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Abstract The abnormal aggregation of TDP-43 into cytoplasmic inclusions in affected neurons is a major pathological hallmark of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Although TDP-43 is aberrantly accumulated in the neurons of most patients with sporadic ALS/FTD and other TDP-43 proteinopathies, how TDP-43 forms cytoplasmic aggregates remains unknown. In this study, we show that a deficiency in DCTN1, a subunit of the microtubule-associated motor protein complex dynactin, perturbs the dynamics of stress granules and drives the formation of TDP-43 cytoplasmic aggregation in cultured cells, leading to the exacerbation of TDP-43 pathology and neurodegeneration in vivo. We demonstrated using a Drosophila model of ALS/FTD that genetic knockdown of DCTN1 accelerates the formation of ubiquitin-positive cytoplasmic inclusions of TDP-43. Knockdown of components of other microtubule-associated motor protein complexes, including dynein and kinesin, also increased the formation of TDP-43 inclusions, indicating that intracellular transport along microtubules plays a key role in TDP-43 pathology. Notably, DCTN1 knockdown delayed the disassembly of stress granules in stressed cells, leading to an increase in the formation of pathological cytoplasmic inclusions of TDP-43. Our results indicate that a deficiency in DCTN1, as well as disruption of intracellular transport along microtubules, is a modifier that drives the formation of TDP-43 pathology through the dysregulation of stress granule dynamics.

This paper proposes a gate drive circuit with a condition monitoring function for detecting the gate oxide degradation in silicon carbide (SiC) metal–oxide–semiconductor field-effect transistors (MOSFETs). Trapped charges in the gate oxide can cause fluctuations in the on-resistance and gate threshold voltages. These phenomena affect the long-term reliability of power conversion circuits. The proposed condition monitoring function detects the degradation of the gate oxide by measuring the input capacitance $C_{\mathrm{iss}}$ versus the gate–source voltage $v_{\mathrm{GS}}$ characteristics ($C_{\mathrm{iss}}$–$v_{\mathrm{GS}}$ characteristics) of SiC MOSFETs implemented in power conversion circuits. Experiments on the proposed gate drive circuit were conducted using a 400 W-rated buck converter circuit in which a SiC MOSFET is implemented. The experimental results show that the gate drive circuit is capable of online measurement of $C_{\mathrm{iss}}$–$v_{\mathrm{GS}}$ characteristics and gate drive at 20 kHz. The online measurement of the $C_{\mathrm{iss}}$–$v_{\mathrm{GS}}$ characteristics corresponds to the offline measurement with a measurement instrument, indicating the effectiveness of the gate drive circuit.

Modern electric railway vehicles are faced with the challenge of achieving electromagnetic compatibility (EMC) compliance with railway signaling systems. Currently, no established countermeasures or design methods that guarantee passing the EMC compliance test are available. Therefore, the enhancement of EMC management during vehicle manufacturing processes is imperative. This study devised a pre-accreditation method to be implemented at the vehicle completion stage, prior to the EMC compliance test. The proposed method entails the substitution of real ground signaling devices, whose parameters are difficult to obtain, with unified coils. The effectiveness of this approach is validated by observing whether the gain difference remains consistent when using both an exciting coil and a test train. To illustrate this method, we selected the platform screen door (PSD) balise as a representative signaling device, which is widely utilized in various railway stations. The unified coil employed in this study can be easily fabricated. First, we measured the gain difference (the ratio between the induced voltage of coils and the exciting coil current) between the PSD balise and unified coil. Next, we measured the unknown magnetic flux induced by an 8-car electric multiple unit test train by utilizing the PSD balise and unified coil. Finally, we calculated the measured difference between them. The gain and measured differences properly agreed (within 6 dB) across a wide frequency range of 200 kHz to 4 MHz.

This paper proposes a solid-state circuit breaker comprising silicon carbide (SiC) MOSFETs and a SiC diode, based on the principle of avalanche voltage clamping. The key challenge in realizing a solid-state circuit breaker lies in reducing conduction loss. A parallel connection of power semiconductor devices is the suitable configuration that can meet these requirements. However, in such a configuration, the current balance during cutoff operation may be affected by the variation in the breakdown voltage characteristics of the power semiconductor devices. To address this issue, the proposed circuit breaker employs clamping with a SiC merged pin Schottky (MPS) diode, with high avalanche tolerance and robust characteristics under repetitive avalanche events. The effectiveness of the proposed solid-state circuit breaker is validated through experiments conducted in an unclamped inductive switching (UIS) test circuit using a 400-V, 50-A DC distribution system. Eventually, the demonstrations indicate that the SiC diode clamping method contributes to more compact implementations for solid-state circuit breakers.

This article proposes an improved overvoltage suppression method for the initial charge of the dc capacitor in voltage source power converters. The proposed method makes multiple short-circuits in each leg, utilizing power devices in the converter. These short-circuits discharge the dc capacitor and suppress overvoltage caused by resonant effects during the initial charge. The utilization of short durations of short-circuits multiple times in each leg reduces the power consumption in the power devices and results in a decrease in the peak junction temperature. Experimental verification using a 200-V, 5-kVA three-phase converter demonstrates that the proposed multiple short-circuit method reduces power consumption by 6% and suppresses device degradation by more than 40 times compared to the previously proposed single short-circuit method. The experimental results exhibit the effective overvoltage suppression capability of the proposed method with modest device degradation. As a result, the proposed method allows for the elimination of the initial charge circuit, leading to reductions in the size and cost of power converters, particularly in PWM rectifiers.

