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  • 1
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    A new dust budget in the Large Magellanic Cloud (2015)
    Oxford University Press
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    Publikationsdatum: 2015-06-07
    Beschreibung: The origin of dust in a galaxy is poorly understood. Recently, surveys of the Large Magellanic Cloud (LMC) have provided astrophysical laboratories for dust studies. Using a method of population synthesis, we investigate the contributions of dust produced by asymptotic giant branch (AGB) stars, common envelope (CE) ejecta and Type II supernovae (SNe II) to the total dust budget in the LMC. Based on our models, the dust production rates (DPRs) of AGB stars in the LMC are between about 2.5 10 –5 and 4.0 10 –6 M yr –1 . The uncertainty mainly results from different models for the dust yields of AGB stars. The DPRs of CE ejecta are about 6.3 10 –6 (the initial binary fraction is 50 per cent). These results are within the large scatter of several observational estimates. AGB stars mainly produce carbon grains, which is consistent with observations. Most of the dust grains manufactured by CE ejecta are silicate and iron grains. The contributions of SNe II are very uncertain. Compared with SNe II without reverse shock, the DPRs of AGB stars and CE ejecta are negligible. However, if only 2 per cent of dust grains produced by SNe II can survive after reverse shock, the contributions of SNe II are very small. The total dust masses produced by AGB stars in the LMC are between 2.8 10 4 and 3.2 10 5 M , and those produced by CE ejecta are about 6.3 10 4 . They are much lower than the values estimated by observations. Therefore, there should be other dust sources in the LMC.
    Print ISSN: 0035-8711
    Digitale ISSN: 1365-2966
    Thema: Physik
    Publiziert von Oxford University Press
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  • 2
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    Estrogen represses gene expression through reconfiguring chromatin structures (2013)
    Oxford University Press
    Details
    Publikationsdatum: 2013-09-26
    Beschreibung: Estrogen regulates over a thousand genes, with an equal number of them being induced or repressed. The distinct mechanisms underlying these dual transcriptional effects remain largely unknown. We derived comprehensive views of the transcription machineries assembled at estrogen-responsive genes through integrating multiple types of genomic data. In the absence of estrogen, the majority of genes formed higher-order chromatin structures, including DNA loops tethered to protein complexes involving RNA polymerase II (Pol II), estrogen receptor alpha (ERα) and ERα-pioneer factors. Genes to be ‘repressed’ by estrogen showed active transcription at promoters and throughout the gene bodies; genes to be ‘induced’ exhibited active transcription initiation at promoters, but with transcription paused in gene bodies. In the presence of estrogen, the majority of estrogen-induced genes retained the original higher-order chromatin structures, whereas most estrogen-repressed genes underwent a chromatin reconfiguration. For estrogen-induced genes, estrogen enhances transcription elongation, potentially through recruitment of co-activators or release of co-repressors with unique roles in elongation. For estrogen-repressed genes, estrogen treatment leads to chromatin structure reconfiguration, thereby disrupting the originally transcription-efficient chromatin structures. Our in silico studies have shown that estrogen regulates gene expression, at least in part, through modifying previously assembled higher-order complexes, rather than by facilitating de novo assembly of machineries.
    Print ISSN: 0305-1048
    Digitale ISSN: 1362-4962
    Thema: Biologie
    Publiziert von Oxford University Press
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  • 3
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    ISL1 and JMJD3 synergistically control cardiac differentiation of embryonic stem cells (2016)
    Oxford University Press
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    Publikationsdatum: 2016-08-20
    Beschreibung: ISL1 is expressed in cardiac progenitor cells and plays critical roles in cardiac lineage differentiation and heart development. Cardiac progenitor cells hold great potential for clinical and translational applications. However, the mechanisms underlying ISL1 function in cardiac progenitor cells have not been fully elucidated. Here we uncover a hierarchical role of ISL1 in cardiac progenitor cells, showing that ISL1 directly regulates hundreds of potential downstream target genes that are implicated in cardiac differentiation, through an epigenetic mechanism. Specifically, ISL1 promotes the demethylation of tri-methylation of histone H3K27 (H3K27me3) at the enhancers of key downstream target genes, including Myocd and Mef2c , which are core cardiac transcription factors. ISL1 physically interacts with JMJD3, a H3K27me3 demethylase, and conditional depletion of JMJD3 leads to impaired cardiac progenitor cell differentiation, phenocopying that of ISL1 depletion. Interestingly, ISL1 is not only responsible for the recruitment of JMJD3 to specific target loci during cardiac progenitor differentiation, but also modulates its demethylase activity. In conclusion, ISL1 and JMJD3 partner to alter the cardiac epigenome, instructing gene expression changes that drive cardiac differentiation.
