The amyloid precursor protein APP plays a key role in the pathogenesis of Alzheimer’s disease (AD), as proteolytical cleavage of APP gives rise to the Aß peptide which is deposited in the brains of Alzheimer patients. Despite this, our knowledge of the normal cell biological and physiological functions of APP and the closely related APLPs is limited. This may have hampered our understanding of AD, since evidence has accumulated that not only the production of the Aß peptide but also the loss of APP-mediated functions may contribute to AD pathogenesis. Thus, it appears timely and highly relevant to elucidate the functions of the APP gene family from the molecular level to their role in the intact organism, i.e. in the context of nervous system development, synapse formation and adult synapse function, as well as neural homeostasis and aging. Why is our understanding of the APP functions so limited? APP and the APLPs are multifunctional proteins that undergo complex proteolytical processing. They give rise to an almost bewildering array of different fragments that may each subserve specific functions. While Aß is aggregation prone and neurotoxic, the large secreted ectodomain APPsa - produced in the non-amyloidogenic a-secretase pathway - has been shown to be neurotrophic, neuroprotective and relevant for synaptic plasticity, learning and memory. Recently, novel APP cleavage pathways and enzymes have been discovered that have gained much attention not only with respect to AD but also regarding their role in normal brain physiology. In addition to the various cleavage products, there is also solid evidence that APP family proteins mediate important functions as transmembrane cell surface molecules, most notably in synaptic adhesion and cell surface signaling. Elucidating in more detail the molecular mechanisms underlying these divers functions thus calls for an interdisciplinary approach ranging from the structural level to the analysis in model organisms. Thus, in this research topic of Frontiers we compile reviews and original studies, covering our current knowledge of the physiological functions of this intriguing and medically important protein family.
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Derry, Maine — 1903. A quiet town smothered in fog. A place where whispers travel faster than the wind… and children vanish without a trace. When fifteen-year-old Caleb Harland’s younger brother disappears, the town offers only silence and shallow sympathy. But Caleb knows the truth hides beneath Derry’s streets — in the shadows, in the sewers, in the places adults refuse to look. At school, Caleb crosses paths with Sam, Martha, Clara, and Henry — five teenagers bound by fear, and curiosity.
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Aufbauend auf einem theoretischen Rahmenmodell, das sowohl positive als auch negative Wachstumseffekte des Finanzsektors berücksichtigt, wird die makroökonomische Effizienz des Finanzsektors definiert. Die empirische Untersuchung des theoretischen Modells anhand von 28 west- und osteuropäischen Ländern zeigt, dass der durch den Finanzsektor ausgelöste Wachstumseffekt durchweg positiv ist, jedoch mit zunehmender Bedeutung des Finanzsektors abnimmt und sich zwischen den Ländern unterscheidet. Der ausgelöste Wachstumseffekt ist kurzfristig. Simulationen für das Jahr 2002 zeigen, dass die makroeffiziente Optimierung der Bedeutung des Finanzsektors insbesondere in osteuropäischen Ländern kräftige Wachstumsimpulse verspricht.
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Australia: A Cultural History, first published in 1988, is still the only short history of Australia from a cultural perspective. It has acquired a unique reputation as an introduction to the development of Australian society and was listed by the historian and public intellectual John Hirst in his ‘First XI: The best Australian history books’. The book focuses on the transmission of values, beliefs and customs amongst the diverse mix of peoples who are today’s Australians. The story begins with the 60,000 years of the Aboriginal presence and their continuing material and spiritual relationship with the land, and takes readers through the turbulent years of British colonisation and the emergence, through prosperity, war and depression, of the cultural accommodations which have been distinctively Australian. This 3rd Edition concludes with a critical review of the challenges facing contemporary Australia and warns that ‘we may get the future we deserve’. [Some images unavailable for OA]
This publication includes the translation of the Plautus’ Mercator, with an introduction and footnotes. In the introduction, the most relevant elements of the play are analyzed aiming at its theoretical contextualization: the question of structure, the father/son rivalry as the central theme of the comedy; the characters; the language and the style; the comic; and the problematic chronology of the play. The study is complemented with an actualized bibliography.
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Unter dem Begriff der Aneignung werden verschiedene Formen der Übernahme urheberrechtlich geschützter Werke untersucht. Schon in den 1970ern nutzten Künstler der Appropriation Art Kopien für ihre Kunstwerke. Mit der Digitalisierung und der Partizipationskultur im Internet sind die Techniken der Appropriation Art demokratisiert und als Memes und GiFs Mittel der Massenkommunikation geworden. Diese Formen der Bildnutzungen – in der Appropriation Art und im Digitalen – werden urheberrechtlich bewertet. Dabei liegt ein Schwerpunkt der Arbeit darin, ob das geltende Urheberrecht der gesellschaftlichen Realität digitaler Kommunikation noch angemessen Rechnung tragen und wie rechtlicher Freiraum für Aneignungshandlungen geschaffen werden kann.
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