A case study in model-driven synthetic biology

We report on a case study in synthetic biology, demonstrating the modeldriven design of a self-powering electrochemical biosensor. An essential result of the design process is a general template of a biosensor, which can be instantiated to be adapted to specific pollutants. This template represents a gene expression network extended by metabolic activity. We illustrate the model-based analysis of this template using qualitative, stochastic and continuous Petri nets and related analysis techniques, contributing to a reliable and robust design

Furthering the understanding of silicate-substitution in α-tricalcium phosphate : an X-ray diffraction, X-ray fluorescence and solid-state nuclear magnetic resonance study

High-purity (SupT) and reagent-grade (ST), stoichiometric and silicate-containing α-tricalcium phosphate (α-TCP: ST0/SupT0 and Si-TCP x = 0.10: ST10/SupT10) were prepared by solid-state reaction based on the substitution mechanism Ca3(PO4)(2-x)(SiO4)x. Samples were determined to be phase pure by X-ray diffraction (XRD), and Rietveld analysis performed on the XRD data confirmed inclusion of Si in the α-TCP structure as determined by increases in unit cell parameters; particularly marked increases in the b-axis and β-angle were observed. X-ray fluorescence (XRF) confirmed the presence of expected levels of Si in Si-TCP compositions as well as significant levels of impurities (Mg, Al and Fe) present in all ST samples; SupT samples showed both expected levels of Si and a high degree of purity. Phosphorus (31P) magic-angle-spinning solid-state nuclear magnetic resonance (MAS NMR) measurements revealed that the high-purity reagents used in the synthesis of SupT0 can resolve the 12 expected peaks in the 31P spectrum of α-TCP compared to the low-purity ST0 that showed significant spectral line broadening; line broadening was also observed with the inclusion of Si which is indicative of induced structural disorder. Silicon (29Si) MAS NMR was also performed on both Si-TCP samples which revealed Q0 species of Si with additional Si Q1/Q2 species that may indicate a potential charge-balancing mechanism involving the inclusion of disilicate groups; additional Q4 Si species were also observed, but only for ST10. Heating and cooling rates were briefly investigated by 31P MAS NMR which showed no significant line broadening other than that associated with the emergence of β-TCP which was only realised with the reagent-grade sample ST0. This study provides an insight into the structural effects of Si-substitution in α-TCP and could provide a basis for understanding how substitution affects the physicochemical properties of the material

Integration of Tmc1/2 into the mechanotransduction complex in zebrafish hair cells is regulated by Transmembrane O-methyltransferase (Tomt).

Transmembrane O-methyltransferase (TOMT / LRTOMT) is responsible for non-syndromic deafness DFNB63. However, the specific defects that lead to hearing loss have not been described. Using a zebrafish model of DFNB63, we show that the auditory and vestibular phenotypes are due to a lack of mechanotransduction (MET) in Tomt-deficient hair cells. GFP-tagged Tomt is enriched in the Golgi of hair cells, suggesting that Tomt might regulate the trafficking of other MET components to the hair bundle. We found that Tmc1/2 proteins are specifically excluded from the hair bundle in tomt mutants, whereas other MET complex proteins can still localize to the bundle. Furthermore, mouse TOMT and TMC1 can directly interact in HEK 293 cells, and this interaction is modulated by His183 in TOMT. Thus, we propose a model of MET complex assembly where Tomt and the Tmcs interact within the secretory pathway to traffic Tmc proteins to the hair bundle

