The chemical signatures underlying host plant discrimination by aphids

The diversity of phytophagous insects is largely attributable to speciation involving shifts between host plants. These shifts are mediated by the close interaction between insects and plant metabolites. However, there has been limited progress in understanding the chemical signatures that underlie host preferences. We use the pea aphid (Acyrthosiphon pisum) to address this problem. Host-associated races of pea aphid discriminate between plant species in race-specific ways. We combined metabolomic profiling of multiple plant species with behavioural tests on two A. pisum races, to identify metabolites that explain variation in either acceptance or discrimination. Candidate compounds were identified using tandem mass spectrometry. Our results reveal a small number of compounds that explain a large proportion of variation in the differential acceptability of plants to A. pisum races. Two of these were identified as L-phenylalanine and L-tyrosine but it may be that metabolically-related compounds directly influence insect behaviour. The compounds implicated in differential acceptability were not related to the set correlated with general acceptability of plants to aphids, regardless of host race. Small changes in response to common metabolites may underlie host shifts. This study opens new opportunities for understanding the mechanistic basis of host discrimination and host shifts in insects

Neighbours of cancer-related proteins have key influence on pathogenesis and could increase the drug target space for anticancer therapies

Even targeted chemotherapies against solid cancers show a moderate success increasing the need to novel targeting strategies. To address this problem, we designed a systems-level approach investigating the neighbourhood of mutated or differentially expressed cancer-related proteins in four major solid cancers (colon, breast, liver and lung). Using signalling and protein–protein interaction network resources integrated with mutational and expression datasets, we analysed the properties of the direct and indirect interactors (first and second neighbours) of cancer-related proteins, not found previously related to the given cancer type. We found that first neighbours have at least as high degree, betweenness centrality and clustering coefficient as cancer-related proteins themselves, indicating a previously unknown central network position. We identified a complementary strategy for mutated and differentially expressed proteins, where the affect of differentially expressed proteins having smaller network centrality is compensated with high centrality first neighbours. These first neighbours can be considered as key, so far hidden, components in cancer rewiring, with similar importance as mutated proteins. These observations strikingly suggest targeting first neighbours as a novel strategy for disrupting cancer-specific networks. Remarkably, our survey revealed 223 marketed drugs already targeting first neighbour proteins but applied mostly outside oncology, providing a potential list for drug repurposing against solid cancers. For the very central first neighbours, whose direct targeting would cause several side effects, we suggest a cancer-mimicking strategy by targeting their interactors (second neighbours of cancer-related proteins, having a central protein affecting position, similarly to the cancer-related proteins). Hence, we propose to include first neighbours to network medicine based approaches for (but not limited to) anticancer therapies

Prolonged survival in patients with breast cancer and a history of brain metastases: results of a preplanned subgroup analysis from the randomized phase III BEACON trial

Purpose: Conventional chemotherapy has limited activity in patients with breast cancer and brain metastases (BCBM). Etirinotecan pegol (EP), a novel long-acting topoisomerase-1 inhibitor, was designed using advanced polymer technology to preferentially accumulate in tumor tissue including brain metastases, providing sustained cytotoxic SN38 levels. Methods: The phase 3 BEACON trial enrolled 852 women with heavily pretreated locally recurrent or metastatic breast cancer between 2011 and 2013. BEACON compared EP with treatment of physician’s choice (TPC; eribulin, vinorelbine, gemcitabine, nab-paclitaxel, paclitaxel, ixabepilone, or docetaxel) in patients previously treated with anthracycline, taxane, and capecitabine, including those with treated, stable brain metastases. The primary endpoint, overall survival (OS), was assessed in a pre-defined subgroup of BCBM patients; an exploratory post hoc analysis adjusting for the diagnosis-specific graded prognostic assessment (GPA) index was also conducted. Results: In the trial, 67 BCBM patients were randomized (EP, n = 36; TPC, n = 31). Treatment subgroups were balanced for baseline characteristics and GPA indices. EP was associated with a significant reduction in the risk of death (HR 0.51; P < 0.01) versus TPC; median OS was 10.0 and 4.8 months, respectively. Improvement in OS was observed in both poorer and better GPA prognostic groups. Survival rates at 12 months were 44.4% for EP versus 19.4% for TPC. Consistent with the overall BEACON population, fewer patients on EP experienced grade ≥3 toxicity (50 vs. 70%). Conclusions: The significant improvement in survival in BCBM patients provides encouraging data for EP in this difficult-to-treat subgroup of patients. A phase three trial of EP in BCBM patients is underway (ClinicalTrials.gov NCT02915744)

Fabrication and optical characterization of polystyrene opal templates for the synthesis of scalable, nanoporous (photo)electrocatalytic materials by electrodeposition

Finding solutions to improve the performance of semiconductor light absorbers and catalyst materials remains an outstanding issue that prevents the realization of solar fuel generators. Nanostructuring approaches of photoelectrocatalytic materials have the potential to reduce bulk recombination and improve electron-hole pair separation in semiconductor light absorbers, as well as to increase the active surface area and influence the activity in catalytic systems. Herein, we propose a versatile approach for the synthesis of reproducible, highly homogeneous, large scale nanoporous (photo)electrocatalytic materials for artificial photosynthesis. By identifying and carefully analyzing critical parameters for forming opal templates from solutions of colloidal polystyrene beads (PS), we are able to reproducibly fabricate large area (&gt;cm2) PS films with high optical quality over a wide diameter range (170-600 nm). Using these PS bead opal films as templates, we demonstrate that electrodeposition is a suitable bottom-up infilling technique to produce scalable, homogeneous, and highly ordered nanoporous (photo)electrocatalytic materials, namely Cu2O, BiVO4, CuBi2O4, and Cu. We provide morphological, structural, and optical characterization of the resulting opal replicas. Finally, we demonstrate preliminary integration of the Cu2O inverse opal film into a working photocathode under CO2 reduction conditions

Fabrication and optical characterization of polystyrene opal templates for the synthesis of scalable, nanoporous (photo)electrocatalytic materials by electrodeposition

Finding solutions to improve the performance of semiconductor light absorbers and catalyst materials remains an outstanding issue that prevents the realization of solar fuel generators. Nanostructuring approaches of photoelectrocatalytic materials have the potential to reduce bulk recombination and improve electron-hole pair separation in semiconductor light absorbers, as well as to increase the active surface area and influence the activity in catalytic systems. Herein, we propose a versatile approach for the synthesis of reproducible, highly homogeneous, large scale nanoporous (photo)electrocatalytic materials for artificial photosynthesis. By identifying and carefully analyzing critical parameters for forming opal templates from solutions of colloidal polystyrene beads (PS), we are able to reproducibly fabricate large area (&gt;cm2) PS films with high optical quality over a wide diameter range (170-600 nm). Using these PS bead opal films as templates, we demonstrate that electrodeposition is a suitable bottom-up infilling technique to produce scalable, homogeneous, and highly ordered nanoporous (photo)electrocatalytic materials, namely Cu2O, BiVO4, CuBi2O4, and Cu. We provide morphological, structural, and optical characterization of the resulting opal replicas. Finally, we demonstrate preliminary integration of the Cu2O inverse opal film into a working photocathode under CO2 reduction conditions