Mathematical model of a serine integrase-controlled toggle switch with a single input

Dual-state genetic switches that can change their state in response to input signals can be used in synthetic biology to encode memory and control gene expression. A transcriptional toggle switch (TTS), with two mutually repressing transcription regulators, was previously used for switching between two expression states. In other studies, serine integrases have been used to control DNA inversion switches that can alternate between two different states. Both of these switches use two different inputs to switch ON or OFF. Here, we use mathematical modelling to design a robust one-input binary switch, which combines a TTS with a DNA inversion switch. This combined circuit switches between the two states every time it receives a pulse of a single-input signal. The robustness of the switch is based on the bistability of its TTS, while integrase recombination allows single-input control. Unidirectional integrase-RDF-mediated recombination is provided by a recently developed integrase-RDF fusion protein. We show that the switch is stable against parameter variations and molecular noise, making it a promising candidate for further use as a basic element of binary counting devices

Investigating corruption charges against womenheads of government

Much of the scholarship on gender and corruption suggests that women in political oÿce are less corrupt than men. However, in just the past five years, corruption accusations against women heads of government, including Brazil’s Dilma Rousse˙ and South Korea’s Park Geun-hye, have made headlines and led to their impeachment. In this article, we examine whether women heads of government are more likely to be charged with corruption and the process by which these charges are levied. Using cross-national data, including recently-available indicators, we first demonstrate that women are significantly more likely to be formally accused of corruption. We then explore the cases of Turkish Prime Minister Tansu Çiller and Brazilian President Dilma Rousse˙ to show that while women heads of government are taxed for perceived role incongruity, the logic and eÿcacy of corruption charges is also associated with the belief that women do not belong in the political sphere and are inherently agents of subversion. These findings make a substantial contribution to the literature on gender, leadership, and politics and corruption

The mechanism of ϕC31 integrase directionality : experimental analysis and computational modelling

Serine integrases, DNA site-specific recombinases used by bacteriophages for integration and excision of their DNA to and from their host genomes, are increasingly being used as tools for programmed rearrangements of DNA molecules for biotechnology and synthetic biology. A useful feature of serine integrases is the simple regulation and unidirectionality of their reactions. Recombination between the phage attP and host attB sites is promoted by the serine integrase alone, giving recombinant attL and attR sites, whereas the 'reverse' reaction (between attL and attR) requires an additional protein, the recombination directionality factor (RDF). Here, we present new experimental data on the kinetics and regulation of recombination reactions mediated by ϕC31 integrase and its RDF, and use these data as the basis for a mathematical model of the reactions. The model accounts for the unidirectionality of the attP × attB and attL × attR reactions by hypothesizing the formation of structurally distinct, kinetically stable integrase-DNA product complexes, dependent on the presence or absence of RDF. The model accounts for all the available experimental data, and predicts how mutations of the proteins or alterations of reaction conditions might increase the conversion efficiency of recombination

Enantioselective isothiourea-catalysed trans-dihydropyridinone synthesis using saccharin-derived ketimines : scope and limitations

The authors thank Syngenta and the EPSRC (grant code EP/K503162/1) (DGS) for funding. The European Research Council under the European Union’s Seventh Framework Programme (FP7/2007-2013) ERC Grant Agreement No. 279850 is also acknowledged (CMY). ADS thanks the Royal Society for a Wolfson Research Merit Award. We also thank the EPSRC UK National Mass Spectrometry Facility at Swansea University.The catalytic enantioselective synthesis of a range of trans-dihydropyridinones from aryl-, heteroaryl- and alkenylacetic acids and saccharin-derived ketimines with good to excellent stereocontrol (15 examples, up to >95:5 dr, up to >99:1 er) is reported. After extensive optimisation, HyperBTM proved the optimal isothiourea catalyst for this transformation at −78 °C, giving trans-dihydropyridones with generally excellent levels of diastereo- and enantioselectivity.Publisher PDFPeer reviewe

A Multi-Perspective Assessment of the Introduction of E-Scooter Sharing in Germany

Electric scooter sharing (e-scooter sharing) is a new urban micro-mobility service that is expected to shape individual urban mobility. The introduction of e-scooter sharing systems poses challenging questions for cities and transportation planners regarding their effects on their transportation system. This study addresses the question concerning the strategies which are applied for the introduction of e-scooter sharing systems in different operation areas in Germany. An interview study with 21 stakeholders with different backgrounds (local transport authorities, public transport providers, e-scooter sharing operators, municipalities, associations, planning offices and consulting companies, and other mobility providers) was conducted to reflect upon the introduction of e-scooter sharing systems in Germany and stakeholders’ involvement in planning. The qualitative content analysis provides insights into the stakeholders’ assessment of the introduction process and thus contributes to a multi-perspective understanding on the topic. Derived hypotheses and recommendations further contribute to knowledge sharing and learning from experience. The paper concludes with a description of three introduction styles: protective, pro-active, and laissez-faire