Persistent Inflammation Subverts Thrombospondin-1–Induced Regulation of Retinal Angiogenesis and Is Driven by CCR2 Ligation

Neovascular retinal disease is a leading cause of blindness orchestrated by inflammatory responses. Although noninfectious uveoretinitis is mediated by CD4(+) T cells, in the persistent phase of disease, angiogenic responses are observed, along with degeneration of the retina. Full clinical manifestation relies on myeloid-derived cells, which are phenotypically distinct from, but potentially sharing common effector responses to age-related macular degeneration. To interrogate inflammation-mediated angiogenesis, we investigated experimental autoimmune uveoretinitis, an animal model for human uveitis. After the initial acute phase of severe inflammation, the retina sustains a persistent low-grade inflammation with tissue-infiltrating leukocytes for over 4 months. During this persistent phase, angiogenesis is observed as retinal neovascular membranes that arise from inflamed venules and postcapillary venules, increase in size as the disease progresses, and are associated with infiltrating arginase-1(+) macrophages. In the absence of thrombospondin-1, retinal neovascular membranes are markedly increased and are associated with arginase-1(-) CD68(+) macrophages, whereas deletion of the chemokine receptor CCR2 resulted in reduced retinal neovascular membranes in association with a predominant neutrophil infiltrate. CCR2 is important for macrophage recruitment to the retina in experimental autoimmune uveoretinitis and promotes chronicity in the form of a persistent angiogenesis response, which in turn is regulated by constitutive expression of angiogenic inhibitors like thrombospondin-1. This model offers a new platform to dissect the molecular and cellular pathology of inflammation-induced ocular angiogenesis.

Testing the role of sensory systems in the migratory heading of a songbird

The identification of the sensory cues and mechanisms by which migratory birds are able to reach the same breeding and wintering grounds year after year has eluded biologists despite more than 50 years of intensive study. While a number of environmental cues have been proposed to play a role in the navigation of birds, arguments still persist about which cues are essential for the experience based navigation shown by adult migrants. To date, few studies have tested the sensory basis of navigational cues used during actual migration in the wild: mainly laboratory based studies or homing during the non-migratory season have been used to investigate this behaviour. Here we tested the role of olfactory and magnetic cues in the migration of the catbird (Dumetella carolinensis) by radio tracking the migration of birds with sensory manipulations during their actual migratory flights. Our data suggest that adult birds treated with zinc sulphate to produce anosmia were unable to show the same orientation as control adults, and instead reverted to a direction similar to that shown by juveniles making their first migration. The magnetic manipulation had no effect on the orientation of either adults or juveniles. These results allow us to propose that the olfactory sense may play a role in experience based migration in adult catbirds. While the olfactory sense has been shown to play a role in the homing of pigeons and other birds, this is the first time it has been implicated in migratory orientation.

The bird GPS - long-range navigation in migrants

Nowadays few people consider finding their way in unfamiliar areas a problem as a GPS (Global Positioning System) combined with some simple map software can easily tell you how to get from A to B. Although this opportunity has only become available during the last decade, recent experiments show that long-distance migrating animals had already solved this problem. Even after displacement over thousands of kilometres to previously unknown areas, experienced but not first time migrant birds quickly adjust their course toward their destination, proving the existence of an experience-based GPS in these birds. Determining latitude is a relatively simple task, even for humans, whereas longitude poses much larger problems. Birds and other animals however have found a way to achieve this, although we do not yet know how. Possible ways of determining longitude includes using celestial cues in combination with an internal clock, geomagnetic cues such as magnetic intensity or perhaps even olfactory cues. Presently, there is not enough evidence to rule out any of these, and years of studying birds in a laboratory setting have yielded partly contradictory results. We suggest that a concerted effort, where the study of animals in a natural setting goes hand-in-hand with lab-based study, may be necessary to fully understand the mechanism underlying the long-distance navigation system of birds. As such, researchers must remain receptive to alternative interpretations and bear in mind that animal navigation may not necessarily be similar to the human system, and that we know from many years of investigation of long-distance navigation in birds that at least some birds do have a GPS-but we are uncertain how it works.

Female choice in the red mason bee, Osmia rufa (L.) (Megachilidae)

Females are often thought to use several cues and more than one modality in selection of a mate, possibly because they offer complementary information on a mate's suitability. In the red mason bee, Osmia rufa, we investigated the criteria a female uses to choose a mating partner. We hypothesized that the female uses male thorax vibrations and size as signs of male viability and male odor for kin discrimination and assessment of genetic relatedness. We therefore compared males that had been accepted by a female for copulation with those rejected, in terms of their size, their immediate precopulatory vibrations (using laser vibrometry), the genetic relatedness of unmated and mated pairs (using microsatellite markers) and emitted volatiles (using chemical analyses). Females showed a preference for intermediate-sized males that were slightly larger than the modal male size. Furthermore, male precopulatory vibration burst duration was significantly longer in males accepted for copulation compared with rejected males. Vibrations may indicate vigor and assure that males selected by females are metabolically active and healthy. Females preferentially copulated with males that were genetically more closely related, possibly to avoid outbreeding depression. Volatiles of the cuticular surface differed significantly between accepted and rejected males in the relative amounts of certain hydrocarbons, although the relationship between male odor and female preference was complex. Females may therefore also use differences in odor bouquet to select among males. Our investigations show that O. rufa females appear to use multiple cues in selecting a male. Future investigations are needed to demonstrate whether odor plays a role in kin recognition and how the multiple cues are integrated in mate choice by females.

