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Find video protocols related to scientific articles indexed in Pubmed.
Low Concentration of Rapamycin Inhibits Hemangioma Endothelial Cell Proliferation, Migration, and Vascular Tumor Formation in Mice.
Curr Ther Res Clin Exp
PUBLISHED: 12-01-2014
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Vascular endothelial cell excessive proliferation is the main biological behavior of hemangioma. Rapamycin regulates the growth of endothelial cells by inhibiting mammalian target of rapamycin (mTOR). Thus hemangioma accompanied by excessive mTOR activation should be sensitive to rapamycin. We aimed to illustrate the effect of low-concentration rapamycin on hemangioma and provide a safe and effective drug therapy.
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Structural insights into the function of a unique tandem GTPase EngA in bacterial ribosome assembly.
Nucleic Acids Res.
PUBLISHED: 11-13-2014
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Many ribosome-interacting GTPases, with proposed functions in ribosome biogenesis, are also implicated in the cellular regulatory coupling between ribosome assembly process and various growth control pathways. EngA is an essential GTPase in bacteria, and intriguingly, it contains two consecutive GTPase domains (GD), being one-of-a-kind among all known GTPases. EngA is required for the 50S subunit maturation. However, its molecular role remains elusive. Here, we present the structure of EngA bound to the 50S subunit. Our data show that EngA binds to the peptidyl transferase center (PTC) and induces dramatic conformational changes on the 50S subunit, which virtually returns the 50S subunit to a state similar to that of the late-stage 50S assembly intermediates. Very interestingly, our data show that the two GDs exhibit a pseudo-two-fold symmetry in the 50S-bound conformation. Our results indicate that EngA recognizes certain forms of the 50S assembly intermediates, and likely facilitates the conformational maturation of the PTC of the 23S rRNA in a direct manner. Furthermore, in a broad context, our data also suggest that EngA might be a sensor of the cellular GTP/GDP ratio, endowed with multiple conformational states, in response to fluctuations in cellular nucleotide pool, to facilitate and regulate ribosome assembly.
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The Relationship between Circulating Irisin Levels and Endothelial Function in Lean and Obese Subjects.
Clin. Endocrinol. (Oxf)
PUBLISHED: 11-11-2014
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Irisin has been shown to turn white adipocytes into brown-like adipocytes, which is emerging as an appealing therapeutic target for obesity. The objective of the study was to determine whether circulating irisin levels are related to endothelial dysfunction in obese subjects.
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Two-stage Nicking Enzyme Signal Amplification Combined with DNAzyme Amplification for the Detection of Bone Morphogenetic Protein 6 mRNA.
Anal Sci
PUBLISHED: 11-11-2014
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Highly sensitive detection of bone morphogenetic protein 6 (BMP6) mRNA is essential to monitor bone regeneration in the regenerating defects. In this work, we proposed a quantitative approach based on two-stage nicking enzyme signal amplification (NESA) and DNAzyme amplification for highly sensitive detection of BMP6 mRNA. The two-stage NESA involves two templates and two-stage amplification reactions under isothermal conditions. The first template contains two repeat sequences that could hybridize to the target RNA, triggering an exponential amplification. The amplified product was a short single-stranded DNA with the same sequence as the target RNA. The single-stranded DNA can trigger another linear NESA and produces a large amount of horseradish peroxidase (HRP)-mimicking G-quadruplex DNAzyme. This proposed assay showed a quantitative analysis of BMP6 mRNA in a wide range from 1 fM to 100 nM with a detection limit of 0.01 fM.
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Selective oxygenation of alkynes: a direct approach to diketones and vinyl acetate.
Org. Biomol. Chem.
PUBLISHED: 10-30-2014
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Arylalkynes can be converted into ?-diketones with the use of a copper catalyst, and also be transformed into vinyl acetates under metal-free conditions, both in the presence of PhI(OAc)2 as an oxidant at room temperature. A series of substituted ?-diketones were prepared in moderate to good yields. A variety of vinyl halides could be regio- and stereo-selectively synthesized under mild conditions, and I, Br and Cl could be all easily embedded into the alkynes.
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[Exploration of lymph node metastasis and appropriate lymph node dissection modes in patients with clinical stage I non-small cell lung cancer].
Zhonghua Zhong Liu Za Zhi
PUBLISHED: 10-21-2014
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To explore the pattern of lymph node metastasis and evaluate the modes and extent of mediastinal lymph node dissection in patients with ? 3 cm, clinical stage I primary non-small cell lung cancer (NSCLC).
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Hypervalent Iodine-Mediated Oxygenation of N,N-Diaryl Tertiary Amines: Intramolecular Functionalization of sp(3) C-H Bonds Adjacent to Nitrogen.
J. Org. Chem.
PUBLISHED: 10-04-2014
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An intramolecular C(sp(3))-O bond formation has been achieved via PhI(OAc)2/NaN3-mediated oxygenation of N,N-diaryl tertiary amines. The appealing features of this method include mild reaction conditions, absence of heavy-metal catalysts, and the direct intramolecular functionalization of sp(3) C-H bonds adjacent to nitrogen.
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miR-200c overexpression is associated with better efficacy of EGFR-TKIs in non-small cell lung cancer patients with EGFR wild-type.
Oncotarget
PUBLISHED: 10-04-2014
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Several randomized trials have demonstrated non-small cell lung cancer (NSCLC) patients with activating epidermal growth factor receptor (EGFR) mutations can achieve favorable clinical outcomes on treatment with EGFR tyrosine kinase inhibitors (TKIs). EGFR mutation is considered as a predictive marker for efficacy of EGFR-TKIs in NSCLC. Here we show miR-200c overexpression was correlated with the epithelial phenotype and sensitivity to gefitinib in EGFR wild-type NSCLC cell lines. Up-regulated miR-200c could regain the sensitivity to gefitinib in the EGFR wild-type cell lines and miR-200c could regulate epithelial to mesenchymal transition through PI3K/AKT and MEK/ERK pathways. NSCLC patients at advanced stage (N=150) who received EGFR-TKIs (gefitinib or erlotinib) as second- or third-line therapy from September 2008 to December 2012 were included in the study. In 66 NSCLC patients with wild-type EGFR, high levels of miR-200c expression was associated with higher disease control rate (DCR), longer progression-free survival (PFS) and longer overall survival (OS) compared with low miR-200c expression subgroup. In the subgroup with EGFR mutation, the trend remained the same but not statistically significant. Overall, these findings indicated that miR-200c might be a predictive biomarker for sensitivity to EGFR-TKIs in advanced NSCLC patients with wild-type EGFR.
