1,720,961 research outputs found
The role of HFE (hemochromatosis) gene mutations in sporadic Alzheimer disease /
No full textAlthough a central etiology for Alzheimer disease (AD) has not yet been determined, support has amassed for the notion that oxidative stress may be involved in the pathogenesis of AD. The disruption of iron homeostasis and iron's excessive deposition in AD brain tissues has received increased attention due to the metal's capacity to promote the production of harmful free radicals. Several studies have recently examined whether DNA mutations involved in the iron overload disorder, hemochromatosis, pose an increased risk of acquiring AD. However, the small sample size and low generalizability of previous studies have warranted further investigation. We genotyped 213 AD patients, 106 Mild Cognitively Impaired (MCI) individuals, and 63 Normal Elderly Control (NEC) subjects for the H63D and C282Y HFE mutations to examine whether a relationship exists between HFE gene status and AD presentation in our patient population. DNA analysis was conducted by polymerase chain reaction (PCR) followed by restriction fragment length polymorphism (RFLP). We did not find any statistically significant associations between HFE gene status and the clinical, demographic, or neuropsychological aspects of AD in our patient population. Interesting trends that fell short of statistical significance included: (a) a deleterious effect of HFE mutations on motor performance, (b) an influence of H63D homozygosity on an earlier onset of cognitive decline, and (c) an influence of H63D homozygosity on an accelerated progression from MCI to AD
Heme oxygenase-1 suppressor (HOS) activity in Alzheimer plasma
No full textHeme oxygenase-1 is a 32 kDa protein that catalyzes the degradation of heme to biliverdin in brain and other tissues. Our laboratory had previously reported significantly decreased HO-1 protein levels in AD plasma and CSF and HO-1 mRNA in AD mononuclear cells (which may be chemically unstable relative to the levels seen in normal elderly control (NEC) subjects). We hypothesized that there exists a heme oxygenase-1 suppressor (HOS) factor in the plasma of AD patients. Using a novel, glial-based bioassay, we showed that plasma HOS activity was detected in 23/24 AD patients, 3/8 mild cognitive impairment (MCI) patients and in 0/21 NEC patients (HOS activity signifying HO-1 suppression of >50% compared to positive controls). Antioxidant exposure and hypercortisolemia did not account for the HOS activity in AD plasma. We investigated the specificity and selectivity of the HOS factor by analyzing plasma derived from patients with non-Alzheimer's dementia's and non-dementing neurological disorders. We conclude that a HOS factor exists in the plasma of sporadic AD and some MCI patients but is undetectable in NEC plasma. The presence of a circulating HOS factor may further signify systemic redox derangements in early sporadic AD and provide a possible biological marker for this condition
The role of astroglial iron in the pathogenesis of Parkinson's disease /
No full textThe excessive deposition of redox-active iron has been amply documented in the basal ganglia of subjects with Parkinson's disease (PD). Yet, much remains to be learned regarding the cellular and subcellular distribution of this metal and the precise role(s) it plays in the pathogenesis of PD. Cysteamine (CSH) induces the appearance of peroxidase-positive cytoplasmic granules in cultured neonatal rat astroglia which are identical to glial inclusions that progressively accumulate in the aging subcortical brain. These inclusions are derived from degenerate mitochondria which sequester iron and other transition metals before undergoing fusion with lysosomes in an autophagic process. Dr. Schipper has previously demonstrated that iron-mediated peroxidase activity in these cells is capable of oxidizing dopamine and other catechols to potentially neurotoxic semiquinone radicals (Schipper et al., 1991). In the present study, we co-cultured PC12 cells, a catecholamine-secreting cell line, atop confluent monolayers of either CSH pre-treated (iron-enriched) or control neonatal rat astroglia. We observed that the PC12 cells grown on the surface of iron enriched (senescent-like) astroglia were far more susceptible to dopamine/H2O 2-related killing than PC12 cells cultured atop control glial substrata. Augmented killing of PC12 cells in the former paradigm was inhibited by the antioxidants, ascorbate, melatonin or resveratrol implicating a free radical mechanism of action. The aging-associated accumulation of iron in mitochondria of subcortical astroglia may facilitate the oxidation of dopamine to neurotoxic free radical intermediates and thereby predispose the senescent nervous system to PD and other neurodegenerative afflictions
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
Dispelling 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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