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1.
  • Abarenkov, Kessy, et al. (författare)
  • Annotating public fungal ITS sequences from the built environment according to the MIxS-Built Environment standard – a report from a May 23-24, 2016 workshop (Gothenburg, Sweden)
  • 2016
  • Ingår i: MycoKeys. - : Pensoft Publishers. - 1314-4057 .- 1314-4049. ; 16, s. 1-15
  • Tidskriftsartikel (refereegranskat)abstract
    • Recent molecular studies have identified substantial fungal diversity in indoor environments. Fungi and fungal particles have been linked to a range of potentially unwanted effects in the built environment, including asthma, decay of building materials, and food spoilage. The study of the built mycobiome is hampered by a number of constraints, one of which is the poor state of the metadata annotation of fungal DNA sequences from the built environment in public databases. In order to enable precise interrogation of such data – for example, “retrieve all fungal sequences recovered from bathrooms” – a workshop was organized at the University of Gothenburg (May 23-24, 2016) to annotate public fungal barcode (ITS) sequences according to the MIxS-Built Environment annotation standard (http://gensc.org/mixs/). The 36 participants assembled a total of 45,488 data points from the published literature, including the addition of 8,430 instances of countries of collection from a total of 83 countries, 5,801 instances of building types, and 3,876 instances of surface-air contaminants. The results were implemented in the UNITE database for molecular identification of fungi (http://unite.ut.ee) and were shared with other online resources. Data obtained from human/animal pathogenic fungi will furthermore be verified on culture based metadata for subsequent inclusion in the ISHAM-ITS database (http://its.mycologylab.org).
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2.
  • Kulma, Katarzyna, et al. (författare)
  • Malaria-infected female collared flycatchers (Ficedula albicollis) do not pay the cost of late breeding
  • 2014
  • Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:1, s. e85822-
  • Tidskriftsartikel (refereegranskat)abstract
    • Life-history theory predicts that the trade-off between parasite defense and other costly traits such as reproduction may be most evident when resources are scarce. The strength of selection that parasites inflict on their host may therefore vary across environmental conditions. Collared flycatchers (Ficedula albicollis) breeding on the Swedish island Oland experience a seasonal decline in their preferred food resource, which opens the possibility to test the strength of life-history trade-offs across environmental conditions. We used nested-PCR and quantitative-PCR protocols to investigate the association of Haemosporidia infection with reproductive performance of collared flycatcher females in relation to a seasonal change in the external environment. We show that despite no difference in mean onset of breeding, infected females produced relatively more of their fledglings late in the season. This pattern was also upheld when considering only the most common malaria lineage (hPHSIB1), however there was no apparent link between the reproductive output and the intensity of infection. Infected females produced heavier-than-average fledglings with higher-than-expected recruitment success late in the season. This reversal of the typical seasonal trend in reproductive output compensated them for lower fledging and recruitment rates compared to uninfected birds earlier in the season. Thus, despite different seasonal patterns of reproductive performance the overall number of recruits was the same for infected versus uninfected birds. A possible explanation for our results is that infected females breed in a different microhabitat where food availability is higher late in the season but also is the risk of infection. Thus, our results suggest that another trade-off than the one we aimed to test is more important for explaining variation in reproductive performance in this natural population: female flycatchers appear to face a trade-off between the risk of infection and reproductive success late in the season.
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3.
  • Nandakumar, Mridula (författare)
  • Pathogen-mediated selection in the immune system of rodents : Exploring selection targets, functional effects and trade-offs
  • 2024
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Pathogens cause disease and play an important role in shaping evolution of the host immune system. They create pressure on host immunity to evolve in numerous ways, most commonly by increasing divergence between species (positive selection) or increasing polymorphisms within a population (balancing selection). Especially with balancing selection, trade-offs between different traits, for example responses to different pathogens, are essential. Across five papers, questions related to what immune genes are under selection, how this translates to an effect on the immune response and what trade-offs occur, are addressed using rodents as study system. Paper I utilised genomes from 30 rodent species to identify signatures of positive selection in immune genes. In general, function of immune genes was a significant determinant for signs of positive selection. This effect was significant even after accounting for potential confounding factors like gene expression and protein-protein interactions. In Paper II, the focus is on a local population of bank voles in Sweden, to look for signatures of balancing selection in the complement system – a branch of innate immunity. One complement gene, FCNA, was found to be under strong balancing selection. In Paper III, FCNA polymorphism was linked to associations with natural infections of Borrelia afzelii, a common pathogen for bank voles. Papers IV and V look at how the immune response of bank voles of various genotypes differ on stimulation with B. afzelii and the human pathogen Streptococcus pyogenes, captured with transcriptome sequencing of spleen cells. In Paper IV, the analysis is focused on various genotypes of TLR2, an immune gene under balancing selection in bank voles and associated with infection prevalence of B. afzelii in the wild. A stimulation-specific effect of TLR2 on immune response was found, where the magnitude of immune response to B. afzelii, but not S. pyogenes, depends on TLR2 expression level in a TLR2 genotype-specific way. In Paper V, tradeoffs at the cis-regulatory level between the response to B. afzelii and S. pyogenes was tested by searching for polymorphisms where the alleles are expressed differently to these two stimulations. Abundant cis-regulatory variation for responses to the two bacteria was found, but there was no evidence for trade-offs. In summary, this work pushes our knowledge of what immune genes can be expected to be under pathogen-mediated selection, as heretofore understudied categories of immune function showed signs of selection. A novel basis – the combination of genotype and expression – was uncovered for functional effects of polymorphic genes. Finally, there was no evidence for trade-offs between responses to different pathogens. Investigating the nature of trade-offs in the immune system further would be necessary towards understanding the causes and consequences of pathogen-mediated selection.
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4.
  • Razaghi, Ali, et al. (författare)
  • Effects of nitrogen on growth and carbohydrate formation in Porphyridium cruentum
  • 2014
  • Ingår i: Central European Journal of Biology. - : Walter de Gruyter GmbH. - 1895-104X .- 1644-3632. ; 9:2, s. 156-162
  • Tidskriftsartikel (refereegranskat)abstract
    • The microalga Porphyridium cruentum (Rhodophyta) has several industrial and pharmaceutical uses, especially for its polysaccharide production. This study aimed to investigate the influence of nitrogen levels as reflected by altered N:P ratios on the production and content of biomass and carbohydrate. N:P molar ratios were altered in batch cultures to range from 1.6 to 50 using the Redfield ratio of 1:16 as reference. Algal growth (estimated as final cell number, biomass concentration and maximum specific growth rate) was negatively affected at low N:P ratios. The optimal N:P ratio for growth was identified at 35-50, with specific growth rates of 0.19 day(-1) and maximum cell concentrations of 59 center dot 10(8) cells L-1 and 1.2 g dry weight of biomass L-1. In addition, variation in cell size was seen. Cells with larger diameters were at higher N:P ratios and smaller cells at lower ratios. The cellular carbohydrate content increased under reduced nitrogen availability. However, because accumulation was moderate at the lowest N:P ratio, 0.4 g per g dry weight biomass compared to 0.24 at the Redfield ratio of 16:1, conditions for increased total carbohydrate formation were identified at the N:P ratios optimal for growth. Additionally, carbohydrates were largely accumulated in late exponential to stationary phase.
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5.
  • Gräns, Albin, 1979, et al. (författare)
  • Behavioural fever boosts the inflammatory response in rainbow trout Oncorhynchus mykiss
  • 2012
  • Ingår i: Journal of Fish Biology. - : Wiley. - 1095-8649 .- 0022-1112. ; 81:3, s. 1111-1117
  • Tidskriftsartikel (refereegranskat)abstract
    • Behavioural fever, manifested as an increased preferred temperature, was shown in rainbow trout Oncorhynchus mykiss following an injection of bacterial lipopolysaccharide. Simulated behavioural fever, through a 2·5° C water temperature rise following bacterial lipopolysaccharide injection, enhanced the expression of the cytokine interleukin-1β, in comparison with an untreated group held at the initial temperature. The present findings show that an important mediator in the immune response can be boosted through behavioural fever in fishes.
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6.
  • Valanne, Susanna, et al. (författare)
  • Genome-Wide RNA Interference in Drosophila Cells Identifies G Protein-Coupled Receptor Kinase 2 as a Conserved Regulator of NF-kappa B Signaling
  • 2010
  • Ingår i: Journal of Immunology. - : The American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 184:11, s. 6188-6198
  • Tidskriftsartikel (refereegranskat)abstract
    • Because NF-kappa B signaling pathways are highly conserved in evolution, the fruit fly Drosophila melanogaster provides a good model to study these cascades. We carried out an RNA interference (RNAi)-based genome-wide in vitro reporter assay screen in Drosophila for components of NF-kappa B pathways. We analyzed 16,025 dsRNA-treatments and identified 10 novel NF-kappa B regulators. Of these, nine dsRNA-treatments affect primarily the Toll pathway. G protein-coupled receptor kinase (Gprk) 2, CG15737/Toll pathway activation mediating protein, and u-shaped were required for normal Drosomycin response in vivo. Interaction studies revealed that Gprk2 interacts with the Drosophila I kappa B homolog Cactus, but is not required in Cactus degradation, indicating a novel mechanism for NF-kappa B regulation. Morpholino silencing of the zebrafish ortholog of Gprk2 in fish embryos caused impaired cytokine expression after Escherichia coli infection, indicating a conserved role in NF-kappa B signaling. Moreover, small interfering RNA silencing of the human ortholog GRK5 in HeLa cells impaired NF-kappa B reporter activity. Gprk2 RNAi flies are susceptible to infection with Enterococcus faecalis and Gprk2 RNAi rescues Toll(10b)-induced blood cell activation in Drosophila larvae in vivo. We conclude that Gprk2/GRK5 has an evolutionarily conserved role in regulating NF-kappa B signaling. The Journal of Immunology, 2010, 184: 6188-6198.
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7.
