New Integrable Sectors in Skyrme and 4-dimensional CP^n Model

The application of a weak integrability concept to the Skyrme and $CP^n$ models in 4 dimensions is investigated. A new integrable subsystem of the Skyrme model, allowing also for non-holomorphic solutions, is derived. This procedure can be applied to the massive Skyrme model, as well. Moreover, an example of a family of chiral Lagrangians providing exact, finite energy Skyrme-like solitons with arbitrary value of the topological charge, is given. In the case of $CP^n$ models a tower of integrable subsystems is obtained. In particular, in (2+1) dimensions a one-to-one correspondence between the standard integrable submodel and the BPS sector is proved. Additionally, it is shown that weak integrable submodels allow also for non-BPS solutions. Geometric as well as algebraic interpretations of the integrability conditions are also given.Comment: 23 page

MAD3 AND MAD4 - NOVEL MAX-INTERACTING TRANSCRIPTIONAL REPRESSORS THAT SUPPRESS C-MYC DEPENDENT TRANSFORMATION AND ARE EXPRESSED DURING NEURAL AND EPIDERMAL DIFFERENTIATION

The basic helix-loop-helix-leucine zipper (bHLHZip) protein Max associates with members of the Myc family, as well as with the related proteins Mad (Mad1) and Mxi1, Whereas both Myc:Max and Mad:Max heterodimers bind related E-box sequences, Myc:Max activates transcription and promotes proliferation while Mad:Max represses transcription and suppresses Myc dependent transformation, Here we report the identification and characterization of two novel Mad1-and Mxi1-related proteins, Mad3 and Mad4. Mad3 and Mad4 interact with both Max and mSin3 and repress transcription from a promoter containing CACGTG binding sites, Using a rat embryo fibroblast transformation assay, we show that both Mad3 and Mad4 inhibit c-Myc dependent cell transformation, An examination of the expression patterns of all mad genes during murine embryogenesis reveals that mad1, mad3 and mad4 are expressed primarily in growth-arrested differentiating cells. mxi1 is also expressed in differentiating cells, but is co-expressed with either c-myc, N-myc, or both in proliferating cells of the developing central nervous system and the epidermis, In the developing central nervous system and epidermis, downregulation of myc genes occurs concomitant with upregulation of mad family genes, These expression patterns, together with the demonstrated ability of Mad family proteins to interfere with the proliferation promoting activities of Myc, suggest that the regulated expression of Myc and Mad family proteins function in a concerted fashion to regulate cell growth in differentiating tissues

Oesophageal adenocarcinoma is associated with a deregulation in the MYC/MAX/MAD network

Oesophageal adenocarcinoma, which arises from an acquired columnar lesion, Barrett's metaplasia, is rising in incidence more rapidly than any other cancer in the Western world. Elevated expression of c-MYC has been demonstrated in oesophageal adenocarcinoma; however, the expression of other members of the MYC/MAX/MAD network has not been addressed. The aims of this work were to characterise the expression of c-MYC, MAX and the MAD family in adenocarcinoma development and assess the effects of overexpression on cellular behaviour. mRNA expression in samples of Barrett's metaplasia and oesophageal adenocarcinoma were examined by qRT–PCR. Semi-quantitative immunohistochemistry and western blotting were used to examine cellular localisation and protein levels. Cellular proliferation and mRNA expression were determined in SEG1 cells overexpressing c-MYCER or MAD1 using a bromodeoxyuridine assay and qRT–PCR, respectively. Consistent with previous work expression of c-MYC was deregulated in oesophageal adenocarcinoma. Paradoxically, increased expression of putative c-MYC antagonists MAD1 and MXI1 was observed in tumour specimens. Overexpression of c-MYC and MAD proteins in SEG1 cells resulted in differential expression of MYC/MAX/MAD network members and reciprocal changes in proliferation. In conclusion, the expression patterns of c-MYC, MAX and the MAD family were shown to be deregulated in the oesophageal cancer model

Myc proteins in brain tumor development and maintenance

Myc proteins are often deregulated in human brain tumors, especially in embryonal tumors that affect children. Many observations have shown how alterations of these pleiotropic Myc transcription factors provide initiation, maintenance, or progression of tumors. This review will focus on the role of Myc family members (particularly c-myc and Mycn) in tumors like medulloblastoma and glioma and will further discuss how to target stabilization of these proteins for future brain tumor therapies

Ets-1 Confers Cranial Features on Neural Crest Delamination

Neural crest cells (NCC) have the particularity to invade the environment where they differentiate after separation from the neuroepithelium. This process, called delamination, is strikingly different between cranial and trunk NCCs. If signalings controlling slow trunk delamination start being deciphered, mechanisms leading to massive and rapid cranial outflow are poorly documented. Here, we show that the chick cranial NCCs delamination is the result of two events: a substantial cell mobilization and an epithelium to mesenchyme transition (EMT). We demonstrate that ets-1, a transcription factor specifically expressed in cranial NCCs, is responsible for the former event by recruiting massively cranial premigratory NCCs independently of the S-phase of the cell cycle and by leading the gathered cells to straddle the basal lamina. However, it does not promote the EMT process alone but can cooperate with snail-2 (previously called slug) to this event. Altogether, these data lead us to propose that ets-1 plays a pivotal role in conferring specific cephalic characteristics on NCC delamination

Amphi-COUP-TF, a nuclear orphan receptor of the lancelet Branchiostoma floridae, is implicated in retinoic acid signaling pathways.

International audienceIn vertebrates, the orphan nuclear receptors of the COUP-TF group function as negative transcriptionalregulators that inhibit the hormonal induction of targetgenes mediated by classical members of the nuclear hor-mone superfamily, such as the retinoic acid receptors(RARs) or the thyroid hormone receptors (TRs). To in-vestigate the evolutionary conservation of the roles of COUP-TF receptors as negative regulators in the retinoidand thyroid hormone pathways, we have characterizedAmphiCOUP-TF, the homologue of COUP-TFI andCOUP-TFII, in the chordate amphioxus ( Branchiostoma floridae ), the closest living invertebrate relative of thevertebrates. Electrophoretic mobility shift assays(EMSA) showed that AmphiCOUP-TF binds to a widevariety of response elements, as do its vertebrate homo-logues. Furthermore, AmphiCOUP-TF is a transcription-al repressor that strongly inhibits retinoic acid-mediatedtransactivation. In situ hybridizations revealed expres-sion of AmphiCOUP-TF in the nerve cord of late larvae,in a region corresponding to hindbrain and probably an-terior spinal cord. Although the amphioxus nerve cordappears unsegmented at the gross anatomical level, thispattern reflects segmentation at the cellular level withstripes of expressing cells occurring adjacent to the endsand the centers of each myotomal segment, which mayinclude visceral motor neurons and somatic motor neu-rons respectively, among other cells. A comparison of the expression pattern of AmphiCOUP-TF with those of its vertebrate homologues, suggests that the roles of COUP-TF in patterning of the nerve cord evolved priorto the split between the amphioxus and vertebrate lineag-es. Furthermore, in vitro data also suggest that Amphi-COUP-TF acts as a negative regulator of signalling byother nuclear receptors such as RAR, TR or ER