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Hideto Matsui, Atsushi Tamura, Mamoru Osawa, Asato Tonegawa, Yoshinori Arisaka, Mitsuaki Matsumura, Hiroyuki Miura, Nobuhiko Yui
Because macrophages are involved in the pathology of many diseases, targeting delivery of therapeutic molecules to macrophages is important issue. Polyrotaxanes (PRXs) composed of multiple cyclodextrins threaded with a linear polymer were utilized as a therapeutic agent for metabolic disease and for regulating cellular metabolism. For targeting delivery of PRXs to macrophages, carboxyethyl ether group-modified PRXs (CEE-PRXs) are designed for promoting interaction to macrophage scavenger receptor class A (SR-A)...
June 13, 2018: Macromolecular Bioscience
Kouki Tomari, Takao Toyokawa, Takuto Takahashi, Tetsuya Kakita, Sho Okano, Hisako Kyan, Naoya Tonegawa, Teppei Okawa, Takashi Matsuoka, Tsutomu Matsumora
Leptospirosis is considered underdiagnosed because of its nonspecific presentation and lack of proper understanding of its epidemiology. Early diagnosis and treatment are crucial. However, few data are available on confirmed leptospirosis cases in children in industrialized countries. We therefore aimed to describe epidemiologic and clinical characteristics of laboratory-confirmed childhood leptospirosis in Okinawa, Japan. We reviewed the national surveillance data of pediatric leptospirosis in Okinawa, Japan from January 2003 through December 2015...
March 2018: PLoS Neglected Tropical Diseases
Akiko Wagatsuma, Teruhiro Okuyama, Chen Sun, Lillian M Smith, Kuniya Abe, Susumu Tonegawa
The memory for a new episode is formed immediately upon experience and can last up to a lifetime. It has been shown that the hippocampal network plays a fundamental role in the rapid acquisition of a memory of a one-time experience, in which the novelty component of the experience promotes the prompt formation of the memory. However, it remains unclear which neural circuits convey the novelty signal to the hippocampus for the single-trial learning. Here, we show that during encoding neuromodulatory input from locus coeruleus (LC) to CA3, but not CA1 or to the dentate gyrus, is necessary to facilitate novel contextual learning...
January 9, 2018: Proceedings of the National Academy of Sciences of the United States of America
Takashi Tonegawa, Eiichiro Araki, Toshinori Kimura, Takeshi Nakamura, Masaru Nakano, Kensuke Suzuki
A low-velocity zone (LVZ) has been detected by seismic exploration surveys within the Nankai accretionary prism toe off the Kii Peninsula, southwestern Japan, and is considered to be a mechanically weak volume at depth. Such mechanical heterogeneities potentially influence seismic and tsunamigenic slips on megathrust earthquakes in the subduction zone. However, the spatial distribution of the LVZ along the trough-parallel direction is still elusive. Here we show sporadic LVZs in the prism toe from one-dimensional shear wave velocity (Vs) profiles obtained at 49 cabled ocean bottom stations, which were estimated by a nonlinear inversion technique, simulated annealing, using the displacement-pressure ratios of the Rayleigh wave...
December 11, 2017: Nature Communications
Dheeraj S Roy, Shruti Muralidhar, Lillian M Smith, Susumu Tonegawa
Recent studies identified neuronal ensembles and circuits that hold specific memory information (memory engrams). Memory engrams are retained under protein synthesis inhibition-induced retrograde amnesia. These engram cells can be activated by optogenetic stimulation for full-fledged recall, but not by stimulation using natural recall cues (thus, amnesia). We call this state of engrams "silent engrams" and the cells bearing them "silent engram cells." The retention of memory information under amnesia suggests that the time-limited protein synthesis following learning is dispensable for memory storage, but may be necessary for effective memory retrieval processes...
November 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
Sangyu Xu, Gishnu Das, Emily Hueske, Susumu Tonegawa
Appropriate choice about delayed reward is fundamental to the survival of animals. Although animals tend to prefer immediate reward, delaying gratification is often advantageous. The dorsal raphe (DR) serotonergic neurons have long been implicated in the processing of delayed reward, but it has been unclear whether or when their activity causally directs choice. Here, we transiently augmented or reduced the activity of DR serotonergic neurons, while mice decided between differently delayed rewards as they performed a novel odor-guided intertemporal choice task...
October 23, 2017: Current Biology: CB
Jun Yamamoto, Susumu Tonegawa
Hippocampal replays have been demonstrated to play a crucial role in memory. Chains of ripples (ripple bursts) in CA1 have been reported to co-occur with long-range place cell sequence replays during the quiet awake state, but roles of neural inputs to CA1 in ripple bursts and replays are unknown. Here we show that ripple bursts in CA1 and medial entorhinal cortex (MEC) are temporally associated. An inhibition of MECIII input to CA1 during quiet awake reduced ripple bursts in CA1 and restricted the spatial coverage of replays to a shorter distance corresponding to single ripple events...
