Details of a Researcher - Tomita, Masaru

Papers - Tomita, Masaru

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Modeling and simulation of developmental changes in contractile apparatus of ventricular cells

Takiguchi M., Toki T., Sano H., Naito Y., Tomita M.

Computing in Cardiology 42 1097 - 1100 2015.02

ISSN 23258861

During development, ventricular cells utilize different isoforms of both myosin heavy chain (MHC) and troponin I. The differences in these isoforms affect Ca2+ sensitivity, ATPase activity, and velocity of contraction. In order to consider the differences in isoforms, we integrated a new contraction model with the Kyoto model. Briefly, the new model considered tropomyosin, which inhibits formation of a cross-bridge between actin and myosin filaments. We varied the level of Ca2+ sensitivity in order to obtain similar traces for contractile force between the original Kyoto model and the modified model. We also modified the new contraction model to consider ATP consumption by myosin-ATPase in order to simulate the changes in ATPase activity caused by the difference in MHC isoforms. The modified model enabled us to compare the contribution of developmental changes in ATP consumption via contraction to excitation-contraction coupling, which is regulated differently in fetal and adult Guinea pigs.

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Sensitivity analysis of ectopic electrical activity in the pulmonary vein myocardium

Sano H., Tanaka Y., Naito Y., Tomita M.

Computing in Cardiology 42 861 - 864 2015.02

ISSN 23258861

The pulmonary vein contains a myocardial layer that is capable of generating spontaneous or triggered action potentials. Although the electrophysiological and pharmacological characteristics of the pulmonary vein myocardium have been compiled in various studies, a comprehensive understanding of the spontaneous action potentials generated in the myocardial layer has yet to be presented. Here we integrated the electrophysiological properties of the pulmonary vein myocardial layer using a Guinea pig ventricular cell model. Based on the preceding research, which reported that approximately half of the isolated pulmonary vein myocardial layer exhibited spontaneous action potentials and the remaining half was quiescent, we constructed various combinations of the pulmonary vein myocardial models to represent variations of the action potential tracings. As a result, we predicted that the spontaneous action potentials, including burst-like action potentials, are observed with varying currents of the relative densities of Na+ (INa), L-type Ca2+ (ICaL), inwardly rectifying K+ (IK1), rapid component of delayed rectifying K+ (IKr), and ACh-activated K+ (IKACh).

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Identification, expression, and molecular evolution of microRNAs in the "living fossil" Triops cancriformis (tadpole shrimp)

Ikeda K., Hirose Y., Hiraoka K., Noro E., Fujishima K., Tomita M., Kanai A.

RNA (RNA) 21 ( 2 ) 230 - 242 2015.02

ISSN 13558382

MicroRNAs have been identified and analyzed in various model species, but an investigation of miRNAs in nonmodel species is required for a more complete understanding of miRNA evolution. In this study, we investigated the miRNAs of the nonmodel species Triops cancriformis (tadpole shrimp), a "living fossil," whose morphological form has not changed in almost 200 million years. Dramatic ontogenetic changes occur during its development. To clarify the evolution of miRNAs, we comparatively analyzed its miRNAs and the components of its RNAi machinery. We used deep sequencing to analyze small RNA libraries from the six different developmental stages of T. cancriformis (egg, first- fourth instars, and adult), and also analyzed its genomic DNA with deep sequencing. We identified 180 miRNAs (87 conserved miRNAs and 93 novel candidate miRNAs), and deduced the components of its RNAi machinery: the DICER1, AGO1-3, PIWI, and AUB proteins. A comparative miRNA analysis of T. cancriformis and Drosophila melanogaster showed inconsistencies in the expression patterns of four conserved miRNAs. This suggests that although the miRNA sequences of the two species are very similar, their roles differ across the species. An miRNA conservation analysis revealed that most of the conserved T. cancriformis miRNAs share sequence similarities with those of arthropods, although T. cancriformis is called a "living fossil." However, we found that let- 7 and DICER1 of T. cancriformis are more similar to those of the vertebrates than to those of the arthropods. These results suggest that miRNA systems of T. cancriformis have evolved in a unique fashion.

