1,720,970 research outputs found
Isolated catatonia-like executive dysfunction in mice with forebrain-specific loss of myelin integrity
No full textNeuronal cholesterol synthesis is essential for repair of chronically demyelinated lesions in mice
No full textGoing Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe 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
Myelin dysfunction drives amyloid-β deposition in models of Alzheimer’s disease
No full textAbstract The incidence of Alzheimer’s disease (AD), the leading cause of dementia, increases rapidly with age, but why age constitutes the main risk factor is still poorly understood. Brain ageing affects oligodendrocytes and the structural integrity of myelin sheaths 1 , the latter of which is associated with secondary neuroinflammation 2,3 . As oligodendrocytes support axonal energy metabolism and neuronal health 4–7 , we hypothesized that loss of myelin integrity could be an upstream risk factor for neuronal amyloid-β (Aβ) deposition, the central neuropathological hallmark of AD. Here we identify genetic pathways of myelin dysfunction and demyelinating injuries as potent drivers of amyloid deposition in mouse models of AD. Mechanistically, myelin dysfunction causes the accumulation of the Aβ-producing machinery within axonal swellings and increases the cleavage of cortical amyloid precursor protein. Suprisingly, AD mice with dysfunctional myelin lack plaque-corralling microglia despite an overall increase in their numbers. Bulk and single-cell transcriptomics of AD mouse models with myelin defects show that there is a concomitant induction of highly similar but distinct disease-associated microglia signatures specific to myelin damage and amyloid plaques, respectively. Despite successful induction, amyloid disease-associated microglia (DAM) that usually clear amyloid plaques are apparently distracted to nearby myelin damage. Our data suggest a working model whereby age-dependent structural defects of myelin promote Aβ plaque formation directly and indirectly and are therefore an upstream AD risk factor. Improving oligodendrocyte health and myelin integrity could be a promising target to delay development and slow progression of AD
Variations on the Author
Full text link“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
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe 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
Ageing-associated myelin dysfunction as a driver of amyloid deposition in Alzheimer’s disease
Full text linkAlzheimer’s disease (AD) is the most common neurodegenerative disease with increasing prevalence due to longer lifespans in the human population. AD manifests as various age-associated cognitive impairments summarised under the syndrome of dementia. Why ageing constitutes the greatest risk factor for the development of AD, however, remains poorly understood. Ageing markedly affects the integrity of myelin at the ultrastructural level, with myelin splitting, outfoldings and secondary low-grade inflammation. In addition to the well-established role of oligodendroglia in producing insulating myelin, these glia cells also provide throphic support to ensheathed axons. Structural breakdown of myelin during ageing likely effects both insulation and metabolic support function of oligodendrocytes. This puts ensheathed axons and their neurons at risk for starvation and malfunction which could contribute to the development of neurodegenerative diseases upon ageing. Intriguingly, age-related myelin breakdown coincides with the beginning of amyloid build-up in the brain, the primary neuropathological hallmark of AD. I propose a mechanistic link between ageing-associated myelin dysfunction and the deposition of amyloid-β (Aβ) and hypothesised that breakdown of myelin - especially in cortical regions – is an upstream driver of amyloid deposition in AD. In my doctorate, I examined this possible link in proof of principle experiments in vivo by combining mouse models of myelin dysfunction with AD mouse models. I here show that in mouse models of AD (5xFAD, APPNLGF) genetically induced myelin defects (knockout of CNP or PLP1) as well as direct demyelinating injuries (experimental autoimmune encephalomyelitis, Cuprizone feeding) are potent drivers of amyloid deposition as shown by quantitative 3D light sheet microscopy. Conversely, lack of compact myelin in forebrain specific MBP knockout animals (“shiverer”) ameliorates plaque deposition. Behavioural analysis revealed synergistic effects of myelin defects and amyloid pathology on the manifestation of impairments. Mechanistically, I show that myelin dysfunction leads to the accumulation of the Aβ producing machinery (APP, β- and ɣ-secretase) in axonal spheroids and enhanced cortical APP cleavage. Additionally, I observed a profound loss of plaque-corralling microglia in AD mice with defective myelin. Transcriptomic analysis of isolated microglia revealed, however, that the disease-associated microglia (DAM) signature found in plaque-corralling microglia in 5xFADs is preserved in microglia additionally challenged with myelin. Indeed, myelin dysfunction alone is sufficient to induce a DAM-like state as shown by single nuclei RNA sequencing. I conclude that upon myelin damage in the brain microglia become primarily engaged in myelin clearance which renders them unresponsive to amyloid and prevents the protective reactions of microglia to Aβ plaques. The work presented in this thesis identifies myelin ageing as a previously overlooked risk factor for AD and makes the case for myelin health-directed therapies to combat AD.2022-11-2
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