1,721,169 research outputs found
Pierre Sabatier - Substance, material, matter = Pierre Sabatier - Une oeuvre de la matière
No full textUpcoming retrospective of French sculptor, Pierre Sabatier. This comprehensive exhibition will be his first in the United States and feature previously unseen works curated by the Magen H Gallery. Sabatier’s work is an exploration and enfoldment of the marriage of materials and movement. From largescale works to functional design, the virtuous nature and range of Sabatier’s work lends itself to an inquiry into the adaptation of forms and materials. It is also a reflection of our willingness as a society to remain flexible in a constantly changing world
Plurifaceted proteomics in studying cellular dynamics and action mechanisms of anticancer drugs
No full textMass spectrometry (MS)-based proteomics has developed tremendously in recent years and was the leading technology for many novel methods to study protein chemistry. Contrary to classical approaches based on Western blot, MS-based approaches are mostly unbiased. In addition to protein expression levels, today several protein chemical properties can be examined by MS-based proteomics making it unique in comparison to transcriptomics approaches. These properties include post-translational modifications (PTMs), protein localization, synthesis/degradation, and lastly protein thermal stability, adding novel dimensions or facets to characterize the proteome. However, these facets are difficult to combine as they are mainly orthogonal and are therefore often analyzed separately. This thesis presents a simplified and higher throughput version of current protein stability analyses and showcases the advantages of combined/merged analysis of proteomics facets including our new method, as well as expression and redox proteomics to study anticancer treatments and cellular dynamics.In paper I, we studied the dynamics of cancer cells in vitro with and without anticancer treatment over the course of 48 h by monitoring protein expression every 6 h. We discovered that naturally occurring proteome variations are on par with anticancer treatment killing 50% of the cells after 48 h. Then, we acquired a deep proteomics dataset of untreated HCT116 and A375 cell lines. Surprisingly, we observed downregulation of proteins involved in cell division and upregulation of proteins involved in metabolism as early as 12 h after treatment, suggesting that growth inhibition happens earlier than usually assumed and even at low cell confluence. In paper II we developed the proteome integral solubility alteration (PISA) assay that increases the throughput of pre-existing drug target deconvolution methods based on protein stability/solubility measurements and reduces the analysis time and cost as well as sample requirements. We provided theoretical calculations showing that the integral of the curve correlates well with melting temperature estimations in Thermal Proteome Profiling (TPP) and tested our assumptions with publicly available TPP datasets. Then we performed a proof of principle experiment using the well-studied methotrexate (MTX) and 5-fluorouracile (5-FU) as test drugs highlighting the targets as outliers with our method. Furthermore, we demonstrated that PISA assay can also be used for concentration series analysis as in 2D-TPP. Finally, we showcased the higher throughput of PISA compared to TPP by simultaneously analyzing nine drugs in one multiplexed analysis. In paper III we used a combination of chemical proteomics approaches to study the target and mechanism of action (MOA) of Auranofin (AF) (Ridaura®). Functional Identification of Target by Expression Proteomics (FITExP), TPP, and redox proteomics combined highlighted that thioredoxin reductase 1 (TXNRD1) is indeed a top target hit of AF, and that the main MOA of the drug is through disruption of the redox balance in the cell. Finally, we showed that protein thermal shifts can be associated with altered cysteine oxidation levels in proteins, suggesting that TPP is suitable to study disulfide bond formation/reduction and map some cysteines to the active sites of sulfiredoxin 1 (SRXN1) and peroxiredoxin 5 (PRDX5) as examples. Overall, our study demonstrates that using only one of the proteomics methods is not sufficient to accurately pinpoint drug target and MOA, but a combination of multiple complementary methods should be used instead.Following the success of our strategy in paper III, we decided to utilize the same strategy in paper IV using PISA developed in paper II instead of TPP, to study two novel inhibitors of TXNRD1, namely TRi-1 and TRi-2. For these studies, we used the mouse cancer cell lines B16-F10 and Lewis lung carcinoma (LLC) to provide a comprehensive analysis of the therapeutic effects of the inhibitors. Since we showed that Txnrd1 (the mouse version of the human TXNRD1 protein) is a main target of AF, we decided to use it as our reference point to evaluate the specificity of the two new compounds. AF had a broader