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  • 51. Giha, H. A.
    et al.
    Nasr, A. A.
    Stockholm University, Faculty of Science, The Wenner-Gren Institute .
    Iriemenam, N. C.
    Stockholm University, Faculty of Science, The Wenner-Gren Institute .
    Berzins, Klavs
    Stockholm University, Faculty of Science, The Wenner-Gren Institute .
    Troye-Blomberg, Marita
    Stockholm University, Faculty of Science, The Wenner-Gren Institute .
    Arnot, D. E.
    ElGhazali, G.
    A malaria serological map indicating the intersection between parasite antigenic diversity and host antibody repertoires2012In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 31, no 11, p. 3117-3125Article in journal (Refereed)
    Abstract [en]

    A malaria vaccine targeting Plasmodium falciparum remains a strategic goal for malaria control. If a polyvalent vaccine is to be developed, its subunits would probably be chosen based on immunogenicity (concentration of elicited antibodies) and associations of selected antigens with protection. We propose an additional possible selection criterion for the inclusion of subunit antigens; that is, coordination between elicited antibodies. For the quantitative estimation of this coordination, we developed a malaria serological map (MSM). Construction of the MSM was based on three categories of variables: (i) malaria antigens, (ii) total IgG and IgG subclasses, (iii) different sources of plasma. To validate the MSM, in this study, we used four malaria antigens (AMA1, MSP2-3D7, MSP2-FC27 and Pf332-C231) and re-grouped the plasma samples into five pairs of subsets based on age, gender, residence, HbAS and malaria morbidity in 9 years. The plasma total IgG and IgG subclasses to the test antigens were measured, and the whole material was used for the MSM construction. Most of the variables in the MSM were previously tested and their associations with malaria morbidity are known. The coordination of response to each antigens pair in the MSM was quantified as the correlation rate (CR = overall number of significant correlations/total number of correlations x 100 %). Unexpectedly, the results showed that low CRs were mostly associated with variables linked with malaria protection and the antigen eliciting the least CRs was the one associated with protection. The MSM is, thus, of potential value for vaccine design and understanding of malaria natural immunity.

  • 52. Giha, Hayder A
    et al.
    ElGhazali, Gehad
    Nasr, Amre
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Iriemenam, Nnaemeka C
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Berzins, Klavs
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Troye-Blomberg, Marita
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Physiology.
    Theander, Thor G
    Arnot, David
    Clustering of malaria treatment failure (TF) in Daraweesh: hints for host genetic susceptibility to TF with emphasis on immune-modulating SNPs2010In: Infection, Genetics and Evolution, ISSN 1567-1348, E-ISSN 1567-7257, Vol. 10, no 4, p. 481-6Article in journal (Refereed)
    Abstract [en]

    In malaria, drug resistance and treatment failure (TF) are not synonymous, although are escalating together. Over 9 years of surveillances for malaria morbidity and TF in Daraweesh village in eastern Sudan (1991-2004), 136 donors (15-78 years) from 43 households, treated for 278 malaria episodes and had experienced 46 incident of TF, were included in this study. Blood obtained from the donors in 2005, was used for measurement of IgG subclasses against Pf332-C231 antigen and GM/KM allotyping and for genotyping of the donors for; FcgammaRIIA 131 (HH, RH, RR), CRP 286 (C

  • 53. Giha, Hayder A
    et al.
    Nasr, Amre
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Ekström, Mattias
    Israelsson, Elisabeth
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Arambepola, Gishanthi
    Arnot, David
    Theander, Thor G
    Troye-Blomberg, Marita
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Berzins, Klavs
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Tornvall, Per
    ElGhazali, Gehad
    Association of a single nucleotide polymorphism in the C-reactive protein gene (-286) with susceptibility to Plasmodium falciparum malaria2010In: Molecular medicine (Cambridge, Mass. Print), ISSN 1076-1551, E-ISSN 1528-3658, Vol. 16, no 1-2, p. 27-33Article in journal (Refereed)
    Abstract [en]

    The role of inflammation in malaria pathogenesis is not fully understood, although C-reactive protein (CRP) may have a negative influence on host immunity to infections. An upstream polymorphism, -286 (C > T > A), in the CRP gene is known to influence CRP levels. In this study, a cohort of 192 Sudanese donors, followed for malaria infection for 9 years, had their CRP -286 gene locus genotyped by pyrosequencing. The number of malaria episodes experienced by each individual over the study period was used as an index for malaria susceptibility. The prevalence of the CRP alleles A, C and T were 21%, 52% and 27%, respectively. Importantly, the A-allele, unlike the C- and T-alleles or CRP genotypes, was significantly associated with an increased number of malaria episodes, P = 0.007. The proportion of A-allele carriers among donors not known to have had malaria during the study period was 18%, whereas it was 43% and 63% among donors who had experienced 1-4 and > or =5 malaria episodes, respectively, over the same period (P = 0.002). Furthermore, the A-allele was associated with higher parasite counts. In conclusion, the CRP -286 A-allele was associated with an increased susceptibility to uncomplicated Plasmodium falciparum malaria.

  • 54. Giha, Hayder A
    et al.
    Nasr, Amre
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Iriemenam, Nnaemeka C
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Arnot, David
    Troye-Blomberg, Marita
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Theander, Thor G
    Berzins, Klavs
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Elghazali, Gehad
    Pandey, Janardan P
    Antigen-specific influence of GM/KM allotypes on IgG isotypes and association of GM allotypes with susceptibility to Plasmodium falciparum malaria.2009In: Malaria journal, ISSN 1475-2875, Vol. 8, no 1, p. 306-Article in journal (Refereed)
    Abstract [en]

    ABSTRACT: BACKGROUND: Plasmodium falciparum malaria is a complex disease in which genetic and environmental factors influence susceptibility. IgG isotypes are in part genetically controlled, and GM/KM allotypes are believed to be involved in this control. METHODS: In this study, 216 individuals from Daraweesh, an area of seasonal malaria transmission in Sudan, were followed for nine years for malaria infection. Total IgG and IgG isotypes against four malaria antigens, MSP2-3D7, MSP2-FC27, AMA1, and Pf332-C231 were measured in plasma obtained from the cohort at the end of the study, during the dry malaria-free period. The GM/KM allotypes of the donors were determined. RESULTS: The GM 1,17 5,13,14,6 phenotype was associated with a higher incidence of malaria compared with the non-1,17 5,13,14,6 phenotypes (P = 0.037). Paradoxically, the carriers of the GM 1,17 5,13,14,6 phenotype had significantly higher baseline levels of total IgG and non-cytophilic IgG isotypes as compared to non-carriers. The KM allotypes influence on IgG isotypes level was limited. Finally, the differences in the baseline concentrations of total IgG and IgG isotypes between the different GK/KM phenotype carriers were antigen-dependent. DISCUSSION: The results show that GM but not KM allotypes appeared to influence host susceptibility to uncomplicated malaria as well as the antibody profile of the donors, and the carriers of the GM 1,17 5,13,14,6 phenotype were the most susceptible CONCLUSIONS: The GM allotypes have significant influence on susceptibility to uncomplicated P. falciparum malaria and antigen-dependent influence on total IgG and IgG subclasses.

  • 55. Giha, Hayder A
    et al.
    Nasr, Amre
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Iriemenam, Nnaemeka C
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Balogun, Halima A
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Arnot, David
    Theander, Thor G
    Troye-Blomberg, Marita
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Berzins, Klavs
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Elghazali, Gehad
    Age-dependent association between IgG2 and IgG3 subclasses to Pf332-C231 antigen and protection from malaria, and induction of protective antibodies by sub-patent malaria infections, in Daraweesh2010In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 28, no 7, p. 1732-1739Article in journal (Refereed)
    Abstract [en]

    The certainty of the protective role of acquired immunity in malaria is the major drive for malaria vaccine development. In this study, we measured the levels of total IgG and IgG subclasses to four candidate malaria vaccine antigens; MSP2-3D7, MSP2-FC27, AMA-1 and Pf332-C231, in plasma obtained from a cohort of 136 donors from Daraweesh in Sudan. The cohort was followed for malaria infection for 9 years. After an initial analysis, the immune response to Pf332-C231 antigen was the only one found associated with protection, thus taken for further analysis. The number of previous clinical malaria episodes experienced by the donors was used as an index for relative protection. The number of these episodes was found to be negatively correlated with the levels of pre-existing total IgG, IgG2 and IgG3 to Pf332-C231 (correlation coefficient, CC - 0.215, p=0.012; CC - 0.195, p=0.023 and CC - 0.211, p=0.014, respectively), and also with age (CC - 0.311, p<0.001). Unexpectedly, equal levels of Pf332-C231 antibodies were induced by both patent and sub-patent infections regardless of the number of previous malaria episodes (1-7). Combining the correlation analysis with a multi-linear regression, three variable markers for protection were emerged, two age-dependent, the antibody response to Pf332-C231 and an unidentified marker (likely immune response to other antigens), and the third was an age-independent unidentified marker (possibly gene polymorphisms). In conclusion, this report suggests a protective effect for IgG subclasses to Pf332-C231 antigen against malaria.

  • 56. Giha, Hayder A.
    et al.
    Nasr, Amre
    Iriemenam, Nnaemeka C.
    Troye-Blomberg, Marita
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Berzins, Klavs
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    ElGhazali, Gehad
    Lack of significant influence for Fc gamma RIIa-RH131 or hemoglobin AA/AS polymorphisms on immunity and susceptibility to uncomplicated malaria and existence of marked linkage between the two polymorphisms in Daraweesh2012In: Microbes and infection, ISSN 1286-4579, E-ISSN 1769-714X, Vol. 14, no 6, p. 537-544Article in journal (Refereed)
    Abstract [en]

    Malaria signature on human genome is marked by several gene polymorphisms. HemoglobinAS (HbAS) is known to protect against severe malaria, but barely proved to protect against uncomplicated malaria (UM). Similarly, the influence of Fc gamma RIIa-RH131 polymorphism on malaria is controversial. Polymorphisms in both genes were examined and levels of IgG subclasses against four malaria antigens were measured for 250 Fulani's from Daraweesh, eastern Sudan. Morbidity data for up to nine years was available for 214 donors. Number of malaria episodes experienced by each individual during the study period was used as indicator for susceptibility to UM. PCR and RFLP were used for donors DNA genotyping and ELISA for antibodies measurement. Results revealed that neither Fc gamma RIIa-RH131 alleles/genotypes nor HbAA/AS was significantly associated with malaria morbidity or with levels of IgG to test antigens. Both polymorphisms were in Hardy-Weinberg Equilibrium, interestingly, there was strong association between the two polymorphisms (linkage disequilibrium - LD) with D' = 0.89. The association between the two polymorphisms was confirmed by analysis of independent material from a neighboring village. In conclusion, in Daraweesh both Fc gamma RIIa-RH131 and HbAA/AS genotypes, independently or together, were not major markers for UM susceptibility, however, marked LD was observed between the two polymorphisms.

