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  • 151.
    Espinosa, Alexander
    et al.
    Rheumatology Unit, Department of Medicine, CMM L8:04, Karolinska Institutet, SE-171 76 Stockholm, Sweden.
    Hennig, Janosch
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Molekylär Bioteknik. Linköpings universitet, Tekniska högskolan.
    Ambrosi, Aurélie
    Rheumatology Unit, Department of Medicine, CMM L8:04, Karolinska Institutet, SE-171 76 Stockholm, Sweden.
    Anandapadamanaban, Madhanagopal
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Sandberg Abelius, Martina
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Sheng, Yi
    Ontario Cancer Institute and Department of Medical Biophysics, University of Toronto, Canada.
    Nyberg, Filippa
    Department of Clinical Sciences at Danderyd Hospital, Karolinska Institute, Stockholm, Sweden.
    Arrowsmith, Cheryl H.
    Ontario Cancer Institute and Department of Medical Biophysics, University of Toronto, Canada.
    Sunnerhagen, Maria
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Molekylär Bioteknik. Linköpings universitet, Tekniska högskolan.
    Wahren-Herlenius, Marie
    Rheumatology Unit, Department of Medicine, CMM L8:04, Karolinska Institutet, SE-171 76 Stockholm, Sweden.
    Anti-Ro52 Autoantibodies from Patients with Sjögren's Syndrome Inhibit the Ro52 E3 Ligase Activity by Blocking the E3/E2 Interface2011Inngår i: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 286, nr 42, s. 36478-36491Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Ro52 (TRIM21) is an E3 ligase of the tripartite motif family that negatively regulates proinflammatory cytokine production by ubiquitinating transcription factors of the interferon regulatory factor family. Autoantibodies to Ro52 are present in patients with lupus and Sjögren's syndrome, but it is not known if these autoantibodies affect the function of Ro52. To address this question, the requirements for Ro52 E3 ligase activity were first analyzed in detail. Scanning a panel of E2 ubiquitin-conjugating enzymes, we found that UBE2D1–4 and UBE2E1–2 supported the E3 ligase activity of Ro52 and that the E3 ligase activity of Ro52 was dependent on its RING domain. We also found that the N-terminal extensions in the class III E2 enzymes affected their interaction with Ro52. Although the N-terminal extension in UBE2E3 made this E2 enzyme unable to function together with Ro52, the N-terminal extensions in UBE2E1 and UBE2E2 allowed for a functional interaction with Ro52. Anti-Ro52-positive patient sera and affinity-purified anti-RING domain autoantibodies inhibited the E3 activity of Ro52 in ubiquitination assays. Using NMR, limited proteolysis, ELISA, and Ro52 mutants, we mapped the interactions between Ro52, UBE2E1, and anti-Ro52 autoantibodies. We found that anti-Ro52 autoantibodies inhibited the E3 ligase activity of Ro52 by sterically blocking the E2/E3 interaction between Ro52 and UBE2E1. Our data suggest that anti-Ro52 autoantibodies binding the RING domain of Ro52 may be actively involved in the pathogenesis of rheumatic autoimmune disease by inhibiting Ro52-mediated ubiquitination.

    Fulltekst (pdf)
    fulltext
  • 152.
    Esteves, A.
    et al.
    Univ Nova Lisboa, Portugal.
    Nordgren, Johan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Tavares, C.
    Univ Nova Lisboa, Portugal.
    Fortes, F.
    DNSP, Angola.
    Dimbu, R.
    DNSP, Angola.
    Saraiva, N.
    DNSP, Angola.
    Istrate, C.
    Univ Nova Lisboa, Portugal.
    Genetic diversity of norovirus in children under 5 years of age with acute gastroenteritis from Angola2018Inngår i: Epidemiology and Infection, ISSN 0950-2688, E-ISSN 1469-4409, Vol. 146, nr 5, s. 551-557Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Norovirus (NoV) is a major cause of acute gastroenteritis (AGE). In this study, we investigated the genetic diversity of NoV strains identified in children under 5 years of age with AGE in four provinces of Angola. Faecal samples from 343 children were screened for NoV by an in house real-time PCR assay and genotyping was performed by partial capsid gene sequencing. NoV was detected in 17.4% (58/334) of the samples, with high detection rates in children amp;lt;6 months old (19%) and in children aged 12-24 months (23%). Genotype diversity was large, as demonstrated by the 11 identified genotypes. GII.4 was the predominant genotype (20% of all NoV-positive samples), followed by GII.6 (15%), GI.3 (12%), GII.7 (10%) and by other genotypes to a lesser extent. Two GII.4 variants, New Orleans 2009 and Sydney 2012, were detected and several genetic clusters were observed for genotypes GI.3, GII.6 and GII.7. The present study shows high detection rates and genetic diversity of circulating NoV genotypes in paediatric AGE samples from Angola. This information emphasises the importance of continuous assessment of NoV burden and evolution in the target population.

  • 153.
    Esteves, Aida
    et al.
    NOVA University of Lisbon, Portugal.
    Nordgren, Johan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Pereira, Joana
    NOVA University of Lisbon, Portugal.
    Fortes, Filomeno
    National Institute Public Heatlh, Angola.
    Dimbu, Rafael
    National Institute Public Heatlh, Angola.
    Saraiva, Nilton
    National Institute Public Heatlh, Angola.
    Mendes, Cristina
    NOVA University of Lisbon, Portugal.
    Istrate, Claudia
    NOVA University of Lisbon, Portugal.
    Molecular Epidemiology of Rotavirus in Four Provinces of Angola Before Vaccine Introduction2016Inngår i: Journal of Medical Virology, ISSN 0146-6615, E-ISSN 1096-9071, Vol. 88, nr 9, s. 1511-1520Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Angola is a sub-Saharan country in southern Africa highly affected by diarrhoeal disease with limited epidemiological data regarding etiologic agents. This study was performed during 2012-2013, prior to rotavirus vaccine introduction, with the objective to detect and characterize the rotavirus strains circulating in four provinces of the country: Huambo, Luanda, Zaire, and Cabinda. A high rotavirus detection rate (35%, 117/334) was observed. G1 was the most common G-genotype (83.6%), whereas P[8] (50.9%) followed by P[6] (38.8%) were the most common P-types. G1P[8] was identified as the predominant combination (50%), followed by the unusual G1P[6] (29.3%). Strains such G2P[4], G8P[6], G9P[6], and G12P[6] were also found in lower frequencies (5.2-1.7%). The P[6] strains did not cluster in the phylogenetic trees according to their geographic origin or even the corresponding G-genotype, suggesting a limited number of recent introductions and extensive reassortment events. Our results represent the first report on rotavirus genotype profiles in Angola, showing a wide circulation of the unusual genotype G1P[6], and underline the importance of RV surveillance after the vaccine introduction. (C) 2016 Wiley Periodicals, Inc.

  • 154.
    Everett, Jake
    et al.
    Department of Surgery, Texas Tech University Health Sciences Center, MS8312, 3601 4th Street, Lubbock, USA.
    Gabrilska, Rebecca
    Department of Surgery, Texas Tech University Health Sciences Center, MS8312, 3601 4th Street, Lubbock, USA.
    Rumbaugh, Kendra P.
    Department of Surgery, Texas Tech University Health Sciences Center, MS8312, 3601 4th Street, Lubbock, USA.
    Vikström, Elena
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Assessing Pseudomonas aeruginosa Autoinducer Effects on Mammalian Epithelial Cells2018Inngår i: Quorum Sensing: Methods and Protocols / [ed] Livia LeoniGiordano Rampioni, Humana Press, 2018, Vol. 1673, s. 213-225Kapittel i bok, del av antologi (Fagfellevurdert)
    Abstract [en]

    The human mucosal environment in the gut is rich with interactions between microbiota and mammalian epithelia. Microbes such as the Gram-negative bacterium Pseudomonas aeruginosa may use quorum sensing to communicate with other microorganisms and mammalian cells to alter gene expression. Here, we present methodologies to evaluate the effects of P. aeruginosa N-(3-oxo-dodecanoyl)-L-homoserine lactone (3O-C12-HSL) on Caco-2 cell monolayers. First, we describe a method for assessing barrier function and permeability of epithelial cells when exposed to 3O-C12-HSL by measuring transepithelial electrical resistance (TER) and paracellular flow using fluorescently labeled dextran. Secondly, we detail methods to investigate the effect of 3O-C12-HSL on protein-protein interactions of epithelial junction proteins. Lastly, we will detail imaging techniques to visualize Caco-2 barrier disruption following exposure to 3O-C12-HSL through the use of confocal laser scanning microscopy (CLSM) and a super resolution technique, stimulated emission depletion (STED) microscopy, to achieve nanoscale visualization of Caco-2 monolayers.

  • 155. Bestill onlineKjøp publikasjonen >>
    Falkeborn, Tina
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Hälsouniversitetet.
    Nasal vaccination using novel mucosal adjuvants: with main focus on influenza A virus2015Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Influenza viruses have sporadically caused pandemics during the last century, with the most severe occurring in 1918 when the “Spanish flu”, an A/H1N1 influenza virus, passed around the globe killing about 20-100 million people. Today 250 000-500 000 deaths occur annually due to influenza virus or secondary infection after influenza, e.g. pneumonia. Influenza viruses cause severe infections in susceptible age groups like children and elderly and in individuals with impaired immune response due to other medical conditions. The best way to prevent an influenza epidemic is by vaccination. Since the 1950´s we have vaccines against seasonal flu, but vaccine efficacy is not 100 % and there is a need to develop better and more effective vaccines, especially for the risk groups. Since the virus enters the host through the nasal cavity, nasal vaccination is a good approach. By stimulating a mucosal immune response already in the nasal cavity, the goal with nasal vaccination is to stop the virus before it enters the host. Nasal vaccination also reduces the risk of transmission of blood-borne diseases, and is less painful and easier to administer, compared to injectable vaccines.

    In order to be able to use less immunogenic antigens, like split and subunit antigens, as nasal vaccine components, an adjuvant is needed to enhance the immune response. At the moment there is no licensed mucosal adjuvant for human use. Several studies are ongoing, but it is a complicated and long way to reach the market. In this thesis nasal vaccination with influenza antigen together with the mucosal adjuvant Endocine™ and other mucosal adjuvants has been evaluated. The Endocine™ adjuvant has been shown to be safe and well tolerated in clinical trials. Depending on the pathogen of interest, different approaches are necessary. For HIV, DNA-vaccination has been evaluated together with a plasmid encoding Salmonella typhimurium flagellin C and the mucosal adjuvant N3. The results found in paper I-IV show that by adding adjuvant to the antigen enhances the protective immune response towards the antigen. Enhanced systemic, mucosal and cell-mediated immunity were observed. Hopefully in the future these adjuvants evaluated in this thesis, will be used in vaccines for humans.

    Delarbeid
    1. Endocine™, N3OA and N3OASq; Three Mucosal Adjuvants That Enhance the Immune Response to Nasal Influenza Vaccination
    Åpne denne publikasjonen i ny fane eller vindu >>Endocine™, N3OA and N3OASq; Three Mucosal Adjuvants That Enhance the Immune Response to Nasal Influenza Vaccination
    Vise andre…
    2013 (engelsk)Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, nr 8Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Annual outbreaks of seasonal influenza are controlled or prevented through vaccination in many countries. The seasonal vaccines used are either inactivated, currently administered parenterally, or live-attenuated given intranasally. In this study three mucosal adjuvants were examined for the influence on the humoral (mucosal and systemic) and cellular influenza A-specific immune responses induced by a nasally administered vaccine. We investigated in detail how the anionic Endocine™ and the cationic adjuvants N3OA and N3OASq mixed with a split inactivated influenza vaccine induced influenza A-specific immune responses as compared to the vaccine alone after intranasal immunization. The study showed that nasal administration of a split virus vaccine together with Endocine™ or N3OA induced significantly higher humoral and cell-mediated immune responses than the non-adjuvanted vaccine. N3OASq only significantly increased the cell-mediated immune response. Furthermore, nasal administration of the influenza vaccine in combination with any of the adjuvants; Endocine™, N3OA or N3OASq, significantly enhanced the mucosal immunity against influenza HA protein. Thus the addition of these mucosal adjuvants leads to enhanced immunity in the most relevant tissues, the upper respiratory tract and the systemic circulation. Nasal influenza vaccination with an inactivated split vaccine can therefore provide an important mucosal immune response, which is often low or absent after traditional parenteral vaccination.

    sted, utgiver, år, opplag, sider
    Public Library of Science, 2013
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-97667 (URN)10.1371/journal.pone.0070527 (DOI)000323124000019 ()
    Merknad

    Funding Agencies|Eurocine Vaccines||Vinnova Research funds||Halsofonden||

    Tilgjengelig fra: 2013-09-19 Laget: 2013-09-19 Sist oppdatert: 2017-12-06
    2. DNA-Encoded Flagellin Activates Toll-Like Receptor 5 (TLR5), Nod-like Receptor Family CARD Domain-Containing Protein 4 (NRLC4), and Acts as an Epidermal, Systemic, and Mucosal-Adjuvant
    Åpne denne publikasjonen i ny fane eller vindu >>DNA-Encoded Flagellin Activates Toll-Like Receptor 5 (TLR5), Nod-like Receptor Family CARD Domain-Containing Protein 4 (NRLC4), and Acts as an Epidermal, Systemic, and Mucosal-Adjuvant
    Vise andre…
    2013 (engelsk)Inngår i: Vaccines, ISSN 2076-393X, Vol. 1, nr 4, s. 415-443Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Eliciting effective immune responses using non-living/replicating DNA vaccines is a significant challenge. We have previously shown that ballistic dermal plasmid DNA-encoded flagellin (FliC) promotes humoral as well as cellular immunity to co-delivered antigens. Here, we observe that a plasmid encoding secreted FliC (pFliC(-gly)) produces flagellin capable of activating two innate immune receptors known to detect flagellin; Toll-like Receptor 5 (TLR5) and Nod-like Receptor family CARD domain-containing protein 4 (NRLC4). To test the ability of pFliC(-gly) to act as an adjuvant we immunized mice with plasmid encoding secreted FliC (pFliC(-gly)) and plasmid encoding a model antigen (ovalbumin) by three different immunization routes representative of dermal, systemic, and mucosal tissues. By all three routes we observed increases in antigen-specific antibodies in serum as well as MHC Class I-dependent cellular immune responses when pFliC(-gly) adjuvant was added. Additionally, we were able to induce mucosal antibody responses and Class II-dependent cellular immune responses after mucosal vaccination with pFliC(-gly). Humoral immune responses elicited by heterologus prime-boost immunization with a plasmid encoding HIV-1 from gp160 followed by protein boosting could be enhanced by use of pFliC(-gly). We also observed enhancement of cross-clade reactive IgA as well as a broadening of B cell epitope reactivity. These observations indicate that plasmid-encoded secreted flagellin can activate multiple innate immune responses and function as an adjuvant to non-living/replicating DNA immunizations. Moreover, the capacity to elicit mucosal immune responses, in addition to dermal and systemic properties, demonstrates the potential of flagellin to be used with vaccines designed to be delivered by various routes.

