Minimum Action Path theory reveals the details of stochastic biochemical transitions out of oscillatory cellular states

Cell state determination is the outcome of intrinsically stochastic biochemical reactions. Tran- sitions between such states are studied as noise-driven escape problems in the chemical species space. Escape can occur via multiple possible multidimensional paths, with probabilities depending non-locally on the noise. Here we characterize the escape from an oscillatory biochemical state by minimizing the Freidlin-Wentzell action, deriving from it the stochastic spiral exit path from the limit cycle. We also use the minimized action to infer the escape time probability density function

Blueprint for a minimal photoautotrophic cell: conserved and variable genes in Synechococcus elongatus PCC 7942

This is an Open Access article distributed under the terms of the Creative Commons Attribution License.-- et al.Abstract Background Simpler biological systems should be easier to understand and to engineer towards pre-defined goals. One way to achieve biological simplicity is through genome minimization. Here we looked for genomic islands in the fresh water cyanobacteria Synechococcus elongatus PCC 7942 (genome size 2.7 Mb) that could be used as targets for deletion. We also looked for conserved genes that might be essential for cell survival. Results By using a combination of methods we identified 170 xenologs, 136 ORFans and 1401 core genes in the genome of S. elongatus PCC 7942. These represent 6.5%, 5.2% and 53.6% of the annotated genes respectively. We considered that genes in genomic islands could be found if they showed a combination of: a) unusual G+C content; b) unusual phylogenetic similarity; and/or c) a small number of the highly iterated palindrome 1 (HIP1) motif plus an unusual codon usage. The origin of the largest genomic island by horizontal gene transfer (HGT) could be corroborated by lack of coverage among metagenomic sequences from a fresh water microbialite. Evidence is also presented that xenologous genes tend to cluster in operons. Interestingly, most genes coding for proteins with a diguanylate cyclase domain are predicted to be xenologs, suggesting a role for horizontal gene transfer in the evolution of Synechococcus sensory systems. Conclusions Our estimates of genomic islands in PCC 7942 are larger than those predicted by other published methods like SIGI-HMM. Our results set a guide to non-essential genes in S. elongatus PCC 7942 indicating a path towards the engineering of a model photoautotrophic bacterial cell.Financial support was provided by grants BFU2009-12895-C02-01/BMC (Ministerio de Ciencia e Innovación, Spain), the European Community’s Seventh Framework Programme (FP7/2007-2013) under grant agreement number 212894 and Prometeo/2009/092 (Conselleria d’Educació, Generalitat Valenciana, Spain) to A. Moya. Work in the FdlC laboratory was supported by grants BFU2008-00995/BMC (Spanish Ministry of Education), RD06/0008/1012 (RETICS research network, Instituto de Salud Carlos III, Spanish Ministry of Health) and LSHM-CT-2005_019023 (European VI Framework Program). Dr. González-Domenech was supported by grant from the University of Granada. LD, thanks to financial support from Facultad de Ciencias, Universidad Nacional Autónoma de México.Peer Reviewe

Spread of blaCTX-M-14 is driven mainly by IncK plasmids disseminated among Escherichia coli phylogroups A, B1, and D in Spain

