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Description: The aim of this paper is to reconstruct the evolution of the early to middle Holocene Rhine-Meuse river mouths in the western Netherlands and to understand the observed spatial and temporal changes in facies. This is achieved by constructing three delta wide cross-sections using a newly accumulated database with thousands of core descriptions and cone penetration test results, together with a large set of pollen/diatom analyses and OSL/14C-dates. Most of the studied deposits accumulated in the fluvial-to-marine transition zone, a highly complex area due to the interaction of terrestrial and marine processes. Understanding how the facies change within this zone, is necessary to make correct palaeogeographic interpretations.We find a well preserved early to middle Holocene coastal prism resting on lowstand valley floors. Aggradation started after 9 ka cal BP as a result of rapid sea-level rise. Around 8 ka most parts of the study area were permanently flooded and under tidal influence. After 8 ka a bay-head delta was formed near Delft, meaning that little sand could reach the North Sea. Several subsequent avulsions resulted in a shift from the constantly retreating Rhine river mouth to the north. When after 6.5 ka the most northerly river course was formed (Oude Rijn), the central part of the palaeovalley was quickly transgressed and transformed into a large tidal basin. Shortly before 6 ka retrogradation of the coastline halted and tidal inlets began to close, marking the end of the early-middle Holocene transgression.This paper describes the transition from a fluvial valley to an estuary in unprecedented detail and enables more precise palaeo-reconstructions, evaluation of relative importance of fluvial and coastal processes in rapid transgressed river mouths, and more accurate sediment-budget calculations. The described and well illustrated (changes in) facies are coupled to lithogenetic units. This will aid detailed palaeogeographic interpretations from sedimentary successions, not only in the Netherlands, but also in other estuarine and deltaic regions.

Print ISSN: 0016-7746

Electronic ISSN: 1573-9708

Topics: Geosciences

Published by Cambridge University Press

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SNPExpress: integrated visualization of genome-wide genotypes, copy numbers and gene expression levels (2008)

Sanders, Mathijs A ; Verhaak, Roel GW ; Geertsma-Kleinekoort, Wendy MC ; [et al.]

BioMed Central

In: BMC Genomics. 2008; 9(1): 41. Published 2008 Jan 25. doi: 10.1186/1471-2164-9-41.

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Publication Date: 2008-01-25

Description: Background Accurate analyses of comprehensive genome-wide SNP genotyping and gene expression data sets is challenging for many researchers. In fact, obtaining an integrated view of both large scale SNP genotyping and gene expression is currently complicated since only a limited number of appropriate software tools are available. Results We present SNPExpress, a software tool to accurately analyze Affymetrix and Illumina SNP genotype calls, copy numbers, polymorphic copy number variations (CNVs) and Affymetrix gene expression in a combinatorial and efficient way. In addition, SNPExpress allows concurrent interpretation of these items with Hidden-Markov Model (HMM) inferred Loss-of-Heterozygosity (LOH)- and copy number regions. Conclusion The combined analyses with the easily accessible software tool SNPExpress will not only facilitate the recognition of recurrent genetic lesions, but also the identification of critical pathogenic genes.

Electronic ISSN: 1471-2164

Topics: Biology

Published by BioMed Central

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A distinct epigenetic signature at targets of a leukemia protein (2007)

Rossetti, Stefano ; Hoogeveen, André T ; Liang, Ping ; [et al.]

BioMed Central

In: BMC Genomics. 2007; 8(1): 38. Published 2007 Feb 01. doi: 10.1186/1471-2164-8-38.

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Publication Date: 2007-02-01

Description: Background Human myelogenous leukemia characterized by either the non random t(8; 21)(q22; q22) or t(16; 21)(q24; q22) chromosome translocations differ for both their biological and clinical features. Some of these features could be consequent to differential epigenetic transcriptional deregulation at AML1 targets imposed by AML1-MTG8 and AML1-MTG16, the fusion proteins deriving from the two translocations. Preliminary findings showing that these fusion proteins lead to transcriptional downregulation of AML1 targets, marked by repressive chromatin changes, would support this hypothesis. Here we show that combining conventional global gene expression arrays with the power of bioinformatic genomic survey of AML1-consensus sequences is an effective strategy to identify AML1 targets whose transcription is epigenetically downregulated by the leukemia-associated AML1-MTG16 protein. Results We interrogated mouse gene expression microarrays with probes generated either from 32D cells infected with a retroviral vector carrying AML1-MTG16 and unable of granulocyte differentiation and proliferation in response to the granulocyte colony stimulating factor (G-CSF), or from 32D cells infected with the cognate empty vector. From the analysis of differential gene expression alone (using as criteria a p value 〈 0.01 and an absolute fold change 〉 3), we were unable to conclude which of the 37 genes downregulated by AML1-MTG16 were, or not, direct AML1 targets. However, when we applied a bioinformatic approach to search for AML1-consensus sequences in the 10 Kb around the gene transcription start sites, we closed on 17 potential direct AML1 targets. By focusing on the most significantly downregulated genes, we found that both the AML1-consensus and the transcription start site chromatin regions were significantly marked by aberrant repressive histone tail changes. Further, the promoter of one of these genes, containing a CpG island, was aberrantly methylated. Conclusion This study shows that a leukemia-associated fusion protein can impose a distinct epigenetic repressive signature at specific sites in the genome. These findings strengthen the conclusion that leukemia-specific oncoproteins can induce non-random epigenetic changes.

