Details of a Researcher - Tomita, Masaru

Papers - Tomita, Masaru

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Metabolic profiling of total physical activity and sedentary behavior in community dwelling men

Fukai, K., Harada, S., Iida, M., Kurihara, A., Takeuchi, A., Kuwabara, K., Sugiyama, D., Okamura, T., Akiyama, M., Nishiwaki, Y., Oguma, Y., Suzuki, A., Suzuki, C., Hirayama, A., Sugimoto, M., Soga, T., Tomita, M. and *Takebayashi, T.

PLoS ONE (PLoS ONE) 11 ( 10 ) e0164877 2016

Joint Work

Objective: Physical activity is known to be preventive against various non-communicable diseases. We investigated the relationship between daily physical activity level and plasma metabolites using a targeted metabolomics approach in a population-based study. Methods: A total of 1,193 participants (male, aged 35 to 74 years) with fasting blood samples were selected from the baseline survey of a cohort study. Information on daily total physical activity, classified into four levels by quartile of metabolic equivalent scores, and sedentary behavior, defined as hours of sitting per day, was collected through a self-administered questionnaire. Plasma metabolite concentrations were quantified by capillary electrophoresis mass spectrometry method. We performed linear regression analysis models with multivariable adjustment and corrected p-values for multiple testing in the original population (n = 808). The robustness of the results was confirmed by replication analysis in a separate population (n = 385) created by random allocation. Results: Higher levels of total physical activity were associated with various metabolite concentrations, including lower concentrations of amino acids and their derivatives, and higher concentrations of pipecolate (FDR p <0.05 in original population). The findings persisted after adjustment for age, body mass index, smoking, alcohol intake, and energy intake. Isoleucine, leucine, valine, 4-methyl-2-oxoisopentanoate, 2-oxoisopentanoate, alanine, and proline concentrations were lower with a shorter sitting time. Conclusions: Physical activity is related to various plasma metabolites, including known biomarkers for future insulin resistance or type 2 diabetes. These metabolites might potentially play a key role in the protective effects of higher physical activity and/or less sedentary behavior on non-communicable diseases.

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Draft genome sequence of Arenibacter sp. strain C-21, an iodine-accumulating bacterium isolated from surface marine sediment

Ito, K., Nakajima, N., Yamamura, S., Tomita, M., Suzuki, H. and Amachi, S.

Genome Announcements (Genome Announcements) 4 ( 5 ) e01155-16 2016

Joint Work, ISSN 2169-8287

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Morphology and phylogeny of a new wall-less freshwater volvocalean flagellate, Hapalochloris nozakii gen. et sp. nov. (Volvocales, Chlorophyceae)

Nakada, T. and Tomita, M.

Journal of Phycology (Journal of Phycology) 53 ( 1 ) JPY12484 - 117 2016

ISSN 00223646

New strains of a wall-less unicellular volvocalean flagellate were isolated from a freshwater environment in Japan. Observations of the alga, described here as Hapalochloris nozakii Nakada, gen. et sp. nov., were made using light, fluorescence, and electron microscopy. Each vegetative cell had two flagella, four contractile vacuoles, and a spirally furrowed cup-shaped chloroplast with an axial pyrenoid, and mitochondria located in the furrows. Based on the morphology, H. nozakii was distinguished from other known wall-less volvocalean flagellates. Under electron microscopy, fibrous material, instead of a cell wall and dense cortical microtubules, was observed outside and inside the cell membrane, respectively. Based on the phylogenetic analyses of 18S rRNA gene sequences, H. nozakii was found to be closely related to Asterococcus, Oogamochlamys, Rhysamphichloris, and “Dunaliella” lateralis and was separated from other known wall-less flagellate volvocaleans, indicating independent secondary loss of the cell wall in H. nozakii. In the combined 18S rRNA and chloroplast gene tree, H. nozakii was sister to Lobochlamys.

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Systematic characterization of artificial small RNA-mediated inhibition of Escherichia coli growth

Noro, E., Mori, M., Makino, G., Takai, Y., Ohnuma, S., Sato, A., Tomita, M., Nakahigashi, K. and Kanai, A.