  • Guerra, Lina, et al. (författare)
  • The biology of the cytolethal distending toxins
  • 2011
  • Ingår i: Toxins. - : MDPI. - 2072-6651 .- 2072-6651. ; 3:3, s. 172-190
  • Forskningsöversikt (refereegranskat)abstract
    • The cytolethal distending toxins (CDTs), produced by a variety of Gram-negative pathogenic bacteria, are the first bacterial genotoxins described, since they cause DNA damage in the target cells. CDT is an A-B(2) toxin, where the CdtA and CdtC subunits are required to mediate the binding on the surface of the target cells, allowing internalization of the active CdtB subunit, which is functionally homologous to the mammalian deoxyribonuclease I. The nature of the surface receptor is still poorly characterized, however binding of CDT requires intact lipid rafts, and its internalization occurs via dynamin-dependent endocytosis. The toxin is retrograde transported through the Golgi complex and the endoplasmic reticulum, and subsequently translocated into the nuclear compartment, where it exerts the toxic activity. Cellular intoxication induces DNA damage and activation of the DNA damage responses, which results in arrest of the target cells in the G1 and/or G2 phases of the cell cycle and activation of DNA repair mechanisms. Cells that fail to repair the damage will senesce or undergo apoptosis. This review will focus on the well-characterized aspects of the CDT biology and discuss the questions that still remain unanswered.
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8.
  • Guidi, Riccardo, et al. (författare)
  • Chronic exposure to the cytolethal distending toxins of Gram-negative bacteria promotes genomic instability and altered DNA damage response
  • 2013
  • Ingår i: Cellular Microbiology. - : John Wiley & Sons. - 1462-5814 .- 1462-5822. ; 15:1, s. 98-113
  • Tidskriftsartikel (refereegranskat)abstract
    • Epidemiological evidence links chronic bacterial infections to the increased incidence of certain types of cancer but the molecular mechanisms by which bacteria contribute to tumour initiation and progression are still poorly characterized. Here we show that chronic exposure to the genotoxin cytolethal distending toxin (CDT) of Gram-negative bacteria promotes genomic instability and acquisition of phenotypic properties of malignancy in fibroblasts and colon epithelial cells. Cells grown for more than 30 weeks in the presence of sublethal doses of CDT showed increased mutation frequency, and accumulation of chromatin and chromosomal aberrations in the absence of significant alterations of cell cycle distribution, decreased viability or senescence. Cell survival was dependent on sustained activity of the p38 MAP kinase. The ongoing genomic instability was associated with impaired activation of the DNA damage response and failure to efficiently activate cell cycle checkpoints upon exposure to genotoxic stress. Independently selected sublines showed enhanced anchorage-independent growth as assessed by the formation of colonies in semisolid agarose. These findings support the notion that chronic infection by CDT-producing bacteria may promote malignant transformation, and point to the impairment of cellular control mechanisms associated with the detection and repair of DNA damage as critical events in the process.
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9.
  • Karawita, Anjana C., et al. (författare)
  • The swan genome and transcriptome, it is not all black and white
  • 2023
  • Ingår i: Genome Biology. - : BioMed Central (BMC). - 1465-6906 .- 1474-760X. ; 24:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundThe Australian black swan (Cygnus atratus) is an iconic species with contrasting plumage to that of the closely related northern hemisphere white swans. The relative geographic isolation of the black swan may have resulted in a limited immune repertoire and increased susceptibility to infectious diseases, notably infectious diseases from which Australia has been largely shielded. Unlike mallard ducks and the mute swan (Cygnus olor), the black swan is extremely sensitive to highly pathogenic avian influenza. Understanding this susceptibility has been impaired by the absence of any available swan genome and transcriptome information.ResultsHere, we generate the first chromosome-length black and mute swan genomes annotated with transcriptome data, all using long-read based pipelines generated for vertebrate species. We use these genomes and transcriptomes to show that unlike other wild waterfowl, black swans lack an expanded immune gene repertoire, lack a key viral pattern-recognition receptor in endothelial cells and mount a poorly controlled inflammatory response to highly pathogenic avian influenza. We also implicate genetic differences in SLC45A2 gene in the iconic plumage of the black swan.ConclusionTogether, these data suggest that the immune system of the black swan is such that should any avian viral infection become established in its native habitat, the black swan would be in a significant peril.
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10.
  • Lesch, Christine, et al. (författare)
  • A role for Hemolectin in coagulation and immunity in Drosophila melanogaster
  • 2007
  • Ingår i: Developmental and Comparative Immunology. - : Elsevier BV. - 0145-305X .- 1879-0089. ; 31:12, s. 1255-1263
  • Tidskriftsartikel (refereegranskat)abstract
    • Hemolectin has been identified as a candidate clotting factor in Drosophila. We reassessed the domain structure of Hemolectin (Hml) and propose that instead of C-type lectin domains, the two discoidin domains are most likely responsible for the protein's lectin activity. We also tested Hml's role in coagulation and immunity in Drosophila. Here we describe the isolation of a new hml allele in a forward screen for coagulation mutants, and our characterization of this and two other hml alleles, one of which is a functional null. While loss of Hml had strong effects on larval hemolymph coagulation ex vivo, mutant larvae survived wounding. Drosophila thus possesses redundant hemostatic mechanisms. We also found that loss of Hml in immune-handicapped adults rendered them more sensitive to Gram(-) bacteria infection. This demonstrates an immunological role of this clotting protein and reinforces the importance of the clot in insect immunity.
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11.
  • Mamontov, Eugen, 1955 (författare)
  • Homeorhesis and evolutionary properties of living systems: From ordinary differential equations to the active-particle generalized kinetics theory
  • 2006
  • Ingår i: 10th Evolutionary Biology Meeting at Marseilles, 20-22 September 2006, Marseilles, France.
  • Konferensbidrag (refereegranskat)abstract
    • Advanced generalized-kinetic-theory (GKT) models for biological systems are developed for populations of active (or living) particles [1]-[5]. These particles are described with both the stochastic variables common in kinetic theory (such as time, the particle random location and velocity) and the stochastic variables related to the internal states of an active particle. Evolution of these states represents biological, ecological, or social properties of the particle behavior. Paper [6] analyzes a number of the well-known statistical-mechanics approaches and shows that the active-particle GKT (APGKT) is the only treatment capable of modelling living systems. Work [2] summarizes the significance of the notion of an active particle in kinetic models. This notion draws attention to the features distinguishing living matter from nonliving matter. They are discussed by many authors (e.g., [7]-[15], [1]-[3], [6], [16]-[18]). Work [11] considers a lot of differences between living and nonliving matters, and the limitations of the modelling approaches developed for nonliving matter. Work [6] mainly focuses on the comparison of a few theoretical mechanics treatments in terms of the key living-matter properties formulated in [15]. One of the necessary properties of the evolution of living systems is homeorhesis. It is, loosely speaking, a peculiar qualitative and quantitative insensitivity of a living system to the exogenous signals acting on it. The earlier notion, homeostasis, was introduced by W. B. Cannon in 1926 who discussed the phenomenon in detail later [7]. Homeorhesis introduced by C. H. Waddington [8, p. 32] generalizes homeostasis and is well known in biology [8], [9], [12]. It is an inherent part of mathematical models for oncogeny (e.g., [16]-[18], [6, Appendix]). Homeorhesis is also discussed in [3, Section 4] in connection with APGKT. Homeorhesis is documented in ecology (e.g., [11], [13, the left column on p. 675]) where it is one of the key notions of the strong Gaia theory, a version of the Gaia theory (e.g., [14, Chapter 8]). The strong Gaia theory “states that the planet with its life, a single living system, is regulated in certain aspects by that life” [14, p. 124]. The very origin of the name “Gaia” is related to homeorhesis or homeostasis [14, p. 118]. These notions are also used in psychology and sociology. If evolution of a system is not homeorhetic, the system can not be living. Work [6, Appendix] derives a preliminary mathematical formulation of homeorhesis in terms of the simplest dynamical systems, i.e. ordinary differential equations (ODEs). The present work complements, extended, and further specify the approach of [6, Appendix]. The work comprises the two main parts. The first part develops the sufficient conditions for ODE systems to describe homeorhesis, and suggests a fairly general structure of the ODE model. It regards homeorhesis as piecewise homeostasis. The model can be specified in different ways depending on specific systems and specific purposes of the analysis. An example of the specification is also noted (the PhasTraM nonlinear reaction-diffusion model for hyperplastic oncogeny [16]-[18]). The second part of the work discusses implementation of the above homeorhesis ODE model in terms of a special version [3] of APGKT (see above). The key feature of this version is that the components of a living population need not be discrete: the subdivision into the components is described with a general, continuous-discrete probability distribution (see also [6]). This enables certain properties of living matter noted in [15]. Moreover, the corresponding APGKT model presents a system of, firstly, a generalized kinetic equation for the conditional distribution function conditioned by the internal states of the population and, secondly, Ito's stochastic differential equations for these states. This treatement employs the results on nonstationary invariant diffusion stochastic processes [19]. The second part of the work also stresses that APGKT is substantially more important for the living-matter analysis than in the case of nonliving matter. One of the reasons is certain limitations in experimental sampling of the living-system modes presented with stochastic processes. A few directions for future research are suggested as well. REFERENCES: [1] Bellomo, N., Bellouquid, A. and Delitala, M., 2004, Mathematical topics on the modelling complex multicellular systems and tumor immune cells competition, Math. Models Methods Appl. Sci., 14, 1683-1733. [2] Bellomo, N., 2006, New hot Paper Comments, Essential Science Indicators, http://www.esi-topics.com/nhp/2006 /may- 06-NicolaBellomo.html. [3] Willander, M., Mamontov, E. and Chiragwandi, Z., 2004, Modelling living fluids with the subdivision into the components in terms of probability distributions, Math. Models Methods Appl. Sci. 14, 1495-1520. [4] Bellomo, N. and Maini, P.K., 2005, Preface and the Special Issue “Multiscale Cancer Modelling-A New Frontier in Applied Mathematics”, Math. Models Methods Appl. Sci., 15, iii-viii. [5] De Angelis, E. and Delitala, M., 2006, Modelling complex systems in applied sciences: Methods and tools of the mathematical kinetic theory for active particles. Mathl Comput. Modelling, 43, 1310-1328. [6] Mamontov, E., Psiuk-Maksymowicz, K. and Koptioug, A., 2006, Stochastic mechanics in the context of the properties of living systems, Mathl Comput. Modelling, Article in Press, 13 pp. [7] Cannon, W.B., 1932, The Wisdom of the Body (New York: Norton). [8] Waddington, C.H., 1957, The Strategy of the Genes. A Discussion of Some Aspects of Theoretical Biology (London, George Allen and Unwin). [9] Waddington, C.H., 1968, Towards a theoretical biology, Nature, 218, 525-527. [10] Cotnoir, P.