HOX transcription factors are potential targets and markers in malignant mesothelioma

YesBackground The HOX genes are a family of homeodomain-containing transcription factors that determine cellular identity during development and which are dys-regulated in some cancers. In this study we examined the expression and oncogenic function of HOX genes in mesothelioma, a cancer arising from the pleura or peritoneum which is associated with exposure to asbestos. Methods We tested the sensitivity of the mesothelioma-derived lines MSTO-211H, NCI-H28, NCI-H2052, and NCI-H226 to HXR9, a peptide antagonist of HOX protein binding to its PBX co-factor. Apoptosis was measured using a FACS-based assay with Annexin, and HOX gene expression profiles were established using RT-QPCR on RNA extracted from cell lines and primary mesotheliomas. The in vivo efficacy of HXR9 was tested in a mouse MSTO-211H flank tumor xenograft model. Results We show that HOX genes are significantly dysregulated in malignant mesothelioma. Targeting HOX genes with HXR9 caused apoptotic cell death in all of the mesothelioma-derived cell lines, and prevented the growth of mesothelioma tumors in a mouse xenograft model. Furthermore, the sensitivity of these lines to HXR9 correlated with the relative expression of HOX genes that have either an oncogenic or tumor suppressive function in cancer. The analysis of HOX expression in primary mesothelioma tumors indicated that these cells could also be sensitive to the disruption of HOX activity by HXR9, and that the expression of HOXB4 is strongly associated with overall survival. Conclusion HOX genes are a potential therapeutic target in mesothelioma, and HOXB4 expression correlates with overall survival.The authors gratefully acknowledge the support of the British Lung Foundation, grant number ICAPPG10-1. KJH acknowledges support from the ICR/RM NIHR Biomedical Research Centre

Frequent fires prime plant developmental responses to burning

Coping with temporal variation in fire requires plants to have plasticity in traits that promote persistence, but how plastic responses to current conditions are affected by past fire exposure remains unknown. We investigate phenotypic divergence between populations of four resprouting grasses exposed to differing experimental fire regimes (annually burnt or unburnt for greater than 35 years) and test whether divergence persists after plants are grown in a common environment for 1 year. Traits relating to flowering and biomass allocation were measured before plants were experimentally burnt, and their regrowth was tracked. Genetic differentiation between populations was investigated for a subset of individuals. Historic fire frequency influenced traits relating to flowering and below-ground investment. Previously burnt plants produced more inflorescences and invested proportionally more biomass below ground, suggesting a greater capacity for recruitment and resprouting than unburnt individuals. Tiller-scale regrowth rate did not differ between treatments, but prior fire exposure enhanced total regrown biomass in two species. We found no consistent genetic differences between populations suggesting trait differences arose from developmental plasticity. Grass development is influenced by prior fire exposure, independent of current environmental conditions. This priming response to fire, resulting in adaptive trait changes, may produce communities more resistant to future fire regime changes

New primary renal diagnosis codes for the ERA-EDTA

The European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Registry has produced a new set of primary renal diagnosis (PRD) codes that are intended for use by affiliated registries. It is designed specifically for use in renal centres and registries but is aligned with international coding standards supported by the WHO (International Classification of Diseases) and the International Health Terminology Standards Development Organization (SNOMED Clinical Terms). It is available as supplementary material to this paper and free on the internet for non-commercial, clinical, quality improvement and research use, and by agreement with the ERA-EDTA Registry for use by commercial organizations. Conversion between the old and the new PRD codes is possible. The new codes are very flexible and will be actively managed to keep them up-to-date and to ensure that renal medicine can remain at the forefront of the electronic revolution in medicine, epidemiology research and the use of decision support systems to improve the care of patients

Large seeds provide an intrinsic growth advantage that depends on leaf traits and root allocation

1. Seed mass and growth rate are important dimensions of plant ecological diversity, but their relationship remains unresolved. Negative relationships between RGR and seed mass are well-established. However, RGR is size dependent, so small-seeded species might achieve fast growth simply because they are initially small. 2. Using a dataset of unprecedented size, sampling 382 grass species, we investigated seed mass and growth rate using both RGR and SGR (RGR at a specific size), accounting for diversity in phylogeny, ecology (e.g. life history, photosynthetic pathway) and environment (mean annual temperature and precipitation). 3. RGR and SGR showed contrasting relationships with seed mass, such that large-seeded species had lower RGR but higher SGR than small-seeded species. However, the relationship between SGR and seed mass depended on leaf dry matter content (LDMC), and was only positive in high-LDMC species. When compared at a common size, the fast growth of large-seeded and low-LDMC species was associated with greater biomass allocation to roots in the hot, high-light environment used for our experiment. Photosynthetic pathway and life history contributed to variation in SGR, with C4 annuals having higher SGRs than C3 perennials regardless of seed size. 4. Large seeds therefore afford an intrinsic growth advantage in species with resource-conserving leaf traits, and may provide a competitive edge in resource-poor environments. This work advances the understanding of how seed mass and growth rate co-evolve with other ecological factors

