DiSCUS: A simulation platform for conjugation computing

© Springer International Publishing Switzerland 2015 In bacterial populations, cells are able to cooperate in order to yield complex collective functionalities. Interest in population-level cellular behaviour is increasing, due to both our expanding knowledge of the underlying biological principles, and the growing range of possible applications for engineered microbial consortia. The ability of cells to interact through small signalling molecules (a mechanism known as quorum sensing) is the basis for the majority of existing engineered systems. However, horizontal gene transfer (or conjugation) offers the possibility of cells exchanging messages (using DNA) that are much more information-rich. The potential of engineering this conjugation mechanism to suit specific goals will guide future developments in this area. Motivated by a lack of computational models for examining the specific dynamics of conjugation, we present a simulation framework for its further study. (This paper was first presented at the Spatial Computing Workshop of the 13th International Conference on Autonomous Agents and Multiagent Systems (AAMAS), Paris, France, May 5–9 2014. There were no published proceedings)

FtsZ of filamentous, heterocyst-forming cyanobacteria has a conserved N-Terminal peptide required for normal FtsZ polymerization and cell division

Filamentous cyanobacteria grow by intercalary cell division, which should involve distinct steps compared to those producing separate daughter cells. The N-terminal region of FtsZ is highly conserved in the clade of filamentous cyanobacteria capable of cell differentiation. A derivative of the model strain Anabaena sp. PCC 7120 expressing only an FtsZ lacking the amino acids 2-51 of the N-terminal peptide (1N-FtsZ) could not be segregated. Strain CSL110 expresses both 1N-FtsZ, from the endogenous ftsZ gene promoter, and the native FtsZ from a synthetic regulated promoter. Under conditions of 1N-FtsZ predominance, cells of strain CSL110 progressively enlarge, reflecting reduced cell division, and show instances of asymmetric cell division and aberrant Z-structures notably differing from the Z-ring formed by FtsZ in the wild type. In bacterial 2-hybrid assays FtsZ interacted with 1N-FtsZ. However, 1N-FtsZ-GFP appeared impaired for incorporation into Z-rings when expressed together with FtsZ. FtsZ, but not 1N-FtsZ, interacted with the essential protein SepF. Both FtsZ and 1N-FtsZ polymerize in vitro exhibiting comparable GTPase activities. However, filaments of FtsZ show a distinct curling forming toroids, whereas 1N-FtsZ form thick bundles of straight filaments. Thus, the N-terminal FtsZ sequence appears to contribute to a distinct FtsZ polymerization mode that is essential for cell division and division plane location in Anabaena.Agencia Estatal de Investigación BFU2013-44686-P BFU2016-77097-

RF plasma cleaning of optical surfaces: A study of cleaning rates on different carbon allotropes as a function of RF powers and distances

An extended study on an advanced method for the cleaning of carbon contaminations on large optical surfaces using a remote inductively coupled low pressure RF plasma source (GV10x downstream asher) is reported in this work. Technical as well as scientific features of this scaled up cleaning process are analyzed, such as the cleaning efficiency for different carbon allotropes (amorphous and diamond-like carbon) as a function of feedstock gas composition, RF power (ranging from 30 to 300W), and source-object distances (415 to 840 mm). The underlying physical phenomena for these functional dependences are discussed.Comment: 16 pages, 9 figure

SynBioHub: A Standards-Enabled Design Repository for Synthetic Biology.

The SynBioHub repository (synbiohub.org) is an open-source software project which facilitates the sharing of information about engineered biological systems. SynBioHub provides computational access for software and data integration, and a graphical user interface that enables users to search for and share designs in a Web browser. By connecting to relevant repositories (e.g. the iGEM repository, JBEI ICE, and other instances of SynBioHub), the software allows users to browse, upload, and download data in various standard formats, regardless of their location or representation. SynBioHub also provides a central reference point for other resources to link to, delivering design information in a standardized format using the Synthetic Biology Open Language (SBOL). The adoption and use of SynBioHub, a community-driven effort, has the potential to overcome the reproducibility challenge across laboratories by helping to address the current lack of information about published designs

An implementation-focused bio/algorithmic workflow for synthetic biology.

