29 research outputs found

    A functional SMAD2/3 binding site in the PEX11β promoter identifies a role for TGFβ in peroxisome proliferation in humans

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    This is the final version. Available on open access from Frontiers Media via the DOI in this recordData availability: The research data supporting this publication are provided within this paper and as supplementary information.In mammals, peroxisomes perform crucial functions in cellular metabolism, signalling and viral defense which are essential to the viability of the organism. Molecular cues triggered by changes in the cellular environment induce a dynamic response in peroxisomes, which manifests itself as a change in peroxisome number, altered enzyme levels and adaptations to the peroxisomal morphology. How the regulation of this process is integrated into the cell’s response to different stimuli, including the signalling pathways and factors involved, remains unclear. Here, a cell-based peroxisome proliferation assay has been applied to investigate the ability of different stimuli to induce peroxisome proliferation. We determined that serum stimulation, long-chain fatty acid supplementation and TGFβ application all increase peroxisome elongation, a prerequisite for proliferation. Time-resolved mRNA expression during the peroxisome proliferation cycle revealed a number of peroxins whose expression correlated with peroxisome elongation, including the β isoform of PEX11, but not the α or γ isoforms. An initial map of putative regulatory motif sites in the respective promoters showed a difference between binding sites in PEX11α and PEX11β, suggesting that these genes may be regulated by distinct pathways. A functional SMAD2/3 binding site in PEX11β points to the involvement of the TGFβ signalling pathway in expression of this gene and thus peroxisome proliferation/dynamics in humans.Biotechnology & Biological Sciences Research Council (BBSRC)Swiss National Science Foundation (SNSF)European Union FP7Medical Research Council (MRC

    Excessive HDAC activation is critical for neurodegeneration in the rd1 mouse

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    Inherited retinal degenerations, collectively termed retinitis pigmentosa (RP), constitute one of the leading causes of blindness in the developed world. RP is at present untreatable and the underlying neurodegenerative mechanisms are unknown, even though the genetic causes are often established. Acetylation and deacetylation of histones, carried out by histone acetyltransferases (HATs) and histone deacetylases (HDACs), respectively, affects cellular division, differentiation, death and survival. We found acetylation of histones and probably other proteins to be dramatically reduced in degenerating photoreceptors in the rd1 human homologous mouse model for RP. Using a custom developed in situ HDAC activity assay, we show that overactivation of HDAC classes I/II temporally precedes photoreceptor degeneration. Moreover, pharmacological inhibition of HDACs I/II activity in rd1 organotypic retinal explants decreased activity of poly-ADP-ribose-polymerase and strongly reduced photoreceptor cell death. These findings highlight the importance of protein acetylation for photoreceptor cell death and survival and propose certain HDAC classes as novel targets for the pharmacological intervention in RP

    Unassisted solar lignin valorisation using a compartmented photo-electro-biochemical cell

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    Lignin is a major component of lignocellulosic biomass. Although it is highly recalcitrant to break down, it is a very abundant natural source of valuable aromatic carbons. Thus, the effective valorisation of lignin is crucial for realising a sustainable biorefinery chain. Here, we report a compartmented photo-electro-biochemical system for unassisted, selective, and stable lignin valorisation, in which a TiO2 photocatalyst, an atomically dispersed Co-based electrocatalyst, and a biocatalyst (lignin peroxidase isozyme H8, horseradish peroxidase) are integrated, such that each system is separated using Nafion and cellulose membranes. This cell design enables lignin valorisation upon irradiation with sunlight without the need for any additional bias or sacrificial agent and allows the protection of the biocatalyst from enzymedamaging elements, such as reactive radicals, gas bubbles, and light. The photo-electrobiochemical system is able to catalyse lignin depolymerisation with a 98.7% selectivity and polymerisation with a 73.3% yield using coniferyl alcohol, a lignin monomer

    The global burden of cancer attributable to risk factors, 2010-19: a systematic analysis for the Global Burden of Disease Study 2019

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    A fuzzy logic method to assess the relationship between landscape patterns and bird richness of the Rolling Pampas

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    The loss of biodiversity in productive ecosystems is a global concern of the last decades. The Rolling Pampas of Argentina is an intensively cropped region that underwent important land use and landscape change, with different impacts on biodiversity of both plants and animals. Land use type and habitat complexity are hypothesized to be the most important factors determining species richness in agro-ecosystems. But it is not easy to define these attributes in an unambiguous fashion, or determine their interactions at different spatial scales. A fuzzy logic approach allows overcoming some of these problems by using linguistic variables and logic rules to relate them and formulate hypothesis. We constructed fuzzy logic models to study how bird species richness in the Rolling Pampas is related to land use and habitat complexity, and how these variables interact at two spatial scales. Results showed that at the local scale, landscape complexity is the most important factor determining species numbers; trees and bodies of water are the most influential complexities. The effect of local scale landscape attributes was modified depending on the context at broader scales, so that agricultural sites were enriched when surrounded by more favorable landscapes. There was a high dispersion in the predicted/observed value relationship, indicating that landscape factors interact in more complex ways than those captured by the models we used. We suggest that the fuzzy logic approach is suitable for working with biological systems, and we discuss the advantages and disadvantages of its use. © 2012 Springer Science+Business Media B.V.Fil: Weyland, Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Fisiológicas y Ecológicas Vinculadas a la Agricultura. Universidad de Buenos Aires. Facultad de Agronomía; ArgentinaFil: Baudry, Jacques. Institut National de la Recherche Agronomique; FranciaFil: Ghersa, Claudio Marco. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Fisiológicas y Ecológicas Vinculadas a la Agricultura. Universidad de Buenos Aires. Facultad de Agronomía; Argentin
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