Monitoring cancer prognosis, diagnosis and treatment efficacy using metabolomics and lipidomics

Introduction: Cellular metabolism is altered during cancer initiation and progression, which allows cancer cells to increase anabolic synthesis, avoid apoptosis and adapt to low nutrient and oxygen availability. The metabolic nature of cancer enables patient cancer status to be monitored by metabolomics and lipidomics. Additionally, monitoring metabolic status of patients or biological models can be used to greater understand the action of anticancer therapeutics. Objectives: Discuss how metabolomics and lipidomics can be used to (i) identify metabolic biomarkers of cancer and (ii) understand the mechanism-of-action of anticancer therapies. Discuss considerations that can maximize the clinical value of metabolic cancer biomarkers including case–control, prognostic and longitudinal study designs. Methods: A literature search of the current relevant primary research was performed. Results: Metabolomics and lipidomics can identify metabolic signatures that associate with cancer diagnosis, prognosis and disease progression. Discriminatory metabolites were most commonly linked to lipid or energy metabolism. Case–control studies outnumbered prognostic and longitudinal approaches. Prognostic studies were able to correlate metabolic features with future cancer risk, whereas longitudinal studies were most effective for studying cancer progression. Metabolomics and lipidomics can help to understand the mechanism-of-action of anticancer therapeutics and mechanisms of drug resistance. Conclusion: Metabolomics and lipidomics can be used to identify biomarkers associated with cancer and to better understand anticancer therapies

Doing participative practitioner-based research

Undertaking participative practitioner-based research in educational contexts can be both rewarding and revealing. The author offers some advice concerning the pitfalls and follies of doing this kind of research and how to avoid them

The use of personal narratives to improve organisational life

Andy Armitage and Alan Thornton carried out a piece of research where they used their own experience of university life as data, and created an on-going narrative between themselves as a source of personal and organisational reflection. Such deepening connections could do much to enhance organisational life

Talking about organisations

Can dialogue reveal hidden truths? This is what prompted Bronwen Rees and Andrew Armitage to experiment with the dialogical process to explore how realities and knowledge about our organisations are created

The rapid structured literature review as a research strategy

A diversity of sources of literature encompassed by the management disciplines appears to result in a growing need for a systematic methodology to map the territory of management theory. As such, when scoping out a study, structured literature review (SLR) can be considered as a means by which any critical, central literature might be considered. However, there is little guidance, or evidence, of this being undertaken for the purposes of small scale projects such as undergraduate or masters’ dissertations. This paper reports four case studies of master’s degree students following management programmes of undertaking a structured literature review (SLR) and the issues and problems they had to encounter during their journey. The findings from the case studies suggest that in terms of time to complete and the volume of output required in terms of word count, Tranfield, et al’s approach to SLRs, whilst suited to doctoral level research is not appropriate generally when dealing with undergraduate and masters research projects. Therefore, this paper provides accounts of the experiences of four students who undertook SLR for their undergraduate or master’s degree dissertation. The paper identifies that these students had to deal with a new set of conceptual problems relating to this “unorthodox” approach to a postgraduate research dissertation in coming to terms with new paradigms of enquiry that are not normally taught as part of a traditional research methods course. This was despite gaining a greater depth of insight into the subject area through a more rigorous and structured manner. The paper presents alternative remedies by way of a rapid structured literature review (RSLR) model. This would appear to be more appropriate to the conducting of small scale literature based research projects when used with undergraduate and master’s degree students than SLR identified for other research activities

Undertaking a structured literature review or structuring a literature review: tales from the field

The diversity of sources of literature within the management disciplines has resulted in a growing need for a systematic methodology to map the territory of its associated theories and models. As such, when scoping out a doctoral or policy based study the Structured Literature Review (SLR) can be considered as a means by which critical literature central to and underpinning the research can be rigorously and systematically mapped out. However, there is little guidance, or evidence, of this being the case when undertaking small scale projects for example undergraduate or masters degree dissertations. This paper reports four case studies using semi-structured interviews of masters degree students following management programmes who undertook a Structured Literature Review based dissertation and the issues and problems they had to encounter during their journey. The findings from the case studies suggest that the approach to SLRs, whilst suited to doctoral level and policy based research is not appropriate when dealing with undergraduate and masters dissertations and projects. The case study findings identified that these students conducting a SLR had to deal with a new set of conceptual, methodological and data collection problems relating to this ‘unorthodox’ approach to conducting a postgraduate research dissertation. The findings show that students had to confront new paradigms of enquiry that are not normally taught or found in ‘traditional’ research texts and research methods courses that are taught on degree programmes. However, the findings do reveal that students gained a greater depth and insight into the subject they were researching through a more rigorous and structured approach. The paper then presents alternative remedies by way of the Rapid Structured Literature Review (RSLR) research strategy which is argued as an appropriate approach in conducting small scale literature based research projects when used with undergraduate and masters degree students rather than the SLR, which is better suited for other types of research such as doctoral and policy based activities

