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Showing papers by "University of Tokyo published in 2008"


Journal ArticleDOI
TL;DR: A set of guidelines for the selection and interpretation of the methods that can be used by investigators who are attempting to examine macroautophagy and related processes, as well as by reviewers who need to provide realistic and reasonable critiques of papers that investigate these processes are presented.
Abstract: Research in autophagy continues to accelerate,(1) and as a result many new scientists are entering the field Accordingly, it is important to establish a standard set of criteria for monitoring macroautophagy in different organisms Recent reviews have described the range of assays that have been used for this purpose(2,3) There are many useful and convenient methods that can be used to monitor macroautophagy in yeast, but relatively few in other model systems, and there is much confusion regarding acceptable methods to measure macroautophagy in higher eukaryotes A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers of autophagosomes versus those that measure flux through the autophagy pathway; thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from fully functional autophagy that includes delivery to, and degradation within, lysosomes (in most higher eukaryotes) or the vacuole (in plants and fungi) Here, we present a set of guidelines for the selection and interpretation of the methods that can be used by investigators who are attempting to examine macroautophagy and related processes, as well as by reviewers who need to provide realistic and reasonable critiques of papers that investigate these processes This set of guidelines is not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to verify an autophagic response

2,310 citations


Journal ArticleDOI
08 Feb 2008-Cell
TL;DR: Time-lapse imaging is performed to explore the spatiotemporal patterns of cell-cycle dynamics during the epithelial-mesenchymal transition of cultured cells, the migration and differentiation of neural progenitors in brain slices, and the development of tumors across blood vessels in live mice.

1,946 citations



Journal ArticleDOI
04 Jan 2008-Science
TL;DR: This comparison reveals genomic changes concomitant with the evolutionary movement to land, including a general increase in gene family complexity; loss of genes associated with aquatic environments; acquisition of genes for tolerating terrestrial stresses; and the development of the auxin and abscisic acid signaling pathways for coordinating multicellular growth and dehydration response.
Abstract: We report the draft genome sequence of the model moss Physcomitrella patens and compare its features with those of flowering plants, from which it is separated by more than 400 million years, and unicellular aquatic algae. This comparison reveals genomic changes concomitant with the evolutionary movement to land, including a general increase in gene family complexity; loss of genes associated with aquatic environments (e.g., flagellar arms); acquisition of genes for tolerating terrestrial stresses (e.g., variation in temperature and water availability); and the development of the auxin and abscisic acid signaling pathways for coordinating multicellular growth and dehydration response. The Physcomitrella genome provides a resource for phylogenetic inferences about gene function and for experimental analysis of plant processes through this plant's unique facility for reverse genetics.

1,749 citations


Journal ArticleDOI
11 Sep 2008-Nature
TL;DR: It is proposed that strigolactones act as a new hormone class—or their biosynthetic precursors—in regulating above-ground plant architecture, and also have a function in underground communication with other neighbouring organisms.
Abstract: Shoot branching is a major determinant of plant architecture and is highly regulated by endogenous and environmental cues. Two classes of hormones, auxin and cytokinin, have long been known to have an important involvement in controlling shoot branching. Previous studies using a series of mutants with enhanced shoot branching suggested the existence of a third class of hormone(s) that is derived from carotenoids, but its chemical identity has been unknown. Here we show that levels of strigolactones, a group of terpenoid lactones, are significantly reduced in some of the branching mutants. Furthermore, application of strigolactones inhibits shoot branching in these mutants. Strigolactones were previously found in root exudates acting as communication chemicals with parasitic weeds and symbiotic arbuscular mycorrhizal fungi. Thus, we propose that strigolactones act as a new hormone class-or their biosynthetic precursors-in regulating above-ground plant architecture, and also have a function in underground communication with other neighbouring organisms.

1,742 citations


Journal ArticleDOI
TL;DR: Hydroamination of Alkenes and Alkynes under Microwave Irradiation and Nitromercuration Reactions 3878 9.8.4.5.
Abstract: 8.4.5. Nitromercuration Reactions 3878 9. Hydroamination of Alkenes and Alkynes under Microwave Irradiation 3878 * To whom correspondence should be addressed. Phone: +49 241 8