    sted, utgiver, år, opplag, sider
    Basel, Switzerland: MDPI AG, 2013
    Emneord
    adaptive immunity; DNA adjuvant; flagellin; NLRC4; TLR5
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-99352 (URN)10.3390/vaccines1040415 (DOI)
    Tilgjengelig fra: 2013-10-16 Laget: 2013-10-16 Sist oppdatert: 2015-05-19bibliografisk kontrollert
    3. Comparison of the mucosal adjuvant Endocine™ with two well-known adjuvants: cholera toxin and alum
    Åpne denne publikasjonen i ny fane eller vindu >>Comparison of the mucosal adjuvant Endocine™ with two well-known adjuvants: cholera toxin and alum
    Vise andre…
    2015 (engelsk)Inngår i: Jacobs Journal of Vaccine and Vaccination, ISSN 2381-2664, Vol. 1, nr 1, artikkel-id 006Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    To enable efficient mucosal vaccination with split or subunit antigens, an adjuvant is often needed. To date, no mucosal adjuvants are approved for human use, however, there are a variety of mucosal adjuvants in development, including the liposome-based adjuvant Endocine™. The aim of this study was to evaluate split influenza antigens together with Endocine™ and in order to assess the potency of Endocine™, the induction of humoral immune responses were compared to those following influenza vaccination with cholera toxin (CT) or aluminum salt (alum). We show that Endocine™ significantly enhances influenza-specific immune responses in intranasally immunized mice compared to nonadjuvanted vaccine. Furthermore, vaccines adjuvanted with Endocine™ evoked comparable serum IgG and virus neutralizing (VN) antibody titers as nasal vaccines adjuvanted with CT. Compared to parenteral vaccination with alum, Endocine™ triggered significantly higher mucosal and serum IgA titers, and similar VN titers. Taken together, these results support further development of Endocine™ as a mucosal adjuvant and as part of a nasal influenza vaccine candidate.

    sted, utgiver, år, opplag, sider
    Jacobs Publishers, 2015
    Emneord
    Mucosal adjuvant; nasal immunization; vaccine; Endocine; influenza; neutralizing antibodies
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-117979 (URN)
    Tilgjengelig fra: 2015-05-19 Laget: 2015-05-19 Sist oppdatert: 2018-01-11bibliografisk kontrollert
    4. The mucosal adjuvant 1 Endocine™ increases immune responses to influenza antigen in aged mice
    Åpne denne publikasjonen i ny fane eller vindu >>The mucosal adjuvant 1 Endocine™ increases immune responses to influenza antigen in aged mice
    (engelsk)Manuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    More effective influenza vaccines for the elderly population is needed. The vaccines used today are less effective in elderly compared to in adults. It is more difficult to stimulate a protective immune response in elderly due to immunosenescence. Elderly people have a decline in both humoral and cell mediated immunity, which make them more susceptible to viral infections. The aim of this study was to evaluate the mucosal adjuvant Endocine™ together with split influenza antigen in different ages of BALB/c mice (15, 20 and 25 months old). The results from this study show that a nasal influenza vaccine  formulated with Endocine™ enhanced both systemic and mucosal immune responses compared to an unadjuvanted vaccine delivered subcutaneously or intra nasal in aged mice. However, in the 25 months old mice only a very modest immune response was detected. Although the influenza-specific immune responses in aged mice were not induced to the same levels as achieved in young mice, the results show that nasal vaccine formulated with Endocine™ could provide benefits for the elderly.

    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-117980 (URN)
    Tilgjengelig fra: 2015-05-19 Laget: 2015-05-19 Sist oppdatert: 2018-01-11bibliografisk kontrollert
    Fulltekst (pdf)
    fulltext
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    presentationsbild
  • 156.
    Falkeborn, Tina
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Hälsouniversitetet.
    Asahara, Naomi
    Advanced Medical Research Laboratory, Mitsubishi Tanabe Pharma Corporation, Japan.
    Hayashi, Masayuki
    Advanced Medical Research Laboratory, Mitsubishi Tanabe Pharma Corporation, Japan.
    Arai, Masaaki
    Advanced Medical Research Laboratory, Mitsubishi Tanabe Pharma Corporation, Japan.
    Hinkula, Jorma
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Hälsouniversitetet.
    Maltais, Anna-Karin
    Eurocine Vaccines AB, Karolinska Institutet Science Park, Solna, Sweden.
    Comparison of the mucosal adjuvant Endocine™ with two well-known adjuvants: cholera toxin and alum2015Inngår i: Jacobs Journal of Vaccine and Vaccination, ISSN 2381-2664, Vol. 1, nr 1, artikkel-id 006Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    To enable efficient mucosal vaccination with split or subunit antigens, an adjuvant is often needed. To date, no mucosal adjuvants are approved for human use, however, there are a variety of mucosal adjuvants in development, including the liposome-based adjuvant Endocine™. The aim of this study was to evaluate split influenza antigens together with Endocine™ and in order to assess the potency of Endocine™, the induction of humoral immune responses were compared to those following influenza vaccination with cholera toxin (CT) or aluminum salt (alum). We show that Endocine™ significantly enhances influenza-specific immune responses in intranasally immunized mice compared to nonadjuvanted vaccine. Furthermore, vaccines adjuvanted with Endocine™ evoked comparable serum IgG and virus neutralizing (VN) antibody titers as nasal vaccines adjuvanted with CT. Compared to parenteral vaccination with alum, Endocine™ triggered significantly higher mucosal and serum IgA titers, and similar VN titers. Taken together, these results support further development of Endocine™ as a mucosal adjuvant and as part of a nasal influenza vaccine candidate.

    Fulltekst (pdf)
    fulltext
  • 157.
    Falkeborn, Tina
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Hälsouniversitetet.
    Brave, Andreas
    Swedish Institute Communicable Disease Control SMI, Sweden.
    Larsson, Marie
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Hälsouniversitetet.
    Åkerlind, Britt
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk mikrobiologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk mikrobiologi.
    Schroder, Ulf
    Eurocine Vaccines AB, Sweden.
    Hinkula, Jorma
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Hälsouniversitetet.
    Endocine™, N3OA and N3OASq; Three Mucosal Adjuvants That Enhance the Immune Response to Nasal Influenza Vaccination2013Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, nr 8Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Annual outbreaks of seasonal influenza are controlled or prevented through vaccination in many countries. The seasonal vaccines used are either inactivated, currently administered parenterally, or live-attenuated given intranasally. In this study three mucosal adjuvants were examined for the influence on the humoral (mucosal and systemic) and cellular influenza A-specific immune responses induced by a nasally administered vaccine. We investigated in detail how the anionic Endocine™ and the cationic adjuvants N3OA and N3OASq mixed with a split inactivated influenza vaccine induced influenza A-specific immune responses as compared to the vaccine alone after intranasal immunization. The study showed that nasal administration of a split virus vaccine together with Endocine™ or N3OA induced significantly higher humoral and cell-mediated immune responses than the non-adjuvanted vaccine. N3OASq only significantly increased the cell-mediated immune response. Furthermore, nasal administration of the influenza vaccine in combination with any of the adjuvants; Endocine™, N3OA or N3OASq, significantly enhanced the mucosal immunity against influenza HA protein. Thus the addition of these mucosal adjuvants leads to enhanced immunity in the most relevant tissues, the upper respiratory tract and the systemic circulation. Nasal influenza vaccination with an inactivated split vaccine can therefore provide an important mucosal immune response, which is often low or absent after traditional parenteral vaccination.

    Fulltekst (pdf)
    fulltext
  • 158.
    Falkeborn, Tina
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Hälsouniversitetet.
    Hinkula, Jorma
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Hälsouniversitetet.
    Lindberg, Alf
    Eurocine Vaccines AB, Karolinska Institutet Science Park, Solna, Sweden.
    Maltais, Anna-Karin
    Eurocine Vaccines AB, Karolinska Institutet Science Park, Solna, Sweden.
    The mucosal adjuvant 1 Endocine™ increases immune responses to influenza antigen in aged miceManuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    More effective influenza vaccines for the elderly population is needed. The vaccines used today are less effective in elderly compared to in adults. It is more difficult to stimulate a protective immune response in elderly due to immunosenescence. Elderly people have a decline in both humoral and cell mediated immunity, which make them more susceptible to viral infections. The aim of this study was to evaluate the mucosal adjuvant Endocine™ together with split influenza antigen in different ages of BALB/c mice (15, 20 and 25 months old). The results from this study show that a nasal influenza vaccine  formulated with Endocine™ enhanced both systemic and mucosal immune responses compared to an unadjuvanted vaccine delivered subcutaneously or intra nasal in aged mice. However, in the 25 months old mice only a very modest immune response was detected. Although the influenza-specific immune responses in aged mice were not induced to the same levels as achieved in young mice, the results show that nasal vaccine formulated with Endocine™ could provide benefits for the elderly.

  • 159.
    Falkeborn, Tina
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Hinkula, Jorma
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Olliver, Marie
    Karolinska Institute, Sweden.
    Lindberg, Alf
    Karolinska Institute, Sweden.
    Maltais, Anna-Karin
    Karolinska Institute, Sweden.
    The intranasal adjuvant Endocine((TM)) enhances both systemic and mucosal immune responses in aged mice immunized with influenza antigen2017Inngår i: Virology Journal, ISSN 1743-422X, E-ISSN 1743-422X, Vol. 14, artikkel-id 44Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Despite availability of annual influenza vaccines, influenza causes significant morbidity and mortality in the elderly. This is at least in part a result of immunosenescence; the age-dependent decrease in immunological competence that results in greater susceptibility to infections and reduced responses to vaccination. To improve protective immune responses in this age group, new vaccines strategies, such as the use of adjuvants, are needed. Here, we evaluated the mucosal vaccine adjuvant Endocine(TM), formulated with split influenza antigen and administered intranasally in aged (20-month old) mice. Humoral immune responses were assessed and compared to unadjuvanted intranasal and subcutaneous vaccines. We show that formulation with Endocine(TM) significantly enhances hemagglutination inhibition (HI) titers, as well as serum IgG and mucosal IgA antibody titers, compared to both types of unadjuvanted vaccines. Thus, our results indicate that intranasal vaccination with Endocine(TM) is a possible approach for the development of mucosal influenza vaccines for the elderly.

    Fulltekst (pdf)
    fulltext
  • 160.
    Faresjö, Åshild
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten.
    Jullander, Miriam
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten.
    Götmalm, Sara
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten.
    Theodorsson, Elvar
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    Higher perceived stress and poorer health reflected in elevated cortisol concentrtions measured in extracts of hair from middle-aged healthy women2014Inngår i: BMC Psychology, ISSN 2050-7283, Vol. 2, nr 30, s. 1-9Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background

    The prevalence of mental strain and stress has increased in modern societies, resulting in increased public health problems. Stress can be measured either by biomarkers or by self-reports. A new biomarker that measures long-term biological stress is cortisol measured in timed hair extracts. Hair grows at approximately 1 cm per month, and retrospectively reflects average stress levels. However, the plausible relationship between perceived stress and self-reported health and this novel biomarker is yet not firmly established. The objective of this study was to investigate the possible relationship between perceived stress, self-reported health, and cortisol in hair extracts in healthy middle-aged women from two different occupations.

    Method

    A cross-sectional study was conducted in 112 middle-aged women working as nurses or librarians in a county in southeast Sweden. The women were invited to fill in a questionnaire covering stress, health, and life situation. The questionnaire included questions on health and disease symptoms, the Perceived Stress Scale (PSS), and the Hospital Anxiety and Depression (HAD) scale. A piece of hair was cut from the vertex posterior area of the head an analysed by a competitive radioimmunoassay method.

    Results

    Middle-aged women who reported high perceived stress (p = 0.031) or lower health (p = 0.029), or had signs of depressiveness (p = 0.016) had significantly higher cortisol concentrations adjusted for age. There were no significant differences in cortisol in hair concentrations or perceived stress between nurses and librarians. Two women with extremely high cortisol concentrations were considered as outliers, but during the interview at follow-up they reported experiences of serious life events in their work or social life during the retrospective time of the sample taken for cortisol measurement.

    Conclusions

    Higher cortisol concentrations measured in the hair of healthy and working middle-aged women were associated with higher perceived stress and generally poorer health and with depressiveness. These findings lend support to the general applicability of cortisol measured in hair extracts as a biomarker in population-based epidemiological studies.

