角度分解光電子分光によるパイロクロア型イリジウム酸化物と層状ルテニウム酸化物で発現する金属絶縁体転移の研究

学位の種別: 課程博士審査委員会委員 : （主査）東京大学教授 辛 埴, 東京大学准教授 近藤 猛, 東京大学教授 中辻 知, 東京大学教授 廣井 善二, 東京大学教授 芝内 孝禎, 東京大学教授 佐々木 裕次University of Tokyo(東京大学

Tuberous Sclerosis 2 Gene Is Expressed at High Levels in Specific Types of Neurons in the Mouse Brain

Tuberous sclerosis (TSC) is an autosomal dominant disorder characterized by mental retardation, epilepsy and hamartomatous growth in many tissues. The gene (TSC2) encoding a tumor suppressor protein whose mutations cause TSC, has been demonstrated to be expressed at high levels in the adult and developing brain, raising the question of whether or not the TSC2 gene product has unique roles in differentiation related to cytoskeletal interactions within the central nervous system, in addition to a tumor suppressor function. To determine the expression of TSC2 in functionally distinct neuron types of the mouse brain, we carried out in situ hybridization with digoxigenin-labeled riboprobes for the detection of TSC2 mRNA. High levels of the TSC2 gene were in neurons of the pyramidal and dentate granular layer in the hippocampus, cerebellar Purkinje cells, neurons of the piriform cortex, motor neurons in the medulla and interneurons in the striatum, while intermediate levels were in cortical neurons, striatal neurons, septal neurons, thalamic neurons and neurons in the substantia nigra compacta. Thus, the high expression of the TSC2 gene has restricted distribution in specific neuronal types which are characterized by well-developed dendrites and rich in use-dependent long-term changes in synaptic efficacy. These results suggest that the function of the TSC2 gene product may be involved on a cellular basis in neuronal plasticity and relevant to mental retardation observed in TSC patients

Predicting the outcome of chronic kidney disease by the estimated nephron number: The rationale and design of PRONEP, a prospective, multicenter, observational cohort study

<p>Abstract</p> <p>Background</p> <p>The nephron number is thought to be associated with the outcome of chronic kidney disease (CKD). If the nephron number can be estimated in the clinical setting, it could become a strong tool to predict renal outcome. This study was designed to estimate the nephron number in CKD patients and to establish a method to predict the outcome by using the estimated nephron number.</p> <p>Methods/Design</p> <p>The hypothesis of this study is that the estimated nephron number can predict the outcome of a CKD patient. This will be a multicenter, prospective (minimum 3 and maximum 5 years follow-up) study. The subjects will comprise CKD patients aged over 14 years who have undergone a kidney biopsy. From January 2011 to March 2013, we will recruit 600 CKD patients from 10 hospitals belonging to the National Hospital Organization of Japan. The primary parameter for assessment is the composite of total mortality, renal death, cerebro-cardiovascular events, and a 50% reduction in the eGFR. The secondary parameter is the rate of eGFR decline per year. The nephron number will be estimated by the glomerular density in biopsy specimens and the renal cortex volume. This study includes one sub-cohort study to establish the equation to calculate the renal cortex volume. Enrollment will be performed at the time of the kidney biopsy, and the data will consist of a medical interview, ultrasound for measurement of the kidney size, blood or urine test, and the pathological findings of the kidney biopsy. Patients will continue to have medical consultations and receive examinations and/or treatment as usual. The data from the patients will be collected once a year after the kidney biopsy until March 2016. All data using this study are easily obtained in routine clinical practice.</p> <p>Discussion</p> <p>This study includes the first trials to estimate the renal cortex volume and nephron number in the general clinical setting. Furthermore, this is the first prospective study to examine whether the nephron number predicts the outcome of CKD patients. The results from this study should provide powerful new tools for nephrologists in routine clinical practice.</p> <p>Trial registration</p> <p>UMIN-Clinical Trial Registration, UMIN000004784.</p

Treatment responses and their predictors in patients with rheumatoid arthritis treated with biological agents

Biological agents represent an important advancement in for the treatment of rheumatoid arthritis (RA), but there is a subset of patients who do not improve despite therapy. This study aimed to determine the efficacy of biological agents for RA and to identify clinical factors that are associated with their response. We studied 98 patients with RA who started an initiating biological agent which was selected from infliximab, etanercept, adalimumab and tociliximab at 4 medical institutions. Etanercept was the most frequently used biological agent followed by infliximab although there was a difference in the selection of the biological agents among medical institutions. We found that etanercept achieved the highest treatment response, remission rate and drug survival rate. A high disease activity in the baseline disease activity score-c-reactive protein (CRP) was shown to be a negative predictor of the treatment response, and high patient global assessment was significantly less likely to achieve a good response. At week 4, decreases in 28 swollen joint counts and CRP were useful as predictors for sustaining the efficacy up to week 48. These data demonstrate that assessments of the disease activity at baseline and the early treatment response may be useful in predicting the efficacy and drug survival rate of biological agents

