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  • 1.
    Al-Bayati, Omar
    University of Skövde, School of Bioscience. Baghdad university.
    Optimizing the Fluorescence In situ hybridization technique for a more rapid inspection of Sepsis causative pathogens by employing DNA probes2014Independent thesis Advanced level (degree of Master (One Year)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Abstract

    Sepsis is a serious clinical condition that is characterized by a systemic inflammatory response syndrome resulting from a known or suspected infection. The major clinical symptoms involve an abnormal WBC count, elevated body temperature, respiration and pulse rate. Reported cases with high mortality rate range between 13 - 20 million. In order to treat Sepsis, the detection of bacteria in blood culture is extremely crucial. Treating patients with broad spectrum antibiotics is usually related to adverse effects, drug resistance, increased mortality, and high cost. In the past decades, researches had detected that E. coli and S. aureus are the major role players that cause sepsis. These microbes are molecularly tested by methods like MALDI TOF, FISH and Microarrays.  

    In this analysis, DNA fluorescence in situ hybridization (FISH) assessment for the identification of S. aureus, one of the most frequent blood pathogens, was optimized in the labs of Högskolan i Skövde. As a result, the growth of S. aureus was observed very carefully, optimizing the FISH procedure for gram positive bacteria was done and the sensitivity, stability and specificity of the DNA probe were examined under variant conditions like the continuous decrease in the bacteria cells number and utilizing a mixture of different types of bacteria cells. 

  • 2.
    Bergkvist, Anders
    et al.
    Biochemistry and Biophysics, Department of Chemistry, Göteborg University, Sweden / Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, USA.
    Ejdebäck, Mikael
    University of Skövde, Department of Natural Sciences. Biochemistry and Biophysics, Department of Chemistry, Göteborg University, Sweden.
    Ubbink, Marcellus
    Leiden Institute of Chemistry, Leiden University, Gorlaeus Laboratories, The Netherlands.
    Karlsson, B. Göran
    Department of Molecular Biotechnology, Chalmers University of Technology, Göteborg, Sweden.
    Surface interactions in the complex between cytochrome f and the E43Q/D44N and E59K/E60Q plastocyanin double mutants as determined by (1)H-NMR chemical shift analysis2001In: Protein Science, ISSN 0961-8368, E-ISSN 1469-896X, Vol. 10, no 12, p. 2623-2626Article in journal (Refereed)
    Abstract [en]

    A combination of site-directed mutagenesis and NMR chemical shift perturbation analysis of backbone and side-chain protons has been used to characterize the transient complex of the photosynthetic redox proteins plastocyanin and cytochrome f. To elucidate the importance of charged residues on complex formation, the complex of cytochrome f and E43Q/D44N or E59K/E60Q spinach plastocyanin double mutants was studied by full analysis of the (1)H chemical shifts by use of two-dimensional homonuclear NMR spectra. Both mutants show a significant overall decrease in chemical shift perturbations compared with wild-type plastocyanin, in agreement with a large decrease in binding affinity. Qualitatively, the E43Q/D44N mutant showed a similar interaction surface as wild-type plastocyanin. The interaction surface in the E59K/E60Q mutant was distinctly different from wild type. It is concluded that all four charged residues contribute to the affinity and that residues E59 and E60 have an additional role in fine tuning the orientation of the proteins in the complex.

  • 3.
    Borghate, Vedant Subhash
    University of Skövde, School of Bioscience.
    Functional analysis of an arsB gene (gene-4251) presumably involved in accumulation of arsenics in Lysinibacillus sphaericus2017Independent thesis Advanced level (degree of Master (One Year)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Many regions of the world are facing the problem with arsenic toxicity. Arsenic contamination has become a considerable threat to the environment triggering various big health issues for every life in that contaminated environment. Lysinibacillus sphaericus (B1-CDA) is an arsenic tolerant strain of bacteria that has been reported and characterized before by the researchers of the University of Skövde, Sweden. The bacteria were found to contain many arsenic responsive genes such as arsB, arsC, and arsR which are responsible for arsenic tolerance in the bacterium. The main focus of the current study was to characterize one of the arsB genes (gene-4251) of Lysinibacillus sphaericus B1-CDA by in silico and in vitro analyses in order to determine the molecular function of this gene. The in silico studies conducted by using the Iterative Threading Assembly and Refinement (I-TASSER) server predicted the tertiary structure of the ArsB protein and suggested that this protein is an intrinsic component of the membrane which primarily helps in the binding of metal ions and liberation of metabolic energy. To validate this predictive results, several in vitro experiments were performed. For complementation studies, the arsB gene was cloned from L. sphaericus B1-CDA and transferred to an arsB knock-out mutant of Escherichia coli JW3469-1. Both, the transgenic and mutant strains were grown under the arsenic stress of 50 mM for 96 hrs followed by measuring their growth and arsenic tolerance after every 24 hrs. Statistical analysis confirmed that there was a significant difference in growth between the transgenic and the mutant E. coli strains. The ICP-MS (Inductive Coupled Plasma-Mass Spectroscopy) analysis revealed that after 24 hrs of culture, the arsenic content in the cell-free broth of transgenic strain was reduced from 50 mM to 9.10 mM (81.8%), whereas the reduction in arsenic content by the mutant strain was from 50 mM to 9.80 mM (80.2%). These results suggest that the arsB gene is partly involved in the accumulation of arsenic inside the cells and this feature could be used for a large scale removal of arsenic from the contaminated environment.

  • 4.
    Burnet, Phil W. J.
    et al.
    Department of Psychiatry, University of Oxford, Warneford Hospital.
    Eastwood, Sharon L.
    Department of Psychiatry, University of Oxford, Warneford Hospital.
    Bristow, Greg C.
    Department of Psychiatry, University of Oxford, Warneford Hospital.
    Godlewska, Beata R.
    Department of Psychiatry, University of Oxford, Warneford Hospital.
    Sikka, Pilleriin
    Department of Psychiatry, University of Oxford, Warneford Hospital.
    Walker, Mary
    Department of Psychiatry, University of Oxford, Warneford Hospital.
    Harrison, Paul J.
    Department of Psychiatry, University of Oxford, Warneford Hospital.
    D-amino acid oxidase activity and expression are increased in schizophrenia2008In: Molecular Psychiatry, ISSN 1359-4184, E-ISSN 1476-5578, Vol. 13, no 7, p. 658-660Article in journal (Refereed)
  • 5.
    Chaudhari, Aditi
    et al.
    Wallenberg Laboratory, Department of Molecular and Clinical Medicine, University of Gothenburg, Sweden.
    Krumlinde, Daniel
    Wallenberg Laboratory, Department of Molecular and Clinical Medicine, University of Gothenburg, Sweden / Scientific Solutions, Stockholm, Sweden.
    Lundqvist, Annika
    Wallenberg Laboratory, Department of Molecular and Clinical Medicine, University of Gothenburg, Sweden.
    Akyurek, Levent M
    Department of Medical Chemistry and Cell Biology, University of Gothenburg, Sweden.
    Bandaru, Sashidahr
    Department of Medical Chemistry and Cell Biology, University of Gothenburg, Sweden.
    Skalen, Kristina
    Wallenberg Laboratory, Department of Molecular and Clinical Medicine, University of Gothenburg, Sweden.
    Stahlman, Marcus
    Wallenberg Laboratory, Department of Molecular and Clinical Medicine, University of Gothenburg, Sweden.
    Boren, Jan
    Wallenberg Laboratory, Department of Molecular and Clinical Medicine, University of Gothenburg, Sweden.
    Wettergren, Yvonne
    Department of Surgery, University of Gothenburg, Sweden.
    Ejeskär, Katarina
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Health and Education. Department of Medical and Clinical Genetics, University of Gothenburg, Sweden.
    Sopasakis, Victoria Rotter
    Wallenberg Laboratory, Department of Molecular and Clinical Medicine, University of Gothenburg, Sweden.
    p110 alpha Hot Spot Mutations E545K and H1047R Exert Metabolic Reprogramming Independently of p110 alpha Kinase Activity2015In: Molecular and Cellular Biology, ISSN 0270-7306, Vol. 35, no 19, p. 3258-3273Article in journal (Refereed)
    Abstract [en]

    The phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) catalytic subunit p110α is the most frequently mutated kinase in human cancer, and the hot spot mutations E542K, E545K, and H1047R are the most common mutations in p110α. Very little is known about the metabolic consequences of the hot spot mutations of p110α in vivo. In this study, we used adenoviral gene transfer in mice to investigate the effects of the E545K and H1047R mutations on hepatic and whole-body glucose metabolism. We show that hepatic expression of these hot spot mutations results in rapid hepatic steatosis, paradoxically accompanied by increased glucose tolerance, and marked glycogen accumulation. In contrast, wild-type p110α expression does not lead to hepatic accumulation of lipids or glycogen despite similar degrees of upregulated glycolysis and expression of lipogenic genes. The reprogrammed metabolism of the E545K and H1047R p110α mutants was surprisingly not dependent on altered p110α lipid kinase activity.

  • 6.
    Das Burman, Anindita
    University of Skövde, School of Life Sciences.
    TGF-β (BETA) AND PERIOSTIN MODULATE EACH OTHER’S EXPRESSION IN BOTH BREAST STROMA AND TUMOR CELLS2013Independent thesis Advanced level (degree of Master (One Year)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Breast cancer is the most common cancer in female population worldwide. In addition to mutations, the breast tumor microenvironment especially the tumor cell - stroma interactions through extracellular matrix components and multiple growth factors have been shown to promote tumor progression. Among those, increases in both TGF-β (transforming growth factor beta) activities and periostin expression were associated with tumor cell survival, proliferation and metastasis. TGF-β role in breast cancer progression including its ability to promote periostin expression has been extensively studied. In contrast, the role of periostin in cancer progression remains to be fully understood. Thus, the present study aimed to determine whether TGF-β and periostin have effect on each other’s expressions in breast tumor and stroma cells using in vitro cell models. Through Western blot analyses and ELISAs, the periostin and TGF-β expressions of both stroma and tumor cells were analyzed following TGF-β and periostin treatments, respectively. The results indicate that TGF-β treatments led to significant increase in periostin expression in fibroblasts (p<0.05). In addition, periostin was differentially expressed by human breast cancer cells following TGF-β1 treatment. The TGF-β activities involved activation of pSMAD2 in both L929 fibroblasts and MCF10A mammary cells. Taken together, all experimental data indicate that within the breast tumor TGF-β and periostin likely participate in a regulation loop. Whether this putative regulation loop is critical to metastasis remains to be determined. Should periostin play a critical role in breast cancer progression, it could become a specific target in the preventive and/or therapeutic development of breast cancer patients.

  • 7.
    Deo, Ameya
    et al.
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences.
    Carlsson, Jessica
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences.
    Lindlof, Angelica
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences.
    HOW TO CHOOSE A NORMALIZATION STRATEGY FOR MIRNA QUANTITATIVE REAL-TIME (QPCR) ARRAYS2011In: Journal of Bioinformatics and Computational Biology, ISSN 0219-7200, E-ISSN 1757-6334, Vol. 9, no 6, p. 795-812Article in journal (Refereed)
    Abstract [en]

    Low-density arrays for quantitative real-time PCR (qPCR) are increasingly being used as an experimental technique for miRNA expression profiling. As with gene expression profiling using microarrays, data from such experiments needs effective analysis methods to produce reliable and high-quality results. In the pre-processing of the data, one crucial analysis step is normalization, which aims to reduce measurement errors and technical variability among arrays that might have arisen during the execution of the experiments. However, there are currently a number of different approaches to choose among and an unsuitable applied method may induce misleading effects, which could affect the subsequent analysis steps and thereby any conclusions drawn from the results. The choice of normalization method is hence an important issue to consider. In this study we present the comparison of a number of data-driven normalization methods for TaqMan low-density arrays for qPCR and different descriptive statistical techniques that can facilitate the choice of normalization method. The performance of the normalization methods was assessed and compared against each other as well as against standard normalization using endogenous controls. The results clearly show that the data-driven methods reduce variation and represent robust alternatives to using endogenous controls.

