BCL2L10 is a predictive factor for resistance to Azacitidine in MDS and AML patients

Azacitidine is the leading compound to treat patients suffering myelodysplastic syndrome (MDS) or AML with less than 30% of blasts, but a majority of patients is primary refractory or rapidly relapses under treatment. These patients have a drastically reduced life expectancy as compared to sensitive patients. Therefore identifying predictive factors for AZA resistance is of great interest to propose alternative therapeutic strategies for non-responsive patients. We generated AZA-resistant myeloid cell line (SKM1-R) that exhibited increased expression of BCL2L10 an anti-apoptotic Bcl-2 family member. Importantly, BCL2L10 knockdown sensitized SKM1-R cells to AZA effect suggesting that increased BCL2L10 expression is linked to AZA resistance in SKM1-R. We next established in 77 MDS patients that resistance to AZA is significantly correlated with the percentage of MDS or AML cells expressing BCL2L10. In addition, we showed that the proportion of BCL2L10 positive bone marrow cells can predict overall survival in MDS or AML patients. We propose a convenient assay in which the percentage of BCL2L10 expressing cells as assessed by flow cytometry is predictive of whether or not a patient will become resistant to AZA. Therefore, systematic determination of BCL2L10 expression could be of great interest in newly diagnosed and AZA-treated MDS patients

Exploring nucleo-cytoplasmic large DNA viruses in Tara Oceans microbial metagenomes

Nucleo-cytoplasmic large DNA viruses (NCLDVs) constitute a group of eukaryotic viruses that can have crucial ecological roles in the sea by accelerating the turnover of their unicellular hosts or by causing diseases in animals. To better characterize the diversity, abundance and biogeography of marine NCLDVs, we analyzed 17 metagenomes derived from microbial samples (0.2–1.6 μm size range) collected during the Tara Oceans Expedition. The sample set includes ecosystems under-represented in previous studies, such as the Arabian Sea oxygen minimum zone (OMZ) and Indian Ocean lagoons. By combining computationally derived relative abundance and direct prokaryote cell counts, the abundance of NCLDVs was found to be in the order of 104–105 genomes ml−1 for the samples from the photic zone and 102–103 genomes ml−1 for the OMZ. The Megaviridae and Phycodnaviridae dominated the NCLDV populations in the metagenomes, although most of the reads classified in these families showed large divergence from known viral genomes. Our taxon co-occurrence analysis revealed a potential association between viruses of the Megaviridae family and eukaryotes related to oomycetes. In support of this predicted association, we identified six cases of lateral gene transfer between Megaviridae and oomycetes. Our results suggest that marine NCLDVs probably outnumber eukaryotic organisms in the photic layer (per given water mass) and that metagenomic sequence analyses promise to shed new light on the biodiversity of marine viruses and their interactions with potential hosts

A Holistic Approach to Marine Eco-Systems Biology

With biology becoming quantitative, systems-level studies can now be performed at spatial scales ranging from molecules to ecosystems. Biological data generated consistently across scales can be integrated with physico-chemical contextual data for a truly holistic approach, with a profound impact on our understanding of life [1]–[5]. Marine ecosystems are crucial in the regulation of Earth's biogeochemical cycles and climate [6],[7]. Yet their organization, evolution, and dynamics remain poorly understood [8],[9]. The Tara Oceans project was launched in September 2009 for a 3-year study of the global ocean ecosystem aboard the ship Tara. A unique sampling programme encompassing optical and genomic methods to describe viruses, bacteria, archaea, protists, and metazoans in their physico-chemical environment has been implemented. Starting as a grassroots initiative of a few scientists, the project has grown into a global consortium of over 100 specialists from diverse disciplines, including oceanography, microbial ecology, genomics, molecular, cellular, and systems biology, taxonomy, bioinformatics, data management, and ecosystem modeling. This multidisciplinary community aims to generate systematic, open access datasets usable for probing the morphological and molecular makeup, diversity, evolution, ecology, and global impacts of plankton on the Earth system

A Reply to My Critics: The Critical Spirit of Bourdieusian Language

Drawing on my article “Bourdieusian reflections on language: Unavoidable conditions of the real speech situation”, this paper provides a detailed response to the above commentaries by Lisa Adkins, Bridget Fowler, Michael Grenfell, David Inglis, Hans-Herbert Kögler, Steph Lawler, William Outhwaite, Derek Robbins and Bryan S. Turner. The main purpose of this “Reply to my critics” is to reflect upon the most important issues raised by these commentators and thereby contribute to a more nuanced understanding of key questions arising from Bourdieu’s analysis of language

Miser sur la transdisciplinarité pour cerner les enjeux éthiques et sociaux de l’IA : développement d’un cours optionnel destiné à tous les étudiants

