Showing papers by "University of Tsukuba published in 2008"

The genome of the model beetle and pest Tribolium castaneum.

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.

ROS-generating mitochondrial DNA mutations can regulate tumor cell metastasis.

Abstract: Mutations in mitochondrial DNA (mtDNA) occur at high frequency in human tumors, but whether these mutations alter tumor cell behavior has been unclear. We used cytoplasmic hybrid (cybrid) technology to replace the endogenous mtDNA in a mouse tumor cell line that was poorly metastatic with mtDNA from a cell line that was highly metastatic, and vice versa. Using assays of metastasis in mice, we found that the recipient tumor cells acquired the metastatic potential of the transferred mtDNA. The mtDNA conferring high metastatic potential contained G13997A and 13885insC mutations in the gene encoding NADH (reduced form of nicotinamide adenine dinucleotide) dehydrogenase subunit 6 (ND6). These mutations produced a deficiency in respiratory complex I activity and were associated with overproduction of reactive oxygen species (ROS). Pretreatment of the highly metastatic tumor cells with ROS scavengers suppressed their metastatic potential in mice. These results indicate that mtDNA mutations can contribute to tumor progression by enhancing the metastatic potential of tumor cells.

The ALICE experiment at the CERN LHC

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.

Cancer related mutations in NRF2 impair its recognition by Keap1-Cul3 E3 ligase and promote malignancy

Abstract: The nuclear factor E2-related factor 2 (Nrf2) is a master transcriptional activator of genes encoding numerous cytoprotective enzymes that are induced in response to environmental and endogenously derived oxidative/electrophilic agents. Under normal, nonstressed circumstances, low cellular concentrations of Nrf2 are maintained by proteasomal degradation through a Keap1-Cul3-Roc1-dependent mechanism. A model for Nrf2 activation has been proposed in which two amino-terminal motifs, DLG and ETGE, promote efficient ubiquitination and rapid turnover; known as the two-site substrate recognition/hinge and latch model. Here, we show that in human cancer, somatic mutations occur in the coding region of NRF2, especially among patients with a history of smoking or suffering from squamous cell carcinoma; in the latter case, this leads to poor prognosis. These mutations specifically alter amino acids in the DLG or ETGE motifs, resulting in aberrant cellular accumulation of Nrf2. Mutant Nrf2 cells display constitutive induction of cytoprotective enzymes and drug efflux pumps, which are insensitive to Keap1-mediated regulation. Suppression of Nrf2 protein levels by siRNA knockdown sensitized cancer cells to oxidative stress and chemotherapeutic reagents. Our results strongly support the contention that constitutive Nrf2 activation affords cancer cells with undue protection from their inherently stressed microenvironment and anti-cancer treatments. Hence, inactivation of the Nrf2 pathway may represent a therapeutic strategy to reinforce current treatments for malignancy. Congruously, the present study also provides in vivo validation of the two-site substrate recognition model for Nrf2 activation by the Keap1-Cul3-based E3 ligase.

Loss of Keap1 Function Activates Nrf2 and Provides Advantages for Lung Cancer Cell Growth

Abstract: Oxidative and electrophilic stresses are sensed by Keap1, which activates Nrf2 to achieve cytoprotection by regulating the expression of drug-metabolizing and antioxidative stress enzymes/proteins. Because oxidative and electrophilic stresses cause many diseases, including cancer, we hypothesized that an abnormality in the Nrf2-Keap1 system may facilitate the growth of cancer cells. We sequenced the KEAP1 gene of 65 Japanese patients with lung cancer and identified five nonsynonymous somatic mutations at a frequency of 8%. We also identified two nonsynonymous somatic KEAP1 gene mutations and two lung cancer cell lines expressing KEAP1 at reduced levels. In lung cancer cells, low Keap1 activity (due to mutations or low-level expression) led to nuclear localization and constitutive activation of Nrf2. The latter resulted in constitutive expression of cytoprotective genes encoding multidrug resistance pumps, phase II detoxifying enzymes, and antioxidative stress enzymes/proteins. Up-regulation of these target genes in lung cancer cells led to cisplatin resistance. Nrf2 activation also stimulated growth of lung cancer-derived cell lines expressing KEAP1 at low levels and in mutant cell lines and in Keap1-null mouse embryonic fibroblasts under homeostatic conditions. Thus, inhibition of NRF2 may provide new therapeutic approaches in lung cancers with activation of Nrf2.