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[Study on safety and feasibility of minimally invasive esophagectomy without the use of postoperative nasogastric tube decompression].
Zhonghua Wei Chang Wai Ke Za Zhi
PUBLISHED: 10-03-2014
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To investigate the safety and feasibility of forgoing postoperative nasogastric tube decompression in minimally invasive esophagectomy for patients with esophagus carcinoma.
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Identification of a Novel NHS Mutation in a Chinese Family with Nance-Horan Syndrome.
Curr. Eye Res.
PUBLISHED: 10-01-2014
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Abstract Purpose: To identiy the disease causing mutation in a Chinese family presenting with early-onset cataract and dental anomalies. Materials and Methods: A specific Hereditary Eye Disease Enrichment Panel (HEDEP) (personalized customization by MyGenostics, Baltimore, MD) based on targeted exome capture technology was used to collect the protein coding regions of 30 early-onset cataract associated genes, and high throughput sequencing was done with Illumina HiSeq 2000 platform. The identified variant was confirmed with Sanger sequencing. Results: A novel deletion in exon 4 (c.852delG) of NHS gene was identified; the identified 1?bp deletion altered the reading frame and was predicted to result in a premature stop codon after the addition of twelve novel amino acid (p.S285PfsX13). This mutation co-segregated in affected males and obligate female carriers, but was absent in 100 matched controls. Conclusions: Our findings broaden the spectrum of NHS mutations causing Nance-Horan syndrome and phenotypic spectrum of the disease in Chinese patients.
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Anti-rheumatic agent auranofin induced apoptosis in chronic myeloid leukemia cells resistant to imatinib through both Bcr/Abl-dependent and -independent mechanisms.
Oncotarget
PUBLISHED: 09-07-2014
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Resistance to Imatinib mesylate (IM) is an emerging problem for patients with chronic myelogenous leukemia (CML). T315I mutation in the Bcr-Abl is the predominant mechanism of the acquired resistance to IM and second generation tyrosine kinase inhibitors (TKI). Therefore it is urgent to search for new measures to overcome TKI-resistance. Auranofin (AF), clinically used to treat rheumatic arthritis, was recently approved by US Food and Drug Administration for Phase II clinical trial to treat cancer. In contrast to the reports that AF induces apoptosis by increasing intracellular reactive oxygen species (ROS) levels via inhibiting thioredoxin reductase, our recent study revealed that AF-induced apoptosis depends on inhibition of proteasomal deubiquitinases (UCHL5 and USP14). Here we report that (i) AF induces apoptosis in both Bcr-Abl wild-type cells and Bcr-Abl-T315I mutation cells and inhibits the growth of IM-resistant Bcr-Abl-T315I xenografts in vivo; (ii) AF inhibits Bcr-Abl through both downregulation of Bcr-Abl gene expression and Bcr-Abl cleavage mediated by proteasome inhibition-induced caspase activation; (iii) proteasome inhibition but not ROS is required for AF-induced caspase activation and apoptosis. These findings support that AF overcomes IM resistance through both Bcr/Abl-dependent and -independent mechanisms, providing great clinical significance for cancer treatment.
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Manifestation of PT symmetry breaking in polarization space with terahertz metasurfaces.
Phys. Rev. Lett.
PUBLISHED: 08-28-2014
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By utilizing the vector nature of light as well as the inherent anisotropy of artificial meta-atoms, we investigate parity time symmetry breaking in polarization space using a metasurface with anisotropic absorption, whose building blocks consist of two orthogonally orientated meta-atoms with the same resonant frequency but different loss coefficients. By varying their coupling strength, we directly observe a phase transition in the eigenpolarization states of the system, across which the long axis of the eigenpolarization ellipses experience a sudden rotation of 45°. Despite the lack of rotational symmetry of the metasurface, precisely at the phase transition, known as the exceptional point, the eigenmodes coalesce into a single circularly polarized state. The PT symmetric metasurfaces are experimentally implemented at terahertz frequencies.
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Protective effects of adiponectin on uncoupling of glomerular VEGF-NO axis in early streptozotocin-induced type 2 diabetic rats.
Int Urol Nephrol
PUBLISHED: 08-15-2014
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To determine whether adiponectin could reduce microalbuminuria and provide renal protective effects by improving endothelial dysfunction and uncoupling of the glomerular vascular endothelial growth factor (VEGF)-nitric oxide (NO) axis in streptozotocin-induced type 2 diabetic rats.
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Integrated analysis of transcriptomes of cancer cell lines and patient samples reveals STK11/LKB1-driven regulation of cAMP phosphodiesterase-4D.
Mol. Cancer Ther.
PUBLISHED: 08-13-2014
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The recent proliferation of data on large collections of well-characterized cancer cell lines linked to therapeutic drug responses has made it possible to identify lineage- and mutation-specific transcriptional markers that can help optimize implementation of anticancer agents. Here, we leverage these resources to systematically investigate the presence of mutation-specific transcription markers in a wide variety of cancer lineages and genotypes. Sensitivity and specificity of potential transcriptional biomarkers were simultaneously analyzed in 19 cell lineages grouped into 228 categories based on the mutational genotypes of 12 cancer-related genes. Among a total of 1,455 category-specific expression patterns, the expression of cAMP phosphodiesterase-4D (PDE4D) with 11 isoforms, one of the PDE4(A-D) subfamilies, was predicted to be regulated by a mutant form of serine/threonine kinase 11 (STK11)/liver kinase B1 (LKB1) present in lung cancer. STK11/LKB1 is the primary upstream kinase of adenine monophosphate-activated protein kinase (AMPK). Subsequently, we found that the knockdown of PDE4D gene expression inhibited proliferation of STK11-mutated lung cancer lines. Furthermore, challenge with a panel of PDE4-specific inhibitors was shown to selectively reduce the growth of STK11-mutated lung cancer lines. Thus, we show that multidimensional analysis of a well-characterized large-scale panel of cancer cell lines provides unprecedented opportunities for the identification of unexpected oncogenic mechanisms and mutation-specific drug targets.