  • 57. Giha, Hayder A
    et al.
    Nasr, Amre
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Iriemenam, Nnaemeka C
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Troye-Blomberg, Marita
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Berzins, Klavs
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Pandey, Janardan P
    Elghazali, Gehad
    Associations of multi-locus polymorphisms in an immune network with susceptibility to uncomplicated Plasmodium falciparum malaria in Daraweesh village, Eastern Sudan2011In: Infection, Genetics and Evolution, ISSN 1567-1348, E-ISSN 1567-7257, Vol. 11, no 7, p. 1674-1681Article in journal (Refereed)
    Abstract [en]

    Susceptibility to uncomplicated malaria (UM), as to other forms of the disease, is genetically determined. Over 9-years of clinical and parasitological follow up of inhabitants of Daraweesh, in Eastern Sudan, the relative susceptibility to UM was estimated in terms of number of episodes experienced by each individual. Previously, we reported that the levels of IgG2 and IgG3 to Pf332-C231 malaria antigen are negatively correlated with number of malaria episodes. In addition, four molecular markers for malaria susceptibility (CRP -286, GM/KM haplotypes, FcγRIIa131 and HbAS) were tested. In this study, the above data were combined and reanalysed. The CRP -286A allele and GM 1,17 5,13,14,6 phenotype were previously found to be associated with increased susceptibility to malaria; however, individuals have both polymorphism together were not more susceptible to UM than the non-carriers of the same double polymorphism. The FcγRIIa-RR131 and HbAA genotypes taken individually or as double polymorphism were not associated with malaria susceptibility; however, their combination with any or both of the former polymorphisms was mostly associated with increased susceptibility to malaria. None of the four markers were associated with the levels of IgG2 and IgG3 against Pf332-C231. In conclusion, while our data support the polygenic nature of susceptibility to UM and highlighted the role of immune markers polymorphisms, the combinations of these markers were not predictable, i.e. the combination of the susceptibility markers will not necessarily render the carriers more susceptible to UM.

  • 58.
    Giusti, Pablo
    et al.
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Troye Blomberg, Marita
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Varani, Stefania
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Plasmodium falciparum-Infected Erythrocytes and beta-Hematin Induce Partial Maturation of Human Dendritic Cells and Increase Their Migratory Ability in Response to Lymphoid Chemokines2011In: Infection and Immunity, ISSN 0019-9567, E-ISSN 1098-5522, Vol. 79, no 7, p. 2727-2736Article in journal (Refereed)
    Abstract [en]

    Acute and chronic Plasmodium falciparum infections alter theimmune competence of the host possibly through changes in dendriticcell (DC) functionality. DCs are the most potent activatorsof T cells, and migration is integral to their function. MatureDCs express lymphoid chemokine receptors (CCRs), expressionof which enables them to migrate to the lymph nodes, where theyencounter naïve T cells. The present study aimed to investigatethe impact of the synthetic analog to malaria parasite pigmenthemozoin, i.e., β-hematin, or infected erythrocytes (iRBCs)on the activation status of human monocyte-derived DCs and ontheir expression of CCRs. Human monocyte-derived DCs partiallymatured upon incubation with β-hematin as indicated byan increased expression of CD80 and CD83. Both β-hematinand iRBCs provoked the release of proinflammatory and anti-inflammatorycytokines, such as interleukin-6 (IL-6), IL-10, and tumor necrosisfactor alpha, but not IL-12, and induced upregulation of thelymphoid chemokine receptor CXCR4, which was coupled to an increasedmigration to lymphoid ligands. Taken together, these resultssuggest that the partial and transient maturation of human myeloidDCs upon stimulation with malaria parasite-derived productsand the increased IL-10 but lack of IL-12 secretion may leadto suboptimal activation of T cells. This may in turn lead toimpaired adaptive immune responses and therefore insufficientclearance of the parasites.

  • 59.
    Giusti, Pablo
    et al.
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Urban, Britta C
    Frascaroli, Giada
    Albrecht, Letusa
    Tinti, Anna
    Troye-Blomberg, Marita
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Varani, Stefania
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Plasmodium falciparum-infected erythrocytes and beta-hematin induce partial maturation of human dendritic cells and increase their migratory ability in response to lymphoid chemokines.2011In: Infection and Immunity, ISSN 0019-9567, E-ISSN 1098-5522, Vol. 79, no 7, p. 2727-2736Article in journal (Refereed)
    Abstract [en]

    Acute and chronic Plasmodium falciparum infections alter the immune competence of the host possibly through changes in dendritic cell (DC) functionality. DCs are the most potent activators of T cells, and migration is integral to their function. Mature DCs express lymphoid chemokine receptors (CCRs), expression of which enables them to migrate to the lymph nodes, where they encounter naïve T cells. The present study aimed to investigate the impact of the synthetic analog to malaria parasite pigment hemozoin, i.e., β-hematin, or infected erythrocytes (iRBCs) on the activation status of human monocyte-derived DCs and on their expression of CCRs. Human monocyte-derived DCs partially matured upon incubation with β-hematin as indicated by an increased expression of CD80 and CD83. Both β-hematin and iRBCs provoked the release of proinflammatory and anti-inflammatory cytokines, such as interleukin-6 (IL-6), IL-10, and tumor necrosis factor alpha, but not IL-12, and induced upregulation of the lymphoid chemokine receptor CXCR4, which was coupled to an increased migration to lymphoid ligands. Taken together, these results suggest that the partial and transient maturation of human myeloid DCs upon stimulation with malaria parasite-derived products and the increased IL-10 but lack of IL-12 secretion may lead to suboptimal activation of T cells. This may in turn lead to impaired adaptive immune responses and therefore insufficient clearance of the parasites.

  • 60. Gryseels, Bruno
    et al.
    Zumla, Alimuddin
    Troye-Blomberg, Marita
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Kieny, Marie Paule
    Quaglio, Gianluca
    Holtel, Andreas
    Laang, Hannu
    Romaris, Manuel
    De Magistris, Maria Teresa
    Nuez, Ana Nieto
    Olesen, Ole F
    Ghalouci, Rachida
    Lönnroth, Anna
    European Union conference on poverty-related diseases research.2009In: The Lancet Infectious Diseases, ISSN 1474-4457, Vol. 9, no 6, p. 334-7Article in journal (Refereed)
  • 61. Guenot, Marianne
    et al.
    Loizon, Séverine
    Howard, Jennifer
    Costa, Giulia
    Baker, David A.
    Mohabeer, Shaneel Y.
    Troye-Blomberg, Marita
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Moreau, Jean-Francois
    Dechanet-Merville, Julie
    Mercereau-Puijalon, Odile
    Mamani-Matsuda, Maria
    Behr, Charlotte
    Phosphoantigen Burst upon Plasmodium falciparum Schizont Rupture Can Distantly Activate V gamma 9V delta 2 T Cells2015In: Infection and Immunity, ISSN 0019-9567, E-ISSN 1098-5522, Vol. 83, no 10, p. 3816-3824Article in journal (Refereed)
    Abstract [en]

    Malaria induces potent activation and expansion of the V gamma 9V delta 2 subpopulation of gamma delta T cells, which inhibit the Plasmodium falciparum blood cycle through soluble cytotoxic mediators, abrogating merozoite invasion capacity. Intraerythrocytic stages efficiently trigger V gamma 9V delta 2 T-cell activation and degranulation through poorly understood mechanisms. P. falciparum blood-stage extracts are known to contain phosphoantigens able to stimulate V gamma 9V delta 2 T cells, but how these are presented by intact infected red blood cells (iRBCs) remains elusive. Here we show that, unlike activation by phosphoantigen-expressing cells, V gamma 9V delta 2 T-cell activation by intact iRBCs is independent of butyrophilin expression by the iRBC, and contact with an intact iRBC is not required. Moreover, blood-stage culture supernatants proved to be as potent activators of V gamma 9V delta 2 T cells as iRBCs. Bioactivity in the microenvironment is attributable to phosphoantigens, as it is dependent on the parasite DOXP pathway, on V gamma 9V delta 2 TCR signaling, and on butyrophilin expression by V gamma 9V delta 2 T cells. Kinetic studies showed that the phosphoantigens were released at the end of the intraerythrocytic cycle at the time of parasite egress. We document exquisite sensitivity of V gamma 9V delta 2 T cells, which respond to a few thousand parasites. These data unravel a novel framework, whereby release of phosphoantigens into the extracellular milieu by sequestered parasites likely promotes activation of distant V gamma 9V delta 2 T cells that in turn exert remote antiparasitic functions.

  • 62.
    Guillén, Sergio
    et al.
    MYSPHERA, Spain.
    Holst, Marita
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Distance- Spanning Technology.
    Ståhlbröst, Anna
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Computer Science.
    Lenz, Olivier
    Federation Internationale de l’Automobile, Region I, Belgium.
    IoT European Large-Scale Pilots: Integration, Experimentation and Testing2017In: Cognitive Hyperconnected Digital Transformation: Internet of Things Intelligence Evolution / [ed] Ovidiu Vermesan, SINTEF, Norway; Joël Bacquet, European Commission, Belgium, River Publishers, 2017Chapter in book (Refereed)
    Abstract [en]

    The IoT European Large-Scale Pilots Programme includes the innovationconsortia that are collaborating to foster the deployment of IoT solutionsin Europe through the integration of advanced IoT technologies across thevalue chain, demonstration of multiple IoT applications at scale and in a usagecontext, and as close as possible to operational conditions.

    The programme projects are targeted, goal-driven initiatives that proposeIoT approaches to specific real-life industrial/societal challenges. They areautonomous entities that involve stakeholders from the supply side to thedemand side, and contain all the technological and innovation elements,the tasks related to the use, application and deployment as well as thedevelopment, testing and integration activities.

    This chapter describes the IoT Large Scale Pilot Programme initiativetogether with all involved actors. These actors include the coordination andsupport actions CREATE-IoT and U4IoT, being them drivers of the programme,and all five IoT Large-Scale Pilot projects, namely ACTIVAGE,IoF2020, MONICA, SynchroniCity and AUTOPILOT.

