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Abstract BackgroundPerfluoroalkyl substances (PFAS) are persistent environmental contaminants previously used for industrial purposes as a non‐stick coating and flame retardant. The stability of these molecules prevents their breakdown, which results in ground water contamination across the globe. Perfluoroalkyl substances molecules are known to bioaccumulate in various organisms. However, the health consequences remain unclear due to the large number of molecules in the PFAS family and different effects on various tissues. Here, we use the frogXenopus laevisto investigate the developmental consequences of exposure to the PFAS molecule perfluoro‐octanoic sulfonate (PFOS). ResultsWe find that exposure to high levels of PFOS results in significant axial shortening of developing tadpoles. Further, we find that PFOS exposure results in a dose‐dependent formation of a cellular mass in the dorsal fin. Unexpectedly, we found that these developmental phenotypes are exacerbated upon co‐exposure with commonly used antibiotics. Specifically, PFOS and gentamicin co‐treatment results in increased apoptosis, loss of cellular integrity, and increased overall lethality. ConclusionsOur results suggest a mechanism whereby gentamicin reaches levels that are toxic to mitochondria only in the presence of PFOS. These findings add to our understanding of PFOS exposure to vertebrate development and present an added concern with potential interactions with antibiotics. 

Plasticity in multicellular organisms involves signaling pathways converting contexts—either natural environmental challenges or laboratory perturbations—into context-specific changes in gene expression. Congruently, the interactions between the signaling molecules and transcription factors (TF) regulating these responses are also context specific. However, when a target gene responds across contexts, the upstream TF identified in one context is often inferred to regulate it across contexts. Reconciling these stable TF–target gene pair inferences with the context-specific nature of homeostatic responses is therefore needed. The induction of the Caenorhabditis elegans genes lipl-3 and lipl-4 is observed in many genetic contexts and is essential to survival during fasting. We find DAF-16/FOXO mediating lipl-4 induction in all contexts tested; hence, lipl-4 regulation seems context independent and compatible with across-context inferences. In contrast, DAF-16–mediated regulation of lipl-3 is context specific. DAF-16 reduces the induction of lipl-3 during fasting, yet it promotes it during oxidative stress. Through discrete dynamic modeling and genetic epistasis, we define that DAF-16 represses HLH-30/TFEB—the main TF activating lipl-3 during fasting. Contrastingly, DAF-16 activates the stress-responsive TF HSF-1 during oxidative stress, which promotes C. elegans survival through induction of lipl-3 . Furthermore, the TF MXL-3 contributes to the dominance of HSF-1 at the expense of HLH-30 during oxidative stress but not during fasting. This study shows how context-specific diverting of functional interactions within a molecular network allows cells to specifically respond to a large number of contexts with a limited number of molecular players, a mode of transcriptional regulation we name “contextualized transcription.” 

Abstract Measuring rates of valley head migration and determining the timing of canyon‐opening are insightful for the evolution of planetary surfaces. Spatial gradients of in situ‐produced cosmogenic nuclide concentrations along horizontal transects provide a framework for assessing the migration of valley networks and similar topographic features. We developed a new derivation for valley head retreat rates from the concentrations of in situ‐produced cosmogenic radionuclides in valley walls. The retreat rate is inversely proportional to the magnitude of the spatial concentration gradient and proportional to local nuclide production rates. By solving for a spatial gradient in concentration along a valley parallel transect, we created an expression for the explicit determination of valley head retreat, which we refer to herein as unzipping. We applied this expression to a seepage‐derived drainage network developing along the Apalachicola River, Florida, USA. Sample concentrations along a valley margin transect varied systematically from 2.9 × 10⁵to 3.5 × 10⁵atoms/g resulting in a gradient of 160 atoms/g/m, and from this value a valley head retreat rate of 0.025 m/y was found. The discrepancy between overall network age and current rates of valley head migration suggests intermittent network growth which is consistent with glacial‐interglacial precipitation variations during the Pleistocene. This method can be applied to a wide range of Earth‐surface environments. For the¹⁰Be system, this method should be sensitive to unzipping rates bounded between 10⁻⁶and 10⁰ m/y.