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ABSTRACT Recently, optically pumped magnetometers (OPMs), which use the spin polarization of alkali metal atoms to measure magnetic fields, have attracted much attention. However, in order to realize high‐sensitivity biomagnetic field measurements using OPMs, it is necessary to reduce environmental magnetic noise and system noise. In this study, we investigate the effectiveness of the noise reduction of OPM signals when principal component analysis, independent component analysis, and empirical mode decomposition are used for signal processing. [ABSTRACT FROM AUTHOR]

Objective: The objective of the study was to evaluate visual outcomes between medical treatment alone (MED) and Ahmed glaucoma valve implantation (AGVI) in Shiba dogs with primary angle closure glaucoma (PACG). Procedures: Records of 65 Shiba dogs (104 eyes) with PACG were retrospectively reviewed. Vision was assessed qualitatively using both the menace response and maze testing. The significance of age, sex, intraocular pressure (IOP), and duration of clinical signs (≤72 h or >72 h) at first presentation (V1) was assessed. Eyes with vision at V1 were divided into groups according to subsequent treatment method (MED versus AGVI), and vision as a survival outcome was compared between group by the Kaplan–Meier method. Results: At V1, 65 eyes (62.5%) of 54 dogs had vision. There was no statistically significant difference in age or sex on the presence of vision at V1. Median IOP was higher in blind (52 mmHg) compared to sighted eyes (28 mmHg) (p <.001). Eyes presenting in ≤72 h of the onset of clinical signs were more likely to have vision (86.7%) compared to those presenting after 72 h (44.1%) (p <.001). By the Kaplan–Meier analysis, the cumulative visual retention rate was significantly higher with AGVI than with MED (69.2% vs. 7.7%; p <.01) at 12 months. The median time to visual loss was 39.9 months with AGVI vs. 1.7 months with MED. Conclusions: AGVI resulted in better visual outcomes than MED and should be considered in Shiba dogs with PACG that are visual at the time of presentation and suitable for surgery. [ABSTRACT FROM AUTHOR]

Recent observations beneath Kanto, Japan have shown that seismic activity and seismic attenuation within the overlying continental plate change with time due to drainage caused by slow‐slip events (SSEs) along the upper boundary of the Philippine Sea plate. However, associated changes in rock properties have not been investigated. In this study, we estimate frequency‐dependent shear‐wave anisotropy to provide a detailed insight into the structural change associated with drainage. We perform shear‐wave splitting analysis in frequency ranges of 1–4, 2–6, and 4–8 Hz for 306 earthquakes that occur during September 2009–August 2021 and recorded at the Metropolitan Seismic Observation network. Obtained time differences between fast and slow S waves (delay time) range from almost zero to 0.16–0.18 s, exhibiting spatio‐temporal variation and frequency dependence. The fast S‐wave polarization directions are generally consistent with the direction of the maximum horizontal compressional axis in the study region, which suggests that the observed anisotropy is probably caused by the NE–SW‐oriented fractures developed under the regional stress field. The temporal variation in delay times is correlated with SSEs activity with a lag time of 0.0–0.1 year. Furthermore, comparisons between observed frequency‐dependent delay times and numerical calculation of fracture‐induced anisotropy suggest that the average fracture radius is almost constant (0.30–0.35 m) over time but fracture density temporally varies from 0.025 to 0.035. We infer that the fracture density is probably enhanced by opening of the NE–SW‐oriented fractures during the upward migration of fluids that are expelled from the plate interface. Plain Language Summary: Measurement of shear‐wave polarization anisotropy characterizes the intensity and orientation of fractures within the rocks beneath the Earth's surface. Furthermore, its frequency dependence provides important information for determining the fracture size and density. This study reveals that the strength of anisotropy shows temporal variations associated with the inferred periodic drainage from the subducting slab. We discuss a possible mechanism of the structural change focusing on the frequency dependence of the observed anisotropy and propose that the opening of fractures occurs immediately above the subducting slab following the periodic drainage. The obtained results will provide important constraints on fluid‐rock interaction above the subducting plate interface. Key Points: Shear‐wave splitting analysis in Kanto, Japan suggests that seismic anisotropy is orientated sub‐parallel to the regional stressAnisotropy above the plate interface is enhanced with a lag of 0.0–0.1 years from the occurrence of slow‐slip eventsThe observed frequency‐dependent anisotropy suggests that fractures open responding to drainage from plate interface [ABSTRACT FROM AUTHOR]

Recent observations beneath central Japan have shown that periodic fluid drainage occurs during slow‐slip events (SSEs) based on temporal variations in QP−1 ${Q}_{P}^{-1}$ above the megathrust boundary of the subducting Philippine Sea slab. However, no previous studies have estimated associated QS−1 ${Q}_{S}^{-1}$. A comparison of QP−1 ${Q}_{P}^{-1}$ and QS−1 ${Q}_{S}^{-1}$ can provide clues to the mechanism of seismic attenuation because of different propagation characteristics of the two waves. We estimate temporal variations in QP−1 ${Q}_{P}^{-1}$ and QS−1 ${Q}_{S}^{-1}$ via spectral analyses of waveform data from November 2009 to August 2021 period. The results indicate that both QP−1 ${Q}_{P}^{-1}$ and QS−1 ${Q}_{S}^{-1}$ exhibit temporal variations at about 1‐year periodicity and there are systematic differences between QP−1 ${Q}_{P}^{-1}$ and QS−1 ${Q}_{S}^{-1}$ that QS−1 ${Q}_{S}^{-1}$ have smaller values, less insignificant variation, and weaker correlations with SSEs. Furthermore, QP−1/QS−1 ${Q}_{P}^{-1}/{Q}_{S}^{-1}$ increases concurrent with SSEs. These differences suggest that attenuation is caused by the wave‐induced fluid flow. QP−1/QS−1 ${Q}_{P}^{-1}/{Q}_{S}^{-1}$ could be an important parameter for detecting the presence of fluid. Plain Language Summary: Q−1 ${Q}^{-1}$ value, which represents energy dissipation of seismic wave, is an important parameter for detecting the anelastic heterogeneity in subsurface rocks. However, few observational studies have revealed the characteristics of both P‐ and S‐wave attenuation (QP−1 ${Q}_{P}^{-1}$ and QS−1 ${Q}_{S}^{-1}$, respectively) related to the presence of fluids in the crust and the uppermost mantle. This study reveals that both QP−1 ${Q}_{P}^{-1}$ and QS−1 ${Q}_{S}^{-1}$ show temporal variations associated with the inferred periodic drainage from the upper surface of a subducting slab but QS−1 ${Q}_{S}^{-1}$ is less fluctuated with time. We discuss a possible attenuation mechanism focusing on the differences in the observed QP−1 ${Q}_{P}^{-1}$ and QS−1 ${Q}_{S}^{-1}$ values and propose that the wave‐induced fluid flow (WIFF) may be a dominant control on the increases in attenuation concurrent with the drainage from the megathrust. The obtained results will provide important constraints on attenuation mechanism that is enhanced by the presence of fluid in rocks. Key Points: We estimated the long‐term temporal variations in QP−1 ${Q}_{P}^{-1}$ and QS−1 ${Q}_{S}^{-1}$ at 20–45 Hz above the megathrust boundary of the Philippine Sea PlateBoth QP−1 ${Q}_{P}^{-1}$ and QS−1 ${Q}_{S}^{-1}$ exhibited temporal variations with about 1‐year periodicity and spatiotemporal correlations with slow‐slip eventsSystematic differences between QP−1 ${Q}_{P}^{-1}$ and QS−1 ${Q}_{S}^{-1}$ may provide important constraints on attenuation mechanism enhanced by fluids [ABSTRACT FROM AUTHOR]

