22 research outputs found
A New Model of Opportunity Recognition: Linking Individual Agency, Entrepreneurial Action, and the Innovation Process
The purpose of this study is to explore how individuals go about identifying new business opportunities, also known as opportunity recognition. Opportunity recognition is the first and most critical step in the entrepreneurship and innovation process. Past models of opportunity recognition took a narrow approach, subscribing to a single perspective of opportunity recognition and tended to overemphasize either the person or the process rather than examining all possible mechanisms and their interaction effects. This study has taken a holistic approach, with a focus on both serial entrepreneurs and intrapreneurs, aimed at exploring a range of conditions present in small startups and large organizations. Data findings were distilled down into ten proposition statements and presented in a visual process model of opportunity recognition. A total of 23 variables emerged in the research study, 12 of which were new concepts not identified in previous models. The most salient and profound insight from the study was the importance of reframing the opportunity until the “real opportunity” emerged. This back and forth reframing process occurred in cycles until a clear problem-solution fit was identified. The major contribution of this model is that it expands upon cognition theory by showing how the idea enactment process feeds back into the individual’s thought process, emphasizing the interaction effects between thinking and action. The resulting model follows a clear flow and sequence of events but also illustrates the organic nature of the ideation process and allows for multiple pathways into an innovative idea. This study bridges an important divide between the entrepreneurship and innovation literature and shows how different perspectives in the literature such as creation and discovery, identification and enactment, and active and passive search can coexist. This research provides the foundation from which to operationalize the model and develop training and educational materials for management, consultants, and educators. The study has the potential to help business leaders and aspiring entrepreneurs unlock new market opportunities, navigate a broad mix of innovation tools and techniques, and enhance cognitive skills that are central to the opportunity recognition process. Cultivating this talent is critical to achieving a sustainable competitive advantage and the successful value creation of new ventures
Dynamic effects of Wolbachia on Drosophila Oogenesis and coordination of infection with stem cell niche morphogenesis
Wolbachia are widespread obligate intracellular bacteria that are maternally transmitted and modulate reproduction of their invertebrate host. Mosquitoes transinfected with Wolbachia have reduced capacity for transmitting vector borne diseases and can replace native populations in the field because of a reproductive advantage. The cellular mechanisms of how reproduction is altered by Wolbachia are poorly understood. In this work Wolbachia-induced reproductive changes in the model organism Drosophila were used to pinpoint underlying cellular processes affected by the bacteria. Specifically, egg production (or fecundity) of Wolbachia-infected Drosophila mauritiana was compared to non-infected flies that had been generated by antibiotic treatment of infected flies. Immediately before the fecundity experiment backcrossing of both fly lines ensured an equivalent nuclear genetic background. Initially egg production in Wolbachia-infected flies was increased by 4-fold but in less than 30 generations this changed to a 0.84 fold decrease with a slight advantage for the non-infected line. Additional backcrossing experiments determined that selection on the host nuclear genome is one of the factors underlying this reversion of fecundity gains. Other non-Mendelian factors, such as the microbiota, may also play a role in this rapid change. Wolbachia alterations in egg production were always linked to Wolbachia induced changes in programmed cell death (PCD) in the germarium during oogenesis and germline stem cell (GSC) division. Germline stem cells are maintained and regulated through their interaction with the germline stem cell niche (GSCN). Interestingly, these cells are both frequently infected with Wolbachia and possess a high bacterial titer. A developmental time course revealed the mechanism of how Wolbachia accumulate in the niche cells. The data suggest that the bacteria actually coordinate their replication with the differentiation of the niche cells. Future work on understanding the cellular and molecular basis of Wolbachia - host interaction will not only give insight into novel mechanisms of host manipulation by a pathogen, but will also expand our current understanding of stem cell niche morphogenesis and modulation of stem cell proliferation.2018-06-05T00:00:00
