Dealing with the genetic load in bacterial synthetic biology circuits: convergences with the Ohm's law.

Synthetic biology seeks to envision living cells as a matter of engineering. However, increasing evidence suggests that the genetic load imposed by the incorporation of synthetic devices in a living organism introduces a sort of unpredictability in the design process. As a result, individual part characterization is not enough to predict the behavior of designed circuits and thus, a costly trial-error process is eventually required. In this work, we provide a new theoretical framework for the predictive treatment of the genetic load. We mathematically and experimentally demonstrate that dependences among genes follow a quantitatively predictable behavior. Our theory predicts the observed reduction of the expression of a given synthetic gene when an extra genetic load is introduced in the circuit. The theory also explains that such dependence qualitatively differs when the extra load is added either by transcriptional or translational modifications. We finally show that the limitation of the cellular resources for gene expression leads to a mathematical formulation that converges to an expression analogous to the Ohm's law for electric circuits. Similitudes and divergences with this law are outlined. Our work provides a suitable framework with predictive character for the design process of complex genetic devices in synthetic biology.

In silico analysis of arginine catabolism as a source of nitric oxide or polyamines in endothelial cells.

We use a modeling and simulation approach to carry out an in silico analysis of the metabolic pathways involving arginine as a precursor of nitric oxide or polyamines in aorta endothelial cells. Our model predicts conditions of physiological steady state, as well as the response of the system to changes in the control parameter, external arginine concentration. Metabolic flux control analysis allowed us to predict the values of flux control coefficients for all the transporters and enzymes included in the model. This analysis fulfills the flux control coefficient summation theorem and shows that both the low affinity transporter and arginase share the control of the fluxes through these metabolic pathways.

Polyamines: metabolism to systems biology and beyond.

Polyamines and the metabolic and physiopathological processes in which they are involved represent an active field of research that has been continuously growing since the seventies. In the last years, the trends in the focused areas of interest within this field since the 1970s have been confirmed. The impact of "-omics" in polyamine research remains too low in comparison with its deep impact on other biological research areas. These high-throughput approaches, along with systems biology and, in general, more systemic and holistic approaches should contribute to a renewal of this research area in the near future.

The usefulness of post-genomics tools for characterization of the amine cross-talk in mammalian cells.

Evidence is growing in favour of a relationship between cancer and chronic inflammation, and particularly of the role of a polyamine and histamine metabolic interplay involved in these physiopathological problems, which are indeed highly complex biological systems. Decodification of the complex inter- and intra-cellular signalling mechanisms that control these effects is not an easy task, which must be helped by systems biology technologies, including new tools for location and integration of database-stored information and predictive mathematical models, as well as functional genomics and other experimental molecular approaches necessary for hypothesis validation. We review the state of the art and present our latest efforts in this area, focused on the amine metabolism field.

[Tracheobronchial lesions due to anesthetic procedures. Report of 2 cases]. / Lesiones traqueobronquiales debidas a procedimientos anestésicos. A propósito de 2 casos.

We have reviewed 48.000 patients who underwent surgery with general anesthesia in our department during the last 12 years. We have found 14 cases of tracheal rupture (2.9%). In 7 cases (1.4%) rupture was due to direct trauma or laceration at the thorax or neck; in 5 patients (1.04%) it was produced by steel blade or firearm; and in the remaining 2 cases (0.4%) tracheal rupture was produced during anesthesia. In one of these two patients rupture was produced by a double lumen Carlens tube used during a right thoracotomy. This patient had previous history of pulmonary tuberculosis and chronic bronchitis. Tracheal rupture occurred at the end of the surgical procedure coinciding with a displacement of the endotracheal tube and was suspected because the presence of air escape. It was verified by exploring the mediastinal pleura. Due to the rapid diagnosis and prompt repair the lesion had no clinical consequences and the surgical intervention was successfully completed. The second patient underwent a diagnostic laparomy and presented tracheal rupture due to severe bronchospasm during and apparently normal intubation procedure. The moment at which the tracheal lesion occurred was unnoticed and the patient suffered a progressive ventilatory deterioration requiring reanimation procedures to preserve the hemodynamic status and to restore blood oxygen concentration and to compensate blood acidoses. Tracheal rupture was repaired during a second intervention and was followed by a clinical recovery. However the patient died later due to a complication unrelated to the anestethetic technique.(ABSTRACT TRUNCATED AT 250 WORDS)