195 research outputs found

    Modulation of FAK and Src adhesion signaling occurs independently of adhesion complex composition

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    Integrin adhesion complexes (IACs) form mechanochemical connections between the extracellular matrix and actin cytoskeleton and mediate phenotypic responses via posttranslational modifications. Here, we investigate the modularity and robustness of the IAC network to pharmacological perturbation of the key IAC signaling components focal adhesion kinase (FAK) and Src. FAK inhibition using AZ13256675 blocked FAK(Y397) phosphorylation but did not alter IAC composition, as reported by mass spectrometry. IAC composition was also insensitive to Src inhibition using AZD0530 alone or in combination with FAK inhibition. In contrast, kinase inhibition substantially reduced phosphorylation within IACs, cell migration and proliferation. Furthermore using fluorescence recovery after photobleaching, we found that FAK inhibition increased the exchange rate of a phosphotyrosine (pY) reporter (dSH2) at IACs. These data demonstrate that kinase-dependent signal propagation through IACs is independent of gross changes in IAC composition. Together, these findings demonstrate a general separation between the composition of IACs and their ability to relay pY-dependent signals

    Photon assisted Levy flights of minority carriers in n-InP

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    We study the photoluminescence spectra of n-doped InP bulk wafers, both in the reflection and the transmission geometries relative to the excitation beam. From the observed spectra we estimate the spatial distribution of minority carriers allowing for the spectral filtering due to re-absorption of luminescence in the wafer. This distribution unambiguously demonstrates a non-exponential drop-off with distance from the excitation region. Such a behavior evidences an anomalous photon-assisted transport of minority carriers enhanced owing to the high quantum efficiency of emission. It is shown that the transport conforms very well to the so-called Levy-flights process corresponding to a peculiar random walk that does not reduce to diffusion. The index gamma of the Levy flights distribution is found to be in the range gamma = 0.64 to 0.79, depending on the doping. Thus, we propose the high-efficiency direct-gap semiconductors as a remarkable laboratory system for studying the anomalous transport.Comment: 12 pages, 9 figure

    To My Daughter

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    <p>Equal numbers of macaque CD34<sup>+</sup> cells were transduced in 3-d transduction cultures with either the HOXB4GFP or YFP vector and then cultured for an additional 9 d (T02266) or 6 d (K03290 and J02152) in the presence of SCF, TPO, Flt-3L, and G-CSF. All the transduced and expanded cells were infused into myeloablated animals. The percentage of HOXB4GFP<sup>+</sup> and YFP<sup>+</sup> granulocytes was assessed by flow cytometry. Shown is the engraftment of HOXB4GFP<sup>+</sup> and YFP<sup>+</sup> granulocytes after transplantation. (A) T02266, (B) K03290, and (C) J02152. </p

    A review of evidence about behavioural and psychological aspects of chronic joint pain among people with haemophilia

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    Joint pain related to haemophilia affects large numbers of people and has a significant impact on their quality of life. This article reviews evidence about behavioural and psychological aspects of joint pain in haemophilia, and considers that evidence in the context of research on other chronic pain conditions. The aim is to inform initiatives to improve pain self-management among people with haemophilia. Reduced pain intensity predicts better physical quality of life, so better pain management should lead to improved physical quality of life. Increased pain acceptance predicts better mental quality of life, so acceptance-based approaches to self-management could potentially be adapted for people with haemophilia. Pain self-management interventions could include elements designed to: improve assessment of pain; increase understanding of the difference between acute and chronic pain; improve adherence to clotting factor treatment; improve knowledge and understanding about the benefits and costs of using pain medications; improve judgments about what is excessive use of pain medication; increase motivation to self-manage pain; reduce negative emotional thinking about pain; and increase pain acceptance. The influence of behavioural and psychological factors related to pain are similar in haemophilia and other chronic pain conditions, so there should be scope for self-management approaches and interventions developed for other chronic pain conditions to be adapted for haemophilia, provided that careful account is taken of the need to respond promptly to acute bleeding pain by administering clotting factor

    Aboriginal Food Security in Northern Canada: An Assessment of the State of Knowledge

