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GORK K+ channel structure and gating vital to informing stomatal engineering
Detection of ferrihydrite in Martian red dust records ancient cold and wet conditions on Mars
Abstract Iron oxide-hydroxide minerals in Martian dust provide crucial insights into Mars’ past climate and habitability. Previous studies attributed Mars’ red color to anhydrous hematite formed through recent weathering. Here, we show that poorly crystalline ferrihydrite (Fe 5 O 8 H · nH 2 O) is the dominant iron oxide-bearing phase in Martian dust, based on combined analyses of orbital, in-situ, and laboratory visible near-infrared spectra. Spectroscopic analyses indicate that a hyperfine mixture of ferrihydrite, basalt and sulfate best matches Martian dust observations. Through laboratory experiments and kinetic calculations, we demonstrate that ferrihydrite remains stable under present-day Martian conditions, preserving its poorly crystalline structure. The persistence of ferrihydrite suggests it formed during a cold, wet period on early Mars under oxidative conditions, followed by a transition to the current hyper-arid environment. This finding challenges previous models of continuous dry oxidation and indicates that ancient Mars experienced aqueous alteration before transitioning to its current desert state.
Ergodic seismic precursors and transfer learning for short term eruption forecasting at data scarce volcanoes
Abstract Seismic data recorded before volcanic eruptions provides important clues for forecasting. However, limited monitoring histories and infrequent eruptions restrict the data available for training forecasting models. We propose a transfer machine learning approach that identifies eruption precursors—signals that consistently change before eruptions—across multiple volcanoes. Using seismic data from 41 eruptions at 24 volcanoes over 73 years, our approach forecasts eruptions at unobserved (out-of-sample) volcanoes. Tested without data from the target volcano, the model demonstrated accuracy comparable to direct training on the target and exceeded benchmarks based on seismic amplitude. These results indicate that eruption precursors exhibit ergodicity, sharing common patterns that allow observations from one group of volcanoes to approximate the behavior of others. This approach addresses data limitations at individual sites and provides a useful tool to support monitoring efforts at volcano observatories, improving the ability to forecast eruptions and mitigate volcanic risks.
Author Correction: A single-cell transcriptomic landscape of primate arterial aging
Fatigue-resistant and super-tough thermocells
Author Correction: Multi-objective observational constraint of tropical Atlantic and Pacific low-cloud variability narrows uncertainty in cloud feedback
Harnessing organic electrolyte for non-corrosive and wide-temperature Na-Cl2 battery
Structural basis for lipid-mediated activation of G protein-coupled receptor GPR55
Abstract GPR55 is an orphan G protein-coupled receptor (GPCR) and represents a promising drug target for cancer, inflammation, and metabolic diseases. The endogenous activation of lipid GPCRs can be solely mediated by membrane components and different lipids have been proposed as endogenous activators of GPR55, such as cannabinoids and lysophosphatidylinositols. Here, we determine high-resolution cryo-electron microscopy structures of the activated GPR55 in complex with heterotrimeric G13 and two structurally diverse ligands: the putative endogenous agonist 1-palmitoyl-2-lysophosphatidylinositol (LPI) and the synthetic agonist ML184. These results reveal insights into ligand recognition at GPR55, G protein coupling and receptor activation. Notably, an orthosteric binding site opening towards the membrane is observed in both structures, enabling direct interaction of the agonists with membrane lipids. The structural observations are supported by mutagenesis and functional experiments employing G protein dissociation assays. These findings will be of importance for the structure-based development of drugs targeting GPR55.