    Print ISSN: 0305-1048
    Digitale ISSN: 1362-4962
    Thema: Biologie
    Publiziert von Oxford University Press
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  • 4
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    Human JC virus small tumour antigen inhibits nucleotide excision repair and sensitises cells to DNA-damaging agents (2015)
    Oxford University Press
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    Publikationsdatum: 2015-06-17
    Beschreibung: The human JC virus (JCV) is potentially carcinogenic to humans as a Group 2B carcinogen, and it is ubiquitous in human populations. To investigate whether the small tumour (ST) antigen of the JCV contributes to genomic instability, we established cell lines stably expressing the JCV ST and examined its role in DNA repair. Results from host cell reactivation (HCR) assay revealed that the established cell lines exhibited lower nucleotide excision repair (NER) activity than the vector control cells did. The presence of -H2AX, a marker of DNA damage, indicated that the established cell line contained more DNA damage foci compared with vector control cells. Furthermore, the results of clonogenic analyses indicated that the JCV ST-expressing cells were more sensitive than the vector control cells to ultraviolet (UV) irradiation and cisplatin treatment. Micronuclei formation assay revealed that the JCV ST-positive cells presented more chromosomal breakages than did the JCV ST-negative cells, particularly after exposure to DNA-damaging agents. The xeroderma pigmentosum Group D protein, a DNA helicase involved in NER, was downregulated in the JCV ST-positive cells in response to UV irradiation. The effect of the protein phosphatase 2A (PP2A) inhibitor okadaic acid on NER was similar to that of the ST, which is a PP2A-binding protein. Therefore, the deactivation of the PP2A might underlie ST-mediated NER inhibition. The results of this study indicate that exposing JCV ST-positive cells to DNA-damaging agents causes genomic instability, which contributes to carcinogenesis. Our data provide further evidence on the association between the JCV ST and human cancer.
    Print ISSN: 0267-8357
    Digitale ISSN: 1464-3804
    Thema: Biologie , Medizin
    Publiziert von Oxford University Press
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  • 5
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    A new dust budget in the Large Magellanic Cloud (2015)
    Oxford University Press
    Details
    Publikationsdatum: 2015-06-12
    Beschreibung: The origin of dust in a galaxy is poorly understood. Recently, surveys of the Large Magellanic Cloud (LMC) have provided astrophysical laboratories for dust studies. Using a method of population synthesis, we investigate the contributions of dust produced by asymptotic giant branch (AGB) stars, common envelope (CE) ejecta and Type II supernovae (SNe II) to the total dust budget in the LMC. Based on our models, the dust production rates (DPRs) of AGB stars in the LMC are between about 2.5 10 –5 and 4.0 10 –6 M yr –1 . The uncertainty mainly results from different models for the dust yields of AGB stars. The DPRs of CE ejecta are about 6.3 10 –6 (the initial binary fraction is 50 per cent). These results are within the large scatter of several observational estimates. AGB stars mainly produce carbon grains, which is consistent with observations. Most of the dust grains manufactured by CE ejecta are silicate and iron grains. The contributions of SNe II are very uncertain. Compared with SNe II without reverse shock, the DPRs of AGB stars and CE ejecta are negligible. However, if only 2 per cent of dust grains produced by SNe II can survive after reverse shock, the contributions of SNe II are very small. The total dust masses produced by AGB stars in the LMC are between 2.8 10 4 and 3.2 10 5 M , and those produced by CE ejecta are about 6.3 10 4 . They are much lower than the values estimated by observations. Therefore, there should be other dust sources in the LMC.
