| 1. |
- Brundin, Peik M.A., et al.
(författare)
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Blood hormones and torque teno virus in peripheral blood mononuclear cells
- 2020
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Ingår i: Heliyon. - : Elsevier. - 2405-8440. ; 6:11
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Tidskriftsartikel (refereegranskat)abstract
- Men and women respond differently to infectious diseases. Women show less morbidity and mortality, partially due to the differences in sex hormone levels which can influence the immune response. Torque teno virus (TTV) is non-pathogenic and ubiquitously present in serum from a large proportion (up to 90%) of adult humans with virus levels correlating with the status of the host immune response. The source of TTV replication is unknown, but T-lymphocytes have been proposed. In this study we investigated the presence and levels of TTV in peripheral blood mononuclear cells (PBMCs) in premenopausal (pre-MP) women, post-menopausal (post-MP) women, and men, and determined their serum sex hormone levels. Of the examined subjects (n = 27), we found presence of TTV in PMBC from 17.6% pre-MP (n = 17), 25.0% post-MP (n = 4) and 50.0% men (n = 6). The levels of TTV/μg DNA were lower among TTV-positive men and post-MP women compared to pre-MP women. All the positive pre-MP women were either anovulatory, hypothyroid, or both. In addition, the TTV-positive pre-MP women had significantly lower progesterone levels compared to TTV-negative pre-MP women. Although our study was performed on a limited number of subjects, the data suggests that TTV in PBMC is associated with an anovulatory menstrual cycle with low progesterone levels, and possibly with male sex.
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| 2. |
- Capo, Eric, et al.
(författare)
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Oxygen-deficient water zones in the Baltic Sea promote uncharacterized Hg methylating microorganisms in underlying sediments
- 2022
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Ingår i: Limnology and Oceanography. - : Wiley. - 1939-5590 .- 0024-3590. ; 67:1
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Tidskriftsartikel (refereegranskat)abstract
- Human-induced expansion of oxygen-deficient zones can have dramatic impacts on marine systems and its resident biota. One example is the formation of the potent neurotoxic methylmercury (MeHg) that is mediated by microbial methylation of inorganic divalent Hg (HgII) under oxygen-deficient conditions. A negative consequence of the expansion of oxygen-deficient zones could be an increase in MeHg production due to shifts in microbial communities in favor of microorganisms methylating Hg. There is, however, limited knowledge about Hg-methylating microbes, i.e., those carrying hgc genes critical for mediating the process, from marine sediments. Here, we aim to study the presence of hgc genes and transcripts in metagenomes and metatranscriptomes from four surface sediments with contrasting concentrations of oxygen and sulfide in the Baltic Sea. We show that potential Hg methylators differed among sediments depending on redox conditions. Sediments with an oxygenated surface featured hgc-like genes and transcripts predominantly associated with uncultured Desulfobacterota (OalgD group) and Desulfobacterales (including Desulfobacula sp.) while sediments with a hypoxic-anoxic surface included hgc-carrying Verrucomicrobia, unclassified Desulfobacterales, Desulfatiglandales, and uncharacterized microbes. Our data suggest that the expansion of oxygen-deficient zones in marine systems may lead to a compositional change of Hg-methylating microbial groups in the sediments, where Hg methylators whose metabolism and biology have not yet been characterized will be promoted and expand.
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| 3. |
- Gio-Batta, Monica, et al.
