Detection chain and electronic readout of the QUBIC instrument

The Q and U Bolometric Interferometer for Cosmology (QUBIC) Technical Demonstrator (TD) aiming to shows the feasibility of the combination of interferometry and bolometric detection. The electronic readout system is based on an array of 128 NbSi Transition Edge Sensors cooled at 350mK readout with 128 SQUIDs at 1K controlled and amplified by an Application Specific Integrated Circuit at 40K. This readout design allows a 128:1 Time Domain Multiplexing. We report the design and the performance of the detection chain in this paper. The technological demonstrator unwent a campaign of test in the lab. Evaluation of the QUBIC bolometers and readout electronics includes the measurement of I-V curves, time constant and the Noise Equivalent Power. Currently the mean Noise Equivalent Power is ~ 2 x 10⁻¹⁶ W/√Hz

Detection chain and electronic readout of the QUBIC instrument

The Q and U Bolometric Interferometer for Cosmology (QUBIC) Technical Demonstrator (TD) aiming to shows the feasibility of the combination of interferometry and bolometric detection. The electronic readout system is based on an array of 128 NbSi Transition Edge Sensors cooled at 350mK readout with 128 SQUIDs at 1K controlled and amplified by an Application Specific Integrated Circuit at 40K. This readout design allows a 128:1 Time Domain Multiplexing. We report the design and the performance of the detection chain in this paper. The technological demonstrator unwent a campaign of test in the lab. Evaluation of the QUBIC bolometers and readout electronics includes the measurement of I-V curves, time constant and the Noise Equivalent Power. Currently the mean Noise Equivalent Power is ~ 2 x 10⁻¹⁶ W/√Hz

Caractérisation des b-(1->3)-glucane synthases de Saprolegnia monoica et de leurs produits de synthèse

GRENOBLE1-BU Sciences (384212103) / SudocSudocFranceF

Three conserved histidyl residues contribute to mitochondrial iron transport through mitoferrins.

International audience: Iron is an essential element for almost all organisms. In eukaryotes, it is mainly used in mitochondria for the biosynthesis of iron-sulphur clusters and heme-group maturation. Iron is delivered into the mitochondrion by mitoferrins, members of the mitochondrial carrier family (MCF), through an unknown mechanism. In this article, the yeast homologs of these proteins, Mrs3p and Mrs4p, were studied by inserting them into liposomes. In this context, they could transport iron (II) across the proteoliposomes membrane, as revealed using the iron-chelator bathophenanthroline. A series of amino acid-modifying reagents were screened for their effects on Mrs3p-mediated iron transport. Results suggested that carboxylic and imidazole groups are essential for iron transport. This was confirmed by in vivo complementation assays, which demonstrated that three highly conserved His residues are important for Mrs3p function. These His residues are not conserved in other MCF members, thus they are likely to play a specific role in iron transport. A model describing how these residues help iron to transit smoothly across the carrier cavity is proposed and compared to structural and biochemical data available for other carriers in this family

A hybrid model to study pathological mutations of the human ADP/ATP carriers

International audienceThe adenine nucleotide carrier (Ancp) plays an essential role in the metabolism of cellular energy by catalyzing the transport of ADP and ATP across the inner mitochondrial membrane. Previous reports have indicated that mutations in the HANC1 gene, encoding the muscle isoform of human Ancp (HAnc1p), are directly involved in several diseases, including autosomal dominant progressive external ophthalmoplegia and cardiomyopathies. In this work, we studied three pathogenic HANC1 mutations at the biochemical level. To do so, we expressed the DdANCA gene, encoding the unique Ancp carrier of Dictyostelium discoideum (DdAncAp), in a yeast strain lacking all endogenous ANC genes. Our results indicate that DdAncAp is a good model for the human protein. It allows the carrier to be studied in yeast, and provides information on how the HANC1 mutations impair ADP/ATP transport in humans. A94D, A126D and V291M mutations, corresponding to A90D, A123D and V289M in HAnc1p, respectively, did not affect levels of DdAncAp in yeast mitochondria. However, while the wild-type DdAncAp fully restored growth of the ANC-null yeast strain on a non-fermentable carbon source, the carriers encompassing either the A94D or the A126D mutation failed to complement the null strain. The effect of the V291M mutation was not as pronounced, but led to impairment mainly of the nucleotide translocation process per se. These findings provide new insights into the mechanisms responsible for the diseases induced by HAnc1p mutations

