idh-1 neomorphic mutation confers sensitivity to vitamin B12 via increased dependency on one-carbon metabolism in Caenorhabditis elegans.

The isocitrate dehydrogenase neomorphic mutation ( idh-1neo ) generates increased levels of cellular D-2-hydroxyglutarate (D-2HG), a proposed oncometabolite. However, the physiological effects of increased D-2HG and whether additional metabolic changes occur in the presence of an idh-1neo mutation are not well understood. We created a C. elegans model to study the effects of the idh-1neo mutation in a whole animal. Comparing the phenotypes exhibited by the idh-1neo to Δdhgd-1 (D-2HG dehydrogenase) mutant animals, which also accumulate D-2HG, we identified a specific vitamin B12 diet-dependent vulnerability in idh-1neo mutant animals that leads to increased embryonic lethality. Through a genetic screen we found that impairment of the glycine cleavage system, which generates one-carbon donor units, exacerbates this phenotype. Additionally, supplementation with an alternate source of one-carbon donors suppresses the lethal phenotype. Our results indicate that the idh-1neo mutation imposes a heightened dependency on the one-carbon pool and provides a further understanding how this oncogenic mutation rewires cellular metabolism.

Antibody Response to Rotavirus C Pre-Farrow Natural Planned Exposure to Gilts and Their Piglets.

A longitudinal study was conducted to investigate the dynamics of genotype-specific (G6 and P[5]) antibody response to different doses (3, 2 and 1) of rotavirus C (RVC) natural planned exposure (NPE) in gilt serum, colostrum/milk and piglet serum, and compare with antibody response to rotavirus A NPE (RVA genotypes G4, G5, P[7] and P[23]). G6 and P[5] antigens of RVC were expressed in mammalian and bacterial cells, and used to develop individual indirect ELISAs. For both antigens, group 1 with 3 doses of NPE resulted in significantly higher IgG and IgA levels in colostrum compared to other groups. In piglet serum, group 1 P[5] IgG levels were significantly higher than other study groups at day 0 and 7. Piglet serum had higher IgA levels for group 1 piglets compared to other groups for both antigens. A comparison of colostrum antibody levels to rotavirus A (RVA) and RVC revealed that colostrum RVC IgG and IgA titers were lower than RVA titers irrespective of the G and P-type. Next generation sequencing (NGS) detected same RVC genotypes (G6 and P[5]) circulating in the piglet population under the window of lactogenic immunity. We conclude that the low RVC load in NPE material (real-time PCR Ct-values 32.55, 29.32 and 30.30) failed to induce sufficient maternal immunity in gilts (low colostrum RVC antibody levels) and passively prevent piglets from natural RVC infection in the farrowing room. To the best of our knowledge, this is the first study comparing differences in antibody response to porcine RVA and RVC in a commercial setting.