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Src, the canonical member of the non-receptor family of tyrosine kinases, is deregulated in numerous cancers, including colon and breast cancers. In addition to its effects on cell proliferation and motility, Src is often considered as an inhibitor of apoptosis, although this remains controversial. Thus, whether the ability of Src to generate malignancies relies on an intrinsic aptitude to inhibit apoptosis or requires preexistent resistance to apoptosis remains somewhat elusive. Here, using mouse fibroblasts transformed with v-Src as a model, we show that the observed Src-dependent resistance to cell death relies on Src ability to inhibit the mitochondrial pathway of apoptosis by specifically increasing the degradation rate of the BH3-only protein Bik. This effect relies on the activation of the Ras-Raf-Mek1/2-Erk1/2 pathway, and on the phosphorylation of Bik on Thr124, driving Bik ubiquitylation on Lys33 and subsequent degradation by the proteasome. Importantly, in a set of human cancer cells with Src-, Kras- or BRAF-dependent activation of Erk1/2, resistances to staurosporine or thapsigargin were also shown to depend on Bik degradation rate via a similar mechanism. These results suggest that Bik could be a rate-limiting factor for apoptosis induction of tumor cells exhibiting deregulated Erk1/2 signaling, which may provide new opportunities for cancer therapies. [ABSTRACT FROM AUTHOR]

Testing the specific migration limits of all substances intentionally added to polymer material according to European Union (EU) regulation is a time-consuming and expensive task. Although mathematical modeling offers an interesting alternative, it can significantly overestimate the migration in situations which are strongly conservative due to significant uncertainty in transport properties. In addition, its application is of little use for end-users or enforcement laboratories, which do not have access to the formulation. This paper revises the paradigm of migration modeling by combining modeling with deformulation experiments and iterative modeling in the framework of decision theory. The complete approach is illustrated for polyolefins in contact with 50% ethanol for eight typical migrants, including hindered phenolic antioxidants and low molecular weight surrogates. Results from a French ACTIA project on the identification of formulation fingerprints and on the prediction of partition coefficients with alcoholic and aqueous stimulants is described. When the true migration was close but still lower than the limit of concern, the proposed compact decision tree, including up to four sources of uncertainty, showed that the chance of demonstrating compliance was about 3 : 4 in the presence of one source of uncertainty, whereas it fell below 2 : 4 and 1 : 4 with two and three sources of uncertainty, respectively. The recommendations for further food packaging safety surveys and future developments are discussed. [ABSTRACT FROM AUTHOR]

Lithium has long been used for the treatment and prophylaxis of bipolar mood disorder. However, nerve cells are not the sole targets of lithium. Indeed, lithium was reported to target numerous cell types, and affect cell proliferation, differentiation and death. Thus, the idea has been raised that lithium may act on signaling pathways involved in neoplastic transformation. Indeed, the effect of lithium on tumor progression is currently being tested in a limited number of clinical trials. However, the molecular mechanisms by which lithium affects neoplastic transformation remain to be characterized. Here, using mouse fibroblasts transformed by the v-src oncogene as a model, we show that lithium drastically inhibits cell motility and compromises the invasive phenotype of v-src-transformed cells. In addition, we show that this effect is mediated by the activation of phosphotyrosine phosphatases, but not by the direct inhibition of the v-Src tyrosine kinase. Finally, we show that lithium activates phosphotyrosine phosphatases by the modulation of the redox status of the cell, independently of the Wnt and the inositol phosphate canonical pathways. Thus, this study supports the idea that lithium, acting similar to an antioxydizer, may have antimetastatic properties in vivo. [ABSTRACT FROM AUTHOR]

Tumor cells are characterized by deregulated proliferation and resistance to proapoptotic stimuli. The Bcl-2 family of antiapoptotic proteins is overexpressed in a large number of chemoresistant tumors. Downregulation or inhibition of antiapoptotic proteins might result in the sensitization of cancer cells to chemotherapeutic agents. In the present study, we took advantage of the peptide aptamer strategy to target Nr-13, a Bcl-2 antiapoptotic protein involved in neoplastic transformation by the Rous sarcoma virus. We isolated peptide aptamers that behave as Nr-13 regulators, in vitro and in mammalian cells in culture. Some of these aptamers have potential proapoptotic activities. These data suggest that peptide aptamers targeting the Bcl-2 family of apoptosis inhibitors may be useful for the development of anticancer molecules.Oncogene (2007) 26, 701–710. doi:10.1038/sj.onc.1209832; published online 14 August 2006 [ABSTRACT FROM AUTHOR]

