Contribution of maternal effects to dietary selection in Mediterranean fruit flies

Individual responses to dietary variation represent a fundamental component of fitness, and nutritional adaptation can occur over just a few generations. Maternal effects can show marked proximate responses to nutrition, but whether they contribute to longer term dietary adaptation is unclear. Here, we tested the hypotheses that maternal effects: (i) contribute to dietary adaptation, (ii) diminish when dietary conditions are constant between generations, (iii) are trait-specific and (iv) interact with high- and low-quality food. We used experimental evolution regimes in the medfly (Ceratitis capitata) to test these predictions by subjecting an outbred laboratory-adapted population to replicated experimental evolution on either constant high calorie sugar (‘A’) or low-calorie starch (‘S’) larval diets, with a standard adult diet across both regimes. We measured the contribution of maternal effects by comparing developmental and adult phenotypes of individuals reared on their own diet with those swapped onto the opposite diet for either one or two generations (high and low maternal effect conditions, respectively), both at the start and after 30 generations of selection. Initially, there were strong maternal effects on female body mass and male mating success but not larval survival. Interestingly, the initial maternal effects observed in female body mass and male mating success showed sex-specific interactions when individuals from high calorie regimes were tested on low calorie diets. However, as populations responded to selection, the effects of maternal provisioning on all traits diminished. The results broadly supported the predictions. They show how the contribution of maternal effects to dietary responses evolves in a context-dependent manner, with significant variation across different fitness-related traits. We conclude that maternal effects can evolve during nutritional adaptation and hence may be an important life history trait to measure, rather than to routinely minimize

Geographical concentration of falciparum malaria treated in the UK and delay to treatment with artesunate in severe cases: an observational study.

OBJECTIVES: To quantify geographical concentration of falciparum malaria cases in the UK at a hospital level. To assess potential delay-to-treatment associated with hub-and-spoke distribution of artesunate in severe cases. DESIGN: Observational study using national and hospital data. SETTING AND PARTICIPANTS: 3520 patients notified to the Malaria Reference Laboratory 2008-2010, 34 patients treated with intravenous artesunate from a tropical diseases centre 2002-2010. MAIN OUTCOME MEASURES: Geographical location of falciparum cases notified in the UK. Diagnosis-to-treatment times for intravenous artesunate. RESULTS: Eight centres accounted for 43.9% of the UK's total cases; notifications from 107 centres accounted for 10.2% of cases; 51.5% of hospitals seeing malaria notified 5 or fewer cases in 3 years. Centres that saw <10 cases/year treat 26.3% of malaria cases; 6.1% of cases are treated in hospitals seeing <2 cases/year. Concentration of falciparum malaria was highest in Greater London (1925, 54.7%), South East (515, 14.6%), East of England (402, 11.4%) and North West (192, 5.4%). The North East and Northern Ireland each notified 5 or fewer cases per year. Median diagnosis-to-treatment time was 1 h (range 0.5-5) for patients receiving artesunate in the specialist centre; 7.5 h (range 4-26) for patients receiving it in referring hospitals via the hub-and-spoke system (p=0.02); 25 h (range 9-45) for patients receiving it on transfer to the regional centre from a referring hospital (p=0.002). CONCLUSIONS: Most UK hospitals see few cases of falciparum malaria and geographical distances are significant. Over 25% of cases are seen in hospitals where malaria is rare, although 60% are seen in hospitals seeing over 50 cases over 3 years. A hub-and-spoke system minimises drug wastage and ensures availability in centres seeing most cases but is associated with treatment delays elsewhere. As with all observational studies, there are limitations, which are discussed

In situ optical measurement of charge transport dynamics in organic photovoltaics.

We present a novel experimental approach which allows extraction of both spatial and temporal information on charge dynamics in organic solar cells. Using the wavelength dependence of the photonic structure in these devices, we monitor the change in spatial overlap between the photogenerated hole distribution and the optical probe profile as a function of time. In a model system we find evidence for a buildup of the photogenerated hole population close to the hole-extracting electrode on a nanosecond time scale and show that this can limit charge transport through space-charge effects under operating conditions.This work was supported by the EPSRC [Grant number EP/ G060738/1].This is the author accepted manuscript. The final published version is available at http://pubs.acs.org/doi/abs/10.1021/nl503687u

Coupled climate–carbon cycle simulation of the Last Glacial Maximum atmospheric CO2 decrease using a large ensemble of modern plausible parameter sets

