Anat Yarden

p27 is involved in N-cadherin-mediated contact inhibition of cell growth and S-phase entry

In this study the direct involvement of cadherins in adhesion-mediated growth inhibition was investigated. It is shown here that overexpression of N-cadherin in CHO cells significantly suppresses their growth rate. Interaction of these cells and two additional fibroblastic lines with synthetic beads coated with N-cadherin ligands (recombinant N-cadherin ectodomain or specific antibodies) leads to growth arrest at the G1 phase of the cell cycle. The cadherin-reactive beads inhibit the entry into S phase and the reduction in the levels of cyclin-dependent kinase (cdk) inhibitors p21 and p27, following serum-stimulation of starved cells. In exponentially growing cells these beads induce G1 arrest accompanied by elevation in p27 only. We propose that cadherin-mediated signaling is involved in contact inhibition of growth by inducing cell cycle arrest at the G1 phase and elevation of p27 levels.

Autocrine β-related interferon controls c-myc suppression and growth arrest during hematopoietic cell differentiation

Different hematopoietic cells produce minute amounts of beta-related interferon (IFN) following induction of differentiation by chemical or natural inducers. The endogenous IFN binds to type I cell surface receptors and modulates gene expression in the producer cells. We show that self-induction of two members of the IFN-induced gene family differs in the dose response sensitivity and the prolonged kinetics of mRNA accumulation from the response to exogenous IFN-beta 1. Production and response to endogenous IFN are also detected when bone marrow precursor cells differentiate to macrophages after exposure to colony stimulating factor 1. In M1 myeloid cells induced to differentiate by lung-conditioned medium, addition of antibodies against IFN-beta partially abrogates the reduction of c-myc mRNA and the loss in cell proliferative activity, which both occur during differentiation. The endogenous IFN therefore functions as an autocrine growth inhibitor that participates in controlling c-myc suppression and the specific G0/G1 arrest during terminal differentiation of hematopoietic cells.

Characterizing children's spontaneous interests in science and technology

This article reports the results of an analysis of 1676 science and technology questions submitted by Israeli children to a series of television programmes. It categorizes the children’s questions with reference to five different coding schemes: field of interest, motivation for asking the question, type of information requested, country‐specific aspects, and source of information. The results point to the popularity of biology, technology, and astrophysics over other sciences, indicate a shift in interests and motivation with age, and reflect a variety of gender‐related differences within the sample. The implications of the findings for some current trends in curriculum development and for informal science education are discussed with reference to the wider context of the pupils’ voice in education.

Interferons and interleukin-6 suppress the DNA-binding activity of E2F in growth-sensitive hematopoietic cells.

Transcription factor E2F binds to cellular promoters of certain growth- and cell cycle-controlling genes and forms distinct heteromeric complexes with other nuclear proteins. We show here that alpha and beta interferons (alpha, beta) and interleukin-6 abolished the E2F-containing DNA-binding complexes in Daudi Burkitt lymphoma cells and in M1 myeloblastic cells, which responded to the cytokines by suppression of c-myc transcription. Time kinetics studies showed that the abolishment of E2F complexes coincided with reduction of c-myc expression and that both molecular events preceded the cell cycle block in G0/G1 phase. In contrast, the pattern of E2F complexes remained unchanged in an interferon-treated growth-resistant Daudi cell mutant that displayed relaxed regulation of c-myc. All of the DNA-binding E2F complexes, including those containing the retinoblastoma protein (pRB), cyclin A-p33cdk2, and the free forms of E2F, were reduced by interferons or interleukin-6. Their abolishment was unperturbed by pharmacological treatments that alleviated the cyclin A and pRB responses to interferon. Thus, changes in cyclin A expression and pRB phosphorylation are not primary events that influence the pattern of E2F responses to cytokines. Addition of EDTA to cell extracts of interferon-treated Daudi cells restored the DNA-binding activity of E2F, resulting in the appearance of a single E2F complex that exclusively contained pRB. It is suggested that the regulation of E2F by growth-inhibitory cytokines that induce cell cycle exit takes place at the level of the DNA-binding activity, and by that mean it differs basically from the phase-specific regulation of E2F in cycling cells.

Primary Literature as a Basis for a High-School Biology Curriculum.

Textbooks, research news from the media, and review articles from popular journals are the most common sources of texts used for high-school biology education. We attempted to adopt primary literature as a means of developing scientific literacy among high-school biology majors. For that purpose, we developed and implemented a primary literature-based curriculum in developmental biology. The process of adapting original research articles to the high-school level, as well as a conversational model developed for learning through research articles, are discussed.

Girls' Biology, Boys' Physics: Evidence from Free-Choice Science Learning Settings.

