Immunophilins are protein chaperones with peptidylprolyl isomerase activity that belong to one of two large families, the cyclosporin-binding cyclophilins (CyPs) and the FK506-binding proteins (FKBPs). Each family displays characteristic and conserved sequence features that differ between the two families. We report a novel group of dual-family immunophilins that contain both CyP and FKBP domains for which we propose the name FCBP (FK506-and cyclosporin-binding protein). The FCBP of Toxoplasma gondii, a protozoan parasite, contained N-terminal FKBP and C-terminal CyP domains joined by tetratricopeptide repeats. Structurefunction analysis revealed that both domains were functional and exhibited family-specific drug sensitivity. The individual domains of FCBP inhibited calcineurin (protein phosphatase 2B) in the presence of the appropriate drugs. In binding studies, FCBP recruited calcineurin in the presence of FK506 and a putative target of rapamycin homolog in the presence of rapamycin. Two additional FCBP sequences in Flavobacterium and one in Treponema (spirochete) were also identified in which the CyP and FKBP domains were in the reverse order. T. gondii growth was inhibited by cyclosporin and FK506 in a moderately synergistic manner. The knockdown of FCBP by RNA interference revealed its essentiality for T. gondii growth. Clearly, the FCBPs are novel chaperones and potential targets of multiple immunosuppressant drugs.
Pediatric intracranial aneurysms are uncommon as compared to in adult patients. Seizures and cranial nerve involvement are seen more often as the presenting features in children. Posterior circulation aneurysms are more common in children, as are the internal carotid artery bifurcation aneurysms. There is high incidence of giant, posttraumatic, and mycotic aneurysms in children.
Surgical excision has excellent outcome in treatment of scalp AVM. Pre-operative embolization reduces vascularity and helps in easy identification of AVM during surgery thus achieving complete excision. The size of AVM has no correlation with the number of feeding vessels. There are high chances of recurrence in large AVM after embolization.
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