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Showing papers by "Kyoto University published in 2009"


Journal ArticleDOI
Lorenzo Galluzzi1, Lorenzo Galluzzi2, Lorenzo Galluzzi3, Stuart A. Aaronson4, John M. Abrams5, Emad S. Alnemri6, David W. Andrews7, Eric H. Baehrecke8, Nicolas G. Bazan9, Mikhail V. Blagosklonny10, Klas Blomgren11, Klas Blomgren12, Christoph Borner13, Dale E. Bredesen14, Dale E. Bredesen15, Catherine Brenner16, Maria Castedo3, Maria Castedo1, Maria Castedo2, John A. Cidlowski17, Aaron Ciechanover18, Gerald M. Cohen19, V De Laurenzi20, R De Maria21, Mohanish Deshmukh22, Brian David Dynlacht23, Wafik S. El-Deiry24, Richard A. Flavell25, Richard A. Flavell26, Simone Fulda27, Carmen Garrido2, Carmen Garrido28, Pierre Golstein16, Pierre Golstein2, Pierre Golstein29, Marie-Lise Gougeon30, Douglas R. Green, Hinrich Gronemeyer16, Hinrich Gronemeyer2, Hinrich Gronemeyer31, György Hajnóczky6, J. M. Hardwick32, Michael O. Hengartner33, Hidenori Ichijo34, Marja Jäättelä, Oliver Kepp3, Oliver Kepp2, Oliver Kepp1, Adi Kimchi35, Daniel J. Klionsky36, Richard A. Knight37, Sally Kornbluth38, Sharad Kumar, Beth Levine25, Beth Levine5, Stuart A. Lipton, Enrico Lugli17, Frank Madeo39, Walter Malorni21, Jean-Christophe Marine40, Seamus J. Martin41, Jan Paul Medema42, Patrick Mehlen43, Patrick Mehlen16, Gerry Melino19, Gerry Melino44, Ute M. Moll45, Ute M. Moll46, Eugenia Morselli3, Eugenia Morselli1, Eugenia Morselli2, Shigekazu Nagata47, Donald W. Nicholson48, Pierluigi Nicotera19, Gabriel Núñez36, Moshe Oren35, Josef M. Penninger49, Shazib Pervaiz50, Marcus E. Peter51, Mauro Piacentini44, Jochen H. M. Prehn52, Hamsa Puthalakath53, Gabriel A. Rabinovich54, Rosario Rizzuto55, Cecília M. P. Rodrigues56, David C. Rubinsztein57, Thomas Rudel58, Luca Scorrano59, Hans-Uwe Simon60, Hermann Steller25, Hermann Steller61, J. Tschopp62, Yoshihide Tsujimoto63, Peter Vandenabeele64, Ilio Vitale2, Ilio Vitale3, Ilio Vitale1, Karen H. Vousden65, Richard J. Youle17, Junying Yuan66, Boris Zhivotovsky67, Guido Kroemer1, Guido Kroemer2, Guido Kroemer3 
University of Paris-Sud1, French Institute of Health and Medical Research2, Institut Gustave Roussy3, Icahn School of Medicine at Mount Sinai4, University of Texas Southwestern Medical Center5, Thomas Jefferson University6, McMaster University7, University of Massachusetts Medical School8, LSU Health Sciences Center New Orleans9, Roswell Park Cancer Institute10, University of Gothenburg11, Boston Children's Hospital12, University of Freiburg13, University of California, San Francisco14, Buck Institute for Research on Aging15, Centre national de la recherche scientifique16, National Institutes of Health17, Technion – Israel Institute of Technology18, University of Leicester19, University of Chieti-Pescara20, Istituto Superiore di Sanità21, University of North Carolina at Chapel Hill22, New York University23, University of Pennsylvania24, Howard Hughes Medical Institute25, Yale University26, University of Ulm27, University of Burgundy28, Aix-Marseille University29, Pasteur Institute30, University of Strasbourg31, Johns Hopkins University32, University of Zurich33, University of Tokyo34, Weizmann Institute of Science35, University of Michigan36, University College London37, Duke University38, University of Graz39, Ghent University40, Trinity College, Dublin41, University of Amsterdam42, University of Lyon43, University of Rome Tor Vergata44, Stony Brook University45, University of Göttingen46, Kyoto University47, Merck & Co.48, Austrian Academy of Sciences49, National University of Singapore50, University of Chicago51, Royal College of Surgeons in Ireland52, La Trobe University53, University of Buenos Aires54, University of Padua55, University of Lisbon56, University of Cambridge57, University of Würzburg58, University of Geneva59, University of Bern60, Rockefeller University61, University of Lausanne62, Osaka University63, University of California, San Diego64, University of Glasgow65, Harvard University66, Karolinska Institutet67
TL;DR: A nonexhaustive comparison of methods to detect cell death with apoptotic or nonapoptotic morphologies, their advantages and pitfalls is provided and the importance of performing multiple, methodologically unrelated assays to quantify dying and dead cells is emphasized.
Abstract: Cell death is essential for a plethora of physiological processes, and its deregulation characterizes numerous human diseases Thus, the in-depth investigation of cell death and its mechanisms constitutes a formidable challenge for fundamental and applied biomedical research, and has tremendous implications for the development of novel therapeutic strategies It is, therefore, of utmost importance to standardize the experimental procedures that identify dying and dead cells in cell cultures and/or in tissues, from model organisms and/or humans, in healthy and/or pathological scenarios Thus far, dozens of methods have been proposed to quantify cell death-related parameters However, no guidelines exist regarding their use and interpretation, and nobody has thoroughly annotated the experimental settings for which each of these techniques is most appropriate Here, we provide a nonexhaustive comparison of methods to detect cell death with apoptotic or nonapoptotic morphologies, their advantages and pitfalls These guidelines are intended for investigators who study cell death, as well as for reviewers who need to constructively critique scientific reports that deal with cellular demise Given the difficulties in determining the exact number of cells that have passed the point-of-no-return of the signaling cascades leading to cell death, we emphasize the importance of performing multiple, methodologically unrelated assays to quantify dying and dead cells

