X-ray monitoring of the radio and gamma-ray loud Narrow-Line Seyfert 1 Galaxy PKS 2004-447

We present preliminary results of the X-ray analysis of XMM-Newton and Swift observations as part of a multi-wavelength monitoring campaign in 2012 of the radio-loud narrow line Seyfert 1 galaxy PKS 2004-447. The source was recently detected in gamma-rays by Fermi/LAT among only four other galaxies of that type. The 0.5-10 keV X-ray spectrum is well-described by a simple absorbed powerlaw (photon index ~ 1.6). The source brightness exhibits variability on timescales of months to years with indications for spectral variability, which follows a 'bluer-when-brighter' behaviour, similar to blazars.Comment: Proceedings for the 'Jet 2013' conference. Includes 3 pages, 3 figure

Collagen Assembly at the Cell Surface: Dogmas Revisited

With the increased awareness about the importance of the composition, organization, and stiffness of the extracellular matrix (ECM) for tissue homeostasis, there is a renewed need to understand the details of how cells recognize, assemble and remodel the ECM during dynamic tissue reorganization events. Fibronectin (FN) and fibrillar collagens are major proteins in the ECM of interstitial matrices. Whereas FN is abundant in cell culture studies, it is often only transiently expressed in the acute phase of wound healing and tissue regeneration, by contrast fibrillar collagens form a persistent robust scaffold in healing and regenerating tissues. Historically fibrillar collagens in interstitial matrices were seen merely as structural building blocks. Cell anchorage to the collagen matrix was thought to be indirect and occurring via proteins like FN and cell surface-mediated collagen fibrillogenesis was believed to require a FN matrix. The isolation of four collagen-binding integrins have challenged this dogma, and we now know that cells anchor directly to monomeric forms of fibrillar collagens via the α1β1, α2β1, α10β1 and α11β1 integrins. The binding of these integrins to the mature fibrous collagen matrices is more controversial and depends on availability of integrin-binding sites. With increased awareness about the importance of characterizing the total integrin repertoire on cells, including the integrin collagen receptors, the idea of an absolute dependence on FN for cell-mediated collagen fibrillogenesis needs to be re-evaluated. We will summarize data suggesting that collagen-binding integrins in vitro and in vivo are perfectly well suited for nucleating and supporting collagen fibrillogenesis, independent of FN.publishedVersio

Age-related dataset on the mechanical properties and collagen fibril structure of tendons from a murine model

Connective tissues such as tendon, ligament and skin are biological fibre composites comprising collagen fibrils reinforcing the weak proteoglycan-rich ground substance in extracellular matrix (ECM). One of the hallmarks of ageing of connective tissues is the progressive and irreversible change in the tissue mechanical properties; this is often attributed to the underlying changes to the collagen fibril structure. This dataset represents a comprehensive screen of the mechanical properties and collagen fibril structure of tendon from the tails of young to old (i.e. 1.6–35.3 month-old) C57BL6/B mice. The mechanical portion consists of the load-displacement data, as well as the derived tensile properties; the structure data consists of transmission electron micrographs of collagen fibril cross section, as well as the derived cross-sectional parameters. This dataset will allow other researchers to develop and demonstrate the utility of innovative multiscale models and approaches of the extra-cellular and physiological events of ageing of current interest to ageing research, by reducing the current reliance on conducting new mammalian experiments

Coalignment of plasma membrane channels and protrusions (fibripositors) specifies the parallelism of tendon

The functional properties of tendon require an extracellular matrix (ECM) rich in elongated collagen fibrils in parallel register. We sought to understand how embryonic fibroblasts elaborate this exquisite arrangement of fibrils. We show that procollagen processing and collagen fibrillogenesis are initiated in Golgi to plasma membrane carriers (GPCs). These carriers and their cargo of 28-nm-diam fibrils are targeted to previously unidentified plasma membrane (PM) protrusions (here designated “fibripositors”) that are parallel to the tendon axis and project into parallel channels between cells. The base of the fibripositor lumen (buried several microns within the cell) is a nucleation site of collagen fibrillogenesis. The tip of the fibripositor is the site of fibril deposition to the ECM. Fibripositors are absent at postnatal stages when fibrils increase in diameter by accretion of extracellular collagen, thereby maintaining parallelism of the tendon. Thus, we show that the parallelism of tendon is determined by the late secretory pathway and interaction of adjacent PMs to form extracellular channels

The contribution of daytime sleepiness to impaired quality of life in NAFLD in an ethnically diverse population

Health-related quality of life (HRQoL) is lower in people with NAFLD compared to the general population. Sleep disturbance resulting in daytime sleepiness is common in patients with NAFLD, but the effect of daytime sleepiness on HRQoL in NAFLD is unclear. The prevalence and natural history of NAFLD vary in different ethnic groups, but there has been limited ethnic diversity in HrQoL studies to date. We aimed to assess whether daytime sleepiness is independently associated with reduced HRQoL in an ethnically diverse UK population. We conducted HRQoL assessments using SF-36 version 2 and Epworth Sleepiness Scale (ESS) questionnaires in 192 people with NAFLD. Multivariate linear regression was used to identify factors independently affecting HRQoL scales. People with NAFLD reported significantly reduced physical health-related SF-36 scores compared to the general UK population. South Asian NAFLD patients reported impairment in physical health, but not mental health, approximately a decade before White NAFLD patients. In multivariate linear regression, daytime sleepiness (ESS score > 10), was the most significant independent predictor of reduced physical health. Age, BMI and liver stiffness score were also significantly associated. HRQoL is impaired earlier in patients of South Asian ethnicity. ESS score > 10, indicative of excessive daytime sleepiness, is an independent predictor of reduced HRQoL in people with NAFLD regardless of ethnicity. Daytime sleepiness should be considered as a contributing factor to reduced HRQoL in clinical practice and when evaluating patient-related outcomes in clinical trials.Grant from the Diabetes Wellness and Research Foundation (WA, WKS). WA was supported by a New Investigator Research Grant from the Medical Research Council