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Rationale: Coronary artery disease (CAD) is a pervasive and critical health care problem. Elevated high-density lipoprotein-associated cholesterol (HDL-C) is associated with improved atherosclerotic cardiovascular disease outcomes on a population level, but clinical trials aimed at HDL-C elevation have not succeeded in improving atherosclerotic cardiovascular disease event risk. Nevertheless, human variants in the HDL receptor, encoded by SCARB1 , are associated with dyslipidemia, suggesting that HDL metabolism, not HDL-C, is a suitable target for therapy. However, variants in SCARB1 have never been directly attributed to CAD by Mendelian inheritance. Objective: To determine if compound heterozygous variants in SCARB1 cause disease in 2 brothers with severe, early-onset CAD. Methods and Results: Using whole exome sequencing, we have identified rare, compound heterozygous variants in SCARB1 that segregate with severe, premature CAD, following patterns of Mendelian inheritance. Using induced pluripotent stem cell–derived hepatocyte-like cells from the proband, we discovered the maternal variant (c.754_755delinsC) to be the first identified SCARB1 null allele, characterized by the absence of RNA and protein expression. Further, we demonstrate that the variant on the paternal allele (c.956G>T [p.G319V]) results in decreased cholesterol uptake, decreased SR-BI:HDL binding, and increased affinity for SR-BI dimerization. Finally, we generated a p.G319V knock-in mouse model that displays nearly 100% homozygous lethality and elevated plasma cholesterol in heterozygous animals, confirming pathogenicity of this variant. Conclusions: In summary, our data provide the first molecular mechanism to show the Mendelian inheritance of CAD as a result of human SCARB1 variants. The rarity of these variants supports pathogenicity in this family. Furthermore, SR-BI p.G319V, which has previously been reported benign in the context of heterozygosity, was uniquely presented alongside a null allele, demonstrating the disease-contributing capability of loss-of-function SCARB1 variants within the population.

Soils are continuously exposed to large amounts of engineered nanoparticles, especially silver nanoparticles (AgNPs), which can affect the activity, stability, and specificity of microbial enzymes. Therefore, the measurement of specific enzyme activity can be used to identify major changes in soil environments. Accordingly, the aim of the present study was to investigate the effects of AgNPs on soil enzymes that play critical roles in mineralizing carbon and nutrients in soil. Soil samples (silt loam and sandy loam) were collected from the surface layer (0–15 cm) of a field at the George Washington Carver Farm, Lincoln University of Missouri, USA. The soils were then treated with AgNP solutions at 0, 1 600, or 3 200 μg Ag kg−1 dry soil, using either 10- or 50-nm AgNPs and a randomized complete block design, with three replicates per treatment. The AgNP-treated soil samples were homogenized and incubated for one month, and soil acid phosphatase, β-glucosaminidase, β-glucosidase, and arylsulfatase activities were measured after one hour, one week, and one month of incubation. The activities of all four enzymes were reduced by AgNP treatment after one hour and one week. However, AgNP size had no effect. After one month of incubation, the AgNP treatments had mixed effects, which suggests that soil enzymes are only affected on a short-term basis. Further studies are required to determine the mechanisms by which AgNPs reduce soil enzyme activity.