Clec9a-mediated ablation of conventional dendritic cells suggests a lymphoid path to generating dendritic cells In Vivo

Conventional dendritic cells (cDCs) are versatile activators of immune responses that develop as part of the myeloid lineage downstream of hematopoietic stem cells. We have recently shown that in mice precursors of cDCs, but not of other leukocytes, are marked by expression of DNGR-1/CLEC9A. To genetically deplete DNGR-1-expressing cDC precursors and their progeny, we crossed Clec9a-Cre mice to Rosa-lox-STOP-lox-diphtheria toxin (DTA) mice. These mice develop signs of age-dependent myeloproliferative disease, as has been observed in other DC-deficient mouse models. However, despite efficient depletion of cDC progenitors in these mice, cells with phenotypic characteristics of cDCs populate the spleen. These cells are functionally and transcriptionally similar to cDCs in wild type control mice but show somatic rearrangements of Ig-heavy chain genes, characteristic of lymphoid origin cells. Our studies reveal a previously unappreciated developmental heterogeneity of cDCs and suggest that the lymphoid lineage can generate cells with features of cDCs when myeloid cDC progenitors are impaired

An Energy Systems Modelling Tool for the Social Simulation Community

The growing importance of links between the social and technical dimensions of the electricity infrastructure mean that many research problems cannot be effectively addressed without joint consideration of social and technical dynamics. This paper motivates the need for and introduces a tool to facilitate the development of linked social and technical models of electric power systems. The tool, called MatpowerConnect, enables the runtime linkage of Netlogo -- an oft-used modelling platform in the social simulation domain -- with Matpower -- a common power flow simulation package in the power systems domain. MatpowerConnect opens up new modelling possibilities for social simulation researchers active in the study of electricity systems. It offers ease of use coupled with a high degree of realism with which electricity infrastructure functionality is captured. We describe the development and use of two demonstration models using MatpowerConnect. These models illustrate two types of problems and system scales that can be addressed. In the first model we explore the consequences of actors' adaptive strategies on the performance of a small-scale power system. In the second model we simulate the effects of different regulatory regimes on network investment in a supra-national electricity transmission system to explore the long-term consequences for network development and social welfare. In both cases, the extension enables capturing a critical functionality of electric power systems, while allowing model development efforts to focus on social simulation aspects. Resources for using the extension are provided in conjunction with this paper

Clec9a-Mediated Ablation of Conventional Dendritic Cells Suggests a Lymphoid Path to Generating Dendritic Cells In Vivo

Conventional dendritic cells (cDCs) are versatile activators of immune responses that develop as part of the myeloid lineage downstream of hematopoietic stem cells. We have recently shown that in mice precursors of cDCs, but not of other leukocytes, are marked by expression of DNGR-1/CLEC9A. To genetically deplete DNGR-1-expressing cDC precursors and their progeny, we crossed Clec9a-Cre mice to Rosa-lox-STOP-lox-diphtheria toxin (DTA) mice. These mice develop signs of age-dependent myeloproliferative disease, as has been observed in other DC-deficient mouse models. However, despite efficient depletion of cDC progenitors in these mice, cells with phenotypic characteristics of cDCs populate the spleen. These cells are functionally and transcriptionally similar to cDCs in wild type control mice but show somatic rearrangements of Ig-heavy chain genes, characteristic of lymphoid origin cells. Our studies reveal a previously unappreciated developmental heterogeneity of cDCs and suggest that the lymphoid lineage can generate cells with features of cDCs when myeloid cDC progenitors are impaired

Cross‐presentation of dead‐cell‐associated antigens by DNGR‐1⁺ dendritic cells contributes to chronic allograft rejection in mice

The purpose of this study was to elucidate whether DC NK lectin group receptor-1 (DNGR-1)-dependent cross-presentation of dead-cell-associated antigens occurs after transplantation and contributes to CD8(+)T cell responses, chronic allograft rejection (CAR), and fibrosis. BALB/c or C57BL/6 hearts were heterotopically transplanted into WT, Clec9a(-/-), or Batf3(-/-)recipient C57BL/6 mice. Allografts were analyzed for cell infiltration, CD8(+)T cell activation, fibrogenesis, and CAR using immunohistochemistry, Western blot, qRT(2)-PCR, and flow cytometry. Allografts displayed infiltration by recipient DNGR-1(+)DCs, signs of CAR, and fibrosis. Allografts in Clec9a(-/-)recipients showed reduced CAR (p < 0.0001), fibrosis (P= 0.0137), CD8(+)cell infiltration (P < 0.0001), and effector cytokine levels compared to WT recipients. Batf3-deficiency greatly reduced DNGR-1(+)DC-infiltration, CAR (P < 0.0001), and fibrosis (P= 0.0382). CD8 cells infiltrating allografts of cytochrome C treated recipients, showed reduced production of CD8 effector cytokines (P < 0.05). Further, alloreactive CD8(+)T cell response in indirect pathway IFN-gamma ELISPOT was reduced in Clec9a(-/-)recipient mice (P= 0.0283). Blockade of DNGR-1 by antibody, similar to genetic elimination of the receptor, reduced CAR (P= 0.0003), fibrosis (P= 0.0273), infiltration of CD8(+)cells (p= 0.0006), and effector cytokine levels. DNGR-1-dependent alloantigen cross-presentation by DNGR-1(+)DCs induces alloreactive CD8(+)cells that induce CAR and fibrosis. Antibody against DNGR-1 can block this process and prevent CAR and fibrosis

