Browse Articles

Archaeal and eukaryotic MCM rings sequentially melt DNA for replication initiation

Abstract DNA replication initiation requires local melting of fully base-paired DNA for a helicase to gain a foothold and initiate processive DNA unwinding. In eukaryotes and archaea, the helicase engine is the hexameric ring minichromosome maintenance (MCM) complex. In eukaryotes, a defined biochemical sequence assembles two Cdc45-MCM-GINS (CMG) complexes that provide limited DNA unwinding as the species that immediately precedes extensive unwinding. A prior structure revealed how MCM subunits interact with this form of DNA, but the atomic progression from undistorted DNA to this melted DNA species is unknown. Here, we present a sequential DNA melting mechanism determined by snapshots of an archaeal MCM ring with DNA in varying degrees of melting. In this mechanism, successive ATP-binding at MCM ATPase sites drives sequential discrete DNA melting steps mediated a specific MCM aromatic residue. Analysis of eukaryotic structures shows loaded MCM rings principally adopt only two molecular arrangements at the ATPase: one that does not melt DNA and one tuned to melt DNA with equivalent aromatic residues, indicating a universal sequential mechanism melts DNA in archaea and eukaryotes for replication initiation.

Disentangling the Janus-faced effects of cations in electrocatalysis

Abstract Cation identity and concentration strongly influence electrocatalytic processes, yet their effects remain insufficiently understood. Taking hydrogen evolution reaction in alkaline media as a model system, variations in cation concentration induce complex, sometimes inverted, activity trends. Increasing cation concentration can either promote or inhibit electrocatalytic activity depending on cation identity, electrode material and solution pH. These Janus-faced effects of cations challenge the current understandings of cation effects in electrocatalysis, which typically emphasize either promotional or inhibitory roles. Here, we propose a mechanistic rationale for the promoter-inhibitor transitions of cation effects and identify cation position in the electric double layer as the key factor governing this behavior. The theoretical framework distinguishes two cation states: cations electrostatically attracted in the diffuse layer, or cations specifically adsorbed at the inner Helmholtz plane. Incorporating the electric field effect on water dissociation beyond the Frumkin corrections, we show that the two cation states modulate the local electric field and thus kinetics in opposite ways. The observed inversions result from their competition, governed by cation size and adsorption strength. The framework and insights will be relevant to other electrocatalytic reactions at strongly negatively charged surfaces, such as CO 2 reduction.

The landscape and regulatory potential of eccDNAs in mammalian preimplantation embryos

Ultrahigh energy-storage in lead-free ceramic capacitors via local structure design

Iontronic click-to-release enables electrically controlled delivery of drugs and biomolecules beyond charge and size limitations

Abstract Dynamic and programmable control of therapeutic delivery is a long-standing goal in medicine. Iontronic devices offer precise electronic control over the dosage of bioactive molecules, yet their use has been confined to charged, low-molecular-weight compounds that are electrochemically stable during transport. Here, we present a hybrid delivery platform that integrates iontronic transport with bioorthogonal click-to-release chemistry. In this system, iontronic pumps electrophoretically deliver charged tetrazines as molecular scissors that selectively react with immobilized trans -cyclooctene (TCO)-linked payloads, enabling on-demand bioorthogonal cleavage of the TCO linker and controlled payload release. This approach retains the electronic precision of iontronics while overcoming molecular size, charge, and stability constraints. We demonstrate tunable tetrazine delivery over several days and electronically controlled release of immobilized payloads from small bioactive molecules, such as the antimitotic agent CA4, to the large protein bovine serum albumin. Hence, by integrating bioorthogonal click-to-release strategies, iontronic delivery is extended to biologically relevant macromolecules, providing a foundation for advanced programmable electroceutical devices.

Humanity is heading back to the Moon — why aren’t more scientists thrilled?