Although the role of the b-cell lymphoma (Bcl)-2 family of apoptosis inhibitors is well documented in tumor cells and tissue morphogenesis, their role during the early development of vertebrates is unknown. Here, we characterize Nrz, a new Bcl-2-related inhibitor of apoptosis in zebrafish. Nrz is a mitochondrial protein, antagonizing the death-accelerator Bax. The nrz gene is mainly expressed during gastrulation and somitogenesis. The knockdown of nrz with antisense morpholinos leads to alterations of the somites, correlated with an increase in apoptosis. In addition, earlier during development, in the zebrafish gastrula, nrz knockdown results in an increase of snail-1 expression at the margin and frequent gastrulation arrest at the shield stage, independently of apoptosis. Together these data suggest that Nrz, in addition to its effect on apoptosis, contributes to cell movements during gastrulation by negatively regulating the expression of Snail-1, a transcription factor that controls cell adhesion.Cell Death and Differentiation (2006) 13, 1128–1137. doi:10.1038/sj.cdd.4401797; published online 11 November 2005 [ABSTRACT FROM AUTHOR]

We present here the results of a study of the separation process in the extraction matrix of a novel high-intensity magnetic separator (HIMS). The matrix uses an ordered array of grooved plates (replacing conventional collectors, which are generally made of wires). Only experimental results are available for grooved plates in the literature, but here we propose a new theoretical approach. We report on the particles' behavior, the existence of a percolation phenomenon, and the filtration efficiency, in order to analyze and compare the performance of matrix structures (Lenoir's and Jones'). We discuss the causes of the percolation phenomenon and its effect on filtration efficiency. Correspondence between the theory and the experiments is good. We suggest appropriate uses of each matrix structure according to the property of the processed particles. [ABSTRACT FROM AUTHOR]

Focuses on a study which presented the modeling of paramagnetic particle capture in high-gradient magnetic separators. Theories considered in the particle approach; Modeling of the capture of a particle on a collector; Simulation of the progressive saturation of an extraction matrix.

Several industrial sectors such as surface treatment, petroleum, chemical, etc. generate effluents containing heavy metal ions (HMI). The main metal ions in such effluents can be zinc, copper, vanadium, etc. Purification of such effluents by magnetic separation is performed by adding a certain proportion of iron salts. These salts precipitates together with those of HMI by increasing the pH. The coprecipitation of this “magnetic carrier” with heavy metals hydroxydes to create a magnetic floc has been studied. The effluent treated passes by a superconducting separator where the flocs are retained in a matrix of steel wires. The purified effluent leaves the separator, and the trapped flocs are collected when the matrix is saturated. The efficiency of HMI separation by this method exceeds 95%. [ABSTRACT FROM AUTHOR]

Discusses the dynamics of the transference in narcissistic restorations. Theory of the transference that constitutes the method used in analytical process; Key concepts of the transference; Analysis on narcissistic restoration that gave rise to a specific form of transference.

Wikstroemia species studied in the present investigation can be broadly divided into two groups (Table III) on the basis of morphological characters such as: length of the petiole, leaves, and the shape of the fruit. These two groups are further substantiated by chromatographic evidence. The result of the present biochemical investigation indicates that within a given species no obvious differences in the chromatographic patterns are associated with differences in sex, location, and collection time. This underlines the validity and utility of biochemical information in the taxonomic treatment of the genus. The exact nature of the compounds appearing in the chromatograms is unknown; however, they seem on the basis of our preliminary tests and references in the current literature, to be coumarins and phenolic glycosides. In general, it appears that species which have a close morphological resemblance show more or less similar biochemical patterns of the acid hydrolysis extracts, as is evident in Fig. 2 and Table IV. On the other hand, species that are morphologically very different gave different chromatographic patterns. [ABSTRACT FROM AUTHOR]

Background: Cell transformation by the Src tyrosine kinase is characterized by extensive changes in gene expression. In this study, we took advantage of several strains of the Rous sarcoma virus (RSV) to characterize the patterns of v-Src-dependent gene expression in two different primary cell types, namely chicken embryo fibroblasts (CEF) and chicken neuroretinal (CNR) cells. We identified a common set of v-Src regulated genes and assessed if their expression is associated with disease-free survival using several independent human tumor data sets.Methods: CEF and CNR cells were infected with transforming, non-transforming, and temperature sensitive mutants of RSV to identify the patterns of gene expression in response to v-Src-transformation. Microarray analysis was used to measure changes in gene expression and to define a common set of v-Src regulated genes (CSR genes) in CEF and CNR cells. A clustering enrichment regime using the CSR genes and two independent breast tumor data-sets was used to identify a 42-gene aggressive tumor gene signature. The aggressive gene signature was tested for its prognostic value by conducting survival analyses on six additional tumor data sets.Results: The analysis of CEF and CNR cells revealed that cell transformation by v-Src alters the expression of 6% of the protein coding genes of the genome. A common set of 175 v-Src regulated genes (CSR genes) was regulated in both CEF and CNR cells. Within the CSR gene set, a group of 42 v-Src inducible genes was associated with reduced disease- and metastasis-free survival in several independent patient cohorts with breast or lung cancer. Gene classes represented within this group include DNA replication, cell cycle, the DNA damage and stress responses, and blood vessel morphogenesis.Conclusion: By studying the v-Src-dependent changes in gene expression in two types of primary cells, we identified a set of 42 inducible genes associated with poor prognosis in breast and lung cancer. The identification of these genes provides a set of biomarkers of aggressive tumor behavior and a framework for the study of cancer cells characterized by elevated Src kinase activity. [ABSTRACT FROM AUTHOR]