Gene expression is controlled at the transcriptional and post-transcriptional levels. The TACC2 gene was known to be associated with tumors but the control of its expression is unclear. We have reported that activity of the intronic promoter p10 of TACC2 in primary lesion of endometrial cancer is indicative of lymph node metastasis among a low-risk patient group. Here, we analyze the intronic promoter derived isoforms in JHUEM-1 endometrial cancer cells, and primary tissues of endometrial cancers and normal endometrium. Full-length cDNA amplicons are produced by long-range PCR and subjected to nanopore sequencing followed by computational error correction. We identify 16 stable, 4 variable, and 9 rare exons including 3 novel exons validated independently. All variable and rare exons reside N-terminally of the TACC domain and contribute to isoform variety. We found 240 isoforms as high-confidence, supported by more than 20 reads. The large number of isoforms produced from one minor promoter indicates the post-transcriptional complexity coupled with transcription at the TACC2 locus in cancer and normal cells. [ABSTRACT FROM AUTHOR]

Recently, the main issue in neuroscience has been the imaging of the functional connectivity in the brain. No modality that can measure functional connectivity directly, however, has been developed yet. Here, we show the novel MRI sequence, called the partial spinlock sequence toward direct measurements of functional connectivity. This study investigates a probable measurement of phase differences directly associated with functional connectivity. By employing partial spinlock imaging, the neural magnetic field might influence the magnetic resonance signals. Using simulation and phantom studies to model the neural magnetic fields, we showed that magnetic resonance signals vary depending on the phase of an externally applied oscillating magnetic field with non-right flip angles. These results suggest that the partial spinlock sequence is a promising modality for functional connectivity measurements. [ABSTRACT FROM AUTHOR]

New application of fluorescence probe to detect apoplastic redox radicals from plant roots were sought. This probe can detect radicals selectively. Calibration curve for radicals was obtained using nitrogen monoxide as radical standard produced by NOC7. Apoplastic radicals released constitutively were quantified and the release rate was 60 μmol L−1 h−1. Oxidative burst triggered by chitin was distinguished from constitutive radical release. [ABSTRACT FROM PUBLISHER]

Recently, optically pumped atomic magnetometers (OPAMs) replacing superconductive quantum interference device-based magnetometers have attracted a considerable amount of attention. To apply the OPAMs to biomagnetic field measurements, simultaneous multilocation measurements are required. To fulfill the specific requirement, we have developed a hybrid cell, which contains potassium and rubidium atoms. The OPAM with a hybrid cell can enhance the spatial homogeneity due to the suppression of pump-beam absorption. Thus, we can have multiple measurement locations inside a hybrid cell with multiple pump and probe lasers. In this paper, we proposed a novel method to accomplish simultaneous multilocation measurements based on pump-beam modulation. Using two optical choppers, we operated a two-channel OPAM with two modulated pump beams. We investigated the signal strength of the OPAM as a function of modulation frequency and found that the signal strength decreased as the modulation frequency increased. Subsequently, we measured the magnetic field distributions generated from a loop coil to validate the proposed method and could confirm that they showed good agreements with the theoretical values. These results demonstrate the feasibility of the proposed method based on pump-beam modulation. [ABSTRACT FROM AUTHOR]

Superconducting quantum interference devices are widely used in basic and clinical biomagnetic measurements such as low-field magnetic resonance imaging and magnetoencephalography primarily because they exhibit high sensitivity at low frequencies and have a wide bandwidth. The main disadvantage of these devices is that they require cryogenic coolants, which are rather expensive and not easily available. Meanwhile, with the advances in laser technology in the past few years, optically pumped atomic magnetometers (OPAMs) have been shown to be a good alternative as they can have adequate noise levels and are several millimeters in size, which makes them significantly easier to use. In this study, we used an OPAM module operating at a Larmor frequency of 5 kHz to acquire NMR and MRI signals. This study presents these initial results as well as our initial attempts at imaging using this OPAM module. In addition, we have designed a liquid-cooled pre-polarizing coil that reduces the measurement time significantly. [ABSTRACT FROM AUTHOR]

Abstract: The interaction between a plasma flow and a small dielectric body with a weak intrinsic global magnetic field is studied by means of a five-dimensional full electromagnetic Vlasov simulation with two configuration spaces and three velocity spaces. In the present study, entry processes of ions into the nightside wake tail are examined. The simulation result shows that the bow shock and the magnetopause are formed on the dayside. However, most of solar-wind ions are reflected at the dayside magnetopause and are picked up by the interplanetary magnetic field. Then, a small part of the reflected ions are taken into the deep wake tail near the body by the E×B cycloid motion. [Copyright &y& Elsevier]

