Correlation between structural parameters and contrast sensitivity vision in patients with multiple sclerosis.

<p>Correlation between structural parameters and contrast sensitivity vision in patients with multiple sclerosis.</p

Correlation between visual acuity as measured with ETDRS optotipe at a contrast level of 100% and the average ganglion cell + inner plexiform layer thickness in patients with multiple sclerosis.

<p>Dark symbols represent data from patients with a previous episode of optic neuritis, whereas light symbols represent patients without a previous episode of optic neuritis.</p

Correlation between the average ganglion cell + inner plexiform layer thickness and contrast sensitivity vision measured with the Pelli Robson test in patients with multiple sclerosis.

<p>Dark symbols represent data from patients with a previous episode of optic neuritis, whereas light symbols represent patients without a previous episode of optic neuritis.</p

Correlation between structural measurements and color vision in patients with multiple sclerosis.

<p>Correlation between structural measurements and color vision in patients with multiple sclerosis.</p

Visual function and structural parameters in healthy controls and subjects with multiple sclerosis.

<p>Visual function and structural parameters in healthy controls and subjects with multiple sclerosis.</p

Correlation between structural parameters and visual acuity in patients with MS.

<p>Correlation between structural parameters and visual acuity in patients with MS.</p

Isolation, Structure, and Biological Activity of Phaeofungin, a Cyclic Lipodepsipeptide from a <i>Phaeosphaeria</i> sp. Using the Genome-Wide <i>Candida albicans</i> Fitness Test

Phaeofungin (<b>1</b>), a new cyclic depsipeptide isolated from <i>Phaeosphaeria</i> sp., was discovered by application of reverse genetics technology, using the <i>Candida albicans</i> fitness test (<i>Ca</i>FT). Phaeofungin is comprised of seven amino acids and a β,γ-dihydroxy-γ-methylhexadecanoic acid arranged in a 25-membered cyclic depsipeptide. Five of the amino acids were assigned with d-configurations. The structure was elucidated by 2D-NMR and HRMS-MS analysis of the natural product and its hydrolyzed linear peptide. The absolute configuration of the amino acids was determined by Marfey’s method by complete and partial hydrolysis of <b>1</b>. The <i>Ca</i>FT profile of the phaeofungin-containing extract overlapped with that of phomafungin (<b>3</b>), another structurally different cyclic lipodepsipeptide isolated from a <i>Phoma</i> sp. using the same approach. Comparative biological characterization further demonstrated that these two fungal lipodepsipeptides are functionally distinct. While phomafungin was potentiated by cyclosporin A (an inhibitor of the calcineurin pathway), phaeofungin was synergized with aureobasidin A (2) (an inhibitor of the sphingolipid biosynthesis) and to some extent caspofungin (an inhibitor of glucan synthase). Furthermore, phaeofungin caused ATP release in wild-type <i>C. albicans</i> strains but phomafungin did not. It showed modest antifungal activity against <i>C. albicans</i> (MIC 16–32 μg/mL) and better activity against <i>Aspergillus fumigatus</i> (MIC 8–16 μg/mL) and <i>Trichophyton mentagrophytes</i> (MIC 4 μg/mL). The linear peptide was inactive, suggesting that the macrocyclic depsipeptide ring is essential for target engagement and antifungal activity