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关键词： Spatial crime analysis   Guerry   Quetelet   19th century france   Local analysis  

摘要： Modern spatial criminology has its roots in the social statistics of 19th century France. Investigating the variation in property and violent crimes across French departments, Guerry (1832, 1833) and Quetelet (1831, 1842) found unique patterns for each crime classification. They also found relationships between crime and a number of social, demographic, economic, and climatic conditions. In this paper we revisit the work of Guerry and Quetelet using modern spatial statistical techniques. We find that the relationships identified by Guerry and Quetelet are robust when employing modern spatial analysis. Additionally, we find the patterns of crime in 19th century France are remarkably similar to contemporary crime patterns in other nations. These findings suggest that the spatial findings of Guerry and Quetelet hold up when using modern advanced spatial methodologies.

关键词： anti-cytokine autoantibodies   dried blood spot   interferon gamma  

摘要： Background High titer, neutralizing anti-cytokine autoantibodies (ACAA) to interferon gamma (IFN gamma) are an emerging cause of adult-onset immunodeficiency, and detection can direct clinical management. Currently, the detection of ACAAs is performed on blood or plasma, which is time-sensitive, relatively expensive to obtain, and must be shipped from remote locations in specialized containers. We have adapted an easier method of collecting blood or plasma onto a paper card as dried blood spots (DBS), which is simple, inexpensive, and does not require a medical facility or special *** Whole blood, either from venipuncture or finger stick, was blotted onto filter paper to yield DBS from which samples were eluted. Samples from 4 groups were analyzed: patients with anti-IFN gamma autoantibodies, either with or without neutralizing activity, disease controls with other ACAAs, and healthy controls (n= 50 total). Eluates and paired plasma samples were then screened for antibodies using a particle-based approach. Neutralizing activity was determined by flow cytometry, which examined immediate downstream effects of cytokine stimulation in healthy control *** Autoantibodies were demonstrated in DBS eluate from 17 previously diagnosed patients with anti-IFN gamma autoantibodies. The autoantibodies recovered from DBS eluate with neutralizing anti-IFN gamma autoantibodies remained fully neutralizing using IFN gamma-induced STAT-1 phosphorylation in healthy control monocytes as a readout. Anti-IFN gamma autoantibodies preserved as DBS were stable for downstream functional testing when stored at either 4 degrees C, room temperature, or 40 degrees C for a *** Dried blood and plasma spots are simple, inexpensive, durable, and allow functional anti-IFN gamma autoantibodies to be easily recovered.

关键词： autoimmunity   migration   myocarditis   IL-23   T cell  

摘要： Th1 and Th17 cell-mediated autoimmunity is critical for myocarditis induction. Antigen-presenting cell (APCs)-released interleukin (IL)-12 and IL-23 are implicated in the differentiation of Th1 and Th17 lineages. In this study, we utilized cardiac self-antigen myosin heavy chain alpha (alpha-MyHC)-pulsed bone marrow-derived dendritic cells (bmDCs) and wild-type, IL-12p35-/-, and IL-23p19-/- mice to investigate the influence of IL-12 and IL-23 on CD4+ T cells in experimental autoimmune myocarditis (EAM). All mice (Mus musculus) receiving alpha-MyHC-pulsed bmDCs developed acute myocarditis and accumulated interferon (IFN)-gamma-positive and IL-17A-positive CD4+ T cells in cardiac tissue. Compared to immunization with wild-type bmDCs, adoptive transfer of alpha-MyHC-pulsed IL-23p19-/- bmDCs resulted in decreased numbers of IL-17A+CD4+ T cells and in a twofold reduction of infiltrating T lymphocytes in the hearts of recipient mice, despite unaffected infiltration count of CD45+ leukocytes. In contrast, IL-12p35-/- bmDCs induced fewer IFN-gamma-producing CD4+ T cells but did not affect T lymphocyte infiltration. Furthermore, IL-23p19-/- recipient mice showed reduced heart-infiltrating CD3+ T cells, but not total CD45+, compared to wild-type mice after adoptive transfer of alpha-MyHC-pulsed IL-23p19-/- bmDCs. Likewise, in the transgenic TCRM model of EAM, TCRMxIL-23p19-/- mice showed reduced myocarditis severity and fewer T lymphocytes in their hearts pointing to impaired T cell trafficking in absence of IL-23. We validated the pro-migratory effect of IL-23 on activated CD4+ T cells in vitro and demonstrated an essential role of Rho GTPases in this process. Our findings provide new insights into the pro-inflammatory activity of IL-23 in autoimmune myocarditis, highlighting its unique role in promoting T cell migration.

