Field homogeneity in OSCAR-MEE

Soil properties at the beginning of the MEE (Multi Environment Experiments) were statistically analyzed in order to verify the field homogeneity. The initial soil properties represent the starting point to interpret the effect of CC and LM on soil fertility during crop cycle.Soil properties of the fields were quite homogeneous at the beginning of crop cycles (first and second). The soil properties of the experimental fields in the selected areas showed a wide variety of pedons to be used for the comparison of CC and LM effect in different climate zones. Soils from the Northern European sites are more acid and richer of nutrients and organic matter with respect to the soils in Southern sites

Phenotypic heterogeneity and genetic modification of P102L inherited prion disease in an international series

The largest kindred with inherited prion disease P102L, historically Gerstmann-Sträussler-Scheinker syndrome, originates from central England, with émigrés now resident in various parts of the English-speaking world. We have collected data from 84 patients in the large UK kindred and numerous small unrelated pedigrees to investigate phenotypic heterogeneity and modifying factors. This collection represents by far the largest series of P102L patients so far reported. Microsatellite and genealogical analyses of eight separate European kindreds support multiple distinct mutational events at a cytosine-phosphate diester-guanidine dinucleotide mutation hot spot. All of the smaller P102L kindreds were linked to polymorphic human prion protein gene codon 129M and were not connected by genealogy or microsatellite haplotype background to the large kindred or each other. While many present with classical Gerstmann-Sträussler-Scheinker syndrome, a slowly progressive cerebellar ataxia with later onset cognitive impairment, there is remarkable heterogeneity. A subset of patients present with prominent cognitive and psychiatric features and some have met diagnostic criteria for sporadic Creutzfeldt-Jakob disease. We show that polymorphic human prion protein gene codon 129 modifies age at onset: the earliest eight clinical onsets were all MM homozygotes and overall age at onset was 7 years earlier for MM compared with MV heterozygotes (P = 0.02). Unexpectedly, apolipoprotein E4 carriers have a delayed age of onset by 10 years (P = 0.02). We found a preponderance of female patients compared with males (54 females versus 30 males, P = 0.01), which probably relates to ascertainment bias. However, these modifiers had no impact on a semi-quantitative pathological phenotype in 10 autopsied patients. These data allow an appreciation of the range of clinical phenotype, modern imaging and molecular investigation and should inform genetic counselling of at-risk individuals, with the identification of two genetic modifiers

A New Measurement of the 1S0 Neutron-Neutron Scattering Length using the Neutron-Proton Scattering Length as a Standard

The present paper reports high-accuracy cross-section data for the 2H(n,nnp) reaction in the neutron-proton (np) and neutron-neutron (nn) final-state-interaction (FSI) regions at an incident mean neutron energy of 13.0 MeV. These data were analyzed with rigorous three-nucleon calculations to determine the 1S0 np and nn scattering lengths, a_np and a_nn. Our results are a_nn = -18.7 +/- 0.6 fm and a_np = -23.5 +/- 0.8 fm. Since our value for a_np obtained from neutron-deuteron (nd) breakup agrees with that from free np scattering, we conclude that our investigation of the nn FSI done simultaneously and under identical conditions gives the correct value for a_nn. Our value for a_nn is in agreement with that obtained in pion-deuteron capture measurements but disagrees with values obtained from earlier nd breakup studies.Comment: 4 pages and 3 figure

Glucosylsphingosine Is a Highly Sensitive and Specific Biomarker for Primary Diagnostic and Follow-Up Monitoring in Gaucher Disease in a Non-Jewish, Caucasian Cohort of Gaucher Disease Patients

