Mediators of monocyte activity in inflammation

C-reactive protein (CRP) is the prototypic acute phase serum protein in humans. CRP is currently one of the best markers of inflammatory disease and disease activity. One of the keys cells involved in inflammation within chronic inflammatory diseases is the monocyte. Monocytes are able to modulate inflammation through cytokine expression, cytosolic peroxide formation, adhesion molecule expression and subsequent adhesion/migration to sites of inflammation. CRP has been previously shown to bind directly to monocytes through Fc receptors. However this observation is not conclusive and requires further investigation. The effects of incubation of CRP with human primary and monocytic cell lines were examined using monocytic cytokine expression, adhesion molecule expression and adhesion to endothelial cells and intracellular peroxide formation, as end points. Monocytic intracellular signalling events were investigated after interaction of CRP with specific CRP receptors on monocytes. These initial signalling events were examined for their role in modulating monocytic adhesion molecule and cytokine expression. Monocyte recruitment and retention in the vasculature is also influenced by oxidative stress. Therefore the effect of 6 weeks of antioxidant intervention in vivo was examined on monocytic adhesion molecule expression, adhesion to endothelial cells ex vivo and on serum CRP concentrations, pre- and post- supplementation with the antioxidants vitamin C and vitaInin E. In summary, CRP is able to bind FcγRIIa. CRP binding FcγR initiates an intracellular signalling cascade that phosphorylates the non-receptor tyrosine kinase, Syk, associated with intracellular tyrosine activating motifs on the cytoplasmic tail of Fcγ receptors. CRP incubations increased phosphatidyl inositol turnover and Syk phosphorylation ultimately lead to Ca2+ mobilisation in monocytes. CRP mediated Syk phosphorylation in monocytes leads to an increase in CD 11b and IL-6 expression. CRP engagement with monocytes also leads to an increase in peroxide production, which can be inhibited in vitro using the antioxidants α-tocopherol and ascorbic acid. CRP mediated CD 11b expression is not redox regulated by CRP mediated changes in cytosolic peroxides. The FcyRIla polymorphism at codon 131 effects the phenotypic driven changes described in monocytes by CRP, where R/R allotypes have a greater increase in CD11b, in response to CRP, which may be involved in promoting the monocytic inflammatory response. CRP leads to an increase in the expression of pro-inflammatory cytokines, which alters the immune phenotype of circulating monocytes. Vitamin C supplementation reduced monocytic adhesion to endothelial cells, but had no effect on serum levels of CRP. Where long-term antioxidant intervention may provide benefit from the risk of developing vascular inflammatory disease, by reducing monocytic adhesion to the vasculature. In conclusion CRP appears to be much more than just a marker of ongoing inflammation or associated inflammatory disease and disease activity. This data suggests that at pathophysiological concentrations, CRP may be able to directly modulate inflammation through interacting with monocytes and thereby alter the inflammatory response associated with vascular inflammatory diseases

The Structure of Koolau Volcano from Seismic Refraction Studies

Volume: 19Start Page: 306End Page: 31

New Alleles in the “RN gene” Associated with Low Glycogen Content in Pig Skeletal Muscle and Improved Meat Quality

Several quantitative trait loci (QTL) affecting muscle glycogen content and related meat quality traits were mapped to pig chromosome 15 (SSC 15) by using a three-generation intercross between Berkshire x Yorkshire pigs. Based on the QTL location, the PRKAG3 (protein kinase AMPactivated, γ3 subunit) or the RN (Rendement Napole) gene, as it is popularly known, was considered to be a good candidate for the observed effects. Differences in the PRKAG3 gene sequences of the founder animals of the intercross were analyzed. The RN- mutation previously reported was not present in the cross but three missense substitutions (changes affecting proteins) were identified. To test the hypothesis that at least one of these mutations was associated with differences in meat quality, more than 1,800 animals from several unrelated commercial lines were genotyped for the candidate gene differences and an association study was performed. The results provide strong support for the presence of new economically important alleles (gene forms) of the PRKAG3 gene affecting the glycogen content in the muscle and the resulting meat quality. Because of their prevalence in the more common commercial breeds, the potential implications for the pig industry and consumers are probably more important than the original discovery of the RN- mutation

