In Alzheimer's disease (AD), amyloid-beta (Aβ) peptides are produced by proteolytic cleavage of the amyloid precursor protein (APP), which can occur during synaptic vesicle (SV) cycling at presynapses. Precisely how amyloidogenic APP processing may impair presynaptic proteostasis and how to therapeutically target this process remains poorly understood. Using knock-in mouse models of early Aβ pathology, we found proteins with hampered degradation accumulate at presynaptic sites.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
September 2023
We used electrophysiology and Ca channel tethering to evaluate the performance of jGCaMP8 genetically encoded Ca indicators (GECIs). Orai1 Ca channel-jGCaMP8 fusions were transfected into HEK 293A cells and jGCaMP8 fluorescence responses recorded by simultaneous total internal reflection fluorescence microscopy and whole-cell patch clamp electrophysiology. Noninactivating currents from the Orai1 Y80E mutant provided a steady flux of Ca controlled on a millisecond time scale by step changes in membrane potential.
View Article and Find Full Text PDFThe electroreduction reaction of CO (ECORR) requires high-performance catalysts to convert CO into useful chemicals. Transition metal-based atomically dispersed catalysts are promising for the high selectivity and activity in ECORR. This work presents a series of atomically dispersed Co, Fe bimetallic catalysts by carbonizing the Fe-introduced Co-zeolitic-imidazolate-framework (C-Fe-Co-ZIF) for the syngas generation from ECORR.
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