Notes

Biophenolic Profile Modulations throughout Olive Flesh as Impacted by Manganese Diet.
Serum/plasma of adult female green turtles had significantly lower δ2H values compared with juveniles, likely due to increased lipid mobilization associated with reproduction. This is the first study to quantify Δ2HNet values in a marine ectotherm, and we anticipate that our results will further refine the use of δ2H analysis to better understand animal resource and habitat use in marine ecosystems, especially coastal areas fueled by a combination of marine (e.g. micro/macroalgae and seagrass) and terrestrial (e.g. mangroves) primary production.Environmental temperature variation generates adaptive phenotypic differentiation in widespread populations. BMS-232632 chemical structure We used a common garden experiment to determine whether offspring with varying parental origins display adaptive phenotypic variation related to different thermal conditions experienced in parental environments. We compared burst swimming performance and critical thermal limits of African clawed frog (Xenopus laevis) tadpoles bred from adults captured at high (∼2000 m above sea level) and low (∼ 5 m above sea level) altitudes. Maternal origin significantly affected swimming performance. Optimal swimming performance temperature (Topt) had a >9°C difference between tadpoles with low altitude maternal origins (pure- and cross-bred, 35.0°C) and high-altitude maternal origins (pure-bred, 25.5°C; cross-bred, 25.9°C). Parental origin significantly affected critical thermal (CT) limits. Pure-bred tadpoles with low-altitude parental origins had higher CTmax (37.8±0.8°C) than pure-bred tadpoles with high-altitude parental origins and all cross-bred tadpoles (37.0±0.8 and 37.1±0.8°C). Pure-bred tadpoles with low-altitude parental origins and all cross-bred tadpoles had higher CTmin (4.2±0.7 and 4.2±0.7°C) than pure-bred tadpoles with high-altitude parental origins (2.5±0.6°C). Our study shows that the varying thermal physiological traits of Xenopus laevis tadpoles are the result of adaptive responses to their parental thermal environments. This study is one of few demonstrating potential intraspecific evolution of critical thermal limits in a vertebrate species. Multi-generation common garden experiments and genetic analyses would be required to further tease apart the relative contribution of plastic and genetic effects to the adaptive phenotypic variation observed in these tadpoles.Immunotherapy (IT) and targeted therapy (TT) are both effective against melanoma, but their combination is frequently toxic. Here, we investigated whether the sequence of IT (anti-PD-1)→ TT (ceritinib-trametinib or dabrafenib-trametinib) was associated with improved antitumor responses in mouse models of BRAF- and NRAS-mutant melanoma. Mice with NRAS-mutant (SW1) or BRAF-mutant (SM1) mouse melanomas were treated with either IT, TT, or the sequence of IT→TT. Tumor volumes were measured, and samples from the NRAS-mutant melanomas were collected for immune-cell analysis, single-cell RNA sequencing (scRNA-seq), and reverse phase protein analysis (RPPA). scRNA-seq demonstrated that the IT→TT sequence modulated the immune environment, leading to increased infiltration of T cells, monocytes, dendritic cells and natural killer cells, and decreased numbers of tumor-associated macrophages, myeloid-derived suppressor cells, and regulatory T cells. Durable responses to the IT→TT sequence were dependent on T-cell activity, with depletion of CD8+, but not CD4+, T cells abrogating the therapeutic response. An analysis of transcriptional heterogeneity in the melanoma compartment showed the sequence of IT→TT enriched for a population of melanoma cells with increased expression of MHC class I and melanoma antigens. RPPA analysis demonstrated that the sustained immune response induced by IT→TT suppressed tumor-intrinsic signaling pathways required for therapeutic escape. These studies establish that upfront IT improves the responses to TT in BRAF- and NRAS-mutant melanoma models.
This study aimed to quantify the incidence rates of common mental and physical health conditions in mothers of children with a life-limiting condition.

Comparative national longitudinal cohort study using linked primary and secondary care data from the Clinical Practice Research Datalink in England. Maternal-child dyads were identified in these data. Maternal physical and mental health outcomes were identified in the primary and secondary care datasets using previously developed diagnostic coding frameworks. Incidence rates of the outcomes were modelled using Poisson regression, adjusting for deprivation, ethnicity and age and accounting for time at risk.

A total of 35 683 mothers; 8950 had a child with a life-limiting condition, 8868 had a child with a chronic condition and 17 865 had a child with no long-term condition.The adjusted incidence rates of all of the physical and mental health conditions were significantly higher in the mothers of children with a life-limiting condition when compared with those mothers with a child with no long-term condition (eg, depression incidence rate ratio (IRR) 1.21, 95% CI 1.13 to 1.30; cardiovascular disease IRR 1.73, 95% CI 1.27 to 2.36; death in mothers IRR 1.59, 95% CI 1.16 to 2.18).

This study clearly demonstrates the higher incidence rates of common and serious physical and mental health problems and death in mothers of children with a life-limiting condition. Further research is required to understand how best to support these mothers, but healthcare providers should consider how they can target this population to provide preventative and treatment services.
This study clearly demonstrates the higher incidence rates of common and serious physical and mental health problems and death in mothers of children with a life-limiting condition. Further research is required to understand how best to support these mothers, but healthcare providers should consider how they can target this population to provide preventative and treatment services.
To examine if gestational age groups predict the development of social competence difficulties (SCDs) from childhood into mid-adolescence and to assess the mediation by maternal psychological distress during infancy on these trajectories.

Nationally representative population-based birth cohort (UK Millennium Cohort Study).

15 821 children born in 2000-2002.

SCDs (derived from peer and prosocial subscales of Strengths and Difficulties Questionnaire) were assessed by parent report when the participants were aged 3, 5, 7, 11 and 14 years. Maternal psychological distress was self-rated using Rutter Malaise Inventory when the children were 9 months of age. Data were modelled using latent growth curve analysis.

Developmental trajectories of SCDs were U-shaped in all groups. Very preterm (VP) children (<32 weeks, n=173) showed pronounced difficulties throughout, with the coefficient difference from the full term at age 14 being 0.94 (95% CI 0.23 to 1.66, equivalent to 0.32 SD of the population average SCDs).
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