The Minimal Autoinhibited Unit of the Guanine Nucleotide Exchange Factor Intersectin

Intersectin-1L is a member of the Dbl homology (DH) domain guanine nucleotide exchange factors (GEF) which control Rho-family GTPase signaling. Intersectin-1L is a GEF that is specific for Cdc42. It plays an important role in endocytosis, and is regulated by several partners including the actin regulator N-WASP. Intact intersectin-1L shows low Cdc42 exchange activity, although the isolated catalytic DH domain shows high activity. This finding suggests that the molecule is autoinhibited. To investigate the mechanism of autoinhibition we have constructed a series of domain deletions. We find that the five SH3 domains of intersectin are important for autoinhibition, with the fifth domain (SH3(E)) being sufficient for the bulk of the autoinhibitory effect. This SH3 domain appears to primarily interact with the DH domain. We have determined the crystal structure of the SH3(E)-DH domain construct, which shows a domain swapped arrangement in which the SH3 from one monomer interacts with the DH domain of the other monomer. Analytical ultracentrifugation and gel filtration, however, show that under biochemical concentrations, the construct is fully monomeric. Thus we propose that the actual autoinhibited structure contains the related intramolecular SH3(E)-DH interaction. We propose a model in which this intramolecular interaction may block or distort the GTPase binding region of the DH domain

RE-positioning English Learners in Teacher Development: A Language Ideologies Approach to Urban Education

As urban schools grow more and more linguistically diverse, there is an increasing need for teachers with expertise in teaching English Learners. Teachers are seeking education and development opportunities to continue to learn about how to address the needs of their students despite increasingly strict regulations on curricula and assessments. This study follows a group of teachers engaged in action research through a year-long professional development model. The teachers in this study work in a Midwestern Chinatown and grapple with issues of language, ethnicity, and other sociological factors they encounter in their classroom. Through a qualitative case study, this inquiry examined how students are positioned in a school in a Chinatown with a specific focus on how national and local features of “Chinatown” are implicated in the way teachers position students throughout an action research project. National and local features of “Chinatown” are emphasized to show how teachers, in a professional development program, learn to re-position the students. In this spirit and drawing on sociocultural models of professional development, positioning theory (van Langenhove & Harré, 1999), Cultural Historical Activity Theory (Engeström, 1999), and Language Ideologies in learning contexts (Razfar & Rumenapp, 2011), I looked specifically at how teachers reposition students into more equitable social and learning roles by engaging in action research. Findings include that there is a dominant ideological construct of “Chinatown” that is reimagined in the school and is implicated in social interaction within the school. As teachers engage in a collaborative research project, looking at students’ funds of knowledge and discourse, they reposition students socially and in the classroom context. Dominant, homogeneous constructs are complicated and challenged. Finally, I present a case study of one teacher to illustrate how she used action research as a form of on-going professional development for working with ELs. This study has implications for professional development and teacher education for teachers of ELs. Specifically, teachers can complicate dominant ideological constructs through visiting homes or doing a close analysis of the students’ cultural practices, thereby repositioning students. Additionally, teachers can reposition students in classrooms by studying the discourse and patterns of talk of classroom activities. Action research, as conceptualized in this study, can be a useful professional development tool. In the current study, this professional development model is seen as useful in the way teachers reposition their EL students

Talking about Language in Pre-school: The Use of Video-Stimulated Recall with Emergent Bilingual Children

After first discussing the ideologies (standard and monolingual) implicit in language education in the United States, we argue for a necessary ideological shift in the way multiple languages and other forms of semiotic communication are understood, used, and supported in preschool for emergent bilinguals. We present examples from a preschool study in Illinois where emergent bilingual children in two classrooms used video-stimulated accounts to make sense of their actions. Students used multiple semiotic resources – including English, Spanish, and embodiment – to collaborate with others and represent their ideas. Our findings include evidence of language awareness and awareness of audience in choosing the language of interaction. We argue that very often, preschool teachers are not taught to support or encourage students’ use of languages other than English, even in classrooms designated as bilingual. Implications are discussed for universal preschool with growing numbers of students with multilingual abilities

Thesaurus for energy and rural development

With the assistance of: Ann Jacobs, Richard Morse, Thammanun Pongsrikul, Jamuna Ramakrishna, Michael T. Santerre, Charles C. Schlegel, Kirk R. Smith. For more about the East-West Center, see http://www.eastwestcenter.org/Revised and expanded edition. Joint publication of the Energy for Rural Development (ERD) Program and the Pacific Island Energy Studies (PIES) Program at the East-West Center. East-West Resource Systems Institute. Energy Program - East-West Center. Pacific Islands Development Progra

Secondary radiation-induced bone tumours demonstrate a high degree of genomic instability predictive of a poor prognosis.

Secondary bone tumours arising in the field of a preceding radiotherapy are a serious late effect, in particular considering the increasing survival times in patients treated for paediatric malignancies. In general, therapy associated tumours are known to show a more aggressive behaviour and a limited response to chemotherapy compared with their primary counterparts. It is not clear however whether this less favourable outcome is caused by inherent genetic factors of the tumour cells or by a general systemic condition of the patient. To elucidate this we analysed a series of bone sarcomas with a history of prior irradiation for the presence of genomic alterations and compared them with the alterations identified earlier in primary osteosarcomas. We analysed seven radiation induced bone sarcomas for genome-wide losses of heterozygosity (LOH) using Affymetrix 10K2 high-density single nucleotide polymorphism (SNP) arrays. Additionally, copy number changes were analysed at two distinct loci on 10q that were recently found to be of major prognostic significance in primary osteosarcomas. All the investigated tumours showed a LOH at 10q21.1 with 86% of cases (6/7) revealing a total genome-wide LOH score above 2400 and more than 24% of the genome being affected. Our results indicate similar genetic alterations in radiation induced sarcomas of bone and primary osteosarcomas with a poor prognosis. We speculate that the high degree of genomic instability found in these tumours causes the poor prognosis irrespective of the initiating event