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Social calibration of sycophantic AI—Response
Wavelength-scale noise-resistant on-chip spectrometer
Structure and evolution-guided design of minimal RNA-guided nucleases
The design of RNA-guided nucleases with properties not limited by evolution can expand programmable genome-editing capabilities. However, generating diverse multidomain proteins with robust enzymatic properties remains challenging. Here, we use a protein design strategy that couples a structure-guided inverse-folding model with evolution-informed residue constraints to generate active, divergent variants of TnpB, a minimal CRISPR-Cas12–like nuclease, termed SynTnpBs. High-throughput screening of artificial intelligence–generated variants yielded editors that retained or exceeded wild-type activity in bacterial, plant, and human cells. Cryo–electron microscopy–based structure determination of the most divergent variant revealed stabilizing contacts in the RNA–DNA interfaces across conformations, demonstrating the design potential of this approach. Together, these results establish a strategy for creating non-natural RNA-guided nucleases and conformationally active nucleic acid binders, enlarging the designable protein space.
Coastal groundwater phosphorus drives global acceleration of algal blooms
Abstract Coastal algal blooms (CABs) are accelerating worldwide. This intensification is particularly puzzling in regions where nitrogen inputs have been curbed, yet blooms persist or worsen. Here we reveal excess dissolved inorganic phosphorus (DIP) from coastal groundwater as a critical, previously overlooked driver. Combining a process-based physical-chemical framework with global datasets, we find decadal CAB trends are more strongly linked to coastal DIP than to nitrogen availability or water-column stability. A global meta-analysis with site-specific time series demonstrates anoxic groundwater releases substantial DIP. This mechanism explains continued CABs under nitrogen control and aligns with a shift toward phosphorus limitation in many coastal regions. Spatial and temporal variation in CAB trends reflects aquifer geochemistry, with reducing groundwater fueling blooms and oxidized systems suppressing them. Our findings establish groundwater as a missing link in the modern coastal nutrient cycle and underscore the urgency for integrated nitrogenphosphorus management to mitigate the escalating impacts of CABs.
A first-in-class pulsatile FXR agonist for bile-acid-related liver diseases
Early fossil eukaryotes were benthic aerobes
Robust single-electron memory with quantum states manipulation
The ultimate goal of information storage is single-electron memory. Quantum mechanics predicts that two distinguishable quantum states can be realized by confining a single electron within an ultrasmall space. However, scaling down such devices paradoxically amplifies fringe capacitance effects, which hinders the experimental observation of single-electron memory. We report a two-dimensional single-electron memory device based on a coplanar drain-channel-source structure that suppressed fringe capacitance, exhibiting a nonvolatile threshold voltage shift of 0.5 volts after the change of a single electron. Two intriguing quantum behaviors have also been verified regarding the programming voltage. Additionally, we have predicted and observed a distinctive quantum memory effect: A quantum state is cut off by density of states scissors.
Pseudo point nodal superconducting gap in spin-triplet UTe2
Direct interaction of Vδ7 TCRs with IL17RA drives the differentiation of T <sub>H</sub> 1-like γδT cells
Of the three classes of lymphocytes that constitute the adaptive immune system, γδT cells are the only class for which the principles of antigen recognition remain enigmatic. Although endogenous γδT cell antigen receptor (γδTCR) ligands are thought to regulate γδT cell development, their identities are largely elusive. Here, we identified the interleukin 17 receptor A chain (IL17RA) as a γδTCR ligand that drove the differentiation of Vδ7 + γδT cells with a T helper 1 (T H 1)–like effector program in mice. IL17RA promoted this differentiation through an interaction involving germline-encoded regions of the Vδ7 chain, enabling the selection of cells with a diverse CDR3 repertoire and thus acting as a nonclonotypic γδTCR ligand. Together with the nonclonotypic mode of γδTCR engagement by butyrophilins, these results suggest that such interactions represent a general biological mechanism shaping the γδT cell compartment.
Permafrost carbon release scales linearly with overshoot warming mediated by AMOC tipping
Restored clearance of senescent neutrophils by tissue-resident macrophages limits organ aging
Aging disrupts tissue homeostasis across organ systems. Here, we identify tissue-resident macrophages (TRMs) as central coordinators of age-related organ decline through impaired clearance of senescent neutrophils, a process regulated by the immunomodulatory prostaglandin E2 (PGE 2 ) receptor EP2. Reducing TRM EP2 signaling in aged mice preserved youthful mitochondrial fitness and prevented cognitive decline, frailty, sarcopenia, adiposity, cardiac impairment, and systemic inflammation. Plasma proteomics implicated the liver as a major source of age-associated immune change, in which reduced TRM EP2 signaling rescued neutrophil efferocytosis and prevented paracrine stress in neighboring cells. Elevated TRM EP2 expression and senescent neutrophils were also observed in aged and diseased human tissues. Pharmacologic EP2 inhibition restored youthful neutrophil clearance, establishing impaired TRM efferocytosis as a reversible driver of organ decline in aging.
Saxiphilin functions as a toxin sponge protein that counteracts the effects of saxitoxin poisoning
Abstract Saxitoxin (STX) is among the most potent toxins known, is classified as a chemical weapon, and is the archetype of the paralytic shellfish toxin (PST) family produced by marine and freshwater harmful algal blooms (HAB). STX causes paralysis and death through inhibition of voltage-gated sodium channels (Na V s), has no antidote, and poses a public health and commercial fishing threat due to its accumulation in seafood and increasing HAB occurrences. Although STX is lethal to varied vertebrates, including humans, certain frogs resist STX poisoning. This phenotype is thought to depend on soluble toxin sponge high-affinity STX binding proteins (saxiphilins, Sxphs) that provide resistance through a competition mechanism different from classic target site ion channel mutation mechanisms. Here, we test this idea and show that a single dose of American bullfrog ( Rana catesbeiana ) Sxph ( Rc Sxph) is sufficient to counteract STX neurotoxicity and lethality in female mice using paradigms where STX and Sxph are administered together or sequentially in either order. Importantly, this function requires the Rc Sxph high-affinity STX binding site. Our findings provide in vivo validation that Sxphs are toxin sponges that protect against STX poisoning and highlight the potential to harness this protein class as antidotes for PSTs and other toxins.
Tree-killing beetle is spreading to urban forests around the world
As researchers piece together the pest’s global trek, countries are working to contain the growing threat
Rational design of polymer film morphology via structure-performance linkage for enhanced condensation performance
What tears can say
GA2AD: a generalized adaptive adversarial training framework considering surrounding hybrid risk field for autonomous driving
Fibromyalgia
Tidying up aging organs
A prostaglandin prevents macrophages from clearing toxic neutrophils in aging organs