Two adaptation mechanisms regulate cellular migration in Dictyostelium discoideum

Dictyostelium discoideum is a simple model widely used to study many cellular functions, including differentiation, gene regulation, cellular trafficking and directional migration. Adaptation mechanisms are essential in the regulation of these cellular processes. The misregulation of adaptation components often results in persistent activation of signaling pathways and aberrant cellular responses. Studying adaptation mechanisms regulating cellular migration will be crucial in the treatment of many pathological conditions in which motility plays a central role, such as tumor metastasis and acute inflammation. I will describe two adaptation mechanisms regulating directional migration in Dictyostelium cells. The Extracellular signal Regulated Kinase 2 (ERK2) plays an essential role in Dictyostelium cellular migration. ERK2 stimulates intracellular cAMP accumulation in chemotaxing cells. Aberrant ERK2 regulation results in aberrant cAMP levels and defective directional migration. The MAP Phosphatase with Leucine-rich repeats (MPL1) is crucial for ERK2 adaptation. Cells lacking, MPL1 (mpl1- cells) displayed higher pre-stimulus and persistent post-stimulus ERK2 phosphorylation, defective cAMP production and reduced cellular migration. Reintroduction of a full length Mpl1 into mpl1- cells restored aggregation, ERK2 regulation, random and directional motility, and cAMP production similar to wild type cells (Wt). These results suggest Mpl1 is essential for proper regulation of ERK2 phosphorylation and optimal motility in Dictyostelium cells. Cellular polarization in Dictyostelium cells in part is regulated by the activation of the AGC-related kinase Protein Kinase Related B1 (PKBR1). The PP2A regulatory subunit, B56, and the Glycogen Synthase Kinase 3 (GSK3) are necessary for PKBR1 adaptation in Dictyostelium cells. Cells lacking B56, psrA-cells, exhibited high basal and post-stimulus persistent phosphorylation of PKBR1, increased phosphorylation of PKBR1 substrates, and aberrant motility. PKBR1 adaptation is also regulated by the GSK3. When the levels of active GSK3 are reduced in Wt and psrA- cells, high basal levels of phosphorylated PKBR1 were observed, in a Ras dependent, but B56 independent mechanism. Altogether, PKBR1 adaptation is regulated by at least two independent mechanisms: one by GSK3 and another by PP2A/B56.

Two Adaptation Mechanisms Regulate Cellular Migration in Dictyostelium discouideum

Dictyostelium discoideum is a simple model widely used to study many cellular functions, including differentiation, gene regulation, cellular trafficking and directional migration. Adaptation mechanisms are essential in the regulation of these cellular processes. The misregulation of adaptation components often results in persistent activation of signaling pathways and aberrant cellular responses. Studying adaptation mechanisms regulating cellular migration will be crucial in the treatment of many pathological conditions in which motility plays a central role, such as tumor metastasis and acute inflammation. I will describe two adaptation mechanisms regulating directional migration in Dictyostelium cells. The Extracellular signal Regulated Kinase 2 (ERK2) plays an essential role in Dictyostelium cellular migration. ERK2 stimulates intracellular cAMP accumulation in chemotaxing cells. Aberrant ERK2 regulation results in aberrant cAMP levels and defective directional migration. The MAP Phosphatase with Leucine-rich repeats (MPL1) is crucial for ERK2 adaptation. Cells lacking, MPL1 (mpl1- cells) displayed higher pre-stimulus and persistent post-stimulus ERK2 phosphorylation, defective cAMP production and reduced cellular migration. Reintroduction of a full length Mpl1 into mpl1- cells restored aggregation, ERK2 regulation, random and directional motility, and cAMP production similar to wild type cells (Wt). These results suggest Mpl1 is essential for proper regulation of ERK2 phosphorylation and optimal motility in Dictyostelium cells. Cellular polarization in Dictyostelium cells in part is regulated by the activation of the AGC-related kinase Protein Kinase Related B1 (PKBR1). The PP2A regulatory subunit, B56, and the Glycogen Synthase Kinase 3 (GSK3) are necessary for PKBR1 adaptation in Dictyostelium cells. Cells lacking B56, psrA-cells, exhibited high basal and post-stimulus persistent phosphorylation of PKBR1, increased phosphorylation of PKBR1 substrates, and aberrant motility. PKBR1 adaptation is also regulated by the GSK3. When the levels of active GSK3 are reduced in Wt and psrA- cells, high basal levels of phosphorylated PKBR1 were observed, in a Ras dependent, but B56 independent mechanism. Altogether, PKBR1 adaptation is regulated by at least two independent mechanisms: one by GSK3 and another by PP2A/B56.