et al.Since its first description in 2000, CTX-M-14 has become one of the most widespread extended-spectrum β-lactamases in Spain. In the present Escherichia coli multilevel population genetic study involving the characterization of phylogroups, clones, plasmids, and genetic platforms, 61 isolates from 16 hospitalized patients and 40 outpatients and healthy volunteers recovered from 2000 to 2005 were analyzed. Clonal relatedness (XbaI pulsed-field gel electrophoresis [PFGE] type, phylogenetic group, multilocus sequence type [MLST]) was established by standard methods. Analysis of transferred plasmids (I-CeuI; S1 nuclease; restriction fragment length polymorphism analysis; and analysis of RNA interference, replicase, and relaxase) was performed by PCR, sequencing, and hybridization. The genetic environment of blaCTX-M-14 was characterized by PCR on the basis of known associated structures (ISEcp1, IS903, ISCR1). The isolates were mainly recovered from patients in the community (73.8%; 45/61) with urinary tract infections (62.2%; 28/45). They were clonally unrelated by PFGE and corresponded to phylogenetic groups A (36.1%), D (34.4%), and B1 (29.5%). MLST revealed a high degree of sequence type (ST) diversity among phylogroup D isolates and the overrepresentation of the ST10 complex among phylogroup A isolates and ST359/ST155 among phylogroup B1 isolates. Two variants of blaCTX-M-14 previously designated blaCTX-M-14a (n = 59/61) and bla CTX-M-14b (n = 2/61) were detected. blaCTX-M-14a was associated with either ISEcp1 within IncK plasmids (n = 27), ISCR1 linked to an IncHI2 plasmid (n = 1), or ISCR1 linked to IncI-like plasmids (n = 3). The blaCTX-M-14b identified was associated with an ISCR1 element located in an IncHI2 plasmid (n = 1) or with ISEcp1 located in IncK (n = 1). The CTX-M-14-producing E. coli isolates in our geographic area are frequent causes of community-acquired urinary tract infections. The increase in the incidence of such isolates is mostly due to the dissemination of IncK plasmids among E. coli isolates of phylogroups A, B1, and D. Copyright © 2009, American Society for Microbiology. All Rights Reserved.A.V. is supported by CIBERESP Network for Biomedical Research in Epidemiology and Public Health (Instituto Carlos III, Spanish Ministry of Science and Innovation). Work by the HRYC group was funded by research grants from the European Commission (grants LSHM-CT-2005-018705, LSHM-CT-2009-223031, and KBBE-2008-2B-227258) and the Spanish Ministry of Health and Innovation (CB06/ 02/0053 and FIS 08/624). Work in the FdlC laboratory was supported by grants from the European Commission (grant LSHM-CT-2005_019023); the Spanish Ministry of Education (grant BFU2008- 00995/BMC); and the RETICS Research Network, Instituto de Salud Carlos III, Spanish Ministry of Health (grant RD06/0008/1012).Peer Reviewe

New Approach for Managing Sustainability in Projects

[Abstract] Despite the work done to date, project sustainability management (PSM) is still at an embryonic stage. The existing literature considers sustainability as a transversal aspect to be incorporated into the traditional management functions (scope, time, cost, quality, etc.). This article proposes sustainability as a key aspect of project management, with three essential components: principles, processes and competences. Regarding principles, the principle of sustainable development should be added to those generally suggested. As for processes, seven are proposed for (1) planning sustainability management; (2) establishing a sustainability breakdown structure; (3) defining the sustainability objective; (4) identifying project alternatives to achieve it; (5) planning and (6) implementing the sustainability strategy; and (7) monitoring and control. The main interrelationships between these processes and those of project initiation, planning, implementation, control, and closure are also analysed. In addition, the competences that the project manager should have in this field are identified, as well as the main criteria to take into account in order to adapt PSM processes to the characteristics of the project and the organisation. Finally, the results of a Delphi analysis carried out to validate these proposals are presented

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Altres ajuts: CERCA Programme/Generalitat de Cataluny

Optimisation Techniques for Managing the Project Sustainability Objective: Application to a Shell and Tube Heat Exchanger

[Abstract] In addition to traditional project management objectives (cost, time, scope and quality, among others), it is now necessary to include a global sustainability objective in all projects, regardless of their nature and scale. The processes for managing this objective may include sub-processes for optimising the sustainability of some or all of the project’s deliverables. In this paper an integrated optimisation technique was applied to optimise the design of a shell and tube heat exchanger (STHE) by taking into account economic, social and environmental indicators. A case study previously analysed in the literature, although with different objectives and scope, was considered for such a purpose. Diverse sets of weights were defined for the environmental impacts, as well as two additional cases. In the first one, all the indicators where assessed in a linear way. Non-linearities were studied in the second one. Both non-nature-inspired (exhaustive search and Monte Carlo simulation) and nature-inspired (Particle Swarm Optimisation, Crow Search Algorithm and Non-dominated Sorting Genetic Algorithm-II) optimisation techniques were used to solve the problem. The results were presented and discussed in depth. The findings show the necessity of applying these kinds of methodologies in the design of energy systems and, in particular, STHE

Plasmid flux in Escherichia coli ST131 sublineages, analyzed by plasmid constellation network (PLACNET), a new method for plasmid reconstruction from whole genome sequences

