Presenilin-2 Mutation Causes Early Amyloid Accumulation and Memory Impairment in a Transgenic Mouse Model of Alzheimer's Disease

In order to clarify the pathophysiological role of presenilin-2 (PS2) carrying the Volga German Kindred mutation (N141I) in a conventional mouse model of Alzheimer's disease (AD) expressing amyloid precursor protein (APP) with the Swedish mutation (Tg2576 line), we generated a double transgenic mouse (PS2Tg2576) by crossbreeding the PS2 mutant with Tg2576 mice. Here, we demonstrate that the PS2 mutation induced the early deposition of amyloid β-protein (Aβ) at 2-3 months of age and progressive accumulation at 4-5 months of age in the brains of the mutant mice. The PS2 mutation also accelerated learning and memory impairment associated with Aβ accumulation at 4-5 months of age in Tg2576 mice. These results suggest that the PS2 mutation causes early cerebral amyloid accumulation and memory dysfunction. PS2Tg2576 mice are a suitable mouse model for studying amyloid-lowering therapies

X-Ray bright optically faint active galactic nuclei in the Subaru Hyper Suprime-Cam wide survey

We construct a sample of X-ray bright optically faint active galactic nuclei by combining Subaru Hyper Suprime-Cam, XMM-Newton, and infrared source catalogs. 53 X-ray sources satisfying i band magnitude fainter than 23.5 mag and X-ray counts with EPIC-PN detector larger than 70 are selected from 9.1 deg^2, and their spectral energy distributions (SEDs) and X-ray spectra are analyzed. 44 objects with an X-ray to i-band flux ratio F_X/F_i>10 are classified as extreme X-ray-to-optical flux sources. SEDs of 48 among 53 are represented by templates of type 2 AGNs or starforming galaxies and show signature of stellar emission from host galaxies in the optical in the source rest frame. Infrared/optical SEDs indicate significant contribution of emission from dust to infrared fluxes and that the central AGN is dust obscured. Photometric redshifts determined from the SEDs are in the range of 0.6-2.5. X-ray spectra are fitted by an absorbed power law model, and the intrinsic absorption column densities are modest (best-fit log N_H = 20.5-23.5 cm^-2 in most cases). The absorption corrected X-ray luminosities are in the range of 6x10^42 - 2x10^45 erg s^-1. 20 objects are classified as type 2 quasars based on X-ray luminsosity and N_H. The optical faintness is explained by a combination of redshifts (mostly z>1.0), strong dust extinction, and in part a large ratio of dust/gas.Comment: 25 pages, 14 figures, 5 tables, accepted for publication in PAS

Replicative capacity of SARS-CoV-2 omicron variants BA.5 and BQ.1.1 at elevated temperatures

新型コロナウイルス・オミクロン株のBA.5系統およびBQ.1.1系統が、高温で増殖しづらいことを解明. 京都大学プレスリリース. 2023-04-27

A Case of Mucosal Cancer of the Stomach Treated by Endoscopic Submucosal Dissection after Which Nodal Metastasis Became Evident

An 82-year-old male was referred to our institution for evaluation and treatment of a protruding lesion in the stomach. Esophagogastroduodenoscopy (EGD) showed a small protruding lesion and a large superficial elevated lesion on the lesser curvature of the stomach (macroscopic type: 0-I and 0-IIa, resp.). CT and endoscopic ultrasonography (EUS) visualized a small round lymph node (LN) 11 mm in size near the lesser curvature, although submucosal invasion was not evident. These two lesions were resected en bloc by endoscopic submucosal dissection (ESD). Pathological examination of the resected specimen showed moderately differentiated tubular adenocarcinoma (tub2) and well-differentiated tubular adenocarcinoma (tub1), respectively, which were limited to the mucosal layer. Because lymphatic-vascular involvement was not detected by hematoxylin and eosin (HE) staining, additional gastrectomy was not performed. Two months after ESD, follow-up EUS and CT showed an enlarged LN. EUS-guided fine needle aspiration (EUS-FNA) for the LN revealed metastasis. Therefore, total gastrectomy with LN dissection was performed. His postoperative course was uneventful. After discharge, he has been followed up at the outpatient department without any sign of recurrence for 5 years. Histological reexamination of the ESD specimen using immunohistochemistry showed lymphatic invasion of cancer cells in the lamina propria of the 0-I lesion 13 mm in size

Clinical significance of ribosomal protein S15 expression in patients with colorectal cancer liver metastases

