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Find video protocols related to scientific articles indexed in Pubmed.
Efficacy and safety of biapenem in treatment of infectious disease: a meta-analysis of randomized controlled trials.
J Chemother
PUBLISHED: 11-20-2014
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Background: Biapenem is a parenteral carbapenem antibiotic that has powerful antibacterial activity. The aim of this study is to evaluate the efficacy and safety of biapenem for the treatment of infection diseases. Methods: We performed a meta-analysis of published randomized-controlled trials (RCTs) identified in Embase, PubMed, and Cochrane library that compared the efficacy and safety of biapenem with other antibiotic regimes for the treatment of patients with infections. Results: Eight RCTs were included in the meta-analysis, involving totally 1685 patients with lower respiratory tract infections (LRTIs), complicated urinary tract infections (cUTIs), and complicated intra-abdominal infections (cIAIs). There was no difference found between the patients with LRTIs, cUTIs, or cIAIs treated with biapenem and comparators, regarding treatment success and adverse events. Conclusion: This meta-analysis provides evidence that biapenem can be used as effectively and safely as imipenem-cilstatin or meropenem, for the treatment of patients with LRTIs, cUTIs, and cIAIs. It may be a considerable option for the treatment of these infections.
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ADAPTATION-DEPENDENT SYNCHRONIZATION TRANSITIONS AND BURST GENERATIONS IN ELECTRICALLY COUPLED NEURAL NETWORKS.
Int J Neural Syst
PUBLISHED: 11-18-2014
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A typical feature of neurons is their ability to encode neural information dynamically through spike frequency adaptation (SFA). Previous studies of SFA on neuronal synchronization were mainly concentrated on the correlated firing between neuron pairs, while the synchronization of neuron populations in the presence of SFA is still unclear. In this study, the influence of SFA on the population synchronization of neurons was numerically explored in electrically coupled networks, with regular, small-world, and random connectivity, respectively. The simulation results indicate that cross-correlation indices decrease significantly when the neurons have adaptation compared with those of nonadapting neurons, similar to previous experimental observations. However, the synchronous activity of population neurons exhibits a rather complex adaptation-dependent manner. Specifically, synchronization strength of neuron populations changes nonmonotonically, depending on the degree of adaptation. In addition, single neurons in the networks can switch from regular spiking to bursting with the increase of adaptation degree. Furthermore, the connection probability among neurons exhibits significant influence on the population synchronous activity, but has little effect on the burst generation of single neurons. Accordingly, the results may suggest that synchronous activity and burst firing of population neurons are both adaptation-dependent.
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Switching at the Nanoscale: Light- and STM-Tip-Induced Switch of a Thiolated Diarylethene Self-Assembly on Au(111).
Langmuir
PUBLISHED: 11-06-2014
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The light-induced and STM-tip-induced switching of photochromic thiol functionalized terphenylthiazole-based diarylethene self-assembly on Au(111) has been investigated in ambient conditions. For such a purpose, we took advantage of the formation of highly ordered domains of opened-ring (1o) or closed-ring (1c) diarylethene isomers. We evidenced a STM-tip-induced switching for the 1o isomer characterized by a tip bias threshold of 1000 mV above which switching of all molecules of the ordered 1o domains occurs into the 1c isomer. In contrast, switching from 1c form into 1o form is not observed at the same tunnelling conditions within a domain formed by ordered 1c molecules. We compared tip-induced switching of ordered 1o domains and switching of single 1o isomers embedded in 1c domains. This led to the demonstration that the process of switching of the 1o isomer is determined by geometry of the molecules but also that the stability of the switched 1c isomer depends on the nature of the surrounding isomers. We also compare tip-induced switching and switching under the action of external UV light irradiation of ordered 1o domains. In contrast with STM tip-induced switching, the UV light induces switching of 1o domains into their stable 1c form, in agreement with a collective switching under irradiation, which cannot occur under the action of STM tip.
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Impact of delay on HIV-1 dynamics of fighting a virus with another virus.
Math Biosci Eng
PUBLISHED: 10-28-2014
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In this paper, we propose a mathematical model for HIV-1 infection with intracellular delay. The model examines a viral-therapy for controlling infections through recombining HIV-1 virus with a genetically modified virus. For this model, the basic reproduction number R0 are identified and its threshold properties are discussed. When R0<1, the infection-free equilibrium E0 is globally asymptotically stable. When R0>1, E0 becomes unstable and there occurs the single-infection equilibrium Es, and E0 and Es exchange their stability at the transcritical point R0=1. If 1R1, Es loses its stability to the double-infection equilibrium Ed. There exist a constant R2 such that Ed is asymptotically stable if R1
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[Relationship between ultrastructural features of endometrial-myometrial interface and pathogenesis of adenomyosis].
Zhonghua Yi Xue Za Zhi
PUBLISHED: 10-21-2014
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To explore the ultrastructural features of endometrial-myometrial interface (EMI) of adenomyosis and normal myometrium.
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The function and regulation of mesenchymal-to-epithelial transition in somatic cell reprogramming.
Curr. Opin. Genet. Dev.
PUBLISHED: 08-28-2014
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The process that converts somatic cells to pluripotent ones has enormous potential not only as a tool to generate cells for disease therapy and modeling, but also as an experimental system to investigate fundamental biological questions. The discovery of mesenchymal-to-epithelial transitions at the initial phase of reprogramming provides a conceptual framework to understand reprogramming in a cellular context and it helps to resolve the mechanistic roles of the original Yamanaka factors as well as newly identified modulators of reprogramming. Emerging concept such as sequential EMT-MET in reprogramming further suggests the value of this model to the understanding of cell fate conversions. We highlight recent advances about the function and regulation of MET in reprogramming and discuss their potential implications here.
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[Activation of p21(WAF1/CIP1) by small activating RNA inhibits cell proliferation and induces apoptosis in BEL-7402 hepatoma cell].
Zhonghua Yi Xue Za Zhi
PUBLISHED: 08-23-2014
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To evaluate the anti neoplastic effects of p21(WAF1/CIP1) transcriptional activation induced by duplex RNAs in hepatocellular carcinoma (HCC) cell line BEL-7402.
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A reciprocal antagonism between miR-376c and TGF-? signaling regulates neural differentiation of human pluripotent stem cells.
FASEB J.
PUBLISHED: 08-11-2014
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Differentiation of neural lineages from human pluripotent stem cells (hPSCs) raises the hope of generating functional cells for the treatment of neural diseases. However, current protocols for differentiating hPSCs into neural lineages remain inefficient and largely variable between different hPSC lines. We report that microRNA 376c (miR-376c) significantly enhanced neural differentiation of hPSCs in a defined condition by suppressing SMAD4, the co-SMAD for TGF-? signaling. Downstream, SMAD4 directly bound and suppressed PAX6, the critical neural lineage specification factor. Interestingly, we also found that SMAD4 binds and suppresses miR-376c clusters in undifferentiated hESCs. In summary, our findings revealed a reciprocal antagonism between miR-376c and SMAD signaling that regulates cell fate during human neural differentiation.-Liu, J., Wang, L., Su, Z., Wu, W., Cai, X., Li, D., Hou, J., Pei, D., Pan, G. A reciprocal antagonism between miR-376c and TGF-? signaling regulates neural differentiation of hPSCs.
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Ternary CuIn7 Se11 : Towards Ultra-Thin Layered Photodetectors and Photovoltaic Devices.
Adv. Mater. Weinheim
PUBLISHED: 07-24-2014
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A few layered ternary Cu-In-Se compound is synthesized, the photoconductivity is measured, and 2D photovoltaic devices are fabricated. Few-layered CuIn7 Se11 has a strong photoresponse and the potential to serve as the active medium in ultra-thin photovoltaic devices.
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Reduced ??2?glycoprotein ? inhibits hypoxia?induced retinal angiogenesis in neonatal mice through the vascular endothelial growth factor pathway.
Mol Med Rep
PUBLISHED: 07-23-2014
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??2?glycoprotein I (?2GPI), also known as apolipoprotein H, is a phospholipid?binding plasma protein consisting of five homologous repeated units. ?2GPI downregulates vascular endothelial growth factor (VEGF) signaling pathways and inhibits angiogenesis in vitro. However, the in vivo roles and effectors of reduced ?2GPI and ?2GPI in retinal angiogenesis are still not fully understood. In this study, an oxygen?induced retinopathy model was used to investigate the effects of reduced ?2GPI and ?2GPI, and to monitor the expression of VEGF, VEGF receptor (VEGFR) 1, VEGFR?2 and hypoxia?inducible factor 1 (HIF?1) mRNA and the phosphorylation of extracellular signal?regulated kinase (ERK) and Akt. The data showed that both ?2GPI and reduced ?2GPI inhibited retinal angiogenesis and suppressed the expression of VEGF, VEGFR?1, VEGFR?2, HIF?1, phosphorylated- (p?) ERK and p?Akt. The effects of reduced ?2GPI were significantly stronger than those of ?2GPI. In conclusion, this study showed that ?2GPI and reduced ?2GPI could inhibit retinal angiogenesis by downregulating the expression of VEGF and its downstream targets. This suggests that ?2GPI and reduced ?2GPI may have potential anti?angiogenic activity in vivo.
