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 ethnographic digital collections

Περιέχει το πλήρες κείμενοΟι λαογραφικές συλλογές αποτελούν πολύτιμη πηγή μελέτης, εξερεύνησης και αξιολόγησης των εθνικών στερεοτύπων των διαφόρων διαμερισμάτων μιας χώρας, δεδομένου ότι στις συλλογές είναι καταχωρημένα ανόθευτα και πηγαία τα εγχώρια εθνοχαρακτηριστικά τους. Κατά κύριο λόγο η λαογραφία αναφέρεται στους μύθους, τα τραγούδια, τη μουσική, τα έθιμα, τη χειροτεχνία, την ενδυμασία, την αρχιτεκτονική και την προφορική παράδοση μιας κοινότητας. Η ιδιαιτερότητα και η ποικιλία ενός τομέα όπως της λαογραφίας δικαιολογεί απόλυτα την ύπαρξη συλλογών και υπο-συλλογών σύνθετης δομής και σημασιολογίας, όπως αυτές που αναφέρουμε παραπάνω. Επομένως η ανάπτυξη ψηφιακών συλλογών απαιτεί τη διατήρηση των στοιχείων που χρειάζονται για: (α) την περιγραφή του περιεχομένου της κάθε συλλογής χωριστά και (β) τη σωστή απεικόνιση της δομής των αντικειμένων στο εσωτερικό αυτής. Στόχος της εργασίας αυτής είναι η παρουσίαση μιας μεθοδολογίας για την ανάπτυξη ενός περιγραφικού μοντέλου μεταδεδομένων για λαογραφικές συλλογές. Το μοντέλο θα αποτελέσει βασικό εργαλείο για την περιγραφή του ψηφιοποιημένου λαογραφικού υλικού, την πρόσβαση σε αυτό από κατανεμημένους χρήστες και φυσικά την επικοινωνία του με άλλα συστήματα. Επιπλέον θα συμβάλλει στη διασύνδεση σύνθετων συλλογών και των αντικειμένων που περιλαμβάνουν είτε σημασιολογικά, είτε χρονικά, είτε θεματικά είτε με οποιονδήποτε άλλο τρόπο απαιτεί η φύση των συλλογών και οι ανάγκες των χρηστών

Differences in the electric potential of pancreatic head cancer tissues

Identifying the electrical properties of cancer relies on the understanding of the electric potential (EP) of cancer tissues. This study aimed to investigate the EP properties in 49 pancreatic head cancer tissues using a digital multimetre. The anode was placed at the central side of the tumour, and the electric potential differences (EPDs) between cancerous and cancerous, cancerous and noncancerous, and noncancerous and noncancerous lesions at approximately 1-cm intervals following resection were evaluated. Pathological evaluation identified 30 of these samples as pancreatic invasive ductal carcinoma (PIDC, 10 without preoperative chemotherapy and 20 after chemotherapy), seven other pancreatic cancers, three tumours of Vater’s ampulla (VA), and eight extrahepatic cholangiocarcinoma (EHCC) samples. We also evaluated the differences in pH for cancerous and noncancerous lesions in nine PIDC samples. Our data suggest that the EP of pancreatic cancerous tissues is higher than that of noncancerous tissues, especially in PIDCs. We also noted that EPD was the highest when comparing cancerous and noncancerous lesions. Additionally, PIDC tissues presented with low pH; the pH difference between cancerous and noncancerous sites was significantly correlated with EPD (P = 0.011). These EPDs were also correlated with tumour size in PIDCs and inversely correlated with their response to chemotherapy. The EP values for both the cancerous and noncancerous sites in both the VA tumours and EHCC samples were not significantly different, whereas EPD in PIDC correlated with tumour extension and viable tumour content, suggesting that EPD might be useful for evaluating the viability and effectiveness of neoadjuvant chemotherapy.This research was partially supported by a Grant-in-Aid for Scientific Research (A) (Nos. 15H02567 and 17H05102) from the Ministry of Education, Culture, Sports, Science, and Technology, and the Ministry of Health, Labour, and Welfare for Japan

PlexinD1 signaling controls domain-specific dendritic development in newborn neurons in the postnatal olfactory bulb

Newborn neurons show immature bipolar morphology and continue to migrate toward their destinations. After the termination of migration, newborn neurons undergo spatially controlled dendrite formation and change into a complex morphology. The mechanisms of dendritic development of newborn neurons have not been fully understood. Here, we show that in the postnatal olfactory bulb (OB), the Sema3E-PlexinD1 signaling, which maintains bipolar morphology of newborn neurons, also regulates their dendritic development after the termination of migration in a dendritic domain-specific manner. Genetic ablation of Sema3E or PlexinD1 enhanced dendritic branching in the proximal domain of the apical dendrites of OB newborn granule cells, whereas PlexinD1 overexpression suppressed it in a Rho binding domain (RBD)-dependent manner. Furthermore, RhoJ, a small GTPase that directly binds to PlexinD1RBD in vascular endothelial cells, is expressed in migrating and differentiating newborn granule cells in the OB and is also involved in the suppression of proximal branching of their apical dendrites. These results suggest that the Sema3E-PlexinD1-RhoJ axis regulates domain-specific dendrite formation of newborn neurons in the postnatal OB