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A Generic Software Platform for Brain-inspired Cognitive Computing

Takahashi, K., Itaya, K., Nakamura, M., Koizumi, M., Arakawa, N., Tomita, M. and Yamakawa, H.

Procedia Computer Science 71 31 - 37 2015

Joint Work

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Analysis of genetic code ambiguity arising from nematode-specific misacylated tRNAs

Hamashima, K., Mori, M., Andachi, Y., Yuji Kohara, Y., M. and Kanai, A.

PLoS ONE (PLoS ONE) 10 ( 1 ) e0116981 2015

Joint Work

The faithful translation of the genetic code requires the highly accurate aminoacylation of transfer RNAs (tRNAs). However, it has been shown that nematode-specific V-arm-containing tRNAs (nev-tRNAs) are misacylated with leucine in vitro in a manner that transgresses the genetic code. nev-tRNAGly (CCC) and nev-tRNAIle (UAU), which are the major nev-tRNA isotypes, could theoretically decode the glycine (GGG) codon and isoleucine (AUA) codon as leucine, causing GGG and AUA codon ambiguity in nematode cells. To test this hypothesis, we investigated the functionality of nev-tRNAs and their impact on the proteome of Caenorhabditis elegans. Analysis of the nucleotide sequences in the 3' end regions of the nev-tRNAs showed that they had matured correctly, with the addition of CCA, which is a crucial posttranscriptional modification required for tRNA aminoacylation. The nuclear export of nev-tRNAs was confirmed with an analysis of their subcellular localization. These results show that nev-tRNAs are processed to their mature forms like common tRNAs and are available for translation. However, a whole-cell proteome analysis found no detectable level of nev-tRNA-induced mistranslation in C. elegans cells, suggesting that the genetic code is not ambiguous, at least under normal growth conditions. Our findings indicate that the translational fidelity of the nematode genetic code is strictly maintained, contrary to our expectations, although deviant tRNAs with misacylation properties are highly conserved in the nematode genome.

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Alteration of metabolomic profiles by titanium dioxide nanoparticles in human gingivitis model

Garcia-Contreras, R., Sugimoto, M., Umemura, N., Kaneko, M., Hatakeyama, Y., Soga, T., Tomita, M., Scougall-Vilchis, R., J., Contreras-Bulnes, R., Nakajima, H. and *Sakagami, H.

Biomaterials (Biomaterials) 57 33 - 40 2015

Joint Work, ISSN 01429612

Although nanoparticles (NPs) has afforded considerable benefits in various fields of sciences, several reports have shown their harmful effects, suggesting the necessity of adequate risk assessment. To clarify the mechanism of titanium dioxide nanoparticles (TiO<inf>2</inf> NPs)-enhanced gingival inflammation, we conducted the full-scale metabolomic analyses of human gingival fibroblast cells treated with IL-1β alone or in combination with TiO<inf>2</inf> NPs. Observation with transmission electron microscope demonstrated the incorporation of TiO<inf>2</inf> NPs into vacuoles of the cells. TiO<inf>2</inf> NPs significantly enhanced the IL-1β-induced prostaglandin E<inf>2</inf> production and COX-1 and COX-2 protein expression. IL-1β reduced the intracellular concentrations of overall primary metabolites especially those of amino acid, urea cycle, polyamine, S-adenosylmethione and glutathione synthetic pathways. The addition of TiO<inf>2</inf> NPs further augmented these IL-1β-induced metabolic changes, recommending careful use of dental materials containing TiO<inf>2</inf> NPs towards patients with gingivitis or periodontitis. The impact of the present study is to identify the molecular targets of TiO<inf>2</inf> NPs for the future establishment of new metabolic markers and therapeutic strategy of gingival inflammation.

