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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).
2.	Mamontov, Eugen, 1955, et al. (författare) Mathematical models and numerical simulation results for oncogeny: Specific problems and different tools for various user communities 2008 Ingår i: Abstracts Booklet. CancerSim2008 — Euroconference on Modelling and Simulation of Cancer Growth and Therapy, 19-21 May, Turin, Italy; N. Bellomo and G. Forni (Chairmen) http://www.cancersim2008.org. Konferensbidrag (refereegranskat)
3.	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.
4.	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.
5.	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.
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.
7.	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.
8.	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.
9.	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.
10.	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.
11.	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.
12.	Hedengren, Marika, et al. (författare) Relish, a central factor in the control of humoral but not cellular immunity in Drosophila. 1999 Ingår i: Mol Cell. - : Elsevier. - 1097-2765. ; 4:5, s. 827-37 Tidskriftsartikel (refereegranskat)abstract The NF-kappa B-like Relish gene is complex, with four transcripts that are all located within an intron of the Nmdmc gene. Using deletion mutants, we show that Relish is specifically required for the induction of the humoral immune response, including both antibacterial and antifungal peptides. As a result, the Relish mutants are very sensitive to infection. A single cell of E. cloacae is sufficient to kill a mutant fly, and the mutants show increased susceptibility to fungal infection. In contrast, the blood cell population, the hematopoietic organs, and the phagocytic, encapsulation, and melanization responses are normal. Our results illustrate the importance of the humoral response in Drosophila immunity and demonstrate that Relish plays a key role in this response.
13.	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.
14.	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.
15.	Guerra, Lina, et al. (författare) The biology of the cytolethal distending toxins 2011 Ingår i: Toxins. - : MDPI. - 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.
16.	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.
17.	Cossarizza, A., et al. (författare) Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition) 2019 Ingår i: European Journal of Immunology. - : Wiley. - 0014-2980 .- 1521-4141. ; 49:10, s. 1457-1973 Tidskriftsartikel (refereegranskat)abstract These guidelines are a consensus work of a considerable number of members of the immunology and flow cytometry community. They provide the theory and key practical aspects of flow cytometry enabling immunologists to avoid the common errors that often undermine immunological data. Notably, there are comprehensive sections of all major immune cell types with helpful Tables detailing phenotypes in murine and human cells. The latest flow cytometry techniques and applications are also described, featuring examples of the data that can be generated and, importantly, how the data can be analysed. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid, all written and peer-reviewed by leading experts in the field, making this an essential research companion.
18.	Feyerabend, Thorsten B, et al. (författare) Loss of histochemical identity in mast cells lacking carboxypeptidase A. 2005 Ingår i: Mol Cell Biol. - 0270-7306. ; 25:14, s. 6199-210 Tidskriftsartikel (refereegranskat)
19.	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.
20.	Nilsson, Elin, et al. (författare) Proteomic characterization of IgY preparations purified with a water dilution method. 2008 Ingår i: Journal of agricultural and food chemistry. - : American Chemical Society (ACS). - 1520-5118 .- 0021-8561. ; 56:24, s. 11638-42 Tidskriftsartikel (refereegranskat)abstract Antigen-specific chicken IgY antibodies have been used for oral immunotherapy as an alternative or complement to antibiotics in several studies. The water dilution (WD) method has several advantages for purifying IgY. It is rapid, efficient, suitable for large-scale production, and nothing but water is added. The water-soluble fraction contains other proteins and lipids besides IgY. The protein content was characterized by two-dimensional gel electrophoresis (2DGE) and nanoflow liquid chromatography coupled offline to matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometry (nanoLC-MALDI TOF/TOF MS). Protein analysis was complicated due to the large dynamic concentration range, but 26 proteins could be identified. The relative protein concentrations in different batches were very similar according to protein patterns on 1D gels and protein concentration determinations. Thus, the purification method has a high reproducibility. The concentrations of cholesterols and triglycerides were low and should not have an effect on the plasma levels of treated patients. Purification of IgY for oral use with WD is therefore a recommended method.