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Lignin dissolution in dialkylimidazolium-based ionic liquid-water mixtures.
Bioresour. Technol.
PUBLISHED: 08-10-2014
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Lignin dissolution in dialkylimidazolium-based ionic liquid (IL)-water mixtures (40wt%-100wt% IL content) at 60°C was investigated. The IL content and type are found to considerably affect lignin solubility. For the IL-water mixtures except 1-butyl-3-methylimidazolium tetrafluoroborate ([C4C1im]BF4), the maximum lignin solubility can be achieved at 70wt% IL content. Lignin solubility in IL-water mixtures with different cations follows the order 1-butyl-3-methylimidazolium ([C4C1im](+))>1-hexyl-3-methylimidazolium ([C6C1im](+))>1-ethyl-3-methylimidazolium ([C2C1im](+))>1-octyl-3-methylimidazolium ([C8C1im](+))>1-butyl-3-ethylimidazolium ([C4C2im](+))>1-butyl-3-propylimidazolium ([C4C3im](+)). For IL mixtures with different anions, lignin solubility decreases in the following order: methanesulfonate (MeSO3(-))>acetate (MeCO2(-))>bromide (Br(-))>dibutylphosphate (DBP(-)). Evaluation using the theory of Hansen solubility parameter (HSP) is consistent with the experimental results, suggesting that HSP can aid in finding the appropriate range of IL content for IL-water mixtures. However, HSP cannot be used to evaluate the effect of IL type on lignin solubility.
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Helicobacter pylori promotes VEGF expression via the p38 MAPK?mediated COX?2?PGE2 pathway in MKN45 cells.
Mol Med Rep
PUBLISHED: 08-06-2014
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Helicobacter pylori has been suggested to be the major cause of gastric malignancy. However, the pathogenesis and molecular mechanisms of gastric tumorigenesis induced by H. pylori infection are yet to be elucidated. In the present study, the expression levels of vascular endothelial growth factor (VEGF), which has been suggested to promote angiogenesis in gastric cancer, were found to be elevated in H. pylori-infected MKN45 cells. Furthermore, it was demonstrated that the expression of VEGF was modulated by the p38 mitogen-activated protein kinases (MAPK) pathway via regulation of the cyclooxygenase (COX)-2 pathway. It was also found that prostaglandin E2 (PGE2) and its receptor EP2/EP4 may mediate the upregulation of VEGF in gastric cells exposed to H. pylori. In combination, these results suggest that VEGF expression is regulated by the p38 MAPK COX?2-PGE2-EP2/EP4 pathway in gastric cancer cells induced by H. pylori. This provides a theoretical basis for the investigation of the pathogenesis of H. pylori?induced gastric cancer.
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Denaturation and renaturation behaviors of short DNA in a confined space.
J Chem Phys
PUBLISHED: 08-03-2014
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A deep understanding to the denaturation and renaturation behaviors of DNA in a confined state is fundamentally important to control the self-assembly of DNA in a chamber or channel for various applications. In this report, we study the denaturation and renaturation behaviors of short DNA confined in cylindrical and spherical spaces with the 3-Site-Per-Nucleotide coarse-grained DNA model applying the replica exchange molecular dynamics technology. It is found that as the confinement size decreases, the melting temperature Tm increases and the transition becomes broad. The analysis of the potential of mean force shows that the confinement increases the relative free energy of the denatured state of DNA and decreases the renaturation energy barrier. Besides the denatured and native states, the metastable parallel-stranded structure is also found. The simulation results show that the shapes of the confinement spaces and the short DNA sequences remarkably affect the renaturation behavior. In the cylindrical space, the DNA renaturation changes from random-binding to slithering-binding with the size of the confinement space decreasing. In contrast, the DNA renaturation in the spherical and symmetrical confinement space proceeds through strand binding and rolling. The relationship between the melting temperature and the confinement size, ?Tm/Tm ? Rc (-?), is estimated and the exponential index ? equals about 1.32 and 1.75 in the cylindrical and spherical confinements, respectively. It is further compared with the theoretical result of the rigid rod model and a qualitative agreement with the simulation is achieved.
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Application of metabonomic strategy to discover an unreported active ingredient in LiuWeiDiHuang pills suppressing beta-glucuronidase.
Anal Bioanal Chem
PUBLISHED: 07-09-2014
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Identification of the bioactive ingredient from traditional Chinese medicine (TCM) remains a challenging task by traditional approach that focuses on chemical isolation coupled with biological activity screening. Here, we present a metabonomics-based approach for bioactive ingredient discovery in LiuWeiDiHuang pills (LWPs). First, a non-targeted high-performance liquid chromatography ultraviolet (HPLC-UV) profiling of rat urine was used to discriminate urinary profiling intervened by LWPs. Orthogonal partial least-squares discriminant analysis (OPLS-DA) revealed that eight chromatographic peaks made a significant contribution to the classification of the LWPs group and the control group. Five of these chromatographic peaks were successfully isolated and identified as hippurate, genistein (GT), daidzein (DZ), and glucuronide conjugate of GT and that of DZ by mass spectroscopy (MS). Subsequently, we found that LWPs significantly decreased the activity of intestinal ?-glucuronidase by 18 % and exerted a dose-dependent inhibitory effect on rat liver lysosomal fraction, suggesting that LWPs were a ?-glucuronidase inhibitor. In the end, by inhibiting ?-glucuronidase-guided isolation, D-glucaro-1,4-lactone, a previously unreported ingredient of LWPs, was identified by MS, MS/MS, and nuclear magnetic resonance spectroscopy. Our findings indicated that metabonomics might increase research productivity toward the drug targets and/or bioactive compounds from TCM.
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Amphipathic lignin derivatives to accelerate simultaneous saccharification and fermentation of unbleached softwood pulp for bioethanol production.
Bioresour. Technol.
