Combinatorial and frequency properties of the ribosome ancestors.

BACKGROUND: The current ribosome has evolved from the primitive stages of life on Earth. Its function is to build proteins and on the basis of this role, we are looking for a universal common ancestor to the ribosome which could: i) present optimal combinatorial properties, and ii) have left vestiges in the current molecules composing the ribosome (rRNA or r-proteins) or helping in its construction and functioning. METHODS: Genomic public databases are used for finding the nucleotide sequences of rRNAs and mRNA of r-proteins and statistical calculations are performed on the occurrence in these genes of some pentamers belonging to the RNA proposed as optimal ribosome ancestor. RESULTS: After having exhibited a possible solution to the problem of an RNA capable of catalyzing peptide genesis, traces of this RNA are found in many rRNAs and mRNA of r-proteins, as well as in factors contributing to the construction of the current ribosome. CONCLUSIONS: The existence of an optimal primordial RNA whose function is to facilitate the creation of peptide bonds between amino acids may have contributed to accelerate the emergence of the first vital processes. Its traces should be found in many living species inside structures structurally and functionally close to the ribosome, which is already the case in the species studied in this article.

Evolution of small and large ribosomal RNAs from accretion of tRNA subelements.

tRNAs presumably accreted into modern ribosomal RNAs. Previous analyses showed similar secondary structures for ancient rRNA subelements and theoretical minimal RNA rings, candidate tRNA ancestors rationally designed from tRNA-unrelated principles. Here, analyses test which tRNA secondary structure subelements resemble ancient/recent rRNA subelements. Results show that ribosomal RNA subelements evolved from structures resembling 1. Upper half part of the tRNA secondary structure; and 2. Towards structures resembling (a) tRNA 5' stem-loop hairpins in large rRNA subunit and (b) tRNA lower half part in small rRNA subunit (stop and start codons conservation model). tRNAs and rRNAs presumably originated from the tRNA upper half part including the acceptor stem. Modern split 5' and 3' tRNA genes (spliced at anticodons) apparently reproduce ancestral-like states, because the acceptor stem protocode suggests acceptor stems evolved from spliced anticodon-like stem-loop hairpins, strengthening central roles for acceptor stem CCA-addition at translation origins. The Root-Bernstein hypothesis on the existence of tRNA structural symmetries presumably reflects late 5' tRNA stem-loop hairpin duplications, some integrating rRNAs. Analyses of tRNA subelements similarities with rRNA subelements suggest tRNAs evolved and re-evolved by different duplication-fusions, along different structural subdivision models. Hence, sequential/parallel processes, perhaps in the same ancestral organism(s) produced polyphyletic tRNAs. Results confirm RNA ring usefulness for understanding prebiotic and early life evolution, and their similarities with primordial protein coding and tRNA genes.

Theoretical minimal RNA rings recapitulate the order of the genetic code's codon-amino acid assignments.

BACKGROUND: Theoretical minimal RNA rings form stem-loop hairpins coding for each of the 20 amino acids and a stop, presumably mimicking life's first minimal coding and self-replicating RNAs. They resemble consensual tRNAs. Mean amino acid positions in proteins follow the genetic code's consensual amino acid inclusion order, a 5'-late-to-3'-early amino acid gradient. HYPOTHESIS: We translated minimal RNA rings to test whether translated peptides share that gradient with modern proteins, using a) ribosomal translation, non-overlapping consecutive codons; and b) frameless translation advancing nucleotide by nucleotide, producing partially overlapping codons. RESULTS: For frameless translation, most RNA rings code for a 5'-late-to-3'early amino acid gradient. Gradients indicate decreasing amino acid metabolic costs, from large to small amino acids. For ribosomal translation, the 5'-late-to-3'early amino acid gradient evolves from early to late RNA rings when ranked according to yields in Miller's experiment of their predicted anticodon's cognate amino acid. CONCLUSIONS: Simulations that produced in silico minimal RNA rings didn't account for coded amino acid properties. Yet, produced peptides remind actual proteins, and suggest ancestral frameless translation of partially overlapping trinucleotides advancing by single nucleotide steps, constrained by resource scarcity. Minimal RNA rings reflect the transition from frameless to ribosomal translation and are realistic candidates for ancestral tRNAs.

Understanding physiological and degenerative natural vision mechanisms to define contrast and contour operators.

BACKGROUND: Dynamical systems like neural networks based on lateral inhibition have a large field of applications in image processing, robotics and morphogenesis modeling. In this paper, we will propose some examples of dynamical flows used in image contrasting and contouring. METHODOLOGY: First we present the physiological basis of the retina function by showing the role of the lateral inhibition in the optical illusions and pathologic processes generation. Then, based on these biological considerations about the real vision mechanisms, we study an enhancement method for contrasting medical images, using either a discrete neural network approach, or its continuous version, i.e. a non-isotropic diffusion reaction partial differential system. Following this, we introduce other continuous operators based on similar biomimetic approaches: a chemotactic contrasting method, a viability contouring algorithm and an attentional focus operator. Then, we introduce the new notion of mixed potential Hamiltonian flows; we compare it with the watershed method and we use it for contouring. CONCLUSIONS: We conclude by showing the utility of these biomimetic methods with some examples of application in medical imaging and computed assisted surgery.

