Author
Hiroki R. Ueda
Other affiliations: Intec, Inc., Osaka University, Nagoya University ...read more
Bio: Hiroki R. Ueda is an academic researcher from University of Tokyo. The author has contributed to research in topics: Circadian clock & Circadian rhythm. The author has an hindex of 59, co-authored 211 publications receiving 18300 citations. Previous affiliations of Hiroki R. Ueda include Intec, Inc. & Osaka University.
Papers published on a yearly basis
Papers
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TL;DR: Detailed polling of transcription start and termination sites and analysis of previously unidentified full-length complementary DNAs derived from the mouse genome provide a comprehensive platform for the comparative analysis of mammalian transcriptional regulation in differentiation and development.
Abstract: This study describes comprehensive polling of transcription start and termination sites and analysis of previously unidentified full-length complementary DNAs derived from the mouse genome. We identify the 5' and 3' boundaries of 181,047 transcripts with extensive variation in transcripts arising from alternative promoter usage, splicing, and polyadenylation. There are 16,247 new mouse protein-coding transcripts, including 5154 encoding previously unidentified proteins. Genomic mapping of the transcriptome reveals transcriptional forests, with overlapping transcription on both strands, separated by deserts in which few transcripts are observed. The data provide a comprehensive platform for the comparative analysis of mammalian transcriptional regulation in differentiation and development.
3,412 citations
TL;DR: Exome sequencing of exomes of 23 initial low-grade gliomas and recurrent tumors resected from the same patients suggests that recurrent tumors are often seeded by cells derived from the initial tumor at a very early stage of their evolution.
Abstract: Tumor recurrence is a leading cause of cancer mortality. Therapies for recurrent disease may fail, at least in part, because the genomic alterations driving the growth of recurrences are distinct from those in the initial tumor. To explore this hypothesis, we sequenced the exomes of 23 initial low-grade gliomas and recurrent tumors resected from the same patients. In 43% of cases, at least half of the mutations in the initial tumor were undetected at recurrence, including driver mutations in TP53, ATRX, SMARCA4, and BRAF; this suggests that recurrent tumors are often seeded by cells derived from the initial tumor at a very early stage of their evolution. Notably, tumors from 6 of 10 patients treated with the chemotherapeutic drug temozolomide (TMZ) followed an alternative evolutionary path to high-grade glioma. At recurrence, these tumors were hypermutated and harbored driver mutations in the RB (retinoblastoma) and Akt-mTOR (mammalian target of rapamycin) pathways that bore the signature of TMZ-induced mutagenesis.
1,116 citations
TL;DR: CUBIC enables time-course expression profiling of whole adult brains with single-cell resolution and develops a whole-brain cell-nuclear counterstaining protocol and a computational image analysis pipeline that enable the visualization and quantification of neural activities induced by environmental stimulation.
1,070 citations
TL;DR: The role of the Rev-ErbA/ROR response element in gene expression during circadian night is demonstrated, which is in phase with Bmal1 and in antiphase to Per2 oscillations.
Abstract: evoked by square pulse stimuli (0.066 Hz, 5‐12 mA, 200 ms) delivered by means of bipolar tungsten electrodes positioned within the lateral amygdala close to the external capsule. Population spikes were recorded in the basolateral amygdala close to lateral amygdala using glass microelectrodes (2‐3 MQ) filled with artificial cerebrospinal fluid (ACSF) 29 . HFS (five trains at 100 Hz for 1 s, 10-s interstimulus interval) was applied to induce LTP, and LFS1 (900 pulses at 1 Hz) was applied to induce LTD. Whole-cell GABA-mediated currents were isolated by adding NBQX (0.005 mM) and D-(-)-2-amino-5phosphopentanoic acid (AP5; 0.05 mM) to ACSF (bubbled with 95% O2/5% CO2 ;p H 7.3), and were recorded from visually identified somata of principal neurons of the basolateral amygdala 30 by glass electrodes (4.5‐5 MQ) 16 containing (in mM): Mg-ATP 2, CsCH3SO3 100, CsCl 60, EGTA 0.2, HEPES 10, MgCl2 1, QX314 5 and Na3GTP 0.3 (pH 7.3). Patch clamp experiments were performed at 24 ^ 1 8C at a holding potential of 270 mV. LTDi was induced by 100 stimuli at 1 Hz (LFS 2). PPF was induced as described 30 . Data are expressed as means ^ s.e.m. We tested significance using the Student’s t-test.