The development of SiC and GaN power devices to achieve high-speed switching operations in power converter circuits is underway. The stray inductance caused by the bus bar geometries between DC capacitors and power devices influences high-speed switching circuits, such as surge voltages and switching losses. Therefore, the evaluation of the parasitic parameters is essential in designing power converter circuits. Currently, parasitic parameters that consider various bus bar geometries are calculated using finite element analysis (FEA) each time, which requires a large calculation time. This article proposes a prediction procedure for the parasitic parameters that easily and quickly consider complex bus bar geometries by performing online machine learning of FEA-based datasets. A laminated bus bar with two apertures to connect DC capacitors or power modules is analyzed, and the parasitic resistance, inductance, and capacitance are predicted. This article describes how large datasets can be obtained from multiple installments and perform online machine learning using XGBoost. To discuss the benefits of online machine learning, the prediction accuracy using test data in multiple machine learning models with different amounts of training data is compared. The mean relative error (MRE) between the predicted and analyzed values improves from 250% to 8% when parasitic parameters are predicted in the frequency range of 50 kHz to 100 MHz.

In the traction system of rolling stock, the common-mode (CM) voltage is over 500 V, so the inductors that suppress the CM current are prone to saturation. To prevent saturation, the traction inverter needs many numbers of cores inside CM inductors, but the required number of cores has been determined empirically. This paper proposes a method calculate the approximate number of nanocrystalline cores to avoid saturation of CM inductors in railway traction inverters without circuit simulation. Using the only the CM capacitance of traction motor and the core characteristics on the datasheet, the maximum flux density of the inductor is calculated. Comparing calculated results of the maximum flux density with the results measured with a 1500 V DC inverter indicates that the proposed method can better identify the occurrence of saturation than the methods based on CM current presented in the literature. Furthermore, for the entire CM voltage range from 500 V to 3000 V, the minimum number of cores which saturation is prevented by the proposed calculation method is shown to be in reasonable agreement with the simulation results.

Abnormal expansions of GGGGCC repeat sequence in the noncoding region of the C9orf72 gene is the most common cause of familial amyotrophic lateral sclerosis and frontotemporal dementia (C9-ALS/FTD). The expanded repeat sequence is translated into dipeptide repeat proteins (DPRs) by noncanonical repeat-associated non-AUG (RAN) translation. Since DPRs play central roles in the pathogenesis of C9-ALS/FTD, we here investigate the regulatory mechanisms of RAN translation, focusing on the effects of RNA-binding proteins (RBPs) targeting GGGGCC repeat RNAs. Using C9-ALS/FTD model flies, we demonstrated that the ALS/FTD-linked RBP FUS suppresses RAN translation and neurodegeneration in an RNA-binding activity-dependent manner. Moreover, we found that FUS directly binds to and modulates the G-quadruplex structure of GGGGCC repeat RNA as an RNA chaperone, resulting in the suppression of RAN translation in vitro. These results reveal a previously unrecognized regulatory mechanism of RAN translation by G-quadruplex-targeting RBPs, providing therapeutic insights for C9-ALS/FTD and other repeat expansion diseases.

Introduction: Spine surgery is challenging in hemodialysis (HD)-dependent patients owing to their poor general condition. However, postoperative complications and the mortality and survival rates have not been specifically evaluated in a wide series. This study aimed to elucidate postoperative complications and the survival rate in cervical spine surgery in HD patients. Methods: This study included 109 HD patients (70 men, 39 women) who had undergone cervical spine surgery between July 1996 and May 2018. Based on radiological diagnosis, we divided them into the destructive spondyloarthropathy (DSA) and non-DSA groups. We investigated the causes of hemodialysis, postoperative complications, postoperative inpatient mortality rate, and survival rate. Results: The DSA and non-DSA groups included 100 surgeries in 89 patients and 21 surgeries in 20 patients, respectively. The mean age at surgery was 62.9 years for the DSA and 55.9 years for the non-DSA group (P=0.97). The DSA group had a shorter hemodialysis period at surgery compared with the non-DSA group (21.7 vs. 26.5 years, P0.05). However, significantly low survival rates were observed in HD caused by diabetes compared with that by chronic glomerulonephritis (P

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the pandemic of the coronavirus disease 2019 (COVID-19), resulting in a global lockdown in 2020. This stagnation in human activities ('anthropause') has been reported to affect the behaviour of wildlife in various ways. The sika deer Cervus nippon in Nara Park, central Japan, has had a unique relationship with humans, especially tourists, in which the deer bow to receive food and sometimes attack if they do not receive it. We investigated how a decrease and subsequent increase in the number of tourists visiting Nara Park affects the number of deer observed in the park and their behaviour (bows and attacks against humans). Compared with the pre-pandemic years, the number of deer in the study site decreased from an average of 167 deer in 2019 to 65 (39%) in 2020 during the pandemic period. Likewise, the number of deer bows decreased from 10.2 per deer in 2016-2017 to 6.4 (62%) in 2020-2021, whereas the proportion of deer showing aggressive behaviour did not change significantly. Moreover, the monthly numbers of deer and their bows both corresponded with the fluctuation in the number of tourists during the pandemic period of 2020 and 2021, whereas the number of attacks did not. Thus, the anthropause caused by the coronavirus altered the habitat use and behaviour of deer that have continuous interactions with humans.