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Using Zebrafish to Study Pathways that Regulate Hematopoietic Stem Cell Self-Renewal and Migration
This perspective describes the usefulness of zebrafish as a model to study interaction of hematopoietic stem cells with the associated niche in vivo, explains how such interactions influence regeneration, migration, and clonality of HSCs, and defines their fate during differentiation
Effects of Acipenserid herpesvirus 2 on the outcome of a Streptococcus iniae co-infection in white sturgeon (Acipenser transmontanus)
Acipenserid herpesvirus 2 (AciHV-2) is a large double-stranded DNA virus in the family Alloherpesviridae that causes catastrophic outbreaks in young naive white sturgeon (Acipenser transmontanus) populations, with mortalities of up to 80%. Survivors of these infections are suspected to remain latently infected. The gram-positive zoonotic bacterium Streptococcus iniae is another important sturgeon pathogen that causes severe myositis and up to 50% mortality during natural outbreaks. Throughout the last decade, co-infections of AciHV-2 and S. iniae have been reported in cultured white sturgeon in California resulting in severe presentations of piscine streptococcosis. This phenomenon of herpesvirus and streptococcus co-infection appears to span multiple taxa since in humans, it is recognized that a Human herpesvirus 3 infection (VZV) is a negative prognostic indicator for pediatric Invasive Group A Streptococcal infections (IGASI). While a decrease in humoral immunity caused by VZV has been hypothesized as a potentially important factor in IGASI cases, no natural animal model exists to study this process. Moreover, no studies have investigated these reported co-infections in white sturgeon. Therefore, the goal of this study was to investigate the effects of a recent AciHV-2 infection on the outcome of a subsequent S. iniae challenge in white sturgeon fingerlings. When fish were infected with 108 colony forming units (CFU) of S. iniae intramuscularly (IM), a statistically significant decrease in survival of 41% was detected in the co-infection group compared to the S. iniae group (p-value < 0.001). This difference was not observed when fish were infected with 106 CFU of S. iniae IM. At this lower infection dose, however, a statistically significant downregulation of tnfα was observed in the spleen of fish in the co-infection group compared to the S. iniae group (p-value = 0.0098). Analysis of serum from survivors revealed a statistically significant reduction in anti-S. iniae serum IgM and serum serotransferrin in fish from the co-infection group compared to the S. iniae group (p-value = 0.0134 and p-value = 0.0183, respectively). Further studies are indicated to determine what interactions lead to the decreased production of pathogen-specific IgM, serotransferrin, and TNFα in the host
PGE2 alters chromatin through H2A.Z-variant enhancer nucleosome modification to promote hematopoietic stem cell fate
Prostaglandin E2 (PGE2) and 16,16-dimethyl-PGE2 (dmPGE2) are important regulators of hematopoietic stem and progenitor cell (HSPC) fate and offer potential to enhance stem cell therapies [C. Cutler et al. Blood 122, 3074–3081(2013); W. Goessling et al. Cell Stem Cell 8, 445–458 (2011); W. Goessling et al. Cell 136, 1136–1147 (2009)]. Here, we report that PGE2-induced changes in chromatin at enhancer regions through histone-variant H2A.Z permit acute inflammatory gene induction to promote HSPC fate. We found that dmPGE2-inducible enhancers retain MNase-accessible, H2A.Z-variant nucleosomes permissive of CREB transcription factor (TF) binding. CREB binding to enhancer nucleosomes following dmPGE2 stimulation is concomitant with deposition of histone acetyltransferases p300 and Tip60 on chromatin. Subsequent H2A.Z acetylation improves chromatin accessibility at stimuli-responsive enhancers. Our findings support a model where histone-variant nucleosomes retained within inducible enhancers facilitate TF binding. Histone-variant acetylation by TF-associated nucleosome remodelers creates the accessible nucleosome landscape required for immediate enhancer activation and gene induction. Our work provides a mechanism through which inflammatory mediators, such as dmPGE2, lead to acute transcriptional changes and modify HSPC behavior to improve stem cell transplantation
Identification of novel regulators of developmental hematopoiesis using Endoglin regulatory elements as molecular probes.
