The TWEAK/Fn14/CD163 axis - Implications for metabolic disease

TWEAK (tumor necrosis factor-like weak inducer of apoptosis) is a member of the TNF superfamily that controls a multitude of cellular events including proliferation, migration, differentiation, apoptosis, angiogenesis, and inflammation. TWEAK control of these events is via an expanding list of intracellular signalling pathways which include NF-κB, ERK/MAPK, Notch, EGFR and AP-1. Two receptors have been identified for TWEAK – Fn14, which targets the membrane bound form of TWEAK, and CD163, which scavenges the soluble form of TWEAK. TWEAK appears to elicit specific events based on the receptor to which it binds, tissue type in which it is expressed, specific extrinsic conditions, and the presence of other cytokines. TWEAK signalling is protective in healthy tissues, but in chronic inflammatory states become detrimental to the tissue. Consistent data show a role for the TWEAK/FN14/CD163 axis in metabolic disease, chronic autoimmune diseases, and acute ischaemic stroke. Low circulating concentrations of soluble TWEAK are predictive of poor cardiovascular outcomes in those with and without diabetes. This review details the current understanding of the TWEAK/Fn14/CD163 axis as one of the chief regulators of immune signalling and its cell-specific role in metabolic disease development and progression

Applying rotorcraft modelling technology to renewable energy research

The perceived need to reduce mankind's impact on the global climate motivates towards a future society in which a significant proportion of its energy needs will be extracted from the winds and the tides of the planet. This paper shows several examples of the application of Brown's Vorticity Transport Model, originally developed to perform simulations of helicopter aeromechanics and wake dynamics, to the analysis of the performance of renewable energy devices and their possible impact on the environment. Prediction of the loading on wind turbines introduces significant additional challenges to such a model, including the need to account fully for the effects of radial flow on blade stall. The wake-mediated aerodynamic interactions that occur within a wind farm can reduce its power output significantly, but this problem is very similar to that where the aerodynamic unsteadiness of the coupled wake of the main and tail rotors of a helicopter can result in significantly increased pilot workload. The helicopter-related problem of brownout, encountered during operations in desert conditions, has its analogue in the entrainment of sediment into the wakes of tidal turbines. In both cases it may be possible to ameliorate the influence of the rotor on its environment by careful and well-informed design. Finally, calculations of the distortion and dispersal of the exhaust plumes of a helicopter by the wake of its rotor allow insight into how wind turbines might interfere with the dispersal of pollutants from nearby industrial sites. These examples show how cross-disciplinary information transfer between the rotorcraft field and the renewable energy community is helping to develop the technologies that will be required by our future society, as well as helping to understand the environmental issues that might need to be faced as these technologies become more prevalent

Stem Cell-Based Approaches for the Treatment of Diabetes

The incidence of diabetes and the associated debilitating complications are increasing at an alarming rate worldwide. Current therapies for type 1 diabetes focus primarily on administration of exogenous insulin to help restore glucose homeostasis. However, such treatment rarely prevents the long-term complications of this serious metabolic disorder, including neuropathy, nephropathy, retinopathy, and cardiovascular disease. Whole pancreas or islet transplantations have enjoyed limited success in some individuals, but these approaches are hampered by the shortage of suitable donors and the burden of lifelong immunosuppression. Here, we review current approaches to differentiate nonislet cell types towards an islet-cell phenotype which may be used for larger-scale cell replacement strategies. In particular, the differentiation protocols used to direct embryonic stem cells, progenitor cells of both endocrine and nonendocrine origin, and induced pluripotent stem cells towards an islet-cell phenotype are discussed

The effect of timing of antibiotic delivery on infection rates related to open limb fractures:a systematic review

Objective To examine whether the timing of delivery of intravenous antibiotics following open limb fractures has an effect on deep infection rates and other outcomes. Design We published an a priori study protocol in PROSPERO. Our search strategy combined terms for antibiotics, timing of administration and fractures. Two independent reviewers screened, selected, assessed quality and extracted data from identified studies. Data sources We searched five electronic databases with no limits and performed grey literature searches. Eligibility criteria for selecting studies Randomised and non-randomised controlled studies, prospective and retrospective observational studies in which the effect of the timing of delivery of antibiotics on the outcome of deep infection in open fractures was considered were included. Results Eight studies were included according to the above criteria. There were no randomised or nonrandomised controlled trials. None of the included studies provided data on patient reported or healthrelated quality of life. The overall deep infection rate ranged from 5% to 17.5%. All of the studies were at substantial risk of bias. One study reported a reduced infection rate with the delivery of antibiotics within 66 min of injury and seven studies reporting no effect. Conclusions Sufficiently robust evidence is not available currently to determine whether the timing of delivery of intravenous antibiotics has an effect on the risk of deep infection or other outcomes ollowing open limb fractures. There is therefore a need for a randomised controlled trial in this area before policy changes should be instigated. Trial registration number PROSPER