-A., 1981, La compétence environnementale: Une affaire d’adaptation. Séminaire en écologie behaviorale, Univeristé du Québec, Montralé. Available online at: http://pac.cam.org/culture.doc . [11] O’Neill, R.V., DeAngelis, D.L., Waide, J.B. and Allen, T.F.H., 1986, A Hierarchical Concept of Ecosystems, Princeton: Princeton Univ. Press). [12] Sauvant, D., 1992, La modélisation systémique en nutrition, Reprod. Nutr. Dev., 32, 217-230. [13] Christensen, N.L., Bartuska, A.M., Brown, J.H., Carpenter, S., D'Antonio, C., Francis, R., Franklin, J.F., MacMahon, J.A., Noss, R.F., Parsons, D.J., Peterson, C.H., Turner, M.G. and Woodmansee, R.G., 1996, The Report of the Ecological Society of America Committee on the Scientific Basis for Ecosystem Management, Ecological Applications, 6, 665-691. Available online at: http://www.esa.org/pao/esaPositions/Papers/ReportOfSBEM.php. [14] Margulis, L., 1998, Symbiotic Planet. A New Look at Evolution (Amherst: Sciencewriters). [15] Hartwell, L.H., Hopfield, J.J., Leibler, S. and Murray, A.W., 1999, From molecular to modular cell biology, Nature, 402, C47-C52. [16] Mamontov, E., Koptioug, A.V. and Psiuk-Maksymowicz, K., 2006, The minimal, phase-transition model for the cell- number maintenance by the hyperplasia-extended homeorhesis, Acta Biotheoretica, 54, 44 pp., (no. 2, May-June, accepted). [17] Psiuk-Maksymowicz, K. and Mamontov, E., 2005, The time-slices method for rapid solving the Cauchy problem for nonlinear reaction-diffusion equations in the competition of homeorhesis with genotoxically activated hyperplasia, In: European Conference on Mathematical and Theoretical Biology - ECMTB05 (July 18-22, 2005) Book of Abstracts, Vol.1 (Dresden: Center for Information Services and High Performance Computing, Dresden Univ. Technol.), p. 429 (http://www.ecmtb05.org/). [18] Psiuk-Maksymowicz, K. and Mamontov, E., 2006, The homeorhesis-based modelling and fast numerical analysis for oncogenic hyperplasia under radiation therapy, submitted. [19] Mamontov, E., 2005, Nonstationary invariant distributions and the hydrodynamic-style generalization of the Kolmogorov-forward/Fokker-Planck equation, Appl. Math. Lett. 18 (9) 976-982.
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13.
  • Hildebrandt, Franziska, 1994- (författare)
  • Host-parasite interactions in space and time
  • 2023
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Unicellular parasites of the apicomplexan phylum have a considerable effect on global health and agriculture. Two prominent examples of this phylum include malaria causing parasites of the Plasmodium genus and the widely prevalent parasite Toxoplasma gondii. While sharing a common ancestor, these parasites occupy unique biological niches, follow distinct life cycles, and result in different courses and outcomes of disease. In response to the parasite, the mammalian host has developed efficient and effective defense strategies. However, both Plasmodium and Toxoplasma have evolved strategies to evade the host’s defense response. Plasmodium parasites infect distinct tissues and cell types whereas T. gondii parasites are highly promiscuous and infect all nucleated cells. The identification of key factors involved in the interaction between the host and parasite is crucial for disease intervention, prevention, and eventually eradication efforts.Next-generation sequencing technologies have proven effective tools to investigate the response in a tissue or cell population of an infected organism. Novel genomics methods such as single-cell RNA-seq and spatial transcriptomics have enabled the investigation of heterogeneous transcriptional responses of individual cells in a population as well as heterogeneous expression profiles at spatially distinct tissue positions across entire tissue sections. This thesis pioneers the exploration of these methods in discerning the enormous complexity underlying host-parasite interplay.In Paper I, we determine spatial components of naive mouse liver in its true tissue context. We define gene expression gradients of pericentral and periportal zones in the liver and predict vein types with ambiguous annotations, based on in situ transcriptional profiles. We further identify novel spatial structures with distinct transcriptional profiles, associated with tissue integrity and integrate cell type proportions across the tissue.In Paper II we investigate host-pathogen interactions in P. berghei infected liver sections with spatiotemporal resolution. We establish spatial gene expression gradients from infection sites exhibiting upregulation of lipid metabolism associated genes 38 hours post-infection, suggesting a potential role of these pathways in immune evasion. We further show that local and systemic inflammation are delayed but not ablated in salivary gland lysate challenged control livers and propose that local inflammatory hotspots may represent an important spatial component for parasite development in the liver.In Paper III we use dual scRNA-seq to investigate heterogeneous transcription of mouse bone marrow-derived dendritic cells (BMDCs) infected with two distinct genotypes of T. gondii parasites. We show differential responses towards the two T. gondii genotypes in two distinct subpopulations of BMDCs over multiple time points post infection. Moreover, we generate co-expression networks that define host and parasite genes, which are likely involved in the modulation of host immunity.In summary, this thesis aims to characterize host-pathogen interactions of two major apicomplexan genera in two distinct cell niches of the murine host with spatiotemporal or single cell resolution. In detail, this encompasses the study of spatial structures of the host in the liver environment and the spatiotemporal consequences of an infection with P. berghei. Furthermore, the aims include deciphering heterogeneous interactions between two distinct T. gondii strains and infected BMDCs.
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14.
  • Mosomtai, Gladys, et al. (författare)
  • Datasets for mapping pastoralist movement patterns and risk zones of Rift Valley fever occurrence
  • 2018
  • Ingår i: Data in Brief. - : Elsevier. - 2352-3409. ; 16, s. 762-770
  • Tidskriftsartikel (refereegranskat)abstract
    • Rift Valley fever (RVF) is a zoonotic disease affecting humans and animals. It is caused by RVF virus transmitted primarily by Aedes mosquitoes. The data presented in this article propose environmental layers suitable for mapping RVF vector habitat zones and livestock migratory routes. Using species distribution modelling, we used RVF vector occurrence data sampled along livestock migratory routes to identify suitable vector habitats within the study region which is located in the central and the north-eastern part of Kenya. Eleven herds monitored with GPS collars were used to estimate cattle utilization distribution patterns. We used kernel density estimator to produce utilization contours where the 0.5 percentile represents core grazing areas and the 0.99 percentile represents the entire home range. The home ranges were overlaid on the vector suitability map to identify risks zones for possible RVF exposure. Assimilating high spatial and temporal livestock movement and vector distribution datasets generates new knowledge in understanding RVF epidemiology and generates spatially explicit risk maps. The results can be used to guide vector control and vaccination strategies for better disease control.
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15.
  • Taheri, Nayyer, et al. (författare)
  • Yersinia pseudotuberculosis Blocks Neutrophil Degranulation
  • 2016
  • Ingår i: Infection and Immunity. - 0019-9567 .- 1098-5522. ; 84:12, s. 3369-3378
  • Tidskriftsartikel (refereegranskat)abstract
    • Neutrophils are essential components of immunity and are rapidly recruited to infected or injured tissue. Upon their activation, neutrophils release granules to the cell's exterior, through a process called degranulation. These granules contain proteins with antimicrobial properties that help combat infection. The enteropathogenic bacterium Yersinia pseudotuberculosis successfully persists as an extracellular bacterium during infection by virtue of its translocation of virulence effectors (Yersinia outer proteins [Yops]) that act in the cytosol of host immune cells to subvert phagocytosis and proinflammatory responses. Here, we investigated the effect of Y. pseudotuberculosis on neutrophil degranulation upon cell contact. We found that virulent Y. pseudotuberculosis was able to prevent secondary granule release. The blocking effect was general, as the release of primary and tertiary granules was also reduced. Degranulation of secondary granules was also blocked in primed neutrophils, suggesting that this mechanism could be an important element of immune evasion. Further, wild-type bacteria conferred a transient block on neutrophils that prevented their degranulation upon contact with plasmid-cured, avirulent Y. pseudotuberculosis and Escherichia coli Detailed analyses showed that the block was strictly dependent on the cooperative actions of the two antiphagocytic effectors, YopE and YopH, suggesting that the neutrophil target structures constituting signaling molecules needed to initiate both phagocytosis and general degranulation. Thus, via these virulence effectors, Yersinia can impair several mechanisms of the neutrophil's antimicrobial arsenal, which underscores the power of its virulence effector machinery.
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16.
