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Supplemental Figures S1-S3. c-Src/STAT3 crosstalk of Met-1 cells (S1); c-Src/STAT3 crosstalk of HCC1954 cells (S2); MEDICA amplifies radiation-suppressed clonogenity of HCC1954 cells (S3).

Supplemental Figure Legends. Legends for Supplemental Figures S1-S3.

Background ErbB2 breast cancer still remains an unmet need due to primary and/or acquired resistance to current treatment strategies. MEDICA compounds consist of synthetic long-chain α,ω-dicarboxylic acids previously reported to suppress breast cancer in PyMT transgenic mice. Methods MEDICA efficacy and mode of action in the ErbB2 context was studied in ErbB2 transgenic mice and human breast cancer cells. Results MEDICA treatment is shown here to suppress ErbB2 breast tumors and lung metastasis in ErbB2/neu MMTV transgenic mice, to suppress ErbB2/neu xenografts in nod/scid mice, and to suppress survival of AU565 and BT474 human ErbB2 breast cancer cells. Suppression of ErbB2 breast tumors by MEDICA is due to lipid raft disruption with loss of ErbB family members, including EGFR, ErbB2, and ErbB3. In addition, MEDICA inhibits mTORC1 activity, independently of abrogating the ErbB receptors and their signaling cascades. The double hit of MEDICA in abrogating ErbB and mTORC1 is partly accounted for by targeting mitochondria complex I. Conclusions Mitochondrial targeting by MEDICA suppresses ErbB2 breast tumors and metastasis due to lipid raft disruption and inhibition of mTORC1 activity. Inhibition of mTORC1 activity by MEDICA avoids the resistance acquired by canonical mTORC1 inhibitors like rapalogs or mTOR kinase inhibitors.

During the last decade we conducted a set of studies following our methodology developed for the analysis of drawings to assess identity. We gathered interviews and asked for Identity Drawing Maps IDM from 184 students aged 20-30 years. This study is based on qualitative analysis of eight IDMs representing the main groups in the Israeli society: Arabs; Christian, Muslim, Druze and Jews (2 maps for each group). We aim to examine the way in which students from different background use hyphenated identities and express messages of peace and co-existence. The findings give some hope that despite the ongoing conflict, Students from different cultural, national and religious backgrounds wish to live in pluralistic society that respects all the members and encourages values of equality, partnership and co-existence.

B-Raf(V600E) activates MEK/MAPK signalling and acts as oncogenic driver of a variety of cancers, including melanoma, colorectal and papillary thyroid carcinoma. Specific B-Raf(V600E) kinase inhibitors (e.g., Vemurafenib) prove initial efficacy in melanoma followed shortly by acquired resistance, while failing in most other B-Raf(V600E) cancers due to primary resistance. Resistance is due to acquired mutations in the Ras/Raf/MEK/MAPK pathway and/or other oncogenic drivers that bypass B-Raf(V600E). Surprisingly, hyper-activation of MAPK by inhibiting its protein phosphatase 2A by a synthetic long-chain fatty acid analogue (MEDICA), results in oncogene-induced growth arrest and apoptosis of B-Raf(V600E) cancer cells. Growth arrest is accompanied by MAPK-mediated serine/threonine phosphorylation and suppression of a variety of oncogenic drivers that resist treatment by B-Raf(V600E) kinase inhibitors, including ErbB members, c-Met, IGFR, IRS, STAT3 and Akt. The combined activities of mutated B-Raf and MEDICA are required for generating hyper-activated MAPK, growth arrest and apoptosis, implying strict specificity for mutated B-Raf cancer cells.

Obesity and type 2 diabetes (T2D) are associated with increased breast cancer incidence and mortality, whereas carbohydrate-restricted ketogenic diets ameliorate T2D and suppress breast cancer. These observations suggest an inherent efficacy of nonesterified long-chain fatty acids (LCFA) in suppressing T2D and breast tumorigenesis. In this study, we investigated novel antidiabetic MEDICA analogues consisting of methyl-substituted LCFA that are neither β-oxidized nor esterified to generate lipids, prompting interest in their potential efficacy as antitumor agents in the context of breast cancer. In the MMTV-PyMT oncomouse model of breast cancer, in which we confirmed that tumor growth could be suppressed by a carbohydrate-restricted ketogenic diet, MEDICA treatment suppressed tumor growth, and lung metastasis, promoting a differentiated phenotype while suppressing mesenchymal markers. In human breast cancer cells, MEDICA treatment attenuated signaling through the STAT3 and c-Src transduction pathways. Mechanistic investigations suggested that MEDICA suppressed c-Src–transforming activity by elevating reactive oxygen species production, resulting in c-Src oxidation and oligomerization. Our findings suggest that MEDICA analogues may offer therapeutic potential in breast cancer and overcome the poor compliance of patients to dietary carbohydrate restriction. Cancer Res; 74(23); 6991–7002. ©2014 AACR.

