Apelin Deficiency Accelerates the Progression of Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the selective loss of motor neurons. Recent studies have implicated that chronic hypoxia and insufficient vascular endothelial growth factor (VEGF)-dependent neuroprotection may lead to the degeneration of motor neurons in ALS. Expression of apelin, an endogenous ligand for the G protein-coupled receptor APJ, is regulated by hypoxia. In addition, recent reports suggest that apelin protects neurons against glutamate-induced excitotoxicity. Here, we examined whether apelin is an endogenous neuroprotective factor using SOD1G93A mouse model of ALS. In mouse CNS tissues, the highest expressions of both apelin and APJ mRNAs were detected in spinal cord. APJ immunoreactivity was observed in neuronal cell bodies located in gray matter of spinal cord. Although apelin mRNA expression in the spinal cord of wild-type mice was not changed from 4 to 18 weeks age, that of SOD1G93A mice was reduced along with the paralytic phenotype. In addition, double mutant apelin-deficient and SOD1G93A displayed the disease phenotypes earlier than SOD1G93A littermates. Immunohistochemical observation revealed that the number of motor neurons was decreased and microglia were activated in the spinal cord of the double mutant mice, indicating that apelin deficiency pathologically accelerated the progression of ALS. Furthermore, we showed that apelin enhanced the protective effect of VEGF on H2O2-induced neuronal death in primary neurons. These results suggest that apelin/APJ system in the spinal cord has a neuroprotective effect against the pathogenesis of ALS

Discovery of widespread transcription initiation at microsatellites predictable by sequence-based deep neural network

Using the Cap Analysis of Gene Expression (CAGE) technology, the FANTOM5 consortium provided one of the most comprehensive maps of transcription start sites (TSSs) in several species. Strikingly, ~72% of them could not be assigned to a specific gene and initiate at unconventional regions, outside promoters or enhancers. Here, we probe these unassigned TSSs and show that, in all species studied, a significant fraction of CAGE peaks initiate at microsatellites, also called short tandem repeats (STRs). To confirm this transcription, we develop Cap Trap RNA-seq, a technology which combines cap trapping and long read MinION sequencing. We train sequence-based deep learning models able to predict CAGE signal at STRs with high accuracy. These models unveil the importance of STR surrounding sequences not only to distinguish STR classes, but also to predict the level of transcription initiation. Importantly, genetic variants linked to human diseases are preferentially found at STRs with high transcription initiation level, supporting the biological and clinical relevance of transcription initiation at STRs. Together, our results extend the repertoire of non-coding transcription associated with DNA tandem repeats and complexify STR polymorphism

Discovery of widespread transcription initiation at microsatellites predictable by sequence-based deep neural network

Using the Cap Analysis of Gene Expression (CAGE) technology, the FANTOM5 consortium provided one of the most comprehensive maps of transcription start sites (TSSs) in several species. Strikingly, ~72% of them could not be assigned to a specific gene and initiate at unconventional regions, outside promoters or enhancers. Here, we probe these unassigned TSSs and show that, in all species studied, a significant fraction of CAGE peaks initiate at microsatellites, also called short tandem repeats (STRs). To confirm this transcription, we develop Cap Trap RNA-seq, a technology which combines cap trapping and long read MinION sequencing. We train sequence-based deep learning models able to predict CAGE signal at STRs with high accuracy. These models unveil the importance of STR surrounding sequences not only to distinguish STR classes, but also to predict the level of transcription initiation. Importantly, genetic variants linked to human diseases are preferentially found at STRs with high transcription initiation level, supporting the biological and clinical relevance of transcription initiation at STRs. Together, our results extend the repertoire of non-coding transcription associated with DNA tandem repeats and complexify STR polymorphism

Impact of age on left ventricular geometry and diastolic function in elderly patients with treated hypertension

Purpose: Left ventricular (LV) remodelling is observed in numerous patients with hypertension and is a principal cause of heart failure in elderly patients. The aim of this study was to determine the relationships between age and structural/functional LV remodelling observed in elderly hypertensive patients. Methods: A total of 557 elderly hypertensive patients (mean age: 74.0 ± 8.6 years) with preserved LV systolic function underwent echocardiography and 24-hour blood pressure (BP) measurement. Results: Overall, 41.1% of patients had LV hypertrophy, 77.9% had increased relative wall thickness (RWT) defined as RWT >0.42, and 31.8% had both. Logistic analysis of the entire study population showed that increased RWT was associated with both 24-hour systolic BP (odds ratio (OR) 1.38, 95% confidence interval (CI) 1.12 to 1.70) and age (OR 1.32, 95%CI 1.08 to 1.61), whereas increased RWT was associated only with age (OR 1.61, 95%CI 1.23 to 2.11) after excluding patients with LV hypertrophy. Univariate and multivariate linear regression analyses of all patients showed that LV diastolic echocardiographic parameters were consistently associated with age (p ≤ .001) alone, even considering LV structural changes. Conclusions: Age was independently correlated with LV concentric/functional changes regardless of LV hypertrophy, suggesting that ageing is independently involved in the progression of LV remodelling

石川県南部地域の手取層群に産する黒色珪質岩脈

金沢大学理工研究域自然システム学系Black-colored rocks (Black-colored Rocks hereafter) occur as veins and a volcanic dike in the Tetori Group, southern Ishikawa Prefecture. The Black-colored Rocks are composed of angular lithic clasts in a fine-grained (<10-50 µm) matrix. The lithic clasts in veins are derived from the Tetori Group (mudstone, sandstone, and conglomerate), whereas those in the volcanic dike are derived from both the volcanic dike and the Tetori Group. The matrix of the Black-colored Rocks consists mainly of very fine-grained quartz (usually 10 µm in size) with minor amounts of feldspar, maghemite, and unidentified carbon-bearing fine-grains. The Black-colored Rocks contain abundant SiO2 relative to the host rocks. The chondrite-normalized rare earth element (REE) pattern of the Black-colored Rocks is similar to that of their host rocks, although the REE abundance is lower in the former

Whole genome sequencing of 45 Japanese patients with intellectual disability

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