21.	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.
22.	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.
23.	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.
24.	Puértolas Balint, Fabiola, 1993- (författare) Impact of a Western-style diet on small-intestinal mucosal barrier function 2024 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract Specialized defense mechanisms at mucosal barriers along the gastrointestinal tract constantly protect us against the trillions of microorganisms living inside the human body. These mechanisms include a mucus layer as a physical barrier that prevents bacteria from reaching the epithelium and the production of antimicrobial peptides (AMPs) as a chemical barrier that helps neutralize or lyse these bacteria. On the other hand, many intestinal bacteria benefit human health by providing colonization resistance against pathogenic bacteria, helping produce vitamins, aiding in the digestion of complex carbohydrates, and producing anti-inflammatory short-chain fatty acids. Therefore, the intestinal mucosal barrier has the challenging task of maintaining a homeostatic interaction between the host and the intestinal microbiota. Alterations in the integrity of the mucus barrier and the expression of AMPs have been associated with inflammatory bowel disease and obesity. This thesis investigates how the intake of a high-fat and low-fiber Western-style diet (WSD) as an exogenous factor can affect the protective function of the mucus barrier and intestinal AMPs in mice with or without modulation of the microbiota.In paper 1 “Intestinal α-Defensins Play a Minor Role in Modulating the Small Intestinal Microbiota Composition as Compared to Diet” we fed wild-type and Mmp7-/- mice, which lack active a-defensins, the major family of AMPs in the small intestine, a control or a WSD. We found that diet had a stronger impact on modulating small intestinal microbiota composition, while defensins only modulated the abundance of specific bacteria. In addition, defensins protected against metabolic dysfunction induced by the intake of a WSD.In paper 2 “Investigating the link between antimicrobial defense, gut microbiota and metabolic dysfunction at the small intestinal mucosal barrier” we investigated the effect of obesogenic diets (Western diet or a high fat diet), obesity itself and other variables, including microbiota composition and sex, on small intestinal AMP expression. We observed that prolonged intake of a WSD had a stronger impact on AMP expression than genetic obesity, and determined that experimental set-up defined by mouse vendor and diet type, may have a larger influence than the specific dietary disturbances.In paper 3 “Muc2-dependent microbial colonization of the jejunal mucus layer is diet sensitive and confers local resistance to enteric pathogen infection” we determined that the mucus layer of the jejunum formed aggregates and became more penetrable to bacteria-sized beads following the intake of a WSD. Both Muc2-/- and WSD-fed mice had an altered microbiota composition and increased susceptibility to enteric infection with Citrobacter rodentium in the jejunum, highlighting the role of the mucus layer as a microbiota- supporting niche that mediates colonization resistance against infection.In summary, our work investigates the mechanisms by which a WSD changes the small intestinal microbiota composition at different intestinal sites while simultaneously disrupting mucus and AMP function. Our findings can aid the development of potential therapeutic avenues for addressing obesity and inflammatory bowel diseases through targeted modulation of mucus function, AMP expression or microbial composition.
25.	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.
26.	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.
27.	Dahlgren, Ulf, 1953, et al. (författare) Expression of a dietary protein in E. coli renders it strongly antigenic to gut lymphoid tissue. 1991 Ingår i: Immunology. - 0019-2805. ; 73:4, s. 394-7 Tidskriftsartikel (refereegranskat)abstract Bacteria that colonize the intestinal mucosa elicit a strong mucosal immune response, whereas food antigens such as ovalbumin are very weakly immunogenic to the gut-associated lymphoid tissue. This may either be due to special physico-chemical properties of bacterial substances versus proteins from animals and plants, or to stimulating properties of the bacteria on, e.g., antigen presentation, rendering all substances contained within bacteria antigenic. To test these hypotheses, ovalbumin was expressed in wild-type Escherichia coli and germ-free female rats were colonized with this strain. The systemic and mucosal antibody response of these rats was compared with that of rats given large amounts of dietary ovalbumin. Biliary IgA antibodies, which reflect the local IgA antibody production in the intestine, were only found in the rats colonized with ovalbumin-synthesizing E. coli. IgG antibodies in the bile were also only seen in these rats. We conclude that mucosal immunogenicity depends on the context in which a protein is presented to the gut-associated lymphoid tissue, rather than to special antigenic characteristics of the protein in itself.
