| 1. |
|
|
| 2. |
- Abarenkov, Kessy, et al.
(author)
-
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
-
In: MycoKeys. - : Pensoft Publishers. - 1314-4057 .- 1314-4049. ; 16, s. 1-15
-
Journal article (peer-reviewed)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).
|
|
| 3. |
|
|
| 4. |
- Svensson, Lena, 1973, et al.
(author)
-
Allergen extracts directly mobilize and activate human eosinophils
- 2004
-
In: Eur J Immunol. ; 34:6, s. 1744-51
-
Journal article (peer-reviewed)abstract
- Allergic diseases are characterized by the presence of eosinophils, which are recruited to the affected tissues by chemoattractants produced by T cells, mast cells and epithelium. Our objective was to evaluate if allergens can directly activate human eosinophils. The capacity of purified allergen extracts to elicit eosinophil chemotaxis, respiratory burst, degranulation and up-regulation of the adhesion molecule complement receptor 3 (CR3) was determined in eosinophils isolated from healthy blood donors. Eosinophils stimulated with an extract from house dust mite (HDM) released the granule protein major basic protein (MBP) and up-regulated the surface expression of CR3. Cat allergen extracts also induced the up-regulation of CR3, but not the release of MBP; instead cat, as well as birch and grass allergens, elicited the release of eosinophil peroxidase (EPO). In addition, grass pollen extract caused the secretion of MBP. None of the allergens stimulated eosinophilic cationic protein release, nor production of free oxygen radicals. Both HDM and birch extracts were chemotactic for eosinophils. These findings establish that common aeroallergens can directly activate eosinophils in vitro. We propose that eosinophil activation in vivo is not exclusively mediated by cytokines and chemokines of the allergic inflammatory reaction, but could partly be the result of direct interaction between allergens and eosinophils.
|
|
| 5. |
- Brundin, Peik M. A., 1975-
(author)
-
Sex differences in immune response and sex hormone receptor expression in healthy individuals and during viral infection
- 2021
-
Doctoral thesis (other academic/artistic)abstract
- There is sex-bias in morbidity and mortality from infectious diseases. Infections kill more men than women and several studies have pointed out differences in the immune system as a reason. The sex hormones estrogen, progesterone and testosterone all shape the effect of the immune response on multiple levels. Women at fertile age have been suggested to have higher proinflammatory responses from inflammatory stimuli compared to men and post-menopausal women, which has been ascribed to their higher estrogen levels. This could possibly lead to a more active pathogen response but may also result in a detrimental immunopathology to infections or development of autoimmune reaction.The overall aim of this thesis is to study the contribution of sex hormones and sex hormone receptors (SHR) to sex differences in immune response. We focus on peripheral blood mononuclear cells (PBMCs) to study such relationships in healthy individuals, as well as in individuals with asymptomatic Torque Teno Virus infection, and individuals with acute Puumala virus infection.In Paper I, we investigated expression of SHR and immune response genes in PBMC from healthy premenopausal (pre-MP) women during the menstrual cycle. The expression levels were estimated using a qPCR Array (Taqman low-density array, TLDA). SHR expression did not change significantly during the menstrual cycle, but several key immune regulatory genes were significantly more expressed during the ovulatory and mid luteal phase. Further, we separated PBMC into cell subsets (CD4+ T-cells, CD8+ T-cells, CD56+ NK-cells, CD14+ monocytes and CD19+ B-cells) and analyzed the expression through qPCR of estrogen receptors (ERs), ERα, ERβ1 (wildtype) and the isoform ERβ2. For the first time and unexpectedly, we demonstrate that the isoform ERβ2 was more abundant than wildtype ERβ1. The data from this paper provides new knowledge on the contribution of the menstrual cycle on immune response.In Paper II, we explored the use of Torque Teno Virus as a secondary functional immune marker in men and women. Expression of viral TTV DNA in PBMCs was estimated using a qPCR kit from Argene (R-gene) and analyzed in relation to serum sex hormone levels. The results showed that 50% of the men, 25% the post-MP women, and 18% of the pre-MP women were TTV+. Interestingly, all pre-MP women that were TTV+ had hormonal aberrances and were either anovulatory and/or hypothyroid. TTV+ pre-MP women also had significantly lower progesterone levels than TTV- pre-MP women. This paper indicates that the prevalence of TTV in PBMC differs between men, pre-MP and post-MP women. Furthermore, hormonal aberrances (at least in pre-MP women) will lead to increased prevalence of TTV.In Paper III we investigated the expression of ERα, ERβ1 and ERβ2 in PBMC from patients with Nephropathia epidemica, the viral zoonotic disease caused by Puumala virus, a Hanta virus known to affect more men than women. Expression of ERs in PBMCs and clinical laboratory results during the acute and convalescent phases were analyzed using a principal component analysis (PCA). The results show differences in ER expression and support previous findings that men and women have a different clinical pictureIn conclusion, the results in this thesis reveal distinct patterns of immune response related to sex hormone levels, SHR expression and the phases of the menstrual cycle supporting that there a link between sex hormone levels and immune responses. Further, we show that the ER isoform ERβ2 is more abundant in PBMCs than what was previously described. The data in this thesis adds to the knowledge to the sex differences in immune response and exemplifies the importance of taking these differences into account in the clinic.
|
|
| 6. |
- Mamontov, Eugen, 1955
(author)
-
Homeorhesis and evolutionary properties of living systems: From ordinary differential equations to the active-particle generalized kinetics theory
- 2006
-
In: 10th Evolutionary Biology Meeting at Marseilles, 20-22 September 2006, Marseilles, France.