We measured the spatial homogeneity of spin polarization, which is directly related to the sensitivity and magnetic linewidth of an optically pumped atomic magnetometer with a hybrid cell of K and Rb atoms. This was done by changing the position of the probe beam. Furthermore, for comparison, we also measured the sensitivity and magnetic linewidth of atomic magnetometers with single K and single Rb cells, and found that optically thick atoms were spin polarized homogeneously with the hybrid cell. Optically thin alkali metal vapor can be spin polarized homogeneously, and the spin polarization transfers to an optically thick alkali metal vapor. An atomic magnetometer with the hybrid cell was found to be more effective in realizing simultaneous signal measurements at different locations with the uniform sensitivity and magnetic linewidth. [ABSTRACT FROM AUTHOR]

Abstract: In this paper, we describe the detection of rotating magnetic fields using optically pumped atomic magnetometers (OPAMs) for measuring magnetic resonance (MR) signals. From the results of rotating- and alternating-magnetic-field measurements, we found that to detect a rotating magnetic field with high sensitivity, the rotation direction of the magnetic field to be measured must select the bias-magnetic-field direction of OPAM. In addition, the OPAM sensitivity for rotating magnetic fields should be twice that for alternating magnetic fields. These results indicate that for measuring MR signals, magnetic fields caused by rotating magnetizations can be detected with the sensitivity of order at 1kHz using OPAMs. [Copyright &y& Elsevier]

An optically pumped atomic magnetometer using a hybrid cell of potassium and rubidium atoms was demonstrated to yield high sensitivity to magnetic fields. We operated the magnetometer with the four possible combinations of optically pumped and optically probed atoms and found that the combination of optically pumped potassium and optically probed rubidium showed the highest sensitivity among the four combinations because the rubidium atoms were denser than those of potassium. Furthermore, we investigated the dependence of the sensitivity on the power densities of the pump and probe beams and the wavelength of the probe beam. The magnetometer using the hybrid cell required higher pump-beam power and had narrower magnetic linewidth than those of the single alkali-metal cell. However, the magnetic linewidth was larger than the theoretical value, ignoring the spin relaxation caused by the spin-exchange collisions. By adjusting the laser conditions, the highest sensitivity approached 30 fTrms/\rm Hz^1/2. [ABSTRACT FROM AUTHOR]

Oligomethylene-tethered w-alkenyl ω-oxobutanoates and 3-oxobutanamides underwent manganese(III)-mediated oxidative intramolecular addition to produce dihydrofuran-fused macrolides and macrocyclic amides from 8 to 26 members. A similar reaction of the oligooxamethylene-tethered ω-alkenyl 3-oxobutanoates also gave dihydrofuran-fused crown ether type macrolides which had a phase-transfer ability with sodium and potassium picrates. The manganese(III)-assisted specific intramolecular addition could be explained by the π-complexation of the w-alkenyl part with the manganese(III) enolate. [ABSTRACT FROM AUTHOR]

Abstract: Plasma enhanced chemical vapor deposition using a non-thermal plasma jet was applied to deposition of ZnO films. Using vaporized bis(octane-2,4-dionato)zinc flow crossed by the plasma jet, the deposition rate was as high as several tens of nm/s. From the results of infrared spectra, the films deposited at the substrate temperature T sub =100°C contained a significant amount of carbon residue, while the films prepared at T sub =250°C showed less carbon fraction. The experimental results confirmed that the plasma jet decomposed bis(octane-2,4-dionato)zinc in the gaseous phase and on the substrate, and that there should be the critical T sub to form high-quality ZnO films in the range from 100 to 250°C. [Copyright &y& Elsevier]

Abstract: Macrocyclic compounds, which have two fused dihydrofuran rings, were synthesized with complete control by the oxidation of α,α,ω,ω-tetraaryl-α,(ω-1)-alkadienes 1 x with manganese(III)-oligomethylenebis(enolate) complexes directly formed by the reaction of the oligomethylene bis(3-oxobutanoate)s 2 y with manganese(III) acetate in situ. The oxamethylene-tethered macrodiolides 5 and 7 were also produced in good to moderate yields by a similar oxidation. The key intermediate, an electron donor–acceptor-like complex, was proposed for the efficient macrocyclization reaction. [Copyright &y& Elsevier]

This paper presents a damage estimation model of an earthquake using a pair of interferometric SAR data. Coherence is defined as a correlation function of two SLC (Single Look Complex) data. The coherence derived from multi-temporal SLCs before and after the earthquake includes a temporal decorrelation in disturbed regions. To estimate a degree of damage using the temporal decorrelation, the proposed model employs a coherence ratio, which is the ratio of the coherence derived from the SLCs before and after the event to the coherence derived from a pair of SLCs before the event. The temporal coherence ratio is computed by compensating the coherence ratio with the spatial decorrelation. The degrees of damage are defined by the logarithmic probability range of the ratio of the damage areas. It is shown that there is a significant relationship between the temporal coherence ratio and the probability of the degree of damage. In the case of the Hyogoken–Nanbu earthquake, its relationship can be represented by a linear function. The parameters of regression lines are set by applying the least-squares method. We have succeeded in estimating the cumulative probability of the degree of damage from the temporal coherence ratio. © 2003 Wiley Periodicals, Inc. Electr Eng Jpn, 143(3): 49–57, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.10138 [ABSTRACT FROM AUTHOR]

Eschericha coli cells, which contain apo-glucose dehydrogenase, were used in constructing a mediated amperometric glucose sensor. The E. coli modified glucose sensor, which was prepared by immobilizing E. coli cells behind a dialysis membrane on a carbon paste electrode containing 2,3-dimethoxy-5-methyl-1,4-benzoquinone (Q0), produced a current for the electrocatalytic oxidation of glucose with Q0 as an electron transfer mediator only after the addition of a trace amount of pyrroloquinoline quinone (PQQ), the cofactor of the enzyme. This allows a novel method of glucose measurements free from the interference of the redox active substances, if contained, in a sample solution. The glucose sensor was insensitive to dioxygen; the currents measured under anaerobic and aerobic conditions, and even under dioxygen saturated conditions were almost the same in magnitude at a given concentration of glucose over the range of 0.2–10 mM. Response time of the glucose sensor was 2 min to attain 90% level of the steady-state current. The E. coli modified glucose sensor was reusable when treated with ethylenediaminetetraacetic acid (EDTA). When E. coli cells were lyophilized, they could be stored at room temperature in a dry box for more than six months without loss of the catalytic activity. [Copyright &y& Elsevier]