  • 63.
    Holst, Marita
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Distance- Spanning Technology. Luleå University of Technology, Department of Business Administration, Technology and Social Sciences, Innovation and Design.
    Enabling boundary-crossing collaboration for innovation: issues for collaborative working environments2007Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    In this thesis, boundary-crossing collaborative knowledge work aiming for innovation and use of ICT is in focus. The starting point for the research was the proposition that we still have much to learn about boundary- crossing collaboration for innovation and the use of ICT before we can design enabling and supporting ICT and collaborative working environments. Thus, the purpose has been to study and understand collaborative boundary- crossing working groups' activities, as a way to extend the possibilities to design enabling and supporting ICT. To meet this purpose, I wanted to answer the question: How can boundary-crossing collaboration aiming for innovation be enabled in collaborative working environments? Three case studies, with somewhat different focuses, methods and also results, have been performed. Different models as frameworks for both analysis and design have been used in the cases. Main conclusions and contributions of the thesis are given as lessons learned, related to four main areas which were identified from analysis of case data. The first set of conclusions is related to processes and factors enabling knowledge work across boundaries. These are: application of energizing factors, use of boundary objects, addressing roles, norms, values and knowledge assets and, finally, creating dedicated places and spaces. The second set of conclusions is related to ICT issues in boundary- crossing knowledge work. These are: choice of technology, shared virtual platform and models for appreciating technology needs. The third set of conclusions is related to the importance of appreciation of user needs, and methods for this, in the process of designing or developing a collaborative working environment. The fourth set of conclusions comes in the form of reflections on the theoretical models that have been used during the research. There is a need for models and methods that enable design of collaborative environments, as well as models and methods that enable this to be done from a user needs perspective. From the lessons learned, some overarching reflections on implications for collaborative working environments are made. Hence, implications for CWEs as a whole, and some ideas on future research, are presented in the form of a tentative model which can be viewed as a model for designing group processes and relevant technology in a CWE. In this model, designing a CWE and its processes imply more that just designing technology. To conclude, the thesis contributes to the understanding of organisational processes for boundary-crossing collaborative knowledge work through lessons learned, which, in turn, give implications for CWEs.

  • 64. Holst, Marita
    Knowledge work across boundaries: inquiring into the processes of creating a shared context2004Licentiate thesis, comprehensive summary (Other academic)
    Abstract [en]

    The problem area focused on in this thesis is knowledge work across boundaries and the processes of information exchange which lead to sharing, creation and use of knowledge and, thus, a shared context. The purpose of the thesis is to explore the management of these processes and which roles information and communication technology are given by the boundary-crossing groups. The relevance of this exploration is based on the importance of learning about knowledge integration in cross-functional projects, since our understanding of how knowledge is integrated within these groups remain limited. In order to inquire into the processes of boundary-crossing knowledge work and information exchange, an interpretative interview study, involving three groups working across knowledge boundaries, was performed. Moreover, the experiences of four student groups were explored. To be able to draw some conclusions from these processes, two models, the POM-model and the Ba- model, focusing on interaction and communication, were used as frameworks for the analysis. The thesis contributes to the existing knowledge of groups working across boundaries and the specific conditions of this, in relation to knowledge sharing, creation and use. Moreover, it makes more explicit the role ICT plays in these processes. Insights and understanding of the processes of creation of a shared context across boundaries give possibilities to more intentionally created conditions for knowledge work. This, in turn, gives support and enables knowledge sharing, creation and use in groups working across boundaries. The lessons learnt from the study are as follows. Different strategies have been used to handle the processes of knowledge creation, sharing and use. In this context I have found that a smaller group that focuses on a boundary object has come furthest in the creation of a shared context. Further, information exchange processes have been the ultimate source for creating the shared context and has been most effectively managed through a balance of physical, virtual and mental contexts. Hence, interplay between different contexts has enabled the groups to create a shared context. ICT has been used to a lesser extent, probably because of the complex nature of the task at hand. In relation to this, the groups argue that the fact that they work across knowledge boundaries has made face-to-face meetings more important. Finally, I have found that the two sense-making-models, used for analysis, complement each other in their respective shortcomings. They offer a potential for designing boundary-crossing knowledge work and its enabling and supporting systems in a holistic way, taking both social and technical aspects into account.

  • 65. Holst, Marita
    Knowledge work across traditional boundaries: a compilation of interviews2004Report (Other academic)
    Abstract [en]

    This report is a compilation of ten interviews made with people active in three new Arenas at Luleå University of Technology. The report is intended for the International Evaluation Group connected to the strategic work at the University of Technology in Luleå (LTU). The collected data will be used in a future licentiate thesis. In this report however the material is not completely processed and analyzed. Therefore the report should be considered as a preliminary report containing empirical findings and an early analysis. The purpose with the report is to give illustrative examples of new boundary crossing groups in order to develop our knowledge of how to design for knowledge work. Through the understanding of what experiences people who work in boundary-crossing groups meet when they interact and communicate and in this way create a shared context important input to which issues to consider when we design or chose systems for boundary- crossing knowledge work will be given. The systems I focus on are human activity systems (Checkland 1981) and their supporting systems, i.e. information systems in Checkland’s vocabulary. The results from the interviews are presented in the context of Arenas as a way to keep the respondents anonymous but still in a rich way with the ambition to give a rich picture of the work within the Arenas. Showing how communication, interaction, knowledge creation and the creation of shared context have been done. The resluts show taht all three Arenas have been successful and innovative in that they all have been able to create new undergraduate programs and new research projects. This work have been supported by the social networking which can be viewed as a communications process in which knowledge is shared and new knowledge is created. The creation of a shared knowledge base within the Arenas have facilitated and made the innovation process possible. The social networking gives possibilities for redundant knowledge and this redundancy is essential since it gives the ability to envisage a social system of joint actions. Information and communication technology (ICT) is used to complement these processes and in this way increase the ability to communicate across boundaries in time and space. It has been a natural process to begin work with face to face meetings as a way to create the shared context for the work and that as the process proceeds the respondents now considers virtual media.

  • 66. Holst, Marita
    Needfinding through narrative inquiry in systems design2005In: Internet and information technology in modern organizations: challenges & answers : proceedings of the 5th International Business Information Management Association Conference, December 13-15, 2005, Cairo, Egypt / [ed] Khalid S. Soliman, International Business Information Management Association (IBIMA), 2005Conference paper (Refereed)
    Abstract [en]

    This paper explicates the process of applying needfinding and narrative inquiry as a way to identify needs and, thus, enable the design of a viable community for knowledge-sharing and creation across boundaries among young entrepreneurs. The specific situation which the design of a knowledge community constitute is discussed and the usefulness of needfinding is thereafter evaluated in relation to the challenges of creating a viable community constructed from participants' identified needs and interests. With a focus on discovering users' needs early on, needfinding involves users throughout the design process, leading to perpetual and persistent user-centred systems.

  • 67.
    Holst, Marita
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Distance- Spanning Technology.
    Project: Advanced Pilots Of Living Labs Operataing in Networks2012Other (Other (popular science, discussion, etc.))
    Abstract [en]

    The main issues addressed by APOLLON are the present lack of Living Lab harmonisation and collaboration, and the serious difficulties of SMEs in engaging in cross-border innovation. APOLLON will demonstrate the positive impacts of cross-border domain-specific Living Lab networks, by setting up an advanced pilot composed of 4 thematically focused European-wide Living Lab experiments. In the experiments, SMEs are enabled to take part in cross-border Living Lab experiments beyond their home markets, and are supported by large industrial companies, academic centres and other stakeholders. The APOLLON pilot aims at the sharing and harmonisation of Living Lab approaches and platforms between networks of exemplary European Living Labs, and the subsequent evaluation results and the set up of sustainable domain-specific networks on a European and global level. APOLLON addresses 4 major domains in which ICT products and services innovation may benefit most from cross-border Living Lab networking. These are: (1) Homecare and Independent Living, (2) Energy Efficiency, (3) eManufacturing and (4) eParticipation.

  • 68. Holst, Marita
    et al.
    Mirijamdotter, Anita
    An application of Ba: deconstructing formative processes in multdisciplinary work groups2005In: International Journal of Knowledge, Culture and Change Management, ISSN 1447-9524, E-ISSN 1447-9575, Vol. 4, p. 1051-59Article in journal (Refereed)
    Abstract [en]

    The paper draws on an empirical study and examines how new multidisciplinary groups interact to create a shared context for knowledge work. Within the context of the campus-wide commitment to transform itself into a "Creative University", Luleå University of Technology explores new ways to further collaborative multidisciplinary knowledge-creation. Multidisciplinary knowledge areas, such as "Media, Music and Technology", have been defined, originating in multifaceted and complex problems. New knowledge will be shaped through enabling organisational processes created among participants dedicated to realising the full potential of the organisational commitment. Enabling the development of organisational knowledge implies that people from different disciplines - e.g., engineering and social sciences - cooperate and thereby share and use information which they convert into knowledge. The fact that these groups work in partnership in a logical, not physical, organisation leads to questions about how they organise their work, how they communicate, and interact, and where they meet physically, mentally and virtually, and for what purposes. The authors conducted semi-structured interviews with selected employees with the intention of learning from group-members in the new multidisciplinary organisational project. Interview data were analysed in terms of Ba elements. Ba is a perception of a place - which can be virtual, mental or physical - with a shared purpose. Ba provides guidance on "making sense of" how an organisation works and why it works the way it does in relation to knowledge-creation. Predicated on grounded theory about cross-functional work transcending traditional boundaries, Ba can also serve as a framework for designing sustainable new processes that create organisational learning, where information and communication technology are the driving forces.

  • 69.
    Holst, Marita
    et al.
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Distance- Spanning Technology.
    Mirijamdotter, Anita
    Luleå University of Technology, Department of Business Administration, Technology and Social Sciences, Innovation and Design.
    Framing multidisciplinary teams: sense making through the POM model2006In: Integrating Visions of Technology: Proceedings of the 12th Annual Working Conference of CPTS / [ed] Andrew Basden; Anita Mirijamdotter; Sytse Strijbos, CPTS , 2006, p. 111-140Conference paper (Refereed)
    Abstract [en]

    In this paper we focus on Living Labs for promoting and developing collaborative working environments (CWEs). The issues we address in this context are related to knowledge-sharing for innovation. More precisely we explore methodologies for appreciative inquiry that stimulate creativity and facilitate the process for co-creative needfinding and innovation. Additionally we contribute to a European state-of-the-art in utilizing Living Labs to user-centric ICT innovation and to establishing a foundation for a European Network of Living Labs. A pan-European Network of Living Labs brings the extreme benefit of leveraging the concept of a Europe of Regions. However, when interactions are conducted at a distance across organisational, geographical and cultural boundaries, placing at risk the overall competiveness of an organisation, the challenge is to develop tools, methods, and work-practices to manage this interaction. This is the aim of this research. The context and content for this paper is transformation processes in higher education in which knowledge from distinct disciplines are integrated into new multidisciplinary education and research. Checkland's and Holwell's model of Process for Organisational Meanings (POM) is used to present and appreciate the efficacy of these set-up processes. The POM-model is found to be useful for making sense of design work across boundaries and for identifying best practices as it visually represents the important processes of making meaning by interactions among participants in various organisational settings and by means of technology. The results of the study point to best practices for creating shared vision across disciplinary boundaries. Shared visions enable knowledge creation and integration, in turn generating common ground for aligned action and design. Important insights for how to cultivate the fragile processes of setting up multidisciplinary teams are currently lacking. Hence, the findings from this study contribute to set up of multidisciplinary teams successfully. Aware of the start up issues, chances of successful implementation will be enhanced.

