Insulin regulates Presenilin 1 localization via PI3K/Akt signaling.

Recently, insulin signaling has been highlighted in the pathology of Alzheimer's disease (AD). Although the association between insulin signaling and Tau pathology has been investigated in several studies, the interaction between insulin signaling and Presenilin 1 (PS1), a key molecule of amyloid beta (Abeta) pathology, has not been elucidated so far. In this study, we demonstrated that insulin inhibited PS1 phosphorylation at serine residues (serine 353, 357) via phosphatidylinositol 3-kinase (PI3K)/Akt signal pathway and strengthened the trimeric complex of PS1/N-cadherin/beta-catenin, consequently relocalizing PS1 to the cell surface. Since our recent report suggests that PS1/N-cadherin/beta-catenin complex regulates Abeta production, it is likely that insulin signaling affects Abeta pathology by regulating PS1 localization

Development of an X-ray HARP–FEA detector system for high-throughput protein crystallography

A new detector system for protein crystallography based on an X-ray HARP–FEA is presented

Decreased ADP-Ribosyl Cyclase Activity in Peripheral Blood Mononuclear Cells from Diabetic Patients with Nephropathy

Aims/hypothesis. ADP-ribosyl-cyclase activity (ADPRCA) of CD38 and other ectoenzymes mainly generate cyclic adenosine 5’diphosphate-(ADP-) ribose (cADPR) as a second messenger in various mammalian cells, including pancreatic beta cells and peripheral blood mononuclear cells (PBMCs). Since PBMCs contribute to the pathogenesis of diabetic nephropathy, ADPRCA of PBMCs could serve as a clinical prognostic marker for diabetic nephropathy. This study aimed to investigate the connection between ADPRCA in PBMCs and diabetic complications. Methods. PBMCs from 60 diabetic patients (10 for type 1 and 50 for type 2) and 15 nondiabetic controls were fluorometrically measured for ADPRCA based on the conversion of nicotinamide guanine dinucleotide (NGD+) into cyclic GDP-ribose. Results. ADPRCA negatively correlated with the level of HbA1c (P = .040, R2 = .073), although ADPRCA showed no significant correlation with gender, age, BMI, blood pressure, level of fasting plasma glucose and lipid levels, as well as type, duration, or medication of diabetes. Interestingly, patients with nephropathy, but not other complications, presented significantly lower ADPRCA than those without nephropathy (P = .0198) and diabetes (P = .0332). ANCOVA analysis adjusted for HbA1c showed no significant correlation between ADPRCA and nephropathy. However, logistic regression analyses revealed that determinants for nephropathy were systolic blood pressure and ADPRCA, not HbA1c. Conclusion/interpretation. Decreased ADPRCA significantly correlated with diabetic nephropathy. ADPRCA in PBMCs would be an important marker associated with diabetic nephropathy

The joint impact on being overweight of self reported behaviours of eating quickly and eating until full : cross sectional survey

Objective To examine whether eating until full or eating quickly or combinations of these eating behaviours are associated with being overweight

Cloning and expression of vacuolar proton-pumping ATPase subunits in the follicular epithelium of the bullfrog endolymphatic sac

金沢大学環日本海域環境研究センター生物多様性研究部門In an investigation aimed at clarifying the mechanism of crystal dissolution of the calcium carbonate lattice in otoconia (the mineral particles embedded in the otolithic membrane) of the endolymphatic sac (ELS) of the bullfrog, cDNAs encoding the A- and E-subunits of bullfrog vacuolar proton-pumping ATPase (V-ATPase) were cloned and sequenced. The cDNA of the A-subunit consisted of an 11-bp 5′-untranslated region (UTR), a 1,854-bp open reading frame (ORF) encoding a protein comprising 617 amino acids with a calculated molecular mass of 68,168 Da, and a 248-bp 3′-UTR followed by a poly(A) tail. The cDNA of the E-subunit consisted of a 72-bp 5′-UTR, a 681-bp ORF encoding a protein of 226 amino acids with a calculated molecular mass of 26,020 Da, and a 799-bp 3′-UTR followed by a poly(A) tail. Western blot and immunofluorescence analyses using specific anti-peptide antisera against the V-ATPase A- and E-subunits revealed that these subunits were present in the ELS, urinary bladder, skin, testes, and kidneys. In the ELS, positive cells were scattered in the follicular epithelium which, as revealed by electron microscopy, corresponds to the location of mitochondria-rich cells. These findings suggest that V-ATPase, including the A- and E-subunits, exists in mitochondria-rich cells of the ELS, which might be involved in dissolution of the calcium carbonate crystals in the lumen of the ELS. © 2007 Zoological Society of Japan