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3D Macroporous Solids from Chemically Cross-linked Carbon Nanotubes.
Small
PUBLISHED: 07-18-2014
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Suzuki reaction for covalently interconnected 3D carbon nanotube (CNT) architectures is reported. The synthesis of 3D macroscopic solids made of CNTs covalently connected via Suzuki cross-coupling, a well-known carbon-carbon covalent bond forming reaction in organic chemistry, is scalable. The resulting solid has a highly porous, interconnected structure of chemically cross-linked CNTs. Its use for the removal of oil from contaminated water is demonstrated.
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Cancer: pathological nuclear reprogramming?
Nat. Rev. Cancer
PUBLISHED: 07-17-2014
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The ability of stem cells to self-renew and generate different lineages during development and organogenesis is a fundamental, tightly controlled, and generally unidirectional process, whereas the 'immortality' of cancer cells could be regarded as pathological self-renewal. The molecular mechanisms that underpin the generation of induced pluripotent stem cells are remarkably similar to those that are deregulated in cancer - so much so that aberrant reprogramming is tumorigenic. The similarities also suggest that mutations in genes implicated in DNA methylation dynamics might represent a hallmark of cancers with a stem cell origin, and they highlight an alternative view of cancer that may be of clinical benefit.
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Where cell fate conversions meet Chinese philosophy.
Cell Res.
PUBLISHED: 07-15-2014
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Accumulating evidence indicates that the mesenchymal-epithelial transition (MET) and epithelial-mesenchymal transition (EMT) are basic mechanisms for cell fate conversion and may help us understand both physiologic and pathologic processes such as development and carcinogenesis. Here, we further suggest that mammalian cells fall into two grand divisions, mesenchymal or epithelial; interconversions between these two grand divisions through EMT/MET resonate with some ancient Chinese philosophic ideas.
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Phase-corrected bipolar gradients in multi-echo gradient-echo sequences for quantitative susceptibility mapping.
MAGMA
PUBLISHED: 07-14-2014
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Large echo spacing of unipolar readout gradients in current multi-echo gradient-echo (GRE) sequences for mapping fields in quantitative susceptibility mapping (QSM) can be reduced using bipolar readout gradients thereby improving acquisition efficiency.
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Structure of human SNX10 reveals insights into its role in human autosomal recessive osteopetrosis.
Proteins
PUBLISHED: 07-03-2014
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Sorting nexin 10 (SNX10), the unique member of the SNX family having vacuolation activity in cells, was shown to be involved in the development of autosomal recessive osteopetrosis (ARO) in recent genetic studies. However, the molecular mechanism of the disease-related mutations affecting the biological function of SNX10 is unclear. Here, we report the crystal structure of human SNX10 to 2.6Å resolution. The structure reveals that SNX10 contains the extended phox-homology domain we previously proposed. Our study provides the structural details of those disease-related mutations. Combined with the vacuolation study of those mutations, we found that Tyr32 and Arg51 are important for the protein stability and both play a critical role in vacuolation activity, while Arg16Leu may affect the function of SNX10 in osteoclast through protein-protein interactions. Proteins 2014; 82:3483-3489. © 2014 Wiley Periodicals, Inc.
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Role of the Wilms' tumor 1 gene in the aberrant biological behavior of leukemic cells and the related mechanisms.
Oncol. Rep.
PUBLISHED: 06-25-2014
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The Wilms' tumor 1 (WT1) gene is one of the regulating factors in cell proliferation and development. It is a double-functional gene: an oncogene and a tumor suppressor. This gene was found to be highly expressed in many leukemic cell lines and in patients with acute myeloid leukemia. In the present study, we demonstrated that the WT1 gene was commonly expressed in leukemic cell lines apart from U937 cells. The K562 cell line which expresses WT1 at a high level (mRNA and protein) was used in the entire experiment. By MTT and colony formation assays, we found that curcumin, an inhibitor of the WT1 protein, inhibited cell proliferation and clonogenicity in a time- and dose-dependent manner. It also caused cell cycle arrest at the G2/M phase. We then designed specific short hairpin RNAs (shRNAs) which could downregulate WT1 by 70-80% at the mRNA and protein levels. Reduction in the WT1 levels attenuated the proliferative ability and clonogenicity. Cell cycle progression analysis indicated that the proportion of cells in the G0/G1 phase increased while the proportion in the S phase decreased distinctively. ChIP-DNA selection and ligation (DSL) experiment identified a cohort of genes whose promoters are targeted by WT1. These genes were classified into different cellular signaling pathways using MAS software and included the Wnt/?-catenin pathway, MAPK signaling pathway, apoptosis pathway, and the cell cycle. We focused on the Wnt/?-catenin signaling pathway, and compared expression of several genes in the K562 cells transfected with the control shRNA and WT1-specific shRNA. ?-catenin, an important gene in the Wnt canonical pathway, was downregulated after WT1 RNAi. Target genes of ?-catenin which participate in cell proliferation and cell cycle regulation, such as CCND1 and MYC, were also significantly downregulated. Collectively, these data suggest that WT1 functions as an oncogene in leukemia cells, and one important mechanism is regulation of the Wnt/?-catenin pathway.
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Bias correction for magnetic resonance images via joint entropy regularization.
Biomed Mater Eng
PUBLISHED: 06-24-2014
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Due to the imperfections of the radio frequency (RF) coil or object-dependent electrodynamic interactions, magnetic resonance (MR) images often suffer from a smooth and biologically meaningless bias field, which causes severe troubles for subsequent processing and quantitative analysis. To effectively restore the original signal, this paper simultaneously exploits the spatial and gradient features of the corrupted MR images for bias correction via the joint entropy regularization. With both isotropic and anisotropic total variation (TV) considered, two nonparametric bias correction algorithms have been proposed, namely IsoTVBiasC and AniTVBiasC. These two methods have been applied to simulated images under various noise levels and bias field corruption and also tested on real MR data. The test results show that the proposed two methods can effectively remove the bias field and also present comparable performance compared to the state-of-the-art methods.
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[Comparison of expression of transforming growth factor-?1 in rat dental pulp during direct pulp capping with 2 capping agents].
Shanghai Kou Qiang Yi Xue
PUBLISHED: 06-18-2014
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To examine and compare the expression of transforming growth factor-?1(TGF-?1) in rat dental pulp after direct pulp capping with calcium hydroxide (CH) and mineral trioxide aggregate (MTA).
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Global gene expression profiling identifies ALDH2, CCNE1 and SMAD3 as potential prognostic markers in upper tract urothelial carcinoma.
BMC Cancer
PUBLISHED: 06-16-2014
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Current knowledge about the molecular properties and prognostic markers of upper tract urothelial carcinoma (UTUC) is sparse and often based on bladder urothelial carcinoma (UC), which is thought to share common risk factors with UTUC. However, studies have suggested that differences exist regarding tumor behavior and molecular biology of these cancers, comprehensive investigations are needed to guide the clinical management of UTUC. In recent years, massively parallel sequencing has allowed insights into the biology of many cancers, and molecular prognostic markers based on this approach are rapidly emerging. The goal of this study was to characterize the gene expression patterns of UTUC using massively parallel sequencing, and identify potential molecular markers for prognosis in patients with UTUC.
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Application of iPS cells in dental bioengineering and beyond.
Stem Cell Rev
PUBLISHED: 06-12-2014
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The stem-cell-based tissue-engineering approaches are widely applied in establishing functional organs and tissues for regenerative medicine. Successful generation of induced pluripotent stem cells (iPS cells) and rapid progress of related technical platform provide great promise in the development of regenerative medicine, including organ regeneration. We have previously reported that iPS cells could be an appealing stem cells source contributing to tooth regeneration. In the present paper, we mainly review the application of iPS technology in dental bioengineering and discuss the challenges for iPS cells in the whole tooth regeneration.
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Synthesis and preliminary biologic activity evaluation of nitric oxide-releasing andrographolide derivatives in RIN-m cells.
Chem. Pharm. Bull.
