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ABSTRACT Background Aim Methods Results Conclusion Blocking IL‐13 is highly efficacious in patients with Th2‐biased atopic dermatitis (AD), and recent clinical data have highlighted that targeting the T cell costimulatory molecules OX40 and OX40L (TNFSF4) holds promise for future treatment of AD.We asked whether targeting another T cell costimulatory molecule, CD30L (TNFSF8), might also be a possible treatment option in AD.Single‐cell RNA‐seq data from human AD skin lesions was analyzed to identify pathogenic IL‐13‐ or IL‐22‐producing T cells and assess expression of CD30 and its ligand in comparison to OX40 and its ligand. Additionally, a murine model of AD with repetitive exposure to house dust mite allergen was used to compare neutralizing antibodies against CD30L with those against IL‐13 or OX40L.Analysis of several scRNA‐seq datasets from skin lesions of AD patients showed that transcripts for CD30 or CD30L were found expressed with OX40 or OX40L in the primary T cell populations that also expressed mRNA for IL13 and/or IL22. Suggesting that this could be therapeutically relevant, mice treated prophylactically with a blocking CD30L antibody were protected from developing maximal allergen‐induced AD features, including epidermal and dermal thickening, immune cell infiltration, and expression of AD‐related genes, similar to mice treated with a blocking IL‐13 antibody. Moreover, therapeutic neutralization of CD30L in mice with experimental AD also reduced all of the pathological skin lesion features to a comparable extent as blocking OX40L.These data suggest that targeting the CD30–CD30L axis might hold promise as a future therapeutic intervention in human AD, similar to targeting the OX40–OX40L axis. [ABSTRACT FROM AUTHOR]

Summary: Climate change is projected to cause increased inflow of terrestrial dissolved organic matter to coastal areas in northerly regions. Estuarine bacterial community will thereby receive larger loads of organic matter and inorganic nutrients available for microbial metabolism. The composition of the bacterial community and its ecological functions may thus be affected. We studied the responses of bacterial community to inflow of terrestrial dissolved organic matter in a subarctic estuary in the northern Baltic Sea, using a 16S rRNA gene metabarcoding approach. Betaproteobacteria dominated during the spring river flush, constituting ~ 60% of the bacterial community. Bacterial diversity increased as the runoff decreased during summer, when Verrucomicrobia, Betaproteobacteria, Bacteroidetes, Gammaproteobacteria and Planctomycetes dominated the community. Network analysis revealed that a larger number of associations between bacterial populations occurred during the summer than in spring. Betaproteobacteria and Bacteroidetes populations appeared to display similar correlations to environmental factors. In spring, freshly discharged organic matter favoured specialists, while in summer a mix of autochthonous and terrestrial organic matter promoted the development of generalists. Our study indicates that increased inflows of terrestrial organic matter‐loaded freshwater to coastal areas would promote specialist bacteria, which in turn might enhance the transformation of terrestrial organic matter in estuarine environments. [ABSTRACT FROM AUTHOR]

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The combination of doxorubicin and cyclophosphamide commonly used to treat breast cancer can cause premature ovarian failure and infertility. α-Tocopherol is a potent antioxidant whereas γ-tocopherol causes apoptosis in a variety of cancer models in vitro including breast cancer. We hypothesised that the combination of doxorubicin (Dox) and 4-hydroperoxycyclophosphamide (4-Cyc) would be more cytotoxic in vitro than each agent alone, and that α-tocopherol would reduce and γ-tocopherol would augment the cytotoxicity of the combined chemotherapeutics. Human MCF-7 breast cancer and KGN ovarian cells were exposed to Dox, 4-Cyc, combined Dox and 4-Cyc, α-tocopherol, γ-tocopherol, or a combination of Dox and 4-Cyc with α-tocopherol or γ–tocopherol. Cell viability was assessed using a crystal violet assay according to four schedules: 24h exposure, 24h exposure + 24h culture in medium, 24h exposure + 48h culture in medium, or 72h continuous exposure. Supernatants from each separate KGN culture experiment (n=3) were examined using an estradiol ELISA. Dox was cytotoxic to both MCF-7 and KGN cells, but 4-Cyc only killed MCF-7 cells. γ-Tocopherol significantly decreased MCF-7 but not KGN cell viability. The combined chemotherapeutics and γ-tocopherol were more cytotoxic to MCF-7 than KGN cells, and α-tocopherol reduced the cytotoxicity of the combined chemotherapeutics towards KGN ovarian cells, but not MCF-7 cells. The addition of both γ-tocopherol and α-tocopherol to the chemotherapeutic combination of Dox and cyclophosphamide has the potential to increase in vitro chemotherapeutic efficacy against breast cancer cells whilst decreasing cytotoxicity towards ovarian granulosa cells. [ABSTRACT FROM AUTHOR]

Variations in the preferred temperatures during the rest periods of Grammostola rosea Walckenaer and Paraphysa parvula Pocock, two mygalomorph spiders occupying different habitats in central Chile, are analyzed. The former inhabits arid and semi-arid lowland near plant communities, composed of shrubs (evergreens with small leathery leaves) and small trees; the latter is found in the central mountains of the Chilean Andes, above 2000 m.a.s.l. The preferred temperatures of these spiders at different times of day and exposure to cold (15 °C) and warm (25 °C) acclimation temperatures are compared. Body mass does not affect the preferred temperature of the larger spider G. rosea, although P. parvula, a spider with half of the body mass of G. rosea, shows a decrease in preferred temperature with body mass. This can be explained by a higher plasticity and thermal sensitivity of the smaller species as result of increased surface : volume ratio. The preferred temperature increases with the hour of the day under both acclimation conditions in P. parvula and in cold-acclimated G. rosea, which is likely associated with crepuscular and nocturnal behaviour in both species. Grammostola rosea shows temperature preferences lower than those of P. parvula under both acclimation conditions. The increase of the acclimation temperature from 15 to 25 °C results in an increment of 2-3 °C in the preferred temperature of P. parvula but only 0.2 °C in that of G. rosea. Two contrasting lifestyle strategies are found: a small mygalomorph spider with phenotypic plasticity and adaptation to the fluctuating environment of high altitude, and a large mygalomorph spider with higher thermal inertia adapted to the more stable environment of lowlands. [ABSTRACT FROM AUTHOR]