A Novel LRRK2 Variant p.G2294R in the WD40 Domain Identified in Familial Parkinson’s Disease Affects LRRK2 Protein Levels

Leucine-rich repeat kinase 2 (LRRK2) is a major causative gene of late-onset familial Parkinson’s disease (PD). The suppression of kinase activity is believed to confer neuroprotection, as most pathogenic variants of LRRK2 associated with PD exhibit increased kinase activity. We herein report a novel LRRK2 variant—p.G2294R—located in the WD40 domain, detected through targeted gene-panel screening in a patient with familial PD. The proband showed late-onset Parkinsonism with dysautonomia and a good response to levodopa, without cognitive decline or psychosis. Cultured cell experiments revealed that p.G2294R is highly destabilized at the protein level. The LRRK2 p.G2294R protein expression was upregulated in the patient’s peripheral blood lymphocytes. However, macrophages differentiated from the same peripheral blood showed decreased LRRK2 protein levels. Moreover, our experiment indicated reduced phagocytic activity in the pathogenic yeasts and α-synuclein fibrils. This PD case presents an example wherein the decrease in LRRK2 activity did not act in a neuroprotective manner. Further investigations are needed in order to elucidate the relationship between LRRK2 expression in the central nervous system and the pathogenesis caused by altered LRRK2 activity.     

Synthesis of thermoresponsive copolymer/silica-coated magnetite nanoparticle composite and its application for heavy metal ion recovery

To enhance chemical stability and suppress of aggregation of magnetite nanoparticles (MNPs), which are used as a support for thermoresponsive copolymer immobilization, silica coating of the MNPs is applied via the electrooxidation method. Although the resulting silica coated-MNPs also formed aggregates, the size distribution of the aggregate shifted to smaller size range. Because of that, the surface area available for copolymer immobilization increased approximately 6.7 times at maximum as compared with that of the uncoated MNPs. It contributed to the increase of the amount of the immobilized copolymer on the silica-coated MNPs, which is approximately four times larger than that on the uncoated MNPs. Fe₃O₄ dissolution test confirmed enhancement of chemical stability of MNPs. The thermoresponsive copolymer immobilized on the silica-coated MNPs shows the ability to recycle Cu(II) ion from Cu(II) containing solution by changing temperature with significantly shorter time than those in other thermoresponsive adsorbents in gel form.     

Wideband and compact folded loop antenna

A simple and successful design method that yields a wideband and compact antenna without a ground plane is proposed. The antenna, referred to as the folded loop antenna, can, with the right parameters, achieve wideband characteristics. Calculated and measured results agree well and more than 50% bandwidth (return loss /spl les/-10 dB) is obtained.     

Operation of superconducting fault current limiter using vacuum interrupter driven by electromagnetic repulsion force for commutating switch

Using conventional high‐temperature superconducting wire, a model superconducting fault current limiter (SFCL) is made and tested. Solenoid coil using Bi2223 silver sheath wire is so made that inductance is as small as possible and a vacuum interrupter is connected in series to it. A conventional reactor coil is connected in parallel. When the fault current flows in this equipment, superconducting wire is quenched and current is transferred into the parallel coil because of voltage drop of superconducting wire. This large current in parallel coil actuates magnetic repulsion mechanism of vacuum interrupter. Due to opening of vacuum interrupter, the current in superconducting wire is broken. By using this equipment, current flow time in superconducting wire can be easily minimized. On the other hand, the fault current is also easily limited by large reactance of parallel coil. © 2008 Wiley Periodicals, Inc. Electr Eng Jpn, 164(1): 52–61, 2008; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/eej.20315     

Percutaneous ethanol injection therapy by ethanol mixed with CO2 microbubble for hepatocellular carcinoma

One of the shortcomings of percutaneous ethanol injection therapy (PEIT) for hepatocellular carcinoma (HCC) is that many sessions are necessary to accomplish the treatment. This may be caused by which the ultrasonography (US) image does not reflect correctly to the kinetics of injected ethanol into HCC nodule. It is considered that number of treatment sessions are able to be reduced if we just enough injected labelled ethanol under US into HCC nodule. Therefore, we tried PEIT by ethanol mixed with CO2 microbubble (CO2 ethanol). The injected CO2 ethanol was aquired as hyperechoic image without strong acoustic shadow to the end of injection. Consequently we could reduce the number of treatment sessions to almost 1 for lesions < or = 3 cm in diameter and markedly reduce total dose of injected ethanol. The detectable rate of CO2 ethanol leaked out HCC nodule was high. No serious complication occurred. There have been only 1 lesion of local recurrence and no case of intrahepatic and peritoneal dissemination for 11.5 months on average of observation after PEIT by CO2 ethanol (CO2PEIT). These findings suggest that CO2PEIT is useful method for reducing the number of treatment sessions and total dose of injected ethanol, moreover preventing complication by ethanol leakage.     

