1,720,957 research outputs found
LRRK2 deficiency impacts ceramide metabolism in brain
Get PDFMutations in LRRK2 gene cause inherited Parkinson's disease (PD) and variations around LRRK2 act as risk factor for disease. Similar to sporadic disease, LRRK2-linked cases show late onset and, typically, the presence of proteinaceous inclusions named Lewy bodies (LBs) in neurons. Recently, defects on ceramide (Cer) metabolism have been recognized in PD. In particular, heterozygous mutations in the gene encoding for glucocerebrosidase (GBA1), a lysosomal enzyme converting glucosyl-ceramides (Glc-Cer) into Cer, increase the risk of developing PD. Although several studies have linked LRRK2 with membrane-related processes and autophagic-lysosomal pathway regulation, whether this protein impinges on the Cer pathway has not been addressed. Here, using a targeted lipidomics approach, we report an altered sphingolipid composition in Lrrk2(-/-) mouse brains. In particular, we observe a significant increase of Cer levels in Lrrk2(-/-) mice and direct effects on GBA1. Collectively, our results suggest a link between LRRK2 and Cer metabolism, providing new insights into the possible role of this protein in sphingolipids metabolism, with implications for PD therapeutics
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
New Analytical Methodologies at the Frontier of Cellular Lipidomics
No full textLipids were once thought to only be the building blocks of cell membranes and to serve as energy reserves. With time however, it became increasingly clear that they are actually involved in many more roles. Not surprisingly, the comprehensive characterisation of lipids in cells and tissues has experienced a growing interest worldwide, to the point that the term "lipidomics" was coined. This field is a subset of metabolomics, and the interesting point about these two sciences is that they are closest to the phenotype as compared to their "omics" counterparts (genomics, trascriptomics, ...), because metabolites and lipids are the end products of the –omics cascade. We have investigated mass spectrometry-based lipidomics from different perspectives: first of all, we have devised a targeted approach in which we have focused on sphingolipids and their perturbations. We started by working on neuronal cell cultures where we inhibited GBA, a key enzyme of the sphingolipid metabolism known to be one of the risk factors for Parkinson's disease. We found a significant sphingolipid unbalance characterised by an accumulation of glycosyl-ceramides. We then moved on by investigating the effects that LRRK2, an important and complex protein known to be related to autosomal-dominant forms of the disease, has on sphingolipids. We worked on mouse models, and we compared the sphingolipid profiles of wild-type (Lrrk2+/+) and knock-out (Lrrk2–/–) mice, finding a marked increase in ceramide levels and, more in general, in all lipids downstream of GBA. Such results hint to a possible interaction between LRRK2 and GBA, with LRRK2 playing a role in GBA regulation.
In a second lipidomics investigation, we tried to understand whether or not anti-cancer treatments affect the lipid composition of tumours. Specifically, we concentrated on a common anti-angiogenic drug, whose aim is to starve cancer cells by inhibiting angiogenesis, a process required by the tumours to grow. We considered four different adenocarcinoma cell lines, which were subcutaneously inoculated into mice; the "control" animals received no treatment, whereas the "treated" ones were periodically given the drug. Interestingly, we found the treatment to have significant effects on the cancer lipidome, although the different lines responded unequally to the drug. Such results may reflect the huge heterogeneity of cancers and of individual responses to the treatment. Finally, we developed an informatics algorithm that deals with labelling experiments. The key point is that mass spectrometry measures isotopic patterns of analytes, which depend on the isotopic distribution of the elements; consequently, if an analyte incorporates the stable isotope employed in a labelling experiment, it will show a modified isotopic pattern. Our algorithm analyses such pattern, estimating the abundance of the incorporated label; we first tested it over carefully planned samples, and then we used it in a biochemical application where we wished to establish whether the rate of de novo lipogenesis is influenced by diet. This was accomplished by designing an experiment where mice were given partially deuterated water, while being fed different diets; we were able to ascertain that diet does indeed affect de novo lipogenesis, with the lowest rates occurring on fat-rich diets. We are confident that our tool may find useful applications, considering that stable isotope-based labelling experiments are becoming more and more popular
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
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
- …
