3,407 research outputs found

    Seeing You, Seeing Me: Social Perspective-Taking as Learning

    Get PDF
    This paper examines the use of social perspective-taking as learning in an education course in an undergraduate teacher education program. Using curriculum documents, student writing, field notes, faculty journals, and focus group interviews, the study identified the foundational/multicultural content understandings and the emotional responses that social perspective-taking activities promoted. Implications of social perspective-taking in teacher education courses and broader programmatic questions about social perspective-taking pedagogy for teaching and learning are addressed

    Vascular smooth muscle contraction in hypertension

    Get PDF
    Hypertension is a major risk factor for many common chronic diseases, such as heart failure, myocardial infarction, stroke, vascular dementia and chronic kidney disease. Pathophysiological mechanisms contributing to the development of hypertension include increased vascular resistance, determined in large part by reduced vascular diameter due to increased vascular contraction and arterial remodelling. These processes are regulated by complex interacting systems such as the renin angiotensin aldosterone system (RAAS), sympathetic nervous system, immune activation and oxidative stress, which influence vascular smooth muscle function. Vascular smooth muscle cells are highly plastic and in pathological conditions undergo phenotypic changes from a contractile to a proliferative state. Vascular smooth muscle contraction is triggered by an increase in intracellular free calcium concentration ([Ca2+]i), promoting actin-myosin cross-bridge formation. Growing evidence indicates that contraction is also regulated by calcium-independent mechanisms involving RhoA-Rho kinase (ROCK), protein kinase C (PKC) and mitogen-activated protein kinase (MAPK) signaling, reactive oxygen species and reorganization of the actin cytoskeleton. Activation of immune/inflammatory pathways and noncoding RNAs are also emerging as important regulators of vascular function. Vascular smooth muscle cell [Ca2+]i, not only determines the contractile state but also influences activity of many calcium-dependent transcription factors and proteins thereby impacting the cellular phenotype and function. Perturbations in vascular smooth muscle cell signaling and altered function influence vascular reactivity and tone, important determinants of vascular resistance and blood pressure. Here we discuss mechanisms regulating vascular reactivity and contraction in physiological and pathophysiological conditions and highlight some new advances in the field, focusing specifically on hypertension

    Co-Stimulation of PAFR and CD36 Is Required for oxLDL-Induced Human Macrophages Activation

    Get PDF
    The oxidative process of LDL particles generates molecules which are structurally similar to platelet-activating factor (PAF), and some effects of oxidized LDL (oxLDL) have been shown to be dependent on PAF receptor (PAFR) activation. In a previous study, we showed that PAFR is required for upregulation of CD36 and oxLDL uptake. In the present study we analyzed the molecular mechanisms activated by oxLDL in human macrophages and the contribution of PAFR to this response. Human adherent monocytes/macrophages were stimulated with oxLDL. Uptake of oxLDL and CD36 expression were determined by flow cytometry; MAP kinases and Akt phosphorylation by Western blot; IL-8 and MCP-1 concentration by ELISA and mRNA expression by real-time PCR. To investigate the participation of the PI3K/Akt pathway, Gαi-coupled protein or PAFR, macrophages were treated with LY294002, pertussis toxin or with the PAFR antagonists WEB2170 and CV3988, respectively before addition of oxLDL. It was found that the addition of oxLDL to human monocytes/macrophages activates the PI3K/Akt pathway which in turn activates the MAPK (p38 and JNK). Phosphorylation of Akt requires the engagement of PAFR and a Gαi-coupled protein. The upregulation of CD36 protein and the uptake of oxLDL as well as the IL-8 production are dependent on PI3K/Akt pathway activation. The increased CD36 protein expression is dependent on PAFR and Gαi-coupled protein. Transfection studies using HEK 293t cells showed that oxLDL uptake occurs with either PAFR or CD36, but IL-8 production requires the co-transfection of both PAFR and CD36. These findings show that PAFR has a pivotal role in macrophages response to oxLDL and suggest that pharmacological intervention at the level of PAFR activation might be beneficial in atherosclerosis

    Vascular Biology of Superoxide-Generating NADPH Oxidase 5—Implications in Hypertension and Cardiovascular Disease

