Neural effects of muscle stretching on the spinal reflexes in multiple lower-limb muscles

While previous studies have shown that muscle stretching suppresses monosynaptic spinal reflex excitability in stretched muscles, its effects on non-stretched muscles is still largely unknown. The purpose of this study was to examine the effects of muscle stretching on monosynaptic spinal reflex in non-stretched muscles. Ten healthy male subjects participated in this study. Muscle stretching of the right triceps surae muscle was performed using a motor torque device for 1 minute. Three different dorsiflexion torques (at approximately 5, 10, and 15 Nm) were applied during muscle stretching. Spinal reflexes evoked by transcutaneous spinal cord stimulation were recorded in both the lower-limb muscles before, during, and at 0 and 5 min following muscle stretching. The amplitudes of the spinal reflexes in both the stretched and non-stretched muscles in the right (ipsilateral) leg were smaller during stretching compared to before, and at 0 and 5 min after stretching. Furthermore, the degree of reduction in the amplitude of the spinal reflexes in the right (ipsilateral) leg muscles increased significantly as the dorsiflexion torque (i.e., stretching of the right triceps surae muscles) increased. In contrast, reduction in the amplitude of the spinal reflexes with increasing dorsiflexion torque was not seen in the left (contralateral) leg muscles. Our results clearly indicate that muscle stretching has inhibitory effects on monosynaptic spinal reflexes, not only in stretched muscles, but also in non-stretched muscles of the ipsilateral leg

SERCA2a過剰発現ラットにおけるイソプロテレノール持続投与誘導肥大心の左室力学的エネルギー学的性質の変化

Overexpression of cardiac sarcoplasmic reticulum Ca2 +-ATPase (SERCA2a) has been suggested as a strategic intervention for cardiac failure. However, its benefit in wild-type (WT) rats with normal SERCA2a levels seems to be small. To investigate whether it would be beneficial in a cardiac failure model with down-regulated SERCA2a levels, we made a cardiac hypertrophy model using isoproterenol infusion (1.2 mg kg− 1 day− 1 for 1 or 4 weeks; TG-ISO1w and TG-ISO4w, respectively) in SERCA2a transgenic (TG) rats and compared these rats with littermate WT rats that underwent the same treatments (WT-ISO1w and WT-ISO4w). We analyzed the left ventricular (LV) mechanoenergetics in the excised heart using our original cross-circulation system. The downward shift of curvilinear LV end-systolic pressure–volume relations (ESPVRs) observed in WT-ISO4w rats was abolished in TG-ISO4w rats. The slope and VO2 intercept of the VO2 (myocardial oxygen consumption per beat)–PVA (systolic pressure–volume area: total mechanical energy per beat) linear relation did not differ in any of the groups. The most important finding was a significantly smaller O2 cost of LV contractility in the TG-ISO4w group, which means that less O2 is needed to exert the same LV contractility, compared with the other groups. The increased ratio of SERCA2a/phospholamban returned to the level of the WT-control group only in the TG-ISO4w group. Longer-term up-regulation of mitochondrial transcription factor A for genes of mitochondrial enzymes producing ATP was observed in TG rats. In conclusion, longer-term overexpression of SERCA2a will be beneficial in the present cardiac failure model with down-regulated SERCA2a levels.博士（医学）・甲619号・平成26年3月17

Generation of High-Purity Millimeter-Wave Orbital Angular Momentum Modes Using Horn Antenna: Theory and Implementation

Twisted electromagnetic waves, of which the helical phase front is called orbital angular momentum (OAM), have been recently explored for quantum information, high speed communication and radar detections. In this context, generation of high purity waves carrying OAM is of great significance and challenge from low frequency band to optical area. Here, a novel strategy of mode combination method is proposed to generate twisted waves with arbitrary order of OAM index. The higher order mode of a circular horn antenna is used to generate the twisted waves with quite high purity. The proposed strategy is verified with theoretical analysis, numerical simulation and experiments. A circular horn antenna operating at millimeter wave band is designed, fabricated, and measured. Two twisted waves with OAM index of l=+1 and l=-1 with a mode purity as high as 87% are obtained. Compared with the other OAM antennas, the antenna proposed here owns a high antenna gain (over 12 dBi) and wide operating bandwidth (over 15%). The high mode purity, high antenna gain and wide operating band make the antenna suitable for the twisted-wave applications, not only in the microwave and millimeter wave band, but also in the terahertz band.Comment: 18 pages, 9 figure