As synthetic biology moves away from trial and error and embraces more formal processes, workflows have emerged that cover the roadmap from conceptualization of a genetic device to its construction and measurement. This latter aspect (i.e. characterization and measurement of synthetic genetic constructs) has received relatively little attention thus far, but it is crucial for their outcome. An end-to-end use case for engineering a simple synthetic device is presented which is supported by information standards and computational methods, and which focuses on such characterization/measurement. This workflow captures the main stages of genetic device design and description and offers standardized tools for both population-based measurement and single-cell analysis. To this end, three separate aspects are addressed. First, the specific vector features. Although device/circuit design has been successfully automated, important structural information is usually overlooked, as is the case of plasmid vectors. The use of the Standard European Vector Architecture (SEVA) is advocated for selecting the optimal carrier of a design and its thorough description, in order to unequivocally correlate digital definitions and molecular devices. A digital version of this plasmid format was developed with the Synthetic Biology Open Language (SBOL) along with a software tool that allows users to embed genetic parts in vector cargoes. This enables annotation of a mathematical model of the device's kinetic reactions formatted with the Systems Biology Markup Language (SBML). From that point onwards the experimental results and their in silico counterparts proceed alongside, with constant feedback to preserve consistency between them. A second aspect involves a framework for the calibration of fluorescence-based measurements. One of the most challenging endeavors in standardization, metrology, is tackled by reinterpreting the experimental output in light of simulation results, allowing us to turn arbitrary fluorescent units into relative measurements. Finally, integration of single-cell methods into a framework for multicellular simulation and measurement is addressed, allowing standardized inspection of the interplay between the carrier chassis and the culture conditions

Birth weight and blood lipid levels in Spanish adolescents: Influence of selected APOE, APOC3 and PPARgamma2 gene polymorphisms. The AVENA Study

Es reproducción del documento publicado en http://dx.doi.org/10.1186/1471-2350-9-98Background: There is increasing evidence indicating that genes involved in certain metabolic processes of cardiovascular diseases may be of particular influence in people with low body weight at birth. We examined whether the apolipoprotein (APO) E, APOC3 and the peroxisome proliferator-activated receptor-gamma-2 (PPAR gamma 2) polymorphisms influence the association between low birth weight and blood lipid levels in healthy adolescents aged 13-18.5 years. Methods: A cross-sectional study of 502 Spanish adolescents born at term was conducted. Total (TC) and high density lipoprotein cholesterol (HDLc), triglycerides (TG), apolipoprotein (apo) A and B, and lipoprotein(a) [ Lp(a)] were measured. Low density lipoprotein cholesterol (LDLc), TC-HDLc, TC/HDLc and apoB/apoA were calculated. Results: Low birth weight was associated with higher levels of TC, LDLc, apoB, Lp(a), TC-HDLc, TC/HDLc and apoB/apoA in males with the APOE epsilon 3 epsilon 4 genotype, whereas in females, it was associated with lower HDLc and higher TG levels. In males with the APOC3 S1/S2 genotype, low birth weight was associated with lower apoA and higher Lp(a), yet this association was not observed in females. There were no associations between low birth weight and blood lipids in any of the PPAR gamma 2 genotypes. Conclusion: The results indicate that low birth weight has a deleterious influence on lipid profile particularly in adolescents with the APOE epsilon 3/epsilon 4 genotype. These findings suggest that intrauterine environment interact with the genetic background affecting the lipid profile in later life.Instituto de Salud Carlos III (FIS PI021830), the Spanish Ministry of Health, FEDER-FSE funds FIS n 00/0015, CSD grants 05/UPB32/0, 109/UPB31/03 and 13/UPB20/04, Ministerio de Educación (AP-2004-2745; EX2007-1124

Trends in socioeconomic inequalities in mortality in small areas of 33 Spanish cities

