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https://www.readbyqxmd.com/read/27811197/phospholamban-inhibition-by-a-single-dose-of-locked-nucleic-acid-antisense-oligonucleotide-improves-cardiac-contractility-in-pressure-overload-induced-systolic-dysfunction-in-mice
#1
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...
November 2, 2016: Journal of Cardiovascular Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/27798858/molecular-pathology-and-novel-clinical-therapy-for-uterine-leiomyosarcoma
#2
REVIEW
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...
October 2016: Anticancer Research
https://www.readbyqxmd.com/read/27749826/antagonistic-negative-and-positive-neurons-of-the-basolateral-amygdala
#3
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...
October 17, 2016: Nature Neuroscience
https://www.readbyqxmd.com/read/27708103/ventral-ca1-neurons-store-social-memory
#4
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
https://www.readbyqxmd.com/read/27197636/what-is-memory-the-present-state-of-the-engram
#5
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
https://www.readbyqxmd.com/read/27144253/remembering-antibodies-coming-of-age
#6
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
https://www.readbyqxmd.com/read/27108760/coupled-instabilities-of-surface-crease-and-bulk-bending-during-fast-free-swelling-of-hydrogels
#7
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
https://www.readbyqxmd.com/read/26982728/memory-retrieval-by-activating-engram-cells-in-mouse-models-of-early-alzheimer-s-disease
#8
Dheeraj S Roy, Autumn Arons, Teryn I Mitchell, Michele Pignatelli, Tomás J Ryan, Susumu Tonegawa
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive memory decline and subsequent loss of broader cognitive functions. Memory decline in the early stages of AD is mostly limited to episodic memory, for which the hippocampus has a crucial role. However, it has been uncertain whether the observed amnesia in the early stages of AD is due to disrupted encoding and consolidation of episodic information, or an impairment in the retrieval of stored memory information. Here we show that in transgenic mouse models of early AD, direct optogenetic activation of hippocampal memory engram cells results in memory retrieval despite the fact that these mice are amnesic in long-term memory tests when natural recall cues are used, revealing a retrieval, rather than a storage impairment...
March 24, 2016: Nature
https://www.readbyqxmd.com/read/26964904/rehebbilitating-memory
#9
Tomás J Ryan, Susumu Tonegawa
No abstract text is available yet for this article.
April 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/26845478/supramolecular-inclusion-complexation-of-simvastatin-with-methylated-%C3%AE-cyclodextrins-for-promoting-osteogenic-differentiation
#10
Masahiko Terauchi, Takasuke Inada, Asato Tonegawa, Atsushi Tamura, Satoshi Yamaguchi, Kiyoshi Harada, Nobuhiko Yui
Statins are recognized as a potential candidate to induce the regeneration of bone. However, statins are a strongly hydrophobic drug and it is difficult to administer at the local sites. In this study, the inclusion complexes of simvastatin (SV) with hydroxypropyl-β-cyclodextrin (HP-β-CD) and randomly methylated β-cyclodextrin (RM-β-CD) were prepared to improve the water-solubility, and the osteogenic differentiation ability of the inclusion complexes in MC3T3-E1 cells were investigated. The water-solubility of SV increased linearly upon the addition of both HP-β-CD and RM-β-CD, due to the formation of inclusion complexes...
February 1, 2016: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/26657949/rehebbilitating-memory
#11
REVIEW
Tomás J Ryan, Susumu Tonegawa
No abstract text is available yet for this article.
January 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/26615801/a-designed-room-temperature-triplet-ligand-from-pyridine-2-6-diyl-bis-tert-butyl-nitroxide
#12
Hinako Kawakami, Asato Tonegawa, Takayuki Ishida
The magnetic study on newly developed 4-mesitylpyridine-2,6-diyl bis(tert-butyl nitroxide) shows that almost the whole population has a ground triplet state at room temperature, and the ability of complex formation as a tridentate triplet ligand was proven with a diamagnetic yttrium(iii) ion.
January 28, 2016: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/26488242/q-a-memory-man
#13
Susumu Tonegawa, Keikantse Matlhagela
No abstract text is available yet for this article.
October 22, 2015: Nature
https://www.readbyqxmd.com/read/26402611/entorhinal-cortical-ocean-cells-encode-specific-contexts-and-drive-context-specific-fear-memory
#14
Takashi Kitamura, Chen Sun, Jared Martin, Lacey J Kitch, Mark J Schnitzer, Susumu Tonegawa
Forming distinct representations and memories of multiple contexts and episodes is thought to be a crucial function of the hippocampal-entorhinal cortical network. The hippocampal dentate gyrus (DG) and CA3 are known to contribute to these functions, but the role of the entorhinal cortex (EC) is poorly understood. Here, we show that Ocean cells, excitatory stellate neurons in the medial EC layer II projecting into DG and CA3, rapidly form a distinct representation of a novel context and drive context-specific activation of downstream CA3 cells as well as context-specific fear memory...