During the Last Glacial Maximum (LGM), atmospheric CO2 was around 90 ppmv lower than during the pre-industrial period. The reasons for this decrease are most often elucidated through factorial experiments testing the impact of individual mechanisms. Due to uncertainty in our understanding of the real system, however, the different models used to conduct the experiments inevitably take on different parameter values and different structures. In this paper, the objective is therefore to take an uncertainty-based approach to investigating the LGM CO2 drop by simulating it with a large ensemble of parameter sets, designed to allow for a wide range of large-scale feedback response strengths. Our aim is not to definitely explain the causes of the CO2 drop but rather explore the range of possible responses. We find that the LGM CO2 decrease tends to predominantly be associated with decreasing sea surface temperatures (SSTs), increasing sea ice area, a weakening of the Atlantic Meridional Overturning Circulation (AMOC), a strengthening of the Antarctic Bottom Water (AABW) cell in the Atlantic Ocean, a decreasing ocean biological productivity, an increasing CaCO3 weathering flux and an increasing deep-sea CaCO3 burial flux. The majority of our simulations also predict an increase in terrestrial carbon, coupled with a decrease in ocean and increase in lithospheric carbon. We attribute the increase in terrestrial carbon to a slower soil respiration rate, as well as the preservation rather than destruction of carbon by the LGM ice sheets. An initial comparison of these dominant changes with observations and paleoproxies other than carbon isotope and oxygen data (not evaluated directly in this study) suggests broad agreement. However, we advise more detailed comparisons in the future, and also note that, conceptually at least, our results can only be reconciled with carbon isotope and oxygen data if additional processes not included in our model are brought into play

Silica coating influences the corona and biokinetics of cerium oxide nanoparticles

Background The physicochemical properties of nanoparticles (NPs) influence their biological outcomes. Methods We assessed the effects of an amorphous silica coating on the pharmacokinetics and pulmonary effects of CeO2 NPs following intratracheal (IT) instillation, gavage and intravenous injection in rats. Uncoated and silica-coated CeO2 NPs were generated by flame spray pyrolysis and later neutron-activated. These radioactive NPs were IT-instilled, gavaged, or intravenously (IV) injected in rats. Animals were analyzed over 28 days post-IT, 7 days post-gavage and 2 days post-injection. Results Our data indicate that silica coating caused more but transient lung inflammation compared to uncoated CeO2. The transient inflammation of silica-coated CeO2 was accompanied by its enhanced clearance. Then, from 7 to 28 days, clearance was similar although significantly more 141Ce from silica-coated (35 %) was cleared than from uncoated (19 %) 141CeO2 in 28 days. The protein coronas of the two NPs were significantly different when they were incubated with alveolar lining fluid. Despite more rapid clearance from the lungs, the extrapulmonary 141Ce from silica-coated 141CeO2 was still minimal (\u3c1 %) although lower than from uncoated 141CeO2 NPs. Post-gavage, nearly 100 % of both NPs were excreted in the feces consistent with very low gut absorption. Both IV-injected 141CeO2 NP types were primarily retained in the liver and spleen. The silica coating significantly altered the plasma protein corona composition and enhanced retention of 141Ce in other organs except the liver. Conclusion We conclude that silica coating of nanoceria alters the biodistribution of cerium likely due to modifications in protein corona formation after IT and IV administration

Powering West Midlands Growth: A Regional Approach to Clean Energy Innovation

The West Midlands is uniquely positioned to lead the UK in taking advantage of the economic opportunities arising from the global transition to a clean energy system. The region’s strengths include: strong and coherent political leadership committed to sustainability; the diversity of economic needs and scale of demand required to build competitive markets to support radical innovation; a world-class concentration of both academic and commercial expertise in the low-carbon energy sector; a massive programme of public and private investment in infrastructure planned for the next decade, and above all, the determination to secure long-term economic benefit from clean energy innovation. This report makes the case for the creation of a small number of Energy Innovation Zones (EIZs) across the region, acting as pathfinders for an approach that might subsequently be adopted across the country as a whole. EIZs enable barriers – such as powerful institutional silos separating transport, digital, planning and energy – to be overcome within designated geographies. They create a risk-managed and commercial-scale context for the development of new local clean energy markets. They also provide a practical mechanism to help attract investment and muster local political support. At a national level, they can help ensure innovation is built into the government’s strategic sector deals and other large scale public investment projects

Autoreactivity and Exceptional CDR Plasticity (but Not Unusual Polyspecificity) Hinder Elicitation of the Anti-HIV Antibody 4E10

