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Lohmann posted an update 1 year, 1 month ago
In general, these results suggest that the HGP in the FG is closely related to the performance of face image recognition.Airway wall remodeling, a main pathology of asthma was linked to vitamin-D deficiency and protein arginine methyltransferase-1 (PRMT1) expression in sub-epithelial cell layers. Calcitriol reduced remodeling in asthma model, but its mode of action is unclear. This study assessed the effect of calcitriol on PRMT1-dependent fibroblast remodeling in human lung fibroblasts, and allergen-induced asthma in E3-rats. Fibroblasts were activated with thymic stromal lymphopoietin (TLSP); asthma was induced by ovalbumin inhalation in rats. The airway structure was assessed by immunohistology. Protein expression in fibroblasts and activation of the mitogen activated protein kinases were detected by Western-blotting. Transcription factor activation was determined by luciferase reporter assay. PRMT1 action was blocked by siRNA and PRMT-inhibition. Ovalbumin upregulated the expression of TSLP, PRMT1, matrix metallopro-teinase-1 (MMP1), interleukin-25, and collagen type-I in sub-epithelial fibroblasts. In isolated fibroblasts, TSLP induced the same proteins, which were blocked by inhibition of Erk1/2 and p38. TLSP induced PRMT1 through activation of signal transducer and activator of transcription-3. PRMT1 inhibition reduced collagen type-I expression and suppressed MMP1. In fibroblasts, calcitriol supplementation over 12 days prevented TSLP-induced remodeling by blocking the PRMT1 levels. Interestingly, short-term calcitriol treatment had no such effect. The data support the beneficial role of calcitriol in asthma therapy.The DYRK (Dual-specificity tYrosine-phosphorylation Regulated protein Kinase) family consists of five related protein kinases (DYRK1A, DYRK1B, DYRK2, DYRK3, DYRK4). DYRKs show homology to Drosophila Minibrain, and DYRK1A in human chromosome 21 is responsible for various neuronal disorders including human Down syndrome. Here we report identification of cellular proteins that associate with specific members of DYRKs. Cellular proteins with molecular masses of 90, 70, and 50-kDa associated with DYRK1B and DYRK4. These proteins were identified as molecular chaperones Hsp90, Hsp70, and Cdc37, respectively. Microscopic analysis of GFP-DYRKs showed that DYRK1A and DYRK1B were nuclear, while DYRK2, DYRK3, and DYRK4 were mostly cytoplasmic in COS7 cells. Overexpression of DYRK1B induced nuclear re-localization of these chaperones with DYRK1B. Treatment of cells with specific Hsp90 inhibitors, geldanamycin and 17-AAG, abolished the association of Hsp90 and Cdc37 with DYRK1B and DYRK4, but not of Hsp70. Inhibition of Hsp90 chaperone activity affected intracellular dynamics of DYRK1B and DYRK4. DYRK1B and DYRK4 underwent rapid formation of cytoplasmic punctate dots after the geldanamycin treatment, suggesting that the chaperone function of Hsp90 is required for prevention of protein aggregation of the target kinases. Prolonged inhibition of Hsp90 by geldanamycin, 17-AAG, or ganetespib, decreased cellular levels of DYRK1B and DYRK4. Finally, DYRK1B and DYRK4 were ubiquitinated in cells, and ubiquitinated DYRK1B and DYRK4 further increased by Hsp90 inhibition with geldanamycin. Taken together, these results indicate that Hsp90 and Cdc37 discriminate specific members of the DYRK kinase family and play an important role in quality control of these client kinases in cells.The protein lysine methyltransferase, SMYD2 is involved in diverse cellular events by regulating protein functions through lysine methylation. Though several substrate proteins of SMYD2 are well-studied, only a limited number of its interaction partners have been identified and characterized. Here, we performed a yeast two-hybrid screening of SMYD2 and found that the ribosomal protein, eL21 could interact with SMYD2. SMYD2-eL21 interaction in the human cells was confirmed by immunoprecipitation methods. In vitro pull-down assays revealed that SMYD2 interacts with eL21 directly through its SET and MYND domain. Computational mapping, followed by experimental studies identified that Lys81 and Lys83 residues of eL21 are important for the SMYD2-eL21 interaction. Evolutionary analysis showed that these residues might have co-evolved with the emergence of SMYD2. We found that eL21 regulates the steady state levels of SMYD2 by promoting its transcription and inhibiting its proteasomal degradation. Importantly, SMYD2-eL21 interaction plays an important role in regulating cell proliferation and its dysregulation might lead to tumorigenesis. Our findings highlight a novel extra-ribosomal function of eL21 on regulating SMYD2 levels and imply that ribosomal proteins might regulate wide range of cellular functions through protein-protein interactions in addition to their core function in translation.An increasing number of studies has focused on the after-effects of acute aerobic exercise on executive function. Rolipram To date, empirical evidence lacks consensus regarding whether acute aerobic exercise has beneficial effects on executive function. To identify possible sources of this discrepancy, the present study focused on executive function demands and pre-test cognitive performance, and performed the first meta-analysis of individual participant data (IPD meta-analysis) in this area of research. Results indicated that the beneficial after-effects of acute aerobic exercise on cognitive performance were greater in participants with lower cognitive performance at pre-test. Acute aerobic exercise offered general benefits to cognitive performance irrespective of executive function demands, when pre-test cognitive performance was appropriately controlled. Thus, the present IPD meta-analysis suggests that pre-test cognitive performance is one possible source of the conflicting findings in acute exercise studies. Future research is encouraged to consider pre-test cognitive performance to avoid underestimating the beneficial after-effects of acute exercise.
Catheter ablation is more effective than antiarrhythmic drug therapy alone in patients with atrial fibrillation (AF). However, there are limited data on the outcomes of AF ablation according to sex. The purpose of this study was to evaluate gender differences in the actual outcomes after catheter ablation for atrial fibrillation.
Of 801,710 patients with AF in the Korean National Health Insurance Service database, we identified 9175 patients without valvular heart disease who underwent AF ablation between 2006 and 2015 and assessed 30-day safety and one-year effectiveness outcomes according to sex.
Of the 9175 patients who underwent AF ablation, 2206 (24%) were female. Women, compared to men, were older (60.8 ± 10.2 vs. 56.0 ± 10.5 years), had higher CHA
DS
-VASc (3.5 ± 1.7 vs. 2.0 ± 1.6), higher HAS-BLED (2.6 ± 1.3 vs. 2.4 ± 1.2), and higher Charlson comorbidity index scores (3.8 ± 2.6 vs. 3.1 ± 2.5) (p < 0.001 for all). Following ablation, there was no significant difference in the risk of 30-day complications, including hemorrhage and tamponade, between women and men.