Gaucher disease (GD) is the most common lysosomal storage disorder (LSD). Based on a deficient β-glucocerebrosidase it leads to an accumulation of glucosylceramide. Standard diagnostic procedures include measurement of enzyme activity, genetic testing as well as analysis of chitotriosidase and CCL18/PARC as biomarkers. Even though chitotriosidase is the most well-established biomarker in GD, it is not specific for GD. Furthermore, it may be false negative in a significant percentage of GD patients due to mutation. Additionally, chitotriosidase reflects the changes in the course of the disease belatedly. This further enhances the need for a reliable biomarker, especially for the monitoring of the disease and the impact of potential treatments.Here, we evaluated the sensitivity and specificity of the previously reported biomarker Glucosylsphingosine with regard to different control groups (healthy control vs. GD carriers vs. other LSDs).Only GD patients displayed elevated levels of Glucosylsphingosine higher than 12 ng/ml whereas the comparison controls groups revealed concentrations below the pathological cut-off, verifying the specificity of Glucosylsphingosine as a biomarker for GD. In addition, we evaluated the biomarker before and during enzyme replacement therapy (ERT) in 19 patients, demonstrating a decrease in Glucosylsphingosine over time with the most pronounced reduction within the first 6 months of ERT. Furthermore, our data reveals a correlation between the medical consequence of specific mutations and Glucosylsphingosine.In summary, Glucosylsphingosine is a very promising, reliable and specific biomarker for GD

Abschätzung der Auswirkungen der Krautfäule auf den Bio-Kartoffelbau in verschiedenen Europäischen Ländern, sowie Inventar der angewendeten Anbau- und Pflanzenschutzstrategien

Problemstellung/Ziele Die Kraut- und Knollenfäule (Phytophthora infestans) ist die Krankheit, die im biologischen (aber auch konventionellen) Kartoffelanbau in Europa die größten Probleme verursacht. Unter günstigen klimatischen Bedingungen breitet sich die Krankheit sehr rasch aus und kann große Ertragsausfälle verursachen. Innerhalb von Europa variiert der durch P. infestans verursachte wirtschaftliche Schaden stark zwischen den Regionen. Dies hängt von verschiedenen Faktoren ab, aber in biologisch bewirtschafteten Anbausystemen immt man an, dass die klimatischen Bedingungen, die verwendeten Sorten sowie die agronomischen Maßnahmen wie Bodenbearbeitung oder die Verwendung von Pflanzenschutzmitteln eine wichtige Rolle spielen. Die Reduktion oder das Verbot des Kupfereinsatzes im biologischen Kartoffelanbau wird deshalb auch unterschiedliche Auswirkungen in den verschiedenen Europäischen Regionen haben. Als Teilprojekt des EU-finanzierten Projektes Blight-MOP (QLRT 31065) wurde eine detaillierte Studie der ökonomischen und gesetzlichen Rahmenbedingungen und ein Inventar der Anbausysteme in 7 Ländern durchgeführt, um (i) Ein Inventar der derzeitigen Anbautechniken zu erstellen, (ii) die Auswirkungen von P. infestans auf Erträge und Wirtschaftlichkeit zu evaluieren und die Auswirkungen eines Kupferverbotes abzuschätzen und um (iii) Pflanzenschutzstrategien von Bioproduzenten zu identifizieren, die bereits jetzt ohne den Einsatz von Kupfer auskommen. Fazit: Diese Betriebsanalyse weist darauf hin, dass eine Optimierung der Einzelmassnahmen und die regionsspezfische Integration von Massnahmen zu einer substanziellen Verbesserung des Anbauerfolges führen können. Die Betriebsanalyse zeigt auch, dass Kupfer bislang eine wichtige Rolle bei der Ertragsbildung gespielt hat. Ein Kupferverbot ohne Angebot von praxistauglichen Alternativlösungen (wie sie innerhalb von Blight-MOP und anderen Projekten erarbeitet werden) würde demnach zu einer starken Destabilisierung des biologischen Kartoffelanbaues und vermutlich zu einer Angebotsvernappung führen. Andere Teilprojekte des Blight-MOP Projektes zielen auf die Verbesserung von anbautechnischen Massnahmen und die Entwicklung von Ersatzprodukten für Kupfer ab

Assessment of the Socio-Economic Impact of Late Blight and State of the Art of Management in European Organic Potato Production Systems