QCD equation of state with almost physical quark masses

Abstract: We present results on the equation of state in QCD with two light quark flavors and a heavier strange quark. Calculations with improved staggered fermions have been performed on lattices with temporal extent ${N}_{\ensuremath{\tau}}=4$ and 6 on a line of constant physics with almost physical quark mass values; the pion mass is about 220 MeV, and the strange quark mass is adjusted to its physical value. High statistics results on large lattices are obtained for bulk thermodynamic observables, i.e. pressure, energy and entropy density, at vanishing quark chemical potential for a wide range of temperatures, $140\text{ }\text{ }\mathrm{MeV}\ensuremath{\le}T\ensuremath{\le}800\text{ }\text{ }\mathrm{MeV}$. We present a detailed discussion of finite cutoff effects which become particularly significant for temperatures larger than about twice the transition temperature. At these high temperatures we also performed calculations of the trace anomaly on lattices with temporal extent ${N}_{\ensuremath{\tau}}=8$. Furthermore, we have performed an extensive analysis of zero temperature observables including the light and strange quark condensates and the static quark potential at zero temperature. These are used to set the temperature scale for thermodynamic observables and to calculate renormalized observables that are sensitive to deconfinement and chiral symmetry restoration and become order parameters in the infinite and zero quark mass limits, respectively.

Aryl hydrocarbon receptor regulates Stat1 activation and participates in the development of Th17 cells

Abstract: IL-17-producing T helper cells (Th17) have been recently identified as a previously undescribed subset of helper T cells. Here, we demonstrate that aryl hydrocarbon receptor (Ahr) has an important regulatory function in the commitment of Th17 cells. Ahr was robustly induced under Th17-polarizing conditions. Ahr-deficient naive T cells showed a considerable loss in the ability to differentiate into Th17 cells when induced by TGF-β plus IL-6. We were able to demonstrate that Ahr interacts with Stat1 and Stat5, which negatively regulate Th17 development. Whereas Stat1 activation returned to its basal level in Ahr wild type naive T cells 24 h after stimulation with TGF-β plus IL-6, Stat1 remained activated in Ahr-deficient naive T cells after stimulation. These results indicate that Ahr participates in Th17 cell differentiation through regulating Stat1 activation, a finding that constitutes additional mechanisms in the modulation of Th17 cell development.

The amphioxus genome illuminates vertebrate origins and cephalochordate biology

Abstract: Cephalochordates, urochordates, and vertebrates evolved from a common ancestor over 520 million years ago To improve our understanding of chordate evolution and the origin of vertebrates, we intensively searched for particular genes, gene families, and conserved noncoding elements in the sequenced genome of the cephalochordate Branchiostoma floridae, commonly called amphioxus or lancelets Special attention was given to homeobox genes, opsin genes, genes involved in neural crest development, nuclear receptor genes, genes encoding components of the endocrine and immune systems, and conserved cis-regulatory enhancers The amphioxus genome contains a basic set of chordate genes involved in development and cell signaling, including a fifteenth Hox gene This set includes many genes that were co-opted in vertebrates for new roles in neural crest development and adaptive immunity However, where amphioxus has a single gene, vertebrates often have two, three, or four paralogs derived from two whole-genome duplication events In addition, several transcriptional enhancers are conserved between amphioxus and vertebrates--a very wide phylogenetic distance In contrast, urochordate genomes have lost many genes, including a diversity of homeobox families and genes involved in steroid hormone function The amphioxus genome also exhibits derived features, including duplications of opsins and genes proposed to function in innate immunity and endocrine systems Our results indicate that the amphioxus genome is elemental to an understanding of the biology and evolution of nonchordate deuterostomes, invertebrate chordates, and vertebrates

