371 research outputs found

    Dynamics of macrophage polarization reveal new mechanism to inhibit IL-1β release through pyrophosphates

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    In acute inflammation, extracellular ATP activates P2X7 ion channel receptors (P2X7R) on M1 polarized macrophages to release pro-inflammatory IL-1β through activation of the caspase-1/nucleotide-binding domain and leucine-rich repeat receptor containing pyrin domain 3 (NLRP3) inflammasome. In contrast, M2 polarized macrophages are critical to the resolution of inflammation but neither actions of P2X7R on these macrophages nor mechanisms by which macrophages switch from pro-inflammatory to anti-inflammatory phenotypes are known. Here, we investigated extracellular ATP signalling over a dynamic macrophage polarity gradient from M1 through M2 phenotypes. In macrophages polarized towards, but not at, M2 phenotype, in which intracellular IL-1β remains high and the inflammasome is intact, P2X7R activation selectively uncouples to the NLRP3-inflammasome activation but not to upstream ion channel activation. In these intermediate M1/M2 polarized macrophages, extracellular ATP now acts through its pyrophosphate chains, independently of other purine receptors, to inhibit IL-1β release by other stimuli through two independent mechanisms: inhibition of ROS production and trapping of the inflammasome complex through intracellular clustering of actin filaments

    What makes you not a Buddhist? : a preliminary mapping of values

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    This study sets out to establish which Buddhist values contrasted with or were shared by adolescents from a non-Buddhist population. A survey of attitude toward a variety of Buddhist values was fielded in a sample of 352 non-Buddhist schoolchildren aged between 13 and 15 in London. Buddhist values where attitudes were least positive concerned the worth of being a monk/nun or meditating, offering candles & incense on the Buddhist shrine, friendship on Sangha Day, avoiding drinking alcohol, seeing the world as empty or impermanent and Nirvana as the ultimate peace. Buddhist values most closely shared by non-Buddhists concerned the Law of Karma, calming the mind, respecting those deserving of respect, subjectivity of happiness, welfare work, looking after parents in old age and compassion to cuddly animals. Further significant differences of attitude toward Buddhism were found in partial correlations with the independent variables of sex, age and religious affiliation. Correlation patterns paralleled those previously described in theistic religions. Findings are applied to spiritual, moral, social and cultural development and for the teaching of religious to pupils of no faith adherence. The study recommends that quantitative psychometrics employed to conceptualize Buddhist values by discriminant validity in this study could be extended usefully to other aspects of the study of Buddhism, particularly in quest of validity in the conceptualization of Buddhist identity within specifically Buddhist populations

    From community to assemblage? : ICT provides a site for inclusion and exclusion in the global south

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    The role of information and communication technology (ICT) in development has been discussed from two distinctly different perspectives: some view it as a means for opening new alleys for the facilitation of development and democracy, while others assess it as counterproductive. Furthermore, it has been emphasised that people in cities and rural areas utilise ICT in different ways, as do people with wealth and education compared to poor people. In Africa, Kenya has declared itself an ICT hub. The state has emphasised ICT in promoting services, much less freedom of expression. This article discusses ICT and development via the filter of assemblage, a key concept developed by Deleuze and Guattari (2004/1980. A Thousand Plateaus: Capitalism and Schizophrenia. London: Continuum.). They emphasised fluidity as well as micro- and macro-level dichotomies. When communities based on sharing and consistent social order meet new technology, the change goes deeper than that of improved services. The basic difference might be the fact that a community is constructed on cultural ties developed over time, which strengthens immobility and stability, while an assemblage is characterised by mobility and fluidity. Thus, a system of values, hierarchies, and inherited traditions is challenged, mixed with ‘new’ problems brought about by individualised behaviour.Peer reviewe

    Tick-borne encephalitis in north-east Italy: a 14-year retrospective study, January 2000 to December 2013

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    Italy is considered at low incidence of tick-borne encephalitis (TBE), and the occurrence of human cases of TBE appears to be geographically restricted to the north east of the country. However, most information to date derives from case series, with no systematic data collection. To estimate incidence rates (IR) and spatial distribution of TBE cases, we conducted a retrospective study in north-eastern Italy. Data were collected through the infectious disease units and public health districts of three regions (Friuli Venezia Giulia, Trentino Alto Adige and Veneto) between 2000 and 2013. Overall, 367 cases were identified (IR: 0.38/100,000). The cases' median age was 56 years and 257 (70%) were male. Central nervous system involvement was reported in 307 cases (84%). Annual fluctuations in case numbers occurred, with peaks in 2006 and in 2013, when 44 and 42 cases were respectively observed. A strong seasonality effect was noted, with the highest number of cases in July. In terms of geographical location, three main endemic foci with high TBE IR (> 10/100,000) were identified in three provinces, namely Belluno (Veneto region), Udine (Friuli Venezia Giulia) and Trento (Trentino Alto-Adige). When investigating the whole study area in terms of altitude, the IR between 400 and 600\u2009m was greater (2.41/100,000) than at other altitudes (p< 0.01). In conclusion, the incidence of TBE in Italy is relatively low, even considering only the three known affected regions. However, three endemic foci at high risk were identified. In these areas, where the risk of TBEV infection is likely high, more active offer of TBE vaccination could be considere