September 27, 2017: Neuron
Dheeraj S Roy, Teruhiro Okuyama, Susumu Tonegawa
No abstract text is available yet for this article.
September 11, 2017: Nature Biotechnology
Takuma Hayashi, Miki Kawano, Kenji Sano, Tomoyuki Ichimura, Gal Gur, Pnina Yaish, Dorit Zharhary, Yae Kanai, Susumu Tonegawa, Tanri Shiozawa, Nobuo Yaegashi, Ikuo Konishi
No abstract text is available yet for this article.
April 2017: Chinese Clinical Oncology
Takashi Kitamura, Sachie K Ogawa, Dheeraj S Roy, Teruhiro Okuyama, Mark D Morrissey, Lillian M Smith, Roger L Redondo, Susumu Tonegawa
Episodic memories initially require rapid synaptic plasticity within the hippocampus for their formation and are gradually consolidated in neocortical networks for permanent storage. However, the engrams and circuits that support neocortical memory consolidation have thus far been unknown. We found that neocortical prefrontal memory engram cells, which are critical for remote contextual fear memory, were rapidly generated during initial learning through inputs from both the hippocampal-entorhinal cortex network and the basolateral amygdala...
April 7, 2017: Science
Joshua Kim, Xiangyu Zhang, Shruti Muralidhar, Sarah A LeBlanc, Susumu Tonegawa
Basolateral amygdala (BLA) principal cells are capable of driving and antagonizing behaviors of opposing valence. BLA neurons project to the central amygdala (CeA), which also participates in negative and positive behaviors. However, the CeA has primarily been studied as the site for negative behaviors, and the causal role for CeA circuits underlying appetitive behaviors is poorly understood. Here, we identify several genetically distinct populations of CeA neurons that mediate appetitive behaviors and dissect the BLA-to-CeA circuit for appetitive behaviors...
March 22, 2017: Neuron
Masahiko Terauchi, Takasuke Inada, Tomoki Kanemaru, Go Ikeda, Asato Tonegawa, Kei Nishida, Yoshinori Arisaka, Atsushi Tamura, Satoshi Yamaguchi, Nobuhiko Yui
Bone reconstruction is a challenging issue in the regeneration of surgically removed bone and disease-related bone defects. Although bone morphogenetic protein-2 (BMP-2) has received considerable attention as a bone regeneration inducer, a high dose of BMP-2 is typically required due to its short life-time under in vivo conditions. We have proposed a method to enhance the osteogenetic differentiation ability of BMP-2 in vitro that is based on supramolecular polyelectrolyte complexation with sulfonated polyrotaxanes (PRXs) consisting of sulfopropyl ether (SPE)-modified α-cyclodextrins threaded along a poly(ethylene glycol) chain capped with terminal bulky stopper molecules...
May 2017: Journal of Biomedical Materials Research. Part A
Kota Tonegawa, Wataru Otsuka, Shohei Kumagai, Sachi Matsunami, Nao Hayamizu, Shota Tanaka, Kazumasa Moriwaki, Masanori Obana, Makiko Maeda, Michio Asahi, Hiroshi Kiyonari, Yasushi Fujio, Hiroyuki Nakayama
Activation of CaMKII induces a myriad of biological processes and plays dominant roles in cardiac hypertrophy. Caveolar microdomain contains many calcium/calmodulin-dependent kinase II (CaMKII) targets, including L-type Ca(2+) channel (LTCC) complex, and serves as a signaling platform. The location of CaMKII activation is thought to be critical; however, the roles of CaMKII in caveolae are still elusive due to lack of methodology for the assessment of caveolae-specific activation. Our aim was to develop a novel tool for the specific analysis of CaMKII activation in caveolae and to determine the functional role of caveolar CaMKII in cardiac hypertrophy...
March 1, 2017: American Journal of Physiology. Heart and Circulatory Physiology
Hirofumi Morihara, Tsuyoshi Yamamoto, Harunori Oiwa, Kota Tonegawa, Daisuke Tsuchiyama, Ikki Kawakatsu, Masanori Obana, Makiko Maeda, Tomomi Mohri, Satoshi Obika, Yasushi Fujio, Hiroyuki Nakayama
BACKGROUND: Phospholamban (PLN) inhibition enhances calcium cycling and is a potential novel therapy for heart failure (HF). Antisense oligonucleotides (ASOs) are a promising tool for unmet medical needs. Nonviral vector use of locked nucleic acid (LNA)-modified ASOs (LNA-ASOs), which shows strong binding to target RNAs and is resistant to nuclease, is considered to have a potential for use in novel therapeutics in the next decades. Thus, the efficacy of a single-dose injection of LNA-ASO for cardiac disease needs to be elucidated...