A myoneural actuator with engineered biophysics for implantable biohybrid systems

In-fibre logic and memory via tuneable passivation–corrosion

Abstract Textile electronics with digital capabilities could sense, process, and store data, while providing immersive interaction with user and their immediate surroundings. However, existing textile electronic systems are typically built on von Neumann architecture and rigid chips, limiting their seamless integration with clothing. Here, we propose a single-fibre logic/memory electronic device based on interface passivation-corrosion whose functions do not depend on traditional carrier heterojunction interfaces. The same fibre can be switched to operate as either a diode or a memristor. The diode mode remains stable under higher voltages and longer cycling periods than the state-of-the-art anion–cation heterojunction fibres. The fibre electronics are highly stretchable (up to 50%), and are compatible with industry-standard weaving techniques. We also demonstrate the application of these fibres in “AND” and “OR” logic gates, neuromorphic synapses, and textile memristor arrays. Regulated passivation-corrosion-enabled logic and memory in fibres offers a promising avenue for the next-generation textile computing.

The archaeal roots of eukaryotic life

Resolving the biological and geological events that led to the origin of eukaryotes is an ongoing challenge in biology. A major step in the evolution of complex cellular life was the merger between an ancestral host cell and a bacterium (that became the mitochondrion) some two billion years ago. Recently, metagenomics has enabled the reconstruction of a broad diversity of genomes, referred to as the Asgard Archaea. The Asgards are monophyletic with eukaryotes on the tree of life. Asgards have an array of genes, previously thought exclusive to eukaryotes, involved in cellular trafficking, the ubiquitin system, endosomal sorting, and cytoskeleton formation, with growing evidence demonstrating the functions of these proteins mirror those in eukaryotes. This gene repertoire suggests that these Archaea are descendants of the archaeal host from which eukaryotes evolved. Increased sampling has revealed that Asgard lineages are metabolically versatile and play key roles in various ecosystems and uncovered evolutionary transitions between Archaea and eukaryotes, such as innovations in eukaryotic defense systems. The positioning of eukaryotes in the Asgards is debated, but eukaryotes appear to branch within the Heimdallarchaeia. Lineages within this group, particularly Hodarchaeales and Kariarchaeaceae, contain a broad repertoire of eukaryote-like traits, including high-energy yielding metabolisms. Observing and studying Asgard interactions with bacterial descendants of mitochondria in a modern setting will transform our understanding of the origin of complex cellular life.

Artemis II mission is about to fly humans to the Moon — here’s the science they’ll do

Natural photosynthetic system for restoring homeostasis of animal organelle interaction network

The ecological and developmental foundations of brood parasitism in a catfish

Abstract Interspecific brood parasitism has evolved repeatedly from parental care. However, many non-avian brood-parasitic lineages have ancestors lacking parental care, leaving the foundations of brood parasitism in these lineages enigmatic. We examine ecological, reproductive, and developmental data from the Lake Tanganyika radiation of Synodontis catfishes, where one species, the cuckoo catfish, exhibits brood parasitism of mouthbrooding cichlid fishes. Our comparative analyses, coupled with experimental parasitism, suggest that a combination of ancestral traits (large eggs and rapid embryo development) enabled the origin of brood parasitism. Evolutionary innovations then presumably enhanced the success of brood parasitism after it emerged. Novel traits comprise frequent production of small clutches to effectively utilize host availability, the evolution of egg mimicry to facilitate host egg adoption, and modifications to development to enhance the performance of catfish embryos in the host’s buccal cavity. Interestingly, despite the distinct ecological and life history contexts of the origin of catfish brood parasitism, its evolutionary and developmental outcomes align with those of canonical avian brood parasites. This suggests that general patterns are repeated in the evolution of brood parasitism, despite disparate starting conditions.

