Crosstalk between astrocytic CXCL12 and microglial CXCR4 contributes to the development of neuropathic pain

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Central administration of C-x-C chemokine receptor type 4 antagonist alleviates the development and maintenance of peripheral neuropathic pain in mice

Aim To explore the roles of C-X-C chemokine receptor type 4 (CXCR4) in spinal processing of neuropathic pain at the central nervous system (CNS). Methods Peripheral neuropathic pain (PNP) induced by partial sciatic nerve ligation (pSNL) model was assessed in mice. Effects of a single intrathecal (central) administration of AMD3100 (intrathecal AMD3100), a CXCR4 antagonist, on pain behavior and pain-related spinal pathways and molecules in the L3-L5 spinal cord segment was studied compare to saline treatment. Results Rotarod test showed that intrathecal AMD3100 did not impair mice motor function. In pSNL-induced mice, intrathecal AMD3100 delayed the development of mechanical allodynia and reversed the established mechanical allodynia in a dose-dependent way. Moreover, intrathecal AMD3100 downregulated the activation of JNK1 and p38 pathways and the protein expression of p65 as assessed by western blotting. Real-time PCR test also demonstrated that substance P mRNA was decreased, while adrenomedullin and intercellular adhesion molecule mRNA was increased following AMD3100 treatment. Conclusion Our results suggest that central (spinal) CXCR4 is involved in the development and maintenance of PNP and the regulation of multiple spinal molecular events under pain condition, implicating that CXCR4 would potentially be a therapeutic target for chronic neuropathic pain.published_or_final_versio

Down-regulated CK8 expression in human intervertebral disc degeneration

As an intermediate filament protein, cytokeratin 8 (CK8) exerts multiple cellular functions. Moreover, it has been identified as a marker of notochord cells, which play essential roles in human nucleus pulposus (NP). However, the distribution of CK8 positive cells in human NP and their relationship with intervertebral disc degeneration (IDD) have not been clarified until now. Here, we found the percentage of CK8 positive cells in IDD (25.7+/-4.14%) was significantly lower than that in normal and scoliosis NP (51.9+/-9.73% and 47.8+/-5.51%, respectively, p<0.05). Western blotting and qRT-PCR results confirmed the down-regulation of CK8 expression in IDD on both of protein and mRNA levels. Furthermore, approximately 37.4% of cell clusters were CK8 positive in IDD. Taken together, this is the first study to show a down-regulated CK8 expression and the percentage of CK8 positive cell clusters in IDD based upon multiple lines of evidence. Consequently, CK8 positive cells might be considered as a potential option in the development of cellular treatment strategies for NP repair.published_or_final_versio

Ultrahard carbon film from epitaxial two-layer graphene

Atomically thin graphene exhibits fascinating mechanical properties, although its hardness and transverse stiffness are inferior to those of diamond. To date, there hasn't been any practical demonstration of the transformation of multi-layer graphene into diamond-like ultra-hard structures. Here we show that at room temperature and after nano-indentation, two-layer graphene on SiC(0001) exhibits a transverse stiffness and hardness comparable to diamond, resisting to perforation with a diamond indenter, and showing a reversible drop in electrical conductivity upon indentation. Density functional theory calculations suggest that upon compression, the two-layer graphene film transforms into a diamond-like film, producing both elastic deformations and sp2-to-sp3 chemical changes. Experiments and calculations show that this reversible phase change is not observed for a single buffer layer on SiC or graphene films thicker than 3 to 5 layers. Indeed, calculations show that whereas in two-layer graphene layer-stacking configuration controls the conformation of the diamond-like film, in a multilayer film it hinders the phase transformation.Comment: Published online on Nature Nanotechnology on December 18, 201

Investigation of Ge nanocrytals in a metal-insulator-semiconductor structure with a HfO₂/SiO₂stack as the tunnel dielectric

Author name used in this publication: Weili LiuAuthor name used in this publication: J. Y. DaiAuthor name used in this publication: P. F. LeeAuthor name used in this publication: Zhitang Song2004-2005 > Academic research: refereed > Publication in refereed journalVersion of RecordPublishe

Magnetism and its microscopic origin in iron-based high-temperature superconductors

High-temperature superconductivity in the iron-based materials emerges from, or sometimes coexists with, their metallic or insulating parent compound states. This is surprising since these undoped states display dramatically different antiferromagnetic (AF) spin arrangements and N$\rm \acute{e}$el temperatures. Although there is general consensus that magnetic interactions are important for superconductivity, much is still unknown concerning the microscopic origin of the magnetic states. In this review, progress in this area is summarized, focusing on recent experimental and theoretical results and discussing their microscopic implications. It is concluded that the parent compounds are in a state that is more complex than implied by a simple Fermi surface nesting scenario, and a dual description including both itinerant and localized degrees of freedom is needed to properly describe these fascinating materials.Comment: 14 pages, 4 figures, Review article, accepted for publication in Nature Physic

Novel insights into the hallmarks of human nucleus pulposus cells with particular reference to cell viability, phagocytic potential and long process formation

General Posters: no. GP88INTRODUCTIONS: As a main cellular component within the disc, nucleus pulposus (NP) cells play important roles in disc physiology. However, little is known on the biologic hallmarks of human NP cells. Therefore, the present study aimed to address the features of human NP ...postprin

Mimotope ELISA for Detection of Broad Spectrum Antibody against Avian H5N1 Influenza Virus