2,218 citations


Journal ArticleDOI
19 Jun 2009-Immunity
TL;DR: The dissection of FoxP3(+) cells into subsets enables one to analyze Treg cell differentiation dynamics and interactions in normal and disease states, and to control immune responses through manipulating particular FoxP 3(+) subpopulations.

1,979 citations


Journal ArticleDOI
TL;DR: The concept of the cooperative integration of 'softness' and 'regularity' and the relationship between the structures and properties of these materials in view of their practical applications are discussed.
Abstract: Encapsulating guest molecules inside host structures ranging from soft, flexible enzymes to rigid, porous zeolites has led to developments in many areas, including catalysis, sensing and separation. This Review highlights how metal–organic frameworks — materials formed by linking metal centres with organic ligands — can combine softness with regularity to produce dynamic, yet crystalline, structures that may prove useful for a range of applications. The field of host–guest complexation is intensely attractive from diverse perspectives, including materials science, chemistry and biology. The uptake and encapsulation of guest species by host frameworks are being investigated for a wide variety of purposes, including separation and storage using zeolites, and recognition and sensing by enzymes in solution. Here we focus on the concept of the cooperative integration of 'softness' and 'regularity'. Recent developments on porous coordination polymers (or metal–organic frameworks) have provided the inherent properties that combine these features. Such soft porous crystals exhibit dynamic frameworks that are able to respond to external stimuli such as light, electric fields or the presence of particular species, but they are also crystalline and can change their channels reversibly while retaining high regularity. We discuss the relationship between the structures and properties of these materials in view of their practical applications.

1,936 citations


Journal ArticleDOI
27 Aug 2009-Nature
TL;DR: Functional analyses of 34 p53-regulated genes demonstrate that the p53–p21 pathway serves as a barrier not only in tumorigenicity, but also in iPS cell generation in mouse and human fibroblasts.
Abstract: Induced pluripotent stem (iPS) cells can be generated from somatic cells by the introduction of Oct3/4 (also known as Pou5f1), Sox2, Klf4 and c-Myc, in mouse and in human. The efficiency of this process, however, is low. Pluripotency can be induced without c-Myc, but with even lower efficiency. A p53 (also known as TP53 in humans and Trp53 in mice) short-interfering RNA (siRNA) was recently shown to promote human iPS cell generation, but the specificity and mechanisms remain to be determined. Here we report that up to 10% of transduced mouse embryonic fibroblasts lacking p53 became iPS cells, even without the Myc retrovirus. The p53 deletion also promoted the induction of integration-free mouse iPS cells with plasmid transfection. Furthermore, in the p53-null background, iPS cells were generated from terminally differentiated T lymphocytes. The suppression of p53 also increased the efficiency of human iPS cell generation. DNA microarray analyses identified 34 p53-regulated genes that are common in mouse and human fibroblasts. Functional analyses of these genes demonstrate that the p53-p21 pathway serves as a barrier not only in tumorigenicity, but also in iPS cell generation.

1,330 citations


Journal ArticleDOI

1,161 citations


Journal ArticleDOI
TL;DR: Catalytic Solvents: Catalyst Disproportionation 4981 2.2.1.
Abstract: 2.1.6. Tacticity and Sequence: Advanced Control 4967 2.2. Transition Metal Catalysts 4967 2.2.1. Overviews of Catalysts 4967 2.2.2. Ruthenium 4967 2.2.3. Copper 4971 2.2.4. Iron 4971 2.2.5. Nickel 4975 2.2.6. Molybdenum 4975 2.2.7. Manganese 4976 2.2.8. Osmium 4976 2.2.9. Cobalt 4976 2.2.10. Other Metals 4976 2.3. Cocatalysts (Additives) 4977 2.3.1. Overview of Cocatalysts 4977 2.3.2. Reducing Agents 4977 2.3.3. Free Radical Initiators 4977 2.3.4. Metal Alkoxides 4977 2.3.5. Amines 4978 2.3.6. Halogen Source 4978 2.4. Initiators 4978 2.4.1. Overview of Initiators: Scope and Design 4978 2.4.2. Alkyl Halides 4978 2.4.3. Arenesulfonyl Halides 4979 2.4.4. N-Chloro Compounds 4979 2.4.5. Halogen-Free Initiators 4979 2.5. Solvents 4980 2.5.1. Overview of Solvents 4980 2.5.2. Catalyst Solubility and Coordination of Solvent 4981 2.5.3. Environmentally Friendly Solvents 4981 2.5.4. Water 4981 2.5.5. Catalytic Solvents: Catalyst Disproportionation 4981

