Browse Articles

Epigenomic and proteomic analyses provide insights into early-life immune regulation and asthma development in infants

Identifying potential risk genes for clear cell renal cell carcinoma with deep reinforcement learning

Patterns and drivers of Holocene moisture variability in mid-latitude eastern North America

Abstract Proxy data for eastern North American hydroclimate indicate strong and persistent multi-millennial droughts during the Holocene, but climate model simulations often fail to reproduce the proxy-inferred droughts. Diagnosing the data–model mismatch can offer valuable insights about the drivers of hydrological variability and different regional sensitivities to hydroclimate forcing. Here we present a proxy–modeling synthesis for Holocene climates in the eastern North American mid-latitudes, including machine-learning-based water balance reconstructions and high-resolution climate simulations. These data-model results resolve prior-generation inconsistencies, show consistent spatiotemporal patterns of Holocene hydroclimate change, and enable assessment of the driving mechanisms. This agreement suggests that the secular summer insolation trend, combined with the Laurentide Ice Sheet deglaciation and its effect on atmospheric circulation, together explain the extent and duration of drier-than-present climates. In addition, our high-resolution proxy data and transient simulations reveal clear multi-centennial climate variability. In our simulations, temperature-driven increases in evapotranspiration exceed regional precipitation gains, drying much of the region during the mid Holocene. This suggests that the mid-Holocene multi-millennial drought was driven by similar processes compared to the drying trajectory projected for mid-latitude North America over this century, which is also primarily driven by warming.

Edge polarization topology integrated with sliding ferroelectricity in Moiré system

Coherent photoelectrical readout of single spins in silicon carbide at room temperature

Abstract Establishing a robust and integratable quantum system capable of sensitive qubit readout at ambient conditions is a key challenge for developing prevalent quantum technologies, including quantum networks and quantum sensing. Paramagnetic colour centres in wide bandgap semiconductors provide optical single-spin detection, yet realising efficient electrical readout technology in scalable material will unchain developing integrated ambient quantum electronics. Here, we demonstrate photoelectrical detection of single spins in silicon carbide, a material amenable to large-scale processing and electronic integration. With efficient photocarrier collection, we achieve a 1.7–2 times better signal-to-noise ratio for single spins of silicon vacancies with electrical detection than with optical detection suffering from saturating fluorescence and internal reflection. Based on our photoionisation dynamics study, further improvement would be expected with enhanced ionisation. We also observe single-defect-like features in the photocurrent image where photoluminescence is absent in the spectrum range of silicon vacancies. The efficient electrical readout in the mature material platform holds promise for developing integrated quantum devices.

Molecular basis for the assembly of the Vps5-Vps17 SNX-BAR proteins with Retromer

Abstract Retromer mediates endosomal retrieval of transmembrane proteins in all eukaryotes and was first discovered in yeast in complex with the Vps5 and Vps17 sorting nexins (SNXs). Cryoelectron tomography (cryoET) studies of Retromer–Vps5 revealed a pseudo-helical coat on membrane tubules where dimers of the Vps26 subunit bind Vps5 membrane-proximal domains. However, the Vps29 subunit is also required for Vps5–Vps17 association despite being far from the membrane. Here, we show that Vps5 binds both Vps29 and Vps35 subunits through its unstructured N-terminal domain. A Pro-Leu (PL) motif in Vps5 binds Vps29 and is required for association with Retromer on membrane tubules in vitro, and for the proper recycling of the Vps10 cargo in Saccharomyces cerevisiae . CryoET of Retromer tubules with Vps5–Vps17 heterodimers show a similar architecture to the coat with Vps5–Vps5 homodimers, however, the spatial relationship between Retromer units is highly restricted, likely due to more limited orientations for docking. These results provide mechanistic insights into how Retromer and SNX-BAR association has evolved across species.

Author Correction: Lifecycle of a predatory bacterium vampirizing its prey through the cell envelope and S-layer

The road to commercial success for neuromorphic technologies

Unconditional advantage of noisy qudit quantum circuits over biased threshold circuits in constant depth

Quantifying hydrogen bonding using electrically tunable nanoconfined water

Abstract Hydrogen bonding plays a crucial role in biology and technology, yet it remains poorly understood and quantified despite its fundamental importance. Traditional models, which describe hydrogen bonds as electrostatic interactions between electropositive hydrogen and electronegative acceptors, fail to quantitatively capture bond strength, directionality, or cooperativity, and cannot predict the properties of complex hydrogen-bonded materials. Here, we introduce a concept of hydrogen bonds as elastic dipoles in an electric field, which captures a wide range of hydrogen bonding phenomena in various water systems. Using gypsum, a hydrogen bond heterostructure with two-dimensional structural crystalline water, we calibrate the hydrogen bond strength through an externally applied electric field. We show that our approach quantifies the strength of hydrogen bonds directly from spectroscopic measurements and reproduces a wide range of key properties of confined water reported in the literature. Using only the stretching vibration frequency of confined water, we can predict hydrogen bond strength, local electric field, O-H bond length, and dipole moment. Our work also introduces hydrogen bond heterostructures – a class of electrically and chemically tunable materials that offer stronger, more directional bonding compared to van der Waals heterostructures, with potential applications in areas such as catalysis, separation, and energy storage.