In Europe, late blight, caused by Phytophthora infestans, is the most devastating disease affecting organic (and conventional) potato production. Under suitable environmental conditions the disease can spread rapidly and it can cause complete crop loss. The extent of damage due to late blight depends on several factors: in organic production systems these factors include climate, choice of variety, soil management and use of crop protection agents such as copper. Therefore, the extent of economic damage varies between European regions. Council Regulation (EEC) No 2092/91, amended by Commission Regulation (EC) No 473/2002 of 15 March 2002 regulates the use of copper in organic agriculture. Copper has been the single most important control agent in organic late blight control. Therefore, the reduction or an eventual phasing out of copper use will have varying impacts in different regions. This report presents the results of a detailed survey that has been conducted in 7 European countries in the year 2001. It is a subproject of the EU-funded project Blight-MOP (QLRT 31065). The survey investigates legislative, socio-economic and production parameters. The aim of this study was: (i) to obtain an inventory of the current organic potato production techniques, (ii) to assess the impact of a potential ban of copper on yields and viability of organic potato production and (iii) to identify alternative plant protection strategies that are used by organic farmers. This report includes: (i) statistics on yields, farm gate prices, and production techniques, (ii) an analysis offarmer observations and experiences on the extent and impact of late blight epidemics, (iii) an analysis of the farmer’s motivations, expectations and their assessment of the potential impact of a copper ban. Using multiple linear regression we identified production factors which appear to consistently contribute to production success

Impacts of climate change on plant diseases – opinions and trends

There has been a remarkable scientific output on the topic of how climate change is likely to affect plant diseases in the coming decades. This review addresses the need for review of this burgeoning literature by summarizing opinions of previous reviews and trends in recent studies on the impacts of climate change on plant health. Sudden Oak Death is used as an introductory case study: Californian forests could become even more susceptible to this emerging plant disease, if spring precipitations will be accompanied by warmer temperatures, although climate shifts may also affect the current synchronicity between host cambium activity and pathogen colonization rate. A summary of observed and predicted climate changes, as well as of direct effects of climate change on pathosystems, is provided. Prediction and management of climate change effects on plant health are complicated by indirect effects and the interactions with global change drivers. Uncertainty in models of plant disease development under climate change calls for a diversity of management strategies, from more participatory approaches to interdisciplinary science. Involvement of stakeholders and scientists from outside plant pathology shows the importance of trade-offs, for example in the land-sharing vs. sparing debate. Further research is needed on climate change and plant health in mountain, boreal, Mediterranean and tropical regions, with multiple climate change factors and scenarios (including our responses to it, e.g. the assisted migration of plants), in relation to endophytes, viruses and mycorrhiza, using long-term and large-scale datasets and considering various plant disease control methods

DAS-28-based EULAR response and HAQ improvement in rheumatoid arthritis patients switching between TNF antagonists

<p>Abstract</p> <p>Introduction</p> <p>No definitive data are available regarding the value of switching to an alternative TNF antagonist in rheumatoid arthritis patients who fail to respond to the first one. The aim of this study was to evaluate treatment response in a clinical setting based on HAQ improvement and EULAR response criteria in RA patients who were switched to a second or a third TNF antagonist due to failure with the first one.</p> <p>Methods</p> <p>This was an observational, prospective study of a cohort of 417 RA patients treated with TNF antagonists in three university hospitals in Spain between January 1999 and December 2005. A database was created at the participating centres, with well-defined operational instructions. The main outcome variables were analyzed using parametric or non-parametric tests depending on the level of measurement and distribution of each variable.</p> <p>Results</p> <p>Mean (± SD) DAS-28 on starting the first, second and third TNF antagonist was 5.9 (± 2.0), 5.1 (± 1.5) and 6.1 (± 1.1). At the end of follow-up, it decreased to 3.3 (± 1.6; Δ = -2.6; p > 0.0001), 4.2 (± 1.5; Δ = -1.1; p = 0.0001) and 5.4 (± 1.7; Δ = -0.7; p = 0.06). For the first TNF antagonist, DAS-28-based EULAR response level was good in 42% and moderate in 33% of patients. The second TNF antagonist yielded a good response in 20% and no response in 53% of patients, while the third one yielded a good response in 28% and no response in 72%. Mean baseline HAQ on starting the first, second and third TNF antagonist was 1.61, 1.52 and 1.87, respectively. At the end of follow-up, it decreased to 1.12 (Δ = -0.49; p < 0.0001), 1.31 (Δ = -0.21, p = 0.004) and 1.75 (Δ = -0.12; p = 0.1), respectively. Sixty four percent of patients had a clinically important improvement in HAQ (defined as ≥ -0.22) with the first TNF antagonist and 46% with the second.</p> <p>Conclusion</p> <p>A clinically significant effect size was seen in less than half of RA patients cycling to a second TNF antagonist.</p

