29 research outputs found

    The NR4A2/VGF pathway fuels inflammation-induced neurodegeneration via promoting neuronal glycolysis

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    A disturbed balance between excitation and inhibition (E/I balance) is increasingly recognized as a key driver of neurodegeneration in multiple sclerosis (MS), a chronic inflammatory disease of the central nervous system. To understand how chronic hyperexcitability contributes to neuronal loss in MS, we transcriptionally profiled neurons from mice lacking inhibitory metabotropic glutamate signaling with shifted E/I balance and increased vulnerability to inflammation-induced neurodegeneration. This revealed a prominent induction of the nuclear receptor NR4A2 in neurons. Mechanistically, NR4A2 increased susceptibility to excitotoxicity by stimulating continuous VGF secretion leading to glycolysis-dependent neuronal cell death. Extending these findings to people with MS (pwMS), we observed increased VGF levels in serum and brain biopsies. Notably, neuron-specific deletion of Vgf in a mouse model of MS ameliorated neurodegeneration. These findings underscore the detrimental effect of a persistent metabolic shift driven by excitatory activity as a fundamental mechanism in inflammation-induced neurodegeneration

    The synergistic impacts of anthropogenic stressors and COVID-19 on aquaculture: a current global perspective

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    The rapid, global spread of COVID-19, and the measures intended to limit or slow its propagation, are having major impacts on diverse sectors of society. Notably, these impacts are occurring in the context of other anthropogenic-driven threats including global climate change. Both anthropogenic stressors and the COVID-19 pandemic represent significant economic challenges to aquaculture systems across the globe, threatening the supply chain of one of the most important sources of animal protein, with potential disproportionate impacts on vulnerable communities. A web survey was conducted in 47 countries in the midst of the COVID-19 pandemic to assess how aquaculture activities have been affected by the pandemic, and to explore how these impacts compare to those from climate change. A positive correlation between the effects of the two categories of drivers was detected, but analysis suggests that the pandemic and the anthropogenic stressors affect different parts of the supply chain. The immediate measurable reported losses varied with aquaculture typology (land vs. marine, and intensive vs. extensive). A comparably lower impact on farmers reporting the use of integrated multitrophic aquaculture (IMTA) methods suggests that IMTA might enhance resilience to multiple stressors by providing different market options under the COVID-19 pandemic. Results emphasize the importance of assessing detrimental effects of COVID-19 under a multiple stressor lens, focusing on areas that have already locally experienced economic loss due to anthropogenic stressors in the last decade. Holistic policies that simultaneously address other ongoing anthropogenic stressors, rather than focusing solely on the acute impacts of COVID-19, are needed to maximize the long-term resilience of the aquaculture sector.publishe

    The aquaculture supply chain in the time of covid-19 pandemic: vulnerability, resilience, solutions and priorities at the global scale

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    The COVID-19 global pandemic has had severe, unpredictable and synchronous impacts on all levels of perishable food supply chains (PFSC), across multiple sectors and spatial scales. Aquaculture plays a vital and rapidly expanding role in food security, in some cases overtaking wild caught fisheries in the production of high-quality animal protein in this PFSC. We performed a rapid global assessment to evaluate the effects of the COVID-19 pandemic and related emerging control measures on the aquaculture supply chain. Socio-economic effects of the pandemic were analysed by surveying the perceptions of stakeholders, who were asked to describe potential supply-side disruption, vulnerabilities and resilience patterns along the production pipeline with four main supply chain components: a) hatchery, b) production/processing, c) distribution/logistics and d) market. We also assessed different farming strategies, comparing land- vs. sea-based systems; extensive vs. intensive methods; and with and without integrated multi-trophic aquaculture, IMTA. In addition to evaluating levels and sources of economic distress, interviewees were asked to identify mitigation solutions adopted at local / internal (i.e., farm-site) scales, and to express their preference on national / external scale mitigation measures among a set of a priori options. Survey responses identified the potential causes of disruption, ripple effects, sources of food insecurity, and socio-economic conflicts. They also pointed to various levels of mitigation strategies. The collated evidence represents a first baseline useful to address future disaster-driven responses, to reinforce the resilience of the sector and to facilitate the design reconstruction plans and mitigation measures, such as financial aid strategies.publishe

    Effect of mefenamic acid on some of the base excision repair enzymes against D-serine-induced neurotoxicity [D-serin ile indüklenen nörotoksisitede mefenamik asit’in baz eksizyon tamir enzimleri üzerine etkisi]

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    N-methyl-D-aspartate receptor (NMDAR) overactivation leads to free radical production, protein degradation, lipid peroxidation and DNA damage. Recently, nonsteroidal antiinflammatory drugs (NSAIDs) are suggested to be good candidates for the treatment of neurological insults. In this study, we aimed to evaluate the effect of mefenamic acid on 8-OHdG levels, the expression of poly(ADP ribose) polymerase-1 (PARP-1) and base excision repair (BER) enzymes; 8-oxoguanine DNA glycosylase 1 (OGG1), apurinic/apyrimidinic endonuclease 1 (APE1) against D-serine. Adult Sprague-Dawley rats were divided into four groups: (i) the control (n=6); (ii) D-serine (n=6); (iii) Mefenamic acid (n=6); (iv) D-serine+Mefenamic acid (n=6). Rats were decapitated 6 hours after the injections. The mRNA and protein expression levels were determined by real-time PCR and western blot techniques, respectively. D-serine increased APE1 mRNA, PARP-1 mRNA and 8-OHdG levels. APE1 and PARP-1 genes were significantly upregulated by mefenamic acid. Protein expression profiles were also consistent with mRNA levels. However neither mRNA nor protein levels of OGG1 were affected by D-serine or mefenamic acid. Our results suggest that NMDA/D-serine signaling triggers DNA repair mechanisms and oxidative DNA damage simultaneously. We may conclude that mefenamic acid have a potential neuroprotective effect and assist to repair NMDAR-mediated DNA damage via modulating DNA repair mechanisms. © 2016, Turkish Pharmacists Association. All rights reserved

    Hatchery performance in a major rainbow trout (Oncorhynchus mykiss, Walbaum, 1792) seed production area of Turkey

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    This study aims to determine the production characteristics and performance of rainbow trout hatcheries in Seydikemer, Muğla, Turkey where over half of the total production of eyed eggs and juveniles take place. For this purpose six hatcheries with different production scales were selected and coded A, B, C, D, E and F (with capacities of 60, 15, 5.6, 4, 0.95 and 0.6 million juveniles per year, respectively). From each hatchery, 20 females were selected and their egg qualities (egg number, diameter and weight, fertilization, eyed egg, hatching, swim-up fry and survival rates at 120 days after hatching) and juvenile growth rates were monitored until the 120th day after hatching under each farms own conditions. The sperm characteristics of 10 broodstock males from each hatchery were also examined. Although fertilization and eyed egg rates were similar among the farms, hatching, swim-up fry, and survival rates at the 120th day after hatching differed significantly. The average eyed egg, hatching and survival rates (calculated from selected 20 females) were 72, 55, and 32%, respectively. While sperm characteristics except duration of motility (s), were significantly different among the farms, average sperm concentration (per ml), motility (%) and duration of motility (s) in the region were 11.8 × 109, 55.3, and 56.4, respectively. The best hatchery performance was observed in Farm A because of better records and management applications than in the other farms. © 2016 Blackwell Verlag Gmb
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