Unveiling cellular communications through rapid pan-membrane-protein labeling

Electrocatalytic N–C–N coupling over a hierarchically ordered open single-atom superstructure toward organonitrogen synthesis

Programmable protein stabilization with language model-derived peptide guides

Recent perspectives in clinical development of malaria vaccines

Mechanism of client loading from BiP to Grp94 and its disruption by select inhibitors

Abstract Hsp90 chaperones are a long-standing cancer drug target with numerous ATP-competitive inhibitors in clinical trials. Client proteins are transferred from Hsp70 to Hsp90 in a stepwise process of client delivery, loading, and trapping, but little is known about how inhibitors influence these steps. By examining the ER-resident BiP/Grp94 system (Hsp70/Hsp90 paralogs), we discover that some inhibitors allow BiP to push Grp94 into the client loading conformation, whereas other inhibitors block this conformational change and destabilize a BiP/client/Grp94 ternary complex. We uncover how BiP drives Grp94 into the client loading state and identify a structural explanation for why only a select group of inhibitors disrupt client loading on Grp94. These results show a client loading mechanism with specific shared features between the Hsp70/Hsp90 systems in the ER and cytosol and open a new avenue for rational Hsp90 drug design.

Environmental and molecular noise buffering by the cyanobacterial clock in individual cells

Abstract Circadian clocks enable organisms to anticipate daily cycles, while being robust to molecular and environmental noise. Here, we show how the clock of the cyanobacterium Synechococcus elongatus PCC 7942 buffers genetic and environmental perturbations through its core KaiABC phosphorylation loop. We first characterise single-cell clock dynamics in clock mutants using a microfluidics device that allows precise control of the microenvironment. We find that known clock regulators are dispensable for clock robustness, whilst perturbations of the core clock reveal that the wild type operates at a noise optimum that we can reproduce in a stochastic model of just the core phosphorylation loop. We then examine how the clock responds to noisy environments, including natural light conditions. The model accurately predicts how the clock filters out environmental noise, including fast light fluctuations, to keep time while remaining responsive to environmental shifts. Our findings illustrate how a simple clock network can exhibit complex noise filtering properties, advancing our understanding of how biological circuits can perform accurately in natural environments.

Dose-response relationship between evening exercise and sleep

Engineering intercellular communication using M13 phagemid and CRISPR-based gene regulation for multicellular computing in Escherichia coli

Abstract Engineering multicellular consortia, where information processing is distributed across specialized cell types, offers a promising strategy for implementing sophisticated biocomputing systems. However, a major challenge remains in establishing orthogonal intercellular communication, or “wires,” within synthetic bacterial consortia. In this study, we address this bottleneck by integrating phagemid-mediated intercellular communication with CRISPR-based gene regulation for multicellular computing in synthetic E. coli consortia. We achieve intercellular communication with high sensitivity by regulating the transfer of single guide RNAs (sgRNAs) encoded on M13 phagemids from sender to receiver cells. Once inside the receiver cells, the transferred sgRNAs mediate gene regulation via CRISPR interference. Leveraging this approach, we successfully constructed one-, two-, and four-input logic gates. Our work expands the toolkit for intercellular communication and paves the way for complex information processing in synthetic microbial consortia, with diverse potential applications, including biocomputing, biosensing, and biomanufacturing.

Water flipping and the oxygen evolution reaction on Fe2O3 nanolayers

Multi-color photonic integrated circuits based on homogeneous integration of quantum cascade lasers

Abstract We demonstrate an InP-based mid-infrared photonic integrated circuit processed from a wafer in which two distinct quantum cascade laser active regions are grown in different areas on the same InP crystal. A passive InGaAs waveguiding layer is epitaxially deposited on top of the entire InP substrate prior to the laser active region growth to optically couple the lasers emission and to multiplex their emission wavelengths to a single output waveguide. The method demonstrated in this work enables the creation of monolithic photonic integrated circuits with emission wavelength spanning the entire 3-15 µm spectral range and it is of interest for a wide range of applications.