    Print ISSN: 0035-8711
    Digitale ISSN: 1365-2966
    Thema: Physik
    Publiziert von Oxford University Press
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  • 6
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    Population synthesis of millisecond X-ray pulsars (2015)
    Oxford University Press
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    Publikationsdatum: 2015-10-09
    Beschreibung: As the evolutionary link between the radio millisecond pulsars and the low-mass X-ray binaries or intermediate-mass X-ray binaries, the millisecond X-ray pulsars (MSXPs) are important objects in testing theories of pulsar formation and evolution. In general, neutron stars in MSXPs can form via core collapse supernova (CC channel) of massive stars or accretion induced collapse (AIC channel) of an accreting ONeMg white dwarf, whose mass reaches the Chandrasekhar limit. Here, in addition to CC and AIC channels we also consider another channel, i.e. evolution induced collapse (EIC channel) of a helium star with mass between 1.4 and 2.5 M . Using a population synthesis code, we have studied MSXPs arising from three different evolutionary channels. We find that the Galactic birthrates of transient MSXPs and persistent MSXPs are about 0.7–1.4 x 10 –4  yr –1 . Our population synthesis calculations have shown that about 50–90 per cent of the MSXPs have undergone CC channel, about 10–40 per cent of them have undergone EIC channel, and the MSXPs via AIC channel are the least.
    Print ISSN: 0035-8711
    Digitale ISSN: 1365-2966
    Thema: Physik
    Publiziert von Oxford University Press
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  • 7
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    Meta-analysis of genome-wide association studies identifies multiple lung cancer susceptibility loci in never-smoking Asian women (2016)
    Wang, Z., Seow, W. J., Shiraishi, K., Hsiung, C. A., Matsuo, K., Liu, J., Chen, K., Yamji, T., Yang, Y., Chang, I.-S., Wu, C., Hong, Y.-C., Burdett, L., Wyatt, K., Chung, C. C., Li, S. A., Yeager, M., Hutchinson, A., Hu, W., Caporaso, N., Landi, M. T., Chatterjee, N., Song, M., Fraumeni, J. F., Kohno, T., Yokota, J., Kunitoh, H., Ashikawa, K., Momozawa, Y., Daigo, Y., Mitsudomi, T., Yatabe, Y., Hida, T., Hu, Z., Dai, J., Ma, H., Jin, G., Song, B., Wang, Z., Cheng, S., Yin, Z., Li, X., Ren, Y., Guan, P., Chang, J., Tan, W., Chen, C.-J., Chang, G.-C., Tsai, Y.-H., Su, W.-C., Chen, K.-Y., Huang, M.-S., Chen, Y.-M., Zheng, H., Li, H., Cui, P., Guo, H., Xu, P., Liu, L., Iwasaki, M., Shimazu, T., Tsugane, S., Zhu, J., Jiang, G., Fei, K., Park, J. Y., Kim, Y. H., Sung, J. S., Park, K. H., Kim, Y. T., Jung, Y. J., Kang, C. H., Park, I. K., Kim, H. N., Jeon, H.-S., Choi, J. E., Choi, Y. Y., Kim, J. H., Oh, I.-J., Kim, Y.-C., Sung, S. W., Kim, J. S., Yoon, H.-I., Kweon, S.-S., Shin, M.-H., Seow, A., Chen, Y., Lim, W.-Y., Liu, J., Wong, M. P., Lee, V. H. F., Bassig, B. A., Tucker, M., Berndt, S. I., Chow, W.-H., Ji, B.-T., Wang, J., Xu, J., Sihoe, A. D. L., Ho, J. C. M., Chan, J. K. C., Wang, J.-C., Lu, D., Zhao, X., Zhao, Z., Wu, J., Chen, H., Jin, L., Wei, F., Wu, G., An, S.-J., Zhang, X.-C., Su, J., Wu, Y.-L., Gao, Y.-T., Xiang, Y.-B., He, X., Li, J., Zheng, W., Shu, X.-O., Cai, Q., Klein, R., Pao, W., Lawrence, C., Hosgood, H. D., Hsiao, C.-F., Chien, L.-H., Chen, Y.-H., Chen, C.-H., Wang, W.-C., Chen, C.-Y., Wang, C.-L., Yu, C.-J., Chen, H.-L., Su, Y.-C., Tsai, F.-Y., Chen, Y.-S., Li, Y.-J., Yang, T.-Y., Lin, C.-C., Yang, P.-C., Wu, T., Lin, D., Zhou, B., Yu, J., Shen, H., Kubo, M., Chanock, S. J., Rothman, N., Lan, Q.
