Müller glia activation in response to inherited retinal degeneration is highly varied and disease-specific

Despite different aetiologies, most inherited retinal disorders culminate in photoreceptor loss, which induces concomitant changes in the neural retina, one of the most striking being reactive gliosis by Müller cells. It is typically assumed that photoreceptor loss leads to an upregulation of glial fibrilliary acidic protein (Gfap) and other intermediate filament proteins, together with other gliosis-related changes, including loss of integrity of the outer limiting membrane (OLM) and deposition of proteoglycans. However, this is based on a mix of both injury-induced and genetic causes of photoreceptor loss. There are very few longitudinal studies of gliosis in the retina and none comparing these changes across models over time. Here, we present a comprehensive spatiotemporal assessment of features of gliosis in the degenerating murine retina that involves Müller glia. Specifically, we assessed Gfap, vimentin and chondroitin sulphate proteoglycan (CSPG) levels and outer limiting membrane (OLM) integrity over time in four murine models of inherited photoreceptor degeneration that encompass a range of disease severities (Crb1rd8/rd8, Prph2+/Δ307, Rho-/-, Pde6brd1/rd1). These features underwent very different changes, depending upon the disease-causing mutation, and that these changes are not correlated with disease severity. Intermediate filament expression did indeed increase with disease progression in Crb1rd8/rd8 and Prph2+/Δ307, but decreased in the Prph2+/Δ307 and Pde6brd1/rd1 models. CSPG deposition usually, but not always, followed the trends in intermediate filament expression. The OLM adherens junctions underwent significant remodelling in all models, but with differences in the composition of the resulting junctions; in Rho-/- mice, the adherens junctions maintained the typical rod-Müller glia interactions, while in the Pde6brd1/rd1 model they formed predominantly between Müller cells in late stage of degeneration. Together, these results show that gliosis and its associated processes are variable and disease-dependent

A Simplified Model of Glycoprotein Production within Cell Culture

Complex biological products, such as those used to treat various forms of cancer, are typically produced by mammalian cells in bioreactors. The most important class of such biological medicines is proteins. These typically bind to sugars (glycans) in a process known as glycosylation, creating glycoproteins, which are more stable and effective medicines. The glycans are large polymers that are formed by a long sequence of enzyme catalysed reactions. This sequence is not always completed, thus leading to a heterogeneous glycoprotein distribution. A better comprehension of this distribution could lead to more efficient production of high quality drugs. To understand how the manufacturing process can affect the extent of glycosylation of protein, a non-linear ODE model of glycoprotein production is developed which describes the bioreactor configuration as well as the protein production and glycosylation reactions within the cell. The entire system evolves eventually to a stable steady state. The earlier evolution is critical however, as the amount of product produced and its quality varies over time. The model is considered as two coupled systems: the bioreactor submodel and the glycosylation submodel. To investigate the early time evolution within the bioreactor submodel, analytical and numerical properties are derived using matched asymptotic expansions and a finite difference scheme for a range of initial conditions. This leads to qualitatively different regimes for aglycosylated protein production, which affect the glycosylation submodel. The discrete glycoprotein distribution is approximated as continuous and written as a first-order PDE, with good agreement between the discrete and continuous models. The PDE is found to admit shocks, but the existence of these shocks is dependent on the early time evolution within the bioreactor submodel and leads to higher levels of glycosylation at early time. This suggests that changing the bioreactor configuration can lead to higher quality product at certain times

The Influence of pH on the Combustion Properties of Bio-Coal Following Hydrothermal Treatment of Swine Manure