This is an open-access article distributed under the terms of the Creative Commons Attribution License.Bacterial whole genome sequence (WGS) methods are rapidly overtaking classical sequence analysis. Many bacterial sequencing projects focus on mobilome changes, since macroevolutionary events, such as the acquisition or loss of mobile genetic elements, mainly plasmids, play essential roles in adaptive evolution. Existing WGS analysis protocols do not assort contigs between plasmids and the main chromosome, thus hampering full analysis of plasmid sequences. We developed a method (called plasmid constellation networks or PLACNET) that identifies, visualizes and analyzes plasmids in WGS projects by creating a network of contig interactions, thus allowing comprehensive plasmid analysis within WGS datasets. The workflow of the method is based on three types of data: assembly information (including scaffold links and coverage), comparison to reference sequences and plasmid-diagnostic sequence features. The resulting network is pruned by expert analysis, to eliminate confounding data, and implemented in a Cytoscape-based graphic representation. To demonstrate PLACNET sensitivity and efficacy, the plasmidome of the Escherichia coli lineage ST131 was analyzed. ST131 is a globally spread clonal group of extraintestinal pathogenic E. coli (ExPEC), comprising different sublineages with ability to acquire and spread antibiotic resistance and virulence genes via plasmids. Results show that plasmids flux in the evolution of this lineage, which is wide open for plasmid exchange. MOBF12/IncF plasmids were pervasive, adding just by themselves more than 350 protein families to the ST131 pangenome. Nearly 50% of the most frequent γ–proteobacterial plasmid groups were found to be present in our limited sample of ten analyzed ST131 genomes, which represent the main ST131 sublineages.Work was financed by the Spanish Ministry of Economy and Competitivity (BFU2011-26608 to FdlC, FIS-PI09/01273 and AGL2013-47852-R to JB and FIS-PI12-01581 and CB06/02/0053 to TMC), by the European Seventh Framework Program (612146/FP7-ICT-2013-10 to FdlC and 282004/FP7-HEALTH-2011-2.3.1-2 to FdlC and TMC); by Red Española de Investigación en Patología­ Infecciosa (REIPI RD06/0008/1018-1016) to JB, by Consellería de Cultura, Educación e Ordenación Universitaria, Xunta de Galicia and European Regional Development Fund, ERDF (CN2012/303 and EM2014/001) to JB and by the regional government of Madrid (PROMPT-S2010/BMD2414) to TMC. We are also grateful to the Spanish Network for the Study of Plasmids and Extrachromosomal Elements (REDEEX) for funding cooperation among Spanish microbiologists working on the biology of MGEs (Spanish Ministry of Science and Innovation BFU2011-14145-E).Peer Reviewe

Triplication of the photocurrent in dye solar cells by increasing the elongation of the π-conjugation in Zn-porphyrin sensitizers

Porphyrins are promising sensitizers for dye solar cells (DSCs) but narrow absorption bands at 400-450 and 500-650 nm limit their light-harvesting properties. Increasing elongation of the π-conjugation and loss of symmetry causes broadening and a red-shift of the absorption bands, which considerably improves the performance of the DSC. Herein we use an oligothienylenevinylene to bridge a Zn-porphyrin system and the anchoring group of the sensitizer. We separately study the performance of the two basic units: oligothienylenevinylene and Zn-porphyrin. The combined system provides a three-fold enhancement of the photocurrent with respect to parent dyes. This is caused by an additional strong absorption in the region 400-650 nm that leads to flat IPCE of 60%. Theoretical calculations support that the addition of the oligothienylenevinylene unit as a linking bridge creates a charge transfer band that transforms a Zn-porphyrin dye into a push-pull type system with highly efficient charge injection propertie

The effects of intrinsic noise on the behaviour of bistable cell regulatory systems under quasi-steady state conditions

We analyse the effect of intrinsic fluctuations on the properties of bistable stochastic systems with time scale separation operating under1 quasi-steady state conditions. We first formulate a stochastic generalisation of the quasi-steady state approximation based on the semi-classical approximation of the partial differential equation for the generating function associated with the Chemical Master Equation. Such approximation proceeds by optimising an action functional whose associated set of Euler-Lagrange (Hamilton) equations provide the most likely fluctuation path. We show that, under appropriate conditions granting time scale separation, the Hamiltonian can be re-scaled so that the set of Hamilton equations splits up into slow and fast variables, whereby the quasi-steady state approximation can be applied. We analyse two particular examples of systems whose mean-field limit has been shown to exhibit bi-stability: an enzyme-catalysed system of two mutually-inhibitory proteins and a gene regulatory circuit with self-activation. Our theory establishes that the number of molecules of the conserved species are order parameters whose variation regulates bistable behaviour in the associated systems beyond the predictions of the mean-field theory. This prediction is fully confirmed by direct numerical simulations using the stochastic simulation algorithm. This result allows us to propose strategies whereby, by varying the number of molecules of the three conserved chemical species, cell properties associated to bistable behaviour (phenotype, cell-cycle status, etc.) can be controlled.Comment: 33 pages, 9 figures, accepted for publication in the Journal of Chemical Physic