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  • 1
    In: ChemPhysChem, Wiley, Vol. 12, No. 3 ( 2011-02-25), p. 673-680
    Kurzfassung: Misfolding and aggregation of amyloidogenic polypeptides lie at the root of many neurodegenerative diseases. Whilst protein aggregation can be readily studied in vitro by established biophysical techniques, direct observation of the nature and kinetics of aggregation processes taking place in vivo is much more challenging. We describe here, however, a Förster resonance energy transfer sensor that permits the aggregation kinetics of amyloidogenic proteins to be quantified in living systems by exploiting our observation that amyloid assemblies can act as energy acceptors for variants of fluorescent proteins. The observed lifetime reduction can be attributed to fluorescence energy transfer to intrinsic energy states associated with the growing amyloid species. Indeed, for α‐synuclein, a protein whose aggregation is linked to Parkinson′s disease, we have used this sensor to follow the kinetics of the self‐association reactions taking place in vitro and in vivo and to reveal the nature of the ensuing aggregated species. Experiments were conducted in vitro, in cells in culture and in living Caenorhabditis elegans . For the latter the readout correlates directly with the appearance of a toxic phenotype. The ability to measure the appearance and development of pathogenic amyloid species in a living animal and the ability to relate such data to similar processes observed in vitro provides a powerful new tool in the study of the pathology of the family of misfolding disorders. Our study confirms the importance of the molecular environment in which aggregation reactions take place, highlighting similarities as well as differences between the processes occurring in vitro and in vivo, and their significance for defining the molecular physiology of the diseases with which they are associated.
    Materialart: Online-Ressource
    ISSN: 1439-4235 , 1439-7641
    URL: Issue
    Sprache: Englisch
    Verlag: Wiley
    Publikationsdatum: 2011
    ZDB Id: 2025223-7
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 2
    Online-Ressource
    Online-Ressource
    Wiley ; 1991
    In:  Acta Paediatrica Vol. 80, No. 8-9 ( 1991-08), p. 786-791
    In: Acta Paediatrica, Wiley, Vol. 80, No. 8-9 ( 1991-08), p. 786-791
    Kurzfassung: ABSTRACT. The efficacy of low‐dose doxapram therapy (0.2 mg/kg/h) in combination with methylxanthines was evaluated in 20 premature infants with idiopathic apnea unresponsive to methylxanthines alone, and in 13 premature infants with secondary apnea. The serum concentrations of doxapram and, in some infants, the simultaneous cerebrospinal fluid and serum concentrations were measured, and the correlation between cerebrospinal fluid and serum concentrations in the postnatal period was determined. The following results were obtained: 1) In idiopathic apnea of prematurity, low‐dose doxapram therapy was as effective as a dose of 1.0‐2.5 mg/kg/h and the side effects were few, mild, and reversible. 2) In premature infants over seven days of age, serum concentrations of doxapram were almost stable but were significantly lower than in infants within the first six days of life. 3) The ratio of the cerebrospinal fluid to serum doxapram concentration was 0.48 ± 0.13 (mean ± SD). There was a good correlation between cerebrospinal fluid and serum concentrations ( r = 0.933, p 〈 0.001). The initial doxapram dose can be set as low as 0.2 mg/kg/h in very young premature infants with idiopathic apnea of prematurity unresponsive to methylxanthines.
    Materialart: Online-Ressource
    ISSN: 0803-5253 , 1651-2227
    URL: Issue
    Sprache: Englisch
    Verlag: Wiley
    Publikationsdatum: 1991
    ZDB Id: 1492629-5
    ZDB Id: 1501466-6
    Standort Signatur Einschränkungen Verfügbarkeit
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