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  • 1
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    Insights into hominid evolution from the gorilla genome sequence (2012)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2012-03-09
    Description: Gorillas are humans' closest living relatives after chimpanzees, and are of comparable importance for the study of human origins and evolution. Here we present the assembly and analysis of a genome sequence for the western lowland gorilla, and compare the whole genomes of all extant great ape genera. We propose a synthesis of genetic and fossil evidence consistent with placing the human-chimpanzee and human-chimpanzee-gorilla speciation events at approximately 6 and 10 million years ago. In 30% of the genome, gorilla is closer to human or chimpanzee than the latter are to each other; this is rarer around coding genes, indicating pervasive selection throughout great ape evolution, and has functional consequences in gene expression. A comparison of protein coding genes reveals approximately 500 genes showing accelerated evolution on each of the gorilla, human and chimpanzee lineages, and evidence for parallel acceleration, particularly of genes involved in hearing. We also compare the western and eastern gorilla species, estimating an average sequence divergence time 1.75 million years ago, but with evidence for more recent genetic exchange and a population bottleneck in the eastern species. The use of the genome sequence in these and future analyses will promote a deeper understanding of great ape biology and evolution.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3303130/" 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/PMC3303130/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Scally, Aylwyn -- Dutheil, Julien Y -- Hillier, LaDeana W -- Jordan, Gregory E -- Goodhead, Ian -- Herrero, Javier -- Hobolth, Asger -- Lappalainen, Tuuli -- Mailund, Thomas -- Marques-Bonet, Tomas -- McCarthy, Shane -- Montgomery, Stephen H -- Schwalie, Petra C -- Tang, Y Amy -- Ward, Michelle C -- Xue, Yali -- Yngvadottir, Bryndis -- Alkan, Can -- Andersen, Lars N -- Ayub, Qasim -- Ball, Edward V -- Beal, Kathryn -- Bradley, Brenda J -- Chen, Yuan -- Clee, Chris M -- Fitzgerald, Stephen -- Graves, Tina A -- Gu, Yong -- Heath, Paul -- Heger, Andreas -- Karakoc, Emre -- Kolb-Kokocinski, Anja -- Laird, Gavin K -- Lunter, Gerton -- Meader, Stephen -- Mort, Matthew -- Mullikin, James C -- Munch, Kasper -- O'Connor, Timothy D -- Phillips, Andrew D -- Prado-Martinez, Javier -- Rogers, Anthony S -- Sajjadian, Saba -- Schmidt, Dominic -- Shaw, Katy -- Simpson, Jared T -- Stenson, Peter D -- Turner, Daniel J -- Vigilant, Linda -- Vilella, Albert J -- Whitener, Weldon -- Zhu, Baoli -- Cooper, David N -- de Jong, Pieter -- Dermitzakis, Emmanouil T -- Eichler, Evan E -- Flicek, Paul -- Goldman, Nick -- Mundy, Nicholas I -- Ning, Zemin -- Odom, Duncan T -- Ponting, Chris P -- Quail, Michael A -- Ryder, Oliver A -- Searle, Stephen M -- Warren, Wesley C -- Wilson, Richard K -- Schierup, Mikkel H -- Rogers, Jane -- Tyler-Smith, Chris -- Durbin, Richard -- 062023/Wellcome Trust/United Kingdom -- 075491/Z/04/Wellcome Trust/United Kingdom -- 077009/Wellcome Trust/United Kingdom -- 077192/Wellcome Trust/United Kingdom -- 077198/Wellcome Trust/United Kingdom -- 089066/Wellcome Trust/United Kingdom -- 090532/Wellcome Trust/United Kingdom -- 095908/Wellcome Trust/United Kingdom -- 15603/Cancer Research UK/United Kingdom -- 202218/European Research Council/International -- A15603/Cancer Research UK/United Kingdom -- G0501331/Medical Research Council/United Kingdom -- G0701805/Medical Research Council/United Kingdom -- HG002385/HG/NHGRI NIH HHS/ -- U54 HG003079/HG/NHGRI NIH HHS/ -- WT062023/Wellcome Trust/United Kingdom -- WT077009/Wellcome Trust/United Kingdom -- WT077192/Wellcome Trust/United Kingdom -- WT077198/Wellcome Trust/United Kingdom -- WT089066/Wellcome Trust/United Kingdom -- Medical Research Council/United Kingdom -- Biotechnology and Biological Sciences Research Council/United Kingdom -- Howard Hughes Medical Institute/ -- Intramural NIH HHS/ -- England -- Nature. 2012 Mar 7;483(7388):169-75. doi: 10.1038/nature10842.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton CB10 1SA, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22398555" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Evolution, Molecular ; Female ; Gene Expression Regulation ; *Genetic Speciation ; Genetic Variation/genetics ; Genome/*genetics ; Genomics ; Gorilla gorilla/*genetics ; Humans ; Macaca mulatta/genetics ; Molecular Sequence Data ; Pan troglodytes/genetics ; Phylogeny ; Pongo/genetics ; Proteins/genetics ; Sequence Alignment ; Species Specificity ; Transcription, Genetic
