Colour break in reverse bicolour daffodils is associated with the presence of Narcissus mosaic virus

<p>Abstract</p> <p>Background</p> <p>Daffodils (<it>Narcissus pseudonarcissus</it>) are one of the world's most popular ornamentals. They also provide a scientific model for studying the carotenoid pigments responsible for their yellow and orange flower colours. In reverse bicolour daffodils, the yellow flower trumpet fades to white with age. The flowers of this type of daffodil are particularly prone to colour break whereby, upon opening, the yellow colour of the perianth is observed to be 'broken' into patches of white. This colour break symptom is characteristic of potyviral infections in other ornamentals such as tulips whose colour break is due to alterations in the presence of anthocyanins. However, reverse bicolour flowers displaying colour break show no other virus-like symptoms such as leaf mottling or plant stunting, leading some to argue that the carotenoid-based colour breaking in reverse bicolour flowers may not be caused by virus infection.</p> <p>Results</p> <p>Although potyviruses have been reported to cause colour break in other flower species, enzyme-linked-immunoassays with an antibody specific to the potyviral family showed that potyviruses were not responsible for the occurrence of colour break in reverse bicolour daffodils. Colour break in this type of daffodil was clearly associated with the presence of large quantities of rod-shaped viral particles of lengths 502-580 nm in tepals. Sap from flowers displaying colour break caused red necrotic lesions on <it>Gomphrena globosa</it>, suggesting the presence of potexvirus. Red necrotic lesions were not observed in this indicator plant when sap from reverse bicolour flowers not showing colour break was used. The reverse transcriptase polymerase reactions using degenerate primers to carla-, potex- and poty-viruses linked viral RNA with colour break and sequencing of the amplified products indicated that the potexvirus <it>Narcissisus mosaic virus </it>was the predominant virus associated with the occurrence of the colour break.</p> <p>Conclusions</p> <p>High viral counts were associated with the reverse bicolour daffodil flowers that were displaying colour break but otherwise showed no other symptoms of infection. <it>Narcissus mosaic virus </it>was the virus that was clearly linked to the carotenoid-based colour break.</p

4 Gy versus 24 Gy radiotherapy for follicular and marginal zone lymphoma (FoRT): long-term follow-up of a multicentre, randomised, phase 3, non-inferiority trial

BACKGROUND: The optimal radiotherapy dose for indolent non-Hodgkin lymphoma is uncertain. We aimed to compare 24 Gy in 12 fractions (representing the standard of care) with 4 Gy in two fractions (low-dose radiation). METHODS: FoRT (Follicular Radiotherapy Trial) is a randomised, multicentre, phase 3, non-inferiority trial at 43 study centres in the UK. We enrolled patients (aged >18 years) with indolent non-Hodgkin lymphoma who had histological confirmation of follicular lymphoma or marginal zone lymphoma requiring radical or palliative radiotherapy. No limit on performance status was stipulated, and previous chemotherapy or radiotherapy to another site was permitted. Radiotherapy target sites were randomly allocated (1:1) either 24 Gy in 12 fractions or 4 Gy in two fractions using minimisation and stratified by histology, treatment intent, and study centre. Randomisation was centralised through the Cancer Research UK and University College London Cancer Trials Centre. Patients, treating clinicians, and investigators were not masked to random assignments. The primary endpoint was time to local progression in the irradiated volume based on clinical and radiological evaluation and analysed on an intention-to-treat basis. The non-inferiority threshold aimed to exclude the chance that 4 Gy was more than 10% inferior to 24 Gy in terms of local control at 2 years (HR 1·37). Safety (in terms of adverse events) was analysed in patients who received any radiotherapy and who returned an adverse event form. FoRT is registered with ClinicalTrials.gov, NCT00310167, and the ISRCTN Registry, ISRCTN65687530, and this report represents the long-term follow-up. FINDINGS: Between April 7, 2006, and June 8, 2011, 614 target sites in 548 patients were randomly assigned either 24 Gy in 12 fractions (n=299) or 4 Gy in two fractions (n=315). At a median follow-up of 73·8 months (IQR 61·9-88·0), 117 local progression events were recorded, 27 in the 24 Gy group and 90 in the 4 Gy group. The 2-year local progression-free rate was 94·1% (95% CI 90·6-96·4) after 24 Gy and 79·8% (74·8-83·9) after 4 Gy; corresponding rates at 5 years were 89·9% (85·5-93·1) after 24 Gy and 70·4% (64·7-75·4) after 4 Gy (hazard ratio 3·46, 95% CI 2·25-5·33; p<0·0001). The difference at 2 years remains outside the non-inferiority margin of 10% at -13·0% (95% CI -21·7 to -6·9). The most common events at week 12 were alopecia (19 [7%] of 287 sites with 24 Gy vs six [2%] of 301 sites with 4 Gy), dry mouth (11 [4%] vs five [2%]), fatigue (seven [2%] vs five [2%]), mucositis (seven [2%] vs three [1%]), and pain (seven [2%] vs two [1%]). No treatment-related deaths were reported. INTERPRETATION: Our findings at 5 years show that the optimal radiotherapy dose for indolent lymphoma is 24 Gy in 12 fractions when durable local control is the aim of treatment. FUNDING: Cancer Research UK