Le projet consiste en la création d’un cours complémentaire au cégep ou d’un cours optionnel à l’université portant sur l’intelligence artificielle (IA) et ses enjeux éthiques ou sociaux. Il pourra être suivi par des étudiants inscrits dans n’importe quel programme d’études. Dans ce cours de nature transdisciplinaire, l’étudiant sera formé sur l’intelligence artificielle, son potentiel et ses limites. À la fin de sa formation, l’étudiant sera en mesure de comprendre les mécanismes utilisés par l’IA, ses biais et les enjeux éthiques et sociaux qu’elle soulève. Ce projet est porté par le cégep de Saint-Laurent, en collaboration avec l’Université de Montréal et le Centre Artenso.The project consists of the creation of a complementary course at CEGEP or an optional course at university dealing with artificial intelligence (AI) and its ethical or social issues. It can be followed by students enrolled in any study program. In this transdisciplinary course, the student will be trained on artificial intelligence, its potential and its limits. At the end of his training, the student will be able to understand the mechanisms used by AI, its biases and the ethical and social issues it raises. This project is led by the Cégep de Saint-Laurent, in collaboration with the University of Montreal and the Artenso Center

Metal Dependence on the Bidirectionality and Reversibility of the Singlet Energy Transfer in Artificial Special Pair-Containing Dyads

The demetalation of a precursor dyad, 3, built upon a zinc(II)-containing artificial special pair and free-base antenna, leads to a new dyad, 4, for singlet energy transfer composed of cofacial free-base porphyrins (acceptor), [Fb] bridged by a 1,4-C H group to a free-base antenna (donor), [Fb]. This dyad exhibits the general structure [M] -C H -[Fb], where [M] = [Fb] , and completes a series reported earlier, where [M] = [Mg] (2) and [Zn] (3). The latter dyads exhibit a bidirectional energy-transfer process at 298 K for 2 and at 77 K for 3. Interestingly, a very scarce case of cycling process is observed for the zinc-containing dyad at 298 K. The newly reported compound 4 exhibits a quasi unidirectional process [Fb]*→[Fb] (major, k = 2 × 10 s at 298 K), where the remaining is [Fb] *→[Fb] (minor, k = 8 × 10 s at 298 K), thus completing all possibilities. The results are analyzed in terms of molecular orbital couplings (density functional theory computations), Förster resonance energy transfer parameters, and temperature dependence of the decay traces. This study brings major insights about artificial special pair-containing dyads and clearly contributes to a better understanding of the communication between the two main components of our models and those already described in the literature

Metal Dependence on the Bidirectionality and Reversibility of the Singlet Energy Transfer in Artificial Special Pair-Containing Dyads

International audienceThe demetalation of a precursor dyad, 3, built upon a zinc(II)-containing artificial special pair and free-base antenna, leads to a new dyad, 4, for singlet energy transfer composed of cofacial free-base porphyrins (acceptor), [Fb](2) bridged by a 1,4-C6H4 group to a free-base antenna (donor), [Fb]. This dyad exhibits the general structure [M](2)-C6H4-[Fb], where [M](2) = [Fh](2), and completes a series reported earlier, where [M](2) = [Mg](2) (2) and [Zn](2) (3). The latter dyads exhibit a bidirectional energy-transfer process at 298 K for 2 and at 77 K for 3. Interestingly, a very scarce case of cycling process is observed for the zinc-containing dyad at 298 K. The newly reported compound 4 exhibits a quasi unidirectional process [Fb]*->[Fb](2), (major, k(ET) = 2 X 10(11) s(-1) at 298 K), where the remaining is [Fb](2)*->[Fb] (minor, k(ET) = 8 X 10(9) s(-1) at 298 K), thus completing all possibilities. The results are analyzed in terms of molecular orbital couplings (density functional theory computations), Forster resonance energy transfer parameters, and temperature dependence of the decay traces. This study brings major insights about artificial special pair-containing dyads and clearly contributes to a better understanding of the communication between the two main components of our models and those already described in the literature

Antenna effects in truxene-bridged BODIPY triarylzinc(II)porphyrin dyads: evidence for a dual Dexter-Forster mechanism

The antenna process from an energy donor (BODIPY; 4',4'-difluoro-1',3',5',7'-tetramethyl-4'-bora- 3a',4a'-diaza-s-indacene) in its singlet state to two acceptors (two zinc(II) 5,15-p-tolyl-10- phenylporphyrin) bridged by a central truxene residue (5',5'',10',10'',15',15''-hexabutyltruxene), 5, has been analysed by means of comparison of the energy transfer rates with those of a structurally similar beta-substituted BODIPY-(zinc(II) 5,10,15-p-tolyl-porphyrin), 6, where no conjugation is present between the donor and the two acceptors using the Forster resonance energy transfer (FRET) approximation. It is estimated that the energy transfer in 5 operates mostly via a Dexter mechanism (>99%), and the remaining proceeds via a Forster mechanism (<1%). This information is useful for the design of future molecular devices aimed at harvesting light