(författare)
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Low Concentration of Fecal Valeric Acid at 1 Year of Age Is Linked with Eczema and Food Allergy at 13 Years of Age : Findings from a Swedish Birth Cohort
- 2022
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Ingår i: International Archives of Allergy and Immunology. - : S. Karger. - 1018-2438 .- 1423-0097. ; , s. 398-408
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Tidskriftsartikel (refereegranskat)abstract
- Background: Short-chain fatty acids (SCFAs) are abundant bacterial metabolites in the gut, with immunomodulatory properties. Hence, they may influence allergy development. Previous studies have linked fecal SCFA pattern during infancy with allergy. However, the association of SCFAs to allergic outcomes in adolescence is not well established. Here, we examined how the fecal SCFA pattern at 1 year of age related to allergy at 13 years of age.Methods: Levels of 8 SCFAs in fecal samples collected at 1 year of age from 110 children were quantified using gas chromatography. The same individuals were evaluated at 13 years of age for allergic symptoms, allergy diagnosis and allergy medication by questionnaire, and for sensitization using skin prick test against egg, milk, fish, wheat and soy, cat, dog, horse, birch, and timothy grass.Results: The concentration of fecal valeric acid at 1 year of age was inversely associated with eczema at 13 years of age (OR 0.6, 95% CI: 0.4-1.0, p = 0.049) and showed a trend for inverse association with food allergy at 13 years of age (OR 0.6, 95% CI: 0.4-1.0, p = 0.057). In a sub-group analysis of children with eczema at 1 year of age, a higher concentration of fecal valeric acid was linked with reduced risk of their eczema remaining at 13 years of age (OR 0.2, 95% CI: 0.0-1.5), although this latter analysis did not reach statistical significance (p = 0.12).Conclusions: Our findings lend further support to the notion of early childhood as a critical period when allergy may be programmed via the gut microbiota. Higher levels of fecal valeric acid may be characteristic of a protective gut microbiota and/or actively contribute to protection from eczema and food allergy.
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| 4. |
- Åhlund, Monika K, et al.
(författare)
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Directed screen of Francisella novicida virulence determinants using Drosophila melanogaster
- 2010
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Ingår i: Infection and Immunity. - : ASM International. - 0019-9567 .- 1098-5522. ; 78:7, s. 3118-3128
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Tidskriftsartikel (refereegranskat)abstract
- Francisella tularensis is a highly virulent, facultative intracellular human pathogen whose virulence mechanisms are not well understood. Occasional outbreaks of tularemia and the potential use of F. tularensis as a bioterrorist agent warrant better knowledge about the pathogenicity of this bacterium. Thus far, genome-wide in vivo screens for virulence factors have been performed in mice, all however restricted by the necessity to apply competition-based, negative-selection assays. We wanted to individually evaluate putative virulence determinants suggested by such assays and performed directed screening of 249 F. novicida transposon insertion mutants by using survival of infected fruit flies as a measure of bacterial virulence. Some 20% of the genes tested were required for normal virulence in flies; most of these had not previously been investigated in detail in vitro or in vivo. We further characterized their involvement in bacterial proliferation and pathogenicity in flies and in mouse macrophages. Hierarchical cluster analysis of mutant phenotypes indicated a functional linkage between clustered genes. One cluster grouped all but four genes of the Francisella pathogenicity island and other loci required for intracellular survival. We also identified genes involved in adaptation to oxidative stress and genes which might induce host energy wasting. Several genes related to type IV pilus formation demonstrated hypervirulent mutant phenotypes. Collectively, the data demonstrate that the bacteria in part use similar virulence mechanisms in mammals as in Drosophila melanogaster but that a considerable proportion of the virulence factors active in mammals are dispensable for pathogenicity in the insect model.
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| 5. |
- Schröder, Björn, et al.
(författare)
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Intestinales Mikrobiom und Schleimhautbarriere bei chronisch entzündlichen Darmerkrankungen
- 2021
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Ingår i: Intestinales Mikrobiom und Innere Medizin. - : UNI-MED Verlag AG. - 9783837416053 ; , s. 46-55
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Das intestinale Mikrobiom repräsentiert aktuell eines der Topthemen, die im Fokus der modernen Humanmedizin stehen. Doch erstaunlicherweise gab es bisher im deutschen Sprachraum keine handliche, aktuelle Übersicht zu diesem Thema. Daher werden in diesem Band zunächst Zusammensetzung und Dynamik des humanen intestinalen Mikrobioms erläutert, ehe in weiteren Kapiteln dann die wichtigsten Veränderungen und vor allem die Rolle des Mikrobioms bei zahlreichen Krankheiten wie chronisch entzündlichen Darmerkrankungen, Reizdarmsyndrom, Leber- und Gallenwegs- sowie Autoimmunerkrankungen diskutiert werden. Es folgen der Komplex Ernährung, Adipositas und Diabetes sowie Atherosklerose mit jeweils eigenen Kapiteln. Schließlich gibt es überraschende Beziehungen der Mikrobiota zur Malignomentstehung. Es folgt ein Abschnitt über Antibiotika und deren Rolle bei zum Teil dauerhaften Störungen der intestinalen Bakterien und Pilze. Am Ende des Buches wird am Beispiel von Mikrobiomtransfer ("Stuhltransplantation") und Probiotika auf die therapeutischen Konsequenzen eingegangen. Alle Kapitel sind auch für sich lesbar und verständlich.