1,685 citations


Journal ArticleDOI
Jennifer K. Adelman-McCarthy1, Marcel A. Agüeros2, S. Allam3, S. Allam1  +170 moreInstitutions (65)
TL;DR: The Sixth Data Release of the Sloan Digital Sky Survey (SDS) as discussed by the authors contains images and parameters of roughly 287 million objects over 9583 deg(2), including scans over a large range of Galactic latitudes and longitudes.
Abstract: This paper describes the Sixth Data Release of the Sloan Digital Sky Survey. With this data release, the imaging of the northern Galactic cap is now complete. The survey contains images and parameters of roughly 287 million objects over 9583 deg(2), including scans over a large range of Galactic latitudes and longitudes. The survey also includes 1.27 million spectra of stars, galaxies, quasars, and blank sky ( for sky subtraction) selected over 7425 deg2. This release includes much more stellar spectroscopy than was available in previous data releases and also includes detailed estimates of stellar temperatures, gravities, and metallicities. The results of improved photometric calibration are now available, with uncertainties of roughly 1% in g, r, i, and z, and 2% in u, substantially better than the uncertainties in previous data releases. The spectra in this data release have improved wavelength and flux calibration, especially in the extreme blue and extreme red, leading to the qualitatively better determination of stellar types and radial velocities. The spectrophotometric fluxes are now tied to point-spread function magnitudes of stars rather than fiber magnitudes. This gives more robust results in the presence of seeing variations, but also implies a change in the spectrophotometric scale, which is now brighter by roughly 0.35 mag. Systematic errors in the velocity dispersions of galaxies have been fixed, and the results of two independent codes for determining spectral classifications and red-shifts are made available. Additional spectral outputs are made available, including calibrated spectra from individual 15 minute exposures and the sky spectrum subtracted from each exposure. We also quantify a recently recognized underestimation of the brightnesses of galaxies of large angular extent due to poor sky subtraction; the bias can exceed 0.2 mag for galaxies brighter than r = 14 mag.

1,602 citations


Journal ArticleDOI
TL;DR: The plasmonic photocatalysis will be of use as a high performance photocatalyst in nearly all current applications but will beof particular importance for applications in locations of minimal light exposure.
Abstract: Titanium dioxide (TiO2) displays photocatalytic behavior under near-ultraviolet (UV) illumination. In another scientific field, it is well understood that the excitation of localized plasmon polaritons on the surface of silver (Ag) nanoparticles (NPs) causes a tremendous increase of the near-field amplitude at well-defined wavelengths in the near UV. The exact resonance wavelength depends on the shape and the dielectric environment of the NPs. We expected that the photocatalytic behavior of TiO2 would be greatly boosted if it gets assisted by the enhanced near-field amplitudes of localized surface plasmon (LSP). Here we show that this is true indeed. We named this new phenomenon "plasmonic photocatalysis". The key to enable plasmonic photocatalysis is to deposit TiO2 on a NP comprising an Ag core covered with a silica (SiO2) shell to prevent oxidation of Ag by direct contact with TiO2. The most appropriate diameter for Ag NPs and thickness for the SiO2 shell giving rise to LSP in the near UV were estimated from Mie scattering theory. Upon implementing a device that took these design considerations into account, the measured photocatalytic activity under near UV illumination of such a plasmonic photocatalyst, monitored by decomposition of methylene blue, was enhanced by a factor of 7. The enhancement of the photocatalytic activity increases with a decreased thickness of the SiO2 shell. The plasmonic photocatalysis will be of use as a high performance photocatalyst in nearly all current applications but will be of particular importance for applications in locations of minimal light exposure.