CO-FREE Alternative Test Products for Copper Reduction in Agriculture

The project CO-FREE (2012-2016) aimed to develop strategies to replace/reduce copper use in organic, integrated and conventional farming. CO-FREE alternative test products (CTPs) were tested and integrated together with decision support systems, disease-tolerant varieties, and innovative breeding goals (ideotypes) into improved management strategies. CO-FREE focused on apple/apple scab (Venturia inaequalis), grape/downy mildew (Plasmopara viticola), and tomato and potato/late blight (Phytophthora infestans). Starting point of the project were ten CTPs with direct or indirect modes of action including Trichoderma atroviride SC1 and protein extract SCNB, Lysobacter spp., yeast-based derivatives, Cladosporium cladosporioides H39, the oligosaccharidic complex COS-OGA, Aneurinibacillus migulanus and Xenorhabdus bovienii, sage (Salvia officinalis) extract, liquorice (Glycyrrhiza glabra) extract, PLEX- and seaweed plant extracts. As the project progressed, further promising CTPs were included by the partners. Field trials were performed in different European countries in 2012-2015 following EPPO standards. In the first years, stand-alone applications of CTPs were tested. In the following years these were integrated into complete strategies. Effects on main and further diseases, on yield and on non-target organisms were assessed. Here, field trial results with CTPs are summarized

Suppression of LPS-induced inflammatory responses in macrophages infected with Leishmania

<p>Abstract</p> <p>Background</p> <p>Chronic inflammation activated by macrophage innate pathogen recognition receptors such as TLR4 can lead to a range of inflammatory diseases, including atherosclerosis, Crohn's disease, arthritis and cancer. Unlike many microbes, the kinetoplastid protozoan pathogen <it>Leishmania </it>has been shown to avoid and even actively suppress host inflammatory cytokine responses, such as LPS-induced IL-12 production. The nature and scope of <it>Leishmania</it>-mediated inflammatory cytokine suppression, however, is not well characterized. Advancing our knowledge of such microbe-mediated cytokine suppression may provide new avenues for therapeutic intervention in inflammatory disease.</p> <p>Methods</p> <p>We explored the kinetics of a range of cytokine and chemokine responses in primary murine macrophages stimulated with LPS in the presence versus absence of two clinically distinct species of <it>Leishmania </it>using sensitive multiplex cytokine analyses. To confirm that these effects were parasite-specific, we compared the effects of <it>Leishmania </it>uptake on LPS-induced cytokine expression with uptake of inert latex beads.</p> <p>Results</p> <p>Whilst <it>Leishmania </it>uptake alone did not induce significant levels of any cytokine analysed in this study, <it>Leishmania </it>uptake in the presence of LPS caused parasite-specific suppression of certain LPS-induced pro-inflammatory cytokines, including IL-12, IL-17 and IL-6. Interestingly, <it>L. amazonensis </it>was generally more suppressive than <it>L. major</it>. We also found that other LPS-induced proinflammatory cytokines, such as IL-1α, TNF-α and the chemokines MIP-1α and MCP-1 and also the anti-inflammatory cytokine IL-10, were augmented during <it>Leishmania </it>uptake, in a parasite-specific manner.</p> <p>Conclusions</p> <p>During uptake by macrophages, <it>Leishmania </it>evades the activation of a broad range of cytokines and chemokines. Further, in the presence of a strong inflammatory stimulus, <it>Leishmania </it>suppresses certain proinflammatory cytokine responses in a parasite-specific manner, however it augments the production of other proinflammatory cytokines. Our findings highlight the complexity of inflammatory cytokine signalling regulation in the context of the macrophage and <it>Leishmania </it>interaction and confirm the utility of the <it>Leishmania</it>/macrophage infection model as an experimental system for further studies of inflammatory regulation. Such studies may advance the development of therapies against inflammatory disease.</p