Non-human primate models of autism spectrum disorder (ASD) are few and not well characterised. Here, the authors describe synaptic function and gene expression changes in a marmoset model of ASD from birth to juvenile, highlighting its similarity to features observed in human ASD.

Introduction: The incidence of remote cerebellar hemorrhage (RCH) in patients with a dural tear during spinal surgery is unclear. The purpose of this study was to determine the incidence of RCH and the causative factors in these patients. Methods: Two hundred and thirty-nine patients underwent spinal surgery at our institution between March 2015 and September 2016. Eleven of these patients needed dural suturing intraoperatively. All patients underwent CT of the head on the first postoperative day and were categorized according to whether they had RCH or not. The mean values for the amount of intraoperative bleeding, maximum perioperative blood pressure, postoperative drainage volume, and complaints of headache during the first 24 h postoperatively were compared between the two groups using the Welch's two-sample t-test and Fisher's exact test. The follow-up duration was 12 months. Results: There were four patients in the RCH group and seven in the non-RCH group. The incidence of RCH was 36.4%. There were three cerebellar hemorrhages and one interhemispheric fissure hemorrhage in the RCH group. The mean intraoperative bleeding volume was 284 mL in the RCH group and 569 mL in the non-RCH group. The mean respective values for maximum perioperative blood pressure and postoperative drainage volume were 132 mmHg and 547 mL in the RCH group and 144 mmHg and 567 mL in the non-RCH group; none of the differences was statistically significant. However, complaints of headache in the first 24 h postoperatively were significantly more common in the RCH group than in the non-RCH group (100% vs. 14.3%; p = 0.01). All patients with intracranial bleeding had recovered 3 months after surgery. Conclusions: The incidence of RCH following a dural tear during spinal surgery was 36.4%. There was a significant association between RCH and increased reporting of headache during the first 24 h postoperatively.

Abstract Background AMPA receptors predominantly mediate fast excitatory synaptic transmission in the mammalian brain. Post‐translational protein S‐palmitoylation of AMPA receptor GluA subunits at their C‐termini reversibly controls the receptors trafficking to and from excitatory glutamatergic synapses. Excitatory inputs to neurons induce the expression of immediate early genes (IEGs), including Arc, with particular spatial patterns. In the hippocampal dentate gyrus, Arc is mainly expressed in the upper (dorsal) blade at the basal state. GluA1 C‐terminal palmitoylation‐deficient (GluA1C811S) mice showed enhanced seizure susceptibility and disturbed synaptic plasticity without impaired gross anatomy or basal synaptic transmission. These mutant mice also exhibited an increased expression of IEG products, c‐Fos and Arc proteins, in the hippocampus and cerebral cortex. In this report, we further analyzed excitability and Arc expression pattern in the dentate gyrus of GluA1C811S mice. Methods and Results Electrophysiological analysis of granule neurons to measure the evoked excitatory postsynaptic current/evoked inhibitory postsynaptic current ratio revealed that excitatory/inhibitory (E/I) balance was normal in GluA1C811S mice. In contrast, immunohistochemical staining showed an abnormal distribution of Arc‐positive cells between upper and lower (ventral) blades of the dentate gyrus in these mutant mice. These data suggest that deficiency of GluA1 palmitoylation causes perturbed neuronal inputs from the entorhinal cortex to the dentate gyrus, which potentially underlies the excessive excitability in response to seizure‐inducing stimulation. Conclusion Our findings conclude that an appropriate regulation of Arc expression in the dentate gyrus, ensured by AMPA receptor palmitoylation, may be critical for stabilizing hippocampal neural circuits and may suppress excess excitation.

The number of elderly people who undergo lumbar fusion surgery (LFS) has been increasing. Postoperative rehabilitation for them can be problematic due to lumbar stiffness. This is the first case report describing exercise therapy using the lumbar-type hybrid assistive limb (HAL) after multiple LFS in an elderly patient. An 83-year-old man underwent LFS at L4-S1. Additional fusion surgery at L2-3 for adjacent segment disease was performed 2 years after the primary surgery. Although the patient’s leg pain declined, he had severe locomotive dysfunction at 3 months after his final surgery. He started exercise therapy using the lumbar-type HAL including sit-to-stand training and squat training 4 months after his final surgery. He performed 3 sets of 20 sit-to-stand and 20 squat repetitions with adequate rests in between sets. The HAL training was safely conducted every day for 12 weeks without adverse event. Timed up and go test (TUG), 1-minute sit to stand test (1MSTS), one-leg stand test (OLST), and Berg balance scale (BBS) were assessed as locomotive function measurement. Before HAL therapy, TUG, 1MSTS, OLST, and BBS were 18.1 sec, 20 times, less than 1 sec, and 47, respectively. He could not walk without assistance. After the exercise therapy with the lumbar-type HAL, his locomotive function dramatically improved. TUG, 1MSTS, OLST, and BBS were 12.2 sec, 25 times, 3.9 sec, and 52, respectively. Moreover, the patient could walk 60 meters continuously without assistance. The unique characteristics of the lumbar-type HAL to prevent the lumbar overload and assist the voluntary hip joint motion during exercise therapy may be effective for this patient with lumbar stiffness after LFS. Sit-to-stand training and squat training using the lumbar-type HAL are promising options to improve locomotive function in elderly patients after LFS.