    Fulltekst (pdf)
    fulltext
  • 161.
    Faxälv, Lars
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk kemi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk kemi.
    Boknäs, Niklas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Hälsouniversitetet.
    Lindahl, Tomas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk kemi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk kemi.
    PAR1, PAR4 and GPIB form functional interdependent units in a receptor complex mediating platelet activation by thrombin in JOURNAL OF THROMBOSIS AND HAEMOSTASIS, vol 9, issue SI, pp 11-112011Inngår i: JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Wiley-Blackwell , 2011, Vol. 9, nr SI, s. 11-11Konferansepaper (Fagfellevurdert)
    Abstract [en]

    n/a

  • 162.
    Faxälv, Lars
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk kemi.
    Boknäs, Niklas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Hälsouniversitetet.
    Ström, Jakob
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk kemi. Linköpings universitet, Hälsouniversitetet.
    Tengvall, Pentti
    University of Gothenburg, Gothenburg, Sweden .
    Theodorsson, Elvar
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Hälsouniversitetet. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    Ramström, Sofia
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Hälsouniversitetet.
    Lindahl, Tomas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk kemi.
    Putting polyphosphates to the test: evidence against platelet-induced activation of factor XII2013Inngår i: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 122, nr 23, s. 3818-3824Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The recent claim that stimulated platelets activate the intrinsic pathway of coagulation by the release of polyphosphates has been considered a breakthrough in hemostasis research. In little more than 3 years, the original publication by Muller et al has been cited greater than100 times. However, none of the citing articles has sought to independently validate this potentially paradigm-shifting concept. To this end, we performed extensive experimentation in vitro and in vivo in an attempt to verify the claim that factor XII (FXII) is primarily activated by stimulated platelets. In contrast to the original assertion, platelet-derived polyphosphates were found to be weak activators of FXII, with a FXIIa-generating activity of less than10% compared with equivalent concentrations of kaolin. Using different coagulation assays, it was shown that platelet contribution to whole blood coagulation was unrelated to the generation of activated FXII in vitro. Additionally, key results used to verify the hypothesis in the original study in vivo were found to be irreproducible. We conclude that platelet-derived polyphosphates are not physiologically relevant activators of FXII.

  • 163.
    Faxälv, Lars
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk kemi.
    Bolin, Maria
    Linköpings universitet, Institutionen för teknik och naturvetenskap. Linköpings universitet, Tekniska högskolan.
    Jager, Edwin
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biosensorer och bioelektronik. Linköpings universitet, Tekniska högskolan. Linköpings universitet, Institutionen för teknik och naturvetenskap, Fysik och elektroteknik. Linköpings universitet, Tekniska fakulteten.
    Lindahl, Tomas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk kemi.
    Berggren, Magnus
    Linköpings universitet, Institutionen för teknik och naturvetenskap, Fysik och elektroteknik. Linköpings universitet, Tekniska högskolan.
    Electronic control of platelet adhesion using conducting polymer microarrays2014Inngår i: Lab on a Chip, ISSN 1473-0197, E-ISSN 1473-0189, Vol. 14, nr 16, s. 3043-3049Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We hereby report a method to fabricate addressable micropatterns of e-surfaces based on the conducting polymer poly(3,4-ethylenedioxythiophene) doped with the anion tosylate (PEDOT:Tos) to gain dynamic control over the spatial distribution of platelets in vitro. With thin film processing and microfabrication techniques, patterns down to 10 mu m were produced to enable active regulation of platelet adhesion at high spatial resolution. Upon electronic addressing, both reduced and oxidized surfaces were created within the same device. This surface modulation dictates the conformation and/or orientation, rather than the concentration, of surface proteins, thus indirectly regulating the adhesion of platelets. The reduced electrode supported platelet adhesion, whereas the oxidized counterpart inhibited adhesion. PEDOT:Tos electrode fabrication is compatible with most of the classical patterning techniques used in printing as well as in the electronics industry. The first types of tools promise ultra-low-cost production of low-resolution (greater than30 mu m) electrode patterns that may combine with traditional substrates and dishes used in a classical analysis setup. Platelets play a pronounced role in cardiovascular diseases and have become an important drug target in order to prevent thrombosis. This clinical path has in turn generated a need for platelet function tests to monitor and assess platelet drug efficacy. The spatial control of platelet adherence presented here could prove valuable for blood cell separation or biosensor microarrays, e.g. in diagnostic applications where platelet function is evaluated.

  • 164.
    Fernius, Josefin
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Starkenberg, Annika
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Pokrzywa, Malgorzata
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Utvecklingsbiologi. Linköpings universitet, Medicinska fakulteten. Airopt Sp Zoo, Poland.
    Thor, Stefan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Human TTBK1, TTBK2 and MARK1 kinase toxicity in Drosophila melanogaster is exacerbated by co-expression of human Tau2017Inngår i: BIOLOGY OPEN, ISSN 2046-6390, Vol. 6, nr 7, s. 1013-1023Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Tau protein is involved in numerous human neurodegenerative diseases, and Tau hyper-phosphorylation has been linked to Tau aggregation and toxicity. Previous studies have addressed toxicity and phospho-biology of human Tau (hTau) in Drosophila melanogaster. However, hTau transgenes have most often been randomly inserted in the genome, thus making it difficult to compare between different hTau isoforms and phospho-mutants. In addition, many studies have expressed hTau also in mitotic cells, causing nonphysiological toxic effects. Here, we overcome these confounds by integrating UAS-hTau isoform transgenes into specific genomic loci, and express hTau post-mitotically in the Drosophila nervous system. Lifespan and locomotor analyses show that all six of the hTau isoforms elicit similar toxicity in flies, although hTau(2N3R) showed somewhat elevated toxicity. To determine if Tau phosphorylation is responsible for toxicity, we analyzed the effects of co-expressing hTau isoforms together with Tau-kinases, focusing on TTBK1, TTBK2 and MARK1. We observed toxicity when expressing each of the three kinases alone, or in combination. Kinase toxicity was enhanced by hTau co-expression, with strongest co-toxicity for TTBK1. Mutagenesis and phosphorylation analysis indicates that hTau-MARK1 combinatorial toxicity may be due to direct phosphorylation of hTau, while hTau-TTBK1/2 combinatorial toxicity may result from independent toxicity mechanisms.

    Fulltekst (pdf)
    fulltext
  • 165.
    Fernius, Josefin
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Starkenberg, Annika
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Thor, Stefan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Bar-coding neurodegeneration: identifying subcellular effects of human neurodegenerative disease proteins using Drosophila leg neurons2017Inngår i: Disease Models and Mechanisms, ISSN 1754-8403, E-ISSN 1754-8411, Vol. 10, nr 8, s. 1027-1038Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Genetic, biochemical and histological studies have identified a number of different proteins as key drivers of human neurodegenerative diseases. Although different proteins are typically involved in different diseases, there is also considerable overlap. Addressing disease protein dysfunction in an in vivo neuronal context is often time consuming and requires labor-intensive analysis of transgenic models. To facilitate the rapid, cellular analysis of disease protein dysfunction, we have developed a fruit fly (Drosophila melanogaster) adult leg neuron assay. We tested the robustness of 41 transgenic fluorescent reporters and identified a number that were readily detected in the legs and could report on different cellular events. To test these reporters, we expressed a number of human proteins involved in neurodegenerative disease, in both their mutated and wild-type versions, to address the effects on reporter expression and localization. We observed strikingly different effects of the different disease proteins upon the various reporters with, for example, A beta(1-42) being highly neurotoxic, tau, parkin and HTT128Q affecting mitochondrial distribution, integrity or both, and A beta(1-42), tau, HTT128Q and ATX1(82Q) affecting the F-actin network. This study provides proof of concept for using the Drosophila adult leg for inexpensive and rapid analysis of cellular effects of neurodegenerative disease proteins in mature neurons.

    Fulltekst (pdf)
    fulltext
  • 166.
    Fleenor, Courtney J.
    et al.
    Natl Jewish Hlth, CO 80206 USA; Univ Colorado, CO 80045 USA; Globeimmune Inc, CO USA.
    Arends, Tessa
    Univ Colorado, CO 80045 USA.
    Lei, Hong
    Natl Jewish Hlth, CO 80206 USA; Univ Colorado, CO 80045 USA.
    Åhsberg, Josefine
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Okuyama, Kazuki
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Kuruvilla, Jacob
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Cristobal, Susana
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Rabe, Jennifer L.
    Univ Colorado, CO 80045 USA.
    Pandey, Ahwan
    Univ Colorado, CO USA; Univ Colorado, CO USA.
    Danhorn, Thomas
    Natl Jewish Hlth, CO USA.
    Straign, Desiree
    Natl Jewish Hlth, CO 80206 USA.
    Espinosa, Joaquin M.
    Univ Colorado, CO USA; Univ Colorado, CO USA.
    Warming, Soren
    Genentech Inc, CA 94080 USA.
    Pietras, Eric M.
    Univ Colorado, CO USA.
    Sigvardsson, Mikael
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Hagman, James R.
    Natl Jewish Hlth, CO 80206 USA; Univ Colorado, CO 80045 USA; Univ Colorado, CO 80045 USA.
    Zinc Finger Protein 521 Regulates Early Hematopoiesis through Cell-Extrinsic Mechanisms in the Bone Marrow Microenvironment2018Inngår i: Molecular and Cellular Biology, ISSN 0270-7306, E-ISSN 1098-5549, Vol. 38, nr 17, artikkel-id UNSP e00603-17Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Zinc finger protein 521 (ZFP521), a DNA-binding protein containing 30 Kruppel-like zinc fingers, has been implicated in the differentiation of multiple cell types, including hematopoietic stem and progenitor cells (HSPC) and B lymphocytes. Here, we report a novel role for ZFP521 in regulating the earliest stages of hematopoiesis and lymphoid cell development via a cell-extrinsic mechanism. Mice with inactivated Zfp521 genes (Zfp521(-/-)) possess reduced frequencies and numbers of hematopoietic stem and progenitor cells, common lymphoid progenitors, and B and T cell precursors. Notably, ZFP521 deficiency changes bone marrow microenvironment cytokine levels and gene expression within resident HSPC, consistent with a skewing of hematopoiesis away from lymphopoiesis. These results advance our understanding of ZFP521s role in normal hematopoiesis, justifying further research to assess its potential as a target for cancer therapies.

    Fulltekst (pdf)
    fulltext
  • 167.
    Flodin, Ulf
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Arbets- och miljömedicin.
    Paues, Jakob
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Infektionskliniken i Östergötland.
    Åkerlind, Britt
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för verksamhetsstöd och utveckling, Smittskydd Vårdhygien.
    Leanderson, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Arbets- och miljömedicin.
    Sjögren, Bengt
    Karolinska Institutet, Arbetsmiljötoxikologi, Institutet för miljömedicin Stockholm, Sweden Institutet för miljömedicin, Karolinska Institutet - Arbetsmiljötoxikologi Stockholm, Sweden.
    Svetsare – en riskgrupp för septisk pneumoni [Welders - a risk group for septic pneumonia]: Vaccination mot pneumokocker kan vara motiverat för yrkesgruppen2017Inngår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 114, nr 6Artikkel i tidsskrift (Fagfellevurdert)
  • 168. Foberg, U
    et al.
    Frydén, Aril
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Infektionsmedicin. Linköpings universitet, Hälsouniversitetet.
    Isaksson, Barbro
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Hälsouniversitetet.
    Jahrling, P
    Johnson, A
    McKee, K
    Niklasson, B
    Normann, Bengt
    Linköpings universitet, Institutionen för klinisk och experimentell medicin.
    Peters, C
    Bengtsson, M
    Viral haemorrhagic fever in Sweden: experiences from management of a case.1991Inngår i: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 23, nr 2, s. 143-151Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The first recognized case in Scandinavia with potential man to man transmission of viral haemorrhagic fever occurred in Linköping, Sweden, in January 1990. Following a visit to Kenya a 21-year-old male student suffered a very severe illness including extremely prolonged high grade fever, rash, disseminated intravascular coagulation with thrombocytopenia and severe bleedings. This necessitated one month of intensive care support including respirator treatment. The patient was discharged after 2 1/2 months in good condition, with a partial femoral nerve paresis. About 100 medical personnel were exposed to aerosol or blood before a strict containment regimen was established. No secondary cases occurred.

  • 169.
    Fomsgaard, Anders
    et al.
    University of Southern Denmark, Denmark .
    Fertner, Mette E
    Statens Serum Institute, Denmark .
    Essbauer, Sandra
    Institute Mikrobiol Bundeswehr, Germany .
    Nielsen, Alex Y
    Statens Serum Institute, Denmark .
    Frey, Stefan
    Institute Mikrobiol Bundeswehr, Germany .
    Lindblom, Pontus
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Hälsouniversitetet.
    Lindgren, Per-Eric
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Hälsouniversitetet.
    Bodker, Rene
    Technical University of Denmark, Denmark .
    Weidmann, Manfred
    University of Medical Gottingen, Germany .
    Dobler, Gerhard
    Institute Mikrobiol Bundeswehr, Germany .
    Letter: Tick-borne Encephalitis Virus, Zealand, Denmark, 20112013Inngår i: Emerging Infectious Diseases, ISSN 1080-6040, E-ISSN 1080-6059, Vol. 19, nr 7, s. 1171-1173Artikkel i tidsskrift (Annet vitenskapelig)
    Abstract [en]

    n/a

  • 170.
    Fransen, Jian
    et al.
    Uppsala University, Sweden.
    Huss, Fredrik R. M.
    Uppsala University, Sweden; University of Uppsala Hospital, Sweden.
    Nilsson, Lennart E
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Rydell, Ulf
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Sjöberg, Folke
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Hand- och plastikkirurgiska kliniken US.
    Hanberger, Håkan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Infektionskliniken i Östergötland.
    Surveillance of antibiotic susceptibility in a Swedish Burn Center 1994-20122016Inngår i: Burns, ISSN 0305-4179, E-ISSN 1879-1409, Vol. 42, nr 6, s. 1295-1303Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Patients with burn trauma are at risk for infections caused by antibiotic resistant bacteria (ABR) with subsequent increase in morbidity and mortality. As part of the Swedish strategic program against antibiotic resistance in intensive care (ICU-Strama), we have surveyed the distribution of species and ABR in isolates from patients admitted to a Swedish burn center at Linkoping University Hospital from 1994 through 2012. In an international comparison Strama has been successful in reducing the antibiotic consumption among animals and humans in primary care. The aim of this study was to investigate the antibiotic consumption pressure and resistance rates in a Swedish burn unit. Methods: Microbiology data, total body surface area (TBSA), patient days, and mortality were collected from a hospital database for all patients admitted to the Burn Center at the University Hospital of Linkoping from April 1994 through December 2012. Results: A total of 1570 patients were admitted with a mean annual admission rate of 83 patients (range: 57-152). 15,006 microbiology cultures (approximately 10 per patient) were collected during the study period and of these 4531 were positive (approximately 3 per patient). The annual mean total body surface area (TBSA) was 13.4% (range 9.5-18.5) with an annual mortality rate of 5.4% (range 1-8%). The MRSA incidence was 1.7% (15/866) which corresponds to an MRSA incidence of 0.34/1000 admission days (TAD). Corresponding figures were for Escherichia coli resistant to 3rd generation cephalosporins (ESBL phenotype) 8% (13/170) and 0.3/TAD, Klebsiella spp. ESBL phenotype 5% (6/134) and 0.14/TAD, carbapenem resistant Pseudomonas aeruginosa 26% (56/209) and 1.28/TAD, and carbapenem resistant Acinetobacter spp. 3% (2/64) and 0.04/TAD. Conclusions: Our results show a sustained low risk for MRSA and high, although not increasing, risk for carbapenem resistant P. aeruginosa. (C) 2016 Elsevier Ltd and ISBI. All rights reserved.

