1,721,319 research outputs found
Novel Therapies for Alzheimer's Disease: Potentially Disease Modifying Drugs
No full textThe two major neuropathologic hallmarks of Alzheimer's disease (AD) are extracellular Amyloid beta (A beta) plaques and intracellular neurofibrillary tangles (NFTs). Several additional pathogenic mechanisms likely play a role in the pathogenesis of the disease, including inflammation, oxidative damage, ion disregulation and cholesterol metabolism. A number of compounds have been developed, trying to interfere with the above mentioned altered mechanisms. Conversely to symptomatic drugs available to date, these new compounds are supposed to modify pathological steps leading to AD, thus acting on the evolution of the disease. Some of them are under clinical testing, others are in preclinical phases of development. In this chapter, the main pathogenic steps leading to neurodegeneration will be discussed, together with an update of potentially disease-modifying drugs under testing
Genetics and Molecular Biology of Alzheimer’s disease and Frontotemporal Lobar Degeneration : analogies and differences
No full textAlzheimer's disease (AD) is the most common cause of dementia in the elderly, whereas Frontotemporal Lobar Degeneration (FTLD) is the most frequent neurodegenerative disorder with a presenile onset. The two major neuropathologic hallmarks of AD are extracellular Amyloid beta (Aβ) plaques and intracellular neurofibrillary tangles (NFTs). Conversely, in FTLD the deposition of tau has been observed in a number of cases, but in several brains there is no deposition of tau but instead a positivity for ubiquitin. In some families these diseases are inherited in an autosomal dominant fashion. Genes responsible for familial AD include the Amyloid Precursor Protein (APP), Presenilin 1 (PS1) and Presenilin 2 (PS2). The majority of mutations in these genes are often associated with a very early onset (40-50 years of age). Regarding FTLD, the first mutations described are located in the Microtubule Associated Protein Tau gene (MAPT). Tau is a component of microtubules, which represent the internal support structures for the transport of nutrients, vesiclces, mitochondria and chromosomes within the cell. Mutations in MAPT are associated with an early onset of the disease (40-50 years), and the clinical phenotype is consistent with Frontotemporal Dementia (FTD). Recently, mutations in a second gene, named progranulin (GRN), have been identified in some families with FTLD. Progranulin is expressed in neurons and microglia and displays anti-inflammatory properties. Nevertheless, it can be cleaved into granulins which, conversely, show inflammatory properties. The pathology associated with these mutations is most frequently characterized by the immunostaining of TAR DNA Binding Protein 43 (TDP-43), which is a transcription factor. The clinical phenotype associated with GRN mutations is highly heterogeneous, including FTD, Progressive Aphasia, Corticobasal Syndrome, and AD. Age at disease onset is variable, ranging from 45 to 85 years of age. The majority of cases of AD and FTLD are however sporadic, and likely several genetic and environmental factors contribute to their development. Concerning AD, it is known that the presence of the ε4 allele of the Apolipoprotein E gene is a susceptibility factor, increasing the risk of about 4 fold. A number of additional genetic factors, including cytokines, chemokines, Nitric Oxide Synthases, contribute to the susceptibility for the disease. Some of them also influence the risk to develop FTLD. In this chapter, current knowledge on molecular mechanisms at the basis of AD and FTLD, as well as the role of genetics, will be presented and discussed
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
Gender-related genetic and biochemical differences: influence on susceptibility and course of multiple sclerosis
No full textMultiple Sclerosis (MS) is a multifactorial disease. Women are more susceptible than men (female to male ratio of 2:1), yet have a slightly better prognosis than men even though inflammatory episodes are associated with greater subsequent disability.
Although the biological background responsible of differences in susceptibility and course of MS between sexes is not fully understood, a number of observations suggests that a role is played by hormones, as well as by genetic and biochemical factors.
Regarding hormones, it has been consistently reported that during pregnancy, when progesterone is continuously present, there are fewer relapses, and disability scores tend to be lower. In addition, during pregnancy, the number of CD8 suppressor T-cells is decreased and the ratio of CD4 helper to CD8 suppressor T-cells increased, indicating reduced disease activity.
A different cytokine profile as well as a gender-specific effect of genetic variants between men and women have been observed. For instance, the chemokine CCL22, which expression in animal models of MS is correlated with clinical manifestations and development of inflammatory lesions, is increased in Cerebrospinal Fluid (CSF) from female, but not male, patients. The frequency of the AT haplotype in CCL22 encoding gene was shown to be significantly decreased in MS patients (P=0.017, OR: 0.49), but, stratifying patients according to gender, the observed association was even more pronounced in male patients compared with male controls (P=0.004, OR=0.18), whereas no significant differences were observed, in females. Other polymorphic variants in several genes related to inflammation, including Interferon-gamma, Brain Derived Neurothropic Factor (BDNF) and the glutathione S-transferase (GST) supergene family, are likely influence the risk to develop MS in a gender-related manner.
These notions suggest that the role of inflammation differs between sexes, possibly mediated by immunomodulatory effects related to female sex hormones. In this chapter, current knowledge about genetic, biochemical and hormonal differences between male and female MS patients will be reviewed and discussed
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
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