28.	Hernroth, Bodil, 1951-, et al. (författare) Impact of ocean acidification on antimicrobial activity in gills of the blue mussel (Mytilus edulis) 2016 Ingår i: Fish and Shellfish Immunology. - : Elsevier. - 1050-4648 .- 1095-9947. ; 55, s. 452-459 Tidskriftsartikel (refereegranskat)abstract Here, we aimed to investigate potential effects of ocean acidification on antimicrobial peptide (AMP) activity in the gills of Mytilus edulis, as gills are directly facing seawater and the changing pH (predicted to be reduced from ∼8.1 to ∼7.7 by 2100). The AMP activity of gill and haemocyte extracts was compared at pH 6.0, 7.7 and 8.1, with a radial diffusion assay against Escherichia coli. The activity of the gill extracts was not affected by pH, while it was significantly reduced with increasing pH in the haemocyte extracts. Gill extracts were also tested against different species of Vibrio (V. parahaemolyticus, V. tubiashii, V. splendidus, V. alginolyticus) at pH 7.7 and 8.1. The metabolic activity of the bacteria decreased by ∼65–90%, depending on species of bacteria, but was, as in the radial diffusion assay, not affected by pH. The results indicated that AMPs from gills are efficient in a broad pH-range. However, when mussels were pre-exposed for pH 7.7 for four month the gill extracts presented significantly lower inhibit of bacterial growth. A full in-depth proteome investigation of gill extracts, using LC-Orbitrap MS/MS technique, showed that among previously described AMPs from haemocytes of Mytilus, myticin A was found up-regulated in response to lipopolysaccharide, 3 h post injection. Sporadic occurrence of other immune related peptides/proteins also pointed to a rapid response (0.5–3 h p.i.). Altogether, our results indicate that the gills of blue mussels constitute an important first line defence adapted to act at the pH of seawater. The antimicrobial activity of the gills is however modulated when mussels are under the pressure of ocean acidification, which may give future advantages for invading pathogens.
29.	Bergman, Ingrid-Maria, et al. (författare) Extensive polymorphism in the porcine Toll-like receptor 10 gene 2012 Ingår i: International Journal of Immunogenetics. - 1744-3121 .- 1744-313X. ; 39:1, s. 68-76 Tidskriftsartikel (refereegranskat)abstract The great importance of the Toll-like receptors (TLRs) in innate immunity is well established, but one family member – TLR10 – remains elusive. TLR10 is expressed in various tissues in several species, but its ligand is not known and its function is still poorly understood. The open reading frame of TLR10 was sequenced in 15 wild boars, representing three populations, and in 15 unrelated domestic pigs of Hampshire, Landrace and Large White origin. Amino acid positions corresponding to detected nonsynonymous single nucleotide polymorphisms (SNPs) were analysed in the crystal structures determined for the human TLR1–TLR2–lipopeptide complex and the human TLR10 Toll/Interleukin 1 receptor (TIR) dimer. SNP occurrence in wild boars and domestic pigs was compared, and haplotypes for the TLR10 gene and the TLR6-1-10 gene cluster were reconstructed. Despite the limited number of animals sequenced in the present study (N = 30), a larger number of SNPs were found in TLR10 than recently reported for TLR1, TLR6 and TLR2. Thirty-three SNPs were detected, of which 20 were nonsynonymous. The relative frequency of nonsynonymous (dN) and synonymous (dS) SNPs between wild boars and domestic pigs was higher in TLR10 than recently reported for TLR1, TLR6 and TLR2. However, the polymorphism reported in the present study seems to leave the function of the TLR10 molecule unaffected. Furthermore, no nonsynonymous SNPs were detected in the part of the gene corresponding to the hinge region of the receptor, probably reflecting rigorously acting functional constraint. The total number of SNPs and the number of nonsynonymous SNPs were significantly lower (P < 0.05) in the wild boars than in the domestic pigs, and fewer TLR10 haplotypes were present in the wild boars. The majority of the TLR6-1-10 haplotypes were specific for either wild boars or domestic pigs, probably reflecting differences in microbial environment and population history.