Summary: Impairments in synapse development are thought to cause numerous psychiatric disorders. Autism susceptibility candidate 2 (AUTS2) gene has been associated with various psychiatric disorders, such as autism and intellectual disabilities. Although roles for AUTS2 in neuronal migration and neuritogenesis have been reported, its involvement in synapse regulation remains unclear. In this study, we found that excitatory synapses were specifically increased in the Auts2-deficient primary cultured neurons as well as Auts2 mutant forebrains. Electrophysiological recordings and immunostaining showed increases in excitatory synaptic inputs as well as c-fos expression in Auts2 mutant brains, suggesting that an altered balance of excitatory and inhibitory inputs enhances brain excitability. Auts2 mutant mice exhibited autistic-like behaviors including impairments in social interaction and altered vocal communication. Together, these findings suggest that AUTS2 regulates excitatory synapse number to coordinate E/I balance in the brain, whose impairment may underlie the pathology of psychiatric disorders in individuals with AUTS2 mutations.

The beneficial effects of omega (ω)-3 polyunsaturated fatty acid (PUFA) supplementation on major depressive disorder have been actively studied, but the underlying mechanism remains unknown. The present study examined the involvement of the nucleus accumbens (NAc) dopaminergic systems in behavioral changes in mice fed a diet high in ω-3 PUFAs. Mice fed a diet containing about double the amount of ω-3 PUFAs (krill oil (KO) diet) exerted shorter immobility times in the forced swim test (FST) than mice fed a control diet, containing only α-linolenic acid (ALA) as ω-3 PUFAs. The shorter immobility times were observed in both male and female mice. A dopamine metabolite, 3,4-dihydroxyphenylacetic acid, increased in the NAc in male mice fed the KO diet when compared with those fed the control diet. In addition, dopamine, 3-methoxytyramine, and homovanillic acid increased in the NAc in female mice fed the KO diet. Notably, the effects of the KO diet on the immobility time in the FST were abolished by microinjection of sulpiride, an antagonist of D2-like receptors, into the NAc. A similar microinjection of an antagonist selective for D1-like receptors, SKF83566, also abolished the reduction in immobility in the FST. Moreover, we found that tyrosine hydroxylase-positive cells increased in the ventral tegmental area (VTA) in mice fed the KO diet. These results suggest that modulation of the VTA-NAc dopaminergic pathway is one of the mechanisms by which a KO diet rich in ω-3 PUFAs reduces the immobility behavior in the mouse FST.

Huntington’s disease (HD) is an intractable neurodegenerative disorder caused by mutant Huntingtin (HTT) proteins that adversely affect various biomolecules and genes. MicroRNAs (miRNAs), which are functional small non-coding RNAs, are also affected by mutant HTT proteins. Here, we show amelioration in motor function and lifespan of HD-model mice, R6/2 mice, by supplying miR-132 to HD brains using a recombinant adeno-associated virus (rAAV) miRNA expression system. miR-132 is an miRNA related to neuronal maturation and function, but the level of miR-132 in the brain of R6/2 mice was significantly lower than that of wild-type mice. Our miR-132 supplemental treatment, i.e., supplying miR-132 to the brain, produced symptomatic improvement or retarded disease progression in R6/2 mice; interestingly, it had little effect on disease-causing mutant HTT mRNA expression and its products. Therefore, the findings suggest that there may be a therapeutic way to treat HD without inhibiting and/or repairing disease-causing HTT genes and gene products. Although miR-132 supplement may not be a definitive treatment for HD, it may become a therapeutic method for relieving HD symptoms and delaying HD progression.

Geniposidic acid (GEA), the main ingredient of several medicinal herbs, has pharmacological effects on hypertension, inflammation, diabetes, atherosclerosis, and cancer. The current study evaluated the mechanism underlying the hypotensive effects of a single oral administration of 100 mg GEA/kg in male spontaneously hypertensive rats. Blood pressure was significantly reduced at 6 h post GEA treatment, as compared with control rats. Plasma levels of atrial natriuretic peptide (ANP) were also upregulated by GEA, indicating that its anti-hypertensive activity involved enhanced ANP secretion from cardiomyocytes. This could reflect GEA-mediated activation of glucagon-like peptide-1 (GLP-1) receptors on atrial cardiomyocytes. Plasma GLP-1 levels were not significantly altered by GEA. This study is the first to report that orally administered GEA produces beneficial effects on heart tissue by increasing plasma ANP levels, although GEA is a known GLP-1 receptor agonist. These effects could underlie the broad physiological effects of medicinal herbs containing GEA.