  • 8.
    Dunne, Aisling
    et al.
    Biochemistry and Biotechnology Institute, Trinity College, Dublin 2, Ireland.
    Ejdebäck, Mikael
    Biochemistry and Biotechnology Institute, Trinity College, Dublin 2, Ireland.
    Ludidi, Phumzile L.
    Department of Biochemistry, University of Cambridge, United Kingdom.
    O'Neill, Luke A. J.
    Biochemistry and Biotechnology Institute, Trinity College, Dublin 2, Ireland.
    Gay, Nicholas J.
    Department of Biochemistry, University of Cambridge, United Kingdom.
    Structural complementarity of Toll/interleukin-1 receptor domains in Toll-like receptors and the adaptors Mal and MyD882003In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 278, no 42, p. 41443-41451Article in journal (Refereed)
    Abstract [en]

    The Toll/interleukin 1 receptor (TIR) domain is a region found in the cytoplasmic tails of members of the Toll-like receptor/interleukin-1 receptor superfamily. The domain is essential for signaling and is also found in the adaptor proteins Mal (MyD88 adaptor-like) and MyD88, which function to couple activation of the receptor to downstream signaling components. Experimental structures of two Toll/interleukin 1 receptor domains reveal a alpha-beta-fold similar to that of the bacterial chemotaxis protein CheY, and other evidence suggests that the adaptors can make heterotypic interactions with both the receptors and themselves. Here we show that the purified TIR domains of Mal and MyD88 can form stable heterodimers and also that Mal homodimers and oligomers are dissociated in the presence of ATP. To identify structural features that may contribute to the formation of signaling complexes, we produced models of the TIR domains from human Toll-like receptor 4 (TLR4), Mal, and MyD88. We found that although the overall fold is conserved the electrostatic surface potentials are quite distinct. Docking studies of the models suggest that Mal and MyD88 bind to different regions in TLRs 2 and 4, a finding consistent with a cooperative role of the two adaptors in signaling. Mal and MyD88 are predicted to interact at a third non-overlapping site, suggesting that the receptor and adaptors may form heterotetrameric complexes. The theoretical model of the interactions is supported by experimental data from glutathione S-transferase pull-downs and co-immunoprecipitations. Neither theoretical nor experimental data suggest a direct role for the conserved proline in the BB-loop in the association of TLR4, Mal, and MyD88. Finally we show a sequence relationship between the Drosophila protein Tube and Mal that may indicate a functional equivalence of these two adaptors in the Drosophila and vertebrate Toll pathways.

  • 9.
    Ejdebäck, Mikael
    Göteborgs Universitet.
    Studies on spinach plastocyanin and mutants: Expression in Escherichia coli, folding and function1999Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Photosynthesis is a process in which photons from sunlight excite chlorophylls in the thylakoid membranes of plants, algae and cyanobacteria. The photo-oxidised reaction centre chlorophyll P700 is re-reduced by an electron transferred from the soluble, blue copper protein plastocyanin. The oxidised plastocyanin dissociates and binds to the cytochrome b6f complex, where it accepts an electron and a new redox cycle can begin. Plastocyanin has three regions of importance for the interaction with its redox partners, a hydrophobic patch and two acidic (negatively charged) patches. Electrostatic interactions between opposite charges are important for the association and the specificity and stability of the formed complexes.

    In this work the interactions with photosystem 1 and cytochrome c have been studied using mutants of plastocyanin. The mutations introduced in the small acidic patch and position 88 of plastocyanin had small effects on the binding to photosystem 1 as compared to the weak binding reported for mutants in the large acidic patch. The affinity was increased by the Glu60Gln, Glu60Lys and Asp61Lys mutations and a more efficient electron transfer was observed for the Gln88Lys mutation. The association between Pc mutated in the small acidic patch and cytochrome c was weakened and the rearrangement hindered by lysines in positions 59 and 60.

    The development of an efficient expression system for spinach plastocyanin in the bacterium Escherichia coli made it possible to produce sufficient amounts of isotopically labelled plastocyanin for NMR experiments. This technique was used for solving the structure of the complex between plastocyanin and cytochrome f. The hydrophobic patch on plastocyanin binds to an area close to the heme on cytochrome f. Electrostatic interactions between opposite charges on the two proteins are also important. The short distance from the heme to the copper ligand His87 suggests an electron transfer from the heme via Tyr1 or Phe4 on cytochrome f.

    The involvement of specific amino-acid residues in copper binding or folding of plastocyanin has also been examined by site-directed mutagenesis. The copper-binding histidines have been replaced by other amino acids, but no blue protein could be produced. The stability of the different redox forms of copper plastocyanin as well as the zinc protein has also been determined by guanidinium-induced unfolding.

  • 10.
    Ejdebäck, Mikael
    et al.
    University of Skövde, Department of Natural Sciences. Biochemistry and Biophysics, Department of Chemistry, Göteborg University, Sweden.
    Bergkvist, Anders
    Biochemistry and Biophysics, Department of Chemistry, Göteborg University, Sweden.
    Karlsson, B. Göran
    Deptartment of Molecular Biotechnology, Chalmers University of Technology, Göteborg, Sweden.
    Ubbink, Marcellus
    Leiden Institute of Chemistry, Leiden University, Gorlaeus Laboratories, Netherlands.
    Side-chain interactions in the plastocyanin-cytochrome f complex2000In: Biochemistry, ISSN 0006-2960, E-ISSN 1520-4995, Vol. 39, no 17, p. 5022-5027Article in journal (Refereed)
    Abstract [en]

    Cytochrome f and plastocyanin are redox partners in the photosynthetic electron-transfer chain. Electron transfer from cytochrome f to plastocyanin occurs in a specific short-lived complex. To obtain detailed information about the binding interface in this transient complex, the effects of binding on the backbone and side-chain protons of plastocyanin have been analyzed by mapping NMR chemical-shift changes. Cytochrome f was added to plastocyanin up to 0.3 M equiv, and the plastocyanin proton chemical shifts were measured. Out of approximately 500 proton resonances, 86% could be observed with this method. Nineteen percent demonstrate significant chemical-shift changes and these protons are located in the hydrophobic patch (including the copper ligands) and the acidic patches of plastocyanin, demonstrating that both areas are part of the interface in the complex. This is consistent with the recently determined structure of the complex [Ubbink, M., Ejdebäck, M., Karlsson, B. G., and Bendall, D. S. (1998) Structure 6, 323-335]. The largest chemical-shift changes are found around His87 in the hydrophobic patch, which indicates tight contacts and possibly water exclusion from this part of the protein interface. These results support the idea that electron transfer occurs via His87 to the copper in plastocyanin and suggest that the hydrophobic patch determines the specificity of the binding. The chemical-shift changes in the acidic patches are significant but small, suggesting that the acidic groups are involved in electrostatic interactions but remain solvent exposed. The existence of small differences between the present data and those used for the structure may imply that the redox state of the metals in both proteins slightly affects the structure of the complex. The chemical-shift mapping is performed on unlabeled proteins, making it an efficient way to analyze effects of mutations on the structure of the complex.

  • 11.
    Ejdebäck, Mikael
    et al.
    Göteborgs universitet.
    Karlsson, B. G.
    Effects of codon usage and vector-host combinations on the expression of spinach plastocyanin in Escherichia coli1997In: / [ed] American Society for Biochemistry and Molecular Biology, Bethesda: Federation of American Societies for Experimental Biology , 1997, Vol. 11, no 9, p. A1373-Conference paper (Other academic)
  • 12.
    Ejdebäck, Mikael
    et al.
    Department of Biochemistry and Biophysics, Göteborg University, Chalmers University of Technology, Göteborg, Sweden.
    Young, Simon
    Department of Biochemistry and Biophysics, Göteborg University, Chalmers University of Technology, Göteborg, Sweden.
    Samuelsson, Anita
    Department of Biochemistry and Biophysics, Göteborg University, Chalmers University of Technology, Göteborg, Sweden.
    Karlsson, B. Göran
    Department of Biochemistry and Biophysics, Göteborg University, Chalmers University of Technology, Göteborg, Sweden.
    Effects of codon usage and vector-host combinations on the expression of spinach plastocyanin in Escherichia coli1997In: Protein Expression and Purification, ISSN 1046-5928, E-ISSN 1096-0279, Vol. 11, no 1, p. 17-25Article in journal (Refereed)
    Abstract [en]

    Spinach plastocyanin has been expressed in Escherichia coli and exported to the periplasmic space. The effects of codon usage, expression system, growth length, and temperature on expression levels in LB medium were investigated. A stretch of codons, rare in E. coli, was identified and replaced with highly expressed codons, increasing the yield by at least 20%. Plastocyanin was more efficiently expressed under the T7 promoter than under the lac promoter. Maximum yields were obtained at 37 degrees C when growing the cells for 16 h after induction. The optimized expression system produced 38 mg holoprotein per liter culture. In this system it was also possible to express plastocyanin in minimal medium, at a yield of 10 mg per liter. N-terminal sequencing and mass spectrometry showed that plastocyanin was correctly processed. The expressed plastocyanin was purified to homogeneity, as shown by an A278/A597 ratio of 1.0, and together with amino acid analysis and the determination of oxidized and total copper contents, both the absorption coefficients for epsilon 278 and for epsilon 597 were determined to be 4700 M-1 cm-1.

  • 13.
    Fagerlind, Magnus
    et al.
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Bioscience.
    Stålhammar, Hans
    VikingGenetics, Skara.
    Olsson, Björn
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Bioscience.
    Klinga-Levan, Karin
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Bioscience.
    Expression of miRNAs in Bull Spermatozoa Correlates with Fertility Rates2015In: Reproduction in domestic animals, ISSN 0936-6768, E-ISSN 1439-0531, Vol. 50, no 4, p. 587-594Article in journal (Refereed)
  • 14.
    Gopalan Nair, Rekha
    University of Skövde, School of Bioscience.
    Cloning and functional analysis of an arsB gene responsible for arsenic sequestration in Lysinibacillus sphaericus2016Independent thesis Advanced level (degree of Master (One Year)), 20 credits / 30 HE creditsStudent thesis
  • 15.
    Guszpit, Emilia
    University of Skövde, School of Life Sciences.
    Localization of AtHOG1 and AtHOG2 in Arabidopsis plants at the tissue and subcellular levels2010Independent thesis Advanced level (degree of Master (One Year)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Plant hormones are responsible for plant growth and adaptation to the environment. Among them the most important are cytokinins. Plants undergo gene silencing processes called homology-dependent gene silencing processes. In Arabidopsis there are two homology-dependent gene silencing genes that were chosen for further study, namely AtHOG1 and AtHOG2. Transgenic plants were generated previously with ten different constructs containing AtHOG1 or AtHOG2 genes and were used in this study. Some of the constructs had GFP attached so that the protein expressed could be visualised in a confocal microscope. Transgenic plants generated were T1 and T2 generations. Their DNA was extracted from leaves. By means of PCR transgenic plants were identified. There were 147 samples. Among them there were 39 positiveswith BAR primers and 32 positives with construct specific primers. The localisation of the HOG2 protein was observed in a confocal microscope. Seeds used were T3 generation and were obtained from the lab. HOG2 protein was found to be localised in cell membrane, root tip and chloroplasts.