Background: In Spain, several ecological studies have analyzed trends in socioeconomic inequalities in mortality from all causes in urban areas over time. However, the results of these studies are quite heterogeneous finding, in general, that inequalities decreased, or remained stable. Therefore, the objectives of this study are: (1) to identify trends in geographical inequalities in all-cause mortality in the census tracts of 33 Spanish cities between the two periods 1996–1998 and 2005–2007; (2) to analyse trends in the relationship between these geographical inequalities and socioeconomic deprivation; and (3) to obtain an overall measure which summarises the relationship found in each one of the cities and to analyse its variation over time.Methods: Ecological study of trends with 2 cross-sectional cuts, corresponding to two periods of analysis: 1996–1998 and 2005–2007. Units of analysis were census tracts of the 33 Spanish cities. A deprivation index calculated for each census tracts in all cities was included as a covariate. A Bayesian hierarchical model was used to estimate smoothed Standardized Mortality Ratios (sSMR) by each census tract and period. The geographical distribution of these sSMR was represented using maps of septiles. In addition, two different Bayesian hierarchical models were used to measure the association between all-cause mortality and the deprivation index in each city and period, and by sex: (1) including the association as a fixed effect for each city; (2) including the association as random effects. In both models the data spatial structure can be controlled within each city. The association in each city was measured using relative risks (RR) and their 95 % credible intervals (95 % CI).Results: For most cities and in both sexes, mortality rates decline over time. For women, the mortality and deprivation patterns are similar in the first period, while in the second they are different for most cities. For men, RRs remain stable over time in 29 cities, in 3 diminish and in 1 increase. For women, in 30 cities, a non-significant change over time in RR is observed. However, in 4 cities RR diminishes. In overall terms, inequalities decrease (with a probability of 0.9) in both men (RR¿=¿1.13, 95 % CI¿=¿1.12–1.15 in the 1st period; RR¿=¿1.11, 95 % CI¿=¿1.09–1.13 in the 2nd period) and women (RR¿=¿1.07, 95 % CI¿=¿1.05–1.08 in the 1st period; RR¿=¿1.04, 95 % CI¿=¿1.02–1.06 in the 2nd period).Conclusions: In the future, it is important to conduct further trend studies, allowing to monitoring trends in socioeconomic inequalities in mortality and to identify (among other things) temporal factors that may influence these inequalities

The two-component system BvrR/BvrS essential for Brucella abortus virulence regulates the expression of outer membrane proteins with counterparts in members of the Rhizobiaceae

The Brucella BvrR/BvrS two-component regulatory system is homologous to the ChvI/ChvG systems of Sinorhizobium meliloti and Agrobacterium tumefaciens necessary for endosymbiosis and pathogenicity in plants. BvrR/BvrS controls cell invasion and intracellular survival. Probing the surface of bvrR and bvrS transposon mutants with monoclonal antibodies showed all described major outer membrane proteins (Omps) but Omp25, a protein known to be involved in Brucella virulence. Absence of Omp25 expression was confirmed by two-dimensional electrophoresis of envelope fractions and by gene reporter studies. The electrophoretic analysis also revealed reduction or absence in the mutants of a second set of protein spots that by matrix-assisted laser desorption ionization MS and peptide mass mapping were identified as a non-previously described Omp (Omp3b). Because bvrR and bvrS mutants are also altered in cell-surface hydrophobicity, permeability, and sensitivity to surf ace-targeted bactericidal peptides, it is proposed that BvrR/BvrS controls cell envelope changes necessary to transit between extracellular and intracellular environments. A genomic search revealed that Omp25 (Omp3a) and Omp3b belong to a family of Omps of plant and animal cell-associated alpha-Proteobacteria, which includes Rhizobium leguminosarum RopB and A. tumefaciens AopB. Previous work has shown that RopB is not expressed in bacteroids, that AopB is involved in tumorigenesis, and that dysfunction of A. tumetaciens ChvI/ChvG alters surface properties. It is thus proposed that the BvrR/BvrS and Omp3 homologues of the cell-associated a-Proteobacteria play a role in bacterial surface control and host cell interactions

Pathways to cellular supremacy in biocomputing

Synthetic biology uses living cells as the substrate for performing human-defined computations. Many current implementations of cellular computing are based on the “genetic circuit” metaphor, an approximation of the operation of silicon-based computers. Although this conceptual mapping has been relatively successful, we argue that it fundamentally limits the types of computation that may be engineered inside the cell, and fails to exploit the rich and diverse functionality available in natural living systems. We propose the notion of “cellular supremacy” to focus attention on domains in which biocomputing might offer superior performance over traditional computers. We consider potential pathways toward cellular supremacy, and suggest application areas in which it may be found.A.G.-M. was supported by the SynBio3D project of the UK Engineering and Physical Sciences Research Council (EP/R019002/1) and the European CSA on biological standardization BIOROBOOST (EU grant number 820699). T.E.G. was supported by a Royal Society University Research Fellowship (grant UF160357) and BrisSynBio, a BBSRC/ EPSRC Synthetic Biology Research Centre (grant BB/L01386X/1). P.Z. was supported by the EPSRC Portabolomics project (grant EP/N031962/1). P.C. was supported by SynBioChem, a BBSRC/EPSRC Centre for Synthetic Biology of Fine and Specialty Chemicals (grant BB/M017702/1) and the ShikiFactory100 project of the European Union’s Horizon 2020 research and innovation programme under grant agreement 814408