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| 6. |
- Wilms, Torben, 1973-
(författare)
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Squamous cell carcinoma of the head and neck, focusing on Epstein-Barr-virus, programmed cell death ligand 1 and serum lipoproteins
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Squamous cell carcinoma of the head and neck (SCCHN)comprises a large group of tumours including the oral cavity and nasopharyngealarea, and typically affects older males in association with alcohol/tobacco usage.Within the oral cavity, the mobile tongue is the most common site for tumourdevelopment. The incidence of squamous cell carcinoma of the oral tongue(SCCOT) is increasing in younger people, which has been suggested to associatewith other than the traditional risk factors for this disease. Two common humanoncogenic viruses, human papillomavirus (HPV) and Epstein-Barr virus (EBV)are connected to certain types of SCCHN, in oropharynx and nasopharynxrespectively. The receptor programmed cell death 1 (PD)-1 and its ligandprogrammed cell death ligand 1 (PD-L1) are particularly relevant in immunecheckpoint control, and elevated levels have been seen in various cancer types. Alink between hyperlipidemia and cancer risk has previously been suggested. Theaim of this thesis was to investigate risk factors and prognostic features forSCCHN, by focusing on EBV, PD-L1 and serum lipoproteins.Materials and methods: Ninety-eight cases of SCCOT and 15 cases of tonsillarsquamous cell carcinoma were examined for the presence of EBV-encodedribonucleic acids (EBERs), EBV deoxyribonucleic acid (DNA) and the proteinEBV-encoded nuclear antigen-1 (EBNA-1), using in situ hybridisation,polymerase chain reaction (PCR) and immunohistochemistry respectively. Onehundred and one cases of SCCOT were examined for expression of PD-L1 intumour and surrounding immune cells using Ventana SP263immunohistochemistry assay and a QuickScore (QS) method. An estimation oftumour-infiltrating immune cells was also performed in 25 of the patients.Circulating levels of PD-L1 were measured using an electrochemiluminescenceassay platform in serum from 30 patients. Finally, serum samples from 106patients and 28 healthy controls were investigated for levels of total cholesterol,low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides andlipoprotein(a).Results: In the first study, using an in situ hybridisation kit no EBER transcriptswere detected. No EBV DNA was identified with PCR analysis, andimmunohistochemistry for EBNA-1 was also negative. In the second study, highertumour cell PD-L1 levels were found in females than males (p = 0.019). Forpatients with low PD-L1 in tumour cells, better survival was shown in males thanfemales (overall survival p = 0.021, disease-free survival p = 0.020). Tumourinfiltrating natural killer (NK) T cells, immature dendritic cells (DCs) and M1macrophages correlated positively with tumour cell PD-L1 (p < 0.05). In the laststudy, the only lipoprotein showing significant difference in concentration iiibetween healthy controls and patients was HDL (p = 0.012). Kaplan-Meiersurvival curves showed that patients with high levels of total cholesterol or LDLhad better survival than patients with normal levels (p = 0.028 and p = 0.007respectively). Adjusting for the effects of age at diagnosis, TNM stage and weightchange, multivariate Cox regression models showed LDL to be an independentprognostic factor for both overall (p = 0.010) and disease-free survival (p =0.018).Conclusion: We excluded EBV as a potential player in SCCOT in both old andyoung patients and highlight the importance of appropriate controls for EBVencoded RNA in-situ hybridization (EBER-ISH) when investigating EBV inhuman diseases. Regarding PD-L1, our data supported the significance of genderon tumour cell PD-L1 expression and demonstrated combined effects of genderand PD-L1 levels on clinical outcome in patients with SCCOT. Data also indicatedthe involvement of specific immune cell types in PD-L1-regulated immuneevasion. Looking at serum lipoproteins, we found high LDL levels to be beneficialfor survival outcome in patients with SCCHN. Furthermore, the use of cholesterollowering medicine for prevention or management of SCCHN needs to be carefullyevaluated.
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| 7. |
- Bray, L., et al.
