424 research outputs found
Primary cilia elongation in response to interleukin-1 mediates the inflammatory response
Primary cilia are singular, cytoskeletal organelles present in the majority of mammalian cell types where they function as coordinating centres for mechanotransduction, Wnt and hedgehog signalling. The length of the primary cilium is proposed to modulate cilia function, governed in part by the activity of intraflagellar transport (IFT). In articular cartilage, primary cilia length is increased and hedgehog signaling activated in osteoarthritis (OA). Here, we examine primary cilia length with exposure to the quintessential inflammatory cytokine interleukin-1 (IL-1), which is up-regulated in OA. We then test the hypothesis that the cilium is involved in mediating the downstream inflammatory response. Primary chondrocytes treated with IL-1 exhibited a 50Â % increase in cilia length after 3Â h exposure. IL-1-induced cilia elongation was also observed in human fibroblasts. In chondrocytes, this elongation occurred via a protein kinase A (PKA)-dependent mechanism. G-protein coupled adenylate cyclase also regulated the length of chondrocyte primary cilia but not downstream of IL-1. Chondrocytes treated with IL-1 exhibit a characteristic increase in the release of the inflammatory chemokines, nitric oxide and prostaglandin E2. However, in cells with a mutation in IFT88 whereby the cilia structure is lost, this response to IL-1 was significantly attenuated and, in the case of nitric oxide, completely abolished. Inhibition of IL-1-induced cilia elongation by PKA inhibition also attenuated the chemokine response. These results suggest that cilia assembly regulates the response to inflammatory cytokines. Therefore, the cilia proteome may provide a novel therapeutic target for the treatment of inflammatory pathologies, including OA
A lytic bacteriophage isolate reduced Clostridium perfringens induced lesions in necrotic enteritis challenged broilers
Background
Bacteriophages are viral predators of bacteria and are common in nature. Their host-specific infections against specific bacteria make them an attractive natural agent to control bacterial pathogens. Interest in the potential of bacteriophages as antibacterial agents in the production animal industries has increased.
Methods
A total of 18 bacteriophages were isolated from Australian commercial poultry environments, from which three highly active phages were chosen for enrichment. Sequencing libraries were prepared using a Nextera XT kit (Illumina) and sequenced on an Illumina MiSeq instrument using 2 Ă— 300 bp paired-end chemistry. The sequence data were then assembled and aligned with a2 bacteriophage as the reference. An animal trial was performed by oral gavaging Clostridium perfringens netB containing strain EHE-NE18 to the Ross 308 broiler chickens prior inoculation with Eimeria species. The chickens were raised following the management guide for Ross 308 from d 0 to d 21 and fed with starter and grower diets met the specific breed nutrient requirements. Body weight gain and feed intake were measured on d 9 and d 21 and FCR adjusted with mortality was calculated.
Results
The isolated bacteriophages only had only 96.7% similarity to the most closely related, previously characterized, Clostridium bacteriophage indicated that they might represent a novel strain of bacteriophage. A “cocktail” containing the three bacteriophages was capable of lysing four known disease-inducing C. perfringens strains in vitro. Oral administration of the bacteriophages cocktail to broilers challenged with necrotic enteritis markedly alleviated intestinal necrotic lesions in the duodenum and jejunum on day 16 post-hatch. The phage treatment significantly reduced the lesion scores of birds challenged with NE (P 0.05). However, no effect on the growth performance was observed during the recorded period of days 9-21.
Conclusion
These findings suggest that bacteriophage treatment is a promising approach to protect intestinal health from C. perfringens induced necrotic enteritis. Further research will be required on the dosing, route of administration, and large scale validation studies to further advance this approach to pathogen control
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The mechanical hybrid vehicle: an investigation of a flywheel-based vehicular regenerative energy capture system
Capturing braking energy by regeneration into an onboard energy storage unit offers the potential to reduce significantly the fuel consumption of vehicles. A common technique is to generate electricity in the motors of a hybrid electric vehicle when braking, and to use this to charge an onboard electrochemical battery. However, such batteries are costly, bulky, and generally not amenable to fast charging as this affects battery life and capacity. In order to overcome these problems, a mechanical energy storage system capable of accepting and delivering surges of power is proposed and investigated. A scale physical model of the system, based around a flywheel, a planetary gear set, and a brake, was built and operated in a laboratory. Tests showed that the proposed system could be used to store and provide braking energy between a flywheel and a vehicle, the latter emulated by an air-drag dynamometer. This validated the operating principle of the system and its computational model. Further, a computational analysis of a full-size vehicle incorporating the mechanical energy storage system was conducted. The results showed that the utilization of this system in a vehicle, when compared with a conventional vehicle, led to reductions in emissions and fuel consumption
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