1,722,132 research outputs found
The Background of Mitochondrial DNA Haplogroup J Increases the Sensitivity of Leber's Hereditary Optic Neuropathy Cells to 2,5-Hexanedione Toxicity
No full textLeber's hereditary optic neuropathy (LHON) is a maternally inherited blinding disease due to mitochondrial DNA (mtDNA) point mutations in complex I subunit genes, whose incomplete penetrance has been attributed to both genetic and environmental factors. Indeed, the mtDNA background defined as haplogroup J is known to increase the penetrance of the 11778/ND4 and 14484/ND6 mutations. Recently it was also documented that the professional exposure to n-hexane might act as an exogenous trigger for LHON. Therefore, we here investigate the effect of the n-hexane neurotoxic metabolite 2,5-hexanedione (2,5-HD) on cell viability and mitochondrial function of different cell models (cybrids and fibroblasts) carrying the LHON mutations on different mtDNA haplogroups. The viability of control and LHON cybrids and fibroblasts, whose mtDNAs were completely sequenced, was assessed using the MTT assay. Mitochondrial ATP synthesis rate driven by complex I substrates was determined with the luciferine/luciferase method. Incubation with 2,5-HD caused the maximal loss of viability in control and LHON cells. The toxic effect of this compound was similar in control cells irrespective of the mtDNA background. On the contrary, sensitivity to 2,5-HD induced cell death was greatly increased in LHON cells carrying the 11778/ND4 or the 14484/ND6 mutation on haplogroup J, whereas the 11778/ND4 mutation in association with haplogroups U and H significantly improved cell survival. The 11778/ND4 mutation on haplogroup U was also more resistant to inhibition of complex I dependent ATP synthesis by 2,5-HD. In conclusion, this study shows that mtDNA haplogroups modulate the response of LHON cells to 2,5-HD. In particular, haplogroup J makes cells more sensitive to its toxic effect. This is the first evidence that an mtDNA background plays a role by interacting with an environmental factor and that 2,5-HD may be a risk element for visual loss in LHON. This proof of principle has broad implications for other neurodegenerative disorders such as Parkinson's disease
Comparison of retinal nerve fibre layers between 11778 and 14484 mutations in Leber's hereditary optic neuropathy
No full textPurposeTo compare retinal nerve fibre layer (RNFL) thickness changes between mitochondrial DNA (mtDNA) mutations at nucleotides 11778 and 14484 in Leber's hereditary optic neuropathy (LHON) using optical coherence tomography (OCT).MethodsThirty LHON patients with mtDNA mutations at nucleotides 11778 or 14484 underwent full ophthalmologic examinations including Stratus OCT. Patients were divided into four groups according to disease duration (early6 months) and mtDNA mutation type (11778 and 14484), and their RNFL thicknesses were compared.ResultsAverage RNFL thickness in the early 11778 group was significantly greater than that in the early 14484 group (P=0.04). Average RNFL thickness in the late 11778 group was significantly less than that in the late 14484 group (P=0.02). Quadrant analysis of the superior, nasal, and inferior quadrant RNFL thickness in the late 11778 group showed more severe RNFL atrophy than in the late 14484 group (P=0.023, 0.015, 0.003, respectively).ConclusionsRNFL thickness was significantly increased in the early stage and decreased in the late stage in the 11778 group than in the 14484 group.Eye advance online publication, 27 February 2009; doi:10.1038/eye.2009.36.This work was supported by the Basic Research Program
of the Korean Science & Engineering Foundation
(Grant no. R01-2005-000-10875-0)
A new ordinary chondrite H5, S2, W1: Northwest Africa 11778
No full textBased on petrological, mineralogical and geochemical analyses, the authors classified the new meteorite Northwest Africa 11778 as an ordinary chondrite H5, S2, W1. It is a single stone with mass 767.5 g and with well-preserved black fusion crust with brown shade (Fig. 1). This meteorite was found in Sahara Desert and it was purchased by Wroclaw University of Science and Technology, Faculty of Geoengineering, Mining and Geology from Moroccan dealer in Zagora in June 2013. The most characteristic component of analyzed chondrite are different types of chondrules (barred olivine – BO, porphyritic olivine – PO, granular olivine – GO, radial pyroxene – RP, porphyritic olivine-pyroxene – POP, cryptocrystalline – C) (Fig. 2), which constitute 75% of meteorite. Their size is in range 0.2–1.2 mm, with average chondrule size ca. 0.6 mm. Bigger porphyritic olivine chondrules with diameter up to 1.5 mm rarely occur. The chemical composition of olivine crystals (Fa 18 mol%) and pyroxene crystals (Fs 16.2 mol%) proves this meteorite to be an H chondrite (Tab. 1, Fig. 4–5, App. 1–2). The averaged concentration of major elements in the classified meteorite is comparable to their mean content in H chondrites (Fig. 8). The meteorite NWA 11778 contains only slightly less Mg and Al than average H chondrites (Tab. 2). Among the other analysed elements, values distinctly out of the range of typical concentrations for H chondrites are characteristic of Hg and Eu (lower concentration in the NWA 11778 meteorite) (Tab. 3, Fig. 8–9). The presence of chondrules with predominantly sharp boundaries (Fig. 2), secondary feldspar crystals with sizes of up to 50 mm, chiefly crystalline mesostasis and only secondarily – devitrified glass in chondrules, and transparent crystalline matrix (with olivine crystals up to 0.26 mm and pyroxenes up to 0.30 mm in size), as well as common occurrence of untwinned rhombic pyroxenes prove the classified meteorite to belong to petrological type 5. It is additionally confirmed by mean Ni content in troilite below 0.5 wt% (0.04 wt%) (Tab. 1, App. 4) and carbon content below 0.2 wt% (0.07 wt%) (Tab. 2). Undulatory extinction in some olivine and pyroxene crystals and the presence of irregular fractures in the NWA 11778 chondrite enables specifying its shock level as S2. The weathering grade adopted for the NWA 11778 chondrite was W1, as visible weathering changes cover only the marginal parts of FeNi alloy grains. As a result of the weathering of 10–20% of FeNi grains, iron oxides and hydroxides are formed. These secondary weathering Fe3+ compounds also fill cracks, forming veins running between chondrules within matrix (Fig. 3)
Going Beyond Counting First Authors in Author Co-citation Analysis
No full textThe 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
No full text“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
Leber's hereditary optic neuropathy (LHON/11778) with myoclonus: report of two cases
No full textThe previously unrecognised association of myoclonus in two patients with LHON with the 11778/ND4 pathogenic mutationis described. EEG failed to disclose epileptic figures, and a back averaging study suggested that myoclonus was cortical inorigin in both patients
Appropriate Similarity Measures for Author Cocitation Analysis
No full textWe 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
Leber hereditary optic neuropathy in 2 of 4 siblings with 11778 mtDNA mutation: clinical variability or effect of toxic exposure?
No full textAlthough mitochondrial (mt) DNA mutation at nucleotide position 11778 accounts for most cases of Leber's hereditary optic neuropathy (LHON), the phenotypic expression may vary greatly even in different members of the same family. The possible influence of exogenous toxicity on phenotypic expression is still debated in LHON. Here we describe 4 siblings carrying the 11778 mtDNA mutation with a different phenotype. The index case developed an atypical optic neuropathy at the age of 60 years after a long history of occupational exposure to polycyclic aromatic hydrocarbons (PAHs). This report underlines a number of unanswered questions about phenotypic variability of LHON including the possible influence of PAH toxicity
Dispelling the Myths Behind First-author Citation Counts
No full textWe 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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