    Get PDF
    Significance: NADPH oxidases (Noxs), of which there are seven isoforms (Nox1–5, Duox1/Duox2), are professional oxidases functioning as reactive oxygen species (ROS)-generating enzymes. ROS are signaling molecules important in physiological processes. Increased ROS production and altered redox signaling in the vascular system have been implicated in the pathophysiology of cardiovascular diseases, including hypertension, and have been attributed, in part, to increased Nox activity. Recent Advances: Nox1, Nox2, Nox4, and Nox5 are expressed and functionally active in human vascular cells. While Nox1, Nox2, and Nox4 have been well characterized in models of cardiovascular disease, little is known about Nox5. This may relate to the lack of experimental models because rodents lack NOX5. However, recent studies have advanced the field by (i) elucidating mechanisms of Nox5 regulation, (ii) identifying Nox5 variants, (iii) characterizing Nox5 expression, and (iv) discovering the Nox5 crystal structure. Moreover, studies in human Nox5-expressing mice have highlighted a putative role for Nox5 in cardiovascular disease. Critical Issues: Although growing evidence indicates a role for Nox-derived ROS in cardiovascular (patho)physiology, the exact function of each isoform remains unclear. This is especially true for Nox5. Future Directions: Future directions should focus on clinically relevant studies to discover the functional significance of Noxs, and Nox5 in particular, in human health and disease. Two important recent studies will impact future directions. First, Nox5 is the first Nox to be crystallized. Second, a genome-wide association study identified Nox5 as a novel blood pressure-associated gene. These discoveries, together with advancements in Nox5 biology and biochemistry, will facilitate discovery of drugs that selectively target Noxs to interfere in uncontrolled ROS generation

    TRPM7, magnesium and signaling

    Get PDF
    The transient receptor potential melastatin-subfamily member 7 (TRPM7) is a ubiquitously expressed chanzyme that possesses an ion channel permeable to the divalent cations Mg2+, Ca2+, and Zn2+, and an α-kinase that phosphorylates downstream substrates. TRPM7 and its homologue TRPM6 have been implicated in a variety of cellular functions and is critically associated with intracellular signaling, including receptor tyrosine kinase (RTK)-mediated pathways. Emerging evidence indicates that growth factors, such as EGF and VEGF, signal through their RTKs, which regulate activity of TRPM6 and TRPM7. TRPM6 is primarily an epithelial-associated channel, while TRPM7 is more ubiquitous. In this review we focus on TRPM7 and its association with growth factors, RTKs, and downstream kinase signaling. We also highlight how interplay between TRPM7, Mg2+ and signaling kinases influences cell function in physiological and pathological conditions, such as cancer and preeclampsia

    Involvement and Image Transfer in Sports Sponsorship

    Get PDF
    Sponsorships have become one of the most important marketing tools. Data show that a majority of sporting events is sponsored and that investment in sponsorship is increasing every year. Companies are demanding more research to better understand their investment efficacy. Involvement is a key element in processing sponsorship information in consumers' minds. This variable affects consumer behavior and moderates the sponsor image transfer. The study of involvement could give guidance for the design of appropriate and functional advertising campaigns. The research proposes segmenting and modelling sport consumer behaviour in sponsorship by their level of involvement with the event. For this task, we propose a model for image transfer between the sponsored entity and the sponsor. Using Finite Mix Partial Least Square methods, two sample segments are achieved. The data were obtained with a web banner during an international tennis event. In conclusion, the least involved individuals do not process the image transfer effect, as opposed to the individuals who are more involved. In the theoretical field, this paper is the first to include segmentation by Finite Mix in sponsorship research. Finally, attraction and involvement strategies are proposed based on the characteristics for each of the variables in this model, for example, regular meetings for fans, autograph signings and weekly chat sessions on the web site. This study provides guidance for companies about how to increase their customers' willingness to purchase, how to improve their image, how to increase supporters' involvement and finally, how to design effective communication for supporters according to their level of involvement

    Vascular biology of superoxide-generating NADPH oxidase 5 (Nox5)- implications in hypertension and cardiovascular disease

    Get PDF
    SIGNIFICANCE: NADPH oxidases (Nox) of which there are 7 isoforms (Nox1-5, Duox1/Duox2) are professional oxidases functioning as ROS-generating enzymes. ROS are signaling molecules important in physiological processes. Increased ROS production and altered redox signaling in the vascular system have been implicated in the pathophysiology of cardiovascular diseases, including hypertension, and have been attributed, in part, to increased Nox activity. RECENT ADVANCES: Nox1,2,4,5 are expressed and functionally active in human vascular cells. While Nox1,2,4 have been well characterized in models of cardiovascular disease, little is known about Nox5. This may relate to the lack of experimental models because rodents lack NOX5. However, recent studies have advanced the field by i) elucidating mechanisms of Nox5 regulation, ii) identifying Nox5 variants, iii) characterizing Nox5 expression and iv) discovery of Nox5 crystal structure. Moreover, studies in human Nox5-expressing mice have highlighted a putative role for Nox5 in cardiovascular disease. CRITICAL ISSUES: Although growing evidence indicates a role for Nox-derived ROS in cardiovascular (patho)physiology, the exact function of each isoform remains unclear. This is especially true for Nox5. FUTURE DIRECTIONS: Future directions should focus on clinically-relevant studies to discover the functional significance of Noxs, and Nox5 in particular, in human health and disease. Two important recent studies will impact future directions. Firstly, Nox5 is the first Nox to be crystalized. Secondly GWAS identified Nox5 as a novel blood pressure-associated gene. These discoveries, together with advancements in Nox5 biology and biochemistry, will facilitate discovery of drugs th at selectively target Noxs to interfere with uncontrolled ROS generation
    • …
    corecore