  • 16.
    Hardy, Matthew P.
    et al.
    Center for Functional Genomics and Human Disease, Monash Institute of Reproduction and Development, Monash University, Monash Medical Centre, Clayton, Victoria, Australia / Department of Biochemistry and Biotechnology Institute, Trinity College, University of Dublin, Dublin 2, Ireland.
    Owczarek, Catherine M.
    Center for Functional Genomics and Human Disease, Monash Institute of Reproduction and Development, Monash University, Monash Medical Centre, Clayton, Victoria, Australia.
    Jermiin, Lars S.
    School of Biological Sciences and Sydney University Biological Informatics and Technology Center, University of Sydney, New South Wales 2006, Australia.
    Ejdebäck, Mikael
    Department of Biochemistry and Biotechnology Institute, Trinity College, University of Dublin, Dublin 2, Ireland.
    Hertzog, Paul J.
    Center for Functional Genomics and Human Disease, Monash Institute of Reproduction and Development, Monash University, Monash Medical Centre, Clayton, Victoria, Australia.
    Characterization of the type I interferon locus and identification of novel genes2004In: Genomics, ISSN 0888-7543, E-ISSN 1089-8646, Vol. 84, no 2, p. 331-345Article in journal (Refereed)
    Abstract [en]

    The human type I interferon (IFN) genes are clustered on human chromosome 9p21 and the mouse genes are located in the region of conserved synteny on mouse chromosome 4. We have identified two novel mouse Ifna genes (Ifna12, Ifna13) and Ifnl2 (IFN-like 2, a homologue of Limitin/IFN-like 1). Another type I IFN gene was designated Ifne1. Mouse Ifne1 was expressed in ovaries and uterus but not in tissues of hematopoietic origin. IFN-epsilon1 has general structural characteristics of a type I IFN. These studies represent the first detailed annotation of the mouse type I IFN locus, and the products of these novel genes may have important functions in reproduction and host defense.

  • 17.
    Hossain, Monayem
    et al.
    Molecular Plant Physiology Laboratory, Department of Botany, University of Rajshahi, Rajshahi, Bangladesh.
    Khatun, Most Amena
    Molecular Plant Physiology Laboratory, Department of Botany, University of Rajshahi, Rajshahi, Bangladesh.
    Haque, Najmul
    Molecular Plant Physiology Laboratory, Department of Botany, University of Rajshahi, Rajshahi, Bangladesh.
    Bari, Azizul
    Molecular Plant Physiology Laboratory, Department of Botany, University of Rajshahi, Rajshahi, Bangladesh / Institute of Biological Sciences, University of Rajshahi, Rajshahi, Bangladesh.
    Alam, Firoz
    Molecular Plant Physiology Laboratory, Department of Botany, University of Rajshahi, Rajshahi, Bangladesh.
    Mandal, Abul
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Kabir, Ahmad Humayan
    Molecular Plant Physiology Laboratory, Department of Botany, University of Rajshahi, Rajshahi, Bangladesh.
    Silicon alleviates arsenic-induced toxicity in wheat through vacuolar sequestration and ROS scavenging2018In: International journal of phytoremediation, ISSN 1522-6514, E-ISSN 1549-7879, Vol. 20, no 8, p. 796-804Article in journal (Refereed)
    Abstract [en]

    Arsenic (As) is a phytotoxic element causing health hazards. This work investigates whether and how silicon (Si) alleviates As toxicity in wheat. The addition of Si under As-stress significantly improved morphophysiological characteristics, total protein, and membrane stability compared to As-stressed plants, suggesting that Si does have critical roles in As detoxification in wheat. Analysis of arsenate reductase activity and phytosiderophore (PS) release reveals their no involvement in the Si-mediated alleviation of As in wheat. Furthermore, Si supplementation in As-stressed plants showed a significant increase of As in roots but not in shoots compared with the plants grown under As stress. Further, gene expression analysis of two chelating molecules, TaPCS1 (phytochelatin synthase) and TaMT1 (metallothionein synthase) showed significant induction due to Si application under As stress compared with As-stressed plants. It is consistent with the physiological observations and suggests that alleviation of As toxicity in rice might be associated with As sequestration in roots leading to reduced As translocation in shoots. Furthermore, increased catalase, peroxidase, and glutathione reductase activities in roots imply the active involvement of reactive oxygen species scavenging for protecting wheat plants from As-induced oxidative injury. The study provides mechanistic evidence on the beneficial effect of Si on As toxicity in wheat plants.

    The full text will be freely available from 2019-06-01 00:01
  • 18.
    Islam, Md Shofikul
    et al.
    University of Rajshahi, Bangladesh / Islamic University, Kushtia-7003, Bangladesh.
    Mohanto, Nayan Chandra
    University of Rajshahi, Rajshahi-6205, Bangladesh.
    Karim, Md Rezaul
    Islamic University, Kushtia-7003, Bangladesh.
    Aktar, Sharmin
    University of Rajshahi, Rajshahi-6205, Bangladesh.
    Hoque, Md Mominul
    University of Rajshahi, Rajshahi-6205, Bangladesh.
    Rahman, Atiqur
    University of Rajshahi, Rajshahi-6205, Bangladesh.
    Jahan, Momotaj
    University of Rajshahi, Rajshahi-6205, Bangladesh.
    Khatun, Rabeya
    University of Rajshahi, Rajshahi-6205, Bangladesh.
    Aziz, Abdul
    University of Rajshahi, Rajshahi-6205, Bangladesh.
    Abdus Salam, Kazi
    University of Rajshahi, Rajshahi-6205, Bangladesh / National institutes of Health, Bethesda, USA.
    Saud, Zahangir Alam
    University of Rajshahi, Rajshahi-6205, Bangladesh.
    Hossain, Mostaque
    Kaliganj Upazila Health Complex, Gazipur, Dhaka, Bangladesh.
    Rahman, Aminur
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Mandal, Abul
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Haque, Azizul
    Medical University of South Carolina, Charleston, SC, USA.
    Miyataka, Hideki
    Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Japan.
    Himeno, Seiichiro
    Laboratory of Molecular Nutrition and Toxicology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Japan.
    Hossain, Khaled
    Department of Biochemistry and Molecular Biology, University of Rajshahi, Bangladesh.
    Elevated concentrations of serum matrix metalloproteinase-2 and -9 and their associations with circulating markers of cardiovascular diseases in chronic arsenic-exposed individuals2015In: Environmental health, ISSN 1476-069X, E-ISSN 1476-069X, Vol. 14, no 1, article id 92Article in journal (Refereed)
    Abstract [en]

    Background: Cardiovascular diseases (CVDs) and cancers are the major causes of chronic arsenic exposure-related morbidity and mortality. Matrix metalloproteinase-2 (MMP-2) and −9 (MMP-9) are deeply involved in the pathogenesis of CVDs and cancers. This study has been designed to evaluate the interactions of arsenic exposure with serum MMP-2 and MMP-9 concentrations especially in relation to the circulating biomarkers of CVDs.

    Methods: A total of 373 human subjects, 265 from arsenic-endemic and 108 from non-endemic areas in Bangladesh were recruited for this study. Arsenic concentrations in the specimens were measured by inductively coupled plasma mass spectroscopy (ICP-MS) and serum MMPs were quantified by immunoassay kits.

    Results: Serum MMP-2 and MMP-9 concentrations in arsenic-endemic population were significantly (p < 0.001) higher than those in non-endemic population. Both MMPs showed significant positive interactions with drinking water (rs = 0.208, p < 0.001 for MMP-2; rs = 0.163, p <0.01 for MMP-9), hair (rs= 0.163, p < 0.01 for MMP-2; rs = 0.173, p < 0.01 for MMP-9) and nail (rs= 0.160, p < 0.01 for MMP-2; rs = 0.182, p < 0.001 for MMP-9) arsenic of the study subjects. MMP-2 concentrations were 1.02, 1.03 and 1.05 times, and MMP-9 concentrations were 1.03, 1.06 and 1.07 times greater for 1 unit increase in log-transformed water, hair and nail arsenic concentrations, respectively, after adjusting for covariates (age, sex, BMI, smoking habit and hypertension). Furthermore, both MMPs were increased dose-dependently when the study subjects were split into three (≤10, 10.1-50 and > 50 μg/L) groups based on the regulatory upper limit of water arsenic concentration set by WHO and Bangladesh Government. MMPs were also found to be significantly (p < 0.05) associated with each other. Finally, the concentrations of both MMPs were correlated with several circulating markers related to CVDs.

    Conclusions: This study showed the significant positive associations and dose–response relationships of arsenic exposure with serum MMP-2 and MMP-9 concentrations. This study also showed the interactions of MMP-2 and MMP-9 concentrations with the circulating markers of CVDs suggesting the MMP-2 and MMP-9 -mediated mechanism of arsenic-induced CVDs.

  • 19.
    Ivković-Jensen, Maja M.
    et al.
    Department of Microbiology, University of Iowa, Iowa City, United States / Department of Chemistry, Iowa State University, Ames, United States.
    Ullmann, G. Matthias
    Institut für Kristallographie, Freie Universität Berlin, Germany.
    Crnogorac, Milan M.
    Department of Microbiology, University of Iowa, Iowa City, United States.
    Ejdebäck, Mikael
    Department of Biochemistry and Biophysics, Lundberg Institute, Göteborg University, Sweden.
    Young, Simon
    Department of Biochemistry and Biophysics, Lundberg Institute, Göteborg University, Sweden.
    Hansson, Örjan
    Department of Biochemistry and Biophysics, Lundberg Institute, Göteborg University, Sweden.
    Kostić, Nenad M.
    Department of Microbiology, University of Iowa, Iowa City, United States.
    Comparing the rates and the activation parameters for the forward reaction between the triplet state of zinc cytochrome c and cupriplastocyanin and the back reaction between the zinc cytochrome c cation radical and cuproplastocyanin1999In: Biochemistry, ISSN 0006-2960, E-ISSN 1520-4995, Vol. 38, no 5, p. 1589-1597Article in journal (Refereed)
    Abstract [en]

    This is a comparative study of the photoinduced (so-called forward) electron-transfer reaction 3Zncyt/pc(II) --> Zncyt+/pc(I), between the triplet state of zinc cytochrome c (3Zncyt) and cupriplastocyanin [pc(II)], and the thermal (so-called back) electron-transfer reaction Zncyt+/pc(I) --> Zncyt/pc(II), between the cation (radical) of zinc cytochrome c (Zncyt+) and cuproplastocyanin [pc(I)], which follows it. Both reactions occur between associated (docked) reactants, and the respective unimolecular rate constants are kF and kB. Our previous studies showed that the forward reaction is gated by a rearrangement of the diprotein complex. Now we examine the back reaction and complare the two. We study the effects of temperature (in the range 273.3-302.9 K) and viscosity (in the range 1.00-17.4 cP) on the rate constants and determine enthalpies (DeltaH), entropies (DeltaS), and free energies (DeltaG) of activation. We compare wild-type spinach plastocyanin, the single mutants Tyr83Leu and Glu59Lys, and the double mutant Glu59Lys/Glu60Gln. The rate constant kB for wild-type spinach plastocyanin and its mutants markedly depends on viscosity, an indication that the back reaction is also gated. The activation parameters DeltaH and DeltaS show that the forward and back reactions have similar mechanisms, involving a rearrangement of the diprotein complex from the initial binding configuration to the reactive configuration. The rearrangements of the complexes 3Zncyt/pc(II) and Zncyt+/pc(I) that gate their respective reactions are similar but not identical. Since the back reaction of all plastocyanin variants is faster than the forward reaction, the difference in free energy between the docking and the reactive configuration is smaller for the back reaction than for the forward reaction. This difference is explained by the change in the electrostatic potential on the plastocyanin surface as Cu(II) is reduced to Cu(I). It is the smaller DeltaH that makes DeltaG smaller for the back reaction than for the forward reaction.