-
Conference paper (peer-reviewed)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.
|
|
| 7. |
- Brundin, Peik M.A., et al.
(author)
-
Blood hormones and torque teno virus in peripheral blood mononuclear cells
- 2020
-
In: Heliyon. - : Elsevier. - 2405-8440. ; 6:11
-
Journal article (peer-reviewed)abstract
- Men and women respond differently to infectious diseases. Women show less morbidity and mortality, partially due to the differences in sex hormone levels which can influence the immune response. Torque teno virus (TTV) is non-pathogenic and ubiquitously present in serum from a large proportion (up to 90%) of adult humans with virus levels correlating with the status of the host immune response. The source of TTV replication is unknown, but T-lymphocytes have been proposed. In this study we investigated the presence and levels of TTV in peripheral blood mononuclear cells (PBMCs) in premenopausal (pre-MP) women, post-menopausal (post-MP) women, and men, and determined their serum sex hormone levels. Of the examined subjects (n = 27), we found presence of TTV in PMBC from 17.6% pre-MP (n = 17), 25.0% post-MP (n = 4) and 50.0% men (n = 6). The levels of TTV/μg DNA were lower among TTV-positive men and post-MP women compared to pre-MP women. All the positive pre-MP women were either anovulatory, hypothyroid, or both. In addition, the TTV-positive pre-MP women had significantly lower progesterone levels compared to TTV-negative pre-MP women. Although our study was performed on a limited number of subjects, the data suggests that TTV in PBMC is associated with an anovulatory menstrual cycle with low progesterone levels, and possibly with male sex.
|
|
| 8. |
|
|
| 9. |
- Mamontov, Eugen, 1955, et al.
(author)
-
Oncogenic hyperplasia caused by combination of various factors: A decision-support software for radionuclide therapy
- 2007
-
In: Workshop "Mathematical Modelling and Analysis of Cancer Invasion of Tissues", Mar 26, 2007 - Mar 30, 2007, Dundee, Scotland.
-
Conference paper (peer-reviewed)abstract
- The present work deals with the software based on the PhasTraM model [1] for oncogenic hyperplasia, the first stage of formation of any solid tumor. The work generalizes the related results of [2]-[6] and discusses application of the software for decision support in radionuclide therapy. The software capabilities to allow for combinations of various causes of oncogeny are emphasized. The causes comprise inflammation, immune dysfunction, and chronic psychological stress. The immune dysfunction is represented with hypogammaglobulenimia expressed in terms of the concentration of the immunoglobulin-G molecules. The level of chronic pychological stress is described with the concentration of the interleukin-6 molecules. The work considers how application of the software can support decisions on the specific radionuclide-therapy setting depending on the tissue-, organ-, and patient-specific data. This is illustrated by a number of numerical-simulation results, also the ones which include the effects of common and fractionation-based radionuclide-therapy modalities. A proper attention is paid to how specifically the input data can be prepared by prospective users of the software, i.e. the specialists who apply radionuclide therapy. The work also formulates a few directions for future research in connection with the features of the everyday work of the prospective users. REFERENCES: [1] E. Mamontov, K. Psiuk-Maksymowicz, A. Koptioug, 2006, Stochastic mechanics in the context of the properties of living systems, Mathl Comput. Modelling, 44(7-8) 595-607. [2] E. Mamontov, A. V. Koptioug, K. Psiuk-Maksymowicz, 2006, The minimal, phase-transition model for the cell-number maintenance by the hyperplasia-extended homeorhesis, Acta Biotheoretica, 54(2) 61-101. [3] K. Psiuk-Maksymowicz and E. Mamontov, 2006, The homeorhesis-based modelling and fast numerical analysis for oncogenic hyperplasia under radiotherapy, Mathl Comput. Modelling, Special Issue
|
|
| 10. |
- Wilms, Torben, 1973-
(author)
-
Squamous cell carcinoma of the head and neck, focusing on Epstein-Barr-virus, programmed cell death ligand 1 and serum lipoproteins
- 2021
-
Doctoral thesis (other academic/artistic)abstract
- Background: Squamous cell carcinoma of the head and neck (SCCHN)comprises a large group of tumours including the oral cavity and nasopharyngealarea, and typically affects older males in association with alcohol/tobacco usage.Within the oral cavity, the mobile tongue is the most common site for tumourdevelopment. The incidence of squamous cell carcinoma of the oral tongue(SCCOT) is increasing in younger people, which has been suggested to associatewith other than the traditional risk factors for this disease. Two common humanoncogenic viruses, human papillomavirus (HPV) and Epstein-Barr virus (EBV)are connected to certain types of SCCHN, in oropharynx and nasopharynxrespectively. The receptor programmed cell death 1 (PD)-1 and its ligandprogrammed cell death ligand 1 (PD-L1) are particularly relevant in immunecheckpoint control, and elevated levels have been seen in various cancer types. Alink between