  • Anderson, Jenna (författare)
  • Development and evaluation of a subunit DIVA vaccine against bluetongue virus serotype 8 in cattle
  • 2014
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Bluetongue virus (BTV) causes the primarily vector-borne bluetongue disease of ruminants, which poses a permanent threat to Europe since new serotypes and strains are frequently introduced. Vaccination of cattle is essential to control BTV outbreaks. Commercial attenuated and inactivated vaccines are efficacious in reducing BTV spread and disease, but do not fulfil all safety, adaptability, or production requirements. Additionally, no current vaccines allow the differentiation of infected from vaccinated animals (DIVA). DIVA vaccines enable surveillance of BTV epidemiology and vaccine efficacy, and facilitate a quick return for countries to a BTV-free status. This thesis presents the development and evaluation of a novel subunit DIVA vaccine against BTV serotype 8 (BTV-8) in cattle. Five His-tagged recombinant BTV proteins (VP2, VP5 of BTV-8; NS1, NS2, NS3 of BTV-2) were produced in baculovirus or E. coli expression systems. Purification protocols were optimized for all but VP5. Based on the feasibility of protein production and the capability of the remaining four proteins to induce humoral or cellular immune responses in mice, VP2, NS1, and NS2 were selected to formulate an experimental vaccine combined to an ISCOM-matrix adjuvant (SubV). Next, cattle were immunized twice at a three-week interval with SubV, a commercial inactivated vaccine, or a placebo. SubV induced humoral immune responses, including virus-neutralizing antibodies, against all three proteins, as well as a cellular immune response directed against NS1. These responses were of similar type and comparable magnitude between both vaccines, suggesting that SubV might provide protection that is at least as effective as the commercial vaccine. Finally, the protective efficacy of SubV was evaluated and complete virological and clinical protection against virulent BTV-8 challenge was observed following vaccination in calves. This was likely due to the induction of virus-neutralizing antibodies directed against VP2 of BTV-8 and cross-serotype T cell responses directed against NS1 and NS2 of BTV-2. Furthermore, SubV was shown to be DIVA-compliant based on the detection of antibodies directed against VP7, by using commercially-available diagnostic assays. This novel BTV subunit vaccine is a promising candidate and should be further developed.
  •  
17.
  • Gorreja, Frida, et al. (författare)
  • The potential role of adherence factors in probiotic function in the gastrointestinal tract of adults and pediatrics: a narrative review of experimental and human studies.
  • 2022
  • Ingår i: Gut microbes. - : Informa UK Limited. - 1949-0984 .- 1949-0976. ; 14:1
  • Forskningsöversikt (refereegranskat)abstract
    • Numerous studies point to the important role of probiotic bacteria in gastrointestinal health. Probiotics act through mechanisms affecting enteric pathogens, epithelial barrier function, immune signaling, and conditioning of indigenous microbiota. Once administered, probiotics reach the gastrointestinal tract and interact with the host through bacterial surface molecules, here called adhesion factors, which are either strain- or specie-specific. Probiotic adhesion, through structural adhesion factors, is a mechanism that facilitates persistence within the gastrointestinal tract and triggers the initial host responses. Thus, an understanding of specific probiotic adhesion mechanisms could predict how specific probiotic strains elicit benefits and the potential of adherence factors as a proxy to predict probiotic function. This review summarizes the present understanding of probiotic adherence in the gastrointestinal tract. It highlights the bacterial adhesion structure types, their molecular communication with the host and the consequent impact on intestinal diseases in both adult and pediatric populations. Finally, we discuss knockout/isolation studies as direct evidence for adhesion factors conferring anti-inflammatory and pathogen inhibition properties to a probiotic.What is known: Probiotics can be used to treat clinical conditions.Probiotics improve dysbiosis and symptoms.Clinical trials may not confirm in vitro and animal studies.What is new: Adhesion structures may be important for probiotic function.Need to systematically determine physical characteristics of probiotics before selecting for clinical trials.Probiotics may be genetically engineered to add to clinical efficacy.
  •  
18.
  • Gupta, G., et al. (författare)
  • Exploiting Mass Spectrometry to Unlock the Mechanism of Nanoparticle-Induced Inflammasome Activation
  • 2023
  • Ingår i: Acs Nano. - : AMER CHEMICAL SOC. - 1936-0851 .- 1936-086X. ; 17:17, s. 17451-17467
  • Tidskriftsartikel (refereegranskat)abstract
    • Nanoparticles (NPs) elicit sterile inflammation, but the underlying signaling pathways are poorly understood. Here, we report that human monocytes are particularly vulnerable to amorphous silica NPs, as evidenced by single-cell-based analysis of peripheral blood mononuclear cells using cytometry by time-of-flight (CyToF), while silane modification of the NPs mitigated their toxicity. Using human THP-1 cells as a model, we observed cellular internalization of silica NPs by nanoscale secondary ion mass spectrometry (nanoSIMS) and this was confirmed by transmission electron microscopy. Lipid droplet accumulation was also noted in the exposed cells. Furthermore, time-of-flight secondary ion mass spectrometry (ToF-SIMS) revealed specific changes in plasma membrane lipids, including phosphatidylcholine (PC) in silica NP-exposed cells, and subsequent studies suggested that lysophosphatidylcholine (LPC) acts as a cell autonomous signal for inflammasome activation in the absence of priming with a microbial ligand. Moreover, we found that silica NPs elicited NLRP3 inflammasome activation in monocytes, whereas cell death transpired through a non-apoptotic, lipid peroxidation-dependent mechanism. Together, these data further our understanding of the mechanism of sterile inflammation.
  •  
19.
  • Gustafsson, Lars, et al. (författare)
  • Infectious disease, reproductive effort and the cost of reproduction in birds
  • 1994
  • Ingår i: Philosophical transactions of the Royal Society of London: Series B. ; :346, s. 1655-1658
  • Tidskriftsartikel (populärvet., debatt m.m.)abstract
    • Reproductive effort can have profound effects on subsequent performance. Field experiments on the collared flycatcher (Ficedula albicollis) have demonstrated a number of trade-offs between life-history traits at different ages. The mechanism by which reproductive effort is mediated into future reproductive performance remains obscure. Anti-parasite adaptations such as cell-mediated immunity may probably also be costly. Hence the possibility exists of a trade-off between reproductive effort and the ability to resist parasitic infection. Serological tests on unmanipulated collared flycatchers show that pre-breeding nutritional status correlates positively with reproductive success and negatively with susceptibility to parasitism (viruses, bacteria and protozoan parasites). Both immune response and several indicators of infectious disease correlate negatively with reproductive success. Similar relations are found between secondary sexual characters and infection parameters. For brood-size-manipulated birds there was a significant interaction between experimentally increased reproductive effort and parasitic infection rate with regard to both current and future fecundity. It seems possible that the interaction between parasitic infection, nutrition and reproductive effort can be an important mechanism in the ultimate shaping of life-history variation in avian populations.
  •  
20.
  • Agianian, Bogos, et al. (författare)
  • Preliminary characterization of hemolymph coagulation in Anopheles gambiae larvae
  • 2007
  • Ingår i: Developmental and Comparative Immunology. - : Elsevier BV. - 0145-305X .- 1879-0089. ; 31:9, s. 879-888
  • Tidskriftsartikel (refereegranskat)abstract
    • Hemolymph coagulation is a first response to injury, impeding infection, and ending bleeding. Little is known about its molecular basis in insects, but clotting factors have been identified in the fruit fly Drosophila melanogaster. Here, we have begun to study coagulation in the aquatic larvae of the malaria vector mosquito Anopheles gambiae using methods developed for Drosophila. A delicate clot was seen by light microscopy, and pullout and proteomic analysis identified phenoloxidase and apolipophorin-I as major candidate clotting factors. Electron microscopic analysis confirmed clot formation and revealed it contains fine molecular sheets, most likely a result of lipophorin assembly. Phenoloxidase appears to be more critical in clot formation in Anopheles than in Drosophila. The Anopheles larval clot thus differs in formation, structure, and composition from the clot in Drosophila, confirming the need to study coagulation in different insect species to learn more about its evolution and adaptation to different lifestyles.
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21.
  • Andersson, Kristina E., et al. (författare)
  • Wholegrain oat diet changes the expression of genes associated with intestinal bile acid transport
  • 2017
  • Ingår i: Molecular Nutrition and Food Research. - : Wiley. - 1613-4125 .- 1613-4133. ; 61:7
  • Tidskriftsartikel (refereegranskat)abstract
    • Scope: The molecular mechanisms underlying the cholesterol-lowering properties of oats are only partly known. To study possible pathways involved, we investigated gene expressions in the liver and small intestine of mice fed oats. Method and results: Cholesterol and bile acids were analyzed in plasma and feces from LDL-receptor deficient (LDLr-/-) mice fed Western diet with wholegrain oats. A transcriptome analysis of mRNA from liver and jejunum was performed together with quantitative RT-PCR. Oat-fed mice had lower levels of plasma lipids and increased levels of bile acids and cholesterol in feces compared with controls. Two hundred thirty nine genes in jejunum and 25 genes in liver were differentially expressed (FDR corrected p < 0.05). The most affected biological process in jejunum was lipid biosynthesis and regulation. The apical sodium-dependent bile acid transporter (ASBT, Slc10a) and the intracellular bile acid binding protein (Fabp6) were both upregulated, whereas small heterodimer partner-1 (Shp-1) and apolipoprotein CII (Apoc2) were downregulated. Conclusions: Whole oats attenuated responses typically induced by high-fat diet. Increased expression of genes for intestinal bile acid uptake following oat consumption suggests retention in the gut lumen rather than decreased uptake capacity as cause for the increased bile acid excretion and the concomitant reduction of plasma cholesterol.
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22.
  • Boal, Frédéric, et al. (författare)
  • PI5P Triggers ICAM-1 Degradation in Shigella Infected Cells, Thus Dampening Immune Cell Recruitment
  • 2016
  • Ingår i: Cell Reports. - : Cell Press. - 2211-1247. ; 14:4, s. 750-759
  • Tidskriftsartikel (refereegranskat)abstract
    • Shigella flexneri, the pathogen responsible for bacillary dysentery, has evolved multiple strategies to control the inflammatory response. Here, we show that Shigella subverts the subcellular trafficking of the intercellular adhesion molecule-1 (ICAM-1), a key molecule in immune cell recruitment, in a mechanism dependent on the injected bacterial enzyme IpgD and its product, the lipid mediator PI5P. Overexpression of IpgD, but not a phosphatase dead mutant, induced the internalization and the degradation of ICAM-1 in intestinal epithelial cells. Remarkably, addition of permeant PI5P reproduced IpgD effects and led to the inhibition of neutrophil recruitment. Finally, these results were confirmed in an in vivo model of Shigella infection where IpgD-dependent ICAM-1 internalization reduced neutrophil adhesion. In conclusion, we describe here an immune evasion mechanism used by the pathogen Shigella to divert the host cell trafficking machinery in order to reduce immune cell recruitment.
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23.
