BCG Vaccinations Upregulate Myc, a Central Switch for Improved Glucose Metabolism in Diabetes.

Myc has emerged as a pivotal transcription factor for four metabolic pathways: aerobic glycolysis, glutaminolysis, polyamine synthesis, and HIF-1α/mTOR. Each of these pathways accelerates the utilization of sugar. The BCG vaccine, a derivative of Mycobacteria-bovis, has been shown to trigger a long-term correction of blood sugar levels to near normal in type 1 diabetics (T1D). Here we reveal the underlying mechanisms behind this beneficial microbe-host interaction. We show that baseline glucose transport is deficient in T1D monocytes but is improved by BCG in vitro and in vivo. We then show, using RNAseq in monocytes and CD4 T cells, that BCG treatment over 56 weeks in humans is associated with upregulation of Myc and activation of nearly two dozen Myc-target genes underlying the four metabolic pathways. This is the first documentation of BCG induction of Myc and its association with systemic blood sugar control in a chronic disease like diabetes.

δ(13) C of leaf-respired CO(2) reflects intrinsic water-use efficiency in barley.

Leaf intrinsic water-use efficiency (WUE), the ratio of photosynthetic rate to stomatal conductance (A/g(s) ), is a key plant trait linking terrestrial carbon and water cycles. A rapid, integrative proxy for A/g(s) is of benefit to crop breeding programmes aiming to improve WUE, but also for ecologists interested in plant carbon-water balance in natural systems. We hypothesize that the carbon isotope composition of leaf-respired CO(2) (δ(13) C(Rl) ), two hours after leaves are transferred to the dark, records photosynthetic carbon isotope discrimination and so provides a proxy for A/g(s) . To test this hypothesis, δ(13) C(Rl) was measured in four barley cultivars grown in the field at two levels of water availability and compared to leaf-level gas exchange (the ratio of leaf intercellular to ambient CO(2) partial pressure, C(i) /C(a) , and A/g(s) ). Leaf-respired CO(2) was more (13) C-depleted in plants grown at higher water availability, varied between days as environmental conditions changed, and was significantly different between cultivars. A strong relationship between δ(13) C(Rl) and δ(13) C of sucrose was observed. δ(13) C(Rl) was converted into apparent photosynthetic discrimination (Δ(13) C(Rl) ) revealing strong relationships between Δ(13) C(Rl) and C(i) /C(a) and A/g(s) during the vegetative stage of growth. We therefore conclude that δ(13) C(Rl) may provide a rapid, integrative proxy for A/g(s) in barley.