(författare)
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Children's pictures of COVID-19 and measures to mitigate its spread: An international qualitative study
- 2021
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Ingår i: Health Education Journal. - : SAGE Publications. - 0017-8969 .- 1748-8176. ; 80:7, s. 811-832
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To gain insight into children's health-related knowledge and understanding of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) and COVID-19, and measures adopted to mitigate transmission. Design: A child-centred qualitative creative element embedded in an online mixed-methods survey of children aged 7-12 years. Setting: Children participated in the study in six countries - the UK, Australia, Sweden, Brazil, Spain and Canada. Method: A qualitative creative component, embedded in an online survey, prompted children to draw and label a picture. Children were recruited via their parents using the researchers' professional social media accounts, through known contacts, media and websites from health organisations within each country. Analysis of the form and content of the children's pictures took place. Results: A total of 128 children (mean age 9.2 years) submitted either a hand-drawn (n = 111) or digitally created (n = 17) picture. Four main themes were identified which related to children's health-related knowledge of (1) COVID-19 and how it is transmitted; (2) measures and actions to mitigate transmission; (3) places of safety during the pandemic; and (4) children's role in mitigating COVID-19 transmission. Conclusion: Children's pictures indicated a good understanding of the virus, how it spreads and how to mitigate transmission. Children depicted their actions during the pandemic as protecting themselves, their families and wider society.
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| 8. |
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| 9. |
- Brindefalk, B., et al.
(författare)
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Bacterial composition in Swedish raw drinking water reveals three major interacting ubiquitous metacommunities
- 2022
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Ingår i: Microbiologyopen. - : Wiley. - 2045-8827. ; 11:5
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Tidskriftsartikel (refereegranskat)abstract
- Background Surface raw water used as a source for drinking water production is a critical resource, sensitive to contamination. We conducted a study on Swedish raw water sources, aiming to identify mutually co-occurring metacommunities of bacteria, and environmental factors driving such patterns. Methods The water sources were different regarding nutrient composition, water quality, and climate characteristics, and displayed various degrees of anthropogenic impact. Water inlet samples were collected at six drinking water treatment plants over 3 years, totaling 230 samples. The bacterial communities of DNA sequenced samples (n = 175), obtained by 16S metabarcoding, were analyzed using a joint model for taxa abundance. Results Two major groups of well-defined metacommunities of microorganisms were identified, in addition to a third, less distinct, and taxonomically more diverse group. These three metacommunities showed various associations to the measured environmental data. Predictions for the well-defined metacommunities revealed differing sets of favored metabolic pathways and life strategies. In one community, taxa with methanogenic metabolism were common, while a second community was dominated by taxa with carbohydrate and lipid-focused metabolism. Conclusion The identification of ubiquitous persistent co-occurring bacterial metacommunities in freshwater habitats could potentially facilitate microbial source tracking analysis of contamination issues in freshwater sources.
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| 10. |
- Kraupner, Nadine, et al.
(författare)
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Selective concentrations for trimethoprim resistance in aquatic environments
- 2020
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Ingår i: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 144
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Tidskriftsartikel (refereegranskat)abstract
- Antibiotic resistance presents a serious and still growing threat to human health. Environmental exposure levels required to select for resistance are unknown for most antibiotics. Here, we evaluated different experimental approaches and ways to interpret effect measures, in order to identify what concentration of trimethoprim that are likely to select for resistance in aquatic environments. When grown in complex biofilms, selection for resistant E. coli increased at 100 mu g/L, whereas there was only a non-significant trend with regards to changes in taxonomic composition within the tested range (0-100 mu g/L). Planktonic co-culturing of 149 different E. coli strains isolated from sewage again confirmed selection at 100 mu g/L. Finally, pairwise competition experiments were performed with engineered E. coli strains carrying different trimethoprim resistance genes (dfr) and their sensitive counterparts. While strains with introduced resistance genes grew slower than the sensitive ones at 0 and 10 mu g/L, a significant reduction in cost was found already at 10 mu g/L. Defining lowest effect concentrations by comparing proportion of resistant strains to sensitive ones at the same time point, rather than to their initial ratios, will reflect the advantage a resistance factor can bring, while ignoring exposure-independent fitness costs. As costs are likely to be highly dependent on the specific environmental and genetic contexts, the former approach might be more suitable as a basis for defining exposure limits with the intention to prevent selection for resistance. Based on the present and other studies, we propose that 1 mu g/L would be a reasonably protective exposure limit for trimethoprim in aquatic environments.
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