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Specific cellular functions mediated by GPCRs are often associated with signalling through a particular G protein or β-arrestin. Here, we examine signalling through a GPCR, protease-activated receptor 2 (PAR2), in a high-grade serous ovarian cancer cell line (OV90).

Human ovarian cancer tissues (n = 1,200) and nine human ovarian cancer cell lines were assessed for PAR2 expression. PAR2 signalling mechanisms leading to cell migration and invasion were dissected using cellular assays, western blots, CRISPR-Cas9 gene knockouts, pharmacological inhibitors of PAR2 and downstream signalling proteins in OV90 cancer cells.

PAR2 was significantly overexpressed in clinical ovarian cancer tissues and in OV90 ovarian cancer cells. PAR2 agonists, an endogenous protease (trypsin) and a synthetic peptide (2f-LIGRL-NH

), induced migration and invasion of OV90 ovarian cancer cells through activating a combination of Gα

, Gα

and β-arrestin1/2, but not Gα

or Gα

. This novel cooperative rather than parallel signapathway.Recent studies suggest that the mycorrhizal type associated with tree species is an important trait influencing ecological processes such as response to environmental conditions and conspecific negative density dependence (CNDD). However, we lack a general understanding of how tree mycorrhizal type influences CNDD strength and the resulting patterns of species abundance and richness at larger spatial scales. We assessed 305 species across 15 large, stem-mapped, temperate forest dynamics plots in Northeastern China and North America to explore the relationships between tree mycorrhizal type and CNDD, species abundance, and species richness at a regional scale. Tree species associated with arbuscular mycorrhizal (AM) fungi showed a stronger CNDD and a more positive relationship with species abundance than did tree species associated with ectomycorrhizal (ECM) fungi. For each plot, both basal area and stem abundance of AM tree species was lower than that of ECM tree species, suggesting that AM tree species were rarer than ECM tree species. Finally, ECM tree dominance showed a negative effect on plant richness across plots. These results provide evidence that tree mycorrhizal type plays an important role in influencing CNDD and species richness, highlighting this trait as an important factor in structuring plant communities in temperate forests.

Human milk as compared to formula reduces morbidity in preterm infants but requires fortification to meet their nutritional needs and to reduce the risk of extrauterine growth failure. Standard fortification methods are not individualized to the infant and assume that breast milk is uniform in nutritional content. Strategies for individualizing fortification are available; however it is not known whether these are safe, or if they improve outcomes in preterm infants.

To determine whether individualizing fortification of breast milk feeds in response to infant blood urea nitrogen (adjustable fortification) or to breast milk macronutrient content as measured with a milk analyzer (targeted fortification) reduces mortality and morbidity and promotes growth and development compared to standard, non-individualized fortification for preterm infants receiving human milk at < 37 weeks' gestation or at birth weight < 2500 grams.

We used the standard search strategy of Cochrane Neonatal to search the Cochranference during the intervention compared with standard non-individualized fortification. Evidence showing important in-hospital and post-discharge clinical outcomes was sparse and of very low certainty, precluding inferences regarding safety or clinical benefits beyond short-term growth.Shifts in reproductive timing are among the most commonly documented responses of organisms to global climate change. However, our knowledge of these responses is biased towards taxa that are easily observable and abundant in existing biodiversity data sets. Mammals are common subjects in reproductive biology, but mammalian phenology and its drivers in the wild remain poorly understood because many species are small, secretive, or too labor-intensive to monitor. We took an informatics-based approach to reconstructing breeding phenology in the widespread North American deer mouse (Peromyscus maniculatus) using individual-level reproductive observations from digitized museum specimens and field censuses spanning >100 yr and >45 degrees of latitude. We reconstructed female phenology in different regions and tested the importance of three environmental variables (photoperiod, temperature, precipitation) as breeding cues. Photoperiod and temperature were strong positive and negative breeding cues, respectively, whereas precipitation was not a significant predictor of breeding phenology. However, phenologies and the use of environmental cues varied substantially among regions, and we found evidence that these cueing repertoires are tuned to ecosystem-specific limiting conditions. Our results reiterate the importance of ecological context in optimizing reproduction and demonstrate how harmonization across biodiversity data resources allows new insight into phenology and its drivers in wild mammals.Soil fungi link above- and belowground carbon (C) fluxes through their interactions with plants and contribute to C and nutrient dynamics through the production, turnover, and activity of fungal hyphae. Despite their importance to ecosystem processes, estimates of hyphal production and turnover rates are relatively uncommon, especially in temperate hardwood forests. Selleckchem Y-27632 We sequentially harvested hyphal ingrowth bags to quantify the rates of Dikarya (Ascomycota and Basidiomycota) hyphal production and turnover in three hardwood forests in the Midwestern United States, where plots differed in their abundance of arbuscular (AM)- vs. ectomycorrhizal (ECM)-associated trees. Hyphal production rates increased linearly with the percentage of ECM trees and annual production rates were 66% higher in ECM- than AM-dominated plots. Hyphal turnover rates did not differ across the mycorrhizal gradient (plots varying in their abundance of AM vs. ECM trees), suggesting that the greater fungal biomass in ECM-dominated plots relates to greater fungal production rather than slower fungal turnover.

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