hyperlipidemia and cancer risk has previously been suggested. Theaim of this thesis was to investigate risk factors and prognostic features forSCCHN, by focusing on EBV, PD-L1 and serum lipoproteins.Materials and methods: Ninety-eight cases of SCCOT and 15 cases of tonsillarsquamous cell carcinoma were examined for the presence of EBV-encodedribonucleic acids (EBERs), EBV deoxyribonucleic acid (DNA) and the proteinEBV-encoded nuclear antigen-1 (EBNA-1), using in situ hybridisation,polymerase chain reaction (PCR) and immunohistochemistry respectively. Onehundred and one cases of SCCOT were examined for expression of PD-L1 intumour and surrounding immune cells using Ventana SP263immunohistochemistry assay and a QuickScore (QS) method. An estimation oftumour-infiltrating immune cells was also performed in 25 of the patients.Circulating levels of PD-L1 were measured using an electrochemiluminescenceassay platform in serum from 30 patients. Finally, serum samples from 106patients and 28 healthy controls were investigated for levels of total cholesterol,low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides andlipoprotein(a).Results: In the first study, using an in situ hybridisation kit no EBER transcriptswere detected. No EBV DNA was identified with PCR analysis, andimmunohistochemistry for EBNA-1 was also negative. In the second study, highertumour cell PD-L1 levels were found in females than males (p = 0.019). Forpatients with low PD-L1 in tumour cells, better survival was shown in males thanfemales (overall survival p = 0.021, disease-free survival p = 0.020). Tumourinfiltrating natural killer (NK) T cells, immature dendritic cells (DCs) and M1macrophages correlated positively with tumour cell PD-L1 (p < 0.05). In the laststudy, the only lipoprotein showing significant difference in concentration iiibetween healthy controls and patients was HDL (p = 0.012). Kaplan-Meiersurvival curves showed that patients with high levels of total cholesterol or LDLhad better survival than patients with normal levels (p = 0.028 and p = 0.007respectively). Adjusting for the effects of age at diagnosis, TNM stage and weightchange, multivariate Cox regression models showed LDL to be an independentprognostic factor for both overall (p = 0.010) and disease-free survival (p =0.018).Conclusion: We excluded EBV as a potential player in SCCOT in both old andyoung patients and highlight the importance of appropriate controls for EBVencoded RNA in-situ hybridization (EBER-ISH) when investigating EBV inhuman diseases. Regarding PD-L1, our data supported the significance of genderon tumour cell PD-L1 expression and demonstrated combined effects of genderand PD-L1 levels on clinical outcome in patients with SCCOT. Data also indicatedthe involvement of specific immune cell types in PD-L1-regulated immuneevasion. Looking at serum lipoproteins, we found high LDL levels to be beneficialfor survival outcome in patients with SCCHN. Furthermore, the use of cholesterollowering medicine for prevention or management of SCCHN needs to be carefullyevaluated.
|
|
| 11. |
- Nowroozalizadeh, Salma, et al.
(author)
-
Short-term HIV-1 treatment interruption is associated with dysregulated TLR-stimuli responsiveness.
- 2013
-
In: Human Vaccines & Immunotherapeutics. - : Informa UK Limited. - 2164-5515 .- 2164-554X. ; 9:10, s. 2103-2110
-
Journal article (peer-reviewed)abstract
- Viremia during human immunodeficiency virus type-1 (HIV-1) infection results in progressive impairment of several components of the immune system. Here a unique model of repeated treatment interruptions (TIs) was used with the aim to reveal the effect of controlled short-term viremia on innate stimuli responsiveness and circulating dendritic cells (DCs). Sequential peripheral blood samples from HIV-1-infected patients on combination antiretroviral therapy, subjected to repeated TI cycles as part of a therapeutic DNA vaccination study, were analyzed. In vitro responsiveness of peripheral blood mononuclear cells to toll-like receptor (TLR) stimuli was analyzed by cytokine secretion, and frequencies of plasmacytoid DCs (pDCs) and myeloid DCs (mDCs) were monitored by flow cytometry. These parameters were found not to be significantly different between the vaccinated and placebo groups. Instead, independent of vaccination altered in vitro TLR responsiveness was observed in parallel with TI cycles. TLR7/8-triggered secretion of IL-12 and IFN-α, as well as TLR9-triggered secretion of IL-12, was hyperactivated. In contrast, expression of IFN-α after TLR9 stimulation decreased during the initial cycle of TI. Reduced frequencies of pDCs and mDCs, compared with baseline, were noted before and during the second TI, respectively. Furthermore, spontaneous ex vivo release of IL-12 from PBMC was noted during cycles of TI. In conclusion, these results suggest that consequences of short-term TI include dysregulated TLR responses and fluctuations in the frequencies of circulating DCs. Knowledge of these immunological factors may influence the continuation of stringent treatment schedules during HIV infections.
|
|
| 12. |
- Grindebacke, Hanna, 1977, et al.
