Uterine estrogen receptor in vivo: phosphorylation of nuclear specific forms on serine residues.

We have characterized further the heterogeneous nuclear-specific doublet forms of the mouse uterine estrogen receptor (ER). Estrogen treatment produced the multiple nuclear ER forms of 65 and 66.5 kDa, which were isolated and analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Soluble ER preparations exhibited only a single 65-kDa form. Isolation of the individual nuclear ER forms and reanalysis demonstrated that formation of the multiple bands was not due to artifacts of nuclear sample preparation or the presence of contaminating proteins. Analysis of individual uterine cell types (epithelial and stromal/myometrium) indicated that both ER forms were present in both cell fractions. Fractionation of nuclear components with low salt showed that both ER forms were found in the salt-resistant fraction. Extraction of nuclei with high salt (0.6 M KCl) solubilized both ER forms. Phosphorylation was studied as a protein modification to account for the multiple forms. Incorporation of 32P into uterine protein both in vivo and in intact tissue incubation indicated 32P labeling of uterine nuclear ER after hormone treatment. Both nuclear ER forms are labeled, although the 66.5-kDa form appears to be more heavily labeled. Phosphoamino acid analysis of the immunopurified 32P-labeled ER from intact uterine tissue indicated phosphoserine as the only phospholabeled residue. These data suggest that phosphorylation is associated with the physiological functioning of the ER in response to hormone and produces the heterogeneous ER forms in the nucleus.

Effectiveness of special education: is placement the critical factor?

Research indicates that various program models, implemented both in special education and general education, can have moderately positive academic and social impacts for students with disabilities. However, no intervention has been designed that eliminates the impact of having a disability. With few exceptions, students with disabilities have not achieved commensurately with their nondisabled peers; even students with learning disabilities as a group have not been able to achieve at the level of low-achieving nondisabled students. In general, the most effective interventions for students with disabilities, whether in special education or general education settings, have employed intensive and reasonably individualized instruction, combined with careful, frequent monitoring of student progress. There is no compelling evidence that placement rather than instruction is the critical factor in student academic or social success. Further, studies have indicated that typical practice in general education is substantially different from practice in the model programs that showed greatest success for students with disabilities. The interventions that were effective in improving academic outcomes for students with disabilities required a considerable investment of resources, including time and effort, as well as extensive support for teachers. The research does not support full-time inclusion for all students with disabilities. On the contrary, it appears that there is a clear need for special education. At the same time, given adequate resources, schools should be able to assist more students to be more successful in general education settings.