30.	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.
31.	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.
32.	Puértolas Balint, Fabiola, et al. (författare) Investigating the link between antimicrobial defense, gut microbiota and metabolic dysfunction at the small intestinal mucosal barrier Annan publikation (övrigt vetenskapligt/konstnärligt)
33.	von Pawel-Rammingen, Ulrich, et al. (författare) IdeS, a novel streptococcal cysteine proteinase with unique specificity for immunoglobulin G. 2002 Ingår i: EMBO Journal. - : Wiley. - 1460-2075. ; 21:7, s. 1607-1615 Tidskriftsartikel (refereegranskat)abstract Recent work from several laboratories has demonstrated that proteolytic mechanisms significantly contribute to the molecular interplay between Streptococcus pyogenes, an important human pathogen, and its host. Here we describe the identification, purification and characterization of a novel extracellular cysteine proteinase produced by S.pyogenes. This enzyme, designated IdeS for Immunoglobulin G-degrading enzyme of S.pyogenes, is distinct from the well-characterized streptococcal cysteine proteinase, SpeB, and cleaves human IgG in the hinge region with a high degree of specificity. Thus, other human proteins, including immunoglobulins M, A, D and E, are not degraded by IdeS. The enzyme efficiently cleaves IgG antibodies bound to streptococcal surface structures, thereby inhibiting the killing of S.pyogenes by phagocytic cells. This and additional observations on the distribution and expression of the ideS gene indicate that IdeS represents a novel and significant bacterial virulence determinant, and a potential therapeutic target.
34.	Salgaonkar, Neeta A., et al. (författare) Use of N,N-diacetylchitobiose in decreasing toxic effects of indoor air pollution by preventing oxidative DNA damage 2016 Ingår i: Biologia. - Bratislava : Springer. - 0006-3088 .- 1336-9563. ; 71:5, s. 505-515 Tidskriftsartikel (refereegranskat)abstract Indoor air pollution occurs due to hazardous pollutants, such as tobacco smoke, pesticides and carbon oxides, sulphur oxides and nitrogen oxides arising from combustion of biomass fuels. Exposure to these pollutants results in respiratory conditions like asthma, chronic obstructive pulmonary disease, lung cancer, pneumonia and other lower respiratory infections. Several of these infections are a result of inflammation and oxidative stress. Here we demonstrate the ability of N,N-diacetylchitobiose in preventing oxidative DNA damage in peripheral blood mononuclear cells exposed to biomass smoke extracts and cigarette smoke extract. The cytotoxic effect of these pollutants was determined by trypan blue exclusion assay in peripheral blood mononuclear cells, where cytotoxicity in decreasing order was garette > wood > sawdust > cowdung. Cytotoxicity could be due to single- and double-strand breaks in the DNA as a result of oxidative stress. Comet assay measures the extent of DNA damage in the cells exposed to toxic agents. When mononuclear cells were treated with N,N-diacetylchitobiose and later exposed to smoke extracts, the extent of DNA damage decreased by 44.5% and 57.5% as compared to untreated cells. The protection offered by N,N-diacetylchitobiose towards oxidative DNA damage was at par with quercetin, a popular herbal medicine. Glutathione-S-transferase activity was determined in mononuclear cells exposed to smoke extracts, where oxidative stress in cells exposed to cigarette smoke extract was maximum. The present study demonstrates for the first time the ability of N,N -diacetylchitobiose to alleviate the harmful effects of indoor air pollutants.