新しいカルパイン阻害剤はラット生体位心における緩和な虚血再灌流による左心室機能障害を保護する

We have previously indicated that a new soluble calpain inhibitor, SNJ-1945 (SNJ), attenuates cardiac dysfunction after cardioplegia arrest-reperfusion by inhibiting the proteolysis of α-fodrin in in vitro study. Nevertheless, the in vivo study design is indispensable to explore realistic therapeutic approaches for clinical use. The aim of the present in situ study was to investigate whether SNJ attenuated left ventricular (LV) dysfunction (stunning) after mild ischemic-reperfusion (mI-R) in rat hearts. SNJ (60 μmol/l, 5 ml i.p.) was injected 30 min before gradual and partial coronary occlusion at proximal left anterior descending artery. To investigate LV function, we obtained curvilinear end-systolic pressure–volume relationship by increasing afterload 60 min after reperfusion. In the mI-R group, specific LV functional indices at midrange LV volume (mLVV), end-systolic pressure (ESPmLVV), and pressure–volume area (PVAmLVV: a total mechanical energy per beat, linearly related to oxygen consumption) significantly decreased, but SNJ reversed these decreases to time control level. Furthermore, SNJ prevented the α-fodrin degradation and attenuated degradation of Ca2+ handling proteins after mI-R. Our results indicate that improvements in LV function following mI-R injury are associated with inhibition of the proteolysis of α-fodrin in in situ rat hearts. In conclusion, SNJ should be a promising tool to protect the heart from the stunning.博士（医学）・甲617号・平成26年3月17

イソプロテレノール誘導肥大心においてNHE-1阻害薬は、ラット左心室の筋スライスのCa2+トランジェントを正常化する

We previously reported that left ventricular (LV) slices from isoproterenol (ISO)-induced hypertrophied rat hearts showed an increase of energy expenditure due to remodeling of Ca2+ handling in excitation–contraction coupling, i.e., suppressed SERCA2a activity and enhanced Na+/Ca2+exchanger-1 (NCX-1) activity. Na+/H+ exchanger-1 (NHE-1) inhibitor (NHEI) has been demonstrated to exert beneficial effects in the development of cardiac remodeling. We hypothesized that a novel NHE-1 selective inhibitor, BIIB723 prevents remodeling of Ca2+ handling in LV slices of ISO-induced hypertrophied rat hearts mediated by inhibiting NCX-1 activity. The significant shortening in duration of multi-cellular Ca2+ transient in ISO group was normalized in ISO + BIIB723 group. The significant increase in amplitude of multi-cellular Ca2+ waves (CaW) generated at high [Ca2+]o of LV slices in ISO group was also normalized in ISO + BIIB723 group. However, the enhanced NCX-1 activity was not antagonized by BIIB723. We recently reported that ISO-induced down-regulation of a Ca2+ handling protein, SERCA2a, was normalized by BIIB723. Therefore, it seems likely that BIIB723 normalized shortened multi-cellular Ca2+ transient duration and increased CaW amplitude in LV slices mediated via normalization of SERCA2a activity. Furthermore, the results presented here suggest the multi-cellular Ca2+ transient duration and CaW amplitude in LV slices might be better indices reflecting SERCA2a activity than SERCA2a protein expression level.博士（医学）・甲618号・平成26年3月17

Direct measurement of spectral shape of Cherenkov light using cosmic muons

The spectral pulse shape of Cherenkov lights was directly measured by using cosmic muons. The observed decay times for early and late timing were 5.0 and 5.2ns, respectively. They were actually shorter than the time of scintillation lights which were also measured as 9.3ns and 9.2ns, respectively. However we could not see the difference of the rise time between scintillation and Cherenkov lights. This was due to the slow response of our DAQ equipment, photomultiplier and FADC digitize

Precise pulse shape measurement of Cherenkov light using sub-MeV electrons from Sr-90/Y-90 beta source

The precise spectral pulse shape from Cherenkov lights was directly measured by using sub-MeV electrons from 90Sr/90Y beta source. The observed shape was clearly different from the shape of scintillation light. The pulse rise and fall （decay） time for Cherenkov light were 0.8 ns and 2.5 ns, respectively. They were actually shorter than those times of scintillation light which were also measured by 1.6 ns and 6.5 ns, respectively. This clear Thisclearclear difference of rise time will be used for the pulse shape discrimination in order to select PMTs which receive Cherenkov lights, and the topological information due to Cherenkov light will be used for the reduction of backgrounds from 208Tl beta decay which should be major backgrounds observed around Q-value （3.35MeV）of 96Zr neutrinoless double beta decay

MicroRNA-451a inhibits gemcitabine-refractory biliary tract cancer progression by suppressing the MIF-mediated PI3K/AKT pathway