  • 20.
    Ivković-Jensen, Maja M.
    et al.
    Department of Chemistry, Iowa State University, Ames, United States.
    Ullmann, G. Matthias
    Institut für Kristallographie, Freie Universität Berlin, Germany.
    Young, Simon
    Department of Biochemistry and Biophysics, Göteborg University, Chalmers University of Technology, Göteborg, Sweden.
    Hansson, Örjan
    Department of Biochemistry and Biophysics, Göteborg University, Chalmers University of Technology, Göteborg, Sweden.
    Crnogorac, Milan M.
    Department of Chemistry, Iowa State University, Ames, United States.
    Ejdebäck, Mikael
    Department of Biochemistry and Biophysics, Göteborg University, Chalmers University of Technology, Göteborg, Sweden.
    Kostić, Nenad M.
    Department of Chemistry, Iowa State University, Ames, United States.
    Effects of single and double mutations in plastocyanin on the rate constant and activation parameters for the rearrangement gating the electron-transfer reaction between the triplet state of zinc cytochrome c and cupriplastocyanin1998In: Biochemistry, ISSN 0006-2960, E-ISSN 1520-4995, Vol. 37, no 26, p. 9557-9569Article in journal (Refereed)
    Abstract [en]

    The unimolecular rate constant for the photoinduced electron-transfer reaction 3Zncyt/pc(II) --> Zncyt+/pc(I) within the electrostatic complex of zinc cytochrome c and spinach cupriplastocyanin is kF. We report the effects on kF of the following factors, all at pH 7.0: 12 single mutations on the plastocyanin surface (Leu12Asn, Leu12Glu, Leu12Lys, Asp42Asn, Asp42Lys, Glu43Asn, Glu59Gln, Glu59Lys, Glu60Gln, Glu60Lys, Gln88Glu, and Gln88Lys), the double mutation Glu59Lys/Glu60Gln, temperature (in the range 273.3-302.9 K), and solution viscosity (in the range 1. 00-116.0 cP) at 283.2 and 293.2 K. We also report the effects of the plastocyanin mutations on the association constant (Ka) and the corresponding free energy of association (DeltaGa) with zinc cytochrome c at 298.2 K. Dependence of kF on temperature yielded the activation parameters DeltaH, DeltaS, and DeltaG. Dependence of kF on solution viscosity yielded the protein friction and confirmed the DeltaG values determined from the temperature dependence. The aforementioned intracomplex reaction is not a simple electron-transfer reaction because donor-acceptor electronic coupling (HAB) and reorganizational energy (lambda), obtained by fitting of the temperature dependence of kF to the Marcus equation, deviate from the expectations based on precedents and because kF greatly depends on viscosity. This last dependence and the fact that certain mutations affect Ka but not kF are two lines of evidence against the mechanism in which the electron-transfer step is coupled with the faster, but thermodynamically unfavorable, rearrangement step. The electron-transfer reaction is gated by the slower, and thus rate determining, structural rearrangement of the diprotein complex; the rate constant kF corresponds to this rearrangement. Isokinetic correlation of DeltaH and DeltaS parameters and Coulombic energies of the various configurations of the Zncyt/pc(II) complex consistently show that the rearrangement is a facile configurational fluctuation of the associated proteins, qualitatively the same process regardless of the mutations in plastocyanin. Correlation of kF with the orientation of the cupriplastocyanin dipole moment indicates that the reactive configuration of the diprotein complex involves the area near the residue 59, between the upper acidic cluster and the hydrophobic patch. Kinetic effects and noneffects of plastocyanin mutations show that the rearrangement from the initial (docking) configuration, which involves both acidic clusters, to the reactive configuration does not involve the lower acidic cluster and the hydrophobic patch but involves the upper acidic cluster and the area near the residue 88.

  • 21.
    James, John R.
    et al.
    Univ Oxford, Weatherall Inst Mol Med, Nuffield Dept Clin Med, Oxford OX3 9DS, England / Univ Oxford, Weatherall Inst Mol Med, Med Res Council Human Immunol Unit, Oxford OX3 9DS, England .
    McColl, James
    Univ Cambridge, Dept Chem, Cambridge CB2 1EW, England .
    Oliveira, Marta I.
    Univ Porto, Inst Biol Mol & Celular, Grp Cell Activat & Gene Express, P-4150180 Oporto, Portugal / Univ Porto, Inst Ciencias Biomed Abel Salazar, P-4099003 Oporto, Portugal .
    Dunne, Paul D.
    Univ Cambridge, Dept Chem, Cambridge CB2 1EW, England .
    Huang, Elizabeth
    Univ Oxford, Weatherall Inst Mol Med, Nuffield Dept Clin Med, Oxford OX3 9DS, England / Univ Oxford, Weatherall Inst Mol Med, Med Res Council Human Immunol Unit, Oxford OX3 9DS, England .
    Jansson, Andreas
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
    Nilsson, Patric
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
    Sleep, David L.
    Univ Oxford, Weatherall Inst Mol Med, Nuffield Dept Clin Med, Oxford OX3 9DS, England / Univ Oxford, Weatherall Inst Mol Med, Med Res Council Human Immunol Unit, Oxford OX3 9DS, England .
    Goncalves, Carine M.
    Univ Porto, Inst Biol Mol & Celular, Grp Cell Activat & Gene Express, P-4150180 Oporto, Portugal / Univ Porto, Inst Ciencias Biomed Abel Salazar, P-4099003 Oporto, Portugal .
    Morgan, Sara H.
    Univ Oxford, Weatherall Inst Mol Med, Nuffield Dept Clin Med, Oxford OX3 9DS, England / Univ Oxford, Weatherall Inst Mol Med, Med Res Council Human Immunol Unit, Oxford OX3 9DS, England .
    Felce, James H.
    Univ Oxford, Weatherall Inst Mol Med, Nuffield Dept Clin Med, Oxford OX3 9DS, England / Univ Oxford, Weatherall Inst Mol Med, Med Res Council Human Immunol Unit, Oxford OX3 9DS, England .
    Mahen, Robert
    Hutchison MRC Res Ctr, Med Res Council Canc Cell Unit, Cambridge CB2 0XZ, England.
    Fernandes, Ricardo A.
    Univ Oxford, Weatherall Inst Mol Med, Nuffield Dept Clin Med, Oxford OX3 9DS, England / Univ Oxford, Weatherall Inst Mol Med, Med Res Council Human Immunol Unit, Oxford OX3 9DS, England .
    Carmo, Alexandre M.
    Univ Porto, Inst Biol Mol & Celular, Grp Cell Activat & Gene Express, P-4150180 Oporto, Portugal / Univ Porto, Inst Ciencias Biomed Abel Salazar, P-4099003 Oporto, Portugal .
    Klenerman, David
    Univ Cambridge, Dept Chem, Cambridge CB2 1EW, England .
    Davis, Simon J.
    Univ Oxford, Weatherall Inst Mol Med, Nuffield Dept Clin Med, Oxford OX3 9DS, England / Univ Oxford, Weatherall Inst Mol Med, Med Res Council Human Immunol Unit, Oxford OX3 9DS, England .
    The T Cell Receptor Triggering Apparatus Is Composed of Monovalent or Monomeric Proteins2011In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 286, no 37, p. 31993-32001Article in journal (Refereed)
    Abstract [en]

    Understanding the component stoichiometry of the T cell antigen receptor (TCR) triggering apparatus is essential for building realistic models of signal initiation. Recent studies suggesting that the TCR and other signaling-associated proteins are preclustered on resting T cells relied on measurements of the behavior of membrane proteins at interfaces with functionalized glass surfaces. Using fluorescence recovery after photo-bleaching, we show that, compared with the apical surface, the mobility of TCRs is significantly reduced at Jurkat T cell/glass interfaces, in a signaling-sensitive manner. Using two biophysical approaches that mitigate these effects, bioluminescence resonance energy transfer and two-color coincidence detection microscopy, we show that, within the uncertainty of the methods, the membrane components of the TCR triggering apparatus, i.e. the TCR complex, MHC molecules, CD4/Lck and CD45, are exclusively monovalent or monomeric in human T cell lines, implying that TCR triggering depends only on the kinetics of TCR/pMHC interactions. These analyses also showed that constraining proteins to two dimensions at the cell surface greatly enhances random interactions versus those between the membrane and the cytoplasm. Simulations of TCR-pMHC complex formation based on these findings suggest how unclustered TCR triggering-associated proteins might nevertheless be capable of generating complex signaling outputs via the differential recruitment of cytosolic effectors to the cell membrane.

  • 22.
    Jansson, Andreas
    et al.
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
    Davis, Simon J.
    Univ Oxford, John Radcliffe Hosp, Nuffield Dept Clin Med, Oxford OX3 9DS, England / Univ Oxford, John Radcliffe Hosp, Med Res Council Human Immunol Unit, Weatherall Inst Mol Med, Oxford OX3 9DS, England.
    Quantitative analysis predicts the relative therapeutic efficacy of different forms of CTLA4Ig2011In: Molecular Immunology, ISSN 0161-5890, E-ISSN 1872-9142, Vol. 49, no 3, p. 527-536Article in journal (Refereed)
    Abstract [en]

    Modulating the activities of costimulatory molecules controlling immune responses holds considerable promise for immunotherapy. CTLA4Ig (abatacept), a soluble version of the T cell-expressed membrane receptor CTLA-4, is approved for the treatment of rheumatoid arthritis. Like natural CTLA-4 molecules, CTLA4Ig ligates B7-1 and B7-2 on antigen presenting cells, preventing CD28-mediated costimulation of T cells. However. CTLA4Ig can also prevent ligation of CTLA-4, potentially blocking vital inhibitory signals, thereby augmenting immunity. There have been no quantitative analyses of the likely effects of CTLA4Ig on costimulatory interactions at the immunological synapse. We present a mathematical model, based on rigorous biophysical and expression data, for simulating the effects of abatacept and a mutated derivative, LEA29Y, on the synaptic interactions of CD28 and CTLA-4. The simulations reveal an unexpectedly large window within which CD28, but not CTLA-4, ligation is blocked by CTLA4Ig, perhaps explaining the efficacy of abatacept at the recommended therapeutic dose (10 mg/kg) and its relative safety. However, the simulations suggest that the present dosing regimen is close to the maximum theoretically safe dose. The simulations also show that, within the therapeutic window, LEA29Y enhances the interaction of CTLA-4 with the more potent of its two native ligands, B7-1. They also suggest that CTLA-4 ligation by B7-1 could, in principle, be enhanced by further decreasing the off-rate of CTLA4Ig for binding to B7-2. Our findings therefore offer molecular explanations for why LEA29Y might prove to be more effective than abatacept in a clinical setting, and suggest ways in which its therapeutic efficacy could be further optimised. (C) 2011 Elsevier Ltd. All rights reserved.

  • 23.
    Junnarkara, Manisha V.
    et al.
    Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Pune, India.
    Thakarea, Prasad M.
    Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Pune, India.
    Yewalea, Priti P.
    Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Pune, India.
    Rahman, Aminur
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Jass, Jana
    Örebro University, Sweden.
    Mandal, Abul
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Nawani, Neelu N.
    Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Pune, India.
    Evaluation of Probiotic Potential of Lactic Acid Bacteria Isolated from Different Sources in Western India2018In: Food biotechnology, ISSN 0890-5436, E-ISSN 1532-4249, Vol. 32, no 2, p. 112-129Article in journal (Refereed)
    Abstract [en]

    Lactic acid bacteria isolated from unconventional sources are often attractive targets in the quest for obtaining better probiotics. In the present study, 16 members of the genus Lactobacillus, isolated from 3 different sources in western India, viz., plants, fermented foods and beverages, and human feces, were evaluated for their probiotic and bioactive properties. The isolates were closely related to Lactobacillus fermentum, Lactobacillus pentosus, and mainly Lactobacillus plantarum. The isolates were tolerant to bile salt, acidic pH and pancreatin, although pancreatin tolerance was generally low. Cellular extracts of several isolates displayed antioxidant activity, while cell-free supernatants displayed antibacterial activity against human pathogens. Antioxidant activity of Lactobacilli of human origin was higher than those from vegetables or fermented foods and beverages. L. plantarum AG40V prevented spoilage of fresh-cut fruits, vegetables and sprouted mung-beans. Lactobacilli from all sources displayed equal probiotic potential and those of human origin displayed superior antioxidant activity over others.

