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  • 1.
    Ericsson, Maja
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Skog, Oskar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology. Uppsala Univ, Dept Immunol Genet & Pathol, Uppsala, Sweden..
    Presence of Human Herpesvirus 6B in the Pancreas of Subjects With and Without Type 1 Diabetes2017In: Pancreas, ISSN 0885-3177, E-ISSN 1536-4828, Vol. 46, no 10, p. 1341-1346Article in journal (Refereed)
    Abstract [en]

    Objectives: The aims of this study were to investigate the presence of human herpesvirus 6 (HHV6) A and B in human pancreata and to search for signs of active infection in this organ of subjects with and without type 1 diabetes (T1D). Methods: Pancreata from brain-dead organ donors with and without T1D were examined for the presence of HHV6 genomic sequences by polymerase chain reaction (PCR), transcripts by reverse transcriptase-PCR, and protein by immunohistochemistry. Quantitative PCR of isolated pancreatic islets and exocrine cell clusters was used to determine the intrapancreatic location of HHV6 DNA. Results: Human herpesvirus 6B genomic sequences were present in 1 of 2 donors who died of acute-onset T1D, 4 of 6 donors with long-standing T1D, and 9 of 12 nondiabetic donors. Higher copy numbers of HHV6B DNA were present in isolated islets than in exocrine tissue from the same donors. No signs of active HHV6 transcription were found. Human herpesvirus 6A was not present in any tested pancreas. Conclusions: The herein presented data demonstrate, for the first time, the presence of a latent HHV6B infection in the pancreas and islets of Langerhans. Whether this virus can contribute to disease in the pancreas remains to be determined.

  • 2.
    Thörnqvist, Per-Ove
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology. Uppsala Univ, Dept Neurosci, Biomed Ctr BMC, Physiol Unit, Box 593, SE-75124 Uppsala, Sweden.
    McCarrick, Sarah
    Karolinska Inst, Inst Environm Med, Biochem Toxicol Unit, Box 210, SE-17177 Stockholm, Sweden.
    Ericsson, Maja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology.
    Roman, Erika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Winberg, Svante
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology.
    Bold zebrafish (Danio rerio) express higher levels of delta opioid and dopamine D2 receptors in the brain compared to shy fish2019In: Behavioural Brain Research, ISSN 0166-4328, E-ISSN 1872-7549, Vol. 359, p. 927-934Article in journal (Refereed)
    Abstract [en]

    Individual variation in coping with environmental challenges is a well-known phenomenon across vertebrates, including teleost fish. Dopamine is the major transmitter in the brain reward networks, and important for motivational processes and stress coping. Functions of the endogenous opioid system are not well studied in teleosts. However, in mammals the activity in the brain reward networks is regulated by the endogenous opioid system. This study aimed at investigating if there was a correlation between risk-taking behavior and the expression of dopamine and opioid receptors in the zebrafish (Danio rerio) brain. Risk-taking behavior was assessed in a novel tank diving test, and the most extreme high risk taking, i.e. bold, and low risk taking, i.e. shy, fish were sampled for qPCR analysis of whole brain gene expression. The expression analysis showed a significantly higher expression of the dopamine D2 receptors (drd2a and drd2b) and the delta opioid receptor (DOR; oprd1b) in bold compared to shy fish. Besides reward and reinforcing properties, DORs are also involved in emotional responses. Dopamine D2 receptors are believed to be important for active stress coping in rodents, and taken together the results of the current study suggest similar functions in zebrafish. However, additional experiments are required to clarify how dopamine and opioid receptor activation affect behavior and stress coping in this species.

  • 3.
    Zhang, Hanqian
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Dermatology and Venereology.
    Ericsson, Maja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Dermatology and Venereology.
    Weström, Simone
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Dermatology and Venereology.
    Vahlquist, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Dermatology and Venereology.
    Virtanen, Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Dermatology and Venereology.
    Törmä, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Dermatology and Venereology.
    Patients with congenital ichthyosis and TGM1 mutations overexpress other ARCI genes in the skin: Part of a barrier repair response?2018In: Experimental dermatology, ISSN 0906-6705, E-ISSN 1600-0625Article in journal (Refereed)
    Abstract [en]

    Autosomal recessive congenital ichthyosis (ARCI) is a group of monogenic skin disorders caused by mutations in any of at least 12 different genes, many of which are involved in the epidermal synthesis of ω-O-acylceramides (acylCer). AcylCer are essential precursors of the corneocyte lipid envelope crosslinked by transglutaminase-1 (TGm-1), or a yet unidentified enzyme, for normal skin barrier formation. We hypothesized that inactivating TGM1 mutations will lead to a compensatory overexpression of the transcripts involved in skin barrier repair, including many other ARCI-causing genes. Using microarray we examined the global mRNA expression profile in skin biopsies from five ARCI-patients with TGM1 mutations and four healthy controls. There were a total of 599 significantly differentially expressed genes (adjusted P<0.05), out of which 272 showed more than 1.5 log2fold-change (FC) up- or down-regulation. Functional classification of the latter group of transcripts showed enrichment of mRNA encoding proteins mainly associated with biological pathways involved in keratinocyte differentiation and immune response. Moreover, the expression of seven out of twelve ARCI-causing genes were significantly increased (FC=0.98-2.05). Also, many of the genes involved in keratinocyte differentiation (cornified envelope formation) and immune response (anti-microbial peptides and proinflammatory cytokines) were upregulated. The results from the microarray analysis were also verified for selected genes at the mRNA level by qPCR and at the protein level by semi-quantitative immunofluorescence. The upregulation of these genes might reflect a compensatory induction of acylCer biosynthesis as a part of a global barrier repair response in the patient´s epidermis.

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