// Anna Algamas-Dimantov 1,* , Einav Yehuda-Shnaidman 1,* , Rachel Hertz 2 , Irena Peri 1 , Jacob Bar-Tana 2 and Betty Schwartz 1 1 Institute of Biochemistry, Food Science and Nutrition, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Israel 2 Department of Human Nutrition and Metabolism, Hebrew University Medical School, Jerusalem, Israel * These authors contributed equally to this work Correspondence: Betty Schwartz, email: // Keywords : Colorectal cancer, diabetes, obesity Received : July 29, 2014 Accepted : September 07, 2014 Published : September 08, 2014 Abstract The global obesity / diabetes epidemic has resulted in robust increase in the incidence of colorectal cancer (CRC). Epidemiological, animal and human studies have indicated efficacy of (n-3) PUFA in chemoprevention of sporadic and genetic-driven CRC. However, diabetes-promoted CRC presents a treatment challenge that surpasses that of sporadic CRC. This report analyzes the efficacy of (n-3) PUFA generated by the fat-1 transgene that encodes an (n-6) to (n-3) PUFA desaturase, and of synthetic (n-3) PUFA mimetic (MEDICA analog), to suppress CRC development in carcinogen-induced diabetes-promoted animal model. Carcinogen-induced CRC is shown here to be promoted by the diabetes context, in terms of increased aberrant crypt foci (ACF) load, cell proliferation and epithelial dedifferentiation, being accompanied by increase in the expression of HNF4α, β-catenin, and β-catenin-responsive genes. Incorporating the fat-1 transgene in the diabetes context, or oral MEDICA treatment, resulted in ameliorating the diabetic phenotype and in abrogating CRC, with decrease in ACF load, cell proliferation and the expression of HNF-4α, β-catenin, and β-catenin-responsive genes. The specificity of (n-3) PUFA in abrogating CRC development, as contrasted with enhancing CRC by (n-6) PUFA, was similarly verified in CRC cell lines. These findings may indicate prospective therapeutic potential of (n-3) PUFA or MEDICA in the management of CRC, in particular diabetes-promoted CRC.

High school science curricula of the 21st century have to include science-technology content and pedagogical content knowledge in a continuous interaction in order to be relevant to students’ needs. Learning units, including science, technology and related societal issues written on the Science, Technology and Society (STS), approach have to use teaching/learning strategies, and learning settings, such as cooperative learning in small groups, individual learning and computer episodes, so students will acquire science-technology literacy connected to societal issues. This approach may provide integration and participation in the advance society, so students will be able to look and find a job based on their learning. Dreyfus (1995) emphasized the importance of moral and ethics education. Science knowledge is not only for academic achievement and mastery of cognitive and meta-cognitive skills, but to educate students on the affective domain being active in the community life based on moral and ethical values, and positive attitudes toward societal issues, like social justice. Preservation of the environment and peace, as other values are addressed in the learning units presented.

The present research examined the effect of nature of orthography on the development of reading acquisition among children acquiring Arabic and Hebrew. Speed and accuracy measures were examined in reading texts in Arabic and in Hebrew. It was found that Arabic speakers showed an almost equal control in reading both languages. Furthermore, it was found that the speed of read- ing texts in Arabic among Arabic speakers was 3 times slower than reading Hebrew texts among Hebrew readers. These findings confirm that there is difficulty in identifying and decoding visual stimuli in Arabic. Furthermore, findings of the present research paper emphasizes that reading in Hebrew is faster and more precise than reading in Arabic, beyond mother tongue groups (Arab and Hebrew speakers). In addition, Hebrew readers showed a significant difference in reading in favor of reading in their mother tongue (both in accuracy and speed). In conclusion, findings of the present research suggest that there is an objective difficulty in acquiring reading of the Arabic language, and there is need for systematic intervention among those who face difficulties in the learning process.

In 2008, we conducted a large scale study following our methodology developed for the analysis of drawings to assess identity (Hertz-Lazarowitz, Farah, & Yosef-Meitav, 2012). We gathered interviews and asked for drawing Identity Drawing Map from 184 students aged from 20-30 years. The symbols in the drawings were grouped in 5 categories: religious, national, emotional, secular-cultural and nature and person figure symbols. The most frequent symbols were related to the nature and person figure category, and the least frequent were symbols from the secular-cultural category. The symbol categories with most indicative of identity conflicts were religious and national. The Arabs had more conflicted and complex IDM messages than Jews and the evaluation of their emotions were less positive and less optimistic than the Jews. The IDM methodology revealed the complex and multi-layered expression of identity construction. These findings can provide better understanding into the mechanism of identity construction in a society and the University context which has been conflict ridden for many decades.

