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

SETD2 loss-of-function promotes renal cancer branched evolution through replication stress and impaired DNA repair

The research leading to these results is supported by Cancer Research UK (XYG, RAB, EG, PM, PE, SG, C Santos, AJR, NM, PAB, AS and C Swanton), Breast Cancer Research Foundation (C Swanton and NK), Medical Research Council (ID: G0902275 to MG and C Santos; ID: G0701935/2 to AJR and C Swanton), the Danish Cancer Society (AMM, J Bartkova and J Bartek), the Lundbeck Foundation (R93-A8990 to J Bartek), the Ministry of the interior of the Czech Republic (grant VG20102014001 to MM and J Bartek), the National Program of Sustainability (grant LO1304 to MM and J Bartek), the Danish Council for Independent Research (grant DFF-1331-00262 to J Bartek), NIHR RMH/ICR Biomedical Research Centre for Cancer (JL), the EC Framework 7 (PREDICT 259303 to XYG, EG, PM, MG, TJ and C Swanton; DDResponse 259892 to J Bartek and J Bartkova and RESPONSIFY ID:259303 to C Swanton), UCL Overseas Research Scholarship (SG). C Swanton is also supported by the European Research Council, Rosetrees Trust and The Prostate Cancer Foundation. This research is supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre

Rationality versus reality: the challenges of evidence-based decision making for health policy makers

<p>Abstract</p> <p>Background</p> <p>Current healthcare systems have extended the evidence-based medicine (EBM) approach to health policy and delivery decisions, such as access-to-care, healthcare funding and health program continuance, through attempts to integrate valid and reliable evidence into the decision making process. These policy decisions have major impacts on society and have high personal and financial costs associated with those decisions. Decision models such as these function under a shared assumption of rational choice and utility maximization in the decision-making process.</p> <p>Discussion</p> <p>We contend that health policy decision makers are generally unable to attain the basic goals of evidence-based decision making (EBDM) and evidence-based policy making (EBPM) because humans make decisions with their naturally limited, faulty, and biased decision-making processes. A cognitive information processing framework is presented to support this argument, and subtle cognitive processing mechanisms are introduced to support the focal thesis: health policy makers' decisions are influenced by the subjective manner in which they individually process decision-relevant information rather than on the objective merits of the evidence alone. As such, subsequent health policy decisions do not necessarily achieve the goals of evidence-based policy making, such as maximizing health outcomes for society based on valid and reliable research evidence.</p> <p>Summary</p> <p>In this era of increasing adoption of evidence-based healthcare models, the rational choice, utility maximizing assumptions in EBDM and EBPM, must be critically evaluated to ensure effective and high-quality health policy decisions. The cognitive information processing framework presented here will aid health policy decision makers by identifying how their decisions might be subtly influenced by non-rational factors. In this paper, we identify some of the biases and potential intervention points and provide some initial suggestions about how the EBDM/EBPM process can be improved.</p

Systematic Review of Potential Health Risks Posed by Pharmaceutical, Occupational and Consumer Exposures to Metallic and Nanoscale Aluminum, Aluminum Oxides, Aluminum Hydroxide and Its Soluble Salts

Aluminum (Al) is a ubiquitous substance encountered both naturally (as the third most abundant element) and intentionally (used in water, foods, pharmaceuticals, and vaccines); it is also present in ambient and occupational airborne particulates. Existing data underscore the importance of Al physical and chemical forms in relation to its uptake, accumulation, and systemic bioavailability. The present review represents a systematic examination of the peer-reviewed literature on the adverse health effects of Al materials published since a previous critical evaluation compiled by Krewski et al. (2007). Challenges encountered in carrying out the present review reflected the experimental use of different physical and chemical Al forms, different routes of administration, and different target organs in relation to the magnitude, frequency, and duration of exposure. Wide variations in diet can result in Al intakes that are often higher than the World Health Organization provisional tolerable weekly intake (PTWI), which is based on studies with Al citrate. Comparing daily dietary Al exposures on the basis of “total Al”assumes that gastrointestinal bioavailability for all dietary Al forms is equivalent to that for Al citrate, an approach that requires validation. Current occupational exposure limits (OELs) for identical Al substances vary as much as 15-fold. The toxicity of different Al forms depends in large measure on their physical behavior and relative solubility in water. The toxicity of soluble Al forms depends upon the delivered dose of Al+ 3 to target tissues. Trivalent Al reacts with water to produce bidentate superoxide coordination spheres [Al(O2)(H2O4)+ 2 and Al(H2O)6 + 3] that after complexation with O2•−, generate Al superoxides [Al(O2•)](H2O5)]+ 2. Semireduced AlO2• radicals deplete mitochondrial Fe and promote generation of H2O2, O2 • − and OH•. Thus, it is the Al+ 3-induced formation of oxygen radicals that accounts for the oxidative damage that leads to intrinsic apoptosis. In contrast, the toxicity of the insoluble Al oxides depends primarily on their behavior as particulates. Aluminum has been held responsible for human morbidity and mortality, but there is no consistent and convincing evidence to associate the Al found in food and drinking water at the doses and chemical forms presently consumed by people living in North America and Western Europe with increased risk for Alzheimer\u27s disease (AD). Neither is there clear evidence to show use of Al-containing underarm antiperspirants or cosmetics increases the risk of AD or breast cancer. Metallic Al, its oxides, and common Al salts have not been shown to be either genotoxic or carcinogenic. Aluminum exposures during neonatal and pediatric parenteral nutrition (PN) can impair bone mineralization and delay neurological development. Adverse effects to vaccines with Al adjuvants have occurred; however, recent controlled trials found that the immunologic response to certain vaccines with Al adjuvants was no greater, and in some cases less than, that after identical vaccination without Al adjuvants. The scientific literature on the adverse health effects of Al is extensive. Health risk assessments for Al must take into account individual co-factors (e.g., age, renal function, diet, gastric pH). Conclusions from the current review point to the need for refinement of the PTWI, reduction of Al contamination in PN solutions, justification for routine addition of Al to vaccines, and harmonization of OELs for Al substances

Non-affirmative Theory of Education as a Foundation for Curriculum Studies, Didaktik and Educational Leadership

This chapter presents non-affirmative theory of education as the foundation for a new research program in education, allowing us to bridge educational leadership, curriculum studies and Didaktik. We demonstrate the strengths of this framework by analyzing literature from educational leadership and curriculum theory/didaktik. In contrast to both socialization-oriented explanations locating curriculum and leadership within existing society, and transformation-oriented models viewing education as revolutionary or super-ordinate to society, non-affirmative theory explains the relation between education and politics, economy and culture, respectively, as non-hierarchical. Here critical deliberation and discursive practices mediate between politics, culture, economy and education, driven by individual agency in historically developed cultural and societal institutions. While transformative and socialization models typically result in instrumental notions of leadership and teaching, non-affirmative education theory, previously developed within German and Nordic education, instead views leadership and teaching as relational and hermeneutic, drawing on ontological core concepts of modern education: recognition; summoning to self-activity and Bildsamkeit. Understanding educational leadership, school development and teaching then requires a comparative multi-level approach informed by discursive institutionalism and organization theory, in addition to theorizing leadership and teaching as cultural-historical and critical-hermeneutic activity. Globalisation and contemporary challenges to deliberative democracy also call for rethinking modern nation-state based theorizing of education in a cosmopolitan light. Non-affirmative education theory allows us to understand and promote recognition based democratic citizenship (political, economical and cultural) that respects cultural, ethical and epistemological variations in a globopolitan era. We hope an American-European-Asian comparative dialogue is enhanced by theorizing education with a non-affirmative approach