1,422 citations


Journal ArticleDOI
TL;DR: In this paper, the authors used the photometric parallax method to estimate the distances to ~48 million stars detected by the Sloan Digital Sky Survey (SDSS) and map their three-dimensional number density distribution in the Galaxy.
Abstract: Using the photometric parallax method we estimate the distances to ~48 million stars detected by the Sloan Digital Sky Survey (SDSS) and map their three-dimensional number density distribution in the Galaxy. The currently available data sample the distance range from 100 pc to 20 kpc and cover 6500 deg2 of sky, mostly at high Galactic latitudes (|b| > 25). These stellar number density maps allow an investigation of the Galactic structure with no a priori assumptions about the functional form of its components. The data show strong evidence for a Galaxy consisting of an oblate halo, a disk component, and a number of localized overdensities. The number density distribution of stars as traced by M dwarfs in the solar neighborhood (D < 2 kpc) is well fit by two exponential disks (the thin and thick disk) with scale heights and lengths, bias corrected for an assumed 35% binary fraction, of H1 = 300 pc and L1 = 2600 pc, and H2 = 900 pc and L2 = 3600 pc, and local thick-to-thin disk density normalization ρthick(R☉)/ρthin(R☉) = 12% . We use the stars near main-sequence turnoff to measure the shape of the Galactic halo. We find a strong preference for oblate halo models, with best-fit axis ratio c/a = 0.64, ρH ∝ r−2.8 power-law profile, and the local halo-to-thin disk normalization of 0.5%. Based on a series of Monte Carlo simulations, we estimate the errors of derived model parameters not to be larger than ~20% for the disk scales and ~10% for the density normalization, with largest contributions to error coming from the uncertainty in calibration of the photometric parallax relation and poorly constrained binary fraction. While generally consistent with the above model, the measured density distribution shows a number of statistically significant localized deviations. In addition to known features, such as the Monoceros stream, we detect two overdensities in the thick disk region at cylindrical galactocentric radii and heights (R,Z) ~ (6.5,1.5) kpc and (R,Z) ~ (9.5,0.8) kpc and a remarkable density enhancement in the halo covering over 1000 deg2 of sky toward the constellation of Virgo, at distances of ~6-20 kpc. Compared to counts in a region symmetric with respect to the l = 0° line and with the same Galactic latitude, the Virgo overdensity is responsible for a factor of 2 number density excess and may be a nearby tidal stream or a low-surface brightness dwarf galaxy merging with the Milky Way. The u − g color distribution of stars associated with it implies metallicity lower than that of thick disk stars and consistent with the halo metallicity distribution. After removal of the resolved overdensities, the remaining data are consistent with a smooth density distribution; we detect no evidence of further unresolved clumpy substructure at scales ranging from ~50 pc in the disk to ~1-2 kpc in the halo.

1,375 citations


Journal ArticleDOI
12 Sep 2008-Science
TL;DR: It is found that the SWNT content can be increased up to 20 weight percent without reducing the mechanical flexibility or softness of the copolymer, and the elastic conductor allows for the construction of electronic integrated circuits, which can be mounted anywhere, including arbitrary curved surfaces and movable parts, such as the joints of a robot's arm.
Abstract: By using an ionic liquid of 1-butyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide, we uniformly dispersed single-walled carbon nanotubes (SWNTs) as chemically stable dopants in a vinylidene fluoride-hexafluoropropylene copolymer matrix to form a composite film. We found that the SWNT content can be increased up to 20 weight percent without reducing the mechanical flexibility or softness of the copolymer. The SWNT composite film was coated with dimethyl-siloxane-based rubber, which exhibited a conductivity of 57 siemens per centimeter and a stretchability of 134%. Further, the elastic conductor was integrated with printed organic transistors to fabricate a rubberlike active matrix with an effective area of 20 by 20 square centimeters. The active matrix sheet can be uniaxially and biaxially stretched by 70% without mechanical or electrical damage. The elastic conductor allows for the construction of electronic integrated circuits, which can be mounted anywhere, including arbitrary curved surfaces and movable parts, such as the joints of a robot's arm.

1,330 citations


Journal ArticleDOI
24 Apr 2008-Nature
TL;DR: Tribolium castaneum is a member of the most species-rich eukaryotic order, a powerful model organism for the study of generalized insect development, and an important pest of stored agricultural products.
Abstract: Tribolium castaneum is a member of the most species-rich eukaryotic order, a powerful model organism for the study of generalized insect development, and an important pest of stored agricultural products. We describe its genome sequence here. This omnivorous beetle has evolved the ability to interact with a diverse chemical environment, as shown by large expansions in odorant and gustatory receptors, as well as P450 and other detoxification enzymes. Development in Tribolium is more representative of other insects than is Drosophila, a fact reflected in gene content and function. For example, Tribolium has retained more ancestral genes involved in cell-cell communication than Drosophila, some being expressed in the growth zone crucial for axial elongation in short-germ development. Systemic RNA interference in T. castaneum functions differently from that in Caenorhabditis elegans, but nevertheless offers similar power for the elucidation of gene function and identification of targets for selective insect control.

