Activation of the ErbB family of receptor tyrosine kinases via cognate Epidermal Growth Factor (EGF)-like peptide ligands constitutes a major group of related signaling pathways that control ...proliferation, survival, angiogenesis and metastasis of breast cancer. In this respect, clinical trials with various ErbB receptor blocking antibodies and specific tyrosine kinase inhibitors have proven to be partially efficacious in the treatment of this heterogeneous disease. Induction of an embryonic program of epithelial-to-mesenchymal transition (EMT) in breast cancer, whereupon epithelial tumor cells convert to a more mesenchymal-like phenotype, facilitates the migration, intravasation, and extravasation of tumor cells during metastasis. Breast cancers which exhibit properties of EMT are highly aggressive and resistant to therapy. Activation of ErbB signaling can regulate EMT-associated invasion and migration in normal and malignant mammary epithelial cells, as well as modulating discrete stages of mammary gland development. The purpose of this review is to summarize current information regarding the role of ErbB signaling in aspects of EMT that influence epithelial cell plasticity during mammary gland development and tumorigenesis. How this information may contribute to the improvement of therapeutic approaches in breast cancer will also be addressed.
The Diabetes Aerobic and Resistance Exercise trial found that aerobic training and resistance training alone each reduced hemoglobin A1c (HbA1c) compared with nonexercising controls, and combined ...aerobic and resistance training caused greater HbA1c reduction than either training type alone. Our objective was to determine whether a dose-response relationship existed between frequency of exercise training and HbA1c change, and whether this varied by exercise modality or participant characteristics.
Post hoc analysis of data from 185 Diabetes Aerobic and Resistance Exercise trial participants with type 2 diabetes randomized to aerobic, resistance or combined training thrice weekly. Dose-response relationships between adherence (percent of prescribed training sessions completed) and HbA1c change were assessed with linear regression.
Median overall adherence was 84.9% (interquartile range, 74.4%-93.6%). Higher exercise adherence was associated with greater HbA1c reduction; a 20% increase in adherence (e.g., an additional two sessions per month) was associated with a 0.15% (2 mmol·mol) decrease in HbA1c (β = -0.0076, R = -0.170, P = 0.021). Significant dose-response relationships were identified for aerobic (β = -0.0142, R = -0.313, P = 0.016) and combined training (β = -0.0109, R = -0.259, P = 0.041), but not resistance training (β = 0.0068, R = 0.153, P = 0.233). Dose-response relationships in all training groups combined were significant in subgroups younger than 55 yr (β = -0.0113, R = -0.286, P = 0.005), males (β = -0.0123, R = -0.234, P = 0.010), and baseline HbA1c ≥7.5% (58 mmol·mol) (β = -0.013, R = -0.263, P = 0.011).
There was a dose-response relationship between adherence to prescribed exercise and HbA1c reduction suggesting that glycemic control is improved more in individuals with type 2 diabetes with a higher training volume. Dose-response relationships existed for aerobic and combined training but not resistance training. These findings support aerobic and combined exercise prescriptions outlined in clinical practice guidelines.
We developed simple, reliable, and highly sensitive assay modifications of commercially available radioimmunoassay kits to measure estradiol in saliva and blood spot specimens. The saliva assay has ...average intra- and interassay coefficients of variation (CV) of 6.45 and 9.01%, with average analytical and serial dilution recoveries 100.65 and 89.25%. The blood spot assay has average intra- and interassay CVs of 7.57 and 8.22%, with analytical and serial dilution recoveries of 80.50 and 108.50%. The analytical sensitivity ranges of the saliva (0.25–7.50 pg/ml) and blood spot (2.00–375 pg/ml) assays are sufficient to determine levels in the majority of pre- and postpubertal males and females. Blood spot assay results are correlated with serum estradiol levels for adult males, r (17) = 0.73, and females, r (18) = 0.96. In contrast, the serum–saliva correlation is only modest for adult females, r (14) = 0.60, and not significant for adult males. Substitution of blood spot assay results for serum values underestimates the known serum estradiol–behavior correlation by only 3.45%, whereas substitution of saliva assay results for serum values underestimates the association by 37.55%. The findings have important implications for the use and potential misuse of noninvasive measures of estradiol in studies of health and human development.