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    As the world’s population increases, as global markets become more interconnected, and as the effects of climate change become clearer, the issue of food insecurity is gaining traction at local, national, and international levels. The recent global economic crisis and increased food prices have drawn attention to the urgent situation of the world’s 870 million chronically undernourished people who face the number one worldwide risk to health: hunger and malnutrition. Although about 75% of the world’s undernourished people live in low-income, rural regions of developing countries, hunger is also an issue in Canada. In 2011, 1.6 million Canadian households, or slightly more than 12%, experienced some level of food insecurity. About one in eight households are affected, including 3.9 million individuals. Of these, 1.1 million are children. Food insecurity presents a particularly serious and growing challenge in Canada’s northern and remote Aboriginal communities (see Figure 1). Evidence from a variety of sources concludes that food insecurity among northern Aboriginal peoples is a problem that requires urgent attention to address and mitigate the serious impacts it has on health and well-being. Results from the 2007–2008 International Polar Year Inuit Health Survey indicate that Nunavut has the highest documented rate of food insecurity for any Indigenous population living in a developed country. According to estimates from the 2011 Canadian Community Health Survey (CCHS), off-reserve Aboriginal households across Canada experience food insecurity at a rate that is more than double that of all Canadian households (27%). Recent data indicate that Canadian households with children have a higher prevalence of food insecurity than households without children, and preliminary evidence indicates that more women than men are affected

    Differential Effects of HOXB4 on Nonhuman Primate Short- and Long-Term Repopulating Cells

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    BACKGROUND: Hematopoietic stem cells (HSCs) or repopulating cells are able to self-renew and differentiate into cells of all hematopoietic lineages, and they can be enriched using the CD34 cell surface marker. Because of this unique property, HSCs have been used for HSC transplantation and gene therapy applications. However, the inability to expand HSCs has been a significant limitation for clinical applications. Here we examine, in a clinically relevant nonhuman primate model, the ability of HOXB4 to expand HSCs to potentially overcome this limitation. METHODS AND FINDINGS: Using a competitive repopulation assay, we directly compared in six animals engraftment of HOXB4GFP (HOXB4 green fluorescent protein) and control (yellow fluorescent protein [YFP])–transduced and expanded CD34 (+) cells. In three animals, cells were infused after a 3-d transduction culture, while in three other animals cells were infused after an additional 6–9 d of ex vivo expansion. We demonstrate that HOXB4 overexpression resulted in superior engraftment in all animals. The most dramatic effect of HOXB4 was observed early after transplantation, resulting in an up to 56-fold higher engraftment compared to the control cells. At 6 mo after transplantation, the proportion of marker gene–expressing cells in peripheral blood was still up to 5-fold higher for HOXB4GFP compared to YFP-transduced cells. CONCLUSIONS: These data demonstrate that HOXB4 overexpression in CD34 (+) cells has a dramatic effect on expansion and engraftment of short-term repopulating cells and a significant, but less pronounced, effect on long-term repopulating cells. These data should have important implications for the expansion and transplantation of HSCs, in particular for cord blood transplantations where often only suboptimal numbers of HSCs are available

    Emotional distress in haemophilia: factors associated with the presence of anxiety and depression symptoms among adults

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    Introduction: Haemophilia is related to several clinical and psychosocial challenges that have been associated with increased emotional distress. These may impact on disease adjustment and health outcomes, reinforcing the attention given to psychosocial health of people with haemophilia (PWH), in the scope of optimal comprehensive care. Aim: To identify potentially modifiable factors associated with the presence of anxiety and depression symptoms among adult PWH. Methods: This was a cross-sectional observational study examining sociodemographic, clinical and psychosocial variables among 102 patients with haemophilia A or B who participated on a mail survey of haemophilia in Portugal. Results: People with haemophilia revealing higher anxiety and depression symptoms were more likely to have had, in the previous year, more urgent hospital visits due to haemophilia, more bleeding episodes, more affected joints and pain, as well as worst levels of perceived functionality and quality of life. After controlling for demographic (age and education) and clinical (haemophilia severity and joint deterioration) variables in multivariate hierarchical logistic regression analyses, professional status (OR = 4.646, P = .004; OR = 3.333, P = .029) and pain interference (OR = 1.397, P = .011; OR = .1.347, P = .037) were significantly associated with both anxiety and depression symptoms. Additionally, physical activity (OR = 0.302, P = .024) and the perception of consequences underlying haemophilia (OR = 1.600, P = .012) also emerged as key factors significantly associated with depression symptoms. Conclusion: Current findings increased knowledge on factors associated with anxiety and depression among PWH. These highlight potential intervention targets, which are amenable to change through evidence-based tailored interventions aiming to decrease emotional distress, promote well-being and improving haemophiliarelated health outcomes among these patients.Novo Nordisk HERO Research, Grant/Award Number: 2015; Portuguese Foundation for Science and Technology, Grant/Award Number: SFRH/BPD/103529/2014info:eu-repo/semantics/publishedVersio
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