Overcoming Obstacles: Women Entrepreneurs Taking the Lead in Nonprofit Businesses

Few theoretical models clarify the ways in which a learning experience contributes to entrepreneurial behavior or directly pursuing entrepreneurism. The purpose of this research is to better recognize how women use values, motivations, and desires, through learning experiences, to start a nonprofit organization. Results reveal that, in order to increase the likelihood of females becoming entrepreneurs, they must put themselves in positions where they can have many different experiences. They must be willing to establish networks, overcome societal barriers as well as self-imposed barriers, and reflect upon the experiences they find themselves in, whether they are positive or negative. Such learning experiences were key to accelerating entrepreneurial endeavors by providing a forum for personal accountability, skill development, and inspiration

Targeted expression of tumor necrosis factor-related apoptosis-inducing ligand TRAIL in skin protects mice against chemical carcinogenesis

<p>Abstract</p> <p>Background</p> <p>Gene ablation studies have revealed that tumor necrosis factor-related apoptosis-inducing ligand (TRAIL, Apo2L, TNFSF10) plays a crucial role in tumor surveillance, as TRAIL-deficient mice exhibit an increased sensitivity to different types of tumorigenesis. In contrast, possible tumor-protective effect of increased levels of endogenous TRAIL expression <it>in vivo </it>has not been assessed yet. Such models will provide important information about the efficacy of TRAIL-based therapies and potential toxicity in specific tissues.</p> <p>Methods</p> <p>To this aim, we engineered transgenic mice selectively expressing TRAIL in the skin and subjected these mice to a two-step chemical carcinogenesis protocol that generated benign and preneoplastic lesions. We were therefore able to study the effect of increased TRAIL expression at the early steps of skin tumorigenesis.</p> <p>Results</p> <p>Our results showed a delay of tumor appearance in TRAIL expressing mice compared to their wild-type littermates. More importantly, the number of tumors observed in transgenic animals was significantly lower than in the control animals, and the lesions observed were mostly benign. Interestingly, Wnt/β-catenin signaling differed between tumors of wild-type and TRAIL transgenics.</p> <p>Conclusion</p> <p>Altogether, these data reveal that, at least in this model, TRAIL is able on its own to act on pre-transformed cells, and reduce their tumorigenic potential.</p

Developmental Expression and Cellular Origin of the Laminin α2, α4, and α5 Chains in the Intestine

AbstractLaminins are extracellular matrix glycoproteins that are involved in various cellular functions, including adhesion, proliferation, and differentiation. In this study, we examine the expression patterns and the cellular origins of the laminin α2, α4, and α5 chains in the developing mouse intestine and inin vitromouse/chick or chick/mouse interspecies hybrid intestines.In situhybridization and Northern blot analysis revealed that mRNA levels for all three laminin α chains are highest in the fetal intestine undergoing intense morphogenetic movements. Laminin α4 mRNA and polypeptide are associated with mesenchyme-derived cell populations such as endothelium and smooth muscle. In contrast, laminin α2 and α5 chains participate in the structural organization of the subepithelial basement membrane and, in the mature intestine, show a complementary pattern of expression. All three laminin α chains occur in the smooth muscle basement membrane, with a differential expression of laminin α5 chain in the circular and longitudinal smooth muscle layers. The cellular origin of laminin α2 and α5 chains found in the subepithelial cell basement membrane was studied by immunocytochemical analysis of mouse/chick or chick/mouse interspecies hybrid intestines at various stages of development using mouse-specific antibodies. Laminin α2 was found to be deposited into the basement membrane exclusively by mesenchymal cells, while the laminin α5 chain was deposited by both epithelial and mesenchymal cells in an apparently developmentally regulated pattern. We conclude that (1) multiple laminin α chains are expressed in the intestine, implying specific roles for individual laminin isoforms during intestinal development, and (2) reciprocal epithelial/mesenchymal interactions are essential for the formation of a structured subepithelial basement membrane

The ‘PINIT’ motif, of a newly identified conserved domain of the PIAS protein family, is essential for nuclear retention of PIAS3L

AbstractPIAS proteins, cytokine-dependent STAT-associated repressors, exhibit intrinsic E3-type SUMO ligase activities and form a family of transcriptional modulators. Three conserved domains have been identified so far in this protein family, the SAP box, the MIZ-Zn finger/RING module and the acidic C-terminal domain, which are essential for protein interactions, DNA binding or SUMO ligase activity. We have identified a novel conserved domain of 180 residues in PIAS proteins and shown that its ‘PINIT’ motif as well as other conserved motifs (in the SAP box and in the RING domain) are independently involved in nuclear retention of PIAS3L, the long form of PIAS3, that we have characterized in mouse embryonic stem cells

Distinct regions of RPB11 are required for heterodimerization with RPB3 in human and yeast RNA polymerase II

