Identification of novel pathway partners of p68 and p72 RNA helicases through Oncomine meta-analysis

<p>Abstract</p> <p>Background</p> <p>The Oncomine™ database is an online collection of microarrays from various sources, usually cancer-related, and contains many "multi-arrays" (collections of analyzed microarrays, in a single study). As there are often many hundreds of tumour samples/microarrays within a single multi-array results from coexpressed genes can be analyzed, and are fully searchable. This gives a potentially significant list of coexpressed genes, which is important to define pathways in which the gene of interest is involved. However, to increase the likelihood of revealing truly significant coexpressed genes we have analyzed their frequency of occurrence over multiple studies (meta-analysis), greatly increasing the significance of results compared to those of a single study.</p> <p>Results</p> <p>We have used the DEAD-box proteins p68(Ddx5) and p72(Ddx17) as models for this coexpression frequency analysis as there are defined functions for these proteins in splicing and transcription (known functions which we could use as a basis for quality control). Furthermore, as these proteins are highly similar, interact together, and may be to some degree functionally redundant, we then analyzed the overlap between coexpressed genes of p68 and p72. This final analysis gave us a highly significant list of coexpressed genes, clustering mainly in splicing and transcription (recapitulating their published roles), but also revealing new pathways such as cytoskeleton remodelling and protein folding. We have further tested a predicted pathway partner, RNA helicase A(Dhx9) in a reciprocal meta-analysis that identified p68 and p72 as being coexpressed, and further show a direct interaction of Dhx9 with p68 and p72, attesting to the predictive nature of this technique.</p> <p>Conclusion</p> <p>In summary we have extended the capabilities of Oncomine™ by analyzing the frequency of coexpressed genes over multiple studies, and furthermore assessing the overlap with a known pathway partner (in this case p68 with p72). We have shown our predictions corroborate previously published studies on p68 and p72, and that novel predictions can be easily tested. These techniques are widely applicable and should increase the quality of data from future meta-analysis studies.</p

Meta-analysis of human cancer microarrays reveals GATA3 is integral to the estrogen receptor alpha pathway

<p>Abstract</p> <p>Background</p> <p>The transcription factor GATA3 has recently been shown to be necessary for mammary gland morphogenesis and luminal cell differentiation. There is also an increasing body of data linking GATA3 to the estrogen receptor α (ERα) pathway. Among these it was shown that GATA3 associates with the promoter of the ERα gene and ERα can reciprocally associate with the GATA3 gene. GATA3 has also been directly implicated in a differentiated phenotype in mouse models of mammary tumourigenesis. The purpose of our study was to compare coexpressed genes, by meta-analysis, of GATA3 and relate these to a similar analysis for ERα to determine the depth of overlap.</p> <p>Results</p> <p>We have used a newly described method of meta-analysis of multiple cancer studies within the Oncomine database, focusing here predominantly upon breast cancer studies. We demonstrate that ERα and GATA3 reciprocally have the highest overlap with one another. Furthermore, we show that when both coexpression meta-analysis lists for ERα and GATA3 are compared there is a significant overlap between both and, like ERα, GATA3 coexpresses with ERα pathway partners such as pS2 (<it>TFF1</it>), <it>TFF3</it>, <it>FOXA1</it>, <it>BCL2</it>, <it>ERBB4</it>, <it>XBP1</it>, <it>NRIP1</it>, <it>IL6ST</it>, keratin 18(<it>KRT18</it>) and cyclin D1 (<it>CCND1</it>). Moreover, as these data are derived from human tumour samples this adds credence to previous cell-culture or murine based studies.</p> <p>Conclusion</p> <p>GATA3 is hypothesized to be integral to the ERα pathway given the following: (1) The large overlap of coexpressed genes as seen by meta-analysis, between GATA3 and ERα, (2) The highest coexpressing gene for GATA3 was ERα and <it>vice-versa</it>, (3) GATA3, like ERα, coexpresses with many well-known ERα pathway partners such as pS2.</p