September 23, 2015: Neuron
https://www.readbyqxmd.com/read/26335640/memory-engram-cells-have-come-of-age
#15
REVIEW
Susumu Tonegawa, Xu Liu, Steve Ramirez, Roger Redondo
The idea that memory is stored in the brain as physical alterations goes back at least as far as Plato, but further conceptualization of this idea had to wait until the 20(th) century when two guiding theories were presented: the "engram theory" of Richard Semon and Donald Hebb's "synaptic plasticity theory." While a large number of studies have been conducted since, each supporting some aspect of each of these theories, until recently integrative evidence for the existence of engram cells and circuits as defined by the theories was lacking...
September 2, 2015: Neuron
https://www.readbyqxmd.com/read/26289908/a-study-of-the-solvation-structure-of-l-leucine-in-alcohol-water-binary-solvents-through-molecular-dynamics-simulations-and-ftir-and-nmr-spectroscopy
#16
Toshiyuki Takamuku, Yohei Hatomoto, Junko Tonegawa, Youichi Tsutsumi, Tatsuya Umecky
The solvation structures of l-leucine (Leu) in aliphatic-alcohol-water and fluorinated-alcohol-water solvents are elucidated for various alcohol contents by using molecular dynamics (MD) simulations and IR, and (1) H and (13) C NMR spectroscopy. The aliphatic alcohols included methanol, ethanol, and 2-propanol, whereas the fluorinated alcohols were 2,2,2-trifluoroethanol and 1,1,1,3,3,3-hexafluoro-2-propanol. The MD results show that the hydrophobic alkyl moiety of Leu is surrounded by the alkyl or fluoroalkyl groups of the alcohol molecules...
October 26, 2015: Chemphyschem: a European Journal of Chemical Physics and Physical Chemistry
https://www.readbyqxmd.com/read/26286654/entorhinal-hippocampal-neuronal-circuits-bridge-temporally-discontiguous-events
#17
REVIEW
Takashi Kitamura, Christopher J Macdonald, Susumu Tonegawa
The entorhinal cortex (EC)-hippocampal (HPC) network plays an essential role for episodic memory, which preserves spatial and temporal information about the occurrence of past events. Although there has been significant progress toward understanding the neural circuits underlying the spatial dimension of episodic memory, the relevant circuits subserving the temporal dimension are just beginning to be understood. In this review, we examine the evidence concerning the role of the EC in associating events separated by time--or temporal associative learning--with emphasis on the function of persistent activity in the medial entorhinal cortex layer III (MECIII) and their direct inputs into the CA1 region of HPC...
September 2015: Learning & Memory
https://www.readbyqxmd.com/read/26280931/memory-engram-storage-and-retrieval
#18
REVIEW
Susumu Tonegawa, Michele Pignatelli, Dheeraj S Roy, Tomás J Ryan
A great deal of experimental investment is directed towards questions regarding the mechanisms of memory storage. Such studies have traditionally been restricted to investigation of the anatomical structures, physiological processes, and molecular pathways necessary for the capacity of memory storage, and have avoided the question of how individual memories are stored in the brain. Memory engram technology allows the labeling and subsequent manipulation of components of specific memory engrams in particular brain regions, and it has been established that cell ensembles labeled by this method are both sufficient and necessary for memory recall...
December 2015: Current Opinion in Neurobiology
https://www.readbyqxmd.com/read/26182489/-effects-of-an-implicit-internal-working-model-on-attachment-in-information-processing-assessed-using-go-no-go-association-task
#19
Tsutomu Fujii, Hisashi Uebuchi, Kotono Yamada, Masahiro Saito, Eriko Ito, Akiko Tonegawa, Marie Uebuchi
The purposes of the present study were (a) to use both a relational-anxiety Go/No-Go Association Task (GNAT) and an avoidance-of-intimacy GNAT in order to assess an implicit Internal Working Model (IWM) of attachment; (b) to verify the effects of both measured implicit relational anxiety and implicit avoidance of intimacy on information processing. The implicit IWM measured by GNAT differed from the explicit IWM measured by questionnaires in terms of the effects on information processing. In particular, in subliminal priming tasks involving with others, implicit avoidance of intimacy predicted accelerated response times with negative stimulus words about attachment...
June 2015: Shinrigaku Kenkyu: the Japanese Journal of Psychology
https://www.readbyqxmd.com/read/26174222/differentiation-of-forebrain-and-hippocampal-dopamine-1-class-receptors-d1r-and-d5r-in-spatial-learning-and-memory
#20
Joshua Sariñana, Susumu Tonegawa
Activation of prefrontal cortical (PFC), striatal, and hippocampal dopamine 1-class receptors (D1R and D5R) is necessary for normal spatial information processing. Yet the precise role of the D1R versus the D5R in the aforementioned structures, and their specific contribution to the water-maze spatial learning task remains unknown. D1R- and D5R-specific in situ hybridization probes showed that forebrain restricted D1R and D5R KO mice (F-D1R/D5R KO) displayed D1R mRNA deletion in the medial (m)PFC, dorsal and ventral striatum, and the dentate gyrus (DG) of the hippocampus...
January 2016: Hippocampus
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