The embryotoxic effect of intermediate frequency (IF) magnetic field (MF) was evaluated using murine embryonic stem (ES) cells and fibroblast cells based on the embryonic stem cell test (EST). The cells were exposed to 21 kHz IF–MF up to magnetic flux density of 3.9 mT during the cell proliferation process (7 days) or the cell differentiation process (10 days) during which an embryonic body differentiated into myocardial cells. As a result, there was no significant difference in the cell proliferation between sham- and IF–MF-exposed cells for both ES and fibroblast cells. Similarly, the ratio of the number of ES-derived cell aggregates differentiated to myocardial cells to total number of cell aggregates was not changed by IF–MF exposure. In addition, the expressions of a cardiomyocytes-specific gene, Myl2, and an early developmental gene, Hba-x, in the exposed cell aggregate were not altered. Since the magnetic flux density adopted in this study is much higher than that generated by an inverter of the electrical railway, an induction heating (IH) cooktop, etc. in our daily lives, these results suggested that IF–MF in which the public is exposed to in general living environment would not have embryotoxic effect. Keywords: Differentiation, Embryonic stem cell, Gene expression, Intermediate frequency magnetic field

Eucommia ulmoides Oliv. leaf is a traditional Chinese antihypertensive and antidiabetic medicine. We examined the effects of chronic Eucommia leaf extract (ELE) administration on artery function and morphology in spontaneously hypertensive rats (SHRs). ELE was orally administered via normal diet ad libitum to six-week-old male SHRs at a concentration of 5% for seven weeks. Acetylcholine (ACh)-induced endothelium-dependent relaxation, sodium nitroprusside (SNP)-induced endothelium-independent relaxation, plasma nitric oxide (NO) levels, and media thickness were assessed. ELE significantly improved ACh-induced aortic endothelium-dependent relaxation but did not affect SNP-induced endothelium-independent relaxation in the SHRs, as compared to the animals receiving normal diet. Plasma NO levels and media thickness were significantly increased and decreased, respectively, in the ELE-treated SHRs. Therefore, long-term ELE administration may effectively improve vascular function by increasing plasma NO levels and bioavailability, and by preventing vascular hypertrophy in the SHR aorta.

Renewable energy systems and electric vehicles (EVs) are receiving much attention in industrial and scholarly communities owing to their roles in reducing pollutant emissions. Integrated energy systems (IES), which connect different types of renewable energies and storages, have become common in many applications, such as the grid-connected photovoltaic (PV) and battery systems, fuel cells and battery/supercapacitor in EVs. The advantages of all energy sources are maximized by utilizing connection and control strategies. Because many storage systems and household loads are mainly direct current (DC) types, the DC grid has considerable potential for increasing the efficiency of distribution grids in the future. In IES and future DC grid systems, the triple active bridge (TAB) converter is an isolated bidirectional DC-DC converter that has many advantages as a core circuit. Therefore, this paper reviews the characteristics of the TAB converter in current applications and suggests next-generation applications. First, the characteristics and operation modes of the TAB converter are introduced. An overview of all current applications of the TAB converter is then presented. The advantages and challenges of the TAB converter in each application are discussed. Thereafter, the potential future applications of the TAB converter with an adaptable power transmission design are presented.

Study DesignA retrospective study.PurposeTo investigate the surgical outcome for hemodialysis-related upper cervical lesions.Overview of LiteratureSurgical outcome of lower cervical lesions in patients undergoing hemodialysis has been reported. However, surgical outcome for upper cervical lesions in hemodialysis patients is unclear.MethodsUpper cervical lesions in nine patients undergoing hemodialysis were surgically treated. Mean age at surgery was 61.6 years (range, 52-68 years), and the mean follow-up period was 45.4 months (range, 2-98 months). Patients had undergone hemodialysis for an average of 25.3 years (range, 16-40 years) at surgery. Seven patients with destructive spondyloarthropathy (DSA) of the upper cervical spine were treated with atlantoaxial or occipitocervical fixation. Two patients with retro-odontoid pseudotumors were treated with C1 posterior arch resection alone. Japanese Orthopedic Association (JOA) scores for cervical myelopathy, postoperative complications, postoperative radiography, and preoperative and postoperative occipital pain were evaluated.ResultsMean preoperative and postoperative JOA score was 3.7 and 8.1, respectively. The seven patients with DSA had severe preoperative occipital pain that disappeared postoperatively. Postoperative radiography showed solid bone union in DSA cases and no instability in pseudotumor cases.ConclusionsSatisfactory surgical outcome was observed for hemodialysis-related upper cervical lesions.

Destructive spondyloarthropathy (DSA) has been reported in patients undergoing long-term hemodialysis. Cervical spinal lesions, including those of the upper cervical spine, are reported to be some of the most common. To our knowledge, we report for the first time, a case of atlanto-occipital subluxation requiring surgical treatment due to severe myelopathy and nuchal pain in a patient undergoing long-term hemodialysis. The patient was a 66-year-old woman who had undergone hemodialysis for 40 years. She visited our hospital due to an acute progression of gait disturbance and severe nuchal pain. Computed tomography showed posterior subluxation of the atlanto-occipital joints. DSA was also observed in the lower cervical spine. Magnetic resonance imaging showed spinal canal stenosis at both the upper and lower cervical levels. We performed Oc-C7 fixation, C1 laminectomy, and C3-C7 laminoplasty. We first recognized that the atlanto-occipital subluxation was caused by the extremely long-term, in this case, 40 years, hemodialysis.

