Type I interferons (IFN‐I) are the principal antiviral molecules of the innate immune system and can be made by most cell types, including central nervous system cells. IFN‐I has been implicated in ...neuroinflammation during neurodegeneration, but its mechanism of induction and its consequences remain unclear. In the current study, we assessed expression of IFN‐I in murine prion disease (ME7) and examined the contribution of the IFN‐I receptor IFNAR1 to disease progression. The data indicate a robust IFNβ response, specifically in microglia, with evidence of IFN‐dependent genes in both microglia and astrocytes. This IFN‐I response was absent in stimulator of interferon genes (STING−/−) mice. Microglia showed increased numbers and activated morphology independent of genotype, but transcriptional signatures indicated an IFNAR1‐dependent neuroinflammatory phenotype. Isolation of microglia and astrocytes demonstrated disease‐associated microglial induction of Tnfα, Tgfb1, and of phagolysosomal system transcripts including those for cathepsins, Cd68, C1qa, C3, and Trem2, which were diminished in IFNAR1 and STING deficient mice. Microglial increases in activated cathepsin D, and CD68 were significantly reduced in IFNAR1−/− mice, particularly in white matter, and increases in COX‐1 expression, and prostaglandin synthesis were significantly mitigated. Disease progressed more slowly in IFNAR1−/− mice, with diminished synaptic and neuronal loss and delayed onset of neurological signs and death but without effect on proteinase K‐resistant PrP levels. Therefore, STING‐dependent IFN‐I influences microglial phenotype and influences neurodegenerative progression despite occurring secondary to initial degenerative changes. These data expand our mechanistic understanding of IFN‐I induction and its impact on microglial function during chronic neurodegeneration.
Main Points
Microglial IFN‐I during chronic neurodegeneration is STING‐dependent.
Microglial phagolysosomal, complement and prostaglandin pathways are suppressed in IFNAR1‐/‐ mice.
Synaptic & neuronal degeneration and motor decline are slowed in IFNAR1‐/‐ mice.
Knowledge of carbon exchange between the atmosphere, land and the oceans is important, given that the terrestrial and marine environments are currently absorbing about half of the carbon dioxide that ...is emitted by fossil-fuel combustion. This carbon uptake is therefore limiting the extent of atmospheric and climatic change, but its long-term nature remains uncertain. Here we provide an overview of the current state of knowledge of global and regional patterns of carbon exchange by terrestrial ecosystems. Atmospheric carbon dioxide and oxygen data confirm that the terrestrial biosphere was largely neutral with respect to net carbon exchange during the 1980s, but became a net carbon sink in the 1990s. This recent sink can be largely attributed to northern extratropical areas, and is roughly split between North America and Eurasia. Tropical land areas, however, were approximately in balance with respect to carbon exchange, implying a carbon sink that offset emissions due to tropical deforestation. The evolution of the terrestrial carbon sink is largely the result of changes in land use over time, such as regrowth on abandoned agricultural land and fire prevention, in addition to responses to environmental changes, such as longer growing seasons, and fertilization by carbon dioxide and nitrogen. Nevertheless, there remain considerable uncertainties as to the magnitude of the sink in different regions and the contribution of different processes.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objective
To estimate the prevalence of painful sex among women in Britain, and to explore associated sexual, relationship and health factors that should be considered in assessment.
Design
...Multi‐stage, clustered and stratified population probability sample survey, using computer‐assisted self‐interview. Sample frame was the British Postcode Address File.
Setting
Participants interviewed at home between 2010 and 2012.
Sample
A total of 15 162 adults aged 16–74 years (8869 women). Data reported from 6669 sexually active women.
Methods
Age‐adjusted logistic regressions to examine associations between painful sex and indicators of sexual, relational, mental and physical health.
Main outcome measure
Physical pain as a result of sex for ≥3 months in the past year, plus measures of symptom severity.
Results
Painful sex was reported by 7.5% (95% CI 6.7–8.3) of sexually active women, of whom one‐quarter experienced symptoms very often or always, for ≥6 months, and causing distress. Reporting painful sex was strongly associated with other sexual function problems, notably vaginal dryness (age adjusted odds ratio 7.9; 6.17–10.12), anxiety about sex (6.34; 4.76–8.46) and lacking enjoyment in sex (6.12; 4.81–7.79). It was associated with sexual relationship factors such as not sharing same level of interest in sex (2.56; 1.97–3.33), as well as with adverse experiences such as non‐volitional sex (2.17; 1.68–2.80). Associations were also found with measures of psychological and physical health, including depressive symptoms (1.68; 1.28–2.21).
Conclusion
Painful sex is reported by a sizeable minority of women in Britain. Health professionals should be supported to undertake holistic assessment and treatment which takes account of the sexual, relationship and health context of symptoms.
Tweetable
Painful sex—reported by 7.5% of women in Britain—is linked to poorer sexual, physical, relational and mental health.
Tweetable
Painful sex–reported by 7.5% of women in Britain–is linked to poorer sexual, physical, relational and mental health.
This article includes Author Insights, a video available at https://vimeo.com/rcog/authorinsights14518.
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