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Search Results: 1 - 10 of 6375 matches for " Nicolas Danchin "
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The bag or the spindle: the cell factory at the time of systems' biology
Antoine Danchin
Microbial Cell Factories , 2004, DOI: 10.1186/1475-2859-3-13
Abstract: At the date of October 30th, 2004 the GOLD (http://www.genomesonline.org/ webcite) site provided links to 1205 ongoing or completed genome programmes, most of which from prokaryotic organisms. More than 40,000 pages are indexed in the WWW Browser Engine Google for the keyword "cell factory". Early in 1999 the European Union launched a research programme on the cell factory (http://europa.eu.int/comm/research/rtdinf21/en/key/03.html webcite), stating that ? The concept of the "bio-product" is as old as the knowledge involved in the making of bread, beer, wine or cheese. However, recent techniques and knowledge in molecular biology and genetics mean that living cells – from bacteria to man – are now becoming real "factories". In vast fermentation vats, engineers can direct and control natural metabolism in order to produce all sorts of substances with a high added value: proteins, amino acids, alcohols, citric acid, solvents and even bio-plastics. This industrial mastery of the mechanisms of life opens up revolutionary perspectives in the development of new kinds of medicines, foodstuffs with specific nutritional properties, and biodegradable biochemical products ? [1].Taken together these pieces of information show that exploration of the potential of microbes as industrial tools is shifting from its former status of traditional biotechnology assets to new high technology devices, meant to perform highly specific tasks, with the highest possible yields and security, and genomics as the background support. We shall not here review the use of microbes in traditional production (bread, beer, cheese and wine have been invented since the origin of the Neolithic, and perhaps even earlier [2]) but, rather, see how the coupling between knowledge of bacterial genome sequences and new genomics techniques such as expression profiling and biotechnology processes have interacted recently. The numbers of works in the domain is growing exponentially (it counts certainly in the thou
Destruction du patrimoine et figure du soldat allemand dans les cartes postales de la Grande Guerre
Emmanuelle Danchin
Amnis , 2010, DOI: 10.4000/amnis.1371
Abstract: Les cartes postales illustrées de la Grande Guerre, et plus particulièrement les vues topographiques de ruines, sont une source négligée qui témoigne aujourd’hui encore, alors que les reconstructions ont effacé depuis longtemps toutes traces de la guerre, des atteintes portées par l’artillerie et les explosifs au patrimoine civil, artistique, religieux et à l’habitat. De part et d’autre du front occidental, les Fran ais comme les Allemands ont utilisé ces vues de destruction comme preuve de la barbarie de l’autre et elles contribuèrent ainsi à la mobilisation des populations en guerre. Une guerre des images et par l’image prenant notamment appui sur la carte postale, sorte de guerre dans la guerre et à laquelle les belligérants eux-mêmes ont participé, s’est ainsi mise en place dès 1914. Ces vues de ruines ont contribué à présenter la guerre comme une guerre de la Civilisation contre la Kultur, et les Allemands comme de nouveaux barbares commettant des atrocités culturelles, dont témoignait la destruction des monuments. A l’accusation de barbare , appuyée par ces images de ruines, les Allemands ont rétorqué par une production de cartes postales valorisant cette terminologie tournée en positif : le mot devenant alors un signe distinctif positif de la représentation de soi. Ils ont également favorisé la diffusion de vues de ruines du front de l'Est qui montraient du doigt cette fois-ci les Russes, accusés à leur tour d’être des barbares . L’étude de ces représentations de la destruction permet d’approcher autrement un aspect de la violence de la mobilisation culturelle. The Great War’s illustrated postcards, specifically concerning topographical views of ruins, in spite of being a neglected source, can still reveal, even after reconstructions have long erased every trace of war, the impacts of artillery and explosives on the civil, artistic and religious heritage, and on the housing environment. On either side of the western front, the French and the German have used these views of destruction as a testimony of the barbaric character of the enemy, thus contributing to the mobilization of the war population. A war of images, told through images, especially postcards, developed from 1914, becoming a sort of war within the war in which belligerents themselves took part. These views of ruins contributed to present the war as a war of civilisation against Kultur, and depicted the German as the ‘new barbarians’ perpetrators of cultural atrocities, displayed by the destruction of monuments. The German defended themselves against these accusations based
Bacteria are not Lamarckian
Antoine Danchin
Quantitative Biology , 2007,
Abstract: Instructive influence of environment on heredity has been a debated topic for centuries. Darwin's identification of natural selection coupled to chance variation as the driving force for evolution, against a formal interpretation proposed by Lamarck, convinced most scientists that environment does not specifically instruct evolution in an oriented direction. This is true for multicellular organisms. In contrast, bacteria were long thought of as prone to receive oriented influences from their environment, although much was in favour of the Darwinian route (1). In this context Cairns et al. raised a passionate debate by suggesting that bacteria generate mutations oriented by the environmental conditions (2). Several independent pieces of work subsequently demonstrated that mutations overcoming specific defects arised as a consequence of cultivation on specific media (3-7). Two diametrically opposed interpretations were proposed to explain these observations : either induction of mutations instructed by the environment (e.g. by a process involving a putative reverse transcription) or selection of variants among a large set of mutant bacteria generated when stress conditions are present. The experiments presented below indicate that the Darwinian paradigm is the most plausible.
