A Simple Self-Maintaining Metabolic System: Robustness, Autocatalysis, Bistability

International audienceA living organism must not only organize itself from within; it must also maintain its organization in the face of changes in its environment and degradation of its components. We show here that a simple (M,R)-system consisting of three interlocking catalytic cycles, with every catalyst produced by the system itself, can both establish a non-trivial steady state and maintain this despite continuous loss of the catalysts by irreversible degradation. As long as at least one catalyst is present at a sufficient concentration in the initial state, the others can be produced and maintained. The system shows bistability, because if the amount of catalyst in the initial state is insufficient to reach the non-trivial steady state the system collapses to a trivial steady state in which all fluxes are zero. It is also robust, because if one catalyst is catastrophically lost when the system is in steady state it can recreate the same state. There are three elementary flux modes, but none of them is an enzyme-maintaining mode, the entire network being necessary to maintain the two catalysts

Testing logarithmic violations to scaling in strongly coupled QED

Using very precise measurements of the critical couplings for the chiral transition of non compact $QED_4$ with up to 8 flavours, we analyse the behaviour of the order parameter at the critical point using the equation of state of a logarithmically improved scalar mean field theory, that of the Nambu-Jona Lasinio theory and a pure power law. The first case is definitively excluded by the numerical data. The stability of the fits for the last two cases, as well as the behaviour with the number of flavours of the exponent of the logarithmic violations to the scaling favour clearly a pure power law scaling with non mean field exponents.Comment: 6 pages, 3 postscript figures, 2 postscript tables (tar-ed, zip-ed, uu-encoded

Magnetic localization system for short-range positioning: a ready-to-use design tool

Magnetic localization is used in many indoor positioning applications, such as industrial, medical, and IoT, for its benefits related to the absence of line of sight needs, multipath and fading, the low cost of transmitters and receivers, and the simple development of setups made of coils and magnetic sensors. In short-range applications, this technology could bring some advantages with respect to ultrasound, laser, or RF ones. Nevertheless, fixed both the desired accuracy and the energy constraints, the optimal design of a localization system based on magnetic measurement depends on several factors: the dimension, the number and the optimal positions of the anchors, the uncertainties due to the sensing elements, and the data acquisition systems (DAQs). To preliminary fix all these parameters, suitable simulation environments allow developers to save time and money in developing localization applications. Many magnetic field simulators are available, but it is rare to find those that, considering the uncertainty due to the receiver and DAQs, are able to provide optimal anchors scenario given a target accuracy. To address this problem, this article presents a simulation tool providing the user with design requirements for given target accuracy. The aim of this article is to perform the first steps in providing a ready-to-use specification framework that given the localization domain, the mobile sensors, the DAQ characteristics, and the target accuracy and helps the developer of indoor magnetic positioning systems. The actual validity of the simulation model has been tested on a real setup.Postprint (published version

Chiral Susceptibilities in noncompact QED: a new determination of the γ\gamma exponent and the critical couplings

We report the results of a measurement of susceptibilities in noncompact $QED_4$ in $8^4, 10^4$ and $12^4$ lattices. Due to the potentialities of the $MFA$ approach, we have done simulations in the chiral limit which are therefore free from arbitrary mass extrapolations. Our results in the Coulomb phase show unambiguously that the susceptibility critical exponent $\gamma=1$ independently of the flavour symmetry group. The critical couplings extracted from these calculations are in perfect agreement with previous determinations based on the fermion effective action and plaquette energy, and outside the predictions of a logarithmically improved scalar mean field theory by eight standard deviations.Comment: 11 pages, figures on reques

Fermionic effective action and the pahse estructure of non compact quantum electrodynamics in 2+1 dimensions

We study the phase diagram of non compact $QED_3$ using the microcanonical fermionic average method described elsewhere. We present evidence for a continuous phase transition line in the $\beta, N$ plane, extending down to arbitrarily small flavour number $N$.Comment: 12 pags + 1 table + 5 figs; Ref: DFTUZ 93.0

Allele-specific gene expression is widespread across the genome and biological processes. PLoS One 4

Abstract Allelic specific gene expression (ASGE) appears to be an important factor in human phenotypic variability and as a consequence, for the development of complex traits and diseases. In order to study ASGE across the human genome, we have performed a study in which genotyping was coupled with an analysis of ASGE by screening 11,500 SNPs using the Mapping 10 K Array to identify differential allelic expression. We found that from the 5,133 SNPs that were suitable for analysis (heterozygous in our sample and expressed in peripheral blood mononuclear cells), 2,934 (57%) SNPs had differential allelic expression. Such SNPs were equally distributed along human chromosomes and biological processes. We validated the presence or absence of ASGE in 18 out 20 SNPs (90%) randomly selected by real time PCR in 48 human subjects. In addition, we observed that SNPs close to -but not included in-segmental duplications had increased levels of ASGE. Finally, we found that transcripts of unknown function or non-coding RNAs, also display ASGE: from a total of 2,308 intronic SNPs, 1510 (65%) SNPs underwent differential allelic expression. In summary, ASGE is a widespread mechanism in the human genome whose regulation seems to be far more complex than expected