1,131 citations


Journal ArticleDOI
TL;DR: New guidelines for the nomenclature of the human HSP families, HSPH (HSP110), HSPC (H SP90), HSPA (HSPA70), DNAJ, and HSPB (small HSP) as well as for the human chaperonin families HSPD/E (Hsp60/HSP10) and CCT (TRiC).
Abstract: The expanding number of members in the various human heat shock protein (HSP) families and the inconsistencies in their nomenclature have often led to confusion. Here, we propose new guidelines for the nomenclature of the human HSP families, HSPH (HSP110), HSPC (HSP90), HSPA (HSP70), DNAJ (HSP40), and HSPB (small HSP) as well as for the human chaperonin families HSPD/E (HSP60/HSP10) and CCT (TRiC). The nomenclature is based largely on the more consistent nomenclature assigned by the HUGO Gene Nomenclature Committee and used in the National Center of Biotechnology Information Entrez Gene database for the heat shock genes. In addition to this nomenclature, we provide a list of the human Entrez Gene IDs and the corresponding Entrez Gene IDs for the mouse orthologs.

1,104 citations


Journal ArticleDOI
21 Aug 2009-Cell
TL;DR: Evidence is presented that the homeodomain protein Nanog mediates acquisition of both embryonic and induced pluripotency, and that this function is recapitulated in the culmination of somatic cell reprogramming.

1,047 citations


Journal ArticleDOI
16 Jul 2009-Nature
TL;DR: Analysis of the 363 megabase nuclear genome of the blood fluke, the first sequenced flatworm, and a representative of the Lophotrochozoa offers insights into early events in the evolution of the animals, including the development of a body pattern with bilateral symmetry, and theDevelopment of tissues into organs.
Abstract: Schistosoma mansoni is responsible for the neglected tropical disease schistosomiasis that affects 210 million people in 76 countries. Here we present analysis of the 363 megabase nuclear genome of the blood fluke. It encodes at least 11,809 genes, with an unusual intron size distribution, and new families of micro-exon genes that undergo frequent alternative splicing. As the first sequenced flatworm, and a representative of the Lophotrochozoa, it offers insights into early events in the evolution of the animals, including the development of a body pattern with bilateral symmetry, and the development of tissues into organs. Our analysis has been informed by the need to find new drug targets. The deficits in lipid metabolism that make schistosomes dependent on the host are revealed, and the identification of membrane receptors, ion channels and more than 300 proteases provide new insights into the biology of the life cycle and new targets. Bioinformatics approaches have identified metabolic chokepoints, and a chemogenomic screen has pinpointed schistosome proteins for which existing drugs may be active. The information generated provides an invaluable resource for the research community to develop much needed new control tools for the treatment and eradication of this important and neglected disease.

997 citations


Journal ArticleDOI
TL;DR: In this article, the authors review recent progress on the holographic understanding of the entanglement entropy in the anti-de Sitter space/conformal field theory (AdS/CFT) correspondence.
Abstract: In this paper, we review recent progress on the holographic understanding of the entanglement entropy in the anti-de Sitter space/conformal field theory (AdS/CFT) correspondence. In general, the AdS/CFT relates physical observables in strongly coupled quantum many-body systems to certain classical quantities in gravity plus matter theories. In the case of our holographic entanglement entropy, its gravity dual turns out to be purely geometric, i.e. the area of minimal area surfaces in AdS spaces. One interesting application is to study various phase transitions by regarding the entanglement entropy as order parameters. Indeed we will see that our holographic calculations nicely reproduce the confinement/deconfinement transition. Our results can also be applied to understanding the microscopic origins of black hole entropy.