Study DesignA retrospective study.PurposeTo clarify the features useful for the differential diagnosis of spinal canal tumoral lesions in patients undergoing hemodialysis.Overview of LiteratureTumoral lesions in the spinal canal are rarely found in hemodialysis patients. Therefore, the differential diagnosis of tumoral lesions in the spinal canal in hemodialysis patients has been very difficult.MethodsSpinal canal tumors in 17 patients undergoing hemodialysis or continuous ambulatory peritoneal dialysis were investigated. Histopathological analysis was conducted for all specimens obtained during surgery. The tumoral lesions were categorized into 3 groups on the basis of histopathology: spinal cord tumor, amyloidoma, and other. Patient medical history and diagnostic images of each group were reviewed.ResultsEight of 17 cases were histopathologically diagnosed as spinal cord tumors and were neurinomas, 6 were amyloidomas, and 3 were classified as other. The rate of spinal cord tumors was 47.1% (8 of 17 cases), which revealed the most frequent lesion type. The rate of amyloidomas and other types was 35.3% (6 of 17 cases) and 17.6% (3 of 17cases), respectively. In the amyloidoma group, the mean duration of hemodialysis (24.3 years) was longer than that of spinal cord tumors and other types (9.2 years and 8.6 years, respectively). All spinal cord tumors were intradural extramedullary, whereas all amyloidomas and other types were extradural.ConclusionsThe rate of each tumoral lesion, the duration of hemodialysis, and the tumoral localization are important features for the differential diagnosis of tumoral lesions in the spinal canal in hemodialysis patients.

Pycnodysostosis is an autosomal recessive disorder characterized by osteosclerosis, small stature, acro-osteolysis of the distal phalanges, loss of the mandibular angle, separated cranial sutures with open fontanels, and frequent fractures. One identified cause of the disease is reduced activity of the cysteine protease cathepsin K. A 48-year-old woman with a history of frequent fractures presented with a severe gait disturbance. Radiography, computed tomography, magnetic resonance imaging, and gene analysis were performed. Physical examination revealed open fontanels, and radiographs showed increased bone density. DNA sequence analysis revealed a deletion mutation of the cathepsin K gene. We diagnosed pycnodysostosis based on these findings. The magnetic resonance and computed tomography images demonstrated multilevel spinal canal stenosis due to ossification of the yellow ligament. We performed a laminectomy, and the patient's neurological signs and symptoms improved. To our knowledge, this is the first case of pycnodysostosis with ossification of the yellow ligament.

Information from the peripheral organs is thought to be transmitted to the brain by humoral factors and neurons such as afferent vagal or spinal nerves. The common hepatic branch of the vagus (CHBV) is one of the main vagus nerve branches, and consists of heterogeneous neuronal fibers that innervate multiple peripheral organs such as the bile duct, portal vein, paraganglia, and gastroduodenal tract. Although, previous studies suggested that the CHBV has a pivotal role in transmitting information on the status of the liver to the brain, the details of its central projections remain unknown. The purpose of the present study was to investigate the brain regions activated by the CHBV. For this purpose, we injected L-arginine or anorexia-associated peptide cholecystokinin-8 (CCK), which are known to increase CHBV electrical activity, into the portal vein of transgenic Arc-dVenus mice expressing the fluorescent protein Venus under control of the activity-regulated cytoskeleton-associated protein (Arc) promotor. The brain slices were prepared from these mice and the number of Venus positive cells in the slices was counted. After that, c-Fos expression in these slices was analyzed by immunohistochemistry using the avidin-biotin-peroxidase complex method. Intraportal administration of L-arginine increased the number of Venus positive or c-Fos positive cells in the insular cortex. This action of L-arginine was not observed in CHBV-vagotomized Arc-dVenus mice. In contrast, intraportal administration of CCK did not increase the number of c-Fos positive or Venus positive cells in the insular cortex. Intraportal CCK induced c-Fos expression in the dorsomedial hypothalamus, while intraportal L-arginine did not. This action of CCK was abolished by CHBV vagotomy. Intraportal L-arginine reduced, while intraportal CCK increased, the number of c-Fos positive cells in the nucleus tractus solitarii in a CHBV-dependent manner. The present results suggest that the CHBV can activate different brain regions depending on the nature of the peripheral stimulus.

Mutations in vacuolar protein sorting 35 (VPS35) have been linked to familial Parkinson's disease (PD). VPS35, a component of the retromer, mediates the retrograde transport of cargo from the endosome to the trans-Golgi network. Here we showed that retromer depletion increases the lysosomal turnover of the mannose 6-phosphate receptor, thereby affecting the trafficking of cathepsin D (CTSD), a lysosome protease involved in α-synuclein (αSYN) degradation. VPS35 knockdown perturbed the maturation step of CTSD in parallel with the accumulation of αSYN in the lysosomes. Furthermore, we found that the knockdown of Drosophila VPS35 not only induced the accumulation of the detergent-insoluble αSYN species in the brain but also exacerbated both locomotor impairments and mild compound eye disorganization and interommatidial bristle loss in flies expressing human αSYN. These findings indicate that the retromer may play a crucial role in αSYN degradation by modulating the maturation of CTSD and might thereby contribute to the pathogenesis of the disease.

