Loss of YAP in Schwann cells improves HNPP pathophysiology.

Rapid nerve conduction in the peripheral nervous system (PNS) is facilitated by the multilamellar myelin sheath encasing many axons of peripheral nerves. Charcot-Marie-Tooth type 1A (CMT1A), and hereditary neuropathy with liability to pressure palsy (HNPP) are common demyelinating inherited peripheral neuropathies and are caused by mutations in the peripheral myelin protein 22 (PMP22) gene. Duplication of PMP22 leads to its overexpression and causes CMT1A, while its deletion results in PMP22 under expression and causes HNPP. Here, we investigated novel targets for modulating the protein level of PMP22 in HNPP. We found that genetic attenuation of the transcriptional coactivator Yap in Schwann cells reduces p-TAZ levels, increased TAZ activity, and increases PMP22 in peripheral nerves. Based on these findings, we ablated Yap alleles in Schwann cells of the Pmp22-haploinsufficient mouse model of HNPP and identified fewer tomacula on morphological assessment and improved nerve conduction in peripheral nerves. These findings suggest YAP modulation may be a new avenue for treatment of HNPP.

Aerobic Exercise Mediates Neural Inefficiency Among Adolescents At Risk for Suicide.

This study examined the electroencephalograpy (EEG) coherence and working memory performance effects of a 9-week exercise program on a small group of adolescents at high suicide risk. We randomly assigned 26 adolescents at high suicide risk (based on their scores on the Adolescents Mental Health Inventory- AMHI) into equal sized exercise and no-exercise groups. Before and after the 9-week exercise program, all participants performed the Sternberg working memory task, during which we recorded their EEGs, with electrodes placed at F3, F4, C3, C4, P3, P4, T3, T4, O1, and O2 regions (using the International 10-20 system of EEG electrode placement). We measured working memory performance and inter-hemispheric (F3-F4, C3-C4, T3-T4, P3-P4, O1-O2) and intra-hemispheric (F3-C3, F3-T3, F3-P3, F3-O1, F4-C4, F4-T4, F4-P4, F4-O2) EEG coherence as an index of the participants' underlying neural efficiency. While we found no significant group differences in working memory performances, the exercise group, relative to the no-exercise group, exhibited lower inter- and intra-hemispheric EEG coherence while performing the working memory task. These EEG differences may reflect a mediating effect of aerobic exercise on these participants' neural efficiency.

Complete Bioconversion of Protopanaxadiol-Type Ginsenosides to Compound K by Extracellular Enzymes from the Isolated Strain Aspergillus tubingensis.

A compound K-producing fungus was isolated from meju (fermented soybean brick) and identified as the generally recognized as safe (GRAS) strain Aspergillus tubingensis. The extracellular enzymes obtained after the cultivation of 6 days in the medium with 20 g/L citrus pectin as an inducer showed the highest compound K-producing activity among the inducers tested. Under the optimized conditions of 0.05 mM MgSO4, 55 °C, pH 4.0, 13.4 mM protopanaxadiol (PPD)-type ginsenosides, and 11 mg/mL enzymes, the extracellular enzymes from A. tubingensis completely converted PPD-type ginsenosides in the ginseng extract to 13.4 mM (8.35 mg/mL) compound K after 20 h, with the highest concentration and productivity among the results reported so far. As far as we know, this is the first GRAS enzyme to completely convert all PPD-type ginsenosides to compound K.

Biotransformation of Protopanaxadiol-Type Ginsenosides in Korean Ginseng Extract into Food-Available Compound K by an Extracellular Enzyme from Aspergillus niger.

Compound K (C-K) is one of the most pharmaceutically effective ginsenosides, but it is absent in natural ginseng. However, C-K can be obtained through the hydrolysis of protopanaxadiol-type ginsenosides (PPDGs) in natural ginseng. The aim of this study was to obtain the high concentration of food-available C-K using PPDGs in Korean ginseng extract by an extracellular enzyme from Aspergillus niger KACC 46495. A. niger was cultivated in the culture medium containing the inducer carboxymethyl cellulose (CMC) for 6 days. The extracellular enzyme extracted from A. niger was prepared from the culture broth by filtration, ammonium sulfate, and dialysis. The extracellular enzyme was used for C-K production using PPDGs. The glycoside-hydrolyzing pathways for converting PPDGs into C-K by the extracellular enzyme were Rb1 → Rd → F2 → C-K, Rb2 → Rd or compound O → F2 or compound Y → C-K, and Rc → Rd or compound Mc1 → F2 or compound Mc → C-K. The extracellular enzyme from A. niger at 8.0 mg/ml, which was obtained by the induction of CMC during the cultivation, converted 6.0 mg/ml (5.6 mM) PPDGs in Korean ginseng extract into 2.8 mg/ml (4.5 mM) food-available C-K in 9 h, with a productivity of 313 mg/l/h and a molar conversion of 80%. To the best of our knowledge, the productivity and concentration of C-K of the extracellular enzyme are the highest among those by crude enzymes from wild-type microorganisms.

