The Creation of an Average 3D Model of the Human Cartilaginous Nasal Septum and Its Biomimetic Applications.

The cartilaginous nasal septum is integral to the overall structure of the nose. Developing our an-atomic understanding of the septum will improve the planning and techniques of septal surgeries. While the basic dimensions of the septum have previously been described, the average shape in the sagittal plane has yet to be established.

Chemistry Manufacturing and Controls Development, Industry Reflections on Manufacture, and Supply of Pandemic Therapies and Vaccines.

This publication provides some industry reflections on experiences from the Chemistry, Manufacturing, and Controls (CMC) development and manufacture and supply of vaccines and therapies in response to the COVID-19 pandemic. It integrates these experiences with the outcomes from the collaborative work between industry and regulators in recent years on innovative science- and risk-based CMC strategies to the development of new, high-quality products for unmet medical needs. The challenges for rapid development are discussed and various approaches to facilitate accelerated development and global supply are collated for consideration.

Biosynthetic precursors of the lipase inhibitor lipstatin.

Three putative intermediates in the biosynthesis of the lipase inhibitor lipstatin were synthesized in stable isotope-labeled form and were added to fermentation cultures of Streptomyces toxytricini. Biosynthetic lipstatin was isolated and analyzed by NMR spectroscopy. [3,10,11,12-(2)H]-(3S,5Z,8Z)-3-hydroxytetradeca-5,8-dienoic acid (9) was shown to serve as a direct biosynthetic precursor of lipstatin.

Biosynthesis of lipstatin. Incorporation of multiply deuterium-labeled (5Z,8Z)-tetradeca-5,8-dienoic acid and octanoic acid.

Fermentation experiments with Streptomyces toxytricini were performed using (5Z,8Z)-[10,11,12,12-(2)H]tetradeca-5,8-dienoic acid or a mixture of [2,2-(2)H(2)]- and [8,8,8-(2)H(3)]octanoic acid as supplements. (2)H NMR and mass spectroscopy confirmed the incorporation of (5Z,8Z)-[10,11,12,12-(2)H]tetradeca-5,8-dienoic acid into the C(13) side chain as well as into the C(6) side chain of lipstatin. Moreover, deuterium was incorporated into the C(6) side chain of lipstatin from the 8-position but not from the 2-position of octanoate.

Biosynthetic origin of hydrogen atoms in the lipase inhibitor lipstatin.

The lipase inhibitor lipstatin is biosynthesized in Streptomyces toxytricini via condensation of a C(14) precursor and a C(8) precursor, which are both obtained from fatty acid catabolism. To study the mechanism of this reaction in more detail, S. toxytricini was grown in medium containing a mixture of U-(13)C,U-(2)H-lipids and unlabeled sunflower oil or in a medium containing 70% D(2)O.