PUBLISHED: 06-03-2014
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Pancreatic ?-cell dysfunction and death are important feature of diabetes mellitus. Beta-cell protection has demonstrated clinical benefits in the treatment of this disease. In the present study, andrographolide derivatives with nitric oxide (NO)-releasing capability were synthesized and their protective effects against tert-butyl hydroperoxide (t-BHP) induced cell damage were investigated in RIN-m cells. Compound 6b was found to release a moderate amount of NO and was more potent than its natural parent andrographolide in inhibiting cell apoptosis. These findings suggested that andrographolide derivatives with NO-releasing capacity may be a potential therapy for diabetes.
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Population activity changes during a trial-to-trial adaptation of bullfrog retinal ganglion cells.
Neuroreport
PUBLISHED: 05-23-2014
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A 'trial-to-trial adaptation' of bullfrog retinal ganglion cells in response to a repetitive light stimulus was investigated in the present study. Using the multielectrode recording technique, we studied the trial-to-trial adaptive properties of ganglion cells and explored the activity of population neurons during this adaptation process. It was found that the ganglion cells adapted with different degrees: their firing rates were decreased in different extents from early-adaptation to late-adaptation stage, and this was accompanied by a decrease in cross-correlation strength. In addition, adaptation behavior was different for ON-response and OFF-response, which implied that the mechanism of the trial-to-trial adaptation might involve bipolar cells and/or their synapses with other neurons and the stronger adaptation in the ganglion cells' OFF-responses might reflect the requirement to avoid possible saturation in the OFF circuit.
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Ionic mechanisms underlying tonic and phasic firing behaviors in retinal ganglion cells: A model study.
Channels (Austin)
PUBLISHED: 04-29-2014
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In the retina, the firing behaviors that ganglion cells exhibit when exposed to light stimuli are very important due to the significant roles they play in encoding the visual information. However, the detailed mechanisms, especially the intrinsic properties that generate and modulate these firing behaviors is not completely clear yet. In this study, 2 typical firing behaviors-i.e., tonic and phasic activities, which are widely observed in retinal ganglion cells (RGCs)-are investigated. A modified computational model was developed to explore the possible ionic mechanisms that underlie the generation of these 2 firing patterns. Computational results indicate that the generation of tonic and phasic activities may be attributed to the collective actions of 2 kinds of adaptation currents, i.e., an inactivating sodium current and a delayed-rectifier potassium current. The concentration of magnesium ions has crucial but differential effects in the modulation of tonic and phasic firings, when the model neuron is driven by N-methyl-D-aspartate (NMDA) -type synaptic input instead of constant current injections. The proposed model has robust features that account for the ionic mechanisms underlying the tonic and phasic firing behaviors, and it may also be used as a good candidate for modeling some other firing patterns in RGCs.
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Improvement of sugar analysis sensitivity using anion-exchange chromatography-electrospray ionization mass spectrometry with sheath liquid interface.
J Chromatogr A
PUBLISHED: 04-18-2014
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A novel interface that enables high-performance anion-exchange chromatography (HPAEC) to be coupled with electrospray ionization (ESI) mass spectrometry (MS) is reported. A sheath liquid consisting of 50mM NH4Ac in isopropanol with 0.05% acetic acid, infused at a flow rate of 3?L/min at the tip of the electrospray probe, requires less ESI source cleaning and promotes efficient ionization of mono- and di-carbohydrates. The results suggest that use of a sheath liquid interface rather than a T-joint allows volatile ammonium salts to replace non-volatile metal salts as modifiers for improving sugar ESI signals. The efficient ionization of mono- and di-carbohydrates in the ESI source is affected by the sheath liquid properties such as buffer concentration and type of organic solvent. HPAEC-ESI-MS was used for the analysis of monocarbohydrates in pectins, particularly co-eluted sugars, and the performance was evaluated. Addition of a make-up solution through the sheath liquid interface proved to be an efficient tool for enhancing the intensities of sugars analyzed using HPAEC-ESI-MS.
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Efficacy of radical cystectomy plus adjuvant intraarterial chemotherapy with gemcitabine and cisplatin on locally advanced bladder cancer.
Chin. Med. J.
PUBLISHED: 04-09-2014
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Bladder cancer is the ninth most common cancer in the world; fewer than 15% of transitional-cell carcinoma patients survive 2 years if left untreated. Although radical cystectomy is the standard treatment of choice, much of them relapse and the necessity of adjuvant chemotherapy is still under debate. The aim of the study was to evaluate the efficacy of adjuvant intraarterial chemotherapy (IAC) with gemcitabine and cisplatin (GC) on locally advanced bladder cancer.
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Bone canalicular network segmentation in 3D nano-CT images through geodesic voting and image tessellation.
Phys Med Biol
PUBLISHED: 04-08-2014
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Recent studies emphasized the role of the bone lacuno-canalicular network (LCN) in the understanding of bone diseases such as osteoporosis. However, suitable methods to investigate this structure are lacking. The aim of this paper is to introduce a methodology to segment the LCN from three-dimensional (3D) synchrotron radiation nano-CT images. Segmentation of such structures is challenging due to several factors such as limited contrast and signal-to-noise ratio, partial volume effects and huge number of data that needs to be processed, which restrains user interaction. We use an approach based on minimum-cost paths and geodesic voting, for which we propose a fully automatic initialization scheme based on a tessellation of the image domain. The centroids of pre-segmented lacunæ are used as Voronoi-tessellation seeds and as start-points of a fast-marching front propagation, whereas the end-points are distributed in the vicinity of each Voronoi-region boundary. This initialization scheme was devised to cope with complex biological structures involving cells interconnected by multiple thread-like, branching processes, while the seminal geodesic-voting method only copes with tree-like structures. Our method has been assessed quantitatively on phantom data and qualitatively on real datasets, demonstrating its feasibility. To the best of our knowledge, presented 3D renderings of lacunæ interconnected by their canaliculi were achieved for the first time.
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Response properties of ON-OFF retinal ganglion cells to high-order stimulus statistics.
Neurosci. Lett.
PUBLISHED: 04-04-2014
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The visual stimulus statistics are the fundamental parameters to provide the reference for studying visual coding rules. In this study, the multi-electrode extracellular recording experiments were designed and implemented on bullfrog retinal ganglion cells to explore the neural response properties to the changes in stimulus statistics. The changes in low-order stimulus statistics, such as intensity and contrast, were clearly reflected in the neuronal firing rate. However, it was difficult to distinguish the changes in high-order statistics, such as skewness and kurtosis, only based on the neuronal firing rate. The neuronal temporal filtering and sensitivity characteristics were further analyzed. We observed that the peak-to-peak amplitude of the temporal filter and the neuronal sensitivity, which were obtained from either neuronal ON spikes or OFF spikes, could exhibit significant changes when the high-order stimulus statistics were changed. These results indicate that in the retina, the neuronal response properties may be reliable and powerful in carrying some complex and subtle visual information.
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Effects of reduced ?2-glycoprotein I on the expression of aortic matrix metalloproteinases and tissue inhibitor matrix metalloproteinases in diabetic mice.
BMC Cardiovasc Disord
PUBLISHED: 03-29-2014
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Reduced ?(2)-glycoprotein I (reduced ?(2)GP I), which has free sulfhydryl groups, is present in plasma and serum; it can protect vascular endothelial cells from damage due to oxidative stress in vitro. We investigated the effects of reduced ?(2)GP I on the expression of various matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) in the aortas of diabetic mice.
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Algorithm for fast monoexponential fitting based on Auto-Regression on Linear Operations (ARLO) of data.
Magn Reson Med
PUBLISHED: 03-26-2014
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To develop a fast and accurate monoexponential fitting algorithm based on Auto-Regression on Linear Operations (ARLO) of data, and to validate its accuracy and computational speed by comparing it with the conventional Levenberg-Marquardt (LM) and Log-Linear (LL) algorithms.
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Transitions between epithelial and mesenchymal states during cell fate conversions.
Protein Cell
PUBLISHED: 03-12-2014
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Cell fate conversion is considered as the changing of one type of cells to another type including somatic cell reprogramming (de-differentiation), differentiation, and trans-differentiation. Epithelial and mesenchymal cells are two major types of cells and the transitions between these two cell states as epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET) have been observed during multiple cell fate conversions including embryonic development, tumor progression and somatic cell reprogramming. In addition, MET and sequential EMT-MET during the generation of induced pluripotent stem cells (iPSC) from fibroblasts have been reported recently. Such observation is consistent with multiple rounds of sequential EMT-MET during embryonic development which could be considered as a reversed process of reprogramming at least partially. Therefore in current review, we briefly discussed the potential roles played by EMT, MET, or even sequential EMT-MET during different kinds of cell fate conversions. We also provided some preliminary hypotheses on the mechanisms that connect cell state transitions and cell fate conversions based on results collected from cell cycle, epigenetic regulation, and stemness acquisition.
