Mutations in the _SC4MOL_ gene encoding a novel methyl sterol oxidase cause autosomal recessive psoriasisiform dermatitis, microcephaly and developmental delay

Disorders of cholesterol biosynthesis have clinical manifestations involving skeleton, eyes, neurologic development, and skin. We describe a patient with congenital cataracts, developmental delay, microcephaly, and low serum cholesterol who developed severe psoriasiform dermatitis and arthralgias beginning at age 3. Her brain MRI indicatedminor gliosis. Quantitative sterol analysis of patient plasma and skin showed marked elevation of 4alpha-methyl- and 4, 4'-dimethylsterols, indicating a deficiency in the first step of sterol C4 demethylation in cholesterol biosynthesis. Molecular studies showed mutations in _SC4MOL_, a gene predicted to encode a sterol C4 methyl oxidase. Thus, our patient has a previously undescribed inborn error of cholesterol biosynthesis. Cellular studies with patient-derived fibroblasts showed higher mitotic rate than control cells in cholesterol-depleted medium, in which _de novo_ cholesterol biosynthesis was increased with the accumulation of methylsterol. Immunologic analyses showed dysregulation of immune-related receptors in the patient and her father. Inhibition of sterol C4 methyl oxidase in human transformed lymphoblasts or in fresh leukocytes induced activation of cell cycle, and immune receptor dysregulation. These findings suggest that methylsterols influence mitotic capacity and immune function. _SC4MOL_ is situated within the psoriasis susceptibility locus _PSORS9_, and is likely a genetic risk factor for common psoriasis

Elastometry of Complex Fluid Pendant Capsules

Oil/water interfaces are ubiquitous in nature. Opposing polarities at these interfaces attract surface-active molecules, which can seed complex viscoelastic or even solid interfacial structure. Biorelevant proteins such as hydrophobin, polymers such as PNIPAM, and the asphaltenes in crude oil (CRO) are examples of some systems where such layers can occur. When a pendant drop of CRO is aged in brine, it can form an interfacial elastic membrane of asphaltenes so stiff that it wrinkles and crumples upon retraction. Most of the work studying CRO/brine interfaces focuses on the viscoelastic liquid regime, leaving a wide range of fully solidified, elastic interfaces largely unexplored. In this work, we quantitatively measure elasticity in all phases of drop retraction. In early retraction, the interface shows a fluid viscoelasticity measurable using a Gibbs isotherm or dilatational rheology. Further retraction causes a phase transition to a 2D elastic solid with nonisotropic, nonhomogeneous surface stresses. In this regime, we use new techniques in the elastic membrane theory to fit for the elasticities of these solid capsules. These elastic measurements can help us develop a deeper understanding not only of CRO interfaces but also of the myriad fluid systems with solid interfacial layers.</p