  • 70. Holst, Marita
    et al.
    Mirijamdotter, Anita
    The creation of a shared context in a multdisciplinary setting2004Conference paper (Refereed)
    Abstract [en]

    The paper draws on an empirical study and examines how new multidisciplinary groups interact to create a shared context for knowledge work. Within the context of the campus-wide commitment to transform into a モCreative Universityヤ, Luleå University of Technology explores new ways to further collaborative multidisciplinary knowledge creation. Multidisciplinary knowledge areas, such as ムMedia, Music and Technologyメ, have been defined, with origins in multifaceted and complex problems. New knowledge will be created through enabling environmental processes created among participants committed to realizing the full potential of the organizational commitment. Enabling the development of organizational knowledge implies that people from different disciplines - e.g., engineering and social sciences - cooperate and thereby share and use information which they convert into knowledge. The fact that these groups work in partnership in a logical, not physical, organization leads to questions about how they organize their work, how they communicate, and interact, and where they meet physically, mentally and virtually, and for what purposes. With the intention of learning from group members in a new multidisciplinary organizational project, the authors conducted semi-structured interviews with selected employees. Interview data were analysed in terms of Ba elements. Ba is a perception of a place - which can be virtual, mental or physical - with a shared purpose. Ba provides guidance on ムmaking senseメ of how an organisation works and why it works the way it does in relation to knowledge creation. Predicated on grounded theory about crossfunctional work transcending traditional boundaries, Ba can also serve as a framework for designing sustainable new processes that create organizational learning, where information and communication technology are driving forces.

  • 71.
    Holst, Marita
    et al.
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Distance- Spanning Technology.
    Ståhlbröst, Anna
    Luleå University of Technology, Department of Business Administration, Technology and Social Sciences, Innovation and Design.
    Appreciating needs for innovative IT design2007In: International Journal of Knowledge, Culture and Change Management, ISSN 1447-9524, E-ISSN 1447-9575, Vol. 6, no 4, p. 37-46Article in journal (Refereed)
    Abstract [en]

    Identifying user needs is important as use of interaction technologies have grown and influence leisure time and work. This paper presents methods for identifying and operationalising needs in design processes

  • 72. Holst, Marita
    et al.
    Ståhlbröst, Anna
    Luleå University of Technology, Department of Business Administration, Technology and Social Sciences, Innovation and Design.
    Enriching the process of appreciating needs with storytelling2006In: International Journal of Technology, Knowledge and Society, ISSN 1832-3669, Vol. 2, no 4, p. 61-68Article in journal (Refereed)
    Abstract [en]

    This paper explicates the possibility to enrich the process of appreciating needs with storytelling. In this way we are able to identify needs and, thus, facilitate the design process of a viable community for knowledge-sharing and creation across boundaries among young entrepreneurs. The specific situation which the design of a knowledge community constitute is discussed and the usefulness of our approach is thereafter valued in relation to the challenges of creating a viable community constructed from participants' identified needs and interests.

  • 73. Holst, Marita
    et al.
    Ståhlbröst, Anna
    Luleå University of Technology, Department of Business Administration, Technology and Social Sciences, Innovation and Design.
    Expanding and enriching needfinding with narrative inquiry2005In: Second International Conference on Technology, Knowledge and Society: The Social Ecology of Digital Technologies, 2005Conference paper (Refereed)
    Abstract [en]

    This paper explicates the process of expanding and enriching needfinding through narrative inquiry. In this way we are able to identify needs and, thus, facilitate the design process of a viable community for knowledge-sharing and creation across boundaries among young entrepreneurs. The specific situation which the design of a knowledge community constitute is discussed and the usefulness of our approach is thereafter valued in relation to the challenges of creating a viable community constructed from participants' identified needs and interests.

  • 74.
    Holst, Marita
    et al.
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Distance- Spanning Technology.
    Ståhlbröst, Anna
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Computer Science.
    Need-finding through narrative inquiry in systems design2005In: Internet and information technology in modern organizations: Internet and information technology in modern organizations : challenges & answers : proceedings of the 5th International Business Information Management Association Conference, December 13-15, 2005, Cairo, Egypt / [ed] Khalid S Soliman, International Business Information Management Association (IBIMA), 2005Conference paper (Refereed)
    Abstract [en]

    This paper explicates the process of expanding and enriching need-finding through narrative inquiry. In this way we are able to identify needs and, thus, facilitate the design process of a knowledge community and its virtual spaces for knowledgesharing and creation across boundaries among young entrepreneurs. The specific situation which the design of a knowledge community constitute is discussed and the usefulness of our approach is thereafter valued in relation to the challenges of creating a viable community constructed from participants' identified needs and interests

  • 75.
    Holst, Marita
    et al.
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Distance- Spanning Technology.
    Ståhlbröst, Anna
    Luleå University of Technology, Department of Business Administration, Technology and Social Sciences, Innovation and Design.
    Bergvall-Kåreborn, Birgitta
    Luleå University of Technology, Department of Business Administration, Technology and Social Sciences, Innovation and Design.
    Openness in living labs: facilitating innovation2010In: Proceedings of the 33rd IRIS Seminar, 2010Conference paper (Refereed)
    Abstract [en]

    Innovation has come to replace efficiency and quality as the main source of competitive advantage for firms from the 1990s onwards. Hence, to an increasing extent, organisations need to consider in which ways they can achieve higher levels of innovative thinking and flexibility. Moreover, the creation of today's complex systems of products, services and processes requires a merging of knowledge from diverse perspectives, e.g. disciplinary or skill-based. One common way to meet these challenges is to set up boundary crossing collaborative groups. The idea is that innovative processes can be fertilised by having people with differentiated knowledge collaborating. Knowledge necessary for innovation and product/service development is, therefore, increasingly distributed both within and across organisations or other types of stakeholders, posing new challenges. To manage these challenges one new approach is evolving, called Living Labs. In this paper we present an innovative development process of a mobile service, taking a Living Lab approach. This paper focus on the effects of openness in an innovation process supported by a Living Lab approach for development of mobile services. The study shows that the innovation process was remarkably shortened in the open and multi-perspective process.

  • 76. Holtel, Andreas
    et al.
    Troye-Blomberg, Marita
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Penas-Jimenez, Inmaculada
    EU-funded malaria research under the 6th and 7th Framework Programmes for research and technological development.2011In: Malaria Journal, ISSN 1475-2875, E-ISSN 1475-2875, Vol. 10, p. 11-Article in journal (Refereed)
    Abstract [en]

    While malaria research has traditionally been strong in Europe, targeted and sustained support for cooperative malaria research at EU level, namely through the EU's 6th and 7th Framework Programmes for research and technological development, FP6 (2002-2006) and FP7 (2007-2013), has boosted both impact and visibility of European malaria research. Most of the European malaria research community is now organized under a number of comprehensive and complementary research networks and projects, assembled around four key areas: (1) fundamental research on the malaria parasite and the disease, (2) development of new malaria drugs, (3) research and development of a malaria vaccine, and (4) research to control the malaria-transmitting mosquito vector. Considerable efforts were undertaken to ensure adequate participation of research groups from disease-endemic countries, in particular from Africa, with the long-term aim to strengthen cooperative links and research capacities in these countries. The concept of organizing European research through major strategic projects to form a "European Research Area" (ERA) was originally developed in the preparation of FP6, and ERA formation has now turned into a major EU policy objective explicitly inscribed into the Lisbon Treaty. EU-funded malaria research may serve as a showcase to demonstrate how ERA formation can successfully be implemented in a given area of science when several surrounding parameters converge to support implementation of this strategic concept: timely coincidence of political stimuli, responsive programming, a clearly defined--and well confined--area of research, and the readiness of the targeted research community who is well familiar with transnational cooperation at EU level. Major EU-funded malaria projects have evolved into thematic and organizational platforms that can collaborate with other global players. Europe may thus contribute more, and better, to addressing the global research agenda for malaria.

  • 77. Howard, Jennifer
    et al.
    Loizon, Séverine
    Tyler, Christopher J.
    Duluc, Dorothée
    Moser, Bernhard
    Mechain, Matthieu
    Duvignaud, Alexandre
    Malvy, Denis
    Troye-Blomberg, Marita
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Moreau, Jean-Francois
    Eberl, Matthias
    Mercereau-Puijalon, Odile
    Déchanet-Merville, Julie
    Behr, Charlotte
    Mamani-Matsuda, Maria
    The Antigen-Presenting Potential of V gamma 9V delta 2 T Cells During Plasmodium falciparum Blood-Stage Infection2017In: Journal of Infectious Diseases, ISSN 0022-1899, E-ISSN 1537-6613, Vol. 215, no 10, p. 1569-1579Article in journal (Refereed)
    Abstract [en]

    During Plasmodium falciparum infections, erythrocyte-stage parasites inhibit dendritic cell maturation and function, compromising effective antimalarial adaptive immunity. Human V gamma 9V delta 2 T cells can act in vitro as antigen-presenting cells (APCs) and induce alpha beta T-cell activation. However, the relevance of this activity in vivo has remained elusive. Because V gamma 9V delta 2 T cells are activated during the early immune response against P. falciparum infection, we investigated whether they could contribute to the instruction of adaptive immune responses toward malaria parasites. In P. falciparum-infected patients, V gamma 9V delta 2 T cells presented increased surface expression of APC-associated markers HLA-DR and CD86. In response to infected red blood cells in vitro, V gamma 9V delta 2 T cells upregulated surface expression of HLA-DR, HLA-ABC, CD40, CD80, CD83, and CD86, induced naive alpha beta T-cell responses, and cross-presented soluble prototypical protein to antigen-specific CD8(+) T cells. Our findings qualify V gamma 9V delta 2 T cells as alternative APCs, which could be harnessed for therapeutic interventions and vaccine design.

  • 78. Ibitokou, Samad A.
    et al.
    Boström, Stephanie
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Brutus, Laurent
    Ndam, Nicaise Tuikue
    Vianou, Bertin
    Agbowai, Carine
    Amadoudji Zin, Martin
    Huynh, Bich Tram
    Massougbodji, Achille
    Deloron, Philippe
    Troye-Blomberg, Marita
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Fievet, Nadine
    Luty, Adrian J. F.
    Submicroscopic Infections with Plasmodium falciparum during Pregnancy and Their Association with Circulating Cytokine, Chemokine, and Cellular Profiles2014In: Clinical and Vaccine Immunology, ISSN 1556-6811, E-ISSN 1556-679X, Vol. 21, no 6, p. 859-866Article in journal (Refereed)
    Abstract [en]

    The immunological consequences of pregnancy-associated malaria (PAM) due to Plasmodium falciparum have been extensively investigated in cross-sectional studies conducted at delivery, but there have been very few longitudinal studies of changes due to PAM during pregnancy. We conducted a prospective study in Benin to investigate the changes associated with PAM in groups of 131 and 111 women at inclusion in the second trimester and at delivery, respectively. Infected women were identified by standard microscopic examinations of blood smears and by quantitative PCR (qPCR) assays and were matched to uninfected control women by age, gestational age, and gravidity. We quantified plasma levels of a panel of soluble immunological mediators and other mediators, as well as the frequencies of peripheral blood mononuclear cell types. Comparisons of these variables in infected and uninfected women used multivariate analyses, and we also assessed the predictive value of variables measured at inclusion for pregnancy outcomes at delivery. In multivariate analyses, peripheral plasma interleukin 10 (IL-10) and gamma interferon-inducible protein 10 (IP-10) levels were associated with PAM at inclusion and at delivery, while higher IL-10 levels distinguished qPCR-detectable submicroscopic infections at inclusion but not at delivery. Maternal anemia at delivery was associated with markers of proinflammatory (increased frequency of monocytes) and anti-inflammatory (increased IL-10 levels and increased activation of regulatory T cells) activity measured at inclusion. Elevated concentrations of IL-10 are associated with the majority of P. falciparum infections during pregnancy, but this marker alone does not identify all submicroscopic infections. Reliably identifying such occult infections will require more sensitive and specific methods.