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A multifunctional photoswitch: 6? electrocyclization versus ESIPT and metalation.
Chemistry
PUBLISHED: 03-03-2014
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A terthiazole-based molecular switch associating 6? electrocyclization, excited state intramolecular proton transfer (ESIPT), and strong metal binding capability was prepared. The photochemical and photophysical properties of this molecule and of the corresponding nickel and copper complexes were thoroughly investigated by steady-state and ultrafast absorption spectroscopy and rationalized by DFT/TDDFT calculations. The switch behaves as a biphotochrome with time-dependent photochemical outcome and displays efficient ESIPT-based fluorescence photoswitching. Both photochemical reactions are suppressed by nickel or copper metalation, and the main factors contributing to the quenching of the electrocyclization are discussed.
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Separation and determination of 4-methylimidazole, 2-methylimidazole and 5-hydroxymethylfurfural in beverages by amino trap column coupled with pulsed amperometric detection.
Food Chem
PUBLISHED: 02-21-2014
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A method for simultaneous determination of 4-methylimidazole (4-MeI), 2-methylimidazole (2-MeI) and 5-hydroxymethylfurfural (HMF) in beverages was developed using solid-phase extraction (SPE) and amino trap column coupled with pulsed amperometric detection (AMTC-PAD). A single amino trap column (P/N: 046122) was first applied to separate the targeted analytes in samples after SPE pretreatment. This method demonstrated low limit of quantification (0.030mg/L for methylimidazoles and 0.300mg/L for HMF) and excellent linearity with correlation of determination (R(2)=0.999 for 2-MeI, 0.997 for 4-MeI and 0.998 for HMF). Nearly no 2-MeI was found in all soft drinks. However, 4-MeI could be detected in cola drinks and soft drinks containing caramel colour (ranging from 0.13 to 0.34mg/L), whereas HMF were only found in cola drinks (ranging from 1.07 to 4.47mg/L). Thus, AMTC-PAD technique would be a valid and inexpensive alternative to analysis of 4-MeI, 2-MeI and HMF.
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Transcriptional Pause Release Is a Rate-Limiting Step for Somatic Cell Reprogramming.
Cell Stem Cell
PUBLISHED: 02-18-2014
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Reactivation of the pluripotency network during somatic cell reprogramming by exogenous transcription factors involves chromatin remodeling and the recruitment of RNA polymerase II (Pol II) to target loci. Here, we report that Pol II is engaged at pluripotency promoters in reprogramming but remains paused and inefficiently released. We also show that bromodomain-containing protein 4 (BRD4) stimulates productive transcriptional elongation of pluripotency genes by dissociating the pause release factor P-TEFb from an inactive complex containing HEXIM1. Consequently, BRD4 overexpression enhances reprogramming efficiency and HEXIM1 suppresses it, whereas Brd4 and Hexim1 knockdown do the opposite. We further demonstrate that the reprogramming factor KLF4 helps recruit P-TEFb to pluripotency promoters. Our work thus provides a mechanism for explaining the reactivation of pluripotency genes in reprogramming and unveils an unanticipated role for KLF4 in transcriptional pause release.
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Short communication: Amino trap column improving the separation of methylimidazoles, 5-hydroxymethyl-2-furaldehyde, and sugars in Maillard reaction.
J. Dairy Sci.
PUBLISHED: 02-18-2014
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A simultaneous analysis of methylimidazoles, reducing sugars, and 5-hydroxymethyl-2-furaldehyde in the Maillard reaction was improved by use of an amino trap column. Analysis was carried out by using high-performance anion exchange chromatography with pulsed amperometric detection (HPAEC-PAD) coupled with an amino trap column. The amino trap column was a useful tool to improve the separation of methylimidazoles, reducing sugars, and 5-hydroxymethyl-2-furaldehyde. This technique is useful for simultaneous analysis of methylimidazoles, reducing sugars, and 5-hydroxymethyl-2-furaldehyde in risk assessment for dairy products.
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Curative use of forequarter amputation for recurrent breast cancer over an axillary area: a case report and literature review.
World J Surg Oncol
PUBLISHED: 02-13-2014
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Axillary recurrence of breast cancer that involves the brachial neurovascular bundle is uncommon. However, for many patients with such recurrence, forequarter amputation can play a palliative role in relieving excruciating pain and paralysis of the upper limb. Further, for those patients who do not have distant metastasis or other local-regional recurrence, forequarter amputation provides a chance for a cure. Only a few case reports of curative amputations for recurrent breast cancer are present in the literature. Here, we report a case of forequarter amputation for curative treatment of axillary recurrent breast cancer, together with a literature review. To date, we have followed the patient for three years after amputation, during which there has been no evidence of recurrence or metastasis. Although radical resection is feasible, it can be accompanied by surgical wound complications and psychosocial stress. Therefore, an organized multidisciplinary approach is needed to ensure the success of radical resection.
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Tet and TDG mediate DNA demethylation essential for mesenchymal-to-epithelial transition in somatic cell reprogramming.
Cell Stem Cell
PUBLISHED: 02-13-2014
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Tet-mediated DNA oxidation is a recently identified mammalian epigenetic modification, and its functional role in cell-fate transitions remains poorly understood. Here, we derive mouse embryonic fibroblasts (MEFs) deleted in all three Tet genes and examine their capacity for reprogramming into induced pluripotent stem cells (iPSCs). We show that Tet-deficient MEFs cannot be reprogrammed because of a block in the mesenchymal-to-epithelial transition (MET) step. Reprogramming of MEFs deficient in TDG is similarly impaired. The block in reprogramming is caused at least in part by defective activation of key miRNAs, which depends on oxidative demethylation promoted by Tet and TDG. Reintroduction of either the affected miRNAs or catalytically active Tet and TDG restores reprogramming in the knockout MEFs. Thus, oxidative demethylation to promote gene activation appears to be functionally required for reprogramming of fibroblasts to pluripotency. These findings provide mechanistic insight into the role of epigenetic barriers in cell-lineage conversion.
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Involvement of thalamus in initiation of epileptic seizures induced by pilocarpine in mice.
Neural Plast.
PUBLISHED: 02-05-2014
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Studies have suggested that thalamus is involved in temporal lobe epilepsy, but the role of thalamus is still unclear. We obtained local filed potentials (LFPs) and single-unit activities from CA1 of hippocampus and parafascicular nucleus of thalamus during the development of epileptic seizures induced by pilocarpine in mice. Two measures, redundancy and directionality index, were used to analyze the electrophysiological characters of neuronal activities and the information flow between thalamus and hippocampus. We found that LFPs became more regular during the seizure in both hippocampus and thalamus, and in some cases LFPs showed a transient disorder at seizure onset. The variation tendency of the peak values of cross-correlation function between neurons matched the variation tendency of the redundancy of LFPs. The information tended to flow from thalamus to hippocampus during seizure initiation period no matter what the information flow direction was before the seizure. In some cases the information flow was symmetrically bidirectional, but none was found in which the information flowed from hippocampus to thalamus during the seizure initiation period. In addition, inactivation of thalamus by tetrodotoxin (TTX) resulted in a suppression of seizures. These results suggest that thalamus may play an important role in the initiation of epileptic seizures.
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Domain I-IV of ?2-glycoprotein I inhibits advanced glycation end product-induced angiogenesis by down-regulating vascular endothelial growth factor 2 signaling.
Mol Med Rep
PUBLISHED: 01-31-2014
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Advanced glycation end products (AGEs) are a contributing factor in the angiogenesis that is characteristic of proliferative diabetic retinopathy. However, a previous study made a promising observation that domain I?IV of ?2?glycoprotein I (DI?IV) inhibits angiogenesis in human umbilical vein cells. The present study aimed to confirm the inhibition of AGE?induced angiogenesis in retinal endothelial cells by DI?IV and to investigate the potential underlying mechanisms. The RF/6A rhesus macaque choroid?retinal vascular endothelial cell line was cultured in vitro and treated with AGEs in the presence or absence of different concentrations of DI?IV. The proliferation, migration and tube formation of the RF/6A cells were evaluated using MTS assays, in vitro wound healing assays and in vitro Matrigel angiogenesis assays, respectively. The mRNA expression of vascular endothelial growth factor (VEGF), VEGF receptor (VEGFR) 2, VEGFR 1 and receptor for AGE (RAGE) were quantified by reverse transcription quantitative polymerase chain reaction. The expression of VEGFR?1, VEGFR?2 and the activation of protein kinase B (Akt) and extracellular signal?regulated kinase (ERK) were also assessed by western blot analysis. The results indicated that AGEs promoted the migration, proliferation and tube formation of RF/6A cells in vitro (P<0.05), increased the expression of VEGF, VEGFR?2 and RAGE (P<0.05) and increased the phosphorylation of Akt and ERK (P<0.05). DI?IV inhibited the increase in VEGFR?2 mRNA and protein, but did not inhibit the increase in VEGF or RAGE mRNAs. These results led to the conclusion that DI?IV inhibited AGE?induced angiogenesis in the RF/6A cells, which was accompanied by a downregulation in the expression of VEGFR?2 and its downstream phosphatidylinosol 3?kinase/Akt and mitogen?activated protein kinase/ERK1/2 pathways. These findings provide further support towards the treatment of proliferative diabetic retinopathy by interventions that act via a mechanism similar to that of DI?IV.
