We measured the serum concentrations of 2 biochemical markers of bone formation, bone Gla-protein (BGP) and bone alkaline phosphatase (BAP), in 164 normal subjects and 164 patients with metabolic bone disorders. The data were reported as Z scores (deviation in SDs from the sex-specific age regression in normal subjects). Both serum BGP and BAP distinguished abnormalities well (mean Z scores for BGP and BAP, respectively) and gave concordant results in patients with hypoparathyroidism (-1.7, -1.4), hyperthyroidism (+1.1, +1.8), primary hyperparathyroidism (+3.6, +2.5), acromegaly (+1.2, +2.8), and postmenopausal osteoporosis (+0.4, +1.9). The 2 markers gave discordant results, however, in patients with glucocorticoid excess (-2.4, +0.9), Paget's disease (+1.8, +41.8), chronic renal failure (+16.3, +0.4), and osteolytic metastases (-1.4, +5.9). These discrepancies may have occurred because serum BGP and BAP concentrations reflect different aspects of osteoblast function or because there are differences in their clearance from the circulation. Consequently, more information is derived about the level of bone formation across the wide range of metabolic bone disorders when both biochemical markers are assayed.

SARS-CoV-2 is a positive-sense single-stranded RNA virus that has exploded throughout the global human population. This pandemic coronavirus strain has taken scientists and public health researchers by surprise and knowledge of its basic biology (e.g. structure/function relationships in its genomic, messenger and template RNAs) and modes for therapeutic intervention lag behind that of other human pathogens. In this report we used a recently-developed bioinformatics approach, ScanFold, to deduce the RNA structural landscape of the SARS-CoV-2 transcriptome. We recapitulate known elements of RNA structure and provide a model for the folding of an essential frameshift signal. Our results find that the SARS-CoV-2 is greatly enriched in unusually stable and likely evolutionarily ordered RNA structure, which provides a huge reservoir of potential drug targets for RNA-binding small molecules. Our results also predict regions that are accessible for intermolecular interactions, which can aid in the design of antisense therapeutics. All results are made available via a public database (the RNAStructuromeDB) where they may hopefully drive drug discovery efforts to inhibit SARS-CoV-2 pathogenesis. Δ G° z-score region is the 3′UTR, which was found to yield mostly positive z-scores; despite a higher than average GC content for this region (0.45 on average; Table S1), MFE values here were less stable than expected, averaging Δ G° z-scores of +0.98 (or roughly one standard deviation less stable than random). Scans were also performed in the negative sense of the genome, revealing slightly less propensity for structure. The MFE values ranged from -42.9 to -6.0 and averaged -23.25 kcal/mol; z-scores in the negative sense had a similar range of Δ G° z-scores as the positive sense (-5.76 to 2.66) but averaged lower at -1.12 (Table S1). Interestingly, Δ G° z-scores for the 3′ UTR in negative sense were more skewed to the negative (finding minimums as low as -2.32) resulting in an average z-score of 0.16 for the region.