Elucidating the genetic basis of antioxidant status in lettuce (Lactuca sativa).

A diet rich in phytonutrients from fruit and vegetables has been acknowledged to afford protection against a range of human diseases, but many of the most popular vegetables are low in phytonutrients. Wild relatives of crops may contain allelic variation for genes determining the concentrations of these beneficial phytonutrients, and therefore understanding the genetic basis of this variation is important for breeding efforts to enhance nutritional quality. In this study, lettuce recombinant inbred lines, generated from a cross between wild and cultivated lettuce (Lactuca serriola and Lactuca sativa, respectively), were analysed for antioxidant (AO) potential and important phytonutrients including carotenoids, chlorophyll and phenolic compounds. When grown in two environments, 96 quantitative trait loci (QTL) were identified for these nutritional traits: 4 for AO potential, 2 for carotenoid content, 3 for total chlorophyll content and 87 for individual phenolic compounds (two per compound on average). Most often, the L. serriola alleles conferred an increase in total AOs and metabolites. Candidate genes underlying these QTL were identified by BLASTn searches; in several cases, these had functions suggesting involvement in phytonutrient biosynthetic pathways. Analysis of a QTL on linkage group 3, which accounted for >30% of the variation in AO potential, revealed several candidate genes encoding multiple MYB transcription factors which regulate flavonoid biosynthesis and flavanone 3-hydroxylase, an enzyme involved in the biosynthesis of the flavonoids quercetin and kaempferol, which are known to have powerful AO activity. Follow-up quantitative RT-PCR of these candidates revealed that 5 out of 10 genes investigated were significantly differentially expressed between the wild and cultivated parents, providing further evidence of their potential involvement in determining the contrasting phenotypes. These results offer exciting opportunities to improve the nutritional content and health benefits of lettuce through marker-assisted breeding

Bcl-3 promotes multi-modal tumour cell migration via NF-κB1 mediated regulation of Cdc42

A key challenge in the implementation of anti-metastatics as cancer therapies is the multi-modal nature of cell migration, which allows tumour cells to evade the targeted inhibition of specific cell motility pathways. The nuclear factor-kappaB (NF-κB) co-factor B-cell lymphoma 3 (Bcl-3) has been implicated in breast cancer cell migration and metastasis, yet it remains to be determined exactly which cell motility pathways are controlled by Bcl-3 and whether migrating tumour cells are able to evade Bcl-3 intervention. Addressing these questions and the mechanism underpinning Bcl-3’s role in this process would help determine its potential as a therapeutic target. Here we identify Bcl-3 as an upstream regulator of the two principal forms of breast cancer cell motility, involving collective and single-cell migration. This was found to be mediated by the master regulator Cdc42 through binding of the NF-κB transcription factor p50 to the Cdc42 promoter. Notably, Bcl-3 depletion inhibited both stable and transitory motility phenotypes in breast cancer cells with no evidence of migratory adaptation. Overexpression of Bcl-3 enhanced migration and increased metastatic tumour burden of breast cancer cells in vivo, whereas overexpression of a mutant Bcl-3 protein, which is unable to bind p50, suppressed cell migration and metastatic tumour burden suggesting that disruption of Bcl-3/NF-κB complexes is sufficient to inhibit metastasis. These findings identify a novel role for Bcl-3 in intrinsic and adaptive multi-modal cell migration mediated by its direct regulation of the Rho GTPase Cdc42 and identify the upstream Bcl-3:p50 transcription complex as a potential therapeutic target for metastatic disease

Suppression of Bcl3 disrupts viability of breast cancer cells through both p53-dependent and p53-independent mechanisms via loss of NF-κB signalling