The currently available indicators—sensitivity and specificity of expert radiological evaluation of MRIs—to identify mesial temporal lobe epilepsy (MTLE) associated with hippocampal sclerosis (HS) are deficient, as they cannot be easily assessed. We developed and investigated the use of a novel convolutional neural network trained on preoperative MRIs to aid diagnosis of these conditions. We enrolled 141 individuals: 85 with clinically diagnosed mesial temporal lobe epilepsy (MTLE) and hippocampal sclerosis International League Against Epilepsy (HS ILAE) type 1 who had undergone anterior temporal lobe hippocampectomy were assigned to the MTLE-HS group, and 56 epilepsy clinic outpatients diagnosed as nonepileptic were assigned to the normal group. We fine-tuned a modified CNN (mCNN) to classify the fully connected layers of ImageNet-pretrained VGG16 network models into the MTLE-HS and control groups. MTLE-HS was diagnosed using MRI both by the fine-tuned mCNN and epilepsy specialists. Their performances were compared. The fine-tuned mCNN achieved excellent diagnostic performance, including 91.1% [85%, 96%] mean sensitivity and 83.5% [75%, 91%] mean specificity. The area under the resulting receiver operating characteristic curve was 0.94 [0.90, 0.98] (DeLong's method). Expert interpretation of the same image data achieved a mean sensitivity of 73.1% [65%, 82%] and specificity of 66.3% [50%, 82%]. These confidence intervals were located entirely under the receiver operating characteristic curve of the fine-tuned mCNN. Deep learning-based diagnosis of MTLE-HS from preoperative MR images using our fine-tuned mCNN achieved a performance superior to the visual interpretation by epilepsy specialists. Our model could serve as a useful preoperative diagnostic tool for ascertaining hippocampal atrophy in patients with MTLE. • Modified convolution neural network (mCNN) MRIs diagnosed MTLE-HS preoperatively. • Diagnostic sensitivity & specificity of fine-tuned mCNN was higher than specialists. • Our model can facilitate the preoperative diagnosis of hippocampal sclerosis. • New deep learning models to correct vanishing gradient by multilayer CNN are needed. [ABSTRACT FROM AUTHOR]

Presents information on a study that proposed an extended Learning Vector Quantization (LVQ) neural networks (NN) to land cover mapping. Description of the LVQ NN; Experimental results of the study; Conclusions.

We have developed a K-Rb hybrid optically pumped atomic magnetometer (OPAM) for biomagnetic measurements. With this hybrid OPAM, we used a linear photodiode array and a charge-coupled device (CCD) sensor to instantaneously measure 1-D and 2-D magnetic field distributions generated by a test coil, respectively. The measured distributions were compared with those calculated using the Biot–Savart law and showed good agreement for the linear photodiode array; however, in the case of the CCD sensor in the area away from the test coil, the intensity of the detected magnetic field was slightly different from the calculated one, possibly because of the diffusion of the spin-polarized atoms as well as smear and blooming in the CCD sensor. The sensitivity of the OPAM was 5–6 pT/Hz ^1/2 using the linear photodiode array and $\sim 10$ pT/Hz ^1/2 using the CCD sensor. In future experiments, we plan to fabricate a sensor cell with a high density of probe atoms and reduce the noise generated in the electronic circuitry of the detectors in order to increase sensitivity. [ABSTRACT FROM AUTHOR]

• MR imaging simulation with spin-lock preparations. • Comparison of the simulated images with experimental ones. • Analytical solution of the Bloch equation during RF pulse and gradient field. • The simulated images with the sufficient sub-voxels agreed with the experimental ones. • GPU parallel computing is effective to avoid the impractical calculation time. Spin-lock preparation was studied to detect tiny oscillatory magnetic fields such as a neural magnetic field without the blood oxygen level-dependent effect. This approach is a direct measurement and independent of static magnetic field strength. Accordingly, it is anticipated as a feasible functional magnetic resonance imaging (fMRI) in low and ultra-low-field MRI. Several reports have been published on spin-lock preparation but reports on imaging simulation are rare. Research in this area can assist in investigating magnetic resonance signal changes and, accordingly, can help to develop new spin-lock methods. In this study, we propose an imaging simulation method with an analytical solution using the Bloch equation. To demonstrate the feasibility of our proposed method, we compared simulated images with experimental results in which the number of sub-voxels and the amplitude and phase of the target oscillatory magnetic fields varied. In addition, we also applied graphics processing unit parallel computing and investigated the feasibility of avoiding an impracticable calculation time by doing so. [ABSTRACT FROM AUTHOR]

• Comparison of two spin-lock methods for low-field functional MRI. • The analytical solution of the Bloch equation under these sequences. • The difference of the methods was clarified experimentally and theoretically. • With 0.3-T MRI scanner, we investigated the detectable strength of the two methods. We demonstrated the feasibility of the spin-lock preparation sequence using low-field magnetic resonance (MR) imaging that prevents interference from blood-oxygenation-level-dependent effects. We focused on two spin-lock preparations: spin-lock Mz (SL-Mz) and stimulus-induced rotary saturation (SIRS) and analyzed the magnetization dynamics during the sequences using the Bloch equation. Next, we performed phantom experiments using a loop coil to investigate the MR signal change as a function of the target signal strength and phase. Furthermore, we performed curve fittings to consider the radio frequency, which agreed with the experimental results. Then, we investigated the detectable strength of the magnetic field, and the SL-Mz detected a signal strength of 2.34 nT. In conclusion, our experimental results showed good agreement with the results obtained using the Bloch equation. [ABSTRACT FROM AUTHOR]

