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.     

Role of Metabolism in Bone Development and Homeostasis

Carbohydrates, fats, and proteins are the underlying energy sources for animals and are catabolized through specific biochemical cascades involving numerous enzymes. The catabolites and metabolites in these metabolic pathways are crucial for many cellular functions; therefore, an imbalance and/or dysregulation of these pathways causes cellular dysfunction, resulting in various metabolic diseases. Bone, a highly mineralized organ that serves as a skeleton of the body, undergoes continuous active turnover, which is required for the maintenance of healthy bony components through the deposition and resorption of bone matrix and minerals. This highly coordinated event is regulated throughout life by bone cells such as osteoblasts, osteoclasts, and osteocytes, and requires synchronized activities from different metabolic pathways. Here, we aim to provide a comprehensive review of the cellular metabolism involved in bone development and homeostasis, as revealed by mouse genetic studies.     

Dynamical Properties of Vortices in a Bose-Einstein Condensate in a Rotating Lattice

We present simulation results of the vortex dynamics in a trapped Bose-Einstein condensate in the presence of a rotating optical lattice. Changing the potential amplitude and the relative rotation frequency between the condensate and the optical lattice, we find a rich variety of dynamical phases of vortices. In particular, when the optical lattice rotates faster than the condensate, the competition between the pinning force and the interactions by nucleated interstitial vortices leads to the melting of vortex lattice, yielding a vortex liquid phase.     

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.     

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.     

Superconductivity in SrTa2S5

A strontium tantalum sulfide, SrTa₂S₅, has a hexagonal structure with lattice constants of a =3.32 and c=24.1 Å. With decreasing temperature the electrical resistivity decreases monotonically and exhibits an abrupt superconducting transition at 3.16 K (midpoint). The diamagnetic susceptibility is observed below T_c. The magnetic susceptibility is nearly independent of temperature above T_c and shows Pauli paramagnetism.     

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)     

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.     

Analytic Approximation to The Standard Error of Swap-Rate

When we select No students from N applicants on the basis of a composite score of subtests, it is important to evaluate the contribution of each subtest. The swap-rate, which is defined as the proportion of the applicants who actually pass the examination but would fail if the j-th subtest were not included in the component to rank the applicants, is one of the measures of the contribution of the j-th subtest.

In this article, first, we derive the characteristics and limiting properties of the population swap-rate. Next, using the properties of the order statistics and the extended hypergeometric distribution, we derive an approximation to the asymptotic variance of the sample swap-rate when the number of applicants is large. Finally, we propose the use of our analytic approximation to the variance of the sample swap-rate in the real data problem and show that it is very efficient.

     

Development of 170 GHz/500 kW gyrotron

A development of 170GHz/500kW level gyrotron was carried out as R&D work of ITER. The oscillation mode is TE_31,8. In a short pulse experiment, the maximum power of 750kW was achieved at 85kV/40A. The efficiency was 22%. In the depressed collector operation, 500kW/36%/50ms was obtained. The maximum efficiency of 40% was obtained at P_RF=470kW whereas the power decrease by the electron trapping was observed. Pulse extension was done up to 10s at P_RF=170kW with the depressed collector operation. The power was limited by the temperature increase of the output window.