Sakano Y., Matoba D., Noda T., et al. Clinical significance of ribosomal protein S15 expression in patients with colorectal cancer liver metastases. Journal of Hepato-Biliary-Pancreatic Sciences, (2024); https://doi.org/10.1002/jhbp.12012.Background: Liver metastasis is the most frequently observed distant metastasis of colorectal cancer, and the residual liver recurrence rate after hepatic resection is still high. To explore the mechanism of liver metastasis to discover potential new treatments, we assessed the relationship between the expression of differentially expressed genes (DEGs) and prognosis in patients with colorectal cancer liver metastasis (CRLM). Methods: The gene expression dataset was extracted from The Cancer Genome Atlas and the Gene Expression Omnibus. Significance analysis of DEGs between tumor and normal samples of colorectum, liver, and lung was conducted. A total of 80 CRLM patients were studied to assess the expression of RPS15, characteristics, and outcomes. We examined the relationships of RPS15 expression to cell viability and apoptosis in vitro and vivo. Results: Significance analysis identified 33 DEGs. In our cohorts, the overall survival rates were significantly lower in the high-RPS15-expression group, and high expression of RPS15 was an independent and unfavorable prognostic factor in recurrence-free survival and overall survival. Knockdown of RPS15 expression reduced the proliferative capacity of colorectal cancer cells and increased BAX-induced apoptotic cell death. Conclusions: RPS15 expression is an independent prognostic factor for CRLM patients and might be a novel therapeutic target for CRLM

Assembly and Budding of Ebolavirus

Ebolavirus is responsible for highly lethal hemorrhagic fever. Like all viruses, it must reproduce its various components and assemble them in cells in order to reproduce infectious virions and perpetuate itself. To generate infectious Ebolavirus, a viral genome-protein complex called the nucleocapsid (NC) must be produced and transported to the cell surface, incorporated into virions, and then released from cells. To further our understanding of the Ebolavirus life cycle, we expressed the various viral proteins in mammalian cells and examined them ultrastructurally and biochemically. Expression of nucleoprotein alone led to the formation of helical tubes, which likely serve as a core for the NC. The matrix protein VP40 was found to be critical for transport of NCs to the cell surface and for the incorporation of NCs into virions, where interaction between nucleoprotein and the matrix protein VP40 is likely essential for these processes. Examination of virus-infected cells revealed that virions containing NCs mainly emerge horizontally from the cell surface, whereas empty virions mainly bud vertically, suggesting that horizontal budding is the major mode of Ebolavirus budding. These data form a foundation for the identification and development of potential antiviral agents to combat the devastating disease caused by this virus

Extracellular and Mixotrophic Symbiosis in the Whale-Fall Mussel Adipicola pacifica: A Trend in Evolution from Extra- to Intracellular Symbiosis

http://www.godac.jamstec.go.jp/darwin/cruise/natsushima/nt05-12/

Measurement of brain concentration of FK960 for development of a novel antidementia drug: A PET study in conscious rhesus monkeys

金沢大学大学院医学系研究科This study used PET to measure the time course of the brain concentration of 18F-labeled N-(4-acetyl-1-piperazinyl)-p-fluorobenzamide monohydrate (FK960), a novel antidementia drug, after oral administration to conscious rhesus monkeys. Methods: Three young-adult male rhesus monkeys were tested. FK960 (0.1 mg/kg) containing about 370 MBq of 18F-FK960 was administered orally to each monkey. Dynamic PET images were acquired for 4 h from 5 min after the administration. Arterial blood samples were withdrawn during PET scanning and were analyzed by an automatic well γ-counter and thin-layer chromatography to determine the time course of authentic 18F-FK960 activity concentration in plasma. FK960 concentrations in brain and plasma were calculated in units of mol/L using the specific activity of FK960 preparations. Results: 18F-FK960 penetrated the blood-brain barrier and underwent perfusion-dependent distribution in the entire brain. Maximal concentrations in the brain and plasma were 1.11 ± 0.30 x 10-7 mol/L (at 3.0 ± 0.6 h after administration) and 4.04 ± 1.29 x 10-7 mol/L (at 2.0 ± 1.1 h after administration), respectively. Conclusion: We succeeded in measuring the FK960 concentration in the brains of conscious monkeys and in plasma after oral administration at a dose of 0.1 mg/kg. The results suggested that this method can measure the FK960 concentration in the human brain, and a potential use of the PET technique in drug development was demonstrated