Mutations in the gene encoding the transient receptor potential vanilloid member 4 (TRPV4), a Ca2+ permeable nonselective cation channel, cause TRPV4‐related disorders. TRPV4 is widely expressed in the brain; however, the pathogenesis underlying TRPV4‐mediated Ca2+ deregulation in neurodevelopment remains unresolved and an effective therapeutic strategy remains to be established. These issues were addressed by isolating mutant dental pulp stem cells from a tooth donated by a child diagnosed with metatropic dysplasia with neurodevelopmental comorbidities caused by a gain‐of‐function TRPV4 mutation, c.1855C > T (p.L619F). The mutation was repaired using CRISPR/Cas9 to generate corrected isogenic stem cells. These stem cells were differentiated into dopaminergic neurons and the pharmacological effects of folic acid were examined. In mutant neurons, constitutively elevated cytosolic Ca2+ augmented AKT‐mediated α‐synuclein (α‐syn) induction, resulting in mitochondrial Ca2+ accumulation and dysfunction. The TRPV4 antagonist, AKT inhibitor, or α‐syn knockdown, normalizes the mitochondrial Ca2+ levels in mutant neurons, suggesting the importance of mutant TRPV4/Ca2+/AKT‐induced α‐syn in mitochondrial Ca2+ accumulation. Folic acid was effective in normalizing mitochondrial Ca2+ levels via the transcriptional repression of α‐syn and improving mitochondrial reactive oxygen species levels, adenosine triphosphate synthesis, and neurite outgrowth of mutant neurons. This study provides new insights into the neuropathological mechanisms underlying TRPV4‐related disorders and related therapeutic strategies. [ABSTRACT FROM AUTHOR]

Melatonin entrainment of suprachiasmatic nucleus-regulating circadian rhythms is mediated by MT1 and MT2 receptors. Melatonin also has neuroprotective and mitochondrial activating effects, suggesting it may affect neurodevelopment. We studied melatonin's pharmacological effects on autism spectrum disorder (ASD) neuropathology. Deciduous tooth-derived stem cells from children with ASD were used to model neurodevelopmental defects and differentiated into dopaminergic neurons (ASD-DNs) with or without melatonin. Without melatonin, ASD-DNs had reduced neurite outgrowth, mitochondrial dysfunction, lower mitochondrial Ca2+ levels, and Ca2+ accumulation in the endoplasmic reticulum (ER) compared to control DNs from typically developing children-derived stem cells. Melatonin enhanced IP3-dependent Ca2+ release from ER to mitochondria, improving mitochondrial function and neurite outgrowth in ASD-DNs. Luzindole, an MT1/MT2 antagonist, blocked these effects. Thus, melatonin supplementation may improve dopaminergic system development in ASD by modulating mitochondrial Ca2+ homeostasis via MT1/MT2 receptors. [Display omitted] • Dopaminergic neurons were differentiated from stem cells with or without melatonin. • ASD-DNs exhibited impaired neurite outgrowth and mitochondrial dysfunction. • Melatonin improved mitochondrial function and neurite outgrowth in ASD-DNs. • Melatonin supplementation may improve dopaminergic system development in ASD. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Analytical solution of magnetization dynamics under SIRS. • Two modes in the analytical solution. • Modes depending on target oscillating field. • The solution agreed with measurements. Abstract We studied stimulus-induced rotary-saturation preparation (which enables measurement of oscillating magnetic fields using MRI) and derived an analytical solution of the Bloch equation to understand magnetization dynamics mathematically and comprehensively and to conduct simulations without sequential-calculation techniques such as the Runge-Kutta method. We formulated the dynamics using the Bloch equation, introducing an additional rotating frame and some approximations to make it into a homogeneous differential equation. Moreover, we found that there are two modes depending on the target oscillating magnetic field. To confirm the validity of the solution, we experimentally investigated its characteristics and performed curve fitting using the analytical model. Considering the constraints on the frame, the analytical solution was found to agree with experimental data. The experimental data indicate that it is necessary to design robust sequences compensating B 0 or B 1 lock spatial inhomogeneity to improve measurements. Therefore, experimenters should consider the dynamics of magnetization with RF pulses to rewind the spin phase for accurate measurements. [ABSTRACT FROM AUTHOR]

Objective We aimed to validate the usefulness of gradient magnetic-field topography (GMFT) for analysis of ictal magnetoencephalography (MEG) in patients with neocortical epilepsy. Methods We identified 13 patients presenting with an ictal event during preoperative MEG. We applied equivalent current dipole (ECD) estimation and GMFT to detect and localize the ictal MEG onset, and compared these methods with the ictal onset zone (IOZ) derived from chronic intracranial electroencephalography. The surgical resection areas and outcomes were also evaluated. Results GMFT detected and localized the ictal MEG onset in all patients, whereas ECD estimation showed localized ECDs in only 2. The delineation of GMFT was concordant with the IOZ at the gyral-unit level in 10 of 12 patients (83.3%). The detectability and precision of delineation of ictal MEG activity by GMFT were significantly superior to those of ECD ( p < 0.05 and p < 0.01, respectively). Complete resection of the IOZ in the concordant group provided seizure freedom in 3 patients, whereas seizures remained in 9 patients who had incomplete resections. Conclusions Because of its higher spatial resolution, GMFT of ictal MEG is superior to conventional ECD estimation in patients with neocortical epilepsy. Significance Ictal MEG study is a useful tool to estimate the seizure onset in patients with neocortical epilepsy. [ABSTRACT FROM AUTHOR]

Objective To study a new approach to indocyanine green ( ICG) angiography for contrasting the ocular fundus in cats. Animals studied Six healthy laboratory cats. Procedures Fluorescein ( FLUO) and ICG angiography were performed using an infrared-sensitive charged coupled device-equipped fundus camera on sedated cats. Results At 12.3 ± 3.4 s after ICG administration, the choroidal arteries could be seen extending radially from the optic disk. The choroidal veins became apparent at 16.2 ± 4.1 s alongside the choroidal arteries. Gradual fading of the choroidal vessels began 5.8 ± 1.5 min postdye administration and diffuse fluorescence of the fundus appeared. Diffuse fluorescence of the optic disk faded at about 18.8 ± 2.9 min. Mean arterial blood pressure at 1 and 3 min after ICG administration showed no significant change when compared to pre-administration ( P > 0.05). However, 5 min ( P = 0.054) and 10 min ( P < 0.05) postadministration, a significant drop in blood pressure occurred. The time lapse between FLUO administration and its appearance in the ocular fundus was 15.7 ± 3.8 s. Retinal veins became apparent at 22.0 ± 3.6 s alongside retinal arteries. At 31.2 ± 4.1 s, full venous fluorescence was visualized throughout the entire fundus. Conclusions While FLUO angiography shows only the retinal vessels, ICG angiography enabled visualization of the choroidal vasculature. ICG angiography provides clear resolution while remaining reliable and simple; thus, a combination of ICG and FLUO angiography shows promise as a diagnostic aid for clinical evaluation of various chorioretinal diseases in cats. [ABSTRACT FROM AUTHOR]

