A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

The two redox states of the human NEET proteins’ [2Fe–2S] clusters

The NEET proteins constitute a unique class of [2Fe–2S] proteins. The metal ions bind to three cysteines and one histidine. The proteins’ clusters exist in two redox states; the oxidized protein (containing two FeIII ions) can transfer the cluster to apo-acceptor protein(s), while the reduced form (containing one ferrous ion) remains bound to the protein frame. Here, we perform in silico and in vitro studies on human NEET proteins in both reduced and oxidized forms. Quantum chemical calculations on all available human NEET proteins structures suggest that reducing the cluster weakens the Fe–NHis and Fe–SCys bonds, similar to what is seen in other Fe–S proteins (e.g., ferredoxin and Rieske protein). We further show that the extra electron in the [2Fe–2S]+ clusters of one of the NEET proteins (mNT) is localized on the His-bound iron ion, consistently with our previous spectroscopic studies. Kinetic measurements demonstrate that the mNT [2Fe–2S]+ is released only by an increase in temperature. Thus, the reduced state of human NEET proteins [2Fe–2S] cluster is kinetically inert. This previously unrecognized kinetic inertness of the reduced state, along with the reactivity of the oxidized state, is unique across all [2Fe–2S] proteins. Finally, using a coevolutionary analysis, along with molecular dynamics simulations, we provide insight on the observed allostery between the loop L2 and the cluster region. Specifically, we show that W75, R76, K78, K79, F82 and G85 in the latter region share similar allosteric characteristics in both redox states

Murine cytomegalovirus infection exacerbates complex IV deficiency in a model of mitochondrial disease

The influence of environmental insults on the onset and progression of mitochondrial diseases is unknown. To evaluate the effects of infection on mitochondrial disease we used a mouse model of Leigh Syndrome, where a missense mutation in the Taco1 gene results in the loss of the translation activator of cytochrome c oxidase subunit I (TACO1) protein. The mutation leads to an isolated complex IV deficiency that mimics the disease pathology observed in human patients with TACO1 mutations. We infected Taco1 mutant and wild-type mice with a murine cytomegalovirus and show that a common viral infection exacerbates the complex IV deficiency in a tissue-specific manner. We identified changes in neuromuscular morphology and tissue-specific regulation of the mammalian target of rapamycin pathway in response to viral infection. Taken together, we report for the first time that a common stress condition, such as viral infection, can exacerbate mitochondrial dysfunction in a genetic model of mitochondrial disease

PTCD1 Is Required for 16S rRNA Maturation Complex Stability and Mitochondrial Ribosome Assembly

Summary: The regulation of mitochondrial RNA life cycles and their roles in ribosome biogenesis and energy metabolism are not fully understood. We used CRISPR/Cas9 to generate heart- and skeletal-muscle-specific knockout mice of the pentatricopeptide repeat domain protein 1, PTCD1, and show that its loss leads to severe cardiomyopathy and premature death. Our detailed transcriptome-wide and functional analyses of these mice enabled us to identify the molecular role of PTCD1 as a 16S rRNA-binding protein essential for its stability, pseudouridylation, and correct biogenesis of the mitochondrial large ribosomal subunit. We show that impaired mitoribosome biogenesis can have retrograde signaling effects on nuclear gene expression through the transcriptional activation of the mTOR pathway and upregulation of cytoplasmic protein synthesis and pro-survival factors in the absence of mitochondrial translation. Taken together, our data show that impaired assembly of the mitoribosome exerts its consequences via differential regulation of mitochondrial and cytoplasmic protein synthesis. : Perks et al. engineered intron-exon boundaries using CRISPR/Cas9 to conditionally knock out Ptcd1 in mice. The RNA-binding protein PTCD1 is essential for heart function and regulates the stability and maturation of the 16S rRNA. PTCD1 is required for mitoribosome biogenesis, mitochondrial function, and coordinated nuclear transcription. Keywords: RNA, cardiomyopathy, regulatory RNAs, RNA-seq, mitochondrial ribosome, RNA-binding proteins, mitochondria, mitochondrial gene expression, ribosome biogenesi

Euclid preparation: TBD. The pre-launch Science Ground Segment simulation framework

International audienceThe European Space Agency's Euclid mission is one of the upcoming generation of large-scale cosmology surveys, which will map the large-scale structure in the Universe with unprecedented precision. The development and validation of the SGS pipeline requires state-of-the-art simulations with a high level of complexity and accuracy that include subtle instrumental features not accounted for previously as well as faster algorithms for the large-scale production of the expected Euclid data products. In this paper, we present the Euclid SGS simulation framework as applied in a large-scale end-to-end simulation exercise named Science Challenge 8. Our simulation pipeline enables the swift production of detailed image simulations for the construction and validation of the Euclid mission during its qualification phase and will serve as a reference throughout operations. Our end-to-end simulation framework starts with the production of a large cosmological N-body & mock galaxy catalogue simulation. We perform a selection of galaxies down to I_E=26 and 28 mag, respectively, for a Euclid Wide Survey spanning 165 deg^2 and a 1 deg^2 Euclid Deep Survey. We build realistic stellar density catalogues containing Milky Way-like stars down to H<26. Using the latest instrumental models for both the Euclid instruments and spacecraft as well as Euclid-like observing sequences, we emulate with high fidelity Euclid satellite imaging throughout the mission's lifetime. We present the SC8 data set consisting of overlapping visible and near-infrared Euclid Wide Survey and Euclid Deep Survey imaging and low-resolution spectroscopy along with ground-based. This extensive data set enables end-to-end testing of the entire ground segment data reduction and science analysis pipeline as well as the Euclid mission infrastructure, paving the way to future scientific and technical developments and enhancements

