Scientists as Midwives to Cluster Emergence: An Institutional Work Framework

The question of how embedded actors can create institutions that support cluster emergence remains unsolved in the cluster and national innovation systems literature. The present paper extends the recent literature on institutional entrepreneurship and institutional work to solve this paradox of embedded agency in the context of science-based clusters. Building on a longitudinal single case study of a functional foods cluster in Finland, we present an institutional work framework for cluster formation. We argue that, in addition to ideational, material and bridging work, authentic leadership work is critical for cluster emergence. The results of the study highlight the opportunities that scientists have to act as midwives to cluster formation, but they also show that well-functioning clusters need a broader support base.Peer reviewe

LYL1 Degradation by the Proteasome Is Directed by a N-Terminal PEST Rich Site in a Phosphorylation-Independent Manner

Background: The Lymphoblastic leukemia 1 (LYL1) gene is a proto-oncogenic transcription factor found upregulated in patients with T-cell acute lymphoblastic leukemia (T-cell ALL). Initially, the upregulation was described to be as a result of a translocation. However, further studies revealed that transcriptional upregulation of LYL1could also occur without translocations. In addition, post-translational mechanisms, such as protein degradation could influence LYL1 expression as well. Methodology/Principal Findings: In this study, we considered possible post-translational regulation of Lyl1, and investigated fundamental mechanisms governing LYL1 degradation in cell-based culture assays. We identify a PEST sequence motif located in the N-terminus of LYL1, which determines the efficiency of LYL1 degradation by the proteasome. The absence of the PEST degradation site leads to accumulation or upregulation of LYL1. We also show that LYL1 is phosphorylated by MAPK at S36, and determined that proteasomal degradation of LYL1 occurs in a phosphorylationindependent manner. Conclusions/Significance: Understanding LYL1 degradation is a step forward not only towards deciphering the normal function and regulation of LYL1, but could suggest post-translational mechanisms for upregulation of LYL1 that ma

Galanin and galanin receptor expression in neuroblastic tumours: correlation with their differentiation status

Neuroblastoma and its benign differentiated counterpart, ganglioneuroma, are paediatric neuroblastic tumours arising in the sympathetic nervous system. Their broad spectrum of clinical virulence is mainly related to heterogeneous biologic background and tumour differentiation. Neuroblastic tumours synthesize various neuropeptides acting as neuromodulators. Previous studies suggested that galanin plays a role in sympathetic tissue where it could be involved in differentiation and development. We investigated the expression and distribution of galanin and its three known receptors (Gal-R1, Gal-R2, Gal-R3) in 19 samples of neuroblastic tumours tissue by immunohistochemistry, in situ hybridization and fluorescent-ligand binding. This study provides clear evidence for galanin and galanin receptor expression in human neuroblastic tumours. The messengers coding for galanin, Gal-R1 and -R3 were highly expressed in neuroblastoma and their amount dramatically decreased in ganglioneuroma. In contrast, Gal-R2 levels remained unchanged. Double labelling studies showed that galanin was mainly co-expressed with its receptors whatever the differentiation stage. In neuroblastic tumours, galanin might promote cell-survival or counteract neuronal differentiation through the different signalling pathways mediated by galanin receptors. Finally, our results suggest that galanin influences neuroblastoma growth and development as an autocrine/paracrine modulator. These findings suggest potential critical implications for galanin in neuroblastic tumours development

Characterization of BCE-1, a Transcriptional Enhancer Regulated by Prolactin and Extracellular Matrix and Modulated by the State of Histone Acetylation

We have previously described a 160-bp enhancer (BCE-1) in the bovine β-casein gene that is activated in the presence of prolactin and extracellular matrix (ECM). Here we report the characterization of the enhancer by deletion and site-directed mutagenesis, electrophoretic mobility shift analysis, and in vivo footprinting. Two essential regions were identified by analysis of mutant constructions: one binds C/EBP-β and the other binds MGF/STAT5 and an as-yet-unidentified binding protein. However, no qualitative or quantitative differences in the binding of these proteins were observed in electrophoretic mobility shift analysis using nuclear extracts derived from cells cultured in the presence or absence of ECM with or without prolactin, indicating that prolactin- and ECM-induced transcription was not dependent on the availability of these factors in the functional cell lines employed. An in vivo footprinting analysis of the factors bound to nuclear chromatin in the presence or absence of ECM and/or prolactin found no differences in the binding of C/EBP-β but did not provide definitive results for the other factors. Neither ECM nor prolactin activated BCE-1 in transient transfections, suggesting that the chromosomal structure of the integrated template may be required for ECM-induced transcription. Further evidence is that treatment of cells with inhibitors of histone deacetylase was sufficient to induce transcription of integrated BCE-1 in the absence of ECM. Together, these results suggest that the ECM induces a complex interaction between the enhancer-bound transcription factors, the basal transcriptional machinery, and a chromosomally integrated template responsive to the acetylation state of the histones

ID1 and ID2 are retinoic acid responsive genes and induce a G0/G1 accumulation in acute promyelocytic leukemia cells.

Contains fulltext : 47334.pdf (publisher's version ) (Closed access)Acute promyelocytic leukemia (APL) is uniquely sensitive to treatment with all-trans retinoic acid (ATRA), which results in the expression of genes that induce the terminal granulocytic differentiation of the leukemic blasts. Here we report the identification of two ATRA responsive genes in APL cells, ID1 and ID2. These proteins act as antagonists of basic helix-loop-helix (bHLH) transcription factors. ATRA induced a rapid increase in ID1 and ID2, both in the APL cell line NB4 as well as in primary patient cells. In addition, a strong downregulation of E2A was observed. E2A acts as a general heterodimerization partner for many bHLH proteins that are involved in differentiation control in various tissues. The simultaneous upregulation of ID1 and ID2, and the downregulation of E2A suggest a role for bHLH proteins in the induction of differentiation of APL cells following ATRA treatment. To test the relevance of this upregulation, ID1 and ID2 were overexpressed in NB4 cells. Overexpression inhibited proliferation and induced a G0/G1 accumulation. These results indicate that ID1 and ID2 are important retinoic acid responsive genes in APL, and suggest that the inhibition of specific bHLH transcription factor complexes may play a role in the therapeutic effect of ATRA in APL