ERRα as a Bridge Between Transcription and Function: Role in Liver Metabolism and Disease

As transcriptional factors, nuclear receptors (NRs) function as major regulators of gene expression. In particular, dysregulation of NR activity has been shown to significantly alter metabolic homeostasis in various contexts leading to metabolic disorders and cancers. The orphan estrogen-related receptor (ERR) subfamily of NRs, comprised of ERRα, ERRβ, and ERRγ, for which a natural ligand has yet to be identified, are known as central regulators of energy metabolism. If AMP-activated protein kinase (AMPK) and mechanistic target of rapamycin (mTOR) can be viewed as sensors of the metabolic needs of a cell and responding acutely via post-translational control of proteins, then the ERRs can be regarded as downstream effectors of metabolism via transcriptional regulation of genes for a long-term and sustained adaptive response. In this review, we will focus on recent findings centered on the transcriptional roles played by ERRα in hepatocytes. Modulation of ERRα activity in both in vitro and in vivo models via genetic or pharmacological manipulation coupled with chromatin-immunoprecipitation (ChIP)-on-chip and ChIP-sequencing (ChIP-seq) studies have been fundamental in delineating the direct roles of ERRα in the control of hepatic gene expression. These studies have identified crucial roles for ERRα in lipid and carbohydrate metabolism as well as in mitochondrial function under both physiological and pathological conditions. The regulation of ERRα expression and activity via ligand-independent modes of action including coregulator binding, post-translational modifications (PTMs) and control of protein stability will be discussed in the context that may serve as valuable tools to modulate ERRα function as new therapeutic avenues for the treatment of hepatic metabolic dysfunction and related diseases

La chapelle Notre-Dame-De-Lourdes de Montréal : histoire, composition et fonction du décor intérieur

Tableau d’honneur de la Faculté des études supérieures et postdoctorales, 2010-2011Cette recherche porte sur le projet de décor mural de la chapelle Notre-Dame-de-Lourdes de Montréal réalisé par Napoléon Bourassa (1827-1916) entre 1872 et 1880. Il met en scène le thème de l'Immaculée Conception et sa proclamation dogmatique par le pape en 1854. Nous étudions les éléments qui ont influencé la composition de l'oeuvre : les contextes historique, intellectuel et artistique de production, le texte du décret dogmatique et sa réélaboration par Bourassa. Nous démontrons comment l'artiste a pensé la narrativité du discours, non seulement par la représentation ou l'iconographie, mais aussi par la formulation stylistique et esthétique de l'ensemble des scènes et des figures. Nous procédons à une analyse intégrée de tous les niveaux de lectures du programme afin de comprendre comment la composition et le vocabulaire formel utilisé par Bourassa répondent à ses objectifs intellectuels et à ceux des commanditaires du projet

Training Deep Learning Algorithms on Synthetic Forest Images for Tree Detection

Vision-based segmentation in forested environments is a key functionality for autonomous forestry operations such as tree felling and forwarding. Deep learning algorithms demonstrate promising results to perform visual tasks such as object detection. However, the supervised learning process of these algorithms requires annotations from a large diversity of images. In this work, we propose to use simulated forest environments to automatically generate 43 k realistic synthetic images with pixel-level annotations, and use it to train deep learning algorithms for tree detection. This allows us to address the following questions: i) what kind of performance should we expect from deep learning in harsh synthetic forest environments, ii) which annotations are the most important for training, and iii) what modality should be used between RGB and depth. We also report the promising transfer learning capability of features learned on our synthetic dataset by directly predicting bounding box, segmentation masks and keypoints on real images. Code available on GitHub (https://github.com/norlab-ulaval/PercepTreeV1).Comment: Work presented at ICRA 2022 Workshop in Innovation in Forestry Robotics: Research and Industry Adoptio

L’image de Rome dans le journal de voyage de Benjamin Pâquet et les collections du Séminaire de Québec entre 1860 et 1900 : définir une culture visuelle par la représentation.

