Notch1 intracellular domain suppresses APP intracellular domain—Tip60–Fe65 complex mediated signaling through physical interaction

AbstractThe amyloid beta-precursor protein (APP) and the Notch receptor are both type 1 integral transmembrane proteins, and both are cleaved by presenilin-dependent gamma-secretase activity. In this study, we have demonstrated that the Notch intracellular domain (Notch1-IC) suppresses APP-intracellular domain (AICD)-mediated ROS generation and cell death after being processed by gamma secretase. Notch1-IC physically interacts with AICD, Fe65, and Tip60, thereby disrupting the association of the AICD–Fe65–Tip60 trimeric transcription activator complex in AICD signaling. AICD–Fe65–Tip60 mediated reactive oxygen species generation was found to be suppressed by Notch1-IC. Furthermore, AICD–Fe65–Tip60 was shown to mediate cell death in human neuroblastoma cells, and the overexpression of Notch1-IC inhibited cell death induced by AICD–Fe65–Tip60. Collectively, our findings indicate that Notch1-IC plays the role of a negative regulator in AICD signaling via the disruption of the AICD–Fe65–Tip60 trimeric complex

Beyond slurry-cast supercapacitor electrodes: PAN/MWNT heteromat-mediated ultrahigh capacitance electrode sheets

Supercapacitors (SCs) have garnered considerable attention as an appealing power source for forthcoming smart energy era. An ultimate challenge facing the SCs is the acquisition of higher energy density without impairing their other electrochemical properties. Herein, we demonstrate a new class of polyacrylonitrile (PAN)/multi-walled carbon tube (MWNT) heteromat-mediated ultrahigh capacitance electrode sheets as an unusual electrode architecture strategy to address the aforementioned issue. Vanadium pentoxide (V2O5) is chosen as a model electrode material to explore the feasibility of the suggested concept. The heteromat V2O5 electrode sheets are produced through one-pot fabrication based on concurrent electrospraying (for V2O5 precursor/MWNT) and electrospinning (for PAN nanofiber) followed by calcination, leading to compact packing of V2O5 materials in intimate contact with MWNTs and PAN nanofibers. As a consequence, the heteromat V2O5 electrode sheets offer three-dimensionally bicontinuous electron (arising from MWNT networks)/ion (from spatially reticulated interstitial voids to be filled with liquid electrolytes) conduction pathways, thereby facilitating redox reaction kinetics of V2O5 materials. In addition, elimination of heavy metallic foil current collectors, in combination with the dense packing of V2O5 materials, significantly increases (electrode sheet-based) specific capacitances far beyond those accessible with conventional slurry-cast electrodes.ope

Improving disclosure of medical error through educational program as a first step toward patient safety

Participant’s Response to medical errors. Description of data: Raw data of participant’s response to medical errors (3 clinical cases with different severity of error outcome), satisfaction and change after the education program. (XLSX 18 kb

Localizing Gravitational Wave Sources with Single-Baseline Atom Interferometers

Localizing sources on the sky is crucial for realizing the full potential of gravitational waves for astronomy, astrophysics, and cosmology. We show that the mid-frequency band, roughly 0.03 to 10 Hz, has significant potential for angular localization. The angular location is measured through the changing Doppler shift as the detector orbits the Sun. This band maximizes the effect since these are the highest frequencies in which sources live several months. Atom interferometer detectors can observe in the mid-frequency band, and even with just a single baseline can exploit this effect for sensitive angular localization. The single baseline orbits around the Earth and the Sun, causing it to reorient and change position significantly during the lifetime of the source, and making it similar to having multiple baselines/detectors. For example, atomic detectors could predict the location of upcoming black hole or neutron star merger events with sufficient accuracy to allow optical and other electromagnetic telescopes to observe these events simultaneously. Thus, mid-band atomic detectors are complementary to other gravitational wave detectors and will help complete the observation of a broad range of the gravitational spectrum.Comment: 16 pages, 3 figures, 2 table

Porcine placenta hydrolysates regulate calcium disturbance in MC3T3-E1 osteoblastic cells

BACKGROUND: In bone metabolism, Ca(2+) disturbance and oxidative damage are the main biochemical factors related to pathology. Osteoblasts are bone-forming cells that also control bone endocrinology. Endocrine hormones and proteins are matured, folded, and secreted in the endoplasmic reticulum (ER). ER stress has emerged as a new pathological mechanism to explain bone disturbance. Here we studied the role of porcine placenta hydrolysates (PPHs) in the regulation of ER stress. METHODS: Cell viability was determined in vitro using trypan blue dye exclusion. ER stress and apoptosis were evaluated using immunoblotting and a caspase kit. The fluorescent Ca(2+)-binding dye Fura-2/AM was used to measure changes in intracellular Ca(2+) ([Ca(2+)](i)). ROS levels, NADPH oxidase activity, and superoxide dismutase (SOD) activity were also measured. RESULTS: PPHs protected MC3T3-E1 osteoblastic cells against thapsigargin (Tg)-induced ER stress. Moreover, PPHs regulated caspase-12 and −3 activities, thereby protecting against cell death, and also regulated Tg-induced Ca(2+) release. The Ca(2+) chelator BAPT/AM also regulated caspase-12 and −3 activities and prevented Ca(2) stress-induced cell death. In the presence of PPHs or BAPTA/AM, Ca(2+)-related ROS were also regulated, as demonstrated by alterations in NADPH oxidase and SOD activity. CONCLUSIONS: PPHs appear to regulate bone metabolism disturbance by controlling Ca(2+) concentrations, and thus ER stress and ROS, in osteoblasts cultured in vitro. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12906-016-1202-1) contains supplementary material, which is available to authorized users

Clinical results of endoscopic sciatic nerve decompression for deep gluteal syndrome: mean 2-year follow-up

BACKGROUND: The purpose of this study is to assess the effectiveness of endoscopic sciatic nerve decompression and evaluated the differences of clinical results between atraumatic and traumatic groups. METHODS: Sixty consecutive patients. We retrospectively reviewed sixty consecutive patients without major trauma (45 hips) or with major trauma (15 hips) groups to compare the outcomes of endoscopic treatment.). The mean follow-up period was 24 ± 2.6 months (range, 24–38.4 months). RESULTS: The mean duration of symptoms was 14.1 months (range, 12 to 32 months). Compromising structures were piriformis muscle, fibrovascular bundles, and adhesion with scar tissues. The mean VAS score for pain decreased from 7.4 ± 1.5 to 2.6 ± 1.5 (P = .001). The mean mHHS increased from 81.7 ± 9.6 to 91.8 ± 7.6 (P = .003). Clinically, positive paresthesia and seated piriformis test were statistically significant to diagnosis sciatic entrapment syndrome. Paresthesia and sitting pain were significantly improved at the final follow-up (P = .002). More favorable outcome was observed a group without major trauma. No complication was observed. CONCLUSIONS: Endoscopic sciatic nerve decompression is a safe and effective procedure for the management of DGS. Patients with major trauma could have poor clinical outcome. Seated piriformis test, FADIR, and tenderness of sciatic notch are maybe useful guide for pre and postoperative evaluation of DGS