13 research outputs found

    New desulfured troglitazone derivatives: Improved synthesis and biological evaluation

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    International audienceBreast cancer is a major medical threat which cannot be sufficiently addressed by current therapies because of spontaneous or acquired treatment resistance. Besides, triple-negative breast cancer (TNBC) tumors do not respond to targeted therapies, thus new therapeutic strategies are needed. In this context, we designed and prepared new desulfured troglitazone (TGZ)-derived molecules and evaluated them in vitro for their anti-proliferative activity, with a special focus on triple-negative breast cancer cell lines. Optimization of the synthetic strategies and deracemization of the lead compound were performed to give highly active compound 10 with low-micromolar potency. Further studies revealed that this compound triggers apoptosis rather than cell cycle arrest as observed with TGZ

    Phylogenetic Diversity of Lhr Proteins and Biochemical Activities of the Thermococcales aLhr2 DNA/RNA Helicase

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    International audienceHelicase proteins are known to use the energy of ATP to unwind nucleic acids and to remodel protein-nucleic acid complexes. They are involved in almost every aspect of DNA and RNA metabolisms and participate in numerous repair mechanisms that maintain cellular integrity. The archaeal Lhr-type proteins are SF2 helicases that are mostly uncharacterized. They have been proposed to be DNA helicases that act in DNA recombination and repair processes in Sulfolobales and Methanothermobacter. In Thermococcales, a protein annotated as an Lhr2 protein was found in the network of proteins involved in RNA metabolism. To investigate this, we performed in-depth phylogenomic analyses to report the classification and taxonomic distribution of Lhr-type proteins in Archaea, and to better understand their relationship with bacterial Lhr. Furthermore, with the goal of envisioning the role(s) of aLhr2 in Thermococcales cells, we deciphered the enzymatic activities of aLhr2 from Thermococcus barophilus (Tbar). We showed that Tbar-aLhr2 is a DNA/RNA helicase with a significant annealing activity that is involved in processes dependent on DNA and RNA transactions

    RNA processing machineries in Archaea: the 5′-3′ exoribonuclease aRNase J of the β-CASP family is engaged specifically with the helicase ASH-Ski2 and the 3′-5′ exoribonucleolytic RNA exosome machinery

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    A network of RNA helicases, endoribonucleases and exoribonucleases regulates the quantity and quality of cellular RNAs. To date, mechanistic studies focussed on bacterial and eukaryal systems due to the challenge of identifying the main drivers of RNA decay and processing in Archaea. Here, our data support that aRNase J, a 5′-3′ exoribonuclease of the β-CASP family conserved in Euryarchaeota, engages specifically with a Ski2-like helicase and the RNA exosome to potentially exert control over RNA surveillance, at the vicinity of the ribosome. Proteomic landscapes and direct protein–protein interaction analyses, strengthened by comprehensive phylogenomic studies demonstrated that aRNase J interplay with ASH-Ski2 and a cap exosome subunit. Finally, Thermococcus barophilus whole-cell extract fractionation experiments provide evidences that an aRNase J/ASH-Ski2 complex might exist in vivo and hint at an association of aRNase J with the ribosome that is emphasised in absence of ASH-Ski2. Whilst aRNase J homologues are found among bacteria, the RNA exosome and the Ski2-like RNA helicase have eukaryotic homologues, underlining the mosaic aspect of archaeal RNA machines. Altogether, these results suggest a fundamental role of β-CASP RNase/helicase complex in archaeal RNA metabolism

    A data science platform to enable time-domain astronomy

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    SkyPortal is an open-source platform designed to efficiently discover interesting transients, manage follow-up, perform characterization, and visualize the results, all in one application. By enabling fast access to archival and catalog data, cross-matching heterogeneous data streams, and the triggering and monitoring of on-demand observations for further characterization, SkyPortal has been operating at scale for > 2 yr for the Zwicky Transient Facility Phase II community, with hundreds of users, containing tens of millions of time-domain sources, interacting with dozens of telescopes, and enabling community reporting. While SkyPortal emphasizes rich user experiences (UX) across common frontend workflows, recognizing that scientific inquiry is increasingly performed programmatically, SkyPortal also surfaces an extensive and well-documented API system. From backend and frontend software to data science analysis tools and visualization frameworks, the SkyPortal design emphasizes the re-use and leveraging of best-in-class approaches, with a strong extensibility ethos. For instance, SkyPortal now leverages ChatGPT large-language models (LLMs) to automatically generate and surface source-level human-readable summaries. With the imminent re-start of the next-generation of gravitational wave detectors, SkyPortal now also includes dedicated multi-messenger features addressing the requirements of rapid multi-messenger follow-up: multi-telescope management, team/group organizing interfaces, and cross-matching of multi-messenger data streams with time-domain optical surveys, with interfaces sufficiently intuitive for the newcomers to the field. (abridged

    A data science platform to enable time-domain astronomy

    No full text
    International audienceSkyPortal is an open-source platform designed to efficiently discover interesting transients, manage follow-up, perform characterization, and visualize the results, all in one application. By enabling fast access to archival and catalog data, cross-matching heterogeneous data streams, and the triggering and monitoring of on-demand observations for further characterization, SkyPortal has been operating at scale for > 2 yr for the Zwicky Transient Facility Phase II community, with hundreds of users, containing tens of millions of time-domain sources, interacting with dozens of telescopes, and enabling community reporting. While SkyPortal emphasizes rich user experiences (UX) across common frontend workflows, recognizing that scientific inquiry is increasingly performed programmatically, SkyPortal also surfaces an extensive and well-documented API system. From backend and frontend software to data science analysis tools and visualization frameworks, the SkyPortal design emphasizes the re-use and leveraging of best-in-class approaches, with a strong extensibility ethos. For instance, SkyPortal now leverages ChatGPT large-language models (LLMs) to automatically generate and surface source-level human-readable summaries. With the imminent re-start of the next-generation of gravitational wave detectors, SkyPortal now also includes dedicated multi-messenger features addressing the requirements of rapid multi-messenger follow-up: multi-telescope management, team/group organizing interfaces, and cross-matching of multi-messenger data streams with time-domain optical surveys, with interfaces sufficiently intuitive for the newcomers to the field. (abridged
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