Antibiotic resistance is a global problem that greatly impacts human health. How resistance persists, even in the absence of antibiotic treatment, is thus a public health problem of utmost importance. In this study, we explored the antibiotic treatment conditions under which cost-free resistance arises, using experimental evolution of the bacterium Pseudomonas aeruginosa and the quinolone antibiotic ciprofloxacin. We found that intermittent antibiotic treatment led to the evolution of cost-free resistance and demonstrate that compensatory evolution is the mechanism responsible for cost-free resistance. Our results suggest that discontinuous administration of antibiotic may be contributing to the high levels of antibiotic resistance currently found worldwide.

Phosphatidylethanolamine N‐methyltransferase (PEMT) is an important enzyme in hepatic phosphatidylcholine (PC) biosynthesis. Pemt−/− mice fed a high‐fat diet are protected from obesity and whole‐body insulin resistance. However, Pemt−/− mice develop severe nonalcoholic steatohepatitis (NASH). Because NASH is often associated with hepatic insulin resistance, we investigated whether the increased insulin sensitivity in Pemt−/− mice was restricted to nonhepatic tissues or whether the liver was also insulin sensitive. Strikingly, the livers of Pemt−/− mice compared with those of Pemt+/+ mice were not insulin resistant, despite elevated levels of hepatic triacylglycerols and diacylglycerols, as well as increased hepatic inflammation and fibrosis. Endogenous glucose production was lower in Pemt−/− mice under both basal and hyperinsulinemic conditions. Experiments in primary hepatocytes and hepatoma cells revealed improved insulin signaling in the absence of PEMT, which was not due to changes in diacylglycerols, ceramides, or gangliosides. On the other hand, the phospholipid composition in hepatocytes seems critically important for insulin signaling such that lowering the PC:phosphatidylethanolamine (PE) ratio improves insulin signaling. Thus, treatments to reduce the PC:PE ratio in liver may protect against the development of hepatic insulin resistance.—Van der Veen, J. N., Lingrell, S., McCloskey, N., LeBlond, N. D., Galleguillos, D., Zhao, Y. Y., Curtis, J. M., Sipione, S., Fullerton, M. D., Vance, D. E., Jacobs, R. L. A role for phosphatidylcholine and phosphatidylethanolamine in hepatic insulin signaling. FASEB J. 33, 5045–5057 (2019). http://www.fasebj.org

Speakers can correct their speech errors, but the mechanisms behind repairs are still unclear. Some findings, such as the speed of repairs and speakers' occasional unawareness of them, point to an automatic repair process. This paper reports a finding that challenges a purely automatic repair process. Specifically, we show that as error rate increases, so does the proportion of repairs. Twenty highlyproficient English-Spanish bilinguals described dynamic visual events in real time (e.g., "The blue bottle disappears behind the brown curtain") in English and Spanish blocks. Both error rates and proportion of corrected errors were higher on (a) noun phrase (NP)2 vs. NP1, and (b) word1 (adjective in English and noun in Spanish) vs. word2 within the NP. These results show a consistent relationship between error and repair probabilities, disentangled from position, compatible with a model in which greater control is recruited in error-prone situations to enhance the effectiveness of repair.

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