The broadly-neutralizing anti-HIV antibody 4E10 recognizes an epitope in the membrane-proximal external region of the HIV envelope protein gp41. Previous attempts to elicit 4E10 by vaccination with envelope-derived or reverse-engineered immunogens have failed. It was presumed that the ontogeny of 4E10-equivalent responses was blocked by inherent autoreactivity and exceptional polyreactivity. We generated 4E10 heavy-chain knock-in mice, which displayed significant B cell dysregulation, consistent with recognition of autoantigen/s by 4E10 and the presumption that tolerance mechanisms may hinder the elicitation of 4E10 or 4E10-equivalent responses. Previously proposed candidate 4E10 autoantigens include the mitochondrial lipid cardiolipin and a nuclear splicing factor, 3B3. However, using carefully-controlled assays, 4E10 bound only weakly to cardiolipin-containing liposomes, but also bound negatively-charged, non-cardiolipin-containing liposomes comparably poorly. 4E10/liposome binding was predominantly mediated by electrostatic interactions rather than presumed hydrophobic interactions. The crystal structure of 4E10 free of bound ligands showed a dramatic restructuring of the combining site, occluding the HIV epitope binding site and revealing profound flexibility, but creating an electropositive pocket consistent with non-specific binding of phospholipid headgroups. These results strongly suggested that antigens other than cardiolipin mediate 4E10 autoreactivity. Using a synthetic peptide library spanning the human proteome, we determined that 4E10 displays limited and focused, but unexceptional, polyspecificity. We also identified a novel autoepitope shared by three ER-resident inositol trisphosphate receptors, validated through binding studies and immunohistochemistry. Tissue staining with 4E10 demonstrated reactivity consistent with the type 1 inositol trisphosphate receptor as the most likely candidate autoantigen, but is inconsistent with splicing factor 3B3. These results demonstrate that 4E10 recognition of liposomes competes with MPER recognition and that HIV antigen and autoepitope recognition may be distinct enough to permit eliciting 4E10-like antibodies, evading autoimmunity through directed engineering. However, 4E10 combining site flexibility, exceptional for a highly-matured antibody, may preclude eliciting 4E10 by conventional immunization strategies

The role of spin in the kinetic control of recombination in organic photovoltaics.

In biological complexes, cascade structures promote the spatial separation of photogenerated electrons and holes, preventing their recombination. In contrast, the photogenerated excitons in organic photovoltaic cells are dissociated at a single donor-acceptor heterojunction formed within a de-mixed blend of the donor and acceptor semiconductors. The nanoscale morphology and high charge densities give a high rate of electron-hole encounters, which should in principle result in the formation of spin-triplet excitons, as in organic light-emitting diodes. Although organic photovoltaic cells would have poor quantum efficiencies if every encounter led to recombination, state-of-the-art examples nevertheless demonstrate near-unity quantum efficiency. Here we show that this suppression of recombination arises through the interplay between spin, energetics and delocalization of electronic excitations in organic semiconductors. We use time-resolved spectroscopy to study a series of model high-efficiency polymer-fullerene systems in which the lowest-energy molecular triplet exciton (T1) for the polymer is lower in energy than the intermolecular charge transfer state. We observe the formation of T1 states following bimolecular recombination, indicating that encounters of spin-uncorrelated electrons and holes generate charge transfer states with both spin-singlet ((1)CT) and spin-triplet ((3)CT) characters. We show that the formation of triplet excitons can be the main loss mechanism in organic photovoltaic cells. But we also find that, even when energetically favoured, the relaxation of (3)CT states to T1 states can be strongly suppressed by wavefunction delocalization, allowing for the dissociation of (3)CT states back to free charges, thereby reducing recombination and enhancing device performance. Our results point towards new design rules both for photoconversion systems, enabling the suppression of electron-hole recombination, and for organic light-emitting diodes, avoiding the formation of triplet excitons and enhancing fluorescence efficiency.This work was supported by the Engineering and Physical Sciences Research Council (EPSRC)This is the accepted version of the original publication available at: http://www.nature.com/nature/journal/v500/n7463/full/nature12339.html

Ontogeny of Recognition Specificity and Functionality for the Broadly Neutralizing Anti-HIV Antibody 4E10

The process of antibody ontogeny typically improves affinity, on-rate, and thermostability, narrows polyspecificity, and rigidifies the combining site to the conformer optimal for binding from the broader ensemble accessible to the precursor. However, many broadly-neutralizing anti-HIV antibodies incorporate unusual structural elements and recognition specificities or properties that often lead to autoreactivity. The ontogeny of 4E10, an autoreactive antibody with unexpected combining site flexibility, was delineated through structural and biophysical comparisons of the mature antibody with multiple potential precursors. 4E10 gained affinity primarily by off-rate enhancement through a small number of mutations to a highly conserved recognition surface. Controverting the conventional paradigm, the combining site gained flexibility and autoreactivity during ontogeny, while losing thermostability, though polyspecificity was unaffected. Details of the recognition mechanism, including inferred global effects due to 4E10 binding, suggest that neutralization by 4E10 may involve mechanisms beyond simply binding, also requiring the ability of the antibody to induce conformational changes distant from its binding site. 4E10 is, therefore, unlikely to be re-elicited by conventional vaccination strategies