Magnetoelectric ordering of BiFeO3 from the perspective of crystal chemistry

In this paper we examine the role of crystal chemistry factors in creating conditions for formation of magnetoelectric ordering in BiFeO3. It is generally accepted that the main reason of the ferroelectric distortion in BiFeO3 is concerned with a stereochemical activity of the Bi lone pair. However, the lone pair is stereochemically active in the paraelectric orthorhombic beta-phase as well. We demonstrate that a crucial role in emerging of phase transitions of the metal-insulator, paraelectric-ferroelectric and magnetic disorder-order types belongs to the change of the degree of the lone pair stereochemical activity - its consecutive increase with the temperature decrease. Using the structural data, we calculated the sign and strength of magnetic couplings in BiFeO3 in the range from 945 C down to 25 C and found the couplings, which undergo the antiferromagnetic-ferromagnetic transition with the temperature decrease and give rise to the antiferromagnetic ordering and its delay in regard to temperature, as compared to the ferroelectric ordering. We discuss the reasons of emerging of the spatially modulated spin structure and its suppression by doping with La3+.Comment: 18 pages, 5 figures, 3 table

<i>Pseudomonas aeruginosa</i> intensive care unit outbreak:winnowing of transmissions with molecular and genomic typing

Bioinformatics and computational biology analyses were supported by the University of St Andrews Bioinformatics Unit which is funded by a Wellcome Trust ISSF award [grant 097831/Z/11/Z]. BJP, KO, MP, MTGH, GP and SHG are funded by the Chief Scientist Office through the Scottish Infection Research Network, a part of the SHAIPI consortium grant reference number SIRN/10.Background: Pseudomonas aeruginosa healthcare outbreaks can be time consuming and difficult to investigate. Guidance does not specify which typing technique is most practical to base decisions on. Aim: We explore the usefulness of whole genome sequencing (WGS) in the investigation of a Pseudomonas aeruginosa outbreak describing how it compares with pulsed-field gel electrophoresis (PFGE) and variable number tandem repeat (VNTR) analysis. Methods: Six patient isolates and six environmental samples from an Intensive Care Unit (ICU) positive for P. aeruginosa over two years underwent VNTR, PFGE and WGS. Findings:  VNTR and PFGE were required to fully determine the potential source of infection and rule out others. WGS results unambiguously distinguished linked isolates giving greater assurance of the transmission route between wash hand basin (WHB) water and two patients supporting control measures employed. Conclusion:  WGS provided detailed information without need for further typing. When allied to epidemiological information it can be used to understand outbreak situations rapidly and with certainty. Implementation of WGS in real-time would be a major advance in day-to-day practice. It could become a standard of care as it becomes more widespread due to its reproducibility and reduction in costs.Publisher PDFPeer reviewe

Commitment versus persuasion in the three-party constrained voter model

In the framework of the three-party constrained voter model, where voters of two radical parties (A and B) interact with "centrists" (C and Cz), we study the competition between a persuasive majority and a committed minority. In this model, A's and B's are incompatible voters that can convince centrists or be swayed by them. Here, radical voters are more persuasive than centrists, whose sub-population consists of susceptible agents C and a fraction zeta of centrist zealots Cz. Whereas C's may adopt the opinions A and B with respective rates 1+delta_A and 1+delta_B (with delta_A>=delta_B>0), Cz's are committed individuals that always remain centrists. Furthermore, A and B voters can become (susceptible) centrists C with a rate 1. The resulting competition between commitment and persuasion is studied in the mean field limit and for a finite population on a complete graph. At mean field level, there is a continuous transition from a coexistence phase when zeta= Delta_c. In a finite population of size N, demographic fluctuations lead to centrism consensus and the dynamics is characterized by the mean consensus time tau. Because of the competition between commitment and persuasion, here consensus is reached much slower (zeta=Delta_c) than in the absence of zealots (when tau\simN). In fact, when zeta<Delta_c and there is an initial minority of centrists, the mean consensus time asymptotically grows as tau\simN^{-1/2} e^{N gamma}, where gamma is determined. The dynamics is thus characterized by a metastable state where the most persuasive voters and centrists coexist when delta_A>delta_B, whereas all species coexist when delta_A=delta_B. When zeta>=Delta_c and the initial density of centrists is low, one finds tau\simln N (when N>>1). Our analytical findings are corroborated by stochastic simulations.Comment: 25 pages, 6 figures. Final version for the Journal of Statistical Physics (special issue on the "applications of statistical mechanics to social phenomena"