1,721,024 research outputs found
Axon pathology in neurological disease: a neglected therapeutic target
No full textIn the C57BL/WldS mouse, a dominant mutation dramatically delays Wallerian degeneration in injury and disease, possibly by influencing multi-ubiquitination. Studies on this mouse show that axons and synapses degenerate by active and regulated mechanisms that are akin to apoptosis. Axon loss contributes to neurological symptoms in disorders as diverse as multiple sclerosis, stroke, traumatic brain and spinal cord injury, peripheral neuropathies and chronic neurodegenerative diseases, but it has been largely neglected in neuroprotective strategies. Defects in axonal transport, myelination or oxygenation could trigger such mechanisms of active axon degeneration. Understanding how these diverse insults might initiate an axon-degeneration process could lead to new therapeutic interventions
The cellular distribution of the Wld(S) chimeric protein and its constituent proteins in the CNS
No full textThe C57BL/Wlds mouse is a mutant strain of mouse that shows greatly slowed Wallerian degeneration both in the central and peripheral nervous system. Using immunohistochemistry, immunofluorescence and Western blotting, we have investigated the distribution of the chimeric Wlds protein and its different components in neurons of the CNS of Wlds mice and wild-type C57BL/6J mice. The expression of the Wlds protein is restricted to the nucleus in Wlds mice. Wlds was not detected in axons. The Wlds mice express both the normal and chimeric forms of ubiquitination factor E4 (Ube 4b) and nicotinamide mononucleotide adenylyltransferase-1 (Nmnat-1). The normal forms were expressed both in the cytoplasm and the nuclei of neurons in Wlds mice and wild-type mice, and were also present in the axon. The normal form of Ube4b, mono- and poly-ubiquitin and I?B?, a substrate of Ube4b, were not differentially expressed in Wlds mice compared with wild-type mice. However, the expression of both the normal and mutant forms of Nmnat-1 was higher in the nuclei of Wlds mice compared with wild-type mice. Therefore, axon protection in Wlds mice does not appear to be controlled by expression of Wlds protein in the axons per se and also is unlikely to be related to the different activity of Ube4b either in general ubiquitination or toward this particular substrate. The increased Nmnat-1 activity in the nucleus of Wlds mice compared with wild-type mice seems to be a significant factor in the axon protection. It is not known whether the expression of the Nmnat-1 in the axon is significant
The journey towards a cancer diagnosis: the experiences of people with cancer, their family and carers.
No full textThis small-scale study aimed to provide an insight into the time between first noticing a symptom, attending a healthcare provider and obtaining a cancer diagnosis. Previous research showed that the pre-diagnostic moments on the illness trajectory were important to people with cancer and could influence levels of satisfaction with subsequent care. This article provides an overview of the qualitative component (phase 2) of a three-pronged study that involved a workshop, a literature review and focus groups and interviews with people affected by cancer. Results highlighted some of the difficulties encountered during the complex journey towards a diagnosis of cancer. These included fear of what might be found, communication of symptoms to healthcare practitioners, the influence of family on decisions to attend a primary care practitioner and the importance of a person's gender on perceptions of health-seeking behaviour. Results presented warrant further investigation and suggest the importance of viewing the 'cancer journey' as including the journey leading up to a diagnosis of cancer
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
An 85-kb tandem triplication in the slow Wallerian degeneration (Wlds) mouse
No full textWallerian degeneration is the degeneration of the distal stump of an injured axon. It normally occurs over a time course of around 24 hr but it is delayed in the slow Wallerian degeneration mutant mouse (C57BL/Wlds) for up to 3 weeks. The gene, which protects from rapid Wallerian degeneration, Wld, previously has been mapped to distal chromosome 4. This paper reports the fine genetic mapping of the Wld locus, the generation of a 1.4-Mb bacterial artificial chromosome and P1 artificial chromosome contig, and the identification of an 85-kb tandem triplication mapping within the candidate region. The mutation is unique to C57BL/Wlds among 36 strains tested and therefore is a strong candidate for the mutation that leads to delayed Wallerian degeneration. There are very few reports of tandem triplications in a vertebrate and no evidence for a mutation mechanism so this unusual mutation was characterized in more detail. Sequence analysis of the boundaries of the repeat unit revealed a minisatellite array at the distal boundary and a matching 8-bp sequence at the proximal boundary. This finding suggests that recombination between short homologous sequences ("illegitimate" or "nonhomologous" recombination) was involved in the rearrangement. In addition, a duplication allele was identified in two Wlds mice, indicating some instability in the repeat copy number and suggesting that the triplication arose from a duplication by unequal crossing over
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
Neurites undergoing Wallerian degeneration show an apoptotic-like process with annexin V positive staining and loss of mitochondrial membrane potential
No full textWallerian degeneration, the disintegration of the distal part of an injured axon, is an important event in many neurodegenerative diseases. We studied Wallerian degeneration in dorsal root ganglion (DRG) explants in culture by separating neurites from their cell bodies with a scalpel. The severed neurites showed Annexin V positive staining, that spreads distally with a rate comparable to that of slow axonal transport in intact neurons in vivo. Moreover, the injured neurites showed loss of mitochondrial membrane potential. These features resemble those seen when cells undergo apoptosis. These data contribute to a new understanding of the mechanism of axonal degeneration, have implications for the response of stromal cells in central nervous system (CNS) and raise the prospect of new pharmacological treatments for those neurodegenerative pathologies where the protection of the cell body alone does not alleviate the disease
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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