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 2
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    ArrayExpress update--trends in database growth and links to data analysis tools (2012)
    Oxford University Press
    Details
    Publication Date: 2012-12-20
    Description: The ArrayExpress Archive of Functional Genomics Data ( http://www.ebi.ac.uk/arrayexpress ) is one of three international functional genomics public data repositories, alongside the Gene Expression Omnibus at NCBI and the DDBJ Omics Archive, supporting peer-reviewed publications. It accepts data generated by sequencing or array-based technologies and currently contains data from almost a million assays, from over 30 000 experiments. The proportion of sequencing-based submissions has grown significantly over the last 2 years and has reached, in 2012, 15% of all new data. All data are available from ArrayExpress in MAGE-TAB format, which allows robust linking to data analysis and visualization tools, including Bioconductor and GenomeSpace. Additionally, R objects, for microarray data, and binary alignment format files, for sequencing data, have been generated for a significant proportion of ArrayExpress data.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 3
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    Expression Atlas update--an integrated database of gene and protein expression in humans, animals and plants (2016)
    Oxford University Press
    Details
    Publication Date: 2016-01-07
    Description: Expression Atlas ( http://www.ebi.ac.uk/gxa ) provides information about gene and protein expression in animal and plant samples of different cell types, organism parts, developmental stages, diseases and other conditions. It consists of selected microarray and RNA-sequencing studies from ArrayExpress, which have been manually curated, annotated with ontology terms, checked for high quality and processed using standardised analysis methods. Since the last update, Atlas has grown seven-fold (1572 studies as of August 2015), and incorporates baseline expression profiles of tissues from Human Protein Atlas, GTEx and FANTOM5, and of cancer cell lines from ENCODE, CCLE and Genentech projects. Plant studies constitute a quarter of Atlas data. For genes of interest, the user can view baseline expression in tissues, and differential expression for biologically meaningful pairwise comparisons—estimated using consistent methodology across all of Atlas. Our first proteomics study in human tissues is now displayed alongside transcriptomics data in the same tissues. Novel analyses and visualisations include: ‘enrichment’ in each differential comparison of GO terms, Reactome, Plant Reactome pathways and InterPro domains; hierarchical clustering (by baseline expression) of most variable genes and experimental conditions; and, for a given gene-condition, distribution of baseline expression across biological replicates.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 4
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    An electron transfer path connects subunits of a mycobacterial respiratory supercomplex (2018)
    American Association for the Advancement of Science (AAAS)
    In: Science
    Details
    Publication Date: 2018
    Description: 〈p〉We report a 3.5-angstrom-resolution cryo–electron microscopy structure of a respiratory supercomplex isolated from 〈i〉Mycobacterium smegmatis.〈/i〉 It comprises a complex III dimer flanked on either side by individual complex IV subunits. Complex III and IV associate so that electrons can be transferred from quinol in complex III to the oxygen reduction center in complex IV by way of a bridging cytochrome subunit. We observed a superoxide dismutase-like subunit at the periplasmic face, which may be responsible for detoxification of superoxide formed by complex III. The structure reveals features of an established drug target and provides a foundation for the development of treatments for human tuberculosis.〈/p〉
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 5
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    Activation of non-myogenic mesenchymal stem cells during the disease progression in dystrophic dystrophin/utrophin knockout mice (2015)
    Oxford University Press
    Details
    Publication Date: 2015-06-09