857 citations
TL;DR: The results indicate that circadian transcriptional circuits are governed by two design principles: regulation of E/E′ boxes and RevErbA/ROR binding elements follows a repressor-precedes-activator pattern, resulting in delayed transcriptional activity, whereas regulation of DBP/E4BP4 binding elements following a repression-antiphasic-to-activators mechanism, which generates high-amplitude transcriptionalactivity.
Abstract: Mammalian circadian clocks consist of complexly integrated regulatory loops, making it difficult to elucidate them without both the accurate measurement of system dynamics and the comprehensive identification of network circuits. Toward a system-level understanding of this transcriptional circuitry, we identified clock-controlled elements on 16 clock and clock-controlled genes in a comprehensive surveillance of evolutionarily conserved cis elements and measurement of their transcriptional dynamics. Here we report the roles of E/E' boxes, DBP/E4BP4 binding elements and RevErbA/ROR binding elements in nine, seven and six genes, respectively. Our results indicate that circadian transcriptional circuits are governed by two design principles: regulation of E/E' boxes and RevErbA/ROR binding elements follows a repressor-precedes-activator pattern, resulting in delayed transcriptional activity, whereas regulation of DBP/E4BP4 binding elements follows a repressor-antiphasic-to-activator mechanism, which generates high-amplitude transcriptional activity. Our analysis further suggests that regulation of E/E' boxes is a topological vulnerability in mammalian circadian clocks, a concept that has been functionally verified using in vitro phenotype assay systems.
748 citations
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28 Jul 2005
TL;DR: PfPMP1）与感染红细胞、树突状组胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作�ly.
Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。
18,940 citations
01 Jan 2006
TL;DR: Probability distributions of linear models for regression and classification are given in this article, along with a discussion of combining models and combining models in the context of machine learning and classification.
Abstract: Probability Distributions.- Linear Models for Regression.- Linear Models for Classification.- Neural Networks.- Kernel Methods.- Sparse Kernel Machines.- Graphical Models.- Mixture Models and EM.- Approximate Inference.- Sampling Methods.- Continuous Latent Variables.- Sequential Data.- Combining Models.
10,141 citations
Ewan Birney, John A. Stamatoyannopoulos1, Anindya Dutta2, Roderic Guigó3 +317 more•Institutions (44)
TL;DR: Functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project are reported, providing convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts.
Abstract: We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.
5,091 citations
TL;DR: An anatomically comprehensive digital atlas containing the expression patterns of ∼20,000 genes in the adult mouse brain is described, providing an open, primary data resource for a wide variety of further studies concerning brain organization and function.
Abstract: Molecular approaches to understanding the functional circuitry of the nervous system promise new insights into the relationship between genes, brain and behaviour. The cellular diversity of the brain necessitates a cellular resolution approach towards understanding the functional genomics of the nervous system. We describe here an anatomically comprehensive digital atlas containing the expression patterns of approximately 20,000 genes in the adult mouse brain. Data were generated using automated high-throughput procedures for in situ hybridization and data acquisition, and are publicly accessible online. Newly developed image-based informatics tools allow global genome-scale structural analysis and cross-correlation, as well as identification of regionally enriched genes. Unbiased fine-resolution analysis has identified highly specific cellular markers as well as extensive evidence of cellular heterogeneity not evident in classical neuroanatomical atlases. This highly standardized atlas provides an open, primary data resource for a wide variety of further studies concerning brain organization and function.
4,944 citations
TL;DR: The rapidly advancing field of long ncRNAs is reviewed, describing their conservation, their organization in the genome and their roles in gene regulation, and the medical implications.
Abstract: In mammals and other eukaryotes most of the genome is transcribed in a developmentally regulated manner to produce large numbers of long non-coding RNAs (ncRNAs). Here we review the rapidly advancing field of long ncRNAs, describing their conservation, their organization in the genome and their roles in gene regulation. We also consider the medical implications, and the emerging recognition that any transcript, regardless of coding potential, can have an intrinsic function as an RNA.
4,911 citations