984 citations


Journal ArticleDOI
TL;DR: Nogi et al. as discussed by the authors proposed an optically transparent paper with low thermal expansion (CTE <8.5 ppm K ) using 15 nm cellulose nanofibers with the same chemical constituents as conventional paper and a production process also similar to conventional paper.
Abstract: M Optically Transparent Nanofiber Paper M U N IC By Masaya Nogi,* Shinichiro Iwamoto, Antonio Norio Nakagaito, and Hiroyuki Yano A T IO N Glass has well-suited low thermal expansion for use in electronic devices, but it is fragile, and the search for a stronger, more flexible optically clear medium has gone on for many years. Plastics have been widely studied; however, most of them have large coefficients of thermal expansion (CTE, approx. 50 ppm K ), and foldable plastics in particular exhibit extremely large CTEs, in excess of 200 ppm K . Further, the functional materials deposited on plastic substrates are prone to be damaged by the temperatures involved in the assembly and mounting processes due to themismatch between CTEs from differentmaterials. This article reports on what might be best described as optically transparent paper. It is a foldable nanofiber material with low thermal expansion (CTE <8.5 ppm K ) prepared using 15 nm cellulose nanofibers with the same chemical constituents as conventional paper and a production process also similar to that of conventional paper. The only difference is in the fiber width and the size of the interstitial cavities (Fig. 1). The foldable, low-CTE, and optically transparent nanofiber paper is the perfect candidate for substrates for continuous roll-to-roll processing in the future production of electronic devices, such as flexible displays, solar cells, e-papers, and a myriad of new flexible circuit technologies, and could replace the costly conventional batch processes based on glass substrates currently used. We project that it will also replace conventional paper as an advanced information medium, which can still be produced using traditional paper-making equipment that is used in production today. Cellulose nanofibers are the main component of plant and wood pulp fibers. These tiny elements with diameters of 15–20 nm are composed of bundles of cellulose microfibrils smaller than 4 nm in width, which, in turn, are composed of long cellulose molecules laterally stabilized by hydrogen bonds forming highly crystalline domains. As such, cellulose nanofibers have a CTE of 0.1 ppm K , which is as low as that of quartz glass, and an estimated strength of 2–3 GPa, rendering it five times stronger than mild steel. The nanofibers also exhibit good heat-transfer properties comparable to glass. Another significant property of the nanofibers is that light scattering can be suppressed. If the cellulose nanofibers are densely packed, and the interstices between the fibers are small enough to avoid

Journal ArticleDOI
TL;DR: Strongly electron-donating perylene carboxylic acid derivatives with amine substituents at their perylene core have allowed us to increase the power conversion efficiency of up to approximately 7% in perylene-sensitized solar cells.
Abstract: Recently, dye-sensitized solar cells have attracted much attention relevant to global environmental issues. Thus far, ruthenium(II) bipyridyl complexes have proven to be the most efficient TiO(2) sensitizers in dye-sensitized solar cells. However, a gradual increment in the highest power conversion efficiency has been recognized in the past decade. More importantly, considering that ruthenium is a rare metal, novel dyes without metal or using inexpensive metal are desirable for highly efficient dye-sensitized solar cells. Large pi-aromatic molecules, such as porphyrins, phthalocyanines, and perylenes, are important classes of potential sensitizers for highly efficient dye-sensitized solar cells, owing to their photostability and high light-harvesting capabilities that can allow applications in thinner, low-cost dye-sensitized solar cells. Porphyrins possess an intense Soret band at 400 nm and moderate Q bands at 600 nm. Nevertheless, the poor light-harvesting properties relative to the ruthenium complexes have limited the cell performance of porphyrin-sensitized TiO(2) cells. Elongation of the pi conjugation and loss of symmetry in porphyrins cause broadening and a red shift of the absorption bands together with an increasing intensity of the Q bands relative to that of the Soret band. On the basis of the strategy, the cell performance of porphyrin-sensitized solar cells has been improved intensively by the enhanced light absorption. Actually, some push-pull-type porphyrins have disclosed a remarkably high power conversion efficiency (6-7%) that was close to that of the ruthenium complexes. Phthalocyanines exhibit strong absorption around 300 and 700 nm and redox features that are similar to porphyrins. Moreover, phthalocyanines are transparent over a large region of the visible spectrum, thereby enabling the possibility of using them as "photovoltaic windows". However, the cell performance was poor, owing to strong aggregation and lack of directionality in the excited state. Novel unsymmetrical zinc phthalocyanine sensitizers with "push" and "pull" groups have made it possible to reduce the aggregation on a TiO(2) surface, tune the level of the excited state, and strengthen the electronic coupling between the phthalocyanine core and the TiO(2) surface. As a result, the power conversion efficiency of up to 3.5% has been achieved. Perylenes are well-known as chemically, thermally, and photophysically stable dyes and have been used in various optical devices and applications. Nevertheless, the power conversion efficiency remained low compared to other organic dyes. The origin of such limited cell performance is the poor electron-donating abilities of the perylenes, which makes it difficult to inject electrons from the excited singlet state of the perylenes to the conduction band of the TiO(2) electrode efficiently. Strongly electron-donating perylene carboxylic acid derivatives with amine substituents at their perylene core have allowed us to increase the power conversion efficiency of up to approximately 7% in perylene-sensitized solar cells. The efficiency of large pi-aromatic molecule-sensitized solar cells could be improved significantly if the dyes with larger red and near-infrared absorption could be developed.

Journal ArticleDOI
TL;DR: In this paper, the authors investigated the effect of biochar application on soil physical properties and grain yields of upland rice (Oryza sativa L.) in northern Laos.