An integrated model for the assessment of global water resources – Part 1: Model description and input meteorological forcing

Abstract: . To assess global water availability and use at a subannual timescale, an integrated global water resources model was developed consisting of six modules: land surface hydrology, river routing, crop growth, reservoir operation, environmental flow requirement estimation, and anthropogenic water withdrawal. The model simulates both natural and anthropogenic water flow globally (excluding Antarctica) on a daily basis at a spatial resolution of 1°×1° (longitude and latitude). This first part of the two-feature report describes the six modules and the input meteorological forcing. The input meteorological forcing was provided by the second Global Soil Wetness Project (GSWP2), an international land surface modeling project. Several reported shortcomings of the forcing component were improved. The land surface hydrology module was developed based on a bucket type model that simulates energy and water balance on land surfaces. The crop growth module is a relatively simple model based on concepts of heat unit theory, potential biomass, and a harvest index. In the reservoir operation module, 452 major reservoirs with >1 km3 each of storage capacity store and release water according to their own rules of operation. Operating rules were determined for each reservoir by an algorithm that used currently available global data such as reservoir storage capacity, intended purposes, simulated inflow, and water demand in the lower reaches. The environmental flow requirement module was newly developed based on case studies from around the world. Simulated runoff was compared and validated with observation-based global runoff data sets and observed streamflow records at 32 major river gauging stations around the world. Mean annual runoff agreed well with earlier studies at global and continental scales, and in individual basins, the mean bias was less than ±20% in 14 of the 32 river basins and less than ±50% in 24 basins. The error in the peak was less than ±1 mo in 19 of the 27 basins and less than ±2 mo in 25 basins. The performance was similar to the best available precedent studies with closure of energy and water. The input meteorological forcing component and the integrated model provide a framework with which to assess global water resources, with the potential application to investigate the subannual variability in water resources.

Physiological significance of reactive cysteine residues of Keap1 in determining Nrf2 activity.

Abstract: Keap1 and Cul3 constitute a unique ubiquitin E3 ligase that degrades Nrf2, a key activator of cytoprotective genes. Upon exposure to oxidants/electrophiles, the enzymatic activity of this ligase complex is inhibited and the complex fails to degrade Nrf2, resulting in the transcriptional activation of Nrf2 target genes. Keap1 possesses several reactive cysteine residues that covalently bond with electrophiles in vitro. To clarify the functional significance of each Keap1 cysteine residue under physiological conditions, we established a transgenic complementation rescue model. The transgenic expression of mutant Keap1(C273A) and/or Keap1(C288A) protein in Keap1 null mice failed to reverse constitutive Nrf2 activation, indicating that cysteine residues at positions 273 and 288 are essential for Keap1 to repress Nrf2 activity in vivo. In contrast, Keap1(C151S) retained repressor activity and mice expressing this molecule were viable. Mouse embryonic fibroblasts from Keap1(C151S) transgenic mice displayed decreased expression of Nrf2 target genes both before and after an electrophilic challenge, suggesting that Cys151 is important in facilitating Nrf2 activation. These results demonstrate critical roles of the cysteine residues in vivo in maintaining Keap1 function, such that Nrf2 is repressed under quiescent conditions and active in response to oxidants/electrophiles.

The Transcription Factor Nrf2 Is a Therapeutic Target against Brain Inflammation

Abstract: Because chronic neuroinflammation is a hallmark of neurodegenerative diseases and compromises neuron viability, it is imperative to discover pharmacologic targets to modulate the activation of immune brain cells, the microglia. In this study, we identify the transcription factor Nrf2, guardian of redox homeostasis, as such target in a model of LPS-induced inflammation in mouse hippocampus. Nrf2 knockout mice were hypersensitive to the neuroinflammation induced by LPS, as determined by an increase in F4/80 mRNA and protein, indicative of an increase in microglial cells, and in the inflammation markers inducible NO synthase, IL-6, and TNF-α, compared with the hippocampi of wild-type littermates. The aliphatic isothiocyanate sulforaphane elicited an Nrf2-mediated antioxidant response in the BV2 microglial cell line, determined by flow cytometry of cells incubated with the redox sensitive probe dihydrodichlorofluorescein diacetate, and by the Nrf2-dependent induction of the phase II antioxidant enzyme heme oxygenase-1. Animals treated with sulforaphane displayed a 2–3-fold increase in heme oxygenase-1, a reduced abundance of microglial cells in the hippocampus and an attenuated production of inflammation markers (inducible NO synthase, IL-6, and TNF-α) in response to LPS. Considering that release of reactive oxygen species is a property of activated microglia, we propose a model in which late induction of Nrf2 intervenes in the down-regulation of microglia. This study opens the possibility of targeting Nrf2 in brain as a means to modulate neuroinflammation.