Treatment for Stable Coronary Artery Disease: A Network Meta-Analysis of Cost-Effectiveness Studies
Thibaut Caruba, Sandrine Katsahian, Catherine Schramm, Ana?s Charles Nelson, Pierre Durieux, Dominique Bégué, Yves Juillière, Olivier Dubourg, Nicolas Danchin, Brigitte Sabatier
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0098371
Abstract: Introduction and Objectives Numerous studies have assessed cost-effectiveness of different treatment modalities for stable angina. Direct comparisons, however, are uncommon. We therefore set out to compare the efficacy and mean cost per patient after 1 and 3 years of follow-up, of the following treatments as assessed in randomized controlled trials (RCT): medical therapy (MT), percutaneous coronary intervention (PCI) without stent (PTCA), with bare-metal stent (BMS), with drug-eluting stent (DES), and elective coronary artery bypass graft (CABG). Methods RCT comparing at least two of the five treatments and reporting clinical and cost data were identified by a systematic search. Clinical end-points were mortality and myocardial infarction (MI). The costs described in the different trials were standardized and expressed in US $ 2008, based on purchasing power parity. A network meta-analysis was used to compare costs. Results Fifteen RCT were selected. Mortality and MI rates were similar in the five treatment groups both for 1-year and 3-year follow-up. Weighted cost per patient however differed markedly for the five treatment modalities, at both one year and three years (P<0.0001). MT was the least expensive treatment modality: US $3069 and 13 864 after one and three years of follow-up, while CABG was the most costly: US $27 003 and 28 670 after one and three years. PCI, whether with plain balloon, BMS or DES came in between, but was closer to the costs of CABG. Conclusions Appreciable savings in health expenditures can be achieved by using MT in the management of patients with stable angina.
Expression profiling in reference bacteria: dreams and reality
Antoine Danchin, Agnieszka Sekowska
Genome Biology , 2000, DOI: 10.1186/gb-2000-1-4-reviews1024
Abstract: Biology has a long history of describing and classifying objects, mostly in structural terms using the techniques and language of systematics. Even genetics, which identifies gene linkage, has often studied genes as individual entities. In these earlier approaches, a cell was considered but a bag of genes and gene products: it was not usual to find biologists asking questions about the collective behavior of these genes and proteins. Because selection pressure may act on any type of organization, the study of whole-genome sequences now enables us to consider whether genomes are simply collections of genes, or whether there is indeed something more to be discovered in terms of the structure and dynamics of cells and organisms at the global level.Functional genomics has emerged as a new discipline that uses innovative technologies for genome-wide analysis supported by information technology. It depends both on experiment and on mathematical and computational methods. High-throughput experimental technologies generate large amounts of data on gene expression, protein structure and protein interactions, for example, and powerful information systems are required to analyze these data efficiently. Transcription expression profiling can be used to investigate either the transcriptome (the totality of genes transcribed) or the proteome (the totality of the proteins produced) of a bacterium. DNA arrays and two-dimensional gel electrophoresis are expected to provide a global, high-throughput approach to revealing which genes are expressed at a detectable level, where they are expressed, and which are over- or under-expressed at a given growth stage or following changes in environmental conditions. The use of different growth conditions, different RNA extraction procedures and different array systems has created problems in comparing results, and highlights the need for benchmarking between different laboratories. Here, we review some recent articles describing expression prof
Genomes are covered with ubiquitous 11 bp periodic patterns, the "class A flexible patterns"
Etienne Larsabal, Antoine Danchin
BMC Bioinformatics , 2005, DOI: 10.1186/1471-2105-6-206
Abstract: Using a technique for analysis of auto-correlations based on linear projection, we identified the sequences responsible for the bias. Prokaryotic and lower eukaryotic genomes are covered with ubiquitous patterns that we termed "class A flexible patterns". Each pattern is composed of up to ten conserved nucleotides or dinucleotides distributed into a discontinuous motif. Each occurrence spans a region up to 50 bp in length. They belong to what we named the "flexible pattern" type, in that there is some limited fluctuation in the distances between the nucleotides composing each occurrence of a given pattern. When taken together, these patterns cover up to half of the genome in the majority of prokaryotes. They generate the previously recognized 11 bp periodic bias.Judging from the structure of the patterns, we suggest that they may define a dense network of protein interaction sites in chromosomes.The distribution of nucleotides in genomes is not random, various biases are affecting the genome sequences from organisms spanning the three domains of life. For example, the G+C content affects the genome as a whole.To visualize the biases in the nucleotides distribution in genomes, investigators have performed a variety of statistical analyses; these operations basically consisted in counting the nucleotides in a variety of subtle ways, while attempting to identify how the counting observed in real examples differed from a random distribution. Relevant statistical methods developed so far include the following: computation of correlations [1], power spectrum analysis [2,3], DNA walking analysis [4], computation of entropy [5,6], Hurst index estimation [7], detrended fluctuation analysis [8], wavelet analysis [9], mutual information function analysis [10], computational linguistics analysis [11].Among the different biases observed in the nucleotides distribution in genomes, two stood out prominently. Both are short-range biases, i.e. correlating nucleotides over a short di