Animal maiming, intimacy and the politics of shared life: the bestial and the beastly in eighteenth- and early nineteenth-century England

The everyday lives of many farm workers in eighteenth- and early nineteenth-century England were intricately and often intimately bound with the lives of animals, the ebb and flow of human life being inseparable from that of animal life. Farmyards, fields, folds as well as barns and stables were all spaces where animals transcended being the mere instruments of capital to instead being obvious co-constituents of the rhythms of existence. Living and working in such close proximity meant that the ‘species barrier’ was crossed and intimacies developed in everyday agricultural practices. Still, the relationship was based upon, if not reducible to, the workings of capital: the animal enrolled as a form of embodied capital, the labourer engaged by the farmer to act upon the animal. And in such relationships intimacies are mirrored by violences: the keeping captive, slaughter, and – occasionally – abuse. In this formative period in which the discourses and policies that continue to inform animal welfare were first formulated, the declining economic and material fortunes of farm workers when juxtaposed to farm animals’ fortune as increasingly ‘cosseted capital’ gave a particular charge to these abuses. Farm animals, and especially horses and cattle, so it is shown, were subjected to a series of violences. Many cases of animal maiming parodied tenderness in their brutality, whilst other attacks on the sexual organs of animals represented complex statements about the ways in which agrarian capitalism regulated all culture. Analysing the changing relationship between humans and animals therefore also helps us to better understand how capitalism mediates – and is mediated by – the non-human as well as the human, and how it defines cultural relations.

Anatomy and physiology of the human eye: effects of mucopolysaccharidoses disease on structure and function - a review

P>The current paper provides an overview of current knowledge on the structure and function of the eye. It describes in depth the different parts of the eye that are involved in the ocular manifestations seen in the mucopolysaccharidoses (MPS). The MPS are a group of rare inheritable lysosomal storage disorders characterized by the accumulation of glycosaminoglycans (GAGs) in cells and tissues all over the body, leading to widespread tissue and organ dysfunction. GAGs also tend to accumulate in several tissues of the eye, leading to various ocular manifestations affecting both the anterior (cornea, conjunctiva) and the posterior parts (retina, sclera, optic nerve) of the eye.

Confirmatory method for the determination of various acetylgestagens in animal kidney fat using liquid chromatography-tandem mass spectrometry

A confirmatory method has been developed and validated that allows for the simultaneous detection of medroxyprogesterone acetate (MPA), megestrol acetate (MGA), melengestrol acetate (MLA), chlormadinone acetate (CMA) and delmadinone acetate (DMA) in animal kidney fat using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The compounds were extracted from kidney fat using acetonitrile, defatted using a hexane wash and subsequent saponification. Extracts were then purified on Isolute CN solid-phase extraction cartridges and analysed by LC-MS/MS. The method was validated in animal kidney fat in accordance with the criteria defined in Commission Decision 2002/657/EC. The decision limit (CC) was calculated to be 0.12, 0.48, 0.40, 0.63 and 0.54 g kg-1, respectively, for MPA, MGA, MLA, DMA and CMA, with respective detection capability (CC) values of 0.20, 0.81, 0.68, 1.07 and 0.92 g kg-1. The measurement uncertainty of the method was estimated at 16, 16, 19, 27 and 26% for MPA, MGA, MLA, DMA and CMA, respectively. Fortifying kidney fat samples (n = 18) in three separate assays showed the accuracy of the method to be between 98 and 100%. The precision of the method, expressed as % RSD, for within-laboratory reproducibility at three levels of fortification (1, 1.5 and 2 g kg-1 for MPA, 5, 7.5 and 10 g kg-1 for MGA, MLA, DMA and CMA) was less than 5% for all analytes.

The identification of potential alternative biomarkers of nitrofurazone abuse in animal derived food products

Semicarbazide (SEM) was considered to be a characteristic protein-bound side-chain metabolite of the banned veterinary drug nitrofurazone and used as a marker of nitrofurazone abuse. It was recently discovered that SEM can arise in food from sources other than nitrofurazone. This uncertainty over the source of SEM may be overcome if alternative markers specific to tissue-bound nitrofurazone residues can be determined. The structure of nitrofurazone metabolites in vivo and particular proteins to which they are bound are not known. These proteins with altered structure due to the presence of the drug metabolites can be considered as potential alternative biomarkers of nitrofurazone abuse. The proteins implicated in the in vivo binding of nitrofurazone were separated and identified. A crude mixture of proteins extracted from the liver of a rat treated with the drug was separated using a series of different techniques such as preparative isoelectric focusing and size exclusion HPLC. Multiple fractions were assayed by LC-MS/MS to detect the presence of SEM. The proteins containing SEM residues were identified by peptide mass mapping using trypsin digestion and MALDI-TOF. The first protein identified as containing high concentration of SEM was albumin. It was also shown that low molecular weight species within a protein mixture whose main constituent was glutathione S-transferase contained a high concentration of SEM. The chemical composition of these components is under investigation. Preliminary data suggest the SEM forms part of a nitrofurazone metabolite conjugated to glutathione. (C) 2008 Elsevier Ltd. All rights reserved.