  • 171. Fransson, G
    et al.
    Edström, M
    Nilsson, L E
    Walther, Sten
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Thorax-kärlkliniken i Östergötland.
    Hanberger, Håkan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Infektionskliniken i Östergötland.
    High mortaility in bacteraemia and candidaemia in critically ill patients - report from Swedish Intensive Care Registry2012Inngår i: Proceedings of the 22nd European Congress of Clinical Microbiology and Infectious Diseases, 2012, s. P1060-Konferansepaper (Annet vitenskapelig)
    Abstract [en]

    Objective: Increasing prevalence of  bacteremia and candidemia with significant resistance to antimicrobial agents is an increasing concern among ICU patients. The objective of this report from Swedish Registry of Intensive care (SIR) was to study the frequency and cause of culture verified sepsis in critically ill patients and to analyse mortality in sepsis caused by Candida albicans, Candida non albicans and bacteria.

    Methods: Setting: Starting 10 years ago an increasing number of ICU:s in Sweden reports each episode of care (EOC) to the Swedish Intensive care Registry (SIR).  Mortality is followed weekly for all patients by link to the Swedish population registry. A specific routine for collection of microbial data directly from the laboratories connected individually to each EOC has been tested and implemented for laboratories covering 1/3 of the Swedish population. Participants: 47 ICU:s reported 1540 EOC:s during the period January 2005 to November 2011, with a diagnosis of sepsis (ICD10: A419, R572 or R651) and a positive blood culture within 14 days before admission until discharge.  For patients with more than one EOC was only the last EOC included which reduced the number of observations included in mortality calculations to 1416.

    Variables: Primary outcome was 30 day mortality calculated from admission to ICU.

    Results: 1 416 patients met inclusion criteria and were included in the analysis. The most common causes of sepsis were:  E. coli (24 %) followed by Coagulase Negative Staphylococci (CoNS) (21 %), Streptococcus spp (19 %), S. aureus (14 %), Klebsiella spp (8 %) and Candida spp (6 %) [Candida albicans 4 % and Candida non albicans 2 %]. The 30-days crude mortality was 34% for patients with sepsis caused by S. aureus. Correspondingly 30 days mortality was for  Candida non albicans 34%, Candida albicans 31%,  Klebsiella spp 26 % , CoNS 25 %, E. coli 22 %. Distribution of species in blood cultures from the 87 patients with candidemia were: C. albicans 62, C. glabrata 11, C. krusei 1, C. tropicalis 4, C. other 4, C. non specified 9.

    Conclusion: The highest (>30%) crude mortality in critically ill patients with sepsis was seen in patients with S. aureus and Candida infections. Further analysis of independent risk factors for mortality in sepsis caused by different pathogens are warranted.

  • 172.
    Fridlund, Jimmy
    et al.
    Kalmar County Hospital, Sweden.
    Woksepp, Hanna
    Kalmar County Hospital, Sweden; Linnaeus University, Sweden.
    Schön, Thomas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten. Kalmar County Hospital, Sweden; Linnaeus University, Sweden.
    A microbiological method for determining serum levels of broad spectrum beta-lactam antibiotics in critically ill patients2016Inngår i: Journal of Microbiological Methods, ISSN 0167-7012, E-ISSN 1872-8359, Vol. 129, s. 23-27Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Recent studies show that suboptimal blood levels of beta-lactam antibiotics are present in intensive care unit (ICU) patients. A common reference method for assessing drug concentrations is liquid chromatography coupled with mass-spectrometry (LC-MS) which is highly accurate but rarely available outside reference centres. Thus, our aim was to develop a microbiological method for monitoring beta-lactam antibiotic serum levels which could be used at any hospital with a microbiological laboratory. Methods: The method was developed as a 96-well broth microdilution format to assess the concentrations of cefotaxime (CTX), meropenem (MER), and piperacillin (PIP). Patient serum containing antibiotics were diluted in suspensions of bacteria with known minimal inhibitory concentrations (MICs). Serum antibiotic concentrations were calculated by dividing the MIC with the dilution factor at which the serum inhibited growth of the bacterial suspension. Serum (n = 88) from ICU patients at four hospitals in south-east Sweden were analysed and compared to LC-MS analysis. Results: The overall accuracy and precision for spiked samples and patient samples was within the pre-set target of +/- 20.0% for all drugs. There was a significant correlation between the microbiological assay and LC-MS for the patient samples (CTX: r = 0.86, n = 31; MER: r = 0.96, n = 11; PIP: r = 0.88, n = 39) and the agreement around the clinical cut-off for CTX (4.0 mg/l), MER (2.0 mg/l) and PIP (16.0 mg/l) was 90%, 100% and 87%, respectively. Conclusion: The microbiological method has a performance for determination of serum levels of meropenem, piperacillin and cefotaxime suitable for clinical use. It is an inexpensive method applicable in any microbiology laboratory. (C) 2016 Elsevier B.V. All rights reserved.

  • 173.
    Frykholm, P.
    et al.
    Uppsala University, Sweden .
    Pikwer, A.
    Lund University, Sweden .
    Hammarskjöld, Fredrik
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Hälsouniversitetet.
    Larsson, A.T.
    Gavle Sandviken County Hospital, Sweden .
    Lindgren, S.
    University of Gothenburg, Sweden .
    Lindwall, R.
    Karolinska Institute, Sweden .
    Taxbro, K.
    Ryhov County Hospital, Sweden .
    Oberg, F.
    Karolinska University Hospital Solna, Sweden .
    Acosta, S.
    Lund University, Sweden .
    Akeson, J.
    Lund University, Sweden .
    Clinical guidelines on central venous catheterisation2014Inngår i: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 58, nr 5, s. 508-524Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Safe and reliable venous access is mandatory in modern health care, but central venous catheters (CVCs) are associated with significant morbidity and mortality, This paper describes current Swedish guidelines for clinical management of CVCs The guidelines supply updated recommendations that may be useful in other countries as well. Literature retrieval in the Cochrane and Pubmed databases, of papers written in English or Swedish and pertaining to CVC management, was done by members of a task force of the Swedish Society of Anaesthesiology and Intensive Care Medicine. Consensus meetings were held throughout the review process to allow all parts of the guidelines to be embraced by all contributors. All of the content was carefully scored according to criteria by the Oxford Centre for Evidence-Based Medicine. We aimed at producing useful and reliable guidelines on bleeding diathesis, vascular approach, ultrasonic guidance, catheter tip positioning, prevention and management of associated trauma and infection, and specific training and follow-up. A structured patient history focused on bleeding should be taken prior to insertion of a CVCs. The right internal jugular vein should primarily be chosen for insertion of a wide-bore CVC. Catheter tip positioning in the right atrium or lower third of the superior caval vein should be verified for long-term use. Ultrasonic guidance should be used for catheterisation by the internal jugular or femoral veins and may also be used for insertion via the subclavian veins or the veins of the upper limb. The operator inserting a CVC should wear cap, mask, and sterile gown and gloves. For long-term intravenous access, tunnelled CVC or subcutaneous venous ports are preferred. Intravenous position of the catheter tip should be verified by clinical or radiological methods after insertion and before each use. Simulator-assisted training of CVC insertion should precede bedside training in patients. Units inserting and managing CVC should have quality assertion programmes for implementation and follow-up of routines, teaching, training and clinical outcome. Clinical guidelines on a wide range of relevant topics have been introduced, based on extensive literature retrieval, to facilitate effective and safe management of CVCs.

  • 174.
    Fälker, Knut
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Klarstrom-Engstrom, Kristin
    University of Örebro, Sweden .
    Bengtsson, Torbjorn
    University of Örebro, Sweden .
    Lindahl, Tomas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk kemi.
    Grenegard, Magnus
    University of Örebro, Sweden .
    The Toll-like receptor 2/1 (TLR2/1) complex initiates human platelet activation via the src/Syk/LAT/PLC gamma 2 signalling cascade2014Inngår i: Cellular Signalling, ISSN 0898-6568, E-ISSN 1873-3913, Vol. 26, nr 2, s. 279-286Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The specific TLR2/1 complex activator Pam3CSK4 has been shown to provoke prominent activation and aggregation of human non-nucleated platelets. As Pam3CSK4-evoked platelet activation does not employ the major signalling pathway established in nucleated immune cells, we investigated if the TLR2/1 complex on platelets may initiate signalling pathways known to be induced by physiological agonists such as collagen via GPVI or thrombin via PARs. We found that triggering TLR2/1 complex-signalling with Pam3CSK4, in common with that induced via GPVI, and in contrast to that provoked by PARS, involves tyrosine phosphorylation of the adaptor protein LAT as well as of PLC gamma 2 in a src- and Syk-dependent manner. In this respect, we provide evidence that Pam3CSK4 does not cross-activate GPVI. Further, by the use of platelets from a Glanzmanns thrombasthenia patient lacking beta(3), in contrast to findings in nucleated immune cells, we show that the initiation of platelet activation by Pam3CSK4 does not involve integrin beta(3) signalling; whereas the latter, subsequent to intermediate TXA2 synthesis and signalling, was found to be indispensable for proper dense granule secretion and full platelet aggregation. Together, our findings reveal that triggering the TLR2/1 complex with Pam3CSK4 initiates human platelet activation by engaging tyrosine kinases of the src family and Syk, the adaptor protein LAT, as well as the key mediator PLC gamma 2.

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  • 175.
    Gabilondo, Hugo
    et al.
    University of Autonoma Madrid, Spain.
    Stratmann, Johannes
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Rubio-Ferrera, Irene
    University of Autonoma Madrid, Spain.
    Millan-Crespo, Irene
    University of Autonoma Madrid, Spain.
    Contero-Garcia, Patricia
    University of Autonoma Madrid, Spain.
    Bahrampour, Shahrzad
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Thor, Stefan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Benito-Sipos, Jonathan
    University of Autonoma Madrid, Spain.
    Neuronal Cell Fate Specification by the Convergence of Different Spatiotemporal Cues on a Common Terminal Selector Cascade2016Inngår i: PLoS biology, ISSN 1544-9173, E-ISSN 1545-7885, Vol. 14, nr 5, s. e1002450-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Specification of the myriad of unique neuronal subtypes found in the nervous system depends upon spatiotemporal cues and terminal selector gene cascades, often acting in sequential combinatorial codes to determine final cell fate. However, a specific neuronal cell subtype can often be generated in different parts of the nervous system and at different stages, indicating that different spatiotemporal cues can converge on the same terminal selectors to thereby generate a similar cell fate. However, the regulatory mechanisms underlying such convergence are poorly understood. The Nplp1 neuropeptide neurons in the Drosophila ventral nerve cord can be subdivided into the thoracic-ventral Tv1 neurons and the dorsal-medial dAp neurons. The activation of Nplp1 in Tv1 and dAp neurons depends upon the same terminal selector cascade: colamp;gt;ap/eyaamp;gt;dimmamp;gt;Nplp1. However, Tv1 and dAp neurons are generated by different neural progenitors (neuroblasts) with different spatiotemporal appearance. Here, we find that the same terminal selector cascade is triggered by Kr/pdmamp;gt;grn in dAp neurons, but by Antp/hth/exd/lbe/cas in Tv1 neurons. Hence, two different spatiotemporal combinations can funnel into a common downstream terminal selector cascade to determine a highly related cell fate.

