SORL1 Is Genetically Associated with Late-Onset Alzheimer’s Disease in Japanese, Koreans and Caucasians

To discover susceptibility genes of late-onset Alzheimer’s disease (LOAD), we conducted a 3-stage genome-wide association study (GWAS) using three populations: Japanese from the Japanese Genetic Consortium for Alzheimer Disease (JGSCAD), Koreans, and Caucasians from the Alzheimer Disease Genetic Consortium (ADGC). In Stage 1, we evaluated data for 5,877,918 genotyped and imputed SNPs in Japanese cases (n = 1,008) and controls (n = 1,016). Genome-wide significance was observed with 12 SNPs in the APOE region. Seven SNPs from other distinct regions with p-values ,261025 were genotyped in a second Japanese sample (885 cases, 985 controls), and evidence of association was confirmed for one SORL1 SNP (rs3781834, P=7.3361027 in the combined sample). Subsequent analysis combining results for several SORL1 SNPs in the Japanese, Korean (339 cases, 1,129 controls) and Caucasians (11,840 AD cases, 10,931 controls) revealed genome wide significance with rs11218343 (P=1.7761029) and rs3781834 (P=1.0461028). SNPs in previously established AD loci in Caucasians showed strong evidence of association in Japanese including rs3851179 near PICALM (P=1.7161025) and rs744373 near BIN1 (P = 1.3961024). The associated allele for each of these SNPs was the same as in Caucasians. These data demonstrate for the first time genome-wide significance of LOAD with SORL1 and confirm the role of other known loci for LOAD in Japanese. Our study highlights the importance of examining associations in multiple ethnic populations

The carboxy-terminal fragment of α1A calcium channel preferentially aggregates in the cytoplasm of human spinocerebellar ataxia type 6 Purkinje cells

Spinocerebellar ataxia type 6 (SCA6) is an autosomal dominant neurodegenerative disease caused by a small polyglutamine (polyQ) expansion (control: 4–20Q; SCA6: 20–33Q) in the carboxyl(C)-terminal cytoplasmic domain of the α1A voltage-dependent calcium channel (Cav2.1). Although a 75–85-kDa Cav2.1 C-terminal fragment (CTF) is toxic in cultured cells, its existence in human brains and its role in SCA6 pathogenesis remains unknown. Here, we investigated whether the small polyQ expansion alters the expression pattern and intracellular distribution of Cav2.1 in human SCA6 brains. New antibodies against the Cav2.1 C-terminus were used in immunoblotting and immunohistochemistry. In the cerebella of six control individuals, the CTF was detected in sucrose- and SDS-soluble cytosolic fractions; in the cerebella of two SCA6 patients, it was additionally detected in SDS-insoluble cytosolic and sucrose-soluble nuclear fractions. In contrast, however, the CTF was not detected either in the nuclear fraction or in the SDS-insoluble cytosolic fraction of SCA6 extracerebellar tissues, indicating that the CTF being insoluble in the cytoplasm or mislocalized to the nucleus only in the SCA6 cerebellum. Immunohistochemistry revealed abundant aggregates in cell bodies and dendrites of SCA6 Purkinje cells (seven patients) but not in controls (n = 6). Recombinant CTF with a small polyQ expansion (rCTF-Q28) aggregated in cultured PC12 cells, but neither rCTF-Q13 (normal-length polyQ) nor full-length Cav2.1 with Q28 did. We conclude that SCA6 pathogenesis may be associated with the CTF, normally found in the cytoplasm, being aggregated in the cytoplasm and additionally distributed in the nucleus

回腸新膀胱の2つのタイプの排尿

回腸新膀胱による禁制型尿路変向術を再発性表在性膀胱腫瘍8例に被膜下前立腺摘出下膀胱摘出後に施行し, 術後の排尿状態を検討した.患者は平均55.3歳, サントリニー静脈叢を結紮切除せず順行性に膀胱を切除後, 前立腺は膀胱頸部より2cm末梢側で切除し被膜下前立腺摘出した.1例で代用膀胱と尿道の間に3cmの腸管部分を残し, その蠕動運動のため排尿が著明に遷延し, 再手術を要した.他7名は脱管腔化した新膀胱を直接前立腺被膜に縫合し, 排尿は良好であった.内圧-尿流検査を7名に施行し, fast bladderとintermittent flowが見られ, 後者は排尿筋・括約筋協調不全様所見がみられたEight patients were evaluated clinically, radiologically, and urodynamically to determine the outcome of continent urinary diversion with ileal neobladder performed to treat the recurrent superficial bladder cancer after cystectomy with subcapsular prostatectomy. The mean age of the patients was 55.3 years. After descending dissection of the urinary bladder without ligation or dissection of Santorini's plexus, the prostate was cut to the bladder neck distally for 2 cm under the subcapular prostatectomy. One patient who had a short 3 cm intestinal segment between the pouch and the urethra, had severely prolonged micturition with peristalsis in this short segment, and required a re-operation. Micturition was good in the other seven patients, all with detubularized neobladder directly to the prostate capsule in anastomosis. Pressure flow studies performed on these seven patients revealed two types of micturition; "fast bladder" and "intermittent flow", the latter resembling detrusor sphincter dyssynergia

Reconstructing Shapes and Appearances of Thin Film Objects Using RGB Images

2016 IEEE Conference on Computer Vision and Pattern Recognition (CVPR),27-30 June 2016,Las Vegas, NV, USAReconstruction of shapes and appearances of thin film objects can be applied to many fields such as industrial inspection, biological analysis, and archaeologic research. However, it comes with many challenging issues because the appearances of thin film can change dramatically depending on view and light directions. The appearance is deeply dependent on not only the shapes but also the optical parameters of thin film. In this paper, we propose a novel method to estimate shapes and film thickness. First, we narrow down candidates of zenith angle by degree of polarization and determine it by the intensity of thin film which increases monotonically along the zenith angle. Second, we determine azimuth angle from occluding boundaries. Finally, we estimate the film thickness by comparing a look-up table of color along the thickness and zenith angle with captured images. We experimentally evaluated the accuracy of estimated shapes and appearances and found that our proposed method is effective