The diagnosis of pituitary carcinoma cannot be made easily histologically, and most cases of pituitary carcinoma are diagnosed only after the clinical detection of metastasis. Distant metastasis of pituitary tumor occurs in 0.1% to 0.2% of cases and has been reported in the liver, bone and central nervous system, with only one case of metastasis to the cauda equine reported. This study describes a rare case of the drop metastasis of adrenocorticotropic hormone-producing pituitary adenocarcinoma to the cauda equina, causing cauda equina syndrome.

Converging evidence suggests that an imbalance of ω3 to ω6 polyunsaturated fatty acid (PUFA) in the brain is involved in mental illnesses such as anxiety disorders. However, the underlying mechanism is unknown. We previously reported that the dietary ratio of ω3 to ω6 PUFA alters this ratio in the brain, and influences contextual fear memory. In addition to behavioral change, enhancement of cannabinoid CB1 receptor-mediated short-term synaptic plasticity and facilitation of the agonist sensitivity of CB1 receptors have been observed in excitatory synaptic responses in the basolateral nucleus of the amygdala. However, it is not known whether long-term synaptic plasticity in the amygdala is influenced by the dietary ratio of ω3 to ω6 PUFA. In the present study, we examined long-term potentiation (LTP) of optogenetically–evoked excitatory synaptic responses in synapses between the terminal of the projection from the auditory cortex and the pyramidal cells in the lateral nucleus of the amygdala. We found that LTP in this pathway was attenuated in mice fed a diet with a high ω3 to ω6 PUFA ratio (0.97), compared with mice fed a diet with a low ω3 to ω6 PUFA ratio (0.14). Furthermore, mice in the former condition showed reduced fear responses in an auditory fear conditioning test, compared with mice in the latter condition. In both electrophysiological and behavioral experiments, the effect of a diet with a high ω3 to ω6 PUFA ratio was completely blocked by treatment with a CB1 receptor antagonist. Furthermore, a significant reduction was observed in cholesterol content, but not in the level of an endogenous CB1 receptor agonist, 2-arachidonoylglycerol, in brain samples containing the amygdala. These results suggest that the balance of ω3 to ω6 PUFA has an impact on fear memory and cortico-amygdala synaptic plasticity, both in a CB1 receptor–dependent manner.

Owing to the acute energy shortage issue and the increasing energy demands of information and communication technology systems worldwide, the development of a DC microgrid that can utilize renewable energy sources, such as wind and photovoltaic power, has been accelerated. Therefore, power management for DC microgrid distributed systems is promoted to achieve high reliability and efficiency in power distribution systems. For industry and power transmission applications such as data centers, power management with the help of DC converters is highly recommended. In this paper, we propose a prototype of a power distribution system with a triple active bridge (TAB) converter for data centers in the DC microgrid. Moreover, we introduce a power management approach for a distribution system using the TAB converter. Finally, we perform simulations of the proposed configuration to verify the controllability of the circuit performance and the high reliability of the system.

Abstract.: Early brain development has a tremendous impact on the success of humans throughout their lives. During early development, neural circuit formation proceeds in a strictly regulated manner. In addition to genetic and epigenetic programs, recent studies using animal models have demonstrated that certain maternal bio-active agents are essential for normal neural development, with deficiencies adversely affecting offspring brain function and behavior. On the basis of these findings, we propose a new viewpoint: that maternal bio-active substances support the development of the fetal and neonatal brain, and the subsequent expression and maintenance of higher brain functions. We term these molecular-based biological conversations between mother and offspring “bio-communications”. Based on findings obtained primarily from animal models, we review the effects of maternal substances on the neural developments and functions. Clarifying the regulatory mechanisms of “bio-communications” will help improve understanding of the mechanisms of human brain functioning and neural development. In addition, these findings will be applied to elucidate the mechanisms of developmental disorders and to explore new medical therapies to treat them. Keywords:: maternal substance, brain, neuron–glia–vascular system, placenta, milk

The α-synuclein (SNCA) gene is a responsible gene for Parkinson's disease (PD); and not only nucleotide variations but also overexpression of SNCA appears to be involved in the pathogenesis of PD. A specific inhibition against mutant SNCA genes carrying nucleotide variations may be feasible by a specific silencing such as an allele-specific RNA interference (RNAi); however, there is no method for restoring the SNCA overexpression to a normal level. Here, we show that an atypical RNAi using small interfering RNAs (siRNAs) that confer a moderate level of gene silencing is capable of controlling overexpressed SNCA genes to return to a normal level; named “expression-control RNAi” (ExCont-RNAi). ExCont-RNAi exhibited little or no significant off-target effects in its treated PD patient's fibroblasts that carry SNCA triplication. To further assess the therapeutic effect of ExCont-RNAi, PD-model flies that carried the human SNCA gene underwent an ExCont-RNAi treatment. The treated PD-flies demonstrated a significant improvement in their motor function. Our current findings suggested that ExCont-RNAi might be capable of becoming a novel therapeutic procedure for PD with the SNCA overexpression, and that siRNAs conferring a moderate level of gene silencing to target genes, which have been abandoned as useless siRNAs so far, might be available for controlling abnormally expressed disease-causing genes without producing adverse effects.