An open issue: the inner mitochondrial membrane (IMM) as a free boundary problem.

The inner mitochondrial membrane (IMM) is structured in cristae, which contributes to the best functioning of ions and adenylates exchange between the matrix and the intermembrane space. The central hypothesis of this paper is that the cristae structure favours a minimal mean free path of adenylates between translocation sites (translocase/ANT sites) and metabolic sites (ATPase sites). We propose a mathematical model and then give simulations. Based on simple hypotheses about cristae growth, they show that we can account for the major features of the IMM organization and functioning by minimizing the mean interdistance between ADP/ATP translocation and transformation sites.

Guiding the surgical gesture using an electro-tactile stimulus array on the tongue: a feasibility study.

Under conventional "open-" surgery, the physician has to take care of the patient, interact with other clinicians and check several monitoring devices. Nowadays, the computer assisted surgery proposes to integrate 3-D cameras in the operating theatre in order to assist the surgeon in performing minimally invasive surgical punctures. The cameras localize the needle and the computer guides the surgeon towards an intracorporeal clinically defined target. A visualization system (screen) is employed to provide the surgeon with indirect visual spatial information about the intracorporeal positions of the needle. The present work proposes to use another sensory modality to guide the surgeon, thus keeping the visual modality fully dedicated to the surgical gesture. For this, the sensory substitution paradigm using the Bach-y-Rita's "Tongue Display Unit" (TDU) is exploited to provide to the surgeon information of the position tool. The TDU device is composed of a 6 x 6 matrix of electrodes transmitting electrotactile information on the tongue surface. The underlying idea consists in transmitting information about the deviation of the needle movement with regard to a preplanned "optimal" trajectory. We present an experiment assessing the guidance effectiveness of an intracorporeal puncture under TDU guidance with respect to the performance evidenced under a usual visual guidance system.

Assessment of insulin resistance in fructose-fed rats with 125I-6-deoxy-6-iodo-D-glucose, a new tracer of glucose transport.

PURPOSE: Insulin resistance, characterised by an insulin-stimulated glucose transport defect, is an important feature of the pre-diabetic state that has been observed in numerous pathological disorders. The purpose of this study was to assess variations in glucose transport in rats using (125)I-6-deoxy-6-iodo-D-glucose (6DIG), a new tracer of glucose transport proposed as an imaging tool to assess insulin resistance in vivo. METHODS: Two protocols were performed, a hyperinsulinaemic-euglycaemic clamp and a normoinsulinaemic-normoglycaemic protocol, in awake control and insulin-resistant fructose-fed rats. The tracer was injected at steady state, and activity in 11 tissues and the blood was assessed ex vivo at several time points. A multicompartmental mathematical model was developed to obtain fractional transfer coefficients of 6DIG from the blood to the organs. RESULTS: Insulin sensitivity of fructose-fed rats, estimated by the glucose infusion rate, was reduced by 40% compared with control rats. At steady state, 6DIG uptake was significantly stimulated by insulin in insulin-sensitive tissues of control rats (basal versus insulin: diaphragm, p < 0.01; muscle, p<0.05; heart, p<0.001), whereas insulin did not stimulate 6DIG uptake in insulin-resistant fructose-fed rats. Moreover, in these tissues, the fractional transfer coefficients of entrance were significantly increased with insulin in control rats (basal vs insulin: diaphragm, p<0.001; muscle, p<0.001; heart, p<0.01) whereas no significant changes were observed in fructose-fed rats. CONCLUSION: This study sets the stage for the future use of 6DIG as a non-invasive means for the evaluation of insulin resistance by nuclear imaging.

IMGT/GeneInfo: enhancing V(D)J recombination database accessibility.

IMGT/GeneInfo is a user-friendly online information system that provides information on data resulting from the complex mechanisms of immunoglobulin (IG) and T cell receptor (TR) V(D)J recombinations. For the first time, it is possible to visualize all the rearrangement parameters on a single page. IMGT/GeneInfo is part of the international ImMunoGeneTics information system (IMGT), a high-quality integrated knowledge resource specializing in IG, TR, major histocompatibility complex (MHC), and related proteins of the immune system of human and other vertebrate species. The IMGT/GeneInfo system was developed by the TIMC and ICH laboratories (with the collaboration of LIGM), and is the first example of an external system being incorporated into IMGT. In this paper, we report the first part of this work. IMGT/GeneInfo_TR deals with the human and mouse TRA/TRD and TRB loci of the TR. Data handling and visualization are complementary to the current data and tools in IMGT, and will subsequently allow the modelling of V(D)J gene use, and thus, to predict non-standard recombination profiles which may eventually be found in conditions such as leukaemias or lymphomas. Access to IMGT/GeneInfo is free and can be found at http://imgt.cines.fr/GeneInfo.