Stellar Abundances for the Galactic Archeology (SAGA) Database — Compilation of the Characteristics of Known Extremely Metal-Poor Stars

Abstract: We describe the construction of a database of extremely metal-poor (EMP) stars in the Galaxy. Our database contains detailed elemental abundances, reported equivalent widths, atmospheric parameters, photometry, and binarity status, compiled from papers in the literature that report on studies of EMP halo stars with [Fe=H] �� 2.5. The compilation procedures for this database were designed to assemble data effectively from electronic tables available from online journals. We have also developed ad ata retrieval system that enables data searches by various criteria and illustrations to explore relationships between stored variables. Currently, our sample includes 1212 unique stars (many of which are studied by more than one group) with more than 15000 individual reported elemental abundances, covering relevant papers published by 2007 December. We discuss the global characteristics of the present database, as revealed by the EMP stars observed to date. For stars with [Fe=H] �� 2.5, the number of giants with reported abundances is larger than that of dwarfs by a factor of two. The fraction of carbon-rich stars (among the sample for which the carbon abundance is reported) amounts to � 30% for [Fe=H] �� 2.5. We find that known binaries exhibit different distributions of the orbital period, according to whether they are giants or dwarfs, and also as a function of the metallicity, although the total sample of such stars is still quite small.

The Stellar Abundances for Galactic Archeology (SAGA) Database - Compilation of the Characteristics of Known Extremely Metal-Poor Stars

Abstract: We describe the construction of a database of extremely metal-poor (EMP) stars in the Galactic halo whose elemental abundances have been determined. Our database contains detailed elemental abundances, reported equivalent widths, atmospheric parameters, photometry, and binarity status, compiled from papers in the recent literature that report studies of EMP halo stars with [Fe/H] < -2.5. The compilation procedures for this database have been designed to assemble the data effectively from electronic tables available from online journals. We have also developed a data retrieval system that enables data searches by various criteria, and permits the user to explore relationships between the stored variables graphically. Currently, our sample includes 1212 unique stars (many of which are studied by more than one group) with more than 15000 individual reported elemental abundances, covering all of the relevant papers published by December 2007. We discuss the global characteristics of the present database, as revealed by the EMP stars observed to date. For stars with [Fe/H] < -2.5, the number of giants with reported abundances is larger than that of dwarfs by a factor of two. The fraction of carbon-rich stars (among the sample for which the carbon abundance is reported) amount to ~30 % for [Fe/H] < -2.5. We find that known binaries exhibit different distributions of orbital period, according to whether they are giants or dwarfs, and also as a function of metallicity, although the total sample of such stars is still quite small.

High incidence of aspiration pneumonia in community- and hospital-acquired pneumonia in hospitalized patients: a multicenter, prospective study in Japan.

Abstract: point that there is no high-level evidence of which vitamin D metabolites are safer and faster in normalizing sHPTH, and more importantly, the optimal dose of vitamin D3 capable of normalizing rapidly sHPTH is still being discussed and has not been established. In addition, a number of studies have demonstrated that the commonly used doses of vitamin D ( 800 UI daily), also suggested by the drug industry, may fail to normalize PTH levels in older adults with sHPTH. The choice of calcitriol in the experimental design of our study was based mainly on the need to use a treatment that could rapidly resolve sHPTH and on the lack of available preparation of vitamin D3 at high concentrations in Italy at the time of the study. In conclusion, although we agree with the statement that plain vitamin D is the treatment of choice for vitamin D deficiency, we disagree with the interpretation of the manuscript given by Dr. Vieth, because the goal of identifying a treatment of choice for sHPTH was outside the scope of our study, whose most relevant outcome consists instead of the observation that persistence of sHPTH reduces BMD response to alendronate. To respond to the issue raised by Dr. Vieth, RCTs are needed to assess the vitamin D metabolite of choice in normalizing PTH.

