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  • 1
    Publication Date: 2012-04-18
    Description: Evolutionary change in gene expression is generally considered to be a major driver of phenotypic differences between species. We investigated innate immune diversification by analyzing interspecies differences in the transcriptional responses of primary human and mouse macrophages to the Toll-like receptor (TLR)–4 agonist lipopolysaccharide (LPS). By using a custom platform permitting cross-species interrogation coupled with deep sequencing of mRNA 5′ ends, we identified extensive divergence in LPS-regulated orthologous gene expression between humans and mice (24% of orthologues were identified as “divergently regulated”). We further demonstrate concordant regulation of human-specific LPS target genes in primary pig macrophages. Divergently regulated orthologues were enriched for genes encoding cellular “inputs” such as cell surface receptors (e.g., TLR6, IL-7Rα) and functional “outputs” such as inflammatory cytokines/chemokines (e.g., CCL20, CXCL13). Conversely, intracellular signaling components linking inputs to outputs were typically concordantly regulated. Functional consequences of divergent gene regulation were confirmed by showing LPS pretreatment boosts subsequent TLR6 responses in mouse but not human macrophages, in keeping with mouse-specific TLR6 induction. Divergently regulated genes were associated with a large dynamic range of gene expression, and specific promoter architectural features (TATA box enrichment, CpG island depletion). Surprisingly, regulatory divergence was also associated with enhanced interspecies promoter conservation. Thus, the genes controlled by complex, highly conserved promoters that facilitate dynamic regulation are also the most susceptible to evolutionary change.
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 2
    Publication Date: 2013-09-11
    Description: Background: Loss of CpG dinucleotides in genomic DNA through methylation-induced mutation is characteristic of vertebrates and plants. However, these and other eukaryotic phyla show a range of other dinucleotide frequency biases with currently uncharacterized underlying mutational or selection mechanisms. We developed a parameterized Markov process to identify what neighbour context-dependent mutations best accounted for patterns of dinucleotide frequency biases in genomic and cytoplasmically expressed mRNA sequences of different vertebrates, other eukaryotic groups and RNA viruses that infect them. Results: Consistently, 11- to 14-fold greater frequencies of the methylation-association mutation of C to T upstream of G (depicted C[rightwards arrow]T,G) than other transitions best modelled dinucleotide frequencies in mammalian genomic DNA. However, further mutations such as G[rightwards arrow]T,T (5-fold greater than the default transversion rate) were required to account for the full spectrum of dinucleotide frequencies in mammalian sequence datasets. Consistent with modeling predictions for these two mutations, instability of both CpG and CpT dinucleotides was identified through SNP frequency analysis of human DNA sequences. Different sets of context-dependent mutations were modelled in other eukaryotes with non-methylated genomic DNA. In contrast to genomic DNA, best-fit models of dinucleotide frequencies in transcribed RNA sequences expressed in the cytoplasm from all organisms were dominated by mutations that eliminated UpA dinucleotides, observations consistent with cytoplasmically driven selection for mRNA stability. Surprisingly, mRNA sequences from organisms with methylated genomes showed evidence for additional selection against CpG through further context-dependent mutations (eg. C[rightwards arrow]A,G). Similar mutation or selection processes were identified among single-stranded mammalian RNA viruses; these potentially account for their previously described but unexplained under-representations of CpG and UpA dinucleotides. Conclusions: Methods we have developed identify mutational processes and selection pressures in organisms provide new insights into nucleotide compositional constraints and a wealth of biochemical and evolutionarily testable predictions for the future.
    Electronic ISSN: 1471-2164
    Topics: Biology
    Published by BioMed Central
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  • 3
    Publication Date: 2013-09-21
    Description: Background: The specialisation of mammalian cells in time and space requires genes associated with specific pathways and functions to be co-ordinately expressed. Here we have combined a large number of publically available microarray datasets derived from human primary cells and analysed large correlation graphs of these data. Results: Using the network analysis tool BioLayout Express3D we identify robust co-associations of genes expressed in a wide variety of cell lineages. We discuss the biological significance of a number of these associations, in particular the coexpression of key transcription factors with the genes that they are likely to control. Conclusions: We consider the regulation of genes in human primary cells and specifically in the human mononuclear phagocyte system. Of particular note is the fact that these data do not support the identity of putative markers of antigen-presenting dendritic cells, nor classification of M1 and M2 activation states, a current subject of debate within immunological field. We have provided this data resource on the BioGPS web site (www.biogps.org) and on macrophages.com (www.macrophages.com).
