Donor age affects proteome composition of tenocyte-derived engineered tendon

All proteins identified by PEAKS in young and old tendon-derived TEC with correpsonding cellular sublocations defined by IPA and Matrisome Project. (XLSX 57 kb

Vascular changes in diabetic retinopathy-a longitudinal study in the Nile rat.

Diabetic retinopathy is the most common microvascular complication of diabetes and is a major cause of blindness, but an understanding of the pathogenesis of the disease has been hampered by a lack of accurate animal models. Here, we explore the dynamics of retinal cellular changes in the Nile rat (Arvicanthis niloticus), a carbohydrate-sensitive model for type 2 diabetes. The early retinal changes in diabetic Nile rats included increased acellular capillaries and loss of pericytes that correlated linearly with the duration of diabetes. These vascular changes occurred in the presence of microglial infiltration but in the absence of retinal ganglion cell loss. After a prolonged duration of diabetes, the Nile rat also exhibits a spectrum of retinal lesions commonly seen in the human condition including vascular leakage, capillary non-perfusion, and neovascularization. Our longitudinal study documents a range and progression of retinal lesions in the diabetic Nile rat remarkably similar to those observed in human diabetic retinopathy, and suggests that this model will be valuable in identifying new therapeutic strategies

How Old is Too Old? Closure of Patent Foramen Ovale in Older Patients

Percutaneous closure of a patent foramen ovale (PFO) reduces the risk of recurrent cryptogenic stroke specifically in younger patients. The three randomized controlled trials that led to the widespread adoption of PFO closure excluded patients over the age of 60 years. Older patients frequently have other cardiac and vascular conditions that are common risk factors for stroke, whereas paradoxical embolism through a PFO is relatively rare. Younger patients theoretically benefit the most from closure due to longer lifetime exposure risk and absence of other traditional risk factors. PFO in older patients with cryptogenic strokes is often encountered in clinical practice, making up an increasing number of cardiology referrals, yet cardiologists lack guidelines and evaluation tools for these patients. This review explores the history of PFO closure – emphasizing data in older adults – and discusses the evaluation and treatment of older people with cryptogenic stroke and PFO while further trials in this important population are awaited

ISO LWS Spectroscopy of M82: A Unified Evolutionary Model

We present the first complete far-infrared spectrum (43 to 197 um) of M82, the brightest infrared galaxy in the sky, taken with the Long Wavelength Spectrometer of the Infrared Space Observatory (ISO). We detected seven fine structure emission lines, [OI] 63 and 145 um, [OIII] 52 and 88 um, [NII] 122 um, [NIII] 57 um and [CII] 158 um, and fit their ratios to a combination starburst and photo-dissociation region (PDR) model. The best fit is obtained with HII regions with n = 250 cm^{-3} and an ionization parameter of 10^{-3.5} and PDRs with n = 10^{3.3} cm^{-3} and a far-ultraviolet flux of G_o = 10^{2.8}. We applied both continuous and instantaneous starburst models, with our best fit being a 3-5 Myr old instantaneous burst model with a 100 M_o cut-off. We also detected the ground state rotational line of OH in absorption at 119.4 um. No excited level OH transitions are apparent, indicating that the OH is almost entirely in its ground state with a column density ~ 4x10^{14} cm^{-2}. The spectral energy distribution over the LWS wavelength range is well fit with a 48 K dust temperature and an optical depth, tau_{Dust} proportional to lambda^{-1}.Comment: 23 pages, 4 figures, accepted by ApJ, Feb. 1, 199

Ex-Vivo Equine Cartilage Explant Osteoarthritis Model - A Metabolomics and Proteomics Study.

Osteoarthritis is an age-related degenerative musculoskeletal disease characterised by loss of articular cartilage, synovitis and subchondral bone sclerosis. Osteoarthritis pathogenesis is yet to be fully elucidated with no osteoarthritis specific biomarkers in clinical use. Ex-vivo equine cartilage explants (n=5) were incubated in TNF-α/IL-1β supplemented culture media for 8 days, with media removed and replaced at 2, 5 and 8 days. Acetonitrile metabolite extractions of 8 day cartilage explants and media samples at all time points underwent 1D 1H nuclear magnetic resonance metabolomic analysis with media samples also undergoing mass spectrometry proteomic analysis. Within the cartilage, glucose and lysine were elevated following TNF-α/IL-1β treatment whilst adenosine, alanine, betaine, creatine, myo-inositol and uridine decreased. Within the culture media, four, four and six differentially abundant metabolites and 154, 138 and 72 differentially abundant proteins were identified at 1-2 days, 3-5 days and 6-8 days respectively, including reduced alanine and increased isoleucine, enolase 1, vimentin and lamin A/C following treatment. Nine potential novel osteoarthritis neopeptides were elevated in treated media. Implicated pathways were dominated by those involved in cellular movement. Our innovative study has provided insightful information on early osteoarthritis pathogenesis, enabling potential translation for clinical markers and possible new therapeutic targets

