It's not just what we don't know: The mapping problem in the acquisition of negation.

How do learners learn what no and not mean when they are only presented with what is? Given its complexity, abstractness, and roles in logic, truth-functional negation might be a conceptual accomplishment. As a result, young children's gradual acquisition of negation words might be due to their undergoing a gradual conceptual change that is necessary to represent those words' logical meaning. However, it's also possible that linguistic expressions of negation take time to learn because of children's gradually increasing grasp of their language. To understand what no and not mean, children might first need to understand the rest of the sentences in which those words are used. We provide experimental evidence that conceptually equipped learners (adults) face the same acquisition challenges that children do when their access to linguistic information is restricted, which simulates how much language children understand at different points in acquisition. When watching a silenced video of naturalistic uses of negators by parents speaking to their children, adults could tell when the parent was prohibiting the child and struggled with inferring that negators were used to express logical negation. However, when provided with additional information about what else the parent said, guessing that the parent had expressed logical negation became easy for adults. Though our findings do not rule out that young learners also undergo conceptual change, they show that increasing understanding of language alone, with no accompanying conceptual change, can account for the gradual acquisition of negation words.

Dominant functional role of the novel phosphorylation site S811 in the human renal NaCl cotransporter.

The NaCl cotransporter (NCC) is essential for electrolyte homeostasis and control of blood pressure. The human SLC12A3 gene, which encodes NCC, gives rise to 3 isoforms, of which only the shortest isoform [NaCl cotransporter isoform 3 (NCC3)] has been studied extensively. All NCC isoforms share key phosphorylation sites at T55 and T60 that are essential mediators of NCC function. Recently, a novel phosphorylation site at S811 was identified in isoforms 1 and 2 [NaCl cotransporter splice variant (NCCSV)], which are only present in humans and higher primates. The aim of the current study, therefore, is to investigate the role of S811 phosphorylation in the regulation of NCC by a combination of biochemical and fluorescent microscopy analyses. We demonstrate that hypotonic low-chloride buffer increases S811 phosphorylation, whereas phosphorylation-deficient S811A mutant hinders phosphorylation at T55 and T60 in NCCSV and NCC3. NCCSV S811A impairs NCC3 activity in a dominant-negative fashion, although it does not affect plasma membrane abundance. This effect may be explained by the heterodimerization of NCCSV with NCC3. Taken together, our study highlights the dominant-negative effect of NCCSV on T55 and T60 phosphorylation and NCC activity. Here, we reveal a new function of NCCSV in humans that broadens the understanding on NCC regulation in blood pressure control.-Tutakhel, O. A. Z., Bianchi, F., Smits, D. A., Bindels, R. J. M., Hoenderop, J. G. J., van der Wijst, J. Dominant functional role of the novel phosphorylation site S811 in the human renal NaCl cotransporter.