    Description: Ectopic calcification as well as fatty and fibrotic tissue accumulation occurs in skeletal muscle during the disease progression of Duchenne muscular dystrophy (DMD), a degenerative muscle disorder caused by mutations in the dystrophin gene. The cellular origin and the environmental cues responsible for this ectopic calcification, fatty and fibrotic infiltration during the disease progression, however, remain unknown. Based on a previously published preplate technique, we isolated two distinct populations of muscle-derived cells from skeletal muscle: (i) a rapidly adhering cell population, which is non-myogenic, Pax7 – and express the mesenchymal stem cell (MSC) marker platelet-derived growth factor receptor alpha; hence, we termed this population of cells non-myogenic MSCs (nmMSCs); and (ii) a slowly adhering cell population which is Pax7 + and highly myogenic, termed muscle progenitor cells (MPCs). Previously, we demonstrated that the rapid progression of skeletal muscle histopathologies in dystrophin/utrophin knockout (dys –/– utro –/– dKO) mice is closely associated with a rapid depletion of the MPC population pool. In the current study, we showed that in contrast to the MPCs, the nmMSCs become activated during the disease progression in dKO mice, displaying increased proliferation and differentiation potentials (adipogenesis, osteogenesis and fibrogenesis). We also found that after co-culturing the dKO-nmMSCs with dKO-MPCs, the myogenic differentiation potential of the dKO-MPCs was reduced. This effect was found to be potentially mediated by the secretion of secreted frizzled-related protein 1 by the dKO-nmMSCs. We therefore posit that the rapid occurrence of fibrosis, ectopic calcification and fat accumulation, in dKO mice, is not only attributable to the rapid depletion of the MPC pool, but is also the consequence of nmMSC activation. Results from this study suggest that approaches to alleviate muscle weakness and wasting in DMD patients should not only target the myogenic MPCs but should also attempt to prevent the activation of the nmMSCs.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
    Published by Oxford University Press
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  • 6
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    Global Oct4 target gene analysis reveals novel downstream PTEN and TNC genes required for drug-resistance and metastasis in lung cancer (2015)
    Oxford University Press
    Details
    Publication Date: 2015-02-18
    Description: Overexpression of Oct4, a stemness gene encoding a transcription factor, has been reported in several cancers. However, the mechanism by which Oct4 directs transcriptional program that leads to somatic cancer progression remains unclear. In this study, we provide mechanistic insight into Oct4-driven transcriptional network promoting drug-resistance and metastasis in lung cancer cell, animal and clinical studies. Through an integrative approach combining our Oct4 chromatin-immunoprecipitation sequencing and ENCODE datasets, we identified the genome-wide binding regions of Oct4 in lung cancer at promoter and enhancer of numerous genes involved in critical pathways which promote tumorigenesis. Notably, PTEN and TNC were previously undefined targets of Oct4. In addition, novel Oct4-binding motifs were found to overlap with DNA elements for Sp1 transcription factor. We provided evidence that Oct4 suppressed PTEN in an Sp1-dependent manner by recruitment of HDAC1/2, leading to activation of AKT signaling and drug-resistance. In contrast, Oct4 transactivated TNC independent of Sp1 and resulted in cancer metastasis. Clinically, lung cancer patients with Oct4 high, PTEN low and TNC high expression profile significantly correlated with poor disease-free survival. Our study reveals a critical Oct4-driven transcriptional program that promotes lung cancer progression, illustrating the therapeutic potential of targeting Oc4 transcriptionally regulated genes.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 7
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    Niche of harmful alga Aureococcus anophagefferens revealed through ecogenomics [Environmental Sciences] (2011)
    National Academy of Sciences
    Details
    Publication Date: 2011-03-16
    Description: Harmful algal blooms (HABs) cause significant economic and ecological damage worldwide. Despite considerable efforts, a comprehensive understanding of the factors that promote these blooms has been lacking, because the biochemical pathways that facilitate their dominance relative to other phytoplankton within specific environments have not been identified. Here, biogeochemical measurements showed that the harmful alga Aureococcus anophagefferens outcompeted co-occurring phytoplankton in estuaries with elevated levels of dissolved organic matter and turbidity and low levels of dissolved inorganic nitrogen. We subsequently sequenced the genome of A. anophagefferens and compared its gene complement with those of six competing phytoplankton species