Sterol Biosynthesis Inhibition in Pregnant Women Taking Prescription Medications.

Sterol biosynthesis is a critical homeostatic mechanism of the body. Sterol biosynthesis begins during early embryonic life and continues throughout life. Many commonly used medications, prescribed >200 million times in the United States annually, have a sterol biosynthesis inhibition side effect. Using our high-throughput LC-MS/MS method, we assessed the levels of post-lanosterol sterol intermediates (lanosterol, desmosterol, and 7-dehydrocholesterol (7-DHC)) and cholesterol in 1312 deidentified serum samples from pregnant women. 302 samples showing elevated 7-DHC were analyzed for the presence of 14 medications known to inhibit the 7-dehydrocholesterol reductase enzyme (DHCR7) and increase 7-DHC. Of the 302 samples showing 7-DHC elevation, 43 had detectable levels of prescription medications with a DHCR7-inhibiting side effect. Taking more than one 7-DHC-elevating medication in specific combinations (polypharmacy) might exacerbate the effect on 7-DHC levels in pregnant women, suggesting a potentially additive or synergistic effect. As 7-DHC and 7-DHC-derived oxysterols are toxic, and as DHCR7-inhibiting medications are considered teratogens, our findings raise potential concerns regarding the use of prescription medication with a DHCR7-inhibiting side effect during pregnancy. The use of prescription medications during pregnancy is sometimes unavoidable, but choosing a medication without a DHCR7-inhibiting side effect might lead to a heathier pregnancy and prevent putatively adverse outcomes for the developing offspring.

Draft Genome Sequence of Methanothermobacter thermautotrophicus WHS, a Thermophilic Hydrogenotrophic Methanogen from Washburn Hot Springs in Yellowstone National Park, USA.

A thermophilic methanogen was enriched in coculture from Washburn Hot Springs (Yellowstone National Park, USA), grown on carbon dioxide and hydrogen, and subsequently sequenced. The reconstructed 1.65-Mb genome sequence for Methanothermobacter thermautotrophicus WHS contributes to our understanding of hydrogenotrophic, CO2-reducing methanogenesis in geothermal ecosystems.

Prescription Medications Alter Neuronal and Glial Cholesterol Synthesis.

Mouse brain contains over 100 million neuronal, glial, and other support cells. Developing neurons and astrocytes synthesize their own cholesterol, and disruption of this process can occur by both genetic and chemical mechanisms. In this study we have exposed cultured murine neurons and astrocytes to six different prescription medications that cross the placenta and blood-brain barriers and analyzed the effects of these drugs on cholesterol biosynthesis by an LC-MS/MS protocol that assays 14 sterols and 7 oxysterols in a single run. Three antipsychotics (haloperidol, cariprazine, aripiprazole), two antidepressants (trazodone and sertraline), and an antiarhythmic (amiodarone) inhibited one or more sterol synthesis enzymes. The result of the exposures was a dose-dependent increase in levels of various sterol intermediates and a decreased level of cholesterol in the cultured cells. Four prescription medications (haloperidol, aripiprazole, cariprazine, and trazodone) acted primarily on the DHCR7 enzyme. The result of this exposure was an increase in 7-dehydrocholesterol in neurons and astrocytes to levels that were comparable to those found in cultured neurons and astrocytes from transgenic mice that carried a Dhcr7 pathogenic mutation modeling the neurodevelopmental disorder Smith-Lemli-Opitz syndrome.

Co-occurring genomic capacity for anaerobic methane and dissimilatory sulfur metabolisms discovered in the Korarchaeota.

Phylogenetic and geological evidence supports the hypothesis that life on Earth originated in thermal environments and conserved energy through methanogenesis or sulfur reduction. Here we describe two populations of the deeply rooted archaeal phylum Korarchaeota, which were retrieved from the metagenome of a circumneutral, suboxic hot spring that contains high levels of sulfate, sulfide, methane, hydrogen and carbon dioxide. One population is closely related to 'Candidatus Korarchaeum cryptofilum OPF8', while the more abundant korarchaeote, 'Candidatus Methanodesulfokores washburnensis', contains genes that are necessary for anaerobic methane and dissimilatory sulfur metabolisms. Phylogenetic and ancestral reconstruction analyses suggest that methane metabolism originated in the Korarchaeota, whereas genes for dissimilatory sulfite reduction were horizontally transferred to the Korarchaeota from the Firmicutes. Interactions among enzymes involved in both metabolisms could facilitate exergonic, sulfite-dependent, anaerobic oxidation of methane to methanol; alternatively, 'Ca. M. washburnensis' could conduct methanogenesis and sulfur reduction independently. Metabolic reconstruction suggests that 'Ca. M. washburnensis' is a mixotroph, capable of amino acid uptake, assimilation of methane-derived carbon and/or CO2 fixation by archaeal type III-b RuBisCO for scavenging ribose carbon. Our findings link anaerobic methane metabolism and dissimilatory sulfur reduction within a single deeply rooted archaeal population and have implications for the evolution of these traits throughout the Archaea.