Beta thalassemia major (βT) is a hereditary anemia characterized by transfusion-dependency, lifelong requirement of chelation, and organ dysfunction. MicroRNA (miRNA) can be packed into extracellular vesicles (EVs) that carry them to target cells. We explored EV-miRNA in βT and their pathophysiologic role. Circulating EVs were isolated from 35 βT-patients and 15 controls. EV miRNA was evaluated by nano-string technology and real-time quantitative polymerase chain reaction (RT-qPCR). We explored effects of EVs on cell culture proliferation, apoptosis, and signal transduction. Higher amounts of small EV (exosomes) were found in patients than in controls. The expression of 21 miRNA was > two-fold higher, and of 17 miRNA < three-fold lower in βT-EVs than control-EVs. RT-qPCR confirmed differential expression of six miRNAs in βT, particularly miR-144-3p, a regulator of erythropoiesis. Exposure of endothelial, liver Huh7, and pancreatic 1.1B4 cells to βT-EVs significantly reduced cell viability and increased cell apoptosis. βT-EV-induced endothelial cell apoptosis involved the MAPK/JNK signal-transduction pathway. In contrast, splenectomized βT-EVs induced proliferation of bone marrow mesenchymal stem cells (BM-MSC). In summary, the miR-144-3p was strongly increased; βT-EVs induced apoptosis and decreased endothelial, pancreatic, and liver cell survival while supporting BM-MSC proliferation. These mechanisms may contribute to βT organ dysfunction and complications. 相似文献
Atotal of 10 managers and their 62 subordinates participated in a field experiment that examined the effects of performance appraisal feedback deriving from two rating formats—behavioral observation scales (BOS) and graphic rating scales—on three goal-setting dimensions. Multivariate analyses of variance and a priori t tests revealed, as hypothesized, that the BOS format yielded significantly higher levels of goal clarity, goal acceptance, and goal commitment, the three goal-setting dimensions. Results are discussed in terms of systemic characteristics, that is, a "built-in" focus on specific behaviors, rather than a translation of generic performance dimensions into specific work behaviors. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献
We describe a simple method to study vortex dynamics that can determine or set an upper limit on the vortex mass. The specific heat of the vortex lattice in layered superconductors has a classical limit of 1 kB per pancake vortex if the vortex mass is zero. If the vortex mass mv is finite, a new Einstein branch of normal modes will appear with a crossover temperature E mv–1, and the specific heat will saturate at a new classical limit of 2 kB per pancake vortex.This work was supported in part by AFOSR under project F49620-92-C-0004 and by NSF under grant DMR 91-20361. We acknowledge helpful discussions with Shoucheng Zhang and S. R. Patel. 相似文献
Many natural specifications use types. We investigate the decidability of fragments of many-sorted first-order logic. We identified some decidable fragments and illustrated their usefulness by formalizing specifications considered in the literature. Often the intended interpretations of specifications are finite. We prove that the formulas in these fragments are valid iff they are valid over the finite structures. We extend these results to logics that allow a restricted form of transitive closure. 相似文献
Invariant assertions play an important role in the analysis and verification of iterative programs. In this paper, we introduce a related but distinct concept, namely that of invariant relation. While invariant assertions are useful to prove the correctness of a loop with respect to a specification (represented by a precondition/ postcondition pair) in Hoare’s logic, invariant relations are useful to derive the function of the loop in Mills’ logic. 相似文献
Discontinuous, island-type gold films (typically < or = 10 nm nominal thickness) prepared by evaporation of the metal on transparent substrates show a localized surface plasmon resonance (LSPR) extinction in the visible-to-NIR range and can be used as optical transducers for monitoring local refractive index change. Such transducers, operated in the transmission configuration, provide an effective scheme for label-free biological sensing using basic spectrophotometric equipment. Optimization of the sensitivity of LPSR transducers requires consideration of the distance between the metal island surface and the bound analyte, strongly affecting the optical response due to the fast decay of the evanescent field of localized plasmons. In the present work Au island based LSPR transducers were used to monitor antibody-antigen interactions, demonstrating the effect of the biorecognition interface thickness. Evaporated Au island films derivatized with IgG or hCG antigens were used as biological recognition elements for selective sensing of antibody binding, distinguishing between specific and nonspecific interactions. The LSPR results are supported by XPS and ellipsometry data as well as by AFM and HRSEM imaging, the latter providing actual visualization of the two protein binding steps. Increase of the recognition interface thickness leads to a concomitant decrease in the extinction and wavelength sensitivity, generally conforming to a model of an exponentially decaying surface plasmon (SP) evanescent field. 相似文献
A glass substrate was coated with silver by ultrasound irradiation. The structure and morphology of the nanoparticles in the deposited film were characterized using methods such as XRD, TEM, HR TEM, HRSEM, AFM, TOF-SIMS and optical spectroscopy. It was demonstrated that nucleation and the ensuing growth of the nanoparticles occurs in solution and is influenced by the concentration of the precursor, temperature and time of sonication. TOF-SIMS measurements revealed that silver nanoparticles passed through the glass interface and diffused within the glass substrate up to ~60?nm. An analysis of the thermal effects accompanying the sonochemical cavitation of micro-bubbles in the solution near the solid surfaces shows that the collision of nanoparticles can lead to their melting and coalescence. Sonochemical deposition takes place layer by layer, so that the completion of the deposition of each layer of nanoparticles is followed by the sintering of adjacent particles and the formation of a close-packed layer. Using PVP as a stabilizing agent, a monolayer coating of silver nanoparticles on the glass surface was obtained. The coated glass demonstrated antibacterial activity. 相似文献
RNA plays important roles as a gene-silencing agent, a therapeutic agent for clinical treatment, and in the differentiation, proliferation, and development of cells. However, RNA is very difficult to work with due to its sensitivity and fragility. Another obstacle in using RNA for gene delivery/silencing is its negative charge, which causes its repulsion by cell membranes, which are also negatively charged. Our recent study showed that miR-125b is upregulated in glioblastoma (GMB) and plays an oncogenic role in GMB cells by promoting cell proliferation and inhibiting apoptosis. Endogenous miR-125b can be blocked by transfection of its antisense RNA molecule, miR-125b antisense (miR-125b-AS). Thus, miR- 125b-AS can be developed as an RNA-based agent for cancer treatment. However, instability during storage and difficulty in delivery into cells has limited the use of RNA-based therapies thus far. In the current work, we demonstrate a short and simple one-step technique for the preparation of positively charged RNA nanospheres (miR-125b-RNS and miR-125b-AS-RNS) coated with a bioavailable polymer, polyethylenimine (PEI). These RNA nanospheres are able to penetrate the cell directly without the use of liposomes. Our study confirmed that converting miR-125b and miR-125b-AS into nanospheres is a viable approach for storing RNA. In addition, this study provides evidence that PEI-coated RNA nanospheres have the potential to be used as a novel class of anticancer agents.
The terpolymer poly(styrene-co-acrylonitrile-co-styrylisocyanate) was synthesized by radical initiation directly from styrene, acrylonitrile, and cinnamoyl azide. The monomer feed–terpolymer composition relationship was determined by Slocombe's triangular graph. The solubility, intrinsic viscosity, and melting range of the various terpolymers and the chemical reactions of the pendant isocyanate groups toward alcohol and amines were investigated. 相似文献