    Electronic ISSN: 1471-2164
    Topics: Biology
    Published by BioMed Central
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  • 4
    Publication Date: 2016-08-11
    Description: Kidney organoids from human iPS cells contain multiple lineages and model human nephrogenesis Nature 536, 7615 (2016). doi:10.1038/nature17982 Authors: Minoru Takasato, Pei X. Er, Han S. Chiu, Barbara Maier, Gregory J. Baillie, Charles Ferguson, Robert G. Parton, Ernst J. Wolvetang, Matthias S. Roost, Susana M. Chuva de Sousa Lopes & Melissa H. Little Nature526, 564–568 (2015); doi:10.1038/nature15695In the Methods of this Letter, ‘5,000’ should have read ‘15,000’ in the sentence: “Then, cells were again plated on a Matrigel-coated at 15,000 cells per cm2 in MEF-CM.” This error
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Springer Nature
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  • 5
    Publication Date: 2012-11-16
    Description: Background: This work describes the first genome-wide analysis of the transcriptional landscape of the pig. A new porcine Affymetrix expression array was designed in order to provide comprehensive coverage of the known pig transcriptome. The new array was used to generate a genome-wide expression atlas of pig tissues derived from 62 tissue/cell types. These data were subjected to network correlation analysis and clustering. Results: The analysis presented here provides a detailed functional clustering of the pig transcriptome where transcripts are grouped according to their expression pattern, so one can infer the function of an uncharacterized gene from the company it keeps and the locations in which it is expressed. We describe the overall transcriptional signatures present in the tissue atlas, where possible assigning those signatures to specific cell populations or pathways. In particular, we discuss the expression signatures associated with the gastrointestinal tract, an organ that was sampled at 15 sites along its length and whose biology in the pig is similar to human. We identify sets of genes that define specialized cellular compartments and region-specific digestive functions. Finally, we performed a network analysis of the transcription factors expressed in the gastrointestinal tract and demonstrate how they sub-divide into functional groups that may control cellular gastrointestinal development. Conclusions: As an important livestock animal with a physiology that is more similar than mouse to man, we provide a major new resource for understanding gene expression with respect to the known physiology of mammalian tissues and cells. The data and analyses are available on the websites http://biogps.org and http://www.macrophages.com/pig-atlas.
    Electronic ISSN: 1741-7007
    Topics: Biology
    Published by BioMed Central
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  • 6
    Publication Date: 2008-10-11
    Description: Knowledge of mammalian diversity is still surprisingly disparate, both regionally and taxonomically. Here, we present a comprehensive assessment of the conservation status and distribution of the world's mammals. Data, compiled by 1700+ experts, cover all 5487 species, including marine mammals. Global macroecological patterns are very different for land and marine species but suggest common mechanisms driving diversity and endemism across systems. Compared with land species, threat levels are higher among marine mammals, driven by different processes (accidental mortality and pollution, rather than habitat loss), and are spatially distinct (peaking in northern oceans, rather than in Southeast Asia). Marine mammals are also disproportionately poorly known. These data are made freely available to support further scientific developments and conservation action.