Physiology and Pathophysiology of CLC-1: Mechanisms of a Chloride Channel Disease, Myotonia

The CLC-1 chloride channel, a member of the CLC-channel/transporter family, plays important roles for the physiological functions of skeletal muscles. The opening of this chloride channel is voltage dependent and is also regulated by protons and chloride ions. Mutations of the gene encoding CLC-1 result in a genetic disease, myotonia congenita, which can be inherited as an autosmal dominant (Thomsen type) or an autosomal recessive (Becker type) pattern. These mutations are scattered throughout the entire protein sequence, and no clear relationship exists between the inheritance pattern of the mutation and the location of the mutation in the channel protein. The inheritance pattern of some but not all myotonia mutants can be explained by a working hypothesis that these mutations may exert a “dominant negative” effect on the gating function of the channel. However, other mutations may be due to different pathophysiological mechanisms, such as the defect of protein trafficking to membranes. Thus, the underlying mechanisms of myotonia are likely to be quite diverse, and elucidating the pathophysiology of myotonia mutations will require the understanding of multiple molecular/cellular mechanisms of CLC-1 channels in skeletal muscles, including molecular operation, protein synthesis, and membrane trafficking mechanisms

Integrin-mediated membrane blebbing is dependent on the NHE1 and NCX1 activities.

Integrin-mediated signal transduction and membrane blebbing have been well studied to modulate cell adhesion, spreading and migration^1-6^. However, the relationship between membrane blebbing and integrin signaling has not been explored. Here we show that integrin-ligand interaction induces membrane blebbing and membrane permeability change. We found that sodium-proton exchanger 1 (NHE1) and sodium-calcium exchanger 1 (NCX1) are located in the membrane blebbing sites and inhibition of NHE1 disrupts membrane blebbing and decreases membrane permeability change. However, inhibition of NCX1 enhances cell blebbing to cause cell swelling which is correlated with an intracellular sodium accumulation induced by NHE17. These data suggest that sodium influx induced by NHE1 is a driving force for membrane blebbing growth, while sodium efflux induced by NCX1 in a reverse mode causes membrane blebbing retraction. Together, these data reveal a novel function of NHE1 and NCX1 in membrane permeability change and blebbing and provide the link for integrin signaling and membrane blebbing

An Efficient Wireless Recharging Mechanism for Achieving Perpetual Lifetime of Wireless Sensor Networks

[[abstract]]Energy recharging has received much attention in recent years. Several recharging mechanisms were proposed for achieving perpetual lifetime of a given Wireless Sensor Network (WSN). However, most of them require a mobile recharger to visit each sensor and then perform the recharging task, which increases the length of the recharging path. Another common weakness of these works is the requirement for the mobile recharger to stop at the location of each sensor. As a result, it is impossible for recharger to move with a constant speed, leading to inefficient movement. To improve the recharging efficiency, this paper takes “recharging while moving” into consideration when constructing the recharging path. We propose a Recharging Path Construction (RPC) mechanism, which enables the mobile recharger to recharge all sensors using a constant speed, aiming to minimize the length of recharging path and improve the recharging efficiency while achieving the requirement of perpetual network lifetime of a given WSN. Performance studies reveal that the proposed RPC outperforms existing proposals in terms of path length and energy utilization index, as well as visiting cycle.[[notice]]補正完

The Behavior of Retaining Walls Under 1999 Chi-Chi Earthquake

This paper reports failure of retaining structures related to the 1999 Chi-Chi earthquake. On September 21 of 1999, an earthquake with a magnitude of 7.3 on the Richter scale struck Taiwan. At the site near Tou-Sheh, overturning failure was observed on a 2.5 m-high gravity wall located near the epicenter. At the site near the Temple of Ten-thousand Buddha, a masonry wall constructed with cobble was damaged. Upper part of wall shifted outward about 0.2 m with respect to its lower part. At the site of Cinema-Culture Town, a gravity wall built on top of the Che-Lung-Pu fault was severely damaged. The heel of the wall was uplifted by the fault rupture. At the parking lot of the Lalu Resort, the retaining wall constructed on a slope moved down the slope during the earthquake. A circular sliding surface can be observed in the collapsed backfill. At the entrance of National Chi-Nan University, a geogrid-reinforced wall was severely damaged during the earthquake. Reinforcing strips were pulled out under the seismic load and fill materials fell out

Effect and Evaluation of an Ultrasonic Atomizer With Large Vibration Amplitude

An ultrasonic atomizer can produce large vibration amplitude is designed. Different from the structure of the usually seen ultrasonic spray nozzle, the atomizer is fundamentally constructed with a hollow tube encircled with several pieces of sectional type piezoelectric actuators, which can radially oscillate the tube to generate desired vibration profile. Atomization is formed on the surface around the liquid outlet of the tube where maximum vibration amplitude occurs. In search of resonance frequency and vibration amplitude, modal and harmonic analyses of the ultrasonic atomizer are carried out by ANSYS. In comparison the simulated results with the experimental results, both are in good agreement. A measurement system is set up for detecting the atomization droplets and calculating the droplet size and distribution. An attempt is to design an ultrasonic atomizer can produce high distribution and small diameter droplets for some application-level requirements, droplet diameter around 20�60 lm is assumed to be the specification for performance verification of the proposed atomizer. In experiment, it is found nearly 90% of atomized droplets fit for the requirement. Besides the most important factor of operating frequency, a relation of amplitude is found to include in the well-known Lang and Rayleigh�s equation