  • 24.
    Kabir, Ahmad H.
    et al.
    Plant and Crop Physiology Laboratory, Department of Botany, University of Rajshahi, Rajshahi, Bangladesh.
    Hossain, Mohammad M.
    Plant and Crop Physiology Laboratory, Department of Botany, University of Rajshahi, Rajshahi, Bangladesh.
    Khatun, Most A.
    Plant and Crop Physiology Laboratory, Department of Botany, University of Rajshahi, Rajshahi, Bangladesh.
    Mandal, Abul
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Haider, Syed A.
    Plant and Crop Physiology Laboratory, Department of Botany, University of Rajshahi, Rajshahi, Bangladesh.
    Role of Silicon Counteracting Cadmium Toxicity in Alfalfa (Medicago sativa L.)2016In: Frontiers in Plant Science, ISSN 1664-462X, E-ISSN 1664-462X, Vol. 7, article id 1117Article in journal (Refereed)
    Abstract [en]

    Cadmium (Cd) is one of the most phytotoxic elements causing an agricultural problem and human health hazards. This work investigates whether and how silicon (Si) ameliorates Cd toxicity in Alfalfa. The addition of Si in Cd-stressed plants caused significant improvement in morpho-physiological features as well as total protein and membrane stability, indicating that Si does have critical roles in Cd detoxification in Alfalfa. Furthermore, Si supplementation in Cd stressed plants showed a significant decrease in Cd and Fe concentrations in both roots and shoots compared with Cd-stressed plants, revealing that Si-mediated tolerance to Cd stress is associated with Cd inhibition in Alfalfa. Results also showed no significant changes in the  expression of two metal chelators [MsPCS1 (phytochelatin synthase) and MsMT2  (metallothionein)] and PC (phytochelatin) accumulation, indicating that there may be no metal sequestration or change in metal sequestration following Si application under Cd stress in  Alfalfa. We further performed a targeted study on the effect of Si on Fe uptake mechanisms. We observed the consistent reduction in Fe reductase activity, expression of Fe-related genes [MsIRT1 (Fe transporter), MsNramp1 (metal transporter) and OsFRO1 (ferric chelate reductase] and Fe chelators (citrate and malate) by Si application to Cd stress in roots of Alfalfa. These results support that limiting Fe uptake through the down-regulation of Fe acquisition mechanisms confers Si-mediated alleviation of Cd toxicity in Alfalfa. Finally, an increase of catalase (CAT), ascorbate peroxidase (APX) and superoxide dismutase (SOD) activities along with elevated methionine and proline subjected to Si application might play roles, at least in part, to reduce H2O2 and to provide antioxidant defense against Cd stress in Alfalfa. The study shows evidence of the effect of Si on alleviating Cd toxicity in Alfalfa and can be further extended for phytoremediation of Cd toxicity in plants.

  • 25.
    Karlsson, Sandra
    et al.
    University of Skövde, School of Life Sciences.
    Klinga-Levan, Karin
    University of Skövde, School of Life Sciences.
    Expression Analysis of Human Endometrial Adenocarcinoma in an Inbred Rat Model2008In: Hormonal Carcinogenesis: Proceedings of the Fifth International Symposium, Springer , 2008, p. 503-509Conference paper (Refereed)
    Abstract [en]

    Endometrial cancer (EC) is the most abundant female gynaecologic malignancy, ranking fourth in incidence among invasive tumors in women. Hormone-related (estrogen-dependent) EC is the prevalent subtype and accounts for approximately 75% of these cancers. Females of the BDII inbred rat strain are extremely prone to endometrial adenocarcinoma, (EAC) and approximately 90% of virgin females spontaneously develop EAC during their life span. Thus, these rats serve as a useful model for the genetic analysis of this malignancy. In the present work, gene expression profiling, by means of cDNA microarrays, was performed on cDNA from endometrial tumor cell lines and from cell lines derived from nonmalignant lesions/normal tissues of the endometrium without specific findings (WSF). We identified numerous genes differentially expressed between endometrial cell lines and WSFs employing clustering analysis and statistical inference analysis. Many of the genes identified are located within or close to the chromosomal regions earlier identified to be associated with EAC susceptibility and development. Several of the genes identified are involved in pathways commonly altered in carcinogenesis, such as the TGF-pathway.

  • 26.
    Meng, N
    et al.
    Department of Surgery, The Forth Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China.
    Li, Y
    Department of Surgery, The Forth Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China.
    Zhang, Hong
    University of Skövde, School of Life Sciences.
    Sun, Xiao-Feng
    Department of Oncology, Institute of Clinical and Experimental Medicine, Linköping University, S-58185 Linköping, Sweden.
    RECK, a novel matrix metalloproteinase regulator2008In: Histology and Histopathology, ISSN 0213-3911, E-ISSN 1699-5848, Vol. 23, no 8, p. 1003-1010Article, review/survey (Refereed)
    Abstract [en]

    Extracellular matrix (ECM) macromolecules are important for creating the cellular environments required during development and morphogenesis of tissues. Matrix metalloproteinases (MMPs) are a family of Zn-dependent endopeptidases that collectively are capable of cleaving virtually all ECM substrates, and play an important role in some physiological and pathological processes. MMP activity can be inhibited by some natural and artificial inhibitors. A newly found membrane-anchored regulator of MMPs, the reversion-inducing-cysteine-rich protein with kazal motifs (RECK), is downregulated when the cells undergo a process of malignant transformation, and is currently the subject of considerable research activity because of its specific structure and function. In this review, we have chosen to concentrate our efforts on the structure, function, regulation, and future prospect of RECK in order to provide a new target for prevention and treatment of tumours

  • 27.
    Monzur, Sadia
    University of Skövde, School of Bioscience.
    The Effect of nox2/4 inhibitors in t98g cells during a mimicked ischemic stroke2018Independent thesis Advanced level (degree of Master (One Year)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Stroke, an immensely complicated cerebrovascular disease is harvesting lives of millions over the globe and has been designated as world’s second largest killer. Improvement of pre and post treatment for this pathology to reduce the death toll has become an urgency since there are very limited therapeutic options for stroke patients, while efforts to give direct neuro-protection to the brain cells on set of ischemic stroke has been hugely unsuccessful. As oxidative stress plays a key role in brain damage during this pathology and NOX enzymes are the main source reactive oxygen species inducing this stress, at present NOX inhibitors have come to lime light for treating this condition but available Nox inhibitors lack of certain qualities and exhibit side effects that hold them back form clinical trials. In this study in vitro efficacy of NOX inhibitors M4, M107 and M114 patented by Glucox Biotech AB was evaluated along with a positive control, VAS2870, in cellular model of ischemic stroke using the T98G cell line through detection of gene expression of Nox2/4 genes, cell viability assay and ROS assay. Results indicate that these inhibitors decrease cell mortality significantly by inhibiting the enzymes activity and lowering the ROS. In the future there is great hope that these inhibitors could be used clinically due to their uniqueness and may hold the key to ameliorate the suffering from stroke, and save lives.

  • 28.
    Nahar, Noor
    et al.
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Rahman, Aminur
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Nawani, Neelu N.
    Microbial Diversity Research Centre, Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Tathawade, Pune, India.
    Ghosh, Sibdas
    School of Arts and Science, Iona College, New Rochelle, NY, USA.
    Mandal, Abul
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Phytoremediation of arsenic from the contaminated soil using transgenic tobacco plants expressing ACR2 gene of Arabidopsis thaliana2017In: Journal of plant physiology (Print), ISSN 0176-1617, E-ISSN 1618-1328, Vol. 218, p. 121-126Article in journal (Refereed)
    Abstract [en]

    We have cloned, characterized and transformed the AtACR2 gene (arsenic reductase 2) of Arabidopsis thaliana into the genome of tobacco (Nicotiana tabacum, var Sumsun). Our results revealed that the transgenic tobacco plants are more tolerant to arsenic than the wild type ones. These plants can grow on culture medium containing 200μM arsenate, whereas the wild type can barely survive under this condition. Furthermore, when exposed to 100μM arsenate for 35days the amount of arsenic accumulated in the shoots of transgenic plants was significantly lower (28μg/g d wt.) than that found in the shoots of non-transgenic controls (40μg/g d wt.). However, the arsenic content in the roots of transgenic plants was significantly higher (2400μg/g d. wt.) than that (2100μg/g d. wt.) observed in roots of wild type plants. We have demonstrated that Arabidopsis thaliana AtACR2 gene is a potential candidate for genetic engineering of plants to develop new crop cultivars that can be grown on arsenic contaminated fields to reduce arsenic content of the soil and can become a source of food containing no arsenic or exhibiting substantially reduced amount of this metalloid.

  • 29.
    Nahar, Nour
    et al.
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Rahman, Aminur
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Ghosh, Sibdas
    School of Arts and Science, Iona College, New Rochelle, NY, USA.
    Nawani, Neelu
    Microbial Diversity Research Centre, Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Tathawade, Pune, India.
    Mandal, Abul
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Functional studies of AtACR2 gene putatively involved in accumulation, reduction and/or sequestration of arsenic species in plants2017In: Biologia (Bratislava), ISSN 0006-3088, E-ISSN 1336-9563, Vol. 72, no 5, p. 520-526Article in journal (Refereed)
    Abstract [en]

    Food-based exposure to arsenic is a human carcinogen and can severely impact human health resulting in many cancerous diseases and various neurological and vascular disorders. This project is a part of our attempts to develop new varieties of crops for avoiding arsenic contaminated foods. For this purpose, we have previously identified four key genes, and molecular functions of two of these, AtACR2 and AtPCSl, have been studied based on both in silico and in vivo experiments. In the present study, a T-DNA tagged mutant, (SALK-143282C with mutation in AtACR2 gene) of Arabidopsis thaliana was studied for further verification of the function of AtACR2 gene. Semi-quantitative RT-PCR analyses revealed that this mutant exhibits a significantly reduced expression of the AtACR2 gene. When exposed to 100 μM of arsenate (AsV) for three weeks, the mutant plants accumulated arsenic approximately three times higher (778 μg/g d. wt.) than that observed in the control plants (235 μg/g d. wt.). In contrast, when the plants were exposed to 100 μM of arsenite (AsIII), no significant difference in arsenic accumulation was observed between the control and the mutant plants (535 μg/g d. wt. and 498 μg/g d. wt., respectively). Also, when arsenate and arsenite was measured separately either in shoots or roots, significant differences in accumulation of these substances were observed between the mutant and the control plants. These results suggest that AtACR2 gene is involved not only in accumulation of arsenic in plants, but also in conversion of arsenate to arsenite inside the plant cells. © 2017 Institute of Molecular Biology, Slovak Academy of Sciences.

