f(R) theories

Over the past decade, f(R) theories have been extensively studied as one of the simplest modifications to General Relativity. In this article we review various applications of f(R) theories to cosmology and gravity - such as inflation, dark energy, local gravity constraints, cosmological perturbations, and spherically symmetric solutions in weak and strong gravitational backgrounds. We present a number of ways to distinguish those theories from General Relativity observationally and experimentally. We also discuss the extension to other modified gravity theories such as Brans-Dicke theory and Gauss-Bonnet gravity, and address models that can satisfy both cosmological and local gravity constraints.Comment: 156 pages, 14 figures, Invited review article in Living Reviews in Relativity, Published version, Comments are welcom

Ergothioneine Biosynthesis and Functionality in the Opportunistic Fungal Pathogen, Aspergillus fumigatus.

Ergothioneine (EGT; 2-mercaptohistidine trimethylbetaine) is a trimethylated and sulphurised histidine derivative which exhibits antioxidant properties. Here we report that deletion of Aspergillus fumigatus egtA (AFUA_2G15650), which encodes a trimodular enzyme, abrogated EGT biosynthesis in this opportunistic pathogen. EGT biosynthetic deficiency in A. fumigatus significantly reduced resistance to elevated H2O2 and menadione, respectively, impaired gliotoxin production and resulted in attenuated conidiation. Quantitative proteomic analysis revealed substantial proteomic remodelling in ΔegtA compared to wild-type under both basal and ROS conditions, whereby the abundance of 290 proteins was altered. Specifically, the reciprocal differential abundance of cystathionine γ-synthase and β-lyase, respectively, influenced cystathionine availability to effect EGT biosynthesis. A combined deficiency in EGT biosynthesis and the oxidative stress response regulator Yap1, which led to extreme oxidative stress susceptibility, decreased resistance to heavy metals and production of the extracellular siderophore triacetylfusarinine C and increased accumulation of the intracellular siderophore ferricrocin. EGT dissipated H2O2 in vitro, and elevated intracellular GSH levels accompanied abrogation of EGT biosynthesis. EGT deficiency only decreased resistance to high H2O2 levels which suggests functionality as an auxiliary antioxidant, required for growth at elevated oxidative stress conditions. Combined, these data reveal new interactions between cellular redox homeostasis, secondary metabolism and metal ion homeostasis

Pathogenesis of Myositis

In this overview of pathogenic mechanisms contributing to the development of idiopathic inflammatory myopathy, we highlight the relative contributions of genetic risk, environmental triggering, adaptive immunity, innate immunity, and “nonimmune” signaling pathways that culminate in muscular as well as extra-muscular tissue pathology. Improved understanding of this complex network will enhance our ability to develop novel therapeutic targets

The incidence and associations of malignancy in a large cohort of patients with biopsy-determined idiopathic inflammatory myositis

The South Australian (SA) myositis database has registered all patients with biopsy-proven inflammatory myositis in SA from 1980 to 2009. We determined the incidence and associations of malignancy in myositis by linking this database with the SA cancer registry. Standardized incidence ratios (SIR) for malignancy were determined using the total SA population over the same time period, stratified by age and gender. The SIR for cancer in the myositis population (n = 373) was 1.39, p = 0.047. There was a trend towards an increased SIR in dermatomyositis but no increased risk of malignancy in polymyositis or inclusion body myositis. Malignancies of the lung and prostate were the commonest and 28 % of malignancies occurred within one year of IIM diagnosis. The odds of developing cancer were significantly raised in the presence of a shawl sign, male gender, and in patients with overlap syndrome or rheumatoid arthritis whilst myalgia was a significant protective factor. HLA-A28 allele was overrepresented in patients with malignancy (11 vs 2 %, p = 0.006). Patients in SA with myositis are at modestly increased risk for malignancy. We report clinical and genetic risk factors allowing the identification of patients at greatest risk for malignancy.Vidya Limaye, Colin Luke, Graeme Tucker, Catherine Hill, Susan Lester, Peter Blumbergs, Peter Roberts-Thomso