Altered m6A Modification of Specific Cellular Transcripts Affects Flaviviridae Infection

The RNA modification N6-methyladenosine (m6A) modulates mRNA fate and thus affects many biological processes. We analyzed m6A across the transcriptome following infection by dengue virus (DENV), Zika virus (ZIKV), West Nile virus (WNV), and hepatitis C virus (HCV). We found that infection by these viruses in the Flaviviridae family alters m6A modification of specific cellular transcripts, including RIOK3 and CIRBP. During viral infection, the addition of m6A to RIOK3 promotes its translation, while loss of m6A in CIRBP promotes alternative splicing. Importantly, viral activation of innate immune sensing or the endoplasmic reticulum (ER) stress response contributes to the changes in m6A in RIOK3 or CIRBP, respectively. Further, several transcripts with infection-altered m6A profiles, including RIOK3 and CIRBP, encode proteins that influence DENV, ZIKV, and HCV infection. Overall, this work reveals that cellular signaling pathways activated during viral infection lead to alterations in m6A modification of host mRNAs to regulate infection. Here, Gokhale, McIntyre et al. identify m6A changes in cellular mRNAs following Flaviviridae infection and demonstrate that infection-activated pathways contribute to these changes. They show that altered m6A modification in RIOK3 and CIRBP mRNAs influence their translation and splicing, respectively, and that RIOK3, CIRBP, and other m6A-altered factors regulate infection

Activity behaviours and quality of life in patients with malignant pleural effusion

Background and objective Accelerometery is used to measure activity behaviours in patients with malignant pleural effusion (MPE). This study aimed to evaluate physical activity and sedentary behaviour profiles of patients with MPE in Hong Kong, and to explore relationships between activity behaviours and quality of life (QoL). We also compared clinician-recorded performance status measures with objective measures of activity levels. Methods Participants wore an Actigraph GT3X+ accelerometer continuously for 7 consecutive days. The EuroQoL 5 Dimensions 5 Levels (EQ-5D-5L) was used to assess five dimensions of QoL and correlate with activity behaviours. The Eastern Cooperative Oncology Group (ECOG) performance status was documented by clinicians at baseline. Results Fifty-one patients with MPE received accelerometers; 94% had ⩾1 valid day of data. Participants spent 76% (SD 2.32) of waking hours sedentary, 23% (SD 1.40) of waking hours in light activity and 0.3% (median, interquartile range 0.0–1.5) in moderate-to-vigorous physical activity (MVPA). Higher light activity and MVPA behaviours were associated with increased participation in self-care tasks (rs =−0.43, p=0.003; rs =−0.45, p=0.001, respectively) and usual activities (rs =−0.42, p=0.003; rs =−0.45, p=0.001, respectively). Patients with an ECOG status of 0 or 1 spent an average of 75% of waking hours sedentary. Conclusion This is the first report of physical activity behaviours in patients with MPE in Hong Kong, demonstrating high sedentary behaviours and low physical activity which correlated to dimensions of QoL. Clinician-rated performance status was not reflected in accelerometery data, suggesting a discrepancy between performance status measures and objective measures of activity in patients with MPE

A First Search for coincident Gravitational Waves and High Energy Neutrinos using LIGO, Virgo and ANTARES data from 2007

We present the results of the first search for gravitational wave bursts associated with high energy neutrinos. Together, these messengers could reveal new, hidden sources that are not observed by conventional photon astronomy, particularly at high energy. Our search uses neutrinos detected by the underwater neutrino telescope ANTARES in its 5 line configuration during the period January - September 2007, which coincided with the fifth and first science runs of LIGO and Virgo, respectively. The LIGO-Virgo data were analysed for candidate gravitational-wave signals coincident in time and direction with the neutrino events. No significant coincident events were observed. We place limits on the density of joint high energy neutrino - gravitational wave emission events in the local universe, and compare them with densities of merger and core-collapse events.Comment: 19 pages, 8 figures, science summary page at http://www.ligo.org/science/Publication-S5LV_ANTARES/index.php. Public access area to figures, tables at https://dcc.ligo.org/cgi-bin/DocDB/ShowDocument?docid=p120000

MTBVAC vaccination protects rhesus macaques against aerosol challenge with M. tuberculosis and induces immune signatures analogous to those observed in clinical studies

A single intradermal vaccination with MTBVAC given to adult rhesus macaques was well tolerated and conferred a significant improvement in outcome following aerosol exposure to M. tuberculosis compared to that provided by a single BCG vaccination. Vaccination with MTBVAC resulted in a significant reduction in M. tuberculosis infection-induced disease pathology measured using in vivo medical imaging, in gross pathology lesion counts and pathology scores recorded at necropsy, the frequency and severity of pulmonary granulomas and the frequency of recovery of viable M. tuberculosis from extrapulmonary tissues following challenge. The immune profiles induced following immunisation with MTBVAC reflect those identified in human clinical trials of MTBVAC. Evaluation of MTBVAC- and TB peptide-pool-specific T-cell cytokine production revealed a predominantly Th1 response from poly- (IFN-¿+TNF-a+IL2+) and multi-(IFN-¿+TNF-a+) functional CD4 T cells, while only low levels of Th22, Th17 and cytokine-producing CD8 T-cell populations were detected together with low-level, but significant, increases in CFP10-specific IFN-¿ secreting cells. In this report, we describe concordance between immune profiles measured in clinical trials and a macaque pre-clinical study demonstrating significantly improved outcome after M. tuberculosis challenge as evidence to support the continued development of MTBVAC as an effective prophylactic vaccine for TB vaccination campaigns

Visualising children’s participation in research: Lego Duplo, rainbows and clouds and moodboards

This article was published in the International Journal of Social Research Methodology [© Taylor & Francis] and the definitive version is available at: http://dx.doi.org/10.1080/13645579.2012.649410This paper examines the use of visual methods during research encounters with children and young people when investigating their perspectives and feelings towards their home and school life. By revealing the advantages and constraints of three visual approaches, including Lego Duplo, rainbows and clouds and moodboards, the paper contributes to the range of techniques available when conducting research with children and young people. In conclusion, the paper highlights the depth of information which can be elicited from visual techniques as well as the oral data which can be obtained through the utilisation of visual methods

Articulating the effect of food systems innovation on the Sustainable Development Goals

Food system innovations will be instrumental to achieving multiple Sustainable Development Goals (SDGs). However, major innovation breakthroughs can trigger profound and disruptive changes, leading to simultaneous and interlinked reconfigurations of multiple parts of the global food system. The emergence of new technologies or social solutions, therefore, have very different impact profiles, with favourable consequences for some SDGs and unintended adverse side-effects for others. Stand-alone innovations seldom achieve positive outcomes over multiple sustainability dimensions. Instead, they should be embedded as part of systemic changes that facilitate the implementation of the SDGs. Emerging trade-offs need to be intentionally addressed to achieve true sustainability, particularly those involving social aspects like inequality in its many forms, social justice, and strong institutions, which remain challenging. Trade-offs with undesirable consequences are manageable through the development of well planned transition pathways, careful monitoring of key indicators, and through the implementation of transparent science targets at the local level