Mechanisms conferring robustness against regulatory variants have been controversial. Previous studies suggested widespread buffering of RNA misexpression on protein levels during translation. We do not find evidence that translational buffering is common. Instead, we find extensive buffering at the level of RNA expression, exerted through negative feedback regulation acting in trans, which reduces the effect of regulatory variants on gene expression. Our approach is based on a novel experimental design in which allelic differential expression in a yeast hybrid strain is compared to allelic differential expression in a pool of its spores. Allelic differential expression in the hybrid is due to cis-regulatory differences only. Instead, in the pool of spores allelic differential expression is not only due to cis-regulatory differences but also due to local trans effects that include negative feedback. We found that buffering through such local trans regulation is widespread, typically compensating for about 15% of cis-regulatory effects on individual genes. Negative feedback is stronger not only for essential genes, indicating its functional relevance, but also for genes with low to middle levels of expression, for which tight regulation matters most. We suggest that negative feedback is one mechanism of Waddington's canalization, facilitating the accumulation of genetic variants that might give selective advantage in different environments.

Hot tubs are a potential source of cutaneous infections with the gram-negative rod Pseudomonas aeruginosa. The most common clinical manifestation of these infections is "hot tub- or jacuzzi-folliculitis" with pustules mainly on the trunk and lymphadenopathy. In children and adolescents, the clinical picture may differ, with a predominance of tender reddish nodules on the palms or soles named "hot hand/hot foot syndrome". In general, the first-line antibiotic in an infection with pseudomonas aeruginosa is ciprofloxacin but it is not recommended in children and adolescents.

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