effect on the proteome than TRi-1 and TRi-2 and had more target hits in PISA analyses. This suggested that AF has lower specificity than TRi-1 and TRi-2. TRi-1 was the most specific Txnrd1 inhibitor with a better target ranking in FITExP and the least target hits in PISA followed by TRi-2 and AF. Thus, we showed that TRi-1 and TRi-2 are indeed more specific inhibitors of Txnrd1. In addition to these findings, we also highlighted that only AF triggers a high nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant response, suggesting that this response is not necessarily Txnrd1-dependent. Finally, we detected selenocysteine-specific elongation factor (Eefsec), mini-chromosome maintenance complex-binding protein (Mcmbp), glycogen synthase kinase-3 (Gsk3) a and b, as target hits of AF, which would explain at least partially three different effects of AF treatment. Collectively, our data represents a resource for redox biologists interested in Txnrd1 inhibition. Our approach provides a framework for target deconvolution using proteomics approaches.Finally, in paper V we studied the dynamics of the proteome in transition between various cell types. We reprogrammed human foreskin fibroblasts (hFF) into induced pluripotent stem cells (iPSCs), which we differentiated through embryoid bodies (EBs) formation. We examined protein expression and stability after each cell type transition using PISA-Express, a new version of the PISA assay developed in paper II. We merged the readout from protein expression and thermal stability in one analysis using Sankey diagrams to detect changes in protein properties during proteome transitions resulting in the ProteoTracker web interface (http://www.proteotracker.genexplain.com/). Using this innovative analysis, we discovered that ribosomes are less stable in pluripotent stem cells (PSCs) compared to differentiated cells and that this difference stems from the deficiency of one ribosome maturation factor, Shwachman-Bodian-Diamond syndrome protein (SBDS). Knock-down (KD) of SBDS slowed down translation and increased expression of the master pluripotency markers homeobox protein NANOG (NANOG), and octamer-binding transcription factor 4 (OCT4). Collectively, we developed a new method for simultaneous analysis of protein thermal stability and expression, a new analysis and visualization tool, and provided evidence that control of translation through ribosome biogenesis is a natural mechanism used by PSCs to maintain the pluripotency state.List of scientific papersI. Pierre Sabatier, Amir A. Saei, Shiyu Wang and Roman A. Zubarev. Dynamic Proteomics Reveals High Plasticity of Cellular Proteome: Growth-Related and Drug-Induced Changes in Cancer Cells are Comparable. Proteomics. 2018 Dec;18(24):e1800118. https://doi.org/10.1002/pmic.201800118 II. Massimiliano Gaetani*, Pierre Sabatier*, Amir A. Saei*, Christian M.Beusch, Zhe Yang, Susanna L. Lundström and Roman A. Zubarev. Proteome Integral Solubility Alteration: A High-Throughput Proteomics Assay for Target Deconvolution. J Proteome Res. 2019 Nov 1;18(11):4027-4037. *These authors contributed equally. https://doi.org/10.1021/acs.jproteome.9b00500 III. Amir A. Saei, Hjalmar Gullberg*, Pierre Sabatier*, Christian M. Beusch*, Katarina Johansson, Bo Lundgren, Per I. Arvidsson, Elias S. J. Arnér and Roman A. Zubarev. Comprehensive chemical proteomics for target deconvolution of the redox active drug auranofin. Redox Biol. 2020 May;32:101491. *These authors contributed equally. https://doi.org/10.1016/j.redox.2020.101491 IV. Pierre Sabatier, Christian M. Beusch, Roman A. Zubarev* and Elias S. J. Arnér*. Comprehensive chemical proteomics reveal that the new TRi-1 and TRi-2 compounds are more specific thioredoxin reductase 1 inhibitors than Auranofin. *These authors contributed equally. [Manuscript]V. Pierre Sabatier, Christian M. Beusch, Amir A. Saei, Mike Aoun, Noah Moruzzi, Niels Leijten, Magnus Nordenskjöld, Patrick Micke, Diana Maltseva, Alexander G. Tonevitsky, Vincent Millischer, J. Carlos Villaescusa, Sandeep Kadekar, Per-Olof Berggren, Oscar Simonson, Karl-Henrik Grinnemo, Rikard Holmdahl, Sergey Rodin* and Roman A. Zubarev*. Plurifaceted proteomics method identifies key regulators of translation during stem cells maintenance and differentiation. *These authors contributed equally. [Manuscript]</p
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
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
04_LESTIENNE_et_al_2019_SUP_MATERIAL – Supplemental material for Fires and human activities as key factors in the high diversity of Corsican vegetation
No full textSupplemental material, 04_LESTIENNE_et_al_2019_SUP_MATERIAL for Fires and human activities as key factors in the high diversity of Corsican vegetation by Marion Lestienne, Isabelle Jouffroy-Bapicot, Déborah Leyssenne, Pierre Sabatier, Maxime Debret, Pierre-Jean Albertini, Daniele Colombaroli, Julien Didier, Christelle Hély and Boris Vannière in The Holocene</p
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