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Search Results: 1 - 10 of 208189 matches for " Bruno P. Klaholz "
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Structure Sorting of Multiple Macromolecular States in Heterogeneous Cryo-EM Samples by 3D Multivariate Statistical Analysis  [PDF]
Bruno P. Klaholz
Open Journal of Statistics (OJS) , 2015, DOI: 10.4236/ojs.2015.57081

Heterogeneity of biological samples is usually considered a major obstacle for three-dimensional (3D) structure determination of macromolecular complexes. Heterogeneity may occur at the level of composition or conformational variability of complexes and affects most 3D structure determination methods that rely on signal averaging. Here, an approach is described that allows sorting structural states based on a 3D statistical approach, the 3D sampling and classification (3D-SC) of 3D structures derived from single particles imaged by cryo electron microscopy (cryo-EM). The method is based on jackknifing & bootstrapping of 3D sub-ensembles and 3D multivariate statistical analysis followed by 3D classification. The robustness of the statistical sorting procedure is corroborated using model data from an RNA polymerase structure and experimental data from a ribosome complex. It allows resolving multiple states within heterogeneous complexes that thus become amendable for a structural analysis despite of their highly flexible nature. The method has important implications for high-resolution structural studies and allows describing structure ensembles to provide insights into the dynamics of multi-component macromolecular assemblies.

Escherichia coli Ribosomal Protein S1 Unfolds Structured mRNAs Onto the Ribosome for Active Translation Initiation
Mélodie Duval,Alexey Korepanov,Olivier Fuchsbauer,Pierre Fechter,Andrea Haller,Attilio Fabbretti,Laurence Choulier,Ronald Micura,Bruno P. Klaholz,Pascale Romby ,Mathias Springer,Stefano Marzi
PLOS Biology , 2013, DOI: 10.1371/journal.pbio.1001731
Abstract: Regulation of translation initiation is well appropriate to adapt cell growth in response to stress and environmental changes. Many bacterial mRNAs adopt structures in their 5′ untranslated regions that modulate the accessibility of the 30S ribosomal subunit. Structured mRNAs interact with the 30S in a two-step process where the docking of a folded mRNA precedes an accommodation step. Here, we used a combination of experimental approaches in vitro (kinetic of mRNA unfolding and binding experiments to analyze mRNA–protein or mRNA–ribosome complexes, toeprinting assays to follow the formation of ribosomal initiation complexes) and in vivo (genetic) to monitor the action of ribosomal protein S1 on the initiation of structured and regulated mRNAs. We demonstrate that r-protein S1 endows the 30S with an RNA chaperone activity that is essential for the docking and the unfolding of structured mRNAs, and for the correct positioning of the initiation codon inside the decoding channel. The first three OB-fold domains of S1 retain all its activities (mRNA and 30S binding, RNA melting activity) on the 30S subunit. S1 is not required for all mRNAs and acts differently on mRNAs according to the signals present at their 5′ ends. This work shows that S1 confers to the ribosome dynamic properties to initiate translation of a large set of mRNAs with diverse structural features.
Phosphatase-Dead Myotubularin Ameliorates X-Linked Centronuclear Myopathy Phenotypes in Mice
Leonela Amoasii equal contributor,Dimitri L. Bertazzi equal contributor,Hélène Tronchère,Karim Hnia,Ga?tan Chicanne,Bruno Rinaldi,Belinda S. Cowling,Arnaud Ferry,Bruno Klaholz,Bernard Payrastre ? ,Jocelyn Laporte ? ,Sylvie Friant ?
PLOS Genetics , 2012, DOI: 10.1371/journal.pgen.1002965
Abstract: Myotubularin MTM1 is a phosphoinositide (PPIn) 3-phosphatase mutated in X-linked centronuclear myopathy (XLCNM; myotubular myopathy). We investigated the involvement of MTM1 enzymatic activity on XLCNM phenotypes. Exogenous expression of human MTM1 in yeast resulted in vacuolar enlargement, as a consequence of its phosphatase activity. Expression of mutants from patients with different clinical progression and determination of PtdIns3P and PtdIns5P cellular levels confirmed the link between vacuolar morphology and MTM1 phosphatase activity, and showed that some disease mutants retain phosphatase activity. Viral gene transfer of phosphatase-dead myotubularin mutants (MTM1C375S and MTM1S376N) significantly improved most histological signs of XLCNM displayed by a Mtm1-null mouse, at similar levels as wild-type MTM1. Moreover, the MTM1C375S mutant improved muscle performance and restored the localization of nuclei, triad alignment, and the desmin intermediate filament network, while it did not normalize PtdIns3P levels, supporting phosphatase-independent roles of MTM1 in maintaining normal muscle performance and organelle positioning in skeletal muscle. Among the different XLCNM signs investigated, we identified only triad shape and fiber size distribution as being partially dependent on MTM1 phosphatase activity. In conclusion, this work uncovers MTM1 roles in the structural organization of muscle fibers that are independent of its enzymatic activity. This underlines that removal of enzymes should be used with care to conclude on the physiological importance of their activity.
