161,036 research outputs found
Early Intraneuronal Beta-Amyloid Pathology: Do Transgenic Mice Represent Valid Model Systems?
No full textWhereas a plethora of studies focusses on extracellular plaque deposition, only a very limited amount of reports deal with intraneuronal accumulation of A peptides in human AD. However, over the past years, accumulating evidence points to a significant role of intraneuronal A triggering the pathological cascade leading to neurodegeneration in Alzheimer’s disease (AD). Much of the data originate from studies on transgenic mouse models of AD, where initial intraneuronal A accumulation which predes extracellular plaque deposition, has been repeatedly reported. The current review discusses the impact of this finding on the future development of novel mouse models for preclinical research as a basis for therapeutic intervention
Review on the APP/PS1KI mouse model: intraneuronal Aβ accumulation triggers axonopathy, neuron loss and working memory impairment
No full textAccumulating evidence points to an important role of intraneuronal A beta as a trigger of the pathological cascade of events leading to neurodegeneration and eventually to Alzheimer's disease (AD) with its typical clinical symptoms, like memory impairment and change in personality. As a new concept, intraneuronal accumulation of A beta instead of extracellular A beta deposition has been introduced to be the disease-triggering event in AD. The present review compiles current knowledge on the amyloid precursor protein (APP)/PS1KI mouse model with early and massive intraneuronal A beta 42 accumulation: (1) The APP/PS1KI mouse model exhibits early robust brain and spinal cord axonal degeneration and hippocampal CA1 neuron loss. (2) At the same time-point, a dramatic, age-dependent reduced ability to perform working memory and motor tasks is observed. (3) The APP/PS1KI mice are smaller and show development of a thoracolumbar kyphosis, together with an incremental loss of body weight. (4) Onset of the observed behavioral alterations correlates well with robust axonal degeneration in brain and spinal cord and with abundant hippocampal CA1 neuron loss
Motor impairment in Alzheimer’s disease and transgenic Alzheimer’s disease mouse models
No full textIn this commentary, we accent the accumulating evidence for motor impairment as a common feature of early Alzheimer's disease (AD) pathology. In addition, we summarize the state of knowledge on this phenotype in experimental mouse models, expressing AD-associated genes like tau or amyloid precursor protein
Variations on the Author
No full text“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Going Beyond Counting First Authors in Author Co-citation Analysis
No full textThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Larry O. Spencer, Conference Author Presentation
No full textGen. Larry O. Spencer, USAF (Ret.), author of Dark Horse: A Journey from the Horseshoe to the Pentago
Dispelling the Myths Behind First-author Citation Counts
No full textWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
Author Under Sail The Imagination of Jack London, 1902-1907
No full textIn this second volume of Author Under Sail Jay Williams investigates the life of Jack London as a professional writer at the turn of the 1900s, as his publications spanned The Call of the Wild to The Iron Heel and The Road. While documenting key life events, especially his rising fame, this biography explores London's necessity to illustrate the inner workings of his own vast imagination through his socialist essays and fiction.Cover -- Title Page -- Copyright Page -- Contents -- Acknowledgments -- Introduction -- 1. Howl, O Heav'nly Muse! -- 2. Jesus in the Theater of Socialism -- 3. Jack London's Place in American Literature -- 4. Theater of War, Theater at Home -- 5. Revolution, Evolution, and the Scene of Writing -- 6. The Jack London Show Goes on the Road -- 7. Red Atavisms and Revolution -- 8. Earthquake Apocalypse and Building the City, Boat, and House Beautiful -- 9. The Future of Socialism and the Death of the Individual -- 10. The Road Never Ends -- Notes -- Bibliography -- IndexIn this second volume of Author Under Sail Jay Williams investigates the life of Jack London as a professional writer at the turn of the 1900s, as his publications spanned The Call of the Wild to The Iron Heel and The Road. While documenting key life events, especially his rising fame, this biography explores London's necessity to illustrate the inner workings of his own vast imagination through his socialist essays and fiction.Description based on publisher supplied metadata and other sources.Electronic reproduction. Ann Arbor, Michigan : ProQuest Ebook Central, YYYY. Available via World Wide Web. Access may be limited to ProQuest Ebook Central affiliated libraries
N-truncated amyloid β (Aβ) 4-42 forms stable aggregates and induces acute and long-lasting behavioral deficits
No full textN-truncated Aβ4-42 is highly abundant in Alzheimer disease (AD) brain and was the first Aβ peptide discovered in AD plaques. However, a possible role in AD aetiology has largely been neglected. In the present report, we demonstrate that Aβ4-42 rapidly forms aggregates possessing a high aggregation propensity in terms of monomer consumption and oligomer formation. Short-term treatment of primary cortical neurons indicated that Aβ4-42 is as toxic as pyroglutamate Aβ3-42 and Aβ1-42. In line with these findings, treatment of wildtype mice using intraventricular Aβ injection induced significant working memory deficits with Aβ4-42, pyroglutamate Aβ3-42 and Aβ1-42. Transgenic mice expressing Aβ4-42 (Tg4-42 transgenic line) developed a massive CA1 pyramidal neuron loss in the hippocampus. The hippocampus-specific expression of Aβ4-42 correlates well with age-dependent spatial reference memory deficits assessed by the Morris water maze test. Our findings indicate that N-truncated Aβ4-42 triggers acute and long-lasting behavioral deficits comparable to AD typical memory dysfunction. © 2013 The Author(s)
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