The evolution of catalytic function

It is very likely that the main driving force of enzyme evolution is the requirement to improve catalytic and regulatory efficiency which results from the intrinsic performance as well as from the spatial and functional organization of enzymes in living cells. Kinetic co-operativity may occur in simple monomeric proteins if they display “slow” conformational transitions, at the cost of catalytic efficiency. Oligomeric enzymes on the other hand can be both efficient and co-operative. We speculate that the main reason for the emergence of co-operative oligomeric enzymes is the need for catalysts that are both cooperative and efficient. As it is not useful for an enzyme to respond to a change of substrate concentration in a complex kinetic way, the emergence of symmetry has its probable origin in a requirement for “functional simplicity”. In a living cell, enzyme are associated with other macromolecules and membranes. The fine tuning of their activity may also be reached through mutations of the microenvironment. Our hypothesis is that these mutations are related to the vectorial transport of molecules, to achieve the hysteresis loops of enzyme reactions generated by the coupling of reaction and diffusion, through the co-operativity brought about by electric interactions between a charged substrate and a membrane, and last but not least, through oscillations. As the physical origins of these effects are very simple and do not require complex molecular devices, it is very likely that the functional advantage generated by the spatial and functional organization of enzyme molecules within the cell have appeared in prebiotic catalysis or very early during the primeval stages of biological evolution. We shall begin this paper by presenting the nature of the probable earliest catalysts in the RNA world

The RNA world: hypotheses, facts and experimental results.

A biochemical world that would have existed before the contemporary DNA-RNA-Protein world, and baptized in 1986 "The RNA World" by Walter Gilbert, such a world had already been proposed during the preceding decades by Carl Woese, Francis Crick and Leslie Orgel. By demonstrating the remarkable diversity of the RNA molecule, Molecular Biology proved these predictions. RNA present in all living cells, performs structural and metabolic functions many of which were unsuspected only a few years ago. A truly modern "RNA world" exists in each cell; it contains RNAs in various forms, short and long fragments, single and double-stranded, endowed with multiple roles (informational, catalytic, that can serve as templates, guides, defense), certain molecules being even capable of carrying out several of these functions

Domestic competition and export performance of manufacturing firms in Côte d’Ivoire

Because of transportation costs, African manufacturing firms benefit from some market power on their domestic market, where they can charge a higher price than the export price, net of transportation cost. We present a simple theoretical model of an exporting firm that discriminates between the export and the domestic markets, where firms engage in Cournot competition. It is then shown that the impact of increased competition on export performance by the firms is ambiguous, and may be negative for a non trivial range of parameter values. Using survey data on Ivoirian firms, our empirical analysis gives some support to this prediction, showing that the probability of a firm exporting decreases with increased competition.

Montmorillonite protection of an UV-irradiated hairpin ribozyme: evolution of the RNA world in a mineral environment

International audienceBACKGROUND: The hypothesis of an RNA-based origin of life, known as the "RNA world", is strongly affected by the hostile environmental conditions probably present in the early Earth. In particular, strong UV and X-ray radiations could have been a major obstacle to the formation and evolution of the first biomolecules. In 1951, J. D. Bernal first proposed that clay minerals could have served as the sites of accumulation and protection from degradation of the first biopolymers, providing the right physical setting for the evolution of more complex systems. Numerous subsequent experimental studies have reinforced this hypothesis. RESULTS: The ability of the possibly widespread prebiotic, clay mineral montmorillonite to protect the catalytic RNA molecule ADHR1 (Adenine Dependent Hairpin Ribozyme 1) from UV-induced damages was experimentally checked. In particular, the self-cleavage reaction of the ribozyme was evaluated after UV-irradiation of the molecule in the absence or presence of clay particles. Results obtained showed a three-fold retention of the self-cleavage activity of the montmorillonite-protected molecule, with respect to the same reaction performed by the ribozyme irradiated in the absence of the clay. CONCLUSION: These results provide a suggestion with which RNA, or RNA-like molecules, could have overcame the problem of protection from UV irradiation in the RNA world era, and suggest that a clay-rich environment could have favoured not only the formation of first genetic molecules, but also their evolution towards increasingly complex molecular organization

SCoRe: a Self-Organizing Multi-Agent System for Decision Making in Dynamic Software Developement Processes

International audienceSoftware systems are becoming more and more complex. A common dilemma faced by software engineers in building complex systems is the lack of method adaptability. However, existing agent-based methodologies and tools are developed for particular system and are not tailored for new problems. This paper proposes an architecture of a new tool based on SME for self-constructing customized method processes. Our approach is based on two pillars: the process fragment and the MAS meta-model. These two elements are both defined and considered under a specific agent-oriented perspective thus creating a peculiar approach. Our work is based on the self-organization of agents, making it especially suited to deal with highly dynamic systems such as the design of an interactive and adaptive software engineering process

Hydrostatic and osmotic pressure study of the hairpin ribozyme.