  • 79. Ibitokou, Samad
    et al.
    Boström, Stéphanie
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Brutus, Laurent
    Ndam, Nicaise
    Vianou, Bertin
    Agbowai, Carine
    Zin, Martin
    Huynh, Bich
    Massougbodji, Achille
    Deloron, Philippe
    Troye-Blomberg, Marita
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Fievet, Nadine
    Luty, Adrian
    Sub-microscopic infections with Plasmodium falciparum during pregnancy and their association with circulating cytokine, chemokine and cellular profilesManuscript (preprint) (Other academic)
  • 80. Ibitokou, Samad
    et al.
    Brutus, Laurent
    Vianou, Bertin
    Oesterholt, Mayke
    Massougbodji, Achille
    Deloron, Philippe
    Troye-Blomberg, Marita
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Fievet, Nadine
    Luty, Adrian J. F.
    Gestational age-related changes in the peripheral blood cell composition of sub-Saharan African women2013In: Journal of Reproductive Immunology, ISSN 0165-0378, E-ISSN 1872-7603, Vol. 98, no 1-2, p. 21-28Article in journal (Refereed)
    Abstract [en]

    Gestational age-related changes in the cellular composition of peripheral blood have not been described in sub-Saharan African settings. We conducted longitudinal cohort studies in Beninese and Tanzanian mothers with quantification of peripheral blood mononuclear cell-types ex vivo using flow cytometry. Between the second trimester and delivery the frequency of CD4(+) T cells declined significantly, contrasting with a non-significant increase in CD8(+) T cells, but no changes in T-regulatory, NK or NKT cell frequencies. Antigen-presenting cell profiles were also unaltered, although non-significant trends were evident. These changes resemble in some respects those reported during pregnancies in developed countries, but differ in others.

  • 81. Ibitokou, Samad
    et al.
    Oesterholt, Mayke
    Brutus, Laurent
    Borgella, Sophie
    Agbowaï, Carine
    Ezinmègnon, Sèm
    Lusingu, John
    Schmiegelow, Christentze
    Massougbodji, Achille
    Deloron, Philippe
    Troye-Blomberg, Marita
    Stockholm University, Faculty of Science, The Wenner-Gren Institute .
    Varani, Stefania
    Stockholm University, Faculty of Science, The Wenner-Gren Institute .
    Luty, Adrian J. F.
    Fievet, Nadine
    Peripheral Blood Cell Signatures of Plasmodium falciparum Infection during Pregnancy2012In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, no 12, p. e49621-Article in journal (Refereed)
    Abstract [en]

    Sequestration of Plasmodium falciparum-infected erythrocytes in placental intervillous spaces causes inflammation and pathology. Knowledge of the profiles of immune cells associated with the physiopathology of pregnancy-associated malaria (PAM) is scarce. We conducted a longitudinal, prospective study, both in Benin and Tanzania, including ∼1000 pregnant women in each site with systematic follow-up at scheduled antenatal visits until delivery. We used ex vivo flow cytometry to identify peripheral blood mononuclear cell (PBMC) profiles that are associated with PAM and anaemia, determining the phenotypic composition and activation status of PBMC in selected sub-groups with and without PAM both at inclusion and at delivery in a total of 302 women. Both at inclusion and at delivery PAM was associated with significantly increased frequencies both of B cells overall and of activated B cells. Infection-related profiles were otherwise quite distinct at the two different time-points. At inclusion, PAM was associated with anaemia, with an increased frequency of immature monocytes and with a decreased frequency of regulatory T cells (Treg). At delivery, infected women presented with significantly fewer plasmacytoid dendritic cells (DC), more myeloid DC expressing low levels of HLA-DR, and more effector T cells (Teff) compared to uninfected women. Independent associations with an increased risk of anaemia were found for altered antigen-presenting cell frequencies at inclusion, but for an increased frequency of Teff at delivery. Our findings emphasize the prominent role played by B cells during PAM whenever it arises during pregnancy, whilst also revealing signature changes in other circulating cell types that, we conclude, primarily reflect the relative duration of the infections. Thus, the acute, recently-acquired infections present at delivery were marked by changes in DC and Teff frequencies, contrasting with infections at inclusion, considered chronic in nature, that were characterized by an abundance of immature monocytes and a paucity of Treg in PBMC.

  • 82.
    Iriemenam, Nnaemeka C.
    et al.
    Stockholm University, Faculty of Science, The Wenner-Gren Institute .
    Khirelsied, Atif H.
    Nasr, Amre
    Stockholm University, Faculty of Science, The Wenner-Gren Institute .
    ElGhazali, Gehad
    Giha, Haider A.
    Elhassan A-Elgadir, Thoraya
    Agab-Aldour, Ahmed A.
    Montgomery, Scott M.
    Anders, Robin F.
    Theisen, Michael
    Troye-Blomberg, Marita
    Stockholm University, Faculty of Science, The Wenner-Gren Institute .
    Elbashir, Mustafa I.
    Berzins, Klavs
    Stockholm University, Faculty of Science, The Wenner-Gren Institute .
    Antibody responses to a panel of Plasmodium falciparum malaria blood-stage antigens in relation to clinical disease outcome in Sudan2009In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 27, no 1, p. 62-71Article in journal (Refereed)
    Abstract [en]

    Despite many intervention programmes aimed at curtailing the scourge, malaria remains a formidable problem of human health. Immunity to asexual blood-stage of Plasmodium falciparum malaria is thought to be associated with protective antibodies of certain immunoglobulin classes and subclasses. We have analysed immunoglobulin G profiles to six leading blood-stage antigens in relation to clinical malaria outcome in a hospital-based study in Sudan. Our results revealed a linear association with anti-AMA-1-IgG1 antibodies in children <5 years and reduced risk of severe malaria, while the responses of the IgG3 antibodies against MSP-2, MSP-3, GLURP in individuals above 5 years were bi-modal. A dominance of IgG3 antibodies in >5 years was also observed. In the final combined model, the highest levels of IgG1 antibodies to AMA-1, GLURP-R0, and the highest levels of IgG3 antibodies to 3D7 MSP-2 were independently associated with protection from clinical malaria. The study provides further support for the potential importance of the studied merozoite vaccine candidate antigens as targets for parasite neutralizing antibody responses of the IgG1 and IgG3 subclasses.

  • 83.
    Iriemenam, Nnaemeka C
    et al.
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Okafor, Christian M F
    Balogun, Halima A
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Ayede, Idowu
    Omosun, Yusuf
    Persson, Jan-Olov
    Hagstedt, Margareta
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Anumudu, Chiaka I
    Nwuba, Roseangela I
    Troye-Blomberg, Marita
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Berzins, Klavs
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Cytokine profiles and antibody responses to Plasmodium falciparum malaria infection in individuals living in Ibadan, southwest Nigeria.2009In: African Health Sciences, ISSN 1680-6905, E-ISSN 1729-0503, Vol. 9, no 2, p. 66-74Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The ability of the host immune system to efficiently clear Plasmodium falciparum parasites during a malaria infection depends on the type of immune response mounted by the host. STUDY DESIGN: In a cross-sectional study, we investigated the cellular-and antibody responses in individuals with P. falciparum infection, in an attempt to identify immunological signs indicative of the development of natural immunity against malaria in Ibadan, Nigeria. Levels of IL-10, IL-12(p70), IFN-gamma, and IgM, IgG and IgG1-4 subclasses in the serum of 36 symptomatic children with microscopically confirmed malaria parasitaemia and 54 asymptomatic controls were analysed by ELISA. RESULTS: IFN-gamma and IL-10 were significantly higher in the symptomatic children (p=0.009, p=0.025 respectively) than in the asymptomatic controls but no differences were seen for IL-12(p70). Estimated higher ratios of IFN-gamma/IL-10 and IFN-gamma/IL-12 were also observed in the symptomatic children while the asymptomatic controls had higher IL-12/IL-10 ratio. The mean concentration levels of anti-P. falciparum IgG1, IgG2, IgG3 antibodies were statistically significantly higher in the individuals >5 years of age than <5 years while anti-P. falciparum IgG3 antibodies were notably low in <5 years category. Children <5 years had higher IgM antibodies than IgG and the expression of IgG subclasses increased with age. CONCLUSION: Taken together, malaria infection is on a delicate balance of pro- and anti-inflammatory cytokines. The higher levels of IFN-gamma seen in the symptomatic children (<6 months) may be instrumental in immune-protection against malaria by limiting parasite replication. The observed variations in immunoglobulin subclass levels were age-dependent and exposure-related.

  • 84.
    Israelsson, Elisabeth
    et al.
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Ekström, Mattias
    Nasr, Amre
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Dolo, Amagana
    Kearsley, Susannah
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Arambepola, Gishanthi
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Homann, Manijeh V.
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Maiga, Bakary
    Doumbo, Ogobara K.
    ElGhazali, Gehad
    Giha, Hayder A.
    Troye-Blomberg, Marita
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Berzins, Klavs
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Tornvall, Per
    Marked differences in CRP genotype frequencies between the Fulani and sympatric ethnic groups in Africa2009In: Malaria Journal, ISSN 1475-2875, E-ISSN 1475-2875, Vol. 8, no 136Article in journal (Refereed)
    Abstract [en]

    Background

    C-reactive protein (CRP) is an acute phase protein that can activate various immune cells and bind to certain Fcγ receptors. The latter may compete with the binding of IgG antibodies to these receptors and could thereby interfere with the antigen-specific immune response. Polymorphisms in the promoter region of the CRP gene have been strongly associated with the plasma concentration of CRP. The known lower susceptibility to malaria in the Fulani ethnic group, as compared to their sympatric neighbours in Africa, has been linked to different genetic backgrounds. The present study was performed to investigate if polymorphisms in the CRP gene could contribute to the lower susceptibility to malaria seen in the Fulani ethnic group.

    Methods

    The CRP -717 T>C, -286 C>T>A, and +1444 C>T polymorphisms were analysed in asymptomatic Fulani and non-Fulani individuals from Mali and Sudan using Pyrosequencing T and TaqMan r MGB probes.