Genetic variation in PSCA is associated with susceptibility to diffuse-type gastric cancer.

Abstract: Gastric cancer is classified into intestinal and diffuse types, the latter including a highly malignant form, linitis plastica. A two-stage genome-wide association study (stage 1: 85,576 SNPs on 188 cases and 752 references; stage 2: 2,753 SNPs on 749 cases and 750 controls) in Japan identified a significant association between an intronic SNP (rs2976392) in PSCA (prostate stem cell antigen) and diffuse-type gastric cancer (allele-specific odds ratio (OR) = 1.62, 95% CI = 1.38-1.89, P = 1.11 x 10(-9)). The association was far less significant in intestinal-type gastric cancer. We found that PSCA is expressed in differentiating gastric epithelial cells, has a cell-proliferation inhibition activity in vitro and is frequently silenced in gastric cancer. Substitution of the C allele with the risk allele T at a SNP in the first exon (rs2294008, which has r(2) = 0.995, D' = 0.999 with rs2976392) reduces transcriptional activity of an upstream fragment of the gene. The same risk allele was also significantly associated with diffuse-type gastric cancer in 457 cases and 390 controls in Korea (allele-specific OR = 1.90, 95% CI = 1.56-2.33, P = 8.01 x 10(-11)). The polymorphism of the PSCA gene, which is possibly involved in regulating gastric epithelial-cell proliferation, influences susceptibility to diffuse-type gastric cancer.

An integrated model for the assessment of global water resources - Part 2: Applications and assessments

Abstract: . To assess global water resources from the perspective of subannual variation in water availability and water use, an integrated water resources model was developed. In a companion report, we presented the global meteorological forcing input used to drive the model and six modules, namely, the land surface hydrology module, the river routing module, the crop growth module, the reservoir operation module, the environmental flow requirement module, and the anthropogenic withdrawal module. Here, we present the results of the model application and global water resources assessments. First, the timing and volume of simulated agriculture water use were examined because agricultural use composes approximately 85% of total consumptive water withdrawal in the world. The estimated crop calendar showed good agreement with earlier reports for wheat, maize, and rice in major countries of production. In major countries, the error in the planting date was ±1 mo, but there were some exceptional cases. The estimated irrigation water withdrawal also showed fair agreement with country statistics, but tended to be underestimated in countries in the Asian monsoon region. The results indicate the validity of the model and the input meteorological forcing because site-specific parameter tuning was not used in the series of simulations. Finally, global water resources were assessed on a subannual basis using a newly devised index. This index located water-stressed regions that were undetected in earlier studies. These regions, which are indicated by a gap in the subannual distribution of water availability and water use, include the Sahel, the Asian monsoon region, and southern Africa. The simulation results show that the reservoir operations of major reservoirs (>1 km3) and the allocation of environmental flow requirements can alter the population under high water stress by approximately −11% to +5% globally. The integrated model is applicable to assessments of various global environmental projections such as climate change.

Lignin degradation in wood-feeding insects

Abstract: The aromatic polymer lignin protects plants from most forms of microbial attack Despite the fact that a significant fraction of all lignocellulose degraded passes through arthropod guts, the fate of lignin in these systems is not known Using tetramethylammonium hydroxide thermochemolysis, we show lignin degradation by two insect species, the Asian longhorned beetle (Anoplophora glabripennis) and the Pacific dampwood termite (Zootermopsis angusticollis) In both the beetle and termite, significant levels of propyl side-chain oxidation (depolymerization) and demethylation of ring methoxyl groups is detected; for the termite, ring hydroxylation is also observed In addition, culture-independent fungal gut community analysis of A glabripennis identified a single species of fungus in the Fusarium solani/Nectria haematococca species complex This is a soft-rot fungus that may be contributing to wood degradation These results transform our understanding of lignin degradation by wood-feeding insects