PUBLISHED: 07-04-2014
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Amphipathic lignin derivatives (A-LDs) were already demonstrated to improve enzymatic saccharification of lignocellulose. Based on this knowledge, two kinds of A-LDs prepared from black liquor of soda pulping of Japanese cedar were applied to a fed-batch simultaneous saccharification and fermentation (SSF) process for unbleached soda pulp of Japanese cedar to produce bioethanol. Both lignin derivatives slightly accelerated yeast fermentation of glucose but not inhibited it. In addition, ethanol yields based on the theoretical maximum ethanol production in the fed-batch SSF process was increased from 49% without A-LDs to 64% in the presence of A-LDs.
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Clinically used antirheumatic agent auranofin is a proteasomal deubiquitinase inhibitor and inhibits tumor growth.
Oncotarget
PUBLISHED: 07-01-2014
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Proteasomes are attractive emerging targets for anti-cancer therapies. Auranofin (Aur), a gold-containing compound clinically used to treat rheumatic arthritis, was recently approved by US Food and Drug Administration for Phase II clinical trial to treat cancer but its anti-cancer mechanism is poorly understood. Here we report that (i) Aur shows proteasome-inhibitory effect that is comparable to that of bortezomib/Velcade (Vel); (ii) different from bortezomib, Aur inhibits proteasome-associated deubiquitinases (DUBs) UCHL5 and USP14 rather than the 20S proteasome; (iii) inhibition of the proteasome-associated DUBs is required for Aur-induced cytotoxicity; and (iv) Aur selectively inhibits tumor growth in vivo and induces cytotoxicity in cancer cells from acute myeloid leukemia patients. This study provides important novel insight into understanding the proteasome-inhibiting property of metal-containing compounds. Although several DUB inhibitors were reported, this study uncovers the first drug already used in clinic that can inhibit proteasome-associated DUBs with promising anti-tumor effects.
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The role of small RNAs on phenotypes in reciprocal hybrids between Solanum lycopersicum and S. pimpinellifolium.
BMC Plant Biol.
PUBLISHED: 06-29-2014
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BackgroundReciprocal hybrids showing different phenotypes have been well documented in previous studies, and many factors accounting for different phenotypes have been extensively investigated. However, less is known about whether the profiles of small RNAs differ between reciprocal hybrids and how these small RNAs affect gene expression and phenotypes. To better understand this mechanism, the role of small RNAs on phenotypes in reciprocal hybrids was analysed.ResultsReciprocal hybrids between Solanum lycopersicum cv. Micro-Tom and S. pimpinellifolium line WVa700 were generated. Significantly different phenotypes between the reciprocal hybrids were observed, including fruit shape index, single fruit weight and plant height. Then, through the high-throughput sequencing of small RNAs, we found that the expression levels of 76 known miRNAs were highly variable between the reciprocal hybrids. Subsequently, a total of 410 target genes were predicted to correspond with these differentially expressed miRNAs. Furthermore, gene ontology (GO) annotation indicated that those target genes are primarily involved in metabolic processes. Finally, differentially expressed miRNAs, such as miR156f and 171a, and their target genes were analysed by qRT-PCR, and their expression levels were well correlated with the different phenotypes.ConclusionsThis study showed that the profiles of small RNAs differed between the reciprocal hybrids, and differentially expressed genes were also observed based on the different phenotypes. The qRT-PCR results of target genes showed that differentially expressed miRNAs negatively regulated their target genes. Moreover, the expression of target genes was well correlated with the observations of different phenotypes. These findings may aid in elucidating small RNAs contribute significantly to different phenotypes through epigenetic modification during reciprocal crossing.
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Complete mitochondrial genome of Empoasca vitis (Hemiptera: Cicadellidae).
Mitochondrial DNA
PUBLISHED: 06-26-2014
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Abstract The complete mitochondrial genome of Empoasca vitis was sequenced. The length of the mitogenome is 15,154?bp with 78.35% AT content (GenBank accession No. KJ815009). The genome encode 37 typical mitochondrial genes including 22 transfer RNA genes, 13 protein-coding genes, 2 ribosomal RNA genes and an A+T-rich region. The gene arrangement is similar to that of Drosophila yakuba, the presumed ancestral insect mitochondrial gene arrangement. Except for cox2 using GTG as start codon, other protein-coding genes (PCGs) share the start codons ATN. Usual termination codon TAA and incomplete stop codon T are using by 13 protein-coding genes. The A+T-rich region has a length of 977?bp with the AT content high to 88.95%.
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Knockdown of filaggrin influences the epidermal terminal differentiation via MAPK pathway in normal human epidermal keratinocytes.
Mol. Biol. Rep.
PUBLISHED: 06-22-2014
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We aimed to gain further insight into the role of the MAPK signaling pathway in terminal differentiation of normal human epidermal keratinocytes (NHEKs) with filaggrin knockdown. Filaggrin expression was knocked down by shRNA technology and the MAPK pathways were inhibited by three different inhibitors in NHEKs. The associated mRNAs and proteins were investigated by RT-PCR and western blot. Filaggrin absence inhibited the expression of differentiation-associated proteins, and blocked the protein expression of p38 MAPK, ERK1/2, JNK, Akt and NF-?B. Moreover, inhibited p38 MAPK, instead of ERK1/2 or JNK, lead to decreases in the expressions of Akt, NF-?B, and differentiation- associated proteins. In conclusion, Filaggrin might affect the epidermal terminal differentiation mainly through the p38-MAPK, NF-?B and Akt pathways. ERK1/2 and JNK might also be involved in the process.
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Structural basis for interaction of a cotranslational chaperone with the eukaryotic ribosome.
Nat. Struct. Mol. Biol.
PUBLISHED: 06-17-2014
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Cotranslational chaperones, ubiquitous in all living organisms, protect nascent polypeptides from aggregation and facilitate their de novo folding. Importantly, emerging data have also suggested that ribosome-associated cotranslational chaperones have active regulatory roles in modulating protein translation. By characterizing the structure of a type of eukaryotic cotranslational chaperone, the ribosome-associated complex (RAC) from Saccharomyces cerevisiae, we show that RAC cross-links two ribosomal subunits, through a single long ?-helix, to limit the predominant intersubunit rotation required for peptide elongation. We further demonstrate that any changes in the continuity, length or rigidity of this middle ?-helix impair RAC function in vivo. Our results suggest a new mechanism in which RAC directly regulates protein translation by mechanically coupling cotranslational folding with the peptide-elongation cycle, and they lay the foundation for further exploration of regulatory roles of RAC in translation control.
