Comparative study of gp130 cytokine effects on corticotroph AtT-20 cells - Redundancy or specificity of neuroimmunoendocrine modulators?

Objective: This comparative in vitro study examined the effects of all known gp130 cytokines on murine corticotroph AtT-20 cell function. Methods: Cytokines were tested at equimolar concentrations from 0.078 to 10 nM. Tyrosine phosphorylation of the signal transducer and activator of transcription ( STAT) 3 and STAT1, the STAT-dependent suppressor of cytokine signaling (SOCS)-3 promoter activity, SOCS-3 gene expression, STAT-dependent POMC promoter activity and adrenocorticotropic hormone ( ACTH) secretion were determined. Results: Leukemia inhibitory factor (LIF), human oncostatin M (OSM) and cardiotrophin (CT)-1 (LIFR/gp130 ligands), as well as ciliary neurotrophic factor ( CNTF) and novel neurotrophin1/B-cell stimulating factor-3 (CNTFRalpha/LIFR/gp130 ligands) are potent stimuli of corticotroph cells in vitro. In comparison, interleukin (IL)-6 (IL-6R/gp130 ligand) and IL-11 (IL-11R/gp130 ligand) exhibited only modest direct effects on corticotrophs, while murine OSM (OSMR/gp130 ligand) showed no effect. Conclusion: (i) CNTFR complex ligands are potent stimuli of corticotroph function, comparable to LIFR complex ligands; (ii) IL-6 and IL-11 are relatively weak direct stimuli of corticotroph function; (iii) differential effects of human and murine OSM suggest that LIFR/gp130 (OSMR type I) but not OSMR/gp130 (OSMR type II) are involved in corticotroph signaling. (iv) CT-1 has the hitherto unknown ability to stimulate corticotroph function, and (v) despite redundant immuno-neuroendocrine effects of different gp130 cytokines, corticotroph cells are preferably activated through the LIFR and CNTFR complexes. Copyright (C) 2004 S. Karger AG, Basel

Large carnivore expansion in Europe is associated with human population density and land cover changes

Aim: The recent recovery of large carnivores in Europe has been explained as resulting from a decrease in human persecution driven by widespread rural land abandonment, paralleled by forest cover increase and the consequent increase in availability of shelter and prey. We investigated whether land cover and human population density changes are related to the relative probability of occurrence of three European large carnivores: the grey wolf (Canis lupus), the Eurasian lynx (Lynx lynx) and the brown bear (Ursus arctos). Location: Europe, west of 64° longitude. Methods: We fitted multi-temporal species distribution models using >50,000 occurrence points with time series of land cover, landscape configuration, protected areas, hunting regulations and human population density covering a 24-year period (1992–2015). Within the temporal window considered, we then predicted changes in habitat suitability for large carnivores throughout Europe. Results: Between 1992 and 2015, the habitat suitability for the three species increased in Eastern Europe, the Balkans, North-West Iberian Peninsula and Northern Scandinavia, but showed mixed trends in Western and Southern Europe. These trends were primarily associated with increases in forest cover and decreases in human population density, and, additionally, with decreases in the cover of mosaics of cropland and natural vegetation. Main conclusions: Recent land cover and human population changes appear to have altered the habitat suitability pattern for large carnivores in Europe, whereas protection level did not play a role. While projected changes largely match the observed recovery of large carnivore populations, we found mismatches with the recent expansion of wolves in Central and Southern Europe, where factors not included in our models may have played a dominant role. This suggests that large carnivores’ co-existence with humans in European landscapes is not limited by habitat availability, but other factors such as favourable human tolerance and policy

Targeting of tumor radioiodine therapy by expression of the sodium iodide symporter under control of the survivin promoter

To test the feasibility of using the survivin promoter to induce specific expression of sodium/iodide symporter (NIS) in cancer cell lines and tumors for targeted use of radionuclide therapy, a recombinant adenovirus, Ad-SUR-NIS, that expressed the NIS gene under control of the survivin promoter was constructed. Ad-SUR-NIS mediating iodide uptake and cytotoxicity was performed in vitro. Scintigraphic, biodistribution and radioiodine therapy studies were performed in vivo. PC-3 (prostate); HepG2 (hepatoma) and A375 (melanoma) cancer cells all exhibited perchlorate-sensitive iodide uptake after infection with Ad-SUR-NIS, ∼50 times higher than that of negative control Ad-CMV-GFP-infected cells. No significant iodide uptake was observed in normal human dental pulp fibroblast (DPF) cells after infection with Ad-SUR-NIS. Clonogenic assays demonstrated that Ad-SUR-NIS-infected cancer cells were selectively killed by exposure to 131I. Ad-SUR-NIS-infected tumors show significant radioiodine accumulation (13.3±2.85% ID per g at 2 h post-injection), and the effective half-life was 3.1 h. Moreover, infection with Ad-SUR-NIS in combination with 131I suppressed tumor growth. These results indicate that expression of NIS under control of the survivin promoter can likely be used to achieve cancer-specific expression of NIS in many types of cancers. In combination with radioiodine therapy, this strategy is a possible method of cancer gene therapy