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Method of preparing an equimolar DNA mixture for one-step DNA assembly of over 50 fragments

Tsuge, K., Sato, Y., Kobayashi, Y., Gondo, M., Hasebe, M., Togashi, T., Tomita, M. and Itaya, M.

Scientific Reports (Scientific Reports) 5 10655 2015

Joint Work

In the era of synthetic biology, techniques for rapidly constructing a designer long DNA from short DNA fragments are desired. To realize this, we attempted to establish a method for one-step DNA assembly of unprecedentedly large numbers of fragments. The basic technology is the Ordered Gene Assembly in Bacillus subtilis (OGAB) method, which uses the plasmid transformation system of B. subtilis. Since this method doesn' t require circular ligation products but needs tandem repeat ligation products, the degree of deviation in the molar concentration of the material DNAs is the only determinant that affects the efficiency of DNA assembly. The strict standardization of the size of plasmids that clone the DNA block and the measurement of the block in the state of intact plasmid improve the reliability of this step, with the coefficient of variation of the molar concentrations becoming 7%. By coupling this method with the OGAB method, one-step assembly of more than 50 DNA fragments becomes feasible.

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Effects of processing and storage conditions on charged metabolomic profiles in blood

Hirayama, A., Sugimoto, M., Suzuki, A., Hatakeyama, Y., Enomoto, A., Harada, S., Soga, T., Tomita, M. and Takebayashi, T.

Electrophoresis (Electrophoresis) 36 ( 18 ) 2148 - 2155 2015

Joint Work, ISSN 01730835

The development of high-throughput metabolite measurement technologies has enabled the use of metabolomics for epidemiologic studies by profiling metabolite concentrations in large cohorts of human blood samples. Standard protocols are necessary to obtain unbiased profiles through multiple runs over long periods of time and to allow reliable statistical analyses. This study assessed the effects of sampling procedures and storage conditions on the stability of metabolomic profiles in plasma and serum. Charged metabolomic profiles were determined by capillary electrophoresis-mass spectrometry (CE-MS) and compared by multivariate analyses. The effects of pre-analytical procedures, including times for clotting and incubation of serum and plasma, respectively; incubation temperatures; and number of freeze-thaw cycles, were assessed. Overall, inter-individual differences in profiles were larger than intra-individual differences, and profiles in plasma showed better stability than those in serum. These quantified datasets of metabolites, along with their stability and variation, may help in interpreting data from long-term cohort studies.

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Metabolomic alterations in human cancer cells by Vitamin C-induced oxidative stress

Uetaki M., Tabata S., Nakasuka F., Soga T., Tomita M.

Scientific Reports (Scientific Reports) 5 13896 2015

Joint Work

Intravenous administration of high-dose vitamin C has recently attracted attention as a cancer therapy. High-dose vitamin C induces pro-oxidant effects and selectively kills cancer cells. However, the anticancer mechanisms of vitamin C are not fully understood. Here, we analyzed metabolic changes induced by vitamin C in MCF7 human breast adenocarcinoma and HT29 human colon cancer cells using capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS). The metabolomic profiles of both cell lines were dramatically altered after exposure to cytotoxic concentrations of vitamin C. Levels of upstream metabolites in the glycolysis pathway and tricarboxylic acid (TCA) cycle were increased in both cell lines following treatment with vitamin C, while adenosine triphosphate (ATP) levels and adenylate energy charges were decreased concentration-dependently. Treatment with N-acetyl cysteine (NAC) and reduced glutathione (GSH) significantly inhibited vitamin C-induced cytotoxicity in MCF7 cells. NAC also suppressed vitamin C-dependent metabolic changes, and NAD treatment prevented vitamin C-induced cell death. Collectively, our data suggests that vitamin C inhibited energy metabolism through NAD depletion, thereby inducing cancer cell death.

