AIRE is a transcriptional activator that directs the ectopic expression of many tissue-specific genes in medullary thymic epithelial cells, which plays an important role in the negative selection of autoreactive T cells. However, its mechanism of action remains poorly understood. In this study, we found that AIRE regulates the step of elongation rather than initiation of RNA polymerase II. For these effects, AIRE bound and recruited P-TEFb to target promoters in medullary thymic epithelial cells. In these cells, AIRE activated the ectopic transcription of insulin and salivary protein 1 genes. Indeed, by chromatin immunoprecipitation, we found that RNA polymerase II was already engaged on these promoters but was unable to elongate in the absence of AIRE. Moreover, the genetic inactivation of cyclin T1 from P-TEFb abolished the transcription of AIRE-responsive genes and led to lymphocytic infiltration of lacrimal and salivary glands in the CycT1 ؊/؊ mouse. Our findings reveal critical steps by which AIRE regulates the transcription of genes that control central tolerance in the thymus.

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Mycoplasma synoviae is a major avian pathogen that synthesizes hemagglutinin VlhA, an abundant immunodominant surface lipoprotein. In most M. synoviae strains, the VlhA protein cleaves into the N-terminal part, a lipoprotein MSPB, and a C-terminal part MSPA, which mediates binding to erythrocytes. VlhA is encoded by the vlhA gene of which the 5'-end is present in the genome as a single copy, which does not change its sequence during recombination of the vlhA gene with pseudogenes. In this study, sequence analyses of the 5'-end vlhA sequences of 30 M. synoviae isolates revealed a highly polymorphic region encoding the proline-rich repeats (PRR) in the N-terminal part of MSPB. Pathogenic strain K1968 had an insertion encoding sequence DNPQNPN in PRR, whereas strains F10-2AS, K2581, K3344 and five strains belonging to two related clusters of strains isolated recently from chickens in Slovenia lacked one PRR repeat of 19 amino acids. The predicted length variations correlated well with the lengths of the corresponding MSPB proteins detected in immunoblots with specific antibodies. Comparison of the 5'-end vlhA sequences of 30 M. synoviae strains showed 11 different types of vlhA sequences indicating that the analysis of this vlhA part is useful for strain differentiation. Distinct sequence motifs seem to be characteristic for vlhA genes of individual M. synoviae strains or clusters of strains and can be used as markers for tracing their spreading between poultry farms.

No abstract

The objective of the present study was to evaluate the effects of different concentrations of T-2 toxin in feed on performance, lipid peroxidation, and genotoxicity in vivo. For a 17-d period, T-2 toxin was added to the diet of the chickens. Fifty 22-d-old male broiler chickens were divided into 5 groups that were supplemented with different concentrations of T-2 toxin: control (0.0 mg/kg of feed), T 0.5 (0.5 mg/kg of feed), T 1.5 (1.5 mg/kg of feed), T 4.5 (4.5 mg/kg of feed), and T 13.5 (13.5 mg/kg of feed). Deoxyribonucleic acid fragmentation in spleen leukocytes, malondialdehyde in plasma and liver, total plasma antioxidative status, glutathione peroxidase activity, and total serum Ig (IgA and IgG) were measured. Feed consumption and BW gain decreased when the concentration of T-2 toxin was 4.5 and 13.5 mg/kg of feed. Compared with the control group, the rate of DNA damage increased significantly in the group fed 13.5 mg of T-2 toxin/kg of feed. In contrast to DNA fragmentation, indicators of oxidative stress did not show differences between groups fed T-2 toxin and the control. More serum IgA was detected in the group T 13.5 compared with the control, whereas there were no differences in serum IgG levels. The results of the present study indicate that impaired performance, DNA fragmentation in spleen leukocytes, and elevated serum IgA levels induced by T-2 toxin are dose-dependent. Based on our results, we could not confirm the hypothesis that oxidative stress is among the mechanisms by which T-2 toxin induces DNA fragmentation.