Extensive metabolic cross-talk in melon fruit revealed by spatial and developmental combinatorial metabolomics.

• Variations in tissue development and spatial composition have a major impact on the nutritional and organoleptic qualities of ripe fleshy fruit, including melon (Cucumis melo). To gain a deeper insight into the mechanisms involved in these changes, we identified key metabolites for rational food quality design. • The metabolome, volatiles and mineral elements were profiled employing an unprecedented range of complementary analytical technologies. Fruits were followed at a number of time points during the final ripening process and tissues were collected across the fruit flesh from rind to seed cavity. Approximately 2000 metabolite signatures and 15 mineral elements were determined in an assessment of temporal and spatial melon fruit development. • This study design enabled the identification of: coregulated hubs (including aspartic acid, 2-isopropylmalic acid, ß-carotene, phytoene and dihydropseudoionone) in metabolic association networks; global patterns of coordinated compositional changes; and links of primary and secondary metabolism to key mineral and volatile fruit complements. • The results reveal the extent of metabolic interactions relevant to ripe fruit quality and thus have enabled the identification of essential candidate metabolites for the high-throughput screening of melon breeding populations for targeted breeding programmes aimed at nutrition and flavour improvement.

A Proposed Mechanism for Neurodegeneration in Movement Disorders Characterized by Metal Dyshomeostasis and Oxidative Stress.

Shared molecular pathologies between distinct neurodegenerative disorders offer unique opportunities to identify common mechanisms of neuron death, and apply lessons learned from one disease to another. Neurotoxic superoxide dismutase 1 (SOD1) proteinopathy in SOD1-associated familial amyotrophic lateral sclerosis (fALS) is recapitulated in idiopathic Parkinson disease (PD), suggesting that these two phenotypically distinct disorders share an etiological pathway, and tractable therapeutic target(s). Despite 25 years of research, the molecular determinants underlying SOD1 misfolding and toxicity in fALS remain poorly understood. The absence of SOD1 mutations in PD highlights mounting evidence that SOD1 mutations are not the sole cause of SOD1 protein misfolding occasioning oligomerization and toxicity, reinforcing the importance of non-genetic factors, including protein metallation and post-translational modification in determining SOD1 stability and function. We propose that these non-genetic factors underlie the misfolding and dysfunction of SOD1 and other proteins in both PD and fALS, constituting a shared and tractable pathway to neurodegeneration.

Inter-laboratory reproducibility of fast gas chromatography-electron impact-time of flight mass spectrometry (GC-EI-TOF/MS) based plant metabolomics.

The application of gas chromatography-mass spectrometry (GC-MS) to the 'global' analysis of metabolites in complex samples (i.e. metabolomics) has now become routine. The generation of these data-rich profiles demands new strategies in data mining and standardisation of experimental and reporting aspects across laboratories. As part of the META-PHOR project's (METAbolomics for Plants Health and OutReach: http://www.meta-phor.eu/) priorities towards robust technology development, a GC-MS ring experiment based upon three complex matrices (melon, broccoli and rice) was launched. All sample preparation, data processing, multivariate analyses and comparisons of major metabolite features followed standardised protocols, identical models of GC (Agilent 6890N) and TOF/MS (Leco Pegasus III) were also employed. In addition comprehensive GCxGC-TOF/MS was compared with 1 dimensional GC-TOF/MS. Comparisons of the paired data from the various laboratories were made with a single data processing and analysis method providing an unbiased assessment of analytical method variants and inter-laboratory reproducibility. A range of processing and statistical methods were also assessed with a single exemplary dataset revealing near equal performance between them. Further investigations of long-term reproducibility are required, though the future generation of global and valid metabolomics databases offers much promise.