Parkinson’s disease (PD) is pathologically characterized by dopaminergic (DA) cell death and the presence of Lewy bodies (LB) in the brain. α-Synuclein (α-syn) and ubiquitin (Ub) are the major components of LB, however, the process of their accumulation and their relationship to DA cell loss has not yet been resolved. Now, in this journal, Inden et al. showed the protective effect of proteasome inhibitors (PSI) on DA cell death in the rat PD model using 6-hydroxyl dopamine (6-OHDA). Co-administration of PSI, lactacystin, or MG-132 significantly prevented the nigral degeneration and apomorphine-induced rotational asymmetry of the model with increased appearance of α-syn- and Ub-positive inclusions in the substantia nigra. This study indicates that in their model, accelerated formation of inclusions via proteasome inhibition protects against DA cell death. Previous literature linked the impairments or inhibitions of the ubiquitin-proteasome system (UPS) and DA cell death. However, this report implies that the relationship between the UPS and the pathogenesis of PD may be more complex than we thought. Keywords:: Parkinson’s disease, 6-hydroxyl dopamine, proteasome, dopamine

The polyglutamine (polyQ) diseases such as Huntington's disease (HD), are neurodegenerative diseases caused by proteins with an expanded polyQ stretch, which misfold and aggregate, and eventually accumulate as inclusion bodies within neurons. Molecules that inhibit polyQ protein misfolding/aggregation, such as Polyglutamine Binding Peptide 1 (QBP1) and molecular chaperones, have been shown to exert therapeutic effects in vivo by crossing of transgenic animals. Towards developing a therapy using these aggregation inhibitors, we here investigated the effect of viral vector-mediated gene therapy using QBP1 and molecular chaperones on polyQ disease model mice. We found that injection of adeno-associated virus type 5 (AAV5) expressing QBP1 or Hsp40 into the striatum both dramatically suppresses inclusion body formation in the HD mouse R6/2. AAV5-Hsp40 injection also ameliorated the motor impairment and extended the lifespan of R6/2 mice. Unexpectedly, we found even in virus non-infected cells that AAV5-Hsp40 appreciably suppresses inclusion body formation, suggesting a non-cell autonomous therapeutic effect. We further show that Hsp40 inhibits secretion of the polyQ protein from cultured cells, implying that it inhibits the recently suggested cell-cell transmission of the polyQ protein. Our results demonstrate for the first time the therapeutic effect of Hsp40 gene therapy on the neurological phenotypes of polyQ disease mice.

α-Synuclein (α-Syn) is a major component of protein inclusions known as Lewy bodies, which are hallmarks of synucleinopathies such as Parkinson's disease (PD). The α-Syn gene is one of the familial PD-causing genes and is also associated with an increased risk of sporadic PD. Numerous studies using α-Syn expressing transgenic animals have indicated that α-Syn plays a critical role in the common pathogenesis of synucleinopathies. Drosophila melanogaster has several advantages for modeling human neurodegenerative diseases and is widely used for studying their pathomechanisms and therapies. In fact, Drosophila models expressing α-Syn have already been established and proven to replicate several features of human PD. In this paper, we review the current research on synucleinopathies using α-Syn Drosophila models and, moreover, explore the possibilities of these models for comprehensive genetic analyses and large-scale drug screening towards elucidating the molecular pathogenesis and developing therapies for synucleinopathies.

Background: his study aimed to clarify the quantitative threshold of intraoperative radiological parameters for suspecting posterior malposition of the oblique lumbar interbody fusion (LF) cage triggering contralateral radiculopathy. Methods: We measured the sagittal center and axial rotation angle () of the cage using postoperative computed tomography () in 130 patients (215 cages) who underwent LF. he location of the cage tip was determined from axial magnetic resonance imaging in selected cases based on simulations to assess whether the cage was in contact with the contralateral exiting nerve or whether the surgical instruments could contact the nerve during intradiscal maneuvers. Results: he sagittal center of the cages was on average 41.5% from the anterior edge of the endplate (shown as / P value: anterior end plate edge-cage center/anterior-posterior endplate edge ×100%), and posterior cage positioning ≥50% occurred in 14% of the cages. he was -2.9°, and posterior oblique rotation of the cages ≥10° ( ≤ -10°) was observed in 13%. simulation showed that the cage tip could directly contact the contralateral nerve when the cage was placed deep in the posterior portion ≥50% of the /P values with concomitant posterior axial rotation ≥10° ( ≤ -10°), or deep in an extremely rare portion ≥60% of the /P values with posterior axial rotation ≥0° ( ≤ 0°). Six percent of the cages (13/215) were placed in these posterior oblique areas (potential contact area: P). hree cages in the P were in direct contact with the contralateral nerves, and 9 were placed deep just anterior to the nerves. Symptomatic contralateral radiculopathy occurred in 2 cages (2/13/215, 15.3%/0.9%). Conclusions: wo intraoperative radiological parameters (/P and ) measurable during LF procedures may become practical indicators for suspecting cage malposition in P and may be available when determining whether to consider cage revision intraoperatively to a more ventral disc space or anteriorly from the opposite endplate edge. Level of Evidence: 4. [ABSTRACT FROM AUTHOR]