1,721,012 research outputs found
Translational studies on Alzheimer’s disease : a focus on cholesterol metabolism, thioredoxin-80 and microglia function
No full textDisturbances in cholesterol metabolism and inflammatory processes may have a negative impact on brain health. These two aspects are considered to be signs of early changes in Alzheimer’s Disease (AD). However, clear molecular links between them as well as mechanisms for their early detection are missing in the context of neurodegeneration and AD. 27-hydroxycholesterol (27-OHC), a cholesterol metabolite and Thioredoxin-80 (Trx80), an antioxidant-derived peptide with immune modulatory properties have been shown to be altered in the brain of AD patients. Thus, this thesis aims to investigate the involvement of 27-OHC and Trx80 in AD.In Papers I, II and IV, we investigated the effect of alterations in cholesterol metabolism and inflammation during aging in relation to cognition and different risk factors for AD. In Paper I we measured 27-OHC levels in serum samples of older adults undergoing a two-year multimodal lifestyle/vascular intervention. At baseline, higher 27-OHC correlated with lower memory scores, total gray matter and hippocampal volume. After the two-year intervention trial, 27-OHC levels decreased in the intervention group. This reduction was positively correlated with improved memory scores among the intervention group. In Paper II, Trx80 was measured in serum samples in the same individuals as the previous study and in patients with varying degrees of dementia. We found that serum Trx80 levels were increased in AD cases and were positively correlated with older age and associated with the presence of ApoE4 genotype, indicating that serum Trx80 levels are sensitive to two main risk factors of AD.Previous studies in our lab showed that Trx80 can prevent amyloid-beta (Aβ) aggregation and inhibit Aβ toxic effects in cell cultures. In view of these findings, in Papers III and IV we investigated whether Trx80 could have a similar effect on Aβ in in vivo models of amyloid pathology by inducing specific activation responses in brain cells. In Paper III, we further explored the anti-amyloidogenic properties of Trx80 in vivo in Drosophila melanogaster models. Trx80 expression in Drosophila brain prevented Aβ42 accumulation and rescued the lifespan reduction and locomotor impairments observed in Aβ42-expressing flies by enhancing the autophagy-lysosomal pathway. In Paper IV, we aimed to further clarify the biological function of Trx80 and its regulation in the brain both under healthy and AD-relevant pathological conditions. We show that neurons are the main source of Trx80 in the brain, and that its levels increase during normal aging, oxidative-stress conditions and in a mouse model of amyloid pathology. RNA-sequencing analysis revealed that Trx80 induces microglia activation into a phenotype compatible with type-I interferon response microglia.These findings highlight the involvement of cholesterol metabolism and inflammation, related to changes in 27-OHC and Trx80, in AD pathogenesis. 27- OHC and Trx80 should be further investigated not only as potential biomarkers for AD, but also as part of therapeutic and preventive strategies in AD.List of scientific papersI. Anna Sandebring-Matton, Julen Goikolea, Ingemar Björkhem, Laura Paternain, Nina Kemppainen, Tiina Laatikainen, Tiia Ngandu, Juha Rinne, Hilkka Soininen, Angel Cedazo-Minguez, Alina Solomon and Miia Kivipelto. 27-Hydroxycholesterol, cognition, and brain imaging markers in the FINGER randomized controlled trial. Alzheimer’s Research and Therapy. 2021, 13:56. https://doi.org/10.1186/s13195-021-00790-y II. Julen Goikolea, Gorka Gerenu, Makrina Daniilidou, Francesca Mangialasche, Patrizia Mecocci, Tiia Ngandu, Juha Rinne, Alina Solomon, Miia Kivipelto, Angel Cedazo-Minguez, Anna Sandebring- Matton, Silvia Maioli. Serum Thioredoxin-80 is associated with age, ApoE4 and neuropathological biomarkers in Alzheimer’s Disease: A potential early sign of AD. [Submitted]III. Gorka Gerenu, Torbjörn Persson, Julen Goikolea, Javier Calvo- Garrido, Raúl Loera-Valencia, Philipp Pottmeier, Cesar Santiago, Helen Poska, Jenny Presto and Angel Cedazo-Minguez. Thioredoxin-80 protects against amyloid-beta pathology through autophagic-lysosomal pathway regulation. Molecular Psychiatry. 2019, 26(4):1410-1423. https://doi.org/10.1038/s41380-019-0521-2 IV. Julen Goikolea, Jean-Pierre Roussarie, Gorka Gerenu, Maria Latorre, Raul Loera-Valencia, Angel Cedazo-Minguez, Patricia Rodriguez- Rodriguez and Silvia Maioli. Neuron-derived Thioredoxin-80: a novel regulator of type-I interferon response in microglia of relevance to Alzheimer’s disease. [Manuscript]</p
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
Variations on the Author
Get PDF“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
Get PDFWe 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
Successful therapies for Alzheimer’s disease: why so many in animal models and none in humans?
No full textDispelling the Myths Behind First-author Citation Counts
Get PDFWe 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
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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