Nonenzymatic gluconeogenesis-like formation of fructose 1,6-bisphosphate in ice

The evolutionary origins of metabolism, in particular the emergence of the sugar phosphates that constitute glycolysis, the pentose phosphate pathway, and the RNA and DNA backbone, are largely unknown. In cells, a major source of glucose and the large sugar phosphates is gluconeogenesis. This ancient anabolic pathway (re-)builds carbon bonds as cleaved in glycolysis in an aldol condensation of the unstable catabolites glyceraldehyde 3-phosphate and dihydroxyacetone phosphate, forming the much more stable fructose 1,6-bisphosphate. We here report the discovery of a nonenzymatic counterpart to this reaction. The in-ice nonenzymatic aldol addition leads to the continuous accumulation of fructose 1,6-bisphosphate in a permanently frozen solution as followed over months. Moreover, the in-ice reaction is accelerated by simple amino acids, in particular glycine and lysine. Revealing that gluconeogenesis may be of nonenzymatic origin, our results shed light on how glucose anabolism could have emerged in early life forms. Furthermore, the amino acid acceleration of a key cellular anabolic reaction may indicate a link between prebiotic chemistry and the nature of the first metabolic enzymes.This work was supported by a University of Cambridge/Wellcome Trust Interdisciplinary fellowship (to C.B.M.). Further support was provided by the Francis Crick Institute, which receives its core funding from Cancer Research UK (Award FC001134), the UK Medical Research Council (Award FC001134), and the Wellcome Trust (Award FC001134)

The origin of large molecules in primordial autocatalytic reaction networks

Large molecules such as proteins and nucleic acids are crucial for life, yet their primordial origin remains a major puzzle. The production of large molecules, as we know it today, requires good catalysts, and the only good catalysts we know that can accomplish this task consist of large molecules. Thus the origin of large molecules is a chicken and egg problem in chemistry. Here we present a mechanism, based on autocatalytic sets (ACSs), that is a possible solution to this problem. We discuss a mathematical model describing the population dynamics of molecules in a stylized but prebiotically plausible chemistry. Large molecules can be produced in this chemistry by the coalescing of smaller ones, with the smallest molecules, the `food set', being buffered. Some of the reactions can be catalyzed by molecules within the chemistry with varying catalytic strengths. Normally the concentrations of large molecules in such a scenario are very small, diminishing exponentially with their size. ACSs, if present in the catalytic network, can focus the resources of the system into a sparse set of molecules. ACSs can produce a bistability in the population dynamics and, in particular, steady states wherein the ACS molecules dominate the population. However to reach these steady states from initial conditions that contain only the food set typically requires very large catalytic strengths, growing exponentially with the size of the catalyst molecule. We present a solution to this problem by studying `nested ACSs', a structure in which a small ACS is connected to a larger one and reinforces it. We show that when the network contains a cascade of nested ACSs with the catalytic strengths of molecules increasing gradually with their size (e.g., as a power law), a sparse subset of molecules including some very large molecules can come to dominate the system.Comment: 49 pages, 17 figures including supporting informatio

Déficit de ornitina transcarbamilasa. Caso clínico

Los trastornos del ciclo de la urea suponen hasta el 60% de las hiperamoniemias graves neonatales. La base de los trastornos de este ciclo deriva en el de´ficit de una de sus enzimas. El de´ficit de la enzima ornitina transcarbamilasa es el ma´s frecuente. Su prono´stico dependera´ del grado de deficiencia enzima´tica, la edad, la precocidad del diagno´stico e inicio del tratamiento. Presentamos el caso de un adolescente que, a partir de un cuadro de para´lisis facial perife´rica tratado con prednisona, presento´ agravamiento de su estado general y fallecio´ a los pocos di´as. Las cifras elevadas de amoniaco en sangre hicieron sospechar tardi´amente de una alteracio´n conge´nita del ciclo de la urea, que fue confirmada por su estudio gene´tico post mortem. Se estudiaron los familiares y se asesoro´ a los afectos y portadores. Reflexionamos sobre la importancia de los programas de cribado neonatal y la posibilidad de aplicarlos en la deteccio´n de los errores conge´nitos del metabolismo