Polymerase-catalyzed synthesis of DNA from phosphoramidate conjugates of deoxynucleotides and amino acids

Some selected amino acids, in particular l-aspartic acid (l-Asp) and l-histidine (l-His), can function as leaving group during polymerase-catalyzed incorporation of deoxyadenosine monophosphate (dAMP) in DNA. Although l-Asp-dAMP and l-His-dAMP bind, most probably, in a different way in the active site of the enzyme, aspartic acid and histidine can be considered as mimics of the pyrophosphate moiety of deoxyadenosine triphosphate. l-Aspartic acid is more efficient than d-aspartic acid as leaving group. Such P-N conjugates of amino acids and deoxynucleotides provide a novel experimental ground for diversifying nucleic acid metabolism in the field of synthetic biology

Glass breaks like metals, but at the nanometer scale

We report in situ Atomic Force Microscopy experiments which reveal the presence of nanoscale damage cavities ahead of a stress-corrosion crack tip in glass. Their presence might explain the departure from linear elasticity observed in the vicinity of a crack tip in glass. Such a ductile fracture mechanism, widely observed in the case of metallic materials at the micrometer scale, might be also at the origin of the striking similarity of the morphologies of fracture surfaces of glass and metallic alloys at different length scales.Comment: 4 pages, 4 figures, to appear in Phys. Rev. Lett, few minor corrections, Fig. 1b change

‘This town’s a different town today’:: Policing and regulating the night-time economy

This article considers recent policing and regulatory responses to the night-time economy in England and Wales. Drawing upon the findings of a broader two-year qualitative investigation of local and national developments in alcohol policy, it identifies a dramatic acceleration of statutory activity, with 12 new or revised powers, and several more in prospect, introduced by the Labour Government within its first decade in office. Interview data and documentary sources are used to explore the degree to which the introduction of such powers, often accompanied by forceful rhetoric and high profile police action, has translated into a sustained expansion of control. Many of the new powers are spatially directed, as well as being focused upon the actions of distinct individuals or businesses, yet the willingness and capacity to apply powers to offending individuals in comparison to businesses is often variable and asymmetrical. The practice of negotiating order in the night-time economy is riddled with tensions and ambiguities that reflect the ad hoc nature and rapid escalation of the regulatory architecture. Night-time urban security governance is understood as the outcome of subtle organizational and interpersonal power-plays. Social orders, normative schemas and apportionments of blame thus arise as a byproduct of patterned (structural) relations

Jean-Luc Mélenchon and France Insoumise: The Manufacturing of Populism

In the run-up to the 2017 presidential election in France, Jean-Luc Mélenchon who, so far, had been associated with the radical left, formed a new movement called France Insoumise (Unbowed France - FI). Mélenchon’s populist strategy in launching FI was blatant. This was an attempt to organise the masses along the lines of an agonistic cleavage between ‘the people’ and ‘the elite’, and this was also a radical break with the collective forms of leadership and action on the French left. The gamble paid off as Mélenchon received significant support from segments of left-wing voters in the first round of the presidential election. In true populist fashion, the FI leader wants to federate ‘the people’, and not simply left-wing voters. He has ceased to use the notion of left altogether. What defines FI’s populism is the role and the centrality of the leader. One may wonder whether populism is the best strategy to broaden the left’s electorate as left-wing and right-wing populisms do not tap in the same culture and do not express the same feelings. On the left, the anger is directed at free market economics. On the far right, the hatred of foreigners and immigrants is the main motivation. Both feelings and mindsets are incompatible: the former has a positive mindset whereas the latter is based on resentment. Mélenchon’s style, strategy and politics have energised fragments of the left-wing electorate (the young and working-class voters notably) but they have also created tensions with other parties of the left. Those organisations fear that Mélenchon’s ‘populist moment’ may be detrimental to the future of left-wing politics in France altogether

The 5-chlorouracil:7-deazaadenine base pair as an alternative to the dT:dA base pair

5-Chloro-2'-deoxyuridine as a possible component of a chemically modified genome has been discussed in terms of its influence on duplex stability and DNA polymerase incorporation properties. The search for its counterpart among different deoxyadenosine analogs (7-deaza-, 8-aza- and 8-aza-7-deaza-2'-deoxyadenosines) showed that the stable duplex formation as well as the synthesis of long constructs, more than 2 kb, were successful with the 5-chloro-2'-deoxyuridine and 7-deaza-2'-deoxyadenosine combination and with Taq DNA polymerase.crosscheck: This document is CrossCheck deposited related_data: Supplementary Information copyright_licence: The Royal Society of Chemistry has an exclusive publication licence for this journal history: Received 18 October 2016; Accepted 28 November 2016; Advance Article published 5 December 2016; Version of Record published 20 December 2016status: publishe

Replication of hexitol oligonucleotides as a prelude to the propagation of a third type of nucleic acid in vivo

No backbone motif other than phospho-ribose and phospho-deoxyribose has been found in natural nucleic acids, currently restricting the molecular types of replicable biopolymers to DNA and RNA. With the aim of propagating and expressing a third type of nucleic acid in vivo, we assessed the replicability of polynucleotides with a phospho-hexitol backbone (HNA) in vivo and in vitro. Faithful polymerisation of up to four deoxynucleotides templated by hexitol oligonucleotides was established in vitro using DNA polymerase from Escherichia coli (PolA Klenow exo-fragment) and Thermus aquaticus (Taq polymerase). Condensation of up to three successive hTTPs (hexitol thymidine triphosphate) in responses to a pentameric hexitol template (hA)5 could also be demonstrated in vitro. Such a marginal HNA-dependent HNA polymerase activity of natural polymerases may be evolved in the future to catalyse in vitro amplification of HNA. The transmission of a two-codon-long genetic message carried on a hexameric hexitol template was also established using a selection screen for restoring thymidylate synthase activity in E. coli. These results exemplify the potential that can be explored by converting artificial substrates with natural enzymes in the field of informational polymer synthesis.status: publishe