Elevating crop disease resistance with cloned genes

Essentially all plant species exhibit heritable genetic variation for resistance to a variety of plant diseases caused by fungi, bacteria, oomycetes or viruses. Disease losses in crop monocultures are already significant, and would be greater but for applications of disease-controlling agrichemicals. For sustainable intensification of crop production, we argue that disease control should as far as possible be achieved using genetics rather than using costly recurrent chemical sprays. The latter imply CO2 emissions from diesel fuel and potential soil compaction from tractor journeys. Great progress has been made in the past 25 years in our understanding of the molecular basis of plant disease resistance mechanisms, and of how pathogens circumvent them. These insights can inform more sophisticated approaches to elevating disease resistance in crops that help us tip the evolutionary balance in favour of the crop and away from the pathogen. We illustrate this theme with an account of a genetically modified (GM) blight-resistant potato trial in Norwich, using the Rpi-vnt1.1 gene isolated from a wild relative of potato, Solanum venturii, and introduced by GM methods into the potato variety Desiree

Inhibition of thrombin on endothelium enhances recruitment of regulatory T cells during IRI and when combined with adoptive Treg transfer, significantly protects against acute tissue injury and prolongs allograft survival

Ischemia-reperfusion injury (IRI) amplifies T cell alloimmune responses after transplantation with thrombin playing a key pro-inflammatory role. To explore the influence of thrombin on regulatory T cell recruitment and efficacy we used a well-established model of IRI in the native murine kidney. Administration of the cytotopic thrombin inhibitor PTL060 inhibited IRI, and by skewing expression of chemokines (reducing CCL2 and CCL3 but increasing CCL17 and CCL22) increased the infiltration of M2 macrophages and Tregs. When PTL060 was combined with infusion of additional Tregs, these effects were further amplified. To test the benefits of thrombin inhibition in a transplant model, BALB/c hearts were transplanted into B6 mice with or without perfusion with PTL060 in combination with Tregs. Thrombin inhibition or Treg infusion alone led to small increments in allograft survival. However, the combined therapy led to modest graft prolongation by the same mechanisms as in renal IRI; graft survival was accompanied by increased numbers of Tregs and anti inflammatory macrophages, and reduced expression of pro-inflammatory cytokines. While the grafts succumbed to rejection associated with the emergence of alloantibody, these data suggest that thrombin inhibition within the transplant vasculature enhances the efficacy of Treg infusion, a therapy that is currently entering the clinic to promote transplant tolerance

Artificial Neural Network to predict mean monthly total ozone in Arosa, Switzerland

Present study deals with the mean monthly total ozone time series over Arosa, Switzerland. The study period is 1932-1971. First of all, the total ozone time series has been identified as a complex system and then Artificial Neural Networks models in the form of Multilayer Perceptron with back propagation learning have been developed. The models are Single-hidden-layer and Two-hidden-layer Perceptrons with sigmoid activation function. After sequential learning with learning rate 0.9 the peak total ozone period (February-May) concentrations of mean monthly total ozone have been predicted by the two neural net models. After training and validation, both of the models are found skillful. But, Two-hidden-layer Perceptron is found to be more adroit in predicting the mean monthly total ozone concentrations over the aforesaid period.Comment: 22 pages, 14 figure

Have regional inequalities in life expectancy widened within the European Union between 1991 and 2008?