  • Dantoft, Widad, et al. (författare)
  • The POU/Oct Transcription Factor Pdm1/nub Is Necessary for a Beneficial Gut Microbiota and Normal Lifespan of Drosophila
  • 2016
  • Ingår i: Journal of Innate Immunity. - : S. Karger AG. - 1662-811X .- 1662-8128. ; 8:4, s. 412-426
  • Tidskriftsartikel (refereegranskat)abstract
    • Maintenance of a stable gut microbial community relies on a delicate balance between immune defense and immune tolerance. We have used Drosophila to study how the microbial gut flora is affected by changes in host genetic factors and immunity. Flies with a constitutively active gut immune system, due to a mutation in the POU transcriptional regulator Pdm1/nubbin (nub) gene, had higher loads of bacteria and a more diverse taxonomic composition than controls. In addition, the microbial composition shifted considerably during the short lifespan of the nub1 mutants. This shift was characterized by a loss of relatively few OTUs (operational taxonomic units) and a remarkable increase in a large number of Acetobacter spp. and Leuconostoc spp. Treating nub1 mutant flies with antibiotics prolonged their lifetime survival by more than 100%. Immune gene expression was also persistently high in the presence of antibiotics, indicating that the early death was not a direct consequence of an overactive immune defense but rather an indirect consequence of the microbial load and composition. Thus, changes in host genotype and an inability to regulate the normal growth and composition of the gut microbiota leads to a shift in the microbial community, dysbiosis and early death.
  •  
24.
  • Dziedziech, Alexis, 1991- (författare)
  • Timing Matters : Wounding and entomopathogenic nematode infection kinetics
  • 2021
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Over time, insects have developed complex strategies to defend themselves against presenting threats. However, in the evolutionary arms race of survival, pathogens have adapted to quickly overcome the immune response mounted by the host. In this thesis, we assess how quickly entomopathogenic nematodes (EPNs) can overcome the host, Drosophila melanogaster. We then look at the clotting reaction at a hypothetical point of entry for the nematode and bring resolution to the order of protein interaction focusing on three proteins important in the anti-nematode defense. Finally, we look closer into detail at how crystal cells secrete one of those proteins, prophenoloxidase (PPOII) using a mode of programmed cell death. (Paper I) In the course of EPN infection, little was known about how quickly the worms can overcome the host immune system. Here we found that after penetrating the host, EPNs cause septicemia within 4 to 6 hours. (Paper II) Three proteins, Glutactin (Glt), Transglutaminase (Tg), and PPOII have been found to be important in the anti-nematode response. Here we created GFP-tagged fly constructs to follow their role in clot formation. In early clot formation, Tg was immediately secreted from hemocytes though it was localized around the cell membrane, Glt then entered clot fibers followed by PPOII which acted in late clot formation. (Paper III) Here we looked closer into Tg and PPOII secretion variability. PPOII from immature, but not mature crystal cells colocalized with a membrane marker. Tg, when driven with a pan tissue driver, was found located in clotting fibers, in contrast with paper II. (Paper IV) In an in vivo immune scenario, crystal cells were recruited to the wound site and burst rapidly in a caspase-dependent manner. We demonstrate that the mode of programmed cell death, pyroptosis, exists in Drosophila by way of convergent evolution.This thesis brings to light the variation found within the infection process for EPNs as well as the clotting response based on larval age, tissue type, and the maturity of a single cell type. Timing in each of these immune scenarios can give very different indications about the kind of immune response mounted and even the role of an individual cell.
  •  
25.
  • Nouri, Mehrnaz, et al. (författare)
  • Cross-reactivity of antibody responses to Borrelia afzelii OspC : Asymmetry and host heterogeneity
  • 2021
  • Ingår i: Infection, Genetics and Evolution. - : Elsevier. - 1567-1348 .- 1567-7257. ; 91, s. 1-6
  • Tidskriftsartikel (refereegranskat)abstract
    • The tick-transmitted bacterium Borrelia afzelii consists of a number of antigenically different strains — often defined by outer surface protein C (OspC) genotype — that coexist at stable frequencies in host populations. To investigate how host antibody responses affect strain coexistence, we measured antibody cross-reactivity to three different OspC types (OspC 2, 3 and 9) in three different strains of laboratory mice (BALB/c, C3H and C57BL/6). The extent of cross-reactivity differed between mouse strains, being higher in C3H than BALB/c and C57BL/6. In one of three pairwise comparisons of OspC types (OspC2 vs OspC9), there was evidence for asymmetry of cross- reactivity, with antibodies to OspC2 cross-reacting more strongly with OspC9 than vice versa. These results indicate that the extent of antibody-mediated competition between OspC types may depend on the composition of the host population, and that such competition may be asymmetric. We discuss the implications of these results for understanding the coexistence of OspC types.
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26.
  • Pang, Yanhong, et al. (författare)
  • Extracellular membrane vesicles from Limosilactobacillus reuteri strengthen the intestinal epithelial integrity, modulate cytokine responses and antagonize activation of TRPV1
  • 2022
  • Ingår i: Frontiers in Microbiology. - : Frontiers Media S.A.. - 1664-302X. ; 13
  • Tidskriftsartikel (refereegranskat)abstract
    • Bacterial extracellular membrane vesicles (MV) are potent mediators of microbe-host signals, and they are not only important in host-pathogen interactions but also for the interactions between mutualistic bacteria and their hosts. Studies of MV derived from probiotics could enhance the understanding of these universal signal entities, and here we have studied MV derived from Limosilactobacillus reuteri DSM 17938 and BG-R46. The production of MV increased with cultivation time and after oxygen stress. Mass spectrometry-based proteomics analyses revealed that the MV carried a large number of bacterial cell surface proteins, several predicted to be involved in host-bacteria interactions. A 5 '-nucleotidase, which catalyze the conversion of AMP into the signal molecule adenosine, was one of these and analysis of enzymatic activity showed that L. reuteri BG-R46 derived MV exhibited the highest activity. We also detected the TLR2 activator lipoteichoic acid on the MV. In models for host interactions, we first observed that L. reuteri MV were internalized by Caco-2/HT29-MTX epithelial cells, and in a dose-dependent manner decreased the leakage caused by enterotoxigenic Escherichia coli by up to 65%. Furthermore, the MV upregulated IL-1 beta and IL-6 from peripheral blood mononuclear cells (PBMC), but also dampened IFN-gamma and TNF-alpha responses in PBMC challenged with Staphylococcus aureus. Finally, we showed that MV from the L. reuteri strains have an antagonistic effect on the pain receptor transient receptor potential vanilloid 1 in a model with primary dorsal root ganglion cells from rats. In summary, we have shown that these mobile nanometer scale MV reproduce several biological effects of L. reuteri cells and that the production parameters and selection of strain have an impact on the activity of the MV. This could potentially provide key information for development of innovative and more efficient probiotic products.
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27.
  • Alfredsson, Johannes, et al. (författare)
  • Isobaric labeling-based quantitative proteomics of FACS-purified immune cells and epithelial cells from the intestine of Crohn's disease patients reveals proteome changes of potential importance in disease pathogenesis.
  • 2023
  • Ingår i: Proteomics. - : Wiley. - 1615-9861 .- 1615-9853. ; 23:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Crohn's disease (CD) is a chronic condition characterized by recurrent flares of inflammation in the gastrointestinal tract. Disease etiology is poorly understood and is characterized by dysregulated immune activation that progressively destroys intestinal tissue. Key cellular compartments in disease pathogenesis are the intestinal epithelial layer and its underlying lamina propria. While the epithelium contains predominantly epithelial cells, the lamina propria is enriched in immune cells. Deciphering proteome changes in different cell populations is important to understand CD pathogenesis. Here, using isobaric labeling-based quantitative proteomics, we perform an exploratory study to analyze in-depth proteome changes in epithelial cells, immune cells and stromal cells in CD patients compared to controls using cells purified by FACS. Our study revealed increased proteins associated with neutrophil degranulation and mitochondrial metabolism in immune cells of CD intestinal mucosa. We also found upregulation of proteins involved in glycosylation and secretory pathways in epithelial cells of CD patients, while proteins involved in mitochondrial metabolism were reduced. The distinct alterations in protein levels in immune- versus epithelial cells underscores the utility of proteome analysis of defined cell types. Moreover, our workflow allowing concomitant assessment of cell-type specific changes on an individual basis enables deeper insight into disease pathogenesis.
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28.
  • Andersson, Sören, 1957-, et al. (författare)
  • CHIMERIC MOMP ANTIGEN
  • 2015
  • Patent (populärvet., debatt m.m.)
  •  
29.
  • Andersson, Sören, 1957-, et al. (författare)
  • Chimeric MOMP antigen
  • 2014
  • Patent (populärvet., debatt m.m.)abstract
    • The present invention regards polypeptides capable of eliciting an immunological response that is protective against Chlamydia trachomatis. The polypeptide comprises a first amino acid sequence which has at least 90% homology with the amino acid sequence according to SEQ ID NO: 1 and a second amino acid sequence which has at least 90% homology with the amino acid sequence according to SEQ ID NO: 2. Furthermore, production of these polypeptides and pharmaceutical compositions comprising them are also provided.
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30.
  • Kalbina, Irina, 1961-, et al. (författare)
  • Arabidopsis thaliana plants expressing Rift Valley fever virus antigens : Mice exhibit systemic immune responses as the result of oraladministration of the transgenic plants
  • 2016
  • Ingår i: Protein Expression and Purification. - San Diego, USA : Elsevier. - 1046-5928 .- 1096-0279. ; 127, s. 61-67
  • Tidskriftsartikel (refereegranskat)abstract
    • The zoonotic Rift Valley fever virus affects livestock and humans in Africa and on the Arabian Peninsula.The economic impact of this pathogen due to livestock losses, as well as its relevance to public health,underscores the importance of developing effective and easily distributed vaccines. Vaccines that can bedelivered orally are of particular interest.Here, we report the expression in transformed plants (Arabidopsis thaliana) of Rift Valley fever virusantigens. The antigens used in this study were the N protein and a deletion mutant of the Gn glycoprotein.Transformed lines were analysed for specific mRNA and protein content by RT-PCR and Westernblotting, respectively. Furthermore, the plant-expressed antigens were evaluated for their immunogenicityin mice fed the transgenic plants. After oral intake of fresh transgenic plant material, a proportionof the mice elicited specific IgG antibody responses, as compared to the control animals that were fedwild-type plants and of which none sero-converted.Thus, we show that transgenic plants can be readily used to express and produce Rift Valley Fever virusproteins, and that the plants are immunogenic when given orally to mice. These are promising findingsand provide a basis for further studies on edible plant vaccines against the Rift Valley fever virus.