    Oxford University Press
    Details
    Publikationsdatum: 2016-01-29
    Beschreibung: Genome-wide association studies (GWAS) of lung cancer in Asian never-smoking women have previously identified six susceptibility loci associated with lung cancer risk. To further discover new susceptibility loci, we imputed data from four GWAS of Asian non-smoking female lung cancer (6877 cases and 6277 controls) using the 1000 Genomes Project (Phase 1 Release 3) data as the reference and genotyped additional samples (5878 cases and 7046 controls) for possible replication. In our meta-analysis, three new loci achieved genome-wide significance, marked by single nucleotide polymorphism (SNP) rs7741164 at 6p21.1 (per-allele odds ratio (OR) = 1.17; P = 5.8 x 10 –13 ), rs72658409 at 9p21.3 (per-allele OR = 0.77; P = 1.41 x 10 –10 ) and rs11610143 at 12q13.13 (per-allele OR = 0.89; P = 4.96 x 10 –9 ). These findings identified new genetic susceptibility alleles for lung cancer in never-smoking women in Asia and merit follow-up to understand their biological underpinnings.
    Print ISSN: 0964-6906
    Digitale ISSN: 1460-2083
    Thema: Biologie , Medizin
    Publiziert von Oxford University Press
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  • 8
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    Community challenges in biomedical text mining over 10 years: success, failure and the future (2016)
    Oxford University Press
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    Publikationsdatum: 2016-01-21
    Beschreibung: One effective way to improve the state of the art is through competitions. Following the success of the Critical Assessment of protein Structure Prediction (CASP) in bioinformatics research, a number of challenge evaluations have been organized by the text-mining research community to assess and advance natural language processing (NLP) research for biomedicine. In this article, we review the different community challenge evaluations held from 2002 to 2014 and their respective tasks. Furthermore, we examine these challenge tasks through their targeted problems in NLP research and biomedical applications, respectively. Next, we describe the general workflow of organizing a Biomedical NLP (BioNLP) challenge and involved stakeholders (task organizers, task data producers, task participants and end users). Finally, we summarize the impact and contributions by taking into account different BioNLP challenges as a whole, followed by a discussion of their limitations and difficulties. We conclude with future trends in BioNLP challenge evaluations.
    Print ISSN: 1467-5463
    Digitale ISSN: 1477-4054
    Thema: Biologie , Informatik
    Publiziert von Oxford University Press
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  • 9
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    Dr.VIS v2.0: an updated database of human disease-related viral integration sites in the era of high-throughput deep sequencing (2015)
    Oxford University Press
    Details
    Publikationsdatum: 2015-01-16
    Beschreibung: Dr.VIS is a database of human d isease- r elated v iral i ntegration s ites (VIS). The number of VIS has grown rapidly since Dr.VIS was first released in 2011, and there is growing recognition of the important role that viral integration plays in the development of malignancies. The updated database version, Dr.VIS v2.0 ( http://www.bioinfo.org/drvis or bminfor.tongji.edu.cn/drvis_v2 ), represents 25 diseases, covers 3340 integration sites of eight oncogenic viruses in human chromosomes and provides more accurate information about VIS from high-throughput deep sequencing results obtained mainly after 2012. Data of VISes for three newly identified oncogenic viruses for 14 related diseases have been added to this 2015 update, which has a 5-fold increase of VISes compared to Dr.VIS v1.0. Dr.VIS v2.0 has 2244 precise integration sites, 867 integration regions and 551 junction sequences. A total of 2295 integration sites are located near 1730 involved genes. Of the VISes, 1153 are detected in the exons or introns of genes, with 294 located up to 5 kb and a further 112 located up to 10 kb away. As viral integration may alter chromosome stability and gene expression levels, characterizing VISes will contribute toward the discovery of novel oncogenes, tumor suppressor genes and tumor-associated pathways.
