MicroRNAs (miRNAs) are small ∼22nt single stranded RNAs that negatively regulate protein expression by binding to partially complementary sequences in the 3' untranslated region (3' UTRs) of target ...gene messenger RNAs (mRNA). Recently, mutations have been identified in both miRNAs and target genes that disrupt regulatory relationships, contribute to oncogenesis and serve as biomarkers for cancer risk. KIT, an established oncogene with a multifaceted role in melanogenesis and melanoma pathogenesis, has recently been shown to be upregulated in some melanomas, and is also a target of the miRNA miR-221. Here, we describe a genetic variant in the 3' UTR of the KIT oncogene that correlates with a greater than fourfold increased risk of acral melanoma. This KIT variant results in a mismatch in the seed region of a miR-221 complementary site and reporter data suggests that this mismatch can result in increased expression of the KIT oncogene. Consistent with the hypothesis that this is a functional variant, KIT mRNA and protein levels are both increased in the majority of samples harboring the KIT variant. This work identifies a novel genetic marker for increased heritable risk of melanoma.
Under defined differentiation conditions, human embryonic stem cells (hESCs) can be directed toward a mesendoderm (ME) or neuroectoderm (NE) fate, the first decision during hESC differentiation. ...Coupled with lineage-specific G1 lengthening, a divergent ciliation pattern emerged within the first 24 hr of induced lineage specification, and these changes heralded a neuroectoderm decision before any neural precursor markers were expressed. By day 2, increased ciliation in NE precursors induced autophagy that resulted in the inactivation of Nrf2 and thereby relieved transcriptional activation of OCT4 and NANOG. Nrf2 binds directly to upstream regions of these pluripotency genes to promote their expression and repress NE derivation. Nrf2 suppression was sufficient to rescue poorly neurogenic iPSC lines. Only after these events had been initiated did neural precursor markers get expressed at day 4. Thus, we have identified a primary cilium-autophagy-Nrf2 (PAN) control axis coupled to cell-cycle progression that directs hESCs toward NE.
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•NE-specific G1 lengthening initiates NE derivation through primary cilia•Increased ciliogenesis activates autophagy and presages NE differentiation•NE precursor-specific autophagy inactivates Nrf2•Nrf2 suppresses NE fate by directly controlling OCT4 and NANOG expression
A primary cilium-autophagy-Nrf2 axis couples with the cell-cycle progression and regulates the inactivation of Oct4 and Nanog, therefore serving as the earliest cascade of triggering events to initiate stem cell differentiation into neuroectoderm.
Long non-coding RNAs (lncRNAs) are a diverse and poorly conserved category of transcripts that have expanded greatly in primates, particularly in the brain. We identified an lncRNA, which has ...acquired 16 microRNA response elements for miR-143-3p in the Catarrhini branch of primates. This lncRNA, termed LncND (neurodevelopment), is expressed in neural progenitor cells and then declines in neurons. Binding and release of miR-143-3p by LncND control the expression of Notch receptors. LncND expression is enriched in radial glia cells (RGCs) in the ventricular and subventricular zones of developing human brain. Downregulation in neuroblastoma cells reduced cell proliferation and induced neuronal differentiation, an effect phenocopied by miR-143-3p overexpression. Gain of function of LncND in developing mouse cortex led to an expansion of PAX6+ RGCs. These findings support a role for LncND in miRNA-mediated regulation of Notch signaling within the neural progenitor pool in primates that may have contributed to the expansion of cerebral cortex.
•Identification of LncND with a Catarrhine insertion of 16 MREs for miR-143-3p•LncND regulates expression of Notch genes by sequestering miR-143-3p•High expression of LncND in radial glia cells in human VZ and OSVZ•LncND appears to be involved in the expansion of radial glia cells in primates
Rani et al. demonstrate the function of a primate lncRNA, designated LncND, as a miRNA reservoir regulating the expression of Notch-1 and Notch-2 by sequestering miR-143-3p. They provide evidence for the involvement of LncND in primate brain expansion.
MicroRNAs (miRNAs) are a large class of small (~22 nt) non-coding RNAs that negatively regulate gene expression most often at the level of translation, and have been shown to be key regulators in a ...variety of processes including development, cell cycle and immunity. The Epstein-Barr virus (EBV) is an oncogenic herpes virus endemic in humans that encodes at least twenty-two of its own miRNAs. Cellular miRNAs have well-established roles in cancer and immune pathways, and multiple cellular miRNAs directly target viral messages. Additionally, multiple viruses express suppressors of cellular RNAi-induced silencing. Here we show that EBV de novo infection of primary cultured human B-cells results in a dramatic down-regulation of cellular miRNA expression, suggesting the virus may encode or activate a suppressor of miRNA expression. We additionally show that the immuno-modulatory microRNA miR-146a, down-regulated on initial infection, is significantly up-regulated more than 100-fold upon induction of the viral lytic cycle, and appears to have inhibitory effects on the progression of the lytic cycle. Our results show that EBV has large effects on cellular miRNA expression.
This study examined the roles of mentors’ and protégés’ emotional intelligence and protégés’ trust in the mentors in formal mentoring relationships. Using reports from both mentors and protégés in ...147 formal mentoring dyads, results of partial least squares analysis indicated that mentors’ emotional intelligence directly and indirectly related to mentoring provided through protégés’ trust in the mentors, whereas protégés’ emotional intelligence was only indirectly associated with the mentoring provided through their trust in the mentors. A complementary interaction effect of mentors’ and protégés’ emotional intelligence on protégés’ trust in the mentors was also found. Finally, mentoring provided was positively associated with protégés’ willingness to mentor others in the future. Implications regarding mentor— protégé matching and development for effective formal mentoring programs and future theory development are discussed.