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  • 176.
    Gallardo Bolanos, Juan M.
    et al.
    University of Extremadura, Spain .
    Balao da Silva, Carolina M.
    University of Extremadura, Spain .
    Martin Munoz, Patricia
    University of Extremadura, Spain .
    Morillo Rodriguez, Antolin
    University of Extremadura, Spain .
    Plaza Davila, Maria
    University of Extremadura, Spain .
    Rodriguez-Martinez, Heriberto
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Hälsouniversitetet. University of Extremadura, Spain .
    Aparicio, Ines M.
    University of Extremadura, Spain .
    Tapia, Jose A.
    University of Extremadura, Spain .
    Ortega Ferrusola, Cristina
    University of Extremadura, Spain .
    Pena, Fernando J.
    University of Extremadura, Spain .
    Phosphorylated AKT preserves stallion sperm viability and motility by inhibiting caspases 3 and 72014Inngår i: Reproduction, ISSN 1470-1626, E-ISSN 1476-3990, Vol. 148, nr 2, s. 221-235Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    AKT, also referred to as protein kinase B (PKB or RAC), plays a critical role in controlling cell survival and apoptosis. To gain insights into the mechanisms regulating sperm survival after ejaculation, the role of AKT was investigated in stallion spermatozoa using a specific inhibitor and a phosphoflow approach. Stallion spermatozoa were washed and incubated in Biggers-Whitten-Whittingham medium, supplemented with 1% polyvinyl alcohol (PVA) in the presence of 0 (vehicle), 10, 20 or 30 mu M SH5, an AKT inhibitor. SH5 treatment reduced the percentage of sperm displaying AKT phosphorylation, with inhibition reaching a maximum after 1 h of incubation. This decrease in phosphorylation was attributable to either dephosphorylation or suppression of the active phosphorylation pathway. Stallion spermatozoa spontaneously dephosphorylated during in vitro incubation, resulting in a lack of a difference in AKT phosphorylation between the SH5-treated sperm and the control after 4 h of incubation. AKT inhibition decreased the proportion of motile spermatozoa (total and progressive) and the sperm velocity. Similarly, AKT inhibition reduced membrane integrity, leading to increased membrane permeability and reduced the mitochondrial membrane potential concomitantly with activation of caspases 3 and 7. However, the percentage of spermatozoa exhibiting oxidative stress, the production of mitochondrial superoxide radicals, DNA oxidation and DNA fragmentation were not affected by AKT inhibition. It is concluded that AKT maintains the membrane integrity of ejaculated stallion spermatozoa, presumably by inhibiting caspases 3 and 7, which prevents the progression of spermatozoa to an incomplete form of apoptosis.

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  • 177.
    Generó, Magalí Martí
    et al.
    Linköpings universitet, Institutionen för tema, Tema Miljöförändring. Linköpings universitet, Filosofiska fakulteten.
    Juottonen, Heli
    MEM-group, Department of Biosciences, University of Helsinki, Helsinki, Finland.
    Robroek, Bjorn J.M.
    Ecology and Biodiversity Group, Institute of Environmental Biology, Utrecht University, CH Utrecht, The Netherlands.
    Yrjälä, Kim
    MEM-group, Department of Biosciences, University of Helsinki, Helsinki, Finland.
    Danielsson, Åsa
    Linköpings universitet, Institutionen för tema, Tema Miljöförändring. Linköpings universitet, Filosofiska fakulteten.
    Lindgren, Per-Eric
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Hälsouniversitetet.
    Svensson, Bo
    Linköpings universitet, Institutionen för tema, Tema Miljöförändring. Linköpings universitet, Filosofiska fakulteten.
    Nitrogen and methanogen community composition within and among three Sphagnum dominated peatlands in Scandinavia2015Inngår i: Soil Biology and Biochemistry, ISSN 0038-0717, E-ISSN 1879-3428, Vol. 81, s. 204-211Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Ombrotrophic raised bogs are nutrient poor acidic peatlands accumulating organic matter. They are widely spread on northern latitudes and are substantial sources of methane emissions to the atmosphere being of great concern from a climate change perspective. We investigated the methanogen community composition along microtopographic gradients within three bogs in Scandinavia, receiving different amounts of nitrogen precipitation. Methanogenic community analyses by terminal restriction fragment length polymorphism of the mcrA gene showed different profiles among the three sites, while no in- fluence of the microtopographic gradients was observed. Peat temperature and dissolved organic carbon were the major edaphic variables explaining 38% of the variation of the methanogenic community di- versity among the bogs. The family Methanoregulaceae (hydrogenotrophic methanogens) showed the largest relative proportion and highest activity in all three sites. Quantitative PCR of the mcrA gene and transcripts showed that the most northern site, receiving the lowest atmospheric nitrogen load, had significantly lower abundance and activity of methanogens (4.7 106 and 2.4 104 mcrA copies per gram of soil, respectively), compared to the most southern site (8.2 107 and 4.6 105 mcrA copies per gram of soil, respectively), receiving the highest nitrogen load. No patterns of the mcrA gene and tran- script abundances were observed along the microtopography. The results indicated that the difference in occurrence of methanogens is mainly due to geoclimatological conditions rather than site intrinsic microtopographic variation. The study further suggests that environmental changes on the site intrinsic topography will not affect the methanogenic activity, while increasing average temperatures in Scan- dinavian ombrotrophic raised bogs might contribute to an increase of the methanogenic archaeal activity resulting in an increase of methane production. 

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  • 178.
    Gia Phan, Tung
    et al.
    Blood Syst Research Institute, CA 94118 USA; University of Calif San Francisco, CA 94118 USA.
    Charlys da Costa, Antonio
    Blood Syst Research Institute, CA 94118 USA; University of Sao Paulo, Brazil.
    del Valle Mendoza, Juana
    University of Peruana Ciencias Aplicadas UPC, Peru.
    Bucardo-Rivera, Filemon
    Institute Invest Nutr, Peru; University of Leon, Nicaragua.
    Nordgren, Johan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    ORyan, Miguel
    University of Chile, Chile.
    Deng, Xutao
    Blood Syst Research Institute, CA 94118 USA.
    Delwart, Eric
    Blood Syst Research Institute, CA 94118 USA; University of Calif San Francisco, CA 94118 USA.
    The fecal virome of South and Central American children with diarrhea includes small circular DNA viral genomes of unknown origin2016Inngår i: Archives of Virology, ISSN 0304-8608, E-ISSN 1432-8798, Vol. 161, nr 4, s. 959-966Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Viral metagenomics of feces collected from 58 Peruvian children with unexplained diarrhea revealed several small circular ssDNA genomes. Two genomes related to sequences previously reported in feces from chimpanzees and other mammals and recently named smacoviruses were characterized and then detected by PCR in 1.7 % (1/58) and 19 % (11/58) of diarrheal samples, respectively. Another three genomes from a distinct small circular ssDNA viral group provisionally called pecoviruses encoded Cap and Rep proteins with < 35 % identity to those in related genomes reported in human, seal, porcine and dromedary feces. Pecovirus DNA was detected in 15.5 % (9/58), 5.9 % (3/51) and 3 % (3/100) of fecal samples from unexplained diarrhea in Peru, Nicaragua and Chile, respectively. Feces containing these ssDNA genomes also contained known human enteric viral pathogens. The cellular origins of these circular ssDNA viruses, whether human cells, ingested plants, animals or fungal foods, or residents of the gut microbiome, are currently unknown.

  • 179.
    Gia Phan, Tung
    et al.
    Blood Syst Research Institute, CA 94118 USA University of Calif San Francisco, CA 94118 USA .
    Nordgren, Johan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Hälsouniversitetet.
    Ouermi, Djeneba
    University of Ouagadougou, Burkina Faso .
    Simpore, Jacques
    University of Ouagadougou, Burkina Faso .
    Nitiema, Leon W.
    University of Ouagadougou, Burkina Faso .
    Deng, Xutao
    Blood Syst Research Institute, CA 94118 USA .
    Delwart, Eric
    Blood Syst Research Institute, CA 94118 USA University of Calif San Francisco, CA 94118 USA .
    New astrovirus in human feces from Burkina Faso2014Inngår i: Journal of Clinical Virology, ISSN 1386-6532, E-ISSN 1873-5967, Vol. 60, nr 2, s. 161-164Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: A significant fraction of cases of diarrhea, a leading cause of childhood mortality worldwide, remain unexplained. Objectives: To identify viruses in unexplained cases of diarrhea using an unbiased metagenomics approach. Study design: Viral nucleic acids were enriched from the feces from 48 cases of unexplained diarrhea from Burkina Faso, sequenced, and compared against all known viral genomes. Results: The full genome of a highly divergent astrovirus was sequenced in a sample co-infected with parechovirus 1. RT-PCR identified a single astrovirus infection in these 48 patients indicating a low prevalence. Human astrovirus-BF34 was most closely related to mamastrovirus species 8 and 9 also found in human with which it shared 62%, 74%, and 57% amino acid identities over its protease, RNA dependent RNA polymerase and capsid proteins, respectively. Conclusions: Burkina Faso astrovirus is proposed as prototype for a novel species in the genus Mamastrovirus, here tentatively called Mamastrovirus 20, representing the fifth human astrovirus species.

  • 180.
    Gjesing Welinder, Karen
    et al.
    Aalborg University, Denmark.
    Hansen, Rasmus
    Aalborg University, Denmark; .
    Toft Overgaard, Michael
    Aalborg University, Denmark.
    Brohus, Malene
    Aalborg University, Denmark.
    Sonderkaer, Mads
    Aalborg University, Denmark.
    von Bergen, Martin
    Aalborg University, Denmark; UFZ Helmholtz Centre Environm Research, Germany; UFZ Helmholtz Centre Environm Research, Germany.
    Rolle-Kampczyk, Ulrike
    UFZ Helmholtz Centre Environm Research, Germany.
    Otto, Wolfgang
    UFZ Helmholtz Centre Environm Research, Germany.
    Lindahl, Tomas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    Arinell, Karin
    University of Örebro, Sweden.
    Evans, Alina L.
    Hedmark University of Coll, Norway.
    Swenson, Jon E.
    Norwegian University of Life Science, Norway; Norwegian Institute Nat Research, Norway.
    Revsbech, Inge G.
    Aarhus University, Denmark.
    Frobert, Ole
    University of Örebro, Sweden.
    Biochemical Foundations of Health and Energy Conservation in Hibernating Free-ranging Subadult Brown Bear Ursus arctos2016Inngår i: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 291, nr 43, s. 22509-22523Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Brown bears (Ursus arctos) hibernate for 5-7 months without eating, drinking, urinating, and defecating at a metabolic rate of only 25% of the summer activity rate. Nonetheless, they emerge healthy and alert in spring. We quantified the biochemical adaptations for hibernation by comparing the proteome, metabolome, and hematological features of blood from hibernating and active free-ranging subadult brown bears with a focus on conservation of health and energy. We found that total plasma protein concentration increased during hibernation, even though the concentrations of most individual plasma proteins decreased, as did the white blood cell types. Strikingly, antimicrobial defense proteins increased in concentration. Central functions in hibernation involving the coagulation response and protease inhibition, as well as lipid transport and metabolism, were upheld by increased levels of very few key or broad specificity proteins. The changes in coagulation factor levels matched the changes in activity measurements. A dramatic 45-fold increase in sex hormone-binding globulin levels during hibernation draws, for the first time, attention to its significant but unknown role in maintaining hibernation physiology. We propose that energy for the costly protein synthesis is reduced by three mechanisms as follows: (i) dehydration, which increases protein concentration without de novo synthesis; (ii) reduced protein degradation rates due to a 6 degrees C reduction in body temperature and decreased protease activity; and (iii) a marked redistribution of energy resources only increasing de novo synthesis of a few key proteins. The comprehensive global data identified novel biochemical strategies for bear adaptations to the extreme condition of hibernation and have implications for our understanding of physiology in general.

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  • 181.
    Gjessing, Kristian
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Hälsouniversitetet.
    Torgé, Cristina Joy
    Linköpings universitet, Institutionen för samhälls- och välfärdsstudier, NISAL - Nationella institutet för forskning om äldre och åldrande. Linköpings universitet, Filosofiska fakulteten.
    Hammar, Mats
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Dahlberg, Johanna
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Hälsouniversitetet.
    Faresjö, Tomas
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Hälsouniversitetet.
    Improvement of quality and safety in health care as a new interprofessional learning module – evaluation from students2014Inngår i: Journal of Multidisciplinary Healthcare, ISSN 1178-2390, E-ISSN 1178-2390, nr 7, s. 341-347Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Interprofessional teamwork is in many ways a norm in modern health care, and needs to be taught during professional education.

    Description: This study is an evaluation of a newly introduced and mandatory learning module where students from different health profession programs used Improvement of Quality and Safety as a way to develop interprofessional competence in a real-life setting. The intention of this learning module was to integrate interprofessional teamwork within the students' basic education, and to give students a basic knowledge about Improvement of Quality and Safety. This report focuses on evaluations from the participating students (n=222), mainly medical and nursing students.

    Materials and methods: To evaluate this new learning module, a questionnaire was developed and analyzed using a mixed methods design, integrating both qualitative and quantitative methods. The evaluation addressed learning concepts, learning objectives, and interprofessional and professional development.

    Results and conclusion: A majority of students responded positively to the learning module as a whole, but many were negative towards specific parts of the learning module and its implementation. Medical students and male students were less positive towards this learning module. Improvements and alterations were suggested. 