May 2017: Journal of Cardiovascular Pharmacology and Therapeutics
Takuma Hayashi, Miki Kawano, Tomoyuki Ichimura, Koichi Ida, Hirofumi Ando, Dorit Zharhary, Yae Kanai, Hiroyuki Aburatani, Susumu Tonegawa, Tanri Shiozawa, Nobuo Yaegashi, Ikuo Konishi
Patients with uterine leiomyosarcoma (LMS) typically present with vaginal bleeding, pain, and a pelvic mass, with atypical presentations of hypercalcemia and eosinophilia also being reported. Radiographic evaluation with combined positron-emission tomography/computed tomography may assist in diagnosis and surveillance in women with uterine LMS; these are commonly used with stage and tumour grade as prognostic indicators and a recently developed risk-assessment index to predict disease-specific survival. Recent studies have shown that the addition of adjuvant therapy after surgical management does not seem to improve survival, and ovarian preservation does not appear to negatively impact outcome...
2016: Anticancer Research
Joshua Kim, Michele Pignatelli, Sangyu Xu, Shigeyoshi Itohara, Susumu Tonegawa
The basolateral amygdala (BLA) is a site of convergence of negative and positive stimuli and is critical for emotional behaviors and associations. However, the neural substrate for negative and positive behaviors and relationship between negative and positive representations in the basolateral amygdala are unknown. Here we identify two genetically distinct, spatially segregated populations of excitatory neurons in the mouse BLA that participate in valence-specific behaviors and are connected through mutual inhibition...
December 2016: Nature Neuroscience
Teruhiro Okuyama, Takashi Kitamura, Dheeraj S Roy, Shigeyoshi Itohara, Susumu Tonegawa
The medial temporal lobe, including the hippocampus, has been implicated in social memory. However, it remains unknown which parts of these brain regions and their circuits hold social memory. Here, we show that ventral hippocampal CA1 (vCA1) neurons of a mouse and their projections to nucleus accumbens (NAc) shell play a necessary and sufficient role in social memory. Both the proportion of activated vCA1 cells and the strength and stability of the responding cells are greater in response to a familiar mouse than to a previously unencountered mouse...
September 30, 2016: Science
Mu-Ming Poo, Michele Pignatelli, Tomás J Ryan, Susumu Tonegawa, Tobias Bonhoeffer, Kelsey C Martin, Andrii Rudenko, Li-Huei Tsai, Richard W Tsien, Gord Fishell, Caitlin Mullins, J Tiago Gonçalves, Matthew Shtrahman, Stephen T Johnston, Fred H Gage, Yang Dan, John Long, György Buzsáki, Charles Stevens
The mechanism of memory remains one of the great unsolved problems of biology. Grappling with the question more than a hundred years ago, the German zoologist Richard Semon formulated the concept of the engram, lasting connections in the brain that result from simultaneous "excitations", whose precise physical nature and consequences were out of reach of the biology of his day. Neuroscientists now have the knowledge and tools to tackle this question, however, and this Forum brings together leading contemporary views on the mechanisms of memory and what the engram means today...
May 19, 2016: BMC Biology
Fritz Melchers
Fifty years ago, Norbert Hilschmann discovered that antibodies have variable immunoglobulin domains to bind antigens, and constant domains to carry out effector functions in the immune system. Just as this happened, the author of this perspective entered the field of immunology. Ten years later, the genetic basis of antibody variability was discovered by Susumu Tonegawa and his colleagues at the Basel Institute for Immunology, where the author had become a scientific member. At the same time, Georges Köhler, a former graduate student of the author's at the Basel Institute, invented with Cesar Milstein at the Laboratory of Molecular Biology in Cambridge, England, the method to produce monoclonal antibodies...
January 2016: European Journal of Immunology
Riku Takahashi, Yumihiko Ikura, Daniel R King, Takayuki Nonoyama, Tasuku Nakajima, Takayuki Kurokawa, Hirotoshi Kuroda, Yoshihiro Tonegawa, Jian Ping Gong
Most studies on hydrogel swelling instability have been focused on a constrained boundary condition. In this paper, we studied the mechanical instability of a piece of disc-shaped hydrogel during free swelling. The fast swelling of the gel induces two swelling mismatches; a surface-inner layer mismatch and an annulus-disc mismatch, which lead to the formation of a surface crease pattern and a saddle-like bulk bending, respectively. For the first time, a stripe-like surface crease that is at a right angle on the two surfaces of the gel was observed...
June 21, 2016: Soft Matter
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