(author)
-
Defective suppression of Th2 cytokines by CD4CD25 regulatory T cells in birch allergics during birch pollen season
- 2004
-
In: Clin Exp Allergy. ; 34:9, s. 1364-72
-
Journal article (peer-reviewed)abstract
- BACKGROUND: CD4(+)CD25+ regulatory T cells suppress proliferation and cytokine production by human T cells both to self-antigens and exogenous antigens. Absence of these cells in human newborns leads to multiple autoimmune and inflammatory disorders together with elevated IgE levels. However, their role in human allergic disease is still unclear. OBJECTIVE: This study aimed to evaluate the capacity of CD4(+)CD25+ regulatory T cells to suppress proliferation and cytokine production outside and during birch-pollen season in birch-allergic patients relative to non-allergic controls. METHODS: CD4+ cells were obtained from blood of 13 birch-allergic patients and six non-allergic controls outside pollen season and from 10 birch-allergic patients and 10 non-allergic controls during birch-pollen season. CD25+ and CD25- fractions were purified with magnetic beads and cell fractions, alone or together in various ratios, were cultured with antigen-presenting cells and birch-pollen extract or anti-CD3 antibody. Proliferation and levels of IFN-gamma, IL-13, IL-5 and IL-10 were measured by thymidin incorporation and ELISA, respectively. Numbers of CD25+ cells were analysed by flow cytometry. RESULTS: CD4(+)CD25+ regulatory T cells from both allergics and non-allergics potently suppressed T cell proliferation to birch allergen both outside and during birch-pollen season. However, during season CD4(+)CD25+ regulatory T cells from allergic patients but not from non-allergic controls were defective in down-regulating birch pollen induced IL-13 and IL-5 production, while their capacity to suppress IFN-gamma production was retained. In contrast, outside pollen season the regulatory cells of both allergics and non-allergic controls were able to inhibit T-helper 2 cytokine production. CONCLUSION: This is the first study to show differential suppression of Th1 and Th2 cytokines, with CD4(+)CD25+ regulatory T cells from birch-pollen-allergic patients being unable to down-regulate Th2, but not Th1 responses during birch-pollen season.
|
|
| 13. |
- Mamontov, Eugen, 1955, et al.
(author)
-
The minimal, phase-transition model for the cell-number maintenance by the hyperplasia-extended homeorhesis
- 2006
-
In: Acta Biotheoretica. - : Springer Science and Business Media LLC. - 0001-5342 .- 1572-8358. ; 54:2, s. 61-101
-
Journal article (peer-reviewed)abstract
- Oncogenic hyperplasia is the first and inevitable stage of formation of a (solid) tumor. This stage is also the core of many other proliferative diseases. The present work proposes the first minimal model that combines homeorhesis with oncogenic hyperplasia where the latter is regarded as a genotoxically activated homeorhetic dysfunction. This dysfunction is specified as the transitions of the fluid of cells from a fluid, homeorhetic state to a solid, hyperplastic-tumor state, and back. The key part of the model is a nonlinear reaction-diffusion equation (RDE) where the biochemical-reaction rate is generalized to the one in the well-known Schlögl physical theory of the non-equilibrium phase transitions. A rigorous analysis of the stability and qualitative aspects of the model, where possible, are presented in detail. This is related to the spatially homogeneous case, i.e. when the above RDE is reduced to a nonlinear ordinary differential equation. The mentioned genotoxic activation is treated as a prevention of the quiescent G0-stage of the cell cycle implemented with the threshold mechanism that employs the critical concentration of the cellular fluid and the nonquiescent-cell-duplication time. The continuous tumor morphogeny is described by a time-space-dependent cellular-fluid concentration. There are no sharp boundaries (i.e. no concentration jumps exist) between the domains of the homeorhesis- and tumor-cell populations. No presumption on the shape of a tumor is used. To estimate a tumor in specific quantities, the model provides the time-dependent tumor locus, volume, and boundary that also points out the tumor shape and size. The above features are indispensable in the quantitative development of antiproliferative drugs or therapies and strategies to prevent oncogenic hyperplasia in cancer and other proliferative diseases. The work proposes an analytical-numerical method for solving the aforementioned RDE. A few topics for future research are suggested.
|
|
| 14. |
- Bjermo, Helena, 1981-
(author)
-
Dietary Fatty Acids and Inflammation : Observational and Interventional Studies
- 2011
-
Doctoral thesis (other academic/artistic)abstract
- Dietary fat quality influences the risk of type 2 diabetes and cardiovascular disease. A low-grade inflammation is suggested to contribute to the disease development, often accompanied by obesity. Whereas n-3 polyunsaturated fatty acids (PUFA) have been considered anti-inflammatory, n-6 PUFA have been proposed to act pro-inflammatory. Saturated fatty acids (SFA) act pro-inflammatory in vitro. This thesis aimed to investigate effects of different fatty acids on low-grade inflammation in observational and interventional studies. In Paper I and II, fatty acid composition in serum cholesterol esters was used as objective marker of dietary fat quality and related to serum C-reactive protein (CRP) and other circulating inflammatory markers in two population-based cohorts, conducted in middle-aged men and elderly men and women, respectively. In Paper III and IV, the impact of diets differing in fat quality on inflammation and oxidative stress was investigated in randomised controlled studies, in subjects with metabolic syndrome and abdominal obesity. In Paper I and II, a low proportion of linoleic acid (18:2 n-6) in serum was associated with higher CRP concentrations, indicating that a low intake of vegetable fats may be related to low-grade inflammation. High CRP concentrations were also associated with high proportions of palmitoleic (16:1) and oleic (18:1) acids and high stearoyl coenzymeA desaturase index, possibly reflecting altered fat metabolism and/or high SFA intake in this population. When comparing two high-fat diets rich in either saturated or monounsaturated fat, and two low-fat diets with or without long-chain n-3 PUFA supplementation during 12 weeks (Paper III), no differences in inflammation or oxidative stress markers were observed. Moreover, a 10-week intervention (Paper IV) with high linoleic acid intake showed no adverse effects on inflammation or oxidative stress. Instead, interleukin-1 receptor antagonist and tumor necrosis factor receptor-2 decreased after linoleic acid intake compared with a diet high in SFA. The results in this thesis indicate that dietary n-6 PUFA found in vegetable fats is associated with lower inflammation marker levels, and to some extent reduces systemic inflammation when compared with SFA. Supplementation of n-3 PUFA did not exert any systemic anti-inflammatory effects, maybe due to a relatively low dose.