The effect of additional albumin with optimal concentration on the reperfusion after preservation of isolated rat hearts

Glucagon has been demonstrated to stimulate the uptake of bile acid in isolated rat hepatocytes (Am. J. Physiol., 249, G427 (1985)). In the present study, we determined the influence of glucagon on the hepatic transport of a bile acid, taurocholate (TCA), in isolated rat livers. A single-pass perfusion and a rapid-injection, multiple indicator dilution method were employed. The hepatic availability at steady-state was 0.04. With the presence of glucagon in the perfusate (from 10(-9) to 10(-7) M), the bile flow rate was stimulated by 30%, while hepatic availability was decreased from 0.04 to 0.02 with a stepwise increase in glucagon concentration. Thirty min after the infusion of glucagon (300 nM), [3H]TCA and [14C]inulin were injected in a bolus state into the portal vein, and the outflow was collected at 1.0 s intervals over 30 s. Glucagon decreased the instantaneous hepatic availability by 50% compared to the control level, and was thus compatible with the steady-state experiments. In the control experiment, the influx clearance (PSinf) was 20 times higher than the efflux clearance (PSeff). Glucagon (300 nM) in the perfusate enhanced PSinf by 50% of the control, whereas sequestration clearance (CLseq) and the biliary excretion rate constant remained unchanged. PSeff was stimulated to 2 times the control, but still remained much smaller than CLseq. Based on the comparison of PSinf, PSeff and CLseq, the rate-determining process of TCA hepatic elimination was the influx process in both the presence and absence of glucagon. Taken together, the enhancement of the influx process was responsible for the decrease in TCA hepatic availability caused by glucagon.(ABSTRACT TRUNCATED AT 250 WORDS)     

A Fuzzy Expert System for Damage Assessment Using Genetic Algorithms and Neural Networks

Abstract: An efficient knowledge-acquisition support method is required for improvement and maintenance of the knowledge base in durability evaluation of an RC bridge deck. Such a method is proposed in this paper to automatically acquire fuzzy production rules. This method makes joint use of genetic algorithms and a neural network. Using a neural network as a subsystem, the evaluation function of genetic algorithms can be provided with the weights of the neural network. Introducing a neural network into genetic algorithms, it is possible to acquire new knowledge so that the method is useful when it is difficult to acquire knowledge in the field.     

Diffusion-controlled size-selective chloride ion sensing in the presence of bromide ion using a thin, nanoporous, plasma-polymerized coating on an Ag/AgCl electrode

We have developed a diffusion-controlled size-selective method for sensing chloride ion in the presence of bromide ion, based on a thin, nanoporous, plasma-polymerized coating of hexamethyldisiloxane on an Ag/AgCl electrode. Sub-nanometer-sized pores responsible for a highly cross-linked polymer network in the plasma-polymerized coating allowed diffusion-controlled permeation of chloride ion while blocking the larger bromide ion. An electrode coating of thickness greater than 70 nm enabled chloride detection in the concentration range 1-10 mM in the presence of 0.63 mM bromide ion. Advantages of this approach are: (1) simple design compared with ionophore-based strategies and (2) compatibility with microfabrication and mass production processes.     

Monte Carlo simulation of hydrogen absorption in palladium and palladium–silver alloys

A modified Monte Carlo (MC) simulation was performed to investigate the hydrogen absorption behavior in Pd and Pd–Ag alloys of the composition Pd_xAg_1−x (x=0.7–0.8) under H₂ pressure (0.1 MPa) at different temperatures. The present method employed can consider the dissociative adsorption of hydrogen molecule and the subsequent absorption of hydrogen atom by formalizing the relationship between the pressure of hydrogen molecule and hydrogen atom. The potential parameters were determined to reproduce the solution enthalpy of hydrogen in pure metals. The results are in good agreement with experimental findings as well as previous theoretical studies. We confirmed that our method is useful to simulate the absorption of hydrogen in metals and alloys.     

ATMPKs: a gene family of plant MAP kinases in Arabidopsis thaliana

We previously reported two cDNAs for MAP kinases (cATMPK1 and cATMPK2) from a dicot plant, Arabidopsis thaliana. We describe here the cloning and characterization of five additional cDNAs encoding novel MAP kinases in Arabidopsis, cATMPK3, cATMPK4, cATMPK5, cATMPK6, and cATMPK7. The amino acid residues corresponding to the sites of phosphorylation (Thr-Glu-Tyr) that are involved in the activation of animal MAP kinases are conserved in all the seven putative ATMPK proteins. Genes for MAP kinases in Arabidopsis constitute a family that contains more than seven members. Sequence analysis suggests that there are at least three subfamilies in the family of Arabidopsis genes for MAP kinases.