Electronic ISSN: 1471-2164

Topics: Biology

Published by BioMed Central

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TF Target Mapper: A BLAST search tool for the identification of Transcription Factor target genes (2006)

Horsman, Sebastiaan ; Moorhouse, Michael J ; de Jager, Victor CL ; [et al.]

BioMed Central

In: BMC Bioinformatics. 2006; 7(1): 120. Published 2006 Mar 08. doi: 10.1186/1471-2105-7-120.

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Publication Date: 2006-03-08

Description: Background In the current era of high throughput genomics a major challenge is the genome-wide identification of target genes for specific transcription factors. Chromatin immunoprecipitation (ChIP) allows the isolation of in vivo binding sites of transcription factors and provides a powerful tool for examining gene regulation. Crosslinked chromatin is immunoprecipitated with antibodies against specific transcription factors, thus enriching for sequences bound in vivo by these factors in the immunoprecipitated DNA. Cloning and sequencing the immunoprecipitated sequences allows identification of transcription factor target genes. Routinely, thousands of such sequenced clones are used in BLAST searches to map their exact location in the genome and the genes located in the vicinity. These genes represent potential targets of the transcription factor of interest. Such bioinformatics analysis is very laborious if performed manually and for this reason there is a need for developing bioinformatic tools to automate and facilitate it. Results In order to facilitate this analysis we generated TF Target Mapper (T ranscription F actor Target Mapper). TF Target Mapper is a BLAST search tool allowing rapid extraction of annotated information on genes around each hit. It combines sequence cleaning/filtering, pattern searching and BLAST searches with extraction of information on genes located around each BLAST hit and comparisons of the output list of genes or gene ontology IDs with user-implemented lists. We successfully applied and tested TF Target Mapper to analyse sequences bound in vivo by the transcription factor GATA-1. We show that TF Target Mapper efficiently extracted information on genes around ChIPed sequences, thus identifying known (e.g. α-globin and ζ-globin) and potentially novel GATA-1 gene targets. Conclusion TF Target Mapper is a very efficient BLAST search tool that allows the rapid extraction of annotated information on the genes around each hit. It can contribute to the comprehensive bioinformatic transcriptome/regulome analysis, by providing insight into the mechanisms of action of specific transcription factors, thus helping to elucidate the pathways these factors regulate.

Electronic ISSN: 1471-2105

Topics: Biology , Computer Science

Published by BioMed Central

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Functional annotation of the human retinal pigment epithelium transcriptome (2009)

Booij, Judith C ; van Soest, Simone ; Swagemakers, Sigrid MA ; [et al.]

BioMed Central

In: BMC Genomics. 2009; 10(1): 164. Published 2009 Apr 20. doi: 10.1186/1471-2164-10-164.

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Publication Date: 2009-04-20

Description: Background To determine level, variability and functional annotation of gene expression of the human retinal pigment epithelium (RPE), the key tissue involved in retinal diseases like age-related macular degeneration and retinitis pigmentosa. Macular RPE cells from six selected healthy human donor eyes (aged 63–78 years) were laser dissected and used for 22k microarray studies (Agilent technologies). Data were analyzed with Rosetta Resolver, the web tool DAVID and Ingenuity software. Results In total, we identified 19,746 array entries with significant expression in the RPE. Gene expression was analyzed according to expression levels, interindividual variability and functionality. A group of highly (n = 2,194) expressed RPE genes showed an overrepresentation of genes of the oxidative phosphorylation, ATP synthesis and ribosome pathways. In the group of moderately expressed genes (n = 8,776) genes of the phosphatidylinositol signaling system and aminosugars metabolism were overrepresented. As expected, the top 10 percent (n = 2,194) of genes with the highest interindividual differences in expression showed functional overrepresentation of the complement cascade, essential in inflammation in age-related macular degeneration, and other signaling pathways. Surprisingly, this same category also includes the genes involved in Bruch's membrane (BM) composition. Among the top 10 percent of genes with low interindividual differences, there was an overrepresentation of genes involved in local glycosaminoglycan turnover. Conclusion Our study expands current knowledge of the RPE transcriptome by assigning new genes, and adding data about expression level and interindividual variation. Functional annotation suggests that the RPE has high levels of protein synthesis, strong energy demands, and is exposed to high levels of oxidative stress and a variable degree of inflammation. Our data sheds new light on the molecular composition of BM, adjacent to the RPE, and is useful for candidate retinal disease gene identification or gene dose-dependent therapeutic studies.

Electronic ISSN: 1471-2164

Topics: Biology

Published by BioMed Central

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Electronic Resource

A new gene, encoding an anion transporter, is mutated in sialic acid storage diseases (1999)

Verbeek, Elly ; Aula, Nina ; Beerens, Cecile E.M.T. ; [et al.]

[s.l.] : Nature America Inc.

Nature genetics 23 (1999), S. 462-465

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ISSN: 1546-1718

Source: Nature Archives 1869 - 2009

Topics: Biology , Medicine

Notes: [Auszug] Sialic acid storage diseases (SASD, MIM 269920) are autosomal recessive neurodegenerative disorders that may present as a severe infantile form (ISSD) or a slowly progressive adult form, which is prevalent in Finland (Salla disease). The main symptoms are hypotonia, cerebellar ataxia and mental ...

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1038/70585

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Paper (German National Licenses)

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