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  • 101. Tatarek-Nossol, Marianna
    et al.
    Yan, Li-Mei
    Schmauder, Anke
    Tenidis, Konstantinos
    Westermark, Gunilla
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Kapurniotu, Aphrodite
    Inhibition of hIAPP amyloid-fibril formation and apoptotic cell death by a designed hIAPP amyloid-core-containing hexapeptide2005In: Chemistry and Biology, ISSN 1074-5521, E-ISSN 1879-1301, Vol. 12, no 7, p. 797-809Article in journal (Refereed)
    Abstract [en]

    The pathogenesis of type II diabetes is associated with the aggregation of the 37-residue human islet amyloid polypeptide (hIAPP) into cytotoxic β sheet aggregates and fibrils. We have recently shown that introduction of two N-methyl rests in the β sheet- and amyloid-core-containing sequence hIAPP(22-27), or NFGAIL converted this amyloidogenic and cytotoxic sequence into nonamyloidogenic and noncytotoxic NF(N-Me)GA(N-Me)IL. Here, we show that NF(N-Me)GA(N-Me)IL is able to bind with high-affinity full-length hIAPP and to inhibit its fibrillogenesis. NF(N-Me)GA(N-Me)IL also inhibits hIAPP-mediated apoptotic β cell death. By contrast, unmodified NFGAIL does not inhibit hIAPP amyloidogenesis and cytotoxicity, suggesting that N-methylation conferred on NFGAIL the properties of NF(N-Me)GA(N-Me)IL. These results support the concept that rational N-methylation of hIAPP amyloid-core sequences may be a valuable strategy to design pancreatic-amyloid diagnostics and therapeutics for type II diabetes. ©2005 Elsevier Ltd All rights reserved.

  • 102.
    Thuswaldner, Sophie
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Lagerstedt, Jens O
    Rojas-Stütz, Marc
    Bouhidel, Karim
    Der, Christophe
    Leborgne-Castel, Nathalie
    Mishra, Arti
    Marty, Francis
    Schoefs, Benoit
    Adamska, Iwona
    Persson, Bengt L
    Spetea Wiklund, Cornelia
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Identification, expression, and functional analyses of a thylakoid ATP/ADP carrier from Arabidopsis2007In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 282, no 12, p. 8848-8859Article in journal (Refereed)
    Abstract [en]

    In plants the chloroplast thylakoid membrane is the site of light-dependent photosynthetic reactions coupled to ATP synthesis. The ability of the plant cell to build and alter this membrane system is essential for efficient photosynthesis. A nucleotide translocator homologous to the bovine mitochondrial ADP/ATP carrier (AAC) was previously found in spinach thylakoids. Here we have identified and characterized a thylakoid ATP/ADP carrier (TAAC) from Arabidopsis. (i) Sequence homology with the bovine AAC and the prediction of chloroplast transit peptides indicated a putative carrier encoded by the At5g01500 gene, as a TAAC. (ii) Transiently expressed TAAC-green fluorescent protein fusion construct was targeted to the chloroplast. Western blotting using a peptide-specific antibody together with immunogold electron microscopy revealed a major location of TAAC in the thylakoid membrane. Previous proteomic analyses identified this protein in chloroplast envelope preparations. (iii) Recombinant TAAC protein specifically imports ATP in exchange for ADP across the cytoplasmic membrane of Escherichia coli. Studies on isolated thylakoids from Arabidopsis confirmed these observations. (iv) The lack of TAAC in an Arabidopsis T-DNA insertion mutant caused a 30-40% reduction in the thylakoid ATP transport and metabolism. (v) TAAC is readily expressed in dark-grown Arabidopsis seedlings, and its level remains stable throughout the greening process. Its expression is highest in developing green tissues and in leaves undergoing senescence or abiotic stress. We propose that the TAAC protein supplies ATP for energy-dependent reactions during thylakoid biogenesis and turnover in plants. © 2007 by The American Society for Biochemistry and Molecular Biology, Inc.

  • 103.
    Tibell, Lena
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Bivall Persson, Petter
    Linköping University, Department of Science and Technology, Visual Information Technology and Applications (VITA). Linköping University, The Institute of Technology.
    Cooper, Matthew
    Linköping University, Department of Science and Technology, Visual Information Technology and Applications (VITA). Linköping University, The Institute of Technology.
    Ynnerman, Anders
    Linköping University, Department of Science and Technology, Visual Information Technology and Applications (VITA). Linköping University, The Institute of Technology.
    Jonsson, Bengt-Harald
    Linköping University, The Institute of Technology. Linköping University, Department of Physics, Chemistry and Biology, Molecular Biotechnology .
    Experience the Aperceptual through Virtual Reality! Tactile and Visual VR Representations as Cognitive Tools in Molecular Life Science2007In: ESERA 2007, 2007Conference paper (Other academic)
  • 104.
    Tibell, Lena
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Lookene, Aivar
    Medical chemistry Umeå.
    Stenlund, Peter
    Biochemistry Umeå.
    Characterization of the Heparin Binding of Human Extracellular Superoxide Dismutase2000In: Biochemistry, ISSN 0006-2960, E-ISSN 1520-4995, Vol. 39, p. 230-236Article in journal (Refereed)
    Abstract [en]

     The C-terminal domain of human extracellular superoxide dismutase (hEC-SOD) plays a crucial role in the protein's interaction with heparin. Here we investigated this interaction in more detail by comparing the heparin-binding characteristics of two variants of hEC-SOD: the two fusion proteins containing the hEC-SOD C-terminal domain and a synthetic peptide homologous to the C-terminal. The interaction studies were performed using a surface plasmon resonance based technique on a BIAcore system. It should be emphasized that this is a model system. However, the kinetic constants, as measured, are valid in a comparative sense. Comparison of affinities for size-fractionated heparins revealed that octa- or decasaccharides are the smallest heparin fragments that can efficiently interact with the C-terminal domain of hEC-SOD. At physiological salt concentration, and pH 7.4, the hEC-SOD/heparin interaction was found to be of a high-affinity type, with an equilibrium dissociation constant, Kd, of 0.12 M, which is 700 and 10-20 times lower than the Kd values for the synthetic peptide and the fusion proteins, respectively. However, when an -helical structure was induced in the synthetic peptide, by addition of 10% trifluoroethanol, the Kd decreased to 0.64 M. The differences in the Kd values were mainly governed by differences in the association rate constants (kass). The hEC-SOD/heparin interaction itself was found to have a fairly high dissociation rate constant (0.1 s-1), and a very high association rate constant (8 × 105 M-1 s-1), suggesting that the interaction is mainly controlled by the association. These results together with circular dichroism spectra of the synthetic peptide suggest that an -helical structure in the C-terminal is essential for optimal binding to heparin and that other parts of hEC-SOD moderate the affinity. Our data also demonstrate that the tetramerization itself does not substantially increase the affinity.

  • 105. Tikkanen, Mikko
    et al.
    Piippo, Mirva
    Suorsa, Marjaana
    Sirpiö, Sari
    Mulo, Paula
    Vainonen, Julia
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Vener, Alexander
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Allahverdiyeva, Yagut
    Aro, Eva-Mari
    State transitions revisited - A buffering system for dynamic low light acclimation of Arabidopsis2006In: Plant Molecular Biology, ISSN 0167-4412, E-ISSN 1573-5028, Vol. 62, no 4-5, p. 779-793Article in journal (Refereed)
    Abstract [en]

    The mobile part of the light-harvesting chlorophyll (chl) a/b protein complex (LHCII), composed of the Lhcb1 and Lhcb2 proteins, is the basic unit of chloroplast state transitions-the short term tuning system in balancing the excitation energy between Photosystem (PS) II and PSI. State transitions are catalysed by the thylakoid associated STN7 kinase, and we show here that besides the phosphorylation of the Lhcb1 and Lhcb2 proteins, also the phosphorylation of Lhcb4.2 (CP29) is under the control of the STN7 kinase. Upon growth of Arabidopsis WT and stn7 mutant plants under low and moderate light conditions, the WT plants favoured state 2 whereas stn7 was locked in state 1. The lack of the STN7 kinase and state transitions in stn7 also modified the thylakoid protein contents upon long-term low light acclimation resulting, for example, in low Lhcb1 and in elevated Lhca1 and Lhca2 protein amounts as compared to WT. Adjustments of thylakoid protein contents probably occurred at post-transcriptional level since the DNA microarray experiments from each growth condition did not reveal any significant differences between stn7 and WT transcriptomes. The resulting high Lhcb2/Lhcb1 ratio in stn7 upon growth at low light was accompanied by lower capacity for NPQ than in WT. On the contrary, higher amounts of PsbS in stn7 under moderate and high light growth conditions resulted in higher NPQ compared to WT and consequently also in a protection of PSII against photoinhibition. STN7 kinase and the state transitions are suggested to have a physiological significance for dynamic acclimation to low but fluctuating growth light conditions. They are shown to function as a buffering system upon short high light illumination peaks by shifting the thylakoids from state 2 to state 1 and thereby down regulating the induction of stress-responsive genes, a likely result from transient over-reduction of PSI acceptors. © 2006 Springer Science+Business Media B.V.

  • 106. Tobin, Gerard
    et al.
    Rosén, Anders
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Rosenquist, Richard
    What is the current evidence for antigen involvement in the development of chronic lymphocytic leukemia?2006In: Hematological Oncology, ISSN 0278-0232, E-ISSN 1099-1069, Vol. 24, no 1Article in journal (Refereed)
    Abstract [en]

    For many years it has been evident that B-cell chronic lymphocytic leukemia (CLL) displays preferential usage of individual immunoglobulin (Ig) variable heavy chain (VJapanese sourceH) genes. The VH1-69 gene was the first to be reported overrepresented in a large number of CLL patients, where the VH1-69+ CLL rearrangements showed characteristic molecular features, such as unmutated VH genes, usage of specific diversity/joining gene segments, and a longer than average complementarity determining region (CDR) 3 with certain common amino acid motifs. Also, biased usage of the VH3-07 and VH4-34 genes with specific rearrangement characteristics was reported in CLL. These findings led to the speculation that antigens could be involved during CLL development by triggering proliferation of B-cells with specific B-cell receptors (BCRs) leading to an increased risk of transforming events. Recently, we characterized a subset of CLL utilizing the VH3-21 gene that also displayed peculiar Ig features, e.g. very short and homologous CDR3s, predominant λ expression and preferential Vλ2-14 gene usage. This VH3- 21+ subgroup also had poor prognosis despite the fact that two-thirds of cases carried mutated VH genes. Moreover, we and others have thereafter described further CLL subsets with very similar heavy and light chain gene rearrangement features. These latter findings of subsets expressing restricted BCRs have emphasized the hypothesis that antigens could play a role during the pathogenesis of CLL. Interestingly, recombinant antibodies produced from these restricted subsets showed similar cytoplasmatic reactivity within each group, thus suggesting recognition of a limited number of autoantigens. Further characterization of antigens is now necessary in order to understand their nature and exact role in CLL development.

  • 107. Torffvit, Ole
    et al.
    Eriksson, Jan W
    Henricsson, Marianne
    Sundkvist, Göran
    Arnqvist, Hans
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Blohmé, Göran
    Bolinder, Jan
    Nyström, Lennart
    Östman, Jan
    Svensson, Maria
    Early changes in glomerular size selectivity in young adults with type 1 diabetes and retinopathy. Results from the Diabetes Incidence Study in Sweden2007In: Journal of diabetes and its complications, ISSN 1056-8727, E-ISSN 1873-460X, Vol. 21, no 4, p. 246-251Article in journal (Refereed)
    Abstract [en]

    Objective: To investigate the relationship between early-onset retinopathy and urinary markers of renal dysfunction. Research Design and Methods: The Diabetes Incidence Study in Sweden (DISS) aims to register all new cases of diabetes in young adults (15-34 years). In 1987-1988, 806 patients were reported and later invited to participate in a follow-up study focusing on microvascular complications after ∼10 years of diabetes. In the present study, 149 patients with type 1 diabetes, completed eye examination, and urine sampling were included. Results: The patients with retinopathy (n=58, 39%) had higher HbA1c (P<.001) and urinary IgG2/creatinine (P<.05) and IgG2/IgG4 ratios (P<.05). Patients with maculopathy had the highest levels. No significant differences in urinary albumin/creatinine, glycosaminoglycans (GAGs)/creatinine, Tamm-Horsfall protein (THP)/creatinine, and IgG4/creatinine ratios were found. Women had higher urinary albumin/creatinine (P<.01) and urinary IgG2/creatinine ratios (P<.01) than men. Conclusions: Young adults with type 1 diabetes and early-onset retinopathy had higher IgG2/creatinine and IgG2/IgG4 ratios than patients without retinopathy indicating that retinopathy is associated with a change in glomerular size selectivity. This was found in association with normal urinary albumin and THP excretion and may be suspected to reflect early general vascular changes. © 2007 Elsevier Inc. All rights reserved.

  • 108.
    Vasilache, Ana-Maria
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Andersson, Josefin
    Nilsberth, Camilla
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Expression of PGE2 EP3 receptor subtypes in the mouse preoptic region2007In: Neuroscience Letters, ISSN 0304-3940, E-ISSN 1872-7972, Vol. 423, no 3, p. 179-183Article in journal (Refereed)
    Abstract [en]

    Inflammatory-induced fever is dependent on prostaglandin E2 (PGE2) binding to its EP3 receptor in the thermoregulatory region of the hypothalamus, but it is not known which EP3 receptor isoform(s) that is/are involved. We identified the EP3 receptor expression in the mouse preoptic region by in situ hybridization and isolated the corresponding area by laser capture microdissection. Real-time RT-PCR analysis of microdissected tissue revealed a predominant expression of the EP3α isoform, but there was also considerable expression of EP3γ, corresponding to approximately 15% of total EP3 receptor expression, whereas EP3β was sparsely expressed. This distribution was not changed by immune challenge induced by peripheral administration of LPS, indicating that EP3 receptor splicing and distribution is not activity dependent. Considering that EP3α and EP3γ are associated with inhibitory and stimulatory G-proteins, respectively, the present data demonstrate that the PGE2 response of the target neurons is intricately regulated. © 2007 Elsevier Ireland Ltd. All rights reserved.

  • 109.
    Vener, Alexander
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Environmentally modulated phosphorylation and dynamics of proteins in photosynthetic membranes2007In: Biochimica et Biophysica Acta - Bioenergetics, ISSN 0005-2728, E-ISSN 1879-2650, Vol. 1767, no 6, p. 449-457Article in journal (Refereed)
    Abstract [en]

    Recent advances in vectorial proteomics of protein domains exposed to the surface of photosynthetic thylakoid membranes of plants and the green alga Chlamydomonas reinhardtii allowed mapping of in vivo phosphorylation sites in integral and peripheral membrane proteins. In plants, significant changes of thylakoid protein phosphorylation are observed in response to stress, particularly in photosystem II under high light or high temperature stress. Thylakoid protein phosphorylation in the algae is much more responsive to the ambient redox and light conditions, as well as to CO2 availability. The light-dependent multiple and differential phosphorylation of CP29 linker protein in the green algae is suggested to control photosynthetic state transitions and uncoupling of light harvesting proteins from photosystem II under high light. The similar role for regulation of the dynamic distribution of light harvesting proteins in plants is proposed for the TSP9 protein, which together with other recently discovered peripheral proteins undergoes specific environment- and redox-dependent phosphorylation at the thylakoid surface. This review focuses on the environmentally modulated reversible phosphorylation of thylakoid proteins related to their membrane dynamics and affinity towards particular photosynthetic protein complexes. © 2006 Elsevier B.V. All rights reserved.

  • 110.
    Vener, Alexander
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Phosphorylation of thylakoid proteins2008In: Photoprotection, photoinhibition, gene regulation, and environment / [ed] Barbara Demmig-Adams, William W. Adams, Autar Mattoo., Holland: Springer , 2008, p. 107-126Chapter in book (Other academic)
    Abstract [en]

    Photoprotection, Photoinhibition, Gene Regulation, and Environment examines the processes whereby plants monitor environmental conditions and orchestrate their response to change, an ability paramount to the life of all plants. "Excess light", absorbed by the light-harvesting systems of photosynthetic organisms, is an integrative indicator of the environment, communicating the presence of intense light and any conditions unfavorable for growth and photosynthesis. Key plant responses are photoprotection and photoinhibition. In this volume, the dual role of photoprotective responses in the preservation of leaf integrity and in redox signaling networks modulating stress acclimation, growth, and development is addressed. In addition, the still unresolved impact of photoinhibition on plant survival and productivity is discussed. Specific topics include dissipation of excess energy via thermal and other pathways, scavenging of reactive oxygen by antioxidants, proteins key to photoprotection and photoinhibition, peroxidation of lipids, as well as signaling by reactive oxygen, lipid-derived messengers, and other messengers that modulate gene expression. Approaches include biochemical, physiological, genetic, molecular, and field studies, addressing intense visible and ultraviolet light, winter conditions, nutrient deficiency, drought, and salinity

  • 111. Waernbaum, I
    et al.
    Blohmé, G
    Östman, J
    Sundkvist, G
    Eriksson, JW
    Arnqvist, Hans
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Bolinder, J
    Nyström, L
    Excess mortality in incident cases of diabetes mellitus aged 15 to 34 years at diagnosis: A population-based study (DISS) in Sweden2006In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 49, no 4, p. 653-659Article in journal (Refereed)
    Abstract [en]