|
|
| 15. |
- Eriksson Ström, Jonas
(author)
-
Epigenetic changes and immunological features of chronic obstructive pulmonary disease
- 2023
-
Doctoral thesis (other academic/artistic)abstract
- Background: Chronic obstructive pulmonary disease (COPD) is a heterogenous and chronic inflammatory syndrome with the lungs as its main target organ. Clinically, COPD is characterized by airflow limitation, chronic respiratory symptoms, and many extrapulmonary comorbidities. Tobacco smoke is the main environmental risk factor, but pollutants and smoke from biomass fuel are also major contributors. Why some, but not all, smokers develop the disease is a key but largely unresolved research question. Genetic factors seem to explain 40—60% of COPD susceptibility, but what additional role epigenetic factors such as DNA methylation might play has not been thoroughly investigated.Immune cells are of vital importance in the COPD pathogenesis. Among airway lymphocytes, cytotoxic CD8+ T cells are the ones most often found to be involved in the disease, but other lymphocyte populations are not as well studied.Among patients with manifest COPD, the rate of decline in lung function differs widely. Smoking cessation decreases the rate, but beyond that, it is not well understood why some patients experience a more rapid and some a much slower disease progression. Rapid decline is associated with a poor prognosis and has been recognized as a separate phenotype of COPD. Aim: The overall aim of this thesis was to examine the immunologic and epigenetic features of COPD with a focus on the rapid decline phenotype, using flow cytometry and measurement of DNA methylation in cells from bronchoalveolar lavage (BAL) fluid together with clinical characteristics such as rate of decline in lung function, use of inhaled corticosteroids and smoking status. The studies included in this thesis were all part of the Respiratory and Cardiovascular Effects in COPD (“KOLIN”) study.Methods: The study population was the same for all studies in this thesis. Subjects were recruited from the Obstructive Lung Disease in Northern Sweden (OLIN) COPD study according to predetermined criteria. OLIN COPD also provided the longitudinal data needed for classification of rapid/non-rapid decliners (decline in forced expiratory volume in the first second [FEV1] ≥60 or ≤30 mL/year respectively). BAL fluid was analyzed for cell type composition using flow cytometry. DNA methylation in BAL cells was measured using the Illumina MethylationEPIC BeadChip. In the statistical analysis, flow cytometry data was analyzed using group-wise comparisons and multivariable regression models. DNA methylation data was analyzed for association with COPD and accelerated epigenetic aging (defined as the difference between chronological and epigenetic age) using multilinear regression models. Differentially methylated positions and regions associated with COPD were analyzed for gene association and pathway enrichment and integrated with data from previous gene expression and genome-wide association studies.Results: Paper I: in this first paper based on flow cytometry, we focused on cytotoxic lymphocytes and found that Natural Killer (NK) cells in BAL were increased in COPD while invariant Natural Killer T (iNKT) and Natural Killer T-like (NKT-like) cells increased with smoking but not with COPD. NK cells were also higher when comparing ex-smokers with and without COPD. No significant differences were found between COPD subjects with a rapid vs. a non-rapid decline in lung function.Paper II: regulatory immune cells were investigated in this second flow cytometry-based paper. We found that FoxP3+ regulatory T cells (Tregs) were significantly lower in COPD subjects with a rapid decline in lung function compared to those with a non-rapid decline. This result was significant before as well as after adjustments for inhaled corticosteroids (ICS) usage and smoking. None of the investigated regulatory immune cell populations (T helper cells, activated T helper cells, and FoxP3+ Tregs) displayed significant differences associated with either COPD or smoking.Paper III: measurements of BAL cell DNA methylation revealed epigenome-wide differential methylation in COPD; 1,155 differentially methylated positions (DMPs) and 7,097 differentially methylated regions. Functional analysis using Kyoto Encyclopedia of Genes and Genomes and Gene Ontology databases identified biologically plausible pathways and gene relationships, including enrichment for transcription factor activity. No correlation was found between COPD and accelerated aging. For 79 unique DMPs, DNA methylation correlated significantly with gene expression in BAL. Thirty-nine percent of DMPs were co-located with single nucleotide polymorphisms (SNPs) associated with COPD.Conclusions: Among cytotoxic cell types, the NK cell population stood out as it 1) was increased in COPD; and 2) did not normalize in COPD subjects that had quit smoking. This indicates that NK cells might contribute to the continued disease progression in COPD even after smoking cessation.COPD subjects with a rapid decline in lung function had significantly lower levels of Fox P3+ Tregs in BAL. Further longitudinal research is needed to establish the causal direction of this relationship, but based on the evidence available to date, I deem it more plausible that a low expression of Fox P3+ Tregs would lead to a rapid decline in lung function, than the other way around.Our epigenome-wide association study (EWAS) identified widespread differential methylation in COPD, and many DMPs displayed a strong correlation with gene expression. Somewhat less than half of DMPs were located in close proximity to COPD-associated SNPs, suggesting that these might be sites where genetic factors regulate methylation status. In sum, our findings suggest strong associations between epigenetic factors and COPD. As this was the first ever published EWAS of COPD based on BAL cells, results must be validated in future studies.
|
|
| 16. |
- Fransén, Karin, 1973-, et al.
