Analysis of a wild mouse promoter variant reveals a novel role for FcγRIIb in the control of the germinal center and autoimmunity.

Genetic variants of the inhibitory Fc receptor FcγRIIb have been associated with systemic lupus erythematosus in humans and mice. The mechanism by which Fcgr2b variants contribute to the development of autoimmunity is unknown and was investigated by knocking in the most commonly conserved wild mouse Fcgr2b promoter haplotype, also associated with autoimmune-prone mouse strains, into the C57BL/6 background. We found that in the absence of an AP-1-binding site in its promoter, FcγRIIb failed to be up-regulated on activated and germinal center (GC) B cells. This resulted in enhanced GC responses, increased affinity maturation, and autoantibody production. Accordingly, in the absence of FcγRIIb activation-induced up-regulation, mice developed more severe collagen-induced arthritis and spontaneous glomerular immune complex deposition. Our data highlight how natural variation in Fcgr2b drives the development of autoimmune disease. They also show how the study of such variants using a knockin approach can provide insight into immune mechanisms not possible using conventional genetic manipulation, in this case demonstrating an unexpected critical role for the activation-induced up-regulation of FcγRIIb in controlling affinity maturation, autoantibody production, and autoimmunity

Lactacidemia e concentrações séricas de aspartato aminotransferase e creatinoquinase em equinos da raça Quarto de Milha usados em provas de laço em dupla

O presente estudo teve por objetivo avaliar a influência do exercício físico de alta intensidade e curta duração (provas de laço em dupla) sobre a lactacidemia e as concentrações séricas de aspartato aminotransferase (AST) e creatinoquinase (CK) em equinos durante competição realizada no estado do Espírito Santo. Para tal foram obtidas amostras de soro e plasma de 20 equinos, da raça Quarto de Milha ou mestiços, em três momentos assim definidos: no repouso, uma semana antes da prova atlética, já com o animal em treinamento (T0); antes da prova atlética (T1) e imediatamente após o término da mesma (T2). As referidas amostras foram encaminhadas ao Laboratório Clínico do Centro Universitário Vila Velha (UVV) para as análises. Na avaliação da lactacidemia, os resultados registrados nos momentos T0, T1 e T2 foram, respectivamente, de 0,49±0,24mmol/L, 0,93±0,16mmol/L e 9,86±2,09mmol/L. Na avaliação da atividade sérica de AST, os resultados registrados nos momentos T0, T1e T2 foram, respectivamente, de 189,1±43,6 UI/L, 210,2±46,7 UI/L e 173,1±33,5 UI/L. Por fim, a avaliação da atividade sérica da CK nos momentos T0,T1 e T2 foram,respectivamente, de 110,9±35,2 UI/L, 51,8±15,4 UI/L e 88,2±33,5 UI/L. A análise dos resultados demonstrou que o exercício físico imposto levou ao aumento significativo de lactato plasmático e CK sérica e não alterou o AST sérico e que a interpretação destes resultados permitiu concluir que os equinos usados estavam aptos ao nível de exercício físico imposto

Quantitative Risk Assessment for Zoonotic Transmission of Cryptosporidium parvum Infection Attributable to Recreational Use of Farmland

Cryptosporidiosis caused by Cryptosporidium parvum infection is a major cause of enteric illness in man and there is a significant reservoir in animals, particularly young ruminant species. To preliminary assess the magnitude of the risk posed by contact with faeces produced by infected livestock, two microbiological risk assessments have been developed: one for the risk of human infection with C. parvum while camping on contaminated land recently grazed by infected suckler cattle and a comparable risk assessment for camping on land recently spread with contaminated cattle slurry. Using a worst-case scenario approach, the upper level of risk was estimated to be one infection in every 6211 person-visits for a camping event on land recently grazed by infected cattle. Translated into camping events of 100 persons, this risk estimate would most likely lead to zero (98% likelihood) or one infection (1% likelihood). The results for cattle slurry model are similar despite different pathways. Sensitivity analysis was conducted for the grazing cattle model only. This suggested that the time between grazing and camping was the most important control strategy, but increasing hand-washing frequency and the removal of cattle faeces before camping would also be beneficial. If the upper level of risk were to be judged unacceptable then further data would be required to more accurately estimate the risk of infection through these scenarios. Further research would also be required to assess the fraction of cases attributable to camping and/or environmental contact with Cryptosporidium oocysts