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Phosphorylation of GATA4 at serine-105 is required for left ventricular remodelling process in angiotensin-II - induced hypertension in rats.In this study, we investigated whether local intramyocardial GATA4 overexpression affects the left ventricular (LV) remodelling process and the importance of phosphorylation at serine-105 (S105) for the actions of GATA4 in an angiotensin II (AngII)-induced hypertension rat model. Adenoviral constructs overexpressing wild type GATA4 or GATA4 mutated at S105 were delivered into the anterior LV free wall. AngII (33.3 µg x kg x h ) was administered via subcutaneously implanted minipumps. Cardiac function and structure were examined by echocardiography, followed by histological immunostainings of LV sections and gene expression measurements by RT-qPCR. The effects of GATA4 on cultured neonatal rat ventricular fibroblasts were evaluated. In AngII-induced hypertension, GATA4 overexpression repressed fibrotic gene expression, reversed the hypertrophic adult-to-foetal isoform switch of myofibrillar genes and prevented apoptosis, whereas histological fibrosis was not affected. Overexpression of GATA4 mutated at S105 resulted in LV chamber dilatation, cardiac dysfunction and had minor effects on expression of myocardial remodelling genes. Fibrotic gene expression in cardiac fibroblasts was differently affected by overexpression of wild type or mutated GATA4. Our results indicate that GATA4 reduces AngII-induced responses by interfering with pro-fibrotic and hypertrophic gene expressions. GATA4 actions on LV remodelling and fibroblasts are dependent on phosphorylation site S105.
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Mass casualty incidents-are you ready? A major incident planning template for diagnostic radiology.Mass casualty incidents (MCIs) create a large number of casualties in a short period of time. Diagnostic radiology plays an important role in major incident responses but is often underrepresented during major incident planning (MIP) and simulation. Surveys suggest radiologists are unfamiliar with their role during an MCI. We aimed to identify key topics for radiology MIP, familiarize radiologists with their role during an MCI and identify areas for future research. The terms "radiology" and "mass casualty incident" were entered into the advanced search builder on PubMed. Abstracts from this primary search were reviewed and papers selected for inclusion. Additional studies of interest were identified upon review of reference sections of relevant articles and from the related article tab on PubMed. MCI and trauma guidelines were reviewed. Key factors that caused issues during prior MCIs were identified including staff alert mechanisms, patient identification strategies, patient tracking, scan ordering and result communication. Limitations of local imaging resources and capacity should be identified and inform plans for the utilization of diagnostic radiology in the MCI setting. Simulation can help identify areas for improvement and familiarize staff with their roles. Further development of reliable MCI alert technology and patient identification strategies are needed as well as prospective validation of trauma CT selection criteria to identify patients who will benefit most from CT. Radiology should take part in MIP to address key issues encountered during prior MCIs and in MCI simulation to optimize major incident response.
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Swelling of cell walls in mature sweet cherry fruit: factors and mechanisms.Swelling of sweet cherry cell walls is a physical process counterbalanced by turgor. Cell turgor prevents swelling in intact cells, whereas loss of turgor allows cell walls to swell. Swelling of epidermal cell walls precedes skin failure in sweet cherry (Prunus avium) cracking. Swollen cell walls lead to diminished cell:cell adhesions. We identify the mechanism of cell wall swelling. Swelling was quantified microscopically on epidermal sections following freeze/thaw treatment or by determining swelling pressure or swelling capacity of cell wall extracts. Releasing turgor by a freeze/thaw treatment increased cell wall thickness 1.6-fold within 2 h. Pressurizing cell wall extracts at > 12 kPa prevented swelling in water, while releasing the pressure increased swelling. The effect was fully reversible. Across cultivars, cell wall thickness before and after turgor release in two subsequent seasons was significantly correlated (before release of turgor: r = 0.71**, n = 14; after release of turgor: r = 0.73**, n = 14) as was the swelling of cell walls upon turgor release (r = 0.71**, n = 14). Close relationships were also identified for cell wall thickness of fruit of the same cultivars grown in the greenhouse and the field (before release of turgor: r = 0.60, n = 10; after release of turgor: r = 0.78**, n = 10). Release of turgor by heating, plasmolysis, incubation in solvents or surfactants resulted in similar swelling (range 2.0-3.1 µm). Cell wall swelling increased from 1.4 to 3.0 µm as pH increased from pH 2.0 to 5.0 but remained nearly constant between pH 5.0 and 8.0. Increasing ethanol concentration decreased swelling. Swelling of sweet cherry cell walls is a physical process counterbalanced by turgor.
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2019 musculoskeletal radiology fellowship match process: initial experiences and lessons learned.To present the 2019 Musculoskeletal (MSK) fellowship Match information most useful to MSK fellowship programs and sections in hopes of optimizing the fellowship application and selection process for MSK fellowship applicants and training programs.
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Less NMDA Receptor Binding in Dorsolateral Prefrontal Cortex and Anterior Cingulate Cortex Associated with Reported Early Life Adversity but Not Suicide.Glutamate, an excitatory neurotransmitter binding to three classes of receptors including the N-methyl, D-aspartate (NMDA) receptor. NMDA receptor binding is lower in major depression (MDD) and suicide. NMDA receptor blocking with ketamine can have antidepressant and anti-suicide effects. Early life adversity (ELA) may cause glutamate mediated excitotoxicity, and is more common with MDD and in suicide decedents. We sought to determine whether NMDA-receptor binding is altered with suicide and ELA.
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