Postnatal intestinal ontogenesis in an animal model of diabesity may recapitulate morphological and transduction features of diabesity-induced intestinal dysplasia and its amelioration by endogenous (n-3) polyunsaturated fatty acids (PUFA). Proliferation, differentiation, and transduction aspects of intestinal ontogenesis have been studied here in obese, insulin-resistant db/db mice, in fat-1 transgene coding for desaturation of (n-6) PUFA into (n-3) PUFA, in db/db crossed with fat-1 mice, and in control mice. Diabesity resulted in increased colonic proliferation and dedifferentiation of epithelial colonocytes and goblet cells, with increased colonic β-catenin and hepatocyte nuclear factor (HNF)-4α transcriptional activities accompanied by enrichment in HNF-4α–bound (n-6) PUFA. In contrast, in fat-1 mice, colonic proliferation was restrained, accompanied by differentiation of crypt stem cells into epithelial colonocytes and goblet cells and by decrease in colonic β-catenin and HNF-4α transcriptional activities, with concomitant enrichment in HNF-4α-bound (n-3) PUFA at the expense of (n-6) PUFA. Colonic proliferation and differentiation, the profile of β-catenin and HNF-4α-responsive genes, and the composition of HNF-4α-bound PUFA of db/db mice reverted to wild-type by introducing the fat-1 gene into the db/db context. Suppression of intestinal HNF-4α activity by (n-3) PUFA may ameliorate diabesity-induced intestinal ontogenesis and offer an effective preventive modality for colorectal cancer.

The theory of “Hyphenated identity” (HI) argues that people living in complex political-social contexts construct HIs with various sub-identities. The University of Haifa (UH) is a meeting space and experience for people of different nationalities and religious backgrounds. Thus they live “on the hyphen”, between identities found in contrast vs. harmony. This study was initiated and carried out as part of a Cooperative Participatory Action Research (CPAR). Nineteen graduate students, all teachers in a multicultural society ridden with conflicts, were interviewed about their life stories, their family background and the development of their identity as shaping their personal and professional lives. At the end of the interview, they were asked to draw an Identity Drawing Map (IDM) and add an explanatory text. Finding indicated that many women transferred their complex identity in order to create a balanced and a challenge in their life; they became leaders in their communities and empower other women to follow them toward self actualization. The study’s contribution is in broadening the understanding of concepts of HI development, by analyzing the similarities and differences within each ethnic/national group. Since identity development influences significantly people life, we can learn about these processes. Using the creative methods of drawing identity fabricated a deeper understanding and emotional presentation of the person.

This study examines attitudes towards bilingual Jewish–Arab education among Jewish and Arab adults in Israel. The sample consisted of 1014 respondents who participated in a national phone survey in late 2006. Results indicate that Arabs are significantly more supportive of bilingual education in Israel than Jews. Positive attitudes regarding the importance and the status of Arabic, integration between Jews and Arabs and civil society were all predictive of positive attitudes towards bilingual education among Arab participants. The same variables, along with lower religiosity, predicted attitudes towards bilingual education among Jewish participants. Attitudes towards integration were the strongest predictors of attitudes towards bilingual education in both groups. Implications and limitations, as well as possible avenues for future research, are discussed.

This paper describes a long‐term research seminar, developed in 2001 by Hertz‐Lazarowitz at the University of Haifa (UH). The goal of the seminar was to involve students in a meaningful, experiential and cooperative–interactive learning environment, based on topics relevant to their development as individuals coming from diverse collectives to the university campus, and to prepare them for life in an increasingly multicultural society. The seminar was based on the principles of the Participative Action Research and Group Investigation methods. The researchers aimed to create a model of learning, teaching, and action to bring awareness and enable change within the university’s community, so that it could become a place of justice, equality, and recognition of the many cultural groups on campus. Since 2001, the Cooperative Participatory Action Research (CPAR) seminar has been offered to students through UH’s Department of Education. This paper describes the theoretical framework and the stages and structure...

PurposeFundamentally, the success of schools depends on first‐rate school leadership, on leaders reinforcing the teachers' willingness to adhere to the school's vision, creating a sense of purpose, binding them together and encouraging them to engage in continuous learning. Leadership, vision and organizational learning are considered to be the key to school improvement. However, systematic empirical evidence of a direct relationship between leadership, vision and organizational learning is limited. The present study aims to explore the influence of principals' leadership style on school organizational learning, using school vision as a mediator.Design/methodology/approachThe data were collected from 1,474 teachers at 104 elementary schools in northern Israel, and aggregated to the school level.FindingsMediating regression analysis demonstrated that the school vision was a significant predictor of school organizational learning and functioned as a partial mediator only between principals' transformational leadership style and school organizational learning. Moreover, the principals' transformational leadership style predicted school organizational vision and school organizational learning processes. In other words, school vision, as shaped by the principal and the staff, is a powerful motivator of the process of organizational learning in school.Research implications/limitationsThe research results have implications for the guidance of leadership practice, training, appraisal and professional development.Originality/valueThe paper explores the centrality of school vision and its effects on the achievement of the school's aims by means of organizational learning processes.