RNA Biology (RNA Biology) 16 ( 2 ) 1 - 13 2016

Joint Work, Accepted, ISSN 15476286

A new screening system for artificial small RNAs (sRNAs) that inhibit the growth of Escherichia coli was constructed. In this system, we used a plasmid library to express RNAs of ∼120 nucleotides, each with a random 30-nucleotide sequence that can recognize its target mRNA(s). After approximately 60,000 independent colonies were screened, several plasmids that inhibited bacterial growth were isolated. To understand the inhibitory mechanism, we focused on one sRNA, S-20, that exerted a strong inhibitory effect. A time-course analysis of the proteome of S-20-expressing E. coli and a bioinformatic analysis were used to identify potential S-20 target mRNAs, and suggested that S-20 binds the translation initiation sites of several mRNAs encoding enzymes such as peroxiredoxin (osmC), glycyl-tRNA synthetase α subunit (glyQ), uncharacterized protein ygiM, and tryptophan synthase β chain (trpB). An in vitro translation analysis of chimeric luciferase-encoding mRNAs, each containing a potential S-20 target sequence, indicated that the translation of these mRNAs was inhibited in the presence of S-20. A gel shift analysis combined with the analysis of a series of S-20 mutants suggested that S-20 targets multiple mRNAs that are responsible for inhibiting E. coli growth. These data also suggest that S-20 acts like an endogenous sRNA and that E. coli can utilize artificial sRNAs.

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Identification of salivary metabolomic biomarkers for oral cancer screening

Ishikawa S., Sugimoto M., Kitabatake K., Sugano A., Nakamura M., Kaneko M., Ota S., Hiwatari K., Enomoto A., Soga T., Tomita M., Iino M.

Scientific Reports (Scientific Reports) 6 31520 2016

Joint Work

The objective of this study was to explore salivary metabolite biomarkers by profiling both saliva and tumor tissue samples for oral cancer screening. Paired tumor and control tissues were obtained from oral cancer patients and whole unstimulated saliva samples were collected from patients and healthy controls. The comprehensive metabolomic analysis for profiling hydrophilic metabolites was conducted using capillary electrophoresis time-of-flight mass spectrometry. In total, 85 and 45 metabolites showed significant differences between tumor and matched control samples, and between salivary samples from oral cancer and controls, respectively (P < 0.05 correlated by false discovery rate); 17 metabolites showed consistent differences in both saliva and tissue-based comparisons. Of these, a combination of only two biomarkers yielded a high area under receiver operating characteristic curves (0.827; 95% confidence interval, 0.726-0.928, P < 0.0001) for discriminating oral cancers from controls. Various validation tests confirmed its high generalization ability. The demonstrated approach, integrating both saliva and tumor tissue metabolomics, helps eliminate pseudo-molecules that are coincidentally different between oral cancers and controls. These combined salivary metabolites could be the basis of a clinically feasible method of non-invasive oral cancer screening.

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Expansion of noncanonical V-Arm-containing tRNAs in eukaryotes

Hamashima K., Tomita M., Kanai A.

Molecular Biology and Evolution (Molecular Biology and Evolution) 33 ( 2 ) 530 - 540 2016

Joint Work, ISSN 07374038

Transfer RNA (tRNA) is essential for the translation of genetic information into proteins, and understanding its molecular evolution is important if we are to understand the genetic code. In general, long variable-arm (V-arm) structures form in tRNALeu, tRNASer, and bacterial and organellar tRNATyr. However, as we have previously reported, noncanonical V-arms occur in nematode tRNAGly and tRNAIle, and potentially affect translational fidelity. Here, we comprehensively analyzed 69 eukaryotic genome sequences and examined the evolutionary divergence of the V-arm-containing tRNAs. In total, 253 V-arm-containing tRNAs, with neither leucine nor serine anticodons, were identified in organisms ranging from nematodes to fungi, plants, and vertebrates. We defined them as "noncanonical V-arm-containing tRNAs" (nov-tRNAs). Moreover, 2,415 nov-tRNA-like sequences lacking some of the conserved features of tRNAs were also identified, largely in vertebrate genomes. These nov-tRNA/nov-tRNA-like sequences can be categorized into three types, based on differences in their possible evolutionary origins. The type A nov-tRNAs in nematodes probably evolved not only from tRNALeu but also from tRNASer and other isotypes on several independent occasions. The type B nov-tRNAs are dispersed abundantly throughout vertebrate genomes, and seem to have originated from retrotransposable elements. The type C nov-tRNAs may have been acquired from plant chloroplasts or from bacteria through horizontal transfer. Our findings provide unexpected insight into the evolution of the tRNA molecule, which was diverse and occurred independently in nematodes, vertebrates, and plants.

