Immortalized Adult Rodent Schwann Cells as In Vitro Models to Study Diabetic Neuropathy

We have established spontaneously immortalized Schwann cell lines from normal adult mice and rats and murine disease models. One of the normal mouse cell lines, IMS32, possesses some biological properties of mature Schwann cells and high proliferative activities. The IMS32 cells under hyperglycemic and/or hyperlipidemic conditions have been utilized to investigate the pathogenesis of diabetic neuropathy, especially the polyol pathway hyperactivity, glycation, increased oxidative stress, and reduced synthesis of neurotrophic factors. In addition to the mouse cell lines, our current study focuses on the characterization of a normal rat cell line, IFRS1, under normal and high glucose conditions. These Schwann cell lines can be valuable tools for exploring the detailed mechanisms leading to diabetic neuropathy and novel therapeutic approaches against that condition

Implantable pneumatically actuated microsystem for renal pressure-mediated transfection in mice.

In vivo transfection is an important technique used in biological research and drug therapy development. Previously, we developed a renal pressure-mediated transfection method performed by pressing a kidney after an intravenous injection of naked nucleic acids. Although this is a useful method because of its safety and wide range of applications, an innovative approach for performing this method without repeatedly cutting open the abdomen is required. In this study, we developed an implantable microsystem fabricated by Micro-Electro-Mechanical Systems (MEMS) technologies for renal pressure-mediated transfection. The system consists of a polydimethylsiloxane pneumatic balloon actuator (PBA) used as an actuator to press the target kidney. The PBA of the implanted microsystem can be actuated without opening the abdomen by applying air pressure from outside the body to the pressure-supplying port via a needle. We successfully performed renal pressure-mediated transfection using the newly developed system when the implanted system was activated at 60kPa for 10s. This is the first report of an implantable MEMS-based microsystem that demonstrates in vivo transfection to a kidney using naked plasmid DNA

A microtubule polymerase cooperates with the kinesin-6 motor and a microtubule cross-linker to promote bipolar spindle assembly in the absence of kinesin-5 and kinesin-14 in fission yeast

Accurate chromosome segregation relies on the bipolar mitotic spindle. In many eukaryotes, spindle formation is driven by the plus-end–directed motor kinesin-5 that generates outward force to establish spindle bipolarity. Its inhibition leads to the emergence of monopolar spindles with mitotic arrest. Intriguingly, simultaneous inactivation of the minus-end–directed motor kinesin-14 restores spindle bipolarity in many systems. Here we show that in fission yeast, three independent pathways contribute to spindle bipolarity in the absence of kinesin-5/Cut7 and kinesin-14/Pkl1. One is kinesin-6/Klp9 that engages with spindle elongation once short bipolar spindles assemble. Klp9 also ensures the medial positioning of anaphase spindles to prevent unequal chromosome segregation. Another is the Alp7/TACC-Alp14/TOG microtubule polymerase complex. Temperature-sensitive alp7cut7pkl1 mutants are arrested with either monopolar or very short spindles. Forced targeting of Alp14 to the spindle pole body is sufficient to render alp7cut7pkl1 triply deleted cells viable and promote spindle assembly, indicating that Alp14-mediated microtubule polymerization from the nuclear face of the spindle pole body could generate outward force in place of Cut7 during early mitosis. The third pathway involves the Ase1/PRC1 microtubule cross-linker that stabilizes antiparallel microtubules. Our study, therefore, unveils multifaceted interplay among kinesin-dependent and -independent pathways leading to mitotic bipolar spindle assembly.This work was supported by the Japan Society for the Promotion of Science (JSPS) (KAKENHI Scientific Research [A] 16H02503 to T.T., a Challenging Exploratory Research grant 16K14672 to T.T., Scientific Research [C] 16K07694 to M.Y.), the Naito Foundation (T.T.), and the Uehara Memorial Foundation (T.T.)