This paper explores the role that entrepreneurial leadership vision plays in the entrepreneurial process of nonprofit and for-profit ventures. The results indicate significant differences in the meaning of vision articulated for each type of venture. Differences between ventures were also found with regard to the relationship that vision has with the ventures' strategies and performance. In the nonprofit organizations vision was associated with a wide-range strategy as well as the ventures' performance and growth. In addition, wide-range strategy partially mediated the relationship between the ventures' vision and its performance and growth. In business enterprises, vision directly predicted only a differentiation strategy, which also mediated the relationship between vision and the ventures' performance and growth. In contrast, a wide-range strategy in these organizations actually reduced growth. These findings contribute both to the literature on vision as well as to the literature on entrepreneurship.

Hepatocyte nuclear factor-4alpha (HNF-4alpha) serves as target for fatty acid nutrients and xenobiotic amphipathic carboxylates and may account for the differential effects of dietary fatty acids on colorectal cancer (CRC). The putative role played by HNF-4alpha in CRC has been verified here by evaluating the effect of HNF-4alpha antagonists and HNF-4alpha siRNA on CRC growth and proliferation in cultured CRC cells and xenotransplanted nude mice in vivo. HNF-4alpha ligand antagonists of the MEDICA series, namely, beta,beta'-tetramethylhexadecanedioic acid (M16betabeta) and gamma,gamma'-tetramethyloctadocanedioic acid (M18gammagamma) as well as HNF-4alpha siRNA are shown here to inhibit growth and proliferation of HT29 and Caco2 CRC cells, accompanied by increased subG1 cell population, downregulated PCNA, activation of caspase-3, upregulation of Bak and cytoplasmic cytochrome-c, and downregulation of Bcl-2 resulting in apoptotic death. Inhibition of CRC growth with concomitant apoptosis was further confirmed in nude mice xenotransplanted with HT29 CRC cells. CRC suppression by HNF-4alpha ligand antagonists and by HNF-4alpha siRNA was accounted for by suppression of HNF-4alpha transcription and protein expression. alpha,alpha'-tetrachlorotetradecanedioic acid (Cl-DICA), a MEDICA analogue that fails to suppress HNF-4alpha, was ineffective in suppressing growth of cultured or xenotransplanted HT29 CRC cells. Hence, increased transcriptional activity of HNF-4alpha converging onto genes coding for antiapoptotic oncogenes and cytokines may promote CRC development. Suppression of HNF-4alpha activity by natural or xenobiotic HNF-4alpha ligand antagonists or by HNF-4alpha siRNA may offer a treatment mode for CRC.

Under the Israeli language education policy, the mother tongue is learned first for several years, followed by a second language (English for Jews, Hebrew for Arabs) and then a third language (English for Arabs, Arabic/French for Jews). This type of limited bilingualism seems to suit the Israeli reality in the context of the Israeli–Arab conflict, the definition and perception of Israel as a Jewish–Zionist state and the complex Jewish–Arab relations within Israel. In 1997, the Hand in Hand Center for Jewish–Arab Education in Israel initiated a new model of Hebrew–Arabic bilingual education in Israel, assuming that direct contact between Arab and Jewish pupils would bring about far-reaching changes in the conflict-ridden Israeli society. Currently, three schools have adopted the new model. Several studies of the new model have provided rich information, mainly about educational, cultural and national issues. However, no systematic study has focused on the implementation of bilingual education in the school...

In this paper a conceptual model of instruction “the six mirrors of the classroom” used as a frame for teaching a learning topic, the microorganisms are depicted. The paper consists of four sections: (a) the six mirrors of the classroom model (SMC); (b) the SMC as implemented in the expository and cooperative modes of instruction in classrooms and results; (c) a “Journey of Inquiry into the Wonderful World of Microorganisms” (JIWWM), developed according to the Science–Technology–Environment–Peace–Society (STEPS) approach; and (d) teaching and learning the JIWWM, in ninth-grade classes, within the SMC model. The results show that science topic can be taught in the frame of the mirrors of the classroom. When the instructional goals of the teachers used the mirror “1, classroom organization” and mirror “6, pupils’ social behavior” and the third ring around the all six mirrors cooperative skills were practiced, academic outcomes were achieved, and attitudes toward environmental preservation and peace improved. The SMC model can serve as a valuable tool for teachers, since it can design their teaching and learning settings in a more controlled environment, in terms of objectives, teachers’ and students’ social behaviors, and academic outcomes.