Suppression Pattern of Neutral Pions at High Transverse Momentum in Au plus Au Collisions at root S-NN=200 GeV and Constraints on Medium Transport Coefficients

Abstract: For Au + Au collisions at 200 GeV, we measure neutral pion production with good statistics for transverse momentum, p(T), up to 20 GeV/c. A fivefold suppression is found, which is essentially constant for 5 in the parton quenching model. The spectral shape is similar for all collision classes, and the suppression does not saturate in Au + Au collisions.

Genetic redundancy in soybean photoresponses associated with duplication of the phytochrome A gene.

Abstract: Gene and genome duplications underlie the origins of evolutionary novelty in plants. Soybean, Glycine max, is considered to be a paleopolyploid species with a complex genome. We found multiple homologs of the phytochrome A gene (phyA) in the soybean genome and determined the DNA sequences of two paralogs designated GmphyA1 and GmphyA2. Analysis of the GmphyA2 gene from the lines carrying a recessive allele at a photoperiod insensitivity locus, E4, revealed that a Ty1/copia-like retrotransposon was inserted in exon 1 of the gene, which resulted in dysfunction of the gene. Mapping studies suggested that GmphyA2 is encoded by E4. The GmphyA1 gene was mapped to a region of linkage group O, which is homeologous to the region harboring E4 in linkage group I. Plants homozygous for the e4 allele were etiolated under continuous far red light, but the de-etiolation occurred partially, indicating that the mutation alone did not cause a complete loss of phyA function. The genetic redundancy suggests that the presence of duplicated copies of phyA genes accounts for the generation of photoperiod insensitivity, while protecting against the deleterious effects of mutation. Thus, this phenomenon provides a link between gene duplication and establishment of an adaptive response of plants to environments.

Clinical practice guidelines for gastrointestinal stromal tumor (GIST) in Japan: English version

Abstract: Diagnostic and treatment strategies for gastrointestinal stromal tumors (GISTs) have evolved greatly since the introduction of molecularly targeted therapies. Although several clinical practice guidelines are extant, such as those published by the National Comprehensive Cancer Network and the European Society of Medical Oncology, it is not clear as to whether these are appropriate for clinical practice in Japan. Therefore, clinical practice guidelines for the optimal diagnosis and treatment of GIST tailored for the Japanese situation have often been requested. For this reason, the Japanese Clinical Practice Guideline for GIST was proposed by the GIST Guideline Subcommittee, with the official approval of the Clinical Practice Guidelines Committee for Cancer of the Japan Society of Clinical Oncology (JSCO), and was published after assessment by the Guideline Evaluation Committee of JSCO. The GIST Guideline Subcommittee consists of members from JSCO, the Japanese Gastric Cancer Association (JGCA), and the Japanese Study Group on GIST, with the official approval of these organizations. The GIST Guideline Subcommittee is not influenced by any other organizations or third parties. Revision of the guideline may be done periodically, with the approval of the GIST Guideline Subcommittee, either every 3 years or when important new evidence that might alter the optimal diagnosis and treatment of GIST emerges. Here we present the English version of the Japanese Clinical Practice Guideline for GIST prepared by the GIST Guideline Subcommittee.

Frost weathering: recent advances and future directions

Abstract: This paper reviews frost-weathering studies in the last five years and proposes key questions to be answered. New techniques have enabled us to monitor moisture contents and crack movements in near-surface hard jointed bedrock and to evaluate seasonal rockfall activity in high mountains. Field monitoring has highlighted the roles of diurnal and annual frost cycles in controlling the timing and magnitude of frost weathering. In the laboratory, bidirectional freezing in soft, porous rocks has produced fractures containing segregated ice layers near the permafrost table, which imply the development of ice-filled fractures in permafrost bedrock over long time-scales. This finding, combined with numerical modelling of the thermal regime in permafrost rock slopes, contributes to the prediction of large-scale rockfalls and rock avalanches triggered by permafrost degradation. Future studies should also focus on explosive shattering, frost weathering of hard-intact rocks, field monitoring of ice segregation and bedrock heave, and the role of frost weathering in landscape evolution.