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Peripheral blood for epidermal growth factor receptor mutation detection in non-small cell lung cancer patients.
Transl Oncol
PUBLISHED: 06-17-2014
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It is important to analyze and track Epidermal Growth Factor Receptor (EGFR) mutation status for predicting efficacy and monitoring resistance throughout EGFR-tyrosine kinase inhibitors (TKIs) treatment in non-small cell lung cancer (NSCLC) patients. The objective of this study was to determine the feasibility and predictive utility of EGFR mutation detection in peripheral blood.
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An iron-regulated and glycosylation-dependent proteasomal degradation pathway for the plasma membrane metal transporter ZIP14.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 06-09-2014
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Protein degradation is instrumental in regulating cellular function. Plasma membrane proteins targeted for degradation are internalized and sorted to multivesicular bodies, which fuse with lysosomes, where they are degraded. ZIP14 is a newly identified iron transporter with multitransmembrane domains. In an attempt to dissect the molecular mechanisms by which iron regulates ZIP14 levels, we found that ZIP14 is endocytosed, extracted from membranes, deglycosylated, and degraded by proteasomes. This pathway did not depend on the retrograde trafficking to the endoplasmic reticulum and thus did not involve the well-defined endoplasmic reticulum-associated protein degradation pathway. Iron inhibited membrane extraction of internalized ZIP14, resulting in higher steady-state levels of ZIP14. Asparagine-linked (N-linked) glycosylation of ZIP14, particularly the glycosylation at N102, was required for efficient membrane extraction of ZIP14 and therefore is necessary for its iron sensitivity. These findings highlight the importance of proteasomes in the degradation of endocytosed plasma membrane proteins.
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Proteomic identification and functional characterization of MYH9, Hsc70, and DNAJA1 as novel substrates of HDAC6 deacetylase activity.
Protein Cell
PUBLISHED: 06-08-2014
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Histone deacetylase 6 (HDAC6), a predominantly cytoplasmic protein deacetylase, participates in a wide range of cellular processes through its deacetylase activity. However, the diverse functions of HDAC6 cannot be fully elucidated with its known substrates. In an attempt to explore the substrate diversity of HDAC6, we performed quantitative proteomic analyses to monitor changes in the abundance of protein lysine acetylation in response to HDAC6 deficiency. We identified 107 proteins with elevated acetylation in the liver of HDAC6 knockout mice. Three cytoplasmic proteins, including myosin heavy chain 9 (MYH9), heat shock cognate protein 70 (Hsc70), and dnaJ homolog subfamily A member 1 (DNAJA1), were verified to interact with HDAC6. The acetylation levels of these proteins were negatively regulated by HDAC6 both in the mouse liver and in cultured cells. Functional studies reveal that HDAC6-mediated deacetylation modulates the actin-binding ability of MYH9 and the interaction between Hsc70 and DNAJA1. These findings consolidate the notion that HDAC6 serves as a critical regulator of protein acetylation with the capability of coordinating various cellular functions.
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A novel proteasome inhibitor suppresses tumor growth via targeting both 19S proteasome deubiquitinases and 20S proteolytic peptidases.
Sci Rep
PUBLISHED: 05-21-2014
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The successful development of bortezomib-based therapy for treatment of multiple myeloma has established proteasome inhibition as an effective therapeutic strategy, and both 20S proteasome peptidases and 19S deubiquitinases (DUBs) are becoming attractive targets of cancer therapy. It has been reported that metal complexes, such as copper complexes, inhibit tumor proteasome. However, the involved mechanism of action has not been fully characterized. Here we report that (i) copper pyrithione (CuPT), an alternative to tributyltin for antifouling paint biocides, inhibits the ubiquitin-proteasome system (UPS) via targeting both 19S proteasome-specific DUBs and 20S proteolytic peptidases with a mechanism distinct from that of the FDA-approved proteasome inhibitor bortezomib; (ii) CuPT potently inhibits proteasome-specific UCHL5 and USP14 activities; (iii) CuPT inhibits tumor growth in vivo and induces cytotoxicity in vitro and ex vivo. This study uncovers a novel class of dual inhibitors of DUBs and proteasome and suggests a potential clinical strategy for cancer therapy.
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The prognostic utility and the association of serum light chains (free and total) and absolute lymphocyte count in patients with newly diagnosed diffuse large B-cell lymphoma.
Leuk. Res.
PUBLISHED: 05-06-2014
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In this study, serum free and total light chains (sFLC/sTLC) were measured in 108 serum samples of therapy-naïve patients with DLBCL. Clinicopathologic data and survival outcomes were analyzed according to the results of sFLC/sTLC measurements. Moreover, the association of sFLC/sTLC with absolute monocyte count (AMC) and absolute lymphocyte count (ALC) was evaluated. Elevated sFLC and abnormal ?/? ratio was present in 42.6% (51/108) and 4.6% (5/108) of patients, respectively. sTLC was successfully measured in 107 serum samples, abnormal sTLC and abnormal ?/? ratio was found in 28.0% (30/107) and 26.2% (28/107) of patients, respectively. Patients with elevated sFLC more frequently displayed adverse clinical characteristics, including age (P=0.001), B symptoms (P=0.022), low ALC (P=0.024) and hyperglobulinemia (P=0.012). Patients with elevated sFLC had an inferior overall survival (OS) (P=0.012) and tended to have shorter progression-free survival (PFS) (P=0.061) compared to patients with normal sFLC. Abnormal sTLC or abnormal sTLC ratio showed no significant association with clinical outcomes, with exception of abnormal concurrent ? and ?. Only association of sFLC and ALC with survival remained significant after adjusting for the International Prognostic Index (IPI). The measurement of sFLC and ALC at diagnosis might be useful for the prognostic stratification of patients and sTLC measurement was of little prognostic utility in DLBCL.
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The role of small RNAs in wide hybridisation and allopolyploidisation between Brassica rapa and Brassica nigra.
BMC Plant Biol.