(author)
-
CRP levels are significantly associated with CRP genotype and estrogen use in The Lifestyle, Biomarker and Atherosclerosis (LBA) study
- 2022
-
In: BMC Cardiovascular Disorders. - : BioMed Central. - 1471-2261 .- 1471-2261. ; 22:1
-
Journal article (peer-reviewed)abstract
- Background: The C‑reactive protein (CRP) is an important biomarker for atherosclerosis and single nucleotide poly‑morphisms (SNPs) in the CRP locus have been associated with altered CRP levels and associated with risk for cardio‑vascular disease. However, the association between genetic variations in the CRP gene, estrogen use and CRP levels orearly signs of atherosclerosis in young healthy individuals is not fully characterized. We aimed to evaluate the influ‑ence of five genetic variants on both plasma CRP levels and carotid intima‑media thickness (cIMT) values, includingaspects on estrogen containing contraceptive use in females.Methods: Genotyping was performed with TaqMan real time PCR and compared with high sensitivity CRP serumlevels in 780 Swedish young, self‑reported healthy individuals. Haplotypes of the SNPs were estimated with the PHASEv 2.1. The cIMT was measured by 12 MHz ultrasound. The contraceptive use was self‑reported.Results: Strong associations between CRP and genotype were observed for rs3091244, rs1800947, rs1130864, andrs1205 in women (all p < 0.001). In men, only rs1800947 was associated with CRP (p = 0.029). The independent effectof genotypes on CRP remained significant also after adjustment for established risk factors. Female carriers of the H1/ATGTG haplotype had higher CRP than non‑carriers. This was specifically pronounced in the estrogen‑using group(p < 0.001), and they had also higher cIMT (p = 0.002) than non‑carriers but with a small cIMT difference between thehaplotype groups (0.02 mm). In parallel, a significant correlation between CRP and cIMT in the estrogen using groupwas observed (r = 0.194; p = 0.026).Conclusions: Estrogen use, genotypes and haplotypes in the CRP locus are significantly associated with CRP levels.Based on an observed interaction effect between sex/estrogen use and the H1/ATGTG haplotype on CRP, and amarginally thicker cIMT in the estrogen using group, our data suggest that both genotypes and estrogen usage couldbe involved in arterial wall structural differences. The causality between CRP levels and cIMT remains unclear, and theobserved difference in cIMT is not clinically relevant in the present state. Future larger and longitudinal studies mayshed further light on the role of more long‑term estrogen use and early atherosclerosis.
|
|
| 17. |
- Anderson, Jenna
(author)
-
Development and evaluation of a subunit DIVA vaccine against bluetongue virus serotype 8 in cattle
- 2014
-
Doctoral thesis (other academic/artistic)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.
|
|
| 18. |
- Gustafsson, Lars, et al.
(author)
-
Infectious disease, reproductive effort and the cost of reproduction in birds
- 1994
-
In: Philosophical transactions of the Royal Society of London: Series B. ; :346, s. 1655-1658
-
Journal article (pop. science, debate, etc.)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.
|
|
| 19. |
- Almkvist, Jenny, 1971, et al.
(author)
-
Newcastle disease virus neuraminidase primes neutrophils for stimulation by galectin-3 and formyl-Met-Leu-Phe
- 2004
-
In: Experimental cell research. - : Elsevier BV. - 0014-4827 .- 1090-2422. ; 298:1, s. 74-82
-
Journal article (peer-reviewed)abstract
- Human neutrophils are activated by the beta-galactoside-binding lectin galectin-3, provided that the cells are primed by in vivo extravasation or by in vitro preactivation with, for example, LPS. Removal of terminal sialic acid can change neutrophil functionality and responsiveness due to exposure of underlying glycoconjugate receptors or change in surface charge. Here, we investigated whether such alteration of the cell surface carbohydrate composition can alter the responsiveness of the cells to galectin-3. Neutrophils were treated with neuraminidases (NA) of different origins: Clostridium perfringens (CP), Salmonella typhimurium, Vibrio cholerae, and Newcastle disease virus (NDV). In the presence of NDV-NA, but no other NA, the otherwise non-responding neutrophils responded readily to galectin-3 by activation of the NADPH-oxidase. The galectin-3 priming effect was inhibited by the sialidase inhibitor 2,3-dehydro-2-deoxy-N-acetyl-neuraminic acid. Earlier studies have shown that priming of the neutrophil response to galectin-3 with, for example, LPS is paralleled by degranulation of intracellular vesicles and granules and upregulation of potential galectin-3 receptors. Also, NDV-NA (but not CP-NA) treatment induced degranulation, shown as an upregulation of complement receptor 3. Since not only the galectin response but also the response to the chemoattractant fMLF was primed, NDV-NA appears to induce a general priming phenomenon, possibly due to receptor upregulation by degranulation.
|
|
| 20. |
- Skovbjerg, Susann, 1973, et al.