Synovial Fluid Metabolites Differentiate between Septic and Nonseptic Joint Pathologies

Osteoarthritis (OA), osteochondrosis (OC), and synovial sepsis in horses cause loss of function and pain. Reliable biomarkers are required to achieve accurate and rapid diagnosis, with synovial fluid (SF) holding a unique source of biochemical information. Nuclear magnetic resonance (NMR) spectroscopy allows global metabolite analysis of a small volume of SF, with minimal sample preprocessing using a noninvasive and nondestructive method. Equine SF metabolic profiles from both nonseptic joints (OA and OC) and septic joints were analyzed using 1D 1H NMR spectroscopy. Univariate and multivariate statistical analyses were used to identify differential metabolite abundance between groups. Metabolites were annotated via 1H NMR using 1D NMR identification software Chenomx, with identities confirmed using 1D 1H and 2D 1H 13C NMR. Multivariate analysis identified separation between septic and nonseptic groups. Acetate, alanine, citrate, creatine phosphate, creatinine, glucose, glutamate, glutamine, glycine, phenylalanine, pyruvate, and valine were higher in the nonseptic group, while glycylproline was higher in sepsis. Multivariate separation was primarily driven by glucose; however, partial-least-squares discriminant analysis plots with glucose excluded demonstrated the remaining metabolites were still able to discriminate the groups. This study demonstrates that a panel of synovial metabolites can distinguish between septic and nonseptic equine SF, with glucose the principal discriminator

Tuberculosis in cattle: the results of the four-area project

<p/> <p>The four-area project was undertaken to further assess the impact of badger removal on the control of tuberculosis in cattle herds in Ireland. It was conducted between 1997 and 2002 in matched removal and reference areas in four counties, namely Cork, Donegal, Kilkenny and Monaghan, representing a wide range of Irish farming environments. In the removal areas, a proactive programme of badger removal was conducted, on two or three occasions each year, whereas in the reference areas, badger removal was entirely reactive following severe outbreaks of tuberculosis amongst cattle. A detailed statistical analysis of this study has already been presented by Griffin <it>et al. </it><abbrgrp><abbr bid="B13">13</abbr></abbrgrp>; this paper presents further, mainly descriptive, findings from the study. In total, 2,360 badgers were captured in the removal areas of which 450 (19.5%) were considered positive for tuberculosis and 258 badgers were captured in the reference areas, with 57 (26.1%) positive for tuberculosis. The annual incidence of confirmed herd restrictions was lower in the removal area compared to the reference area in every year of the study period in each of the four counties. These empirical findings were consistent with the hazard ratios found by Griffin <it>et al. </it><abbrgrp><abbr bid="B13">13</abbr></abbrgrp>. Further, the effect of proactive badger removal on cattle tuberculosis in the four-area project and in the earlier east-Offaly project, as measured using the number of reactors per 1,000 cattle tested, were very similar, providing compelling evidence of the role of badgers in the epidemiology of tuberculosis in Irish cattle herds. The validity of the four-area project was discussed in detail. Efforts to minimise badger-to-cattle transmission in Ireland must be undertaken in association with the current comprehensive control programme, which has effectively minimised opportunities for cattle-to-cattle transmission.</p

Global Governance Behind Closed Doors : The IMF Boardroom, the Enhanced Structural Adjustment Facility, and the Intersection of Material Power and Norm Change in Global Politics

Up on the 12th floor of its 19th Street Headquarters, the IMF Board sits in active session for an average of 7 hours per week. Although key matters of policy are decided on in the venue, the rules governing Boardroom interactions remain opaque, resting on an uneasy combination of consensual decision-making and weighted voting. Through a detailed analysis of IMF Board discussions surrounding the Enhanced Structural Adjustment Facility (ESAF), this article sheds light on the mechanics of power in this often overlooked venue of global economic governance. By exploring the key issues of default liability and loan conditionality, I demonstrate that whilst the Boardroom is a more active site of contestation than has hitherto been recognized, material power is a prime determinant of both Executive Directors’ preferences and outcomes reached from discussions. And as the decisions reached form the backbone of the ‘instruction sheet’ used by Fund staff to guide their everyday operational decisions, these outcomes—and the processes through which they were reached—were factors of primary importance in stabilizing the operational norms at the heart of a controversial phase in the contemporary history of IMF concessional lending