Expression of neurturin, glial cell line-derived neurotrophic factor, and their receptor components

PURPOSE. Dysregulation of neurturin (NTN) expression has been linked to photoreceptor apoptosis in a mouse model of inherited retinal degeneration. To investigate the extent to which any such dysregulation depends on the nature of the apoptotic trigger, the expression of NTN, glial cell line-derived neurotrophic factor (GDNF), and their corresponding receptor components were compared in a rat model of light-induced retinal degeneration. METHODS. Retinal expression of NTN, GDNF, their corresponding receptors GFR␣-2 and -1, the transmembrane receptor tyrosine kinase (Ret), and cSrc-p60, a member of the cytoplasmic protein-tyrosine kinases family, were analyzed by Western blot analysis and immunocytochemistry in cyclic light-and dark-reared rats in the presence and absence of intense light exposure. RESULTS. All components for NTN-mediated signaling activation are present in rat photoreceptors and retinal pigment epithelium, the cells primarily affected by light-induced damage. The expression levels of GDNF, its receptor components, and NTN, were not affected by light-induced stress. However, GFR␣-2 expression strikingly increased with the extent of retinal damage, especially at the photoreceptors, in contrast to decreased levels that were observed previously in an inherited degeneration model. CONCLUSIONS. The present study indicates that the expression of receptors of the GDNF family is independently regulated in normal and light-damaged rat retina, and in conjunction with previous work, suggests that the pattern of modulation of these genes during photoreceptor degeneration is determined by the nature of the apoptotic trigger. Such differential responses to different modes of retinal degeneration may reflect influences of the neurotrophic system on photoreceptor survival or in the regulation of neuronal plasticity. (Invest Ophthalmol Vis Sci. 2004;45:1240 -1246) DOI:10.1167/iovs.03-1122 G DNF and neurturin (NTN) are members of the glial cell line-derived neurotrophic factor (GDNF) family ligands (GFL) of neurotrophic factors. GFLs have been shown to influence the development of enteric, sympathetic, parasympathetic, and sensory neurons (for review see Ref. 1). They generally signal through a multicomponent receptor system consisting of the receptor tyrosine kinase Ret and a highaffinity ligand binding glycosyl-phosphatidylinositol (GPI)-linked coreceptor (GFR␣). GDNF-mediated bioactivity involves signaling molecules of the src-family of protein-tyrosine kinases; and, in particular, p60 Src has been shown to interact with activated Ret. 2 GDNF and NTN are expressed in a wide variety of tissues including the retina, suggesting an implication in diverse biological processes. 6 Upregulation of NTN mRNA expression was associated with progressive retinal neurodegeneration, but GFR␣-2 mRNA levels remained lower than in age-matched nondegenerative control retinas. On the assumption that increased NTN expression is a survivalpromoting response of the retina to the onset of degeneration, its potential neurotrophic effect on photoreceptors might be constrained by the persistently low GFR␣-2 levels in rd retinas. Alternatively, because NTN also signals through the GDNF receptor (GFR␣-1) but through a low-affinity interaction, 1 it is possible that increased NTN is limited in its efficacy by failure to activate sufficient survival-promoting pathways through the GFR␣-1 receptors. To assess the extent to which such modulations of expression of GFL members and their receptors are dependent on the nature of the apoptotic trigger, we have compared expression patterns of NTN, GDNF, and their receptor components in a model of photoreceptor cell death induced by exposure to intense light. In rats, light-induced retinal damage is rhodopsinmediated and dependent on light intensity, wave length and duration of the exposure, period of dark adaptation before exposure, and the exposure schedule. 8 -12 The effects were studied of both the type I (damaging both the photoreceptors and the retinal pigment epithelium) and type II (characterized by the loss of visual cells only) light-induced damage regimens on the expression of two members of the GDNF family. The retinal distributions of NTN, GDNF, and their receptor components were assessed by immunoblot and immunocytochemistry in control and light-stressed rat retinas

Velocity-space sensitivity of the time-of-flight neutron spectrometer at JET

The velocity-space sensitivities of fast-ion diagnostics are often described by so-called weight functions. Recently, we formulated weight functions showing the velocity-space sensitivity of the often dominant beam-target part of neutron energy spectra. These weight functions for neutron emission spectrometry (NES) are independent of the particular NES diagnostic. Here we apply these NES weight functions to the time-of-flight spectrometer TOFOR at JET. By taking the instrumental response function of TOFOR into account, we calculate time-of-flight NES weight functions that enable us to directly determine the velocity-space sensitivity of a given part of a measured time-of-flight spectrum from TOFOR