    Results

    The rare -286 A allele, previously shown to be associated with increased CRP expression and plasma levels, was shown to be more frequent in the non-Fulani ethnic groups as compared to the sympatric Fulani ethnic group both in Mali and Sudan. The common -717 T allele was more prevalent in the non-Fulani ethnic group compared to the sympatric Fulani ethnic group, but only in Mali. The parasite prevalence was increased for the -286 A allele, but not for the -717 T allele. No differences regarding genotype frequency or parasite prevalence were seen for +1444 C>T.

    Conclusion

    This study indicate that CRP may play an important role in the immune responses to malaria, and that the -286 C/T/A CRP polymorphism may be a contributing factor to the lower susceptibility to malaria seen in the Fulani.

  • 85.
    Israelsson, Elisabeth
    et al.
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Maiga, Bakary
    Kearsley, Susannah
    Dolo, Amagana
    Homann, Manijeh Vafa
    Doumbo, Ogobara K
    Troye-Blomberg, Marita
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Tornvall, Per
    Berzins, Klavs
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Cytokine gene haplotypes with a potential effect on susceptibility to malaria in sympatric ethnic groups in Mali2011In: Infection, Genetics and Evolution, ISSN 1567-1348, E-ISSN 1567-7257, Vol. 11, no 7, p. 1608-1615Article in journal (Refereed)
    Abstract [en]

    Cytokines are important players in the immune responses, and an unbalance in pro- and anti-inflammatory cytokine responses may affect parasitemia and pathology in a Plasmodium falciparum infection. Polymorphisms in cytokine genes may affect not only the levels of the protein, but many down-stream functions, such as production of C-reactive protein and immunoglobulin isotype switching. Susceptibility to malaria has been shown to differ between individuals with different genetic backgrounds, as indicated by studies in Fulani and non-Fulani ethnic groups. The aim of this study was to investigate possible interethnic differences in totally twelve single nucleotide polymorphisms (SNPs) in the genes encoding the cytokines IL-1β, IL-6, IL-10 and TNF. These SNPs are present in the promoter region of the genes, and have previously been associated with cytokine expression and with disease outcome in malaria. The results from the present study suggest that the Fulani ethnic group has a more pro-inflammatory response, due to high frequencies of high-producing alleles of IL1β and low-producing alleles of IL10. IL-6 could potentially also contribute to the relatively lower susceptibility to malaria in the Fulani ethnic group, whereas the TNF polymorphisms analysed in this study rather seem to associate with the severity of the infection and not the susceptibility for the infection itself. We therefore suggest that the polymorphisms analysed in this study all show a potential to influence the relatively lower susceptibility to malaria seen in the Fulani ethnic group as compared to the other sympatric ethnic groups.

  • 86.
    Israelsson, Elisabeth
    et al.
    Stockholm University, Faculty of Science, The Wenner-Gren Institute .
    Vafa, Manijeh
    Maiga, Bakary
    Lysén, Anna
    Iriemenam, Nnaemeka C.
    Dolo, Amagana
    Doumbo, Ogobara K.
    Troye-Blomberg, Marita
    Stockholm University, Faculty of Science, The Wenner-Gren Institute .
    Berzins, Klavs
    Differences in Fcγ receptor IIa genotypes and IgG subclass pattern of anti-malarial antibodies between sympatric ethnic groups in Mali2008In: Malaria Journal, ISSN 1475-2875, E-ISSN 1475-2875, Vol. 7, no 175Article in journal (Refereed)
  • 87. Jallow, Muminatou
    et al.
    Teo, Yik Ying
    Small, Kerrin S
    Rockett, Kirk A
    Deloukas, Panos
    Clark, Taane G
    Kivinen, Katja
    Bojang, Kalifa A
    Conway, David J
    Pinder, Margaret
    Sirugo, Giorgio
    Sisay-Joof, Fatou
    Usen, Stanley
    Auburn, Sarah
    Bumpstead, Suzannah J
    Campino, Susana
    Coffey, Alison
    Dunham, Andrew
    Fry, Andrew E
    Green, Angela
    Gwilliam, Rhian
    Hunt, Sarah E
    Inouye, Michael
    Jeffreys, Anna E
    Mendy, Alieu
    Palotie, Aarno
    Potter, Simon
    Ragoussis, Jiannis
    Rogers, Jane
    Rowlands, Kate
    Somaskantharajah, Elilan
    Whittaker, Pamela
    Widden, Claire
    Donnelly, Peter
    Howie, Bryan
    Marchini, Jonathan
    Morris, Andrew
    Sanjoaquin, Miguel
    Achidi, Eric Akum
    Agbenyega, Tsiri
    Allen, Angela
    Amodu, Olukemi
    Corran, Patrick
    Djimde, Abdoulaye
    Dolo, Amagana
    Doumbo, Ogobara K
    Drakeley, Chris
    Dunstan, Sarah
    Evans, Jennifer
    Farrar, Jeremy
    Fernando, Deepika
    Hien, Tran Tinh
    Horstmann, Rolf D
    Ibrahim, Muntaser
    Karunaweera, Nadira
    Kokwaro, Gilbert
    Koram, Kwadwo A
    Lemnge, Martha
    Makani, Julie
    Marsh, Kevin
    Michon, Pascal
    Modiano, David
    Molyneux, Malcolm E
    Mueller, Ivo
    Parker, Michael
    Peshu, Norbert
    Plowe, Christopher V
    Puijalon, Odile
    Reeder, John
    Reyburn, Hugh
    Riley, Eleanor M
    Sakuntabhai, Anavaj
    Singhasivanon, Pratap
    Sirima, Sodiomon
    Tall, Adama
    Taylor, Terrie E
    Thera, Mahamadou
    Troye-Blomberg, Marita
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Williams, Thomas N
    Wilson, Michael
    Kwiatkowski, Dominic P
    Genome-wide and fine-resolution association analysis of malaria in West Africa.2009In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, p. 657-665Article in journal (Refereed)
    Abstract [en]

    We report a genome-wide association (GWA) study of severe malaria in The Gambia. The initial GWA scan included 2,500 children genotyped on the Affymetrix 500K GeneChip, and a replication study included 3,400 children. We used this to examine the performance of GWA methods in Africa. We found considerable population stratification, and also that signals of association at known malaria resistance loci were greatly attenuated owing to weak linkage disequilibrium (LD). To investigate possible solutions to the problem of low LD, we focused on the HbS locus, sequencing this region of the genome in 62 Gambian individuals and then using these data to conduct multipoint imputation in the GWA samples. This increased the signal of association, from P = 4 x 10(-7) to P = 4 x 10(-14), with the peak of the signal located precisely at the HbS causal variant. Our findings provide proof of principle that fine-resolution multipoint imputation, based on population-specific sequencing data, can substantially boost authentic GWA signals and enable fine mapping of causal variants in African populations.

  • 88.
    Johansson, Maria A
    et al.
    Stockholm University, Faculty of Science, The Wenner-Gren Institute, Immunology.
    Saghafian-Hedengren, Shanie
    Stockholm University, Faculty of Science, The Wenner-Gren Institute, Immunology.
    Haileselassie, Yeneneh
    Stockholm University, Faculty of Science, The Wenner-Gren Institute, Immunology.
    Roos, Stefan
    Troye-Blomberg, Marita
    Stockholm University, Faculty of Science, The Wenner-Gren Institute, Immunology.
    Nilsson, Caroline
    Sverremark-Ekström, Eva
    Stockholm University, Faculty of Science, The Wenner-Gren Institute, Immunology.
    Early-Life Gut Bacteria Associate with IL-4-, IL-10- and IFN-γ Production at Two Years of Age2012In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, no 11, p. e49315-(9 pp)Article in journal (Refereed)
    Abstract [en]

    Microbial exposure early in life influences immune maturation and potentially also the development of immune-mediated disease. Here we studied early-life gut colonization in relation to cytokine responses at two years of age. Fecal samples were collected from infants during the first two months of life. DNA was extracted from the fecal samples and Bifidobacterium (B.) adolescentis, B. breve, B. bifidum, a group of lactobacilli (L. casei, L. paracasei and L. rhamnosus) as well as Staphylococcus (S.) aureus were detected with real time PCR. Peripheral mononuclear cells were stimulated with phytohaemagglutinin (PHA) and numbers of IL-4-, IL-10- and IFN-γ secreting cells were evaluated using ELISpot. We further stimulated peripheral blood mononuclear cells with bacterial supernatants in vitro and assessed the IL-4-, IL-10- and IFN-γ inducing capacity by flow cytometry and ELISA. Early S. aureus colonization associated with higher numbers of IL-4- (p = 0.022) and IL-10 (p = 0.016) producing cells at two years of age. In contrast to colonization with S. aureus alone, co-colonization with lactobacilli associated with suppression of IL-4- (p = 0.004), IL-10- (p = 0.004) and IFN-γ (p = 0.034) secreting cells. In vitro stimulations of mononuclear cells with bacterial supernatants supported a suppressive role of L. rhamnosus GG on S. aureus-induced cytokine responses. We demonstrate that the early gut colonization pattern associates with the PHA-induced cytokine profile at two years of age and our in vitro findings support that specific bacterial species influence the T helper cell subsets. This suggests that dysbiosis in the early microbiota may modulate the risk of developing inflammatory conditions like allergy.

  • 89. Kaneko, Akira
    et al.
    Chaves, Luis F.
    Taleo, George
    Kalkoa, Morris
    Isozumi, Rie
    Wickremasinghe, Renu
    Perlmann, Hedvig
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Takeo, Satoru
    Tsuboi, Takafumi
    Tachibana, Shin-Ichiro
    Kimura, Masatsugu
    Björkman, Anders
    Troye-Blomberg, Marita
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Tanabe, Kazuyuki
    Drakeley, Chris
    Characteristic Age Distribution of Plasmodium vivax Infections after Malaria Elimination on Aneityum Island, Vanuatu2014In: Infection and Immunity, ISSN 0019-9567, E-ISSN 1098-5522, Vol. 82, no 1, p. 243-252Article in journal (Refereed)
    Abstract [en]

    Resurgence is a major concern after malaria elimination. After the initiation of the elimination program on Aneityum Island in 1991, microscopy showed that Plasmodium falciparum disappeared immediately, whereas P. vivax disappeared from 1996 onward, until P. vivax cases were reported in January 2002. By conducting malariometric surveys of the entire population of Aneityum, we investigated the age distribution of individuals with parasites during this epidemic in the context of antimalarial antibody levels and parasite antigen diversity. In July 2002, P. vivax infections were detected by microscopy in 22/759 individuals: 20/298 born after the beginning of the elimination program in 1991, 2/126 born between 1982 and 1991, and none of 335 born before 1982. PCR increased the number of infections detected to 77, distributed among all age groups. Prevalences were 12.1%, 16.7%, and 6.0%, respectively (P<0.001). In November, a similar age pattern was found, but with fewer infections: 6/746 and 39/741 individuals were found to be infected by microscopy and PCR, respectively. The frequencies of antibody responses to P. vivax were significantly higher in individuals born before 1991 than in younger age groups and were similar to those on Malakula Island, an area of endemicity. Remarkably low antigen diversity (h, 0.15) of P. vivax infections was observed on Aneityum compared with the other islands (h, 0.89 to 1.0). A P. vivax resurgence was observed among children and teenagers on Aneityum, an age distribution similar to those before elimination and on islands where P. vivax is endemic, suggesting that in the absence of significant exposure, immunity may persist, limiting infection levels in adults. The limited parasite gene pool on islands may contribute to this protection.