Evolution of Penicillin-Binding Protein 2 Concentration and Cell Shape during a Long-Term Experiment with Escherichia coli▿

Peptidoglycan is the major component of the bacterial cell wall and is involved in osmotic protection and in determining cell shape. Cell shape potentially influences many processes, including nutrient uptake as well as cell survival and growth. Peptidoglycan is a dynamic structure that changes during the growth cycle. Penicillin-binding proteins (PBPs) catalyze the final stages of peptidoglycan synthesis. Although PBPs are biochemically and physiologically well characterized, their broader effects, especially their effects on organismal fitness, are not well understood. In a long-term experiment, 12 populations of Escherichia coli having a common ancestor were allowed to evolve for more than 40,000 generations in a defined environment. We previously identified mutations in the pbpA operon in one-half of these populations; this operon encodes PBP2 and RodA proteins that are involved in cell wall elongation. In this study, we characterized the effects of two of these mutations on competitive fitness and other phenotypes. By constructing and performing competition experiments with strains that are isogenic except for the pbpA alleles, we showed that both mutations that evolved were beneficial in the environment used for the long-term experiment and that these mutations caused parallel phenotypic changes. In particular, they reduced the cellular concentration of PBP2, thereby generating spherical cells with an increased volume. In contrast to their fitness-enhancing effect in the environment where they evolved, both mutations decreased cellular resistance to osmotic stress. Moreover, one mutation reduced fitness during prolonged stationary phase. Therefore, alteration of the PBP2 concentration contributed to physiological trade-offs and ecological specialization during experimental evolution

Nicotine-induced cellular stresses and autophagy in human cancer colon cells: A supportive effect on cell homeostasis via up-regulation of Cox-2 and PGE2 production

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Yeast ADP/ATP carrier isoform 2: conformational dynamics and role of the RRRMMM signature sequence methionines

International audienceThe mitochondrial ADP/ATP carrier, or Ancp, is a member of the mitochondrial carrier family responsible for exchanging ADP and ATP across the mitochondrial inner membrane. ADP/ATP transport involves Ancp switching between two conformational states. These can be analyzed using specific inhibitors, carboxyatractyloside (CATR) and bongkrekic acid (BA). The high resolution three-dimensional structure of bovine Anc1p (bAnc1p), as a CATR-carrier complex, has been solved. However, because the structure of the BA-carrier complex has not yet been determined, the detailed mechanism of transport remains unknown. Recently, sample processing for hydrogen/deuterium exchange experiments coupled to mass spectrometry was improved, providing novel insights into bAnc1p conformational transitions due to inhibitor binding. In this work we performed both hydrogen/deuterium exchange-mass spectrometry experiments and genetic manipulations. Because these are very difficult to apply with bovine Anc1p, we used Saccharomyces cerevisiae Anc isoform 2 (ScAnc2p). Significant differences in solvent accessibility were observed throughout the amino acid sequence for ScAnc2p complexed to either CATR or BA. Interestingly, in detergent solution, the conformational dynamics of ScAnc2p were dissimilar to those of bAnc1p, in particular for the upper half of the cavity, toward the intermembrane space, and the m2 loop, which is thought to be easily accessible to the solvent from the matrix in bAnc1p. Our study then focused on the methionyl residues of the Ancp signature sequence, RRRMMM. All our results indicate that the methionine cluster is involved in the ADP/ATP transport mechanism and confirm that the Ancp cavity is a highly dynamic structure

Advances in bacterial pathways for the biosynthesis of ubiquinone

International audienceUbiquinone is an important component of the electron transfer chains in proteobacteria and eukaryotes. The biosynthesis of ubiquinone requires multiple steps, most of which are common to bacteria and eukaryotes. Whereas the enzymes of the mitochondrial pathway that produces ubiquinone are highly similar across eu-karyotes, recent results point to a rather high diversity of pathways in bacteria. This review focuses on ubi-quinone in bacteria, highlighting newly discovered functions and detailing the proteins that are known to participate to its biosynthetic pathways. Novel results showing that ubiquinone can be produced by a pathway independent of dioxygen suggest that ubiquinone may participate to anaerobiosis, in addition to its well-established role for aerobiosis. We also discuss the supramolecular organization of ubiquinone biosynthesis proteins and we summarize the current understanding of the evolution of the ubiquinone pathways relative to those of other isoprenoid quinones like menaquinone and plastoquinone