Journal ArticleDOI
TL;DR: This study evaluated the teratoma-forming propensity of secondary neurospheres generated from 36 mouse induced pluripotent stem (iPS) cell lines derived in 11 different ways, which correlated with the persistence of undifferentiated cells.
Abstract: We evaluated the teratoma-forming propensity of secondary neurospheres (SNS) generated from 36 mouse induced pluripotent stem (iPS) cell lines derived in 11 different ways. Teratoma-formation of SNS from embryonic fibroblast-derived iPS cells was similar to that of SNS from embryonic stem (ES) cells. In contrast, SNS from iPS cells derived from different adult tissues varied substantially in their teratoma-forming propensity, which correlated with the persistence of undifferentiated cells.

Journal ArticleDOI
20 Feb 2009-Immunity
TL;DR: Current understanding of Fas-induced apoptosis signaling is described and experimental strategies for future advances are proposed.

Journal ArticleDOI
TL;DR: This work proposes that there may be a key suppressive mechanism that is shared by every forkhead box p3 (Foxp3)(+) Treg in vivo and in vitro in mice and humans and will help to design effective ways for controlling immune responses by targeting Treg suppressive functions.
Abstract: Regulatory T cells (Tregs), either natural or induced, suppress a variety of physiological and pathological immune responses. One of the key issues for understanding Treg function is to determine how they suppress other lymphocytes at the molecular level in vivo and in vitro. Here we propose that there may be a key suppressive mechanism that is shared by every forkhead box p3 (Foxp3) 1 Treg in vivo and in vitro in mice and humans. When this central mechanism is abrogated, it causes a breach in self-tolerance and immune homeostasis. Other suppressive mechanisms may synergistically operate with this common mechanism depending on the environment and the type of an immune response. Further, Treg-mediated suppression is a multi-step process and impairment or augmentation of each step can alter the ultimate effectiveness of Treg-mediated suppression. These findings will help to design effective ways for controlling immune responses by targeting Treg suppressive functions.

Book
Jun Kigami1
22 Sep 2009
TL;DR: In this paper, the authors provide a self-contained introduction to fractals, starting from the basic geometry of self-similar sets and going on to discuss recent results, including the properties of eigenvalues and eigenfunctions of the Laplacians, and the asymptotical behaviors of heat kernels on selfsimilar sets.
Abstract: This book covers analysis on fractals, a developing area of mathematics which focuses on the dynamical aspects of fractals, such as heat diffusion on fractals and the vibration of a material with fractal structure. The book provides a self-contained introduction to the subject, starting from the basic geometry of self-similar sets and going on to discuss recent results, including the properties of eigenvalues and eigenfunctions of the Laplacians, and the asymptotical behaviors of heat kernels on self-similar sets. Requiring only a basic knowledge of advanced analysis, general topology and measure theory, this book will be of value to graduate students and researchers in analysis and probability theory. It will also be useful as a supplementary text for graduate courses covering fractals.

Journal ArticleDOI
TL;DR: Document S1.

Journal ArticleDOI
TL;DR: The early silylene research was concerned largely with comparing the chemistry of the dihalosilylenes with that of carbenes, so it might be difficult to isolate metallylenes as stable compounds under ambient conditions.
Abstract: In recent decades, it has generally been recognized that carbenes play an important role as transient intermediates. As a result of a number of stable carbenes having been isolated and investigated in detail, it is not an exaggeration to say that the chemistry of carbenes has been thoroughly investigated and is now well-understood.1 In addition, much attention has also been paid to the heavier analogues of carbenes, i.e., silylenes (R2Si:), germylenes (R2Ge:), stannylenes (R2Sn:), and plumbylenes (R2Pb:). These so-called metallylenes are monomeric species of the polymetallanes. This is especially true of the silylenes, which are believed to be monomers of polysilane. The metallylenes could be expected to be of great importance in fundamental and applied chemistry as a result of their many differences and similarities to carbenes. The valency of the central atom of the heavier carbene analogues (R2M:, M ) Si, Ge, Sn, Pb) is two. That is, its oxidation state is MII and its stability increases as the principal quantum number (n) increases. In fact, dichloroplumbylene and dichlorostannylene, PbCl2 and SnCl2, respectively, are very stable ionic compounds. However, these dihalides exist as polymers or ion pairs both in solution and in the solid state. The dichlorogermylene complex GeCl2 · (dioxane)3 is also known to be stable and isolable, whereas the dihalosilylenes are barely isolable compounds.2 The early silylene research was concerned largely with comparing the chemistry of the dihalosilylenes with that of carbenes. Hence, the chemistry of the metallylenes has been considered mainly from the molecular chemistry point of view.4 In contrast to the carbon atom, the heavier group 14 atoms have a low ability to form hybrid orbitals. They therefore prefer the (ns)2(np)2 valence electron configurations in their divalent species.5 Since two electrons remain as a singlet pair in the ns orbital, the ground state of H2M: (M ) Si, Ge, Sn, Pb) is a singlet, unlike the case of H2C:, where the ground state is a triplet (Figure 1).1a On the basis of theoretical calculations, the singlet-triplet energy differences ∆EST for H2M, [∆EST ) E(triplet) E(singlet)], are found to be 16.7 (M ) Si), 21.8 (M ) Ge), 24.8 (M ) Sn), and 34.8 (M ) Pb) kcal/mol, respectively. That of H2C: is estimated as -14.0 kcal/mol.6 Furthermore, the relative stabilities of the singlet species of R2M: (M ) C, Si, Ge, Sn, Pb; R ) alkyl or aryl) compared to the corresponding dimer, R2MdMR2, are estimated to increase as the element row descends, C < Si < Ge < Sn < Pb. It follows, therefore, that one can expect that a divalent organolead compound such as plumbylene should be isolable as a stable compound. However, some plumbylenes, without any electronic or steric stabilization effects, are known to be thermally unstable and undergo facile disproportionation reactions, giving rise to elemental lead and the corresponding tetravalent organolead compounds.7 On this basis, it could be concluded that it might be difficult to isolate metallylenes as stable compounds under ambient conditions, since they generally exhibit extremely high reactivity toward other molecules as well as themselves. Metallylenes have a singlet ground state with a vacant p-orbital and a lone pair of valence orbitals. This extremely high reactivity must be due to their vacant p-orbitals, since 6 valence electrons is less than the 8 electrons of the “octet rule”. Their lone pair is expected to be inert due to its high s-character. In order to stabilize metallylenes enough to be isolated, either some thermodynamic and/or kinetic stabilization of the reactive vacant p-orbital is required (Figure 2). A range of “isolable” metallylenes have been synthesized through the thermodynamic stabilization of coordinating Cp* ligands, the inclusion of heteroatoms such as N, O, and P, * To whom correspondence should be addressed. Phone: +81-774-38-3200. Fax: +81-774-38-3209. E-mail: tokitoh@boc.kuicr.kyoto-u.ac.jp. Chem. Rev. 2009, 109, 3479–3511 3479