The NF-κB co-factor Bcl3 is a proto-oncogene that promotes breast cancer proliferation, metastasis and therapeutic resistance, yet its role in breast cancer cell survival is unclear. Here, we sought to determine the effect of Bcl3 suppression alone on breast cancer cell viability, with a view to informing future studies that aim to target Bcl3 therapeutically. Bcl3 was suppressed by siRNA in breast cancer cell lines before changes in viability, proliferation, apoptosis and senescence were examined. Bcl3 suppression significantly reduced viability and was shown to induce apoptosis in all cell lines tested, while an additional p53-dependent senescence and senescence-associated secretory phenotype was also observed in those cells with functional p53. The role of the Bcl3/NF-κB axis in this senescence response was confirmed via siRNA of the non-canonical NF-κB subunit NFKB2/p52, which resulted in increased cellular senescence and the canonical subunit NFKB1/p50, which induced the senescence-associated secretory phenotype. An analysis of clinical data showed a correlation between reduced relapse-free survival in patients that expressed high levels of Bcl3 and carried a p53 mutation. Together, these data demonstrate a dual role for Bcl3/NF-κB in the maintenance of breast cancer cell viability and suggests that targeting Bcl3 may be more beneficial to patients with tumours that lack functional p53

A hydrothermally stable Ytterbium metal-organic framework as a bifunctional solid-acid catalyst for glucose conversion

Yb6(BDC)7(OH)4(H2O)4 contains both bridging hydroxyls and metal-coordinated waters, possessing Brønsted and Lewis acid sites. The material crystallises from water at 200C. Using the solid as a heterogenous catalyst, glucose is converted into 5-hydroxymethylfurfural, via fructose, with a total selectivity of ~70 % after 24 hours at 140 C in water alone: the material is recyclable with no loss of crystallinity

Nonredox CO2 fixation in solvent-free conditions using a Lewis acid metal–organic framework constructed from a sustainably sourced ligand

CO2 epoxidation to cyclic carbonates under mild, solvent-free conditions is a promising pathway toward sustainable CO2 utilization. Metal–organic frameworks (MOFs) explored for such applications so far are commonly composed of nonrenewable ligands such as benzene dicarboxylate (BDC) or synthetically complex linkers and therefore are not suitable for commercial utilization. Here, we report new yttrium 2,5-furandicarboxylate (FDC)-based MOFs: “UOW-1” and “UOW-2” synthesized via solvothermal assembly, with the former having a unique structural topology. The FDC linker can be derived from biomass and is a green and sustainable alternative to conventionally used BDC ligands, which are sourced exclusively from fossil fuels. UOW-1, owing to unique coordination unsaturation and a high density of Lewis active sites, promotes a high catalytic activity (∼100% conversion; ∼99% selectivity), a high turnover frequency (70 h–1), and favorable first-order kinetics for CO2 epoxidation reactions using an epichlorohydrin model substrate under solvent-free conditions within 6 h and a minimal cocatalyst amount. A systematic catalytic study was carried out by broadening the epoxide substrate scope to determine the influence of electronic and steric factors on CO2 epoxidation. Accordingly, higher conversion efficiencies were observed for substrates with high electrophilicity on the carbon center and minimal steric bulk. The work presents the first demonstration of sustainable FDC-based MOFs used for efficient CO2 utilization

A Review of the N-bound and the Maximal Mass Conjectures Using NUT-Charged dS Spacetimes

The proposed dS/CFT correspondence remains an intriguing paradigm in the context of string theory. Recently it has motivated two interesting conjectures: the entropic N-bound and the maximal mass conjecture. The former states that there is an upper bound to the entropy in asymptotically de Sitter spacetimes, given by the entropy of pure de Sitter space. The latter states that any asymptotically de Sitter spacetime cannot have a mass larger than the pure de Sitter case without inducing a cosmological singularity. Here we review the status of these conjectures and demonstrate their limitation. We first describe a generalization of gravitational thermodynamics to asymptotically de Sitter spacetimes, and show how to compute conserved quantities and gravitational entropy using this formalism. From this we proceed to a discussion of the N-bound and maximal mass conjectures. We then illustrate that these conjectures are not satisfied for certain asymptotically de Sitter spacetimes with NUT charge. We close with a presentation of explicit examples in various spacetime dimensionalities.Comment: 49 pages, 17 figures, a few typos corrected, addendum added with regard to some references that were later brought to our attentio

