Structure and Mechanism of a Metal-Sensing Regulatory RNA

SummaryOrganisms maintain the correct balance of intracellular metals primarily through metal-sensing proteins that control transport and storage of the target ion(s). Here, we reveal the basis of metal sensing and genetic control by a metalloregulatory RNA. Our data demonstrate that a previously uncharacterized orphan riboswitch, renamed the “M-box,” is a divalent metal-sensing RNA involved in Mg2+ homeostasis. A combination of genetic, biochemical, and biophysical techniques demonstrate that Mg2+ induces a compacted tertiary architecture for M-box RNAs that regulates the accessibility of nucleotides involved in genetic control. Molecular details are provided by crystallographic structure determination of a Mg2+-bound M-box RNA. Given the distribution of this RNA element, it may constitute a common mode for bacterial metal ion regulation, and its discovery suggests the possibility of additional RNA-based metal sensors in modern and primordial organisms

Language intermediaries and local agency: peacebuilding, translation/interpreting and political disempowerment in 'mature' post-Dayton Bosnia-Herzegovina

The peace negotiations that ended the 1992–95 war in Bosnia-Herzegovina established a constitutional system of ethnic power-sharing that satisfied its signatories (the presidents of Serbia, Croatia and Bosnia) enough for war to cease and provided for international military and civilian peacebuilding to play a significant role in post-conflict Bosnia’s governance and economy. This indefinite peacebuilding mission, still ongoing in a downsized form, depended – like any other form of intervention where foreigners work across linguistic boundaries – on interlinguistic mediation by locally-recruited translators/interpreters, an aspect of knowledge production that even current peace and conflict research into peacebuilding’s micropolitics often neglects. On an individual level, locally-recruited interpreters’ frequently-overlooked agency was integral to peacebuilding practice. Yet theorising their agency must also acknowledge the macrosocial level, where the post-war constitutional system has often been argued to have stripped Bosnians of political agency, since it foreclosed political participation as anything but an ethnic subject corresponding to the three institutionalised ethnic identities (Bosniak, Croat or Serb). The entrenched and growing disconnect between political elites and the public, expressed through social protest in 2014, foregrounds the problem of agency and dis/empowerment in Bosnian society more sharply than research on the politics of translation/interpreting and peacebuilding in Bosnia before 2014 took into account, yet reveals further articulations of how international peacebuilding and domestic political contestation were intertwined

The early extra petals1 Mutant Uncovers a Role for MicroRNA miR164c in Regulating Petal Number in Arabidopsis

Background: MicroRNAs (miRNAs) are small 20–25 nucleotide non-protein-coding RNAs that negatively regulate expression of genes in many organisms, ranging from plants to humans. The MIR164 family of miRNAs in Arabidopsis consists of three members that share sequence complementarity to transcripts of NAC family transcription factors, including CUP-SHAPED COTYLEDON1 (CUC1) and CUC2. CUC1 and CUC2 are redundantly required for the formation of boundaries between organ primordia. The analysis of transgenic plants that either overexpress miR164a or miR164b or express a miRNA-resistant version of CUC1 or CUC2 has shown that miRNA regulation of CUC1 and CUC2 is necessary for normal flower development. A loss-of-function allele of MIR164b did not result in a mutant phenotype, possibly because of functional redundancy among the three members of the MIR164 family. Results: In this study, we describe the characterization of the early extra petals1 (eep1) Arabidopsis mutant, whose predominant phenotype is the formation of extra petals in early-arising flowers. We demonstrate that eep1 is a loss-of-function allele of MIR164c, one of three known members of the MIR164 family. Our analyses of miR164c function and eep1 mir164b double mutants reveal that miR164c controls petal number in a nonredundant manner by regulating the transcript accumulation of the transcription factors CUC1 and CUC2. Conclusions: The data presented in this study indicate that closely related miRNA family members that are predicted to target the same set of genes can have different functions during development, possibly because of nonoverlapping expression patterns