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Quantitative susceptibility mapping of multiple sclerosis lesions at various ages.
Radiology
PUBLISHED: 01-31-2014
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To assess multiple sclerosis (MS) lesions at various ages by using quantitative susceptibility mapping (QSM) and conventional magnetic resonance (MR) imaging.
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Effect of the entorhinal cortex on ictal discharges in low-Mg²?-induced epileptic hippocampal slice models.
Neural Plast.
PUBLISHED: 01-30-2014
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The hippocampus plays an important role in the genesis of mesial temporal lobe epilepsy, and the entorhinal cortex (EC) may affect the hippocampal network activity because of the heavy interconnection between them. However, the mechanism by which the EC affects the discharge patterns and the transmission mode of epileptiform discharges within the hippocampus needs further study. Here, multielectrode recording techniques were used to study the spatiotemporal characteristics of epileptiform discharges in adult mouse hippocampal slices and combined EC-hippocampal slices and determine whether and how the EC affects the hippocampal neuron discharge patterns. The results showed that low-Mg²? artificial cerebrospinal fluid induced interictal discharges in hippocampal slices, whereas, in combined EC-hippocampal slices the discharge pattern was alternated between interictal and ictal discharges, and ictal discharges initiated in the EC and propagated to the hippocampus. The pharmacological effect of the antiepileptic drug valproate (VPA) was tested. VPA reversibly suppressed the frequency of interictal discharges but did not change the initiation site and propagation speed, and it completely blocked ictal discharges. Our results suggested that EC was necessary for the hippocampal ictal discharges, and ictal discharges were more sensitive than interictal discharges in response to VPA.
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Visual pattern discrimination by population retinal ganglion cells' activities during natural movie stimulation.
Cogn Neurodyn
PUBLISHED: 01-28-2014
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In the visual system, neurons often fire in synchrony, and it is believed that synchronous activities of group neurons are more efficient than single cell response in transmitting neural signals to down-stream neurons. However, whether dynamic natural stimuli are encoded by dynamic spatiotemporal firing patterns of synchronous group neurons still needs to be investigated. In this paper we recorded the activities of population ganglion cells in bullfrog retina in response to time-varying natural images (natural scene movie) using multi-electrode arrays. In response to some different brief section pairs of the movie, synchronous groups of retinal ganglion cells (RGCs) fired with similar but different spike events. We attempted to discriminate the movie sections based on temporal firing patterns of single cells and spatiotemporal firing patterns of the synchronous groups of RGCs characterized by a measurement of subsequence distribution discrepancy. The discrimination performance was assessed by a classification method based on Support Vector Machines. Our results show that different movie sections of the natural movie elicited reliable dynamic spatiotemporal activity patterns of the synchronous RGCs, which are more efficient in discriminating different movie sections than the temporal patterns of the single cells' spike events. These results suggest that, during natural vision, the down-stream neurons may decode the visual information from the dynamic spatiotemporal patterns of the synchronous group of RGCs' activities.
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Genome-wide CNV analysis in mouse induced pluripotent stem cells reveals dosage effect of pluripotent factors on genome integrity.
BMC Genomics
PUBLISHED: 01-24-2014
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Induced pluripotent stem cells (iPSCs) derived from somatic cells have enormous potential for clinical applications. Notably, it was recently reported that reprogramming from somatic cells to iPSCs can induce genomic copy number variation (CNV), which is one of the major genetic causes of human diseases. However it was unclear if this genome instability is dependent on reprogramming methods and/or the genetic background of donor cells. Furthermore, genome-wide CNV analysis is technically challenging and CNV data need to be interpreted with care.
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Exogenous expression of WT1 gene influences U937 cell biological behaviors and activates MAPK and JAK-STAT signaling pathways.
Leuk. Res.
PUBLISHED: 01-19-2014
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Wilms' tumor 1 (WT1) gene plays important roles in leukemogenesis. To further explore its underlying mechanisms, we transfected two WT1 isoforms, WT1(+17AA/-KTS) and WT1(+17AA/+KTS) into U937, a WT1-null monoblastic cell line, studied their effects on migration, colony formation, apoptosis, gene expression and pertinent signaling pathways of U937 cells. The results showed that WT1(+17AA/-KTS), but not WT1(+17AA/+KTS), enhanced migration and colony forming abilities of U937 cells, and suppressed etoposide-induced U937 cell apoptosis. Transfection of WT1 isoforms activated gene expressions of chemokine, and induced up-regulation of signaling molecules involved in JAK-STAT and MAPK signaling pathways. This study showed that exogenous expression of WT1 gene remarkably affected biological behaviors of U937 cells, and these effects are possibly mediated by up-regulation of genes related to chemokine, JAK-STAT and MAPK signaling pathways.
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The role of the entorhinal cortex in epileptiform activities of the hippocampus.
Theor Biol Med Model
PUBLISHED: 01-19-2014
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Temporal lobe epilepsy (TLE) is the commonest type of epilepsy in adults, and the hippocampus is indicated to have a close relationship with TLE. Recent researches also indicate that the entorhinal cortex (EC) is involved in epilepsy. To explore the essential role that the EC may play in epilepsy, a computational model of the hippocampal CA3 region was built, which consisted of pyramidal cells and two types of interneurons. By changing the input signals from the EC, the effects of EC on epileptiform activities of the hippocampus were investigated. Additionally, recent studies have found that the antiepileptic drug valproate (VPA) can block ictal discharges but cannot block interictal discharges in vitro, and the mechanism under this phenomenon is still confusing. In our model, the effects of VPA on epileptiform activities were simulated and some mechanisms were explored.
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Neural progenitor cells from human induced pluripotent stem cells generated less autogenous immune response.
Sci China Life Sci
PUBLISHED: 01-17-2014
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The breakthrough development of induced pluripotent stem cells (iPSCs) raises the prospect of patient-specific treatment for many diseases through the replacement of affected cells. However, whether iPSC-derived functional cell lineages generate a deleterious immune response upon auto-transplantation remains unclear. In this study, we differentiated five human iPSC lines from skin fibroblasts and urine cells into neural progenitor cells (NPCs) and analyzed their immunogenicity. Through co-culture with autogenous peripheral blood mononuclear cells (PBMCs), we showed that both somatic cells and iPSC-derived NPCs do not stimulate significant autogenous PBMC proliferation. However, a significant immune reaction was detected when these cells were co-cultured with allogenous PBMCs. Furthermore, no significant expression of perforin or granzyme B was detected following stimulation of autogenous immune effector cells (CD3(+)CD8(-) T cells, CD3(+)CD8(+) T cells or CD3(-)CD56(+) NK cells) by NPCs in both PBMC and T cell co-culture systems. These results suggest that human iPSC-derived NPCs may not initiate an immune response in autogenous transplants, and thus set a base for further preclinical evaluation of human iPSCs.
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Modeling of hemophilia A using patient-specific induced pluripotent stem cells derived from urine cells.
Life Sci.
PUBLISHED: 01-07-2014
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Hemophilia A (HA) is a severe, congenital bleeding disorder caused by the deficiency of clotting factor VIII (FVIII). For years, traditional laboratory animals have been used to study HA and its therapies, although animal models may not entirely mirror the human pathophysiology. Human induced pluripotent stem cells (iPSCs) can undergo unlimited self-renewal and differentiate into all cell types. This study aims to generate hemophilia A (HA) patient-specific iPSCs that differentiate into disease-affected hepatocyte cells. These hepatocytes are potentially useful for in vitro disease modeling and provide an applicable cell source for autologous cell therapy after genetic correction.
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Response dynamics of bullfrog ON-OFF RGCs to different stimulus durations.
