770 research outputs found

    Expression of Protease-Activated Receptor 1 and 2 and Anti-Tubulogenic Activity of Protease-Activated Receptor 1 in Human Endothelial Colony-Forming Cells

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    Endothelial colony-forming cells (ECFCs) are obtained from the culture of human peripheral blood mononuclear cell (hPBMNC) fractions and are characterised by high proliferative and pro-vasculogenic potential, which makes them of great interest for cell therapy. Here, we describe the detection of protease-activated receptor (PAR) 1 and 2 amongst the surface proteins expressed in ECFCs. Both receptors are functionally coupled to extracellular signal-regulated kinase (ERK) 1 and 2, which become activated and phosphorylated in response to selective PAR1- or PAR2-activating peptides. Specific stimulation of PAR1, but not PAR2, significantly inhibits capillary-like tube formation by ECFCs in vitro, suggesting that tubulogenesis is negatively regulated by proteases able to stimulate PAR1 (e.g. thrombin). The activation of ERKs is not involved in the regulation of tubulogenesis in vitro, as suggested by use of the MEK inhibitor PD98059 and by the fact that PAR2 stimulation activates ERKs without affecting capillary tube formation. Both qPCR and immunoblotting showed a significant downregulation of vascular endothelial growth factor 2 (VEGFR2) in response to PAR1 stimulation. Moreover, the addition of VEGF (50–100 ng/ml) but not basic Fibroblast Growth Factor (FGF) (25–100 ng/ml) rescued tube formation by ECFCs treated with PAR1-activating peptide. Therefore, we propose that reduction of VEGF responsiveness resulting from down-regulation of VEGFR2 is underlying the anti-tubulogenic effect of PAR1 activation. Although the role of PAR2 remains elusive, this study sheds new light on the regulation of the vasculogenic activity of ECFCs and suggests a potential link between adult vasculogenesis and the coagulation cascade

    Meta-analysis of gender performance gaps in undergraduate natural science courses

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    To investigate patterns of gender-based performance gaps, we conducted a meta-analysis of published studies and unpublished data collected across 169 undergraduate biology and chemistry courses. While we did not detect an overall gender gap in performance, heterogeneity analyses suggested further analysis was warranted, so we investigated whether attributes of the learning environment impacted performance disparities on the basis of gender. Several factors moderated performance differences, including class size, assessment type, and pedagogy. Specifically, we found evidence that larger classes, reliance on exams, and undisrupted, traditional lecture were associated with lower grades for women. We discuss our results in the context of natural science courses and conclude by making recommendations for instructional practices and future research to promote gender equity

    Asymptotic bounds for the sizes of constant dimension codes and an improved lower bound

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    We study asymptotic lower and upper bounds for the sizes of constant dimension codes with respect to the subspace or injection distance, which is used in random linear network coding. In this context we review known upper bounds and show relations between them. A slightly improved version of the so-called linkage construction is presented which is e.g. used to construct constant dimension codes with subspace distance d=4d=4, dimension k=3k=3 of the codewords for all field sizes qq, and sufficiently large dimensions vv of the ambient space, that exceed the MRD bound, for codes containing a lifted MRD code, by Etzion and Silberstein.Comment: 30 pages, 3 table

    Mammals adjust diel activity across gradients of urbanization

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    Time is a fundamental component of ecological processes. How animal behavior changes over time has been explored through well-known ecological theories like niche partitioning and predator–prey dynamics. Yet, changes in animal behavior within the shorter 24-hr light–dark cycle have largely gone unstudied. Understanding if an animal can adjust their temporal activity to mitigate or adapt to environmental change has become a recent topic of discussion and is important for effective wildlife management and conservation. While spatial habitat is a fundamental consideration in wildlife management and conservation, temporal habitat is often ignored. We formulated a temporal resource selection model to quantify the diel behavior of 8 mammal species across 10 US cities. We found high variability in diel activity patterns within and among species and species-specific correlations between diel activity and human population density, impervious land cover, available greenspace, vegetation cover, and mean daily temperature. We also found that some species may modulate temporal behaviors to manage both natural and anthropogenic risks. Our results highlight the complexity with which temporal activity patterns interact with local environmental characteristics, and suggest that urban mammals may use time along the 24-hr cycle to reduce risk, adapt, and therefore persist, and in some cases thrive, in human-dominated ecosystems

    Reinventing grounded theory: some questions about theory, ground and discovery

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    Grounded theory’s popularity persists after three decades of broad-ranging critique. In this article three problematic notions are discussed—‘theory,’ ‘ground’ and ‘discovery’—which linger in the continuing use and development of grounded theory procedures. It is argued that far from providing the epistemic security promised by grounded theory, these notions—embodied in continuing reinventions of grounded theory—constrain and distort qualitative inquiry, and that what is contrived is not in fact theory in any meaningful sense, that ‘ground’ is a misnomer when talking about interpretation and that what ultimately materializes following grounded theory procedures is less like discovery and more akin to invention. The procedures admittedly provide signposts for qualitative inquirers, but educational researchers should be wary, for the significance of interpretation, narrative and reflection can be undermined in the procedures of grounded theory

    Emergence of Variability in Isogenic Escherichia coli Populations Infected by a Filamentous Virus

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    The spread of epidemics not only depends on the average number of parasites produced per host, but also on the existence of highly infectious individuals. It is widely accepted that infectiousness depends on genetic and environmental determinants. However, even in clonal populations of host and viruses growing in homogeneous conditions, high variability can exist. Here we show that Escherichia coli cells commonly display high differentials in viral burst size, and address the kinetics of emergence of such variability with the non-lytic filamentous virus M13. By single-cell imaging of a virally-encoded fluorescent reporter, we monitor the viral charge distribution in infected bacterial populations at different time following infection. A mathematical model assuming autocatalytic virus replication and inheritance of bacterial growth rates quantitatively reproduces the experimental distributions, demonstrating that deterministic amplification of small host inhomogeneities is a mechanism sufficient to explain large and highly skewed distributions. This mechanism of amplification is general and may occur whenever a parasite has an initial phase of exponential growth within its host. Moreover, it naturally reproduces the shift towards higher virulence when the host is experimenting poor conditions, as observed commonly in host-parasite systems
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