min) and improved tumor suppression compared with envafolimab and atezolizumab. Similarly, we engineered a fast-acting covalent interleukin-18 (IL-18) (<i>k</i>_obs = 0.54 min^-1, t_1/2 = 1.3 min) and a covalent miniprotein targeting the receptor binding domain (RBD) of SARS-CoV-2, demonstrating applicability across protein modalities.

mRNA can be engineered to overcome cancer evolution.

More than 60 countries are off track to meet U.N. target for 2030-even though solutions exist.

The integrated stress response (ISR) is essential for cellular homeostasis and cognitive function. We investigated how persistent ISR activation affects cognitive performance by studying the PPP1R15B^R658C genetic variant associated with intellectual disability. To model this condition, we generated a mouse line with the pathogenic allele inserted. This variant destabilized the PPP1R15B•PP1 phosphatase complex, causing persistent ISR activation, impaired protein synthesis, and long-term memory deficits. We demonstrated that the cognitive and synaptic impairments in <i>Ppp1r15b</i>^R658C mice arise directly from ISR activation. Furthermore, we characterized DP71L, a viral ortholog of PPP1R15B, which acted as a potent pan-ISR inhibitor. DP71L reversed the cognitive and synaptic deficits across mouse models of Down syndrome, Alzheimer's disease, and aging, and enhanced synaptic plasticity and memory in healthy mice.

Biocompatible integration of synthetic materials with living tissue remains a major challenge for bioelectronics. In this case, substrate-free conducting polymer (CP) interfaces could help bridge this gap. We report in vivo assembly of n-doped poly(benzodifurandione) (n-PBDF) using whole blood-catalyzed polymerization in awake zebrafish and mice. This approach leverages endogenous catalysts, specifically hemoproteins, to form stable, thermally and ionically sensitive CP networks, ensuring long-term compatibility throughout the lifespan. We showcase the impact of this interface through reversible, cellular, and subcellular neuromodulation using near-infrared (NIR) light, including in vivo polymerized n-PBDF. Electrophysiological studies confirmed that n-PBDF alters intrinsic sodium ion channel excitability, and NIR light stimulation amplifies this modulation through thermoionic-induced shunting, providing on-demand, millisecond-scale reversible inhibitory control of excitability, a feature recapitulated in actively behaving mice.

Every year, AAAS members vote in the AAAS annual election for leaders who can serve the scientific community and advance the AAAS mission. Following are the results of the most recent election, which was held 27 January 2026 through 2 February 2026. Terms began on 25 February 2026.

Transient membrane constrictions, or "pearling," underlie the regular spacing of mitochondrial genomes.

Stellar explosions seemingly replayed as gravity bends their light could resolve a dispute over the speed of the expanding universe.

Long-read sequencing of cancer genomes reveals genomic rearrangements driven by mobile elements

A light-sensitive semiconductive polymer is synthesized within living animals by a blood protein catalyst.

The structure and dynamics of adsorbed atoms (adatoms) at solid-liquid interfaces determine the performance of advanced catalysts, electrochemical devices, molecular separation technologies, and metal extraction from waste streams. However, in situ investigations of atomically dispersed metals in various chemical environments have been prevented by insufficient imaging resolution and solvent incompatibility. In this study, we combined a specimen design that provides atomic resolution in liquid-phase electron microscopy with deep learning-enabled analysis to explore the interactions between gold adatoms, graphite support, and the solvent collectively. We tracked the locations of >10⁶ graphite-supported gold adatoms, dimers, and larger clusters in five solvents. Although their initial atomic dispersion was determined by the solvent polarity, fast drying kinetics at low temperature was required for optimizing catalytic performance.

Sensory systems for mate recognition maintain species boundaries and influence diversification. Thus, uncovering how molecules and receptors evolve to mediate this critical function is essential to understanding biodiversity. Male octopuses use a specialized arm called the hectocotylus to identify females and navigate their internal organs to reach the oviduct and deliver sperm. Here, we discovered that the hectocotylus is a dual sensory and mating organ that uses contact-dependent chemosensation of progesterone, a conserved ovarian hormone. We identified chemotactile receptors for progesterone and resolved the structural basis for their evolution from ancestral neurotransmitter receptors and subsequent expansion and tuning across cephalopods. These findings reveal principles by which sensory innovations shape reproductive behavior and suggest mechanisms for how sensory evolution contributes to the diversification of life.

Animal diversification across the Ediacaran-Cambrian transition was a crucial event in Earth history, fundamentally altering our planet and its biosphere. However, Ediacaran fossil assemblages show limited overlap with those from the Cambrian, obscuring the critical interval when the animal phyla were diversifying. We report a new terminal Ediacaran fossil assemblage preserved as carbonaceous films from the Jiangchuan Biota, Yunnan, Southwest China. This assemblage diverges from coeval sites, preserving Ediacaran body fossils alongside recognizable nonbilaterians and bilaterian body and trace fossils. These include diverse vermiform animals and the oldest deuterostomes (stem-group ambulacrarians). Our discovery provides insight into the radiation of Bilateria, the most diverse and disparate animal clade.

Antiphage defense systems protect bacteria from viral infection and have inspired important biotechnologies such as CRISPR-Cas9 while also revealing the evolutionary roots of eukaryotic innate immunity. Many systems have been discovered by genomic colocalization, but this approach cannot identify systems outside of defense islands. We present DefensePredictor, a machine learning model that uses protein language model embeddings to classify proteins as defensive. Applying DefensePredictor to 69 diverse <i>Escherichia coli</i> strains, we predicted hundreds of previously unknown systems and experimentally validated 42 of them. Analysis of 1000 diverse prokaryotic genomes identified nearly 3000 protein clusters lacking homology to known systems, revealing a vast, uncharacterized defense repertoire. DefensePredictor will facilitate the comprehensive discovery of antiphage defense systems, which promises to reveal additional connections between prokaryotic and eukaryotic immunity and accelerate biotechnology development.

The distribution of mitochondrial DNA-containing nucleoids is essential for mitochondrial function and genome inheritance; however, no known mechanisms can explain nucleoid segregation or their regular positioning. In this work, we found that mitochondria frequently undergo a reversible biophysical instability termed "pearling," transforming from a tubular into a regularly spaced beads morphology. Physiological pearling imposed a characteristic length scale and simultaneously mediated nucleoid disaggregation and established internucleoid distancing with high precision. Pearling onset was triggered by calcium influx, whereas the density of lamellar cristae invaginations modulated pearling prevalence and preserved nucleoid spacing following recovery. The dysregulation of mitochondrial calcium influx or inner membrane cristae integrity caused aberrant nucleoid clustering. Our results identify pearling as a mechanism governing nucleoid distribution and inheritance and offer insights into its regulation.

Flexible, abstract rhythm perception underpins human music, dance, and speech, but thus far, it has only been demonstrated in a few birds and mammals. In this work, we show that bumble bees also form robust abstract rhythm representations. Free-flying bees learned to discriminate two arbitrary repeating flashing light sequences, balanced to preclude the use of any local cues. Bees successfully recognized these learned rhythmic patterns at new, faster, and slower tempi. Bees trained on vibrational patterns transferred their learning to equivalent flashing light patterns, demonstrating cross-modal rhythm perception. These findings suggest that an insect brain can encode and generalize arbitrary complex temporal patterns, which suggests that abstract rhythm perception can emerge from relatively simple neural architectures and points to deep evolutionary roots for a domain-general rhythm cognition across animals.