Chronic inflammatory arthritis drives systemic changes in circadian energy metabolism

SignificanceRheumatoid arthritis (RA) is a debilitating chronic inflammatory disease in which symptoms exhibit a strong time-of-day rhythmicity. RA is commonly associated with metabolic disturbance and increased incidence of diabetes and cardiovascular disease, yet the mechanisms underlying this metabolic dysregulation remain unclear. Here, we demonstrate that rhythmic inflammation drives reorganization of metabolic programs in distal liver and muscle tissues. Chronic inflammation leads to mitochondrial dysfunction and dysregulation of fatty acid metabolism, including accumulation of inflammation-associated ceramide species in a time-of-day-dependent manner. These findings reveal multiple points for therapeutic intervention centered on the circadian clock, metabolic dysregulation, and inflammatory signaling

What lies beneath: exploring links between asylum policy and hate crime in the UK

This paper explores the link between increasing incidents of hate crime and the asylum policy of successive British governments with its central emphasis on deterrence. The constant problematisation of asylum seekers in the media and political discourse ensures that 'anti-immigrant' prejudice becomes mainstr earned as a common-sense response. The victims are not only the asylum seekers hoping for a better life but democratic society itself with its inherent values of pluralism and tolerance debased and destabilised

Choice of Structure, Business Model and Portfolio: Organizational Models of Knowledge Transfer Offices in British Universities

This paper addresses the gap in the knowledge transfer literature around how universities choose specific organizational models for their knowledge transfer offices (KTOs). Organization theory points towards strong interlinkages between strategy, structure and processes in organizations. This motivates an exploration of similar links within the organizational setup of KTOs. In doing so, the paper provides a unified theoretical framework around a university's choice of structure, business model and strategic preferences for their KTOs linked to university-specific contextual factors. A qualitative approach is used wherein four very distinct British universities are examined as individual case studies. The authors find that strategic aims of the university around practitioner engagement, the quantity of applied research and research specialization are key factors in determining the organizational characteristics of the KTO. The theoretical framework derived from the cases makes two key contributions to the university knowledge transfer literature. First, it links the university-level contextual factors to the local model of knowledge transfer. Second, it allows us to develop a set of generic models of knowledge transfer, which can potentially guide universities to develop their own specific models

Autoimmune aspects of psoriasis: Heritability and autoantigens

Chronic immune-mediated disorders (IMDs) constitute a major health burden. Understanding IMD pathogenesis is facing two major constraints: Missing heritability explaining familial clustering, and missing autoantigens. Pinpointing IMD risk genes and autoimmune targets, however, is of fundamental importance for developing novel causal therapies. The strongest association of all IMDs is seen with human leukocyte antigen (HLA) alleles. Using psoriasis as an IMD model this article reviews the pathogenic role HLA molecules may have within the polygenic predisposition of IMDs. It concludes that disease-associated HLA alleles account for both missing heritability and autoimmune mechanisms by facilitating tissue-specific autoimmune responses through autoantigen presentation. (C) 2017 The Author. Published by Elsevier B.V

The effect of the dilution rate on CHO cell physiology and recombinant interferon-gamma production in glucose-limited chemostat culture

The physiology of a recombinant Chinese hamster ovary cell line in glucose-limited chemostat culture was studied over a range of dilution rates (D = 0.008 to 0.20 h-1). The specific growth rate (mu) deviated from D at low dilution rates due to an increased specific death rate. Extrapolation of these data suggested a minimum specific growth rate of 0.011 h-1 (mu(max) = 0.025 h-1) The metabolism at each steady state was characterized by determining the metabolic quotients for glucose, lactate, ammonia, amino acids, and interferon-gamma (IFN-gamma). The specific rate of glucose uptake increased linearly with mu and the saturation constant for glucose (K(s)) was calculated to be 59.6 muM. There was a linear increase in the rate of lactate production with a higher yield of lactate from glucose at high growth rates. The decline in the rate of production of lactate, alanine, and serine at low growth rate was consistent with the limitation of the glycolytic pathway by glucose. The specific rate of IFN-gamma production increased with mu in a manner indicative of a growth-related product. Despite changes in the IFN-gamma production rate and cell physiology, the pattern of IFN-gamma glycosylation was similar at all except the lowest growth rates where there was increased production of nonglycosylated IFN-gamma. (C) 1993 John Wiley & Sons, Inc