4,756 research outputs found
8-Chloroadenosine induces apoptosis in human coronary artery endothelial cells through the activation of the unfolded protein response
© 2019 The Authors Infiltration of leukocytes within the vessel at sites of inflammation and the subsequent generation of myeloperoxidase-derived oxidants, including hypochlorous acid, are key characteristics of atherosclerosis. Hypochlorous acid is a potent oxidant that reacts readily with most biological molecules, including DNA and RNA. This results in nucleic acid modification and the formation of different chlorinated products. These products have been used as biomarkers of inflammation, owing to their presence in elevated amounts in different inflammatory fluids and diseased tissue, including atherosclerotic lesions. However, it is not clear whether these materials are simply biomarkers, or could also play a role in the development of chronic inflammatory pathologies. In this study, we examined the reactivity of different chlorinated nucleosides with human coronary artery endothelial cells (HCAEC). Evidence was obtained for the incorporation of each chlorinated nucleoside into the cellular RNA or DNA. However, only 8-chloro-adenosine (8ClA) had a significant effect on the cell viability and metabolic activity. Exposure of HCAEC to 8ClA decreased glycolysis, and resulted in a reduction in ATP, with a corresponding increase in the chlorinated analogue, 8Cl-ATP in the nucleotide pool. 8ClA also induced sustained endoplasmic reticulum stress within the HCAEC, which resulted in activation of the unfolded protein response, the altered expression of antioxidant genes and culminated in the release of calcium into the cytosol and cell death by apoptosis. Taken together, these data provide new insight into pathways by which myeloperoxidase activity and resultant hypochlorous acid generation could promote endothelial cell damage during chronic inflammation, which could be relevant to the progression of atherosclerosis
Mechanical Stimulation: A Crucial Element of Organ-on-Chip Models
Organ-on-chip (OOC) systems recapitulate key biological processes and responses in vitro exhibited by cells, tissues, and organs in vivo. Accordingly, these models of both health and disease hold great promise for improving fundamental research, drug development, personalized medicine, and testing of pharmaceuticals, food substances, pollutants etc. Cells within the body are exposed to biomechanical stimuli, the nature of which is tissue specific and may change with disease or injury. These biomechanical stimuli regulate cell behavior and can amplify, annul, or even reverse the response to a given biochemical cue or drug candidate. As such, the application of an appropriate physiological or pathological biomechanical environment is essential for the successful recapitulation of in vivo behavior in OOC models. Here we review the current range of commercially available OOC platforms which incorporate active biomechanical stimulation. We highlight recent findings demonstrating the importance of including mechanical stimuli in models used for drug development and outline emerging factors which regulate the cellular response to the biomechanical environment. We explore the incorporation of mechanical stimuli in different organ models and identify areas where further research and development is required. Challenges associated with the integration of mechanics alongside other OOC requirements including scaling to increase throughput and diagnostic imaging are discussed. In summary, compelling evidence demonstrates that the incorporation of biomechanical stimuli in these OOC or microphysiological systems is key to fully replicating in vivo physiology in health and disease
The space group classification of topological band insulators
Topological band insulators (TBIs) are bulk insulating materials which
feature topologically protected metallic states on their boundary. The existing
classification departs from time-reversal symmetry, but the role of the crystal
lattice symmetries in the physics of these topological states remained elusive.
Here we provide the classification of TBIs protected not only by time-reversal,
but also by crystalline symmetries. We find three broad classes of topological
states: (a) Gamma-states robust against general time-reversal invariant
perturbations; (b) Translationally-active states protected from elastic
scattering, but susceptible to topological crystalline disorder; (c) Valley
topological insulators sensitive to the effects of non-topological and
crystalline disorder. These three classes give rise to 18 different
two-dimensional, and, at least 70 three-dimensional TBIs, opening up a route
for the systematic search for new types of TBIs.Comment: Accepted in Nature Physic
Protection of lethal toxicity of endotoxin by Salvia miltiorrhiza BUNGE is via reduction in tumor necrosis factor alpha release and liver injury
Lipopolysaccharide (LPS) has been implicated as one of the major cause of Gram-negative bacteria-induced sepsis that are life-threatening syndromes occurring in intensive care unit patients. Many natural products derived from medicinal plants may contain therapeutic values on protecting endotoxemia-induced sepsis by virtue their ability to modulate multiple pro-inflammatory cytokines. In the present study, we show that Salvia miltiorrhiza (SM) BUNGE or Danshen, used in treatment of various systemic and surgical infections in the hospitals of China, was able to block the lethal toxicity of LPS in mice via suppression of TNF-α release and protection on liver injury. The ability of SM to suppress LPS-induced TNF-α release is further confirmed by in vitro experiments conducted on human peripheral blood leukocytes (PBL) and the RAW 264.7 macrophage cell line. Immunophenotyping by flow cytometry shows improved T-helper cell (CD4) and T-suppressor cells (CD8) ratio in SM-treated PBL and splenocytes of LPS-challenged mice. The drop in plasma glutamate-pyruvate transaminase (GPT) induced by LPS provides evidence that SM can protect hepatic damage. The present study explains some known biological activities of SM, and supports the clinical application of SM in the prevention of inflammatory diseases induced by Gram-negative bacteria. © 2005 Elsevier B.V. All rights reserved.postprin
The Effectiveness and Sustainability of a Universal School-Based Programme for Preventing Depression in Chinese Adolescents: A Follow-Up Study Using Quasi-Experimental Design
published_or_final_versio
Topological Crystalline Insulators in the SnTe Material Class
Topological crystalline insulators are new states of matter in which the
topological nature of electronic structures arises from crystal symmetries.
