Abstract The molecular causes of deteriorating oocyte quality during aging are poorly defined. Since oocyte developmental competence relies on post-transcriptional regulations, we tested whether defective mRNA translation contributes to this decline in quality. Disruption in ribosome loading on maternal transcripts is present in old oocytes. Using a candidate approach, we detect altered translation of 3’-UTR-reporters and altered poly(A) length of the endogenous mRNAs. mRNA polyadenylation depends on the cytoplasmic polyadenylation binding protein 1 (CPEB1). Cpeb1 mRNA translation and protein levels are decreased in old oocytes. This decrease causes de-repression of Ccnb1 translation in quiescent oocytes, premature CDK1 activation, and accelerated reentry into meiosis. De-repression of Ccnb1 is corrected by Cpeb1 mRNA injection in old oocytes. Oocyte-specific Cpeb1 haploinsufficiency in young oocytes recapitulates all the translation phenotypes of old oocytes. These findings demonstrate that a dysfunction in the oocyte translation program is associated with the decline in oocyte quality during aging.
Abstract Deleted in azoospermia-like (DAZL) is an RNA-binding protein critical for gamete development. In full-grown oocytes, the DAZL protein increases 4-fold during reentry into the meiotic cell cycle. Here, we have investigated the functional significance of this accumulation at a genome-wide level. Depletion of DAZL causes a block in maturation and widespread disruption in the pattern of ribosome loading on maternal transcripts. In addition to decreased translation, DAZL depletion also causes translational activation of a distinct subset of mRNAs both in quiescent and maturing oocytes, a function recapitulated with YFP-3′UTR reporters. DAZL binds to mRNAs whose translation is both repressed and activated during maturation. Injection of recombinant DAZL protein in DAZL-depleted oocytes rescues the translation and maturation to MII. Mutagenesis of putative DAZL-binding sites in these mRNAs mimics the effect of DAZL depletion. These findings demonstrate that DAZL regulates translation of maternal mRNAs, functioning both as the translational repressor and activator during oocyte maturation.
Abstract During oocyte maturation, changes in gene expression depend exclusively on translation and degradation of maternal mRNAs rather than transcription. Execution of this translation program is essential for assembling the molecular machinery required for meiotic progression, fertilization, and embryo development. With the present study, we used a RiboTag/RNA-Seq approach to explore the timing of maternal mRNA translation in quiescent oocytes as well as in oocytes progressing through the first meiotic division. This genome-wide analysis reveals a global switch in maternal mRNA translation coinciding with oocyte re-entry into the meiotic cell cycle. Messenger RNAs whose translation is highly active in quiescent oocytes invariably become repressed during meiotic re-entry, whereas transcripts repressed in quiescent oocytes become activated. Experimentally, we have defined the exact timing of the switch and the repressive function of CPE elements, and identified a novel role for CPEB1 in maintaining constitutive translation of a large group of maternal mRNAs during maturation.
Cyclins associate with CDK1 to generate the M-phase-promoting factor (MPF) activity essential for progression through mitosis and meiosis. Although CCNB1 is required for embryo development, previous studies concluded that CCNB2 is dispensable for cell cycle progression. Given our findings of high CcnB2 mRNA translation rates in prophase-arrested oocytes, we have reevaluated the role of this cyclin during meiosis. CcnB2−/- oocytes undergo delayed germinal vesicle breakdown and show defects during metaphase to anaphase transition. This defective maturation is associated with compromised CcnB1 and Mos mRNA translation, delayed spindle assembly, and increased errors in chromosome segregation. Given these defects, a significant percentage of oocytes fail to complete meiosis I because the SAC remains active and APC function is inhibited. In vivo, CCNB2 depletion cause ovulation of immature oocytes, compromised female fecundity, and premature ovarian failure. These findings demonstrate that CCNB2 is required to assemble sufficient pre-MPF for timely meiosis reentry and progression. Although endogenous cyclins cannot compensate, overexpression of CCNB1/2 rescues the meiotic phenotypes, indicating similar molecular properties but divergent modes of regulation of these cyclins.
A partir de 9 matrices mots x mots ou matrices co-occurrentielles (une par man-dat présidentiel depuis 1958), nous produisons une matrice de dissimilarité consignant les distances entre les présidents de la Vème République. On donne une représentation ar-borée de cette matrice et on améliore ici les performances de la représentation grâce à une nouvelle approche topologique. On présente alors l'outil logiciel qui permet de tracer le graphe et au terme du parcours méthodologique, on produit une première description socio-linguistique du discours de François Hollande qui reste selon les observateurs poli-tiques encore difficile à définir dans l'histoire présidentielle française. Abstract From 9 matrices of co-occurrences (one for each french president since 1958), we produce a dissimilarities matrix of distances between presidents of the fifth republic. We give a tree analysis of this matrix and we improve the performances due a new topo-logical approach. We present a new software that provide a graphical visualization with this tree analysis. Finally we suggest a first socio-linguistic description of the François Hollande discourse which stay, according to political reporters, still difficult to define in the presidential history.
Hung Nguyen Quoc Viet, Hoai Xuan Luong, Zoltan Miklos, Thanh Tho Quan, Karl Aberer
article
21st International Conference on Cooperative Information Systems (CoopIS 2013), Sep 2013, Graz, Austria
annee_publi
2013
resume
Schema matching is the process of establishing correspondences between the attributes of database schemas for data integration purpose. Although several schema matching tools have been developed, their results are often incomplete or erroneous. To obtain correct attribute correspondences, in practice, human experts edit the mapping results and fix the mapping problems. As the scale and complexity of data integration tasks have increased dramatically in recent years, the reconciliation phase becomes more and more a bottleneck. Moreover, one often needs to establish the correspondences in not only between two but a network of schemas simultaneously. In such reconciliation settings, it is desirable to involve several experts. In this paper, we propose a tool that supports a group of experts to collaboratively reconcile a set of matched correspondences. The experts might have conflicting views whether a given correspondence is correct or not. As one expects global consistency conditions in the network, the conflict resolution might require discussion and negotiation among the experts to resolve such disagreements. We have developed techniques and a tool that allow approaching this reconciliation phase in a systematic way. We represent the expert's views as arguments to enable formal reasoning on the assertions of the experts. We detect complex dependencies in their arguments, guide and present them the possible consequences of their decisions. These techniques thus can greatly help them to overlook the complex cases and work more e ectively.
Hung Nguyen Quoc Viet, Hoai Xuan Luong, Zoltan Miklos, Karl Aberer, Thanh Tho Quan
article
The Twelfth International Conference on Autonomous Agents and Multiagent Systems, May 2013, Saint Paul, Minnesota, United States
annee_publi
2013
resume
Database schema matching is the process of establishing correspondences between attributes of schemas for data integration purpose. Though various commercial tools have been developed, their results are inherently uncertain. In practice, to obtain correct attribute correspondences, there is a need for collecting human input, after the use of automatic matching tools, to reconcile erroneous mappings. We present a negotiation support tool that enables not a single expert but an expert team, whose members might have conflicting views, can work collaboratively to reconcile the output of the automatic tools. In an attempt to facilitate and support cooperation in team integration, our tool sets the goal to compute all possible decisions from expert inputs as well as explanations for each decision. Moreover, it also shows the foreseeable consequences of choosing a particular decision. Technically, this tool is developed on top of an argumentation framework.