The Saccharomyces cerevisiae Sln1 protein is a 'twocomponent' regulator involved in osmotolerance. Twocomponent regulators are a family of signal-transduction molecules with histidine kinase activity common in prokaryotes and recently identified in eukaryotes. Phosphorylation of Sln1p inhibits the HOG1 MAP kinase osmosensing pathway via a phosphorelay mechanism including Ypd1p and the response regulator, Ssk1p. SLN1 also activates an MCM1-dependent reporter gene, P-lacZ, but this function is independent of Ssk1p. We present genetic and biochemical evidence that Skn7p is the response regulator for this alternative Sln1p signaling pathway. Thus, the yeast Sln1 phosphorelay is actually more complex than appreciated previously; the Sln1 kinase and Ypd1 phosphorelay intermediate regulate the activity of two distinct response regulators, Ssk1p and Skn7p. The established role of Skn7p in oxidative stress is independent of the conserved receiver domain aspartate, D427. In contrast, we show that Sln1p activation of Skn7p requires phosphorylation of D427. The expression of TRX2, previously shown to exhibit Skn7p-dependent oxidative-stress activation, is also regulated by the SLN1 phosphorelay functions of Skn7p. The identification of genes responsive to both classes of Skn7p function suggests a central role for Skn7p and the SLN1-SKN7 pathway in integrating and coordinating cellular response to various types of environmental stress.

Purpose To determine whether children with specific language impairment (SLI) show deficits in lexical–semantic organization and, if so, whether these deficits are commensurate with their delay in vocabulary size and whether the deficits affect all children with SLI. Method Fourteen children with SLI, 14 age matches (AM), and 14 expressive vocabulary matches (VM) generated 3 associations to each of 48 words. Associations were coded as semantic (e.g., dog–pet), clang (e.g., cow–how), or erroneous (e.g., spoon–Disney). Results Relative to the AM children, children with SLI produced fewer semantic responses, more clangs, and more errors. Relative to the VM children, fewer semantic responses and more errors in the children with SLI were found in by-item analyses. Across elicitation trials, semantic responses decreased in the AM and VM children but remained stable in the SLI children. Examination of individual performance in the SLI group revealed that poor semantic performance was associated with a deficit in expressive vocabulary and a gap between receptive and expressive vocabularies. Conclusions Significant variability in lexical–semantic organization skills exists among children with SLI. Deficits in lexical–semantic organization were demonstrated by a subgroup of children with SLI who likely had concomitant word-finding difficulties.

Results support previous studies in finding parallel development in bilinguals' 1st- and 2nd-language lexical-semantic skills and provide preliminary evidence that bilingualism may enhance paradigmatic organization of the semantic lexicon.

A promising approach for treating Duchenne muscular dystrophy (DMD) is by autologous cell transplantation of myogenic stem cells transduced with a therapeutic expression cassette. Development of this method has been hampered by a low frequency of cellular engraftment, the difficulty of tracing transplanted cells, the rapid loss of autologous cells carrying marker genes that are unable to halt muscle necrosis and the difficulty of stable transfer of a large dystrophin gene into myogenic stem cells. We engineered a 5.7 kb miniDys-GFP fusion gene by replacing the dystrophin C-terminal domain (DeltaCT) with an eGFP coding sequence and removing much of the dystrophin central rod domain (DeltaH2-R19). In a transgenic mdx(4Cv) mouse expressing the miniDys-GFP fusion protein under the control of a skeletal muscle-specific promoter, the green fusion protein localized on the sarcolemma, where it assembled the dystrophin-glycoprotein complex and completely prevented the development of dystrophy in transgenic mdx(4Cv) muscles. When myogenic and other stem cells from these mice were transplanted into mdx(4Cv) recipients, donor cells can be readily identified in skeletal muscle by direct green fluorescence or by using antibodies against GFP or dystrophin. In mdx(4Cv) mice reconstituted with bone marrow cells from the transgenic mice, we monitored engraftment in various muscle groups and found the number of miniDys-GFP(+) fibers increased with time. We suggest that these transgenic mdx(4Cv) mice are highly useful for developing autologous cell therapies for DMD.