J Comput Neurosci
PUBLISHED: 01-04-2014
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Stimulus duration is an important feature of visual stimulation. In the present study, response properties of bullfrog ON-OFF retinal ganglion cells (RGCs) in exposure to different visual stimulus durations were studied. By using a multi-electrode recording system, spike discharges from ON-OFF RGCs were simultaneously recorded, and the cells' ON and OFF responses were analyzed. It was found that the ON response characteristics, including response latency, spike count, as well as correlated activity and relative latency between pair-wise cells, were modulated by different light OFF intervals, while the OFF response characteristics were modulated by different light ON durations. Stimulus information carried by the ON and OFF responses was then analyzed, and it was found that information about different light ON durations was more carried by transient OFF response, whereas information about different light OFF intervals were more carried by transient ON response. Meanwhile, more than 80 % information about stimulus durations was carried by firing rate. These results suggest that ON-OFF RGCs are sensitive to different stimulus durations, and they can efficiently encode the information about visual stimulus duration by firing rate.
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Human RAD6 Promotes G1-S Transition and Cell Proliferation through Upregulation of Cyclin D1 Expression.
PLoS ONE
PUBLISHED: 01-01-2014
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Protein ubiquitinylation regulates protein stability and activity. RAD6, an E2 ubiquitin-conjugating enzyme, which that has been substantially biochemically characterized, functions in a number of biologically relevant pathways, including cell cycle progression. In this study, we show that RAD6 promotes the G1-S transition and cell proliferation by regulating the expression of cyclin D1 (CCND1) in human cells. Furthermore, our data indicate that RAD6 influences the transcription of CCND1 by increasing monoubiquitinylation of histone H2B and trimethylation of H3K4 in the CCND1 promoter region. Our study presents, for the first time, an evidence for the function of RAD6 in cell cycle progression and cell proliferation in human cells, raising the possibility that RAD6 could be a new target for molecular diagnosis and prognosis in cancer therapeutics.
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Characterization of a novel cell penetrating peptide derived from human Oct4.
Cell Regen (Lond)
PUBLISHED: 01-01-2014
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Oct4 is a transcription factor that plays a major role for the preservation of the pluripotent state in embryonic stem cells as well as for efficient reprogramming of somatic cells to induced pluripotent stem cells (iPSC) or other progenitors. Protein-based reprogramming methods mainly rely on the addition of a fused cell penetrating peptide. This study describes that Oct4 inherently carries a protein transduction domain, which can translocate into human and mouse cells.
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Protein Network Signatures Associated with Exogenous Biofuels Treatments in Cyanobacterium Synechocystis sp. PCC 6803.
Front Bioeng Biotechnol
PUBLISHED: 01-01-2014
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Although recognized as a promising microbial cell factory for producing biofuels, current productivity in cyanobacterial systems is low. To make the processes economically feasible, one of the hurdles, which need to be overcome is the low tolerance of hosts to toxic biofuels. Meanwhile, little information is available regarding the cellular responses to biofuels stress in cyanobacteria, which makes it challenging for tolerance engineering. Using large proteomic datasets of Synechocystis under various biofuels stress and environmental perturbation, a protein co-expression network was first constructed and then combined with the experimentally determined protein-protein interaction network. Proteins with statistically higher topological overlap in the integrated network were identified as common responsive proteins to both biofuels stress and environmental perturbations. In addition, a weighted gene co-expression network analysis was performed to distinguish unique responses to biofuels from those to environmental perturbations and to uncover metabolic modules and proteins uniquely associated with biofuels stress. The results showed that biofuel-specific proteins and modules were enriched in several functional categories, including photosynthesis, carbon fixation, and amino acid metabolism, which may represent potential key signatures for biofuels stress responses in Synechocystis. Network-based analysis allowed determination of the responses specifically related to biofuels stress, and the results constituted an important knowledge foundation for tolerance engineering against biofuels in Synechocystis.
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Liraglutide ameliorates renal injury in streptozotocin?induced diabetic rats by activating endothelial nitric oxide synthase activity via the downregulation of the nuclear factor??B pathway.
Mol Med Rep
PUBLISHED: 01-01-2014
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Accumulating evidence has implicated that liraglutide, one of the human glucagon?like peptide?1 (GLP?1) analogues, elicits protective effects on diabetic nephropathy; however, the mechanism has yet to be fully elucidated. The present study aimed to assess the effect and underlying mechanisms of liraglutide in diabetic nephropathy. Wistar rats with streptozotocin?induced diabetes mellitus were subcutaneously injected with liraglutide or phosphate buffer for 12 weeks at a dose of 0.3 mg/kg/12 h. The biochemical parameters were determined, renal histological examination was performed by hematoxylin and eosin and periodic acid Schiff base staining, and the mRNA levels of nuclear factor ?B (NF??B) and endothelial nitric oxide synthase (eNOS) were assessed by quantitative polymerase chain reaction. Furthermore, the protein expression of NF??B and eNOS as well as eNOS phosphorylation were examined by western blot analysis and the levels of inflammatory cytokines downstream of NF??B were evaluated by fluorescence-assisted cell sorting and finally, the eNOS activity and nitric oxide (NO) production were evaluated by ELISA. Liraglutide decreased the levels of total cholesterol, urine, 24-h urinary albumin, blood urea nitrogen, serum creatinine and histological damage. Liraglutide also reduced the expression of NF??B at mRNA and protein levels; the expression of tumor necrosis factor??, interferon??, interleukin?6 and monocyte chemoattractant protein?1 were also reduced. By contrast, eNOS phosphorylation, eNOS activity and NO production appeared to have increased. Liraglutide may have a direct beneficial effect on diabetic nephropathy by improving eNOS activity by inhibiting the NF??B pathway without eliciting a glucose lowering effect.
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Effects of dopamine on response properties of ON-OFF RGCs in encoding stimulus durations.
Front Neural Circuits
PUBLISHED: 01-01-2014
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Single retinal ganglion cell's (RGCs) response properties, such as spike count and response latency, are known to encode some features of visual stimuli. On the other hand, neuronal response can be modulated by dopamine (DA), an important endogenous neuromodulator in the retina. In the present study, we investigated the effects of DA on the spike count and the response latency of bullfrog ON-OFF RGCs during exposure to different stimulus durations. We found that neuronal spike count and response latency were both changed with stimulus durations, and exogenous DA (10 ?M) obviously attenuated the stimulus-duration-dependent response latency change. Information analysis showed that the information about light ON duration was mainly carried by the OFF response and vice versa, and the stimulation information was carried by both spike count and response latency. However, during DA application, the information carried by the response latency was greatly decreased, which suggests that dopaminergic pathway is involved in modulating the role of response latency in encoding the information about stimulus durations.
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Multichromophoric sugar for fluorescence photoswitching.
Beilstein J Org Chem
PUBLISHED: 01-01-2014
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A multichromophoric glucopyranoside 2 bearing three dicyanomethylenepyran (DCM) fluorophores and one diarylethene (DAE) photochrome has been prepared by Cu(I)-catalyzed alkyne-azide cycloaddition reaction. The fluorescence of 2 was switched off upon UV irradiation, in proportion with the open to closed form (OF to CF) conversion extent of the DAE moiety. A nearly 100% Förster-type resonance energy transfer (FRET) from all three DCM moieties to a single DAE (in its CF) moiety was achieved. Upon visible irradiation, the initial fluorescence intensity was recovered. The observed photoswiching is reversible, with excellent photo resistance.
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Caffeine-induced Ca2+ oscillations in type I horizontal cells of the carp retina and the contribution of the store-operated Ca2+ entry pathway.
PLoS ONE
PUBLISHED: 01-01-2014
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The mechanisms of release, depletion, and refilling of endoplasmic reticulum (ER) Ca2+ were investigated in type I horizontal cells of the carp retina using a fluo-3-based Ca2+ imaging technique. Exogenous application of caffeine, a ryanodine receptor agonist, induced oscillatory intracellular free Ca2+ concentration ([Ca2+]i) responses in a duration- and concentration-dependent manner. In Ca2+-free Ringer's solution, [Ca2+]i transients could also be induced by a brief caffeine application, whereas subsequent caffeine application induced no [Ca2+]i increase, which implied that extracellular Ca2+ was required for ER refilling, confirming the necessity of a Ca2+ influx pathway for ER refilling. Depletion of ER Ca2+ by thapsigargin triggered a Ca2+ influx which could be blocked by the store-operated channel inhibitor 2-APB, which proved the existence of the store-operated Ca2+ entry pathway. Taken together, these results suggested that after being depleted by caffeine, the ER was replenished by Ca2+ influx via store-operated channels. These results reveal the fine modulation of ER Ca2+ signaling, and the activation of the store-operated Ca2+ entry pathway guarantees the replenishment of the ER so that the cell can be ready for response to the subsequent stimulus.
