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  • 1
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    Hippocampal dysfunction in the Euchromatin histone methyltransferase 1 heterozygous knockout mouse model for Kleefstra syndrome (2013)
    Oxford University Press
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    Publication Date: 2013-02-02
    Description: Euchromatin histone methyltransferase 1 (EHMT1) is a highly conserved protein that catalyzes mono- and dimethylation of histone H3 lysine 9, thereby epigenetically regulating transcription. Kleefstra syndrome (KS), is caused by haploinsufficiency of the EHMT1 gene, and is an example of an emerging group of intellectual disability (ID) disorders caused by genes encoding epigenetic regulators of neuronal gene activity. Little is known about the mechanisms underlying this disorder, prompting us to study the Euchromatin histone methyltransferase 1 heterozygous knockout ( Ehmt1 +/– ) mice as a model for KS. In agreement with the cognitive disturbances observed in patients with KS, we detected deficits in fear extinction learning and both novel and spatial object recognition in Ehmt1 +/– mice. These learning and memory deficits were associated with a significant reduction in dendritic arborization and the number of mature spines in hippocampal CA1 pyramidal neurons of Ehmt1 +/– mice. In-depth analysis of the electrophysiological properties of CA3-CA1 synapses revealed no differences in basal synaptic transmission or theta-burst induced long-term potentiation (LTP). However, paired-pulse facilitation (PPF) was significantly increased in Ehmt1 +/– neurons, pointing to a potential deficiency in presynaptic neurotransmitter release. Accordingly, a reduction in the frequency of miniature excitatory post-synaptic currents (mEPSCs) was observed in Ehmt1 +/– neurons. These data demonstrate that Ehmt1 haploinsufficiency in mice leads to learning deficits and synaptic dysfunction, providing a possible mechanism for the ID phenotype in patients with KS.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
    Published by Oxford University Press
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  • 2
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    Bellman's GAP--a language and compiler for dynamic programming in sequence analysis (2013)
    Oxford University Press
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    Publication Date: 2013-02-27
    Description: Motivation: Dynamic programming is ubiquitous in bioinformatics. Developing and implementing non-trivial dynamic programming algorithms is often error prone and tedious. Bellman’s GAP is a new programming system, designed to ease the development of bioinformatics tools based on the dynamic programming technique. Results: In Bellman’s GAP, dynamic programming algorithms are described in a declarative style by tree grammars, evaluation algebras and products formed thereof. This bypasses the design of explicit dynamic programming recurrences and yields programs that are free of subscript errors, modular and easy to modify. The declarative modules are compiled into C++ code that is competitive to carefully hand-crafted implementations. This article introduces the Bellman’s GAP system and its language, GAP-L. It then demonstrates the ease of development and the degree of re-use by creating variants of two common bioinformatics algorithms. Finally, it evaluates Bellman’s GAP as an implementation platform of ‘real-world’ bioinformatics tools. Availability: Bellman’s GAP is available under GPL license from http://bibiserv.cebitec.uni-bielefeld.de/bellmansgap . This Web site includes a repository of re-usable modules for RNA folding based on thermodynamics. Contact: robert@techfak.uni-bielefeld.de Supplementary information: Supplementary data are available at Bioinformatics online
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
    Published by Oxford University Press
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  • 3
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    Contributions of knowledge products to health policy: a case study on the Public Health Status and Forecasts Report 2010 (2016)
    Oxford University Press
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    Publication Date: 2016-12-21
    Description: Background: The Dutch Public Health Status and Forecasts report (PHSF Report) integrates research data and identifies future trends affecting public health in the Netherlands. To investigate how PHSF contributions to health policy can be enhanced, we analysed the development process whereby the PHSF Report for 2010 was produced (PHSF-2010). Method : To collect data, a case study approach was used along the lines of Contribution Mapping including analysis of documents from the PHSF-2010 process and interviews with actors involved. All interviews were recorded and transcribed ad verbatim and coded using an inductive code list. Results: The PHSF-2010 process included activities aimed at alignment between researchers and policy-makers, such as informal meetings. However, we identified three issues that are easily overlooked in knowledge development, but provide suggestions for enhancing contributions: awareness of divergent; continuously changing actor scenarios; vertical alignment within organizations involved and careful timing of draft products to create early adopters. Conclusion : To enhance the contributions made by an established public health report, such as the PHSF Report, it is insufficient to raise the awareness of potential users. The knowledge product must be geared to policy-makers’ needs and must be introduced into the scenarios of actors who may be less familiar. The demand for knowledge product adaptations has to be considered. This requires continuous alignment efforts in all directions: horizontal and vertical, external and internal. The findings of this study may be useful to researchers who aim to enhance the contributions of their knowledge products to health policy.
    Print ISSN: 1101-1262
    Electronic ISSN: 1464-360X
    Topics: Medicine
    Published by Oxford University Press
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  • 4
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    The RNA shapes studio (2015)
    Oxford University Press
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    Publication Date: 2015-01-29
    Description: Motivation : Abstract shape analysis, first proposed in 2004, allows one to extract several relevant structures from the folding space of an RNA sequence, preferable to focusing in a single structure of minimal free energy. We report recent extensions to this approach. Results : We have rebuilt the original RNA shapes as a repository of components that allows us to integrate several established tools for RNA structure analysis: RNA shapes , RNA alishapes and pknots RG, including its recent extension p K iss . As a spin-off, we obtain heretofore unavailable functionality: e. g. with p K iss , we can now perform abstract shape analysis for structures holding pseudoknots up to the complexity of kissing hairpin motifs. The new tool p A li K iss can predict kissing hairpin motifs from aligned sequences. Along with the integration, the functionality of the tools was also extended in manifold ways. Availability and implementation : As before, the tool is available on the Bielefeld Bioinformatics server at http://bibiserv.cebitec.uni-bielefeld.de/rnashapesstudio . Contact : bibi-help@cebitec.uni-bielefeld.de
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
    Published by Oxford University Press
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