Journal ArticleDOI
K. Aamodt1, A. Abrahantes Quintana, R. Achenbach2, S. Acounis3  +1151 moreInstitutions (76)
TL;DR: The Large Ion Collider Experiment (ALICE) as discussed by the authors is a general-purpose, heavy-ion detector at the CERN LHC which focuses on QCD, the strong-interaction sector of the Standard Model.
Abstract: ALICE (A Large Ion Collider Experiment) is a general-purpose, heavy-ion detector at the CERN LHC which focuses on QCD, the strong-interaction sector of the Standard Model. It is designed to address the physics of strongly interacting matter and the quark-gluon plasma at extreme values of energy density and temperature in nucleus-nucleus collisions. Besides running with Pb ions, the physics programme includes collisions with lighter ions, lower energy running and dedicated proton-nucleus runs. ALICE will also take data with proton beams at the top LHC energy to collect reference data for the heavy-ion programme and to address several QCD topics for which ALICE is complementary to the other LHC detectors. The ALICE detector has been built by a collaboration including currently over 1000 physicists and engineers from 105 Institutes in 30 countries. Its overall dimensions are 161626 m3 with a total weight of approximately 10 000 t. The experiment consists of 18 different detector systems each with its own specific technology choice and design constraints, driven both by the physics requirements and the experimental conditions expected at LHC. The most stringent design constraint is to cope with the extreme particle multiplicity anticipated in central Pb-Pb collisions. The different subsystems were optimized to provide high-momentum resolution as well as excellent Particle Identification (PID) over a broad range in momentum, up to the highest multiplicities predicted for LHC. This will allow for comprehensive studies of hadrons, electrons, muons, and photons produced in the collision of heavy nuclei. Most detector systems are scheduled to be installed and ready for data taking by mid-2008 when the LHC is scheduled to start operation, with the exception of parts of the Photon Spectrometer (PHOS), Transition Radiation Detector (TRD) and Electro Magnetic Calorimeter (EMCal). These detectors will be completed for the high-luminosity ion run expected in 2010. This paper describes in detail the detector components as installed for the first data taking in the summer of 2008.

Journal ArticleDOI
TL;DR: It is concluded that the multiple spin-fluctuation modes arising from the nesting across the disconnected Fermi surfaces realize an extended s-wave Pairing, while d-wave pairing can also be another candidate.
Abstract: For a newly discovered iron-based high ${T}_{c}$ superconductor ${\mathrm{LaFeAsO}}_{1\ensuremath{-}x}{\mathrm{F}}_{x}$, we have constructed a minimal model, where inclusion of all five Fe $d$ bands is found to be necessary. The random-phase approximation is applied to the model to investigate the origin of superconductivity. We conclude that the multiple spin-fluctuation modes arising from the nesting across the disconnected Fermi surfaces realize an extended $s$-wave pairing, while $d$-wave pairing can also be another candidate.

Journal ArticleDOI
14 Feb 2008-Nature
TL;DR: It is proposed that cohesin functions as a transcriptional insulator, and it is speculated that subtle deficiencies in this function contribute to ‘cohesinopathies’ such as Cornelia de Lange syndrome.
Abstract: Cohesin complexes mediate sister-chromatid cohesion in dividing cells but may also contribute to gene regulation in postmitotic cells. How cohesin regulates gene expression is not known. Here we describe cohesin-binding sites in the human genome and show that most of these are associated with the CCCTC-binding factor (CTCF), a zinc-finger protein required for transcriptional insulation. CTCF is dispensable for cohesin loading onto DNA, but is needed to enrich cohesin at specific binding sites. Cohesin enables CTCF to insulate promoters from distant enhancers and controls transcription at the H19/IGF2 (insulin-like growth factor 2) locus. This role of cohesin seems to be independent of its role in cohesion. We propose that cohesin functions as a transcriptional insulator, and speculate that subtle deficiencies in this function contribute to 'cohesinopathies' such as Cornelia de Lange syndrome.

Journal ArticleDOI
TL;DR: Although both cytokines regulated CXC chemokines and granulocyte colony–stimulating factor production in the lung, only IL-22 increased lung epithelial cell proliferation and increased transepithelial resistance to injury, and data support the concept that the TH17 cell lineage and its effector molecules have evolved to effect host defense against extracellular pathogens at mucosal sites.
Abstract: Emerging evidence supports the concept that T helper type 17 (TH17) cells, in addition to mediating autoimmunity, have key roles in mucosal immunity against extracellular pathogens. Interleukin-22 (IL-22) and IL-17A are both effector cytokines produced by the TH17 lineage, and both were crucial for maintaining local control of the Gram-negative pulmonary pathogen, Klebsiella pneumoniae. Although both cytokines regulated CXC chemokines and granulocyte colony–stimulating factor production in the lung, only IL-22 increased lung epithelial cell proliferation and increased transepithelial resistance to injury. These data support the concept that the TH17 cell lineage and its effector molecules have evolved to effect host defense against extracellular pathogens at mucosal sites.