Many of the explanations for girls’ disinterest in physics focus on the role of the educational system in creating this situation. Here, we use evidence from free‐choice science learning settings to study if this lack of interest is also expressed in non‐school settings. Three sets of self‐generated questions raised by children, adolescents and adults in the fields of biology and physics were used. The outcomes of this analysis show that the polar pattern previously described in school science settings, in which physics proves significantly less interesting to girls than to boys, while biology is of greater interest to girls than to boys, also appears in free‐choice science learning settings. While boys develop an interest in physics with age, girls do not develop such an interest to the same degree. Thus, the initial gap in interest is probably not based on school‐related causes, but its widening in later years probably is. A difference was also found between the genders in the type of information requested and in the motivation for raising the questions. Using topics that appeal to girls’ interest as the context of science learning could prove beneficial in the process of mainstreaming science education. These topics can be identified using girls’ spontaneous questions.

Autogenous production of interferon-beta switches on HLA genes during differentiation of histiocytic lymphoma U937 cells.

The expression of class I HLA genes was measured during the in vitro differentiation of human U937 lymphoma cells towards macrophages. Following the onset of differentiation by phorbol myristate acetate the levels of cytoplasmic mRNA that hybridized with a [32P]HLA‐B cDNA probe increased by a factor of nine. Elevation in HLA mRNA accumulation was followed by an increase in the rate of synthesis of HLA proteins and also by a dramatic increase in class I HLA cell surface antigen expression, as shown by cytofluorimetric analysis. The elevation in HLA mRNA and surface antigens could be prevented by adding antibodies against human interferon‐beta (IFN‐beta) to the culture medium at the onset of differentiation. Interferon antiviral activity was detected in the medium of differentiated U937 cells. The same anti‐IFN‐beta antibodies prevented the increase in (2′‐5′)oligo(A) synthetase activity which also takes place in differentiating U937 cells. Accumulation of the IFN‐induced (2′‐5′)oligo(A) synthetase in U937 cells is preceded by an increase in its specific 1.6‐kb mRNA as shown by hybridization to cloned (2′‐5′)‐oligo(A) synthetase cDNA. The enzyme was preferentially found in the nuclear fraction of differentiating U937 cells. We suggest that an autogenous production of interferon‐beta by the differentiating cells, switches on expression of the class I HLA genes as well as that of the (2′‐5′)oligo(A) synthetase.

The learning processes of two high‐school biology students when reading primary literature

Biology education, like education in any other discipline, strives to make students familiar with the knowledge, activities, and ways of thinking of the community of biologists. We produced a curriculum in developmental biology based on learning through primary literature, in an attempt to develop biological literacy among highschool students. Here we characterize the way in which two high‐school biology students read a research article in developmental biology. Mere reading resulted in superficial comprehension. In contrast, when the students answered questions about the text, deeper comprehension evolved. The students could overcome readingcomprehension problems by applying well‐established reading strategies, but encountered difficulties resulting from the classical structure of research articles. We hope that our characterization of the learning process of research articles by high‐school students will enable the use of these complex texts in high‐school biology classrooms.

Zebrafish cyclin D1 is differentially expressed during early embryogenesis.

We have isolated and determined the nucleotide sequence of a cDNA containing the complete coding region of cyclin D1 from embryonic zebrafish cDNA library. The cyclin D1 gene is a single copy gene within the zebrafish genome, which undergoes an alternative polyadenylation process. The initial expression of cyclin D1 transcript occurs at the presumed onset of G1 phase in the developing zebrafish embryo.

ZEBRAFISH CYCLIN E REGULATION DURING EARLY EMBRYOGENESIS

Cyclin E cDNA, cloned from a zebrafish embryonic cDNA library, was used for analysis of cyclin E regulation during early embryogenesis. During the rapid cell cycles of the early cleavage stage, which lacks a G1 phase, the cyclin E mRNA, protein, and associated H1 kinase activity were found to be constitutive, in contrast to their reported cyclic behavior during the cycle of cultured mammalian cells. These results suggest an additional role for cyclin E during early embryogenesis, in addition to its established role during the G1/S transition in somatic cells. These results support previous identification of cyclin E in early cleaving Drosophila and Xenopus embryos, and provide for the first time the direct demonstration of constitutive cyclin E activity throughout the M/S cycles of the embryonic cleavage stage. Cyclin E mRNA was reduced during epiboly (approximately 6–8 hr postfertilization, HPF), concomitantly with a marked reduction in cell division rates. In contrast, the cyclin E protein and cyclin E‐CDK complexes remained constant throughout the first 24 hr, implying that the cyclin E protein is regulated post translationally and is not immediately affected by the levels of the corresponding mRNA. However, the cyclin E‐CDK complexes present in 26 somite embryos (22 HPF) did not exhibit histone H1 kinase activity. This discrepancy between high levels of cyclin E‐CDK complexes and low enzymatic activity may be explained by the presence of putative cyclin E‐CDK inhibitory mechanism. Here we show that multiple levels of regulation of the cyclin E mRNA, protein, and associated kinase activity are present during the first 24 hr of zebrafish embryonic development.