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  • 1.
    Lundh, Dan
    et al.
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
    Larsson, Dennis
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
    Nahar, Noor
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
    Mandal, Abul
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
    Arsenic accumulation in plants - Outlining strategies for developing improved variety of crops for avoiding arsenic toxicity in foods2010In: Journal of biological systems, ISSN 0218-3390, Vol. 18, no 1, p. 223-241Article in journal (Refereed)
    Abstract [en]

    Contamination of food with arsenics is a potential health risk for both humans and animals in many regions of the world, especially in Asia. Arsenics can be accumulated in humans, animals and plants for a longer period and a long-term exposure of humans to arsenics results in severe damage of kidney, lever, heart etc. and many other vascular diseases. Arsenic contamination in human may also lead to development of cancer. In this paper we report our results on data mining approach (an in silico analysis based on searching of the existing genomic databases) for identification and characterization of genes that might be responsible for uptake, accumulation or metabolism of arsenics. For these in silico analyses we have involved the model plant Arabidopsis thaliana in our investigation. By employing a system biology model (a kinetic model) we have studied the molecular mechanisms of these processes in this plant. This model contains equations for uptake, metabolism and sequestration of different types of arsenic; As(V), As(III), MMAA and DMAA. The model was then implemented in the software XPP. The model was also validated against the data existing in the literatures. Based on the results of these in silico studies we have developed some strategies that can be used for reducing arsenic contents in different parts of the plant. Data mining experiments resulted in identification of two candidate genes (ACR2, arsenate reductase 2 and PCS1, phytochelatin synthase 1) that are involved either in uptake, transport or cellular localization of arsenic in A. thaliana. However, our system biology model revealed that by increasing the level of arsenate reductase together with an increased rate of arsenite sequestration in the vacuoles (by involving an arsenite efflux pump MRP1/2), it is possible to reduce the amount of arsenics in the shoots of A. thaliana to 11–12%.

  • 2.
    Sögård, Peter
    et al.
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences. Department of Molecular Medicine and Surgery, Section for Integrative Physiology, Karolinska Institutet, Stockholm, Sweden.
    Harlén, Mikael
    University of Skövde, School of Life Sciences.
    Long, Yun Chau
    Department of Molecular Medicine and Surgery, Section for Integrative Physiology, Karolinska Institutet, Stockholm, Sweden.
    Szekeres, Ferenc
    Department of Molecular Medicine and Surgery, Section for Integrative Physiology, Karolinska Institutet, Stockholm, Sweden.
    Barnes, Brian R.
    Department of Molecular Medicine and Surgery, Section for Integrative Physiology, Karolinska Institutet, Stockholm, Sweden.
    Chibalin, Alexander V.
    Department of Molecular Medicine and Surgery, Section for Integrative Physiology, Karolinska Institutet, Stockholm, Sweden.
    Zierath, Juleen R.
    Department of Molecular Medicine and Surgery, Section for Integrative Physiology, Karolinska Institutet, Stockholm, Sweden.
    Validation of the in vitro incubation of extensor digitorum longus muscle from mice with a mathematical model2010In: Journal of biological systems, ISSN 0218-3390, Vol. 18, no 3, p. 687-707Article in journal (Refereed)
    Abstract [en]

    In vitro incubation of tissues; in particular, skeletal muscles from rodents, is a widely-used experimental method in diabetes research. This experimental method has previously been validated, both experimentally and theoretically. However, much of the method's experimental data remains unclear, including the high-rate of lactate production and the lack of an observable increase in glycogen content, within a given time. The predominant hypothesis explaining the high-rate of lactate production is that this phenomenon is dependent on a mechanism in glycolysis that works as a safety valve, producing lactate when glucose uptake is super-physiological. Another hypothesis is that existing anoxia forces more ATP to be produced from glycolysis, leading to an increased lactate concentration. The lack of an observable increase in glycogen content is assumed to be dependent on limitations in sensitivity of the measuring method used. We derived a mathematical model to investigate which of these hypotheses is most likely to be correct. Using our model, data analysis indicates that the in vitro incubated muscle specimens, most likely are sensing the presence of existing anoxia, rather than an overflow in glycolysis. The anoxic milieu causes the high lactate production. The model also predicts an increased glycogenolysis. After mathematical analyses, an estimation of the glycogen concentration could be made with a reduced model. In conclusion, central anoxia is likely to cause spatial differences in glycogen concentrations throughout the entire muscle. Thus, data regarding total glycogen levels in the incubated muscle do not accurately represent the entire organ. The presented model allows for an estimation of total glycogen, despite spatial differences present in the muscle specimen.

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