Journal ArticleDOI
TL;DR: The specific criteria required for the annotation of plant miRNAs are updated, including experimental and computational data, as well as refinements to standard nomenclature.
Abstract: MicroRNAs (miRNAs) are ∼21 nucleotide noncoding RNAs produced by Dicer-catalyzed excision from stem-loop precursors. Many plant miRNAs play critical roles in development, nutrient homeostasis, abiotic stress responses, and pathogen responses via interactions with specific target mRNAs. miRNAs are not the only Dicer-derived small RNAs produced by plants: A substantial amount of the total small RNA abundance and an overwhelming amount of small RNA sequence diversity is contributed by distinct classes of 21- to 24-nucleotide short interfering RNAs. This fact, coupled with the rapidly increasing rate of plant small RNA discovery, demands an increased rigor in miRNA annotations. Herein, we update the specific criteria required for the annotation of plant miRNAs, including experimental and computational data, as well as refinements to standard nomenclature.

Journal ArticleDOI
TL;DR: The role of several IRF family members in the regulation of the cell cycle and apoptosis has important implications for understanding susceptibility to and progression of several cancers.
Abstract: The interferon regulatory factor (IRF) family, consisting of nine members in mammals, was identified in the late 1980s in the context of research into the type I interferon system. Subsequent studies over the past two decades have revealed the versatile and critical functions performed by this transcription factor family. Indeed, many IRF members play central roles in the cellular differentiation of hematopoietic cells and in the regulation of gene expression in response to pathogen-derived danger signals. In particular, the advances made in understanding the immunobiology of Toll-like and other pattern-recognition receptors have recently generated new momentum for the study of IRFs. Moreover, the role of several IRF family members in the regulation of the cell cycle and apoptosis has important implications for understanding susceptibility to and progression of several cancers.

Book
01 Jan 2008
TL;DR: In this article, the authors present a classification of group von Neumann algebras based on the following properties: weak expectation property, local lifting property, and local reflexivity.
Abstract: Fundamental facts Basic theory: Nuclear and exact $\textrm{C}^*$-algebras: Definitions, basic facts and examples Tensor products Constructions Exact groups and related topics Amenable traces and Kirchberg's factorization property Quasidiagonal C*-algebras AF embeddablity Local reflexivity and other tensor product conditions Summary and open problems Special topics: Simple $\textrm{C}^*$-algebras Approximation properties for groups Weak expectation property and local lifting property Weakly exact von Neumann algebras Applications: Classification of group von Neumann algebras Herrero's approximation problem Counterexamples in $\textrm{K}$-homology and $\textrm{K}$-theory Appendices: Ultrafilters and ultraproducts Operator spaces, completely bounded maps and duality Lifting theorems Positive definite functions, cocycles and Schoenberg's Theorem Groups and graphs Bimodules over von Neumann algebras Bibliography Notation index Subject index.

Journal ArticleDOI
TL;DR: The aim of this review is to summarize and provide the state of the art of research in this field, addressing aspects such as cell isolation protocols and characteristics of these cells, as well as providing preliminary indications of the possibilities for use ofThese cells in future clinical applications.
Abstract: Placental tissue draws great interest as a source of cells for regenerative medicine because of the phenotypic plasticity of many of the cell types isolated from this tissue. Furthermore, placenta, which is involved in maintaining fetal tolerance, contains cells that display immunomodulatory properties. These two features could prove useful for future cell therapy-based clinical applications. Placental tissue is readily available and easily procured without invasive procedures, and its use does not elicit ethical debate. Numerous reports describing stem cells from different parts of the placenta, using nearly as numerous isolation and characterization procedures, have been published. Considering the complexity of the placenta, an urgent need exists to define, as clearly as possible, the region of origin and methods of isolation of cells derived from this tissue. On March 23-24, 2007, the first international Workshop on Placenta Derived Stem Cells was held in Brescia, Italy. Most of the research published in this area focuses on mesenchymal stromal cells isolated from various parts of the placenta or epithelial cells isolated from amniotic membrane. The aim of this review is to summarize and provide the state of the art of research in this field, addressing aspects such as cell isolation protocols and characteristics of these cells, as well as providing preliminary indications of the possibilities for use of these cells in future clinical applications.

