Notch signaling is required for maintaining stem-cell features of neuroprogenitor cells derived from human embryonic stem cells

<p>Abstract</p> <p>Background</p> <p>Studies have provided important findings about the roles of Notch signaling in neural development. Unfortunately, however, most of these studies have investigated the neural stem cells (NSCs) of mice or other laboratory animals rather than humans, mainly owing to the difficulties associated with obtaining human brain samples. It prompted us to focus on neuroectodermal spheres (NESs) which are derived from human embryonic stem cell (hESC) and densely inhabited by NSCs. We here investigated the role of Notch signaling with the hESC-derived NESs.</p> <p>Results</p> <p>From hESCs, we derived NESs, the <it>in-vitro </it>version of brain-derived neurospheres. NES formation was confirmed by increased levels of various NSC marker genes and the emergence of rosette structures in which neuroprogenitors are known to reside. We found that Notch signaling, which maintains stem cell characteristics of <it>in-vivo</it>-derived neuroprogenitors, is active in these hESC-derived NESs, similar to their <it>in-vivo </it>counterpart. Expression levels of Notch signaling molecules such as NICD, DLLs, JAG1, HES1 and HES5 were increased in the NESs. Inhibition of the Notch signaling by a γ-secretase inhibitor reduced rosette structures, expression levels of NSC marker genes and proliferation potential in the NESs, and, if combined with withdrawal of growth factors, triggered differentiation toward neurons.</p> <p>Conclusion</p> <p>Our results indicate that the hESC-derived NESs, which share biochemical features with brain-derived neurospheres, maintain stem cell characteristics mainly through Notch signaling, which suggests that the hESC-derived NESs could be an <it>in-vitro </it>model for <it>in-vivo </it>neurogenesis.</p

Polarity-tunable magnetic tunnel junctions based on ferromagnetism at oxide heterointerfaces

Complex oxide systems have attracted considerable attention because of their fascinating properties, including the magnetic ordering at the conducting interface between two band insulators, such as LaAlO3 (LAO) and SrTiO3 (STO). However, the manipulation of the spin degree of freedom at the LAO/STO heterointerface has remained elusive. Here, we have fabricated hybrid magnetic tunnel junctions consisting of Co and LAO/STO ferromagnets with the insertion of a Ti layer in between, which clearly exhibit magnetic switching and the tunnelling magnetoresistance (TMR) effect below 10 K. The magnitude and the of the TMR are strongly dependent on the direction of the rotational magnetic field parallel to the LAO/STO plane, which is attributed to a strong Rashba-type spin orbit coupling in the LAO/STO heterostructure. Our study provides a further support for the existence of the macroscopic ferromagnetism at LAO/STO heterointerfaces and opens a novel route to realize interfacial spintronics devices.Comment: 25 pages, 5 figure

Observation of liquid crystals confined in an elliptic cylinder

We present the observation of liquid crystals confined in elliptic cylinders. To fabricate the elliptic cylinder, poly(dimethlysiloxane) micro-channels having circular cross sections are stretched uniaxially along the direction of the diameter. Upon increasing the aspect ratio of the elliptic cross section, confined nematic liquid crystals maintain their escaped-radial configuration with homeotropic anchoring. In smectic-A liquid crystals, defect regions of focal conic domains appear as a function of the aspect ratio. We propose a model to understand the formation of these defects in terms of the confinement-induced misorientation, and resultant tilt grain boundaries. (C) 2012 American Institute of Physics.close3

Efficacy of two different self-expanding nitinol stents for atherosclerotic femoropopliteal arterial disease (SENS-FP trial): study protocol for a randomized controlled trial

BACKGROUND: There have been few randomized control trials comparing the incidence of stent fracture and primary patency among different self-expanding nitinol stents to date. The SMART™ CONTROL stent (Cordis Corp, Miami Lakes, Florida, United States) has a peak-to-valley bridge and inline interconnection, whereas the COMPLETE™-SE stent (Medtronic Vascular, Santa Rosa, California, United States) crowns have been configured to minimize crown-to-crown interaction, increasing the stent's flexibility without compromising radial strength. Further, the 2011 ESC (European society of cardiology) guidelines recommend that dual antiplatelet therapy with aspirin and a thienopyridine such as clopidogrel should be administered for at least one month after infrainguinal bare metal stent implantation. Cilostazol has been reported to reduce intimal hyperplasia and subsequent repeat revascularization. To date, there has been no randomized study comparing the safety and efficacy of two different antiplatelet regimens, clopidogrel and cilostazol, following successful femoropopliteal stenting. METHODS/DESIGN: The primary purpose of our study is to examine the incidence of stent fracture and primary patency between two different major representative self-expanding nitinol stents (SMART™ CONTROL versus COMPLETE™-SE) in stenotic or occlusive femoropopliteal arterial lesion. The secondary purpose is to examine whether there is any difference in efficacy and safety between aspirin plus clopidogrel versus aspirin plus cilostazol for one month following stent implantation in femoropopliteal lesions. This is a prospective, randomized, multicenter trial to assess the efficacy of the COMPLETE™-SE versus SMART™ CONTROL stent for provisional stenting after balloon angioplasty in femoropopliteal arterial lesions. The study design is a 2x2 randomization design and a total of 346 patients will be enrolled. The primary endpoint of this study is the rate of binary restenosis in the treated segment at 12 months after intervention as determined by catheter angiography or duplex ultrasound. DISCUSSION: This trial will provide powerful insight into whether the design of the COMPLETE™-SE stent is more fracture-resistant or effective in preventing restenosis compared with the SMART™ CONTROL stent. Also, it will determine the efficacy and safety of aspirin plus clopidogrel versus aspirin plus cilostazol in patients undergoing stent implantation in femoropopliteal lesions. TRIAL REGISTRATION: Registered on 2 April 2012 with the National Institutes of Health Clinical Trials Registry (ClinicalTrials.gov identifier# NCT01570803)