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De novo assembly and comparative transcriptome analysis of Euglena gracilis in response to anaerobic conditions

Yoshida Y., Tomiyama T., Maruta T., Tomita M., Ishikawa T., Arakawa K.

BMC Genomics (BMC Genomics) 17 ( 1 ) 182 2016

Joint Work

Background: The phytoflagellated protozoan, Euglena gracilis, has been proposed as an attractive feedstock for the accumulation of valuable compounds such as β-1,3-glucan, also known as paramylon, and wax esters. The production of wax esters proceeds under anaerobic conditions, designated as wax ester fermentation. In spite of the importance and usefulness of Euglena, the genome and transcriptome data are currently unavailable, though another research group has recently published E.gracilis transcriptome study during our submission. We herein performed an RNA-Seq analysis to provide a comprehensive sequence resource and some insights into the regulation of genes including wax ester metabolism by comparative transcriptome analysis of E.gracilis under aerobic and anaerobic conditions. Results: The E.gracilis transcriptome analysis was performed using the Illumina platform and yielded 90.3 million reads after the filtering steps. A total of 49,826 components were assembled and identified as a reference sequence of E.gracilis, of which 26,479 sequences were considered to be potentially expressed (having FPKM value of greater than 1). Approximately half of all components were estimated to be regulated in a trans-splicing manner, with the addition of protruding spliced leader sequences. Nearly 40 % of 26,479 sequences were annotated by similarity to Swiss-Prot database using the BLASTX program. A total of 2080 transcripts were identified as differentially expressed genes (DEGs) in response to anaerobic treatment for 24 h. A comprehensive pathway enrichment analysis using the KEGG pathway revealed that the majority of DEGs were involved in photosynthesis, nucleotide metabolism, oxidative phosphorylation, fatty acid metabolism. We successfully identified a candidate gene set of paramylon and wax esters, including novel β-1,3-glucan and wax ester synthases. A comparative expression analysis of aerobic- and anaerobic-treated E.gracilis cells indicated that gene expression changes in these components were not extensive or dynamic during the anaerobic treatment. Conclusion: The RNA-Seq analysis provided comprehensive transcriptome information on E.gracilis for the first time, and this information will advance our understanding of this unique organism. The comprehensive analysis indicated that paramylon and wax ester metabolic pathways are regulated at post-transcriptional rather than the transcriptional level in response to anaerobic conditions.

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Taxonomic revision of Chlamydomonas subg. Amphichloris (Volvocales, Chlorophyceae), with resurrection of the genus Dangeardinia and descriptions of Ixipapillifera gen. nov. and Rhysamphichloris gen. nov

Nakada, T., Tomita, M., Wu, J. T. and Nozaki, H.

Journal of Phycology (Journal of Phycology) 52 ( 2 ) 208 - 304 2016

Research paper (scientific journal), Joint Work, ISSN 00223646

Chlamydomonas (Cd.) is one of the largest but most polyphyletic genera of freshwater unicellular green algae. It consists of 400-600 morphological species and requires taxonomic revision. Toward reclassification, each morphologically defined classical subgenus (or subgroup) should be examined using culture strains. Chlamydomonas subg. Amphichloris is characterized by a central nucleus between two axial pyrenoids, however, the phylogenetic structure of this subgenus has yet to be examined using molecular data. Here, we examined 12 strains including six newly isolated strains, morphologically identified as Chlamydomonas subg. Amphichloris, using 18S rRNA gene phylogeny, light microscopy, and mitochondria fluorescent microscopy. Molecular phylogenetic analyses revealed three independent lineages of the subgenus, separated from the type species of Chlamydomonas, Cd. reinhardtii. These three lineages were further distinguished from each other by light and fluorescent microscopy-in particular by the morphology of the papillae, chloroplast surface, stigmata, and mitochondria-and are here assigned to three genera: Dangeardinia emend., Ixipapillifera gen. nov., and Rhysamphichloris gen. nov. Based on the molecular and morphological data, two to three species were recognized in each genus, including one new species, I. pauromitos. In addition, Cd. deasonii, which was previously assigned to subgroup "Pleiochloris," was included in the genus Ixipapillifera as I. deasonii comb. nov.

