Absence of system xc⁻ on immune cells invading the central nervous system alleviates experimental autoimmune encephalitis

Background: Multiple sclerosis (MS) is an autoimmune demyelinating disease that affects the central nervous system (CNS), leading to neurodegeneration and chronic disability. Accumulating evidence points to a key role for neuroinflammation, oxidative stress, and excitotoxicity in this degenerative process. System x(c)- or the cystine/glutamate antiporter could tie these pathological mechanisms together: its activity is enhanced by reactive oxygen species and inflammatory stimuli, and its enhancement might lead to the release of toxic amounts of glutamate, thereby triggering excitotoxicity and neurodegeneration. Methods: Semi-quantitative Western blotting served to study protein expression of xCT, the specific subunit of system x(c)-, as well as of regulators of xCT transcription, in the normal appearing white matter (NAWM) of MS patients and in the CNS and spleen of mice exposed to experimental autoimmune encephalomyelitis (EAE), an accepted mouse model of MS. We next compared the clinical course of the EAE disease, the extent of demyelination, the infiltration of immune cells and microglial activation in xCT-knockout (xCT(-/-)) mice and irradiated mice reconstituted in xCT(-/-) bone marrow (BM), to their proper wild type (xCT(+/+)) controls. Results: xCT protein expression levels were upregulated in the NAWM of MS patients and in the brain, spinal cord, and spleen of EAE mice. The pathways involved in this upregulation in NAWM of MS patients remain unresolved. Compared to xCT(+/+) mice, xCT(-/-) mice were equally susceptible to EAE, whereas mice transplanted with xCT(-/-) BM, and as such only exhibiting loss of xCT in their immune cells, were less susceptible to EAE. In none of the above-described conditions, demyelination, microglial activation, or infiltration of immune cells were affected. Conclusions: Our findings demonstrate enhancement of xCT protein expression in MS pathology and suggest that system x(c)- on immune cells invading the CNS participates to EAE. Since a total loss of system x(c)- had no net beneficial effects, these results have important implications for targeting system x(c)- for treatment of MS

Promising Oldest Ice sites in East Antarctica based on thermodynamical modelling

To resolve the mechanisms behind the major climate reorganisation, which occurred between 0.9 and 1.2&thinsp;Ma, the recovery of a suitable 1.5 million-year-old ice core is fundamental. The quest for an Oldest Ice core requires a number of key boundary conditions, of which the poorly known basal geothermal heat flux (GHF) is lacking. We use a transient thermodynamical 1-D vertical model that solves for the rate of change of temperature in the vertical, with surface temperature and modelled GHF as boundary conditions. For each point on the ice sheet, the model is forced with variations in atmospheric conditions over the last 2&thinsp;Ma and modelled ice-thickness variations. The process is repeated for a range of GHF values to determine the value of GHF that marks the limit between frozen and melting conditions over the whole ice sheet, taking into account 2&thinsp;Ma of climate history. These threshold values of GHF are statistically compared to existing GHF data sets. The new probabilistic GHF fields obtained for the ice sheet thus provide the missing boundary conditions in the search for Oldest Ice. High spatial resolution radar data are examined locally in the Dome Fuji and Dome C regions, as these represent the ice core community's primary drilling sites. GHF, bedrock variability, ice thickness and other essential criteria combined highlight a dozen major potential Oldest Ice sites in the vicinity of Dome Fuji and Dome C, where GHF could allow for Oldest Ice.</p

Effective monitoring of freshwater fish

Freshwater ecosystems constitute only a small fraction of the planet’s water resources, yet support much of its diversity, with freshwater fish accounting for more species than birds, mammals, amphibians, or reptiles. Fresh waters are, however, particularly vulnerable to anthropogenic impacts, including habitat loss, climate and land use change, nutrient enrichment, and biological invasions. This environmental degradation, combined with unprecedented rates of biodiversity change, highlights the importance of robust and replicable programmes to monitor freshwater fish assemblages. Such monitoring programmes can have diverse aims, including confirming the presence of a single species (e.g. early detection of alien species), tracking changes in the abundance of threatened species, or documenting long-term temporal changes in entire communities. Irrespective of their motivation, monitoring programmes are only fit for purpose if they have clearly articulated aims and collect data that can meet those aims. This review, therefore, highlights the importance of identifying the key aims in monitoring programmes, and outlines the different methods of sampling freshwater fish that can be used to meet these aims. We emphasise that investigators must address issues around sampling design, statistical power, species’ detectability, taxonomy, and ethics in their monitoring programmes. Additionally, programmes must ensure that high-quality monitoring data are properly curated and deposited in repositories that will endure. Through fostering improved practice in freshwater fish monitoring, this review aims to help programmes improve understanding of the processes that shape the Earth's freshwater ecosystems, and help protect these systems in face of rapid environmental change

Inventariserend veldonderzoek, deel karterend : Kerkstraat te Moergestel

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