In Saccharomyces cerevisiae, RNA polymerase II assembly is probably initiated by the formation of the RPB3–RPB11 heterodimer. RPB3 is encoded by a single copy gene in the yeast, mouse and human genomes. The RPB11 gene is also unique in yeast and mouse, but in humans a gene family has been identified that potentially encodes several RPB11 proteins differing mainly in their C-terminal regions. We compared the abilities of both yeast and human proteins to heterodimerize. We show that the yeast RPB3/RPB11 heterodimer critically depends on the presence of the C-terminal region of RPB11. In contrast, the human heterodimer tolerates significant changes in RPB11 C-terminus, allowing two human RPB11 variants to heterodimerize with the same efficiency with RPB3. In keeping with this observation, the interactions between the conserved N-terminal ‘α-motifs’ is much more important for heterodimerization of the human subunits than for those in yeast. These data indicate that the heterodimerization interfaces have been modified during the course of evolution to allow a recent diversification of the human RPB11 subunits that remains compatible with heterodimerization with RPB3

Functional interaction between the homeoprotein CDX1 and the transcriptional machinery containing the TATA-binding protein

We have previously reported that the CDX1 homeoprotein interacts with the TATA-box binding protein (TBP) on the promoter of the glucose-6-phosphatase (G6Pase) gene. We show here that CDX1 interacts with TBP via the homeodomain and that the transcriptional activity additionally requires the N-terminal domain upstream of the homeodomain. CDX1 interacting with TBP is connected to members of the TFIID and Mediator complexes, two major elements of the general transcriptional machinery. Transcription luciferase assays performed using an altered-specificity mutant of TBP provide evidence for the functionality of the interaction between CDX1 and TBP. Unlike CDX1, CDX2 does not interact with TBP nor does it transactivate the G6Pase promoter. Swapping experiments between the domains of CDX1 and CDX2 indicate that, despite opposite functional effects of the homeoproteins on the G6Pase promoter, the N-terminal domains and homeodomains of both CDX1 and CDX2 have the intrinsic ability to activate transcription and to interact with TBP. However, the carboxy domains define the specificity of CDX1 and CDX2. Thus, intra-molecular interactions control the activity and partner recruitment of CDX1 and CDX2, leading to different molecular functions

A human RNA polymerase II subunit is encoded by a recently generated multigene family

BACKGROUND: The sequences encoding the yeast RNA polymerase II (RPB) subunits are single copy genes. RESULTS: While those characterized so far for the human (h) RPB are also unique, we show that hRPB subunit 11 (hRPB11) is encoded by a multigene family, mapping on chromosome 7 at loci p12, q11.23 and q22. We focused on two members of this family, hRPB11a and hRPB11b: the first encodes subunit hRPB11a, which represents the major RPB11 component of the mammalian RPB complex ; the second generates polypeptides hRPB11bα and hRPB11bβ through differential splicing of its transcript and shares homologies with components of the hPMS2L multigene family related to genes involved in mismatch-repair functions (MMR). Both hRPB11a and b genes are transcribed in all human tissues tested. Using an inter-species complementation assay, we show that only hRPB11bα is functional in yeast. In marked contrast, we found that the unique murine homolog of RPB11 gene maps on chromosome 5 (band G), and encodes a single polypeptide which is identical to subunit hRPB11a. CONCLUSIONS: The type hRPB11b gene appears to result from recent genomic recombination events in the evolution of primates, involving sequence elements related to the MMR apparatus

Sumoylation delays the ATF7 transcription factor subcellular localization and inhibits its transcriptional activity

Over the past few years, small ubiquitin-like modifier (SUMO) modification has emerged as an important regulator of diverse pathways and activities including protein localization and transcriptional regulation. We identified a consensus sumoylation motif (IKEE), located within the N-terminal activation domain of the ATF7 transcription factor and thus investigated the role of this modification. ATF7 is a ubiquitously expressed transcription factor, homologous to ATF2, that binds to CRE elements within specific promoters. This protein is able to heterodimerize with Jun or Fos proteins and its transcriptional activity is mediated by interaction with TAF12, a subunit of the general transcription factor TFIID. In the present article, we demonstrate that ATF7 is sumoylated in vitro (using RanBP2 as a E3-specific ligase) and in vivo. Moreover, we show that ATF7 sumoylation affects its intranuclear localization by delaying its entry into the nucleus. Furthermore, SUMO conjugation inhibits ATF7 transactivation activity by (i) impairing its association with TAF12 and (ii) blocking its binding-to-specific sequences within target promoters

Transcription of Muscle Actin Genes by a Nuclear Form of Mitochondrial RNA Polymerase

Actins are the major constituent of the cytoskeleton. In this report we present several lines of evidence that muscle actin genes are transcribed by nuclear isoform of mitochondrial RNA polymerase (spRNAP-IV) whereas the non-muscle actin genes are transcribed by the conventional RNA polymerase II (PolII). We show that mRNA level of muscle actin genes are resistant to PolII inhibitors α-amanitin and triptolide as well as insensitive to knockdown of PolII but not to knockdown of spRNAP-IV, in contrast to non-muscle actin genes in several cell lines. Similar results are obtained from nuclear run-on experiments. Reporter assay using muscle actin or PolII gene promoters also demonstrate the differential sensitivity to PolII inhibitors. Finally, chromatin-immunoprecipitation experiment was used to demonstrate that spRNAP-IV is associated with promoter of muscle actin genes but not with that of non-muscle gene and knockdown of spRNAP-IV depleted this polymerase from muscle actin genes. In summary, these experiments indicate that the two types of actin genes are transcribed by different transcription machinery. We also found that POLRMT gene is transcribed by spRNAP-IV, and actin genes are sensitive to oligomycin, suggesting a transcription coupling between mitochondria and nucleus