Relationship of edge localized mode burst times with divertor flux loop signal phase in JET

A phase relationship is identified between sequential edge localized modes (ELMs) occurrence times in a set of H-mode tokamak plasmas to the voltage measured in full flux azimuthal loops in the divertor region. We focus on plasmas in the Joint European Torus where a steady H-mode is sustained over several seconds, during which ELMs are observed in the Be II emission at the divertor. The ELMs analysed arise from intrinsic ELMing, in that there is no deliberate intent to control the ELMing process by external means. We use ELM timings derived from the Be II signal to perform direct time domain analysis of the full flux loop VLD2 and VLD3 signals, which provide a high cadence global measurement proportional to the voltage induced by changes in poloidal magnetic flux. Specifically, we examine how the time interval between pairs of successive ELMs is linked to the time-evolving phase of the full flux loop signals. Each ELM produces a clear early pulse in the full flux loop signals, whose peak time is used to condition our analysis. The arrival time of the following ELM, relative to this pulse, is found to fall into one of two categories: (i) prompt ELMs, which are directly paced by the initial response seen in the flux loop signals; and (ii) all other ELMs, which occur after the initial response of the full flux loop signals has decayed in amplitude. The times at which ELMs in category (ii) occur, relative to the first ELM of the pair, are clustered at times when the instantaneous phase of the full flux loop signal is close to its value at the time of the first ELM

26th Annual Computational Neuroscience Meeting (CNS*2017): Part 3 - Meeting Abstracts - Antwerp, Belgium. 15–20 July 2017

This work was produced as part of the activities of FAPESP Research,\ud Disseminations and Innovation Center for Neuromathematics (grant\ud 2013/07699-0, S. Paulo Research Foundation). NLK is supported by a\ud FAPESP postdoctoral fellowship (grant 2016/03855-5). ACR is partially\ud supported by a CNPq fellowship (grant 306251/2014-0)

From Middens to Modern Estuaries, Oyster Shells Sequester Source-Specific Nitrogen

Oysters (Crassostrea virginica) were an important food resource for native peoples of the northern Gulf of Mexico, who deposited waste shells in middens. Nitrogen (N) stable isotopes (δ15N) in bivalve shells have been used as modern proxies for estuarine N sources because they approximate δ15N in suspended particulate matter. We tested the use of midden shell δ15N as a proxy for ancient estuarine N sources. We hypothesized that isotopic signatures in ancient shells from coastal Mississippi would differ from modern shells due to increased anthropogenic N sources, such as wastewater, through time. We decalcified shells using an acidification technique previously developed for modern bivalves, but modified to determine δ15N, δ13C, %N, and % organic C of these low-N, high-C specimens. The modified method resulted in the greatest percentage of usable data from midden shells. Our results showed that oyster shell δ15N did not significantly differ between ancient (500–2100 years old) and modern oysters from the same locations where the sites had undergone relatively little land-use change. δ15N values in modern shells, however, were positively correlated with water column nitrate concentrations associated with urbanization. When N content and total shell mass were combined, we estimated that middens sequestered 410–39,000 kg of relic N, buried at a rate of up to 5 kg N m−2 yr−1. This study provides a relatively simple technique to assess baseline conditions in ecosystems over long time scales by demonstrating that midden shells can be an indicator of pre-historic N source to estuariesand are a potentially significant but previously uncharacterized estuarine N sink

Discoursive Alibis: Human rights, millennium development goals and poverty reduction strategy papers

Susan Mathews examines the complex and largely unsettled relationship between the millennium development goals (MDGs), poverty reduction strategy papers (PRSPs) and human rights discourse, partly through analysing the proposal that PRSPs be aligned to MDGs. A major risk is that the MDGs and PRSPs aligned create an amalgam of policy formulae that bring together the goal stringency of the former and the macroeconomic and structural reform orthodoxy of the latter, which could seriously hamper poverty reduction and disempower low-income countries and its poor peoples. Development (2007) 50, 76–82. doi:10.1057/palgrave.development.1100362