Structural variability of C3larvin toxin. Intrinsic dynamics of the α/β fold of the C3-like group of mono-ADP-ribosyltransferase toxins

C3larvin toxin is a new member of the C3 class of the mono-ADP-ribosyltransferase toxin family. The C3 toxins are known to covalently modify small G-proteins, e.g. RhoA, impairing their function, and serving as virulence factors for an offending pathogen. A full-length X-ray structure of C3larvin (2.3 Å) revealed that the characteristic mixed α/β fold consists of a central β-core flanked by two helical regions. Topologically, the protein can be separated into N and C lobes, each formed by a β-sheet and an α-motif, and connected by exposed loops involved in the recognition, binding, and catalysis of the toxin/enzyme, i.e. the ADP-ribosylation turn–turn and phosphate–nicotinamide PN loops. Herein, we provide two new C3larvin X-ray structures and present a systematic study of the toxin dynamics by first analyzing the experimental variability of the X-ray data-set followed by contrasting those results with theoretical predictions based on Elastic Network Models (GNM and ANM). We identify residues that participate in the stability of the N-lobe, putative hinges at loop residues, and energy-favored deformation vectors compatible with conformational changes of the key loops and 3D-subdomains (N/C-lobes), among the X-ray structures. We analyze a larger ensemble of known C3bot1 conformations and conclude that the characteristic ‘crab-claw’ movement may be driven by the main intrinsic modes of motion. Finally, via computational simulations, we identify harmonic and anharmonic fluctuations that might define the C3larvin ‘native state.’ Implications for docking protocols are derived.     

Simultaneous modelling of distributional patterns in a guild of eastern-Australian cicadas

Summary The distributions, with respect to habitat structure, of nine species of eastern-Australian cicadas have been shown to be non-random. The most striking consequence of this non-randomness is a marked inverse relationship between habitat breadth and habitat position (terms defined in text). Eight basic models and 12 derived models were used in conjunction with a canonical space to try to account for the ways in which the species of cicadas were distributed with respect to habitat. Several models produced results that were in reasonable agreement with the observed data. The most parsimonious of these corresponds to analytical results of other workers, such as Diamond's (1975) incidence curves, occurrence sequences (Schoener and Schoener 1983), and probability functions (Adler and Wilson 1985). The distributions of cicadas can be modelled by assuming that the species occupy sites independently of one another. These species of cicadas are unlikely to engage in interspecific competition, which is consistent with independence of distributions.     

Effect of Zeitgeber Intensity Reduction on a Simulated Dual-Oscillator Human Circadian System: Classical and Dynamic Analysis

The two-oscillator model of human circadian rhythmicity was analyzed when a zeitgeber relative intensity of 1, 0.5, or 0.1 was introduced into the equations. Fourier analysis was compared with dynamic analysis such as attractor reconstruction or Liapunov exponent calculation. After a 50 or 90% reduction in zeitgeber intensity, the dynamics of the system became equivalent and differed significantly from those of a system with maximal zeitgeber intensity. When 10% aleatory noise was added to the data, the analysis was still applicable, and the results obtained were essentially the same as in the absence of noise. Dynamic analysis could thus provide a distinct classification for periodic data, based on the type of analysis.     

A real-time database/models base/expert system in predictive microbiology

Summary This paper describes the development and operation of a database/models base/expert system funded by the Ministry of Agriculture, Fisheries and Food in the UK. As part of an on-going coordinated program on predictive microbiology, the system being established involves storage of data and models relevant to changes in populations of food-borne pathogens under given conditions. The system is due to be completed by March 1994.     

Selection versus random drift: long-term polymorphism persistence in small populations (evidence and modelling)

Our data on a subterranean mammal, Spalax ehrenbergi, and other evidence, indicate that appreciable polymorphism can be preserved in small isolated populations consisting of several dozens of, or a hundred, individuals. Current theoretical models predict fast gene fixation in small panmictic populations without selection, mutation, or gene inflow. Using simple multilocus models, we demonstrate here that moderate stabilizing selection (with stable or fluctuating optimum) for traits controlled by additive genes could oppose random fixation in such isolates during thousands of generations. We also show that in selection-free models polymorphism persists only for a few hundred generations even under high mutation rates. Our multi-chromosome models challenge the hitchhiking hypothesis of polymorphism maintenance for many neutral loci due to close linkage with few selected loci.     

On the RNA World: Evidence in Favor of an Early Ribonucleopeptide World

A highly complex RNA world, as is sometimes presented in view of the widespread and diversified use of RNA enzymes, would have encountered many difficulties in passing to a world with catalysis mediated by proteins. These difficulties can be overcome by postulating a very early relationship between the nucleotide and the amino acid components. In particular, after asserting that some characteristics expressed by (nucleotide) coenzymes in catalysis are easier to understand if a close and early relationship between these coenzymes and amino acids is hypothesized, a model is presented for the origin of the enzyme–coenzyme complex. This model is essentially based on an intermediate formed by a tRNA-like molecule covalently linked to a polypeptide. The model attributes the majority of the catalytic role in the ribonucleoprotein world to the latter complex and thus it takes into account the birth of the key intermediate in the origin of protein synthesis—namely, peptidyl-tRNA, which would have otherwise been extremely difficult to select. The predictions of the model are discussed along with its robustness, using the data derived from the study of intermediary metabolism and those from molecular biology. Finally, the appearance of the genetic code in the late phase of the ribonucleopeptide world is discussed. Received: 13 January 1997 / Accepted: 25 July 1997     

A Murine Model of Stent Implantation in the Carotid Artery for the Study of Restenosis

Despite the considerable progress made in the stent development in the last decades, cardiovascular diseases remain the main cause of death in western countries. Beside the benefits offered by the development of different drug-eluting stents, the coronary revascularization bears also the life-threatening risks of in-stent thrombosis and restenosis. Research on new therapeutic strategies is impaired by the lack of appropriate methods to study stent implantation and restenosis processes. Here, we describe a rapid and accessible procedure of stent implantation in mouse carotid artery, which offers the possibility to study in a convenient way the molecular mechanisms of vessel remodeling and the effects of different drug coatings.