Fluorescence nanoscopy, or super-resolution microscopy, has become an important tool in cell biological research. However, because of its usually inferior resolution in the depth direction (50–80 nm) ...and rapidly deteriorating resolution in thick samples, its practical biological application has been effectively limited to two dimensions and thin samples. Here, we present the development of whole-cell 4Pi single-molecule switching nanoscopy (W-4PiSMSN), an optical nanoscope that allows imaging of three-dimensional (3D) structures at 10- to 20-nm resolution throughout entire mammalian cells. We demonstrate the wide applicability of W-4PiSMSN across diverse research fields by imaging complex molecular architectures ranging from bacteriophages to nuclear pores, cilia, and synaptonemal complexes in large 3D cellular volumes.
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•Whole-cell 4Pi single-molecule switching nanoscopy allows 10- to 20-nm 3D resolution•Refined hardware and new data analysis allow imaging of cells as thick as ∼10 μm•Using structure-averaging, the 3D shape of a bacteriophage can be resolved•Wide applicability across diverse research fields is demonstrated
A new super-resolution microscope opens a window deep into cells to image organelles and subcellular structures spanning large volumes.
Isotope pool dilution studies are increasingly reported in the soils and ecology literature as a means of measuring gross rates of nitrogen (N) mineralization, nitrification, and inorganic N ...assimilation in soils. We assembled data on soil characteristics and gross rates from 100 studies conducted in forest, shrubland, grassland, and agricultural systems to answer the following questions: What factors appear to be the major drivers for production and consumption of inorganic N as measured by isotope dilution studies? Do rates or the relationships between drivers and rates differ among ecosystem types? Across a wide range of ecosystems, gross N mineralization is positively correlated with microbial biomass and soil C and N concentrations, while soil C:N ratio exerts a negative effect on N mineralization only after adjusting for differences in soil C. Nitrification is a log-linear function of N mineralization, increasing rapidly at low mineralization rates but changing only slightly at high mineralization rates. In contrast, NH4
+assimilation by soil microbes increases nearly linearly over the full range of mineralization rates. As a result, nitrification is proportionately more important as a fate for NH4
+at low mineralization rates than at high mineralization rates. Gross nitrification rates show no relationship to soil pH, with some of the fastest nitrification rates occurring below pH 5 in soils with high N mineralization rates. Differences in soil organic matter (SOM) composition and concentration among ecosystem types influence the production and fate of mineralized N. Soil organic matter from grasslands appears to be inherently more productive of ammonium than SOM from wooded sites, and SOM from deciduous forests is more so than SOM in coniferous forests, but differences appear to result primarily from differing C:N ratios of organic matter. Because of the central importance of SOM characteristics and concentrations in regulating rates, soil organic matter depletion in agricultural systems appears to be an important determinant of gross process rates and the proportion of NH4
+that is nitrified. Addition of15N appears to stimulate NH4
+consumption more than NO3
-consumption processes; however, the magnitude of the stimulation may provide useful information regarding the factors limiting microbial N transformations.
Trauma-Informed Care Forkey, Heather; Szilagyi, Moira; Kelly, Erin T ...
Pediatrics (Evanston),
08/2021, Letnik:
148, Številka:
2
Journal Article
Recenzirano
Most children will experience some type of trauma during childhood, and many children suffer from significant adversities. Research in genetics, neuroscience, and epidemiology all provide evidence ...that these experiences have effects at the molecular, cellular, and organ level, with consequences on physical, emotional, developmental, and behavioral health across the life span. Trauma-informed care translates that science to inform and improve pediatric care and outcomes. To practically address trauma and promote resilience, pediatric clinicians need tools to assess childhood trauma and adversity experiences as well as practical guidance, resources, and interventions. In this clinical report, we summarize current, practical advice for rendering trauma-informed care across varied medical settings.
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