  • 30.
    Olesen, K.
    et al.
    Göteborgs universitet.
    Ejdebäck, Mikael
    Göteborgs universitet.
    Hansson, Örjan
    Electron transfer from genetically modified plastocyanin to photosystem 11998In: Photosynthesis: Mechanisms and effects / [ed] Garab, G., Dordrecht: Kluwer Academic Publishers, 1998, p. 1597-1600Conference paper (Other academic)
  • 31.
    Olesen, Kenneth
    et al.
    Biochemistry and Biophysics, Department of Chemistry, Göteborg University, Sweden.
    Ejdebäck, Mikael
    University of Skövde, Department of Natural Sciences. Biochemistry and Biophysics, Department of Chemistry, Göteborg University, Sweden.
    Crnogorac, Milan M.
    Department of Chemistry, Iowa State University, Ames, United States.
    Kostić, Nenad M.
    Department of Chemistry, Iowa State University, Ames, United States.
    Hansson, Örjan
    Biochemistry and Biophysics, Department of Chemistry, Göteborg University, Sweden.
    Electron transfer to photosystem 1 from spinach plastocyanin mutated in the small acidic patch: ionic strength dependence of kinetics and comparison of mechanistic models1999In: Biochemistry, ISSN 0006-2960, E-ISSN 1520-4995, Vol. 38, no 50, p. 16695-16705Article in journal (Refereed)
    Abstract [en]

    A set of plastocyanin (Pc) mutants, probing the small acidic patch (Glu59, Glu60, and Asp61) and a nearby residue, Gln88, has been constructed to provide further insight into the electron transfer process between Pc and photosystem 1. The negatively charged residues were changed into their neutral counterparts or to a positive lysine. All mutant proteins exhibited electron transfer kinetics qualitatively similar to those of the wild type protein over a wide range of Pc concentrations. The kinetics were slightly faster for the Gln88Lys mutant, while they were significantly slower for the Glu59Lys mutant. The data were analyzed with two different models: one involving a conformational change of the Pc-photosystem 1 complex that precedes the electron transfer step (assumed to be irreversible) [Bottin, H., and Mathis, P. (1985) Biochemistry 24, 6453-6460] and another where no conformational change occurs, the electron transfer step is reversible, and dissociation of products is explicitly taken into account [Drepper, F., Hippler, M., Nitschke, W., and Haehnel, W. (1996) Biochemistry 35, 1282-1295]. Both models can account for the observed kinetics in the limits of low and high Pc concentrations. To discriminate between the models, the effects of added magnesium ions on the kinetics were investigated. At a high Pc concentration (0.7 mM), the ionic strength dependence was found to be consistent with the model involving a conformational change but not with the model where the electron transfer is reversible. One residue in the small acidic patch, Glu60, seems to be responsible for the major part of the ionic strength dependence of the kinetics.

  • 32.
    Olivé, Montse
    et al.
    Institute of Neuropathology, Department of Pathology and Neuromuscular Unit, Department of Neurology / CIBERNED, Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, Instituto Carlos III, Barcelona, Spain.
    Abdul-Hussein, Saba
    Department of Pathology, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Oldfors, Anders
    Department of Pathology, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden.
    González-Costello, José
    Department of Cardiology, Barcelona, Spain.
    van der Ven, Peter F. M.
    Department of Molecular Cell Biology, Institute for Cell Biology, University of Bonn, Bonn, Germany.
    Fürst, Dieter O.
    Department of Molecular Cell Biology, Institute for Cell Biology, University of Bonn, Bonn, Germany.
    González, Laura
    Institute of Neuropathology, Department of Pathology and Neuromuscular Unit, Department of Neurology.
    Moreno, Dolores
    Institute of Neuropathology, Department of Pathology, Barcelona, Spain.
    Torrejón-Escribano, Benjamín
    Scientific and Technical Services Facility, Biology Unit, CCiTUB, IDIBELL-University of Barcelona, Barcelona, Spain.
    Alió, Josefina
    Department of Cardiology, Barcelona, Spain.
    Pou, Adolf
    Department of Neurology, Hospital del Mar, Barcelona, Spain.
    Ferrer, Isidro
    Institute of Neuropathology, Department of Pathology, Barcelona, Spain / CIBERNED, Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, Instituto Carlos III, Barcelona, Spain.
    Tajsharghi, Homa
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. Department of Pathology, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden / Department of Clinical and Medical Genetics, University of Gothenburg, Gothenburg, Sweden.
    New cardiac and skeletal protein aggregate myopathy associated with combined MuRF1 and MuRF3 mutations2015In: Human Molecular Genetics, ISSN 0964-6906, E-ISSN 1460-2083, Vol. 24, no 13, p. 3638-3650, article id 108Article in journal (Refereed)
    Abstract [en]

    Protein aggregate myopathies (PAMs) define muscle disorders characterized by protein accumulation in muscle fibres. We describe a new PAM in a patient with proximal muscle weakness and hypertrophic cardiomyopathy, whose muscle fibres contained inclusions containing myosin and myosin-associated proteins, and aberrant distribution of microtubules. These lesions appear as intact A- and M-bands lacking thin filaments and Z-discs. These features differ from inclusions in myosin storage myopathy (MSM), but are highly similar to those in mice deficient for the muscle-specific RING finger proteins MuRF1 and MuRF3. Sanger sequencing excluded mutations in the MSM-associated gene MYH7 but identified mutations in TRIM63 and TRIM54, encoding MuRF1 and MuRF3, respectively. No mutations in other potentially disease-causing genes were identified by Sanger and whole exome sequencing. Analysis of seven family members revealed that both mutations segregated in the family but only the homozygous TRIM63 null mutation in combination with the heterozygous TRIM54 mutation found in the proband caused the disease phenotype. Both MuRFs are microtubule-associated proteins localizing to sarcomeric M-bands and Z-discs. They are E3 ubiquitin ligases that play a role in degradation of sarcomeric proteins, stabilization of microtubules and myogenesis. Lack of ubiquitin and the 20S proteasome subunit in the inclusions found in the patient suggested impaired turnover of thick filament proteins. Disruption of microtubules in cultured myotubes was rescued by transient expression of wild-type MuRF1. The unique features of this novel myopathy point to defects in homeostasis of A-band proteins in combination with instability of microtubules as cause of the disease.

  • 33.
    O'Neill, Luke A. J.
    et al.
    Department of Biochemistry, Trinity College Dublin, Ireland.
    Dunne, Aisling
    Department of Biochemistry, Trinity College Dublin, Ireland.
    Ejdebäck, Mikael
    Department of Biochemistry, Trinity College Dublin, Ireland.
    Gray, Pearl
    Department of Biochemistry, Trinity College Dublin, Ireland.
    Jefferies, Caroline
    Department of Biochemistry, Trinity College Dublin, Ireland.
    Wietek, Claudia
    Department of Biochemistry, Trinity College Dublin, Ireland.
    Mal and MyD88: adapter proteins involved in signal transduction by Toll-like receptors2003In: Journal of Endotoxin Research, ISSN 0968-0519, E-ISSN 1743-2839, Vol. 9, no 1, p. 55-59Article in journal (Refereed)
    Abstract [en]

    Signal transduction processes activated by Toll-like receptors (TLRs) include the important transcription factor NF-kappaB and 2 MAP kinases, p38 and Jun N-terminal kinase. These signals ultimately give rise to increased expression of a multitude of pro-inflammatory proteins. Receptor-proximal proteins involved in signalling by all TLRs include the adapter MyD88, 3 IRAKs (IRAK-4, IRAK and IRAK-2), Tollip, Traf-6 and TAK-1. Differences between signals generated by TLRs are emerging, with both TLR4 and TLR2 signalling requiring an additional adapter termed MyD88-adapter-like (Mal; also known as TIRAP). MyD88 and Mal both have a homologous Toll/IL-1 receptor (TIR) domain although they differ in their N-termini, with MyD88 possessing a death domain. In addition, structural models reveal marked differences in surface charges which, when taken with surface charge differences between TLR2 and TLR4 TIR domains, may indicate that TLR4 but not TLR2 recruits Mal directly. Another difference is that Mal can become phosphorylated. Future studies on Mal will reveal specificities in signal transduction by different TLRs, which may ultimately provide molecular explanations for specificities in the innate immune response to infection.

  • 34.
    Rahman, Aminur
    University of Skövde, School of Bioscience.
    Cloning and characterization of an Arabidopsis thaliana arsenic reductase gene (ACR2) 2010Independent thesis Advanced level (degree of Master (One Year)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Arsenic is a toxic metalloid existing everywhere in the nature. It is toxic to most organisms and considered as human carcinogen. Arsenic contamination leads to severe health problems with diseases like damage of skin, lung, bladder, liver and kidney as well as central nervous system. It is very likely that too much chemicals such as cadmium and arsenic in the consumed foods can also lead to increased birth defects like spinal bifida. In some regions of South-East Asia, like Bangladesh, Burma, Thailand and India, arsenic contamination of human population via either food chain or drinking water is now considered as a national threat for mankind. As arsenic can be found everywhere in nature it may come in contact with food chain very easily through either water or cultivated crops. In South-East Asia the major cultivated crop is rice and it is the staple food for people in many countries like Bangladesh, Burma and Thailand. Cultivation of rice plants requires water either from rainfall or irrigation. Irrigated water in some regions of South-East Asia is highly contaminated with arsenic and by this way arsenic is accumulated in the rice corn which consumed not only by human but also by animals, birds and fishes. In order to avoid arsenic contamination in human food it is essential to find out a way to inhibit arsenic uptake in cultivated plants. Alternatively, we can also find out a way to metabolize arsenic "in plant". In my experiment I have used Arabidopsis thaliana as a model plant to isolate an arsenic reductase (ACR2) gene. This gene has been reported to be involved in metabolism, transport and sequestration of arsenic in plants. My thesis works include studies of the ACR2 gene based on characterization of the corresponding SALK mutants. All plants were exposed to arsenics under in vitro conditions. It was observed that the SALK mutants were more sensitive to arsenics in comparison with the wild type control plants. ACR2 gene was cloned from the genomic DNA of A. thaliana by using Phire Plant Direct PCR kits using database sequences as primers. The amplified product was first ligated to the vector pKOH152 and then transferred to E. coli DH5α competent cells. Recombinant bacterial colonies were screened by colony PCR to confirm the insertion of ACR2. The band (1.3 kb) obtained in gel image indicates that the ACR2 gene was cloned successfully. For further confirmation of these results the cloned gene should be sequenced.

  • 35.
    Rahman, Aminur
    et al.
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. Örebro University.
    Nahar, Noor
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Nawani, Neelu N.
    Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, India.
    Jass, Jana
    Örebro University.
    Ghosh, Sibdas
    Iona College, New Rochelle, NY, USA.
    Olsson, Björn
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Mandal, Abul
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Comparative genome analysis of Lysinibacillus B1-CDA, a bacterium that accumulates arsenics2015In: Genomics, ISSN 0888-7543, E-ISSN 1089-8646, Vol. 106, no 6, p. 384-392Article in journal (Refereed)
    Abstract [en]

    Previously, we reported an arsenic resistant bacterium Lysinibacillus sphaericus B1-CDA, isolated from an arsenic contaminated lands. Here, we have investigated its genetic composition and evolutionary history by using massively parallel sequencing and comparative analysis with other known Lysinibacillus genomes. Assembly of the sequencing reads revealed a genome of ~ 4.5 Mb in size encompassing ~ 80% of the chromosomal DNA. We found that the set of ordered contigs contains abundant regions of similarity with other Lysinibacillus genomes and clearly identifiable genome rearrangements. Furthermore, all genes of B1-CDA that were predicted be involved in its resistance to arsenic and/or other heavy metals were annotated. The presence of arsenic responsive genes was verified by PCR in vitro conditions. The findings of this study highlight the significance of this bacterium in removing arsenics and other toxic metals from the contaminated sources. The genetic mechanisms of the isolate could be used to cope with arsenic toxicity.