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Efficacy and safety of vildagliptin, Saxagliptin or Sitagliptin as add-on therapy in Chinese patients with type 2 diabetes inadequately controlled with dual combination of traditional oral hypoglycemic agents.
Diabetol Metab Syndr
PUBLISHED: 01-01-2014
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The oral DPP-4 inhibitors are new incretin-based therapies for treatment of type 2 diabetes. To assess the efficacy and safety of three DPP-4 inhibitors (Saxagliptin, Sitagliptin and Vildagliptin) as add-on therapy to dual combination of traditional oral hypoglycemic agents in Chinese type 2 diabetes patients.
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Ultrastructural features of endometrial-myometrial interface and its alteration in adenomyosis.
Int J Clin Exp Pathol
PUBLISHED: 01-01-2014
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The endometrial-myometrial interface (EMI) is a specific functional region of uterus. However, our knowledge on EMI ultrastructure both in normal uterus and adenomyosis is far from enough to understand its pathology. In this study, used the samples of EMI and outer myometrium (OM) from the adenomyosis hysterectomy specimens and the subjects from the control uteri, we prospectively compared the ultrastructure of myocytes from EMI and OM, the ultrastructural changes of EMI between the proliferative and secretory phases, and the ultrastructural difference of EMI between adenomyosis and the control group. In both adenomyosis and control group, there were differences in ultrastructure between myocytes from EMI and OM. Specifically, the myocytes from EMI were rich in organelles. In contrast, the myocytes from OM had abundant contractile structural components. In the proliferative phase, the myocytes from EMI in adenomyosis had significantly smaller cell and nucleus diameter than those from the control group, but in the secretory phase, the difference was not significant. In the control group, the various ultrastructural features of myocytes from EMI including the mean diameter of cell and nuclei and the myofilaments/cytoplasm ratio exhibited cyclical changes, but in adenomyosis, the normal cyclical changes were absent. In conclusions, there are significant ultrastructural differences between the myocytes from EMI and OM. The myocytes in women with adenomyosis were significantly different to the control subjects, primarily because the normal cyclical changes were absent.
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Effective connectivity of hippocampal neural network and its alteration in Mg2+-free epilepsy model.
PLoS ONE
PUBLISHED: 01-01-2014
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Understanding the connectivity of the brain neural network and its evolution in epileptiform discharges is meaningful in the epilepsy researches and treatments. In the present study, epileptiform discharges were induced in rat hippocampal slices perfused with Mg2+-free artificial cerebrospinal fluid. The effective connectivity of the hippocampal neural network was studied by comparing the normal and epileptiform discharges recorded by a microelectrode array. The neural network connectivity was constructed by using partial directed coherence and analyzed by graph theory. The transition of the hippocampal network topology from control to epileptiform discharges was demonstrated. Firstly, differences existed in both the averaged in- and out-degree between nodes in the pyramidal cell layer and the granule cell layer, which indicated an information flow from the pyramidal cell layer to the granule cell layer during epileptiform discharges, whereas no consistent information flow was observed in control. Secondly, the neural network showed different small-worldness in the early, middle and late stages of the epileptiform discharges, whereas the control network did not show the small-world property. Thirdly, the network connectivity began to change earlier than the appearance of epileptiform discharges and lasted several seconds after the epileptiform discharges disappeared. These results revealed the important network bases underlying the transition from normal to epileptiform discharges in hippocampal slices. Additionally, this work indicated that the network analysis might provide a useful tool to evaluate the neural network and help to improve the prediction of seizures.
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Alterations of mass density and 3D osteocyte lacunar properties in bisphosphonate-related osteonecrotic human jaw bone, a synchrotron µCT study.
PLoS ONE
PUBLISHED: 01-01-2014
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Osteonecrosis of the jaw, in association with bisphosphonates (BRONJ) used for treating osteoporosis or cancer, is a severe and most often irreversible side effect whose underlying pathophysiological mechanisms remain largely unknown. Osteocytes are involved in bone remodeling and mineralization where they orchestrate the delicate equilibrium between osteoclast and osteoblast activity and through the active process called osteocytic osteolysis. Here, we hypothesized that (i) changes of the mineralized tissue matrix play a substantial role in the pathogenesis of BRONJ, and (ii) the osteocyte lacunar morphology is altered in BRONJ. Synchrotron µCT with phase contrast is an appropriate tool for assessing both the 3D morphology of the osteocyte lacunae and the bone matrix mass density. Here, we used this technique to investigate the mass density distribution and 3D osteocyte lacunar properties at the sub-micrometer scale in human bone samples from the jaw, femur and tibia. First, we compared healthy human jaw bone to human tibia and femur in order to assess the specific differences and address potential explanations of why the jaw bone is exclusively targeted by the necrosis as a side effect of BP treatment. Second, we investigated the differences between BRONJ and control jaw bone samples to detect potential differences which could aid an improved understanding of the course of BRONJ. We found that the apparent mass density of jaw bone was significantly smaller compared to that of tibia, consistent with a higher bone turnover in the jaw bone. The variance of the lacunar volume distribution was significantly different depending on the anatomical site. The comparison between BRONJ and control jaw specimens revealed no significant increase in mineralization after BP. We found a significant decrease in osteocyte-lacunar density in the BRONJ group compared to the control jaw. Interestingly, the osteocyte-lacunar volume distribution was not altered after BP treatment.
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Zfyve9a regulates the proliferation of hepatic cells during zebrafish embryogenesis.
Int. J. Dev. Biol.
PUBLISHED: 12-06-2013
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Zfyve9 is a FYVE domain protein first identified as a binding partner for SMAD2/3. In vitro studies indicate that it can function either positively or negatively in the TGF-beta signaling pathway depending on the cell lines used. However, the in vivo function of this protein remains to be investigated. We first analyzed the tissue distribution of zebrafish zfyve9a by in situ hybridization. To investigate the in vivo function of this gene, we performed morpholino mediated loss-of-function assays. We analyzed the expression patterns of liver (cp and fabp10a), pancreas (trypsin and insulin) or gut (fabp2) specific markers to determine whether the formation of these organs is affected by zfyve9a knockdown. We determined the specification of hepatoblast in the zfyve9a morphants (prox1a) and investigated the proliferation and survival of hepatic cells in the morphants by P-H3 staining and TUNEL assay respectively. We report here that zfyve9a is enriched in the zebrafish embryonic liver and required for hepatogenesis. Morpholino mediated knockdown of zfyve9a inhibits the formation of liver by day 4 while the other endoderm-derived organs appear unaffected. We demonstrated that the specification of hepatoblasts is normal in the zfyve9a morphants; however, the proliferation rate of these cells is reduced. Thus, our results reveal the liver-specific function of zfyve9a during early embryogenesis and indicate that the zfyve9a mediated signal is essential for the proliferation of hepatic cells during the expansion of liver bud.
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Transcription Activator-like Effector Nuclease (TALEN)-mediated Gene Correction in Integration-free ?-Thalassemia Induced Pluripotent Stem Cells.
J. Biol. Chem.
PUBLISHED: 10-23-2013
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?-Thalassemia (?-Thal) is a group of life-threatening blood disorders caused by either point mutations or deletions of nucleotides in ?-globin gene (HBB). It is estimated that 4.5% of the population in the world carry ?-Thal mutants (1), posing a persistent threat to public health. The generation of patient-specific induced pluripotent stem cells (iPSCs) and subsequent correction of the disease-causing mutations offer an ideal therapeutic solution to this problem. However, homologous recombination-based gene correction in human iPSCs remains largely inefficient. Here, we describe a robust process combining efficient generation of integration-free ?-Thal iPSCs from the cells of patients and transcription activator-like effector nuclease (TALEN)-based universal correction of HBB mutations in situ. We generated integration-free and gene-corrected iPSC lines from two patients carrying different types of homozygous mutations and showed that these iPSCs are pluripotent and have normal karyotype. We showed that the correction process did not generate TALEN-induced off targeting mutations by sequencing. More importantly, the gene-corrected ?-Thal iPS cell lines from each patient can be induced to differentiate into hematopoietic progenitor cells and then further to erythroblasts expressing normal ?-globin. Our studies provide an efficient and universal strategy to correct different types of ?-globin mutations in ?-Thal iPSCs for disease modeling and applications.
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Magnetic resonance image restoration via dictionary learning under spatially adaptive constraints.