Metabolic model integration of the bibliome, genome, metabolome and reactome of Aspergillus niger

The release of the genome sequences of two strains of Aspergillus niger has allowed systems-level investigations of this important microbial cell factory. To this end, tools for doing data integration of multi-ome data are necessary, and especially interesting in the context of metabolism. On the basis of an A. niger bibliome survey, we present the largest model reconstruction of a metabolic network reported for a fungal species. The reconstructed gapless metabolic network is based on the reportings of 371 articles and comprises 1190 biochemically unique reactions and 871 ORFs. Inclusion of isoenzymes increases the total number of reactions to 2240. A graphical map of the metabolic network is presented. All levels of the reconstruction process were based on manual curation. From the reconstructed metabolic network, a mathematical model was constructed and validated with data on yields, fluxes and transcription. The presented metabolic network and map are useful tools for examining systemwide data in a metabolic context. Results from the validated model show a great potential for expanding the use of A. niger as a high-yield production platform

Fractional Euler-Lagrange differential equations via Caputo derivatives

We review some recent results of the fractional variational calculus. Necessary optimality conditions of Euler-Lagrange type for functionals with a Lagrangian containing left and right Caputo derivatives are given. Several problems are considered: with fixed or free boundary conditions, and in presence of integral constraints that also depend on Caputo derivatives.Comment: This is a preprint of a paper whose final and definite form will appear as Chapter 9 of the book Fractional Dynamics and Control, D. Baleanu et al. (eds.), Springer New York, 2012, DOI:10.1007/978-1-4614-0457-6_9, in pres

Fractional variational calculus of variable order

We study the fundamental problem of the calculus of variations with variable order fractional operators. Fractional integrals are considered in the sense of Riemann-Liouville while derivatives are of Caputo type.Comment: Submitted 26-Sept-2011; accepted 18-Oct-2011; withdrawn by the authors 21-Dec-2011; resubmitted 27-Dec-2011; revised 20-March-2012; accepted 13-April-2012; to 'Advances in Harmonic Analysis and Operator Theory', The Stefan Samko Anniversary Volume (Eds: A. Almeida, L. Castro, F.-O. Speck), Operator Theory: Advances and Applications, Birkh\"auser Verlag (http://www.springer.com/series/4850

Occurrence and distribution of pepper veinal mottle virus and cucumber mosaic virus in pepper in Ibadan, Nigeria

Viral diseases constitute obstacles to pepper production in the world. In Nigeria, pepper plants are primarily affected by pepper veinal mottle virus (PVMV), Cucumber mosaic virus (CMV), Pepper leaf curl Virus (TLCV), Tobacco mosaic virus (TMV), Pepper mottle virus (PMV) and a host of other viruses. The experiment was carried out with a diagnostic survey on the experimental field of the National Horticultural Research Institute, Ibadan, Nigeria and on pepper farms in six local government areas within Ibadan Oyo State, Nigeria, forty samples were collected from each of the farms. Diseased samples were obtained from the field and taken to the laboratory for indexing. In ELISA test some of the samples from the pepper farms showed positive reaction to single infection with PVMV (36.79%), CMV (22.14%) while some others showed positive reaction to mixed infection of the two viruses (10%) but some also negative reaction to PVMV and CMV antisera (31.07)