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31.
  • Skovbjerg, Susann, 1973, et al. (författare)
  • Gram-positive and gram-negative bacteria induce different patterns of cytokine production in human mononuclear cells irrespective of taxonomic relatedness.
  • 2010
  • Ingår i: Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research. - New York, USA : Mary Ann Liebert Inc. - 1557-7465 .- 1079-9907. ; 30:1, s. 23-32
  • Tidskriftsartikel (refereegranskat)abstract
    • Upon bacterial stimulation, tissue macrophages produce a variety of cytokines that orchestrate the immune response that clears the infection. We have shown that Gram-positives induce higher levels of interleukin-12 (IL-12), interferon-gamma (IFN-gamma), and tumor necrosis factor (TNF) from human peripheral blood mononuclear cells (PBMCs) than do Gram-negatives, which instead induce more of IL-6, IL-8, and IL-10. Here, we study whether these patterns follows or crosses taxonomic borders. PBMCs from blood donors were incubated with UV-inactivated bacteria representing 37 species from five phyla. IL-12, TNF, IL-1beta, IL-6, IL-8, and IL-10 were measured in the supernatants after 24 h and IFN-gamma after 5 days. Irrespective of phylogenetic position, Gram-positive bacteria induced much more IL-12 (nine times more on average) and IFN-gamma (seven times), more TNF (three times), and slightly more IL-1beta (1.5 times) than did Gram-negatives, which instead induced more IL-6 (1.5 times), IL-8 (1.9 times), and IL-10 (3.3 times) than did Gram-positives. A notable exception was the Gram-positive Listeria monocytogenes, which induced very little IL-12, IFN-gamma, and TNF. The results confirm the fundamental difference in innate immune responses to Gram-positive and Gram-negative bacteria, which crosses taxonomic borders and probably reflects differences in cell wall structure.
  •  
32.
  • Andersson, Måns Sverker, et al. (författare)
  • Glycosylated haemoglobin: a new measure of condition in birds
  • 1995
  • Ingår i: Proceedings of the Royal Society of London. ; :260, s. 299-303
  • Tidskriftsartikel (refereegranskat)abstract
    • Abstract: The influence of condition on time of breeding and reproductive success has been discussed since Darwin first suggested a relation in 1871. We used a novel method to investigate the influence of condition on the timing of breeding and reproductive success by measuring a relatively inert physiological parameter - the amount of glycosylated haemoglobin - in blood samples taken from the collared flycatcher Ficedula albicollis. The percentage of glycosylated haemoglobin (%HbG) was assumed to be proportional to the average blood glucose level, during the 3-5 weeks before the blood sampling. The %HbG was influenced neither by sex nor age. Date of arrival at the breeding ground was negatively correlated with %HbG so that early-arriving birds had significantly higher %HbG than those arriving later. Clutch size, corrected for the effect of laying date, correlated positively with %HbG in females, as did the number of fledged young, corrected for the effect of laying date, for both sexes. We found no correlation between body mass and the %HbG. We suggest that prebreeding condition influences the timing of breeding and subsequent reproductive performance and that %HbG can be used as an indicator of prebreeding-condition in migrating birds.
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33.
  • Bassères, Eugénie, et al. (författare)
  • The ubiquitin C-terminal hydrolase UCH-L1 promotes bacterial invasion by altering the dynamics of the actin cytoskeleton
  • 2010
  • Ingår i: Cellular Microbiology. - : Wiley-Blackwell. - 1462-5814 .- 1462-5822. ; 12:11, s. 1622-1633
  • Tidskriftsartikel (refereegranskat)abstract
    • Invasion of eukaryotic target cells by pathogenic bacteria requires extensive remodelling of the membrane and actin cytoskeleton. Here we show that the remodelling process is regulated by the ubiquitin C-terminal hydrolase UCH-L1 that promotes the invasion of epithelial cells by Listeria monocytogenes and Salmonella enterica. Knockdown of UCH-L1 reduced the uptake of both bacteria, while expression of the catalytically active enzyme promoted efficient internalization in the UCH-L1-negative HeLa cell line. The entry of L. monocytogenes involves binding to the receptor tyrosine kinase Met, which leads to receptor phosphorylation and ubiquitination. UCH-L1 controls the early membrane-associated events of this triggering cascade since knockdown was associated with altered phosphorylation of the c-cbl docking site on Tyr1003, reduced ubiquitination of the receptor and altered activation of downstream ERK1/2- and AKT-dependent signalling in response to the natural ligand Hepatocyte Growth Factor (HGF). The regulation of cytoskeleton dynamics was further confirmed by the induction of actin stress fibres in HeLa expressing the active enzyme but not the catalytic mutant UCH-L1(C90S). These findings highlight a previously unrecognized involvement of the ubiquitin cycle in bacterial entry. UCH-L1 is highly expressed in malignant cells that may therefore be particularly susceptible to invasion by bacteria-based drug delivery systems.
  •  
34.
  • Benktander, John, et al. (författare)
  • Stress impairs skin barrier function and induces α2-3 linked n-acetylneuraminic acid and core 1 o-glycans on skin mucins in atlantic salmon, salmo salar
  • 2021
  • Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 22:3
  • Tidskriftsartikel (refereegranskat)abstract
    • © 2021 by the authors. Licensee MDPI, Basel, Switzerland. The skin barrier consists of mucus, primarily comprising highly glycosylated mucins, and the epithelium. Host mucin glycosylation governs interactions with pathogens and stress is associated with impaired epithelial barrier function. We characterized Atlantic salmon skin barrier function during chronic stress (high density) and mucin O-glycosylation changes in response to acute and chronic stress. Fish held at low (LD: 14–30 kg/m3) and high densities (HD: 50-80 kg/m3) were subjected to acute stress 24 h before sampling at 17 and 21 weeks after start of the experiment. Blood parameters indicated primary and secondary stress responses at both sampling points. At the second sampling, skin barrier function towards molecules was reduced in the HD compared to the LD group (Papp mannitol; p < 0.01). Liquid chromatography–mass spectrometry revealed 81 O-glycan structures from the skin. Fish subjected to both chronic and acute stress had an increased proportion of large O-glycan structures. Overall, four of the O-glycan changes have potential as indicators of stress, especially for the combined chronic and acute stress. Stress thus impairs skin barrier function and induces glycosylation changes, which have potential to both affect interactions with pathogens and serve as stress indicators.
  •  
35.
  • Benton, Jeanne, et al. (författare)
  • Cells from the Immune System Generate Adult-Born Neurons in Crayfish
  • 2014
  • Ingår i: Developmental Cell. - : Cell Press. - 1534-5807 .- 1878-1551. ; 30:3, s. 322-333
  • Tidskriftsartikel (refereegranskat)abstract
    • Neurogenesis is an ongoing process in the brains of adult decapod crustaceans. However, the first-generation precursors that produce adult-born neurons, which reside in a neurogenic niche, are not self-renewing in crayfish and must be replenished. The source of these neuronal precursors is unknown. Here, we report that adult-born neurons in crayfish can be derived from hemocytes. Following adoptive transfer of 5-ethynyl-2′-deoxyuridine (EdU)-labeled hemocytes, labeled cells populate the neurogenic niche containing the first-generation neuronal precursors. Seven weeks after adoptive transfer, EdU-labeled cells are located in brain clusters 9 and 10 (where adult-born neurons differentiate) and express appropriate neurotransmitters. Moreover, the number of cells composing the neurogenic niche in crayfish is tightly correlated with total hemocyte counts (THCs) and can be manipulated by raising or lowering THC. These studies identify hemocytes as a source of adult-born neurons in crayfish and demonstrate that the immune system is a key contributor to adult neurogenesis.
  •  
36.
  • Chapman, Joanne R., et al. (författare)
  • The Evolution of Innate Immune Genes : Purifying and Balancing Selection on beta-Defensins in Waterfowl
  • 2016
  • Ingår i: Molecular biology and evolution. - : Oxford University Press (OUP). - 0737-4038 .- 1537-1719. ; 33:12, s. 3075-3087
  • Tidskriftsartikel (refereegranskat)abstract
    • In disease dynamics, high immune gene diversity can confer a selective advantage to hosts in the face of a rapidly evolving and diverse pathogen fauna. This is supported empirically for genes involved in pathogen recognition and signalling. In contrast, effector genes involved in pathogen clearance may be more constrained. beta-Defensins are innate immune effector genes; their main mode of action is via disruption of microbial membranes. Here, five beta-defensin genes were characterized in mallards (Anas platyrhynchos) and other waterfowl; key reservoir species for many zoonotic diseases. All five genes showed remarkably low diversity at the individual-, population-, and species-level. Furthermore, there was widespread sharing of identical alleles across species divides. Thus, specific beta-defensin alleles were maintained not only spatially but also over long temporal scales, with many amino acid residues being fixed across all species investigated. Purifying selection to maintain individual, highly efficacious alleles was the primary evolutionary driver of these genes in waterfowl. However, we also found evidence for balancing selection acting on the most recently duplicated beta-defensin gene (AvBD3b). For this gene, we found that amino acid replacements were more likely to be radical changes, suggesting that duplication of beta-defensin genes allows exploration of wider functional space. Structural conservation to maintain function appears to be crucial for avian beta-defensin effector molecules, resulting in low tolerance for new allelic variants. This contrasts with other types of innate immune genes, such as receptor and signalling molecules, where balancing selection to maintain allelic diversity has been shown to be a strong evolutionary force.
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37.