Conf Proc IEEE Eng Med Biol Soc
PUBLISHED: 10-11-2013
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This paper proposes a spatially adaptive constrained dictionary learning (SAC-DL) algorithm for Rician noise removal in magnitude magnetic resonance (MR) images. This algorithm explores both the strength of dictionary learning to preserve image structures and the robustness of local variance estimation to remove signal-dependent Rician noise. The magnitude image is first separated into a number of partly overlapping image patches. The statistics of each patch are collected and analyzed to obtain a local noise variance. To better adapt to Rician noise, a correction factor is formulated with the local signal-to-noise ratio (SNR). Finally, the trained dictionary is used to denoise each image patch under spatially adaptive constraints. The proposed algorithm has been compared to the popular nonlocal means (NLM) filtering and unbiased NLM (UNLM) algorithm on simulated T1-weighted, T2-weighted and PD-weighted MR images. Our results suggest that the SAC-DL algorithm preserves more image structures while effectively removing the noise than NLM and it is also superior to UNLM at low noise levels.
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A new quantitative approach for estimating bone cell connections from nano-CT images.
Conf Proc IEEE Eng Med Biol Soc
PUBLISHED: 10-11-2013
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Recent works highlighted the crucial role of the osteocyte system in bone fragility. The number of canaliculi of osteocyte lacuna (Lc.NCa) is an important parameter that reflects the functionality of bone tissue, but rarely reported due to the limitations of current microscopy techniques, and only assessed from 2D histology sections. Previously, we showed the Synchrotron Radiation nanotomography (SR-nanoCT) is a promising technique to image the 3D lacunar-canalicular network. Here we present, for the first time, an automatic method to quantify the connectivity of bone cells in 3D. After segmentation, our method first separates and labels each lacuna in the network. Then, by creating a bounding surface around lacuna, the Lc.NCa is calculated through estimating 3D topological parameters. The proposed method was successfully applied to a 3D SR-nanoCT image of cortical femoral bone. Statistical results on 165 lacunae are reported, showing a mean of 51, which is consistent with the literature.
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Fenchel duality based dictionary learning for restoration of noisy images.
IEEE Trans Image Process
PUBLISHED: 10-11-2013
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Dictionary learning based sparse modeling has been increasingly recognized as providing high performance in the restoration of noisy images. Although a number of dictionary learning algorithms have been developed, most of them attack this learning problem in its primal form, with little effort being devoted to exploring the advantage of solving this problem in a dual space. In this paper, a novel Fenchel duality based dictionary learning (FD-DL) algorithm has been proposed for the restoration of noise-corrupted images. With the restricted attention to the additive white Gaussian noise, the sparse image representation is formulated as an 2-1 minimization problem, whose dual formulation is constructed using a generalization of Fenchel’s duality theorem and solved under the augmented Lagrangian framework. The proposed algorithm has been compared with four state-of-the-art algorithms, including the local pixel grouping-principal component analysis, method of optimal directions, K-singular value decomposition, and beta process factor analysis, on grayscale natural images. Our results demonstrate that the FD-DL algorithm can effectively improve the image quality and its noisy image restoration ability is comparable or even superior to the abilities of the other four widely-used algorithms.
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Reduced beta2-glycoprotein I protects macrophages from ox-LDL-induced foam cell formation and cell apoptosis.
Lipids Health Dis
PUBLISHED: 08-10-2013
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Reduced beta2-glycoprotein I (beta2-GPI) is a free thiol-containing form of beta2-GPI that displays a powerful effect in protecting endothelial cells from oxidative stress-induced cell death. The present study aims to investigate the effect of beta2-GPI or reduced beta2-GPI on ox-LDL-induced foam cell formation and on cell apoptosis and to determine the possible mechanisms.
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Draft Genome Sequence of Lactococcus lactis subsp. lactis Strain YF11.
Genome Announc
PUBLISHED: 08-10-2013
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Lactococcus lactis subsp. lactis strain YF11 is a food preservative bacterium with a high capacity to produce nisin. Here, we announce the draft genome sequence of Lactococcus lactis subsp. lactis YF11 (2,527,433 bp with a G+C content of 34.81%).
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Radical cystectomy for treating bladder cancer: oncological outcome in 271 Chinese patients.
Chin J Cancer
PUBLISHED: 08-06-2013
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Few large scale studies have reported the oncological outcome of radical cystectomy for treating bladder cancer in China; hence, we lack long-term prognostic information. The aim of the current study was to determine the survival rate and prognostic factors of patients who received radical cystectomy for bladder cancer in a Chinese medical center. We retrospectively analyzed clinicopathologic data from 271 bladder cancer patients who underwent radical cystectomy between 2000 and 2011. Univariate and multivariate analyses were conducted to identify independent prognostic predictors for this cohort. Median follow-up was 31.7 months (range, 0.2--139.1 months). Thirty-day mortality was (1.4%). The 5-year recurrence-free survival, cancer-specific survival (CSS), and overall survival were 61.6%, 72.9%, and 68.0%, respectively. The 5-year CSS of patients with T1--T4 disease was 90.7%, 85.0%, 51.0%, and 18.0%, respectively. Patients with organ-confined disease had a higher 5-year CSS than those with extravesical disease (81.4% vs. 34.9%, P < 0.001). For the 38 patients (14%) with lymph node involvement, the 5-year CSS was 27.7%--significantly lower than that of patients without lymph node metastasis (P< 0.001). The 5-year CSS was much higher in patients with low grade tumor than in those with high grade tumor (98.1% vs. 68.1%, P < 0.001). Multivariate Cox regression showed that patient age (hazard ratio, 2.045; P = 0.013) and T category (hazard ratio, 2.213; P < 0.001) were independent predictors for CSS. These results suggest that radical cystectomy is a safe and effective method for treating bladder cancer in Chinese patients. High age and T category were associated with poor prognosis in bladder cancer patients who received radical cystectomy.
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Ribosomal RNA gene transcription mediated by the master genome regulator protein CCCTC-binding factor (CTCF) is negatively regulated by the condensin complex.
J. Biol. Chem.
PUBLISHED: 07-24-2013
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CCCTC-binding factor (CTCF) is a ubiquitously expressed "master weaver" and plays multiple functions in the genome, including transcriptional activation/repression, chromatin insulation, imprinting, X chromosome inactivation, and high-order chromatin organization. It has been shown that CTCF facilitates the recruitment of the upstream binding factor onto ribosomal DNA (rDNA) and regulates the local epigenetic state of rDNA repeats. However, the mechanism by which CTCF modulates rRNA gene transcription has not been well understood. Here we found that wild-type CTCF augments the pre-rRNA level, cell size, and cell growth in cervical cancer cells. In contrast, RNA interference-mediated knockdown of CTCF reduced pre-rRNA transcription. CTCF positively regulates rRNA gene transcription in a RNA polymerase I-dependent manner. We identified an RRGR motif as a putative nucleolar localization sequence in the C-terminal region of CTCF that is required for activating rRNA gene transcription. Using mass spectrometry, we identified SMC2 and SMC4, two subunits of condensin complexes that interact with CTCF. Condensin negatively regulates CTCF-mediated rRNA gene transcription. Knockdown of SMC2 expression significantly facilitates the loading of CTCF and the upstream binding factor onto the rDNA locus and increases histone acetylation across the rDNA locus. Taken together, our study suggests that condensin competes with CTCF in binding to a specific rDNA locus and negatively regulates CTCF-mediated rRNA gene transcription.
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[Efficacy analysis of three therapeutic modes on clinical stage Ia nonseminomatous germ cell testicular tumors].
Zhonghua Wai Ke Za Zhi
PUBLISHED: 07-18-2013
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To investigate the oncologic outcomes of surveillance, retroperitoneal lymph node dissection (RPLND) and primary chemotherapy in patients with clinical stage Ia nonseminomatous germ cell testicular tumors (CS Ia NSGCT) and to analyze risk factors for relapse.
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Shifted encoding strategy in retinal luminance adaptation: from firing rate to neural correlation.
J. Neurophysiol.
PUBLISHED: 07-17-2013
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Neuronal responses to prolonged stimulation attenuate over time. Here, we ask a fundamental question: is adaptation a simple process for the neural system during which sustained input is ignored, or is it actually part of a strategy for the neural system to adjust its encoding properties dynamically? After simultaneously recording the activities of a group of bullfrogs retinal ganglion cells (dimming detectors) in response to sustained dimming stimulation, we applied a combination of information analysis approaches to explore the time-dependent nature of information encoding during the adaptation. We found that at the early stage of the adaptation, the stimulus information was mainly encoded in firing rates, whereas at the late stage of the adaptation, it was more encoded in neural correlations. Such a transition in encoding properties is not a simple consequence of the attenuation of neuronal firing rates, but rather involves an active change in the neural correlation strengths, suggesting that it is a strategy adopted by the neural system for functional purposes. Our results reveal that in encoding a prolonged stimulation, the neural system may utilize concerted, but less active, firings of neurons to encode information.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.