A two-year (1998–2000) School–Family Partnership for Coexistence (SFPC) programme was implemented in Acre, a mixed Jewish-Arab city in Israel, to promote parents' role as facilitators of their children literacy development and to empower parents to advance coexistence and inter-group relations. The SFPC program was part of a five-year (1995–2000) holistic project, designed to bring about a systemic change in Acre. Two studies are presented. In the first (1999), 174 Arab parents and 111 Jewish parents of first-grade children responded to a 31 item Parents' Literacy Questionnaire (Horovitz & Hertz-Lazarowitz, 1998). In addition, interviews were conducted with mothers, teachers, and children. The questionnaire yielded seven factors related to home literacy and learning environment, and to School-Family Partnership. Findings indicated that Arab parents perceived themselves as more effective facilitators of literacy development of their children than Jewish parents. In the second study (2000), 120 Arab parents...

Sociocultural anthropology has long been concerned with the dynamics of change in so-called traditional societies. This article examines the gendered aspects of change within Israeli Arab society, analyzing the life stories of six women originally studied by Shapira (1999). The women came from traditional, male-dominant Muslim families living in villages or small cities in Israel as members of a national and political minority. They varied in age and socioeconomic and marital status, yet all were motivated to fulfill their educational and career aspirations. Negotiating cultural constraints, they assumed important leadership roles in their communities. We begin with a discussion of the segregated Arab educational system in Israel, highlighting historical and recent educational trends. We then discuss women's status in Arab society and Israel in particular, noting that teaching is a primary route for women's professional growth. Next we discuss life history in terms of a collective case study methodology and present the women's biographical profiles as related to educational-anthropological theories of change in traditional societies. We then examine women's higher education as a springboard for change through modeling and caring within the contexts of the family, school, and community. Finally, we propose thematic interpretations of the strategies the women used to advance themselves professionally and to promote changes within their society that will afford greater opportunities for women in positions of leadership.

Strategies are actions and behaviours used by the writer to solve problems in the writing process. These actions and behaviours reflect four clusters: meta-cognitive, cognitive, social, and affecti...

HNF-4α (hepatocyte nuclear factor-4α) is required for tissue-specific expression of many of the hepatic, pancreatic, enteric and renal traits. Heterozygous HNF-4α mutants are inflicted by MODY-1 (maturity onset diabetes of the young type-1). HNF-4α expression is reported here to be negatively autoregulated by HNF-4α1 and to be activated by dominant-negative HNF-4α1. Deletion and chromatin immunoprecipitation analysis indicated that negative autoregulation by HNF-4α1 was mediated by its association with the TATA-less HNF-4α core promoter enriched in Sp1, but lacking DR-1 response elements. Also, negative autoregulation by HNF-4α1 was independent of its transactivation function, being similarly exerted by transcriptional-defective MODY-1 missense mutants of HNF-4α1, or under conditions of suppressing or enhancing HNF-4α activity by small heterodimer partner or by inhibiting histone deacetylase respectively. Negative autoregulation by HNF-4α1 was abrogated by overexpressed Sp1. Transcriptional suppression by HNF-4α1 independently of its transactivation function may extend the scope of its transcriptional activity to interference with docking of the pre-transcriptional initiation complex to TATA-less promoters.

Microsomal triglyceride transfer protein (MTP) catalyzes the assembly of triglyceride (TG)-rich apolipoprotein B-containing liver (e.g., VLDL) and intestinal (e.g., chylomicron) lipoproteins. The human MTP gene promoter is reported here to associate in vivo with endogenous hepatocyte nuclear factor-4alpha (HNF-4alpha) and to be transactivated or transsuppressed by overexpressed or by dominant negative HNF-4alpha, respectively. Human MTP (hMTP) transactivation by HNF-4alpha is accounted for by the concerted activity of distal (-83/-70) and proximal (-50/-38) direct repeat 1 elements of the hMTP promoter that bind HNF-4alpha. Transactivation by HNF-4alpha is specifically antagonized by chicken ovalbumin upstream promoter. Transcriptional activation of hMTP by HNF-4alpha is mediated by HNF-4alpha domains engaged in ligand binding and ligand-driven transactivation and is further complemented by HNF-4alpha/HNF-1alpha synergism that involves the HNF-4alpha activation function 1 (AF-1) domain. hMTP transactivation by HNF-4alpha is specifically inhibited by beta,beta-tetramethyl-hexadecanedioic acid acting as an HNF-4alpha antagonist ligand. hMTP transactivation by HNF-4alpha may account for the activation or inhibition of MTP expression and the production of TG-rich lipoproteins by agonist (e.g., saturated fatty acids) or antagonist [e.g., (n-3) PUFA, hypolipidemic fibrates, or Methyl-substituted dicarboxylic acid (Medica) compounds] HNF-4alpha ligands.

