Production of α-Bisabolol from metabolically engineered Escherichia coli

α-Bisabolol is a natural-occurring sesquiterpenoid with applications in cosmetics as whitening and soothing agent. It is synthesized from the universal precursors, isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP), which are generated either through the mevalonate (MVA) pathway or the 2C-methyl-D-erythritol-4-phosphate (MEP) pathway. Farnesyl pyrophosphate (FPP) synthase (IspA) then catalyzes the condensation of IPP and DMAPP to the linear FPP, which is rearranged and cyclized to α-bisabolol by bisabolol synthases. Here, we compared the capacity of 5 α-bisabolol synthases from Lippia dulcis, Streptomyces citricolor, Santalum spicatum, Matricaria recutita, and Artemisia annua for α-bisabolol production. MVA pathway and FPP synthase were also overexpressed to supply sufficient FPP for bisabolol synthesis in the recombinant E. coli. Bisabolol synthase from M. recutita (MrBBS) shows the highest activity of bisabolol synthesis, and 75 mg/L/OD600 of bisabolol was produced in a test-tube culture. We further optimized the expression level of IspA and MrBBS by modulation their RBS strength. The 24 bisabolol synthesis operons with different RBSs were assessed for their performance on bisabolol synthesis. By this approach, the best strain is able to produce bisabolol with a capacity of 220mg/L/OD600 in a test tube culture. The consequence of host strain optimization led to an increase in bisabolol production to 300 mg/L/OD600, which presents a 4-fold increase over the initial engineered strain. This work was supported by a grant (NRF-2016R1A2B2010678) from the National Research Foundation, MSIP, Korea

Negative Life Events and Problematic Internet Use as Factors Associated With Psychotic-Like Experiences in Adolescents

Objectives: Psychotic-like experiences (PLEs) and problematic internet use (PIU) are common in adolescents. However, little is known about the association between PLEs and PIU among adolescents. The present study examined the associations between PLEs and PIU and negative life events among adolescents.Methods: In total, 1,678 adolescents attending high school were recruited for a cross-sectional survey. They completed self-reported assessments of PLEs using the Prodromal Questionnaire-16 (PQ-16) and measures of depression, anxiety, self-esteem, internet use, and negative life events using the Center for Epidemiological Studies Depression Scale (CES-D), the State-Trait Anxiety Inventory (STAI), the Rosenberg Self-Esteem Scale (RSES), the Korean Scale for Internet Addiction (K-scale), and the Lifetime Incidence of Traumatic Events for Children (LITE-C), including cybersexual harassment and school violence.Results: A total of 1,239 subjects (73.8%) scored at least 1 on the PQ-16. The mean total and distress PQ-16 scores were significantly higher in students who used mental health services. The total and distress prodromal questionnaire-16 (PQ-16) scores were positively correlated with the CES-D, STAI-S, STAI-T, LITE-C, and K-scale scores but negatively correlated with the RSES score. Hierarchical linear regression analysis revealed that PLEs were significantly associated with a high K-scale score and the incidence of negative life events, such as LITE-C, cybersexual harassment, and bully–victims.Conclusion: Our results demonstrate that PIU and negative life experiences were significantly associated with PLEs in adolescents. Assessment and therapeutic intervention with regard to internet use as a coping strategy for stress are needed to prevent the development of clinical psychotic symptoms

Biomimetic Thermal-sensitive Multi-transform Actuator

Controllable and miniaturised mechanical actuation is one of the main challenges facing various emerging technologies, such as soft robotics, drug delivery systems, and microfluidics. Here we introduce a simple method for constructing actuating devices with programmable complex motions. Thermally responsive hydrogels based on poly(N-isopropylacrylamide) (PNIPAM) and its functionalized derivatives (f-PNIPAM) were used to control the lower critical solution temperature (LCST) or the temperature at which the gel volume changes. Techniques for ultra-violet crosslinking the monomer solutions were developed to generate gel sheets with controllable crosslink density gradients that allowed bending actuation to specified curvatures by heating through the LCST. Simple molding processes were then used to construct multi-transform devices with complex shape changes, including a bioinspired artificial flower that shows blossoming and reverse blossoming with a change in temperature