Basal rot of narcissus : understanding pathogenicity in fusarium oxysporum f. sp. narcissi

Fusarium oxysporum is a globally distributed soilborne fungal pathogen causing root rots, bulb rots, crown rots and vascular wilts on a range of horticultural plants. Pathogenic F. oxysporum isolates are highly host specific and are classified as formae speciales. Narcissus is an important ornamental crop and both the quality and yield of flowers and bulbs can be severely affected by a basal rot caused by F. oxysporum f. sp. narcissi (FON); 154 Fusarium isolates were obtained from different locations and Narcissus cultivars in the United Kingdom, representing a valuable resource. A subset of 30 F. oxysporum isolates were all found to be pathogenic and were therefore identified as FON. Molecular characterisation of isolates through sequencing of three housekeeping genes, suggested a monophyletic origin with little divergence. PCR detection of 14 Secreted in Xylem (SIX) genes, previously shown to be associated with pathogenicity in other F. oxysporum f. spp., revealed different complements of SIX7, SIX9, SIX10, SIX12 and SIX13 within FON isolates which may suggest a race structure. SIX gene sequences were unique to FON and SIX10 was present in all isolates, allowing for molecular identification of FON for the first time. The genome of a highly pathogenic isolate was sequenced and lineage specific (LS) regions identified which harboured putative effectors including the SIX genes. Real-time RT-PCR, showed that SIX genes and selected putative effectors were expressed in planta with many significantly upregulated during infection. This is the first study to characterise molecular variation in FON and provide an analysis of the FON genome. Identification of expressed genes potentially associated with virulence provides the basis for future functional studies and new targets for molecular diagnostics

Annotated draft genome sequence of the apple scab pathogen Venturia inaequalis

Apple scab is one of the most economically important diseases of ap- ples worldwide. The disease is caused by the haploid ascomycete Venturia inaequalis. We present here an annotated V. inaequalis whole-genome sequence of 72 Mb, assembled into 238 contigs, with 13,761 predicted genes

CRISPR/Cas9-mediated mutagenesis of phytoene desaturase in diploid and octoploid strawberry

Background: Gene editing using CRISPR/Cas9 is a simple and powerful tool for elucidating genetic controls and for crop improvement and its use has been reported in a growing number of important food crops, including recently Fragaria. In order to inform application of the technology in Fragaria, we targeted the visible endogenous marker gene PDS (phytoene desaturase) in diploid Fragaria vesca ssp. vesca ‘Hawaii 4’ and octoploid F. × ananassa ‘Calypso’. Results: Agrobacterium-mediated transformation of leaf and petiole explants was used for efficient stable integration of constructs expressing plant codon-optimised Cas9 and single guide sequences under control of the Arabidopsis U6-26 consensus promoter and terminator or Fragaria vesca U6III regulatory sequences. More than 80% (‘Hawaii 4’) and 50% (‘Calypso’) putative transgenic shoot lines (multiple shoots derived from a single callus) exhibited mutant phenotypes. Of mutant shoot lines selected for molecular analysis, approximately 75% (‘Hawaii 4’) and 55% (‘Calypso’) included albino regenerants with bi-allelic target sequence variants. Our results indicate the PDS gene is functionally diploid in ‘Calypso’. Conclusion: We demonstrate that CRISPR/Cas9 may be used to generate biallelic mutants at high frequency within the genomes of diploid and octoploid strawberry. The methodology, observations and comprehensive data set pre- sented will facilitate routine application of this technology in Fragaria to single and multiple gene copy targets where mutant phenotypes cannot be identified visually