Our ability to see fine detail at depth in tissues is limited by scattering and other refractive characteristics of the tissue. For fixed tissue, we can limit scattering with a variety of clearing ...protocols. This allows us to see deeper but not necessarily clearer. Refractive aberrations caused by the bulk index of refraction of the tissue and its variations continue to limit our ability to see fine detail. Refractive aberrations are made up of spherical and other Zernike modes, which can be significant at depth. Spherical aberration that is common across the imaging field can be corrected using an objective correcting collar, although this can require manual intervention. Other aberrations may vary across the imaging field and can only be effectively corrected using adaptive optics. Adaptive optics can also correct other aberrations simultaneously with the spherical aberration, eliminating manual intervention and speeding imaging. We use an adaptive optics two-photon microscope to examine the impact of the spherical and higher order aberrations on imaging and contrast the effect of compensating only for spherical aberration against compensating for the first 22 Zernike aberrations in two tissue types. Increase in image intensity by 1.6× and reduction of root mean square error by 3× are demonstrated.
Social entrepreneurship and community leadership Litzky, Barrie E; Godshalk, Veronica M; Walton-Bongers, Cynthia
Journal of management education,
02/2010, Letnik:
34, Številka:
1
Journal Article
Recenzirano
This article provides a “how to” guide for developing and teaching a service-learning course in social entrepreneurship and community leadership. As the framework of the course, service-learning ...operates through faculty to student, student to student, and student to client interactions. The discussion articulates the planning and faculty commitment necessary as well as the goals, objectives, project examples, and outcomes associated with the class. A unique aspect of the course, the pairing of graduate student mentors with high school student protégés within teams, is described. The service-learning activities required throughout the course are generalizable to several management education contexts that wish to enhance learning and leadership by creating partnerships between the university, its students, and its community.
Essays are an important measure of complex learning, but pronouns can confound an author's intended meaning for both readers and text analysis software. This descriptive investigation considers the ...effect of pronouns on a computer-based text analysis approach, ALA-Reader, which uses students' essays as the data source for deriving individual and group knowledge representations. Participants in an undergraduate business course (n = 45) completed an essay as part of the course final examination. The investigators edited the essays to replace the most common pronouns (their, it, and they) with the appropriate referent. The original unedited and the edited essays were processed with ALAReader using two different approaches, sentence and linear aggregate. These data were then analyzed using a Pathfinder network approach. The average group network similarity values comparing the original to the edited essays were large (i. e., about 90% overlap) but the linear aggregate approach obtained larger values than the sentence aggregate approach. The linear aggregate approach also provided a better measure of individual essay scores (e. g., r = 0.74 with composite rater scores). This data provides some support that the ALA Reader linear approach is adequate for capturing group knowledge structure representations from essays. Further development of the ALA-Reader approach is warranted.
This report summarizes the information presented at the 2009 Keystone Conference on MicroRNAs and Cancer, held in Keystone, Colorado, USA, June 10th to 15th 2009. Soon after microRNAs (miRNAs) ...emerged as an abundant new class of non-coding RNAs (ncRNAs), evidence started to mount supporting important roles for these regulatory RNAs in human health and disease. Mis-regulation of specific miRNA pathways has been linked to diverse cancers. The recent Keystone meeting highlighted progress in understanding the role of miRNAs in normal development and oncogenesis. Recurring themes included the complexities associated with miRNA biogenesis, target recognition, elucidation of genetic networks where miRNAs play pivotal roles often within feedback loops, and the promise of small RNAs as diagnostics and therapeutics in combating cancer.
Isozymes and restriction fragment length polymorphisms (RFLPs) have been proposed for use in varietal identification and selection for agronomic traits. Although the use of isozymes for these ...purposes has been well documented, evaluation of the efficacy of RFLP technology as applied to crop improvement is far from complete. This investigation was conducted to study the relationship between RFLP-derived genotypes and heterotic patterns of a group of maize (Zea mays L.) inbred lines. A total of 22 inbreds was crossed to four testers (B73, B76, Mo17, and Va26) in combinations that minimized crossing within heterotic groups. Forty-seven single-cross progeny were subsequently evaluated for several agronomic traits (including grain yield and moisture, ear height, and root lodging) over 2-4 consecutive years at two to four Iowa locations in a randomized complete-block design. The inbred lines were subjected to RFLP analysis, which involved 47 genomic clones and the restriction enzymes EcoRI and HindIII. Hybrid RFLP patterns were predicted from their inbred parents. Modified Roger's distances were computed to estimate genetic distance among the inbred lines. Principal component analysis facilitated ascertainment of relative dispersion of the inbreds based on the frequency of variants at specific RFLP loci. Evident associations of variants with genes affecting agronomic traits were identified by principal component regression analysis, in which adjusted hybrid means were regressed on the matrix of hybrid variants frequencies. The hybrid means were adjusted by removing environmental effects, using residuals as dependent variables in the regression analysis. Results from this study suggest that RFLP analysis may be of value in allocating maize inbreds to heterotic groups, but no relationship between RFLP-based genetic distance and hybrid performance was apparent. Principal component regression identified variants potentially linked to genes that control specific agronomic traits.
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