Israeli Jewish and Arab experts within Israel have developed innovative intergroup relations programs, educational efforts designed to improve relations between Israeli Jews and Israeli Arabs. Social scientists, educators, and practitioners on both sides of the Arab-Jewish conflict have dedicated themselves to lessening the hostility between these two groups within Israel through coexistence educational training. This issue presents theory, methods, and data from these coexistence educational programs. The introductory article presents a brief history of this conflict; the groups' differing perceptions regarding the dispute; some information about the role of culture, socioeconomic status, and ethnicity in the discord; and some of the social psychological processes that perpetuate and recreate the hostilities. Last, it provides a brief preface of this issue's articles.

This article presents a five-year action-research project of systemic change toward coexistence in Acre, a mixed Arab-Jewish city in Israel. Educational activism was the basis for this project. Because education in Acre was closely interwoven with discriminative politics, this project used a citywide systemic approach consisting of three layers: (a) work in schools that used cooperative learning to increase achievement, (b) work with parents in school-family literacy partnerships, and (c) work with the city's educational and political leadership for citywide change. Data presented for each layer show the potential of this long-term holistic approach to bring coexistence to the community even though regional and political factors worked against community coexistence.

Research literature on writingstorybooks overlooks first graders. This ispuzzling as children enter first grade havingemergent literacy, in reading, writing, andstory composition. It may reflect the belief that at thisage children should learn to read and write(conventionally) as the curriculum demands,while elaborate writing is assumed be taughtand developed in higher grades. This study investigated story writing by Arab(N = 184) and Jewish (N = 321) first graders inIsrael. The children were presented with fourrelated pictures, asked to paste them in thesequence of their choice in a booklet, and thento write a narrative in their first language(Arabic or Hebrew). Writing the storybook wasperceived as a space for literacy development,and was tested in the contextof two instruction methods: Success For All(SFA) and whole-class Active Learning (AL). Theclasses were observed and teachers wereinterviewed on writing instruction.Nineteen categories of writing yieldedthree clusters–factors: book print awareness,writing conventions, and story quality. Thesethen served as measures for writing outcomes. Jewish and Arab children in SFA achieved higherscores than AL students; the Jews were higherthan the Arabs on most categories, but theestimate gain was highest for Arabs in SFA. The effect of SFA was highest for at-riskJewish students and lowest for at-risk Arabstudents. The results are discussed against thelinguistic and cultural background of the twogroups and in respect of their implications forwriting instruction in a bilingual context.

Similarities and differences in children’s interpersonal relationships were assessed through examination of the effects of culture and gender as reflected in the quality of children’s relationships in their social network at school. Two cultural contexts representing collectivistic and individualistic orientations were studied. Questionnaires were completed by 1449 fourth- and fifth-grade students (604 Arab and 845 Jewish students) regarding their best friend, their class peers, their homeroom teacher, and their class climate. As expected, findings demonstrated better quality of peer relationships among Arab students (from a relatively collectivistic culture) and among boys, whereas Jewish students (from a relatively individualistic culture) and girls showed better quality of best-friend relationships than their counterparts. The results also highlighted a similarity in children’s relationships for both cultures and both genders, reflected in the highest intimacy of best-friend relationships.

Although acyl-CoA-binding protein (ACBP) has been detected in the nucleus, the physiological significance of this observation is unknown. As shown herein for the first time, ACBP in the nucleus physically and functionally interacted with hepatocyte nuclear factor-4 alpha (HNF-4 alpha), a nuclear binding protein that regulates transcription of genes involved in both lipid and glucose metabolism. Five lines of evidence showed that ACBP bound HNF-4 alpha in vitro and in the nucleus of intact cells. (i) ACBP interaction with HNF-4 alpha elicited significant changes in secondary structure. (ii) ACBP and HNF-4 alpha were coimmunoprecipitated by antibodies to each protein. (iii) Double immunolabeling and laser scanning confocal microscopy (LSCM) of rat hepatoma cells and transfected COS-7 cells significantly colocalized ACBP and HNF-4 alpha within the nucleus and in the perinuclear region close to the nuclear membrane. (iv) LSCM fluorescence resonance energy transfer determined an intermolecular distance of 53 A between ACBP and HNF-4 alpha in rat hepatoma cell nuclei. (v) Immunogold electron microscopy detected ACBP within 43 A of HNF-4 alpha. These interactions were specific since ACBP did not interact with Sp1 or glucocorticoid receptor in these assays. The functional significance of ACBP interaction with HNF-4 alpha was evidenced by mammalian two-hybrid and transactivation assays. ACBP overexpression in COS-7 or rat hepatoma cells enhanced transactivation of an HNF-4 alpha-dependent luciferase reporter plasmid by 3.2- and 1.6-fold, respectively. In contrast, cotransfection with antisense ACBP expression vector inhibited transactivation. LSCM of the individual triple fluorescent-labeled (HNF-4 alpha, ACBP, and luciferase) rat hepatoma cells showed a high correlation (r2, 0.936) between the level of luciferase and the level of ACBP expression. In summary, ACBP physically interacted with HNF-4 alpha in vitro and in intact cells, although ACBP expression level directly correlated with HNF-4 alpha-mediated transactivation in individual cells.