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Evaluation of the impact of RNA preservation methods of spiders for de novo transcriptome assembly

Kono N., Nakamura H., Ito Y., Tomita M., Arakawa K.

Molecular Ecology Resources (Molecular Ecology Resources) 16 ( 3 ) 662 - 672 2016

Research paper (scientific journal), Joint Work, ISSN 1755098X

With advances in high-throughput sequencing technologies, de novo transcriptome sequencing and assembly has become a cost-effective method to obtain comprehensive genetic information of a species of interest, especially in nonmodel species with large genomes such as spiders. However, high-quality RNA is essential for successful sequencing, and sample preservation conditions require careful consideration for the effective storage of field-collected samples. To this end, we report a streamlined feasibility study of various storage conditions and their effects on de novo transcriptome assembly results. The storage parameters considered include temperatures ranging from room temperature to -80°C; preservatives, including ethanol, RNAlater, TRIzol and RNAlater-ICE; and sample submersion states. As a result, intact RNA was extracted and assembly was successful when samples were preserved at low temperatures regardless of the type of preservative used. The assemblies as well as the gene expression profiles were shown to be robust to RNA degradation, when 30 million 150-bp paired-end reads are obtained. The parameters for sample storage, RNA extraction, library preparation, sequencing and in silico assembly considered in this work provide a guideline for the study of field-collected samples of spiders.

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Draft Genome Sequences of 37 Salmonella enterica Strains Isolated from Poultry Sources in Nigeria

Useh, N.,M., Ngbede, E.,O., Akange, N., Thomas, M., Foley, A., Keena, M., C., Nelson, E., Christopher-Hennings, J., Tomita, M., *Suzuki, H. and *Scaria, J.

Genome Announc 4 ( 3 ) e00315 - e00316 2016

Joint Work

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Mice carrying a human GLUD2 gene recapitulate aspects of human transcriptome and metabolome development

Li Q., Guo S., Jiang X., Bryk J., Naumann R., Enard W., Tomita M., Sugimoto M., Khaitovich P., Pääbo S.

Proc Natl Acad Sci U S A (Proceedings of the National Academy of Sciences of the United States of America) 113 ( 19 ) 5358 - 5363 2016

Joint Work, ISSN 00278424

Whereas all mammals have one glutamate dehydrogenase gene (GLUD1), humans and apes carry an additional gene (GLUD2), which encodes an enzyme with distinct biochemical properties. We inserted a bacterial artificial chromosome containing the human GLUD2 gene into mice and analyzed the resulting changes in the transcriptome and metabolome during postnatal brain development. Effects were most pronounced early postnatally, and predominantly genes involved in neuronal development were affected. Remarkably, the effects in the transgenic mice partially parallel the transcriptome and metabolome differences seen between humans and macaques analyzed. Notably, the introduction of GLUD2 did not affect glutamate levels in mice, consistent with observations in the primates. Instead, the metabolic effects of GLUD2 center on the tricarboxylic acid cycle, suggesting that GLUD2 affects carbon flux during early brain development, possibly supporting lipid biosynthesis.

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Simultaneous analysis of consumer variables, acceptability and sensory characteristics of dry-cured ham

Sugimoto, M., Obiya, S., Kaneko, M., Enomoto, A., Honma, M., Wakayama, M., and Tomita, M.

Meat Science (Meat Science) 120 210 - 215 2016

Joint Work, ISSN 03091740

We conducted a consumer acceptability analysis of dry-cured ham based on sensory evaluation. Consumer acceptability data are rendered heterogeneous by the diverse backgrounds and assessment abilities of the participants, requiring versatile analytical methods for their interpretation. Totally, 9 sensory attributes of 12 kinds of dry-cured ham samples collected from Japan (n = 9), Italy (n = 1), Spain (n = 1), and Germany (n = 1) were tasted by 117 Japanese consumers who showed acceptable evaluation abilities during blind sampling. Common techniques, such as hierarchical clustering, principal component analysis, and external preference mapping, were simultaneously utilized to analyze each characteristics scored in modified hedonic scale. These analyses revealed the relationships between the features and preferences of the assessors. For example, consumers aged 20–30 with smoking and drinking habits preferred sweetness and saltiness, and gave high ratings to Spanish Jómon serrano and Italian prosciutto. Our approach could assist ham marketers to identify potential purchasers and the preferred characteristics of their products.

