The Potential Of High-Resolution BAC-FISH In Banana Breeding

Abstract The genetic complexity in the genus Musa has been subject of study in many breeding programs worldwide. Parthenocarpy, female sterility, polyploidy in different cultivars and limited amount of genetic and genomic information make the production of new banana cultivars difficult and time consuming. In addition, it is known that part of the cultivars and related wild species in the genus contain numerous chromosomal rearrangements. In order to produce new cultivars more effectively breeders must better understand the genetic differences of the potential crossing parents for introgression hybridization, but extensive genetic information is lacking. As an alternative to achieve information on genetic collinearity we make use of modern chromosome map technology known as high-resolution fluorescent in situ hybridization (FISH). This article presents the technical aspects and applications of such a technology in Musa species. The technique deals with BAC clone positioning on pachytene chromosomes of Calcutta 4 (Musa acuminata ssp. burmanicoides, A genome group, section Eumusa) and M. velutina (section Rodochlamys). Pollen mother cells digestion with pectolytic enzymes and maceration with acetic acid were optimized for making cell spread preparations appropriate for FISH. As an example of this approach we chose BAC clones that contain markers to known resistance genes and hybridize them for establishing their relative positions on the two species. Technical challenges for adapting existing protocols to the banana cells are presented. We also discuss how this technique can be instrumental for validating collinearity between potential crossing parents and how the method can be helpful in future mapping initiatives, and how this method allows identification of chromosomal rearrangements between related Musa species and cultivar

Embrapa Agrienergy oil palm research platform focuses in developing biotechnology and bioinformatics to assist breeding.

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Aggregation of measures to produce an overall assessment of animal welfare. Part 1: a review of existing methods

Several systems have been proposed for the overall assessment of animal welfare at the farm level for the purpose of advising farmers or assisting public decision-making. They are generally based on several measures compounded into a single evaluation, using different rules to assemble the information. Here we discuss the different methods used to aggregate welfare measures and their applicability to certification schemes involving welfare. Data obtained on a farm can be (i) analysed by an expert who draws an overall conclusion; (ii) compared with minimal requirements set for each measure; (iii) converted into ranks, which are then summed; or (iv) converted into values or scores compounded in a weighted sum (e.g. TGI35L) or using ad hoc rules. Existing methods used at present (at least when used exclusively) may be insufficiently sensitive or not routinely applicable, or may not reflect the multidimensional nature of welfare and the relative importance of various welfare measures. It is concluded that different methods may be used at different stages of the construction of an overall assessment of animal welfare, depending on the constraints imposed on the aggregation proces

A phase I study of a new polyamine biosynthesis inhibitor, SAM486A, in cancer patients with solid tumours

Because tumour cell proliferation is highly dependent upon up-regulation of de-novo polyamine synthesis, inhibition of the polyamine synthesis pathway represents a potential target for anticancer therapy. SAM486A (CGP 48664) is a new inhibitor of the polyamine biosynthetic enzyme S-adenosylmethionine decarboxylase (SAMDC), more potent and specific than the first-generation SAMDC inhibitor methylglyoxal (bis) guanylhydrazone (MGBG). Preclinical testing confirmed promising antiproliferative activity. In this phase I study, SAM486A was given 4-weekly as a 120 h infusion. 39 adult cancer patients were enrolled with advanced/refractory disease not amenable to established treatments, PS ≤ 2, adequate marrow, liver, renal and cardiac function. Doses were escalated in 100% increments without toxicity in 24 pts from 3 mg m–2cycle–1up to 400 mg m–2cycle–1. At 550 and 700 mg m–2cycle–1reversible dose-limiting neutropenia occurred. Other toxicities included mild fatigue, nausea and vomiting. No objective remission was seen. Pharmakokinetic analysis showed a terminal half-life of approximately 2 days. AUC and Cmax were related to dose; neutropenia correlated with AUC. The recommended dose for further phase II studies on this schedule is 400 mg m–2cycle–1. © 2000 Cancer Research Campaig

Predictors of orphan drug approval in the European Union

Objective: To encourage the development of drugs for rare diseases, orphan drug legislation has been introduced in the USA (1983) and in the EU (2000). Recent literature discusses factors that may influence the development of new orphan medicinal products in the EU. This study aims to identify predictors for successful marketing authorisation of potential orphan drugs in the EU. Methods: A comparison between randomly selected authorised and a matched sample of not-yet-authorised orphan drug designations has been performed. Determinants in the study included characteristics of the indication, of the product and of the sponsor. Data were collected from the public domain only. Results: Orphan drug approval was strongly associated with previous experience of the sponsor in obtaining approval for another orphan drug (OR=17.3, 95% CI=5.6-53.1). Furthermore, existing synthetic entities compared to biotechnology products tended to have a higher likelihood of reaching approval status (OR=3.9, 95% CI=0.9-16.6). Conclusion: This study showed that experience of a company in developing orphan drugs is an important predictor for subsequent authorisation of other orphan drugs. The same applies for existing (synthetic) molecules, for which much knowledge is available. Further research should be directed towards studying the quality of the clinical development program of those designated orphan medicinal products not reaching approval status

Identification and characterization of a resistance gene analog (RGA) from the Caricaceae Dumort family.

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Cost–utility analysis of imatinib mesilate for the treatment of advanced stage chronic myeloid leukaemia

Imatinib mesilate (Glivec®, Novartis Pharmaceuticals) is a novel therapy for the treatment of chronic myeloid leukaemia (CML). We evaluated the cost-effectiveness of imatinib (600 mg daily) when used for the treatment of patients in advanced stages of CML (accelerated phase and blast crisis) against conventional therapies of combination chemotherapy (DAT) and palliative care in hospital or at home. A Markov model simulated the transitions of hypothetical patient cohorts and outcomes were modelled for 5 years from the start of treatment. Costs were estimated from the perspective of the UK National Health Service. Over 5 years, a patient in accelerated phase will, on average, accrue an additional 2.09 QALYs with imatinib compared to conventional therapies, while patients in blast crisis will accrue an additional 0.58 quality-adjusted life-years (QALYs) with imatinib compared to conventional therapies. The costs per additional QALY gained from treatment with imatinib compared with conventional therapies were £29 344 (accelerated phase) and £42 239 (blast crisis). The results were particularly sensitive to the price of imatinib, improvements in quality of life, and the duration of haematological responses. We conclude that treatment of CML with imatinib confers considerably greater survival and quality of life than conventional treatments but at a cost