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Dundee, United Kingdom
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Haegeman A.,Ghent University | Jones J.T.,SCRI | Danchin E.G.J.,French National Institute for Agricultural Research
Molecular Plant-Microbe Interactions | Year: 2011

The origin of plant parasitism within the phylum Nematoda is intriguing. The ability to parasitize plants has originated independently at least three times during nematode evolution and, as more molecular data has emerged, it has become clear that multiple instances of horizontal gene transfer (HGT) from bacteria and fungi have played a crucial role in the nematode's adaptation to this new lifestyle. The first reported HGT cases in plant-parasitic nematodes were genes encoding plant cell wall-degrading enzymes. Other putative examples of HGT were subsequently described, including genes that may be involved in the modulation of the plant's defense system, the establishment of a nematode feeding site, and the synthesis or processing of nutrients. Although, in many cases, it is difficult to pinpoint the donor organism, candidate donors are usually soil dwelling and are either plant-pathogenic or plant-associated microorganisms, hence occupying the same ecological niche as the nematodes. The exact mechanisms of transfer are unknown, although close contacts with donor microorganisms, such as symbiotic or trophic interactions, are a possibility. The widespread occurrence of horizontally transferred genes in evolutionarily independent plant-parasitic nematode lineages suggests that HGT may be a prerequisite for successful plant parasitism in nematodes. © 2011 The American Phytopathological Society.


Berry P.,ADAS High Mowthorpe | Teakle G.,University of Warwick | Foulkes J.,University of Nottingham | White P.,SCRI | Spink J.,ADAS Rosemaund
Acta Horticulturae | Year: 2010

Oilseed rape has a high requirement for nitrogen (N) fertiliser relative to its seed yield. This paper uses published and unpublished work to explore the extent to which the N use efficiency (seed yield + N supply) of oilseed rape could be improved without reducing seed yield. It was estimated that if the concentration of N in the stem and pod wall at crop maturity could be reduced from 1.0 to 0.6%, the root length density increased to 1 cm/cm to 100 cm soil depth and the post flowering N uptake increased by 20 kg N/ha then the fertiliser requirement could be reduced from 191 to 142 kg N/ha and the N use efficiency could be increased from 15.2 to 22.4 kg of seed dry matter per kg N. Genetic variation was found for all of the traits that were estimated to be important for N use efficiency. This indicates that there is significant scope for plant breeders to reduce N use efficiency in oilseed rape.


Squire G.R.,SCRI | Breckling B.,University of Bremen | Pfeilstetter A.D.,Julius Kuhn Institute | Jorgensen R.B.,Technical University of Denmark | And 8 more authors.
Environmental Science and Pollution Research | Year: 2011

Purpose: Feral oilseed rape has become widespread in Europe on waysides and waste ground. Its potential as a source of GM impurity in oilseed rape harvests is quantified, for the first time, by a consistent analysis applied over a wide range of study areas in Europe. Methods: The maximum contribution of feral oilseed rape to impurities in harvested crops was estimated by combining data on feral abundance and crop yield from five established, demographic studies in agricultural habitats in Denmark, Germany (2), France and the UK, constituting over 1,500 ha of land and 16 site-years of observations. Persistence of feral populations over time was compared by visual and molecular methods. Results: Ferals had become established in all regions, forming populations 0.2 to 15 km-2. The seed they produced was always <0.0001% of the seed on crops of oilseed rape in each region. The contribution of ferals to impurity in crops through accidental harvest of seed and through cross-pollination would be an even smaller percentage. Feral oilseed rape nevertheless showed a widespread capacity to persist in all regions and retain traits from varieties no longer grown. Conclusions: Feral oilseed rape is not a relevant source of macroscopic impurity at its present density in the landscape but provides opportunity for genetic recombination, stacking of transgenes and the evolution of genotypes that under strong selection pressure could increase and re-occupy fields to constitute an economic weed burden and impurity in future crops. © 2010 Springer-Verlag.


