Role of Fractalkine/CX3CR1 Interaction in Light-Induced Photoreceptor Degeneration through Regulating Retinal Microglial Activation and Migration

Background: Excessive exposure to light enhances the progression and severity of some human retinal degenerative diseases. While retinal microglia are likely to be important in neuron damage associated with these diseases, the relationship between photoreceptor damage and microglial activation remains poorly understood. Some recent studies have indicated that the chemokine fractalkine is involved in the pathogenesis of many neurodegenerative diseases. The present study was performed to investigate the cross-talk between injured photoreceptors and activated retinal microglia, focusing on the role of fractalkine and its receptor CX3CR1 in light-induced photoreceptor degeneration. Methodology/Principal Findings: Both in vivo and in vitro experiments were involved in the research. In vivo, Sprague– Dawley rats were exposed to blue light for 24 hours. In vitro, the co-culture of primary retinal microglia and a photoreceptor cell line (661W cell) was exposed to blue light for five hours. Some cultures were pretreated by the addition of anti-CX3CR1 neutralizing antibody or recombinant fractalkine. Expression of fractalkine/CX3CR1 and inflammatory cytokines was detected by immunofluorescence, real-time PCR, Western immunoblot analysis, and ELISA assay. TUNEL method was used to detect cell apoptosis. In addition, chemotaxis assay was performed to evaluate the impact of soluble fractalkine on microglial migration. Our results showed that the expression of fractalkine that was significantly upregulated after exposure to light, located mainly at the photoreceptors. The extent of photoreceptor degeneration and microglial migratio

Late Holocene environmental reconstruction of St. Michiel saline lagoon, Curacao (Dutch Antilles)

From the 18th International Radiocarbon Conference held in Wellington, New Zealand, September 1-5, 2003.Two sediment cores collected from the saline lagoon St. Michiel on Curaçao (Dutch Antilles) preserve a approximately 5000-yr record of environmental change. Investigation of radiocarbon-dated sections by accelerator mass spectrometry (AMS) is based on faunal assemblage analyses, sediment mineralogy, and the interpretation of sedimentary facies. The cores recovered from different parts of the lagoon demonstrate different development. Initially, in the proximal part of the lagoon (core STM-2), the sediment accumulated in a coastal, semi-protected bay with strong marine influence, whereas the distal part (STM-1) was dominated by chemical precipitation (gypsum, aragonite). By about 3500-3400 BP, connection with the open sea became very limited due to the gradual formation of a coral rubble barrier at the coastline. Subsequently, the record reveals undisturbed sedimentation in the highly restricted shallow lagoon. Around 1100-1000 BP, biological and sedimentological records indicate a change to less evaporitic conditions. Stages of increased salinity are intercalated with intervals of episodic freshening due to increased runoff and precipitation. The authors demonstrate that since permanent human settlements were established on the island about 1100 BP, the watershed has undergone intensive deforestation, especially during the European colonization at the beginning of the 16th century. Deforestation resulting from agriculture and construction caused increased erosion, which was translated to increased sediment accumulation rates and a shift in lagoon sedimentation from almost entirely endogenic to mostly detrital.The Radiocarbon archives are made available by Radiocarbon and the University of Arizona Libraries. Contact [email protected] for further information.Migrated from OJS platform February 202

Human REXO2 controls short mitochondrial RNAs generated by mtRNA processing and decay machinery to prevent accumulation of double-stranded RNA

RNA decay is a key element of mitochondrial RNA metabolism. To date, the only well-documented machinery that plays a role in mtRNA decay in humans is the complex of polynucleotide phosphorylase (PNPase) and SUV3 helicase, forming the degradosome. REXO2, a homolog of prokaryotic oligoribonucleases present in humans both in mitochondria and the cytoplasm, was earlier shown to be crucial for maintaining mitochondrial homeostasis, but its function in mitochondria has not been fully elucidated. In the present study, we created a cellular model that enables the clear dissection of mitochondrial and non-mitochondrial functions of human REXO2. We identified a novel mitochondrial short RNA, referred to as ncH2, that massively accumulated upon REXO2 silencing. ncH2 degradation occurred independently of the mitochondrial degradosome, strongly supporting the hypothesis that ncH2 is a primary substrate of REXO2. We also investigated the global impact of REXO2 depletion on mtRNA, revealing the importance of the protein for maintaining low steady-state levels of mitochondrial antisense transcripts and double-stranded RNA. Our detailed biochemical and structural studies provide evidence of sequence specificity of the REXO2 oligoribonuclease. We postulate that REXO2 plays dual roles in human mitochondria, ‘scavenging’ nanoRNAs that are produced by the degradosome and clearing short RNAs that are generated by RNA processing