Visualization of Alzheimer’s Disease Related α-/β-/γ-Secretase Ternary Complex by Bimolecular Fluorescence Complementation Based Fluorescence Resonance Energy Transfer

The competitive ectodomain shedding of amyloid-β precursor protein (APP) by α-secretase and β-secretase, and the subsequent regulated intramembrane proteolysis by γ-secretase are the key processes in amyloid-β peptides (Aβ) generation. Previous studies indicate that secretases form binary complex and the interactions between secretases take part in substrates processing. However, whether α-, β- and γ-secretase could form ternary complex remains to be explored. Here, we adopted bimolecular fluorescence complementation in combination with fluorescence resonance energy transfer (BiFC-FRET) to visualize the formation of triple secretase complex. We show that the interaction between α-secretase ADAM10 and β-secretase BACE1 could be monitored by BiFC assay and the binding of APP to α-/β-secretase binary complex was revealed by BiFC-FRET. Further, we observed that γ-secretase interacts with α-/β-secretase binary complex, providing evidence that α-, β- and γ-secretase might form a ternary complex. Thus our study extends the interplay among Alzheimer’s disease (AD) related α-/β-/γ-secretase

Potential of performance improvement of concentrated solar power plants by optimizing the parabolic trough receiver

This paper proposes a comprehensive thermodynamic and economic model to predict and compare the performance of concentrated solar power plants with traditional and novel receivers with different configurations involving operating temperatures and locations. The simulation results reveal that power plants with novel receivers exhibit a superior thermodynamic and economic performance compared with traditional receivers. The annual electricity productions of power plants with novel receivers in Phoenix, Sevilla, and Tuotuohe are 8.5%, 10.5%, and 14.4% higher than those with traditional receivers at the outlet temperature of 550°C. The levelized cost of electricity of power plants with double-selective-coated receivers can be decreased by 6.9%, 8.5%, and 11.6%. In Phoenix, the optimal operating temperature of the power plants is improved from 500°C to 560°C by employing a novel receiver. Furthermore, the sensitivity analysis of the receiver heat loss, solar absorption, and freeze protection temperature is also conducted to analyze the general rule of influence of the receiver performance on power plants performance. Solar absorption has a positive contribution to annual electricity productions, whereas heat loss and freeze protection temperature have a negative effect on electricity outputs. The results indicate that the novel receiver coupled with low melting temperature molten salt is the best configuration for improving the overall performance of the power plants

Identification of alternative splicing variants of the β subunit of human Ca2+/calmodulin-dependent protein kinase II with different activities

AbstractThe β subunit of human Ca2+/calmodulin-dependent protein kinase II (β CaMKII) was identified by searching through an expressed sequence tag database and rapid amplification of cDNA 5′-ends and was assigned to chromosome 7. Reverse transcription-polymerase chain reaction and sequencing analysis identified at least five alternative splicing variants of β CaMKII (β, β6, βe, β′e, and β7) in brain and two of them (β6 and β7) were first detected in any species. When expressed in HEK 293 cells, the Ca2+/calmodulin-dependent kinase activity of β7, the shortest variant, was much lower than that of either β (the longest one) or βe (the medium one), suggesting possible regulation of β CaMKII activity by alternative splicing

Alendronate (ALN) combined with Osteoprotegerin (OPG) significantly improves mechanical properties of long bone than the single use of ALN or OPG in the ovariectomized rats

<p>Abstract</p> <p>Background</p> <p>Alendronate (ALN) is the most common form of bisphosphonates used for the treatment of osteoporosis. Osteoprotegerin (OPG) has also been shown to reduce osteoporotic changes in both humans and experimental animals after systemic administration. The aim of this current study was to test if the anti-resorption effects of ALN may be enhanced when used in combination with OPG.</p> <p>Objectives</p> <p>To investigate the effects of ALN, OPG or combined on bone mass and bone mechanical properties in ovariectomized (OVX) rats.</p> <p>Methods</p> <p>OVX rats were treated with ALN, OPG-Fc, or OPG-Fc and ALN. Biochemical markers, trabecular bone mass, biomechanics, histomorphometry and RANKL expression in the bone tissues were examined following the treatments.</p> <p>Results</p> <p>The treatment of ALN, OPG-Fc and ALN+OPG-Fc all prevented bone loss in the OVX-rats, there was no statistical difference among the three treatment groups in terms of vertebrae BMD, mineralizing surfaces, mineral apposition rate, BFR/BS. The ALN+OPG-Fc treatment group had significantly increased the mechanical strength of lumber vertebral bodies and femoral shafts when compared to the ALN and OPG-Fc treatment groups. The RANKL protein expression in the vertebral bones was significantly decreased in the ALN and ALN+OPG-Fc treatment groups, suggesting the combined use of OPG-Fc and ALN might have amplified inhibition of bone resorption through inhibiting RANKL-dependent osteoclastogenesis.</p> <p>Conclusion</p> <p>The combined use of OPG-Fc and ALN may be a new treatment strategy for reversing bone loss and restoring bone quality in osteoprotic disorders.</p