The methionine salvage pathway in Bacillus subtilis
Agnieszka Sekowska, Antoine Danchin
BMC Microbiology , 2002, DOI: 10.1186/1471-2180-2-8
Abstract: Using in silico genome analysis and transposon mutagenesis in B. subtilis we have experimentally uncovered the major steps of the dioxygen-dependent methionine salvage pathway, which, although similar to that found in Klebsiella pneumoniae, recruited for its implementation some entirely different proteins. The promoters of the genes have been identified by primer extension, and gene expression was analyzed by Northern blotting and lacZ reporter gene expression. Among the most remarkable discoveries in this pathway is the role of an analog of ribulose diphosphate carboxylase (Rubisco, the plant enzyme used in the Calvin cycle which recovers carbon dioxide from the atmosphere) as a major step in MTR recycling.A complete methionine salvage pathway exists in B. subtilis. This pathway is chemically similar to that in K. pneumoniae, but recruited different proteins to this purpose. In particular, a paralogue or Rubisco, MtnW, is used at one of the steps in the pathway. A major observation is that in the absence of MtnW, MTR becomes extremely toxic to the cell, opening an unexpected target for new antimicrobial drugs. In addition to methionine salvage, this pathway protects B. subtilis against dioxygen produced by its natural biotope, the surface of leaves (phylloplane).The fate of methylthioribose (MTR), the end-product of spermidine and spermine metabolism, as well as of ethylene biosynthesis has not yet been fully explored in most organisms. In Escherichia coli this molecule is excreted in the medium [1] while in Klebsiella pneumoniae it constitutes the methionine salvage pathway, being metabolized back into methionine [2,3]. In eukaryotic parasites it is also recycled into methionine, presumably through a pathway similar to that in K. pneumoniae[4]. In Bacillus subtilis we found that MTR is an excellent sulfur source [5] and we unraveled some of the steps involved in its metabolism, which starts from phosphorylation of MTR, mediated by the MtnK protein [6].It has been
On the well-posedness of the incompressible density-dependent Euler equations in the $L^p$ framework
Rapha?l Danchin
Mathematics , 2009,
Abstract: The present paper is devoted to the study of the well-posedness issue for the density-dependent Euler equations in the whole space. We establish local-in-time results for the Cauchy problem pertaining to data in the Besov spaces embedded in the set of Lipschitz functions, including the borderline case $B^{\frac Np+1}_{p,1}(\R^N).$ A continuation criterion in the spirit of the celebrated one by Beale-Kato-Majda for the classical Euler equations, is also proved. In contrast with the previous work dedicated to this system in the whole space, our approach is not restricted to the $L^2$ framework or to small perturbations of a constant density state: we just need the density to be bounded away from zero. The key to that improvement is a new a priori estimate in Besov spaces for an elliptic equation with nonconstant coefficients.
Inhomogeneous Navier-Stokes equations in the half-space, with only bounded density
Raphael Danchin,Ping Zhang
Mathematics , 2013,
Abstract: In this paper, we establish the global existence of small solutions to the inhomogeneous Navier-Stokes system in the half-space. The initial density only has to be bounded and close enough to a positive constant, and the initial velocity belongs to some critical Besov space. With a little bit more regularity for the initial velocity, those solutions are proved to be unique. In the last section of the paper, our results are partially extended to the bounded domain case.
The Leray and Fujita-Kato theorems for the Boussinesq system with partial viscosity
R. Danchin,M. Paicu
Mathematics , 2008,
Abstract: We are concerned with the so-called Boussinesq equations with partial viscosity. These equations consist of the ordinary incompressible Navier-Stokes equations with a forcing term which is transported {\it with no dissipation} by the velocity field. Such equations are simplified models for geophysics (in which case the forcing term is proportional either to the temperature, or to the salinity or to the density). In the present paper, we show that the standard theorems for incompressible Navier-Stokes equations may be extended to Boussinesq system despite the fact that there is no dissipation or decay at large time for the forcing term. More precisely, we state the global existence of finite energy weak solutions in any dimension, and global well-posedness in dimension $N\geq3$ for small data. In the two-dimensional case, the finite energy global solutions are shown to be unique for any data in $L^2(\R^2).$
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