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Comprehensive analysis of microbes and metabolites in human tear fluids

Murakami, S., Baba, F., Fukuda, S., Soga, T., Fujishima, H. and Tomita, M.

KEIO SFC JOURNAL 382 - 400 2015

Joint Work

Particle Simulation of Oxidation Induced Band 3 Clustering in Human Erythrocytes

Shimo H., Arjunan S.N.V., Machiyama H., Nishino T., Suematsu M., Fujita H., Tomita M., Takahashi K.

PLoS Computational Biology (PLoS Computational Biology) 11 ( 6 ) e1004210 2015

Joint Work, ISSN 1553734X

Oxidative stress mediated clustering of membrane protein band 3 plays an essential role in the clearance of damaged and aged red blood cells (RBCs) from the circulation. While a number of previous experimental studies have observed changes in band 3 distribution after oxidative treatment, the details of how these clusters are formed and how their properties change under different conditions have remained poorly understood. To address these issues, a framework that enables the simultaneous monitoring of the temporal and spatial changes following oxidation is needed. In this study, we established a novel simulation strategy that incorporates deterministic and stochastic reactions with particle reaction-diffusion processes, to model band 3 cluster formation at single molecule resolution. By integrating a kinetic model of RBC antioxidant metabolism with a model of band 3 diffusion, we developed a model that reproduces the time-dependent changes of glutathione and clustered band 3 levels, as well as band 3 distribution during oxidative treatment, observed in prior studies. We predicted that cluster formation is largely dependent on fast reverse reaction rates, strong affinity between clustering molecules, and irreversible hemichrome binding. We further predicted that under repeated oxidative perturbations, clusters tended to progressively grow and shift towards an irreversible state. Application of our model to simulate oxidation in RBCs with cytoskeletal deficiency also suggested that oxidation leads to more enhanced clustering compared to healthy RBCs. Taken together, our model enables the prediction of band 3 spatio-temporal profiles under various situations, thus providing valuable insights to potentially aid understanding mechanisms for removing senescent and premature RBCs.

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Precise mapping and dynamics of tRNA-derived fragments (tRFs) in the development of Triops cancriformis (tadpole shrimp)

Hirose Y., Ikeda K., Noro E., Hiraoka K., Tomita M., Kanai A.

BMC Genetics (BMC Genetics) 16 ( 1 ) 83 2015

Joint Work

Background: In a deep sequencing analysis of small RNAs prepared from a living fossil, the tadpole shrimp Triops cancriformis, a 32-nt small RNA was specifically detected in the adult stage. A nucleotide sequence comparison between the 32-nt small RNA and predicted tRNA sequences in the draft nuclear genomic DNA showed that the small RNA was derived from tRNAGly(GCC). To determine the overall features of the tRNA-derived fragments (tRFs) of T. cancriformis, the small RNA sequences in each of the six developmental stages (egg, 1st - 4th instar larvae, and adult) were compared with the mitochondrial and nuclear tRNA sequences. Results: We found that the tRFs were derived from mitochondrial and nuclear tRNAs corresponding to 16 and 39 anticodons, respectively. The total read number of nuclear tRFs was approximately 400 times larger than the number of mitochondrial tRFs. Interestingly, the main regions in each parental tRNA from which these tRFs were derived differed, depending on the parental anticodon. Mitochondrial tRFSer(GCU)s were abundantly produced from the 5' half regions of the parental tRNA, whereas mitochondrial tRFVal(UAC)s were mainly produced from the 3' end regions. Highly abundant nuclear tRFs, tRFGly(GCC)s, tRFGly(CCC)s, tRFGlu(CUC)s, and tRFLys(CUU)s were derived from the 5' half regions of the parental tRNAs. Further analysis of the tRF read counts in the individual developmental stages suggested that the expression of mitochondrial and nuclear tRFs differed during the six stages. Based on these data, we precisely summarized the positions of the tRFs in their parental tRNAs and their expression changes during development. Conclusions: Our results reveal the entire dynamics of the tRFs from both the nuclear and mitochondrial genomes of T. cancriformis and indicate that the majority of tRFs in the cell are derived from nuclear tRNAs. This study provides the first examples of developmentally expressed mitochondrial tRFs.

