Transient DNA wrapping process from local contact deformation

The transient process of DNA wrapping of a nanoparticle as a simplified model of nucleosomal DNA can offer the necessary condition to access the reversible and stimuli-responsive helical buckling conformation. Elaborating Marko and Shiggia model applied to this simplified wrapping conformation explains the role of coupling elasticity between 3DNA variables and the range of the artificial thermal fluctuation, which is quantitatively shown as one of the necessary conditions for the wrapping process in coarse-grained molecular dynamics (CGMD) simulation whose small random energy is found to be quintessential to form wrapping conformation. The activation of wrapping and its propagation along the dsDNA strand is analyzed using each type of bend-twist coupling based on how much energy is consumed to draw a curvature for 1.7 turns. The spatiotemporal distribution from each type of rotational and translational variables from the trajectory calculated by CGMD perceives the role of major-minor groove to form 1.7 turns and the mechanism of the relatively slow wrapping speed caused by several sequence components in dsDNA strand parallel to the importance of curvature coupling for forming superhelix

Roles of zinc and metallothionein-3 in oxidative stress-induced lysosomal dysfunction, cell death, and autophagy in neurons and astrocytes

Zinc dyshomeostasis has been recognized as an important mechanism for cell death in acute brain injury. An increase in the level of free or histochemically reactive zinc in astrocytes and neurons is considered one of the major causes of death of these cells in ischemia and trauma. Although zinc dyshomeostasis can lead to cell death via diverse routes, the major pathway appears to involve oxidative stress

Intramuscular botulinum toxin-A reduces hemiplegic shoulder pain: a randomized, double-blind, comparative study versus intraarticular triamcinolone acetonide

BACKGROUND AND PURPOSE: Shoulder pain is frequent after stroke and interferes with the rehabilitative process and outcome. However, treatments used for hemiplegic shoulder pain are limited and largely ineffective. This prospective, randomized, double-blind controlled study was conducted to compare the efficacies of botulinum toxin type A (BoNT-A) and triamcinolone acetonide (TA) on hemiplegic shoulder pain and their effects on arm function in patients with stroke. METHODS: Twenty-nine hemiplegic stroke patients with shoulder pain (duration or=6/10) were randomized into 2 groups. One group received intramuscular injections of BoNT-A (BOTOX 100 U total) during one session to the infraspinatus, pectoralis and subscapularis muscles in conjunction with an intraarticular injection of normal saline to painful shoulder joint, whereas the other group received an intraarticular injection of TA (40 mg) and an intramuscular injection of normal saline to the same muscles. Outcome measures were pain (measured using a numeric rating scale), physician's global rating scale, shoulder range of motion (ROM) in 4 directions, arm function measured using Fugl-Meyer score, and spasticity measured using the modified Ashworth scale. Measurements were made at baseline and 2, 6, and 12 weeks after injection. RESULTS: At 12 weeks after treatment mean decrease in pain was 4.2 in the BoNT-A-treated group versus 2.5 in the TA-treated group (P=0.051), and improvements in overall ROM were 82.9 degrees versus 51.8 degrees in these groups (P=0.059), showing a strong trend toward there being less pain and better ROM among those treated with BoNT-A than with TA. However, no significant differences were observed between the 2 groups in terms of improvement in physician global rating, Fugl-Meyer score or modified Ashworth scales. No adverse effect was observed in either group. CONCLUSIONS: Results from this study suggest that injection of BoNT-A into selected muscles of the shoulder girdle might provide more pain relief and ROM improvement than intraarticular steroid in patients with hemiplegic shoulder pain. A larger clinical trial needs to be undertaken to confirm the benefits of this approach

Angiopoietin-1 is an apoptosis survival factor for endothelial cells

AbstractWe examined the effect of angiopoietin-1 (Ang1) on apoptosis in human umbilical vein endothelial cells (HUVECs). Ang1 (5–1000 ng/ml) dose-dependently inhibited apoptosis under a serum-deprived state. A significant apoptotic inhibition occurred with as low as 50 ng/ml. Two hundred ng/ml of Ang1 inhibited to approximately 50% of the control apoptotic rates for 96 h. Furthermore, an augmented antiapoptotic effect of Ang1 by the addition of 20 ng/ml vascular endothelial growth factor was observed. This Ang1-induced strong antiapoptotic effect in endothelial cells is a novel and intriguing finding and could be an additional description of Ang1-induced direct biological function

Real-Time Monitoring of Neural Differentiation of Human Mesenchymal Stem Cells by Electric Cell-Substrate Impedance Sensing

Stem cells are useful for cell replacement therapy. Stem cell differentiation must be monitored thoroughly and precisely prior to transplantation. In this study we evaluated the usefulness of electric cell-substrate impedance sensing (ECIS) for in vitro real-time monitoring of neural differentiation of human mesenchymal stem cells (hMSCs). We cultured hMSCs in neural differentiation media (NDM) for 6 days and examined the time-course of impedance changes with an ECIS array. We also monitored the expression of markers for neural differentiation, total cell count, and cell cycle profiles. Cellular expression of neuron and oligodendrocyte markers increased. The resistance value of cells cultured in NDM was automatically measured in real-time and found to increase much more slowly over time compared to cells cultured in non-differentiation media. The relatively slow resistance changes observed in differentiating MSCs were determined to be due to their lower growth capacity achieved by induction of cell cycle arrest in G0/G1. Overall results suggest that the relatively slow change in resistance values measured by ECIS method can be used as a parameter for slowly growing neural-differentiating cells. However, to enhance the competence of ECIS for in vitro real-time monitoring of neural differentiation of MSCs, more elaborate studies are needed