The effects of self-monitoring on homework completion and accuracy rates of students with disabilities in an inclusive general education classroom

This study investigated the effects of self-monitoring on the homework completion and accuracy rates of four, fourth-grade students with disabilities in an inclusive general education classroom. A multiple baseline across subjects design was utilized to examine four dependent variables: completion of spelling homework, accuracy of spelling homework, completion of math homework, accuracy of math homework. Data were collected and analyzed during baseline, three phases of intervention, and maintenance. ^ Throughout baseline and all phases, participants followed typical classroom procedures, brought their homework to school each day and gave it to the general education teacher. During Phase I of the intervention, participants self-monitored with a daily sheet at home and on the computer at school in the morning using KidTools (Fitzgerald & Koury, 2003); a student friendly, self-monitoring program. They also participated in brief daily conferences to review their self-monitoring sheets with the investigator, their special education teacher. Phase II followed the same steps except conferencing was reduced to two days a week, which were randomly selected by the researcher and Phase III conferencing was one random day a week. Maintenance data were taken over a two-to-three week period subsequent to the end of the intervention. ^ Results of this study demonstrated self-monitoring substantially improved spelling and math homework completion and accuracy rates of students with disabilities in an inclusive, general education classroom. On average, completion and accuracy rates were highest over baseline in Phase III. Self-monitoring led to higher percentages of completion and accuracy during each phase of the intervention compared to baseline, group percentages also rose slightly during maintenance. Therefore, results suggest self-monitoring leads to short-term maintenance in spelling and math homework completion and accuracy. ^ This study adds to the existing literature by investigating the effects of self-monitoring of homework for students with disabilities included in general education classrooms. Future research should consider selecting participants with other demographic characteristics, using peers for conferencing instead of the teacher, and the use of self-monitoring with other academic subjects (e.g., science, history). Additionally, future research could investigate the effects of each of the two self-monitoring components used alone, with or without the conferencing.^

Teacher perception of self -determination skills in the inclusive and special education classroom

It has been proposed that special education teachers, who promote self-determination and link it to educational standards, help students with a disability succeed in school. The current school reform movement has focused on accountability through mandates such as the No Child Left Behind Act, 2001, and has emphasized participation in the general curriculum through amendments to the Individuals with Disabilities Education Act (IDEA) of 1997 and 2004. This study informs educators if educational setting, students' type of disability, and subject area taught, influence teachers' opinions about the importance of teaching components leading to self-determination and self-management. ^ The research questions that drive this study are: (1) do secondary school teachers who instruct students with a disability think that self-determination components taught in the classroom will make an important difference in students' school and later postsecondary achievements? and (2) does the type of classroom setting, students' type of disability, or specific subject matter influence teachers' opinions regarding the importance of teaching components related to self-determination and self-management? The collection and interpretation of data were done using descriptive and quantitative methods employing a teacher survey. The survey was administered to secondary teachers who instruct students with disabilities. Data were analyzed using descriptive and inferential statistics. The sample consisted of 97 special education teachers currently teaching at the secondary level. ^ The results of the study indicated that teachers believe that self-determination is important for both school life and post school life. However teachers thought these skills to be more important for post school success. Teachers believe that self-determination is more important than self-management skills. Type of disability, educational environment, and subject area were not significant factors. ^

Alternative service organizations: Funding environment, strategies, and patterns of adaptation

This study explored the strategies that community-based, consumer-focused advocacy, alternative service organizations (ASOs), implemented to adapt to the changes in the nonprofit funding environment (Oliver & McShane, 1979; Perlmutter, 1988a, 1994). It is not clear as to the extent to which current funding trends have influenced ASOs as little empirical research has been conducted in this area (Magnus, 2001; Marquez, 2003; Powell, 1986). ^ This study used a qualitative research design to investigate strategies implemented by these organizations to adapt to changes such as decreasing government, foundation, and corporate funding and an increasing number of nonprofit organizations. More than 20 community informants helped to identify, locate, and provide information about ASOs. Semi-structured interviews were conducted with a sample of 30 ASO executive directors from diverse organizations in Miami-bade and Broward Counties, in South Florida. ^ Data analysis was facilitated by the use of ATLAS.ti, version 5, a qualitative data analysis computer software program designed for grounded theory research. This process generated five major themes: Funding Environment; Internal Structure; Strategies for Survival; Sustainability; and Committing to the Cause, Mission, and Vision. ^ The results indicate that ASOs are struggling to survive financially by cutting programs, decreasing staff, and limiting service to consumers. They are also exploring ways to develop fundraising strategies; for example, increasing the number of proposals written for grants, focusing on fund development, and establishing for-profit ventures. Even organizations that state that they are currently financially stable are concerned about their financial vulnerability. There is little flexibility or cushioning to adjust to "funding jolts." The fear of losing current funding levels and being placed in a tenuous financial situation is a constant concern for these ASOs. ^ Further data collected from the self-administered Funding Checklist and demographic forms were coded and analyzed using Statistical Package for the Social Sciences (SPSS). Descriptive information and frequencies generated findings regarding the revenue, staff compliment, use of volunteers and fundraising consultants, and fundraising practices. The study proposes a model of funding relationships and presents implications for social work practice, and policy, along with recommendations for future research. ^