Direct interaction of DNMT inhibitors to PrP^C suppresses pathogenic process of prion

The conversion of the normal cellular prion protein(PrP^C) to the misfolded pathogenic scrapie prion protein(Pr PSc) is the biochemical hallmark of prion replication. So far, various chemical compounds that inhibit this conformational conversion have been identified. Here, we report the novel anti-prion activity of SGI-1027 and its meta/meta analogue(M/M), previously known only as potent inhibitors of DNA methyltransferases(DNMTs). These compounds effectively decreased the level of Pr PSc in cultured cells with permanent prion infection, without affecting PrP^Cat the transcriptional or translational levels. Furthermore, SGI-1027 prevented effective prion infection of the cells. In a Pr P aggregation assay, both SGI-1027 and M/M blocked the formation of misfolded Pr P aggregates, implying that binding of these compounds hinders the Pr P conversion process. A series of binding and docking analyses demonstrated that both SGI-1027 and M/M directly interacted with the C-terminal globular domain of PrP^C, but only SGI-1027 bound to a specific region of PrP^C with high affinity, which correlates with its potent antiprion efficacy. Therefore, we report SGI-1027 and related compounds as a novel class of potential antiprion agents that preferentially function through direct interaction with PrP^C.

Simultaneous blood flow and oxygenation measurements using an off-the-shelf spectrometer

Blood oxygenation and flow are both important parameters in a living body. In this Letter, we introduce a simple configuration to simultaneously measure blood flow and oxygenation using an off-the-shelf spectrometer. With the integration time of 10 ms, flow phantom measurements, a liquid blood phantom test, and an arm cuff occlusion paradigm were performed to validate the feasibility of the system. We expect this proof-of-concept study would be widely adopted by other researchers for acquiring both blood flow and oxygenation changes due to its straightforward configuration and the possibility of multimodal measurement.

Invariant submanifolds for systems of vector fields of constant rank

Given a system of vector fields on a smooth manifold that spans a plane field of constant rank, we present a systematic method and an algorithm to find submanifolds that are invariant under the flows of the vector fields. We present examples of partition into invariant submanifolds, which further gives partition into orbits. We use the method of generalized Frobenius theorem by means of exterior differential systems.