35.	Belov, Katherine, et al. (författare) Evolution of the major histocompatibility complex : Isolation of class II beta cDNAs from two monotremes, the platypus and the short-beaked echidna. 2003 Ingår i: Immunogenetics. - 0093-7711. ; 55:6, s. 402-11 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
36.	Andersson, Sören, 1957-, et al. (författare) CHIMERIC MOMP ANTIGEN 2015 Patent (populärvet., debatt m.m.)
37.	Looman, Camilla, et al. (författare) MZF6D, a novel KRAB zinc-finger gene expressed exclusively in meiotic male germ cells. 2003 Ingår i: DNA and Cell Biology. - 1044-5498. ; 22, s. 489-496 Tidskriftsartikel (refereegranskat)
38.	Belles, A., et al. (författare) Lactoferrin modulates gut microbiota and Toll-like receptors (TLRs) in mice with dysbiosis induced by antibiotics 2022 Ingår i: Food & Function. - : Royal Society of Chemistry (RSC). - 2042-6496 .- 2042-650X. ; 13, s. 5854-5869 Tidskriftsartikel (refereegranskat)abstract Background: Antibiotic administration can result in gut microbiota and immune system alterations that impact health. Bovine lactoferrin is a milk protein with anticancer, anti-inflammatory, antimicrobial and immune modulatory activities. The aim was to study the ability of native and iron-saturated lactoferrin to reverse the effects of clindamycin on gut microbiota and intestinal Toll-like receptor (TLR) expression in a murine model. Methods: Male C57BL/6 mice were treated with vehicle, clindamycin (Clin), native bovine lactoferrin (nLf), nLf + clindamycin (nLf_Clin), iron-saturated bovine lactoferrin (sLf) and sLf + clindamycin (sLf_Clin). Fecal samples of each group were collected, and bacterial DNA was extracted. Sequencing of 16s rRNA V4 hypervariable gene regions was conducted to assess the microbial composition. mRNA expression levels of TLRs (1-9) were determined in mouse colon by qPCR. Pearson's correlation test was carried out between bacteria showing differences in abundance among samples and TLR2, TLR8 and TLR9. Results: Beta-diversity analysis showed that the microbial community of the vehicle was different from the communities of Clin, nLf_Clin and sLf_Clin. At the family level, Bacteroidaceae, Prevotellaceae and Rikenellaceae decreased in the Clin group, and treatment with nLf or sLf reverted these effects. Clin reduced the expression of TLR2, TLR8 and TLR9 and sLf reverted the decrease in the expression of these receptors. Finally, TLR8 was positively correlated with Rikenellaceae abundance. Conclusion: In a situation of intestinal dysbiosis induced by clindamycin, lactoferrin restores the normal levels of some anti-inflammatory bacteria and TLRs and, therefore, could be a good ingredient to be added to functional foods.
39.	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.
40.	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.
41.	Fransén, Karin, 1973-, et al. (författare) Association between C10X polymorphism in the CARD8 gene and inflammatory markers in young healthy individuals in the LBA study 2024 Ingår i: BMC Cardiovascular Disorders. - : BioMed Central (BMC). - 1471-2261. ; 24:1 Tidskriftsartikel (refereegranskat)abstract Background: The Caspase activation and recruitment domain 8 (CARD8) protein is a component of innate immunity as a negative regulator of NF- ĸB, and has been associated with regulation of proteins involved in inflammation. Expression of CARD8 mRNA and protein has been identified in human atherosclerotic lesions, and the truncated T30A variant (rs2043211) of CARD8 has been associated with lower C-reactive (CRP) and MCP-1 levels in myocardial infarction patients. The present study examines the role of a genetic variation in the CARD8 gene in relation to a selection of markers of inflammation.Methods: In a cross-sectional study of young healthy individuals (18.0-25.9 yrs, n = 744) the association between the rs2043211 variant in the CARD8 gene and protein markers of inflammation was assessed. Genotyping of the CARD8 C10X (rs2043211) polymorphism was performed with TaqMan real time PCR on DNA from blood samples. Protein levels were studied via Olink inflammation panel ( https://olink.com/ ). Using linear models, we analyzed men and two groups of women with and without estrogen containing contraceptives separately, due to previous findings indicating differences between estrogen users and non-estrogen using women. Genotypes were analyzed by additive, recessive and dominant models.Results: The minor (A) allele of the rs2043211 polymorphism in the CARD8 gene was associated with lower levels of CCL20 and IL-6 in men (CCL20, Additive model: p = 0.023; Dominant model: p = 0.016. IL-6, Additive model: p = 0.042; Dominant model: p = 0.039). The associations remained significant also after adjustment for age and potential intermediate variables.Conclusions: Our data indicate that CARD8 may be involved in the regulation of CCL20 and IL-6 in men. No such association was observed in women. These findings strengthen and support previous in vitro data on IL-6 and CCL20 and highlight the importance of CARD8 as a factor in the regulation of inflammatory proteins. The reason to the difference between sexes is however not clear, and the influence of estrogen as a possible factor important for the inflammatory response needs to be further explored.