PUBLISHED: 05-05-2014
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BackgroundAn allopolyploid formation consists of the two processes of hybridisation and chromosome doubling. Hybridisation makes a different genome combined in the same cell, and genome ¿shock¿ and instability occur during this process, whereas chromosome doubling results in doubling and reconstructing the genome dosage. Recent studies have demonstrated that small RNAs, play an important role in maintaining the genome reconstruction and stability. However, to date, little is known regarding the role of small RNAs during the process of wide hybridisation and chromosome doubling, which is essential to elucidate the mechanism of polyploidisation. Therefore, the genetic and DNA methylation alterations and changes in the siRNA and miRNA were assessed during the formation of an allodiploid and its allotetraploid between Brassica rapa and Brassica nigra in the present study.ResultsThe phenotypic analysis exhibited that the allotetraploid had high heterosis compared with their parents and the allodiploid. The methylation-sensitive amplification polymorphism (MSAP) analysis indicated that the proportion of changes in the methylation pattern of the allodiploid was significantly higher than that found in the allotetraploid, while the DNA methylation ratio was higher in the parents than the allodiploid and allotetraploid. The small RNAs results showed that the expression levels of miRNAs increased in the allodiploid and allotetraploid compared with the parents, and the expression levels of siRNAs increased and decreased compared with the parents B. rapa and B. nigra, respectively. Moreover, the percentages of miRNAs increased with an increase in the polyploidy levels, but the percentages of siRNAs and DNA methylation alterations decreased with an increase in the polyploidy levels. Furthermore, qRT-PCR analysis showed that the expression levels of the target genes were negatively corrected with the expressed miRNAs.ConclusionsThe study showed that siRNAs and DNA methylation play an important role in maintaining the genome stability in the formation of an allotetraploid. The miRNAs regulate gene expression and induce the phenotype variation, which may play an important role in the occurrence of heterosis in the allotetraploid. The findings of this study may provide new information for elucidating that the allotetraploids have a growth advantage over the parents and the allodiploids.
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Structural and functional insights into the mode of action of a universally conserved Obg GTPase.
PLoS Biol.
PUBLISHED: 05-01-2014
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Obg proteins are a family of P-loop GTPases, conserved from bacteria to human. The Obg protein in Escherichia coli (ObgE) has been implicated in many diverse cellular functions, with proposed molecular roles in two global processes, ribosome assembly and stringent response. Here, using pre-steady state fast kinetics we demonstrate that ObgE is an anti-association factor, which prevents ribosomal subunit association and downstream steps in translation by binding to the 50S subunit. ObgE is a ribosome dependent GTPase; however, upon binding to guanosine tetraphosphate (ppGpp), the global regulator of stringent response, ObgE exhibits an enhanced interaction with the 50S subunit, resulting in increased equilibrium dissociation of the 70S ribosome into subunits. Furthermore, our cryo-electron microscopy (cryo-EM) structure of the 50S·ObgE·GMPPNP complex indicates that the evolutionarily conserved N-terminal domain (NTD) of ObgE is a tRNA structural mimic, with specific interactions with peptidyl-transferase center, displaying a marked resemblance to Class I release factors. These structural data might define ObgE as a specialized translation factor related to stress responses, and provide a framework towards future elucidation of functional interplay between ObgE and ribosome-associated (p)ppGpp regulators. Together with published data, our results suggest that ObgE might act as a checkpoint in final stages of the 50S subunit assembly under normal growth conditions. And more importantly, ObgE, as a (p)ppGpp effector, might also have a regulatory role in the production of the 50S subunit and its participation in translation under certain stressed conditions. Thus, our findings might have uncovered an under-recognized mechanism of translation control by environmental cues.
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A crucial role for DOK1 in PDGF-BB-stimulated glioma cell invasion through p130Cas and Rap1 signalling.
J. Cell. Sci.
PUBLISHED: 04-24-2014
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DOK1 regulates platelet-derived growth factor (PDGF)-BB-stimulated glioma cell motility. Mechanisms regulating tumour cell motility are essential for invasion and metastasis. We report here that PDGF-BB-mediated glioma cell invasion and migration are dependent on the adaptor protein downstream of kinase 1 (DOK1). DOK1 is expressed in several glioma cell lines and in tumour biopsies from high-grade gliomas. DOK1 becomes tyrosine phosphorylated upon PDGF-BB stimulation of human glioma cells. Knockdown of DOK1 or expression of a DOK1 mutant (DOK1FF) containing Phe in place of Tyr at residues 362 and 398, resulted in inhibition of both the PDGF-BB-induced tyrosine phosphorylation of p130Cas (also known as BCAR1) and the activation of Rap1 (also known as TERF2IP). DOK1 colocalises with tyrosine phosphorylated p130Cas at the cell membrane of PDGF-BB-treated cells. Expression of a non-tyrosine-phosphorylatable substrate domain mutant of p130Cas (p130Cas15F) inhibited PDGF-BB-mediated Rap1 activation. Knockdown of DOK1 and Rap1 inhibited PDGF-BB-induced chemotactic cell migration, and knockdown of DOK1 and Rap1 and expression of DOK1FF inhibited PDGF-mediated three-dimensional (3D) spheroid invasion. These data show a crucial role for DOK1 in the regulation of PDGF-BB-mediated tumour cell motility through a p130Cas-Rap1 signalling pathway.
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[A cross-sectional survey of coagulation factor VIII inhibitor in children with hemophilia A].
Zhonghua Er Ke Za Zhi
PUBLISHED: 04-18-2014
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To study the current situation of coagulation factor VIII (FVIII) inhibitor development in children with hemophilia A (HA) through a cross-sectional survey, and to explore the risk factors of inhibitor development in order to provide evidence for further prevention and management strategies.
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Design, synthesis and evaluation of phenethylaminoheterocycles as K(v)1.5 inhibitors.
Bioorg. Med. Chem. Lett.
PUBLISHED: 04-17-2014
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Phenethylaminoheterocycles have been prepared and assayed for inhibition of the Kv1.5 potassium ion channel as a potential approach to the treatment of atrial fibrillation. A diverse set of heterocycles were identified as potent Kv1.5 inhibitors and were advanced to pharmacodynamic evaluation based on selectivity and pharmacokinetic profile. Heterocycle optimization and template modification lead to the identification of compound 24 which demonstrated increased atrial effective refractory period in the rabbit pharmacodynamic model with mild effects on blood pressure and heart rate.
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Application of functional microsphere in human hepatitis B virus surface antigen detection.
