23 research outputs found

    Presenilin Controls CBP Levels in the Adult Drosophila Central Nervous System

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    Background: Dominant mutations in both human Presenilin (Psn) genes have been correlated with the formation of amyloid plaques and development of familial early-onset Alzheimer’s disease (AD). However, a definitive mechanism whereby plaque formation causes the pathology of familial and sporadic forms of AD has remained elusive. Recent discoveries of several substrates for Psn protease activity have sparked alternative hypotheses for the pathophysiology underlying AD. CBP (CREB-binding protein) is a haplo-insufficient transcriptional co-activator with histone acetly-transferase (HAT) activity that has been proposed to be a downstream target of Psn signaling. Individuals with altered CBP have cognitive deficits that have been linked to several neurological disorders. Methodology/Principal Findings: Using a transgenic RNA-interference strategy to selectively silence CBP, Psn, and Notch in adult Drosophila, we provide evidence for the first time that Psn is required for normal CBP levels and for maintaining specific global acetylations at lysine 8 of histone 4 (H4K8ac) in the central nervous system (CNS). In addition, flies conditionally compromised for the adult-expression of CBP display an altered geotaxis behavior that may reflect a neurological defect. Conclusions/Significance: Our data support a model in which Psn regulates CBP levels in the adult fly brain in a manner that is independent of Notch signaling. Although we do not understand the molecular mechanism underlying th

    Role for Circadian Clock Genes in Seasonal Timing: Testing the Bunning Hypothesis

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    A major question in chronobiology focuses around the “Bünning hypothesis” which implicates the circadian clock in photoperiodic (day-length) measurement and is supported in some systems (e.g. plants) but disputed in others. Here, we used the seasonally-regulated thermotolerance of Drosophila melanogaster to test the role of various clock genes in day-length measurement. In Drosophila, freezing temperatures induce reversible chill coma, a narcosis-like state. We have corroborated previous observations that wild-type flies developing under short photoperiods (winter-like) exhibit significantly shorter chill-coma recovery times (CCRt) than flies that were raised under long (summer-like) photoperiods. Here, we show that arrhythmic mutant strains, per01, tim01 and ClkJrk, as well as variants that speed up or slow down the circadian period, disrupt the photoperiodic component of CCRt. Our results support an underlying circadian function mediating seasonal daylength measurement and indicate that clock genes are tightly involved in photo- and thermo-periodic measurements

    Immissionsmessungen von faserigen Stäuben in der Bundesrepublik Deutschland. Faserige Immissionen in der Umgebung von Objekten und Gebäuden mit asbesthaltigem Baumaterial

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    Immissionen von faserigen Stäuben wurden in den Jahren 1983 - 1985 in der nahen Umgebung von Gebäuden mit abwitterten und korrodierten Asbestzement-Produkten durchgeführt. Die Asbestfaserkonzentration (Fasern länger als 5 mym) lagen im Bereich von 50 - 5000 Fasern/cbm. (IUCT

    Immissionsmessungen von faserigen Stäuben in der Bundesrepublik Deutschland - Asbest-Immissionsmessungen in Niedersachsen

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    Asbestfaser - Konzentrationen wurden an 8 ausgewaehlten Orten in Niedersachsen in den Jahren 1985/1986 gemessen. Fast 50% der gemessenen Aussenluftkonzentrationen lagen im Bereich 100 bis 1000 Asbestfaser/cbm. (IUCT
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