42.	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.
43.	Volk, Joana K., et al. (författare) The Nlrp6 inflammasome is not required for baseline colonic inner mucus layer formation or function 2019 Ingår i: Journal of Experimental Medicine. - : Rockefeller University Press. - 0022-1007 .- 1540-9538. ; 216:11, s. 2602-2618 Tidskriftsartikel (refereegranskat)abstract The inner mucus layer (IML) is a critical barrier that protects the colonic epithelium from luminal threats and inflammatory bowel disease. Innate immune signaling is thought to regulate IML formation via goblet cell Nlrp6 inflammasome activity that controls secretion of the mucus structural component Muc2. We report that isolated colonic goblet cells express components of several inflammasomes; however, analysis of IML properties in multiple inflammasome-deficient mice, including littermate-controlled Nlrp6(-/-), detect a functional IML barrier in all strains. Analysis of mice lacking inflammasome substrate cytokines identifies a defective IML in Il18(-/-) mice, but this phenotype is ultimately traced to a microbiota-driven, Il18-independent effect. Analysis of phenotypic transfer between IML-deficient and IML-intact mice finds that the Bacteroidales family S24-7 (Muribaculaceae) and genus Adlercrutzia consistently positively covary with IML barrier function. Together, our results demonstrate that baseline IML formation and function is independent of inflammasome activity and highlights the role of the microbiota in determining IML barrier function.
44.	van Dijk, Jacintha G. B., et al. (författare) A Comparative Study of the Innate Humoral Immune Response to Avian Influenza Virus in Wild and Domestic Mallards 2020 Ingår i: Frontiers in Microbiology. - : Frontiers Media S.A.. - 1664-302X. ; 11, s. 1-13 Tidskriftsartikel (refereegranskat)abstract Domestic mallards (Anas platyrhynchos domesticus) are traditionally used as a model to investigate infection dynamics and immune responses to low pathogenic avian influenza viruses (LPAIVs) in free-living mallards. However, it is unclear whether the immune response of domestic birds reflects the response of their free-living counterparts naturally exposed to these viruses. We investigated the extent to which the innate humoral immune response was similar among (i) wild-type domestic mallards in primary and secondary infection with LPAIV H4N6 in a laboratory setting (laboratory mallards), (ii) wild-type domestic mallards naturally exposed to LPAIVs in a semi-natural setting (sentinel mallards), and (iii) free-living mallards naturally exposed to LPAIVs. We quantified innate humoral immune function by measuring non-specific natural antibodies (agglutination), complement activity (lysis), and the acute phase protein haptoglobin. We demonstrate that complement activity in the first 3 days after LPAIV exposure was higher in primary-exposed laboratory mallards than in sentinel and free-living mallards. LPAIV H4N6 likely activated the complement system and the acute phase response in primary-exposed laboratory mallards, as lysis was higher and haptoglobin lower at day 3 and 7 post-exposure compared to baseline immune function measured prior to exposure. There were no differences observed in natural antibody and haptoglobin concentrations among laboratory, sentinel, and free-living mallards in the first 3 days after LPAIV exposure. Our study demonstrates that, based on the three innate humoral immune parameters measured, domestic mallards seem an appropriate model to investigate innate immunology of their free-living counterparts, albeit the innate immune response of secondary-LPAIV exposed mallards is a better proxy for the innate immune response in pre-exposed free-living mallards than that of immunologically naive mallards.