Journal ArticleDOI
Shinya Yamanaka1
03 Apr 2009-Cell
TL;DR: The potential of induced pluripotent stem cells is enormous, but many obstacles remain before their medical and pharmaceutical applications can be fully realized.

Journal ArticleDOI
TL;DR: It is shown that p53 expression in adipose tissue is crucially involved in the development of insulin resistance, which underlies age-related cardiovascular and metabolic disorders and suggests that cellular aging signals in adipOSE tissue could be a new target for the treatment of diabetes.
Abstract: A role for cell senescence and p53 in the development of insulin resistance (or prediabetes) has been obscure. Issei Komuro and colleagues now show that premature cell senescence occurs in the adipose tissue of obese mice and humans and that genetic deficiency of p53 is sufficient to prevent insulin resistance in mouse models of obesity, suggesting a new target to treat diabetes. Various stimuli, such as telomere dysfunction and oxidative stress, can induce irreversible cell growth arrest, which is termed 'cellular senescence'1,2. This response is controlled by tumor suppressor proteins such as p53 and pRb. There is also evidence that senescent cells promote changes related to aging or age-related diseases3,4,5,6. Here we show that p53 expression in adipose tissue is crucially involved in the development of insulin resistance, which underlies age-related cardiovascular and metabolic disorders. We found that excessive calorie intake led to the accumulation of oxidative stress in the adipose tissue of mice with type 2 diabetes–like disease and promoted senescence-like changes, such as increased activity of senescence-associated β-galactosidase, increased expression of p53 and increased production of proinflammatory cytokines. Inhibition of p53 activity in adipose tissue markedly ameliorated these senescence-like changes, decreased the expression of proinflammatory cytokines and improved insulin resistance in mice with type 2 diabetes–like disease. Conversely, upregulation of p53 in adipose tissue caused an inflammatory response that led to insulin resistance. Adipose tissue from individuals with diabetes also showed senescence-like features. Our results show a previously unappreciated role of adipose tissue p53 expression in the regulation of insulin resistance and suggest that cellular aging signals in adipose tissue could be a new target for the treatment of diabetes ( pages 996–967 ).

Journal ArticleDOI
TL;DR: It is demonstrated that individual dopaminergic neurons of the substantia nigra can broadcast a dopamine signal and exert strong influence over a large number of striatal neurons and suggests that neurodegeneration of individual nigral neurons can affect multiple neurons in the striatum.
Abstract: The axonal arbors of single nigrostriatal dopaminergic neurons were visualized with a viral vector expressing membrane-targeted green fluorescent protein in rat brain. All eight reconstructed tyrosine hydroxylase-positive dopaminergic neurons possessed widely spread and highly dense axonal arborizations in the neostriatum. All of them emitted very little axon collateral arborization outside of the striatum except for tiny arborization in the external pallidum. The striatal axonal bush of each reconstructed dopaminergic neuron covered 0.45-5.7% (mean +/- SD = 2.7 +/- 1.5%) of the total volume of the neostriatum. Furthermore, all the dopaminergic neurons innervated both striosome and matrix compartments of the neostriatum, although each neuron's arborization tended to favor one of these compartments. Our findings demonstrate that individual dopaminergic neurons of the substantia nigra can broadcast a dopamine signal and exert strong influence over a large number of striatal neurons. This divergent signaling should be a key to the function of the nigrostriatal system in dopamine-based learning and suggests that neurodegeneration of individual nigral neurons can affect multiple neurons in the striatum. Thus, these results would also contribute to understanding the clinicopathology of Parkinson's disease and related syndromes.