Is vehicle automation enough to prevent crashes? Role of traffic operations in automated driving environments for traffic safety.

Automated driving systems (ADSs) are expected to prevent traffic accidents caused by driver carelessness on freeways. There is no doubt regarding this safety benefit if all vehicles in the transportation system were equipped with ADSs; however, it is implausible to expect that ADSs will reach 100% market penetration rate (MPR) in the near future. Therefore, the following question arises: 'Can ADSs, which consider only situations in the vicinity of an equipped vehicle, really contribute to a significant reduction in traffic accidents?' To address this issue, the interactions between equipped and unequipped vehicles must be investigated, which is the purpose of this study. This study evaluated traffic safety at different MPRs based on a proposed index to represent the overall rear-end crash risk of the traffic stream. Two approaches were evaluated for adjusting longitudinal vehicle maneuvers: vehicle safety-based maneuvering (VSM), which considers the crash risk of an equipped vehicle and its neighboring vehicles, and traffic safety-based maneuvering (TSM), which considers the overall crash risk in the traffic stream. TSM assumes that traffic operational agencies are able to monitor all the vehicles and to intervene in vehicle maneuvering. An optimization process, which attempts to obtain vehicle maneuvering control parameters to minimize the overall crash risk, is integrated into the proposed evaluation framework. The main purpose of employing the optimization process for vehicle maneuvering in this study is to identify opportunities to improve traffic safety through effective traffic management rather than developing a vehicle control algorithm that can be implemented in practice. The microscopic traffic simulator VISSIM was used to simulate the freeway traffic stream and to conduct systematic evaluations based on the proposed methodology. Both TSM and VSM achieved significant reductions in the potential for rear-end crashes. However, TSM obtained much greater reductions when the MPR was greater than 50%. This study should inspire transportation researchers and engineers to develop effective traffic operations strategies for automated driving environments.

Evaluating the effectiveness of active vehicle safety systems.

Advanced vehicle safety systems have been widely introduced in transportation systems and are expected to enhance traffic safety. However, these technologies mainly focus on assisting individual vehicles that are equipped with them, and less effort has been made to identify the effect of vehicular technologies on the traffic stream. This study proposed a methodology to assess the effectiveness of active vehicle safety systems (AVSSs), which represent a promising technology to prevent traffic crashes and mitigate injury severity. The proposed AVSS consists of longitudinal and lateral vehicle control systems, which corresponds to the Level 2 vehicle automation presented by the National Highway Safety Administration (NHTSA). The effectiveness evaluation for the proposed technology was conducted in terms of crash potential reduction and congestion mitigation. A microscopic traffic simulator, VISSIM, was used to simulate freeway traffic stream and collect vehicle-maneuvering data. In addition, an external application program interface, VISSIM's COM-interface, was used to implement the AVSS. A surrogate safety assessment model (SSAM) was used to derive indirect safety measures to evaluate the effectiveness of the AVSS. A 16.7-km freeway stretch between the Nakdong and Seonsan interchanges on Korean freeway 45 was selected for the simulation experiments to evaluate the effectiveness of AVSS. A total of five simulation runs for each evaluation scenario were conducted. For the non-incident conditions, the rear-end and lane-change conflicts were reduced by 78.8% and 17.3%, respectively, under the level of service (LOS) D traffic conditions. In addition, the average delay was reduced by 55.5%. However, the system's effectiveness was weakened in the LOS A-C categories. Under incident traffic conditions, the number of rear-end conflicts was reduced by approximately 9.7%. Vehicle delays were reduced by approximately 43.9% with 100% of market penetration rate (MPR). These results imply that from the perspective of traffic operations and control to address the safety and congestion issues of a traffic stream, smarter management strategies that consider both traffic conditions and MPR are required to fully exploit the effectiveness of the AVSS in the field.