Dual functional POGases from bacteria encompassing broader O-glycanase and adhesin activities
Abstract Mucin-type O-glycans on glycoproteins are pivotal for biology and impact the quality of biotherapeutics. Furthermore, glycans on host cells serve as ligands for lectins/adhesins on bacteria for bacterium-host interactions in the colonization or attachment/invasion of bacteria. Defining the structure-function relationship of O-glycans is hindered by a lack of enzyme(s) to release sialylated O-glycans from glycoproteins. Here we show identification of endo-α-N-acetylgalactosaminidases (O-glycanases, GH101) with broad substrate specificities, termed Peptide:O-Glycosidase (POGase). In 5 POGase orthologs identified, we characterize one that releases sialylated O-glycans from glycopeptides, glycoproteins and biotherapeutics. Three peptide motifs differentiate the POGase existing in phylum Actinomycetota from known O-glycanases in other bacteria. While the GH101 domain classifies POGases, other domains confer the efficient enzyme activity and binding to major glycans decorating epithelial cells. The dual functional POGases encompassing broader O-glycanase and adhesin activities will facilitate the study of O-glycomics, quality assessment of biotherapeutics, and development of microbiology and medicine.
Highly efficient and eco-friendly green quantum dot light-emitting diodes through interfacial potential grading
Interdecadal modulation of Ningaloo Niño/Niña strength in the Southeast Indian Ocean by the Atlantic Multidecadal Oscillation
The TaCLE24b peptide signaling cascade modulates lateral root development and drought tolerance in wheat
Correlated states controlled by a tunable van Hove singularity in moiré WSe2 bilayers
Abstract Twisted transition metal dichalcogenide (TMD) bilayers have enabled the discovery of superconductivity, ferromagnetism, correlated insulators, and a series of new topological phases of matter. However, the connection between these electronic phases of matter and the underlying band structure singularities has remained largely unexplored. Here, combining magnetic circular dichroism and exciton sensing measurements, we investigate the influence of a van Hove singularity (vHS) on the correlated phases in bilayer WSe2 with twist angle between 2 and 3 degrees. By tuning the vHS across the Fermi level using electric and magnetic fields, we observe Stoner ferromagnetism below moiré lattice filling one and Chern insulators at filling one. The experimental observations are supported by the continuum model band structure calculations. Our results highlight the prospect of engineering electronic phases of matter in moiré materials by tunable van Hove singularities.
Functional proteoform group deconvolution reveals a broader spectrum of ibrutinib off-targets
Abstract Proteome-wide profiling has revealed that targeted drugs can have complex protein interaction landscapes. However, it’s a challenge to profile drug targets while systematically accounting for the dynamic protein variations that produce populations of multiple proteoforms. We address this problem by combining thermal proteome profiling (TPP) with functional proteoform group detection to refine the target landscape of ibrutinib. In addition to known targets, we implicate additional specific functional proteoform groups linking ibrutinib to mechanisms in immunomodulation and cellular processes like Golgi trafficking, endosomal trafficking, and glycosylation. Further, we identify variability in functional proteoform group profiles in a CLL cohort, linked to treatment status and ex vivo response and resistance. This offers deeper insights into the impacts of functional proteoform groups in a clinical treatment setting and suggests complex biological effects linked to off-target engagement. These results provide a framework for interpreting clinically observed off-target processes and adverse events, highlighting the importance of functional proteoform group-level deconvolution in understanding drug interactions and their functional impacts with potential applications in precision medicine.
A column-like organization for ocular dominance in mouse visual cortex
Abstract The columnar organization of response properties is a fundamental feature of the mammalian visual cortex. However, columns have not been observed universally across all mammalian species. Here, we report the discovery of clusters of ipsilateral eye preferring neurons in layer 4 of the mouse primary visual cortex. These clusters extend into layer 2/3 and upper layer 5, forming a column-like pattern for ocular dominance. Our observation of such structures in this minute cortical area sets a new boundary condition for models explaining the emergence of functional organizations in the neocortex.