Science and Technology Foundation of Fujian Province [2009YZ0002]; National Natural Science Foundation of China [30901077]; National High Technology Research and Development Program [2010AA022801]Background: We have raised a panel of broad spectrum neutralizing monoclonal antibodies against the highly pathogenic H5N1 avian influenza virus, which neutralize the infectivity of, and afford protection against infection by, most of the major genetic groups of the virus evolved since 1997. Peptide mimics reactive with one of these broad spectrum H5N1 neutralizing antibodies, 8H5, were identified from random phage display libraries. Method: The amino acid residues of the most reactive 12mer peptide, p125 (DTPLTTAALRLV), were randomly substituted to improve its mimicry of the natural 8H5 epitope. Result: 133 reactive peptides with unique amino acid sequences were identified from 5 sub-libraries of p125. Four residues (2,4,5.9) of the parental peptide were preserved among all the derived peptides and probably essential for 8H5 binding. These are interspersed among four other residues (1,3,8,10), which exhibit restricted substitution and probably could contribute to binding, and another four (6,7,11,12) which could be randomly substituted and probably are not essential for binding. One peptide, V-1b, derived by substituting 5 of the latter residues is the most reactive and has a binding constant of 3.16x10(-9) M, which is 38 fold higher than the affinity of the parental p125. Immunoassay produced with this peptide is specifically reactive with 8H5 but not also the other related broad spectrum H5N1 avian influenza virus neutralizing antibodies. Serum samples from 29 chickens infected with H5N1 avian influenza virus gave a positive result by this assay and those from 12 uninfected animals gave a negative test result. Conclusion: The immunoassay produced with the 12 mer peptide, V1-b, is specific for the natural 8H5 epitope and can be used for detection of antibody against the broad spectrum neutralization site of H5N1 avian influenza virus

Controllable Synthesis of Magnesium Oxysulfate Nanowires with Different Morphologies

One-dimensional magnesium oxysulfate 5Mg(OH)2 · MgSO4 · 3H2O (abbreviated as 513MOS) with high aspect ratio has attracted much attention because of its distinctive properties from those of the conventional bulk materials. 513MOS nanowires with different morphologies were formed by varying the mixing ways of MgSO4 · 7H2O and NH4OH solutions at room temperature followed by hydrothermal treatment of the slurries at 150 °C for 12 h with or without EDTA. 513MOS nanowires with a length of 20–60 μm and a diameter of 60–300 nm were prepared in the case of double injection (adding MgSO4 · 7H2O and NH4OH solutions simultaneously into water), compared with the 513MOS with a length of 20–30 μm and a diameter of 0.3–1.7 μm in the case of the single injection (adding MgSO4 · 7H2O solution into NH4OH solution). The presence of minor amount of EDTA in the single injection method led to the formation of 513MOS nanowires with a length of 100–200 μm, a diameter of 80–200 nm, and an aspect ratio of up to 1000. The analysis of the experimental results indicated that the hydrothermal solutions with a lower supersaturation were favorable for the preferential growth of 513MOS nanowires along b axis

Using a human cardiovascular-respiratory model to characterize cardiac tamponade and pulsus paradoxus

<p>Abstract</p> <p>Background</p> <p>Cardiac tamponade is a condition whereby fluid accumulation in the pericardial sac surrounding the heart causes elevation and equilibration of pericardial and cardiac chamber pressures, reduced cardiac output, changes in hemodynamics, partial chamber collapse, pulsus paradoxus, and arterio-venous acid-base disparity. Our large-scale model of the human cardiovascular-respiratory system (H-CRS) is employed to study mechanisms underlying cardiac tamponade and pulsus paradoxus. The model integrates hemodynamics, whole-body gas exchange, and autonomic nervous system control to simulate pressure, volume, and blood flow.</p> <p>Methods</p> <p>We integrate a new pericardial model into our previously developed H-CRS model based on a fit to patient pressure data. Virtual experiments are designed to simulate pericardial effusion and study mechanisms of pulsus paradoxus, focusing particularly on the role of the interventricular septum. Model differential equations programmed in C are solved using a 5^th-order Runge-Kutta numerical integration scheme. MATLAB is employed for waveform analysis.</p> <p>Results</p> <p>The H-CRS model simulates hemodynamic and respiratory changes associated with tamponade clinically. Our model predicts effects of effusion-generated pericardial constraint on chamber and septal mechanics, such as altered right atrial filling, delayed leftward septal motion, and prolonged left ventricular pre-ejection period, causing atrioventricular interaction and ventricular desynchronization. We demonstrate pericardial constraint to markedly accentuate normal ventricular interactions associated with respiratory effort, which we show to be the distinct mechanisms of pulsus paradoxus, namely, series and parallel ventricular interaction. Series ventricular interaction represents respiratory variation in right ventricular stroke volume carried over to the left ventricle via the pulmonary vasculature, whereas parallel interaction (via the septum and pericardium) is a result of competition for fixed filling space. We find that simulating active septal contraction is important in modeling ventricular interaction. The model predicts increased arterio-venous CO₂due to hypoperfusion, and we explore implications of respiratory pattern in tamponade.</p> <p>Conclusion</p> <p>Our modeling study of cardiac tamponade dissects the roles played by septal motion, atrioventricular and right-left ventricular interactions, pulmonary blood pooling, and the depth of respiration. The study fully describes the physiological basis of pulsus paradoxus. Our detailed analysis provides biophysically-based insights helpful for future experimental and clinical study of cardiac tamponade and related pericardial diseases.</p