Institution
Tohoku University
Education•Sendai, Japan•
About: Tohoku University is a education organization based out in Sendai, Japan. It is known for research contribution in the topics: Magnetization & Population. The organization has 72116 authors who have published 170791 publications receiving 3941714 citations. The organization is also known as: Tōhoku daigaku.
Topics: Magnetization, Population, Alloy, Amorphous solid, Amorphous metal
Papers published on a yearly basis
Papers
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Harvard University1, Massachusetts Institute of Technology2, Case Western Reserve University3, Kanazawa University4, Tokyo Medical and Dental University5, Jichi Medical University6, Tohoku University7, University of Melbourne8, University of Edinburgh9, University of Göttingen10, Ludwig Maximilian University of Munich11, Carlos III Health Institute12, University of Paris13, University of Bologna14, Istituto Superiore di Sanità15, University of Michigan16, University of Eastern Finland17, University of North Carolina at Chapel Hill18, Karolinska Institutet19, Broad Institute20, Icahn School of Medicine at Mount Sinai21, Erasmus University Rotterdam22, Utrecht University23
TL;DR: It is shown that missense variants in PRNP previously reported to be pathogenic are at least 30 times more common in the population than expected on the basis of genetic prion disease prevalence, a finding that supports the safety of therapeutic suppression of prion protein expression.
Abstract: More than 100,000 genetic variants are reported to cause Mendelian disease in humans, but the penetrance-the probability that a carrier of the purported disease-causing genotype will indeed develop the disease-is generally unknown. We assess the impact of variants in the prion protein gene (PRNP) on the risk of prion disease by analyzing 16,025 prion disease cases, 60,706 population control exomes, and 531,575 individuals genotyped by 23andMe Inc. We show that missense variants in PRNP previously reported to be pathogenic are at least 30 times more common in the population than expected on the basis of genetic prion disease prevalence. Although some of this excess can be attributed to benign variants falsely assigned as pathogenic, other variants have genuine effects on disease susceptibility but confer lifetime risks ranging from <0.1 to ~100%. We also show that truncating variants in PRNP have position-dependent effects, with true loss-of-function alleles found in healthy older individuals, a finding that supports the safety of therapeutic suppression of prion protein expression.
369 citations
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TL;DR: In this article, the authors reviewed the current literature on the function of Rab isoforms and their effectors in regulated secretory vesicle traffic and showed that Rab3 is not the sole Rab isoform that regulates secretory VEs traffic.
Abstract: Secretion is a fundamental biological activity of all eukaryotic cells by which they release certain substances in the extracellular space. It is considered a specialized mode of membrane trafficking that is achieved by docking and fusion of secretory vesicles to the plasma membrane (i.e., exocytosis). Secretory vesicle traffic is thought to be regulated by a family of Rab small GTPases, which are regulators of membrane traffic that are common to all eukaryotic cells. Classically, mammalian Rab3 subfamily members were thought to be critical regulators of secretory vesicle exocytosis in neurons and endocrine cells, but recent genetic and proteomic studies indicate that Rab3 is not the sole Rab isoform that regulates secretory vesicle traffic. Rather, additional Rab isoforms, especially Rab27 subfamily members, are required for this process. In this article I review the current literature on the function of Rab isoforms and their effectors in regulated secretory vesicle traffic.
369 citations
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TL;DR: The results demonstrate that ischemic insult activates autophagy and an autophagic mechanism may contribute to isChemic neuronal injury and may be a potential target for developing a novel therapy for stroke.
Abstract: It has been reported that ischemic insult increases the formation of autophagosomes and activates autophagy. However, the role of autophagy in ischemic neuronal damage remains elusive. This study was taken to assess the role of autophagy in ischemic brain damage. Focal cerebral ischemia was introduced by permanent middle cerebral artery occlusion (pMCAO). Activation of autophagy was assessed by morphological and biochemical examinations. To determine the contribution of autophagy/lysosome to ischemic neuronal death, rats were pretreated with a single intracerebral ventricle injection of the autophagy inhibitors 3-methyl-adenine (3-MA) and bafliomycin A1 (BFA) or the cathepsin B inhibitor Z-FA-fmk after pMCAO. The effects of 3-MA and Z-FA-fmk on brain damage, expression of proteins involved in regulation of autophagy and apoptosis were assessed with 2,3,5-triphenyltetrazolium chloride (TTC) staining and immunoblotting. The results showed that pMACO increased the formation of autophagosomes and autolysosome...
369 citations
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TL;DR: The image analysis of the delivery processes of single particles in vivo provides valuable information on antibody-conjugated therapeutic nanoparticles, which will be useful in increasing therapeutic efficacy.
Abstract: Studies with tracking of single nanoparticles are providing new insights into the interactions and processes involved in the transport of drug carriers in living mice. Here, we report the tracking of a single particle quantum dot (Qdot) conjugated with tumor-targeting antibody in tumors of living mice using a dorsal skinfold chamber and a high-speed confocal microscope with a high-sensitivity camera. Qdot labeled with the monoclonal anti-HER2 antibody was injected into mice with HER2-overexpressing breast cancer to analyze the molecular processes of its mechanistic delivery to the tumor. Movement of single complexes of the Qdot-antibody could be clearly observed at 30 frames/s inside the tumor through a dorsal skinfold chamber. We successfully identified six processes of delivery: initially in the circulation within a blood vessel, during extravasation, in the extracelullar region, binding to HER2 on the cell membrane, moving from the cell membrane to the perinuclear region, and in the perinuclear region. The six processes were quantitatively analyzed to understand the rate-limiting constraints on Qdot-antibody delivery. The movement of the complexes at each stage was "stop-and-go." The image analysis of the delivery processes of single particles in vivo provides valuable information on antibody-conjugated therapeutic nanoparticles, which will be useful in increasing therapeutic efficacy.
369 citations
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TL;DR: It is suggested that adjuvant gemcitabine contributes to prolonged disease-free survival (DFS) in patients undergoing macroscopically curative resection of pancreatic cancer.
Abstract: A randomised phase III trial comparing gemcitabine with surgery-only in patients with resected pancreatic cancer: Japanese Study Group of Adjuvant Therapy for Pancreatic Cancer
368 citations
Authors
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Name | H-index | Papers | Citations |
---|---|---|---|
John Q. Trojanowski | 226 | 1467 | 213948 |
Aaron R. Folsom | 181 | 1118 | 134044 |
Marc G. Caron | 173 | 674 | 99802 |
Masayuki Yamamoto | 171 | 1576 | 123028 |
Kenji Watanabe | 167 | 2359 | 129337 |
Rodney S. Ruoff | 164 | 666 | 194902 |
Frederik Barkhof | 154 | 1449 | 104982 |
Takashi Taniguchi | 152 | 2141 | 110658 |
Yoshio Bando | 147 | 1234 | 80883 |
Thomas P. Russell | 141 | 1012 | 80055 |
Ali Khademhosseini | 140 | 887 | 76430 |
Marco Colonna | 139 | 512 | 71166 |
David H. Barlow | 133 | 786 | 72730 |
Lin Gu | 130 | 868 | 56157 |
Yoichiro Iwakura | 129 | 705 | 64041 |