Expression analysis of mitotic spindle checkpoint genes in breast carcinoma: role of NDC80/HEC1 in early breast tumorigenicity, and a two-gene signature for aneuploidy

<p>Abstract</p> <p>Background</p> <p>Aneuploidy and chromosomal instability (CIN) are common abnormalities in human cancer. Alterations of the mitotic spindle checkpoint are likely to contribute to these phenotypes, but little is known about somatic alterations of mitotic spindle checkpoint genes in breast cancer.</p> <p>Methods</p> <p>To obtain further insight into the molecular mechanisms underlying aneuploidy in breast cancer, we used real-time quantitative RT-PCR to quantify the mRNA expression of 76 selected mitotic spindle checkpoint genes in a large panel of breast tumor samples.</p> <p>Results</p> <p>The expression of 49 (64.5%) of the 76 genes was significantly dysregulated in breast tumors compared to normal breast tissues: 40 genes were upregulated and 9 were downregulated. Most of these changes in gene expression during malignant transformation were observed in epithelial cells.</p> <p>Alterations of nine of these genes, and particularly <it>NDC80</it>, were also detected in benign breast tumors, indicating that they may be involved in pre-neoplastic processes.</p> <p>We also identified a two-gene expression signature (<it>PLK1 </it>+ <it>AURKA</it>) which discriminated between DNA aneuploid and DNA diploid breast tumor samples. Interestingly, some DNA tetraploid tumor samples failed to cluster with DNA aneuploid breast tumors.</p> <p>Conclusion</p> <p>This study confirms the importance of previously characterized genes and identifies novel candidate genes that could be activated for aneuploidy to occur. Further functional analyses are required to clearly confirm the role of these new identified genes in the molecular mechanisms involved in breast cancer aneuploidy. The novel genes identified here, and/or the two-gene expression signature, might serve as diagnostic or prognostic markers and form the basis for novel therapeutic strategies.</p

The ocean sampling day consortium.

Ocean Sampling Day was initiated by the EU-funded Micro B3 (Marine Microbial Biodiversity, Bioinformatics, Biotechnology) project to obtain a snapshot of the marine microbial biodiversity and function of the world's oceans. It is a simultaneous global mega-sequencing campaign aiming to generate the largest standardized microbial data set in a single day. This will be achievable only through the coordinated efforts of an Ocean Sampling Day Consortium, supportive partnerships and networks between sites. This commentary outlines the establishment, function and aims of the Consortium and describes our vision for a sustainable study of marine microbial communities and their embedded functional traits

The ocean sampling day consortium

Ocean Sampling Day was initiated by the EU-funded Micro B3 (Marine Microbial Biodiversity, Bioinformatics, Biotechnology) project to obtain a snapshot of the marine microbial biodiversity and function of the world’s oceans. It is a simultaneous global mega-sequencing campaign aiming to generate the largest standardized microbial data set in a single day. This will be achievable only through the coordinated efforts of an Ocean Sampling Day Consortium, supportive partnerships and networks between sites. This commentary outlines the establishment, function and aims of the Consortium and describes our vision for a sustainable study of marine microbial communities and their embedded functional traits

The Ocean Sampling Day Consortium

Ocean Sampling Day was initiated by the EU-funded Micro B3 (Marine Microbial Biodiversity, Bioinformatics, Biotechnology) project to obtain a snapshot of the marine microbial biodiversity and function of the world’s oceans. It is a simultaneous global mega-sequencing campaign aiming to generate the largest standardized microbial data set in a single day. This will be achievable only through the coordinated efforts of an Ocean Sampling Day Consortium, supportive partnerships and networks between sites. This commentary outlines the establishment, function and aims of the Consortium and describes our vision for a sustainable study of marine microbial communities and their embedded functional traits

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Etre partisan. Loyauté, prise de parole et défection dans les partis politiques et les mouvements sociaux