  • Edsman, Lennart (författare)
  • The crayfish plague pathogen can infect freshwater-inhabiting crabs
  • 2014
  • Ingår i: Freshwater Biology. - : Wiley. - 0046-5070 .- 1365-2427. ; 59, s. 918-929
  • Tidskriftsartikel (refereegranskat)abstract
    • The potential for A.astaci transmission in the opposite direction, from crabs to crayfish, and potential impact of this pathogen on populations of freshwater crabs require further investigations, because of possible consequences for crayfish and freshwater crab conservation and aquaculture.
  •  
38.
  • Franz, F, et al. (författare)
  • The Transcriptional Regulation of FOXO Genes in Thyrocytes.
  • 2016
  • Ingår i: Hormone and Metabolic Research. - Stuttgart : Georg Thieme Verlag. - 0018-5043 .- 1439-4286. ; 48:9, s. 601-6
  • Tidskriftsartikel (refereegranskat)abstract
    • FOXO transcription factors are key regulators of DNA damage repair, proliferation and apoptosis in thyrocytes. Thyroid malignancies show impaired FOXO function. In this study, we investigated the transcriptional regulation of FOXO isoforms in thyroid epithelial cells. mRNA expression of FOXO isoforms (FOXO1, 3 and 4) was determined in FRTL-5 cells stimulated with different growth factors and H2O2. Furthermore, the impact of PI3K/AKT signalling on FOXO transcription was investigated in PI3K p110α mutant FRTL-5 cells and regulatory dependence of FOXO transcription on FOXO was studied in FRTL-5 cells with hFOXO3 overexpression. Finally, mRNA expression levels of FOXO isoforms were determined in human epithelial thyroid tumours. Growth factor deprivation induced transcription of FOXO1, 3 and 4, whereas insulin stimulation decreased FOXO1 and FOXO4 transcription in FRTL-5 cells. Inhibition of the PI3K/AKT cascade amplified FOXO1 and FOXO4 expression. In contrast, H2O2 and TSH did not influence FOXO transcription in thyrocytes. Overexpression of PI3K p110α inhibited FOXO3 and induced FOXO4 transcription. In human thyroid tumours, FOXO1 and FOXO3 mRNA levels were significantly downregulated in papillary thyroid carcinoma when compared to normal tissues. In contrast, follicular thyroid carcinomas showed significant upregulation of FOXO4 mRNA.In this paper, we demonstrate an influence of PI3K signalling on FOXO transcription in thyrocytes. Moreover, we show that thyroid cancers exhibit alterations in FOXO transcription besides the previously reported alterations in posttranslational FOXO3 regulation. These findings may add to the concept of targeting the PI3K pathway in advanced thyroid cancers.
  •  
39.
  • Gebremariam, Hanna Gebreegziabher, 1987- (författare)
  • Role of lactobacilli in Helicobacter pylori pathogenesis and host cell responses
  • 2020
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Helicobacter pylori is well adapted to the harsh environment of the human stomach, allowing it to persistently colonize the gastric mucosa of at least 50% of the global population for decades. Long-term colonization induces chronic inflammation that can eventually lead to development of peptic ulcer and gastric cancer. The interaction between host, bacterial and environmental factors are crucial for the pathogenesis of H. pylori. In contrast, Lactobacillus species are members of the human microbiota and act as a first line of defense against pathogens. However, the underlying mechanisms behind lactobacilli-mediated pathogen inhibition still need further investigation.This thesis focuses on understanding the interplay between commensal and pathogenic bacteria with the human host. In Paper I, we investigated the effect of different Lactobacillus strains on the initial attachment of H. pylori to gastric epithelial cells and found that certain Lactobacillus strains can prevent the adhesion of the pathogen by decreasing the expression of SabA. In Paper II, the anti-inflammatory activity of Lactobacillus strains against H. pylori-induced production of proinflammatory cytokines was explored. We demonstrated the ability of L. gasseri Kx110A1 to reduce the level of TNF and IL-6 in human macrophages through suppression of ADAM17, a metalloproteinase responsible for releasing transmembrane proteins. Lactobacilli-mediated inhibition of these cytokines was not H. pylori-specific, suggesting a general anti-inflammatory property of L. gasseri Kx110A1. In Paper III, we characterized the role of sortase-dependent proteins in L. gasseri Kx110A1. We showed that the deletion of sortase A in lactobacilli resulted in the reduction of auto-aggregation and attachment to host gastric epithelial cells. Moreover, sortase A mutant lactobacilli were not effective in preventing H. pylori initial adherence. Finally, in Paper IV, we showed that lactate can affect the expression of H. pylori adherence genes and the production of bacterial-induced proinflammatory cytokines.
  •  
40.
  • Guerra, Lina, et al. (författare)
  • Do bacterial genotoxins contribute to chronic inflammation, genomic instability and tumor progression?
  • 2011
  • Ingår i: The FEBS Journal. - : John Wiley & Sons. - 1742-464X .- 1742-4658. ; 278:23, s. 4577-4588
  • Forskningsöversikt (refereegranskat)abstract
    • Cytolethal distending toxin, produced by several Gram-negative bacteria, and colibactin, secreted by several commensal and extraintestinal pathogenic Escherichia coli strains, are the first bacterial genotoxins to be described to date. Exposure to cytolethal distending toxin and colibactin induces DNA damage, and consequently activates the DNA damage response, resulting in cell cycle arrest of the intoxicated cells and DNA repair. Irreversible DNA damage will lead to cell death by apoptosis or to senescence. It is well established that chronic exposure to DNA damaging agents, either endogenous (reactive oxygen species) or exogenous (ionizing radiation), may cause genomic instability as a result of the alteration of genes coordinating the DNA damage response, thus favoring tumor initiation and progression. In this review, we summarize the state of the art of the biology of cytolethal distending toxin and colibactin, focusing on the activation of the DNA damage response and repair pathways, and discuss the cellular responses induced in intoxicated cells, as well as how prolonged intoxication may lead to chronic inflammation, the accumulation of genomic instability, and tumor progression in both in vitro and in vivo models.
  •  
41.
  • Guerra, Lina, et al. (författare)
  • Myc is required for activation of the ATM-dependent checkpoints in response to DNA damage
  • 2010
  • Ingår i: PLOS ONE. - : Public Library Science. - 1932-6203. ; 5:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The MYC protein controls cellular functions such as differentiation, proliferation, and apoptosis. In response to genotoxic agents, cells overexpressing MYC undergo apoptosis. However, the MYC-regulated effectors acting upstream of the mitochondrial apoptotic pathway are still unknown.PRINCIPAL FINDINGS: In this study, we demonstrate that expression of Myc is required to activate the Ataxia telangiectasia mutated (ATM)-dependent DNA damage checkpoint responses in rat cell lines exposed to ionizing radiation (IR) or the bacterial cytolethal distending toxin (CDT). Phosphorylation of the ATM kinase and its downstream effectors, such as histone H2AX, were impaired in the myc null cell line HO15.19, compared to the myc positive TGR-1 and HOmyc3 cells. Nuclear foci formation of the Nijmegen Breakage Syndrome (Nbs) 1 protein, essential for efficient ATM activation, was also reduced in absence of myc. Knock down of the endogenous levels of MYC by siRNA in the human cell line HCT116 resulted in decreased ATM and CHK2 phosphorylation in response to irradiation. Conversely, cell death induced by UV irradiation, known to activate the ATR-dependent checkpoint, was similar in all the cell lines, independently of the myc status.CONCLUSION: These data demonstrate that MYC contributes to the activation of the ATM-dependent checkpoint responses, leading to cell death in response to specific genotoxic stimuli.
  •  
42.
  • Guidi, Riccardo, et al. (författare)
  • Salmonella enterica delivers its genotoxin through outer membrane vesicles secreted from infected cells
  • 2013
  • Ingår i: Cellular Microbiology. - : Wiley-Blackwell. - 1462-5814 .- 1462-5822. ; 15:12, s. 2034-2050
  • Tidskriftsartikel (refereegranskat)abstract
    • Cytolethal-distending toxins (CDTs) belong to a family of DNA damage inducing exotoxins that are produced by several Gram-negative bacteria. Salmonella enterica serovar Typhi expresses its CDT (named as Typhoid toxin) only in the Salmonella-containing vacuole (SCV) of infected cells, which requires its export for cell intoxication. The mechanisms of secretion, release in the extracellular space and uptake by bystander cells are poorly understood. We have addressed these issues using a recombinant S. Typhimurium strain, MC71-CDT, where the genes encoding for the PltA, PltB and CdtB subunits of the Typhoid toxin are expressed under control of the endogenous promoters. MC71-CDT grown under conditions that mimic the SCV secreted the holotoxin in outer membrane vesicles (OMVs). Epithelial cells infected with MC71-CDT also secreted OMVs-like vesicles. The release of these extracellular vesicles required an intact SCV and relied on anterograde transport towards the cellular cortex on microtubule and actin tracks. Paracrine internalization of Typhoid toxin-loaded OMVs by bystander cells was dependent on dynamin-1, indicating active endocytosis. The subsequent induction of DNA damage required retrograde transport of the toxin through the Golgi complex. These data provide new insights on the mode of secretion of exotoxins by cells infected with intracellular bacteria.
  •  
43.