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  • 182.
    Govender, Melissa
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten. ICGEB, South Africa; Univ Cape Town, South Africa; Univ Cape Town, South Africa; Univ Cape Town, South Africa.
    Hurdayal, Ramona
    ICGEB, South Africa; Univ Cape Town, South Africa; Univ Cape Town, South Africa; Univ Cape Town, South Africa; Univ Cape Town, South Africa.
    Martinez-Salazar, Berenice
    ICGEB, South Africa; Univ Cape Town, South Africa; Univ Cape Town, South Africa; Univ Cape Town, South Africa; Univ Lausanne, Switzerland; Univ Lausanne, Switzerland.
    Gqada, Kaya
    ICGEB, South Africa; Univ Cape Town, South Africa; Univ Cape Town, South Africa; Univ Cape Town, South Africa.
    Pillay, Shandre
    ICGEB, South Africa; Univ Cape Town, South Africa; Univ Cape Town, South Africa; Univ Cape Town, South Africa.
    Gcanga, Lorna
    ICGEB, South Africa; Univ Cape Town, South Africa; Univ Cape Town, South Africa; Univ Cape Town, South Africa.
    Passelli, Katiuska
    Univ Lausanne, Switzerland; Univ Lausanne, Switzerland.
    Nieuwenhuizen, Natalie E.
    ICGEB, South Africa; Univ Cape Town, South Africa; Univ Cape Town, South Africa; Univ Cape Town, South Africa; Max Planck Inst Infect Biol, Germany.
    Tacchini-Cottier, Fabienne
    Univ Lausanne, Switzerland.
    Guler, Reto
    ICGEB, South Africa; Univ Cape Town, South Africa; Univ Cape Town, South Africa; Univ Cape Town, South Africa.
    Brombacher, Frank
    ICGEB, South Africa; Univ Cape Town, South Africa; Univ Cape Town, South Africa; Univ Cape Town, South Africa.
    Deletion of Interleukin-4 Receptor Alpha-Responsive Keratinocytes in BALB/c Mice Does Not Alter Susceptibility to Cutaneous Leishmaniasis2018Inngår i: Infection and Immunity, ISSN 0019-9567, E-ISSN 1098-5522, Vol. 86, nr 12, artikkel-id e00710-18Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The skin microenvironment at the site of infection plays a role in the early events that determine protective T helper 1/type 1 immune responses during cutaneous leishmaniasis (CL) infection. During CL in nonhealing BALB/c mice, early interleukin-4 (IL-4) can instruct dendritic cells for protective Th1 immunity. Additionally, keratinocytes, which are the principal cell type in the skin epidermis, have been shown to secrete IL-4 early after Leishmania major infection. Here, we investigated whether IL-4/1L-13 signaling via the common IL-4 receptor alpha chain (IL-4R alpha) on keratinocytes contributes to susceptibility during experimental CL. To address this, keratinocyte-specific IL-41R alpha-deficient (KRT14(cre) IL-4R alpha(-/lox)) mice on a BALB/c genetic background were generated by gene targeting and site-specific recombination (Cre/loxP) under the control of the keratinocyte-specific krt14 locus. Following high-dose infection with L. major IL-81 and LV39 promastigotes subcutaneously in the footpad, footpad swelling, parasite burden, IFN-gamma/IL-4/IL-13 cytokine production, and type 1 and type 2 antibody responses were similar between KRT14(cre) IL-4R alpha(-)(lox) and littermate control IL-4R alpha(-) (lox) BALB/c mice. An intradermal infection with low-dose L. major IL-81 and LV39 promastigotes in the ear showed results in infected KRT14(cre) IL-4R alpha(-)(/)(lox) BALB/c mice similar to those of littermate control IL-4R alpha(-)(/)(lox) BALB/c mice, with the exception of a significant decrease observed in parasite burden only at the site of LV39 infection in the ear. Collectively, our results show that autocrine and paracrine signaling of IL-4/1L-13 through the IL-4R alpha chain on keratinocytes does not influence the establishment of a nonhealing Th2 immune response in BALB/c mice during L. major infection.

  • 183.
    Govorov, Igor
    et al.
    Karolinska Inst, Sweden.
    Bremme, Katarina
    Karolinska Inst, Sweden.
    Lindahl, Tomas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    Holmstrom, Margareta
    Karolinska Univ, Sweden.
    Komlichenko, Eduard
    Almazov Natl Med Res Ctr, Russia.
    Chaireti, Roza
    Karolinska Inst, Sweden.
    Mints, Miriam
    Karolinska Inst, Sweden.
    Thrombin generation during a regular menstrual cycle in women with von Willebrand disease2018Inngår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, artikkel-id 17467Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Fluctuations of the sex steroids during the menstrual cycle might significantly influence hemostasis. This association, derived from a number of the observations on healthy women, is yet to be described in females affected by bleeding disorders. The aim of the current study was to assess the changes in hemostatic variables in women with vWD during two phases of the menstrual cycle (follicular and luteal) and to compare it with healthy controls. The study group included 12 vWD-affected females with regular menstrual cycle, with none of them being prescribed any hormonal treatment. The control group consisted of 102 healthy females, matched for age and BMI. Within the vWD group FVIII and FX were both significantly higher during follicular phase than in luteal phase (p=0.013 and p=0.033 respectively). AT, FII, FVII and FX were higher in women with vWD, compared with controls during both phases of the menstrual cycle (pamp;lt;0.0005, pamp;lt;0.0005, p=0.001 and pamp;lt;0.0005). In women with vWD, lag time and time to peak were prolonged during both phases of the menstrual cycle(pamp;lt;0.0005), while peak thrombin concentration was reduced (p=0.003 and p=0.002 during follicular and luteal phase respectively) compared to healthy peers. Lower levels of FVIII and FX during luteal phase may predispose women to the development of the menorrhagia - common complication of vWD. Women with vWD need more time to reach the peak thrombin concentration, while the latter still remains less than in healthy women. Higher levels of AT in vWD-affected females, compared to controls, may also contribute to the existing bleeding tendency in this cohort.

    Fulltekst (pdf)
    fulltext
  • 184.
    Grandell, Ida
    et al.
    National Board Forens Med, Department Forens Genet and Forens Toxicol, Artillerigatan 12, SE-58758 Linkoping, Sweden.
    Samara, Raed
    QIAGEN Science Inc, MD 21703 USA.
    Tillmar, Andreas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten. National Board Forens Med, Department Forens Genet and Forens Toxicol, Artillerigatan 12, SE-58758 Linkoping, Sweden.
    A SNP panel for identity and kinship testing using massive parallel sequencing2016Inngår i: International journal of legal medicine (Print), ISSN 0937-9827, E-ISSN 1437-1596, Vol. 130, nr 4, s. 905-914Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Within forensic genetics, there is still a need for supplementary DNA marker typing in order to increase the power to solve cases for both identity testing and complex kinship issues. One major disadvantage with current capillary electrophoresis (CE) methods is the limitation in DNA marker multiplex capability. By utilizing massive parallel sequencing (MPS) technology, this capability can, however, be increased. We have designed a customized GeneRead DNASeq SNP panel (Qiagen) of 140 previously published autosomal forensically relevant identity SNPs for analysis using MPS. One single amplification step was followed by library preparation using the GeneRead Library Prep workflow (Qiagen). The sequencing was performed on a MiSeq System (Illumina), and the bioinformatic analyses were done using the software Biomedical Genomics Workbench (CLC Bio, Qiagen). Forty-nine individuals from a Swedish population were genotyped in order to establish genotype frequencies and to evaluate the performance of the assay. The analyses showed to have a balanced coverage among the included loci, and the heterozygous balance showed to have less than 0.5 % outliers. Analyses of dilution series of the 2800M Control DNA gave reproducible results down to 0.2 ng DNA input. In addition, typing of FTA samples and bone samples was performed with promising results. Further studies and optimizations are, however, required for a more detailed evaluation of the performance of degraded and PCR-inhibited forensic samples. In summary, the assay offers a straightforward sample-to-genotype workflow and could be useful to gain information in forensic casework, for both identity testing and in order to solve complex kinship issues.

  • 185.
    Grankvist, Anna
    et al.
    University of Gothenburg, Sweden; Sahlgrens University Hospital, Sweden.
    Labbe Sandelin, Lisa
    Kalmar County Hospital, Sweden; Uppsala University, Sweden.
    Andersson, Jennie
    University of Gothenburg, Sweden; Sahlgrens University Hospital, Sweden.
    Fryland, Linda
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Wilhelmsson, Peter
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Lindgren, Per-Eric
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten. County Hospital Ryhov, Sweden.
    Forsberg, Pia
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Infektionskliniken i Östergötland.
    Wenneras, Christine
    University of Gothenburg, Sweden; Sahlgrens University Hospital, Sweden.
    Infections with Candidatus Neoehrlichia mikurensis and Cytokine Responses in 2 Persons Bitten by Ticks, Sweden2015Inngår i: Emerging Infectious Diseases, ISSN 1080-6040, E-ISSN 1080-6059, Vol. 21, nr 8, s. 1462-1465Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The prevalence of Candidatus Neoehrlichia mikurensis infection was determined in 102 persons bitten by ticks in Sweden. Two infected women had erythematous rashes; 1 was co-infected with a Borrelia sp., and the other showed seroconversion for Anaplasma phagocytophilum. Both patients had increased levels of Neoehrlichia DNA and serum cytokines for several months.

  • 186.
    Grankvist, Kjell
    et al.
    Institutionen för medicinsk biovetenskap, Umeå universitet.
    Hammarsten, Ola
    Avdelningen för Laboratoriemedicin vid Institutionen för biomedicin, Göteborgs universitet.
    Maria, Berggren Söderlund
    Region Kronoberg, Klinisk kemi och transfusionsmedicin.
    Theodorsson, Elvar
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    Laboratoriernas verksamhet2018Inngår i: Laurells klinisk kemi i praktisk medicin / [ed] Elvar Theodorsson, Maria Berggren Söderlund, Lund: Studentlitteratur AB, 2018, 10, s. 13-30Kapittel i bok, del av antologi (Annet vitenskapelig)
  • 187.
    Granquist, Erik G.
    et al.
    Norwegian University of Life Science, Norway.
    Kristiansson, Malin
    Ryhov County Hospital, Sweden.
    Lindgren, Per-Eric
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Hälsouniversitetet.
    Matussek, Andreas
    Ryhov County Hospital, Sweden.
    Nodtvedt, Ane
    Norwegian University of Life Science, Norway.
    Okstad, Wenche
    Norwegian University of Life Science, Norway.
    Stuen, Snorre
    Norwegian University of Life Science, Norway.
    Evaluation of microbial communities and symbionts in Ixodes ricinus and ungulate hosts (Cervus elaphus and Ovis aries) from shared habitats on the west coast of Norway2014Inngår i: Ticks and Tick-borne Diseases, ISSN 1877-959X, E-ISSN 1877-9603, Vol. 5, nr 6, s. 780-784Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Recent reports suggest a potential for transmission of a newly discovered rickettsial endosymbiont, Midichloria mitochondrii, to animals and humans from feeding ticks (Ixodes ricinus). Using molecular methods: I. ricinus, sheep and red deer in Anaplasma phagocytophilum-endemic areas of Norway, were examined to see if they were infected by M. mitochondrii or related organisms like Wolbachia pipientis and Rickettsia spp. A total of 532 ticks collected from pastures, 76 blood samples from grazing lambs and 12 organ samples from hunted deer, were analyzed during the study. All larval pools, 60.4% pooled nymphs and 35.1% of adult ticks were positive for M. mitochondrii. There was a significant difference between geographical areas in the prevalence of M. mitochondrii infection among nymphs. A total of 2.2% pooled nymphs and 5.3% adult ticks were positive for A. phagocytophilum. Eleven percent of pooled nymphs were positive for Borrelia spp, 2.2% of pooled nymphs and 3.5% of adult ticks were positive for Rickettsia spp. and none of the ticks were positive for W. pipientis. The prevalence of A. phagocytophilum infection was 54% and 75% in grazing lambs and deer, respectively. No animals were positive for Borrelia spp., M. mitochondrii, Rickettsia spp. or W. pipientis. The reported findings suggest that M. mitochondrii is widespread in tick populations at different geographical sites, and may appear in co-infection with A. phagocytophilum, Borrelia spp. and Rickettsia spp. in ticks.

  • 188.
    Greaves, Ronda F
    et al.
    School of Health and Biomedical Sciences, RMIT University, Bundoora, Australia.
    Smith, Janet M
    Beastall, Graham
    Laboratory Medicine Consulting, Glasgow, UK.
    Florkowski, Chris
    Clinical Biochemistry Unit, Canterbury Health Laboratories, Christchurch, New Zealand.
    Langman, Loralie
    Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, United States.
    Sheldon, Joanna
    Protein Reference Unit, St. George’s Hospital, London, UK.
    Theodorsson, Elvar
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    The IFCC Curriculum - phase 1.2018Inngår i: EJIFCC, ISSN 1650-3414, Vol. 29, nr 1, s. 55-93Artikkel i tidsskrift (Fagfellevurdert)
  • 189.
    Griekspoor, Petra
    et al.
    Linnaeus University, Sweden.
    Olsson Engvall, Eva
    National Vet Institute SVA, Sweden.
    Åkerlind, Britt
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk mikrobiologi.
    Olsen, Bjorn
    Uppsala University, Sweden; Uppsala University, Sweden.
    Waldenstrom, Jonas
    Linnaeus University, Sweden.
    Genetic diversity and host associations in Campylobacter jejuni from human cases and broilers in 2000 and 20082015Inngår i: Veterinary Microbiology, ISSN 0378-1135, E-ISSN 1873-2542, Vol. 178, nr 1-2, s. 94-98Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Campylobacter jejuni is an important food-borne pathogen, with a global distribution. It can colonize numerous host species, including both domestic and wild animals, but is particularly associated with birds (poultry and wild birds). For human campylobacteriosis, poultry products are deemed the most significant risk factor for acquiring infection. We conducted a genotyping and host attribution study of a large representative collection of C jejuni isolated from humans and broilers in Sweden in the years 2000 and 2008. In total 673 broiler and human isolates from 10 different abattoirs and 6 different hospitals were genotyped with multilocus sequence typing. Source attribution analyses confirmed the strong linkage between broiler C jejuni and domestic human cases, but also indicated a significant association to genotypes more commonly found in wild birds. Genotype distributions did not change dramatically between the two study years, suggesting a stable population of infecting bacteria. (C) 2015 Elsevier B.V. All rights reserved.

  • 190.
    Gudlur, Sushanth
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Hälsouniversitetet.
    Sandén, Camilla
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Molekylär fysik. Linköpings universitet, Tekniska fakulteten.
    Matouskova, Petra
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Molekylär fysik. Linköpings universitet, Tekniska fakulteten.
    Fasciani, Chiara
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Molekylär fysik. Linköpings universitet, Tekniska fakulteten.
    Aili, Daniel
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Molekylär fysik. Linköpings universitet, Tekniska fakulteten.
    Liposomes as nanoreactors for the photochemical synthesis of gold nanoparticles2015Inngår i: Journal of Colloid and Interface Science, ISSN 0021-9797, E-ISSN 1095-7103, Vol. 456, s. 206-209Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A simple and novel method for the photochemical synthesis of AuNPs in liposomes is described. Gold salt is co-encapsulated with the photoinitiator Irgacure-2959 in POPC liposomes prepared via traditional thin-film hydration technique. UVA irradiation for 15 min results in encapsulated AuNPs of 2.8 +/- 1.6 nm in diameter that are primarily dispersed in the aqueous interior of the liposomes. (C) 2015 Elsevier Inc. All rights reserved.