(author)
-
Gram-positive and gram-negative bacteria induce different patterns of cytokine production in human mononuclear cells irrespective of taxonomic relatedness.
- 2010
-
In: 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
-
Journal article (peer-reviewed)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.
|
|
| 21. |
- Bhandage, Amol K., 1988-
(author)
-
Glutamate and GABA signalling components in the human brain and in immune cells
- 2016
-
Doctoral thesis (other academic/artistic)abstract
- Glutamate and γ-aminobutyric acid (GABA) are the principal excitatory and inhibitory neurotransmitters in the central nervous system (CNS). They both can activate their ionotropic and metabotropic receptors. Glutamate activates ionotropic glutamate receptors (iGlu - AMPA, kainate and NMDA receptors) and GABA activates GABA-A receptors which are modulated by many types of drugs and substances including alcohol. Using real time quantitative polymerase chain reaction, I have shown that iGlu and/or GABA-A receptor subunits were expressed in the hippocampus dentate gyrus (HDG), orbitofrontal cortex (OFC), dorsolateral prefrontal cortex (DL-PFC), central amygdala (CeA), caudate and putamen of the human brain and their expression was altered by chronic excessive alcohol consumption. It indicates that excitatory and inhibitory neurotransmission may have been altered in the brain of human alcoholics. It is possible that changes in one type of neurotransmitter system may drive changes in another. These brain regions also play a role in brain reward system. Any changes in them may lead to changes in the normal brain functions.Apart from the CNS, glutamate and GABA are also present in the blood and can be synthesised by pancreatic islet cells and immune cells. They may act as immunomodulators of circulating immune cells and can affect immune function through glutamate and GABA receptors. I found that T cells from human, rat and mouse lymph nodes expressed the mRNAs and proteins for specific GABA-A receptor subunits. GABA-evoked transient and tonic currents recorded using the patch clamp technique demonstrate the functional GABA-A channel in T cells. Furthermore, the mRNAs for specific iGlu, GABA-A and GABA-B receptor subunits and chloride cotransporters were detected in peripheral blood mononuclear cells (PBMCs) from men, non-pregnant women, healthy and depressed pregnant women. The results indicate that the expression of iGlu, GABA-A and GABA-B receptors is related to gender, pregnancy and mental health and support the notion that glutamate and GABA receptors may modulate immune function. Intra- and interspecies variability exists in the expression and it is further influenced by physiological conditions.
|
|
| 22. |
- Ågren, Rasmus, 1982, et al.
(author)
-
Identification of anticancer drugs for hepatocellular carcinoma through personalized genome-scale metabolic modeling
- 2014
-
In: Molecular Systems Biology. - : EMBO. - 1744-4292. ; 10:3
-
Journal article (peer-reviewed)abstract
- Synopsis Personalized GEMs for six hepatocellular carcinoma patients are reconstructed using proteomics data and a task-driven model reconstruction algorithm. These GEMs are used to predict antimetabolites preventing tumor growth in all patients or in individual patients. The presence of proteins encoded by 15,841 genes in tumors from 27 HCC patients is evaluated by immunohistochemistry. Personalized GEMs for six HCC patients and GEMs for 83 healthy cell types are reconstructed based on HMR 2.0 and the tINIT algorithm for task-driven model reconstruction. 101 antimetabolites are predicted to inhibit tumor growth in all patients. Antimetabolite toxicity is tested using the 83 cell type-specific GEMs. Genome-scale metabolic models (GEMs) have proven useful as scaffolds for the integration of omics data for understanding the genotype-phenotype relationship in a mechanistic manner. Here, we evaluated the presence/absence of proteins encoded by 15,841 genes in 27 hepatocellular carcinoma (HCC) patients using immunohistochemistry. We used this information to reconstruct personalized GEMs for six HCC patients based on the proteomics data, HMR 2.0, and a task-driven model reconstruction algorithm (tINIT). The personalized GEMs were employed to identify anticancer drugs using the concept of antimetabolites; i.e., drugs that are structural analogs to metabolites. The toxicity of each antimetabolite was predicted by assessing the in silico functionality of 83 healthy cell type-specific GEMs, which were also reconstructed with the tINIT algorithm. We predicted 101 antimetabolites that could be effective in preventing tumor growth in all HCC patients, and 46 antimetabolites which were specific to individual patients. Twenty-two of the 101 predicted antimetabolites have already been used in different cancer treatment strategies, while the remaining antimetabolites represent new potential drugs. Finally, one of the identified targets was validated experimentally, and it was confirmed to attenuate growth of the HepG2 cell line.
|
|
| 23. |
- Barman, Malin, 1983, et al.
(author)
-
Single Nucleotide Polymorphisms in the FADS Gene Cluster but not the ELOVL2 Gene are Associated with Serum Polyunsaturated Fatty Acid Composition and Development of Allergy (in a Swedish Birth Cohort).
