Symbiont-mediated RNA interference in insects.

RNA interference (RNAi) methods for insects are often limited by problems with double-stranded (ds) RNA delivery, which restricts reverse genetics studies and the development of RNAi-based biocides. We therefore delegated to insect symbiotic bacteria the task of: (i) constitutive dsRNA synthesis and (ii) trauma-free delivery. RNaseIII-deficient, dsRNA-expressing bacterial strains were created from the symbionts of two very diverse pest species: a long-lived blood-sucking bug, Rhodnius prolixus, and a short-lived globally invasive polyphagous agricultural pest, western flower thrips (Frankliniella occidentalis). When ingested, the manipulated bacteria colonized the insects, successfully competed with the wild-type microflora, and sustainably mediated systemic knockdown phenotypes that were horizontally transmissible. This represents a significant advance in the ability to deliver RNAi, potentially to a large range of non-model insects.

Epilepsy and deprivation, a data linkage study.

OBJECTIVE: To investigate whether the link between epilepsy and deprivation is due to factors associated with deprivation (social causation) or factors associated with a diagnosis of epilepsy (social drift). METHODS: We reviewed electronic primary health care records from 2004 to 2010, identifying prevalent and incident cases of epilepsy and recording linked deprivation scores. Logistic and Poisson regression models were used to calculate odds ratios and incidence rate ratios. The change in deprivation was measured 10 years after the initial diagnosis of epilepsy for a cohort of people. RESULTS: Between 2004 and 2010, 8.1 million patient-years of records were reviewed. Epilepsy prevalence and incidence were significantly associated with deprivation. Epilepsy prevalence ranged from 1.13% (1.07-1.19%) in the most deprived decile to 0.49% (0.45-0.53%) in the least deprived decile (adjusted odds ratio 0.92, p < 0.001). Epilepsy incidence ranged from 40/100,000 per year in the most deprived decile to 19/100,000 per year in the least deprived decile (adjusted incidence rate ratio 0.94, p < 0.001). There was no statistically significant change in deprivation index decile 10 years after a new diagnosis of epilepsy (mean difference -0.04, p = 0.85). SIGNIFICANCE: Epilepsy prevalence and incidence are strongly associated with deprivation; the deprivation score remains unchanged 10 years after a diagnosis of epilepsy. These findings suggest that increasing rates of epilepsy in deprived areas are more likely explained by social causation than by social drift. The nature of the association between incident epilepsy and social deprivation needs further exploration.

Multi-decadal range changes vs. thermal adaptation for north east Atlantic oceanic copepods in the face of climate change.

Populations may potentially respond to climate change in various ways including moving to new areas or alternatively staying where they are and adapting as conditions shift. Traditional laboratory and mesocosm experiments last days to weeks and thus only give a limited picture of thermal adaptation, whereas ocean warming occurring over decades allows the potential for selection of new strains better adapted to warmer conditions. Evidence for adaptation in natural systems is equivocal. We used a 50-year time series comprising of 117 056 samples in the NE Atlantic, to quantify the abundance and distribution of two particularly important and abundant members of the ocean plankton (copepods of the genus Calanus) that play a key trophic role for fisheries. Abundance of C. finmarchicus, a cold-water species, and C. helgolandicus, a warm-water species, were negatively and positively related to sea surface temperature (SST) respectively. However, the abundance vs. SST relationships for neither species changed over time in a manner consistent with thermal adaptation. Accompanying the lack of evidence for thermal adaptation there has been an unabated range contraction for C. finmarchicus and range expansion for C. helgolandicus. Our evidence suggests that thermal adaptation has not mitigated the impacts of ocean warming for dramatic range changes of these key species and points to continued dramatic climate induced changes in the biology of the oceans.

Local modelling techniques for assessing micro-level impacts of risk factors in complex data: understanding health and socioeconomic inequalities in childhood educational attainments.

Although inequalities in health and socioeconomic status have an important influence on childhood educational performance, the interactions between these multiple factors relating to variation in educational outcomes at micro-level is unknown, and how to evaluate the many possible interactions of these factors is not well established. This paper aims to examine multi-dimensional deprivation factors and their impact on childhood educational outcomes at micro-level, focusing on geographic areas having widely different disparity patterns, in which each area is characterised by six deprivation domains (Income, Health, Geographical Access to Services, Housing, Physical Environment, and Community Safety). Traditional health statistical studies tend to use one global model to describe the whole population for macro-analysis. In this paper, we combine linked educational and deprivation data across small areas (median population of 1500), then use a local modelling technique, the Takagi-Sugeno fuzzy system, to predict area educational outcomes at ages 7 and 11. We define two new metrics, "Micro-impact of Domain" and "Contribution of Domain", to quantify the variations of local impacts of multidimensional factors on educational outcomes across small areas. The two metrics highlight differing priorities. Our study reveals complex multi-way interactions between the deprivation domains, which could not be provided by traditional health statistical methods based on single global model. We demonstrate that although Income has an expected central role, all domains contribute, and in some areas Health, Environment, Access to Services, Housing and Community Safety each could be the dominant factor. Thus the relative importance of health and socioeconomic factors varies considerably for different areas, depending on the levels of each of the other factors, and therefore each component of deprivation must be considered as part of a wider system. Childhood educational achievement could benefit from policies and intervention strategies that are tailored to the local geographic areas' profiles.

Influence of DNA repair on nonlinear dose-responses for mutation.

Recent evidence has challenged the default assumption that all DNA-reactive alkylating agents exhibit a linear dose-response. Emerging evidence suggests that the model alkylating agents methyl- and ethylmethanesulfonate and methylnitrosourea (MNU) and ethylnitrosourea observe a nonlinear dose-response with a no observed genotoxic effect level (NOGEL). Follow-up mechanistic studies are essential to understand the mechanism of cellular tolerance and biological relevance of such NOGELs. MNU is one of the most mutagenic simple alkylators. Therefore, understanding the mechanism of mutation induction, following low-dose MNU treatment, sets precedence for weaker mutagenic alkylating agents. Here, we tested MNU at 10-fold lower concentrations than a previous study and report a NOGEL of 0.0075 µg/ml (72.8nM) in human lymphoblastoid cells, quantified through the hypoxanthine (guanine) phosphoribosyltransferase assay (OECD 476). Mechanistic studies reveal that the NOGEL is dependent upon repair of O(6)-methylguanine (O(6)MeG) by the suicide enzyme O(6)MeG-DNA methyltransferase (MGMT). Inactivation of MGMT sensitizes cells to MNU-induced mutagenesis and shifts the NOGEL to the left on the dose axis.