    Fulltekst (pdf)
    fulltext
  • 191.
    Gunaydin, Gokce
    et al.
    Karolinska Institute, Sweden.
    Nordgren, Johan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Sharma, Sumit
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Hammarstrom, Lennart
    Karolinska Institute, Sweden.
    Association of elevated rotavirus-specific antibody titers with HBGA secretor status in Swedish individuals: The FUT2 gene as a putative susceptibility determinant for infection2016Inngår i: Virus Research, ISSN 0168-1702, E-ISSN 1872-7492, Vol. 211, s. 64-68Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The histo-blood group antigens (HBGAs) have recently been suggested to serve as attachment factors for rotavirus VP8* (P-genotype) in vitro and associated with susceptibility in vivo. We thus investigated whether rotavirus antibody titers and genotype specific neutralization titers correlate with HBGA status in Swedish individuals. We investigated the effect of inactivating mutations in the secretor FUT2 (rs601338) and Lewis FUT3 genes (rs28362459, rs3894326, rs812936 and rs778986) on serum IgG antibody titers and neutralizing antibody titers to rotavirus strains of the P[8] and P[6] genotypes in Swedish healthy blood donors and patients with IgA deficiency using genotyping, enzyme linked immunosorbent assay and a neutralization assay. Rotavirus-specific serum IgG and neutralizing antibody titers to the Wa strain (G1P[8]), but not to the ST3 (G4P[6]) strain, were significantly higher in secretors (with at least one functional FUT2 gene) than in non-secretors (P<0.001) (with homozygous nonsense mutation in the FUT2 gene). Thus, our results represent that secretors show elevated rotavirus specific serum antibodies, suggesting a higher susceptibility to rotavirus infections, as compared to non-secretors in Sweden. (C) 2015 Elsevier B.V. All rights reserved.

  • 192.
    Gunaydin, Gokce
    et al.
    Karolinska University Hospital, Sweden .
    Nordgren, Johan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Hälsouniversitetet.
    Svensson, Lennart
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Hälsouniversitetet.
    Hammarstrom, Lennart
    Karolinska University Hospital, Sweden .
    Mutations in Toll-Like Receptor 3 Are Associated with Elevated Levels of Rotavirus-Specific IgG Antibodies in IgA-Deficient but Not IgA-Sufficient Individuals2014Inngår i: Clinical and Vaccine Immunology, ISSN 1556-6811, E-ISSN 1556-679X, Vol. 21, nr 3, s. 298-301Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Double-stranded RNA (dsRNA) triggers immune-mediated responses through toll-like receptor 3 (TLR3), which is involved in innate antiviral defense. Low expression of TLR3 was recently suggested to contribute to susceptibility to rotavirus infection. Thus, we investigated the role of two TLR3 polymorphisms (rs3775291 and rs5743305), both of which resulted in reduced protein function or expression, in healthy blood donors and IgA-deficient (IgAD) individuals. These polymorphisms were associated with elevated rotavirus-specific IgG titers in IgAD individuals but not in healthy individuals. Thus, we propose that TLR3 signaling does not contribute to the rotavirus-specific antibody response in IgA-sufficient individuals, whereas it is associated with elevated antibody titers in IgAD individuals.

    Fulltekst (pdf)
    fulltext
  • 193. Bestill onlineKjøp publikasjonen >>
    Gunnar, Erika
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Regulatory programs controlling profileration during Drosophila nervous system development2017Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    The central nervous system (CNS) is the most complex organ in the body, responsible for complex functions, including thinking, reasoning and memory. The CNS contains cells of many different types, often generated in vast numbers. Hence, CNS development requires precise genetic control of both cell fate and of cell proliferation, to generate the right number of cells, with the proper identity, and in the proper location. The cells also need to make connections with each other for correct signaling and function. This complexity evokes the question of how this is regulated. How does the stem cells, responsible for building the CNS, know how many times to divide, and how does the daughters know which identity to acquire and in which location they shall end up? During Drosophila melanogaster development, the neuroblasts (NBs) are responsible for generating the CNS. In each hemisegment, every NB is unique in identity, and generates a predetermined number of daughters with specific identities. The lineages of different NBs vary in size, but are always the same for each specific NB, and the division modes of each NBs is hence stereotyped. Most NBs start dividing by renewing themselves while generating daughters that will in turn divide once to generate two neurons and/or glia (denoted type I mode). Many, maybe all, NBs later switch to generating daughters that will differentiate directly into a neuron or glia (denoted type 0 mode). This type I>0 switch occurs at different time-points during lineage progression, and influences the total numbers of cells generated from a single NB.

    The work presented in this thesis aimed at investigating the genetic regulation of proliferation, with particular focus on the type I>0 switch. In the first project, the implication of the Notch pathway on the type I>0 switch was studied. Mutants of the Notch pathway do not switch, and the results show that the Notch pathway regulates the switch by activation of several target genes, both regulators and cell cycle genes. One of the target genes, the E(spl)-C genes, have been difficult to study due to functional redundancy. This study reveals that even though they can functionally compensate for each other, they have individual functions in different lineages. Regarding cell cycle genes, both Notch and E(spl)-C regulate several key cell cycle genes, and molecular analysis indicated that this regulation is direct. In the second project we studied the seq gene, previously identified in a genetic screen. We found that seq controls the type I>0 switch by regulating the key cell cycle genes, but also through interplay with the Notch pathway. Notch and seq stop proliferation, and in the third project we wanted to identify genes that drive proliferation. We found that there is battery of early NB genes, socalled early factors, which activate the cell cycle, and drive NB and daughter proliferation. These are gradually replaced by late regulators, and the interplay between early and late factors acts to achieve precise control of lineage progression.

    The work presented here increases our understanding of how regulatory programs act to control the development of the CNS; to generate the right number of cells of different identities. These results demonstrate the importance of correct regulation of proliferation in both stem cells and daughters. Problems in this control can result in either an underdeveloped CNS or loss of control such as in cancer. Knowledge about these regulatory programs can contribute to the development of therapeutics against these diseases.

    Delarbeid
    1. Control of Neural Daughter Cell Proliferation by Multi-level Notch/Su(H)/E(spl)-HLH Signaling
    Åpne denne publikasjonen i ny fane eller vindu >>Control of Neural Daughter Cell Proliferation by Multi-level Notch/Su(H)/E(spl)-HLH Signaling
    Vise andre…
    2016 (engelsk)Inngår i: PLoS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 12, nr 4, artikkel-id e1005984Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    The Notch pathway controls proliferation during development and in adulthood, and is frequently affected in many disorders. However, the genetic sensitivity and multi-layered transcriptional properties of the Notch pathway has made its molecular decoding challenging. Here, we address the complexity of Notch signaling with respect to proliferation, using the developing Drosophila CNS as model. We find that a Notch/Su(H)/E(spl)-HLH cascade specifically controls daughter, but not progenitor proliferation. Additionally, we find that different E(spl)-HLH genes are required in different neuroblast lineages. The Notch/Su(H)/E(spl)-HLH cascade alters daughter proliferation by regulating four key cell cycle factors: Cyclin E, String/Cdc25, E2f and Dacapo (mammalian p21(CIP1)/p27(KIP1)/p57(Kip2)). ChIP and DamID analysis of Su(H) and E(spl)-HLH indicates direct transcriptional regulation of the cell cycle genes, and of the Notch pathway itself. These results point to a multi-level signaling model and may help shed light on the dichotomous proliferative role of Notch signaling in many other systems.

    sted, utgiver, år, opplag, sider
    PUBLIC LIBRARY SCIENCE, 2016
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-128759 (URN)10.1371/journal.pgen.1005984 (DOI)000375231900032 ()27070787 (PubMedID)
    Merknad

    Funding Agencies|Knut and Alice Wallenberg Foundation [KAW2012.0101]; Swedish Research Council [621-2010-5214]; Swedish Cancer Foundation [120531]

    Tilgjengelig fra: 2016-05-31 Laget: 2016-05-30 Sist oppdatert: 2019-03-13
    2. sequoia controls the type I>0 daughter proliferation switch in the developing Drosophila nervous system
    Åpne denne publikasjonen i ny fane eller vindu >>sequoia controls the type I>0 daughter proliferation switch in the developing Drosophila nervous system
    2016 (engelsk)Inngår i: Development, ISSN 0950-1991, E-ISSN 1477-9129, Vol. 143, nr 20, s. 3774-3784Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Neural progenitors typically divide asymmetrically to renew themselves, while producing daughters with more limited potential. In the Drosophila embryonic ventral nerve cord, neuroblasts initially produce daughters that divide once to generate two neurons/glia (type I proliferation mode). Subsequently, many neuroblasts switch to generating daughters that differentiate directly (type 0). This programmed type I>0 switch is controlled by Notch signaling, triggered at a distinct point of lineage progression in each neuroblast. However, how Notch signaling onset is gated was unclear. We recently identified Sequoia (Seq), a C2H2 zinc-finger transcription factor with homology to Drosophila Tramtrack (Ttk) and the positive regulatory domain (PRDM) family, as important for lineage progression. Here, we find that seq mutants fail to execute the type I>0 daughter proliferation switch and also display increased neuroblast proliferation. Genetic interaction studies reveal that seq interacts with the Notch pathway, and seq furthermore affects expression of a Notch pathway reporter. These findings suggest that seq may act as a context-dependent regulator of Notch signaling, and underscore the growing connection between Seq, Ttk, the PRDM family and Notch signaling.

    sted, utgiver, år, opplag, sider
    The Company of Biologists Ltd, 2016
    Emneord
    Lineage tree, Cell cycle, Asymmetric division, Combinatorial control, Notch
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-132739 (URN)10.1242/dev.139998 (DOI)000393452500013 ()27578794 (PubMedID)
    Merknad

    Funding agencies: Swedish Research Council (Vetenskapsradet); Knut and Alice Wallenberg Foundation (Knut och Alice Wallenbergs Stiftelse); Swedish Cancer Foundation (Cancerfonden)

    Tilgjengelig fra: 2016-11-22 Laget: 2016-11-22 Sist oppdatert: 2019-03-13bibliografisk kontrollert
    Fulltekst (pdf)
    Regulatory programs controlling profileration during Drosophila nervous system development
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  • 194.
    Gunnar, Erika
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Bivik Stadler, Caroline
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Starkenberg, Annika
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Thor, Stefan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    sequoia controls the type I>0 daughter proliferation switch in the developing Drosophila nervous system2016Inngår i: Development, ISSN 0950-1991, E-ISSN 1477-9129, Vol. 143, nr 20, s. 3774-3784Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Neural progenitors typically divide asymmetrically to renew themselves, while producing daughters with more limited potential. In the Drosophila embryonic ventral nerve cord, neuroblasts initially produce daughters that divide once to generate two neurons/glia (type I proliferation mode). Subsequently, many neuroblasts switch to generating daughters that differentiate directly (type 0). This programmed type I>0 switch is controlled by Notch signaling, triggered at a distinct point of lineage progression in each neuroblast. However, how Notch signaling onset is gated was unclear. We recently identified Sequoia (Seq), a C2H2 zinc-finger transcription factor with homology to Drosophila Tramtrack (Ttk) and the positive regulatory domain (PRDM) family, as important for lineage progression. Here, we find that seq mutants fail to execute the type I>0 daughter proliferation switch and also display increased neuroblast proliferation. Genetic interaction studies reveal that seq interacts with the Notch pathway, and seq furthermore affects expression of a Notch pathway reporter. These findings suggest that seq may act as a context-dependent regulator of Notch signaling, and underscore the growing connection between Seq, Ttk, the PRDM family and Notch signaling.

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    fulltext
  • 195.
    Gupta, Shipra
    et al.
    Jamia Hamdard, India.
    Krishnan, Anuja
    Jamia Hamdard, India.
    Sharma, Sumit
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Kumar, Praveen
    Kalawati Saran Childrens Hospital, India.
    Aneja, Satinder
    Kalawati Saran Childrens Hospital, India.
    Ray, Pratima
    Jamia Hamdard, India.
    Changing pattern of prevalence, genetic diversity, and mixed infections of viruses associated with acute gastroenteritis in pediatric patients in New Delhi, India2018Inngår i: Journal of Medical Virology, ISSN 0146-6615, E-ISSN 1096-9071, Vol. 90, nr 3, s. 469-476Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    There are very few studies that have assessed multiple viral agents causing Acute-Gastroenteritis (AGE) in India. The present study compared the changing pattern of prevalence and genetic diversity of five enteric viruses associated with acute-diarrhea in Delhi children within a gap of 5 years. Fecal samples were collected from diarrheal children (amp;lt;4 years) during two winter seasons: year 2009-2010 (n=59) and year 2014-2015 (n=85). Samples were individually tested for rotavirus-A, norovirus, astrovirus, adenovirus, and sapovirus using EIA/RT-PCR and genetically characterized by phylogenetic analysis. Rotavirus was the most predominant (54.9%) virus followed by norovirus (25.7%), astrovirus (8.3%), and adenovirus (4.9%) with rare detection of sapovirus (0.7%). While detection rate increased for both rotavirus (49.2-58.8%) and astrovirus (5.1-10.6%), norovirus detection rate decreased (30.5-22.4%) from 2009 to 2015. During the same time period, adenovirus detection remained low (4.7-5.1%). Interestingly, mixed infections increased from 8.5% to 16.5% after 5 years. G1P[8] rotavirus strain was found most predominant (40%). Both type-1 and 8 astroviruses were detected. Single sapovirus detected was of genotype GII.1. Both GI (GI.5, GI.3) and GII (GII.1, GII.4, GII.7, GII.21, GII.13) genogroups of norovirus were detected. Of particular significance was the first detection of other NoV genotypes (besides GII.4 and GI.3) in Delhi. This is also the first report of NoV GI.5 from India. A change in prevalence pattern and increased diversity from 2009 to 2015 emphasizes the need for continued enteric virus surveillance to help measure the impact of new diarrhea vaccine(s) introduced in India.

