A novel inhibitory mechanism of MRTF-A/B on the ICAM-1 gene expression in vascular endothelial cells

The roles of myocardin-related transcription factor A (MRTF-A) and MRTF-B in vascular endothelial cells are not completely understood. Here, we found a novel regulatory mechanism for MRTF-A/B function. MRTF-A/B tend to accumulate in the nucleus in arterial endothelial cells in vivo and human aortic endothelial cells (HAoECs) in vitro. In HAoECs, nuclear localization of MRTF-A/B was not significantly affected by Y27632 or latrunculin B, primarily due to the reduced binding of MRTF-A/B to G-actin and in part, to the low level of MRTF-A phosphorylation by ERK. MRTF-A/B downregulation by serum depletion or transfection of siRNA against MRTF-A and/or MRTF-B induced ICAM-1 expression in HAoECs. It is known that nuclear import of nuclear factor-kappa B (NF-kappa B) plays a key role in ICAM-1 gene transcription. However, nuclear accumulation of NF-kappa B p65 was not observed in MRTF-A/B-depleted HAoECs. Our present findings suggest that MRTF-A/B inhibit ICAM-1 mRNA expression by forming a complex with NF-kappa B p65 in the nucleus. Conversely, downregulation of MRTF-A/B alleviates this negative regulation without further translocation of NF-kappa B p65 into the nucleus. These results reveal the novel roles of MRTF-A/B in the homeostasis of vascular endothelium

Evidence-based bioethics: delineating the connections between science, practice, and values in medicine.

<p><b>A.</b> Secretion of FABP5 from adipose-derived stem cells (ADSC) after adipocyte differentiation at Day 0, Day 4 and Day 8 (n = 4 in each). Values were normalized to total protein concentration of the cell lysate. *P < 0.05 vs. Day 0. <b>B.</b> Flowchart of microarray analysis in ADSC treated with 1 μM recombinant FABP5 for 24 h. <b>C.</b> Gene ontology (GO) enrichment analysis. Significantly (Z-score > 0, P < 0.05) upregulated and downregulated GO terms of three GO categories, including cellular component, molecular function and biological process, were picked up and listed by a sort of lower P-value in each category. The abscissa of the bar plot was the number of annotated genes within the GO category. <b>D.</b> Cascade of the protein-protein interaction (PPI) network using a transcription factor binding site search data.</p

Prevention of hypoglycemia by intermittent-scanning continuous glucose monitoring device combined with structured education in patients with type 1 diabetes mellitus : A randomized, crossover trial

Aims: We conducted a randomized, crossover trial to compare intermittent-scanning continuous glucose monitoring (isCGM) device with structured education (Intervention) to self-monitoring of blood glucose (SMBG) (Control) in the reduction of time below range. Methods: This crossover trial involved 104 adults with type 1 diabetes mellitus (T1DM) using multiple daily injections. Participants were randomly allocated to either sequence Intervention/Control or sequence Control/Intervention. During the Intervention period which lasted 84 days, participants used the first-generation FreeStyle Libre (Abbott Diabetes Care, Alameda, CA, USA) and received structured education on how to prevent hypoglycemia based on the trend arrow and by frequent sensor scanning (≥10 times a day). Confirmatory SMBG was conducted before dosing insulin. The Control period lasted 84 days. The primary endpoint was the decrease in the time below range (TBR; <70 mg/dL). Results: The time below range was significantly reduced in the Intervention arm compared to the Control arm (2.42 ± 1.68 h/day [10.1 %±7.0 %] vs 3.10 ± 2.28 h/day [12.9 %±9.5 %], P = 0.012). The ratio of high-risk participants with low blood glucose index >5 was significantly reduced (8.6 % vs 23.7 %, P < 0.001). Conclusions: The use of isCGM combined with structured education significantly reduced the time below range in patients with T1DM

Preliminary Study of Uncertainty-Driven Plasma Diffusion II

We have constructed a semiclassical collisional diffusion model. In this model, a field particle is treated as either a point charge or a spatially distributed charge. The test particle is treated as a distributed point charge with Gaussian distribution. It was shown that the collisional changes in velocity in our model is of the same order as the classical theory for a typical proton in a fusion plasma of T = 10 keV and n = 1020 m−3. It was also shown that the spatial extent of the distribution, or the quantum-mechanical uncertainty in position, for the test particle obtained in our model grows in time, and becomes of the order of the average interparticle separation Δ ≡ n−1/3 during a time interval τr ∼×107Δ /gth, where gth = √ 2T/m is the thermal speed, with m being the mass of the particle under consideration. The time interval is 3-4 order of magnitudes smaller than the collision time. This suggests that particle transport cannot be understood in the framework of classical mechanics, and that the quantum-mechanical distribution of individual particles in plasmas may cause the anomalous diffusio

Quantum Mechanical Plasma Scattering

We have solved the two-dimensional time-dependent Schödinger equation for a particle with and without the interparticle potential in a fusion plasma. It was shown that spatial extent of a free particle grows monotonically in time. Such expansion leads to a spatial extent or size of a proton of the order of the average interparticle separation Δl ≡ n−1/3 ∼ 2 × 10−7 m in a time interval of 106 × Δl/vth ∼ 10−7 sec for a plasma with a density n ∼ 1020 m−3 and a temperature T = mvth2/2 ∼ 10 keV. It was also shown that, under a Coulomb potential, the wavefunction of a charged particle first shrink and expand in time. In the expansion phase, at times t ≥ 10−10 sec, the size of particle in the presence of a Coulomb potential is much larger than that in the absence of it