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Exploration of Metastable A-Site-Ordered Perovskites (Ca,Ba)FeO_3−δ by Computationally Guided Multistep Synthesis

Coronin1A Regulates the Trafficking of Alpha Synuclein in Microglia

Microglia respond to cytotoxic protein aggregates associated with the progression of neurodegenerative disease. Pathological protein aggregates activate the microglial NLRP3 inflammasome resulting in proinflammatory signaling, secretion, and potentially pyroptotic cell death. We characterized mixed sex primary mouse microglia exposed to microbial stressors and alpha synuclein preformed fibrils (αsyn PFFs) to identify cellular mechanisms related to Parkinson's disease. Microglia package and release the endosome fate regulator Coronin1A (Coro1A) in EVs in an Nlrp3 -dependent manner in widely used experimental activation conditions. We were surprised to find that Coro1A packaging and release was not Nlrp3 -dependent in αsyn PFF exposure conditions. Coro1A −/− microglia exposed to αsyn PFFs trafficked more αsyn to the lysosomal compartment increasing lysosomal membrane permeabilization. This corresponds to a decrease in αsyn released in EVs suggesting that Coro1A functions to shunt pathological proteins to a secretory pathway to attenuate lysosomal stress. αsyn PFF-driven lysosomal stress resulting from Coro1a loss was associated with enhanced cytotoxicity. Intrinsic apoptosis signaling was unaffected, but we observed elevated cytosolic cathepsin B and the presence of a cathepsin-associated 55 kD PARP cleavage product. Postmortem analysis of the PD mesencephalon supported a role for Coro1A in microglia, revealing elevated levels of Coro1A protein in human PD brains compared with those of healthy donors. Findings are relevant to the distribution of pathological αsyn and indicate that Coro1a protects microglia from lysosomal overload, inflammasome activation, and pyroptotic demise.

Enantioselective Total Syntheses of (+)-Kobusine, (+)-Spirasine IX and the Purported Structure of (+)-Orgetine: Strategic Use of C–H Bonds

Solar-Driven Paired CO₂ Reduction–Alcohol Oxidation Using Semiartificial Suspension, Photocatalyst Sheet, and Photoelectrochemical Devices

Balancing Electronic Spin State via Atomically-Dispersed Heteronuclear Fe–Co Pairs for High-Performance Sodium–Sulfur Batteries

Ancient DNA shows Stone Age Europeans voyaged by sea to Africa

Selective Stepwise Reduction of Nitrate and Nitrite to Dinitrogen or Ammonia

Iron(III) Complexes with Luminescence Lifetimes of up to 100 ns to Enhance Upconversion and Photocatalysis

Diatomic C₂/NC Ligand Induced Conformation Variation of Trimetallic Clusters within a Carbon Cage

Magnetic Hysteresis in a Dysprosium Bis(amide) Complex

Transition State Analysis of SAMHD1 from Primary ¹⁸O, ³³P, and Solvent Kinetic Isotope Effects

Structural Influence of the Chemical Fueling System on a Catalysis-Driven Rotary Molecular Motor

Industrialization of Covalent Organic Frameworks

Photothermal Cavitation-Driven Micromotor to Penetrate Cell Membrane

Probing the Dynamics of Yersinia Adhesin A (YadA) in Outer Membranes Hints at Requirements for β-Barrel Membrane Insertion

Neural Dynamics of the Processing of Speech Features: Evidence for a Progression of Features from Acoustic to Sentential Processing

When we listen to speech, our brain’s neurophysiological responses “track” its acoustic features, but it is less well understood how these auditory responses are enhanced by linguistic content. Here, we recorded magnetoencephalography responses while subjects of both sexes listened to four types of continuous speechlike passages: speech envelope–modulated noise, English-like nonwords, scrambled words, and a narrative passage. Temporal response function (TRF) analysis provides strong neural evidence for the emergent features of speech processing in the cortex, from acoustics to higher-level linguistics, as incremental steps in neural speech processing. Critically, we show a stepwise hierarchical progression of progressively higher-order features over time, reflected in both bottom-up (early) and top-down (late) processing stages. Linguistically driven top-down mechanisms take the form of late N400-like responses, suggesting a central role of predictive coding mechanisms at multiple levels. As expected, the neural processing of lower-level acoustic feature responses is bilateral or right lateralized, with left lateralization emerging only for lexicosemantic features. Finally, our results identify potential neural markers, linguistic-level late responses, derived from TRF components modulated by linguistic content, suggesting that these markers are indicative of speech comprehension rather than mere speech perception.

Rational Construction of Layered Two-Dimensional Conjugated Metal–Organic Frameworks with Room-Temperature Quantum Coherence

Ion transport in helical-helical polypeptide polymerized ionic liquid block copolymers

Functional Design of Peptide Materials Based on Supramolecular Cohesion

Structure and function relationships of mucociliary clearance in human and rat airways