<b>BACKGROUND:</b> Health inequalities have widened within and between many European countries over recent decades, but Europe-wide sub-national trends have been largely overlooked. For regions across the European Union (EU), we assess how geographical inequalities (i.e., between regions) and sociospatial inequalities (i.e., between regions grouped by an area-level measure of average household income) in male and female life expectancy have changed between 1991 and 2008.<p></p> <b>METHODS:</b> Household income, life expectancy at birth and population count data were obtained for 129 regions (level 2 Nomenclature of Statistical Territorial Units, 'NUTS') in 13 European countries with 1991-2008 data (2008 population = 272 million). We assessed temporal changes in the range of life expectancies, for all regions and for Western and Eastern European regions separately.<p></p> <b>RESULTS:</b> Between 1991 and 2008, the geographical range of life expectancies found among European regions remained relatively constant, with the exception of life expectancy among male Eastern Europeans, for whom the range widened by 2.8 years. Sociospatial inequalities in life expectancy (1999-2008 data only) remained constant for all regions combined and for Western Europe, but more than doubled in size for male Eastern Europeans. For female Eastern Europeans, life expectancy was unrelated to regional household income.<p></p> <b>CONCLUSIONS:</b>Regional life-expectancy inequalities in the EU have not narrowed over 2 decades, despite efforts to reduce them. Household income differences across European regions may partly explain these inequalities. As inequalities transcend national borders, reduction efforts may require EU-wide coordination in addition to national efforts.<p></p&gt

National priority setting partnership using a Delphi consensus process to develop neonatal research questions suitable for practice-changing randomised trials in the UK

BACKGROUND: The provision of neonatal care is variable and commonly lacks adequate evidence base; strategic development of methodologically robust clinical trials is needed to improve outcomes and maximise research resources. Historically, neonatal research topics have been selected by researchers; prioritisation processes involving wider stakeholder groups have generally identified research themes rather than specific questions amenable to interventional trials. OBJECTIVE: To involve stakeholders including parents, healthcare professionals and researchers to identify and prioritise research questions suitable for answering in neonatal interventional trials in the UK. DESIGN: Research questions were submitted by stakeholders in population, intervention, comparison, outcome format through an online platform. Questions were reviewed by a representative steering group; duplicates and previously answered questions were removed. Eligible questions were entered into a three-round online Delphi survey for prioritisation by all stakeholder groups. PARTICIPANTS: One hundred and eight respondents submitted research questions for consideration; 144 participants completed round one of the Delphi survey, 106 completed all three rounds. RESULTS: Two hundred and sixty-five research questions were submitted and after steering group review, 186 entered into the Delphi survey. The top five ranked research questions related to breast milk fortification, intact cord resuscitation, timing of surgical intervention in necrotising enterocolitis, therapeutic hypothermia for mild hypoxic ischaemic encephalopathy and non-invasive respiratory support. CONCLUSIONS: We have identified and prioritised research questions suitable for practice-changing interventional trials in neonatal medicine in the UK at the present time. Trials targeting these uncertainties have potential to reduce research waste and improve neonatal care

Acute and Chronic Effects of Exercise on Appetite, Energy Intake, and Appetite-Related Hormones: The Modulating Effect of Adiposity, Sex, and Habitual Physical Activity.

Exercise facilitates weight control, partly through effects on appetite regulation. Single bouts of exercise induce a short-term energy deficit without stimulating compensatory effects on appetite, whilst limited evidence suggests that exercise training may modify subjective and homeostatic mediators of appetite in directions associated with enhanced meal-induced satiety. However, a large variability in responses exists between individuals. This article reviews the evidence relating to how adiposity, sex, and habitual physical activity modulate exercise-induced appetite, energy intake, and appetite-related hormone responses. The balance of evidence suggests that adiposity and sex do not modify appetite or energy intake responses to acute or chronic exercise interventions, but individuals with higher habitual physical activity levels may better adjust energy intake in response to energy balance perturbations. The effect of these individual characteristics and behaviours on appetite-related hormone responses to exercise remains equivocal. These findings support the continued promotion of exercise as a strategy for inducing short-term energy deficits irrespective of adiposity and sex, as well as the ability of exercise to positively influence energy balance over the longer term. Future well-controlled studies are required to further ascertain the potential mediators of appetite responses to exercise

Area and individual differences in personal crime victimization incidence: The role of individual, lifestyle/routine activities and contextual predictors