Longitudinal effects of violent video games on aggression in Japan and the United States.

Abstract: CONTEXT. Youth worldwide play violent video games many hours per week. Previous research suggests that such exposure can increase physical aggression. OBJECTIVE. We tested whether high exposure to violent video games increases physical aggression over time in both high- (United States) and low- (Japan) violence cultures. We hypothesized that the amount of exposure to violent video games early in a school year would predict changes in physical aggressiveness assessed later in the school year, even after statistically controlling for gender and previous physical aggressiveness. DESIGN. In 3 independent samples, participants’ video game habits and physically aggressive behavior tendencies were assessed at 2 points in time, separated by 3 to 6 months. PARTICIPANTS. One sample consisted of 181 Japanese junior high students ranging in age from 12 to 15 years. A second Japanese sample consisted of 1050 students ranging in age from 13 to 18 years. The third sample consisted of 364 United States 3rd-, 4th-, and 5th-graders ranging in age from 9 to 12 years. RESULTS. Habitual violent video game play early in the school year predicted later aggression, even after controlling for gender and previous aggressiveness in each sample. Those who played a lot of violent video games became relatively more physically aggressive. Multisample structure equation modeling revealed that this longitudinal effect was of a similar magnitude in the United States and Japan for similar-aged youth and was smaller (but still significant) in the sample that included older youth. CONCLUSIONS. These longitudinal results confirm earlier experimental and cross-sectional studies that had suggested that playing violent video games is a significant risk factor for later physically aggressive behavior and that this violent video game effect on youth generalizes across very different cultures. As a whole, the research strongly suggests reducing the exposure of youth to this risk factor. Pediatrics 2008;122: e1067–e1072

The Arabidopsis Histone Deacetylases HDA6 and HDA19 Contribute to the Repression of Embryonic Properties after Germination

Abstract: Histone deacetylase (HDAC) is a chromatin-remodeling factor that contributes to transcriptional repression in eukaryotes. In Arabidopsis (Arabidopsis thaliana), the transcription factors LEAFY COTYLEDON1 (LEC1), FUSCA3 (FUS3), and ABSCISIC ACID INSENSITIVE3 (ABI3) play key roles in embryogenesis. Although the repression of embryogenesis-related genes during germination has been proposed to occur, the role of HDAC in this process has not been elucidated. To address this question, the effects of an HDAC inhibitor and suppression of the Arabidopsis HDAC genes on this process were investigated. Here, we show that treatment of an HDA6 repression line with the HDAC inhibitor trichostatin A resulted in growth arrest and elevated transcription of LEC1, FUS3, and ABI3 during germination. The growth-arrest phenotype of the repression line was suppressed by lec1, fus3, and abi3. An HDA6/HDA19 double-repression line displayed arrested growth after germination and the formation of embryo-like structures on the true leaves of 6-week-old plants even without trichostatin A. The growth-arrest phenotype of this line was rescued by lec1. These results suggest that during germination in Arabidopsis, HDA6 and HDA19 redundantly regulate the repression of embryonic properties directly or indirectly via repression of embryo-specific gene function.

Distributed Self-Reconfiguration of M-TRAN III Modular Robotic System

Abstract: A new prototype of a self-reconfigurable modular robot, M-TRAN III, has been developed, with an improved fast and rigid connection mechanism. Using a distributed controller, various control modes are possible: single-master, globally synchronous control or parallel asynchronous control. Self-reconfiguration experiments using up to 24 modules were undertaken by centralized or decentralized control. Experiments using decentralized control examined a modular structure moved in a given direction as a flow produced by local self-reconfigurations. In all experiments, system homogeneity and scalability were maintained: modules used identical software except for their ID numbers. Identical self-reconfiguration was realized when different modules were used in initial configurations.