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schipper, Jan -- Chanson, Janice S -- Chiozza, Federica -- Cox, Neil A -- Hoffmann, Michael -- Katariya, Vineet -- Lamoreux, John -- Rodrigues, Ana S L -- Stuart, Simon N -- Temple, Helen J -- Baillie, Jonathan -- Boitani, Luigi -- Lacher, Thomas E Jr -- Mittermeier, Russell A -- Smith, Andrew T -- Absolon, Daniel -- Aguiar, John M -- Amori, Giovanni -- Bakkour, Noura -- Baldi, Ricardo -- Berridge, Richard J -- Bielby, Jon -- Black, Patricia Ann -- Blanc, J Julian -- Brooks, Thomas M -- Burton, James A -- Butynski, Thomas M -- Catullo, Gianluca -- Chapman, Roselle -- Cokeliss, Zoe -- Collen, Ben -- Conroy, Jim -- Cooke, Justin G -- da Fonseca, Gustavo A B -- Derocher, Andrew E -- Dublin, Holly T -- Duckworth, J W -- Emmons, Louise -- Emslie, Richard H -- Festa-Bianchet, Marco -- Foster, Matt -- Foster, Sabrina -- Garshelis, David L -- Gates, Cormack -- Gimenez-Dixon, Mariano -- Gonzalez, Susana -- Gonzalez-Maya, Jose Fernando -- Good, Tatjana C -- Hammerson, Geoffrey -- Hammond, Philip S -- Happold, David -- Happold, Meredith -- Hare, John -- Harris, Richard B -- Hawkins, Clare E -- Haywood, Mandy -- Heaney, Lawrence R -- Hedges, Simon -- Helgen, Kristofer M -- Hilton-Taylor, Craig -- Hussain, Syed Ainul -- Ishii, Nobuo -- Jefferson, Thomas A -- Jenkins, Richard K B -- Johnston, Charlotte H -- Keith, Mark -- Kingdon, Jonathan -- Knox, David H -- Kovacs, Kit M -- Langhammer, Penny -- Leus, Kristin -- Lewison, Rebecca -- Lichtenstein, Gabriela -- Lowry, Lloyd F -- Macavoy, Zoe -- Mace, Georgina M -- Mallon, David P -- Masi, Monica -- McKnight, Meghan W -- Medellin, Rodrigo A -- Medici, Patricia -- Mills, Gus -- Moehlman, Patricia D -- Molur, Sanjay -- Mora, Arturo -- Nowell, Kristin -- Oates, John F -- Olech, Wanda -- Oliver, William R L -- Oprea, Monik -- Patterson, Bruce D -- Perrin, William F -- Polidoro, Beth A -- Pollock, Caroline -- Powel, Abigail -- Protas, Yelizaveta -- Racey, Paul -- Ragle, Jim -- Ramani, Pavithra -- Rathbun, Galen -- Reeves, Randall R -- Reilly, Stephen B -- Reynolds, John E 3rd -- Rondinini, Carlo -- Rosell-Ambal, Ruth Grace -- Rulli, Monica -- Rylands, Anthony B -- Savini, Simona -- Schank, Cody J -- Sechrest, Wes -- Self-Sullivan, Caryn -- Shoemaker, Alan -- Sillero-Zubiri, Claudio -- De Silva, Naamal -- Smith, David E -- Srinivasulu, Chelmala -- Stephenson, Peter J -- van Strien, Nico -- Talukdar, Bibhab Kumar -- Taylor, Barbara L -- Timmins, Rob -- Tirira, Diego G -- Tognelli, Marcelo F -- Tsytsulina, Katerina -- Veiga, Liza M -- Vie, Jean-Christophe -- Williamson, Elizabeth A -- Wyatt, Sarah A -- Xie, Yan -- Young, Bruce E -- New York, N.Y. -- Science. 2008 Oct 10;322(5899):225-30. doi: 10.1126/science.1165115.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉International Union for Conservation of Nature (IUCN) Species Programme, IUCN, 28 Rue Mauverney, 1196 Gland, Switzerland. jan.schipper@iucn.org〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18845749" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biodiversity ; Body Size ; Conservation of Natural Resources ; Databases, Factual ; Ecosystem ; *Extinction, Biological ; *Mammals/anatomy & histology/classification/physiology ; Marine Biology ; Phylogeny ; Population Dynamics ; Seawater
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 7
    Publication Date: 2015-10-08
    Description: The human kidney contains up to 2 million epithelial nephrons responsible for blood filtration. Regenerating the kidney requires the induction of the more than 20 distinct cell types required for excretion and the regulation of pH, and electrolyte and fluid balance. We have previously described the simultaneous induction of progenitors for both collecting duct and nephrons via the directed differentiation of human pluripotent stem cells. Paradoxically, although both are of intermediate mesoderm in origin, collecting duct and nephrons have distinct temporospatial origins. Here we identify the developmental mechanism regulating the preferential induction of collecting duct versus kidney mesenchyme progenitors. Using