Insights into the Mutation-Induced HHH Syndrome from Modeling Human Mitochondrial Ornithine Transporter-1

Human mitochondrial ornithine transporter-1 is reported in coupling with the hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome, which is a rare autosomal recessive disorder. For in-depth understanding of the molecular mechanism of the disease, it is crucially important to acquire the 3D structure of human mitochondrial ornithine transporter-1. Since no such structure is available in the current protein structure database, we have developed it via computational approaches based on the recent NMR structure of human mitochondrial uncoupling protein (Berardi MJ, Chou JJ, et al. Nature 2011, 476:109–113). Subsequently, we docked the ligand L-ornithine into the computational structure to search for the favorable binding mode. It was observed that the binding interaction for the most favorable binding mode is featured by six remarkable hydrogen bonds between the receptor and ligand, and that the most favorable binding mode shared the same ligand-binding site with most of the homologous mitochondrial carriers from different organisms, implying that the ligand-binding sites are quite conservative in the mitochondrial carriers family although their sequences similarity is very low with 20% or so. Moreover, according to our structural analysis, the relationship between the disease-causing mutations of human mitochondrial ornithine transporter-1 and the HHH syndrome can be classified into the following three categories: (i) the mutation occurs in the pseudo-repeat regions so as to change the region of the protein closer to the mitochondrial matrix; (ii) the mutation is directly affecting the substrate binding pocket so as to reduce the substrate binding affinity; (iii) the mutation is located in the structural region closer to the intermembrane space that can significantly break the salt bridge networks of the protein. These findings may provide useful insights for in-depth understanding of the molecular mechanism of the HHH syndrome and developing effective drugs against the disease

Exercise-Induced Changes in Exhaled NO Differentiates Asthma With or Without Fixed Airway Obstruction From COPD With Dynamic Hyperinflation.

Asthmatic patients with fixed airway obstruction (FAO) and patients with chronic obstructive pulmonary disease (COPD) share similarities in terms of irreversible pulmonary function impairment. Exhaled nitric oxide (eNO) has been documented as a marker of airway inflammation in asthma, but not in COPD. To examine whether the basal eNO level and the change after exercise may differentiate asthmatics with FAO from COPD, 27 normal subjects, 60 stable asthmatics, and 62 stable COPD patients were studied. Asthmatics with FAO (n = 29) were defined as showing a postbronchodilator FEV(1)/forced vital capacity (FVC) ≤70% and FEV(1) less than 80% predicted after inhaled salbutamol (400 μg). COPD with dynamic hyperinflation (n = 31) was defined as a decrease in inspiratory capacity (ΔIC%) after a 6 minute walk test (6MWT). Basal levels of eNO were significantly higher in asthmatics and COPD patients compared to normal subjects. The changes in eNO after 6MWT were negatively correlated with the percent change in IC (r = −0.380, n = 29, P = 0.042) in asthmatics with FAO. Their levels of basal eNO correlated with the maximum mid-expiratory flow (MMEF % predicted) before and after 6MWT. In COPD patients with air-trapping, the percent change of eNO was positively correlated to ΔIC% (rs = 0.404, n = 31, P = 0.024). We conclude that asthma with FAO may represent residual inflammation in the airways, while dynamic hyperinflation in COPD may retain NO in the distal airspace. eNO changes after 6MWT may differentiate the subgroups of asthma or COPD patients and will help toward delivery of individualized therapy for airflow obstruction

Efficient Coding Tree Unit (CTU) Decision Method for Scalable High-Efficiency Video Coding (SHVC) Encoder

High-efficiency video coding (HEVC or H.265) is the latest video compression standard developed by the joint collaborative team on video coding (JCT-VC), finalized in 2013. HEVC can achieve an average bit rate decrease of 50% in comparison with H.264/AVC while still maintaining video quality. To upgrade the HEVC used in heterogeneous access networks, the JVT-VC has been approved scalable extension of HEVC (SHVC) in July 2014. The SHVC can achieve the highest coding efficiency but requires a very high computational complexity such that its real-time application is limited. To reduce the encoding complexity of SHVC, in this chapter, we employ the temporal-spatial and inter-layer correlations between base layer (BL) and enhancement layer (EL) to predict the best quadtree of coding tree unit (CTU) for quality SHVC. Due to exist a high correlation between layers, we utilize the coded information from the CTU quadtree in BL, including inter-layer intra/residual prediction and inter-layer motion parameter prediction, to predict the CTU quadtree in EL. Therefore, we develop an efficient CTU decision method by combing temporal-spatial searching order algorithm (TSSOA) in BL and a fast inter-layer searching algorithm (FILSA) in EL to speed up the encoding process of SHVC. The simulation results show that the proposed efficient CTU decision method can achieve an average time improving ratio (TIR) about 52–78% and 47–69% for low delay (LD) and random access (RA) configurations, respectively. It is clear that the proposed method can efficiently reduce the computational complexity of SHVC encoder with negligible loss of coding efficiency with various types of video sequences

The Organizational Context, Job Embeddedness, And Effectiveness Of Managing Knowledge Work Teams

The relationships between organizational context, job embeddedness, and knowledge work team effectiveness are examined in this paper. We proposed a research model and tested the model empirically based on a sample of 144 enterprises from the Taiwanese Information Service Industry. The results show that open-mindedness and organizational commitment are positively related to job embeddedness. Job embeddedness also has strong relationship with knowledge work team effectiveness. However, the link between job autonomy and job embeddedness is not significant