Partial acetalization of cyclic imides using an intramolecular oxetanyl group

Acetalization of only one carbonyl group of cyclic imides has been achieved in good yields by the Lewis acid catalyzed isomerization of easily accessible N-(3-oxetanylmethyl)-substituted imides.Embargo Period 12 month

Reversal of neuroinflammation in novel GS model mice by single i.c.v. administration of CHO-derived rhCTSA precursor protein

Galactosialidosis (GS) is a lysosomal cathepsin A (CTSA) deficiency. It associates with a simultaneous decrease of neuraminidase 1 (NEU1) activity and sialylglycan storage. Central nervous system (CNS) symptoms reduce the quality of life of juvenile/adult-type GS patients, but there is no effective therapy. Here, we established a novel GS model mouse carrying homozygotic Ctsa IVS6+1g→a mutation causing partial exon 6 skipping with concomitant deficiency of Ctsa/Neu1. The GS mice developed juvenile/adult GS-like symptoms, such as gargoyle-like face, edema, proctoprosia due to sialylglycan accumulation, and neurovisceral inflammation, including activated microglia/macrophage appearance and increase of inflammatory chemokines. We produced human CTSA precursor proteins (proCTSA), a homodimer carrying terminal mannose 6-phosphate (M6P)-type N-glycans. The CHO-derived proCTSA was taken up by GS patient-derived fibroblasts via M6P receptors and delivered to lysosomes. Catalytically active mature CTSA showed a shorter half-life due to intralysosomal proteolytic degradation. Following single i.c.v. administration, proCTSA was widely distributed, restored the Neu1 activity, and reduced the sialylglycans accumulated in brain regions. Moreover, proCTSA suppressed neuroinflammation associated with reduction of activated microglia/macrophage and up-regulated Mip1α. The results show therapeutic effects of intracerebrospinal enzyme replacement utilizing CHO-derived proCTSA and suggest suppression of CNS symptoms

Tunable inverse spin Hall effect in nanometer-thick platinum films by ionic gating

金属が半導体に化ける可能性 --超薄膜の白金がトランジスタ特性を発揮することを発見--. 京都大学プレスリリース. 2018-08-08.Electric gating can strongly modulate a wide variety of physical properties in semiconductors and insulators, such as significant changes of conductivity in silicon, appearance of superconductivity in SrTiO3, the paramagnet–ferromagnet transition in (In, Mn)As, and so on. The key to such modulation is charge accumulation in solids. Thus, it has been believed that such modulation is out of reach for conventional metals where the number of carriers is too large. However, success in tuning the Curie temperature of ultrathin cobalt gave hope of finally achieving such a degree of control even in metallic materials. Here, we show reversible modulation of up to two orders of magnitude of the inverse spin Hall effect—a phenomenon that governs interconversion between spin and charge currents—in ultrathin platinum. Spin-to-charge conversion enables the generation and use of electric and spin currents in the same device, which is crucial for the future of spintronics and electronics