关键词： CD4(+) T cells   IL-12p35   immune thrombocytopenia   JAK2/STAT3/HIF-1 alpha   regulatory B cells  

摘要： Primary immune thrombocytopenia (ITP) is a condition characterized by immune-mediated platelet loss due to excessive destruction and/or insufficient production. IL-12p35 is involved in autoimmune uveitis;however, its role in ITP remains unknown. In the study, CD19(+) B and CD4(+) T cells were isolated from peripheral blood mononuclear cells (PBMCs) of patients with ITP and healthy individuals. CD4(+)CD25(-) T cells were cocultured with the CD19(+) B cells treated with anti-IL-12p35 antibody or IL-12p35 recombinant protein. The impact of IL-12p35 on CD19(+) B cells was assessed by enzyme-linked immunosorbent assay, Western blotting, quantitative real-time PCR and flow cytometry. PBMCs from patients with ITP showed lower proportions of IL-10(+)CD19(+) B cells and decreased mRNA levels of IL-12p35-coding gene IL12A than those from healthy individuals. Anti-IL-12p35 antibody-treated CD19(+) B cells could reduce the population of IL-10(+) in CD19(+) B cells and regulate the differentiation of CD4(+)CD25(-) T cells, while recombinant IL-12p35 demonstrated the opposite effects. Moreover, the increased IL-10(+) B-cell population and HIF-1 alpha expression in CD19(+) B cells induced by recombinant IL-12p35 were reversed by HIF-1 alpha and JAK2/STAT3 inhibitors. In conclusion, CD19(+)IL-10(+) B cells induced by IL-12p35 regulate CD4(+) T-cell subsets in patients with ITP via the JAK2/STAT3/HIF-1 alpha signalling pathway.

摘要： We read with great the article by Elhani et al. recently published in the European Journal of Internal Medicine [ 1]. This study attempts to establish the relationship between interleukin-18 (IL-18) and autoinflammatory diseases (AIDs) using serum...

关键词： Deoxynivalenol   Pyroptosis   Gasdermin D   IL-1 beta secretion  

摘要： Deoxynivalenol (DON), a trichothecene mycotoxin, exerts pro-inflammatory and immunomodulatory activity. Interleukin (IL)-1 beta serves a crucial part as a gate keeper of inflammation in DON-induced macrophages, but an overview of how DON exposure elicits IL-1 beta secretion from RAW264.7 cells has not been fully illustrated. Here we found that the cellular phenomenon, involved with a type of programmed cell death known as pyroptosis, contains: 1) increase of pro-IL-1 beta expression, 2) motivation of caspase-1, 3) caspase-1-dependent maturement of IL-1 beta, 4) caspase-1 fragmentation of gasdermin D (GSDMD), and 5) IL-1 beta secretion through GSDMD pore. Mechanistically, the present study certified that DON both as first and second signals engaged in IL-1 beta release is mediated by purinergic P2X7 receptor (P2X7R)-Src signaling. During this process, P2X7R signal is required for GSDMD pore forming course in ASC-independent manner. Moreover, blocking of K+ efflux, ROS formation, as well as cathepsin B activity decreases IL-1 beta export. Our data show that exposure to DON does cause pyroptosis and IL-1 beta secretion via P2X7R signal in RAW264.7 macrophages. Overall, these results provide new mechanistic clue for DON as a pro-inflammatory factor in innate immune signaling events.