Lees A.K.,SCRI | Brierley J.L.,SCRI | Stewart J.A.,SCRI | Hilton A.J.,SAC | And 5 more authors.
Plant Pathology | Year: 2010

Controlled-environment and field experiments were done to quantify the individual contribution of seed-tuber and soilborne inoculum of Colletotrichum coccodes in causing black dot disease of potato tubers. Seed-tuber and soilborne inocula of C. coccodes were quantified using an existing real-time PCR assay and related to subsequent incidence and severity of disease. In four field trials, a controlled-environment experiment and through the monitoring of 122 commercial crops, seed-tuber inoculum was found to be relatively less important than soilborne inoculum in causing black dot, and the level of seed-tuber inoculum did not significantly affect either the incidence or severity of disease or the percentage of progeny tubers deemed unmarketable. By contrast, soilborne inoculum had the potential to result in high levels of disease and the level of C. coccodes soil infestation (pg DNA g-1 soil) was found to have a significant effect. At soil infestation levels below 100 pg DNA C. coccodes g-1 soil, 7% of commercial crops had an incidence of black dot greater than 20%, increasing to 40% and 57% of crops at levels of 100-1000 pg g-1 and >1000 pg g-1 soil, respectively. These arbitrary threshold levels for soilborne inoculum related to disease risk are discussed. Interpretation of disease risk based on inoculum levels must, in the future, be informed by agronomic variables and potential control strategies. Journal compilation © 2010 BSPP.


Pant S.,University of Oklahoma | Burris III H.A.,Tennessee Oncology PLLC | Moore K.,University of Oklahoma | Bendell J.C.,Tennessee Oncology PLLC | And 6 more authors.
Investigational New Drugs | Year: 2014

Background: ME-143, a second-generation tumor-specific NADH oxidase inhibitor, is broadly active against human cancers in vitro and in vivo. This first-in-human dose-escalation study evaluated the dose-limiting toxicities (DLTs), pharmacokinetics, safety, tolerability, and preliminary anti-tumor activity of ME-143 in patients with advanced solid tumors. Methods: Patients with advanced solid tumors were treated in a 3+3 escalation design. ME-143 was administered via intravenous infusion on days 1, 8, and 15 of the first 28-daycycle, and weekly thereafter; the final cohort received twice-weekly treatment. Samples for pharmacokinetic analysis were collected during cycle 1. Treatment continued until disease progression or unacceptable toxicity. Results: Eighteen patients were treated: 2.5 mg/kg (n = 3); 5 mg/kg (n = 3); 10 mg/kg (n = 3); 20 mg/kg (n = 6); 20 mg/kg twice-weekly (n =3). There were no DLTs observed. Nearly all treatment-related toxicities were grade 1/2, specifically (all grades) nausea (22%) and fatigue (17%). Two patients experienced infusion reactions at the 20mg/kg dose level, one of which was grade 4. Stable disease was documented in three patients with colorectal cancer, cholangiocarcinoma, and anal cancer. Pharmacokinetic exposures were linear and dose-dependent, with a half-life of approximately 5 h. Conclusions: ME-143 was well-tolerated when administered intravenously at the maximally administered/recommended phase 2 dose of 20 mg/kg once weekly to patients with advanced solid tumors. Though limited clinical activitywas observed with monotherapy, inhibitors of tumor-specific NADH oxidase such as ME-143 may derive their greatest benefit in combination with cytotoxic chemotherapy. © The Author(s) 2013.


Bendell J.C.,Sarah Cannon Research Institute SCRI | Bendell J.C.,Tennessee Oncology PLLC | Meluch A.,Tennessee Oncology | Peyton J.,Tennessee Oncology | And 4 more authors.
Clinical Advances in Hematology and Oncology | Year: 2012

