Graduate University for Advanced Studies
Tokyo, Japan

The Graduate University for Advanced Studies is one of the national universities of Japan, located in the town of Hayama in Kanagawa Prefecture. Sōkendai , as it is generally called in its abbreviated form, was established in the year 1988. From 1988 to 1995 the university maintained its headquarters in Nagatsuta, Midori-ku, Yokohama at Tokyo Institute of Technology later shifting to the present location. Wikipedia.

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Ohtsuki H.,Graduate University for Advanced Studies
Philosophical Transactions of the Royal Society B: Biological Sciences | Year: 2014

One of the core concepts in social evolution theory is kin selection. Kin selection provides a perspective to understand hownatural selection operates when genetically similar individuals are likely to interact. A family-structured population is an excellent example of this, where relatives are engaged in social interactions. Consequences of such social interactions are often described in game-theoretical frameworks, but there is a growing consensus that a naive inclusive fitness accounting with dyadic relatedness coefficients are of limited use when non-additive fitness effects are essential in those situations. Here, I provide a general framework to analyse multiplayer interactions among relatives. Two important results follow from my analysis. First, it is generally necessary to know the n-tuple genetic association of family members when n individuals are engaged in social interactions. However, as a second result, I found that, for a special class of games, we need only measures of lower-order genetic association to fully describe its evolutionary dynamics. I introduce the concept of degree of the game and showhowthis degree is related to the degree of genetic association. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

Fukagawa T.,Graduate University for Advanced Studies | Earnshaw W.C.,University of Edinburgh
Developmental Cell | Year: 2014

Since discovery of the centromere-specific histone H3 variant CENP-A, centromeres have come to be defined as chromatin structures that establish the assembly site for the complex kinetochore machinery. In most organisms, centromere activity is defined epigenetically, rather than by specific DNA sequences. In this review, we describe selected classic work and recent progress in studies of centromeric chromatin with a focus on vertebrates. We consider possible roles for repetitive DNA sequences found at most centromeres, chromatin factors and modifications that assemble and activate CENP-A chromatin for kinetochore assembly, plus the use of artificial chromosomes and kinetochores to study centromere function. © 2014 The Authors.

Yoshida S.,Graduate University for Advanced Studies
Development Growth and Differentiation | Year: 2010

Mammalian testes continually produce a huge number of sperm over a long reproductive period. This constant spermatogenesis is supported by a highly robust stem cell system. Morphological analyses in the 1960s and 70s established the basis of mammalian spermatogenesis and the associated stem cell research. Subsequently, from the 1990s on, functional analyses, which have included post-transplantation colony formation, in vitro spermatogonial culture with persisting stem cell activity, in vivo lineage tracing, and live imaging, and also lines of molecular-genetic analyses, have contributed greatly to our understanding of mammalian spermatogenic stem cells. This review will provide a brief overview of the history of this field and then go on to describe in detail the progress made in recent years. © 2010 Japanese Society of Developmental Biologists.

Innan H.,Graduate University for Advanced Studies | Innan H.,Japan Science and Technology Agency | Kondrashov F.,Center for Genomic Regulation
Nature Reviews Genetics | Year: 2010

Gene duplications and their subsequent divergence play an important part in the evolution of novel gene functions. Several models for the emergence, maintenance and evolution of gene copies have been proposed. However, a clear consensus on how gene duplications are fixed and maintained in genomes is lacking. Here, we present a comprehensive classification of the models that are relevant to all stages of the evolution of gene duplications. Each model predicts a unique combination of evolutionary dynamics and functional properties. Setting out these predictions is an important step towards identifying the main mechanisms that are involved in the evolution of gene duplications. © 2010 Macmillan Publishers Limited. All rights reserved.

Kondo S.,Graduate University for Advanced Studies | Ueda R.,Graduate University for Advanced Studies
Genetics | Year: 2013

We report a simple yet extremely efficient platform for systematic gene targeting by the RNA-guided endonuclease Cas9 in Drosophila. The system comprises two transgenic strains: one expressing Cas9 protein from the germline-specific nanos promoter and the other ubiquitously expressing a custom guide RNA (gRNA) that targets a unique site in the genome. The two strains are crossed to form an active Cas9-gRNA complex specifically in germ cells, which cleaves and mutates the target site. We demonstrate rapid generation of mutants in seven neuropeptide and two microRNA genes in which no mutants have been described. Founder animals stably expressing Cas9-gRNA transmitted germline mutations to an average of 60% of their progeny, a dramatic improvement in efficiency over the previous methods based on transient Cas9 expression. Simultaneous cleavage of two sites by co-expression of two gRNAs efficiently induced internal deletion with frequencies of 4.3-23%. Our method is readily scalable to high-throughput gene targeting, thereby accelerating comprehensive functional annotation of the Drosophila genome. © 2013 by the Genetics Society of America.