Mercury's Magnetopause and Bow Shock from MESSENGER Magnetometer Observations

We have established the average shape and location of Mercury's magnetopause and bow shock from orbital observations by the MESSENGER Magnetometer. We fit empirical models to midpoints of boundary crossings and probability density maps of the magnetopause and bow shock positions. The magnetopause was fit by a surface for which the position R from the planetary dipole varies as [1 + cos(theta)]-alpha, where theta is the angle between R and the dipole-Sun line, the subsolar standoff distance Rss is 1.45 RM (where RM is Mercury's radius), and the flaring parameter alpha = 0.5. The average magnetopause shape and location were determined under a mean solar wind ram pressure PRam of 14.3 nPa. The best fit bow shock shape established under an average Alfvén Mach number (MA) of 6.6 is described by a hyperboloid having Rss = 1.96 RM and an eccentricity of 1.02. These boundaries move as PRam and MA vary, but their shapes remain unchanged. The magnetopause Rss varies from 1.55 to 1.35 RM for PRam in the range of 8.8-21.6 nPa. The bow shock Rss varies from 2.29 to 1.89 RM for MA in the range of 4.12-11.8. The boundaries are well approximated by figures of revolution. Additional quantifiable effects of the interplanetary magnetic field are masked by the large dynamic variability of these boundaries. The magnetotail surface is nearly cylindrical, with a radius of ~2.7 RM at a distance of 3 RM downstream of Mercury. By comparison, Earth's magnetotail flaring continues until a downstream distance of ~10 Rss

Beyond the island story? the opening ceremony of the London 2012 Olympic Games as public history

This paper evaluates the opening ceremony of the London 2012 Olympic Games as an exercise in public history. Public events have been widely identified within the study of nationalism as festivals that attempt to reinforce national identity and belonging. Contemporary Olympic Games figure in this literature as a specific form of event where the nature and content of a host state's identity is displayed for the global gaze of other nations. While opening ceremonies perform a rich display of national identity in any case, London 2012 is particularly significant for taking place at a time of major political contestation in the United Kingdom and has frequently been interpreted as an expression of radical patriotism. Traces of such patriotic thought associated particularly with England can be found in the opening ceremony's historical pageant and overall concept, showing resonances with the work of Raphael Samuel, who argued for a radical patriotism grounded in a multiplicity of accounts of the national past from many social positions. Depicting the nation through a multiplicity of biographical narratives produces a ‘mosaic' mode of representation which can be seen in other documentary and public history projects and in the political context of British public multiculturalism in the 2000s. This responds to the need for any national narrative to be composed through compressing the lives of millions of people into one coherent story, but complicates attempts to read a text such as the opening ceremony for what they ‘really' mean. A model for understanding narratives of the past as being produced in interaction between their initial creator(s) and their reader(s) is necessary for understanding not only the London 2012 opening ceremony in particular but public history and narratives of the national past in general

What is the 'problem' that outreach work seeks to address and how might it be tackled? Seeking theory in a primary health prevention programme

<b>Background</b> Preventive approaches to health are disproportionately accessed by the more affluent and recent health improvement policy advocates the use of targeted preventive primary care to reduce risk factors in poorer individuals and communities. Outreach has become part of the health service response. Outreach has a long history of engaging those who do not otherwise access services. It has, however, been described as eclectic in its purpose, clientele and mode of practice; its effectiveness is unproven. Using a primary prevention programme in the UK as a case, this paper addresses two research questions: what are the perceived problems of non-engagement that outreach aims to address; and, what specific mechanisms of outreach are hypothesised to tackle these.<p></p> <b>Methods</b> Drawing on a wider programme evaluation, the study undertook qualitative interviews with strategically selected health-care professionals. The analysis was thematically guided by the concept of 'candidacy' which theorises the dynamic process through which services and individuals negotiate appropriate service use.<p></p> <b>Results</b> The study identified seven types of engagement 'problem' and corresponding solutions. These 'problems' lie on a continuum of complexity in terms of the challenges they present to primary care. Reasons for non-engagement are congruent with the concept of 'candidacy' but point to ways in which it can be expanded.<p></p> <b>Conclusions</b> The paper draws conclusions about the role of outreach in contributing to the implementation of inequalities focused primary prevention and identifies further research needed in the theoretical development of both outreach as an approach and candidacy as a conceptual framework

cAMP-Signalling Regulates Gametocyte-Infected Erythrocyte Deformability Required for Malaria Parasite Transmission.