Au cours de son histoire, le Séminaire de Québec acquiert des œuvres d’art par voie d’achats, de dons ou d’importants legs des collections personnelles des prêtres qui en sont des membres agrégés. Qu’elles soient des objets de consultation personnelle, de collections d’étude pour l’Université Laval – institution d’enseignement fondée par le Séminaire en 1852 – ou des éléments de décor des espaces communs, certaines images se démarquent par le sujet qu’elles représentent et appellent une réflexion sur les valeurs qu’elles peuvent constituer au sein de l’institution. La forte représentativité de Rome dans les collections d’estampes s’est imposée comme un questionnement au vu de la démultiplication des objets. Ce constat est également contemporain de l’accroissement de la circulation des prêtres vers la Ville éternelle au cours de la seconde moitié du XIXe siècle. Les récits de voyages de ces derniers permettent de situer les perceptions qu’ils ont de Rome, de ses monuments, ses musées, ses églises, sa religiosité et ses mœurs. De ces récits, générateurs d’images mentales, se démarque le journal de voyage de l’archevêque de Québec, Mgr Joseph-Octave Plessis, tenu en 1819-1820, un document qui permet d’assoir des hypothèses sur la préparation du voyage des prêtres à Rome au XIXe siècle. Tout aussi pertinent, celui de l’abbé Benjamin Pâquet, rédigé entre 1863 et 1866 durant ses études de doctorat en théologie au Collège romain, est une source à partir de laquelle des faits concrets guident la définition de la visualité de Rome, comprise comme un ensemble urbain et un lieu idéal et mythique. À partir des descriptions des expériences sensorielles que les prêtres voyageurs font des lieux et des objets, les images physiques représentant Rome conservées au Séminaire et à l’Université prennent de la valeur et du sens. La concordance des objets et des commentaires génère un corpus représentatif d’une visualité de Rome et du Vatican au Séminaire et à l’Université durant la période ciblée. À ce titre, des œuvres graphiques de monuments romains par Giuseppe Vasi ou Giovanni Battista Piranesi, des portraits de prélats de la curie romaine et du pape par le peintre Vincenzo Pasqualoni et des albums de gravures ou de photographies souvenirs, participent à créer un ensemble de références pour l’institution dont la portée visuelle et culturelle repose sur des faits et une phénoménologie du sensible. L’entretien de rapports diplomatiques entre le Saint-Siège et les membres de l’institution est une constance qui ressort à l’analyse des sources textuelles. À la même époque que le voyage de l’abbé Pâquet, le pape poursuit l’application de stratégies pour consolider son autorité morale et symbolique, alors que son autorité temporelle est affaiblie par les bouleversements politiques en Italie. Ces stratégies se caractérisent, entre autres, par des décrets dogmatiques, le financement de chantiers archéologiques, la restauration de monuments, des commandes artistiques et des rééditions d’estampes à Rome, lesquelles ont influencé le développement de la bibliothèque et des collections du Séminaire. Pour analyser ces modes de correspondance à la fois physique (objets), symbolique (images), spirituel et politique, nous avons fait appel aux règles du monde commun domestique définies par Luc Boltanski et Laurent Thévenot (1991) qui se caractérisent par le respect et la reconnaissance de l’autorité et de la filiation. Celles-ci permettent de comprendre le fonctionnement de la vie en commun auprès d’une micro-société comme le Séminaire; des règles qui influencent également le système de valeurs de celle-ci. Un arrimage intellectuel sur les valeurs idéologiques, humanistes et artistiques, promues par le Saint-Siège explique les formes que peuvent prendre la présence du pape et d’œuvres célèbres du Vatican dans l’imaginaire du Séminaire. La culture visuelle de Rome et du Vatican, dans les collections de l’institution, se trouve ainsi définie par la présence de l’autorité papale garante des humanités classiques, qui s’incarne à travers des actions et des