Suppression of endothelial ceramide de novo biosynthesis by Nogo-B contributes to cardiometabolic diseases
A single-cell atlas to map sex-specific gene-expression changes in blood upon neurodegeneration
Abstract The clinical course and treatment of neurodegenerative disease are complicated by immune-system interference and chronic inflammatory processes, which remain incompletely understood. Mapping immune signatures in larger human cohorts through single-cell gene expression profiling supports our understanding of observed peripheral changes in neurodegeneration. Here, we employ single-cell gene expression profiling of over 909k peripheral blood mononuclear cells (PBMCs) from 121 healthy individuals, 48 patients with mild cognitive impairment (MCI), 46 with Parkinson’s disease (PD), 27 with Alzheimer’s disease (AD), and 15 with both PD and MCI. The dataset is interactively accessible through a freely available website (https://www.ccb.uni-saarland.de/adrcsc). In this work, we identify disease-associated changes in blood cell type composition and the gene expression in a sex-specific manner, offering insights into peripheral and solid tissue signatures in AD and PD.
Attenuated growth factor signaling during cell death initiation sensitizes membranes towards peroxidation
Abstract Cell death programs such as apoptosis and ferroptosis are associated with aberrant redox homeostasis linked to lipid metabolism and membrane function. Evidence for cross-talk between these programs is emerging. Here, we show that cytotoxic stress channels polyunsaturated fatty acids via lysophospholipid acyltransferase 12 into phospholipids that become susceptible to peroxidation under additional redox stress. This reprogramming is associated with altered acyl-CoA synthetase isoenzyme expression and caused by a decrease in growth factor receptor tyrosine kinase (RTK)-phosphatidylinositol-3-kinase signaling, resulting in suppressed fatty acid biosynthesis, for specific stressors via impaired Akt-SREBP1 activation. The reduced availability of de novo synthesized fatty acids favors the channeling of polyunsaturated fatty acids into phospholipids. Growth factor withdrawal by serum starvation mimics this phenotype, whereas RTK ligands counteract it. We conclude that attenuated RTK signaling during cell death initiation increases cells’ susceptibility to oxidative membrane damage at the interface of apoptosis and alternative cell death programs.
Assessing the climate benefits of afforestation in the Canadian Northern Boreal and Southern Arctic
Abstract Afforestation greatly influences several earth system processes, making it essential to understand these effects to accurately assess its potential for climate change mitigation. Although our understanding of forest-climate system interactions has improved, significant knowledge gaps remain, preventing definitive assessments of afforestation's net climate benefits. In this review, focusing on the Canadian northern boreal and southern arctic, we identify these gaps and synthesize existing knowledge. The review highlights regional realities, Earth's climatic history, uncertainties in biogeochemical (BGC) and biogeophysical (BGP) changes following afforestation, and limitations in current assessment methodologies, emphasizing the need to reconcile these uncertainties before drawing firm conclusions about the climate benefits of afforestation. Finally, we propose an assessment framework which considers multiple forcing components, temporal analysis, future climatic contexts, and implementation details. We hope that the research gaps and assessment framework discussed in this review inform afforestation policy in Canada and other circumpolar nations.
Local halide heterogeneity drives surface wrinkling in mixed-halide wide-bandgap perovskites
Abstract Compositional heterogeneity in wide-bandgap (1.8 − 2.1 eV) mixed-halide perovskites is a key bottleneck in the processing of high-quality solution-processed thin films and prevents their application in efficient multijunction solar cells. Notably, mixed-cation (formamidinium-methylammonium) wide-bandgap perovskite films are prone to form micrometer-scale wrinkles which can interfere with the smooth surfaces ideal for multijunction devices. Here, we study the formation dynamics of wrinkled mixed-halide perovskite films and its impact on the local composition and optoelectronic properties. We use in situ X-ray scattering during perovskite film formation to show that crystallization of bromide-rich perovskites precedes that of mixed-halide phases in wrinkled films cast using an antisolvent-based process. Using nanoscopic X-ray fluorescence and hyperspectral photoluminescence imaging, we also demonstrate the formation of iodide- and bromide-rich phases in the wrinkled domains. This intrinsic spatial halide segregation results in an increased local bandgap variation and Urbach energy. Morphological disorder and compositional heterogeneity also aggravate the formation of sub-bandgap electronic defects, reducing photostability and accelerating light-induced segregation of iodide and bromide ions in thin films and solar cells.