Regulation of MRTF-A by JMY via a nucleation-independent mechanism.

BACKGROUND: MRTF-A (myocardin-related transcription factor A) is a coactivator for SRF-mediated gene expression. The activity of MRTF-A is critically dependent on the dissociation of G-actin from N-terminal RPEL motifs. MRTF-SRF induction often correlates with enhanced polymerization of F-actin. Here we investigate MRTF regulation by the multifunctional JMY protein, which contains three WASP/verprolin homology 2 (WH2/V) domains and facilitates Arp2/3-dependent and -independent actin nucleation. METHODS: Co-immunoprecipitation experiments, immunofluorescence and luciferase reporter assays were combined with selective inhibitors to investigate the effect of JMY and its domains on MRTF-A in NIH 3 T3 mouse fibroblasts. RESULTS: JMY induced MRTF-A transcriptional activity and enhanced its nuclear translocation. Unexpectedly, MRTF-A was hyperactivated when the Arp2/3-recruiting CA region of JMY was deleted or mutated, suggesting an autoinhibitory mechanism for full-length JMY. Moreover, isolated WH2/V domains which are unable to nucleate actin were sufficient for nuclear accumulation and SRF activation. Recombinant WH2/V regions of JMY biochemically competed with MRTF-A for actin binding. Activation of MRTF-A by JMY was unaffected by Arp3 knockdown, by an Arp2/3 inhibitor, and by latrunculin which disassembles cellular F-actin. Restriction of JMY to the nucleus abrogated its MRTF-A activation. Finally, JMY RNAi reduced basal and stimulated transcriptional activation via MRTF-A. CONCLUSIONS: Our results suggest that JMY activates MRTF-SRF independently of F-actin via WH2/V-mediated competition with the RPEL region for G-actin binding in the cytoplasm. Furthermore, the C-terminal region facilitates an autoinhibitory effect on full-length JMY, possibly by intramolecular folding.

Predictive value of the APACHE II score in cardiogenic shock patients treated with a percutaneous left ventricular assist device.

Background: The APACHE II score assesses patient prognosis in intensive care units. Different disease entities are predictable by using a specific factor called Diagnostic Category Weight (DCW). We aimed to validate the prognostic value of the APACHE II score in patients treated with a percutaneous left ventricular assist device because of refractory cardiogenic shock (CS). Methods: From the Dresden Impella Registry, we analyzed 180 patients receiving an Impella CP®. The main outcome was the observed intrahospital mortality ( S ^ ( t h o s p ) ), which was compared to the predicted mortality estimated by the APACHE II score. Results: The APACHE II score, which was 33.5 ± 0.6, significantly overestimated intrahospital mortality ( S ^ ( t h o s p ) 54.4 ± 3.7% vs. APACHE II 74.6 ± 1.6%; p < 0.001). Nevertheless, the APACHE II score showed an acceptable accuracy to predict intrahospital mortality (ROC AUC 0.70; 95% CI 0.62-0.78). Thus, we adapted the formula for calculation of predicted mortality by adjusting DCW. The total registry cohort was randomly divided into derivation group for calculation of adjusted DCW and validation group for testing. Intrahospital mortality was much more precisely predicted using the adjusted DCW compared to the conventional DCW (difference of predicted and observed mortality: -4.7 ± 2.4% vs. -23.2 ± 2.3%; p < 0.001). The new calculated DCW was -1.183 for the total cohort. Conclusion: The APACHE II score has an acceptable accuracy for the prediction of intrahospital mortality but overestimates its total amount in CS patients. Adjustment of the DCW can lead to a much more precise prediction of prognosis.

Data for validation and adjustment of APACHE II score in cardiogenic shock patients treated with a percutaneous left ventricular assist device.

A precise prognosis is of imminent importance in intensive care medicine. This article provides data showing the overestimation of intrahospital mortality by APACHE II score in various subgroups of cardiogenic shock patients treated with a percutaneous left ventricular assist device. The data set includes additional baseline characteristics regarding age, pre-existing diseases, characteristics of coronary artery disease, characteristics of cardiopulmonary resuscitation, and hemodynamic parameter not included in the APACHE II score. Further data were provided which characterize derivation and validation group. Both groups were used for adjustment of the APACHE II approach. The data are supplemental to our original research article titled "Predictive value of the APACHE II score in cardiogenic shock patients treated with a percutaneous left ventricular assist device" (Mierke et al., IJC Heart & Vasculature. 40 (2022) 101013. https://doi.org/10.1016/j.ijcha.2022.101013).

Changes of Adipose Tissue Morphology and Composition during Late Pregnancy and Early Lactation in Dairy Cows.

Dairy cows mobilize large amounts of body fat during early lactation to overcome negative energy balance which typically arises in this period. As an adaptation process, adipose tissues of cows undergo extensive remodeling during late pregnancy and early lactation. The objective of the present study was to characterize this remodeling to get a better understanding of adaptation processes in adipose tissues, affected by changing metabolic conditions including lipid mobilization and refilling as a function of energy status. This was done by determining adipocyte size in histological sections of subcutaneous and retroperitoneal adipose tissue biopsy samples collected from German Holstein cows at 42 days prepartum, and 1, 21, and 100 days postpartum. Characterization of cell size changes was extended by the analysis of DNA, triacylglycerol, and protein content per gram tissue, and ß-actin protein expression in the same samples. In both adipose tissue depots cell size was becoming smaller during the course of the study, suggesting a decrease in cellular triacylglycerol content. Results of DNA, triacylglycerol, and protein content, and ß-actin protein expression could only partially explain the observed differences in cell size. The retroperitoneal adipose tissue exhibited a greater extent of time-related differences in cell size, DNA, and protein content, suggesting greater dynamics and metabolic flexibility for this abdominal depot compared to the investigated subcutaneous depot.