45.	Yang, Xuyue (författare) Coevolution and molecular background of species interactions in geographic mosaics 2021 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract In complex food webs, species often interact with each other indirectly through mediating species. As a result of geographic mosaic of coevolution, such interactions are often evolutionarily unstable and the traits governing the interaction sometimes vary over time. A common example is the interactions between hosts and endoparasitoids, in which the phenotypic variation has been studied in terms of both host immunity and parasitoid virulence. This thesis focuses on characterizing the genetic background underlying the coevolution between host immune response and parasitoid virulence in a host-parasitoid interaction system. For this purpose, I used Galerucella-Asecodes system, which contains three leaf beetle species (Galerucella calmariensis, G. pusilla and G. tenella) and their shared parasitic wasp, Asecodes parviclava as the study model. By integrating next generation sequencing techniques and ab initio evidence-driven annotation approach, I generated genome assemblies and annotation of both the wasp and the three Galerucella species (Paper I & IV). In order to study variation in immune capacity at the expression level, I de novo assembled and annotated the transcriptome of G. pusilla and G. calmariensis, which have contrasting immunocompetence against the Asecodes wasp (Paper II). Using a time-course differential expression analysis, I investigated gene expression in parasitized larvae of G. pusilla and G. calmariensis after the wasp attack, and suggested that signaling and hematopoiesis genes play a key role in the host immunity in Galerucella against wasps (Paper II). Using comparative analysis of Galerucella species, I identified important genes and pathways under natural selection which potentially explain the divergence in their morphology and immunity (Paper III). I also focused on the geographic variation in the Asecodes wasp using population comparisons and identified several candidate regions of the genome for host adaptation. We also detected that genes involved in the inhibition of host immune systems and odorant/gustatory receptors are associated with variation in virulence (Paper IV).
46.	Fromell, Karin, et al. (författare) The lectin pathway of complement and the contact/kallikrein system are integrated 2018 Ingår i: Molecular Immunology. - : Elsevier. - 0161-5890 .- 1872-9142. ; 102, s. 151-152 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
47.	Gallwitz, Maike, et al. (författare) Rapid species-specific diversification of the mast cell chymase locus during mammalian evolution. 2006 Ingår i: Immunogenetics. ; 58, s. 641-654 Tidskriftsartikel (refereegranskat)
48.	Hamad, Osama A., 1978-, et al. (författare) Non-proteolytically activated C3 promotes binding of activated platelets and platelet-derived microparticles to leukocytes via CD11b/CD18 2012 Ingår i: Immunobiology. - : Elsevier BV. - 0171-2985 .- 1878-3279. ; 217:11, s. 1191-1191 Tidskriftsartikel (refereegranskat)abstract Background:We have previously demonstrated that complement component C3 binds to the surface of activated platelets, independent of proteolytic activation. The resulting form of C3, termed C3(H2O), was shown to be a ligand for recombinant CD35 (complement receptor 1, CR1). Previous studies by others have indicated that platelet-leukocyte complex (PLC) formation is dependent on the interaction between platelet exposed P-selectin (CD62P) and its ligand, PSGL-1, on leukocytes. In addition, CD11b/CD18 (Mac-1 or CR3) has been shown to participate in this reaction, but its ligand has not yet been identified.Objective:To test the hypothesis that C3 bound to activated platelets and platelet-derived microparticles (PMPs) can act as a ligand for CD11b/CD18 (CR3) and contribute to PLC formation.Methods and results:Blood cells were depleted of plasma proteins. After extensive washing, C3 was added, and the leukocytes were activated with C5a and the platelets with thrombin receptor-activating peptide (TRAP). PLC formation was detected by flow cytometry (monocytes: CD14+/CD42a+, granulocytes: CD16+/CD42a+). For both granulocytes and monocytes, the addition of C3 significantly enhanced PLC formation. Formation of PLC was inhibited by both anti-P-selectin and anti-CD11b monoclonal antibodies. In addition, PMPs isolated from serum, were found to expose C3(H2O) and bind to leukocytes in a fashion similar to activated platelets.Conclusion:We have identified proteolytically non-activated C3 as a ligand for CD11b in the formation of PLC and possibly the binding of PMPs to leukocytes. This observation most likely has pathophysiological implications for the recently reported links between thrombotic disease and the complement system.