Exchange interaction parameters and adiabatic spin-wave spectra of ferromagnets: A "renormalized magnetic force theorem"
P. Bruno
Physics , 2002, DOI: 10.1103/PhysRevLett.90.087205
Abstract: The ``magnetic force theorem'' is frequently used to compute exchange interaction parameters and adiabatic spin-wave spectra of ferromagnets. The interest of this approach is that it allows to obtain these results from a non-self-consistent calculation of the (single-electron) band energy only, which greatly reduces the computational effort. However, as discussed by various authors, this approach entail some systematic error. Here, a ``renormalized magnetic force theorem'' allowing to remove this systematic error without increasing significantly the computational effort is presented. For systems with one atom per unit cell, it amounts to a simple renormalization of the spin-wave spectrum. This renormalization greatly improves the agreement between calculated and experimental Curie temperatures of Fe and Ni.
Long-range magnetic interaction due to the Casimir effect
P. Bruno
Physics , 2002, DOI: 10.1103/PhysRevLett.88.240401
Abstract: The zero-point quantum fluctuations of the electromagnetic field in vacuum are known to give rise to a long-range attractive force between metal plates (Casimir effect). For ferromagnetic layers separated by vacuum, it is shown that the interplay of the Casimir effect and of the magneto-optical Kerr effect gives rise to a long-range magnetic interaction. The Casimir magnetic force is found to decay as $D^{-1}$ in the limit of short distances, and as $D^{-5}$ in the limit of long distances. Explicit expressions for realistic systems are given in the large and small distance limits. An experimental test of the Casimir magnetic interaction is proposed.
Configuración de la patria y de las letras cubanas en el siglo diecinueve
Anclajes , 2009,
Abstract: the shaping of cuban motherland imaginary had its foundational stage during the third decade of the ninetenth century. it was a group of cuban literates, coming from different fields of study -but joined in the ideals of liberal reformism- who consciously developed an initial symbolic mould on which a certain conception of the motherland will be founded. in literary texts and essays, these intellectuals capture their concerns and doubts, while sketching and delimiting early blueprints of a nation. this paper proposes to analyze a letter written by cuban poet josé jacinto milanés (1814-1863) adressed to domingo del monte (1804-1853), since it allows us to capture the discussions held by these intellectuals around the building of an identity and a patriotic literature, as well as the process of writing itself, in relation to the shaping of human relationships typical of those literate circles at that period of time.
Going home in peace: the economy of virtues, and apathy as a right
Reis,Bruno P. W.;
Brazilian Political Science Review (Online) , 2007,
Abstract: this article proceeds from the premise that, even if you accept the principle that justice is impossible in the complete absence of virtue, a good political system ought to be parsimonious in any requirement of virtue as an input, so as not to impose undue restrictions on its own ability to function. assuming a more or less random distribution of virtue through time and space, it would be preferable, all other things being equal, to have a system equipped to operate not only in periods of abundant moral and ethical virtue, but also - and particularly - in periods of scarcity, when such qualities seem depleted in human nature. this exigency grows critical in the context of a modern society, in which the ever-increasing complexity and impersonal nature of social relations will produce anonymity that would urge extreme caution in the presumption of virtue as an element of social relations - a caution that sociology unanimously teaches us. in such a context - one in which not all issues will involve everyone equally, nor will all voices be always audible - prudence advises and tolerance demands that political apathy - or, rather, mere abstention - should be recognized, if not as a new modality of virtue, at least as a basic right: in the exercise of which, i will respectfully silence myself whenever appropriate before the judgment of actors more intensely immersed than i, and let myself hope for silence from a few so as to be heard when i see fit to express myself.
O mercado e a norma: o Estado moderno e a interven??o pública na economia
Reis, Bruno P. W.;
Revista Brasileira de Ciências Sociais , 2003, DOI: 10.1590/S0102-69092003000200004
Abstract: this article starts from a discussion on the weberian conception of the market as a means by excellence to foment "socialization among strangers" to then reflect theoretically on modernization and market. beyond evident suggestions involved in the reflexion on the role of market in the contemporary world, it aims to establish some specific nexus - despite all the tensions involved - between market archetype and the operation of the modern democratic political systems.
La sociologie de l'art et de la culture en France: un état des lieux
Péquignot, Bruno;
Sociedade e Estado , 2005, DOI: 10.1590/S0102-69922005000200003
Abstract: la sociologie des arts et de la culture s'est très t?t développée en france, puisque dès la fin du 19è siècle il y a plusieurs publications. puis on peut distinguer deux grandes périodes, la première va des années 30 du vingtième siècle à 1985 et voit se développer plusieurs tendances importantes qui continuent à marquer cette sous-discipline; la seconde commence avec les journées internationales organisées par mme raymonde moulin à marseille en 1985, c'est le début d'un développement tout à fait spectaculaire sans doute permis par un soutien fort du ministère de la culture depuis jack lang. l'article cherche à présenter cette histoire et l'état des débats aujourd'hui dans ce secteur dynamique de la sociologie en france.
Howard S. Becker : un sociologue de la haute mer
Bruno Péquignot
SociologieS , 2010,
Abstract: Une révolution psychique vient s rement de se produire en ce siècle ; la raison humaine vient d’être désancrée et la connaissance a quitté les rives du réel immédiat. N’y a-t-il pas alors anachronisme à cultiver le go t du port, de la certitude, du système ?Gaston Bachelard (1936, p. 11).Terminant la lecture du dernier livre (traduit en fran ais) de Howard S. Becker, cette phrase de Gaston Bachelard, que j’ai souvent citée et qui me poursuit comme le texte d’où elle est issue depuis bien long...
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