Impact of commercial cigarette smoke condensate on brain tissue co-cultured with astrocytes and blood-brain barrier endothelial cells

The purpose of the current study was to investigate the effect of two commercial cigarette smoke condensates (CCSC) on oxidative stress and cell cytotoxicity in human brain (T98G) or astrocytes (U-373 MG) in the presence of human brain microvascular endothelial cells (HBMEC). Cell viability of mono-culture of T98G or U-373 MG was markedly decreased in a concentration-dependent manner, and T98G was more susceptible than U-373 MG to CCSC exposure. Cytotoxicity was less prominent when T98G was co-cultured with HBMEC than when T98G was co-cultured with U-373 MG. Significant reduction in trans-epithelial electric resistance (TEER), a biomarker of cellular integrity was noted in HBMEC co-cultured with T98G (HBMEC-T98G co-culture) and U-373 MG co-cultured with T98G (U-373 MG-T98G co-culture) after 24 or 48 hr CCSC exposure, respectively. TEER value of U-373 MG co-cultured with T98G (79-84%) was higher than HBMEC co-cultured with T98G (62-63%) within 120-hr incubation with CCSC. Reactive oxygen species (ROS) generated by CCSC in mono-culture of T98G and U-373 MG reached highest levels at 4 and 16 mg/ml, respectively. ROS production by T98G fell when co-cultured with HBMEC or U-373MG. These findings suggest that adverse consequences of CCSC treatment on brain cells may be protected by blood-brain barrier or astrocytes, but with chronic exposure toxicity may be worsened due to destruction of cellular integrity.

Efficient hybrid organic-inorganic light emitting diodes with self-assembled dipole molecule deposited metal oxides

We investigate the effect of self-assembled dipole molecules (SADMs) on ZnO surface in hybrid organic-inorganic polymeric light-emitting diodes (HyPLEDs). Despite the SADM being extremely thin, the magnitude and orientation of SADM dipole moment effectively influenced the work function of the ZnO. As a consequence, the charge injection barrier between the conduction band of the ZnO and the lowest unoccupied molecular orbital of poly(9,9(')-dioctylfluorene)-co-benzothiadiazole could be efficiently controlled resulting that electron injection efficiency is remarkably enhanced. The HyPLEDs modified with a negative dipolar SADM exhibited enhanced device performances, which correspond to approximately a fourfold compared to those of unmodified HyPLEDs.open442

Ordinary kriging approach to predicting long-term particulate matter concentrations in seven major Korean cities

Objectives Cohort studies of associations between air pollution and health have used exposure prediction approaches to estimate individual-level concentrations. A common prediction method used in Korean cohort studies is ordinary kriging. In this study, performance of ordinary kriging models for long-term particulate matter less than or equal to 10 μm in diameter (PM10) concentrations in seven major Korean cities was investigated with a focus on spatial prediction ability. Methods We obtained hourly PM10 data for 2010 at 226 urban-ambient monitoring sites in South Korea and computed annual average PM10 concentrations at each site. Given the annual averages, we developed ordinary kriging prediction models for each of the seven major cities and for the entire country by using an exponential covariance reference model and a maximum likelihood estimation method. For model evaluation, cross-validation was performed and mean square error and R-squared (R2) statistics were computed. Results Mean annual average PM10 concentrations in the seven major cities ranged between 45.5 and 66.0 μg/m3 (standard deviation=2.40 and 9.51 μg/m3, respectively). Cross-validated R2 values in Seoul and Busan were 0.31 and 0.23, respectively, whereas the other five cities had R2 values of zero. The national model produced a higher crossvalidated R2 (0.36) than those for the city-specific models. Conclusions In general, the ordinary kriging models performed poorly for the seven major cities and the entire country of South Korea, but the model performance was better in the national model. To improve model performance, future studies should examine different prediction approaches that incorporate PM10 source characteristics