The tetracycline class of antibiotics is widely used for treating bacterial diseases including Lyme disease, anthrax, acne vulgaris, and pneumonia. Using a series of high-resolution cryo-electron microscopy (cryo-EM) structures, we show that tetracyclines can simultaneously target the mRNA decoding center in the 30S subunit and the nascent peptide exit tunnel (NPET) in the 50S...
Coral reefs face a perilous future due to global climate change compounded by the increasing prevalence of local stressors. Prominent among these is nutrient pollution, particularly nitrate eutrophication, which disrupts the coral-algal symbiosis and escalates reef degradation. While microbial denitrification is hypothesized to mitigate nitrate stress, the mechanisms underlying...
Precise temporal control of protein abundance is essential for dissecting dynamic cellular processes. While degron-based systems enable rapid protein depletion in eukaryotic cells, comparable tools are lacking for bacterial effectors delivered into host cells during infection. Here, we establish AIDE (Auxin-Inducible Degradation of Effectors), a host-directed degradation platform...
Pregnancy-related cardiovascular complications cause substantial morbidity and account for a large proportion of maternal deaths. The relationship between maternal age and pregnancy-related cardiovascular complications remains unclear. Most prior studies categorized patients using an age threshold, and previous studies did not delineate patients’ baseline cardiovascular risk...
Redox-related molecules, such as quinones and reactive oxygen species (ROS), are important signaling molecules for all living organisms. A plant-specific leucine-rich repeat receptor-like kinase (LRR-RLK) CANNOT RESPOND TO DMBQ 1 (CARD1), also known as HYDROGEN-PEROXIDE-INDUCED Ca2+ INCREASES (HPCA1), perceives both quinones and ROS, but the mechanism by which it distinguishes...
Nicotine is a neuroactive alkaloid produced by tobacco (Nicotiana tabacum) as a defence against herbivory, and an addictive stimulant that has been used by humans for millennia. Despite its significance, the core steps of its biosynthesis have remained elusive. Here, we demonstrate the in vitro reconstruction of a four-enzyme stereoselective biocatalytic cascade that forms (S...
The COP28 decision called for transitioning away from fossil fuels, sparking a growing interest in their full phase-out. However, energy system transformation pathways towards a phase-out of fossil fuels, which may reduce the reliance on carbon dioxide removal to meet the 1.5 °C goal, remain unclear. Here, we employ two global energy system models to explore energy system...
At planets that possess strong dipole magnetic fields, the Zwan-Wolf effect acts to squeeze plasma along magnetic flux tubes, aiding in the deflection of the solar wind flow about the planet. While the effect has been most studied at Earth, candidate observations have also been made at the outer planets. Here we present observations of the Zwan-Wolf effect occurring at Mars, an...
A quantum critical point develops when matter undergoes a continuous transformation between distinct ground states at absolute zero. It hosts pronounced quantum fluctuations, which render the system highly susceptible to external perturbations. While light-matter coupling has rapidly moved forward as a means to probe and control quantum materials, the capacity of quantum critical...
Ribosome arrest peptides undergo programmed translational stalling in response to changes in the cellular environment to feedback-regulate gene expression. CliM, an arrest peptide in Clostridia, is encoded upstream of the YidC membrane protein insertase gene, but its function and mechanism remain unclear. Here we show that CliM monitors YidC activity to maintain adequate cellular...
DKC1, a key coordinator of RNA modification and telomerase activity, has been implicated in colorectal cancer (CRC), yet its role in disease pathogenesis remains incompletely understood. We show that DKC1 drives CRC by promoting cell cycle progression, suppressing apoptosis, conferring stemness and drug resistance. Elevated DKC1 in CRC associates with poor prognosis and WNT...
Demyelinating diseases, including multiple sclerosis (MS), are characterized by loss of myelin and progressive neurodegeneration. It remains unclear if demyelination mouse models, such as cuprizone (CPZ) and lysophosphatidylcholine (LPC) elicit distinct responses or are comparable to human disease. Here, we integrate new and published single-cell transcriptomic datasets from CPZ...
Unsupervised learning—learning through repeated exposure without instruction or reward—is central to both machine learning and human cognition, including language acquisition and statistical learning. However, its role in visual perceptual learning (VPL) remains debated, as previous studies have not shown VPL for task-irrelevant but visible features, particularly in artificial...
Despite its strong influence on relative sea-level (RSL) rise, there is still low confidence in estimates of vertical land motion (VLM) and its contribution to RSL change. To address this problem, we synergize diverse VLM data, which now cover almost 65% of the coastal population, and are key to resolve small scale subsidence, including East, South, and Southeast Asian cities and...
Polyethylene terephthalate (PET) plastic waste causes serious environmental pollution due to insufficient recycling rates. Enzymatic PET depolymerization offers a sustainable recycling strategy, but limited stability and activity of current PET-degrading enzymes restrict practical implementation. Here, we engineer Polyester Hydrolase Leipzig 7 (PHL7), a PET hydrolase from a...
Lymphatic vessels are essential for tissue homoeostasis and their growth is regulated by vascular endothelial growth factor C (VEGF-C) signalling through VEGFR3. However, how VEGF-C balances lymphatic endothelial cells (LECs) proliferation versus sprouting to ensure functional vessel formation has remained unclear. Using high-fidelity conditional genetics and receptor-specific...
Brominated trityl radicals form stable enantiomers and present promising candidates for molecular qubits in spintronic and quantum technologies. However, their inherently weak photoluminescence (ϕ < 3 %) limits optical spin readout. Here, we report the synthesis of three carbazole-functionalized tris(2,4,6-tribromophenyl)methyl (TTBrM) radicals via Buchwald-Hartwig cross-coupling...
Nuclear-embedded mitochondrial DNA segments (NUMT) preserve a record of ongoing mitochondrial-to-nuclear DNA transfer during evolution, with important implications for disease mechanisms and genome organization. Here, we develop a pangenome graph-based NUMT detection approach, achieving a 2.52-fold improvement in sensitivity and generating a high-resolution human NUMT map...
The 3D spatiotemporal dynamics of tubular membrane protrusions are crucial for understanding phagocytosis, cellular communication and mechanobiology. Confocal microscopy, despite its prevalent use in membrane protrusion studies, presents limitations due to its inherently low axial resolution and high phototoxicity, which significantly hinder live imaging of tubular protrusion...
Electrocatalyst degradation, often caused by oxidative processes, forms a large barrier for the wide-spread application of electrolysers and fuel cells, which are crucial for a sustainable energy society. A detailed understanding of the catalyst surface structure under oxygen evolution reaction (OER) conditions is, therefore, required to design more stable catalysts. Here, we...
Proteolysis-targeting chimeras (PROTACs) co-op the ubiquitin system for targeted protein degradation, creating opportunities to interrogate cellular functions of proteins through “chemical knockdown”. However, matched pairs of protein degraders and inhibitors, that possess high specificity and chemical complementarity, for individual components of the ubiquitin system have...
The cerebellum’s involvement in cognitive functions is increasingly recognized, yet its developmental contribution to cognition remains poorly understood. The cerebellum undergoes rapid development in early life, paralleling major cognitive and behavioral changes. Although clinical studies have linked early cerebellar disruptions to profound developmental deficits, it remains...