1,721,027 research outputs found
Taxonomy of SERM activity in vivo
No full textThe limited success, in terms of prevention of diseases associated to menopause, of hormone replacement therapies imposes further research aimed at better defining the risks and real advantages. SERMs (Selective Estrogen Receptor Modulators) are a class of estrogen mimetics prescribed for the treatment of the menopause. SERMs do not fall into distinct categories of agonists and antagonists, since their action is regulated by tissue-specific expression of a number of auxiliary proteins called coactivators or corepressors. This complexity limits the systemic analysis of their activities, and SERMs development may fail in the late stages of drug development as a result of unforeseen toxicity. The recent description of reporter mice (ERE-luc) for in vivo analysis of hormone receptor activity opens new horizons for drug discovery. The aim of the present thesis was to obtain a taxonomy of drug activity in vivo by developing a method to profile the interaction of SERMs on the transcriptional activity of the ER in ovarectomized ERE-luc female mice as a model of menopause. These novel animal models, in association with in vivo imaging technologies, provided a global view of the target tissues allowing to discover specific signatures of SERM action following acute and repeated drug treatment. This new knowledge lead to propose a new ontology for hormone replacement therapy regimens based on their closeness with the physiological ER activity picture observed in intact cycling females
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
Reporter Mice for the Study of Intracellular Receptor Activity
No full textDuring the past decade the remarkable progress in molecular genetics and the possibility to engineer cells to express genes reporting on the activity of specific promoters has produced major changes in biological research. The description and validation of reporter mice for non-invasive assessment of biological and biochemical processes in living subjects and the results obtained with the models reporting on the activity of estrogen and peroxisome proliferator receptors clearly showed that such technologies have the potential to enhance our understanding of disease and drug activity. Although reporter-gene technology is in its infancy, reporter animals already represent a valuable tool for biomedical investigation. The present chapter aims at critically illustrating the methodology to be applied when dealing with reporter systems and in vivo imagin
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
Molecular Imaging, an Innovative Methodology for Whole-Body Profiling of Endocrine Disrupter Action
No full textEndocrine disrupters (EDs) are environment and food contaminants known to alter metabolic functions of mammals by interfering with specific endocrine pathways. Many EDs act on steroid hormone target cells by interacting with intracellular receptors (IRs) like estrogen receptors, androgen receptors, and thyroid hormone receptors; other receptors may be engaged. IRs are ligand-operated transcription factors acting in concert with general or cell-specific coregulators. The newly acquired awareness on the panoply of IR functions has increased the concern on potential, unsought, harmful effects of EDs on human health and has questioned the capability of currently available methodologies to identify and study EDs in the environment and in the food chain. Indeed, current in vivo and in vitro methodologies restrict the analysis to very specific organs or cell systems, with obvious limitations in predicting the systemic metabolic consequences of ED exposure. The emphasis recently laid by Regulatory Authorities, including European Center for the Validation of Alternative Methods, on the generation of in vitro model systems for toxicological analyses discouraged the development of models suitable to envision the whole spectrum of ED body actions required when studying compounds acting through IRs. Molecular imaging now provides the opportunity to quantify ED effects in living organisms enabling, for the first time, to acquire a full comprehension of the systemic effects of acute and prolonged exposure to EDs, solving the issue of the potential harm due to repeated low-dose exposure. The systems here reviewed are of unquestionable toxicological relevance and need to be taken into consideration to improve the methodology currently available and in us
Automatic Segmentation of Mouse Images
Full text linkGenetic engineering has enabled the generation of organisms where molecular reactions in response to patho-physiological events can be measured in real-time by means of molecular imaging. This novel technology with the generation of reporter cell systems, that is cells engineered to express a bioluminescent protein in response to selected stimuli, had a major impact in pharmacological research. The recent generation of reporter mice, where the activity of a specific drug can be studied systematically, hold the promise to strengthen preclinical studies, providing a very rapid and comprehensive view on drug pharmacokinetics and activity in whole organisms. To date, a major limitation to the use of in vivo imaging for pharmaco-toxicological purposes resides in the limited throughput of the methodology: even if up to 100 animals can be reasonably processed in a day by some imaging techniques, the analysis of the data, including the identification and quantification of signals belonging to different mouse body areas, requires time and trained personnel, to manually identify specific body areas where drug effects can be measured. For this reason, we have developed an algorithm to automatically identify (segment) the body areas of a given reporter mouse. Automatic segmentation is obtained by combining classical image processing and pattern recognition techniques. The algorithm has been tested on more than 1000 mouse images differing for sex, pose and lighting conditions, and acquired by devices of different companies. Our algorithm, not only increases processivity (the whole dataset analyzed by a trained scientist in a week was processed overnight by our software), but also provides more accurate results. In conclusion, automatic systems may outperform current manual image analysis, allowing to obtain a detailed comprehension of real-time molecular processes in living animals with a standardized, rapid, and cost-effective approach.
This work was supported by EC. (STREP EWA LSHM-CT-2005-518245) NIH (RO1AG027713) to A.M
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
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