  • 90.
    Krogstie, John
    et al.
    Norwegian University of Science and Technology (NTNU), Trondheim.
    Ståhlbröst, Anna
    Luleå University of Technology, Department of Business Administration, Technology and Social Sciences, Innovation and Design.
    Holst, Marita
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Distance- Spanning Technology.
    Jelle, Tomas
    Wireless Trondheim.
    Kulseng, Lars
    Wireless Trondheim.
    Gudmundsdottir, Ásta
    Innovation Centre Iceland.
    Braskus, Laruynas
    Sunrise Valley.
    Olesen, Annie
    A9 Consulting.
    Using a Living Lab Methodology for Developing Energy Savings Solutions2013In: 19th Americas Conference on Information Systems, AMCIS 2013: Chicago, IL; 15 -17 August 2013, 2013, Vol. V, p. 3872-3879Conference paper (Refereed)
    Abstract [en]

    It is becoming increasingly important to create a sustainable environment. One important step is to reduce the energyconsumption. In Europe, 25% of the energy used is consumed by private households. How energy is produced and consumedin different European countries varies a lot, thus it is hard to develop general solutions based on country-specific traits. Theaim of this paper is to describe an approach to cross-country development of an energy savings solution. This paper reportson the usage of a method based on collecting users needs related to their current energy consumption, the actions they cantake, and the possible future solutions they want to see.

  • 91. Kumsiri, Ratchanok
    et al.
    Troye-Blomberg, Marita
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Pattanapanyasat, Kovit
    Krudsood, Srivicha
    Maneerat, Yaowapa
    IgE low affinity receptor (CD23) expression, Plasmodium falciparum specific IgE and tumor necrosis factor-alpha production in Thai uncomplicated and severe falciparum malaria patients2016In: Acta Tropica, ISSN 0001-706X, E-ISSN 1873-6254, Vol. 154, p. 25-33Article in journal (Refereed)
    Abstract [en]

    Previous studies have suggested that Plasmodium falciparum (P. falciparum) specific IgE in the form of immune complexes crosslinking the low-affinity receptor (CD23) on monocyte results in tumor necrosis factor (TNF)-alpha and nitric oxide (NO) production. However, the roles of these parameters in severity and immune protection are still unclear. This study aimed to determine the association between CD23 expression on monocytes, plasma soluble CD23 (sCD23), total IgE, malaria-specific IgE and IgG, and TNF-alpha levels in P. falciparum infected patients. We evaluated 64 uncomplicated (UC) and 25 severe patients (S), admitted at the Hospital for Tropical Diseases, Mahidol University, and 34 healthy controls (C) enrolled in 2001. Flow cytometry and enzyme linked immunosorbent assays (ELISA) demonstrated that trends of the CD23 expression, levels of sCD23 and specific IgE were higher in the S group as compared to those in the UC and C groups. Plasma levels of P. falciparum specific IgE in the UC (p = 0.011) and S groups (p = 0.025) were significantly higher than those in C group. In contrast the TNF-alpha levels tended to be higher in the UC than those in the S (p = 0343) and significantly higher than those in C (p = 0.004) groups. The specific IgG levels in UC were significantly higher than those in S and C (p < 0.001) groups. At admission, a strong significant negative correlation was found between specific IgG and sCD23 (r = -0.762, p = 0.028), and TNF-alpha and IgE-IgG complexes (r=-0.715, p = 0.002). Significant positive correlations between levels of specific IgE and TNF-alpha (r=0.575, p = 0.010); and sCD23 (r=0.597, p = 0.000) were also observed. In conclusion, our data suggest that CD23 expression and malaria-specific IgE levels may be involved in the severity of the disease while TNF-alpha and the malaria-specific IgG may correlate with protection against falciparum malaria.

  • 92. Lokki, A Inkeri
    et al.
    Järvelä, Irma
    Israelsson, Elisabeth
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Maiga, Bakary
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Troye-Blomberg, Marita
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Dolo, Amagana
    Doumbo, Ogobara K
    Meri, Seppo
    Holmberg, Ville
    Lactase persistence genotypes and malaria susceptibility in Fulani of Mali.2011In: Malaria Journal, ISSN 1475-2875, E-ISSN 1475-2875, Vol. 10, p. 9-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Fulani are a widely spread African ethnic group characterized by lower susceptibility to Plasmodium falciparum, clinical malaria morbidity and higher rate of lactase persistence compared to sympatric tribes. Lactase non-persistence, often called lactose intolerance, is the normal condition where lactase activity in the intestinal wall declines after weaning. Lactase persistence, common in Europe, and in certain African people with traditions of raising cattle, is caused by polymorphisms in the enhancer region approximately 14 kb upstream of the lactase gene.

    METHODS: To evaluate the relationship between malaria and lactase persistence genotypes, a 400 bp region surrounding the main European C/T-13910 polymorphism upstream of the lactase gene was sequenced. DNA samples used in the study originated from 162 Fulani and 79 Dogon individuals from Mali.

    RESULTS: Among 79 Dogon only one heterozygote of the lactase enhancer polymorphism was detected, whereas all others were homozygous for the ancestral C allele. Among the Fulani, the main European polymorphism at locus C/T-13910 was by far the most common polymorphism, with an allele frequency of 37%. Three other single-nucleotide polymorphisms were found with allele frequencies of 3.7%, 1.9% and 0.6% each. The novel DNA polymorphism T/C-13906 was seen in six heterozygous Fulani. Among the Fulani with lactase non-persistence CC genotypes at the C/T-13910 locus, 24% had malaria parasites detectable by microscopy compared to 18% for lactase persistent genotypes (P = 0.29). Pooling the lactase enhancer polymorphisms to a common presumptive genotype gave 28% microscopy positives for non-persistent and 17% for others (P = 0.11).

    CONCLUSIONS: Plasmodium falciparum parasitaemia in asymptomatic Fulani is more common in individuals with lactase non-persistence genotypes, but this difference is not statistically significant. The potential immunoprotective properties of dietary cow milk as a reason for the partial malaria resistance of Fulani warrant further investigation.

  • 93.
    Maiga, Bakary
    et al.
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute. Malaria Research and Training Center, Department of Epidemiology of Parasitic Diseases/Faculty of Medicine, Pharmacy and Odonto, Stomatology, Bamako, Mali.
    Dolo, A
    Touré, O
    Dara, V
    Tapily, A
    Campino, S
    Sepulveda, N
    Corran, P
    Rockett, K
    Clark, T G
    Troye Blomberg, Marita
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Doumbo, O K
    Fc gamma Receptor IIa-H131R Polymorphism and Malaria Susceptibility in Sympatric Ethnic Groups, Fulani and Dogon of Mali2014In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 79, no 1, p. 43-50Article in journal (Refereed)
    Abstract [en]

    It has been previously shown that there are some interethnic differences in susceptibility to malaria between two sympatric ethnic groups of Mali, the Fulani and the Dogon. The lower susceptibility to Plasmodium falciparum malaria seen in the Fulani has not been fully explained by genetic polymorphisms previously known to be associated with malaria resistance, including haemoglobin S (HbS), haemoglobin C (HbC), alpha-thalassaemia and glucose-6-phosphate dehydrogenase (G6PD) deficiency. Given the observed differences in the distribution of FcγRIIa allotypes among different ethnic groups and with malaria susceptibility that have been reported, we analysed the rs1801274-R131H polymorphism in the FcγRIIa gene in a study of Dogon and Fulani in Mali (n = 939). We confirm that the Fulani have less parasite densities, less parasite prevalence, more spleen enlargement and higher levels of total IgG antibodies (anti-CSP, anti-AMA1, anti-MSP1 and anti-MSP2) and more total IgE (P < 0.05) compared with the Dogon ethnic group. Furthermore, the Fulani exhibit higher frequencies of the blood group O (56.5%) compared with the Dogon (43.5%) (P < 0.001). With regard to the FcγRIIa polymorphism and allele frequency, the Fulani group have a higher frequency of the H allele (Fulani 0.474, Dogon 0.341, P < 0.0001), which was associated with greater total IgE production (P = 0.004). Our findings show that the FcγRIIa polymorphism might have an implication in the relative protection seen in the Fulani tribe, with confirmatory studies required in other malaria endemic settings.

  • 94.
    Maiga, Bakary
    et al.
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute. Universités de Bamako, Bali.
    Dolo, Amagana
    Campino, Susana
    Sepulveda, Nuno
    Corran, Patrick
    Rockett, Kirk A.
    Troye-Blomberg, Marita
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Doumbo, Ogobara K.
    Clark, Taane G.
    Glucose-6-phosphate dehydrogenase polymorphisms and susceptibility to mild malaria in Dogon and Fulani, Mali2014In: Malaria Journal, ISSN 1475-2875, E-ISSN 1475-2875, Vol. 13, p. 270-Article in journal (Refereed)
    Abstract [en]

    Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is associated with protection from severe malaria, and potentially uncomplicated malaria phenotypes. It has been documented that G6PD deficiency in sub-Saharan Africa is due to the 202A/376G G6PD A-allele, and association studies have used genotyping as a convenient technique for epidemiological studies. However, recent studies have shown discrepancies in G6PD202/376 associations with severe malaria. There is evidence to suggest that other G6PD deficiency alleles may be common in some regions of West Africa, and that allelic heterogeneity could explain these discrepancies. Methods: A cross-sectional epidemiological study of malaria susceptibility was conducted during 2006 and 2007 in the Sahel meso-endemic malaria zone of Mali. The study included Dogon (n = 375) and Fulani (n = 337) sympatric ethnic groups, where the latter group is characterized by lower susceptibility to Plasmodium falciparum malaria. Fifty-three G6PD polymorphisms, including 202/376, were genotyped across the 712 samples. Evidence of association of these G6PD polymorphisms and mild malaria was assessed in both ethnic groups using genotypic and haplotypic statistical tests. Results: It was confirmed that the Fulani are less susceptible to malaria, and the 202A mutation is rare in this group (< 1% versus Dogon 7.9%). The Betica-Selma 968C/376G (similar to 11% enzymatic activity) was more common in Fulani (6.1% vs Dogon 0.0%). There are differences in haplotype frequencies between Dogon and Fulani, and association analysis did not reveal strong evidence of protective G6PD genetic effects against uncomplicated malaria in both ethnic groups and gender. However, there was some evidence of increased risk of mild malaria in Dogon with the 202A mutation, attaining borderline statistical significance in females. The rs915942 polymorphism was found to be associated with asymptomatic malaria in Dogon females, and the rs61042368 polymorphism was associated with clinical malaria in Fulani males. Conclusions: The results highlight the need to consider markers in addition to G6PD202 in studies of deficiency. Further, large genetic epidemiological studies of multi-ethnic groups in West Africa across a spectrum of malaria severity phenotypes are required to establish who receives protection from G6PD deficiency.