Acute cholecystitis in high risk surgical patients: percutaneous cholecystostomy versus laparoscopic cholecystectomy (CHOCOLATE trial): Study protocol for a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Laparoscopic cholecystectomy in acute calculous cholecystitis in high risk patients can lead to significant morbidity and mortality. Percutaneous cholecystostomy may be an alternative treatment option but the current literature does not provide the surgical community with evidence based advice.</p> <p>Methods/Design</p> <p>The CHOCOLATE trial is a randomised controlled, parallel-group, superiority multicenter trial. High risk patients, defined as APACHE-II score 7-14, with acute calculous cholecystitis will be randomised to laparoscopic cholecystectomy or percutaneous cholecystostomy. During a two year period 284 patients will be enrolled from 30 high volume teaching hospitals. The primary endpoint is a composite endpoint of major complications within three months following randomization and need for re-intervention and mortality during the follow-up period of one year. Secondary endpoints include all other complications, duration of hospital admission, difficulty of procedures and total costs.</p> <p>Discussion</p> <p>The CHOCOLATE trial is designed to provide the surgical community with an evidence based guideline in the treatment of acute calculous cholecystitis in high risk patients.</p> <p>Trial Registration</p> <p>Netherlands Trial Register (NTR): <a href="http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2666">NTR2666</a></p

Discordance between Liver Biopsy and FibroScan® in Assessing Liver Fibrosis in Chronic Hepatitis B: Risk Factors and Influence of Necroinflammation

BACKGROUND: Few studies have investigated predictors of discordance between liver biopsy (LB) and liver stiffness measurement (LSM) using FibroScan®. We assessed predictors of discordance between LB and LSM in chronic hepatitis B (CHB) and investigated the effects of necroinflammatory activity. METHODS: In total, 150 patients (107 men, 43 women) were prospectively enrolled. Only LSM with ≥ 10 valid measurements was considered reliable. Liver fibrosis was evaluated using the Laennec system. LB specimens <15 mm in length were considered ineligible. Reference cutoff LSM values to determine discordance were calculated from our cohort (6.0 kPa for ≥ F2, 7.5 kPa for ≥ F3, and 9.4 kPa for F4). RESULTS: A discordance, defined as a discordance of at least two stages between LB and LSM, was identified in 21 (14.0%) patients. In multivariate analyses, fibrosis stages F3-4 and F4 showed independent negative associations with discordance (P = 0.002; hazard ratio [HR], 0.073; 95% confidence interval [CI], 0.014-0.390 for F3-4 and P = 0.014; HR, 0.067; 95% CI, 0.008-0.574 for F4). LSM values were not significantly different between maximal activity grades 1-2 and 3-4 in F1 and F2 fibrosis stages, whereas LSM values were significantly higher in maximal activity grade 3-4 than 1-2 in F3 and F4 fibrosis stage (median 8.6 vs. 11.3 kPa in F3, P = 0.049; median 11.9 vs. 19.2 kPa in F4, P = 0.009). CONCLUSION: Advanced fibrosis stage (F3-4) or cirrhosis (F4) showed a negative correlation with discordance between LB and LSM in patients with CHB, and maximal activity grade 3-4 significantly influenced LSM values in F3 and F4

HIV patients stable on ART retain evidence of a high CMV load but changes to Natural Killer cell phenotypes reflect both HIV and CMV

Background: Whilst ART corrects many effects of HIV disease, T cell populations retain features of accelerated immunological aging. Methods: Here we analyse phenotypic changes to natural killer (NK) cells in HIV patients who began ART with <200 CD4 T-cells/µl and maintained virological control for 12-17 years, compared with CMV seropositive and seronegative healthy control donors. Results: Humoral responses to CMV antigens (lysate, gB, IE-1) remain elevated in the patients (P <0.0001) despite the long duration of ART. Patient's NK cells responded poorly to K562 cells when assessed by CD107a and IFNγ, but this could not be attributed to CMV as responses were low in CMV-seronegative controls. Moreover HIV (and not CMV) increased expression of CD57 on CD56lo cells. Conclusions: Comparisons with published studies suggest that CMV accelerates age-related increases in CD57 expression but levels plateau by 60-70 years of age, so the effect of CMV disappears. In HIV patients the plateau is higher and perhaps reached sooner