Loss of LEUCINE CARBOXYL METHYLTRANSFERASE 1 interferes with metal homeostasis in Arabidopsis and enhances susceptibility to environmental stresses

The biochemical function of LEUCINE CARBOXYL METHYLTRANSFERASE 1 (LCMT1) is to transfer a methyl group from the methyl donor S-adenosylmethionine (SAM) to the catalytic subunits of PROTEIN PHOSPHATASE 2A (PP2Ac), PP4 and PP6. This post-translational modification by LCMT1 is found throughout eukaryotes from yeast to animals and plants, indicating that its function is essential. However, Arabidopsis with knocked out LCMT1 still grows and develops almost normally, at least under optimal growth conditions. We therefore proposed that the presence of LCMT1 would be important under non-optimal growth conditions and favoured plant survival during evolution. To shed light on the physiological functions of plant LCMT1, phenotypes of the lcmt1 mutant and wild type Arabidopsis were compared under various conditions including exposure to heavy metals, variable chelator concentrations, and increased temperature. The lcmt1 mutant was found to be more susceptible to these environmental changes than wild type and resulted in poor growth of seedlings and rosette stage plants. Element analysis of rosette stage plants mainly showed a difference between the lcmt1 mutant and wild type regarding concentrations of sodium and boron, two-fold up or halved, respectively. In both lcmt1 and wild type, lack of EDTA in the growth medium resulted in enhanced concentration of copper, manganese, zinc and sulphur, and especially lcmt1 growth was hampered by these conditions. The altered phenotype in response to stress, the element and mRNA transcript analysis substantiate that LCMT1 has an important role in metal homeostasis and show that functional LCMT1 is necessary to prevent damages from heat, heavy metals or lack of chelator.publishedVersio

Implementation, demonstration and validation of a user-defined wall function for direct precipitation fouling in ANSYS fluent

Abstract In a previous paper (Johnsen et al., 2015) and presentation (Johnsen et al., 2016), we developed and demonstrated a generic modelling framework for the modelling of direct precipitation fouling from multi-component fluid mixtures that become super-saturated at the wall. The modelling concept involves the 1-dimensional transport of the fluid species through the turbulent boundary layer close to the wall. The governing equations include the Reynolds-averaged (RANS) advection-diffusion equations for each fluid species, and the axial momentum and energy equations for the fluid mixture. The driving force for the diffusive transport is the local gradient in the species’ chemical potential. Adsorption mechanisms are not modelled per se, but the time-scale of adsorption is reflected in the choice of Dirichlet boundary conditions for the depositing species, at the fluid-solid interface. In this paper, the modelling framework is implemented as a user-defined function (UDF) for the CFD software ANSYS Fluent, to act as a wall boundary condition for mass-transfer to the wall. The subgrid, 1-dimensional formulation of the model reduces the computational cost associated with resolving the fine length-scales at which the boundary-layer mass transfer is determined, and allows for efficient modelling of industry-scale heat exchangers suffering from fouling. The current paper describes the modelling framework, and demonstrates and validates its applicability in a simplified 2D heat exchanger geometry (experimental and detailed CFD modelling data by Pääkkönen et al. (2012, 2016)). By tuning the diffusivity, only, good agreement with the experimental data and the detailed CFD model was obtained, in terms of area-averaged deposition rates

Expertise: No Longer a Sine Qua Non for Guideline Authors?

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Expertise: no longer a sine qua non for guideline authors?

: Several sets of guidelines have been published recently and more are in the works. The very recent American College of Physicians/American Academy of Family Practitioners guidelines were put together by a set of authors and consultants without any expertise in the topic under discussion, that is, hypertension. Although we are not maintaining that all guidelines should be written exclusively by experts, complete lack of expertise among guideline authors is not acceptable.status: publishe

EGFR wild-type amplification and activation promote invasion and development of glioblastoma independent of angiogenesis

Angiogenesis is regarded as a hallmark of cancer progression and it has been postulated that solid tumor growth depends on angiogenesis. At present, however, it is clear that tumor cell invasion can occur without angiogenesis, a phenomenon that is particularly evident by the infiltrative growth of malignant brain tumors, such as glioblastomas (GBMs). In these tumors, amplification or overexpression of wild-type (wt) or truncated and constitutively activated epidermal growth factor receptor (EGFR) are regarded as important events in GBM development, where the complex downstream signaling events have been implicated in tumor cell invasion, angiogenesis and proliferation. Here, we show that amplification and in particular activation of wild-type EGFR represents an underlying mechanism for non-angiogenic, invasive tumor growth. Using a clinically relevant human GBM xenograft model, we show that tumor cells with EGFR gene amplification and activation diffusely infiltrate normal brain tissue independent of angiogenesis and that transient inhibition of EGFR activity by cetuximab inhibits the invasive tumor growth. Moreover, stable, long-term expression of a dominant-negative EGFR leads to a mesenchymal to epithelial-like transition and induction of angiogenic tumor growth. Analysis of human GBM biopsies confirmed that EGFR activation correlated with invasive/non-angiogenic tumor growth. In conclusion, our results indicate that activation of wild-type EGFR promotes invasion and glioblastoma development independent of angiogenesis, whereas loss of its activity results in angiogenic tumor growth. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00401-013-1101-1) contains supplementary material, which is available to authorized users