1,720,958 research outputs found
Innovative therapeutic approaches for neurodegenerative disorders: drug repurposing and cell therapy
No full textNeurodegenerative diseases (NDs) are a group of heterogeneous disorders characterized by progressive dysfunction and loss of neurons that encompass many different entities. Due to a neuron’s impossibility of renewing itself, this loss is irreversible and is usually followed by the collapse of the structure and function of neural networks, triggering the breakdown of the core communicative circuitry. Involvement of functional systems differs between disorders and is associated with a broad spectrum of clinical presentations.
At present, the management of neurodegenerative disorders is often disease-specific, and research into therapy mainly focuses on classical pharmacological approaches and advanced therapies (cell and gene therapy). Several pharmacological therapies are currently accepted, which either target the disease pathogenesis or try to improve the symptoms experienced. Current treatments cannot prevent or completely arrest the progression of NDs; thus, with time, the efficacy of these treatments may be reduced. Hence, the detection of new targets for drug action is a priority. Drug repurposing, the application of an existing therapeutic to a new disease indication, is a recent and valuable strategy that overcomes several shortcomings of the de novo development of new drugs; indeed, it holds the promise of rapid clinical impact at a lower cost, by accelerating the discovery of new candidate molecules while reducing its economic impact and increasing the chances of clinical development and testing phases. This strategy has various advantages and has opened new scenarios, particularly in the context of rare diseases, such as mitochondrial or neurodegenerative diseases. Finding new indications can rapidly benefit patients for either approved or failed drugs for which safety has already been established.
An engaging alternative therapeutical option is cell therapy, which involves the transplantation of stem cells for the regeneration of neural tissue, the stabilization of the neuronal networks, and the provision of neurotrophic support. Cell therapy aims to improve the repair response of dysfunctional and damaged tissue; however, restoring neuronal connectivity, both local and long-range, remains a substantial problem. Recently, 3D organoid technology has emerged as the latest frontier in regenerative medicine for treating CNS disorders. Most of the research on cell-based therapy for neurodegenerative diseases has been conducted preclinically in animal models, in which there are positive signs that, despite disrupted organization, connections with host cells can improve functionality. However, significant challenges remain regarding whether and how promising preclinical findings can be translated into clinical trials. Developing innovative approaches to treat neurodegenerative disorders.
My PhD is focused on testing two different strategies to treat neurodegenerative disorders:
(1) a drug-repurposing strategy for neurodegenerative disorders caused by OXPHOS-related defects
and (2) the regeneration of brain damage by tissue graft.
For the first aim, we demonstrated that neuronal progenitor cells derived from patients who carry different homoplasmic mutations in the ATP6 gene all present constant biochemical and phenotypic traits that are independent of the pathogenic variant, confirming their suitability as tools for phenotypic drug screening. Sildenafil was able to ameliorate the abnormalities in all patient-derived cell lines. Our data strongly suggest that the therapeutic effect is being carried out through the activation of the cGMP cascade. We were also able to demonstrate that dopaminergic neurons derived from patient-NPCs exhibited a branching defect and that this phenotype was positively affected by treatment with Sildenafil. Overall, these data point to Sildenafil being a good candidate for managing Leigh Syndrome.
For the second aim, we focused on the self-repair process of dysfunctional brain circuits with the use of transplantable brain tissue, in the context of Temporal Lobe Epilepsy, which presents several symptoms mainly affecting the hippocampus, and is often resistant to anti-epileptic drugs. As a starting point we derived rat-brain organoids and evaluated their growth, morphology, cellular composition, differentiation, maturation, and functionality. As a second step, we started to set up a protocol for brain organoid transplantation in a rat model. Preliminary results showed that after transplantation, organoids can differentiate within the host brain, highlighting the potential for integration with the host networks and further boosting the potential use of organoids for brain regeneration
Going 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
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
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
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
Author Under Sail The Imagination of Jack London, 1893-1902
No full textIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Intro -- Title Page -- Copyright Page -- Dedication -- Contents -- Acknowledgments -- Introduction -- 1. Spirit Truth -- 2. From Absorption to Theatricality and Back Again -- 3. "I Will Build a New Present" -- 4. Sons as Authors -- 5. Fathers as Publishers -- 6. The Daughter as Author -- 7. Lovers as Authors -- 8. At Sea with the Family -- 9. Yellow News, Yellow Stories -- 10. The Return Home -- Notes -- Bibliography -- Index -- About Jay WilliamsIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.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
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