Mathematical modelling of fibre-enhanced perfusion inside\ud a tissue-engineering bioreactor

We develop a simple mathematical model for forced flow of culture medium through a porous scaffold in a tissue- engineering bioreactor. Porous-walled hollow fibres penetrate the scaffold and act as additional sources of culture medium. The model, based on Darcy’s law, is used to examine the nutrient and shear-stress distributions throughout the scaffold. We consider several configurations of fibres and inlet and outlet pipes. Compared with a numerical solution of the full Navier–Stokes equations within the complex scaffold geometry, the modelling approach is cheap, and does not require knowledge of the detailed microstructure of the particular scaffold being used. The potential of this approach is demonstrated through quantification of the effect the additional flow from the fibres has on the nutrient and shear-stress distribution

Ontology mapping for semantically enabled applications

In this review, we provide a summary of recent progress in ontology mapping (OM) at a crucial time when biomedical research is under a deluge of an increasing amount and variety of data. This is particularly important for realising the full potential of semantically enabled or enriched applications and for meaningful insights, such as drug discovery, using machine-learning technologies. We discuss challenges and solutions for better ontology mappings, as well as how to select ontologies before their application. In addition, we describe tools and algorithms for ontology mapping, including evaluation of tool capability and quality of mappings. Finally, we outline the requirements for an ontology mapping service (OMS) and the progress being made towards implementation of such sustainable services

How do undergraduate medical students perceive social accountability?

Aim: The concept of social accountability within undergraduate training is embedded within the remit of medical schools. Little is known of how medical students perceive social accountability, recognize aspects of their training contributing to the development of this concept and cultivate the underpinning values. Methods: Students nearing graduation were recruited to participate in focus groups designed to explore their perceptions of social accountability, which curricular aspects had contributed to their understanding, and to investigate the implications of individual variations in training. Results: Students expressed limited appreciation of the concept of social accountability and acknowledged little explicit teaching around underpinning core concepts such as awareness of local health needs, advocacy and nurturing of altruism. However, participants recognized numerous aspects of the course and learning initiatives as impacting on their attitudes towards this concept implicitly. Conclusion: This study highlights areas of their undergraduate training that students recognize as having the greatest impact on their development into socially accountable professionals. It poses some significant challenges for health care educators in addressing unintended consequences, including an outcome-driven educational approach, in reducing students’ capacity or willingness to engage in curricular challenges often designed to embed this concept

Review of Naturaleza creativa

The short monograph Creative Nature (Francisco Javier Novo, Rubén Pereda, and Javier Sánchez -Cañizares. 2018. Naturaleza Creativa. Madrid: Rialp. ISBN: 978-84- 321-4916-0. 196 pp. Paperback, €14.25) is a welcome contribution to the philosophy of nature that arose from interdisciplinary conversations between authors who are both up-to-date in the scientific literature and deeply grounded in the western intellectual tradition. The authors draw from modern physics, biochemistry, evolutionary biology, developmental biology and ecology to argue that nature is creative in the sense that an “open future” of our evolving world lies ahead. In this review essay, divided into two parts, we offer a chapter-by-chapter summary covering Nature, Life, Change, Limits, Functions and Creativity. In conclusion, we offer some pedagogical possibilities. The second part proposes certain points for deeper reflection

Pierre Duhem and scientific truth: contextual, partial and real

Mariano Artigas understood scientific truth as real, but at the same time contextual and partial. Artigas shared some research interests and a general outlook with Pierre Duhem. We summarize the evaluation of Duhem’s thought by relevant authors and demonstrate how the way Artigas understood scientific truth in actual scientific research offers a suitable framework for capturing the realism towards which Duhem tended. This reading of Duhem runs counter to tendencies of the philosophy of science in Duhem’s time which employed expressions that sometimes framed him as a conventionalist