1,720,974 research outputs found
Going Beyond Counting First Authors in Author Co-citation Analysis
The 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
Cardiac effects of NRG-1β in a doxorubicin-therapy model – focus on early molecular events and sex-differences
Doxorubicin (dox) is one of the most potent chemotherapeutic drugs nowadays. However, dox use in clinics is limited by its high myocardial toxicity. Recent evidence suggests that dox-induced early disturbance of metabolic pathways in cardiomyocytes conditions the later development of chronic heart failure (CHF) in patients. Interestingly, circulating levels of neuregulin-1β (NRG-1) are correlated with the development of chronic heart failure in cancer patients after dox-therapy. Moreover, inhibition of the NRG-1 co-receptor ErbB2 worsens cardiac outcomes, indicating a cardioprotective role of NRG-1 in these patients. In the present study, our aim was to 1) characterize an in vivo model of dox-induced cardiac dysfunction in male and female mice, and 2) investigate whether NRG-1 protects against dox-induced cardiotoxicity by modulating acute metabolic mechanisms, especially autophagy.
C57BL/6J male and female mice were assigned to a CTL, dox or NRG/dox group. Mice were injected intraperitoneally with vehicle or dox (4 mg/kg) at day 0, 2, 5, 8, 10, 12 yielding a cumulative dose of 24 mg/kg. NRG-1 (20 μg/kg) or vehicle (PBS) were injected 30 min before each dox injection and continued every other day until sacrifice. Heart function and architecture were measured using echocardiography at multiple timepoints before sacrifice. Body weight loss was observed in males and females, indicative of systemic toxicity. These effects were stronger in males than in females. In males, dox increased cardiac ejection fractions and left ventricular wall thickness at 2 weeks after treatment-begin and NRG-1 prevented this. In contrast, in females dox did not modulate cardiac function, however, dox decreased LV wall thickness and NRG-1 did not affect this at 3 weeks. These results were associated with increased GLUT1 and β-MHC mRNA in dox-treated males, while dox-treated females only showed an increase in β-MHC mRNA levels. Yet, NRG-1 did not modify any of these molecular responses neither in males nor in females. Our data show that dox-induced cardiac remodeling is sex-dependent: males respond with stronger cardiac compensation to dox than females at the functional and molecular level.
For our mechanistic studies, additional mice were sacrificed at day 1 after the dox injection, 1 h after NRG-1 stimulation. In males, the single dox injection was enough to decrease the cardiac LC3II/I ratios. On the other hand, female mice did not show any dox-induced cardiac modulation of the LC3II/I ratios at day 1. While NRG-1 had no effects in males, in females it significantly decreased LC3II/I and enhanced the phosphorylation of ULK1 at its inhibitory S757 site, suggesting that NRG-1 reduces autophagy in dox-treated females.
To investigate underlying mechanisms, neonatal rat ventricular myocytes (NRVM) were used as a model. NRVM were pre-treated in serum-free medium with E64D/pepstatin A inhibitors to study autophagic flux, or directly stimulated with NRG-1. After NRG-1 stimulation, NRVM were treated with dox (1 μM). At 16 h the NRVM model mimicked the molecular response observed in females at 24 h. At 1 h, NRG-1 alleviated a dox-induced increase of LC3II protein, and this was associated with increased ULK1-pS757 as well as decreased FoxO1 nuclear location. Consistently, at 6 h, NRG/dox-treated NRVM showed decreased expression of the FoxO1 target genes LC3 and ULK1 in comparison to dox-treated cells. Furthermore, our preliminary data obtained with MTT and luciferin-based CELL TITER GLO assays showed that dox induced an increase in succinate synthetase activity, without changing ATP content at 3 h. Interestingly, this was associated with decreased mitochondrial/nuclear DNA ratios at 3 and 16 h, and NRG-1 alleviated it at 3 h.
In conclusion, our study showed that the NRG-1 treatment regimen that we used might not be suitable for males to alleviate dox-induced early cardiac autophagy disturbances. In females, evidence for NRG-1 inhibition of the autophagic pathway were uncovered upon dox-therapy and surprisingly, might be independent of the mTORC1 pathway. Our study highlighted the need to characterize sex-differences upon dox-therapy and NRG-1 preventive treatment to promote personalized medicine
Variations on the Author
“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
We 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
We 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
Mécanismes moléculaires de la régulation du récepteur nucléaire humain PPAR alpha (un rôle clef des modifications post-traductionnelles)
Le récepteur nucléaire PPARa joue un rôle majeur dans la régulation du métabolisme des lipides et dans le contrôle de la réponse inflammatoire au travers de mécanismes génomiques de cis-activation et non-génomiques de trans-répression, respectivement. L'activité cis-activatrice de PPARa peut être augmentée par le recrutement de coactivateurs (SRC-1 et CBP) et inhibée par les corépresseurs (NCoR et SMRT). Cette activité peut dépendre de la présence de ligand (acides gras, fibrates). En plus de la liaison du ligand, l'activité de PPARa est régulée par des modifications post-traductionnelles telles que la phosphorylation et l'ubiquitination. Cependant, les mécanismes moléculaires liés à la régulation de l'activité de PPARa restent cependant peu connus. Nous nous sommes plus particulièrement intéressés à la SUMOylation et nous avons montré que l'activité de PPARa peut être régulée par cette modification post-traductionnelle. De manière très intéressante, nous avons montré que le site de SUMOylation de PPARa est très proche des sites de phosphorylation par les Protéines Kinases C (PKC) du récepteur. Nous nous sommes donc intéressés aux rôles de la phosphorylation de PPARa humain par les PKC sur la régulation de l'activité et de la SUMOylation du récepteur. Dans un premier temps, nous avons montré que la protéine hPPARa est SUMOylée par SUMO-1 (Small Ubiquitin-like MOdifier-1) sur la lysine 185 de son domaine charnière. L'inhibition spécifique de la SUMOylation sur ce site augmente l'activité cis-activatrice de PPARa en inhibant le recrutement du corépresseur NCoR mais pas celui de SMRT. Enfin, la SUMOylation de hPPARa est régulée par la présence de ligand spécifique, par la SUMO E3 ligase PIASy. De plus, il a été montré au laboratoire que les PKC-a et -bII phosphorylent le son domaine charnière de hPPARa au niveau des sérines 179 et 230. Cependant, les mécanismes moléculaires liés à la régulation de hPPARa par les PKC restaient inconnus. Ainsi, nous avons montré que la phosphorylation des sérines 179 et 230 inhibe l'activité cis-activatrice de hPPARa en favorisant le recrutement du corépresseur SMRT mais pas de NCoR. Nous avons également montré que la phosphorylation par les PKC diminue la SUMOylation de PPARa, suggérant une interconnexion entre ces deux modifications post-traductionnelles. En conclusion, la phosphorylation et la SUMOylation de hPPARa au niveau de sa région charnière agiraient comme un interrupteur moléculaire régulant spécifiquement l'activité transcriptionnelle de hPPARa au travers du recrutement spécifique de ses cofacteursLILLE2-BU Santé-Recherche (593502101) / SudocSudocFranceF
koamabayili/VECTRON-author-checklist: VECTRON author checklist
We 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.
Author-wise bibliometric analysis based on entropy.</p
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