Reward and punishment learning in daily life:A replication study

Day-to-day experiences are accompanied by feelings of Positive Affect (PA) and Negative Affect (NA). Implicitly, without conscious processing, individuals learn about the reward and punishment value of each context and activity. These associative learning processes, in turn, affect the probability that individuals will re-engage in such activities or seek out that context. So far, implicit learning processes are almost exclusively investigated in controlled laboratory settings and not in daily life. Here we aimed to replicate the first study that investigated implicit learning processes in real life, by means of the Experience Sampling Method (ESM). That is, using an experience-sampling study with 90 time points (three measurements over 30 days), we prospectively measured time spent in social company and amount of physical activity as well as PA and NA in the daily lives of 18-24-year-old young adults (n = 69 with anhedonia, n = 69 without anhedonia). Multilevel analyses showed a punishment learning effect with regard to time spent in company of friends, but not a reward learning effect. Neither reward nor punishment learning effects were found with regard to physical activity. Our study shows promising results for future research on implicit learning processes in daily life, with the proviso of careful consideration of the timescale used. Shortterm retrospective ESM design with beeps approximately six hours apart may suffer from mismatch noise that hampers accurate detection of associative learning effects over time

Elucidation of the RamA Regulon in Klebsiella pneumoniae Reveals a Role in LPS Regulation

Klebsiella pneumoniae is a significant human pathogen, in part due to high rates of multidrug resistance. RamA is an intrinsic regulator in K. pneumoniae established to be important for the bacterial response to antimicrobial challenge; however, little is known about its possible wider regulatory role in this organism during infection. In this work, we demonstrate that RamA is a global transcriptional regulator that significantly perturbs the transcriptional landscape of K. pneumoniae, resulting in altered microbe-drug or microbe-host response. This is largely due to the direct regulation of 68 genes associated with a myriad of cellular functions. Importantly, RamA directly binds and activates the lpxC, lpxL-2 and lpxO genes associated with lipid A biosynthesis, thus resulting in modifications within the lipid A moiety of the lipopolysaccharide. RamA-mediated alterations decrease susceptibility to colistin E, polymyxin B and human cationic antimicrobial peptide LL-37. Increased RamA levels reduce K. pneumoniae adhesion and uptake into macrophages, which is supported by in vivo infection studies, that demonstrate increased systemic dissemination of ramA overexpressing K. pneumoniae. These data establish that RamA-mediated regulation directly perturbs microbial surface properties, including lipid A biosynthesis, which facilitate evasion from the innate host response. This highlights RamA as a global regulator that confers pathoadaptive phenotypes with implications for our understanding of the pathogenesis of Enterobacter, Salmonella and Citrobacter spp. that express orthologous RamA proteins