Missense mutations of the ligand binding domain of hepatocyte nuclear factor (HNF)-4alpha result in maturity onset diabetes of the young (MODY)-1. We show here that MODY-1 as well as Gln-185 missense mutants of the ligand binding domain of HNF-4alpha fail to transactivate transcription of HNF-4alpha-responsive genes. Defective transactivation by these mutants is accounted for by their reduced binding affinities for fatty acyl agonist ligands of HNF-4alpha. These mutants may be rescued by exogenous fatty acid agonist ligands of HNF-4alpha, yielding transcriptional activities in the wild type range. The effect of added ligands is synergistic with that of transcriptional coactivators of HNF-4alpha. These findings may indicate the means for treating selected MODY-1 subjects with HNF-4alpha agonist nutrients and drugs.

Haifa University (HU) is the stage for a prolonged social drama between Arabs (20%) and Jews. 86 students (38 Arabs and 48 Jews) were interviewed on their experiences of injustice. Three major differences emerged. For the Arabs, 92% of injustice took place on campus compared to 40% for the Jews. Arabs attributed injustice to discrimination (60%), Jews to the actors' personal characteristics (58%); the Arabs transformed injustice events into a political struggle for national recognition, identity, and narratives. The analysis intimates that Arabs' “social being” is developing through the staging of negative expressive acts, namely, respect/contempt and power/weakness. Thus actors at HU can stage social processes, and change sites of surveillance and injustice into places of reconciliation and coexistence.

Writing has become central in today's schools as a measure for academic success. In this study 599 5th- and 6th-grade students, 210 Jews and 389 Arabs (310 boys and 289 girls), studied in three learning environments: cooperative learning (CL), computer-mediated communication (CMC), and the combination of CMC and CL. The students reported on their perception of and attitudes to writing. Their teachers evaluated their students as writers, and scored their portfolio writing outcomes. Measures included (1) students' perceptions of writing (SPWC), a 38-item self-report measure on writing apprehension, efficacy, self-regulation, and writing with computer derived from the study of writing; Alpha coefficient 0.90; (2) teachers' assessments of their students as writers (6 items);(3) portfolio evaluation. All students answered the SPWC twice in a pre-post test design in their first language (Arabic or Hebrew), and teachers gave their evaluation at the end of the year. Repeated measure of Manova was used for students' data and Anova for teachers' data. Findings using Multivariate repeated measures showed those students in CMC-CL scored higher on all measures. Teachers' evaluation was similar for CMC and the combined learning environment. Arab students were similar to Jewish students on some of the measures. Surprisingly, no differences were found for gender. The findings indicate that the power of peer interaction in cooperative learning with CMC was greater than each learning environment by itself. The quality implementation of these two (computer and peers) is the key element for students' writing development.

Hepatic nuclear factor-4alpha (HNF-4alpha) controls the expression of genes encoding proteins involved in lipid and carbohydrate metabolism. Fatty acyl-CoA thioesters have recently been proposed to be naturally occurring ligands of HNF-4alpha and to regulate its transcriptional activity as function of their chain length and degree of unsaturation (Hertz, R., Magenheim, J., Berman, I., and Bar-Tana, J. (1998) Nature 392, 512-516). However, the apparent low affinities (microm K(d) values) obtained with a radiolabeled fatty acyl-CoA ligand binding assay raised questions regarding the physiological significance of this finding. Furthermore, it is not known whether interaction with fatty acyl-CoA alters the structure of HNF-4alpha. These issues were examined using rat recombinant HNF-4alpha ligand-binding domain (HNF-4alphaLBD) in conjunction with photon counting fluorescence and circular dichroism. First, fluorescence resonance energy transfer between HNF-4alphaLBD tryptophan (Trp) and cis-parinaroyl-CoA yielded an intermolecular distance ofor=42 A, thus pointing to direct molecular interaction rather than nonspecific coaggregation. Second, quenching of HNF-4alphaLBD intrinsic Trp fluorescence by fatty acyl-CoAs (e.g. pamitoyl-, stearoyl-, linoleoyl-, and arachidonoyl-CoAs) yielded a single binding site with K(d) values of 1.6-4.0 nm. These affinities were 2-3 orders of magnitude higher than those previously derived by radiolabeled fatty acyl-CoA ligand binding assay. Third, binding of fatty acyl-CoAs was specific as the binding affinities of the respective free fatty acids or free CoA (K(d) values of 421-742 nm) were significantly lower. Fourth, circular dichroism demonstrated that the HNF-4alphaLBD secondary structure was significantly and differentially altered by fatty acyl-CoA binding. The opposite effects of saturated versus polyunsaturated fatty acyl-CoAs on HNF-4alpha LBD secondary structure correlated with their opposite regulatory effects on HNF-4alpha function. Fifth, the CoA thioesters of some hypolipidemic peroxisome proliferators bind with high affinity (K(d) values as low as 2.6 nm) to HNF-4alpha LBD, thus indicating that HNF-4alpha may serve as target for these drugs. In summary, these data demonstrate for the first time high affinity binding to HNF-4alpha of fatty and xenobiotic acyl-CoAs in the physiological range, resulting in significantly altered HNF-4alpha conformation.