J Nanosci Nanotechnol
PUBLISHED: 04-17-2014
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A novel and simple emulsifier-free emulsion polymerization technique was developed for preparation of mono-dispersed amino functionalized polymer microspheres with well defined diameters (about 400 nm). Various characterization methods demonstrated that the obtained amino microspheres had a uniform size and good dispersity which were confirmed by scanning electron microscope (SEM). Zeta potential and Fourier transform infrared spectrometer (FT-IR) demonstrated that amino groups have been successfully introduced to the microsphere surface. These functionalized microspheres have been shown to be efficient and controllable carriers capable of immobilizing and enriching monoclonal antibodies. Moreover, a newest chemiluminescent enzyme-linked immunoassay (ELISA) approach has been developed for human Hepatitis B virus surface antigen (HBsAg) detection. HBsAg was sandwiched between goat anti-HBsAg polyclonal antibody and mouse anti-HBsAg antibody. Alkaline phosphatase (ALP) conjugated horse anti-mouse immunnogloblin was used to bond with monoclonal antibody. Finally, chemiluminesent (CL) signals were recorded after adding 3-(2-spiroadamantane)-4-methoxy-4-(3-phosphoryloxy) phenyl-1,2-dioxetane (AMPPD) which was used as a chemiluminescent substrate reagent of ALP. This novel chemiluminescent ELISA assay was proved to be of excellent specificity and high sensitivity when using ALP and AMPPD luminescence systems for specific HBsAg detection.
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Targeted biopharmaceuticals for cancer treatment.
Cancer Lett.
PUBLISHED: 04-05-2014
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Cancer is a complex invasive genetic disease that causes significant mortality rate worldwide. Protein-based biopharmaceuticals have significantly extended the lives of millions of cancer patients. This article reviews the biological function and application of targeted anticancer biopharmaceuticals. We first discuss the specific antigens and core pathways that are used in the development of targeted cancer therapy. The innovative monoclonal antibodies, non-antibody proteins, and small molecules targeting these antigens or pathways are then reviewed. Finally, the current challenges in anticancer biopharmaceuticals development and the potential solutions to address these challenges are discussed.
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Broadband metasurfaces with simultaneous control of phase and amplitude.
Adv. Mater. Weinheim
PUBLISHED: 04-02-2014
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By combining the freedom of both the structural design and the orientation of split ring resonator antennas, we demonstrate terahertz metasurfaces that are capable of controlling both the phase and amplitude profiles over a very broad bandwidth. As an example, we show that the phase-amplitude metasurfaces can be engineered to control the diffraction orders arbitrarily.
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Thermodynamic and conformational insights into the phase transition of a single flexible homopolymer chain using replica exchange Monte Carlo method.
J Mol Model
PUBLISHED: 03-19-2014
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The phase transition of a single flexible homopolymer chain in the limit condition of dilute solution is systematically investigated using a coarse-grained model. Replica exchange Monte Carlo method is used to enhance the performance of the conformation space exploration, and thus detailed investigation of phase behavior of the system can be provided. With the designed potentials, the coil-globule transition and the liquid-solid-like transition are identified, and the transition temperatures are measured with the conformational and thermodynamic analyses. Additionally, by extrapolating the coil-globule transition temperature, T ? , and the liquid-solid-like transition temperature T(L ? S) to the thermodynamic limit, N????, we found no "tri-critical" point in the current model.
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Thoracoscopic purse string technique for minimally invasive Ivor Lewis esophagectomy.
J Thorac Dis
PUBLISHED: 03-08-2014
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Thoracolaparoscopic esophagectomy with chest anastomosis (TLE-chest) is increasingly performed for middle and lower esophageal cancer; however, gastroesophageal anastomosis for this surgery remains both challenging and inefficient. To address this issue, we previously reported our MIE technique with Ivor-Lewis anastomosis. Here we present the video to introduce our TLE-chest operation procedures.
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The changes of serum sKlotho and NGAL levels and their correlation in type 2 diabetes mellitus patients with different stages of urinary albumin.
Diabetes Res. Clin. Pract.
PUBLISHED: 02-27-2014
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To investigate the changes of serum anti-aging protein Klotho and neutrophil gelatinase-associated lipocalin (NGAL) levels and their correlation in type 2 diabetes mellitus (T2DM) patients at different stages of diabetic kidney disease (DKD) determined by urinary albuminuria.
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Anacardic acid induces cell apoptosis associated with induction of ATF4-dependent endoplasmic reticulum stress.
Toxicol. Lett.
PUBLISHED: 02-24-2014
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Anacardic acid (6-pentadecylsalicylic acid, AA), a natural compound isolated from the traditional medicine Amphipterygium adstringens, has been reported to possess antitumor activities. However, its molecular targets have not been thoroughly studied. Here, we report that AA is a potent inducer of endoplasmic reticulum (ER) stress, leading to apoptosis in hepatoma HepG2 and myeloma U266 cells. Induction of ER stress by AA was supported by a dose- and time-dependent increase in expression of the ER signaling downstream molecules, such as GRP78/BiP, phosphorylated eIF2?, ATF4 and CHOP in both HepG2 and U266 cell lines. Blockage of ATF4 expression by siRNA partially inhibited, while knockdown of CHOP expression by siRNA slightly increased AA-induced cell death in these cells. In addition, AA suppressed HepG2 xenograft tumor growth, associated with increased ER stress in vivo. These results suggest that AA induces tumor cell apoptosis associated with ATF4-dependent ER stress.
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Gene expression profiling and bioinformatics analysis of gastric carcinoma.
Exp. Mol. Pathol.