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Effects of 3-styrylchromones on metabolic profiles and cell death in oral squamous cell carcinoma cells

Sakagami, H., Shimada, C., Kanda, Y., Amano, O., Sugimoto, M., Ota, S., Soga, T., Tomita, M., Sato, A., Tanuma, S., Takao, K., and Sugita, Y.

Toxicology Reports (Toxicology Reports) 2 1281 - 1290 2015

Joint Work, ISSN 22147500

4H-1-benzopyran-4-ones (chromones) are important naturally-distributing compounds. As compared with flavones, isoflavones and 2-styrylchromones, there are only few papers of 3-styrylchromones that have been published. We have previously reported that among fifteen 3-styrylchromone derivatives, three new synthetic compounds that have OCH3 group at the C-6 position of chromone ring, (E)-3-(4-hydroxystyryl)-6-methoxy-4H-chromen-4-one (compound 11), (E)-6-methoxy-3-(4-methoxystyryl)-4H-chromen-4-one (compound 4), (E)-6-methoxy-3-(3,4,5-trimethoxystyryl)-4H-chromen-4-one (compound 6) showed much higher cytotoxicities against four epithelial human oral squamous cell carcinoma (OSCC) lines than human normal oral mesenchymal cells. In order to further confirm the tumor specificities of these compounds, we compared their cytotoxicities against both human epithelial malignant and non-malignant cells, and then investigated their effects on fine cell structures and metabolic profiles and cell death in human OSCC cell line HSC-2. Cytotoxicities of compounds 4, 6, 11 were assayed with MTT method. Fine cell structures were observed under transmission electron microscope. Cellular metabolites were extracted with methanol and subjected to CE-TOFMS analysis. Compounds 4, 6, 11 showed much weaker cytotoxicity against human oral keratinocyte and primary human gingival epithelial cells, as compared with HSC-2, confirming their tumor-specificity, whereas doxorubicin and 5-FU were highly cytotoxic to these normal epithelial cells, giving unexpectedly lower tumor-specificity. The most cytotoxic compound 11, induced the mitochondrial vacuolization, autophagy suppression followed by apoptosis induction, and changes in the metabolites involved in amino acid and glycerophospholipid metabolisms. Chemical modification of lead compound 11 may be a potential choice for designing new type of anticancer drugs.

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The Consumption of Bicarbonate-Rich Mineral Water Improves Glycemic Control

Murakami S, Goto Y, Ito K, Hayasaka S, Kurihara S, Soga T, Tomita M, Fukuda S.

Evid Based Complement Alternat Med. (Evidence-based Complementary and Alternative Medicine) 2015 10 2015

ISSN 1741427X

Hot spring water and natural mineral water have been therapeutically used to prevent or improve various diseases. Specifically, consumption of bicarbonate-rich mineral water (BMW) has been reported to prevent or improve type 2 diabetes (T2D) in humans. However, the molecular mechanisms of the beneficial effects behind mineral water consumption remain unclear. To elucidate the molecular level effects of BMW consumption on glycemic control, blood metabolome analysis and fecal microbiome analysis were applied to the BMW consumption test. During the study, 19 healthy volunteers drank 500 mL of commercially available tap water (TW) or BMW daily. TW consumption periods and BMW consumption periods lasted for a week each and this cycle was repeated twice. Biochemical tests indicated that serum glycoalbumin levels, one of the indexes of glycemic controls, decreased significantly after BMW consumption. Metabolome analysis of blood samples revealed that 19 metabolites including glycolysis-related metabolites and 3 amino acids were significantly different between TW and BMW consumption periods. Additionally, microbiome analysis demonstrated that composition of lean-inducible bacteria was increased after BMW consumption. Our results suggested that consumption of BMW has the possible potential to prevent and/or improve T2D through the alterations of host metabolism and gut microbiota composition.