Blocking Plasmodium falciparum transmission to mosquitoes has been designated a strategic objective in the global agenda of malaria elimination. Transmission is ensured by gametocyte-infected erythrocytes (GIE) that sequester in the bone marrow and at maturation are released into peripheral blood from where they are taken up during a mosquito blood meal. Release into the blood circulation is accompanied by an increase in GIE deformability that allows them to pass through the spleen. Here, we used a microsphere matrix to mimic splenic filtration and investigated the role of cAMP-signalling in regulating GIE deformability. We demonstrated that mature GIE deformability is dependent on reduced cAMP-signalling and on increased phosphodiesterase expression in stage V gametocytes, and that parasite cAMP-dependent kinase activity contributes to the stiffness of immature gametocytes. Importantly, pharmacological agents that raise cAMP levels in transmissible stage V gametocytes render them less deformable and hence less likely to circulate through the spleen. Therefore, phosphodiesterase inhibitors that raise cAMP levels in P. falciparum infected erythrocytes, such as sildenafil, represent new candidate drugs to block transmission of malaria parasites

A 1.8 million year history of Amazon vegetation

During the Pleistocene, long-term trends in global climate were controlled by orbital cycles leading to high amplitude glacial-interglacial variability. The history of Amazonian vegetation during this period is largely unknown since no continuous record from the lowland basin extends significantly beyond the last glacial stage. Here we present a paleoenvironmental record spanning the last 1800 kyr based on palynological data, biome reconstructions, and biodiversity metrics from a marine sediment core that preserves a continuous archive of sediments from the Amazon River. Tropical rainforests dominated the Amazonian lowlands during the last 1800 ka interchanging with surrounding warm-temperate rainforests and tropical seasonal forests. Between 1800 and 1000 ka, rainforest biomes were present in the Amazon drainage basin, along with extensive riparian wetland vegetation. Tropical rainforest expansion occurred during the relatively warm Marine Isotope Stages 33 and 31 (ca. 1110 to 1060 ka), followed by a contraction of both forests and wetlands until ca. 800 ka. Between 800 and 400 ka, low pollen concentration and low diversity of palynological assemblages renders difficult the interpretation of Amazonian vegetation. A strong synchronicity between vegetation changes and glacial-interglacial global climate cycles was established around 400 ka. After 400 ka, interglacial vegetation was dominated by lowland tropical rainforest in association with warmer temperatures and higher CO2. During cooler temperatures and lower CO2 of glacial stages, tropical seasonal forests expanded, presumably towards eastern Amazonia. While this study provides no evidence supporting a significant expansion of savanna or steppe vegetation within the Amazonian lowlands during glacial periods, there were changes in the rainforest composition in some parts of the basin towards a higher proportion of deciduous elements, pointing to less humid conditions and/or greater seasonality of precipitation. Nevertheless, rainforest persisted during both glacial and interglacial periods. These findings confirm the sensitivity of tropical lowland vegetation to changes in CO2, temperature, and moisture availability and the most suitable conditions for tropical rainforests occurred during the warmest stages of the Mid Pleistocene Transition and during the interglacial stages of the past 400 kyr

Solar wind forcing at Mercury: WSA‐ENLIL model results

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/97237/1/jgra50070.pd

Solar wind forcing at Mercury: WSA-ENLIL model results

Analysis and interpretation of observations from the MESSENGER spacecraft in orbit about Mercury require knowledge of solar wind “forcing” parameters. We have utilized the Wang-Sheeley-Arge (WSA)-ENLIL solar wind modeling tool in order to calculate the values of interplanetary magnetic field (IMF) strength (B), solar wind velocity (V) and density (n), ram pressure (~nV2), cross-magnetosphere electric field (V × B), Alfvén Mach number (MA), and other derived quantities of relevance for solar wind-magnetosphere interactions. We have compared upstream MESSENGER IMF and solar wind measurements to see how well the ENLIL model results compare. Such parameters as solar wind dynamic pressure are key for determining the Mercury magnetopause standoff distance, for example. We also use the relatively high-time-resolution B-field data from MESSENGER to estimate the strength of the product of the solar wind speed and southward IMF strength (Bs) at Mercury. This product VBs is the electric field that drives many magnetospheric dynamical processes and can be compared with the occurrence of energetic particle bursts within the Mercury magnetosphere. This quantity also serves as input to the global magnetohydrodynamic and kinetic magnetosphere models that are being used to explore magnetospheric and exospheric processes at Mercury. Moreover, this modeling can help assess near-real-time magnetospheric behavior for MESSENGER or other mission analysis and/or ground-based observational campaigns. We demonstrate that this solar wind forcing tool is a crucial step toward bringing heliospheric science expertise to bear on planetary exploration programs