Structural genomic variants in thoracic aortic disease.

PURPOSE OF REVIEW: Structural genomic variants have emerged as a relevant cause for several disorders, including intellectual disability, neuropsychiatric disorders, cancer and congenital heart disease. In this review, we will discuss the current knowledge about the involvement of structural genomic variants and, in particular, copy number variants in the development of thoracic aortic and aortic valve disease. RECENT FINDINGS: There is a growing interest in the identification of structural variants in aortopathy. Copy number variants identified in thoracic aortic aneurysms and dissections, bicuspid aortic valve related aortopathy, Williams-Beuren syndrome and Turner syndrome are discussed in detail. Most recently, the first inversion disrupting FBN1 has been reported as a cause for Marfan syndrome. SUMMARY: During the past 15 years, the knowledge on the role of copy number variants as a cause for aortopathy has grown significantly, which is partially due to the development of novel technologies including next-generation sequencing. Although copy number variants are now often investigated on a routine basis in diagnostic laboratories, more complex structural variants such as inversions, which require the use of whole genome sequencing, are still relatively new to the field of thoracic aortic and aortic valve disease.

Biocatalytic and semisynthetic optimization of the anti-invasive tobacco (1S,2E,4R,6R,7E,11E)-2,7,11-cembratriene-4,6-diol.

Tobacco cembranoids were reported to inhibit tumorigenesis. Biocatalysis of (1S,2E,4R,6R,7E,11E)-2,7,11-cembratriene-4,6-diol (1) using the symbiotic Bacillus sp. NC5, Bacillus sp. NK8, and Bacillus sp. NK7, isolated from the Red Sea sponge Negombata magnifica, afforded two new and four known hydroxylated metabolites 3-8. The use of symbiotic marine bacteria as biocatalysts for bioactive natural product scaffolds is very rare. Cembranoid 1 carbamate analogs 9-11 were prepared by its reaction with corresponding isocyanates. Cembranoid 1 and its bioconversion and carabamate products show anti-invasive activity against the human highly metastatic prostate PC-3M cancer cell line at 10-50 nM doses in Matrigel assay.