四肢動脈でみるサイン (バージャー病におけるコークスクリューサイン)

金沢大学医薬保健研究域医学系Thromboangitis obliterans (Buerger\u27s disease) is a non-atherosclerotic, segmental inflammatory disease that commonly affects small and medium-sized distal arteries, veins, and nerves of the upper and lower extremities in heavy tobacco smokers before the age of 50 years. As with atherosclerotic obliterans, manifestations of Buerger\u27s disease are intermittent claudication, leg pain at rest, and ulceration of extremities. Therefore, accurate diagnosis of Buerger\u27s disease is important to provide appropriate therapy to the patient. The presence of the corkscrew sign, collateralization around areas of occlusion, is a characteristic finding of Buerger\u27s disease. This paper presents the corkscrew sign involving both the upper and lower limbs.バージャー病は, 四肢の中, 小血管に好発し, 非特異的な原因不明の慢性血管炎により, 狭窄, 閉塞を来す疾患である. 本疾患は50歳未満の喫煙者において発症し, 虚血症状に伴う冷感, 知覚異常, 間歇性跛行, 安静時疼痛, 潰瘍等の症状を呈する. 診断は, 血管造影検査による動脈の形態学的所見が重要で, 末梢動脈の閉塞と側副血管路の所見からなされる. 特にコルク栓抜き状の側副血行路の所見はcorkscrew signと称され, 本疾患の特徴的な所見である. 本稿では, corkscrew signについて言及する. 「1. 疾患概念」バージャー病は, 四肢の中, 小血管に好発し, 非特異的な原因不明の慢性血管炎により, 狭窄, 閉塞を来す疾患である. バージャー病によって障害される血管は, 下肢では膝関節より末梢, 上肢では肘関節より末梢の動脈であり, しばしば周囲の静脈に遊走性静脈炎を合併する.出版者照会後に全文公

Turicibacter and Acidaminococcus predict immune-related adverse events and efficacy of immune checkpoint inhibitor

IntroductionImmune checkpoint inhibitors have had a major impact on cancer treatment. Gut microbiota plays a major role in the cancer microenvironment, affecting treatment response. The gut microbiota is highly individual, and varies with factors, such as age and race. Gut microbiota composition in Japanese cancer patients and the efficacy of immunotherapy remain unknown. MethodsWe investigated the gut microbiota of 26 patients with solid tumors prior to immune checkpoint inhibitor monotherapy to identify bacteria involved in the efficacy of these drugs and immune-related adverse events (irAEs).ResultsThe genera Prevotella and Parabacteroides were relatively common in the group showing efficacy towards the anti-PD-1 antibody treatment (effective group). The proportions of Catenibacterium (P = 0.022) and Turicibacter (P = 0.049) were significantly higher in the effective group than in the ineffective group. In addition, the proportion of Desulfovibrion (P = 0.033) was significantly higher in the ineffective group. Next, they were divided into irAE and non-irAE groups. The proportions of Turicibacter (P = 0.001) and Acidaminococcus (P = 0.001) were significantly higher in the group with irAEs than in those without, while the proportions of Blautia (P = 0.013) and the unclassified Clostridiales (P = 0.027) were significantly higher in the group without irAEs than those with. Furthermore, within the Effective group, Acidaminococcus and Turicibacter (both P = 0.001) were more abundant in the subgroup with irAEs than in those without them. In contrast, Blautia (P = 0.021) and Bilophila (P= 0.033) were statistically significantly more common in those without irAEs.DiscussionOur Study suggests that the analysis of the gut microbiota may provide future predictive markers for the efficacy of cancer immunotherapy or the selection of candidates for fecal transplantation for cancer immunotherapy

Dungey/interchange hybrid-type magnetic flux circulation mode in the magnetosphere

第3回極域科学シンポジウム/第36回極域宙空圏シンポジウム 11月27日（火） 国立極地研究所 2階大会議

Origin of the nightside By-controlled convection system during northward interplanetary magnetic field periods

第2回極域科学シンポジウム/第35回極域宙空圏シンポジウム 11月15日（火） 国立極地研究所 2階大会議室前フロ