Saga Y.,Graduate University for Advanced Studies
Cellular and Molecular Life Sciences | Year: 2010

Nanos is known as an evolutionarily conserved RNA-binding protein, the function of which is implicated in germ cell development. This includes the maintenance of both the primordial germ cells (PGCs) and germline stem cells. In mice, Nanos2 exhibits a unique feature in which its expression is induced only in the germ cells within the sexually determined male gonad. Nanos2 promotes male germ cell differentiation, while simultaneously suppressing a female program. In addition, Nanos2 is also expressed in the spermatogonial stem cells and functions as an intrinsic factor to maintain the stem cell population during spermatogenesis. Detailed cytological and biochemical analyses in embryonic male gonads in the mouse have revealed that Nanos2 localizes to the P-bodies, a center of RNA processing. It has also been shown that the Nanos2 interacts with protein components of the deadenylation complex involved in the initial step of the RNA degradation pathway. © 2010 Springer Basel AG.

Kobayashi T.,Graduate University for Advanced Studies
Proceedings of the Japan Academy Series B: Physical and Biological Sciences | Year: 2014

The ribosomal RNA gene (rDNA) repeats form a historically well-researched region in the chromosome. Their highly repetitive structure can be identified easily which has enabled studies on DNA replication, recombination, and transcription. The region is one of the most unstable regions in the genome because of deleterious recombination among the repeats. The ribosomal RNA gene repeats use a unique gene amplification system to restore the copy number after this has been reduced due to recombination. It has been shown that unstable features in the genome can accelerate cellular senescence that restricts the lifespan of a cell. Here, I will introduce a study by our group that shows how the stability of rDNA is maintained and affects lifespan. I propose that the ribosomal RNA gene repeats constitute a center from which the stability of the whole genome is regulated and the lifespan of the cell is controlled. © 2014 The Japan Academy.

Kobayashi T.,Graduate University for Advanced Studies
Cellular and Molecular Life Sciences | Year: 2011

The genes encoding ribosomal RNA (rRNA) are the most abundant genes in the eukaryotic genome. They reside in tandem repetitive clusters, in some cases totaling hundreds of copies. Due to their repetitive structure and highly active transcription, the rRNA gene repeats are some of the most fragile sites in the chromosome. A unique gene amplification system compensates for loss of copies, thus maintaining copy number, albeit with some fluctuations. The unusual nature of rRNA gene repeats affects cellular functions such as senescence. In addition, we recently found that the repeat number determines sensitivity to DNA damage. In this review, I would like to introduce a new aspect of the rRNA gene repeat (called rDNA) as a center of maintenance of genome integrity and discuss its contribution to evolution. © 2010 The Author(s).

Kobayashi T.,Graduate University for Advanced Studies
Genes to Cells | Year: 2011

The genome is composed not only of genes but also of several noncoding functional elements (NOCs/ncFE, here I use NOCs), such as transcriptional promoters, enhancers, replication origins, centromeres and telomeres. rDNA has both gene and NOC characteristics. Thus, the rDNA encodes ribosomal RNAs, components of the ribosomes, that account for approximately 80% of the total RNA in a cell. However, rDNA may also act as a NOC with respect to cellular senescence by limiting the number of times a cell can divide. Here, I discuss how rDNA might function as a NOC to influence life span in a manner analogous to telomeres. © 2011 The Author. Journal compilation © 2011 by the Molecular Biology Society of Japan/Blackwell Publishing Ltd.

Muratsugu S.,Graduate University for Advanced Studies | Tada M.,Graduate University for Advanced Studies
Accounts of Chemical Research | Year: 2013

Selective catalysis is critical for the development of green chemical processes, and natural enzymes that possess specialized three-dimensional reaction pockets with catalytically active sites represent the most sophisticated systems for selective catalysis. A reaction space in an enzyme consists of an active metal center, functional groups for molecular recognition (such as amino acids), and a surrounding protein matrix to prepare the reaction pocket. The artificial design of such an integrated catalytic unit in a non-enzymatic system remains challenging. Molecular imprinting of a supported metal complex provides a promising approach for shape-selective catalysis. In this process, an imprinted cavity with a shape matched to a template molecule is created in a polymer matrix with a catalytically active metal site.In this Account, we review our studies on molecularly imprinted metal complex catalysts, focusing on Ru complexes, on oxide surfaces for shape-selective catalysis. Oxide surface-attached transition metal complex catalysts not only improve thermal stability and catalyst dispersion but also provide unique catalytic performance not observed in homogeneous precursors. We designed molecularly imprinted Ru complexes by using surface-attached Ru complexes with template ligands and inorganic/organic surface matrix overlayers to control the chemical environment around the active metal complex catalysts on oxide surfaces. We prepared the designed, molecularly imprinted Ru complexes on SiO2 surfaces in a step-by-step manner and characterized them with solid-state (SS) NMR, diffuse-reflectance (DR) UV-vis, X-ray photoelectron spectroscopy (XPS), Brunauer-Emmett-Teller isotherm (BET), X-ray fluorescence (XRF), and Ru K-edge extended X-ray absorption fine structure (EXAFS). The catalytic performances of these Ru complexes suggest that this process of molecular imprinting facilitates the artificial integration of catalytic functions at surfaces. Further advances such as the imprinting of a transition state structure or the addition of multiple binding sites could lead to systems that can achieve 100% selective catalysis. © 2012 American Chemical Society.

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