QTLs for shelf life in lettuce co-locate with those for leaf biophysical properties but not with those for leaf developmental traits

Developmental and biophysical leaf characteristics that influence post-harvest shelf life in lettuce, an important leafy crop, have been examined. The traits were studied using 60 informative F9 recombinant inbed lines (RILs) derived from a cross between cultivated lettuce (Lactuca sativa cv. Salinas) and wild lettuce (L. serriola acc. UC96US23). Quantitative trait loci (QTLs) for shelf life co-located most closely with those for leaf biophysical properties such as plasticity, elasticity, and breakstrength, suggesting that these are appropriate targets for molecular breeding for improved shelf life. Significant correlations were found between shelf life and leaf size, leaf weight, leaf chlorophyll content, leaf stomatal index, and epidermal cell number per leaf, indicating that these pre-harvest leaf development traits confer post-harvest properties. By studying the population in two contrasting environments in northern and southern Europe, the genotype by environment interaction effects of the QTLs relevant to leaf development and shelf life were assessed. In total, 107 QTLs, distributed on all nine linkage groups, were detected from the 29 traits. Only five QTLs were common in both environments. Several areas where many QTLs co-located (hotspots) on the genome were identified, with relatively little overlap between developmental hotspots and those relating to shelf life. However, QTLs for leaf biophysical properties (breakstrength, plasticity, and elasticity) and cell area correlated well with shelf life, confirming that the ideal ideotype lettuce should have small cells with strong cell walls. The identification of QTLs for leaf development, strength, and longevity will lead to a better understanding of processability at a genetic and cellular level, and allow the improvement of salad leaf quality through marker-assisted breeding

Optimised synthesis and further structural diversity of ytterbium benzene-1,4-dicarboxylate MOFs

The optimisation of the crystallisation of the hydrothermally-stable metal–organic framework Yb6-MOF (Yb6(BDC)7(OH)4(H2O)4) to provide a reproducible one-step synthesis is achieved by use of the sodium salt of benzene-1,4-dicarboxylate (Na2BDC) as ligand precursor and control of pH with aqueous NaOH at 190 °C over 3 days. Phase purity is confirmed using powder X-ray diffraction (PXRD) and thermogravimetric analysis (TGA). During exploration of synthesis conditions from the same set of chemical reagents, three further ytterbium benzene-1,4-dicarboxylates have been isolated and structurally characterised using single-crystal X-ray diffraction, with phase purity assessed by PXRD and TGA. UOW-3 (Yb2(H2O)6(BDC)3) crystallises by lowering pH, and has a relatively dense three-dimensionally connected structure with no Yb–O–Yb linkages but dimers of Yb bridged by BDC linkers lying in the ab plane with a pseudo, pillared-layered structure, where BDC connects along c. UOW-4 (Yb4(BDC)6(H2O)6) forms under the same chemical conditions but upon lowering the temperature to 100 °C, and this material again contains no Yb–O–Yb linkages, but chains of BDC-bridged Yb centres cross-linked to give a dense three-dimensional structure. Upon increasing pH of the synthesis mixture, the material UOW-5 forms, Yb5O(OH)8(BDC)2(HBDC), consisting of dense inorganic layers of ytterbium oxyhydroxide, cross linked by BDC and HBDC pillars. The formulation is supported by infrared spectroscopy, which provides evidence for the HBDC monoanion, and also the presence of a short O–O distance indicative of hydrogen bonding between a carboxylate OH and an oxide anion of the inorganic layer. UOW-3 and UOW-4 both convert to Yb6-MOF upon heating in water above their synthesis temperature, whereas UOW-5 is hydrothermally stable at 240 °C. The structures of the new materials are discussed in terms of ligand binding modes, and connectivity of metal centres, with comparison to other reported Yb-BDC phases in order to relate structural chemistry to their synthesis conditions and the hydrothermal stability of the materials