Here we predict the first material realization of topological crystalline
insulator in the semiconductor SnTe, by identifying its nonzero topological
index. We predict that as a manifestation of this nontrivial topology, SnTe has
metallic surface states with an even number of Dirac cones on high-symmetry
crystal surfaces such as {001}, {110} and {111}. These surface states form a
new type of high-mobility chiral electron gas, which is robust against disorder
and topologically protected by reflection symmetry of the crystal with respect
to {110} mirror plane. Breaking this mirror symmetry via elastic strain
engineering or applying an in-plane magnetic field can open up a continuously
tunable band gap on the surface, which may lead to wide-ranging applications in
thermoelectrics, infrared detection, and tunable electronics. Closely related
semiconductors PbTe and PbSe also become topological crystalline insulators
after band inversion by pressure, strain and alloying.Comment: submitted on Feb. 10, 2012; to appear in Nature Communications; 5
pages, 4 figure
Gate-tuned normal and superconducting transport at the surface of a topological insulator
Three-dimensional topological insulators are characterized by the presence of
a bandgap in their bulk and gapless Dirac fermions at their surfaces. New
physical phenomena originating from the presence of the Dirac fermions are
predicted to occur, and to be experimentally accessible via transport
measurements in suitably designed electronic devices. Here we study transport
through superconducting junctions fabricated on thin Bi2Se3 single crystals,
equipped with a gate electrode. In the presence of perpendicular magnetic field
B, sweeping the gate voltage enables us to observe the filling of the Dirac
fermion Landau levels, whose character evolves continuously from electron- to
hole-like. When B=0, a supercurrent appears, whose magnitude can be gate tuned,
and is minimum at the charge neutrality point determined from the Landau level
filling. Our results demonstrate how gated nano-electronic devices give control
over normal and superconducting transport of Dirac fermions at an individual
surface of a three-dimensional topological insulator.Comment: 28 pages, 5 figure
Topological Surface States Protected From Backscattering by Chiral Spin Texture
Topological insulators are a new class of insulators in which a bulk gap for
electronic excitations is generated by strong spin orbit coupling. These novel
materials are distinguished from ordinary insulators by the presence of gapless
metallic boundary states, akin to the chiral edge modes in quantum Hall
systems, but with unconventional spin textures. Recently, experiments and
theoretical efforts have provided strong evidence for both two- and
three-dimensional topological insulators and their novel edge and surface
states in semiconductor quantum well structures and several Bi-based compounds.
A key characteristic of these spin-textured boundary states is their
insensitivity to spin-independent scattering, which protects them from
backscattering and localization. These chiral states are potentially useful for
spin-based electronics, in which long spin coherence is critical, and also for
quantum computing applications, where topological protection can enable
fault-tolerant information processing. Here we use a scanning tunneling
microscope (STM) to visualize the gapless surface states of the
three-dimensional topological insulator BiSb and to examine their scattering
behavior from disorder caused by random alloying in this compound. Combining
STM and angle-resolved photoemission spectroscopy, we show that despite strong
atomic scale disorder, backscattering between states of opposite momentum and
opposite spin is absent. Our observation of spin-selective scattering
demonstrates that the chiral nature of these states protects the spin of the
carriers; they therefore have the potential to be used for coherent spin
transport in spintronic devices.Comment: to be appear in Nature on August 9, 200
Aharonov-Bohm interference in topological insulator nanoribbons
Topological insulators represent novel phases of quantum matter with an
insulating bulk gap and gapless edges or surface states. The two-dimensional
topological insulator phase was predicted in HgTe quantum wells and confirmed
by transport measurements. Recently, Bi2Se3 and related materials have been
proposed as three-dimensional topological insulators with a single Dirac cone
on the surface and verified by angle-resolved photoemission spectroscopy
experiments. Here, we show unambiguous transport evidence of topological
surface states through periodic quantum interference effects in layered
single-crystalline Bi2Se3 nanoribbons. Pronounced Aharonov-Bohm oscillations in
the magnetoresistance clearly demonstrate the coverage of two-dimensional
electrons on the entire surface, as expected from the topological nature of the
surface states. The dominance of the primary h/e oscillation and its
temperature dependence demonstrate the robustness of these electronic states.
Our results suggest that topological insulator nanoribbons afford novel
promising materials for future spintronic devices at room temperature.Comment: 5 pages, 4 figures, RevTex forma
MR Safe Robotic Manipulator for MRI-Guided Intracardiac Catheterization
This paper introduces a robotic manipulator to realize robot-assisted intracardiac catheterization in magnetic resonance imaging (MRI) environment. MRI can offer high-resolution images to visualize soft tissue features such as scars or edema. We hypothesize that robotic catheterization, combined with the enhanced monitoring of lesions creation using MRI intraoperatively, will significantly improve the procedural safety, accuracy, and effectiveness. This is designed particularly for cardiac electrophysiological (EP) intervention, which is an effective treatment of arrhythmia. We present the first MR Safe robot for intracardiac EP intervention. The robot actuation features small hysteresis, effective force transmission, and quick response, which has been experimentally verified for its capability to precisely telemanipulate a standard clinically used EP catheter. We also present timely techniques for real-time positional tracking in MRI and intraoperative image registration, which can be integrated with the presented manipulator to im prove the performance of teleoperated robotic catheterization
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