The recent discovery of numerous catalytically active RNAs in various living species as well as the in vitro selection of a large series of RNA aptamers able to bind specifically various molecules such as metabolites and co-factors, emphasize the adaptability of RNAs through the plasticity of their secondary structure. Furthermore, all these observations give support to the “RNA world” hypothesis as a step in the primitive development of life on Earth. On this background, we used high pressure to study the mechanism of action of a model hairpin ribozyme which exhibits self-cleavage and ligation. The activation volume (ΔV≠) of the cleavage reaction (34 ± 4 ml/mol) indicates that an important compaction of the RNA molecule occurs during the reaction and must be accompanied by a significant movement of water molecules . Indeed, such a release of 78 ± 4 water molecules per RNA molecule could be measured by complementary osmotic shock experiments. These results are consistent with the information provided by the structural studies which indicate that two loops of the RNA molecule should come into contact for the reaction to occur .The high pressure study of a modified form of the ribozyme whose activity is strictly dependent on the presence of adenine as a co-factor should bring some information about the structural significance of this important ΔV≠ of activation

Self-assembly Controls Self-cleavage of HHR from ASBVd (−): a Combined SANS and Modeling Study

International audienceIn the Avocado Sunblotch Viroid (ASBVd: 249-nt) from the Avsunviroidae family, a symmetric rolling-circle replication operates through an autocatalytic mechanism mediated by hammerhead ribozymes (HHR) embedded in both polarity strands. The concatenated multimeric ASBVd (+) and ASBVd (−) RNAs thus generated are processed by cleavage to unit-length where ASBVd (−) self-cleaves with more efficiency. Absolute scale small angle neutron scattering (SANS) revealed a temperature-dependent dimer association in both ASBVd (−) and its derived 79-nt HHR (−). A joint thermodynamic analysis of SANS and catalytic data indicates the rate-determining step corresponds to the dimer/monomer transition. 2D and 3D models of monomeric and dimeric HHR (−) suggest that the inter-molecular contacts stabilizing the dimer (between HI and HII domains) compete with the intra-molecular ones stabilizing the active conformation of the full-length HHR required for an efficient self-cleavage. Similar competing intra- and inter-molecular contacts are proposed in ASBVd (−) though with a remoter region from an extension of the HI domain

SCoRe: a Self-Organizing Multi-Agent System for Decision Making in Dynamic Software Developement Processes

Software systems are becoming more and more complex. A common dilemma faced by software engineers in building complex systems is the lack of method adaptability. However, existing agent-based methodologies and tools are developed for particular system and are not tailored for new problems. This paper proposes an architecture of a new tool based on SME for self-constructing customized method processes. Our approach is based on two pillars: the process fragment and the MAS meta-model. These two elements are both defined and considered under a specific agent-oriented perspective thus creating a peculiar approach. Our work is based on the self-organization of agents, making it especially suited to deal with highly dynamic systems such as the design of an interactive and adaptive software engineering process

A Pattern based Modelling for Self-Organizing Multi-Agent Systems with Event-B

International audienceSelf-Organizing Multi-Agent Systems (SO-MAS) are defined as a set of autonomous entities called agents interacting together in order to achieve a given task. Generally, the development process of these systems is based on the bottom-up approach which focuses on the design of the entities individual behavior. The main question arising when developing SO-MAS is how to insure that the designed entities, when interacting together, will give rise to the desired behavior? Our proposition to deal with this question is to use formal methods. We propose a correct by construction method for systematic design of SO-MAS based on the use of design patterns and formal stepwise refinements. Our work gives guidelines to assist the designer when developing the individual behavior of the entities and prove its correctness at the early stages of the design process. The method is illustrated with the foraging ants’ case study

Structure tertiaire des acides nucleiques en simple brin : mise en evidence au moyen d'un intercalant fluorescent, le bromure d'ethidium

SIGLECNRS T 58658 / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc