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  • Agmon-Levin, Nancy, et al. (författare)
  • Antitreponemal Antibodies Leading to Autoantibody Production and Protection from Atherosclerosis in Kitavans from Papua New Guinea
  • 2009
  • Ingår i: Contemporary Challenges in Autoimmunity. - : Wiley-Blackwell. - 0077-8923. ; 1173, s. 675-682
  • Konferensbidrag (refereegranskat)abstract
    • The objective of our study was to determine the prevalence of anti-infectious agent antibodies and autoantibodies in a unique non-Westernized population from Kitava, Papua New Guinea (PNG), compared to Western populations. We matched 120 serum samples from Kitavans with 437 samples from four healthy control groups. Sera were tested for the presence of anti-infectious agent antibodies (treponema, toxoplsmosis, Epstein-Barr virus, cytomegalovirus, rubella) and autoantiobodies [anti-double-stranded (ds)DNA, anti-chromatin, anti-ribonucleoprotein (RNP), anti-SSB, anti-SSA, anti-Scl-70, anti-Smith, anti-centromer, anti-SmRNP, anti-Jo-1, and anti-ribosomal-P] using the Bio-Rad BioPlex 2200. Antitreponemal antibodies were detected in 87% of PNG sera versus 0-6% of controls (P < 0.0001). Anti-dsDNA antibodies were detected in 31% of PNG samples, which was significantly higher than in three of the control groups (<10%). The outstanding high rate of antitreponemal antibodies detected in Kitavans possibly represents prior yaws disease. A low prevalence of cardiovascular disease was previously documented in Kitavans and has been attributed, in addition to their diet, to the high prevalence of natural cardioprotective autoantibodies (the IgM-antiphosphorylcholine antibodies) in this population. Treponemal infection has been shown to induce the appearance of antiphosphorylcholine antibodies. These protective autoantibodies may cross-react with the pathogenic anti-dsDNA antibodies. Thus, it is suggested that infection with treponema is associated with the presence of protective as well as pathogenic autoantibodies.
  • Horak, Fay B, et al. (författare)
  • Vibrotactile biofeedback improves tandem gait in patients with unilateral vestibular loss.
  • 2009
  • Ingår i: Annals of the New York Academy of Sciences. - 1749-6632. ; 1164, s. 279-81
  • Tidskriftsartikel (refereegranskat)abstract
    • In a crossover design, subjects with unilateral vestibular loss (UVL) practiced tandem gait with eyes closed on two days, two weeks apart, with and without vibrotactile biofeedback (BF) applied to the lateral trunk. Results showed an immediate improvement in postural stability (reduction of lateral center-of-mass displacement, trunk tilt, and medial-lateral step width) that was significantly larger than effects of practice alone. However, BF did not increase the rate of improvement or retention of improved stability during gait.
  • Koch, Stefan, et al. (författare)
  • Dynamic regulation of epithelial cell fate and barrier function by intercellular junctions
  • 2009
  • Ingår i: Annals of the New York Academy of Sciences. - : Wiley-Blackwell Publishing Inc.. - 0077-8923 .- 1749-6632. ; 1165, s. 220-227
  • Tidskriftsartikel (refereegranskat)abstract
    • In the intestine, a single layer of epithelial cells effectively separates potentially harmful luminal content from the underlying tissue. The importance of an intact mucosal layer is highlighted by pathological disorders of the gut such as inflammatory bowel disease, in which disruption of the epithelial barrier leads to severe inflammation of the submucosal tissue compartments. Epithelial barrier function is provided by tightly regulated intercellular junctions, which consist of a plethora of membrane-associated and transmembrane proteins organized in discreet, spatially restricted complexes. Classically, these complexes are known to be dynamic seals for fluids and small molecules, as well as to provide mechanical strength by anchoring cell-cell contacts to the cytoskeleton. Rather than just acting as simple gates and adapters, however, junctional complexes themselves can relay extracellular stimuli to the epithelium and initiate cellular responses such as differentiation and apoptosis. In this review, we will highlight recent studies by our group and others which discuss how junctional proteins can promote outside-to-inside signaling and modulate epithelial cell fate. Unraveling the complex crosstalk between epithelial cells and their intercellular junctions is essential to understanding how epithelial barrier function is maintained in vivo and might provide new strategies for the treatment of inflammatory disorders of the intestine.
  • Gustafsson, Mika, et al. (författare)
  • Reverse Engineering of Gene Networks with LASSO and Nonlinear Basis Functions
  • 2009
  • Tidskriftsartikel (refereegranskat)abstract
    • The quest to determine cause from effect is often referred to as reverse engineering in the context of cellular networks. Here we propose and evaluate an algorithm for reverse engineering a gene regulatory network from time-series kind steady-state data. Our algorithmic pipeline, which is rather standard in its parts but not in its integrative composition, combines ordinary differential equations, parameter estimations by least angle regression, and cross-validation procedures for determining the in-degrees and selection of nonlinear transfer functions. The result of the algorithm is a complete directed net-work, in which each edge has been assigned a score front it bootstrap procedure. To evaluate the performance, we submitted the outcome of the algorithm to the reverse engineering assessment competition DREAM2, where we used the data corresponding to the InSillico1 and InSilico2 networks as input. Our algorithm outperformed all other algorithms when inferring one of the directed gene-to-gene networks.
  • Araç, Demet, et al. (författare)
  • Dissecting signaling and functions of adhesion G protein-coupled receptors
  • 2012
  • Ingår i: Annals of the New York Academy of Sciences. - 0077-8923 .- 1749-6632. ; 1276:1, s. 1-25
  • Tidskriftsartikel (refereegranskat)abstract
    • G protein-coupled receptors (GPCRs) comprise an expanded superfamily of receptors in the human genome. Adhesion class G protein-coupled receptors (adhesion-GPCRs) form the second largest class of GPCRs. Despite the abundance, size, molecular structure, and functions in facilitating cell and matrix contacts in a variety of organ systems, adhesion-GPCRs are by far the most poorly understood GPCR class. Adhesion-GPCRs possess a unique molecular structure, with extended N-termini containing various adhesion domains. In addition, many adhesion-GPCRs are autoproteolytically cleaved into an N-terminal fragment (NTF, NT, α-subunit) and C-terminal fragment (CTF, CT, β-subunit) at a conserved GPCR autoproteolysis-inducing (GAIN) domain that contains a GPCR proteolysis site (GPS). These two features distinguish adhesion-GPCRs from other GPCR classes. Though active research on adhesion-GPCRs in diverse areas, such as immunity, neuroscience, and development and tumor biology has been intensified in the recent years, the general biological and pharmacological properties of adhesion-GPCRs are not well known, and they have not yet been used for biomedical purposes. The "6th International Adhesion-GPCR Workshop," held at the Institute of Physiology of the University of Würzburg on September 6-8, 2012, assembled a majority of the investigators currently actively pursuing research on adhesion-GPCRs, including scientists from laboratories in Europe, the United States, and Asia. The meeting featured the nascent mechanistic understanding of the molecular events driving the signal transduction of adhesion-GPCRs, novel models to evaluate their functions, and evidence for their involvement in human disease.
  • Bark, C, et al. (författare)
  • SNAP-25 and gene-targeted mouse mutants
  • 2009
  • Ingår i: Annals of the New York Academy of Sciences. - 1749-6632. ; 1152, s. 145-153
  • Tidskriftsartikel (refereegranskat)
  • Bemark, Mats, 1967, et al. (författare)
  • Induction of gut IgA production through T cell-dependent and T cell-independent pathways.
  • 2012
  • Ingår i: Annals of the New York Academy of Sciences. - 1749-6632. ; 1247, s. 97-116
  • Tidskriftsartikel (refereegranskat)abstract
    • The gut immune system protects against mucosal pathogens, maintains a mutualistic relationship with the microbiota, and establishes tolerance against food antigens. This requires a balance between immune effector responses and induction of tolerance. Disturbances of this strictly regulated balance can lead to infections or the development inflammatory diseases and allergies. Production of secretory IgA is a unique effector function at mucosal surfaces, and basal mechanisms regulating IgA production have been the focus of much recent research. These investigations have aimed at understanding how long-term IgA-mediated mucosal immunity can best be achieved by oral or sublingual vaccination, or at analyzing the relationship between IgA production, the composition of the gut microbiota, and protection from allergies and autoimmunity. This research has lead to a better understanding of the IgA system; but at the same time seemingly conflicting data have been generated. Here, we discuss how gut IgA production is controlled, with special focus on how differences between T cell-dependent and T cell-independent IgA production may explain some of these discrepancies.
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