Novel Class 1 Integron Harboring Antibiotic Resistance Genes in Wastewater-Derived Bacteria as Revealed by Functional Metagenomics

Combatting antibiotic resistance is critical to our ability to treat infectious diseases. Here, we identified and characterized diverse antimicrobial resistance genes, including potentially mobile elements, from synthetic wastewater treatment microcosms exposed to the antibacterial agent triclosan. After seven weeks of exposure, the microcosms were subjected to functional metagenomic selection across 13 antimicrobials. This was achieved by cloning the combined genetic material from the microcosms, introducing this genetic library into E. coli, and selecting for clones that grew on media supplemented with one of the 13 antimicrobials. We recovered resistant clones capable of growth on media supplemented with a single antimicrobial, yielding 13 clones conferring resistance to at least one antimicrobial agent. Antibiotic susceptibility analysis revealed resistance ranging from 4 to \u3e50 fold more resistant, while one clone showed resistance to multiple antibiotics. Using both Sanger and SMRT sequencing, we identified the predicted active gene(s) on each clone. One clone that conferred resistance to tetracycline contained a gene encoding a novel tetA-type efflux pump that was named TetA(62). Three clones contained predicted active genes on class 1 integrons. One integron had a previously unreported genetic arrangement and was named In1875. This study demonstrated the diversity and potential for spread of resistance genes present in human-impacted environments

Charged pion production in nu(mu) interactions on hydrocarbon at \u3c E-nu \u3e=4.0 GeV

Charged pion production via charged-current nu(mu) interactions on plastic scintillator (CH) is studied using the MINERvA detector exposed to the NuMI wideband neutrino beam at Fermilab. Events with hadronic invariant massW \u3c 1.4 GeV and W \u3c 1.8 GeV are selected in separate analyses: the lower W cut isolates single pion production, which is expected to occur primarily through the Delta(1232) resonance, while results from the higher cut include the effects of higher resonances. Cross sections as functions of pion angle and kinetic energy are compared to predictions from theoretical calculations and generator-based models for neutrinos ranging in energy from 1.5-10 GeV. The data are best described by calculations which include significant contributions from pion intranuclear rescattering. These measurements constrain the primary interaction rate and the role of final state interactions in pion production, both of which need to be well understood by neutrino oscillation experiments

Identification, Motivation and Facilitation of Domestic Tourism in a Small Island

This paper presents a case concerning domestic tourism in the Isle of Man, British Isles; a small maritime nation with Norse heritage. Qualitative interviews find the existence of considerable domestic tourism activity conducted by island residents, including daytrips and overnight stays, and explore the motivational and facilitating factors which underpin this. Such behaviour is identified by residents as touristic and distinct from other leisure pursuits. Yet recognition of domestic tourism in small geographic spaces is currently almost entirely absent. This article attempts to highlight the issue and draw attention to attendant benefits of domestic tourism which include economic and social inputs. These may be relevant to a small island community, and in the case of the Isle of Man help to support an otherwise ailing tourism industry

miR-122 Stimulates Hepatitis C Virus RNA Synthesis by Altering the Balance of Viral RNAs Engaged in Replication versus Translation

SummaryThe liver-specific microRNA, miR-122, stabilizes hepatitis C virus (HCV) RNA genomes by recruiting host argonaute 2 (AGO2) to the 5′ end and preventing decay mediated by exonuclease Xrn1. However, HCV replication requires miR-122 in Xrn1-depleted cells, indicating additional functions. We show that miR-122 enhances HCV RNA levels by altering the fraction of HCV genomes available for RNA synthesis. Exogenous miR-122 increases viral RNA and protein levels in Xrn1-depleted cells, with enhanced RNA synthesis occurring before heightened protein synthesis. Inhibiting protein translation with puromycin blocks miR-122-mediated increases in RNA synthesis, but independently enhances RNA synthesis by releasing ribosomes from viral genomes. Additionally, miR-122 reduces the fraction of viral genomes engaged in protein translation. Depleting AGO2 or PCBP2, which binds HCV RNA in competition with miR-122 and promotes translation, eliminates miR-122 stimulation of RNA synthesis. Thus, by displacing PCBP2, miR-122 reduces HCV genomes engaged in translation while increasing the fraction available for RNA synthesis

Infectious disease and health systems modelling for local decision making to control neglected tropical diseases

Most neglected tropical diseases (NTDs) have complex life cycles and are challenging to control. The “2020 goals” of control and elimination as a public health programme for a number of NTDs are the subject of significant international efforts and investments. Beyond 2020 there will be a drive to maintain these gains and to push for true local elimination of transmission. However, these diseases are affected by variations in vectors, human demography, access to water and sanitation, access to interventions and local health systems. We therefore argue that there will be a need to develop local quantitative expertise to support elimination efforts. If available now, quantitative analyses would provide updated estimates of the burden of disease, assist in the design of locally appropriate control programmes, estimate the effectiveness of current interventions and support ‘real-time’ updates to local operations. Such quantitative tools are increasingly available at an international scale for NTDs, but are rarely tailored to local scenarios. Localised expertise not only provides an opportunity for more relevant analyses, but also has a greater chance of developing positive feedback between data collection and analysis by demonstrating the value of data. This is essential as rational program design relies on good quality data collection. It is also likely that if such infrastructure is provided for NTDs there will be an additional impact on the health system more broadly. Locally tailored quantitative analyses can help achieve sustainable and effective control of NTDs, but also underpin the development of local health care systems

Negotiating imitation: Examining the interactions of consultants and their clients to understand institutionalization as translation

Organizational scholars increasingly view institutionalization as a process through which actors adapt or translate seemingly successful practices in a field to create variations that are specific to their own organization. Yet little is known about how outsiders who seek to diffuse ‘best practice’ affect translation. We examined interactions between management consultants and their clients in two different consulting projects, which focused on embedding the practice of ‘lean’ in one and the practice of a quality improvement framework in the other. Our findings provide insights into the processes of translation through which promoters and adopters iterate at different stages to reach a compromise, illuminating how the evolution of an imported practice signals the outcome of a negotiation. Furthermore, we demonstrate that management practices are not translated in isolation but enveloped by peripheral practices that are adopted by association. We highlight how the peripheral practice of benchmarking, in both cases, was rarely contested or negotiated and thus proved more resistant to translation. Our analysis allows us to unpack the agency inherent within translation-as-negotiation and integrate research on diffusion and translation