Meeting of the Ecosystem Approach Correspondence Group on on Pollution Monitoring (CorMon Pollution)

In accordance with the UNEP/MAP Programme of Work adopted by COP 21 for the biennium 2020-2021, the United Nations Environment Programme/Mediterranean Action Plan-Barcelona Convention Secretariat (UNEP/MAP) and its Programme for the Assessment and Control of Marine Pollution in the Mediterranean (MED POL) organized the Meeting of the Ecosystem Approach Correspondence Group on Pollution Monitoring (CorMon on Pollution Monitoring). The Meeting was held via videoconference on 26-27 April 2021. 2. The main objectives of the Meeting were to: a) Review the Monitoring Guidelines/Protocols for IMAP Common Indicator 18, as well as the Monitoring Guidelines/Protocols for Analytical Quality Assurance and Reporting of Monitoring Data for IMAP Common Indicators 13, 14, 17, 18 and 20; b) Take stock of the state of play of inter-laboratory testing and good laboratory practice related to IMAP Ecological Objectives 5 and 9; c) Analyze the proposal for the integration and aggregation rules for IMAP Ecological Objectives 5, 9 and 10 and assessment criteria for contaminants and nutrients; d) Recommend the ways and means to strengthen implementation of IMAP Pollution Cluster towards preparation of the 2023 MED Quality Status Report

The genetic epidemiology of joint shape and the development of osteoarthritis

Congruent, low-friction relative movement between the articulating elements of a synovial joint is an essential pre-requisite for sustained, efficient, function. Where disorders of joint formation or maintenance exist, mechanical overloading and osteoarthritis (OA) follow. The heritable component of OA accounts for ~ 50% of susceptible risk. Although almost 100 genetic risk loci for OA have now been identified, and the epidemiological relationship between joint development, joint shape and osteoarthritis is well established, we still have only a limited understanding of the contribution that genetic variation makes to joint shape and how this modulates OA risk. In this article, a brief overview of synovial joint development and its genetic regulation is followed by a review of current knowledge on the genetic epidemiology of established joint shape disorders and common shape variation. A summary of current genetic epidemiology of OA is also given, together with current evidence on the genetic overlap between shape variation and OA. Finally, the established genetic risk loci for both joint shape and osteoarthritis are discussed

Global implications of crop-based bioenergy with carbon capture and storage for terrestrial vertebrate biodiversity

Bioenergy with carbon capture and storage (BECCS) based on purpose‐grown lignocellulosic crops can provide negative CO(2) emissions to mitigate climate change, but its land requirements present a threat to biodiversity. Here, we analyse the implications of crop‐based BECCS for global terrestrial vertebrate species richness, considering both the land‐use change (LUC) required for BECCS and the climate change prevented by BECCS. LUC impacts are determined using global‐equivalent, species–area relationship‐based loss factors. We find that sequestering 0.5–5 Gtonne of CO(2) per year with lignocellulosic crop‐based BECCS would require hundreds of Mha of land, and commit tens of terrestrial vertebrate species to extinction. Species loss per unit of negative emissions decreases with: (i) longer lifetimes of BECCS systems, (ii) less overall deployment of crop‐based BECCS and (iii) optimal land allocation, that is prioritizing locations with the lowest species loss per negative emission potential, rather than minimizing overall land use or prioritizing locations with the lowest biodiversity. The consequences of prevented climate change for biodiversity are based on existing climate response relationships. Our tentative comparison shows that for crop‐based BECCS considered over 30 years, LUC impacts on vertebrate species richness may outweigh the positive effects of prevented climate change. Conversely, for BECCS considered over 80 years, the positive effects of climate change mitigation on biodiversity may outweigh the negative effects of LUC. However, both effects and their interaction are highly uncertain and require further understanding, along with the analysis of additional species groups and biodiversity metrics. We conclude that factoring in biodiversity means lignocellulosic crop‐based BECCS should be used early to achieve the required mitigation over longer time periods, on optimal biomass cultivation locations, and most importantly, as little as possible where conversion of natural land is involved, looking instead to sustainably grown or residual biomass‐based feedstocks and alternative strategies for carbon dioxide removal

Large carnivore expansion in Europe is associated with human population density and land cover changes

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