SummaryThe ESX-1 secretion system plays a critical role in the virulence of Mycobacterium tuberculosis and M. marinum. To date, three proteins are known to be secreted by ESX-1 and necessary for virulence, two of which are CFP-10 and ESAT-6. The ESX-1 secretion and the virulence mechanisms are not well understood. In this study, we have examined the M. marinum secretomes and identified four proteins specific to ESX-1. Two of those are CFP-10 and ESAT-6, and the other two are novel: MM1553 (homologous to Rv3483c) and Mh3881c (homologous to Rv3881c). We have shown that Mh3881c, CFP-10 and ESAT-6 are co-dependent for secretion. Mh3881c is being cleaved at close to the C-terminus during secretion, and the C-terminal portion is critical to the co-dependent secretion, the ESAT-6 cellular levels, and interaction with ESAT-6. The co-dependent secretion is required for M. marinum intracellular growth in macrophages, where the Mh3881c C-terminal portion plays a critical role. The role of the co-dependent secretion in intracellular growth correlates with its role in inhibiting phagosome maturation. Both the secretion and the virulence defects of the Mh3881c mutant are complemented by Mh3881c or its M. tuberculosis homologue Rv3881c, suggesting that in M. tuberculosis, Rv3881c has similar functions.
The etiology and pathophysiology of preeclampsia are not fully understood. However, oxidative stress has been strongly linked to the occurrence of this multi-system disease. This has led to many theories of the pathogenesis of preeclampsia involving placental oxidative stress. In this study, we hypothesized that polymorphisms of anti-oxidant genes in the placental tissue contributed to susceptibility to preeclampsia. Polymorphisms in copper/zinc superoxide dismutase (CuZn-SOD), manganese superoxide dismutase (MnSOD), glutathione-s-transferase M1 (GSTM1), and glutathione-s-transferase T1 (GSTT1) in the umbilical cord tissue were assayed by polymerase chain reaction (PCR) in 23 nulliparous preeclampsia cases and 32 nulliparous normotensive controls. Corresponding enzyme activity levels and an oxidative stress biomarker (8-isoprostane) of the placental tissue were also measured. In addition, maternal plasma 8-isoprostane levels were also determined. Our results showed that no significant differences in polymorphism frequency of the tested genes, enzyme activity levels or 8-isoprostane levels in the placental tissue were detected between the cases and controls. However, maternal plasma 8-isoprostane level was significantly higher in the cases than in the controls (105.8 vs. 27.9 pg/ml, p = 0.03). In conclusion, our study showed that polymorphisms of CuZn-SOD, MnSOD, GSTM1 and GSTT1 in the placental tissue were not associated with preeclampsia.
Imaging of the endocrine pancreas is dominated by neuroendocrine tumors, a diverse category of neoplasms that may or may not cause symptoms from hormone hypersecretion. These tumors may also be evidence of several different genetic syndromes. Understanding the usefulness of different imaging modalities and entities that simulate neuroendocrine tumors is key for both radiologists and referring physicians.
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