Impact of Gba2 on neuronopathic Gaucher’s disease and α-synuclein accumulation in medaka (Oryzias latipes)

Homozygous mutations in the lysosomal glucocerebrosidase gene, GBA1, cause Gaucher's disease (GD), while heterozygous mutations in GBA1 are a strong risk factor for Parkinson's disease (PD), whose pathological hallmark is intraneuronal α-synuclein (asyn) aggregates. We previously reported that gba1 knockout (KO) medaka exhibited glucosylceramide accumulation and neuronopathic GD phenotypes, including short lifespan, the dopaminergic and noradrenergic neuronal cell loss, microglial activation, and swimming abnormality, with asyn accumulation in the brains. A recent study reported that deletion of GBA2, non-lysosomal glucocerebrosidase, in a non-neuronopathic GD mouse model rescued its phenotypes. In the present study, we generated gba2 KO medaka and examined the effect of Gba2 deletion on the phenotypes of gba1 KO medaka. The Gba2 deletion in gba1 KO medaka resulted in the exacerbation of glucosylceramide accumulation and no improvement in neuronopathic GD pathological changes, asyn accumulation, or swimming abnormalities. Meanwhile, though gba2 KO medaka did not show any apparent phenotypes, biochemical analysis revealed asyn accumulation in the brains. gba2 KO medaka showed a trend towards an increase in sphingolipids in the brains, which is one of the possible causes of asyn accumulation. In conclusion, this study demonstrated that the deletion of Gba2 does not rescue the pathological changes or behavioral abnormalities of gba1 KO medaka, and GBA2 represents a novel factor affecting asyn accumulation in the brains

Suppression of HBV replication by the expression of nickase-and nuclease dead-Cas9

Kurihara, T., Fukuhara, T., Ono, C. et al. Suppression of HBV replication by the expression of nickase- and nuclease dead-Cas9. Sci Rep 7, 6122 (2017). https://doi.org/10.1038/s41598-017-05905-

Percutaneous Transluminal Angioscopy During Coronary Intervention

To investigate the feasibility of angioscopic-guided percutaneous transluminal coronary angioplasty and to elucidate the mechanism of efficacy of coronary stenting for acute myocardial infarction, we performed coronary angioscopy in 102 patients with stable angina or acute myocardial infarction. Thrombi and intimal flaps were observed in most patients after coronary angioplasty. Large intimal splits were seen in one third of patients. Stents were inserted in 10 patients who were revealed to have a large flap or protruding split to the inner lumen. Thrombolytic agents were administered in 2 patients with large thrombi. Additional treatments were required in 32% of patients. No acute myocardial infarction or unstable angina occurred in patients during hospitalization. Thus, angioscopy of the coronary lumen enables clinicians to determine the most appropriate and least risky coronary intervention strategy. In patients with acute myocardial infarction, angioscopy revealed occlusive or protruding thrombi in 34 of 35 patients. The protruding thrombi disappeared after stenting. The frequency of large intimal flaps increased after predilatation with balloon, but these disappeared after stenting. The present angioscopic study demonstrates that the coronary stent compresses the occlusive or protruding thrombi and covers the ruptured thrombogenic plaque Consequently, smooth-surfaced and wide vessel lumen are obtained

Polymorphisms and Body Mass Index Across Life Course

Background: Obesity is a reported risk factor for various health problems. Genome-wide association studies (GWASs) have identified numerous independent loci associated with body mass index (BMI). However, most of these have been focused on Europeans, and little evidence is available on the genetic effects across the life course of other ethnicities. Methods: We conducted a cross-sectional study to examine the associations of 282 GWAS-identified single nucleotide polymorphisms with three BMI-related traits, current BMI, BMI at 20 years old (BMI at 20), and change in BMI (BMI change), among 11,586 Japanese individuals enrolled in the Japan Multi-Institutional Collaborative Cohort study. Associations were examined using multivariable linear regression models. Results: We found a significant association (P < 0.05/282 = 1.77 × 10−4) between BMI and 11 polymorphisms in or near FTO, BDNF, TMEM18, HS6ST3, and BORCS7. The trend was similar between current BMI and BMI change, but differed from that of the BMI at 20. Among the significant variants, those on FTO were associated with all BMI traits, whereas those on TMEM18 and HS6SR3 were only associated with BMI at 20. The association of FTO loci with BMI remained, even after additional adjustment for dietary energy intake. Conclusions: Previously reported BMI-associated loci discovered in Europeans were also identified in the Japanese population. Additionally, our results suggest that the effects of each loci on BMI may vary across the life course and that this variation may be caused by the differential effects of individual genes on BMI via different pathways