Purpose: To evaluate the efficacy of bevacizumab (Avastin, Genentech) and erlotinib (Tarceva, Genentech/Roche) when added to preoperative chemoradiation therapy with paclitaxel, carboplatin, and infusional 5-fluorouracil (5-FU) in the treatment of localized cancers of the esophagus or gastroesophageal (GE) junction. The primary endpoint was the pathologic complete response (pCR) rate. Methods: Eligible patients had previously untreated localized squamous cell, adenocarcinoma, or adenosquamous carcinoma of the esophagus or GE junction, and were considered surgical candidates at enrollment. Daily erlotinib (100 mg orally) was administered on days 1-42 of preoperative treatment. Patients received paclitaxel (200 mg/m2 intravenously [IV]), carboplatin (area under the curve [AUC] 5.0 IV), and bevacizumab (15 mg/kg IV) on days 1 and 22, and 5-FU by continuous infusion (225 mg/m2/day IV) on days 1-35, with radiation therapy in 1.8-Gy single fractions, Monday-Friday (to a total of 45 Gy). Those who were deemed surgical candidates proceeded to resection during weeks 12-14. Results: Between February 2007 and September 2009, 62 patients (median age, 64 years; 92% male; 94% adenocarcinoma) were enrolled; 44 patients (71%) completed neoadjuvant treatment and proceeded to surgery. Eighteen patients (29%) achieved pCR, with partial pathologic remission in an additional 22 patients (35%). Common grade 3/4 toxicities included leukopenia (64%), neutropenia (44%), mucositis/stomatitis (42%), diarrhea (27%), and esophagitis (27%). There were 40 instances of treatment-related hospitalization, and 2 postoperative deaths. Conclusions: The addition of bevacizumab and erlotinib to neoadjuvant chemoradiation did not demonstrate survival benefit or improved pCR rate over similar regimens. While the overall rates of toxicity were not increased, targeted agent-specific toxicity was evident. Further study of this specific regimen is not warranted.


Spigel D.R.,Sarah Cannon Research Institute | Greco F.A.,Sarah Cannon Research Institute | Waterhouse D.,Internal Medicine at Oncology Hematology Care | Shipley D.,Internal Medicine at Tennessee Oncology PLLC | And 7 more authors.
Clinical Advances in Hematology and Oncology | Year: 2010

Purpose: To examine FOLFOX/bevacizumab/cetuximab in the first-line treatment of metastatic colorectal cancer (mCRC). Methods: Design: Randomized phase II trial aimed at achieving a 60% objective response rate (ORR). Due to frequent cetuximab-related hypersensitivity reactions the trial was amended to a single-arm design. Eligibility: Previously untreated mCRC, measurable disease, Eastern Cooperative Oncology Group performance status (ECOGPS) 0-1. Treatment: Modified FOLFOX6 (oxaliplatin 85 mg/m2, leucovorin 350 mg, and 5-fluorouracil 400 mg/m2 bolus; 2.4 g/m2 infusion, 46 h) day 1; bevacizumab 5 mg/kg on day 1; cetuximab 400 mg/m2 on day 1, then 250 mg/m2 on days 1 and 8, every 14 days (1 cycle) until progressive disease (PD); restaging occurred every 4 cycles. Results: With emerging negative progression-free survival (PFS) data from a similarly designed trial, this trial closed early. Enrollment (N=31) was from August 2005-June 2008. Patient characteristics: Median age was 55 years (29-78); 58% were male; 71% were ECOG-PS 0. Ten cycles (median) were completed (range 2-62). The ORR was 55% (95% confidence interval [CI], 36-73%); 11 patients (35%) had stable disease; 1 patient (3%) had PD; 2 patients (6%) were unevaluable. Median PFS was 9 months (95% CI, 8.3-15.2 months); median overall survival was 25.7 months (95% CI, 15.4- 27.6 months). Grade 3/4 toxicities (>1 patient) included neutropenia (25%), rash (23%; grade 2 events, 45%), diarrhea (19%), fatigue (16%), pain (16%), anemia (13%), sensory neuropathy (13%), deepvein thrombosis (10%), nausea (10%), pulmonary embolism (7%), anorexia (6%), and vomiting (6%). Conclusion: In this limited trial, it is unclear whether cetuximab contributed to FOLFOX/bevacizumab efficacy, although the response rate, PFS, and overall survival were high. The regimen was generally well-tolerated, with expected skin effects; thromboembolic rates should be assessed in larger analyses. Cetuximab's role in first-line mCRC treatment is likely best guided by K-RAS testing in future clinical trials.