This article examines how personal crime differences between areas and between individuals are predicted by area and population heterogeneity and their synergies. It draws on lifestyle/routine activities and social disorganization theories to model the number of personal victimization incidents over individuals including routine activities and area characteristics, respectively, as well as their (cross-cluster) interactions. The methodology employs multilevel or hierarchical negative binomial regression with extra binomial variation using data from the British Crime Survey and the UK Census. Personal crime rates differ substantially across areas, reflecting to a large degree the clustering of individuals with measured vulnerability factors in the same areas. Most factors suggested by theory and previous research are conducive to frequent personal victimization except the following new results. Pensioners living alone in densely populated areas face disproportionally high numbers of personal crimes. Frequent club and pub visits are associated with more personal crimes only for males and adults living with young children, respectively. Ethnic minority individuals experience fewer personal crimes than whites. The findings suggest integrating social disorganization and lifestyle theories and prioritizing resources to the most vulnerable, rather than all, residents of poor and densely populated areas to prevent personal crimes

Small Big Data: Using multiple data-sets to explore unfolding social and economic change

Bold approaches to data collection and large-scale quantitative advances have long been a preoccupation for social science researchers. In this commentary we further debate over the use of large-scale survey data and official statistics with ‘Big Data’ methodologists, and emphasise the ability of these resources to incorporate the essential social and cultural heredity that is intrinsic to the human sciences. In doing so, we introduce a series of new data-sets that integrate approximately 30 years of survey data on victimisation, fear of crime and disorder and social attitudes with indicators of socio-economic conditions and policy outcomes in Britain. The data-sets that we outline below do not conform to typical conceptions of ‘Big Data’. But, we would contend, they are ‘big’ in terms of the volume, variety and complexity of data which has been collated (and to which additional data can be linked) and ‘big’ also in that they allow us to explore key questions pertaining to how social and economic policy change at the national level alters the attitudes and experiences of citizens. Importantly, they are also ‘small’ in the sense that the task of rendering the data usable, linking it and decoding it, required both manual processing and tacit knowledge of the context of the data and intentions of its creators

Piketty's Calibration Economics: Inequality and the Dissolution of Solutions?

© 2015 Taylor & Francis. Abstract: By popularising interest in inequality, Thomas Piketty's Capital in the Twenty-First Century has made a significant contribution. It has helped to change the basic terms of debate regarding wealth and income. However, Capital exhibits several weaknesses. The overall statement of Piketty's 3 laws tends to confuse the reader by conflating capital with all forms of wealth, and capital with the current market valuation of wealth assets. The whole creates a form of empiricism by metrics or calibration. The aggregation also lends itself to data as history rather than as historically grounded explanation of evidence. Concomitantly, it lacks a theorisation of capitalism, of power, of the state, of social movements, and of social transformations. This affects the way in which possible solutions to inequality are conceived. However, it does provoke further grounds for ethical counterargument productive of more progressive solutions to the problems it highlights

B lymphocytes contribute to indirect pathway T cell sensitisation via acquisition of extracellular vesicles

B cells have been implicated in transplant rejection via antibody‐mediated mechanisms and more recently by presenting donor‐antigens to T cells. We have shown in patients with chronic antibody‐mediated rejection that B cells control the indirect T cell alloresponses. To understand more about the role of B cells as antigen presenting cells for CD4⁺ T cell with indirect allospecificity, B cells were depleted in C57BL/6 mice, using an anti‐CD20 antibody, prior to receiving MHC‐class I‐mismatched (Kᵈ) skin. The absence of B cells at the time of transplantation prolonged skin graft survival. To study the mechanisms behind this observation, T cells with indirect allospecificity were transferred in mice receiving a Kᵈ skin transplant. T cell proliferation was markedly inhibited in the absence of recipient B cells, suggesting that B cells contribute to indirect pathway sensitisation. Furthermore, we have shown that a possible way in which B cells present alloantigens is via acquisition of MHC‐peptide complexes. Finally, we demonstrate that the addition of B cell depletion to the transfer of Tregs with indirect alloresponse further prolonged skin graft survival. This study supports an important role for B cells in indirect T cell priming and further emphasises the advantage of combination therapies in prolonging transplant survival