Journal ArticleDOI
24 Apr 2008-Nature
TL;DR: Evidence is provided that heteromeric insect ORs comprise a new class of ligand-activated non-selective cation channels and the fast response kinetics and OR-subunit-dependent K+ ion selectivity of the insect OR complex support the hypothesis that the complex between OR and Or83b itself confers channel activity.
Abstract: In many organisms, from worms to humans, olfactory cues are detected by large families of seven transmembrane-spanning receptors, which have until now been classified as G protein-coupled receptors. Insects, however, have evolved a surprisingly simple and efficient sense of smell in which the odorant receptors require a second component — the ion-channel-forming chaperone protein Or83b — for correct function. In the first of two related papers, Sato et al. show that these heteromeric receptors form ligand-gated cation channels that are not dependent on G protein-coupled second messengers, and speculate that other seven transmembrane-spanning proteins may show similar ion channel activity. Wicher et al. show that, in addition to direct channel activation, ligand binding to odorant receptors causes G protein-coupled channel activation. This work has implications for the search for insect odorant receptor inhibitors for possible use in controlling host seeking behaviour of disease carrying insects such as the mosquito. Olfactory cues are detected by large families of seven transmembrane-spanning receptors, which have until now been classified as G-protein-coupled receptors. In insects, these odorant receptors require a second protein (Or83b) for correct function. These heteromeric receptors form ligand-gated cation channels that are not dependent on G protein-coupled second messengers and it is speculated that seven other transmembrane-spanning proteins may show similar ion channel activity. In insects, each olfactory sensory neuron expresses between one and three ligand-binding members of the olfactory receptor (OR) gene family, along with the highly conserved and broadly expressed Or83b co-receptor1,2,3,4,5,6,7,8,9. The functional insect OR consists of a heteromeric complex of unknown stoichiometry but comprising at least one variable odorant-binding subunit and one constant Or83b family subunit10,11,12,13,14,15,16. Insect ORs lack homology to G-protein-coupled chemosensory receptors in vertebrates17 and possess a distinct seven-transmembrane topology with the amino terminus located intracellularly10,18. Here we provide evidence that heteromeric insect ORs comprise a new class of ligand-activated non-selective cation channels. Heterologous cells expressing silkmoth, fruitfly or mosquito heteromeric OR complexes showed extracellular Ca2+influx and cation-non-selective ion conductance on stimulation with odorant. Odour-evoked OR currents are independent of known G-protein-coupled second messenger pathways. The fast response kinetics and OR-subunit-dependent K+ ion selectivity of the insect OR complex support the hypothesis that the complex between OR and Or83b itself confers channel activity. Direct evidence for odorant-gated channels was obtained by outside-out patch-clamp recording of Xenopus oocyte and HEK293T cell membranes expressing insect OR complexes. The ligand-gated ion channel formed by an insect OR complex seems to be the basis for a unique strategy that insects have acquired to respond to the olfactory environment.

Journal ArticleDOI
TL;DR: It is suggested that continuous neurogenesis is required for the maintenance and reorganization of the whole interneuron system in the olfactory bulb, the modulation and refinement of the existing neuronal circuits in the dentate gyrus and the normal behaviors involved in hippocampal-dependent memory.
Abstract: Neurogenesis occurs continuously in the forebrain of adult mammals, but the functional importance of adult neurogenesis is still unclear. Here, using a genetic labeling method in adult mice, we found that continuous neurogenesis results in the replacement of the majority of granule neurons in the olfactory bulb and a substantial addition of granule neurons to the hippocampal dentate gyrus. Genetic ablation of newly formed neurons in adult mice led to a gradual decrease in the number of granule cells in the olfactory bulb, inhibition of increases in the granule cell number in the dentate gyrus and impairment of behaviors in contextual and spatial memory, which are known to depend on hippocampus. These results suggest that continuous neurogenesis is required for the maintenance and reorganization of the whole interneuron system in the olfactory bulb, the modulation and refinement of the existing neuronal circuits in the dentate gyrus and the normal behaviors involved in hippocampal-dependent memory.

Journal ArticleDOI
TL;DR: The Japanese versions of the K6 and K10 demonstrated screening performances essentially equivalent to those of the original English versions, and Stratum‐specific likelihood ratios (SSLRs) were strikingly similar between the Japanese and the original versions.
Abstract: Two new screening scales for psychological distress, the K6 and K10, have been developed using the item response theory and shown to outperform existing screeners in English. We developed their Japanese versions using the standard back-translaton method and included them in the World Mental Health Survey Japan (WMH-J), which is a psychiatric epidemiologic study conducted in seven communities across Japan with 2436 participants. The WMH-J used the WMH Survey Initiative version of the Composite International Diagnostic Interview (CIDI) to assess the 30-day Diagnostic and Statistical Manual of Mental Disorders--Fourth Edition (DSM-IV). Performance of the two screening scales in detecting DSM-IV mood and anxiety disorders, as assessed by the areas under receiver operating characteristic curves (AUCs), was excellent, with values as high as 0.94 (95% confidence interval = 0.88 to 0.99) for K6 and 0.94 (0.88 to 0.995) for K10. Stratum-specific likelihood ratios (SSLRs), which express screening test characteristics and can be used to produce individual-level predicted probabilities of being a case from screening scale scores and pretest probabilities in other samples, were strikingly similar between the Japanese and the original versions. The Japanese versions of the K6 and K10 thus demonstrated screening performances essentially equivalent to those of the original English versions.

