Regulation of mRNA translation by a photoriboswitch.

Optogenetic tools have revolutionized the study of receptor-mediated processes, but such tools are lacking for RNA-controlled systems. In particular, light-activated regulatory RNAs are needed for spatiotemporal control of gene expression. To fill this gap, we used in vitro selection to isolate a novel riboswitch that selectively binds the trans isoform of a stiff-stilbene (amino-tSS)-a rapidly and reversibly photoisomerizing small molecule. Structural probing revealed that the RNA binds amino-tSS about 100-times stronger than the cis photoisoform (amino-cSS). In vitro and in vivo functional analysis showed that the riboswitch, termed Werewolf-1 (Were-1), inhibits translation of a downstream open reading frame when bound to amino-tSS. Photoisomerization of the ligand with a sub-millisecond pulse of light induced the protein expression. In contrast, amino-cSS supported protein expression, which was inhibited upon photoisomerization to amino-tSS. Reversible photoregulation of gene expression using a genetically encoded RNA will likely facilitate high-resolution spatiotemporal analysis of complex RNA processes

Southern Africa Consortium for Research Excellence (SACORE): successes and challenges

Copyright © Mandala et al. Open access article distributed under the terms of CC BY.Published Online November 13, 2014 http://dx.doi.org/10.1016/S2214-109X(14)70321-

The impact of biogenic, anthropogenic, and biomass burning volatile organic compound emissions on regional and seasonal variations in secondary organic aerosol

The global secondary organic aerosol (SOA) budget is highly uncertain, with global annual SOA production rates, estimated from global models, ranging over an order of magnitude and simulated SOA concentrations underestimated compared to observations. In this study, we use a global composition-climate model (UKCA) with interactive chemistry and aerosol microphysics to provide an in-depth analysis of the impact of each VOC source on the global SOA budget and its seasonality. We further quantify the role of each source on SOA spatial distributions, and evaluate simulated seasonal SOA concentrations against a comprehensive set of observations. The annual global SOA production rates from monoterpene, isoprene, biomass burning, and anthropogenic precursor sources is 19.9, 19.6, 9.5, and 24.6Tg (SOA) a⁻¹, respectively. When all sources are included, the SOA production rate from all sources is 73.6Tg (SOA) a⁻¹, which lies within the range of estimates from previous modelling studies. SOA production rates and SOA burdens from biogenic and biomass burning SOA sources peak during Northern Hemisphere (NH) summer. In contrast, the anthropogenic SOA production rate is fairly constant all year round. However, the global anthropogenic SOA burden does have a seasonal cycle which is lowest during NH summer, which is probably due to enhanced wet removal. Inclusion of the new SOA sources also accelerates the ageing by condensation of primary organic aerosol (POA), making it more hydrophilic, leading to a reduction in the POA lifetime. With monoterpene as the only source of SOA, simulated SOA and total organic aerosol (OA) concentrations are underestimated by the model when compared to surface and aircraft measurements. Model agreement with observations improves with all new sources added, primarily due to the inclusion of the anthropogenic source of SOA, although a negative bias remains. A further sensitivity simulation was performed with an increased anthropogenic SOA reaction yield, corresponding to an annual global SOA production rate of 70.0Tg (SOA) a⁻¹. Whilst simulated SOA concentrations improved relative to observations, they were still underestimated in urban environments and overestimated further downwind and in remote environments. In contrast, the inclusion of SOA from isoprene and biomass burning did not improve model–observations biases substantially except at one out of two tropical locations. However, these findings may reflect the very limited availability of observations to evaluate the model, which are primarily located in the NH mid-latitudes where anthropogenic emissions are high. Our results highlight that, within the current uncertainty limits in SOA sources and reaction yields, over the NH mid-latitudes, a large anthropogenic SOA source results in good agreement with observations. However, more observations are needed to establish the importance of biomass burning and biogenic sources of SOA in model agreement with observations

Exploring the context of sedentary behaviour in older adults (what, where, why, when and with whom)

BACKGROUND: Older adults are the most sedentary segment of the population. Little information is available about the context of sedentary behaviour to inform guidelines and intervention. There is a dearth of information about when, where to intervene and which specific behaviours intervention should target. The aim of this exploratory study was to obtain objective information about what older adults do when sedentary, where and when they are sedentary and in what social context. METHODS: The study was a cross-sectional data collection. Older adults (Mean age = 73.25, SD ± 5.48, median = 72, IQR = 11) volunteers wore activPAL monitors and a Vicon Revue timelapse camera between 1 and 7 days. Periods of sedentary behaviour were identified using the activPAL and the context extracted from the pictures taken during these periods. Analysis of context was conducted using the Sedentary Behaviour International Taxonomy classification system. RESULTS: In total, 52 days from 36 participants were available for analysis. Participants spent 70.1 % of sedentary time at home, 56.9 % of sedentary time on their own and 46.8 % occurred in the afternoon. Seated social activities were infrequent (6.9 % of sedentary bouts) but prolonged (18 % of sedentary time). Participants appeared to frequently have vacant sitting time (41 % of non-screen sedentary time) and screen sitting was prevalent (36 % of total sedentary time). CONCLUSIONS: This study provides valuable information to inform future interventions to reduce sedentary behaviour. Interventions should consider targeting the home environment and focus on the afternoon sitting time, though this needs confirmation in a larger study. Tackling social isolation may also be a target to reduce sedentary time

Impact of inhaled corticosteroids on growth in children with asthma: systematic review and meta-analysis