Journal ArticleDOI
TL;DR: This update reviews new information about acne pathophysiology and treatment-such as lasers and light therapy-and relevant topics where published data were sparse in 2003 but are now available including combination therapy, revision of acne scarring, and maintenance therapy.
Abstract: The Global Alliance to Improve Outcomes in Acne published recommendations for the management of acne as a supplement to the Journal of the American Academy of Dermatology in 2003. The recommendations incorporated evidence-based strategies when possible and the collective clinical experience of the group when evidence was lacking. This update reviews new information about acne pathophysiology and treatment–such as lasers and light therapy–and relevant topics where published data were sparse in 2003 but are now available including combination therapy, revision of acne scarring, and maintenance therapy. The update also includes a new way of looking at acne as a chronic disease, a discussion of the changing role of antibiotics in acne management as a result of concerns about microbial resistance, and factors that affect adherence to acne treatments. Summary statements and recommendations are provided throughout the update along with an indication of the level of evidence that currently supports each finding. As in the original supplement, the authors have based recommendations on published evidence as much as possible.

Journal ArticleDOI
TL;DR: The Monitor of All-sky X-ray Image (MAXI) mission is the first astronomical payload to be installed on the Japanese Experiment Module-exposed Facility (JEM-EF or Kibo-EF) on the International Space Station as mentioned in this paper.
Abstract: The Monitor of All-sky X-ray Image (MAXI) mission is the first astronomical payload to be installed on the Japanese Experiment Module — Exposed Facility (JEM-EF or Kibo-EF) on the International Space Station. It has two types of X-ray slit cameras with wide FOVs and two kinds of X-ray detectors consisting of gas proportional counters covering the energy range of 2 to 30 keV and X-ray CCDs covering the energy range of 0.5 to 12 keV. MAXI will be more powerful than any previous X-ray All Sky Monitor payloads, being able to monitor hundreds of Active Galactic Nuclei. A realistic simulation under optimal observation conditions suggests that MAXI will provide all-sky images of X-ray sources of � 20 mCrab (� 7 � 10 � 10 erg cm � 2 s � 1 in the energy band of 2–30 keV) from observations during one ISS orbit (90 min), � 4.5 mCrab for one day, and � 2 mCrab for one week. The final detectability of MAXI could be � 0.2 mCrab for two years, which is comparable to the source confusion limit of the MAXI field of view (FOV). The MAXI objectives are: (1) to alert the community to X-ray novae and transient X-ray sources, (2) to monitor long-term variabilities of X-ray sources, (3) to stimulate multi-wavelength observations of variable objects, (4) to create unbiased X-ray source cataloges, and (5) to observe diffuse cosmic X-ray emissions, especially with better energy resolution for soft X-rays down to 0.5 keV.

Journal ArticleDOI
TL;DR: This work suggests that the combination of guest molecules and a variety of microporous frameworks would afford highly mobile proton carriers in solids and gives an idea for designing a new type of proton conductor, particularly for high-temperature and anhydrous conditions.
Abstract: The development of anhydrous proton-conductive materials operating at temperatures above 80 degrees C is a challenge that needs to be met for practical applications. Herein, we propose the new idea of encapsulation of a proton-carrier molecule--imidazole in this work--in aluminium porous coordination polymers for the creation of a hybridized proton conductor under anhydrous conditions. Tuning of the host-guest interaction can generate a good proton-conducting path at temperatures above 100 degrees C. The dynamics of the adsorbed imidazole strongly affect the conductivity determined by (2)H solid-state NMR. Isotope measurements of conductivity using imidazole-d4 showed that the proton-hopping mechanism was dominant for the conducting path. This work suggests that the combination of guest molecules and a variety of microporous frameworks would afford highly mobile proton carriers in solids and gives an idea for designing a new type of proton conductor, particularly for high-temperature and anhydrous conditions.