esthétiques valorisant le patrimoine romain antique christianisé, l’historicisme, le purisme et le raphaélisme.Throughout its history, Séminaire de Québec acquired works of art by way of purchases, donations, and legacies from the personal collections of priests who are members of the religious community of the institution. Whether these were objects of personal consultation, study collections for Université Laval — founded by the Séminaire in 1852 — or decorative artifacts in common spaces, some images stand out for the subject they represent and call for a reflection on the values that they can constitute within the institution.The strong representatives of Rome in the collection of prints imposes a questioning on the multiplication of objects on the same subject. This observation is also contemporary to the increase of the long-stay of priests in the Eternal City during the second half of the 19th century. Their travel reports allow them to state their perceptions of Rome, its monuments, its museums, its churches, its religiosity and its customs. From these stories, themselves generators of mental images, stands out the travel diary of the Archbishop of Quebec, Mgr. Joseph-Octave Plessis. Written in 1819-1820, this document allows to formulate hypotheses on the preparation of the journey of priests in Rome in the 19th century. Equally relevant, the travel diary of Abbot Benjamin Pâquet, written between 1863 and 1866 during his doctoral studies in theology at the Roman College, is a source from which concrete facts guide the definition of the visuality of Rome, understood as a urban ensemble and as an ideal and mythical place. From the descriptions of the sensory experiences that traveling priests make of places and objects, the physical images representing Rome kept at the Séminaire and at the Université acquire value and meaning. Concordance of objects and comments generates a corpus representative of a visualization of Rome and the Vatican at the Séminaire and at the Université during the targeted period. As such, graphic works of Roman monuments by Giuseppe Vasi or Giovanni Battista Piranesi, portraits of prelates of the Roman curia and of the Pope by the painter Vincenzo Pasqualoni, and albums of prints or souvenir photographs, create a set of references for the institution whose visual and cultural significance is based on facts and on a phenomenology of the sensitive experience. The fostering of diplomatic relations between the Holy See and the members of the Séminaire is a constancy that emerges from the analysis of textual sources. Around the same time of Abbot Pâquet’s journey, the Pope continued to apply strategies to consolidate his moral and symbolic authority, while his temporal authority was weakened by political upheavals in Italy. These strategies were characterized, among other things, by dogmatic decrees, the funding of archaeological sites, the restoration of monuments, artistic commissions, and reissues of prints in Rome, which influenced the development of the library and of the collections of Séminaire de Québec. To analyze these modes of correspondence which are both physical (objects), symbolic (images), spiritual and political, we have used the rules of the “common domestic world” defined by Luc Boltanski and Laurent Thévenot (1991) which are characterized by respect and recognition of authority and filiation. These make possible to understand the functioning of a life in common within a micro-society, like at the Séminaire; rules also influence its system of values. An intellectual link with the ideological, humanist and artistic values promoted by the Holy See explains the forms that the presence of the Pope and famous Vatican works can take in the imagination of the priests of the Séminaire. The visual culture of Rome and the Vatican, in the collections of the institution, is thus defined by the presence of a papal authority, guardian of the classical humanities, which is embodied through actions and aesthetics valuing Christianized ancient Roman heritage, historicism, purism and Raphael ism

