Background and aims: Currently there is considerable interest in ketone metabolism owing to recently reported benefits of ketosis for human health. Traditionally, ketosis has been achieved by following a high-fat, low-carbohydrate “ketogenic” diet, but adherence to such diets can be difficult. An alternative way to increase blood D-β-hydroxybutyrate (D-βHB) concentrations is ketone drinks, but the metabolic effects of exogenous ketones are relatively unknown. Here, healthy human volunteers took part in three randomized metabolic studies of drinks containing a ketone ester (KE); (R)-3-hydroxybutyl (R)-3-hydroxybutyrate, or ketone salts (KS); sodium plus potassium βHB.Methods and Results: In the first study, 15 participants consumed KE or KS drinks that delivered ~12 or ~24 g of βHB. Both drinks elevated blood D-βHB concentrations (D-βHB Cmax: KE 2.8 mM, KS 1.0 mM, P < 0.001), which returned to baseline within 3–4 h. KS drinks were found to contain 50% of the L-βHB isoform, which remained elevated in blood for over 8 h, but was not detectable after 24 h. Urinary excretion of both D-βHB and L-βHB was <1.5% of the total βHB ingested and was in proportion to the blood AUC. D-βHB, but not L-βHB, was slowly converted to breath acetone. The KE drink decreased blood pH by 0.10 and the KS drink increased urinary pH from 5.7 to 8.5. In the second study, the effect of a meal before a KE drink on blood D-βHB concentrations was determined in 16 participants. Food lowered blood D-βHB Cmax by 33% (Fed 2.2 mM, Fasted 3.3 mM, P < 0.001), but did not alter acetoacetate or breath acetone concentrations. All ketone drinks lowered blood glucose, free fatty acid and triglyceride concentrations, and had similar effects on blood electrolytes, which remained normal. In the final study, participants were given KE over 9 h as three drinks (n = 12) or a continuous nasogastric infusion (n = 4) to maintain blood D-βHB concentrations greater than 1 mM. Both drinks and infusions gave identical D-βHB AUC of 1.3–1.4 moles.min.Conclusion: We conclude that exogenous ketone drinks are a practical, efficacious way to achieve ketosis.
Core fucosylation of the TCR is required for T-cell signaling and production of inflammatory cytokines and induction of colitis in mice. Levels of TCR core fucosylation are increased on T cells from intestinal tissues of patients with IBD; this process might be blocked as a therapeutic strategy.
We consider a confined space molecular communication system, where molecules or information carrying particles are used to transfer information on a microfluidic chip. Considering that information-carrying particles can follow two main propagation schemes: passive transport, and active transport, it is not clear which achieves a better information transmission rate. Motivated by this problem, we compare and analyze both propagation schemes by deriving a set of analytical and mathematical tools to measure the achievable information rates of the on-chip molecular communication systems employing passive to active transport. We also use this toolbox to optimize design parameters such as the shape of the transmission area, to increase the information rate. Furthermore, the effect of separation distance between the transmitter and the receiver on information rate is examined under both propagation schemes, and a guidepost to design an optimal molecular communication setup and protocol is presented.
We aimed to create autonomous on-chip systems that perform targeted translocations of nano- or microscale particles in parallel using machinery that mimics biological systems. By exploiting biomolecular-motor-based motility and DNA hybridization, we demonstrate that single-stranded DNA-labeled microtubules gliding on kinesin-coated surfaces acted as cargo translocators and that single-stranded DNA-labeled cargoes were loaded/unloaded onto/from gliding microtubules at micropatterned loading/unloading sites specified by DNA base sequences. Our results will help to create autonomous molecular sorters and sensors.
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