An Energy Systems Modelling Tool for the Social Simulation Community

The growing importance of links between the social and technical dimensions of the electricity infrastructure mean that many research problems cannot be effectively addressed without joint consideration of social and technical dynamics. This paper motivates the need for and introduces a tool to facilitate the development of linked social and technical models of electric power systems. The tool, called MatpowerConnect, enables the runtime linkage of Netlogo -- an oft-used modelling platform in the social simulation domain -- with Matpower -- a common power flow simulation package in the power systems domain. MatpowerConnect opens up new modelling possibilities for social simulation researchers active in the study of electricity systems. It offers ease of use coupled with a high degree of realism with which electricity infrastructure functionality is captured. We describe the development and use of two demonstration models using MatpowerConnect. These models illustrate two types of problems and system scales that can be addressed. In the first model we explore the consequences of actors' adaptive strategies on the performance of a small-scale power system. In the second model we simulate the effects of different regulatory regimes on network investment in a supra-national electricity transmission system to explore the long-term consequences for network development and social welfare. In both cases, the extension enables capturing a critical functionality of electric power systems, while allowing model development efforts to focus on social simulation aspects. Resources for using the extension are provided in conjunction with this paper

Older individuals' views on their personal screening results for complex health problems: a qualitative study

Background: Providing older persons with information about their health status may increase their involvement in their own health and enhance self-management. However, we need a better understanding of how older persons view their personal results after completing a screening questionnaire on complex health, of their (lack of) motivation and their subsequent action.Methods: In this qualitative study community-dwelling older persons (>= 80 years,n = 13) who completed a screening questionnaire on complex health problems were interviewed regarding their perception of the results, the actions they considered taking and their personal motivations. Data were analysed thematically (qualitative content analyses).Results: Participants expressed interest in feedback, as an objective questionnaire might substantiate their own views regarding their personal health. They were mostly unsurprised by the results and/or had already taken precautions and were therefore not inclined to undertake additional action. They admitted difficulty with and appreciated advice from a professional regarding preparation of an action plan. Unexpected negative results would lead them to discuss matters with family and/or their general practitioner, provided they had a good relationship with their GP.Conclusion: Older people were interested in direct feedback regarding their screening questionnaire results and in subsequent advice on possible additional measures. General practices could consider inviting older persons to complete a screening questionnaire and discuss activities and personal goals. This information could serve to better shape future interventions aimed at increasing self-management amongst older persons

Self-Reported Hindering Health Complaints of Community-Dwelling Older Persons: A Cross-Sectional Study

Geriatrics in primary car

Warts transmitted in families and schools: a prospective cohort

Item does not contain fulltextBACKGROUND AND OBJECTIVE: Cutaneous warts are common in primary schoolchildren; however, knowledge on the routes of transmission of human papillomavirus (HPV) causing warts is scarce. This study examines the association between the degree of HPV exposure and incidence of warts in primary schoolchildren to support evidence-based recommendations on wart prevention. METHODS: In this prospective cohort study, the hands and feet of all children in grades 1 to 7 (aged 4-12 years) of 3 Dutch primary schools were inspected for the presence of warts at baseline and after 11 to 18 months of follow-up. Data on the degree of HPV exposure included information obtained from parental questionnaires: preexistent warts, warts in family, prevalence of warts at baseline in the class, and use of public places (eg, swimming pools). RESULTS: Of the 1134 eligible children, 97% participated; the response rate from parental questionnaires was 77%, and loss to follow-up was 9%. The incidence for developing warts was 29 per 100 person-years at risk (95% confidence interval [CI] 26-32). Children with a white skin type had an increased risk of developing warts (hazard ratio [HR] 2.3, 95% CI 1.3-3.9). Having family members with warts (HR 2.08, 95% CI 1.52-2.86) and wart prevalence in the class (HR 1.20 per 10% increase, 95% CI 1.03-1.41) were independent environmental risk factors. CONCLUSIONS: The degree of HPV exposure in the family and school class contributes to the development of warts in schoolchildren. Preventive recommendations should focus more on limiting HPV transmission in families and school classes, rather than in public places