1,720,982 research outputs found
Targeting phosphoglycerate kinases by tatridin A, a natural sesquiterpenoid endowed with anti-cancer activity, using a proteomic platform
Full text linkTatridin A (TatA) is a germacrane sesquiterpenoid containing one E-double bond and one Z-double bond in its 10-membered ring, which is fused to a 3- methylene-dihydrofuran-2-one moiety. Tatridin A bioactivity has been poorly investigated despite its interesting chemical structure. Here, a functional proteomic platform was adapted to disclose its most reliable targets in leukemia monocytic cells, and phosphoglycerate kinases were recognized as the most affine enzymes. Through a combination of limited proteolysis and molecular docking, it has been discovered that tatridin A interacts with the active domains of phosphoglycerate kinase 1, altering its hinge region, and it can be accountable for tatridin A inhibition potency on enzyme activity. A more detailed tatridin A biological profile showed that it is also fully active against gastric cancer cells, downregulating the mRNA levels of chemokine receptor 4 and β-catenin and inhibiting the invasiveness of living KATO III cells as a direct consequence of phosphoglycerate kinase 1 antagonism
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
Targeted and untargeted proteomic approaches to disclose small molecules interactome
Full text link2021 - 2022The identification of natural products and synthetic compounds target proteins is pivotal to
understand their mechanism of action for the development of molecular probes and/or potential drugs.
Functional proteomics is a mass spectrometry-based discipline focused on the analysis of the
interactome of small molecules and their targets discovery. Functional proteomics has become an
invaluable tool in targets identification of small molecules since Fishing for Partners strategy, also
named affinity purification mass spectrometry coupled approach (AP-MS), successfully disclosed a
multitude of bioactive compounds interacting proteins in the past 15 years (Rix and Superti-Furga,
2009).
Unfortunately, this strategy is not universally applicable being limited by the need of a covalent
modification of the molecular probe that should contain at least one reactive chemical group and,
most importantly, the compound modification should not influence its original bioactivity. Thus, an
alternative functional proteomics platform, based on a combination of untargeted Drug Affinity
Responsive Target Stability (DARTS) with targeted Limited Proteolysis coupled to Multiple
Reaction Monitoring (t-LiP-MRM), has been exploited during my PhD project to disclose and
characterize the interacting proteins of bioactive compounds (Lomenick et al., 2009; Feng et al.,
2014).
At first, DARTS has been exploited to identify small molecules most reliable cellular partners, then
t-LiP-MRM has been carried out to investigate the molecules/target proteins interaction features.
Moreover, the proteomics results were validated by Western Blotting to confirm small molecules
interaction with their DARTS-identified targets and by in silico molecular docking to corroborate t-
LiP-MRM information about the target region(s) involved in the binding. For an in-deep analysis of
the binding between the investigated compounds and their protein counterparts and for moving
through the activity of such compounds on their putative targets, proper in vitro and/or in cell
biological assays were also employed.
In particular, during this PhD project, MS-based proteomics approaches have been exploited to profile
the interactomes of two natural compounds (Artemetin and Tatridin A), abundant in the extracts from
Achillea millefolium (De Souza et al., 2011) and from Anthemis melanolepis (Saroglou et al., 2010),
respectively, and a synthetic benzodiazepine derivative, called 1g (Parenti et.al., 2016). The
interactomes of Artemetin, 1g and Tatridin A in HeLa, U87MG and THP-1 cells proteome have been
examined unveiling, respectively, the Filamin A and Filamin B (crucial role in the organization of
the cytoskeleton interacting with F-actin) (Zhou et al., 2021; Xu et al., 2017), the Brain Glycogen
Phosphorylase (crucial role in the degradation of the glycogen clusters in the brain and in the
regulation of the cellular glucose concentrations) (Mathieu et al., 2017) and the Phosphoglycerate
Kinase 1 (crucial role in glycolysis) (Zieker et al., 2010) as their principal cellular interactors. [edited by Author]XXX
A Proteomic Platform Unveils the Brain Glycogen Phosphorylase as a Potential Therapeutic Target for Glioblastoma Multiforme
Full text linkIn the last few years, several efforts have been made to identify original strategies against glioblastoma multiforme (GBM): this requires a more detailed investigation of the molecular mechanism of GBM so that novel targets can be identified for new possible therapeutic agents. Here, using a combined biochemical and proteomic approach, we evaluated the ability of a blood–brain barrier-permeable 2,3-benzodiazepin-4-one, called 1g, to interfere with the activity and the expression of brain glycogen phosphorylase (PYGB) on U87MG cell line in parallel with the capability of this compound to inhibit the cell growth and cycle. Thus, our results highlighted PYGB as a potential therapeutic target in GBM prompting 1g as a capable anticancer drug thanks to its ability to negatively modulate the uptake and metabolism of glucose, the so-called “Warburg effect”, whose increase is considered a common feature of cancer cells in respect of their normal counterparts
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
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
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