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Genome sequencing of a single tardigrade Hypsibius dujardini individual

Arakawa, K., Yoshida, Y., Tomita, M.

Scientific Data (Scientific Data) 3 160063 2016

Joint Work

Tardigrades are ubiquitous microscopic animals that play an important role in the study of metazoan phylogeny. Most terrestrial tardigrades can withstand extreme environments by entering an ametabolic desiccated state termed anhydrobiosis. Due to their small size and the non-axenic nature of laboratory cultures, molecular studies of tardigrades are prone to contamination. To minimize the possibility of microbial contaminations and to obtain high-quality genomic information, we have developed an ultra-low input library sequencing protocol to enable the genome sequencing of a single tardigrade Hypsibius dujardini individual. Here, we describe the details of our sequencing data and the ultra-low input library preparation methodologies.

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Bri CA: A modular software platform for whole brain architecture

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

Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics) 9947 LNCS 334 - 341 2016

ISSN 03029743

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Curing the megaplasmid pTT27 from Thermus thermophilus HB27 and maintaining exogenous plasmids in the plasmid-free strain

Ohtani N, Tomita M, Itaya M.

Applied and Environmental Microbiology (Applied and Environmental Microbiology) 28;82 ( 5 ) 1537 - 48 2015.12

ISSN 00992240

Stepwise deletions in the only plasmid in Thermus thermophilus HB27, megaplasmid pTT27, showed that two distantly located loci were important for maintenance of the plasmid. One is a minimum replicon including one gene, repT, coding a replication initiator, and the other encodes subunits of class I ribonucleotide reductase (RNR) for deoxynucleoside triphosphate (dNTP) synthesis. Since the initiator protein, RepT, bound to direct repeats downstream from its own gene, it was speculated that a more-downstream A+T-rich region, which was critical for replication ability, could be unwound for replication initiation. On the other hand, the class I RNR is not necessarily essential for cell growth, as evidenced by the generation of the plasmid-free strain by the loss of pTT27. However, the plasmid-free strain culture has fewer viable cells than the wild-type culture, probably due to a dNTP pool imbalance in the cell. This is because of the introduction of the class I RNR genes or the supplementation of 5'-deoxyadenosylcobalamin, which stimulated class II RNR encoded in the chromosome, resolved the decrease in the number of viable cells in the plasmid-free strain. Likewise, these treatments dramatically enhanced the efficiency of transformation by exogenous plasmids and the stability of the plasmids in the strain. Therefore, the class I RNR would enable the stable maintenance of plasmids, including pTT27, as a result of genome replication normalized by reversing the dNTP pool imbalance. The generation of this plasmid-free strain with great natural competence and its analysis in regard to exogenous plasmid maintenance will expand the availability of HB27 for thermophilic cell factories.

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The application of omics technologies in the functional evaluation of inulin and inulin-containing prebiotics dietary supplementation

Tsurumaki M., Kotake M., Iwasaki M., Saito M., Tanaka K., Aw W., Fukuda S., Tomita M.

Nutrition and Diabetes (Nutrition and Diabetes) 5 ( 11 ) e185 2015.11

ISSN 2044-4052

Inulin, a natural renewable polysaccharide resource produced by various plants in nature, has been reported to possess a significant number of diverse pharmaceutical and food applications. Recently, there has been rapid progress in high-throughput technologies and platforms to assay global mRNA, proteins, metabolites and gut microbiota. In this review, we will describe the current status of utilizing omics technologies of elucidating the impact of inulin and inulin-containing prebiotics at the transcriptome, proteome, metabolome and gut microbiome levels. Although many studies in this review have addressed the impact of inulin comprehensively, these omics technologies only enable us to understand physiological information at each different stage of mRNA, protein, metabolite and gut microbe. We believe that a synergistic approach is vital in order to fully illustrate the intricate beauty behind the relatively modest influence of food factors like inulin on host health.

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Taxonomic revision of oil-producing green algae, Chlorococcum oleofaciens (Volvocales, Chlorophyceae), and its relatives

Kawasaki Y, Nakada T, Tomita M.