Numerous mast cells are present in the choroid, but the effects of mast cell mediators on retinal pigment epithelial (RPE) cells are not well understood. We investigated the influence of mast cell mediators on RPE cells in vitro, focusing on tryptase. Expression of receptors was examined by the reverse transcription polymerase chain reaction. We also assessed production of interleukin 8 and vascular endothelial growth factor (VEGF) after RPE cells were stimulated with mast cell mediators by using an antibody array and enzyme-linked immunosorbent assay. Furthermore, we investigated the influence of tryptase on RPE cell migration and integrity by the scratch assay and the transepithelial resistance. RPE cells expressed protease-activated receptor 2 (PAR2), histamine receptor 1, tumor necrosis factor-α (TNF-α) receptor 1, and CCR 1, 3, 4, 8, and 11. Tryptase, PAR2 agonists, histamine, and TNF-α all enhanced interleukin 8 production by RPE cells, while only tryptase enhanced VEGF production. Tryptase also enhanced expression of phosphorylated extracellular signal-regulated kinases 1/2, resulting in increased migration of RPE cells. However, tryptase did not alter epithelial integrity or the expression of zonula occludens-1 and junctional adhesion molecule-A by RPE cells. Mast cell mediators, especially tryptase, may influence RPE cell inflammation. [ABSTRACT FROM AUTHOR]

Focal cortical dysplasia is the most common malformation during cortical development, sometimes excised by epilepsy surgery and often caused by somatic variants of the mTOR pathway genes. In this study, we performed a genetic analysis of epileptogenic brain malformed lesions from 64 patients with focal cortical dysplasia, hemimegalencephy, brain tumors, or hippocampal sclerosis. Targeted sequencing, whole-exome sequencing, and single nucleotide polymorphism microarray detected four germline and 35 somatic variants, comprising three copy number variants and 36 single nucleotide variants and indels in 37 patients. One of the somatic variants in focal cortical dysplasia type IIB was an in-frame deletion in MTOR, in which only gain-of-function missense variants have been reported. In focal cortical dysplasia type I, somatic variants of MAP2K1 and PTPN11 involved in the RAS/MAPK pathway were detected. The in-frame deletions of MTOR and MAP2K1 in this study resulted in the activation of the mTOR pathway in transiently transfected cells. In addition, the PTPN11 missense variant tended to elongate activation of the mTOR or RAS/MAPK pathway, depending on culture conditions. We demonstrate that epileptogenic brain malformed lesions except for focal cortical dysplasia type II arose from somatic variants of diverse genes but were eventually linked to the mTOR pathway. [ABSTRACT FROM AUTHOR]

Highly sensitive magnetic sensors for biomagnetic measurements are often used in gradiometers to suppress the magnetic noise from the environment. We propose a differential measurement method in optically pumped atomic magnetometers, where the frequency responses from the two magnetometers are balanced separately and the signals are subtracted. A magnetometer system that has two pairs of pump and probe beams was constructed to confirm the noise reduction experimentally. A general form for the transfer function of the magnetometer was derived and the parameters were experimentally fitted for the two magnetometers. The frequency responses were balanced with the inverse of the transfer function in the frequency domain, and the differential measurement improved the signal-to-noise ratio of the magnetometer system, even when the resonance frequency at the two sensing volumes differed by several hertz. This method considerably relaxes the requirement for the uniformity of the magnetic bias field at the two sensing volumes, which previously needed to be identical. [ABSTRACT FROM PUBLISHER]

Abstract: Idiopathic pulmonary fibrosis (IPF) involves pulmonary injury associated with inflammatory responses, fibrosis and dysfunction. Myofibroblasts and transforming growth factor (TGF)-β1 play major roles in the pathogenesis of this disease. Endoplasmic reticulum (ER) stress response is induced in the lungs of IPF patients. One of ER chaperones, the 150-kDa oxygen-regulated protein (ORP150), is essential for the maintenance of cellular viability under stress conditions. In this study, we used heterozygous ORP150-deficient mice (ORP150+/− mice) to examine the role of ORP150 in bleomycin-induced pulmonary fibrosis. Treatment of mice with bleomycin induced the expression of ORP150 in the lung. Bleomycin-induced inflammatory responses were slightly exacerbated in ORP150+/− mice compared to wild-type mice. On the other hand, bleomycin-induced pulmonary fibrosis, alteration of lung mechanics and respiratory dysfunction was clearly ameliorated in the ORP150+/− mice. Bleomycin-induced increases in pulmonary levels of both active TGF-β1 and myofibroblasts were suppressed in ORP150+/− mice. These results suggest that although ORP150 is protective against bleomycin-induced lung injury, this protein could stimulate bleomycin-induced pulmonary fibrosis by increasing pulmonary levels of TGF-β1 and myofibroblasts. [Copyright &y& Elsevier]

Continuous translation elongation, irrespective of amino acid sequences, is a prerequisite for living organisms to produce their proteomes. However, nascent polypeptide products bear an inherent risk of elongation abortion. For example, negatively charged sequences with occasional intermittent prolines, termed intrinsic ribosome destabilization (IRD) sequences, weaken the translating ribosomal complex, causing certain nascent chain sequences to prematurely terminate translation. Here, we show that most potential IRD sequences in the middle of open reading frames remain cryptic and do not interrupt translation, due to two features of the nascent polypeptide. Firstly, the nascent polypeptide itself spans the exit tunnel, and secondly, its bulky amino acid residues occupy the tunnel entrance region, thereby serving as a bridge and protecting the large and small ribosomal subunits from dissociation. Thus, nascent polypeptide products have an inbuilt ability to ensure elongation continuity. Synopsis: Acidic‐rich amino acid sequences destabilize the translating ribosome, stochastically inducing elongation abortion. This study unveils a positive feedback system mediated by the nascent chain within the ribosomal tunnel, which ensures elongation continuity by stabilizing the ribosome. Translation of acidic or proline‐intermitted intrinsic ribosome destabilization (IRD) sequences favors premature elongation cessation.Nascent peptide within the ribosomal exit tunnel helps to ensure translation continuity by counteracting IRD.IRD‐counteracting mechanisms include the exit tunnel‐spanning nascent polypeptide and its bulky amino acid residues that occupy the tunnel entrance region.Selection for length and bulkiness in nascent chains to minimize the risk of nonproductive translation discontinuation affects amino acid distribution throughout the proteome. [ABSTRACT FROM AUTHOR]

