Browse Articles
Discover research articles across all indexed journals
Lactam Framework Editing via Formal Methylene Deletion
Graphene oxide-polydopamine membranes with controlled interlayer spacing
Correction to “In Vivo Multiplexed Analysis of Aminopeptidase Activities by Hyperpolarized Molecular Probes for Tumor Diagnostic Applications”
Regression to the mean can explain saturation of geomagnetic storms
Abstract Extreme space weather events on Earth occur during intervals of strong solar wind driving 1 . The solar wind drives plasma convection and currents in the near-Earth space environment 2 . For low values of the driver, the Earth’s response is linear, estimated by parameters such as the polar cap index based on ground magnetometer activity 3 . Curiously, for extreme solar wind driving, the Earth’s response appears not to increase beyond a saturation limit 4 . Theorists have advanced a host of explanations for this saturation effect, but there is no consensus 5 . Here we demonstrate that this saturation is a manifestation of the regression to the mean effect 6 arising from random uncertainty in the timing and magnitude of solar wind measurements. Our results reveal that data analysis underpinning the saturation theories is nonlinearly biased, thereby challenging the validity of the theories. Correcting for the uncertainties reveals that the Earth’s response to solar wind driving is linear throughout, and that the impact of extreme geomagnetic storms can be twice as large as previously thought. We show that regression to the mean is a fundamental property of the relationship between measurement and the truth, where the truth corresponding to the measurement is closer to the mean. This effect is particularly pronounced for uncertain measurements of extreme values and is likely to manifest across various fields, from extreme climate studies to chronic medical pain.
Dynamic Covalent Programming at DNA Base-Pairing Interfaces
Selectivity Emerges from Indiscriminate Photoreduction
Proximity-Driven Protein Ligation Beyond the Concentration Limit
An ATPγS recycling strategy for practical biocatalytic thiophosphorylation
Small-Molecule Adhesives with Strong and Ductile Adhesion to PTFE, Yet Allowing Easy Wipe-Off Removal
Flatband λ-Ti <sub>3</sub> O <sub>5</sub> Nanoparticles Unlocking Near-Unity Solar Absorptivity for Ultrarobust Photothermal Antibiofouling
Metabolite glues as a means of purine sensing and chemotherapeutic response
Abstract Molecular glues stabilize weak interactions to impart new functionalities to complexes 1–3 . Although molecular glues have been described in plant signalling and as human therapeutics 4,5 , it is unclear whether this modality provides endogenous regulation in human cells. Here we show that purine nucleotides are molecular glues that tether the rate-limiting enzyme in purine biosynthesis—phosphoribosyl pyrophosphate amidotransferase (PPAT)—to its inhibitor NUDT5. This mechanism allows cells to sense the levels of purines and to establish essential feedback control of their synthesis. We refer to such molecules as metabolite glues. Thiopurine chemotherapeutics 6 , which have been in clinical use since the 1950s, glue the same complex but adopt distinct orientations for enhanced function. Unlike most known glues, the PPAT–NUDT5 metabolite-glue pocket can adjust its conformation to notable compound alterations, enabling increased glue potency and improved on-target activity. We therefore identify endogenous metabolite glues as a mode of nutrient sensing that can be exploited for therapeutic benefit.