Journal of Phycology (Journal of Phycology) 51 ( 5 ) 1000 - 16 2015.10

ISSN 00223646

Historically, species in Volvocales were classified based primarily on morphology. Although the taxonomy of Chlamydomonas has been re-examined using a polyphasic approach including molecular phylogeny, that of Chlorococcum (Cc.), the largest coccoid genus in Volvocales, has yet to be reexamined. Six species thought to be synonymous with the oil-producing alga Cc. oleofaciens were previously not confirmed by molecular phylogeny. In this study, seven authentic strains of Cc. oleofaciens and its putative synonyms, along with 11 relatives, were examined based on the phylogeny of the 18S ribosomal RNA (rRNA) gene, comparisons of secondary structures of internal transcribed spacer 1 (ITS1) and ITS2 rDNA, and morphological observations by light microscopy. Seven 18S rRNA types were recognized among these strains and three were distantly related to Cc. oleofaciens. Comparisons of ITS rDNA structures suggested possible separation of the remaining four types into different species. Shapes of vegetative cells, thickness of the cell walls in old cultures, the size of cells in old cultures, and stigma morphology of zoospores also supported the 18S rRNA grouping. Based on these results, the 18 strains examined were reclassified into seven species. Among the putative synonyms, synonymy of Cc. oleofaciens, Cc. croceum, and Cc. granulosum was confirmed, and Cc. microstigmatum, Cc. rugosum, Cc. aquaticum, and Cc. nivale were distinguished from Cc. oleofaciens. Furthermore, another related strain is described as a new species, Macrochloris rubrioleum sp. nov.

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Tracking global gene expression responses in T cell differentiation

Simeoni O., Piras V., Tomita M., Selvarajoo K.

Gene (Gene) 569 ( 2 ) 259 - 266 2015.09

ISSN 03781119

Upon receiving antigens from the innate immune cells, CD4+ T cells differentiate into distinct effector cells. To probe the global responses of distinct effector cells, we analyzed transcriptome-wide expressions of Th1, Th2, Treg and Th17 using Pearson correlation, entropy and principal component analyses, with Th0 as a control. Although the global response of Th0 was quite distinct from Th17, surprisingly, it was highly similar to Th1, Th2 and Treg. Moreover, 8 major temporal groups consisting of 5704 differentially expressed genes were revealed for both Th0 and Th17. Gene functional enrichment analysis showed immune responses and metabolic processes were mainly activated between Th0 and Th17, while genes related to cell cycle and replication were differentially regulated. Moreover, we found the upregulation of several novel genes for Th0 and Th17. Overall, we deduce that Th0 is globally similar to Th1, Th2 and Treg. Our results indicate that Th0 is a differentiated state and, therefore, may not be used as a control cell type.

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Operation of a 130-MHz/9-mm Compact HTS Annulus Magnet With a Micro-NMR Probe.

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

IEEE transactions on applied superconductivity : a publication of the IEEE Superconductivity Committee 25 ( 3 ) 1 - 5 2015.06

ISSN 1051-8223

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Organization and Evolution of Brain Lipidome Revealed by Large-Scale Analysis of Human, Chimpanzee, Macaque, and Mouse Tissues

Bozek K., Wei Y., Yan Z., Liu X., Xiong J., Sugimoto M., Tomita M., Pääbo S., Sherwood C., Hof P., Ely J., Li Y., Steinhauser D., Willmitzer L., Giavalisco P., Khaitovich P.

Neuron (Neuron) 85 ( 4 ) 695 - 702 2015.02

ISSN 08966273

Lipids are prominent components of the nervous system. Here we performed a large-scale mass spectrometry-based analysis of the lipid composition of three brain regions as well as kidney and skeletal muscle of humans, chimpanzees, rhesus macaques, and mice. The human brain shows the most distinct lipid composition: 76% of 5,713 lipid compounds examined in our study are either enriched or depleted in the human brain. Concentration levels of lipids enriched in the brain evolve approximately four times faster among primates compared with lipids characteristic of non-neural tissues and show further acceleration of change in human neocortical regions but not in the cerebellum. Human-specific concentration changes are supported by human-specific expression changes for corresponding enzymes. These results provide the first insights into the role of lipids in human brain evolution.

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