    Aims/hypothesis: The objective of the study was to analyse the mortality, survival and cause of death patterns in incident cases of diabetes in the 15-34-year age group that were reported to the nationwide prospective Diabetes Incidence Study in Sweden (DISS). Methods: During the study period 1983-1999, 6,771 incident cases were reported. Identification of deaths was made by linking the records to the nationwide Cause of Death Register. Results: With an average follow-up of 8.5 years, resulting in 59,231 person-years, 159 deaths were identified. Diabetes was reported as the underlying cause of death in 51 patients (32%), and as a contributing cause of death in another 42 patients (26%). The standardised mortality ratio (SMR) was significantly elevated (RR=2.4, 95% CI: 2.0-2.8). The SMR was higher for patients classified by the reporting physician as having type 2 diabetes at diagnosis than for those classified as type 1 diabetic (2.9 and 1.8, respectively). Survival analysis showed significant differences in survival curves between males and females (p=0.0003) as well as between cases with different types of diabetes (p=0.005). This pattern was also reflected in the Cox regression model showing significantly increased hazard for males vs females (p=0.0002), and for type 2 vs type 1 (p=0.015) when controlling for age. Conclusions/ interpretation: This study shows a two-fold excess mortality in patients with type 1 diabetes and a three-fold excess mortality in patients with type 2 diabetes. Thus, despite advances in treatment, diabetes still carries an increased mortality in young adults, even in a country with a good economic and educational patient status and easy access to health care. © Springer-Verlag 2006.

  • 112. Westermark, Per
    et al.
    Andersson, Arne
    Westermark, Gunilla
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Is aggregate IAPP a cause of beta-cell failure in transplanted human pancreatic islets?2005In: Current Diabetes Reports, ISSN 1534-4827, E-ISSN 1539-0829, Vol. 5, no 3, p. 184-188Article in journal (Refereed)
    Abstract [en]

    Aggregation of the β-cell product islet amyloid polypeptide (IAPP) is believed to be an important event in the development of the β-cell lesion in type 2 diabetes. Preamyloidotic oligomeric IAPP assemblies exert toxic effects on β cells that die, leading to reduced β-cell mass. Normal human islets, when isolated and cultured in vitro or transplanted into nude mice, also develop amyloid deposits, which are associated with increased β-cell death and reduced β-cell mass. The possible role of IAPP aggregation and amyloid formation in loss of islet transplant function should be taken into consideration and studied further. Copyright © 2005 by Current Science Inc.

  • 113.
    Yin, Lan
    et al.
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, The Institute of Technology.
    Lundin, Björn
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, The Institute of Technology.
    Bertrand, Martine
    National Institute for Marine Science and Technology, France .
    Nurmi, Markus
    University of Turku.
    Solymosi, Katalin
    Eotvos Lorand University.
    Kangasjarvi, Saijaliisa
    University of Turku.
    Aro, Eva-Mari
    University of Turku.
    Schoefs, Benoit
    University of Bourgogne.
    Spetea Wiklund, Cornelia
    Linköping University, Department of Biomedicine and Surgery, Division of cell biology. Linköping University, The Institute of Technology.
    Role of Thylakoid ATP/ADP Carrier in Photoinhibition and Photoprotection of Photosystem II in Arabidopsis2010In: PLANT PHYSIOLOGY, ISSN 0032-0889, Vol. 153, no 2, p. 666-677Article in journal (Refereed)
    Abstract [en]

    The chloroplast thylakoid ATP/ADP carrier (TAAC) belongs to the mitochondrial carrier superfamily and supplies the thylakoid lumen with stromal ATP in exchange for ADP. Here, we investigate the physiological consequences of TAAC depletion in Arabidopsis (Arabidopsis thaliana). We show that the deficiency of TAAC in two T-DNA insertion lines does not modify the chloroplast ultrastructure, the relative amounts of photosynthetic proteins, the pigment composition, and the photosynthetic activity. Under growth light conditions, the mutants initially displayed similar shoot weight, but lower when reaching full development, and were less tolerant to high light conditions in comparison with the wild type. These observations prompted us to study in more detail the effects of TAAC depletion on photoinhibition and photoprotection of the photosystem II (PSII) complex. The steady-state phosphorylation levels of PSII proteins were not affected, but the degradation of the reaction center II D1 protein was blocked, and decreased amounts of CP43-less PSII monomers were detected in the mutants. Besides this, the mutant leaves displayed a transiently higher nonphotochemical quenching of chlorophyll fluorescence than the wild-type leaves, especially at low light. This may be attributed to the accumulation in the absence of TAAC of a higher electrochemical H+ gradient in the first minutes of illumination, which more efficiently activates photoprotective xanthophyll cycle-dependent and independent mechanisms. Based on these results, we propose that TAAC plays a critical role in the disassembly steps during PSII repair and in addition may balance the trans-thylakoid electrochemical H+ gradient storage.

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