Enhancers are the primary determinants of cell identity, and specific promoter/enhancer combinations of Endoglin (ENG) have been shown to target blood and endothelium in the embryo. Here, we generated a series of embryonic stem cell lines, each targeted with reporter constructs driven by specific promoter/enhancer combinations of ENG, to evaluate their discriminative potential and value as molecular probes of the corresponding transcriptome. The Eng promoter (P) in combination with the -8/+7/+9-kb enhancers, targeted cells in FLK1 mesoderm that were enriched for blast colony forming potential, whereas the P/-8-kb enhancer targeted TIE2+/c-KIT+/CD41- endothelial cells that were enriched for hematopoietic potential. These fractions were isolated using reporter expression and their transcriptomes profiled by RNA-seq. There was high concordance between our signatures and those from embryos with defects at corresponding stages of hematopoiesis. Of the 6 genes that were upregulated in both hemogenic mesoderm and hemogenic endothelial fractions targeted by the reporters, LRP2, a multiligand receptor, was the only gene that had not previously been associated with hematopoiesis. We show that LRP2 is indeed involved in definitive hematopoiesis and by doing so validate the use of reporter gene-coupled enhancers as probes to gain insights into transcriptional changes that facilitate cell fate transitions.National Health and Medical Research Council of Australia, Australian Research Council, Dr Tom Bee Stem Cell Research Fund, Cancer Research UK, Biotechnology and Biological Sciences Research Council, Leukaemia and Lymphoma Research, The Leukaemia and Lymphoma Society, core support grants by the Wellcome Trust to the Cambridge Institute for Medical Research and Wellcome Trust - MRC Cambridge Stem Cell Institute (Grant IDs: R01 HL04880, P015PO1HL32262-32, 5P30 DK49216, 5R01 DK53298, 5U01 HL10001-05, R24 DK092760)This is the author accepted manuscript. The final version is available from the American Society of Hematology via http://dx.doi.org/10.1182/blood-2016-02-69787
A qualitative study of how Danish drug consumption rooms influence health and well-being among people who use drugs
A Short Pulse of Prostaglandin E2 (PGE2) Induces Long Term Chromatin Changes in Hematopoietic Stem Cells Leading to Increased Self-Renewal and Engraftment
DataSheet_1_Effects of Acipenserid herpesvirus 2 on the outcome of a Streptococcus iniae co-infection in white sturgeon (Acipenser transmontanus).docx
Acipenserid herpesvirus 2 (AciHV-2) is a large double-stranded DNA virus in the family Alloherpesviridae that causes catastrophic outbreaks in young naive white sturgeon (Acipenser transmontanus) populations, with mortalities of up to 80%. Survivors of these infections are suspected to remain latently infected. The gram-positive zoonotic bacterium Streptococcus iniae is another important sturgeon pathogen that causes severe myositis and up to 50% mortality during natural outbreaks. Throughout the last decade, co-infections of AciHV-2 and S. iniae have been reported in cultured white sturgeon in California resulting in severe presentations of piscine streptococcosis. This phenomenon of herpesvirus and streptococcus co-infection appears to span multiple taxa since in humans, it is recognized that a Human herpesvirus 3 infection (VZV) is a negative prognostic indicator for pediatric Invasive Group A Streptococcal infections (IGASI). While a decrease in humoral immunity caused by VZV has been hypothesized as a potentially important factor in IGASI cases, no natural animal model exists to study this process. Moreover, no studies have investigated these reported co-infections in white sturgeon. Therefore, the goal of this study was to investigate the effects of a recent AciHV-2 infection on the outcome of a subsequent S. iniae challenge in white sturgeon fingerlings. When fish were infected with 108 colony forming units (CFU) of S. iniae intramuscularly (IM), a statistically significant decrease in survival of 41% was detected in the co-infection group compared to the S. iniae group (p-value 6 CFU of S. iniae IM. At this lower infection dose, however, a statistically significant downregulation of tnfα was observed in the spleen of fish in the co-infection group compared to the S. iniae group (p-value = 0.0098). Analysis of serum from survivors revealed a statistically significant reduction in anti-S. iniae serum IgM and serum serotransferrin in fish from the co-infection group compared to the S. iniae group (p-value = 0.0134 and p-value = 0.0183, respectively). Further studies are indicated to determine what interactions lead to the decreased production of pathogen-specific IgM, serotransferrin, and TNFα in the host.</p