1,721,001 research outputs found
F86. INTEGRATIVE ANALYSIS OF MICRORNA EXPRESSION PROFILES REVEALS POTENTIAL MOLECULAR MECHANISMS UNDERLYING BROAD DIAGNOSTIC GROUPS
No full textIntegrative analysis of miRNA expression profiles reveals distinct and common molecular mechanisms underlying broad diagnostic groups of severe mental disorders
No full textThe role of the peptidyl prolyl isomerase Rrd1 in the transcriptional stress response
No full textLa régulation de la transcription est un processus complexe qui a évolué pendant des millions
d’années permettant ainsi aux cellules de s’adapter aux changements environnementaux. Notre
laboratoire étudie le rôle de la rapamycine, un agent immunosuppresseur et anticancéreux, qui
mime la carence nutritionelle. Afin de comprendre les mécanismes impliqués dans la réponse a
la rapamycine, nous recherchons des mutants de la levure Saccaromyces cerevisiae qui ont un
phenotype altérée envers cette drogue. Nous avons identifié le gène RRD1, qui encode une
peptidyl prolyl isomérase et dont la mutation rend les levures très résistantes à la rapamycine et il
semble que se soit associé à une réponse transcriptionelle alterée. Mon projet de recherche de
doctorat est d’identifier le rôle de Rrd1 dans la réponse à la rapamycine. Tout d’abord nous
avons trouvé que Rrd1 interagit avec l’ARN polymérase II (RNAPII), plus spécifiquement avec
son domaine C-terminal. En réponse à la rapamycine, Rrd1 induit un changement dans la
conformation du domaine C-terminal in vivo permettant la régulation de l’association de RNAPII
avec certains gènes. Des analyses in vitro ont également montré que cette action est directe et
probablement liée à l’activité isomérase de Rrd1 suggérant un rôle pour Rrd1 dans la régulation
de la transcription. Nous avons utilisé la technologie de ChIP sur micropuce pour localiser Rrd1
sur la majorité des gènes transcrits par RNAPII et montre que Rrd1 agit en tant que facteur
d’élongation de RNAPII. Pour finir, des résultats suggèrent que Rrd1 n’est pas seulement
impliqué dans la réponse à la rapamycine mais aussi à differents stress environnementaux, nous
permettant ainsi d’établir que Rrd1 est un facteur d’élongation de la transcription requis pour la
régulation de la transcription via RNAPII en réponse au stress.Transcriptional regulation is a complex process that has evolved over millions of years of
evolution. Cells have to sense environmental conditions and adapt to them by altering their
transcription. Herein, we study the role of rapamycin, an immunosuppressant and anticancer
molecule that mimics cellular starvation. To understand how the action of rapamycin is
mediated, we analyzed gene deletion mutants in the yeast Saccharomyces cerevisiae that have an
altered response to this drug. Deletion of RRD1, a gene encoding a peptidyl prolyl isomerase,
causes strong resistance to rapamycin and this was associated with a role of Rrd1 in the
transcriptional response towards rapamycin. The main focus of my PhD was therefore to unravel
the role of Rrd1 in response to rapamycin. First, we discovered that Rrd1 interacts with RNA
polymerase II (RNAPII), more specifically with its C-terminal domain and we showed that in
response to rapamycin, Rrd1 alters the structure of this C-terminal domain. This phenomenon
was confirmed to be directly mediated by Rrd1 in vitro, presumably through its peptidyl prolyl
isomerase activity. Further, we demonstrated that Rrd1 is capable of altering the occupancy of
RNAPII on genes in vivo and in vitro. With the use of ChIP on chip technology, we show that
Rrd1 is actually a transcription elongation factor that is associated with RNAPII on actively
transcribed genes. In addition, we demonstrate that Rrd1 is indeed required to regulate the
expression of a large subset of genes in response to rapamycin. This data let us propose a novel
mechanism by which Rrd1 regulates RNAPII during transcription elongation. Finally, we
provide evidence that Rrd1 is not only required for an efficient response towards rapamycin but
to a larger variety of environmental stress conditions, thus establishing Rrd1 as a transcriptional