Focal cortical dysplasia (FCD) is an important etiology of focal epilepsy in children and adults. However, only a few preclinical models sufficiently reproduce the characteristic histopathologic features of FCD. To improve the success rate of clinical trials for antiseizure medications (ASMs) in patients with FCD, more human-relevant preclinical models are needed, and epileptic foci resected from patients are a powerful tool for this purpose. Here, we conducted ex vivo studies using epileptic foci resected from patients with FCD type II to evaluate the pharmacologic effects of the ASM candidate E2730, a selective uncompetitive inhibitor of γ-aminobutyric acid transporter 1. We used the same ex vivo assay system to assess carbamazepine (CBZ), an ASM often prescribed for focal epilepsy, as a reference. At the higher dose tested (200 µM), both E2730 and CBZ suppressed spontaneous epileptiform activities almost completely. At the lower dose (100 µM), CBZ reduced the area of brain tissue showing epileptiform activity, whereas E2730 significantly decreased the number of epileptiforms. These findings suggest that E2730—both as a single agent and in combination with CBZ—merits evaluation in clinical trials involving patients with FCD. • Epileptiform activities in surgical specimen taken from the patient of Focal cortical dysplasia (FCD) is investigated. • Pharmacological effects of E2730 against epileptiform activities in the focal tissue of FCD type II were evaluated. • At low concentrations, different mechanism for anti-seizure effects was revealed between E2730 and carbamazepine. • Combination therapy of E2730 and carbamazepine may be effective for seizure termination in FCD type II. [ABSTRACT FROM AUTHOR]

• Dependence of spin-lock-based fMRI sensitivity on target magnetic fields direction. • Spin-lock-based fMRI is insensitive to the magnetic fields perpendicular to B 0. • Same tendency was expected to appear in similar spin-lock sequences for fMRI. • Low-field MRI with pancake-type MRI scanners may overcome the issue by head rotation. Several noninvasive techniques for the direct measurement of the neuronal activity using magnetic resonance imaging (MRI) have recently been reported. As a promising candidate, we focus on a spin-lock MRI sequence (i.e., stimulus-induced rotary saturation (SIRS)) directly measuring a tiny oscillating magnetic field. Previous phantom studies on SIRS have applied the target oscillating magnetic field parallel to the direction of the static magnetic field B 0 . However, in practice, the neuromagnetic fields are not always aligned in the same direction as in such a condition. This study investigates the MR signal changes during SIRS when the target magnetic field direction is not the same as that of the B 0 field through both phantom experiments and Bloch simulations. The experimental results indicate that only the target magnetic field component along the B 0 field affects the signal change, indicating that SIRS has partial sensitivity, even if the target magnetic fields are tilted from the B 0 field. Furthermore, the simulation results show good agreements with the experimental results. These results clarify the sensitivity direction of SIRS-based fMRI and lead to the possibility that the direction of the generated neuromagnetic fields can be estimated, such that we can separate directional information from the other information contained in neuromagnetic fields (e.g., phase information). [ABSTRACT FROM AUTHOR]

Objective To determine the predictors of cognitive function in patients with drug-resistant gelastic seizures ( GS) related to hypothalamic hamartoma ( HH) before and after stereotactic radiofrequency thermocoagulation surgery ( SRT). Methods We studied 88 patients with HH who underwent SRT between October 1997 and December 2014. Patients received neuropsychological tests preoperatively and postoperatively. Based on the preoperative measures, patients were categorized as 'high-functioning' (full-scale intelligence quotient [ FSIQ] ≥70; n = 48) and 'low-functioning' group ( FSIQ <70; n = 40). Univariate and multivariate linear regression analyses determined the clinical, electroencephalography ( EEG), and imaging factors associated with preoperative cognitive function as well as postoperative cognitive change. Results Eighty-seven patients (98.8%) were followed postoperatively for an average of 3.3 years, and 75 (85.2%) of them achieved GS remission at the last hospital visit. Neuropsychological performance was significantly improved after surgery in both groups. Multivariate linear regression analysis showed that a smaller HH size (p = 0.002) and a smaller number of antiepileptic drugs (p < 0.001) were preoperatively associated with better neuropsychological performance. Multivariate linear regression analysis showed that better postoperative improvement in cognition was associated with a shorter duration of epilepsy (p = 0.03). Significance Cognitive impairment related to epileptic encephalopathy may improve following SRT in substantial proportions of HH patients. Reduced improvement in postoperative cognitive function in patients with longer duration of epilepsy warrants further studies to determine if earlier SRT provides a greater chance of postoperative cognitive improvement in patients with HH. [ABSTRACT FROM AUTHOR]

Objective It is well-known that there is a correlation between the neuropathological grade of hippocampal sclerosis (HS) and neuroradiological atrophy of the hippocampus in mesial temporal lobe epilepsy (mTLE) patients. However, there is no strict definition or criterion regarding neuron loss and atrophy of the amygdala neighboring the hippocampus. We examined the relationship between HS and neuronal loss in the amygdala. Materials and methods Nineteen mTLE patients with neuropathological proof of HS were assigned to Group A, while seven mTLE patients without HS were assigned to Group B. We used FreeSurfer software to measure amygdala volume automatically based on pre-operation magnetic resonance images. Neurons observed using Klüver-Barrera (KB) staining in resected amygdala tissue were counted. and the extent of immunostaining with stress marker antibodies was semiquantitatively evaluated. Results There was no significant difference in amygdala volume between the two groups (Group A: 1.41 ± 0.24; Group B: 1.41 ± 0.29 cm 3 ; p = 0.98), nor in the neuron cellularity of resected amygdala specimens (Group A: 3.98 ± 0.97; Group B: 3.67 ± 0.67 10 × −4 number of neurons/μm 2 ; p = 0.40). However, the HSP70 level, representing acute stress against epilepsy, in Group A patients was significantly larger than that in Group B. There was no significant difference in the level of Bcl-2, which is known as a protein that inhibits cell death, between the two groups. Conclusions Neuronal loss and volume loss in the amygdala may not necessarily follow hippocampal sclerosis. From the analysis of stress proteins, epileptic attacks are as likely to damage the amygdala as the hippocampus but do not lead to neuronal death in the amygdala. [ABSTRACT FROM AUTHOR]