  • Hellgren, Olof, et al. (författare)
  • Evolution of a cluster of innate immune genes (beta-defensins) along the ancestral lines of chicken and zebra finch
  • 2010
  • Ingår i: Immunome Research. - : Springer Science and Business Media LLC. - 1745-7580. ; 6:3
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Avian beta-defensins (AvBDs) represent a group of innate immune genes with broad antimicrobial activity. Within the chicken genome, previous work identified 14 AvBDs in a cluster on chromosome three. The release of a second bird genome, the zebra finch, allows us to study the comparative evolutionary history of these gene clusters between from two species that shared a common ancestor about 100 million years ago.RESULTS: A phylogenetic analysis of the beta-defensin gene clusters in the chicken and the zebra finch identified several cases of gene duplication and gene loss along their ancestral lines. In the zebra finch genome a cluster of 22 AvBD genes were identified, all located within 125 Kbp on chromosome three. Ten of the 22 genes were found to be highly conserved with orthologous genes in the chicken genome. The remaining 12 genes were all located within a cluster of 58 Kbp and are suggested to be a result of recent gene duplication events that occurred after the galliformes- passeriformes split (G-P split). Within the chicken genome, AvBD6 was found to be a duplication of AvBD7, whereas the gene AvDB14 seems to have been lost along the ancestral line of the zebra finch. The duplicated beta-defensin genes have had a significantly higher accumulation of non-synonymous over synonymous substitutions compared to the genes that have not undergone duplication since the G-P split. The expression patterns of avian beta-defensin genes seem to be well conserved between chicken and zebra finch.CONCLUSION: The genomic comparisons of the beta-defensins gene clusters of the chicken and zebra finch illuminate the evolutionary history of this gene complex. Along their ancestral lines, several gene duplication events have occurred in the passerine line after the galliformes-passeriformes split giving rise to 12 novel genes compared to a single duplication event in the galliformes line. After the duplication events, the duplicated genes have been subject to a relaxed selection pressure compared to the non-duplicated genes, thus supporting models of evolution by gene duplication.
  •  
44.
  • Hildebrandt, Franziska, 1994-, et al. (författare)
  • scDual-Seq of Toxoplasma gondii-infected mouse BMDCs reveals heterogeneity and differential infection dynamics
  • 2023
  • Ingår i: Frontiers in Immunology. - : Frontiers Media S.A.. - 1664-3224. ; 14
  • Tidskriftsartikel (refereegranskat)abstract
    • Dendritic cells and macrophages are integral parts of the innate immune system and gatekeepers against infection. The protozoan pathogen, Toxoplasma gondii, is known to hijack host immune cells and modulate their immune response, making it a compelling model to study host-pathogen interactions. Here we utilize single cell Dual RNA-seq to parse out heterogeneous transcription of mouse bone marrow-derived dendritic cells (BMDCs) infected with two distinct genotypes of T. gondii parasites, over multiple time points post infection. We show that the BMDCs elicit differential responses towards T. gondii infection and that the two parasite lineages distinctly manipulate subpopulations of infected BMDCs. Co-expression networks define host and parasite genes, with implications for modulation of host immunity. Integrative analysis validates previously established immune pathways and additionally, suggests novel candidate genes involved in host-pathogen interactions. Altogether, this study provides a comprehensive resource for characterizing host-pathogen interplay at high-resolution.
  •  
45.
  •  
46.
  • Junkunlo, Kingkamon, et al. (författare)
  • PDGF/VEGF-related receptor affects transglutaminase activity to control cell migration during crustacean hematopoiesis
  • 2017
  • Ingår i: Stem Cells and Development. - : Mary Ann Liebert Inc. - 1547-3287 .- 1557-8534. ; 26:20, s. 1449-1459
  • Tidskriftsartikel (refereegranskat)abstract
    • The platelet-derived growth factor (PDGF) receptor, a tyrosine kinase (TK) receptor whose ligand is PDGF, is crucial in the transduction of extracellular signals into cells and mediates numerous processes, such as cell proliferation, differentiation, survival, and migration. We demonstrate the important roles of a receptor TK related to the PDGF/VEGF family protein (PVR) in controlling hematopoietic progenitor cell migration by affecting extracellular transglutaminase (TGase) activity. Pl_PVR1, GenBank accession No. KY444650, is highly expressed in hemocytes and the hematopoietic tissue (HPT). Sunitinib malate was used to block the PVF/PVR downstream pathway in HPT cell culture. The addition of Sunitinib also caused the HPT cells to increase in size and begin spreading. An increase in extracellular TGase activity on the HPT cell membrane was observed in a dose-dependent manner after treatment with Sunitinib malate. The presence of crude Ast1 provided a combinatorial beneficial effect that enhanced the number of spreading cells after inhibition of the Pl_PVR downstream signaling cascade. In addition, an increased immunoreactivity for beta-tubulin and elongation of beta-tubulin filaments were found in Pl_PVR signaling-inhibited cells. The potential roles of PVF/PVR signaling in controlling progenitor cell activity during hematopoiesis in crayfish were investigated and discussed.
  •  
47.
  • Levi, Laura, et al. (författare)
  • Bacterial genotoxins promote inside-out integrin β1 activation, formation of focal adhesion complexes and cell spreading
  • 2015
  • Ingår i: PLOS ONE. - : Public Library Science. - 1932-6203. ; 10:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Integrins are membrane bound receptors that regulate several cellular processes, such as cell adhesion, migration, survival and proliferation, and may contribute to tumor initiation/progression in cells exposed to genotoxic stress. The extent of integrin activation and its role in cell survival upon intoxication with bacterial genotoxins are still poorly characterized. These toxins induce DNA strand breaks in the target cells and activate the DNA damage response (DDR), coordinated by the Ataxia Telangectasia Mutated (ATM) kinase. In the present study, we demonstrate that induction of DNA damage by two bacterial genotoxins promotes activation of integrin β1, leading to enhanced assembly of focal adhesions and cell spreading on fibronectin, but not on vitronectin. This phenotype is mediated by an ATM-dependent inside-out integrin signaling, and requires the actin cytoskeleton remodeler NET1. The toxin-mediated cell spreading and anchorage-independent survival further relies on ALIX and TSG101, two components of the endosomal sorting complex required for transport (ESCRT), known to regulate integrin intracellular trafficking. These data reveal a novel aspect of the cellular response to bacterial genotoxins, and provide new tools to understand the carcinogenic potential of these effectors in the context of chronic intoxication and infection.
  •  
48.
  • Mortezaei, Narges, et al. (författare)
  • P-fimbriae in the presence of anti-PapA antibodies : new insight of antibodies action against pathogens
  • 2013
  • Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 3
  • Tidskriftsartikel (refereegranskat)abstract
    • Uropathogenic strains of Escherichia coli establish urinary tract infections by attaching to host epithelial cells using adhesive organelles called fimbriae. Fimbriae are helix-like structures with a remarkable adaptability, offering safeguarding for bacteria exposed to changing fluid forces in the urinary tract. We challenged this property of P-fimbriae by cross-linking their subunits with shaft-specific antibodies and measuring the corresponding force response at a single organelle level. Our data show compromised extension and rewinding of P-fimbriae in the presence of antibodies and reduced fimbrial elasticity, which are important properties of fimbriae contributing to the ability of bacteria to cause urinary tract infections. The reduced elasticity found by cross-linking fimbrial subunits could thus be another assignment for antibodies; in addition to marking bacteria as foreign, antibodies physically compromise fimbrial function. We suggest that our assay and results will be a starting point for further investigations aimed at inhibiting sustained bacterial adhesion by antibodies.
  •  
49.
  • Månsson, Johan, et al. (författare)
  • Sarcoptic mange in the Scandinavian wolf Canis lupus population
  • 2016
  • Ingår i: BMC Veterinary Research. - : Springer Science and Business Media LLC. - 1746-6148. ; 12
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Sarcoptic mange, a parasitic disease caused by the mite Sarcoptes scabiei, is regularly reported on wolves Canis lupus in Scandinavia. We describe the distribution and transmission of this parasite within the small but recovering wolf population by analysing 269 necropsy reports and performing a serological survey on 198 serum samples collected from free-ranging wolves between 1998 and 2013.Results: The serological survey among 145 individual captured Scandinavian wolves (53 recaptures) shows a consistent presence of antibodies against sarcoptic mange. Seropositivity among all captured wolves was 10.1 % (CI. 6.4 %-15.1 %). Sarcoptic mange-related mortality reported at necropsy was 5.6 % and due to secondary causes, predominantly starvation. In the southern range of the population, seroprevalence was higher, consistent with higher red fox densities. Female wolves had a lower probability of being seropositive than males, but for both sexes the probability increased with pack size. Recaptured individuals changing from seropositive to seronegative suggest recovery from sarcoptic mange. The lack of seropositive pups (8-10 months, N = 56) and the occurrence of seropositive and seronegative individuals in the same pack indicates interspecific transmission of S. scabiei into this wolf population.Conclusions: We consider sarcoptic mange to have little effect on the recovery of the Scandinavian wolf population. Heterogenic infection patterns on the pack level in combination with the importance of individual-based factors (sex, pack size) and the north-south gradient for seroprevalence suggests low probability of wolf-to-wolf transmission of S. scabiei in Scandinavia.
  •  
50.
  • Nord, Andreas, et al. (författare)
  • Reduced immune responsiveness contributes to winter energy conservation in an Arctic bird
  • 2020
  • Ingår i: Journal of Experimental Biology. - : The Company of Biologists. - 1477-9145 .- 0022-0949. ; 223:8
  • Tidskriftsartikel (refereegranskat)abstract
    • Animals in seasonal environments must prudently manage energyexpenditure to survive the winter. This may be achieved throughreductions in the allocation of energy for various purposes (e.g.thermoregulation, locomotion, etc.). We studied whether such tradeoffsalso include suppression of the innate immune response, bysubjecting captive male Svalbard ptarmigan (Lagopus mutahyperborea) to bacterial lipopolysaccharide (LPS) during exposureto either mild temperature (0°C) or cold snaps (acute exposure to−20°C), in constant winter darkness when birds were in energyconservingmode, and in constant daylight in spring. The innateimmune response was mostly unaffected by temperature. However,energy expenditure was below baseline when birds were immunechallenged in winter, but significantly above baseline in spring. Thissuggests that the energetic component of the innate immuneresponse was reduced in winter, possibly contributing to energyconservation. Immunological parameters decreased (agglutination,lysis, bacteriostatic capacity) or did not change (haptoglobin/PIT54)after the challenge, and behavioural modifications (anorexia, massloss) were lengthy (9 days). While we did not study the mechanismsexplaining these weak, or slow, responses, it is tempting to speculatethey may reflect the consequences of having evolved in anenvironment where pathogen transmission rate is presumably lowfor most of the year. This is an important consideration if climatechange and increased exploitation of the Arctic would alter pathogencommunities at a pace outwith counter-adaption in wildlife.
  •  
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