Obstacle-Resistant Deployment Algorithms for Wireless Sensor Networks

[[abstract]]Node deployment is an important issue in wireless sensor networks (WSNs). Sensor nodes should be efficiently deployed in a predetermined region in a low-cost and high-coverage-quality manner. Random deployment is the simplest way to deploy sensor nodes but may cause unbalanced deployment and, therefore, increase hardware costs and create coverage holes. This paper presents the efficient obstacle-resistant robot deployment (ORRD) algorithm, which involves the design of a node placement policy, a serpentine movement policy, obstacle-handling rules, and boundary rules. By applying the proposed ORRD, the robot rapidly deploys a near-minimal number of sensor nodes to achieve full sensing coverage, even though there exist unpredicted obstacles with regular or irregular shapes. Performance results reveal that ORRD outperforms the existing robot deployment mechanism in terms of power conservation and obstacle resistance and, therefore, achieves better deployment performance.[[incitationindex]]SC

Simple and robust downstream purification process for cell-derived influenza vaccines

New emerging influenza viruses with pandemic potentials were occurred in recent years, e.g. H5N1 in 1997, H1N1 in 2009, and H7N9 in 2013. The demand of producing pandemic influenza vaccines for human use with quick supply is high. For the cell-based pandemic influenza vaccines, we proposed a flow-through chromatography purification process. This process has only involved few purification steps and is easy to operate. Vero- and MDCK- cell derived avian influenza viruses including H5N1 and H7N9 were purified efficiently by the process proposed. The presented purification process consisted of clarification, inactivation, concentration, anion exchange chromatography (Capto Q), size exclusion and adsorption chromatography (Capto Core 700), diafiltration and sterile filtration. In the chromatography steps, cell DNA and protein were removed remarkably, and the virus were flowed through these columns. The flow rate was set as fast as 250 cm/min. The loading volume of virus solution was up to 50 times of column volume (CV).The DNA was removed over 90% after using Capto Q column, and was further removed by Capto Core 700 column. The overall removal rate of cellular DNA was more than 99%. The HA recovery rates of H5N1 and H7N9 influenza virus from Vero and MDCK cells were 20 to 40%. The DNA concentration of all purified bulks met the regulatory requirement of 10ng per dose. The developed purification process is simple and efficient, and it is suitable for purification of various influenza virus strains and can be used for the pandemic influenza vaccine production

An Obstacle-Free and Power Efficient Deployment Algorithm for Wireless Sensor Networks

[[abstract]]This paper proposes a robot-deployment algorithm that overcomes unpredicted obstacles and employs full-coverage deployment with a minimal number of sensor nodes. Without the location information, node placement and spiral movement policies are proposed for the robot to deploy sensors efficiently to achieve power conservation and full coverage, while an obstacle surrounding movement policy is proposed to reduce the impacts of an obstacle upon deployment. Simulation results reveal that the proposed robot-deployment algorithm outperforms most existing robot-deployment mechanisms in power conservation and obstacle resistance and therefore achieves a better deployment performance.[[notice]]補正完

Regulation of CLC-1 chloride channel biosynthesis by FKBP8 and Hsp90β.

Mutations in human CLC-1 chloride channel are associated with the skeletal muscle disorder myotonia congenita. The disease-causing mutant A531V manifests enhanced proteasomal degradation of CLC-1. We recently found that CLC-1 degradation is mediated by cullin 4 ubiquitin ligase complex. It is currently unclear how quality control and protein degradation systems coordinate with each other to process the biosynthesis of CLC-1. Herein we aim to ascertain the molecular nature of the protein quality control system for CLC-1. We identified three CLC-1-interacting proteins that are well-known heat shock protein 90 (Hsp90)-associated co-chaperones: FK506-binding protein 8 (FKBP8), activator of Hsp90 ATPase homolog 1 (Aha1), and Hsp70/Hsp90 organizing protein (HOP). These co-chaperones promote both the protein level and the functional expression of CLC-1 wild-type and A531V mutant. CLC-1 biosynthesis is also facilitated by the molecular chaperones Hsc70 and Hsp90β. The protein stability of CLC-1 is notably increased by FKBP8 and the Hsp90β inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG) that substantially suppresses cullin 4 expression. We further confirmed that cullin 4 may interact with Hsp90β and FKBP8. Our data are consistent with the idea that FKBP8 and Hsp90β play an essential role in the late phase of CLC-1 quality control by dynamically coordinating protein folding and degradation