  • 36.
    Rahman, Aminur
    et al.
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. Örebro University.
    Nahar, Noor
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Nawani, Neelu N.
    Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, India.
    Jass, Jana
    Örebro University.
    Ghosh, Sibdas
    Iona College, New Rochelle, NY, USA.
    Olsson, Björn
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Mandal, Abul
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Data in support of the comparative genome analysis of Lysinibacillus B1-CDA, a bacterium that accumulates arsenics2015In: Data in Brief, ISSN 2352-3409, Vol. 5, p. 579-585Article in journal (Refereed)
    Abstract [en]

    This study is a part of our long term project on bioremediation of toxic metals and other pollutants for protection of human health and the environment from severe contamination. The information and results presented in this data article are based on both in vitro and in silico experiments. In vitro experiments were used to investigate the presence of arsenic responsive genes in a bacterial strain B1-CDA that is highly resistant to arsenics. However, in silico studies were used to annotate the function of the metal responsive genes. By using this combined study consisting of in vitro and in silico experiments we have identified and characterized specific genes from B1-CDA that can be used as a potential tool for removal of arsenics as well as other heavy metals from the contaminated environment.

  • 37.
    Rakesh, Dessy
    University of Skövde, School of Bioscience.
    Role of EZH2 in regulating MET proto-oncogene in chronic lymphocytic leukemia2018Independent thesis Advanced level (degree of Master (One Year)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Mesenchymal–epithelial transition factor (c-MET) is a receptor tyrosine kinase (RTK) naturally activated by the binding of hepatocyte growth factor (HGF) and was shown to regulate many essential cellular processes including cell proliferation, motility, invasion, angiogenesis, and apoptosis. According to the recent ChIP sequencing data on EZH2 using CLL samples from the current lab, MET gene was shown to be direct target of EZH2 in CLL. In this study, we investigated if EZH2 is regulating the MET gene expression through histone methyl transferase activity (H3K27me3) in chronic lymphocytic leukemia (CLL).We performed down-regulated of EZH2 using siRNA and analyzed the expression levels of both EZH2 and MET gene at mRNA and protein levels using Real time-quantitative PCR, and western blot analysis respectively. In addition, we also analyzed if MET gene is regulated by DNA methylation using Pyrosequencing method. Our analysis showed that EZH2 directly regulated MET gene expression and DNA in the LINE1 region located at intron 2 regulates MET promoter, using CLL cell lines. Moreover, treatment of CLL cell with DNA methyl inhibitor drug, 5’-Deoxy 2’Azacytidine (DAC) drug induces the MET expression in CLL cell lines. Finally, this study shows that MET gene is regulated by both hypermethylation at intronic region and EZH2 binding on gene promoter resulting in gene silencing.

  • 38.
    Rodriguez, David Alcala
    University of Skövde, School of Bioscience.
    The synergistic effect of ketone bodies and vitamin D on pancreas cancer cells.2018Independent thesis Advanced level (degree of Master (One Year)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Cancer is one of the biggest burdens for modern societies. Its diagnosis causes grief to patients and relatives and despite the research on the area incidences keep increasing. Pancreatic cancer is the 14th most common cancer type worldwide it tops for the 4th one in cancer related deaths in Europe. A large proportion of the patients die within a year after the clinical diagnosis. Cancer cells suffer from faulty cell respiration and exhibit an increased usage of glucose, the so-called Warburg effect, that allows them to boost their growth rate, survival and proliferation. This metabolic pathway consisting of an aerobic glycolysis to produce pyruvate, followed by lactate fermentation could be a therapeutic target. Reducing the glucose intake and feeding cancer with ketone bodies, a bypass to the cancer metabolism, could reduce cancer growth by limiting their energy source. On the other hand, vitamin D has shown beneficial effects when treating cancer. Outcomes from trials have shown that cancer could be inhibited or delayed by dietary supplements of vitamin D. Here we hypothesise that the treatment of pancreas cancer cells with ketone bodies together with vitamin D reduces cell proliferation. In vitro culture of Panc1 cells treated in combination with 1,25-vitamin D has shown significant effects, both for sodium-3-hydroxybutyrate and lithium-acetoacetate (p<0,01). Findings show that a ketogenic approach to fight cancer is very promising, but foremost totally normal for the organism. 

  • 39.
    Saha, Ananda Kumar
    et al.
    Department of Zoology, University of Rajshahi, Rajshahi-6205, Bangladesh.
    Sultana, Nahida
    Department of Zoology, University of Rajshahi, Rajshahi-6205, Bangladesh.
    Mohanta, Moni Krishno
    Department of Zoology, University of Rajshahi, Rajshahi-6205, Bangladesh.
    Mandal, Abul
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Haque, Fazlul
    Identification and Characterization of Azo Dye Decolourizing Bacterial Strains, Alcaligenes faecalis E5.Cd and A. faecalis Fal.3 Isolated from Textile Effluents2017In: American Scientific Research Journal for Engineering, Technology, and Sciences (ASRJETS), ISSN 2313-4410, Vol. 31, no 1, p. 163-175Article in journal (Refereed)
    Abstract [en]

    The study was designed for isolation and characterization of azo dye decolourizing bacteria which is a prerequisite for developing a microorganism-facilitated treatment of polluting dyes. In this study nine types of bacteria which were able to decolourize three types of azo dyes (Blue H/C, Red 3B and Yellow 3R dye) were isolated from textile effluents collected from Gazipur industrial area in Bangladesh. Depending on 16S rDNA analysis, the most efficient decolourizing bacterium for the Blue H/C and the Red 3B dye was identified as Alcaligenesfaecalis strain E5.Cd while that for the Yellow 3R dye was identified as Alcaligenesfaecalis strain Fal.3. After characterization, both A. faecalis E5.Cdand A. faecalis Fal.3 were found to grow optimally at 35 0 C and at pH 7 and pH 8, respectively. Both of these strains were sensitive to all antibiotics studied except for Bacitracin. Also, both strains showed maximum decolourization activities after 96 hours incubation in MS media at pH 7 (up to 93%) and pH 8 (up to 94%), at 35 0 C temperature ( up to 91%), at 50 ppm initial dye concentration (up to 92%), at 20% inoculum size (up to 93%), and at supplementation of 1% co-substrate (up to 93%).

  • 40.
    Shumkova, E. S.
    et al.
    A N Bach Institute of Biochemistry, RAS, Moscow, Russia / Perm State National Research University, Perm, Russia.
    Olsson, Björn E.
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. Perm State National Research University, Perm, Russia.
    Plotnikova, E. G.
    Perm State National Research University, Perm, Russia / Institute of Ecology and Genetics of Microorganisms, UB RAS, Perm, Russia.
    Organization of Biphenyl and Polychlorinated Biphenyls Destruction Genes in Rhodococcus ruber P252015In: Russian Journal of Immunology, ISSN 1028-7221, Vol. 9, no 2, p. 624-626Article in journal (Refereed)
  • 41.
    Sigfridsson, Kalle
    et al.
    Department of Biochemistry and Biophysics, Lundberg Laboratory, Göteborg University / Chalmers University of Technology, Göteborg, Sweden.
    Ejdebäck, Mikael
    Department of Biochemistry and Biophysics, Lundberg Laboratory, Göteborg University / Chalmers University of Technology, Göteborg, Sweden.
    Sundahl, Mikael
    Department of Organic Chemistry, Chalmers University of Technology, Göteborg, Sweden.
    Hansson, Örjan
    Department of Biochemistry and Biophysics, Lundberg Laboratory, Göteborg University / Chalmers University of Technology, Göteborg, Sweden.
    Electron transfer in ruthenium-modified spinach plastocyanin mutants1998In: Archives of Biochemistry and Biophysics, ISSN 0003-9861, E-ISSN 1096-0384, Vol. 351, no 2, p. 197-206Article in journal (Refereed)
    Abstract [en]

    Four site-directed mutants of spinach plastocyanin, Pc(Leu12His), Pc(Leu15His), Pc(Thr79His), and Pc(Lys81His), have been modified by covalent attachment of a photoactive [Ru(bpy)2(im)]2+ complex at the surface-exposed histidine residues. The Pc-Ru complexes were characterized with optical absorption, CD, and EPR spectroscopy and their spectra were found to be similar to the unmodified proteins except in the case of the Pc(Leu12His) mutant which lost the Cu ion irreversibly during the Ru modification. Electron transfer (ET) within the other Pc-Ru complexes was studied with time-resolved optical spectroscopy, using an external-quencher approach. The fully reduced [Cu(I), Ru(II)] proteins were photoexcited and subsequently oxidized by an external quencher, [Ru(NH3)6]Cl3, forming the [Cu(I), Ru(III)] proteins. This was followed by an internal ET from Cu(I) to Ru(III). The rates of the internal ET reactions exhibit an exponential dependence on metal-to-metal separation, with a decay factor of 1.1 A-1. From a temperature-dependence study of the Ru-modified Pc(Lys81His) protein, a reorganization energy for the Cu-to-Ru ET reaction of 1.2 eV was determined. In this analysis it was found necessary to include an appreciable temperature dependence in the driving force of the ET reaction.

  • 42.
    Sikka, Pilleriin
    et al.
    Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, United Kingdom.
    Walker, Rosie
    Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, United Kingdom.
    Cockayne, Rebecca
    Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, United Kingdom.
    Wood, Matthew J. A.
    Department of Physiology, University of Oxford, Warneford Hospital, Oxford, United Kingdom.
    Harrison, Paul J.
    Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, United Kingdom.
    Burnet, Philip W. J.
    Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, United Kingdom.
    D-Serine metabolism in C6 glioma cells: Involvement of alanine-serine-cysteine transporter (ASCT2) and serine racemase (SRR) but not D-amino acid oxidase (DAO)2010In: Journal of Neuroscience Research, ISSN 0360-4012, E-ISSN 1097-4547, Vol. 88, no 8, p. 1829-1840Article in journal (Refereed)
    Abstract [en]

    D-serine is an endogenous N-methyl-D-aspartate (NMDA) receptor coagonist. It is synthesized from L-serine by serine racemase (SRR), but many aspects of its metabolism remain unclear, especially in the forebrain, which lacks active D-amino acid oxidase (DAO), the major D-serine degradative enzyme. Candidate mechanisms include SRR operating in alpha,beta-eliminase mode (converting D-serine to pyruvate) and regulation by serine transport, in which the alanine-serine-cysteine transporter ASCT2 is implicated. Here we report studies in C6 glioma cells, which "simulate" the forebrain, in that the cells express SRR and ASCT2 but lack DAO activity. We measured D-serine, ASCT2, SRR, and DAO expression and DAO activity in two situations: after incubation of cells for 48 hr with serine isomers and after increased or decreased SRR expression by transfection and RNA interference, respectively. Incubation with serine enantiomers decreased [(3)H]D-serine uptake and ASCT2 mRNA and increased SRR immunoreactivity but did not alter DAO immunoreactivity, and DAO activity remained undetectable. SRR overexpression increased D-serine and pyruvate and decreased [(3)H]D-serine uptake and ASCT2 mRNA but did not affect DAO. SRR knockdown did not alter any of the parameters. Our data suggest that D-serine transport mediated by ASCT2 contributes prominently to D-serine homeostasis when DAO activity is absent. The factors regulating D-serine are important for understanding normal NMDA receptor function and because D-serine, along with DAO and SRR, is implicated in the pathogenesis and treatment of schizophrenia.