A Butterfly-Shaped Primary Cardiac Lymphoma That Showed Bi-Atrial Involvement

We described here a patient who presented with symptoms of heart failure who was found to have severe bilateral impairment of atrioventricular inflow. Primary cardiac lymphoma (PCL) with extensive involvement of the two atria, pericardium and myocardium is an extremely rare tumor in immunocompetent patients. We report here a case of PCL in an immunocompetent patient with involvement of both atria and the atrial septum. The tumor had a butterfly shape. We could not do surgical excision because of the massive pericardiac invasion. The diagnosis was B-cell lymphoma and this was confirmed by the pericardiac biopsy

Confinement-Induced Transition of Topological Defects in Smectic Liquid Crystals: From a Point to a Line and Pearls

We report a study on the confinement-induced transition of the topological defects of liquid crystals (LCs) using smectic-A LCs confined in prolate spheroids with homeotropic anchoring. Upon increasing the aspect ratio of a LC droplet, dispersed in a stretched elastomer film, the topological defect undergoes a transition from a point to a line of which the length is a function of the aspect ratio. Additionally, when the size of a droplet is larger than a certain value, the defect has a pearl-necklace-like texture. We propose a simple model to understand the formation of these defects in terms of the misorientation and undulation instability of the smectic layersclose9

Inter-arm arterial pressure difference caused by prone position in the thoracic outlet syndrome patient -A case report-

Thoracic outlet syndrome has neurologic symptoms caused by compression of brachial plexus, blood vessel symptoms are caused by compression of the artery or vein. The authors report a case of sudden decrease in blood pressure of the left arm after turning the patient from supine position to prone position. They confirmed that the patient had thoracic outlet syndrome after performing computed tomography

Reduced Mortality With Antiplatelet Therapy Deescalation After Percutaneous Coronary Intervention in Acute Coronary Syndromes: A Meta-Analysis

Background:Antiplatelet therapy deescalation has been suggested as an alternative to standard treatment with potent dual antiplatelet therapy (DAPT) for 1 year in low bleeding risk patients with acute coronary syndromes undergoing percutaneous coronary intervention to mitigate the increased risk of bleeding. Whether this strategy preserves the ischemic and survival benefits of potent DAPT is uncertain. Methods:We performed a pairwise meta-analysis in patients with acute coronary syndrome undergoing percutaneous coronary intervention treated with either 1-year standard potent DAPT versus deescalation therapy (potent DAPT for 1-3 months followed by either reduced potency DAPT or ticagrelor monotherapy for up to 1 year). Randomized trials comparing standard DAPT versus deescalation therapy in patients with acute coronary syndrome undergoing percutaneous coronary intervention were searched through MEDLINE, EMBASE, Cochrane databases, and proceedings of international meetings. The primary end point was 1-year all-cause mortality. Results:The meta-analysis included 6 trials in which 20 837 patients were randomized to potent DAPT for 1 to 3 months followed by deescalation therapy for up to 1 year (n=10 392) or standard potent DAPT for 1 year (n=10 445). Deescalation therapy was associated with lower 1-year rates of all-cause mortality compared with standard therapy (odds ratio, 0.75 [95% CI, 0.59-0.95]; P=0.02). Deescalation therapy was also associated with lower rates of major bleeding (odds ratio, 0.59 [95% CI, 0.48-0.72]; P<0.0001), with no significant difference in major adverse cardiac events (major adverse cardiovascular events; odds ratio, 0.89 [95% CI, 0.77-1.04]; P=0.14). Conclusions:In low bleeding risk patients with acute coronary syndrome undergoing percutaneous coronary intervention, compared with 1-year of potent DAPT, antiplatelet therapy deescalation therapy after 1 to 3 months was associated with decreased mortality and major bleeding with similar rates of major adverse cardiovascular events

Comparative effect of genistein and daidzein on the expression of MCP-1, eNOS, and cell adhesion molecules in TNF-α-stimulated HUVECs

We compared the effects of genistein and daidzein on the expression of chemokines, cell adhesion molecules (CAMs), and endothelial nitric oxide synthase (eNOS) in tumor necrosis factor (TNF)-α-stimulated human umbilical vascular endothelial cells (HUVECs). TNF-α exposure significantly increased expression of monocyte chemoattractant protein (MCP)-1, vascular adhesion molecule (VCAM)-1, and intercellular adhesion molecule-1. Genistein significantly decreased MCP-1 and VCAM-1 production in a dose-dependent manner, whereas CAM expression was not significantly lowered by genistein treatment. However, daidzein slightly decreased MCP-1 production. The effects of genistein and daidzein on MCP-1 secretion coincided with mRNA expression. Pre-treatment with either genistein or daidzein elevated eNOS expression and nitric oxide production disturbed by TNF-α exposure. A low concentration of isoflavones significantly inhibited nuclear factor (NF)κB activation, whereas a high dose slightly ameliorated these inhibitive effects. These results suggest that genistein had a stronger effect on MCP-1 and eNOS expression than that of daidzein. Additionally, NFκB transactivation might be partially related to the down-regulation of these mRNAs in TNF-α-stimulated HUVECs