PubMed | SCRI
Type: Journal Article | Journal: Environmental science and pollution research international | Year: 2011

Feral oilseed rape has become widespread in Europe on waysides and waste ground. Its potential as a source of GM impurity in oilseed rape harvests is quantified, for the first time, by a consistent analysis applied over a wide range of study areas in Europe.The maximum contribution of feral oilseed rape to impurities in harvested crops was estimated by combining data on feral abundance and crop yield from five established, demographic studies in agricultural habitats in Denmark, Germany (2), France and the UK, constituting over 1,500 ha of land and 16 site-years of observations. Persistence of feral populations over time was compared by visual and molecular methods.Ferals had become established in all regions, forming populations 0.2 to 15 km. The seed they produced was always <0.0001% of the seed on crops of oilseed rape in each region. The contribution of ferals to impurity in crops through accidental harvest of seed and through cross-pollination would be an even smaller percentage. Feral oilseed rape nevertheless showed a widespread capacity to persist in all regions and retain traits from varieties no longer grown.Feral oilseed rape is not a relevant source of macroscopic impurity at its present density in the landscape but provides opportunity for genetic recombination, stacking of transgenes and the evolution of genotypes that under strong selection pressure could increase and re-occupy fields to constitute an economic weed burden and impurity in future crops.


PubMed | SCRI
Type: Journal Article | Journal: TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik | Year: 2011

An association panel consisting of 185 accessions representative of the barley germplasm cultivated in the Mediterranean basin was used to localise quantitative trait loci (QTL) controlling grain yield and yield related traits. The germplasm set was genotyped with 1,536 SNP markers and tested for associations with phenotypic data gathered over 2 years for a total of 24 year location combinations under a broad range of environmental conditions. Analysis of multi-environmental trial (MET) data by fitting a mixed model with kinship estimates detected from two to seven QTL for the major components of yield including 1000 kernel weight, grains per spike and spikes per m(2), as well as heading date, harvest index and plant height. Several of the associations involved SNPs tightly linked to known major genes determining spike morphology in barley (vrs1 and int-c). Similarly, the largest QTL for heading date co-locates with SNPs linked with eam6, a major locus for heading date in barley for autumn sown conditions. Co-localization of several QTL related to yield components traits suggest that major developmental loci may be linked to most of the associations. This study highlights the potential of association genetics to identify genetic variants controlling complex traits.


PubMed | SCRI
Type: Journal Article | Journal: Annals of botany | Year: 2011

The three-dimensional distributions of mineral elements in potato tubers provide insight into their mechanisms of transport and deposition. Many of these minerals are essential to a healthy human diet, and characterizing their distribution within the potato tuber will guide the effective utilization of this staple foodstuff.The variation in mineral composition within the tuber was determined in three dimensions, after determining the orientation of the harvested tuber in the soil. The freeze-dried tuber samples were analysed for minerals using inductively coupled plasma-mass spectrometry (ICP-MS). Minerals measured included those of nutritional significance to the plant and to human consumers, such as iron, zinc, copper, calcium, magnesium, manganese, phosphorus, potassium and sulphur.The concentrations of most minerals were higher in the skin than in the flesh of tubers. The potato skin contained about 17 % of total tuber zinc, 34 % of calcium and 55 % of iron. On a fresh weight basis, most minerals were higher in tuber flesh at the stem end than the bud end of the tuber. Potassium, however, displayed a gradient in the opposite direction. The concentrations of phosphorus, copper and calcium decreased from the periphery towards the centre of the tuber.The distribution of minerals varies greatly within the potato tuber. Low concentrations of some minerals relative to those in leaves may be due to their low mobility in phloem, whereas high concentrations in the skin may reflect direct uptake from the soil across the periderm. In tuber flesh, different minerals show distinct patterns of distribution in the tuber, several being consistent with phloem unloading in the tuber and limited onward movement. These findings have implications both for understanding directed transport of minerals in plants to stem-derived storage organs and for the dietary implications of different food preparation methods for potato tubers.

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