Notes

Ion-dependent composition, dynamics, as well as allosteric coupling in the non-selective cation channel.
Cellular senescence is associated with inflammation and the senescence-associated secretory phenotype (SASP) of secreted proteins. Vascular smooth muscle cell (VSMC) expressing the SASP contributes to chronic vascular inflammation, loss of vascular function, and the developments of age-related diseases. Although VSMC senescence is well recognized, the mechanism of VSMC senescence and inflammation has not been established. In this study, we aimed to determine whether prednisolone (PD) attenuates adriamycin (ADR)-induced VSMC senescence and inflammation through the SIRT1-AMPK signaling pathway. We found that PD inhibited ADR-induced VSMC senescence and inflammation response by decreasing p-NF-κB expression through the SIRT1-AMPK signaling pathway. In addition, Western blotting revealed PD not only increased SIRT1 expression but also increased the phosphorylation of AMPK at Ser485 in ADR-treated VSMC. Furthermore, siRNA-mediated downregulation or pharmacological inhibitions of SIRT1 or AMPK significantly augmented ADR-induced inflammatory response and senescence in VSMC despite PD treatment. In contrast, the overexpression of SIRT1 or constitutively active AMPKα (CA-AMPKα) attenuated cellular senescence and p-NF-κB expression. Taken together, the inhibition of p-NF-κB by PD through the SIRT1 and p-AMPK (Ser485) pathway suppressed VSMC senescence and inflammation. Collectively, our results suggest that anti-aging effects of PD are caused by reduced VSMC senescence and inflammation due to reciprocal regulation of the SIRT1/p-AMPK (Ser485) signaling pathway.The Human T-cell leukemia virus type 1 (HTLV-1) orf I-encoded accessory protein p8 is cleaved from its precursor p12, and both proteins contribute to viral persistence. p8 induces cellular protrusions, which are thought to facilitate transfer of p8 to target cells and virus transmission. Host factors interacting with p8 and mediating p8 transfer are unknown. Here, we report that vasodilator-stimulated phosphoprotein (VASP), which promotes actin filament elongation, is a novel interaction partner of p8 and important for p8 and HTLV-1 Gag cell-to-cell transfer. VASP contains an Ena/VASP homology 1 (EVH1) domain that targets the protein to focal adhesions. Bioinformatics identified a short stretch in p8 (amino acids (aa) 24-45) which may mediate interactions with the EVH1 domain of VASP. Co-immunoprecipitations confirmed interactions of VASPp8 in 293T, Jurkat and HTLV-1-infected MT-2 cells. Co-precipitation of VASPp8 could be significantly blocked by peptides mimicking aa 26-37 of p8. Mutational studies revealed that the EVH1-domain of VASP is necessary, but not sufficient for the interaction with p8. Further, deletion of the VASP G- and F-actin binding domains significantly diminished co-precipitation of p8. Imaging identified areas of partial co-localization of VASP with p8 at the plasma membrane and in protrusive structures, which was confirmed by proximity ligation assays. Co-culture experiments revealed that p8 is transferred between Jurkat T-cells via VASP-containing conduits. Imaging and flow cytometry revealed that repression of both endogenous and overexpressed VASP by RNA interference or by CRISPR/Cas9 reduced p8 transfer to the cell surface and to target Jurkat T-cells. Stable repression of VASP by RNA interference in chronically infected MT-2 cells impaired both p8 and HTLV-1 Gag transfer to target Jurkat T-cells, while virus release was unaffected. Thus, we identified VASP as a novel interaction partner of p8, which is important for transfer of HTLV-1 p8 and Gag to target T-cells.Patellofemoral pain (PFP) is commonly caused by abnormal pressure on the knee due to excessive load while standing, squatting, or going up or down stairs. To better understand the pathophysiology of PFP, we conducted a noninvasive patellar tracking study using a C-arm computed tomography (CT) scanner to assess the non-weight-bearing condition at 0° knee flexion (NWB0°) in supine, weight-bearing at 0° (WB0°) when upright, and at 30° (WB30°) in a squat. Three-dimensional (3D) CT images were obtained from patients with PFP (12 women, 6 men; mean age, 31 ± 9 years; mean weight, 68 ± 9 kg) and control subjects (8 women, 10 men; mean age, 39 ± 15 years; mean weight, 71 ± 13 kg). Six 3D-landmarks on the patella and femur were used to establish a joint coordinate system (JCS) and kinematic degrees of freedom (DoF) values on the JCS were obtained patellar tilt (PT, °), patellar flexion (PF, °), patellar rotation (PR, °), patellar lateral-medial shift (PTx, mm), patellar proximal-distal shift (PTy, mm), and patellar anterior-posterior shift (PTz, mm). Tests for statistical significance (p less then 0.05) showed that the PF during WB30°, the PTy during NWB0°, and the PTz during NWB0°, WB0°, and WB30° showed clear differences between the patients with PFP and healthy controls. In particular, the PF during WB30° (17.62°, extension) and the PTz during WB0° (72.5‬0 mm, posterior) had the largest rotational and translational differences (JCS Δ = patients with PFP-controls), respectively. The JCS coordinates with statistically significant difference can serve as key biomarkers of patellar motion when evaluating a patient suspected of having PFP. see more The proposed method could reveal diagnostic biomarkers for accurately identifying PFP patients and be an effective addition to clinical diagnosis before surgery and to help plan rehabilitation strategies.Music is considered a vital element in young people's lives. It functions as an important means for expressing the emotions and feelings they experience in a daily basis. As such, this study explores the music preferences of high school Brazilian students (N = 940), 530 female (56.9%) and 410 male (43.1%) participants between 14 and 20 years old (M = 16.14 years old, SD = 1.22). The main instrument for data collection was the Questionnaire on Musical Style Preferences, which was adapted to the Brazilian context and encompassed 33 different music styles. A principal component analysis resulted in five dimensions representing different musical styles (1) Intense, (2) Unique, (3) Sophisticated, (4) Contemporary, and (5) Mellow. The results of this study reinforced theory of the five-factor model of musical preference. Results also suggest that Mellow music was the most preferred while Sophisticated music was the least preferred among participants. Regarding gender, male participants showed a greater preference towards Contemporary, Intense, and Sophisticated music, whereas women generally preferred Mellow and Unique.
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