The profile of liver acyl-CoAs induced by dietary fats of variable compositions or by xenobiotic hypolipidemic amphipathic carboxylates was evaluated in vivo using a novel electrospray ionization tandem mass spectrometry methodology of high resolution, sensitivity, and reliability. The composition of liver fatty acyl-CoAs was found to reflect the composition of dietary fat. Treatment with hypolipidemic carboxylates resulted in liver dominant abundance of their respective acyl-CoAs accompanied by an increase in liver fatty acyl-CoAs. Cellular effects exerted by dietary fatty acids and/or xenobiotic carboxylic drugs may be transduced in vivo by their respective acyl-CoAs.

Maturity onset diabetes of the young, subtype 1 (MODY1), is associated with defective glucose-dependent insulin secretion from pancreatic beta cells. MODY1 is caused by mutation in the transcription factor hepatocyte nuclear factor 4 alpha (HNF4 alpha). To understand better the MODY1 phenotype, we tested whether HNF4 alpha was able to modulate directly the insulin gene promoter. Transfection of cultured 293T cells with an HNF4 alpha expression vector led to 10-fold activation of a cotransfected reporter plasmid containing the rat insulin I gene promoter. Computer analysis revealed a potential HNF4 alpha-binding site between nucleotides -57 and -69 of the promoter; mutation of this sequence led to reduced ability of HNF4 alpha to activate the promoter. The ability of HNF4 alpha to bind this sequence was confirmed using gel shift analysis. In transfected INS-1 beta cells, mutation of either the HNF1 alpha site or the HNF4 alpha site in the insulin gene promoter led to 50-75% reduction in reporter gene activity; expression of dominant negative HNF4 alpha led to significant reduction in the activity of wild type and both mutated promoters. Thus, in addition to the previously described indirect action of HNF4 alpha on insulin gene expression mediated through elevated HNF1 alpha levels, HNF4 alpha also activates the insulin gene directly, through a previously unrecognized cis element.

This case study explored the way principals in Israel organized a forum and assumed roles beyond their educational responsibility. This occurred as an unexpected result of a state‐wide project that was initiated and operated by the Ministry of Education. The aim of the project was to strengthen local educational systems by developing local educational leaderships and by improving scholastic achievements. Participant observation, interviews, and reading of documents and newspapers revealed that the principals changed their role in a three‐phase process. First, the project unintentionally raised principals’ awareness of the social‐political nature of their work. Second, principals organized into an interest group that cooperated with other community groups. Third, they sought to revitalize their respective communities, beyond their educational leadership. They extended their turf from school to community, and their role from school leadership to community avant‐garde.

(1999). Cooperative learning in Israels Jewish and Arab schools: A community approach. Theory Into Practice: Vol. 38, Building Community Through Cooperative Learning, pp. 105-113.

In this study we evaluated the effects of a cooperative learning program, Bilingual Cooperative Integrated Reading and Composition (BCIRC), on the Spanish and English reading, writing, and language achievement of 222 limited English proficient second and third graders in Spanish bilingual programs. We expected BCIRC to improve student achievement during the transition from Spanish to English by giving students daily opportunities to use language to find meanings and solve problems and by enabling teachers to apply well-established principles of cooperative learning to increase student motivation and achievement. A comparison of standardized test scores in matched BCIRC (N = 3) and comparison (N = 4) schools generally supported these expectations. On the Spanish Texas Assessment of Academic Skills, second graders scored significantly better than comparison students in writing and marginally better (p < .06) in reading. On the English Norm-Referenced Assessment Program for Texas, third graders scored signif...