Journal ArticleDOI
TL;DR: Wen et al. as discussed by the authors classified the landslide failure surfaces into concave, convex, terraced, and terraced failure surfaces based on their overall shape, and analyzed the capacity of landslide lakes, the height of landslide dams and the composition and structure of materials that blocked rivers.
Abstract: The 2008 Wenchuan earthquake (Ms = 8.0; epicenter located at 31.0° N, 103.4° E), with a focal depth of 19.0 km was triggered by the reactivation of the Longmenshan fault in Wenchuan County, Sichuan Province, China on 12 May 2008. This earthquake directly caused more than 15,000 geohazards in the form of landslides, rockfalls, and debris flows which resulted in about 20,000 deaths. It also caused more than 10,000 potential geohazard sites, especially for rockfalls, reflecting the susceptibility of high and steep slopes in mountainous areas affected by the earthquake. Landslide occurrence on mountain ridges and peaks indicated that seismic shaking was amplified by mountainous topography. Thirty-three of the high-risk landslide lakes with landslide dam heights greater than 10 m were classified into four levels: extremely high risk, high risk, medium risk, and low risk. The levels were created by comprehensively analyzing the capacity of landslide lakes, the height of landslide dams, and the composition and structure of materials that blocked rivers. In the epicenter area which was 300 km long and 10 km wide along the main seismic fault, there were lots of landslides triggered by the earthquake, and these landslides have a common characteristic of a discontinuous but flat sliding surface. The failure surfaces can be classified into the following three types based on their overall shape: concave, convex, and terraced. Field evidences illustrated that the vertical component of ground shaking had a significant effect on both building collapse and landslide generation. The ground motion records show that the vertical acceleration is greater than the horizontal, and the acceleration must be larger than 1.0 g in some parts along the main seismic fault. Two landslides are discussed as high speed and long runout cases. One is the Chengxi landslide in Beichuan County, and the other is the Donghekou landslide in Qingchuan County. In each case, the runout process and its impact on people and property were analyzed. The Chengxi landslide killed 1,600 people and destroyed numerous houses. The Donghekou landslide is a complex landslide–debris flow with a long runout. The debris flow scoured the bank of the Qingjiang River for a length of 2,400 m and subsequently formed a landslide dam. This landslide buried seven villages and killed more than 400 people.

Journal ArticleDOI
02 Apr 2009-Nature
TL;DR: The crystal structure of the gap junction channel formed by human connexin 26 (Cx26), also known as GJB2, is reported at 3.5 Å resolution, and structural determinants of solute transport through the channel are discussed.
Abstract: Gap junctions consist of arrays of intercellular channels between adjacent cells that permit the exchange of ions and small molecules. Here we report the crystal structure of the gap junction channel formed by human connexin 26 (Cx26, also known as GJB2) at 3.5 A resolution, and discuss structural determinants of solute transport through the channel. The density map showed the two membrane-spanning hemichannels and the arrangement of the four transmembrane helices of the six protomers forming each hemichannel. The hemichannels feature a positively charged cytoplasmic entrance, a funnel, a negatively charged transmembrane pathway, and an extracellular cavity. The pore is narrowed at the funnel, which is formed by the six amino-terminal helices lining the wall of the channel, which thus determines the molecular size restriction at the channel entrance. The structure of the Cx26 gap junction channel also has implications for the gating of the channel by the transjunctional voltage.

Journal ArticleDOI
TL;DR: In this paper, the authors present a summary of experimental reports on newly discovered iron-based superconductors as they were known at the end of 2008 and introduce experimental results that reveal basic physical properties in the normal and superconducting states.
Abstract: In this review, the authors present a summary of experimental reports on newly discovered iron-based superconductors as they were known at the end of 2008. At the same time, this paper is intended to be useful for experimenters to know the current status of these superconductors. The authors introduce experimental results that reveal basic physical properties in the normal and superconducting states. The similarities and differences between iron-pnictide superconductors and other unconventional superconductors are also discussed.

Journal ArticleDOI
TL;DR: 1 demonstrated a combination of two of the concepts by introducing NH(4)(+) ions using the anionic framework and putting carboxyl end groups of adipic acid in a honeycomb-shaped void, showing a superprotonic conductivity of 10(-2) S cm(-1) at ambient temperature.
Abstract: A novel metal−organic framework (MOF), (NH4)2(adp)[Zn2(ox)3]·3H2O (1) was synthesized and its structure was determined. We propose three types of rational design to introduce proton carriers into MOFs. The simplest method is to introduce them directly as counterions such as NH4+, H3O+, and HSO4− into the pores of frameworks (type I). The second is to put acid groups on frameworks, the protons being provided from them (type II). The third is to incorporate acidic molecules into voids (type III). 1 demonstrated a combination of two of the concepts by introducing NH4+ ions using the anionic framework (type I) and putting carboxyl end groups of adipic acid in a honeycomb-shaped void (type III). 1 showed a superprotonic conductivity of 10−2 S cm−1 at ambient temperature, comparable to organic polymers such as Nafion, which is in practical use in fuel cells. This is the first example of an MOF to exhibit a superprotonic conductivity of 10−2 S cm−1 at ambient temperature.

Journal ArticleDOI
TL;DR: This review discusses promising approaches to multiple controls of polymer structures, analysis systems for low-dimensional polymer assemblies and the construction of PCP-polymer nanohybrids, which are strong enticements to researchers in the areas of inorganic, materials and polymer chemistry.
Abstract: Recent developments in polymerizations within the nanochannels of porous coordination polymers (PCPs) are covered in this tutorial review. The characteristic features of PCPs are regular structures, controllable channel sizes and shapes, a designable surface functionality, and flexible frameworks, which can be utilized for precision polymer synthesis and specific polymer confinement. This review discusses promising approaches to multiple controls of polymer structures, analysis systems for low-dimensional polymer assemblies and the construction of PCP–polymer nanohybrids, which are strong enticements to researchers in the areas of inorganic, materials and polymer chemistry.