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G-Links: A gene-centric link acquisition service

Arakawa K., Oshita K., Tomita M.

F1000Research (F1000Research) 3 285 2015

ISSN 20461402

With the availability of numerous curated databases, researchers are now able to efficiently use the multitude of biological data by integrating these resources via hyperlinks and cross-references. A large proportion of bioinformatics research tasks, however, may include labor-intensive tasks such as fetching, parsing, and merging datasets and functional annotations from distributed multi-domain databases. This data integration issue is one of the key challenges in bioinformatics. We aim to provide an identifier conversion and data aggregation system as a part of solution to solve this problem with a service named G-Links, 1) by gathering resource URI information from 130 databases and 30 web services in a gene-centric manner so that users can retrieve all available links about a given gene, 2) by providing RESTful API for easy retrieval of links including facet searching based on keywords and/or predicate types, and 3) by producing a variety of outputs as visual HTML page, tab-delimited text, and in Semantic Web formats such as Notation3 and RDF. G-Links as well as other relevant documentation are available at http://link.g-language.org/.

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Taxonomic reassessment of strains formerly classified as chloromonas insignis (Volvocales, chlorophyceae) and description of Gloeomonas anomalipyrenoides sp. nov.

Nakada T., Matsuzaki R., Krienitz L., Tomita M., Nozaki H.

Acta Phytotaxonomica et Geobotanica 66 ( 1 ) 23 - 33 2015

ISSN 13467565

Two strains previously identified as Chloromonas insignis, NIES-447 and ACOI-3241, and two new strains related to NIES-447 were examined using light microscopy. The molecular phylogeny of their 18S rRNA gene sequences were also examined, and their identifications are reassessed. The strains represent two independent species, both of which can be distinguished from Chloromonas insignis. Strain NIES-447 and the two new strains each have large, irregular atypical pyrenoids without associated starch granules. They are described here as Gloeomonas anomalipyrenoides Nakada et al. sp. nov. Strain ACOI-3241, which has small atypical pyrenoids on the tips of the chloroplast lobes, was identified as C. vernalis (Skuja) Nakada comb. nov. The identity of the three strains of G. anomalipyrenoides was verified by their identical ITS-2 rDNA sequences. Both G. anomalipyrenoides and C. vernalis of the clade Chloromonadinia in the Volvocales (Chlorophyceae) are closely related to other species of Gloeomonas and to C. kasaiae Matsuzaki, Nakada, Y. Hara & Nozaki, respectively.

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Systems biology strategy reveals PKCd is key for sensitizing TRAIL-resistant human fibrosarcoma

Hayashi K., Tabata S., Piras V., Tomita M., Selvarajoo K.

Frontiers in Immunology (Frontiers in Immunology) 6 ( JAN ) 659 2015

ISSN 1664-3224

Cancer cells are highly variable and largely resistant to therapeutic intervention. Recently, the use of the tumor necrosis factor related apoptosis-inducing ligand (TRAIL) induced treatment is gaining momentum due to TRAIL's ability to specifically target cancers with limited effect on normal cells. Nevertheless, several malignant cancer types still remain non-sensitive to TRAIL. Previously, we developed a dynamic computational model, based on perturbation-response differential equations approach, and predicted protein kinase C (PKC) as the most effective target, with over 95% capacity to kill human fibrosarcoma (HT1080) in TRAIL stimulation (1). Here, to validate the model prediction, which has significant implications for cancer treatment, we conducted experiments on two TRAIL-resistant cancer cell lines (HT1080 and HT29). Using PKC inhibitor bisindolylmaleimide I, we demonstrated that cell viability is significantly impaired with over 95% death of both cancer types, in consistency with our previous model. Next, we measured caspase-3, Poly (ADP-ribose) polymerase (PARP), p38, and JNK activations in HT1080, and confirmed cell death occurs through apoptosis with significant increment in caspase-3 and PARP activations. Finally, to identify a crucial PKC isoform, from 10 known members, we analyzed each isoform mRNA expressions in HT1080 cells and shortlisted the highest 4 for further siRNA knock-down (KD) experiments. From these KDs, PKCd produced the most cancer cell death in conjunction with TRAIL. Overall, our approach combining model predictions with experimental validation holds promise for systems biology based cancer therapy.