  • 196.
    Gurbel, Paul A.
    et al.
    Sinai Centre Thrombosis Research, MD 21215 USA.
    Bergmeijer, Thomas O.
    St Antonius Hospital, Netherlands.
    Tantry, Udaya S.
    Sinai Centre Thrombosis Research, MD 21215 USA.
    ten Berg, Jurrien M.
    St Antonius Hospital, Netherlands.
    Angiolillo, Dominick J.
    University of Florida, FL USA.
    James, Stefan
    Uppsala University, Sweden.
    Lindahl, Tomas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk kemi.
    Svensson, Peter
    Lund University, Sweden.
    Jakubowski, Joseph A.
    Eli Lilly and Co, IN 46285 USA.
    Brown, Patricia B.
    Eli Lilly and Co, IN 46285 USA.
    Duvvuru, Suman
    Eli Lilly and Co, IN 46285 USA.
    Sundseth, Scott
    Cabernet Pharmaceut, NC USA.
    Walker, Joseph R.
    Daiichi Sankyo Pharma Dev, NJ USA.
    Small, David
    Eli Lilly and Co, IN 46285 USA.
    Moser, Brian A.
    Eli Lilly and Co, IN 46285 USA.
    Winters, Kenneth J.
    Eli Lilly and Co, IN 46285 USA.
    Erlinge, David
    Lund University, Sweden.
    The effect of CYP2C19 gene polymorphisms on the pharmacokinetics and pharmacodynamics of prasugrel 5-mg, prasugrel 10-mg and clopidogrel 75-mg in patients with coronary artery disease2014Inngår i: Thrombosis and Haemostasis, ISSN 0340-6245, Vol. 112, nr 3, s. 589-597Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    CYP2C19 genotype has been shown to impact response to clopidogrel 75-mg but not prasugrel 10-mg. Here, we assessed effects of CYP2C19 metaboliser status on pharmacokinetics (PK) and pharmacodynamic (PD) responses to prasugrel 5-mg and 10-mg and clopidogrel 75-mg using data from two PK/PD studies in stable coronary artery disease (CAD) patients (GENERATIONS and FEATHER). Active metabolite concentrations (area under the curve, AUC([0-tlast])), maximum platelet aggregation (MPA) measured by light transmission aggregometry, vasodilator-stimulated phosphoprotein platelet reactivity index, and VerifyNow P2Y12-platelet reaction units (VN-PRU) were analysed by CYP2C19-predicted phenotype (extensive metaboliser [EM; N=154], *2-*8 non-carriers, vs reduced metaboliser [RM; N=41],*2-*8 carriers/*17 non-carriers). AUC((0-tlast)) was unaffected by metaboliser status for prasugrel 5-mg and 10-mg (geometric mean EM/RM ratios 1.00, 95% confidence interval [Cl]: 0.86,1.17, pgreater than0.99; and 0.97, 95% CI:0.85,1.12, p=0.71, respectively), but was lower among RMs receiving clopidogrel 75-mg (1.37, 95% CI:1.14,1.65, pless than0.001). Platelet reactivity was not significantly affected by CYP2C19 metaboliser status for prasugrel 5-mg, or for prasugrel 10-mg by MPA and VN-PRU, but for clopidogrel 75-mg was significantly higher in reduced metabolisers (all measures pless than0.01). Prasugrel 10-mg showed greater antiplatelet effects vs clopidogrel 75-mg (all comparisons pless than0.001). Prasugrel 5-mg showed greater antiplatelet effects vs clopidogrel 75-mg in RMs (all pless than0.001), and comparable effects in EMs (all p greater than= 0.37). In contrast to clopidogrel, prasugrel active metabolite PK was not influenced by CYP2C19 genotype. Antiplatelet effect for prasugrel 10-mg was greater irrespective of metaboliser status and for prasugrel 5-mg was greater for RMs and comparable for EMs as compared to clopidogrel 75-mg.

    Fulltekst (pdf)
    fulltext
  • 197.
    Gustafsson, Mika
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Bioinformatik. Linköpings universitet, Tekniska fakulteten.
    Gawel, Danuta
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten.
    Alfredsson, Lars
    Karolinska Institute, Sweden.
    Baranzini, Sergio
    University of Calif San Francisco, CA, USA.
    Bjorkander, Janne
    County Council Jonköping, Sweden.
    Blomgran, Robert
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Hellberg, Sandra
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Eklund, Daniel
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Ernerudh, Jan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    Kockum, Ingrid
    Karolinska Institute, Sweden; Centre Molecular Med, Sweden.
    Konstantinell, Aelita
    Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Arctic University of Norway, Norway.
    Lahesmaa, Riita
    University of Turku, Finland; Abo Akad University, Finland.
    Lentini, Antonio
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten.
    Liljenström, H. Robert I.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten.
    Mattson, Lina
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten.
    Matussek, Andreas
    County Council Jonköping, Sweden.
    Mellergård, Johan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Mendez, Melissa
    University of Peruana Cayetano Heredia, Peru.
    Olsson, Tomas
    Karolinska Institute, Sweden; Centre Molecular Med, Sweden.
    Pujana, Miguel A.
    Catalan Institute Oncol, Spain.
    Rasool, Omid
    University of Turku, Finland; Abo Akad University, Finland.
    Serra-Musach, Jordi
    Catalan Institute Oncol, Spain.
    Stenmarker, Margaretha
    County Council Jonköping, Sweden.
    Tripathi, Subhash
    University of Turku, Finland; Abo Akad University, Finland.
    Viitala, Miro
    University of Turku, Finland; Abo Akad University, Finland.
    Wang, Hui
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. University of Texas MD Anderson Cancer Centre, TX 77030 USA.
    Zhang, Huan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten.
    Nestor, Colm
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten.
    Benson, Mikael
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Allergicentrum US.
    A validated gene regulatory network and GWAS identifies early regulators of T cell-associated diseases2015Inngår i: Science Translational Medicine, ISSN 1946-6234, E-ISSN 1946-6242, Vol. 7, nr 313, artikkel-id 313ra178Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Early regulators of disease may increase understanding of disease mechanisms and serve as markers for presymptomatic diagnosis and treatment. However, early regulators are difficult to identify because patients generally present after they are symptomatic. We hypothesized that early regulators of T cell-associated diseases could be found by identifying upstream transcription factors (TFs) in T cell differentiation and by prioritizing hub TFs that were enriched for disease-associated polymorphisms. A gene regulatory network (GRN) was constructed by time series profiling of the transcriptomes and methylomes of human CD4(+) T cells during in vitro differentiation into four helper T cell lineages, in combination with sequence-based TF binding predictions. The TFs GATA3, MAF, and MYB were identified as early regulators and validated by ChIP-seq (chromatin immunoprecipitation sequencing) and small interfering RNA knockdowns. Differential mRNA expression of the TFs and their targets in T cell-associated diseases supports their clinical relevance. To directly test if the TFs were altered early in disease, T cells from patients with two T cell-mediated diseases, multiple sclerosis and seasonal allergic rhinitis, were analyzed. Strikingly, the TFs were differentially expressed during asymptomatic stages of both diseases, whereas their targets showed altered expression during symptomatic stages. This analytical strategy to identify early regulators of disease by combining GRNs with genome-wide association studies may be generally applicable for functional and clinical studies of early disease development.

    Fulltekst (pdf)
    fulltext
  • 198.
    Gustavsson, O.
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk mikrobiologi. Innlandet Hospital Trust, Norway.
    Johansson, A. V.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Monstein, Hans-Jurg
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk mikrobiologi.
    Nilsson, Lennart E
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Bredberg, A.
    Innlandet Hospital Trust, Norway; Lund University, Sweden.
    A wide spectrum of fastidious and ampicillin-susceptible bacteria dominate in animal-caused wounds2016Inngår i: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 35, nr 8, s. 1315-1321Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The main purpose of this study was to assess the actual occurrence of Gram-negative oxidase-positive bacteria (GNOP) in human wounds caused by animals, mostly cat and dog bites and scratches, and with signs of infection. We report a prospective series of 92 wound samples. Routine culturing was combined with a procedure optimised for fastidious GNOP. All GNOP isolates were identified by 16S rDNA sequencing to the species level. We observed a more prominent role of GNOP, including at least 30 species mostly in the families Flavobacteriaceae, Neisseriaceae and Pasteurellaceae, and less of Staphylococcus aureus and streptococci. The antibiotic susceptibility pattern was investigated, as GNOP are associated with sudden onset of serious infections, making an early decision on antibiotic treatment vital. All GNOP isolates judged to be clinically relevant displayed susceptibility to ampicillin and meropenem, but resistance to oxacillin, clindamycin and gentamicin was frequent. Our findings emphasise the need to cover GNOP as recommended in guidelines, and not only common wound pathogens, when treating an animal-caused wound.

    Fulltekst (pdf)
    fulltext
  • 199.
    Guzzi, Nicola
    et al.
    Lund Univ, Sweden.
    Ciesla, Maciej
    Lund Univ, Sweden.
    Thi Ngoc, Phuong Cao
    Lund Univ, Sweden.
    Lang, Stefan
    Lund Univ, Sweden.
    Arora, Sonali
    Univ Washington, WA 98195 USA.
    Dimitriou, Marios
    Karolinska Inst, Sweden.
    Pimkova, Kristyna
    Lund Univ, Sweden.
    Sommarin, Mikael N. E.
    Lund Univ, Sweden.
    Munita, Roberto
    Lund Univ, Sweden.
    Lubas, Michal
    Univ Copenhagen, Denmark.
    Lim, Yiting
    Univ Washington, WA 98195 USA.
    Okuyama, Kazuki
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Soneji, Shamit
    Lund Univ, Sweden.
    Karlsson, Goran
    Lund Univ, Sweden.
    Hansson, Jenny
    Lund Univ, Sweden.
    Jonsson, Goran
    Lund Univ, Sweden.
    Lund, Anders H.
    Univ Copenhagen, Denmark.
    Sigvardsson, Mikael
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten. Lund Univ, Sweden.
    Hellstrom-Lindberg, Eva
    Karolinska Inst, Sweden.
    Hsieh, Andrew C.
    Univ Washington, WA 98195 USA.
    Bellodi, Cristian
    Lund Univ, Sweden.
    Pseudouridylation of tRNA-Derived Fragments Steers Translational Control in Stem Cells2018Inngår i: Cell, ISSN 0092-8674, E-ISSN 1097-4172, Vol. 173, nr 5, s. 1204-+Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Pseudouridylation (J) is the most abundant and widespread type of RNA epigenetic modification in living organisms; however, the biological role of J remains poorly understood. Here, we show that a J-driven posttranscriptional program steers translation control to impact stem cell commitment during early embryogenesis. Mechanistically, the J "writer PUS7 modifies and activates a novel network of tRNA-derived small fragments (tRFs) targeting the translation initiation complex. PUS7 inactivation in embryonic stem cells impairs tRF-mediated translation regulation, leading to increased protein biosynthesis and defective germ layer specification. Remarkably, dysregulation of this posttranscriptional regulatory circuitry impairs hematopoietic stem cell commitment and is common to aggressive subtypes of human myelodysplastic syndromes. Our findings unveil a critical function of J in directing translation control in stem cells with important implications for development and disease.

  • 200.
    Gyllemark, Paula
    et al.
    Department of Infectious Diseases, Region Jönköping County, Jönköping, Sweden.
    Forsberg, Pia
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Infektionskliniken i Östergötland.
    Ernerudh, Jan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    Henningsson, Anna J.
    Clinical Microbiology, Division of Medical Services, Jönköping, Region Jönköping County, Sweden.
    Intrathecal Th17- and B cell-associated cytokine and chemokine responses in relation to clinical outcome in Lyme neuroborreliosis: a large retrospective study.2017Inngår i: Journal of Neuroinflammation, ISSN 1742-2094, E-ISSN 1742-2094, Vol. 14, nr 1Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: B cell immunity, including the chemokine CXCL13, has an established role in Lyme neuroborreliosis, and also, T helper (Th) 17 immunity, including IL-17A, has recently been implicated.

    METHODS: We analysed a set of cytokines and chemokines associated with B cell and Th17 immunity in cerebrospinal fluid and serum from clinically well-characterized patients with definite Lyme neuroborreliosis (group 1, n = 49), defined by both cerebrospinal fluid pleocytosis and Borrelia-specific antibodies in cerebrospinal fluid and from two groups with possible Lyme neuroborreliosis, showing either pleocytosis (group 2, n = 14) or Borrelia-specific antibodies in cerebrospinal fluid (group 3, n = 14). A non-Lyme neuroborreliosis reference group consisted of 88 patients lacking pleocytosis and Borrelia-specific antibodies in serum and cerebrospinal fluid.

    RESULTS: Cerebrospinal fluid levels of B cell-associated markers (CXCL13, APRIL and BAFF) were significantly elevated in groups 1, 2 and 3 compared with the reference group, except for BAFF, which was not elevated in group 3. Regarding Th17-associated markers (IL-17A, CXCL1 and CCL20), CCL20 in cerebrospinal fluid was significantly elevated in groups 1, 2 and 3 compared with the reference group, while IL-17A and CXCL1 were elevated in group 1. Patients with time of recovery <3 months had lower cerebrospinal fluid levels of IL-17A, APRIL and BAFF compared to patients with recovery >3 months.

    CONCLUSIONS: By using a set of markers in addition to CXCL13 and IL-17A, we confirm that B cell- and Th17-associated immune responses are involved in Lyme neuroborreliosis pathogenesis with different patterns in subgroups. Furthermore, IL-17A, APRIL and BAFF may be associated with time to recovery after treatment.

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