    High expression of CXCR4 may predict poor survival in resected pancreatic adenocarcinoma

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    Chemokines and their receptors are involved in tumourigenicity and clinicopathological significance of chemokines receptor expression in pancreatic adenocarcinoma (PA) is not fully understood. This study was conducted to determine patients' outcome according to the expressions of CXCR4, CXCR7 and HIF-1α after resection of PA. Immunohistochemistry for CXCR4, CXCR7 and HIF-1α expressions as well as cell proliferative index (Ki-67) was conducted in 71 resected (R0) PA and their 48 related lymph nodes (LN) using tissue microarray. CXCR4 and CXCR7 expressions were positively correlated to HIF-1α suggesting a potential role of HIF-1α in CXCR4 and CXCR7 transcription activation. Patients with CXCR4high tumour expression had shorter OS than those with low expression (median survival: 9.7 vs 43.2 months, P=0.0006), a higher risk of LN metastases and liver recurrence. In multivariate analysis, high CXCR4 expression, LN metastases and poorly differentiated tumour are independent negative prognosis factors. In a combining analysis, patients with CXCR4low/CXCR7low tumour had a significantly shorter DFS and OS than patients with a CXCR7high/CXCR4high tumour. CXCR4 in resected PA may represent a valuable prognostic factor as well as an attractive target for therapeutic purpose

    CXCL12 expression by healthy and malignant ovarian epithelial cells

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    <p>Abstract</p> <p>Background</p> <p>CXCL12 has been widely reported to play a biologically relevant role in tumor growth and spread. In epithelial ovarian cancer (EOC), CXCL12 enhances tumor angiogenesis and contributes to the immunosuppressive network. However, its prognostic significance remains unclear. We thus compared CXCL12 status in healthy and malignant ovaries, to assess its prognostic value.</p> <p>Methods</p> <p>Immunohistochemistry was used to analyze CXCL12 expression in the reproductive tracts, including the ovaries and fallopian tubes, of healthy women, in benign and borderline epithelial tumors, and in a series of 183 tumor specimens from patients with advanced primary EOC enrolled in a multicenter prospective clinical trial of paclitaxel/carboplatin/gemcitabine-based chemotherapy (GINECO study). Univariate COX model analysis was performed to assess the prognostic value of clinical and biological variables. Kaplan-Meier methods were used to generate progression-free and overall survival curves.</p> <p>Results</p> <p>Epithelial cells from the surface of the ovary and the fallopian tubes stained positive for CXCL12, whereas the follicles within the ovary did not. Epithelial cells in benign, borderline and malignant tumors also expressed CXCL12. In EOC specimens, CXCL12 immunoreactivity was observed mostly in epithelial tumor cells. The intensity of the signal obtained ranged from strong in 86 cases (47%) to absent in 18 cases (<10%). This uneven distribution of CXCL12 did not reflect the morphological heterogeneity of EOC. CXCL12 expression levels were not correlated with any of the clinical parameters currently used to determine EOC prognosis or with HER2 status. They also had no impact on progression-free or overall survival.</p> <p>Conclusion</p> <p>Our findings highlight the previously unappreciated constitutive expression of CXCL12 on healthy epithelia of the ovary surface and fallopian tubes, indicating that EOC may originate from either of these epithelia. We reveal that CXCL12 production by malignant epithelial cells precedes tumorigenesis and we confirm in a large cohort of patients with advanced EOC that CXCL12 expression level in EOC is not a valuable prognostic factor in itself.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00052468">NCT00052468</a></p

    Developing a collaborative agenda for humanities and social scientific research on laboratory animal science and welfare.

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    Improving laboratory animal science and welfare requires both new scientific research and insights from enquiry in the humanities and social sciences. Whilst scientific research provides evidence to replace, reduce and refine procedures involving laboratory animals (the ‘3Rs’), work in the humanities and social sciences can help understand the social, economic and cultural processes that enhance or impede humane ways of knowing and working with laboratory animals. However, communication across these disciplinary perspectives is currently limited, and they frame questions, generate results, engage users, and seek to influence policy in different ways. To facilitate dialogue and future research at this interface, we convened an interdisciplinary group of 45 life scientists, social scientists, humanities scholars, non-governmental organisations and policy-makers to generate a collaborative research agenda. This drew on other agenda-setting exercises in science policy, using a collaborative and deliberative approach for the identification of research priorities. Participants were recruited from across the community, invited to submit research questions and vote on their priorities. They then met at an interactive workshop in the UK, discussed all 136 questions submitted, and collectively defined the 30 most important issues for the group. The output is a collaborative future agenda for research in the humanities and social sciences on laboratory animal science and welfare. The questions indicate a demand for new research in the humanities and social sciences to inform emerging discussions and priorities on the governance and practice of laboratory animal research, including around: international harmonisation, openness and public engagement, ‘cultures of care’, harm-benefit analysis and the future of the 3Rs. The process underlines the value of interdisciplinary exchange for improving mutual understanding of different research cultures and identifies ways of enhancing the effectiveness of future research at the interface between the humanities, social sciences, science and science policy
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