Euclid preparation: TBD. The pre-launch Science Ground Segment simulation framework

International audienceThe European Space Agency's Euclid mission is one of the upcoming generation of large-scale cosmology surveys, which will map the large-scale structure in the Universe with unprecedented precision. The development and validation of the SGS pipeline requires state-of-the-art simulations with a high level of complexity and accuracy that include subtle instrumental features not accounted for previously as well as faster algorithms for the large-scale production of the expected Euclid data products. In this paper, we present the Euclid SGS simulation framework as applied in a large-scale end-to-end simulation exercise named Science Challenge 8. Our simulation pipeline enables the swift production of detailed image simulations for the construction and validation of the Euclid mission during its qualification phase and will serve as a reference throughout operations. Our end-to-end simulation framework starts with the production of a large cosmological N-body & mock galaxy catalogue simulation. We perform a selection of galaxies down to I_E=26 and 28 mag, respectively, for a Euclid Wide Survey spanning 165 deg^2 and a 1 deg^2 Euclid Deep Survey. We build realistic stellar density catalogues containing Milky Way-like stars down to H<26. Using the latest instrumental models for both the Euclid instruments and spacecraft as well as Euclid-like observing sequences, we emulate with high fidelity Euclid satellite imaging throughout the mission's lifetime. We present the SC8 data set consisting of overlapping visible and near-infrared Euclid Wide Survey and Euclid Deep Survey imaging and low-resolution spectroscopy along with ground-based. This extensive data set enables end-to-end testing of the entire ground segment data reduction and science analysis pipeline as well as the Euclid mission infrastructure, paving the way to future scientific and technical developments and enhancements

Euclid preparation: TBD. The pre-launch Science Ground Segment simulation framework

International audienceThe European Space Agency's Euclid mission is one of the upcoming generation of large-scale cosmology surveys, which will map the large-scale structure in the Universe with unprecedented precision. The development and validation of the SGS pipeline requires state-of-the-art simulations with a high level of complexity and accuracy that include subtle instrumental features not accounted for previously as well as faster algorithms for the large-scale production of the expected Euclid data products. In this paper, we present the Euclid SGS simulation framework as applied in a large-scale end-to-end simulation exercise named Science Challenge 8. Our simulation pipeline enables the swift production of detailed image simulations for the construction and validation of the Euclid mission during its qualification phase and will serve as a reference throughout operations. Our end-to-end simulation framework starts with the production of a large cosmological N-body & mock galaxy catalogue simulation. We perform a selection of galaxies down to I_E=26 and 28 mag, respectively, for a Euclid Wide Survey spanning 165 deg^2 and a 1 deg^2 Euclid Deep Survey. We build realistic stellar density catalogues containing Milky Way-like stars down to H<26. Using the latest instrumental models for both the Euclid instruments and spacecraft as well as Euclid-like observing sequences, we emulate with high fidelity Euclid satellite imaging throughout the mission's lifetime. We present the SC8 data set consisting of overlapping visible and near-infrared Euclid Wide Survey and Euclid Deep Survey imaging and low-resolution spectroscopy along with ground-based. This extensive data set enables end-to-end testing of the entire ground segment data reduction and science analysis pipeline as well as the Euclid mission infrastructure, paving the way to future scientific and technical developments and enhancements

Euclid preparation: TBD. The pre-launch Science Ground Segment simulation framework

International audienceThe European Space Agency's Euclid mission is one of the upcoming generation of large-scale cosmology surveys, which will map the large-scale structure in the Universe with unprecedented precision. The development and validation of the SGS pipeline requires state-of-the-art simulations with a high level of complexity and accuracy that include subtle instrumental features not accounted for previously as well as faster algorithms for the large-scale production of the expected Euclid data products. In this paper, we present the Euclid SGS simulation framework as applied in a large-scale end-to-end simulation exercise named Science Challenge 8. Our simulation pipeline enables the swift production of detailed image simulations for the construction and validation of the Euclid mission during its qualification phase and will serve as a reference throughout operations. Our end-to-end simulation framework starts with the production of a large cosmological N-body & mock galaxy catalogue simulation. We perform a selection of galaxies down to I_E=26 and 28 mag, respectively, for a Euclid Wide Survey spanning 165 deg^2 and a 1 deg^2 Euclid Deep Survey. We build realistic stellar density catalogues containing Milky Way-like stars down to H<26. Using the latest instrumental models for both the Euclid instruments and spacecraft as well as Euclid-like observing sequences, we emulate with high fidelity Euclid satellite imaging throughout the mission's lifetime. We present the SC8 data set consisting of overlapping visible and near-infrared Euclid Wide Survey and Euclid Deep Survey imaging and low-resolution spectroscopy along with ground-based. This extensive data set enables end-to-end testing of the entire ground segment data reduction and science analysis pipeline as well as the Euclid mission infrastructure, paving the way to future scientific and technical developments and enhancements