SNP-induced Dilation Following a Short-term Intraluminal Pressure Increase in Aged Skeletal Muscle Feed Arteries

A decline in peripheral vascular function occurs with age and is associated with an increased risk for cardiovascular disease. Moderate, aerobic exercise has been documented to improve or reverse the age-related decline in vascular function. The signal(s) associated with exercise responsible for the improvement in vascular function is not known; however, increased intraluminal pressure that occurs during a bout of exercise has been proposed to play an integral role. Previously, we reported that exposure to a short-term increase in intraluminal pressure improves endothelium-dependent vasodilator responses in aged arteries. The purpose of this study was to determine whether pressure treatment enhances endothelium-independent vasodilator responses. We hypothesized that a short-term (1 h) increase in intraluminal pressure, to mimic the intraluminal pressure believed to be present during a 1 h bout of exercise, would not improve endothelium-independent vasodilator responses. Soleus muscle feed arteries from young (4 month) and old (24 month) Fischer 344 rats were isolated, cannulated, and pressurized at 90 (P90) or 130 (P130) cmH20 for 1 h. Following the 1 h pressure treatment, intraluminal pressure was lowered to 90 cmH20 for all vessels and SNP-induced vasodilation was assessed immediately or following a 2 h recovery period. SNP-induced dilation was significantly blunted in old P90 SFA when compared to young P90 SFA. Pre-treatment with increased intraluminal pressure for 1 h improved SNP-induced vasodilator responses and abolished the age group difference between the old and young SFA. Maximal dilation to SNP was greater in the young P130 compared to the young P90 SFA. The effects of the 1 h increased intraluminal pressure treatment were no longer present following a 2 h recovery period. Collectively, these results indicate that treatment of aged arteries with a short-term increase in intraluminal pressure to mimic pressure during a bout of exercise improves endothelium-independent dilation in aged arteries. In addition, these results suggest that a short-term increase in intraluminal pressure, associated with a single bout of exercise, is one signal contributing to the beneficial effect of exercise on vasodilator responses in aged arteries

Self-cleaning and colour-preserving efficiency of photocatalytic concrete: case study of the Jubilee Church in Rome

The Jubilee Church in the south-eastern outskirts of Rome is one of the first buildings constructed with super white reinforced concrete with self-cleaning photocatalytic cement. However, 16 years after the opening of the building, the self-cleaning and colour-preserving properties arising from the titania particles (TiO2) within the concrete mix are not meeting the design requirements and the concrete is showing premature evidence of decay. While the form of the decay is affecting the appearance of the building and not its structural soundness, the ageing pattern of the building's components is resulting in a high maintenance cost, one not easily affordable within the ordinary budget supported by a small parish. This study comprises the first comprehensive step in understanding the causes of the accelerated ageing pattern of the concrete, highlighting methods to improve the long-term durability of the concrete and therefore reduce the cost of its maintenance. Moreover, this research offered the opportunity to test the durability and the effectiveness of the TiO2 in the real conditions on an actual building featuring non-standard geometries. The findings highlight how the ageing pattern directly connects with the geometry of the building and inadequate consideration of the local weathering at the design stage

Ethics of Engagement and Insider-Outsider Perspectives: Issues and Dilemmas in Cross-Cultural Interpretation

This article offers insights into the ethics of engagement and methodological issues and dilemmas in cross-cultural interpretation for researchers who are positioned at different points of the insider-outsider spectrum. The discussion uses examples from qualitative research with Sikh families in Britain and focuses on the design of the methodology and co-interpretation of data from in-depth interviews, both during the interactive data gathering phase and the post-interview analysis and interpretation phase. The researchers represent differing degrees of insider-outsiderness in relation to the British Sikh community; one is a cultural insider (a Sikh) whilst the other is an outsider (non-Sikh). In other respects they share a number of characteristics, including gender, a history of migration, bilingualism and living and teaching in superdiverse communities which all impact on the nature of their engagement with the research participants and with each other as co-researchers. Our reflexive analysis shows that established binary distinctions and polarities in research practice, such as insider/outsider, are inadequate for conceptualising the fluidity and complexity of the ethics of engagement in co-researching. We argue that both theoretically and empirically a more nuanced conceptualisation reflects the realities of multiple researcher positionalities, interpretations and power relations

A critical role for endocytosis in Wnt signaling

BACKGROUND: The Wnt signaling pathway regulates many processes during embryonic development, including axis specification, organogenesis, angiogenesis, and stem cell proliferation. Wnt signaling has also been implicated in a number of cancers, bone density maintenance, and neurological conditions during adulthood. While numerous Wnts, their cognate receptors of the Frizzled and Arrow/LRP5/6 families and downstream pathway components have been identified, little is known about the initial events occurring directly after receptor activation. RESULTS: We show here that Wnt proteins are rapidly endocytosed by a clathrin- and dynamin-mediated process. While endocytosis has traditionally been considered a principal mechanism for receptor down-regulation and termination of signaling pathways, we demonstrate that interfering with clathrin-mediated endocytosis actually blocks Wnt signaling at the level of β-catenin accumulation and target gene expression. CONCLUSION: A necessary component of Wnt signaling occurs in a subcellular compartment distinct from the plasma membrane. Moreover, as internalized Wnts transit partially through the transferrin recycling pathway, it is possible that a "signaling endosome" serves as a nexus for activated Wnt pathway components