pathophysiological mechanisms underlying lathosterolosis neurological symptoms are studies using quantitative proteomics analysis of lathosterolosis mouse brain tissue of Dhcr7 mutant mice. Multiple biological pathways are affected including alterations in mevalonate metabolism, apoptosis, glycolysis, oxidative stress, protein biosynthesis, intracellular trafficking, and cytoskeleton. Increased expression of isoprenoid and cholesterol synthetic enzymes is shown, suggesting that although cholesterol synthesis is impaired in both Dhcr7 mutant mice the synthesis of nonsterol isoprenoids may be increased and thus contribute to lathosterolosis pathology
a mechanism of antifungal resistance in this organism affecting susceptibility to azole and echinocandin antifungals is found in a clinical isolate obtained from a patient with prosthetic valve endocarditis. Transcriptome analysis indicates differential expression of several genes in the resistant isolate, including upregulation of ergosterol biosynthesis pathway genes ERG2, ERG5, ERG6, ERG11, ERG24, ERG25, and UPC2. Whole-genome sequencing reveals that the resistant isolate possesses an ERG3 mutation resulting in a G111R amino acid substitution. Sterol profiles indicate a reduction in sterol desaturase activity as a result of this mutation. Replacement of both mutant alleles in the resistant isolate with the susceptible isolate's allele restores wild-type susceptibility to all azoles and echinocandins tested
mice deleted for keratinocyte Sc5d lose the ability to increase circulating D3 following UVR exposure of the skin. Unlike in control mice, acute UVR exposure does not affect circulating D3 level in inducible Sc5dk14KOi mice. Phenotypes, overview
a mechanism of antifungal resistance in this organism affecting susceptibility to azole and echinocandin antifungals is found in a clinical isolate obtained from a patient with prosthetic valve endocarditis. Transcriptome analysis indicates differential expression of several genes in the resistant isolate, including upregulation of ergosterol biosynthesis pathway genes ERG2, ERG5, ERG6, ERG11, ERG24, ERG25, and UPC2. Whole-genome sequencing reveals that the resistant isolate possesses an ERG3 mutation resulting in a G111R amino acid substitution. Sterol profiles indicate a reduction in sterol desaturase activity as a result of this mutation. Replacement of both mutant alleles in the resistant isolate with the susceptible isolate's allele restores wild-type susceptibility to all azoles and echinocandins tested
mice deleted for keratinocyte Sc5d lose the ability to increase circulating D3 following UVR exposure of the skin. Unlike in control mice, acute UVR exposure does not affect circulating D3 level in inducible Sc5dk14KOi mice. Phenotypes, overview
one gene essential to ergosterol biosynthesis is ERG3, which encodes the DELTA7-sterol-C5 (6)-desaturase responsible for introducing a double bond at C-5 in the B ring of episterol. DELTA7-sterol-C5(6)-desaturase is a membrane-bound enzyme that catalyzes introduction of a C-5 double bond into the B ring of DELTA7-sterols to yield the corresponding DELTA5,7-sterols