Dirac returns: non-Abelian statistics of vortices with Dirac fermions

Topological superconductors classified as type D admit zero-energy Majorana fermions inside vortex cores, and consequently the exchange statistics of vortices becomes non-Abelian, giving a promising example of non-Abelian anyons. On the other hand, types C and DIII admit zero-energy Dirac fermions inside vortex cores. It has been long believed that an essential condition for the realization of non-Abelian statistics is non-locality of Dirac fermions made of two Majorana fermions trapped inside two well-separated vortices as in the case of type D. Contrary to this conventional wisdom, however, we show that vortices with local Dirac fermions also obey non-Abelian statistics.Comment: 5 pages, 1 figure, published versio

<ORIGINAL ARTICLE>The effects of sagittal ramus osteotomy for mandibular prognathism on maximum mouth opening and condylar movement

Maximum mouth opening and condylar movement before and more than 6 months after surgery were analyzed in 23 cases of sagittal ramus osteotomy of the mandible for correction of mandibular prognathism. Condylar movement (translation and rotation) did not show postoperatively a significant difference pre-and postoperatively, and then was a tendency to a reduction of maximum mouth opening was found

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Evaluation of the difference-correction effect of the gamma camera systems used by easy Z-score Imaging System (eZIS) analysis

Objective: We examined the difference of the effect by data to revise a gamma camera difference. The difference-correction method of the camera is incorporated in eZIS analysis. Methods: We acquired single photon emission computed tomography (SPECT) data from the three-dimensional (3D) Hoffman brain phantom (Hoffman), the three-dimensional brain phantom (3D-Brain), Pool phantom (pool) and from normal subjects (Normal-SPECT) to investigate compensating for a difference in gamma camera systems. We compared SPECT counts of standard camera with the SPECT counts that revised the difference of the gamma camera system (camera). Furthermore, we compared the "Z-score map (Z-score)". To verify the effect of the compensation, we examined digitally simulated data designed to represent a patient with Alzheimer\u27s dementia. We carried out both eZIS analysis and "Specific Volume of interest Analysis (SVA)". Results: There was no great difference between the correction effect using Hoffman phantom data and that using 3D-Brain phantom data. Furthermore, a good compensation effect was obtained only over a limited area. The compensation based on the pool was found to be less satisfactory than any of the other compensations according to all results of the measurements examined in the study. The compensation based on the Normal-SPECT data resulted in a Z-score map (Z-score) for the result that approximated that from the standard camera. Therefore, we concluded that the effect of the compensation based on Normal-SPECT data was the best of the four methods tested. Conclusions: Based on eZIS analysis, the compensation using the pool data was inferior to the compensations using the other methods tested. Based on the results of the SAV analysis, the effect of the compensation using the Hoffman data was better than the effect of the compensation using the 3D-Brain data. By all end-point measures, the compensation based on the Normal-SPECT data was more accurate than the compensation based on any of the other three phantoms. © 2014 The Author(s).発行後1年より全文公

ErbB2 and NFκB Overexpression as Predictors of Chemoradiation Resistance and Putative Targets to Overcome Resistance in Muscle-Invasive Bladder Cancer

Radical cystectomy for muscle-invasive bladder cancer (MIBC) patients frequently impairs their quality of life (QOL) due to urinary diversion. To improve their QOL, a bladder-sparing alternative strategy using chemoradiation has been developed. In bladder-sparing protocols, complete response (CR) to induction chemoradiation is a prerequisite for bladder preservation and favorable survival. Thus predicting chemoradiation resistance and overcoming it would increase individual MIBC patients' chances of bladder preservation. The aim of this study is to investigate putative molecular targets for treatment aimed at improving chemoradiation response. Expression levels of erbB2, NFκB, p53, and survivin were evaluated immunohistochemically in pretreatment biopsy samples from 35 MIBC patients in whom chemoradiation sensitivity had been pathologically evaluated in cystectomy specimens, and associations of these expression levels with chemoradiation sensitivity and cancer-specific survival (CSS) were investigated. Of the 35 patients, 11 (31%) achieved pathological CR, while tumors in the remaining 24 patients (69%) were chemoradiation-resistant. Multivariate analysis identified erbB2 and NFκB overexpression and hydronephrosis as significant and independent risk factors for chemoradiation resistance with respective relative risks of 11.8 (P = 0.014), 15.4 (P = 0.024) and 14.3 (P = 0.038). The chemoradiation resistance rate was 88.5% for tumors overexpressing erbB2 and/or NFκB, but only 11.1% for those negative for both (P <0.0001). The 5-year CSS rate was 74% overall. Through multivariate analysis, overexpression of erbB2 and/or NFκB was identified as an independent risk factor for bladder cancer death with marginal significance (hazard ratio 21.5, P = 0.056) along with chemoradiation resistance (P = 0.003) and hydronephrosis (P = 0.018). The 5-year CSS rate for the 11 patients achieving pathological CR was 100%, while that for the 24 with chemoradiation-resistant disease was 61% (P = 0.018). Thus, erbB2 and NFκB overexpression are relevant to chemoradiation resistance and are putative targets aimed at overcoming chemoradiation resistance in MIBC