A standardized response to biological invasions

Centre of Excellence for Invasion Biolog

The recent and rapid spread of Themeda triandra

Tropical savannas cover over 20% of land surface. They sustain a high diversity of mammalian herbivores and promote frequent fires, both of which are dependent on the underlying grass composition. These habitats are typically dominated by relatively few taxa, and the evolutionary origins of the dominant grass species are largely unknown. Here, we trace the origins of the genus Themeda, which contains a number of widespread grass species dominating tropical savannas. Complete chloroplast genomes were assembled for seven samples and supplemented with chloroplast and nuclear ITS markers for 71 samples representing 18 of the 27 Themeda species. Phylogenetic analysis supports a South Asian origin for both the genus and the widespread dominant T. triandra. This species emerged ~1.5 Ma from a group that had lived in the savannas of Asia for several million years. It migrated to Australia ~1.3 Ma and to mainland Africa ~0.5 Ma, where it rapidly spread in pre-existing savannas and displaced other species. Themeda quadrivalvis, the second most widespread Themeda species, is nested within T. triandra based on whole chloroplast genomes, and may represent a recent evolution of an annual growth form that is otherwise almost indistinguishable from T. triandra. The recent spread and modern-day dominance of T. triandra highlight the dynamism of tropical grassy biomes over millennial time-scales that has not been appreciated, with dramatic shifts in species dominance in recent evolutionary times. The ensuing species replacements likely had profound effects on fire and herbivore regimes across tropical savannas

Resprouting grasses are associated with less frequent fire than seeders

Plant populations persist under recurrent fire via resprouting from surviving tissues (resprouters) or seedling recruitment (seeders). Woody species are inherently slow maturing, meaning that seeders are confined to infrequent fire regimes. However, for grasses, which mature faster, the relationships between persistence strategy and fire regime remain unknown. Globally, we analysed associations between fire regimes experienced by hundreds of grass species and their persistence strategy, within a phylogenetic context. We also tested whether persistence strategies are associated with morphological and physiological traits. Resprouters were associated with less frequent fire than seeders. Whilst modal fire frequencies were similar (fire return interval of 4–6 yr), seeders were restricted to regions with more frequent fire than resprouters, suggesting that greater competition with long‐lived resprouters restricts seeder recruitment and survival when fire is rare. Resprouting was associated with lower leaf N, higher C:N ratios and the presence of belowground buds, but was unrelated to photosynthetic pathway. Differences between the life histories of grasses and woody species led to a contrasting prevalence of seeders and resprouters in relation to fire frequency. Rapid sexual maturation in grasses means that seeder distributions, relative to fire regime, are determined by competitive ability and recruitment, rather than time to reproductive maturity

Competition between Fusion and Quasi-fission in the Formation of Super-heavy Elements

Quasifission is a non-equilibrium dynamical process resulting in rapid separation of the dinuclear system initially formed after capture and sticking of two colliding heavy nuclei. This can inhibit fusion by many orders of magnitude, thus suppressing the cross section for formation of superheavy elements. Measurements with projectiles from C to Ni, made at the Australian National University Heavy Ion Accelerator Facility, have mapped out quasifission characteristics and systematics using mass-angle distributions (MAD) - the fission mass-split as a function of centre-of-mass angle. These provide information on quasifission dynamics in the least model-dependent way. Quasifission time-scale information in the MAD has been compared with TDHF calculations of the collisions, with good agreement being found. Most significantly, the nuclear structure of the two colliding nuclei has a dramatic effect on quasifission probabilities and characteristics in gentle collisions at near-barrier energies. The effect of static deformation alignment, closed shells and N/Z matching can completely change reaction outcomes. The realization of this strong dependence makes modelling quasifission and superheavy element formation a challenging task, but should ultimately allow more reliable prediction of superheavy element formation cross sections

CO2-fertilisation enhances resilience to browsing in the recruitment phase of an encroaching savanna tree

CO2-fertilisation is implicated in the widespread and significant woody encroachment of savannas due to CO2-stimulated increases in below-ground reserves that enhance sapling regrowth after fire. However, the effect of CO2 concentration ([CO2]) on tree responses to the other major disturbance in savannas, herbivory, is poorly understood. Herbivory responses cannot be predicted from fire responses, as herbivore effects occur earlier during establishment and are moderated by plant palatability and defence rather than below-ground carbon accumulation. The relationship between herbivory and [CO2] is explored here using a widespread, strongly encroaching savanna tree, Vachellia karroo. Using greenhouse-grown seedlings under past—through to predicted future—[CO2] (180–1000 ppm) and field-grown seedlings under ambient [CO2], we assessed plant survival, growth, defence and palatability. Increasing [CO2] improves the tolerance of greenhouse-grown seedlings to herbivory by stimulating growth and allowing a critical size threshold associated with survival to be reached earlier, thereby decreasing the probability of fatal herbivory during the vulnerable recruitment phase. Elevated [CO2] also decreases the time taken to reach a second size threshold linked to accelerated recovery of field-grown seedlings following herbivory. Seedling growth responses to increasing [CO2] are nonlinear, suggesting that historic growth and survival enhancements are smaller than those predicted for the future. Increasing [CO2] is associated with greater resistance to herbivores (more branched shoot architecture) but not leaf palatability (C:N ratio) or defence (leaf tannins and spine density). Increasing V. karroo densities already constitute a major land management problem in southern African savannas. However, encroachment by this species, and likely other savanna tree species, may be greatly exacerbated under future [CO2], as tolerance to herbivory at the recruitment stage is further enhanced