Dataset Information

StemPanTox: A fast and wide-target drug assessment system for tailor-made safety evaluations using personalized iPS cells.

ABSTRACT: An alternative model that reliably predicts human-specific toxicity is necessary because the translatability of effects on animal models for human disease is limited to context. Previously, we developed a method that accurately predicts developmental toxicity based on the gene networks of undifferentiated human embryonic stem (ES) cells. Here, we advanced this method to predict adult toxicities of 24 chemicals in six categories (neurotoxins, cardiotoxins, hepatotoxins, two types of nephrotoxins, and non-genotoxic carcinogens) and achieved high predictability (AUC = 0.90-1.00) in all categories. Moreover, we screened for an induced pluripotent stem (iPS) cell line to predict the toxicities based on the gene networks of iPS cells using transfer learning of the gene networks of ES cells, and predicted toxicities in four categories (neurotoxins, hepatotoxins, glomerular nephrotoxins, and non-genotoxic carcinogens) with high performance (AUC = 0.82-0.99). This method holds promise for tailor-made safety evaluations using personalized iPS cells.

SUBMITTER: Yamane J

PROVIDER: S-EPMC9218511 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

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StemPanTox: A fast and wide-target drug assessment system for tailor-made safety evaluations using personalized iPS cells.

Yamane Junko J Wada Takumi T Otsuki Hironori H Inomata Koji K Suzuki Mutsumi M Hisaki Tomoka T Sekine Shuichi S Kouzuki Hirokazu H Kobayashi Kenta K Sone Hideko H Yamashita Jun K JK Osawa Mitsujiro M Saito Megumu K MK Fujibuchi Wataru W

iScience 20220606 7

An alternative model that reliably predicts human-specific toxicity is necessary because the translatability of effects on animal models for human disease is limited to context. Previously, we developed a method that accurately predicts developmental toxicity based on the gene networks of undifferentiated human embryonic stem (ES) cells. Here, we advanced this method to predict <i>adult</i> toxicities of 24 chemicals in six categories (neurotoxins, cardiotoxins, hepatotoxins, two types of nephro ...[more]

PMID: 35754715

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Project description:Organic matter management is key to sustain ecosystem services provided by soils. However, it is rarely considered in a holistic view, considering local resources, agro-environmental effects and harmonization with farmers' needs. Organic inputs, like compost and biochar, could represent a sustainable solution to massive current challenges associated to the intensification of agriculture, in particular for tropical regions. Here we assess the potential of agricultural residues as a resource for farmer communities in southwestern India to reduce their dependency on external inputs and sustain ecosystem services. We propose a novel joint evaluation of farmers' aspirations together with agro-environmental effects of organic inputs on soils. Our soil quality evaluation showed that biochar alone or with compost did not improve unilaterally soils in the tropics (Anthroposol, Ferralsol and Vertisol). Many organic inputs led to an initial decrease in water-holding capacities of control soils (-27.3%: coconut shell biochar with compost on Anthroposol). Responses to organic matter inputs for carbon were strongest for Ferralsols (+33.4% with rice husk biochar), and mostly positive for Anthroposols and Vertisols (+12.5% to +13.8% respectively). Soil pH responses were surprisingly negative for Ferralsols and only positive if biochar was applied alone (between -5.6% to +1.9%). For Anthroposols and Vertisols, highest increases were achieved with rice husk biochar + vermicomposts (+7.2% and +5.2% respectively). Our socio-economic evaluation showed that farmers with a stronger economical position showed greater interest towards technology like biochar (factor 1.3 to 1.6 higher for farmers cultivating Anthroposols and/or Vertisols compared to Ferralsols), while poorer farmers more skepticism, which may lead to an increased economical gap within rural communities if technologies are not implemented with long-term guidance. These results advocate for an interdisciplinary evaluation of agricultural technology prior to its implementation as a development tool in the field.

Project description:BackgroundDuring the kraft process to obtain cellulosic pulp from wood, most of the lignin is removed by high-temperature alkaline cooking, released in the black liquors and usually incinerated for energy. However, kraft lignins are a valuable source of phenolic compounds that can be valorized in new bio-based products. The aim of this work is to develop laccases capable of working under the extreme conditions of high temperature and pH, typical of the industrial conversion of wood into kraft pulp and fibreboard, in order to provide extremophilic biocatalysts for depolymerising kraft lignin, and enzyme-assisted technologies for kraft pulp and fibreboard production.ResultsThrough systematic enzyme engineering, combining enzyme-directed evolution and rational design, we changed the optimal pH of the laccase for oxidation of lignin phenols from acidic to basic, enhanced the catalytic activity at alkaline pH and increased the thermal tolerance of the enzyme by accumulating up to eight mutations in the protein sequence. The extremophilic laccase variants show maximum activity at 70 °C and oxidize kraft lignin at pH 10. Their integration into industrial-type processes saves energy and chemicals. As a pre-bleaching stage, the enzymes promote kraft pulp bleachability and significantly reduce the need for chlorine dioxide compared to the industrial sequence. Their application in wood chips during fibreboard production, facilitates the defibering stage, with less energy required.ConclusionsA set of new alkaliphilic and thermophilic fungal laccases has been developed to operate under the extreme conditions of high temperature and pH typical of industrial wood conversion processes. For the first time basidiomycete laccases of high-redox potential show activity on lignin-derived phenols and polymeric lignin at pH 10. Considering the extreme conditions of current industrial processes for kraft pulp and fibreboard production, the new tailor-made laccases constitute a step forward towards turning kraft pulp mills into biorefineries. Their use as biocatalysts in the wood conversion sector is expected to support the development of more environmentally sound and efficient processes, and more sustainable products.

Dataset Information

StemPanTox: A fast and wide-target drug assessment system for tailor-made safety evaluations using personalized iPS cells.

Publications

StemPanTox: A fast and wide-target drug assessment system for tailor-made safety evaluations using personalized iPS cells.

Similar Datasets

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