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  • 1
    Online Resource
    Online Resource
    Induced Pluripotent Stem Cells Generated from Patients with ALS Can Be Differentiated into Motor Neurons
    American Association for the Advancement of Science (AAAS) ; 2008
    In:  Science Vol. 321, No. 5893 ( 2008-08-29), p. 1218-1221
    Details
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 321, No. 5893 ( 2008-08-29), p. 1218-1221
    Abstract: The generation of pluripotent stem cells from an individual patient would enable the large-scale production of the cell types affected by that patient's disease. These cells could in turn be used for disease modeling, drug discovery, and eventually autologous cell replacement therapies. Although recent studies have demonstrated the reprogramming of human fibroblasts to a pluripotent state, it remains unclear whether these induced pluripotent stem (iPS) cells can be produced directly from elderly patients with chronic disease. We have generated iPS cells from an 82-year-old woman diagnosed with a familial form of amyotrophic lateral sclerosis (ALS). These patient-specific iPS cells possess properties of embryonic stem cells and were successfully directed to differentiate into motor neurons, the cell type destroyed in ALS.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
    URL: Article
    DOI: 10.1126/science.1158799
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2008
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    SSG: 11
    Location Call Number Limitation Availability
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  • 2
    Online Resource
    Online Resource
    Transient 2D IR spectroscopy of ubiquitin unfolding dynamics
    Proceedings of the National Academy of Sciences ; 2007
    In:  Proceedings of the National Academy of Sciences Vol. 104, No. 36 ( 2007-09-04), p. 14237-14242
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 104, No. 36 ( 2007-09-04), p. 14237-14242
    Abstract: Transient two-dimensional infrared (2D IR) spectroscopy is used as a probe of protein unfolding dynamics in a direct comparison of fast unfolding experiments with molecular dynamics simulations. In the experiments, the unfolding of ubiquitin is initiated by a laser temperature jump, and protein structural evolution from nanoseconds to milliseconds is probed using amide I 2D IR spectroscopy. The temperature jump prepares a subensemble near the unfolding transition state, leading to quasi-barrierless unfolding (the “burst phase”) before the millisecond activated unfolding kinetics. The burst phase unfolding of ubiquitin is characterized by a loss of the coupling between vibrations of the β-sheet, a process that manifests itself in the 2D IR spectrum as a frequency blue-shift and intensity decrease of the diagonal and cross-peaks of the sheet's two IR active modes. As the sheet unfolds, increased fluctuations and solvent exposure of the β-sheet amide groups are also characterized by increases in homogeneous linewidth. Experimental spectra are compared with 2D IR spectra calculated from the time-evolving structures in a molecular dynamics simulation of ubiquitin unfolding. Unfolding is described as a sequential unfolding of strands in ubiquitin's β-sheet, using two collective coordinates of the sheet: ( i ) the native interstrand contacts between adjacent β-strands I and II and ( ii ) the remaining β-strand contacts within the sheet. The methods used illustrate the general principles by which 2D IR spectroscopy can be used for detailed dynamical comparisons of experiment and simulation.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.0700959104
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2007
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    SSG: 11
    SSG: 12
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  • 3
    Online Resource
    Online Resource
    Stability Regulation of mRNA and the Control of Gene Expression
    Wiley ; 2005
    In:  Annals of the New York Academy of Sciences Vol. 1058, No. 1 ( 2005-11), p. 196-204
    Details
    In: Annals of the New York Academy of Sciences, Wiley, Vol. 1058, No. 1 ( 2005-11), p. 196-204
    Abstract: Microarray technology has become highly valuable for identifying complex global changes in gene expression patterns. Standard techniques measure changes in total cellular poly(A) mRNA levels. The assumption that changes in gene expression as measured by these techniques are directly and well correlated with changes in rates of new gene synthesis form the basis of attempts to connect coordinated changes in gene expression with shared transcription regulatory elements. Yet systematic attempts at this approach remain difficult to demonstrate convincingly. One reason for this difficulty may result from the intricate convergence of both transcriptional and mRNA turnover events which, together, directly influence steady‐state mRNA levels. Recent technical advances have led to the successful scale‐up and application of nuclear run‐on procedures directly to microarrays. This development has allowed a gene‐by‐gene comparison between new gene synthesis in the nucleus and measured changes in total cellular polyA mRNA. Results from these studies have begun to challenge the strict interpretation of changes in gene expression measured by conventional microarrays as being closely correlated with changes in mRNA transcription rate, but rather they tend to support the significant expansion of the role played by changes in mRNA stability regulation to standard analyses of gene expression. Gene expression profiles obtained from both polyA mRNA (whole‐cell) and nuclear run‐on (newly transcribed) RNA across a time course of one hour following the activation of human Jurkat T cells with PMA plus ionomycin revealed that regulation of mRNA stability may account for as much as 50% of all measurements of changes in total cellular polyA mRNA in this system. Stability regulation was inferred by the absence of corresponding regulation of nuclear gene transcription activity for groups of genes strongly regulated at the whole cell level and which were also resistant to inhibition by Actinomycin D pre‐treatment. Consistent patterns across the time course were observed for both transcribed and stability‐regulated genes. It is proposed that the regulation of mRNA stability in response to external stimuli contributes significantly to observed changes in gene expression as measured by high throughput systems.
    Type of Medium: Online Resource
    ISSN: 0077-8923 , 1749-6632
    URL: Article
    DOI: 10.1196/annals.1359.026
    RVK:
    TD 7650
    Language: English
    Publisher: Wiley
    Publication Date: 2005
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    detail.hit.zdb_id: 2071584-5
    SSG: 11
    Location Call Number Limitation Availability
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