Journal ArticleDOI
16 May 2008-Science
TL;DR: Although ∼10% of the ocean's drawdown of atmospheric anthropogenic carbon dioxide may result from this atmospheric nitrogen fertilization, leading to a decrease in radiative forcing, up to about two-thirds of this amount may be offset by the increase in N2O emissions.
Abstract: Increasing quantities of atmospheric anthropogenic fixed nitrogen entering the open ocean could account for up to about a third of the ocean's external (nonrecycled) nitrogen supply and up to 3% of the annual new marine biological production, 0.3 petagram of carbon per year. This input could account for the production of up to 1.6 teragrams of nitrous oxide (N2O) per year. Although 10% of the ocean's drawdown of atmospheric anthropogenic carbon dioxide may result from this atmospheric nitrogen fertilization, leading to a decrease in radiative forcing, up to about two-thirds of this amount may be offset by the increase in N2O emissions. The effects of increasing atmospheric nitrogen deposition are expected to continue to grow in the future.

Journal ArticleDOI
TL;DR: In this article, the authors synthesize palaeoclimate records from the mid-latitude arid Asian region dominated today by the Westerlies ("arid central Asia" (ACA)) to evaluate spatial and temporal patterns of moisture changes during the Holocene.

Journal ArticleDOI
01 Jul 2008
TL;DR: This article characterize four classes of drug–target interaction networks in humans involving enzymes, ion channels, G-protein-coupled receptors (GPCRs) and nuclear receptors, and reveal significant correlations between drug structure similarity, target sequence similarity and the drug– target interaction network topology.
Abstract: Motivation: The identification of interactions between drugs and target proteins is a key area in genomic drug discovery. Therefore, there is a strong incentive to develop new methods capable of detecting these potential drug–target interactions efficiently. Results: In this article, we characterize four classes of drug–target interaction networks in humans involving enzymes, ion channels, G-protein-coupled receptors (GPCRs) and nuclear receptors, and reveal significant correlations between drug structure similarity, target sequence similarity and the drug–target interaction network topology. We then develop new statistical methods to predict unknown drug–target interaction networks from chemical structure and genomic sequence information simultaneously on a large scale. The originality of the proposed method lies in the formalization of the drug–target interaction inference as a supervised learning problem for a bipartite graph, the lack of need for 3D structure information of the target proteins, and in the integration of chemical and genomic spaces into a unified space that we call ‘pharmacological space’. In the results, we demonstrate the usefulness of our proposed method for the prediction of the four classes of drug–target interaction networks. Our comprehensively predicted drug–target interaction networks enable us to suggest many potential drug–target interactions and to increase research productivity toward genomic drug discovery. Availability: Softwares are available upon request. Contact: Yoshihiro.Yamanishi@ensmp.fr Supplementary information: Datasets and all prediction results are available at http://web.kuicr.kyoto-u.ac.jp/supp/yoshi/drugtarget/.

Journal ArticleDOI
TL;DR: In this article, a two-step aqueous route consisting of a first precipitation of nanoporous Cd(OH)2 intermediates and a subsequent S2−/OH− ion-exchange conversion of the obtained CdS2 used as template was described.
Abstract: Nanoporous CdS nanostructures, including nanosheets and hollow nanorods, have been prepared by a two-step aqueous route, which consists of a first precipitation of nanoporous Cd(OH)2 intermediates and a subsequent S2−/OH− ion-exchange conversion of the obtained Cd(OH)2 used as template either to nanoporous CdS nanosheets with sizes up to 60 nm and an average thickness of about 9 nm or to CdS hollow nanorods with lengths up to 30 nm and outer diameters in the range 7–14 nm. The obtained CdS nanostructures containing nanopores with diameters of ∼3 nm exhibit a very large BET surface area of about 112.8 m2 g−1. A very high hydrogen yield of about 4.1 mmol h−1 under visible light irradiation (λ ≥ 420 nm), corresponding to the highest apparent quantum yield of about 60.34% measured at 420 nm so far reported, has been attained over the obtained nanoporous CdS nanostructures loaded with monodisperse 3–5 nm Pt nanocrystals, which is due to an efficient charge separation, a fast transport of the photogenerated car...

