1,720,955 research outputs found
The US9-Derived Protein gPTB9TM Modulates APP Processing Without Targeting Secretase Activities
Full text link: Alteration of neuronal protein processing is often associated with neurological disorders and is highly dependent on cellular protein trafficking. A prime example is the amyloidogenic processing of amyloid precursor protein (APP) in intracellular vesicles, which plays a key role in age-related cognitive impairment. Most approaches to correct this altered processing aim to limit enzymatic activities that lead to toxic products, such as protein cleavage by β-secretase and the resulting amyloid β production. A viable alternative is to direct APP to cellular compartments where non-amyloidogenic mechanisms are favored. To this end, we exploited the molecular properties of the herpes simplex virus 1 (HSV-1) transport protein US9 to guide APP interaction with preferred endogenous targets. Specifically, we generated a US9 chimeric construct that facilitates APP processing through the non-amyloidogenic pathway and tested it in primary cortical neurons. In addition to reducing amyloid β production, our approach controls other APP-dependent biochemical steps that lead to neuronal deficits, including phosphorylation of APP and tau proteins. Notably, it also promotes the release of neuroprotective soluble αAPP. In contrast to other neuroprotective strategies, these US9-driven effects rely on the activity of endogenous neuronal proteins, which lends itself well to the study of fundamental mechanisms of APP processing/trafficking. Overall, this work introduces a new method to limit APP misprocessing and its cellular consequences without directly targeting secretase activity, offering a novel tool to reduce cognitive decline in pathologies such as Alzheimer's disease and HIV-associated neurocognitive disorders
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
Collagen-X: ein neuer spezifischer Biomarker für den Nachweis maligner kolorektaler Karzinome
Full text linkColorectal Carcinoma (CRC) is the second most common malignant tumor in the Western world. It has been well documented that the tumor microenvironment plays an important role in tumor progression via the co-evolution of tumor cells and tumor stroma. The extracellular matrix (ECM) is the major component of stroma and acts as a key regulator of cell and tissue functions. During cancer progression, the ECM is deregulated and becomes disorganized, resulting in an abnormal ECM that promotes cellular transformation and metastasis, deregulates behavior of stromal cells, and facilitates inflammation and angiogenesis.
This thesis aims at the elucidation of the origin and role of collagen X, which has been unexpectedly discovered in the stroma of malignant colorectal carcinomas. Collagen-X (Col-X) is a network-forming collagen with a short triple-helical core flanked by two non-collagenous domains: C-terminal NC1 and N-terminal NC2. Its expression is normally limited to hypertrophic chondrocytes in the growth plate cartilage in long bones, ribs and vertebrate, but under pathological conditions. It is also expressed in osteoarthritic cartilage and chondrosarcomas. At present, only incomplete information is available regarding Col-X and cancer. Chapman et al. showed in 2012 that Col-X expression is elevated in diverse solid tumor types, and others proposed Col-X as a new biomarker for colon cancer. The exact cellular origin of type X collagen in CRC tissues and the putative role of Col-X in tumor progression, however, remains undefined.
In this thesis I present data confirming a correlation of high levels of Col-X protein and Col10A1 mRNA expression in two cohorts of human CRC samples with poor tumor prognosis. Immunohistochemical staining of CRC tissues indicated that Col-X was primarily deposited in the stroma, suggesting stroma cells as the main source of the protein. This was confirmed by in situ hybridization analysis using a COL10A1 specific probe which revealed intense signals exclusively in stromal cells, displaying the typical spindle-shaped morphology of fibroblast like cells. Immunofluorescence co-localization studies of Col-X with Vimentin and alpha-SMA antibodies indicated that fibroblast –like cells and smooth muscle cells were the main source of the protein.
First indications for a tumor-promoting role of Col-X were obtained from in vitro cell motility assays showing that recombinant purified Col-X enhances the motility of colorectal cancer cells. Altogether the results show that Col-X represents a novel specific biomarker for the detection of malignant colorectal carcinomas and opens the prospective that COL10A1 analysis could be used in routinely processed primary tumor tissues as prognostic profiler to identify high risk patients. Further studies are required to clarify its specific role in tumor progression
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
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