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Development of quantitative method for determination of γ-glutamyl peptides by capillary electrophoresis tandem mass spectrometry: An efficient approach avoiding matrix effect

Hirayama A., Igarashi K., Tomita M., Soga T.

Journal of Chromatography A (Journal of Chromatography A) 1369 161 - 169 2014.11

ISSN 00219673

Serum γ-glutamyl di- and tripeptides have proven to be useful biomarkers to accurately predict nine different forms of liver disease. Using liquid chromatography-tandem mass spectrometry (LC-MS/MS) with multiple reaction monitoring (MRM), serum and liver samples spiked with γ-glutamyl peptide standards were analyzed to estimate accuracy. Unexpectedly, the recovery rates for several γ-glutamyl peptides in the serum samples were quite low, whereas values for some γ-glutamyl peptides in the liver samples were highly elevated. Most of these peptides were barely retained on the reverse-phase column, resulting in significant ion suppression or enhancement. In contrast, a capillary electrophoresis tandem mass spectrometry (CE-MS/MS) method with MRM was minimally affected by matrix effects. Of the 39 tested compounds, most of γ-glutamyl peptides that did not contain a thiol substituent in its structure gave acceptable recoveries (70-120%), and limits of detection for the analytes were between 3.6 and 800. nmol/l with pressure injection at 5. kPa for 10. s (ca. 10. nl). The CE-MS/MS method provided high resolution and proved to be highly selective and sensitive, its utility being demonstrated by the determination of γ-glutamyl di- and tripeptides in serum and liver samples.

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Time resolved DNA occupancy dynamics during the respiratory oscillation uncover a global reset point in the yeast growth program

Amariei C., Machné R., Stolc V., Soga T., Tomita M., Murray D.B.

Microbial Cell (Microbial Cell) 1 ( 9 ) 279 - 288 2014.09

ISSN 2311-2638

The structural dynamics of chromatin have been implicated in the regulation of fundamental eukaryotic processes, such as DNA transcription, replication and repair. Although previous studies have revealed that the chromatin landscape, nucleosome remodeling and histone modification events are intimately tied into cellular energetics and redox state, few studies undertake defined time-resolved measurements of these state variables. Here, we use metabolically synchronous, continuously-grown yeast cultures to measure DNA occupancy and track global patterns with respect to the metabolic state of the culture. Combined with transcriptome analyses and ChIP-qPCR experiments, these paint an intriguing picture where genome-wide nucleosome focusing occurs during the recovery of energy charge, followed by clearance of the promoter regions and global transcriptional slow-down, thus indicating a nucleosome-mediated “reset point” for the cycle. The reset begins at the end of the catabolic and stress-response transcriptional programs and ends prior to the start of the anabolic and cell-growth transcriptional program, and the histones on genes from both the catabolic and anabolic superclusters are deacetylated.

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Temporal Enhancement of Trapped Field in a Compact NMR Magnet Comprising YBCO Annuli.

Hahn S, Kim Y, Voccio JP, Song J, Bascuñán J, Tomita M, Iwasa Y

IEEE transactions on applied superconductivity : a publication of the IEEE Superconductivity Committee 24 ( 3 ) 2014.06

ISSN 1051-8223

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