  • 95.
    Maiga, Bakary
    et al.
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute. University of Science, Technique and Technologies of Bamako (USTTB), Mali.
    Dolo, Amagana
    Toure, Ousmane
    Dara, Victor
    Tapily, Amadou
    Campino, Susana
    Sepulveda, Nuno
    Risley, Paul
    Silva, Nipula
    Corran, Patrick
    Rockett, Kirk A.
    Kwiatkowski, Dominic
    Clark, Taane G.
    Troye-Blomberg, Marita
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Doumbo, Ogobara K.
    Human Candidate Polymorphisms in Sympatric Ethnic Groups Differing in Malaria Susceptibility in Mali2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 10, article id e75675Article in journal (Refereed)
    Abstract [en]

    Malaria still remains a major public health problem in Mali, although disease susceptibility varies between ethnic groups, particularly between the Fulani and Dogon. These two sympatric groups share similar socio-cultural factors and malaria transmission rates, but Fulani individuals tend to show significantly higher spleen enlargement scores, lower parasite prevalence, and seem less affected by the disease than their Dogon neighbours. We have used genetic polymorphisms from malaria-associated genes to investigate associations with various malaria metrics between the Fulanai and Dogon groups. Two cross sectional surveys (transmission season 2006, dry season 2007) were performed. Healthy volunteers from the both ethnic groups (n=939) were recruited in a rural setting. In each survey, clinical (spleen enlargement, axillary temperature, weight) and parasitological data (malaria parasite densities and species) were collected, as well as blood samples. One hundred and sixty six SNPs were genotyped and 5 immunoassays (AMA1, CSP, MSP1, MSP2, total IgE) were performed on the DNA and serum samples respectively. The data confirm the reduced malaria susceptibility in the Fulani, with a higher level of the protective O-blood group, and increased circulating antibody levels to several malaria antigens (p<10(-15)). We identified SNP allele frequency differences between the 2 ethnic groups in CD36, IL4, RTN3 and ADCY9. Moreover, polymorphisms in FCER1A, RAD50, TNF, SLC22A4, and IL13 genes were correlated with antibody production (p-value<0.003). Further work is required to understand the mechanisms underpinning these genetic factors.

  • 96. McCall, Matthew B B
    et al.
    Ferwerda, Bart
    Hopman, Joost
    Ploemen, Ivo
    Maiga, Boubacar
    Daou, Modibo
    Dolo, Amagana
    Hermsen, Cornelus C
    Doumbo, Ogobara K
    Bedu-Addo, George
    van der Meer, Jos W
    Troye-Blomberg, Marita
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    van der Ven, André J A M
    Schumann, Ralf R
    Sauerwein, Robert W
    Mockenhaupt, Frank P
    Netea, Mihai G
    Persistence of full-length caspase-12 and its relation to malaria in West and Central African populations.2010In: European Cytokine Network, ISSN 1148-5493, E-ISSN 1952-4005, Vol. 21, no 2, p. 77-83Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The full-length (L-) variant of caspase-12 is believed to predispose to sepsis. It has been replaced in the genome of most human populations by the (S-) variant, which leads to premature termination of translation. Strikingly, the L-allele is still widely prevalent in African populations, presumably due to a counterbalancing selective force specific to this continent, for which malaria is a prime candidate. METHODS: We investigated associations between caspase-12 genotype and malarial parameters in three West-African populations, in studies encompassing immunological, clinical and obstetric data. RESULTS: The caspase-12 L-allele was found at frequencies of 11-34%. Plasmodium falciparum-stimulated mononuclear cells from S/L heterozygote donors produced stronger interferon-gamma and interleukin-10 responses than S/S homozygotes (p = 0.011 and p = 0.023 in uninfected and infected donors respectively). Nevertheless, we found no association between caspase-12 genotype and either the presentation of severe malaria or individual clinical parameters in sick children. Amongst pregnant women, the caspase-12 genotype did not influence peripheral or placental malaria infection, or basic obstetric parameters. Interestingly, perinatal mortality was more frequent in children of both S/S and L/L than S/L mothers, independent of placental P. falciparum-infection. CONCLUSION: We find little clinical or epidemiological evidence that malaria has contributed to the persistence of functional caspase-12 in Africa, suggesting either that alternative selective forces are at work or that genetic drift underlies its current global distribution.

  • 97. McCall, Matthew B B
    et al.
    Hopman, Joost
    Daou, Modibo
    Maiga, Boubacar
    Dara, Victor
    Ploemen, Ivo
    Nganou-Makamdop, Krystelle
    Niangaly, Amadou
    Tolo, Youssouf
    Arama, Charles
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Bousema, J Teun
    van der Meer, Jos W
    van der Ven, André J A M
    Troye-Blomberg, Marita
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Dolo, Amagana
    Doumbo, Ogobara K
    Sauerwein, Robert W
    Early interferon-gamma response against Plasmodium falciparum correlates with interethnic differences in susceptibility to parasitemia between sympatric Fulani and Dogon in Mali.2010In: Journal of Infectious Diseases, ISSN 0022-1899, E-ISSN 1537-6613, Vol. 201, no 1, p. 142-52Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Interethnic differences in susceptibility to malaria provide a unique opportunity to explore immunological correlates of protection. The Fulani of Sahelian Africa are known for their reduced susceptibility to Plasmodium falciparum, compared with surrounding tribes, yet the immunology underlying this is still poorly understood. METHODS AND RESULTS: Here, we show that mononuclear cells from Fulani elicit >10-fold stronger interferon (IFN)-gamma production following a 24-h in vitro coincubation with asexual parasites than cells from sympatric Dogon. This response appears to be specific for P. falciparum among a panel of other human pathogens and is independent of the lower number of regulatory T cell counts present in Fulani. IFN-gamma responses in both tribes were inversely correlated with peripheral parasite density as quantified by nucleic acid sequenced-based amplification, but responses of Fulani remained significantly stronger than those of Dogon after adjustment for concurrent parasitemia, suggesting that hard-wired immunological differences underlie the observed protection. CONCLUSIONS: These results underscore the value of early IFN-gamma responses to P. falciparum as a correlate of anti-parasite immunity, not only in this setting but also in the wider context of malaria, and support the development of malaria vaccines aimed at inducing such responses.

  • 98. Mirijamdotter, Anita
    et al.
    Somerville, Mary
    Holst, Marita
    An interactive evaluation approach for the creation of collaborative learning commons2005In: Proceedings of 12th European Conference on Information Technology Evaluation (ECITE 2005), 2005, p. 337-347Conference paper (Refereed)
    Abstract [en]

    This paper reports on the interactive design and evaluation of Internet2-enabled international students' cooperation/collaboration projects involving students and faculty from four disciplines and from three campuses, two in California, U.S.A. and one in the North of Sweden. The purpose of the collaboration is to collect and exchange information and produce knowledge on what would constitute a student-centered physical and virtual ‘learning commons'. The project construct reflects lessons learned in the 3-year Creative University initiative at Luleå University of Technology, Sweden, as well as the growing shift from academic information commons to ‘learning commons', where the focus is on learning rather than technology. Our distributed, international design and evaluation process is based on principles and practices for action research and builds on theories for knowledge exchange embedded in the concept of Ba, as advanced by Nonaka and others. The Ba model recognizes four stages for making tacit knowledge explicit to enable information sharing and produce new knowledge within shared physical, virtual and mental contexts. To explore the practical feasibility of constituting and linking learning communities to create new disciplinary knowledge, share it across disciplinary communities, and co-create dynamic technology-enabled learning environments, we intentionally employed systems thinking methodology involving discourse, dialogue and communication through which faculty and students created shared meanings. Our report includes reflections on applied interactive evaluation framework and process as well as observations on the efficacy of a variety of technology supported tools for initiating and advancing distributed cooperative and collaborative learning. Our research results are further enriched by commentary on the social implementation factors affecting tool utility. For this kind of endeavour to succeed we need to pay explicit attention to the creation of viable group processes including knowledge assessment activities, influencing infrastructure for enabling technology, and integrate this with pedagogical insights on improving student learning.

  • 99. Mirijamdotter, Anita
    et al.
    Somerville, Mary M.
    Dr. Martin Luther King Jr. Library, San José State University.
    Holst, Marita
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Distance- Spanning Technology.
    An interactive and iterative evaluation approach for creating collaborative learning environments2012In: Leading issues in ICT evaluation, Reading: Academic Conferences and Publishing International Limited, 2012, p. 60-81Chapter in book (Refereed)
  • 100.
    Mirijamdotter, Anita
    et al.
    Luleå University of Technology, Department of Business Administration, Technology and Social Sciences, Innovation and Design.
    Somerville, Mary M.
    San José State University.
    Holst, Marita
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Distance- Spanning Technology.
    An interactive and iterative evaluation approach for creating collaborative learning environments2006In: Electronic Journal of Information Systems Evaluation, ISSN 1566-6379, E-ISSN 1566-6379, Vol. 9, no 2, p. 83-92Article in journal (Refereed)
    Abstract [en]

    Inspired by a three-year Creative University ‘arena' initiative at Luleå University of Technology in Sweden, an international team of faculty researchers conducted an exploratory study in 2005, which aimed to investigate the efficacy of an interactive design and evaluation process for technology-enabled collaborative learning environments. This applied research approach was designed as a collaborative evaluation process for co-creation of technology-enabled, learningfocused physical and virtual ‘learning commons.' Faculty researchers from Sweden and the United States used Soft Systems Methodology tools, including the Process for Organisational Meanings (POM) model, to guide sixty-two students' participatory co-design and evaluation activities. In this paper, the POM evaluation model is explained and related to the Japanese concept Ba. Application of the models is illustrated within the context of student learning through boundary crossing information exchange and knowledge creation. As evidenced in their iterative and interactive evaluative recommendations, students' learning outcomes included development of improved capabilities for identifying socio-technical elements of distributed learning environments, suggesting that student beneficiaries can successfully reflect upon their experiences and provide valuable evaluation insights. In addition, when this evaluation is iterative, students' insights into project management, software needs, and services design can improve their technology-enabled learning experiences. Concluding comments explore the efficacy of the POM model implementation for guiding other learning-focused, user-centric initiatives, which aim to promote interdisciplinary, or boundary crossing, exchanges concurrent with advancing team-based knowledge creation proficiencies among project participants.

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