Gemcitabine is an effective chemotherapeutic agent for biliary tract cancers (BTCs), including gallbladder cancer (GBC) and cholangiocarcinoma (CCA). However, few other effective agents are currently available, particularly for GEM-refractory BTCs. We previously identified microRNA-451a (miR-451a) as a potential therapeutic target in GBC. To elucidate the antineoplastic effects of miR-451a and its underlying mechanisms, we transfected miR-451a into GBC, gemcitabine-resistant GBC (GR-GBC), and gemcitabine-resistant CCA (GR-CCA) cell lines. Furthermore, mimicking in vivo conditions, tumorigenic GBC organoids and three-dimensional (3D) cell culture systems were employed to investigate the anti-proliferative effects of miR-451a on BTCs, and its effect on stem cell properties. We found that miR-451a significantly inhibited cell proliferation, induced apoptosis, and reduced chemoresistant phenotypes, such as epithelial-mesenchymal transition, in both GBC and GR-GBC. The principal mechanism is probably the negative regulation of the phosphatidylinositol 3-kinase/AKT pathway, partially accomplished by directly downregulating macrophage migration inhibitory factor. The Gene Expression Omnibus database revealed that miR-451a was the most significantly downregulated microRNA in CCA tissues. The introduction of miR-451a resulted in similar antineoplastic effects in GR-CCA. Furthermore, miR-451a reduced cell viability in 3D spheroid models and tumorigenic GBC organoids. These findings suggest that the supplementation of miR-451a is a potential treatment strategy for GEM-refractory BTCs

Development of pulse shape discrimination for Cherenkov lights in liquid scintillator

With a liquid scintillation used for ZICOS experiment, we measured pulse shapes in case of several radio isotopes, 60Co, 137Cs, 133Ba, and 57Co. Taking FADC timing at 60 nsec for the peak position, FADC spectra from 58.5 nsec to 80 nsec were almost same shape for each RI, however, before 58.5 nsec, we have found that those were different shape. Especially, in case of 57Co, the energy is lower than Cherenkov threshold, so that the spectra should not include Cherenkov light. Using those spectra between 57.0 nsec and 58.0 nsec（3 bins）, we calculated simply χ2 and it was clearly discriminated that χ2 ≥ 0.1 should be include Cherenkov lights. This was also confirmed by Compton electrons with fixed energy and fixed direction. Obtained detection inefficiency of Cherenkov lights was observed by 21.4 ± 9.6 %. According to Compton edge events which have almost same direction as the incident γ and backgrounds events which should have isotropic direction, the detection inefficiency were 10.4 ± 0.5 % and 49.1 ± 1.4 %, respectively. They were quite different values and the inefficiency of both fixed energy and Compton edge events were statistically same. This is a direct evidence that Cherenkov lights should keep their topology even if they are emitted by around 1 MeV electron

Squamous cell carcinoma initially occurring on the tongue dorsum: a case series report with molecular analysis

Ono Sawako, Hirose Katsutoshi, Sukegawa Shintaro, et al. Squamous cell carcinoma initially occurring on the tongue dorsum: a case series report with molecular analysis. Diagnostic Pathology 19, 63 (2024); https://doi.org/10.1186/s13000-024-01487-0.Background: Squamous cell carcinoma (SCC) of the dorsum of the tongue is extremely rare, and it clinically resembles various benign lesions. Somatic mutations in TP53 and some driver genes were implicated in the development of SCC; however, the somatic genetic characteristics of dorsal tongue SCC remain unknown. With a detailed analysis of gene mutations in dorsal tongue SCC, we aimed to better understand its biology. Methods: Four cases of SCC initially occurring on the tongue dorsum were evaluated for clinical and histological findings and immunohistochemical expression of p53 and p16. Gene mutations were analyzed using next-generation sequencing with a custom panel of driver genes.Results: We retrospectively investigated 557 cases of tongue SCC, and only four cases of SCC initially occurred on the tongue dorsum. The four patients (cases 1–4) were one woman and three men with a mean age of 53.75 years (range: 15–74 years). Histological analysis revealed well-differentiated SCC. Through molecular analysis, we identified pathogenic somatic mutations, namely, TP53 p.C176F (c.527G > T) in case 3 and TP53 p.R282W (c.844 C > T) in case 4. No pathogenic variants were identified in the PI3K/AKT or RAS/RAF pathways. The p53 immunohistochemical examination revealed a wild-type expression pattern in cases 1–3 and strong expression in case 4. The results of p16 immunostaining were negative in all cases. Conclusions: We described four previously unreported genetic characteristics of dorsal tongue SCC. Somatic TP53 mutations may contribute to the development of a subset of dorsal tongue SCC; however, more cases with genetic analysis need to be accumulated