elongation factor required to fine tune the transcriptional stress response of RNAPII
The role of the peptidyl prolyl isomerase Rrd1 in the transcriptional stress response
Full text linkLa régulation de la transcription est un processus complexe qui a évolué pendant des millions
d’années permettant ainsi aux cellules de s’adapter aux changements environnementaux. Notre
laboratoire étudie le rôle de la rapamycine, un agent immunosuppresseur et anticancéreux, qui
mime la carence nutritionelle. Afin de comprendre les mécanismes impliqués dans la réponse a
la rapamycine, nous recherchons des mutants de la levure Saccaromyces cerevisiae qui ont un
phenotype altérée envers cette drogue. Nous avons identifié le gène RRD1, qui encode une
peptidyl prolyl isomérase et dont la mutation rend les levures très résistantes à la rapamycine et il
semble que se soit associé à une réponse transcriptionelle alterée. Mon projet de recherche de
doctorat est d’identifier le rôle de Rrd1 dans la réponse à la rapamycine. Tout d’abord nous
avons trouvé que Rrd1 interagit avec l’ARN polymérase II (RNAPII), plus spécifiquement avec
son domaine C-terminal. En réponse à la rapamycine, Rrd1 induit un changement dans la
conformation du domaine C-terminal in vivo permettant la régulation de l’association de RNAPII
avec certains gènes. Des analyses in vitro ont également montré que cette action est directe et
probablement liée à l’activité isomérase de Rrd1 suggérant un rôle pour Rrd1 dans la régulation
de la transcription. Nous avons utilisé la technologie de ChIP sur micropuce pour localiser Rrd1
sur la majorité des gènes transcrits par RNAPII et montre que Rrd1 agit en tant que facteur
d’élongation de RNAPII. Pour finir, des résultats suggèrent que Rrd1 n’est pas seulement
impliqué dans la réponse à la rapamycine mais aussi à differents stress environnementaux, nous
permettant ainsi d’établir que Rrd1 est un facteur d’élongation de la transcription requis pour la
régulation de la transcription via RNAPII en réponse au stress.Transcriptional regulation is a complex process that has evolved over millions of years of
evolution. Cells have to sense environmental conditions and adapt to them by altering their
transcription. Herein, we study the role of rapamycin, an immunosuppressant and anticancer
molecule that mimics cellular starvation. To understand how the action of rapamycin is
mediated, we analyzed gene deletion mutants in the yeast Saccharomyces cerevisiae that have an
altered response to this drug. Deletion of RRD1, a gene encoding a peptidyl prolyl isomerase,
causes strong resistance to rapamycin and this was associated with a role of Rrd1 in the
transcriptional response towards rapamycin. The main focus of my PhD was therefore to unravel
the role of Rrd1 in response to rapamycin. First, we discovered that Rrd1 interacts with RNA
polymerase II (RNAPII), more specifically with its C-terminal domain and we showed that in
response to rapamycin, Rrd1 alters the structure of this C-terminal domain. This phenomenon
was confirmed to be directly mediated by Rrd1 in vitro, presumably through its peptidyl prolyl
isomerase activity. Further, we demonstrated that Rrd1 is capable of altering the occupancy of
RNAPII on genes in vivo and in vitro. With the use of ChIP on chip technology, we show that
Rrd1 is actually a transcription elongation factor that is associated with RNAPII on actively
transcribed genes. In addition, we demonstrate that Rrd1 is indeed required to regulate the
expression of a large subset of genes in response to rapamycin. This data let us propose a novel
mechanism by which Rrd1 regulates RNAPII during transcription elongation. Finally, we
provide evidence that Rrd1 is not only required for an efficient response towards rapamycin but
to a larger variety of environmental stress conditions, thus establishing Rrd1 as a transcriptional
elongation factor required to fine tune the transcriptional stress response of RNAPII
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
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