this knowledge, we have generated kidney organoids that contain nephrons associated with a collecting duct network surrounded by renal interstitium and endothelial cells. Within these organoids, individual nephrons segment into distal and proximal tubules, early loops of Henle, and glomeruli containing podocytes elaborating foot processes and undergoing vascularization. When transcription profiles of kidney organoids were compared to human fetal tissues, they showed highest congruence with first trimester human kidney. Furthermore, the proximal tubules endocytose dextran and differentially apoptose in response to cisplatin, a nephrotoxicant. Such kidney organoids represent powerful models of the human organ for future applications, including nephrotoxicity screening, disease modelling and as a source of cells for therapy.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Takasato, Minoru -- Er, Pei X -- Chiu, Han S -- Maier, Barbara -- Baillie, Gregory J -- Ferguson, Charles -- Parton, Robert G -- Wolvetang, Ernst J -- Roost, Matthias S -- Chuva de Sousa Lopes, Susana M -- Little, Melissa H -- England -- Nature. 2015 Oct 22;526(7574):564-8. doi: 10.1038/nature15695. Epub 2015 Oct 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Murdoch Childrens Research Institute, The Royal Children's Hospital Melbourne, Parkville, Victoria 3052, Australia. ; Institute for Molecular Bioscience, The University of Queensland, St Lucia, Queensland 4072, Australia. ; Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, St Lucia, Queensland 4072, Australia. ; Department of Anatomy and Embryology, Leiden University Medical Center, Einthovenweg 20, 2333 ZC Leiden, The Netherlands. ; Department of Paediatrics, The University of Melbourne, Parkville, Victoria 3010, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26444236" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Cell Lineage ; Coculture Techniques ; Feeder Cells ; Fetus/anatomy & histology/cytology/embryology ; Fibroblasts/cytology ; Humans ; Induced Pluripotent Stem Cells/*cytology ; Kidney Tubules, Collecting/cytology ; Kidney Tubules, Proximal/cytology/embryology/physiology ; Mesoderm/cytology ; Mice ; *Models, Biological ; Nephrons/anatomy & histology/*cytology/*embryology/physiology ; *Organogenesis ; Organoids/*cytology/embryology ; Tissue Culture Techniques
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 8
    Publication Date: 2016-04-28
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Takasato, Minoru -- Er, Pei X -- Chiu, Han S -- Maier, Barbara -- Baillie, Gregory J -- Ferguson, Charles -- Parton, Robert G -- Wolvetang, Ernst J -- Roost, Matthias S -- Lopes, Susana M Chuva de Sousa -- Little, Melissa H -- Nature. 2016 Apr 27. doi: 10.1038/nature17982.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27120161" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Human genetics 〈Berlin〉 37 (1977), S. 299-302 
    ISSN: 1432-1203
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Chromosomal analysis from aborted tissue has become an important diagnostic aid. However, the necessary cultures are frequently unsuccessful due to the condition of the aborted tissue. Polyploidy, in particular triploidy, in the conceptus is a common cause of early pregnancy loss and unlike aneuploidy does not appear to be associated with an increased recurrence risk. The necessity to monitor a subsequent pregnancy with amniocentesis is therefore eliminated. Therefore, in cases where a chromosomal anomaly is probable, a fast simple method of identification of a polyploid karyotype would be valuable. In this presentation, we describe a method using a scanning light microscope and histologic tissue preparations. This method can accurately determine the ploidy of the aborted material in 5 days.
    Type of Medium: Electronic Resource
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  • 10
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