    Print ISSN: 0305-1048
    Digitale ISSN: 1362-4962
    Thema: Biologie
    Publiziert von Oxford University Press
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  • 10
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    Regulatory networks define phenotypic classes of human stem cell lines (2008)
    Nature Publishing Group (NPG)
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    Publikationsdatum: 2008-08-30
    Beschreibung: Stem cells are defined as self-renewing cell populations that can differentiate into multiple distinct cell types. However, hundreds of different human cell lines from embryonic, fetal and adult sources have been called stem cells, even though they range from pluripotent cells-typified by embryonic stem cells, which are capable of virtually unlimited proliferation and differentiation-to adult stem cell lines, which can generate a far more limited repertoire of differentiated cell types. The rapid increase in reports of new sources of stem cells and their anticipated value to regenerative medicine has highlighted the need for a general, reproducible method for classification of these cells. We report here the creation and analysis of a database of global gene expression profiles (which we call the 'stem cell matrix') that enables the classification of cultured human stem cells in the context of a wide variety of pluripotent, multipotent and differentiated cell types. Using an unsupervised clustering method to categorize a collection of approximately 150 cell samples, we discovered that pluripotent stem cell lines group together, whereas other cell types, including brain-derived neural stem cell lines, are very diverse. Using further bioinformatic analysis we uncovered a protein-protein network (PluriNet) that is shared by the pluripotent cells (embryonic stem cells, embryonal carcinomas and induced pluripotent cells). Analysis of published data showed that the PluriNet seems to be a common characteristic of pluripotent cells, including mouse embryonic stem and induced pluripotent cells and human oocytes. Our results offer a new strategy for classifying stem cells and support the idea that pluripotency and self-renewal are under tight control by specific molecular networks.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2637443/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2637443/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Muller, Franz-Josef -- Laurent, Louise C -- Kostka, Dennis -- Ulitsky, Igor -- Williams, Roy -- Lu, Christina -- Park, In-Hyun -- Rao, Mahendra S -- Shamir, Ron -- Schwartz, Philip H -- Schmidt, Nils O -- Loring, Jeanne F -- K12 5K12HD000849-20/HD/NICHD NIH HHS/ -- P20 GM075059/GM/NIGMS NIH HHS/ -- P20 GM075059-01/GM/NIGMS NIH HHS/ -- England -- Nature. 2008 Sep 18;455(7211):401-5. doi: 10.1038/nature07213. Epub 2008 Aug 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Regenerative Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA. fj.mueller@zip-kiel.de〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18724358" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Algorithms ; Animals ; Artificial Intelligence ; Cell Differentiation ; Cell Line ; Computational Biology ; Databases, Factual ; Embryonic Stem Cells/classification/metabolism ; *Gene Expression Profiling ; Humans ; Mice ; Multipotent Stem Cells/classification/metabolism ; Oligonucleotide Array Sequence Analysis ; Oocytes/classification/metabolism ; Phenotype ; Pluripotent Stem Cells/classification/metabolism ; Protein Binding ; Stem Cells/*classification/*metabolism
    Print ISSN: 0028-0836
    Digitale ISSN: 1476-4687
    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
    Publiziert von Nature Publishing Group (NPG)
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