identified through metaproteomics. Using an ecogenomic approach, we specifically focused on gene sets that may facilitate dominance within the environmental conditions present during blooms. A. anophagefferens possesses a larger genome (56 Mbp) and has more genes involved in light harvesting, organic carbon and nitrogen use, and encoding selenium- and metal-requiring enzymes than competing phytoplankton. Genes for the synthesis of microbial deterrents likely permit the proliferation of this species, with reduced mortality losses during blooms. Collectively, these findings suggest that anthropogenic activities resulting in elevated levels of turbidity, organic matter, and metals have opened a niche within coastal ecosystems that ideally suits the unique genetic capacity of A. anophagefferens and thus, has facilitated the proliferation of this and potentially other HABs.
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 8
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    ArrayExpress update--simplifying data submissions (2015)
    Oxford University Press
    Details
    Publication Date: 2015-01-16
    Description: The ArrayExpress Archive of Functional Genomics Data ( http://www.ebi.ac.uk/arrayexpress ) is an international functional genomics database at the European Bioinformatics Institute (EMBL-EBI) recommended by most journals as a repository for data supporting peer-reviewed publications. It contains data from over 7000 public sequencing and 42 000 array-based studies comprising over 1.5 million assays in total. The proportion of sequencing-based submissions has grown significantly over the last few years and has doubled in the last 18 months, whilst the rate of microarray submissions is growing slightly. All data in ArrayExpress are available in the MAGE-TAB format, which allows robust linking to data analysis and visualization tools and standardized analysis. The main development over the last two years has been the release of a new data submission tool Annotare, which has reduced the average submission time almost 3-fold. In the near future, Annotare will become the only submission route into ArrayExpress, alongside MAGE-TAB format-based pipelines. ArrayExpress is a stable and highly accessed resource. Our future tasks include automation of data flows and further integration with other EMBL-EBI resources for the representation of multi-omics data.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 9
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    An electron transfer path connects subunits of a mycobacterial respiratory supercomplex (2018)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2018
    Description: 〈p〉We report a 3.5-Å resolution cryo-EM structure of a respiratory supercomplex isolated from 〈i〉Mycobacterium smegmatis.〈/i〉 It comprises a complex III dimer flanked on either side by individual complex IV subunits. Complex III and IV associate such that electrons can be transferred from quinol in complex III to the oxygen reduction center in complex IV via a bridging cytochrome subunit. We observe a superoxide dismutase-like subunit at the periplasmic face, which may be responsible for detoxification of superoxide formed by complex III. The structure reveals features of an established drug target and provides a foundation for development of treatments for human tuberculosis.〈/p〉
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Natural Sciences in General
    Published by American Association for the Advancement of Science (AAAS)
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  • 10
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    An electron transfer path connects subunits of a mycobacterial respiratory supercomplex (2018)
    American Association for the Advancement of Science (AAAS)
    In: Science
    Details
    Publication Date: 2018-11-30
    Description: We report a 3.5-angstrom-resolution cryo–electron microscopy structure of a respiratory supercomplex isolated from Mycobacterium smegmatis. It comprises a complex III dimer flanked on either side by individual complex IV subunits. Complex III and IV associate so that electrons can be transferred from quinol in complex III to the oxygen reduction center in complex IV by way of a bridging cytochrome subunit. We observed a superoxide dismutase-like subunit at the periplasmic face, which may be responsible for detoxification of superoxide formed by complex III. The structure reveals features of an established drug target and provides a foundation for the development of treatments for human tuberculosis.
    Keywords: Biochemistry, Online Only
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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