Background: Long-term inhaled corticosteroids (ICS) may reduce growth velocity and final height of children with asthma. We aimed to evaluate the association between ICS use of >12 months and growth. Methods: We initially searched MEDLINE and EMBASE in July 2013, followed by a PubMed search updated to December 2014. We selected RCTs and controlled observational studies of ICS use in patients with asthma. We conducted random effects meta-analysis of mean differences in growth velocity (cm/year) or final height (cm) between groups. Heterogeneity was assessed using the I2 statistic. Results: We found 23 relevant studies (twenty RCTs and three observational studies) after screening 1882 hits. Meta-analysis of 16 RCTs showed that ICS use significantly reduced growth velocity at one year follow-up (mean difference -0.48 cm/year (95% CI -0.66 to -0.29)). There was evidence of a dose-response effect in three RCTs. Final adult height showed a mean reduction of -1.20 cm (95% CI -1.90 cm to -0.50 cm) with budesonide versus placebo in a high quality RCT. Meta-analysis of two lower quality observational studies revealed uncertainty in the association between ICS use and final adult height, pooled mean difference -0.85 cm (95% CI -3.35 to 1.65). Conclusion: Use of ICS for >12 months in children with asthma has a limited impact on annual growth velocity. In ICS users, there is a slight reduction of about a centimeter in final adult height, which when interpreted in the context of average adult height in England (175 cm for men and 161 cm for women), represents a 0.7% reduction compared to non-ICS users

“Am I my genes?”: Questions of identity among individuals confronting genetic disease

Purpose: To explore many questions raised by genetics concerning personal identities that have not been fully investigated. Methods: We interviewed in depth, for 2 hours each, 64 individuals who had or were at risk for Huntington disease, breast cancer, or alpha-1 antitrypsin deficiency. Results: These individuals struggled with several difficult issues of identity. They drew on a range of genotypes and phenotypes (e.g., family history alone; mutations, but no symptoms; or symptoms). They often felt that their predicament did not fit preexisting categories well (e.g., “sick,” “healthy,” “disabled,” “predisposed”), due in part to uncertainties involved (e.g., unclear prognoses, since mutations may not produce symptoms). Hence, individuals varied in how much genetics affected their identity, in what ways, and how negatively. Factors emerged related to disease, family history, and other sources of identity. These identities may, in turn, shape disclosure, coping, and other health decisions. Conclusions: Individuals struggle to construct a genetic identity. They view genetic information in highly subjective ways, varying widely in what aspects of genetic information they focus on and how. These data have important implications for education of providers (to assist patients with these issues), patients, and family members; and for research, to understand these issues more fully

Management of children’s fever by parents and caregivers: practical measurement of functional health literacy

Functional health literacy is founded on general and numerical literacy and practical skills and is required for the appropriate and effective management of health symptoms in children. This study aimed to assess the health literacy skills of parents and caregivers of preschool-aged children, using a progressive scenario describing a child with fever and presenting tasks relating to selection of a medicine and hypothetical dosing of their child. Participants (n ¼ 417) from 33 childcare- and health-related sites in Sydney, Brisbane, Melbourne and Auckland completed the study. Participants’ responses were largely appropriate regarding actions in response to worsening symptoms, selection of an appropriate product (from a limited range), whereby 84.5% of responses were for a single-ingredient paracetamol product and use of the package directions to state the frequency of dosing (93.1% of frequencies appropriate for paracetamol and 66.7% for ibuprofen). However, in only 50.8% of cases was an appropriate weight-based dose calculated, and doses were not measured to within 10% of the stated dose in 16.7% of cases. Future studies should focus on skill development via educational campaigns for parents and caregivers

Cerebellar Integrity in the Amyotrophic Lateral Sclerosis - Frontotemporal Dementia Continuum

Amyotrophic lateral sclerosis (ALS) and behavioural variant frontotemporal dementia (bvFTD) are multisystem neurodegenerative disorders that manifest overlapping cognitive, neuropsychiatric and motor features. The cerebellum has long been known to be crucial for intact motor function although emerging evidence over the past decade has attributed cognitive and neuropsychiatric processes to this structure. The current study set out i) to establish the integrity of cerebellar subregions in the amyotrophic lateral sclerosis-behavioural variant frontotemporal dementia spectrum (ALS-bvFTD) and ii) determine whether specific cerebellar atrophy regions are associated with cognitive, neuropsychiatric and motor symptoms in the patients. Seventy-eight patients diagnosed with ALS, ALS-bvFTD, behavioural variant frontotemporal dementia (bvFTD), most without C9ORF72 gene abnormalities, and healthy controls were investigated. Participants underwent cognitive, neuropsychiatric and functional evaluation as well as structural imaging using voxel-based morphometry (VBM) to examine the grey matter subregions of the cerebellar lobules, vermis and crus. VBM analyses revealed: i) significant grey matter atrophy in the cerebellum across the whole ALS-bvFTD continuum; ii) atrophy predominantly of the superior cerebellum and crus in bvFTD patients, atrophy of the inferior cerebellum and vermis in ALS patients, while ALS-bvFTD patients had both patterns of atrophy. Post-hoc covariance analyses revealed that cognitive and neuropsychiatric symptoms were particularly associated with atrophy of the crus and superior lobule, while motor symptoms were more associated with atrophy of the inferior lobules. Taken together, these findings indicate an important role of the cerebellum in the ALS-bvFTD disease spectrum, with all three clinical phenotypes demonstrating specific patterns of subregional atrophy that associated with different symptomology