Hypothalamic hamartoma (HH), composed of neurons and glia without apparent cytologic abnormalities, is a rare developmental malformation in humans. Patients with HH often have characteristic medically refractory gelastic seizures, and intrinsic epileptogenesis within the lesions has been speculated. Herein we provide evidence to suggest that in HH neurons, Ca2+ permeability through α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors is aberrantly elevated. In needle biopsy specimens of HH tissue, field potential recordings demonstrated spontaneous epileptiform activities similar to those observed in other etiologically distinct epileptogenic tissues. In HH, however, these activities were clearly abolished by application of Joro Spider Toxin (JSTX), a specific inhibitor of the Ca2+-permeable AMPA receptor. Consistent with these physiologic findings, the neuronal nuclei showed disappearance of adenosine deaminase acting on RNA 2 (ADAR2) immunoreactivity. Furthermore, examination of glutamate receptor 2 (GluA2) messenger RNA (mRNA) revealed that editing efficiency at the glutamine/arginine site was significantly low. These results suggest that neurons in HH may bear Ca2+-permeable AMPA receptors due to dislocation of ADAR2. [ABSTRACT FROM AUTHOR]

Objective In patients with hemifacial spasm, stimulation of a branch of the affected facial nerve elicits an abnormal response in the muscles innervated by another branch. We tested the hypothesis that this anomaly results from lateral spread of impulses from one motor axon to another at the site of the nerve compression by the offending artery. Methods In a preoperative study of 21 patients, we delivered a series of stimuli, in short increments, successively distally along the temporal branch of the facial nerve to record abnormal muscle responses from the orbicularis oculi and mentalis muscles. In intraoperative monitoring of 10 patients during microvascular decompression, we monitored propagating nerve action potentials with a handheld electrode placed on the facial nerve 3 mm distal to the vascular compression site. Results With incremental shifts of stimulating points distally, the latency of abnormal muscle responses increased by 0.3 ± 0.1 ms/cm. This finding implicates the antidromic motor impulse as the trigger for lateral spread. The nerve action potentials recorded during surgery comprised the initial antidromic signal followed by one or more additional peaks. The latter immediately abated, together with abnormal muscle responses, after microvascular decompression. Thus, the secondary peaks must represent the orthodromic impulses generated by ephaptic transmission. An average inter-peak interval of 1.1 ms between the first and secondary peaks is consistent with the estimated conduction time from the stimulation point to the site of vascular compression but not to the facial nucleus and return. Conclusion An abnormal muscle response results from lateral spread of impulses between motor axons at the site of vascular compression rather than at the facial nucleus. Significance This study establishes the mechanism of lateral spread responsible for abnormal muscle responses and contributes to the understanding of pathophysiology underlying hemifacial spasm. [ABSTRACT FROM AUTHOR]

The patterns of ictal high-frequency oscillation (HFO) of intracranial EEGs in epilepsy patients due to various etiologies were investigated. All patients underwent resective epilepsy surgery, and the pathological diagnoses were confirmed as follows: focal cortical dysplasia (FCD), 5; tumor, 3; tuberous sclerosis (TS), 2; cavernous angioma (CA), 1; and no significant alteration (NSA), 1. EEGs were recorded at a sampling rate of 1 kHz. Ictal HFOs were analyzed by visual inspection and time–frequency analysis (multiple band frequency analysis; MBFA). Ictal HFOs were divided based on the maximum frequency on MBFA: <100 Hz, NSA ( n = 1); 100–150 Hz, FCD type I ( n = 2), FCD type IIA ( n = 1), tumor ( n = 1), CA ( n = 1); 150–200 Hz, FCD type IIB ( n = 1), tumor ( n = 3), TS ( n = 1); 200–250 Hz, FCD type IIB ( n = 1) and TS ( n = 1). FCD type IIB and TS had HFO with a higher frequency, whereas FCD type I and CA had HFO with a lower frequency. The results of this study suggest that the frequency of HFO reflects the epileptogenic substrate and its pathophysiological mechanism. Further investigation of a large series is necessary to determine the relationship between HFO and ictogenesis. [ABSTRACT FROM AUTHOR]

A 68-year-old man who underwent living-unrelated kidney transplantation from his spousal donor was immunosuppressed with tacrolimus and mycophenolate mofetil. Despite his uneventful clinical course, protocol biopsy at 2 years post transplant showed de novo CNI tubulotoxicity despite low tacrolimus exposure. Everolimus was added in order to discontinue TACER. However, prominent proteinuria impeded continuation of everolimus since biopsy showed diffuse glomerular endocapillary proliferation without C4d deposition. No donor-specific antibody was detected. Pulse steroids were given and proteinuria returned to normal with histological reversal. [ABSTRACT FROM AUTHOR]

Objective To test a hypothesis that an abnormal muscle response (AMR) results from ephaptic transmission at the compression site in hemifacial spasm (HFS). Methods We recorded AMRs from the orbicularis oculi and mentalis muscles during intraoperative of facial nerve action potential (NAP) monitoring performed in 5 patients with HFS. Before microvascular decompression (MVD), facial nerve was stimulated to give rise, antidromic NAP and orthodromic NAP. Results Facial NAPs recorded 3 mm distal to the compression site, comprised a double peak with an average interval of 1.1 ms before MVD. The second peak abated together with AMRs immediately after MVD. An average inter-peak interval of 1.1 ms falls short of the estimated conduction time to the facial nucleus, implicating, as the origin, an ephaptic transmission at the compression site. Conclusion The lateral spread of impulse by ephapsis at the compression site gives rise to an AMR in HFS, with estimate transmission time of 1.0 ms Significance This study establishes the primary mechanism of the lateral spread responsible for generation of AMR and contributes to the understanding of the pathophysiology of HFS. [ABSTRACT FROM AUTHOR]