  • 43.
    Sireesha, Dommaraju
    University of Skövde, School of Life Sciences.
    An Investigation of the Nano-Organization of Glucose Transporters, Glut1 and Glut3, in the Mammalian Plasma Membrane2008Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Glucose is a monosaccharide and fuel for body, it cannot pass through membrane by simple diffusion so, integral transmembrane proteins named glucose transporters (Gluts) are involved in the regulation of the movement of glucose between the extracellular and intracellular spaces within the body. GLUT1 and GLUT3 have previously been shown by cold detergent extraction methods to reside in distinct plasma membrane domains in non-polarized mammalian cells, with GLUT1, but not GLUT3, residing  in detergent-resistant membrane (DRM) domains. To confirm this observation under less invasive conditions, molecular fusion tags are inserted in the first external loop in Glut1 with biotin ligase acceptor peptide (BLAP) between Ser-55 and Ile-56 and in Glut3 with Acyl carrier peptide (ACP) in between Val-57 and Leu-58 respectively. These Glut fusion proteins will be used in order to confirm these observations by fluorescence recovery after photobleaching (FRAP) and single molecule fluorescence microscopy in live cells. hGLUT1-EGFP, hGLUT1 (AgeI)-EGFP recombinants were constructed and transfected human embryonic kidney cells (HEK-293) quantum dot images supports the fact that EGFP transfected cells uniformly and is distributed in the cell cytoplasm, hGLUT1-EGFP transfected cells and is localized to the cell membrane and hGLUT1 (AgeI)-EGFP transfected cells and located to the plasma membrane with high intensity.

  • 44.
    Ubbink, Marcellus
    et al.
    Leiden University.
    Ejdebäck, Mikael
    Göteborgs universitet.
    Crowley, Peter B.
    Schlarb, B. G.
    Howe, C. J.
    Karlsson, B. G.
    Bendall, D. S.
    Canters, G. W.
    The transient complex of the redox proteins cytochrome f and plastocyanin studied by NMR1999In: Journal of Inorganic Biochemistry, ISSN 0162-0134, E-ISSN 1873-3344, Vol. 74, no 1-4, p. 321-Article in journal (Other academic)
  • 45.
    Ubbink, Marcellus
    et al.
    Department of Biochemistry and Cambridge Centre for Molecular Recognition, University of Cambridge, England / Leiden Institute of Chemistry, Leiden University, Gorlaeus Laboratories, The Netherlands.
    Ejdebäck, Mikael
    Department of Biochemistry and Biophysics, Göteborg University, Sweden / Chalmers University of Technology, Lundbergslaboratoriet, Göteborg, Sweden.
    Karlsson, B. Göran
    Department of Biochemistry and Biophysics, Göteborg University, Sweden / Chalmers University of Technology, Lundbergslaboratoriet, Göteborg, Sweden.
    Bendall, Derek S.
    Department of Biochemistry and Cambridge Centre for Molecular Recognition, University of Cambridge, England.
    The structure of the complex of plastocyanin and cytochrome f, determined by paramagnetic NMR and restrained rigid-body molecular dynamics1998In: Structure, ISSN 0969-2126, E-ISSN 1878-4186, Vol. 6, no 3, p. 323-335Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The reduction of plastocyanin by cytochrome f is part of the chain of photosynthetic electron transfer reactions that links photosystems II and I. The reaction is rapid and is influenced by charged residues on both proteins. Previously determined structures show that the plastocyanin copper and cytochrome f haem redox centres are some distance apart from the relevant charged sidechains, and until now it was unclear how a transient electrostatic complex can be formed that brings the redox centres sufficiently close for a rapid reaction.

    RESULTS: A new approach was used to determine the structure of the transient complex between cytochrome f and plastocyanin. Diamagnetic chemical shift changes and intermolecular pseudocontact shifts in the NMR spectrum of plastocyanin were used as input in restrained rigid-body molecular dynamics calculations. An ensemble of ten structures was obtained, in which the root mean square deviation of the plastocyanin position relative to cytochrome f is 1.0 A. Electrostatic interaction is maintained at the same time as the hydrophobic side of plastocyanin makes close contact with the haem area, thus providing a short electron transfer pathway (Fe-Cu distance 10.9 A) via residues Tyr1 or Phe4 (cytochrome f) and the copper ligand His87 (plastocyanin).

    CONCLUSIONS: The combined use of diamagnetic and paramagnetic chemical shift changes makes it possible to obtain detailed information about the structure of a transient complex of redox proteins. The structure suggests that the electrostatic interactions 'guide' the partners into a position that is optimal for electron transfer, and which may be stabilised by short-range interactions.

  • 46.
    Ulfenborg, Benjamin
    University of Skövde, School of Life Sciences.
    Investigation of the implications of nitric oxide on biofilm development2008Independent thesis Advanced level (degree of Master (One Year)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Biofilms are communities of sessile microorganisms attached to a surface and imbeddedin a matrix of extracellular polysaccharide substances. These communities can be foundin diverse aquatic environments, such as in industrial pipes and in humans. By formingmicrocolony structures, which are highly resistant to adverse physical conditions as wellas antimicrobial agents, biofilms are very problematic when associated with e.g.persistent infections. In order to find new ways of controlling biofilm growth, theprocesses involved in biofilm development must be investigated further. The maininterest of this study is the occurrence of void formation inside biofilms. Thisphenomenon has been observed in several studies and has been correlated to cell deathinside the microcolonies. The occurrence of cell death has recently been associated withthe presence of nitric oxide in the biofilm. In this study, the implications of nitric oxideaccumulation on biofilm development were investigated using an individual-basedmodel. Specifically, the role of nitric oxide in void formation was considered. A largenumber of simulations were run using different parameter settings in order to determine ifnitric oxide could account for the occurrence of void formation observed experimentally.The general predictions made by the model system showed agreement to someexperimental data, but not to others. Sloughing, the detachment of chunks of cells fromthe biofilm, was observed in the majority of simulations. In some cases, the model alsopredicted the presence of live cells inside the voids, which has been observedexperimentally.

  • 47.
    Wallenhammar, Ann-Charlotte
    et al.
    HS Konsult AB, Örebro, Sweden.
    Algerin, Maria
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Tilevik, Diana
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Ny metod bedömer risk för bomullsmögel2017In: Arvensis, ISSN 2000-0871, no 3Article in journal (Other academic)
  • 48.
    Wobst, Heike J.
    et al.
    AstraZeneca, Tufts Laboratory for Basic and Translational Neuroscience, Tufts University, Boston, United States.
    Delsing, Louise
    AstraZeneca-Tufts Laboratory for Basic and Translational Neuroscience, Tufts University, Boston, MA, United States of America / AstraZeneca, Discovery Science, Innovative Medicines and Early Development Biotech Unit, Mölndal, Sweden.
    Brandon, Nicholas J.
    AstraZeneca, Tufts Laboratory for Basic and Translational Neuroscience, Tufts University, Boston, United States / AstraZeneca, Neuroscience, Innovative Medicines and Early Development, Waltham, United States.
    Moss, Stephen J.
    AstraZeneca, Tufts Laboratory for Basic and Translational Neuroscience, Tufts University, Boston, United States / Department of Neuroscience, Tufts University, School of Medicine, Boston, MA, United States.
    Truncation of the TAR DNA-binding protein 43 is not a prerequisite for cytoplasmic relocalization, and is suppressed by caspase inhibition and by introduction of the A90V sequence variant2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 5, article id e0177181Article in journal (Refereed)
    Abstract [en]

    The RNA-binding and -processing protein TAR DNA-binding protein 43 (TDP-43) is heavily linked to the underlying causes and pathology of neurodegenerative diseases such as amyotrophic lateral sclerosis and frontotemporal lobar degeneration. In these diseases, TDP-43 is mislocalized, hyperphosphorylated, ubiquitinated, aggregated and cleaved. The importance of TDP-43 cleavage in the disease pathogenesis is still poorly understood. Here we detail the use of D-sorbitol as an exogenous stressor that causes TDP-43 cleavage in HeLa cells, resulting in a 35 kDa truncated product that accumulates in the cytoplasm within one hour of treatment. We confirm that the formation of this 35 kDa cleavage product is mediated by the activation of caspases. Inhibition of caspases blocks the cleavage of TDP-43, but does not prevent the accumulation of full-length protein in the cytoplasm. Using D-sorbitol as a stressor and caspase activator, we also demonstrate that the A90V variant of TDP-43, which lies adjacent to the caspase cleavage site within the nuclear localization sequence of TDP-43, confers partial resistance against caspase-mediated generation of the 35 kDa cleavage product.

  • 49.
    Wobst, Heike J.
    et al.
    AstraZeneca-Tufts Laboratory for Basic and Translational Neuroscience, Tufts University School of Medicine, Boston, United States.
    Wesolowski, Steven S.
    IMED Biotech Unit, AstraZeneca Neuroscience IMED, AstraZeneca, Cambridge, United States.
    Chadchankar, Jayashree
    AstraZeneca-Tufts Laboratory for Basic and Translational Neuroscience, Tufts University School of Medicine, Boston, United States.
    Delsing, Louise
    AstraZeneca-Tufts Laboratory for Basic and Translational Neuroscience, Department of Neuroscience, Tufts University School of Medicine, Boston, MA, USA / IMED Biotech Unit, AstraZeneca Discovery Science, Mölndal, Sweden.
    Jacobsen, Steven
    IMED Biotech Unit, AstraZeneca Neuroscience IMED, AstraZeneca, Cambridge, United States.
    Mukherjee, Jayanta
    AstraZeneca-Tufts Laboratory for Basic and Translational Neuroscience, Tufts University School of Medicine, Boston, United States.
    Deeb, Tarek Z.
    AstraZeneca-Tufts Laboratory for Basic and Translational Neuroscience, Tufts University School of Medicine, Boston, United States.
    Dunlop, John
    IMED Biotech Unit, AstraZeneca Neuroscience IMED, AstraZeneca, Cambridge, United States.
    Brandon, Nicholas J.
    IMED Biotech Unit, AstraZeneca Neuroscience IMED, AstraZeneca, Cambridge, United States.
    Moss, Stephen J.
    AstraZeneca-Tufts Laboratory for Basic and Translational Neuroscience, Tufts University School of Medicine, Boston, United States / Department of Neuroscience, Tufts University School of Medicine, Boston, United States.
    Cytoplasmic Relocalization of TAR DNA-Binding Protein 43 Is Not Sufficient to Reproduce Cellular Pathologies Associated with ALS In vitro2017In: Frontiers in Molecular Neuroscience, ISSN 1662-5099, Vol. 10, article id 46Article in journal (Refereed)
    Abstract [en]

    Mutations in the gene TARDBP, which encodes TAR DNA-binding protein 43 (TDP-43), are a rare cause of familial forms of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). While the majority of mutations are found in the C-terminal glycine-rich domain, an alanine to valine amino acid change at position 90 (A90V) in the bipartite nuclear localization signal (NLS) of TDP-43 has been described. This sequence variant has previously been shown to cause cytoplasmic mislocalization of TDP-43 and decrease protein solubility, leading to the formation of insoluble aggregates. Since the A90V mutation has been described both in patients as well as healthy controls, its pathogenic potential in ALS and FTD remains unclear. Here we compare properties of overexpressed A90V to the highly pathogenic M337V mutation. Though both mutations drive mislocalization of the protein to the cytoplasm to the same extent, M337V produces more significant damage in terms of protein solubility, levels of pathogenic phosphorylation, and formation of C-terminal truncated protein species. Furthermore, the M337V, but not the A90V mutant, leads to a downregulation of histone deacetylase 6 and Ras GTPase-activating protein-binding protein. We conclude that in the absence of another genetic or environmental 'hit' the A90V variant is not sufficient to cause the deleterious phenotypes associated with ALS and FTD, despite prominent cytoplasmic protein relocalization of TDP-43.

  • 50. Young, S
    et al.
    Ejdebäck, Mikael
    Göteborgs universitet.
    Sigfridsson, K
    Samuelson, A
    Hansson, Örjan
    Spectroscopic and kinetic characterization of site-specific mutants of plastocyanin1995In: Photosynthesis: From Light To Biosphere, Vol. 2 / [ed] Mathis, P., Dordrecht: Kluwer Academic Publishers, 1995, p. 669-672Conference paper (Other academic)
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