Preventing peritendinous adhesions using lubricious supramolecular hydrogels

Many small climate change impacts presage rapid population extinction in a common iconic bird

Induction and regulation of reversible suspended animation in C. elegans

Abstract Suspended animation, a state of profound metabolic, behavioral and developmental quiescence, is a remarkable yet poorly understood stress resilience strategy in animals. Here, we describe a previously uncharacterized form of suspended animation inducible by high-population density in isosmotic liquids in C. elegans throughout larval development and adulthood. Transcriptomic, metabolomic, and live-cell activity reporter imaging analyses reveal striking molecular and cellular landscape changes caused by such liquid-induced suspended animation (LISA), including remodeling of gene expression programs, energy metabolites, lysosomal and mitochondrial morphology. Genetic screens identify mutants with altered stress responses and survival against LISA. While key endo-lysosomal regulators promote survival during LISA, organelle remodeling and a neuronal axis via downstream neuropeptide and cAMP/PKA signaling orchestrate behavioral awakening from LISA. Our findings define a facile paradigm for reversible SA, providing a powerful model system to uncover key molecular and cellular mechanisms governing an extreme case of reversible life arrest and dormancy.

Exploiting underpotential deposited hydrogen enables energy-efficient nitrate electroreduction to ammonia

Disparities in childhood human capital investments in the United States

Roadmap of phase transitions in hafnia-based superlattice films

Abstract Hafnia-based ferroelectrics hold significant promise for next-generation non-volatile memory. However, their functional properties are critically limited by uncontrollable phase transitions due to the poorly understood atomistic mechanisms driving specific transformations. Here, using single-crystalline HfO 2 -based superlattice films as the prototype system, we propose an asynchronous sublattice distortion mechanism underlying the complex phase transitions in HfO 2 -based materials. Aberration-corrected transmission electron microscopy reveals that sublattice preferential distortion behaviors trigger various phase transitions among orthorhombic, tetragonal and monoclinic phases, processes governed by the direction of orthorhombic phase. Critically, the complex lattice distortion pathways underlying the orthorhombic-to-monoclinic transition are elucidated, revealing their fundamental dependence on the monoclinic projection direction. Furthermore, polar-antipolar transition within the orthorhombic phase requires only oxygen sub-lattice dipole-order reversal, enabling polarization flipping. This work systematically clarifies the core mechanisms of structural phase transitions in HfO 2 -based films, resolving previous controversies and providing a guidance for designing high-performance HfO 2 -based electronic devices.

The global phylogeography of rapidly expanding multidrug resistant Ural lineage 4.2 Mycobacterium tuberculosis

Abstract Multidrug resistant tuberculosis (MDR-TB) epidemics are sustained by transmission of reproductively fit MDR M. tuberculosis ( Mtb ) strains. We search a large publicly available dataset of ~200,000 Mtb whole genome sequences to identify strains related to a highly successful MDR clade circulating in Moldova belonging to lineage 4.2.1/Ural. We characterize a clade of 1604 drug-resistant Mtb sequences harboring conserved resistance-conferring mutations. We identify the Russian Federation as the most likely country of origin for this clade and infer several independent migration events from Russia and Moldova to other European and Asian countries. We estimate that this clade is expanding more rapidly than comparable clades of lineage 4.2.1/Ural. The broad dispersal of this highly successful clade is an urgent global health threat. Genomic surveillance is essential to track the evolution and spread of this and other strains of concern.

Structures of ZYG11B-EloB-EloC-substrate complex reveal mechanisms of CRL2ZYG11B assembly and function

Abstract ZYG11B is a substrate receptor of the Cullin2-RING E3 ligase (CRL2), mediating the Gly/N-degron pathway and contributing to diverse processes including cell cycle control, protein homeostasis, apoptosis, and innate immunity. While previous studies resolved the structure of its truncated ARM domain, how full-length ZYG11B coordinates substrate engagement and CRL2 ZYG11B assembly remains unclear. Here, we present cryo-EM structures of full-length human ZYG11B in complex with the EloB–EloC adaptor and a Gly/N-degron peptide, revealing a seahorse-like architecture with distinct interfaces for adaptor and substrate binding. Unexpectedly, ZYG11B adopts both monomeric and dimeric assemblies, with the dimer stabilizing two substrate-binding sites in opposite orientations. Functional assays demonstrate that interfaces mediating adaptor recruitment, substrate binding, and dimerization are essential for substrate degradation, suggesting a dynamic mechanism involving both assembly states. These findings provide a structural framework for understanding CRL2 ZYG11B -mediated ubiquitination and offer mechanistic insights that may inform the rational design of ZYG11B-based applications.