Estimation of fungal diversity and identification of major abiotic drivers influencing fungal richness and communities in northern temperate and boreal Quebec forests

Fungi play important roles in forest ecosystems and understanding fungal diversity is crucial to address essential questions about species conservation and ecosystems management. Changes in fungal diversity can have severe impacts on ecosystem functionality. Unfortunately, little is known about fungal diversity in northern temperate and boreal forests, and we have yet to understand how abiotic variables shape fungal richness and composition. Our objectives were to make an overview of the fungal richness and the community composition in the region and identify their major abiotic drivers. We sampled 262 stands across the northern temperate and boreal Quebec forest located in the region of Abitibi-Témiscamingue, Mauricie, and Haute-Mauricie. At each site, we characterized fungal composition using Illumina sequencing, as well as several potential abiotic drivers (e.g., humus thickness, soil pH, vegetation cover, etc.). We tested effects of abiotic drivers on species richness using generalized linear models, while difference in fungal composition between stands was analyzed with permutational multivariate analysis of variance and beta-diversity partitioning analyses. Fungi from the order Agaricales, Helotiales, and Russulales were the most frequent and sites from the north of Abitibi-Témiscamingue showed the highest OTUs (Operational Taxonomic Unit) richness. Stand age and moss cover were the best predictors of fungal richness. On the other hand, the strongest drivers of fungal community structure were soil pH, average cumulative precipitation, and stand age, although much of community variance was left unexplained in our models. Overall, our regional metacommunity was characterized by high turnover rate, even when rare OTUs were removed. This may indicate strong environmental filtering by several unmeasured abiotic filters, or stronger than expected dispersal limitations in soil fungal communities. Our results show how difficult it can be to predict fungal community assembly even with high replication and efforts to include several biologically relevant explanatory variables

Stereoselective synthesis of fluorinated galactopyranosides as potential molecular probes for galactophilic proteins : assessment of monofluorogalactoside–LecA interactions

The replacement of hydroxyl groups by fluorine atoms on hexopyranoside scaffolds may allow access to invaluable tools for studying various biochemical processes. As part of ongoing activities toward the preparation of fluorinated carbohydrates, a systematic investigation involving the synthesis and biological evaluation of a series of mono‐ and polyfluorinated galactopyranosides is described. Various monofluorogalactopyranosides, a trifluorinated, and a tetrafluorinated galactopyranoside have been prepared using a Chiron approach. Given the scarcity of these compounds in the literature, in addition to their synthesis, their biological profiles were evaluated. Firstly, the fluorinated compounds were investigated as antiproliferative agents using normal human and mouse cells in comparison with cancerous cells. Most of the fluorinated compounds showed no antiproliferative activity. Secondly, these carbohydrate probes were used as potential inhibitors of galactophilic lectins. The first transverse relaxation‐optimized spectroscopy (TROSY) NMR experiments were performed on these interactions, examining chemical shift perturbations of the backbone resonances of LecA, a virulence factor from Pseudomonas aeruginosa. Moreover, taking advantage of the fluorine atom, the 19F NMR resonances of the monofluorogalactopyranosides were directly monitored in the presence and absence of LecA to assess ligand binding. Lastly, these results were corroborated with the binding potencies of the monofluorinated galactopyranoside derivatives by isothermal titration calorimetry experiments. Analogues with fluorine atoms at C‐3 and C‐4 showed weaker affinities with LecA as compared to those with the fluorine atom at C‐2 or C‐6. This research has focused on the chemical synthesis of “drug‐like” low‐molecular‐weight inhibitors that circumvent drawbacks typically associated with natural oligosaccharides

Molecular and Genetic Crosstalks between mTOR and ERRα Are Key Determinants of Rapamycin-Induced Nonalcoholic Fatty Liver

SummarymTOR and ERRα are key regulators of common metabolic processes, including lipid homeostasis. However, it is currently unknown whether these factors cooperate in the control of metabolism. ChIP-sequencing analyses of mouse liver reveal that mTOR occupies regulatory regions of genes on a genome-wide scale including enrichment at genes shared with ERRα that are involved in the TCA cycle and lipid biosynthesis. Genetic ablation of ERRα and rapamycin treatment, alone or in combination, alter the expression of these genes and induce the accumulation of TCA metabolites. As a consequence, both genetic and pharmacological inhibition of ERRα activity exacerbates hepatic hyperlipidemia observed in rapamycin-treated mice. We further show that mTOR regulates ERRα activity through ubiquitin-mediated degradation via transcriptional control of the ubiquitin-proteasome pathway. Our work expands the role of mTOR action in metabolism and highlights the existence of a potent mTOR/ERRα regulatory axis with significant clinical impact