Journal ArticleDOI
TL;DR: The preliminary results suggest that CAL is effective and safe for soft tissue augmentation and superior to conventional lipoinjection.
Abstract: Background Lipoinjection is a promising treatment but has some problems, such as unpredictability and a low rate of graft survival due to partial necrosis. Methods To overcome the problems with lipoinjection, the authors developed a novel strategy known as cellassisted lipotransfer (CAL). In CAL, autologous adiposederived stem (stromal) cells (ASCs) are used in combination with lipoinjection. A stromal vascular fraction (SVF) containing ASCs is freshly isolated from half of the aspirated fat and recombined with the other half. This process converts relatively ASC-poor aspirated fat to ASC-rich fat. This report presents the findings for 40 patients who underwent CAL for cosmetic breast augmentation. Results Final breast volume showed augmentation by 100 to 200 ml after a mean fat amount of 270 ml was injected. Postoperative atrophy of injected fat was minimal and did not change substantially after 2 months. Cyst formation or microcalcification was detected in four patients. Almost all the patients were satisfied with the soft and naturalappearing augmentation. Conclusions The preliminary results suggest that CAL is effective and safe for soft tissue augmentation and superior to conventional lipoinjection. Additional study is necessary to evaluate the efficacy of this technique further.

Journal ArticleDOI
16 Oct 2008-Nature
TL;DR: It is demonstrated that downregulation of ALK through RNA interference suppresses proliferation of neuroblastoma cells harbouring mutated ALK, and that ALK-specific kinase inhibitors might improve its clinical outcome.
Abstract: Neuroblastoma in advanced stages is one of the most intractable paediatric cancers, even with recent therapeutic advances Neuroblastoma harbours a variety of genetic changes, including a high frequency of MYCN amplification, loss of heterozygosity at 1p36 and 11q, and gain of genetic material from 17q, all of which have been implicated in the pathogenesis of neuroblastoma However, the scarcity of reliable molecular targets has hampered the development of effective therapeutic agents targeting neuroblastoma Here we show that the anaplastic lymphoma kinase (ALK), originally identified as a fusion kinase in a subtype of non-Hodgkin's lymphoma (NPM-ALK) and more recently in adenocarcinoma of lung (EML4-ALK), is also a frequent target of genetic alteration in advanced neuroblastoma According to our genome-wide scans of genetic lesions in 215 primary neuroblastoma samples using high-density single-nucleotide polymorphism genotyping microarrays, the ALK locus, centromeric to the MYCN locus, was identified as a recurrent target of copy number gain and gene amplification Furthermore, DNA sequencing of ALK revealed eight novel missense mutations in 13 out of 215 (61%) fresh tumours and 8 out of 24 (33%) neuroblastoma-derived cell lines All but one mutation in the primary samples (12 out of 13) were found in stages 3-4 of the disease and were harboured in the kinase domain The mutated kinases were autophosphorylated and displayed increased kinase activity compared with the wild-type kinase They were able to transform NIH3T3 fibroblasts as shown by their colony formation ability in soft agar and their capacity to form tumours in nude mice Furthermore, we demonstrate that downregulation of ALK through RNA interference suppresses proliferation of neuroblastoma cells harbouring mutated ALK We anticipate that our findings will provide new insights into the pathogenesis of advanced neuroblastoma and that ALK-specific kinase inhibitors might improve its clinical outcome

Journal ArticleDOI
TL;DR: In this paper, the authors defined severe plastic deformation (SPD) as metal forming processes in which a very large plastic strain is imposed on a bulk process in order to make an ultra-fine grained metal.
Abstract: Processes of severe plastic deformation (SPD) are defined as metal forming processes in which a very large plastic strain is imposed on a bulk process in order to make an ultra-fine grained metal The objective of the SPD processes for creating ultra-fine grained metal is to produce lightweight parts by using high strength metal for the safety and reliability of micro-parts and for environmental harmony In this keynote paper, the fabrication process of equal channel angular pressing (ECAP), accumulative roll-bonding (ARB), high pressure torsion (HPT), and others are introduced, and the properties of metals processed by the SPD processes are shown Moreover, the combined processes developed recently are also explained Finally, the applications of the ultra-fine grained (UFG) metals are discussed

Journal ArticleDOI
TL;DR: The implications of projected climate change for freshwater resources and their management are discussed in this article, where the authors present an analysis of the potential impacts of climate change on freshwater resources in terms of their management.
Abstract: (2008). The implications of projected climate change for freshwater resources and their management. Hydrological Sciences Journal: Vol. 53, No. 1, pp. 3-10.