Ribose 2′-O-methylation provides a molecular signature for the distinction of self and non-self mRNA dependent on the RNA sensor Mda5

The 5'-cap-structures of higher eukaryote mRNAs are ribose 2'-O-methylated. Likewise, a number of viruses replicating in the cytoplasm of eukayotes have evolved 2'-O-methyltransferases to modify autonomously their mRNAs. However, a defined biological role of mRNA 2'-O-methylation remains elusive. Here we show that viral mRNA 2'-O-methylation is critically involved in subversion of type-I-interferon (IFN-I) induction. We demonstrate that human and murine coronavirus 2'-O-methyltransferase mutants induce increased IFN-I expression, and are highly IFN-I sensitive. Importantly, IFN-I induction by 2'-O-methyltransferase-deficient viruses is dependent on the cytoplasmic RNA sensor melanoma differentiation-associated gene 5 (MDA5). This link between MDA5-mediated sensing of viral RNA and mRNA 2'-O-methylation suggests that RNA modifications, such as 2'-O-methylation, provide a molecular signature for the discrimination of self and non-self mRNA.

Western Containment Policies in the Cold War; The Yugoslav Case, 1948-1953

Containment, as conceived by the US government official George Kennan, was an aggressive attempt to cause the Soviet Cold War empire to disintegrate. This can is demonstrated by the case study of how the USA, Britain, and France tried to instrumentalise renegade Tito's Yugoslavia as a wedge to break up the cohesion of the Communist regimes within the Soviet sphere. They supported Tito against subversion and planned Soviet-orchestrated military attack from its neighbouring states; Western plans for the support of Yugoslavia included plans for a selective use of nuclear weapons.

A Lagrangian model of air-mass photochemistry and mixing using a trajectory ensemble: the Cambridge Tropospheric Trajectory model of Chemistry And Transport (CiTTyCAT) version 4.2

A Lagrangian model of photochemistry and mixing is described (CiTTyCAT, stemming from the Cambridge Tropospheric Trajectory model of Chemistry And Transport), which is suitable for transport and chemistry studies throughout the troposphere. Over the last five years, the model has been developed in parallel at several different institutions and here those developments have been incorporated into one "community" model and documented for the first time. The key photochemical developments include a new scheme for biogenic volatile organic compounds and updated emissions schemes. The key physical development is to evolve composition following an ensemble of trajectories within neighbouring air-masses, including a simple scheme for mixing between them via an evolving "background profile", both within the boundary layer and free troposphere. The model runs along trajectories pre-calculated using winds and temperature from meteorological analyses. In addition, boundary layer height and precipitation rates, output from the analysis model, are interpolated to trajectory points and used as inputs to the mixing and wet deposition schemes. The model is most suitable in regimes when the effects of small-scale turbulent mixing are slow relative to advection by the resolved winds so that coherent air-masses form with distinct composition and strong gradients between them. Such air-masses can persist for many days while stretching, folding and thinning. Lagrangian models offer a useful framework for picking apart the processes of air-mass evolution over inter-continental distances, without being hindered by the numerical diffusion inherent to global Eulerian models. The model, including different box and trajectory modes, is described and some output for each of the modes is presented for evaluation. The model is available for download from a Subversion-controlled repository by contacting the corresponding authors.

Artisanal mining's democratizing directions and deviations

Artisanal miners have tended to be portrayed in the literature and media as people who work hard and play hard, not infrequently depicted as ‘rough diamonds’ likely to cross the boundaries of appropriate behaviour through pursuit of wealth and flamboyant living, often at the cost of local environmental damage. A popular alternative image is that of marginalised labourers, driven by poverty to toil in harsh conditions and pursuing mining livelihoods in the face of national governments and large-scale mining companies’ subversion of their land and mineral rights. Both views reflect partial realities, but are inclined to exaggerate the position of miners as mischief-making rogues or victims. Through documentation of the multi-faceted nature of Tanzanian artisanal miners’ work and home lives during the country’s on-going economic mineralisation, we endeavour to convey a balanced rendering of their aspirations, occupational identity and social ties. Our emphasis is on their working lives as artisans, how they organise themselves and contend with the risks of their occupation, including their engagement with government policy and large-scale mining interests.