Evidence supporting a role for N-epsilon-(3-formyl-3,4-dehydropiperidino)lysine accumulation in Muller glia dysfunction and death in diabetic retinopathy

Purpose: Recent evidence suggests that neuroglial dysfunction and degeneration contributes to the etiology and progression of diabetic retinopathy. Advanced lipoxidation end products (ALEs) have been implicated in the pathology of various diseases, including diabetes and several neurodegenerative disorders. The purpose of the present study was to investigate the possible link between the accumulation of ALEs and neuroretinal changes in diabetic retinopathy.

Methods: Retinal sections obtained from diabetic rats and age-matched controls were processed for immunohistochemistry using antibodies against several well defined ALEs. In vitro experiments were also performed using a human Muller (Moorfields/Institute of Ophthalmology-Muller 1 [ MIO-M1]) glia cell line. Western blot analysis was used to measure the accumulation of the acrolein-derived ALE adduct N epsilon-(3-formyl-3,4-dehydropiperidino)lysine (FDP-lysine) in Muller cells preincubated with FDP-lysine-modified human serum albumin (FDP-lysine-HSA). Responses of Muller cells to FDP-lysine accumulation were investigated by analyzing changes in the protein expression of heme oxygenase-1 (HO-1), glial fibrillary acidic protein (GFAP), and the inwardly rectifying potassium channel Kir4.1. In addition, mRNA expression levels of vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF alpha) were determined by reverse transcriptase PCR (RT-PCR). Apoptotic cell death was evaluated by fluorescence-activated cell sorting (FACS) analysis after staining with fluorescein isothiocyanate (FITC)-labeled annexin V and propidium iodide.

Results: No significant differences in the levels of malondialdehyde-, 4-hydroxy-2-nonenal-, and 4-hydroxyhexenal-derived ALEs were evident between control and diabetic retinas after 4 months of diabetes. By contrast, FDP-lysine immunoreactivity was markedly increased in the Muller glia of diabetic rats. Time-course studies revealed that FDP-lysine initially accumulated within Muller glial end feet after only a few months of diabetes and thereafter spread distally throughout their inner radial processes. Exposure of human Muller glia to FDP-lysine-HSA led to a concentration-dependent accumulation of FDP-lysine-modified proteins across a broad molecular mass range. FDP-lysine accumulation was associated with the induction of HO-1, no change in GFAP, a decrease in protein levels of the potassium channel subunit Kir4.1, and upregulation of transcripts for VEGF, IL-6, and TNF-alpha. Incubation of Muller glia with FDP-lysine-HSA also caused apoptosis at high concentrations.

Conclusions: Collectively, these data strongly suggest that FDP-lysine accumulation could be a major factor contributing to the Muller glial abnormalities occurring in the early stages of diabetic retinopathy.

Projecto, montagem e teste de uma unidade modular de detecção de radiação Geiger-Muller

Dissertação para obtenção do grau de Mestre em Engenharia Electrotécnica Ramo de Automação e Electrónica Industrial

[Dick] Landon, gagnant du saut [en hauteur, porté par Harold Muller et Bo Ekelund, Jeux olympiques d'Anvers, 17/8/20] : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 60592

Chris Critelli

Chris Critelli is going into her 23rd season as the Women's Basketball Head Coach.

Daniel Weinstock interviews Lisa Eckenwiler and Chris Macdonald -- music by General International

Daniel Weinstock, director of CRÉUM, interviews two professors that were invited to pursue their work at CRÉUM during the summer of 2008. His invitees are Lisa Eckenwiler, Associate Professor of Philosophy in the Department of Philosophy and in the Department of Health Administration and Policy at George Mason University; and Chris Macdonald, Associate Professor of Philosophy at Saint Mary’s University in Halifax. You will also hear General International, an experimental/avant-garde music band that was formed only a few months ago.

Automated synthesis of delay-reduced Reed-Muller universal logic module networks

This paper presents a new approach to implement Reed-Muller Universal Logic Module (RM-ULM) networks with reduced delay and hardware for synthesizing logic functions given in Reed-Muller (RM) form. Replication of single control line RM-ULM is used as the only design unit for defining any logic function. An algorithm is proposed that does exhaustive branching to reduce the number of levels and modules required to implement any logic function in RM form. This approach attains a reduction in delay, and power over other implementations of functions having large number of variables.

A muller galega no meio labrego. 'La mujer gallega en el ambiente rural'.

Ver la mujer a nivel general en todo el mundo. La mujer en el trabajo y la mujer en el medio social, cómo triunfa o cómo fracasa ante la presion ambiental. Comprobar, a continuación, a la mujer gallega en el trabajo. Cómo vive, cuáles son sus derechos y sus deberes. Y por último, qué es lo que dijo la mujer gallega. Mujeres de Galicia. Sondeo a través de cincuenta preguntas. Dibujos, láminas. La situación de la mujer en el mundo es resultado, en parte, querido por ella, en parte, provocado por la sociedad machista. Los movimientos de liberación de la mujer son formas poco válidas. Pues, la revolución de la mujer se tiene que hacer desde la universidad y por ella misma, aunque hoy por hoy lo tiene muy difícil.

Muller e traballo. 'Mujer y trabajo'.

Este material pretende ser una ayuda para que profesor@s y alumn@s de secundaria reflexionen sobre la actual situación de las mujeres trabajadoras y se pregunten sobre las posibles causas de la misma. Para ello hacen una breve panorámica de las trabajadoras en diferentes períodos históricos, presentando textos para trabajar en clase.