49.	Tjärnlund, Anna, et al. (författare) Polymeric Ig receptor knockout mice are more susceptible to mycobacteria infection in the respiratory tract 2006 Ingår i: International Immunology. - : Oxford university press. - 0953-8178 .- 1460-2377. ; 18:5, s. 807-816 Tidskriftsartikel (refereegranskat)abstract It is generally accepted that cellular, and not humoral immunity, plays the crucial role in defense against intracellular bacteria. However, accumulating data indicate the importance of humoral immunity for the defense against a number of intracellular bacteria, including mycobacteria. We have investigated the role of secretory IgA, the main isotype found in mucosal tissues, in protection against mycobacterial infection, using polymeric IgR (pIgR)-deficient mice. Characterization of the humoral response induced after intra-nasal immunizations with the mycobacterial antigen PstS-1 revealed a loss of antigen-specific IgA response in saliva from the knockout mice. IgA level in the bronchoalveolar lavage of knockout mice was similar to wild-type level, although the IgA antibodies must have reached the lumen by other means than pIgR-mediated transport. Infection with Mycobacterium bovis bacillus Calmette–Guérin (BCG) demonstrated that the immunized pIgR−/− mice were more susceptible to BCG infection than immunized wild-type mice, based on higher bacterial loads in the lungs. This was accompanied by a reduced production of both IFN-γ and tumor necrosis factor-alpha (TNF-α) in the lungs. Additionally, the pIgR−/− mice displayed reduced natural resistance to mycobacterial infection proved by significantly higher bacterial growth in their lungs compared with wild-type mice after infection with virulent Mycobacterium tuberculosis. The knockout mice appeared to have a delayed mycobacteria-induced immune response with reduced expression of protective mediators, such as IFN-γ, TNF-α, inducible nitric oxide synthase and regulated upon activation normal T cell sequence, during early infection. Collectively, our results show that actively secreted IgA plays a role in protection against mycobacterial infections in the respiratory tract, by blocking entrance of bacilli into the lungs, in addition to modulation of the mycobacteria-induced pro-inflammatory response.
50.	Toda, Shota, et al. (författare) Optimization of Islet Microencapsulation with Thin Polymer Membranes for Long-Term Stability 2019 Ingår i: Micromachines. - : MDPI. - 2072-666X. ; 10:11, s. 1-10 Tidskriftsartikel (refereegranskat)abstract Microencapsulation of islets can protect against immune reactions from the host immune system after transplantation. However, sufficient numbers of islets cannot be transplanted due to the increase of the size and total volume. Therefore, thin and stable polymer membranes are required for the microencapsulation. Here, we undertook the cell microencapsulation using poly(ethylene glycol)-conjugated phospholipid (PEG-lipid) and layer-by-layer membrane of multiple-arm PEG. In order to examine the membrane stability, we used different molecular weights of 4-arm PEG (10k, 20k and 40k)-Mal to examine the influence on the polymer membrane stability. We found that the polymer membrane made of 4-arm PEG(40k)-Mal showed the highest stability on the cell surface. Also, the polymer membrane did not disturb the insulin secretion from beta cells.

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