- 2015
-
In: Nutrients. - : MDPI AG. - 2072-6643. ; 7:12, s. 10100-10115
-
Journal article (peer-reviewed)abstract
- Exposure to polyunsaturated fatty acids (PUFA) influences immune function and may affect the risk of allergy development. Long chain PUFAs are produced from dietary precursors catalyzed by desaturases and elongases encoded by FADS and ELOVL genes. In 211 subjects, we investigated whether polymorphisms in the FADS gene cluster and the ELOVL2 gene were associated with allergy or PUFA composition in serum phospholipids in a Swedish birth-cohort sampled at birth and at 13 years of age; allergy was diagnosed at 13 years of age. Minor allele carriers of rs102275 and rs174448 (FADS gene cluster) had decreased proportions of 20:4 n-6 in cord and adolescent serum and increased proportions of 20:3 n-6 in cord serum as well as a nominally reduced risk of developing atopic eczema, but not respiratory allergy, at 13 years of age. Minor allele carriers of rs17606561 in the ELOVL2 gene had nominally decreased proportions of 20:4 n-6 in cord serum but ELOVL polymorphisms (rs2236212 and rs17606561) were not associated with allergy development. Thus, reduced capacity to desaturase n-6 PUFAs due to FADS polymorphisms was nominally associated with reduced risk for eczema development, which could indicate a pathogenic role for long-chain PUFAs in allergy development.
|
|
| 24. |
- Heyman, Lovisa
(author)
-
Berries in Prevention of Metabolic Disease – focus on obesity, diabetes and gut microbiota
- 2015
-
Doctoral thesis (other academic/artistic)abstract
- The increasing prevalence of obesity is a worldwide health problem closely linked to diet and lifestyle factors. Obesity is associated with increased risk of several metabolic disorders including insulin resistance, nonalcoholic fatty liver disease and type 2 diabetes. Hence, there is a great need to identify dietary strategies for the prevention of obesity and related diseases. This thesis investigates the potential of different berries to mediate beneficial health effects in a mouse model of diet-induced obesity and prediabetes. We found that supplementation with lingonberries, blackcurrants and bilberries reduced body weight gain, insulin resistance, low-grade inflammation and hepatic lipid accumulation in C57BL/6J mice fed a high-fat diet. Supplementation with raspberries, crowberries, blackberries or prunes had no or small effects, whereas açai berries promoted development of obesity and fatty liver compared to the control group receiving high-fat diet without berries. Global hepatic gene expression analysis revealed that the phenotype in the lingonberry and bilberry groups was coupled to an anti-inflammatory effect, including downregulation of acute-phase proteins and inflammatory mediators. Mice receiving açai displayed an upregulation of steatosis markers and genes related to lipid synthesis, in line with the exacerbation of high-fat-induced fatty liver in these mice. The HELP-tagging assay was used to identify differentially methylated CpG sites in the lingonberry group compared to the high-fat control group. Lingonberries induced genome-wide and specific alterations of DNA methylation, however the significance of these findings remains to be established. Furthermore, different batches of lingonberries were found to have different capacity to prevent obesity. However lingonberries prevented low-grade inflammation, metabolic endotoxemia and modified the gut microbiota of high-fat fed mice, including increasing the Firmicutes/Bacteroidetes ratio. These findings were independent of effects on body weight gain and achieved regardless of the source of berries. The capacity of lingonberries to counteract negative outcomes of an unhealthy diet should be further evaluated in humans, including assessment of anti-inflammation and microbiota modulation. The generated knowledge about berries and their effects on metabolism may be useful in designing future dietary strategies aimed at preventing metabolic disease.
|
|
| 25. |
- Rönmark, Eva, et al.
(author)
-
High incidence and persistence of airborne allergen sensitization up to age 19 years
- 2017
-
In: Allergy. European Journal of Allergy and Clinical Immunology. - : Wiley-Blackwell. - 0105-4538 .- 1398-9995. ; 72:5, s. 723-730
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Longitudinal population-based studies about the natural history of allergic sensitization are rare. The aim was to study incidence and persistence of airborne allergen sensitization up to young adulthood and risk factors for early and late onset of sensitization.METHODS: All children aged 7-8 years in two municipalities in Northern Sweden were invited to a parental questionnaire and skin prick tests (SPTs) to ten airborne allergens, and 2148 (88%) participated. The protocol was repeated at age 11-12 and 19 years, and 1516 participated in all three examinations.RESULTS: Prevalence of any positive SPT increased from 20.6% at age 7-8 years to 30.6% at 11-12 years, and 42.1% at 19 years. Animals were the primary sensitizers at age 7-8 years, 16.3%, followed by pollen, 12.4%. Mite and mold sensitization was low. Mean annual incidence of any positive SPT varied between 2.8 and 3.4/100 per year, decreased by age for animal, and was stable for pollen. Sensitization before age 7-8 years was independently associated with family history of allergy, OR 2.1 (95% CI 1.6-2.8), urban living, OR 1.9 (95% CI 1.2-2.9), and male sex, OR 1.3 (95% CI 1.0-1.7), and negatively associated with birth order, OR 0.8 (95% CI 0.7-1.0), and furry animals at home, OR 0.7 (95% CI 0.7-0.9). Incidence after age 11-12 years was associated only with family history of allergy. Multisensitization at age 19 years was significantly associated with early age at sensitization. Remission of sensitization was uncommon.CONCLUSION: The increasing prevalence of allergic sensitization by age was explained by high incidence and persistence. After age 11-12 years, the factors urban living, number of siblings, and male sex lost their importance.
|
|