ソクド チョウリョク ノ ビショウ ヘンカ ケンシュツ ト ソノ オウヨウ

A sinker with a non-stretched fine flexible string fall down with the sinker naturally, and both the speed and tension of its drawing-out string are individually measured. It is thought that a sinker will meet with an obstacle, if both sudden irregularities are observed at the same time upon motion of the string. In this case, a general stepping motor are employed in measurments of the speed and a tork-less special encorder are used in detection of the tension as sensors

The Japanese space gravitational wave antenna; DECIGO

DECi-hertz Interferometer Gravitational wave Observatory (DECIGO) is the future Japanese space gravitational wave antenna. DECIGO is expected to open a new window of observation for gravitational wave astronomy especially between 0.1 Hz and 10 Hz, revealing various mysteries of the universe such as dark energy, formation mechanism of supermassive black holes, and inflation of the universe. The pre-conceptual design of DECIGO consists of three drag-free spacecraft, whose relative displacements are measured by a differential Fabry– Perot Michelson interferometer. We plan to launch two missions, DECIGO pathfinder and pre- DECIGO first and finally DECIGO in 2024

DECIGO pathfinder

DECIGO pathfinder (DPF) is a milestone satellite mission for DECIGO (DECi-hertz Interferometer Gravitational wave Observatory) which is a future space gravitational wave antenna. DECIGO is expected to provide us fruitful insights into the universe, in particular about dark energy, a formation mechanism of supermassive black holes, and the inflation of the universe. Since DECIGO will be an extremely large mission which will formed by three drag-free spacecraft with 1000m separation, it is significant to gain the technical feasibility of DECIGO before its planned launch in 2024. Thus, we are planning to launch two milestone missions: DPF and pre-DECIGO. The conceptual design and current status of the first milestone mission, DPF, are reviewed in this article

Genome-wide association study revealed novel loci which aggravate asymptomatic hyperuricaemia into gout

Objective The first ever genome-wide association study (GWAS) of clinically defined gout cases and asymptomatic hyperuricaemia (AHUA) controls was performed to identify novel gout loci that aggravate AHUA into gout. Methods We carried out a GWAS of 945 clinically defined gout cases and 1003 AHUA controls followed by 2 replication studies. In total, 2860 gout cases and 3149 AHUA controls (all Japanese men) were analysed. We also compared the ORs for each locus in the present GWAS (gout vs AHUA) with those in the previous GWAS (gout vs normouricaemia). Results This new approach enabled us to identify two novel gout loci (rs7927466 of CNTN5 and rs9952962 of MIR302F) and one suggestive locus (rs12980365 of ZNF724) at the genome-wide significance level (p<5.0×10– 8). The present study also identified the loci of ABCG2, ALDH2 and SLC2A9. One of them, rs671 of ALDH2, was identified as a gout locus by GWAS for the first time. Comparing ORs for each locus in the present versus the previous GWAS revealed three ‘gout vs AHUA GWAS’-specific loci (CNTN5, MIR302F and ZNF724) to be clearly associated with mechanisms of gout development which distinctly differ from the known gout risk loci that basically elevate serum uric acid level. Conclusions This meta-analysis is the first to reveal the loci associated with crystal-induced inflammation, the last step in gout development that aggravates AHUA into gout. Our findings should help to elucidate the molecular mechanisms of gout development and assist the prevention of gout attacks in high-risk AHUA individuals

Genome-wide meta-analysis identifies multiple novel loci associated with serum uric acid levels in Japanese individuals

Gout is a common arthritis caused by elevated serum uric acid (SUA) levels. Here we investigated loci influencing SUA in a genome-wide meta-analysis with 121,745 Japanese subjects. We identified 8948 variants at 36 genomic loci (P<5 × 10–8) including eight novel loci. Of these, missense variants of SESN2 and PNPLA3 were predicted to be damaging to the function of these proteins; another five loci—TMEM18, TM4SF4, MXD3-LMAN2, PSORS1C1-PSORS1C2, and HNF4A—are related to cell metabolism, proliferation, or oxidative stress; and the remaining locus, LINC01578, is unknown. We also identified 132 correlated genes whose expression levels are associated with SUA-increasing alleles. These genes are enriched for the UniProt transport term, suggesting the importance of transport-related genes in SUA regulation. Furthermore, trans-ethnic meta-analysis across our own meta-analysis and the Global Urate Genetics Consortium has revealed 15 more novel loci associated with SUA. Our findings provide insight into the pathogenesis, treatment, and prevention of hyperuricemia/gout