AIRE Functions As an E3 Ubiquitin Ligase

Autoimmune regulator (AIRE) gene mutation is responsible for the development of autoimmune-polyendocrinopathy-candidiasis ectodermal dystrophy, an organ-specific autoimmune disease with monogenic autosomal recessive inheritance. AIRE is predominantly expressed in medullary epithelial cells of the thymus and is considered to play important roles in the establishment of self-tolerance. AIRE contains two plant homeodomain (PHD) domains, and the novel role of PHD as an E3 ubiquitin (Ub) ligase has just emerged. Here we show that the first PHD (PHD1) of AIRE mediates E3 ligase activity. The significance of this finding was underscored by the fact that disease-causing missense mutations in the PHD1 (C311Y and P326Q) abolished its E3 ligase activity. These results add a novel enzymatic function for AIRE and suggest an indispensable role of the Ub proteasome pathway in the establishment of self-tolerance, in which AIRE is involved

Seismicity controlled by resistivity structure : the 2016 Kumamoto earthquakes, Kyushu Island, Japan

The M JMA 7.3 Kumamoto earthquake that occurred at 1:25 JST on April 16, 2016, not only triggered aftershocks in the vicinity of the epicenter, but also triggered earthquakes that were 50–100 km away from the epicenter of the main shock. The active seismicity can be divided into three regions: (1) the vicinity of the main faults, (2) the northern region of Aso volcano (50 km northeast of the mainshock epicenter), and (3) the regions around three volcanoes, Yufu, Tsurumi, and Garan (100 km northeast of the mainshock epicenter). Notably, the zones between these regions are distinctively seismically inactive. The electric resistivity structure estimated from one-dimensional analysis of the 247 broadband (0.005–3000 s) magnetotelluric and telluric observation sites clearly shows that the earthquakes occurred in resistive regions adjacent to conductive zones or resistive-conductive transition zones. In contrast, seismicity is quite low in electrically conductive zones, which are interpreted as regions of connected fluids. We suggest that the series of the earthquakes was induced by a local accumulated stress and/or fluid supply from conductive zones. Because the relationship between the earthquakes and the resistivity structure is consistent with previous studies, seismic hazard assessment generally can be improved by taking into account the resistivity structure. Following on from the 2016 Kumamoto earthquake series, we suggest that there are two zones that have a relatively high potential of earthquake generation along the western extension of the MTL

Study of learning environment development of the way to become the foundation of inclusive education system : From teaching practice in a special classroom by teachers in regular class

本校では特別支援学級と複式学級の教科による交流及び共同学習の導入や，学級交流や縦割り学習，運動会等の校内行事での交流などに取り組んできている。本研究は，これまでの成果を基に，通常の学級に在籍する児童の多様性や障害の理解を促す実践を交流及び共同学習や教科学習の中で行い，その効果を検証することを目的とした。特別支援学級の担任ではない教員が，特別支援学級の指導案を作成することを通して，日頃の交流だけではとらえられない特別支援児童の実態に気づき，支援の在り方について検討する。また実際に授業を行うことで特別支援領域に関する見方・考え方を活用し，それぞれの学級の児童支援に生かし，共有できるようにした。授業を行う教員の研究教科が算数科であることから算数科で授業を行うこととし，都合５時間の特別支援学級教員による算数科の授業を観察，児童の実態把握を行い，聞き取りも含め授業構想を行っていった。実際の授業から，子どもたちの中に価値に関する概念が育成されているかどうかの違いがあることに気付く。価値概念の育成や獲得方法を明らかにしていくことによって小学校の教科の指導をより充実させていくことができると考えた。Do the practice of promoting an understanding of the children of diversity and disorder enrolled in regular classes in the exchange and collaborative learning and subject learning, was aimed to verify the effect. Special support is not a homeroom class faculty, through to create a lesson plan of the special support class, noticed the actual situation of the special support children that cannot be captured only daily exchanges, as well as consider the way of support, the teaching plan actually take advantage of the special support area on the perspective, the concept by making the class alive, it was decided to continue making the child support of each class. It was thought to be able to go to enrich more the guidance of the subjects of elementary school by going to reveal the development and acquisition method of one person a child of the value of the concept

Two genetic variants of CD38 in subjects with autism spectrum disorder and controls

