Abnormal expression of REST/NRSF and Myc in neural stem/progenitor cells causes cerebellar tumors by blocking neuronal differentiation.

Medulloblastoma, one of the most malignant brain tumors in children, is thought to arise from undifferentiated neural stem/progenitor cells (NSCs) present in the external granule layer of the cerebellum. However, the mechanism of tumorigenesis remains unknown for the majority of medulloblastomas. In this study, we found that many human medulloblastomas express significantly elevated levels of both myc oncogenes, regulators of neural progenitor proliferation, and REST/NRSF, a transcriptional repressor of neuronal differentiation genes. Previous studies have shown that neither c-Myc nor REST/NRSF alone could cause tumor formation. To determine whether c-Myc and REST/NRSF act together to cause medulloblastomas, we used a previously established cell line derived from external granule layer stem cells transduced with activated c-myc (NSC-M). These immortalized NSCs were able to differentiate into neurons in vitro. In contrast, when the cells were engineered to express a doxycycline-regulated REST/NRSF transgene (NSC-M-R), they no longer underwent terminal neuronal differentiation in vitro. When injected into intracranial locations in mice, the NSC-M cells did not form tumors either in the cerebellum or in the cerebral cortex. In contrast, the NSC-M-R cells did produce tumors in the cerebellum, the site of human medulloblastoma formation, but not when injected into the cerebral cortex. Furthermore, the NSC-M-R tumors were blocked from terminal neuronal differentiation. In addition, countering REST/NRSF function blocked the tumorigenic potential of NSC-M-R cells. To our knowledge, this is the first study in which abnormal expression of a sequence-specific DNA-binding transcriptional repressor has been shown to contribute directly to brain tumor formation. Our findings indicate that abnormal expression of REST/NRSF and Myc in NSCs causes cerebellum-specific tumors by blocking neuronal differentiation and thus maintaining the "stemness" of these cells. Furthermore, these results suggest that such a mechanism plays a role in the formation of human medulloblastoma.

Strengthening Families: Parents' Voices on Discipline and Child Rearing

This qualitative study conducted semi-structured, multi-session focus groups and interviews with twenty-seven participants to explore in-depth, participant constructs of child discipline and punishment methods and reasons for the continuing support for corporal punishment of U.S. children. The research assumed that parents want to parent well and utilized the strengths perspective as the instrument to listen to participants' voices. Narratives revealed that participants were thoughtful about discipline and parenting strategies and viewed their parent role as a serious commitment. Non-violent discipline strategies, particularly communication, were often used. However, parents generally framed use of physical punishment as “when children need spanking” versus articulating the view that corporal punishment is a choice. Parents were unfamiliar with risks associated with physical punishment and only three parents, as a result of their foster parent training, had ever heard, “Do not spank.” Participants enumerated services and recommendations that would support and inform their own parenting, as well as, benefit children and the eighty percent of women and men in the United States who become mothers and fathers. Recommendations included: creation of a national campaign to build on parent strengths and the intentionality of effective parenting; child development education and increased public awareness of positive discipline methods; parenting supports, including respite and venues for dialogue and discourse about parenting. Recommendations are intended to inform child welfare practice and policy, particularly child abuse prevention. Creating, funding, and implementing a national campaign as described would challenge the dominant child welfare paradigm from one currently perceived as punitive and focused on parents' deficits to a strengths-based paradigm that provides supports and assistance to parents and children.

Safety of lntensive In-Home Family Workers

Violence against social workers and other helping professionals has increased. Within this context, intensive in-home family workers were asked about their safety in working with clients. If family workers stated that that they felt only somewhat safe or not safe at all, they were asked to explain where they are likely to feel unsafe. Findings include concerns about safety. The author suggests comprehensive educational curriculum be integrated in agency training for new hires and seasoned employees; also, training should be implemented to increase worker awareness of potentially violent situations and how to de-escalate and defuse potentially violent clients.

An assessment of self-concept and violence within a delinquent adolescent population

The purpose of this study was to provide further data on the relationship between self-concept and violence focusing on a delinquent adolescent population. Recent research has explored the relationship between self-concept and violence with most of the research being done with adult populations. Within the literature, there are two opposing views on the question of this relationship. The traditional view supports the idea that low self-esteem is a cause of violent behavior while the non-traditional view supports the idea that high self-esteem may be a contributor to violent behavior. ^ Using a sample of 200 delinquent adolescents 100 of whom had committed acts of violence and 100 who had not, a group comparison study was done which addressed the following questions, (1) within a delinquent population of violent and non-violent adolescents, is there a relationship between violence and self-concept? (2) what is that relationship; (3) using the Piers-Harris Children's Self-Concept Scale, can it be determined that attributes such as behavior, anxiety, popularity, happiness, and physical appearance as they relate to self-concept are more predictive than others in determining who within a delinquent population will commit acts of violence. For the purposes of this study, delinquent adolescents were those who had official records of misconduct with either the school or juvenile authorities. Adolescents classified as violent were those who had committed acts such as assault, use of a weapon, use of deadly force, and sexual assault while adolescents classified as non-violent had committed anti-social acts such as, truancy, talking back and rule breaking. ^ The study concluded that there is a relationship between adolescent violence and self-concept. However, there was insufficient statistical evidence that self-concept is a predictor of violence. ^

Parents' impressions of inappropriate television content for Hispanic preschool children

Rates of childhood obesity have increased three-fold in the last 20 years, and experts estimate that well over half of adolescents with a Body Mass Index at or above the 95th percentile become obese adults. These trends are even more pronounced in ethnic minority and lower income populations that are disproportionately impacted by obesity and its complications. It would be appropriate, then, to focus obesity interventions on Hispanic children. Television viewing, especially, has been shown to contribute to obesity by increasing caloric intake and decreasing physical activity. Parent involvement has proven to be a critical component in changing children’s health behaviors. In order to explore parents’ motivations for limiting their children’s television viewing, I qualitatively analyzed data from twenty-five interviews with Houston area Head Start parents. Using Grounded Theory, four main categories of concern emerged from the audio-recorded conversations: developmentally inappropriate content, the influence of television, poor health behaviors/outcomes, and general disapproval with television. Developmentally inappropriate content was the most frequently mentioned category with 119 mentions. This included violence, the most common sub-theme. In all, parents were more concerned with television content that produced proximate consequences such as modeling violent behavior or inappropriate language. Content that encouraged behaviors that led to obesity or other delayed consequences were of less concern to the parents. This suggests that future interventions aimed at encouraging Hispanic parents to reduce their children’s television viewing should draw motivation from parents’ concerns about developmentally inappropriate content, rather than focusing on deleterious health outcomes such as obesity. ^