1,720,957 research outputs found
Effects of metformin and 2-deoxy-D-glucose on MDA-MB-231 cells and model T lymphocytes in vitro
No full textPresnovne spremembe in izogibanje imunskemu sistemu so temeljne lastnosti raka. Metformin in 2-deoksi-D-glukoza (2DG) sta presnovni učinkovini z različnimi obetavnimi protirakavimi in imunomodulatornimi učinki. Njuna kombinacija povzroči odlepljanje živih celic raka dojke MDA-MB-231 z ohranjeno sposobnostjo proliferacije in vitro. Od podlage neodvisna rast rakavih celic in vitro korelira z metastaziranjem in vivo. Obenem zahteva mitohondrijsko biogenezo, vendar presnovne spremembe pri odlepljanju, ter učinek metformina in 2DG na mitohondrije niso znani. Z metabolomiko smo identificirali presnovne spremembe v celicah MDA-MB-231, tretiranih z metforminom in 2DG. Visoka 2DG in kombinacija metformina in nizke 2DG (metformin+2DG) sta spremenili presnovni profil podobno kot metformin. To ne razloži odlepljanja, ki je posledica zmanjšanja N-glikozilacije proteinov z 2DG in njegovega potenciranja z metforminom. Odlepljene celice so bile mehkejše in presenetljivo presnovno bližje kontroli kot pritrjenim tretiranim celicam. Imele so spremenjen nivo NADPH, glutamina in presnove maščobnih kislin, kar je značilno za rast v odlepljenem stanju. Metformin+2DG in visoka koncentracija 2DG sta povečala mitohondrijsko maso celic raka dojke preko aktivacije mitohondrijske biogeneze in povečane velikosti, ne pa tudi števila mitohondrijev. 2DG in metformin+2DG sta inducirala stres endoplazmatskega retikuluma, ki je bil potencialni sprožilec mitohondrijske biogeneze skupaj z energijsim stresom. Aktivacija z adenozin monofosfatom aktivirane proteinske kinaze je pri tem igrala vlogo, a ni bila zadostna za sprožitev mitohondrijske biogeneze. Metformin in 2DG tako povzročita presnovni stres in mitohondrijske prilagoditve, kar omogoča preživetje rakavih celic ob odlepljanju in energijskem stresu. Vzporedno sta 2DG in metformin+2DG zmanjšala izražanje liganda 1 za receptor programirane smrti 1 (PD-L1) na celicah MDA-MB-231 preko zavrte N-glikozilacije in zmanjšala izražanje receptorja programirane celične smrti 1 (PD-1) na celicah Jurkat. Metformin, visoka koncetracija 2DG in metformin+2DG so zavrli proliferacijo, aktivacijo in izločanje interlevkina 2 preko zmanjšanja proizvodnje adenozin trifosfata, nizka 2DG pa je ohranila izločanje interlevkina 2 in povečala izločanje interferona ?. Nizka koncetracija glukoze je okrepila učinek metformina, medtem kot supra-fiziološka koncentracija glukoze ali eksogeni piruvat nista imela učinka. Presnovne učinkovine delno zavrejo funkcijo celic Jurkat, specifične kombinacije pa bi lahko izboljšale protitumorsko imunost preko osi PD-1/PD-L1.Metabolic alterations and immune evasion are emerging hallmarks of cancer. Metformin and 2-deoxy-D-glucose (2DG) are metabolic drugs with several promising anti-cancer and immunomodulatory effects. Their combination induces detachment of viable MDA-MB-231 breast cancer cells retaining proliferation capacity in vitro. Anchorage-independent growth of cancer cells in vitro is correlated to metastasis formation in vivo and requires mitochondrial biogenesis, but the metabolic changes involved in detachment and the effect of metformin and 2DG on mitochondria are unknown. We used liquid chromatography-mass spectrometry metabolomics to identify alterations in metformin and 2DG treated MDA-MB-231 cells. High concentration of 2DG and the combination of metformin and low concentration of 2DG (metformin+2DG) altered the metabolic profile similarly to metformin. These alterations could not explain detachment, which was actually induced by suppressed protein N-glycosylation by 2DG and its potentiation by metformin. The detached cells were softer and, surprisingly, metabolically closer to control than their attached counterparts. They exhibited altered NADPH, glutamine and fatty acid metabolism characteristic for anchorage-independent growth. Metformin+2DG and high 2DG increased mitochondrial mass in breast cancer cells by activating mitochondrial biogenesis and increasing mitochondrial size, but not their number. 2DG and metformin+2DG induced endoplasmic reticulum stress which could trigger mitochondrial biogenesis together with energy stress. Adenosine monophosphate activated protein kinase activation was also involved but not sufficient for mitochondrial biogenesis. Overall, metformin and 2DG induce metabolic and mitochondrial adaptations enabling breast cancer cell survival in detachment and energy stress. In parallel, 2DG and metformin+2DG reduced programmed death ligand 1 (PD-L1) expression in MDA-MB-231 cells by suppressing N-glycosylation and reduced programmed death 1 (PD-1) expression in Jurkat cells. Metformin, high 2DG and metformin+2DG inhibited Jurkat cell proliferation, activation and interleukin 2 secretion by reducing adenosine triphosphate production, but low 2DG preserved interleukin 2 and boosted interferon γ secretion. Low glucose concentration potentiated the effect of metformin, while supra-physiological glucose levels or exogenous pyruvate had no effect. While metabolic drugs partially inhibit Jurkat function, specific combinations could improve anti-tumor immunity via PD-1/PD-L1 axis inhibition
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
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
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