金沢大学医薬保健研究域医学系The neurobiological basis of autism spectrum disorder (ASD) remains poorly understood. Given the role of CD38 in social recognition through oxytocin (OT) release, we hypothesized that CD38 may play a role in the etiology of ASD. Here, we first examined the immunohistochemical expression of CD38 in the hypothalamus of post-mortem brains of non-ASD subjects and found that CD38 was colocalized with OT in secretory neurons. In studies of the association between CD38 and autism, we analyzed 10 single nucleotide polymorphisms (SNPs) and mutations of CD38 by re-sequencing DNAs mainly from a case-control study in Japan, and Caucasian cases mainly recruited to the Autism Genetic Resource Exchange (AGRE). The SNPs of CD38, rs6449197 (p 70; designated as high-functioning autism (HFA)) in the U.S. 104 AGRE family trios, but not with Japanese 188 HFA subjects. A mutation that caused tryptophan to replace arginine at amino acid residue 140 (R140W; (rs1800561, 4693C>T)) was found in 0.6-4.6% of the Japanese population and was associated with ASD in the smaller case-control study. The SNP was clustered in pedigrees in which the fathers and brothers of T-allele-carrier probands had ASD or ASD traits. In this cohort OT plasma levels were lower in subjects with the T allele than in those without. One proband with the T allele who was taking nasal OT spray showed relief of symptoms. The two variant CD38 poloymorphysms tested may be of interest with regard of the pathophysiology of ASD. © 2010 Elsevier Ireland Ltd and the Japan Neuroscience Society

Quantitative evaluation of gait ataxia by accelerometers

An appropriate biomarker for spinocerebellar degeneration (SCD) has not been identified. Here, we performed gait analysis on patients with pure cerebellar type SCD and assessed whether the obtained data could be used as a neurophysiological biomarker for cerebellar ataxia. We analyzed 25 SCD patients, 25 patients with Parkinson's disease as a disease control, and 25 healthy control individuals. Acceleration signals during 6 min of walking and 1 min of standing were measured by two sets of triaxial accelerometers that were secured with a fixation vest to the middle of the lower and upper back of each subject. We extracted two gait parameters, the average and the coefficient of variation of motion trajectory amplitude, from each acceleration component. Then, each component was analyzed by correlation with the Scale for the Assessment and Rating of Ataxia (SARA) and the Berg Balance Scale (BBS). Compared with the gait control of healthy subjects and concerning correlation with severity and disease specificity, our results suggest that the average amplitude of medial-lateral (upper back) of straight gait is a physiological biomarker for cerebellar ataxia. Our results suggest that gait analysis is a quantitative and concise evaluation scale for the severity of cerebellar ataxia

Self-Potential Studies in Volcanic Areas(3) : Miyake-jima, Esan and Usu

Self-potential (S.P.) measurements exhibit that the large and positive S.P. anom· aly is observed on the summit area of Miyake-jima volcano, while the significant anomaly related with the volcanic activity is not found on Esan volcano. A repeated measurement of the S.P. field on Usu volcano reveals the large and positive anomaly has been maintained during this decade. Different aspect of the S.P. fields probably depends on the differences in the hydrothermal system of each volcano. 1

Magmatic–hydrothermal system of Aso Volcano, Japan, inferred from electrical resistivity structures

We investigated the magmatic–hydrothermal system of Aso Volcano, Japan, using broadband magnetotelluric (MT) data. To establish the nature of the shallow crust, a previous resistivity model based on data from 100 measurement sites in and around Aso volcano was revised using data from 9 additional sites near Naka-dake crater, which is located in the central part of the volcano. The components of MT impedance and the tipper vector were used to obtain the resistivity structure by three-dimensional inversion. The resistivity structure shows a subvertical low-resistivity (< 1 Ωm) column-shaped body beneath Naka-dake crater that extends from − 600 m to 10 km below sea level (BSL) and dips steeply to the north-northeast. The position of the upper part of the column is displaced eastward compared with the previous model and does not overlap the position of the presumed magma reservoir inferred previously from seismic and geodetic observations underneath the western side of Naka-dake crater at a depth of 5 km. We interpret this low-resistivity column to be a magmatic–hydrothermal system composed of brine and magma that were transported to Naka-dake crater from the main deep-seated magma reservoir. A horizontal low-resistivity (< 10 Ωm) layer occurs beneath post-caldera cones at the depths of 0–2 km BSL, and this layer extends laterally from the upper part of the low-resistivity column. We interpret this low-resistivity layer as representing a shallow hydrothermal system that has developed around the central column-shaped magmatic–hydrothermal system