Punicic Acid a Conjugated Linolenic Acid Inhibits TNFα-Induced Neutrophil Hyperactivation and Protects from Experimental Colon Inflammation in Rats

BACKGROUND:Neutrophils play a major role in inflammation by releasing large amounts of ROS produced by NADPH-oxidase and myeloperoxidase (MPO). The proinflammatory cytokine TNFalpha primes ROS production through phosphorylation of the NADPH-oxidase subunit p47phox on Ser345. Conventional anti-inflammatory therapies remain partially successful and may have side effects. Therefore, regulation of neutrophil activation by natural dietary components represents an alternative therapeutic strategy in inflammatory diseases such as inflammatory bowel diseases. The aim of this study was to assess the effect of punicic acid, a conjugated linolenic fatty acid from pomegranate seed oil on TNFalpha-induced neutrophil hyperactivation in vitro and on colon inflammation in vivo. METHODOLOGY AND PRINCIPAL FINDINGS:We analyzed the effect of punicic acid on TNFalpha-induced neutrophil upregulation of ROS production in vitro and on TNBS-induced rat colon inflammation. Results show that punicic acid inhibited TNFalpha-induced priming of ROS production in vitro while preserving formyl-methionyl-leucyl-phenylalanine (fMLP)-induced response. This effect was mediated by the inhibition of Ser345-p47phox phosphorylation and upstream kinase p38MAPK. Punicic acid also inhibited fMLP- and TNFalpha+fMLP-induced MPO extracellular release from neutrophils. In vivo experiments showed that punicic acid and pomegranate seed oil intake decreased neutrophil-activation and ROS/MPO-mediated tissue damage as measured by F2-isoprostane release and protected rats from TNBS-induced colon inflammation. CONCLUSIONS/SIGNIFICANCE:These data show that punicic acid exerts a potent anti-inflammatory effect through inhibition of TNFalpha-induced priming of NADPH oxidase by targeting the p38MAPKinase/Ser345-p47phox-axis and MPO release. This natural dietary compound may provide a novel alternative therapeutic strategy in inflammatory diseases such as inflammatory bowel diseases

The ISQoS Grid Broker for Temporal and Budget Guarantees

We introduce our Grid broker that uses SLAs in job submission with the aim of ensuring jobs are computed on time and on budget. We demonstrate our broker's ability to perform negotiation and to select preferentially higher priority jobs, in a tender market and discuss the architecture that makes this possible. We additionally show the effects of rescheduling and how careful consideration is required in order to avoid price instability. We therefore make recommendations upon how to maintain this stability, given rescheduling

Cold ablation driven by localized forces in alkali halides

Laser ablation has been widely used for a variety of applications. Since the mechanisms for ablation are strongly dependent on the photoexcitation level, so called cold material processing has relied on the use of high-peak-power laser fluences for which nonthermal processes become dominant; often reaching the universal threshold for plasma formation of ∼1 J cm-2 in most solids. Here we show single-shot time-resolved femtosecond electron diffraction, femtosecond optical reflectivity and ion detection experiments to study the evolution of the ablation process that follows femtosecond 400 nm laser excitation in crystalline sodium chloride, caesium iodide and potassium iodide. The phenomenon in this class of materials occurs well below the threshold for plasma formation and even below the melting point. The results reveal fast electronic and localized structural changes that lead to the ejection of particulates and the formation of micron-deep craters, reflecting the very nature of the strong repulsive forces at play

Vibroacoustic performance of multi-storey buildings : A comparison of lightweight and heavy structures in the early design phase

With the construction sector being responsible for about 40% of the energy and material use, the sector has a great responsibility for lowering the consumption if we are to succeed in our global pursuit for the green transition. However, buildings must still comply with the demands of users. For long-span, openspace lightweight, multi-storey buildings, this provides a potential risk related to annoyance caused by vibration and structure borne noise. This paper addresses the multilateral effects of building typology in terms of the vibroacoustic performance and the environmental impact. Based on an automized digital framework, multistorey buildings made of cross-laminated timber and/or concrete are modelled and compared. Finite-element analysis is used for the dynamic structural analysis, and the architectural design tool Rhino is used for material take-offs and visualisation. The aim of the paper is to provide insight into the advantages and disadvantages of different building typologies to be used for informed decision making in the early stages of design