La disparition des partis politiques a souvent été annoncée. Pourtant les « gouvernés du 21ème siècle » demeurent sous le pouvoir de gouvernants sélectionnés par les partis. La section thématique s’intéresse dès lors au gouvernement partisan, et plus précisément au gouvernement dans les partis. Elle part du constat que les partis sont des miniature political systems (Eldersveld 1964 :1). Ils ne peuvent être considérés comme des acteurs unitaires et sont composés de différentes strates ou groupes. L’objectif de cette section est d’examiner les relations que chaque entité (strate, facette, faction, etc.) entretient avec l’organisation à laquelle elle appartient (Katz & Mair 1993, Sartori 2005, Boucek 2009). Pour aborder cette question, la réflexion s’organise autour de la trilogie proposée par Hirschman (1970) :défection, prise de parole et loyauté. En effet, les relations que les différents groupes entretiennent avec l’organisation peuvent être saisies à l’aide de ces trois catégories. Dès lors, la section thématique encourage les propositions s’articulant autour de trois axes, chacun dédié à un aspect de la trilogie. Un premier axe porte sur la question de la loyauté au sein des partis politiques. Parent pauvre de la trilogie d’Hirschman (Lehingue 2001), le concept mérite une attention particulière. Ambigü, le concept comporte plusieurs niveaux :loyalisme inconscient ou inconditionnel, résignés ou fidèles par conviction (Bajoit 1988). En veillant à demeurer attentif à cette complexité, plusieurs questions se posent. Comment et par quels instruments la loyauté se construit-elle au sein des partis ?Quel est le rôle joué par les élites dans la formation de cette loyauté ?Quels facteurs favorisent la loyauté et l’unité des partis ?Outre l’étude de ses conditions, il importe d’analyser la manière dont la loyauté s’exprime au sein des partis. Quel type d’actions ou de participation interne génère-t-elle ?Vers qui s’exprime-t-elle ?Enfin, les mécanismes de loyauté au sein des organisations ne sont sans doute pas sans conséquences sur la manière dont ces organisations sont perçues par l’extérieur. Quelles en sont les conséquences, tant pour l’organisation que pour l’action du parti dans la sphère publique ?Le deuxième axe est consacré à la question de la prise de parole, chaînon manquant dans l’étude des partis. En effet, lorsque la base des partis est étudiée, elle l’est essentiellement à l’aide des théories issues du champ de la participation politique. Dès lors, très peu d’études sont consacrées à la situation des adhérents une fois que la démarche d’adhésion est opérée. Les recherches existantes laissent très peu de place à la question du doute et de la critique. Dès lors, cette session s’intéressera aux groupes porteurs de critique aussi bien externe qu’interne, à la façon dont celle-ci s’organise (constitution de factions formelles ou informelles, motions, expression de la critique à l’occasion d’élections interne, etc.), mais aussi aux conséquences – notamment électorales – de la contestation interne. Enfin, la question du désengagement a récemment été investie (Fillieule 2005), mais les travaux ne concernent que marginalement le désengagement partisan. La compréhension du phénomène de la désaffiliation et de la défection est primordiale pour décrypter les dynamiques à l’œuvre en termes de participation politique. L’exit peut être volontaire ou involontaire, individuel ou collectif, silencieux ou bruyant, passif ou actif (Fillieule 2005). Dès lors, il convient de soulever des questions méthodologiques liées à l’étude de cette catégorie particulière de citoyens, de s’intéresser aux formes et aux degrés du désengagement, mais aussi de s’interroger sur les processus menant un individu à renoncer à son engagement politique formel (Taylor 2005).info:eu-repo/semantics/nonPublishe

Different exposure windows to low doses of genistein and/or vinclozolin result in contrasted disorders of testis function and gene expression of exposed rats and their unexposed progeny

International audienceLiving species including humans are continuously exposed to low levels of a myriad of endocrine active compounds that may affect their reproductive function. In contrast, experimental designs scrutinizing this question mostly consider the gestational/lactational period, select high unrealistic doses and, have rarely investigated the possible reproductive consequences in the progeny. The present study aimed at assessing comparatively a set of male reproductive endpoints according to exposure windows, gestational/lactational versus pre-pubertal to adulthood, using low doses of endocrine active substances in male rats as well as their unexposed male progeny. Animals were orally exposed to 1 mg/kg bw/d of genistein and/or vinclozolin, from conception to weaning or from prepuberty to young adulthood. A number of reproductive endpoints were assessed as well as testicular mRNA expression profiles, in the exposed rats and their unexposed progeny. Overall, the low dosage used only affected weakly most of classical reproductive endpoints. However, the gestational/lactational exposure to vinclozolin alone or combined to genistein significantly delayed the puberty onset. Contrasting with the gestational/lactational exposure, a decreased sperm production was found in the animals exposed to genistein and vinclozolin from the pre-pubertal period but also in their progeny for vinclozolin and the mixture. The expression level of several genes involved in meiosis, apoptosis and steroidogenesis was also affected differentially as a function of the exposure window in both exposed rats and unexposed offspring. We also provide further evidence that doses of endocrine active substances relevant with human exposure may affect the male reproductive phenotype and testicular transcriptome in the exposed generation as well as in the indirectly exposed offspring