Capacity of Bicycle Platoon Flow at Two-Phase Signalized Intersection: a Case Analysis of Xi’an City

Although much is known about the operation of signalized intersections, little or no empirical research has been conducted regarding bicycle capacity at these locations and the correspondent contributory factors. The purpose of this study is to accurately quantify the capacity of bikeway at signalized intersection through a fluid dispersion approach, and ultimately the lane group capacity. Using this total dispersion of bicycle flow, a relationship is also described between bicycle volume per hour and per unit width, signal parameters (length of signal cycle and green time), bicycle flow (arrival rate, density, moving velocity) and geometric intersection distance. Through the videotaping of four intersections that have significant bicycle traffic around Xiaozhai in Xi’an, China, it is ascertained that bicycle capacity varies linearly (but limited by an asymptote domain) associated with the adjustment of these parameters. The analytical results indicate that the impact saturation flow of lane groups containing right-turning vehicles and pedestrian flow at signalized intersections on bicycles is being underestimated. If this is the case, then capacity is being overestimated through the HCM 2000 capacity model and JJ37-90 approach and intersections are not being adequately designed, due to the neglect of conflict nature of mixed traffic arrivals in competing for space

Extending the Propagation Distance of a Silver Nanowire Plasmonic Waveguide with a Dielectric Multilayer Substrate

Chemical synthesized silver nanowires have been proved to be the efficient architecture for Plasmonic waveguides, but the high propagation loss prevents their widely applications. Here, we demonstrate that the propagation distance of the plasmons along the Ag NW can be extended if the Ag NW was placed on a dielectric multilayer substrate containing a photonic band gap, but not placed on a commonly used glass substrate. The propagation distance at 630 nm wavelength can reach 16 um even that the Ag NW is as thin as 90 nm in diameter. Experimental and simulation results further show that the polarization of this propagating plasmon mode was nearly parallel to the surface of the dielectric multilayer, so it was excited by a transverse-electric polarized Bloch surface wave propagating along a polymer nanowire with diameter at only about 170 nm on the same dielectric multilayer. Numerical simulations were also carried out and consistent with the experiment results. Our work provides a platform to extend the propagation distance of plasmonic waveguide and also for the integration between photonic and plasmonic waveguides on the nanometre scale.Comment: 5 pages, 4 figure

Relationship of Body Fat and Cardiorespiratory Fitness with Cardiovascular Risk in Chinese Children

Backgrounds/Objectives: Cardiorespiratory fitness (CRF) and body fat play an important role in elevated risk for cardiovascular disease (CVD). However, the combined effects of CRF and obesity on metabolic health in Chinese children are unclear. The purpose of this study was to investigate the independent and combined associations between body fat, CRF, and CVD risk in Chinese schoolchildren. Methods: The study subjects comprised 676 schoolchildren (392 boys and 284 girls, aged 9.6±0.7 yrs old) in Wuhan, China. Their body mass index (BMI), waist circumference (WC), CRF, blood pressure (BP), lipids, glucose, and pubertal status were assessed. Children were categorized into different groups based on their BMI, WC, and CRF using Chinese obesity cut-off points and CRF sex-specific median points. Metabolic Risk Score (MRS) was computed based on the standardized scores of BP, lipids, and glucose. Results: Multiple linear regression models showed that, in the separate models, body fat was positively associated with MRS while CRF was inversely associated with MRS (p<0.001). However, when assessed simultaneously, only body fat had a significant association with MRS (p<0.001). In general, low-fit children had a lower MRS compared to their counterparts, and a significant difference between the two extreme groups was observed (low CRF and high fat vs. high CRF and low fat, p<0.001). Conclusions: These findings suggest that both body fat and CRF should be considered when interpreting CVD risk in Chinese children, while body fat may be correlated with CVD risk more than CRF. © 2011 Wang et al

Artifactual pyrosequencing reads in multiple-displacement-amplified sediment metagenomes from the Red Sea

The Multiple Displacement Amplification (MDA) protocol is reported to introduce different artifacts into DNA samples with impurities. In this study, we report an artifactual effect of MDA with sediment DNA samples from a deep-sea brine basin in the Red Sea. In the metagenomes, we showed the presence of abundant artifactual 454 pyrosequencing reads over sizes of 50 to 220 bp. Gene fragments translocated from neighboring gene regions were identified in these reads. Occasionally, the translocation occurred between the gene fragments from different species. Reads containing these gene fragments could form a strong stem-loop structure. More than 60% of the artifactual reads could fit the structural models. MDA amplification is probably responsible for the massive generation of the artifactual reads with the secondary structure in the metagenomes. Possible sources of the translocations and structures are discussed