The application of excessive amounts of manure to soil prompted interest in using alternative approaches for treating slurry. One promising technology is hydrothermal carbonisation (HTC) which can recover nutrients such as phosphorus and nitrogen while simultaneously making a solid fuel. Processing manure under acidic conditions can facilitate nutrient recovery; however, very few studies considered the implications of operating at low pH on the combustion properties of the resulting bio-coal. In this work, swine manure was hydrothermally treated at temperatures ranging from 120 to 250 °C in either water alone or reagents including 0.1 M NaOH, 0.1 M H2SO4, and finally 0.1 M organic acid (CH3COOH and HCOOH). The influence of pH on the HTC process and the combustion properties of the resulting bio-coals was assessed. The results indicate that pH has a strong influence on ash chemistry, with decreasing pH resulting in an increased removal of ash. The reduction in mineral matter influences the volatile content of the bio-coal and its energy content. As the ash content in the final bio-coal reduces, the energy density increases. Treatment at 250 °C results in a more “coal like” bio-coal with fuel properties similar to that of lignite coal and a higher heating value (HHV) ranging between 21 and 23 MJ/kg depending on pH. Processing at low pH results in favourable ash chemistry in terms of slagging and fouling. Operating at low pH also appears to influence the level of dehydration during HTC. The level of dehydration increases with decreasing pH, although this effect is reduced at higher temperatures. At higher-temperature processing (250 °C), operating at lower pH increases the yield of bio-coal; however, at lower temperatures (below 200 °C), the reverse is true. The lower yields obtained below 200 °C in the presence of acid may be due to acid hydrolysis of carbohydrate in the manure, whereas, at the higher temperatures, it may be due to the acid promoting polymerisation

'I was in control of it from the start: A qualitative study of mens experiences of positive adjustment following a heart attack

A qualitative design was used to explore the experience of positive adjustment following a heart attack. Ten men attending a cardiac rehabilitation programme completed in-depth semi-structured interviews. An overarching theme: ‘I was in control of it from the start’ emerged with six subthemes, relating to intrapersonal and interpersonal factors and processes. The subthemes reflected the importance of identifying controllable versus non-controllable factors and employing adaptive coping strategies

Echinoderms have bilateral tendencies

Echinoderms take many forms of symmetry. Pentameral symmetry is the major form and the other forms are derived from it. However, the ancestors of echinoderms, which originated from Cambrian period, were believed to be bilaterians. Echinoderm larvae are bilateral during their early development. During embryonic development of starfish and sea urchins, the position and the developmental sequence of each arm are fixed, implying an auxological anterior/posterior axis. Starfish also possess the Hox gene cluster, which controls symmetrical development. Overall, echinoderms are thought to have a bilateral developmental mechanism and process. In this article, we focused on adult starfish behaviors to corroborate its bilateral tendency. We weighed their central disk and each arm to measure the position of the center of gravity. We then studied their turning-over behavior, crawling behavior and fleeing behavior statistically to obtain the center of frequency of each behavior. By joining the center of gravity and each center of frequency, we obtained three behavioral symmetric planes. These behavioral bilateral tendencies might be related to the A/P axis during the embryonic development of the starfish. It is very likely that the adult starfish is, to some extent, bilaterian because it displays some bilateral propensity and has a definite behavioral symmetric plane. The remainder of bilateral symmetry may have benefited echinoderms during their evolution from the Cambrian period to the present

Preliminary design studies of an advanced general aviation aircraft

The preliminary design results are presented of the advanced aircraft design project. The goal was to take a revolutionary look into the design of a general aviation aircraft. Phase 1 of the project included the preliminary design of two configurations, a pusher, and a tractor. Phase 2 included the selection of only one configuration for further study. The pusher configuration was selected on the basis of performance characteristics, cabin noise, natural laminar flow, and system layouts. The design was then iterated to achieve higher levels of performance

Guest Encapsulation within Surface-Adsorbed Self-Assembled Cages

Coordination cages encapsulate a wide variety of guests in the solution state. This ability renders them useful for applications such as catalysis and the sequestration of precious materials. A simple and general method for the immobilization of coordination cages on alumina is reported. Cage loadings are quantified via adsorption isotherms and guest displacement assays demonstrate that the adsorbed cages retain the ability to encapsulate and separate guest and non-guest molecules. Finally, a system of two cages, adsorbed on to different regions of alumina, stabilizes and separates a pair of Diels-Alder reagents. The addition of a single competitive guest results in the controlled release of the reagents, thus triggering their reaction. This method of coordination cage immobilization on solid phases is envisaged to be applicable to the extensive library of reported cages, enabling new applications based upon selective solid-phase molecular encapsulation