PUBLISHED: 02-21-2014
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Gastric cancer remains one of the major health problems worldwide, and it is one of the most common cancers and the leading cause of cancer-related deaths in China. This study was to analyze the expression profiles of genes in gastric carcinoma, and predict potential regulating factors. The gene expression profile data GSE13911 was downloaded from Gene Expression Omnibus and the differentially expressed genes (DEGs) were identified by t-test. Gene modules were constructed using hierarchical clustering in R based on average linkage and Pearson's correlation coefficient and functional analysis for these genes were performed with DAVID. Genes in each module with Pearson's correlation coefficient >0.3 were obtained to construct co-expression network. Protein-protein interactions (PPIs) were identified by comparing protein-protein interaction (PPI) network with co-expression networks. In addition, the potential regulatory microRNAs and the transcription factors for each module were screened out. In this study, six modules associated with protein degradation, cell cycle, protein trafficking and immunoreaction were identified. COPS5 (COP9 Subunit 5) was the core protein in the largest PPI network of module 1. The transcription factors MYC and MAZ (Myc-associated zinc-finger protein) were enriched in module 1. A total of 9 microRNA-target bi-clusters were identified and module 1 enriched 20 genes targeting to miR-17-92 gene cluster(miR-17/20ab)and miR-106b-25 gene cluster (miR-106b/93). In conclusion, we constructed 6 gene modules and screened out some genes, transcriptional factors and microRNAs that may be used as potential molecular biomarkers for gastric carcinoma.
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The Bim deletion polymorphism clinical profile and its relation with tyrosine kinase inhibitor resistance in Chinese patients with non-small cell lung cancer.
Cancer
PUBLISHED: 02-20-2014
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Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are widely used for the treatment of patients with advanced non-small cell lung cancer (NSCLC) who have EGFR mutations. Recent studies have indicated that some patients with positive mutations were refractory to EGFR TKIs if they harbored a B-cell chronic lymphocytic leukemia/lymphoma (Bcl-2)-like 11 (Bim) deletion polymorphism. The objective of the current work was to retrospectively study the Bim deletion polymorphism in Chinese patients with NSCLC and its correlation with the efficacy of EGFR TKIs.
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Clinical and epidemiological characteristics of individuals resistant to M. tuberculosis infection in a longitudinal TB household contact study in Kampala, Uganda.
BMC Infect. Dis.
PUBLISHED: 02-18-2014
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Despite sustained exposure to a person with pulmonary tuberculosis (TB), some M. tuberculosis (Mtb) exposed individuals maintain a negative tuberculin skin test (TST). Our objective was to characterize these persistently negative TST (PTST-) individuals and compare them to TST converters (TSTC) and individuals who are TST positive at study enrollment.
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Quantitative versus semiquantitative MR imaging of cartilage in blood-induced arthritic ankles: preliminary findings.
Pediatr Radiol
PUBLISHED: 02-13-2014
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Recent advances in hemophilia prophylaxis have raised the need for accurate noninvasive methods for assessment of early cartilage damage in maturing joints to guide initiation of prophylaxis. Such methods can either be semiquantitative or quantitative. Whereas semiquantitative scores are less time-consuming to be performed than quantitative methods, they are prone to subjective interpretation.
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Structural insights into the assembly of the 30S ribosomal subunit in vivo: functional role of S5 and location of the 17S rRNA precursor sequence.
Protein Cell
PUBLISHED: 02-11-2014
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The in vivo assembly of ribosomal subunits is a highly complex process, with a tight coordination between protein assembly and rRNA maturation events, such as folding and processing of rRNA precursors, as well as modifications of selected bases. In the cell, a large number of factors are required to ensure the efficiency and fidelity of subunit production. Here we characterize the immature 30S subunits accumulated in a factor-null Escherichia coli strain (?rsgA?rbfA). The immature 30S subunits isolated with varying salt concentrations in the buffer system show interesting differences on both protein composition and structure. Specifically, intermediates derived under the two contrasting salt conditions (high and low) likely reflect two distinctive assembly stages, the relatively early and late stages of the 3' domain assembly, respectively. Detailed structural analysis demonstrates a mechanistic coupling between the maturation of the 5' end of the 17S rRNA and the assembly of the 30S head domain, and attributes a unique role of S5 in coordinating these two events. Furthermore, our structural results likely reveal the location of the unprocessed terminal sequences of the 17S rRNA, and suggest that the maturation events of the 17S rRNA could be employed as quality control mechanisms on subunit production and protein translation.
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Significance of combined detection of LunX mRNA and tumor markers in diagnosis of lung carcinoma.
Chin. J. Cancer Res.
PUBLISHED: 02-07-2014
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To evaluate the significance of combined detection of LunX mRNA, carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), and cytokeratin 21-1 fragment (CYFRA21-1) in clinical diagnosis of lung carcinoma.
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Sensitive Pb(2+) probe based on the fluorescence quenching by graphene oxide and enhancement of the leaching of gold nanoparticles.
ACS Appl Mater Interfaces
PUBLISHED: 02-07-2014
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A novel strategy was developed for fluorescent detection of Pb(2+) in aqueous solution based on the fact that graphene oxide (GO) could quench the fluorescence of amino pyrene (AP)-grafted gold nanoparticles (AP-AuNPs) and Pb(2+) could accelerate the leaching rate of AuNPs in the presence of S2O3(2-). In this system, fluorescence reporter AP was grafted on AuNPs through the Au-N bond. In the presence of GO, the system shows fluorescence quenching because of ?-? stacking between AP and GO. With the addition of Pb(2+) and S2O3(2-), the system displays fluorescence recovery, which is attributed to the fact that Pb(2+) could accelerate the leaching of the AuNPs from GO surfaces and release of AP into aqueous solution. Interestingly, the concentration of GO could control the fluorescence "turn-off" or "turn-on" for Pb(2+) detection. In addition, GO is also an excellent promoter for the acceleration of the leaching of AuNPs and shortening the analytical time to ?15 min. Under the optimal conditions, the fluorescence Pb(2+) sensor shows a linear range from 2.0 × 10(-9) to 2.3 × 10(-7) mol/L, with a detection limit of 1.0 × 10(-10) mol/L.
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A red fluorescent nude mouse model of human endometriosis: advantages of a non-invasive imaging method.
Eur. J. Obstet. Gynecol. Reprod. Biol.
PUBLISHED: 02-05-2014
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To establish red fluorescent human endometriosis lesions in a nude mouse model and dynamically and non-invasively to compare intraperitoneal and subcutaneous injection models.
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An improved FCM medical image segmentation algorithm based on MMTD.
Comput Math Methods Med
PUBLISHED: 02-04-2014
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Image segmentation plays an important role in medical image processing. Fuzzy c-means (FCM) is one of the popular clustering algorithms for medical image segmentation. But FCM is highly vulnerable to noise due to not considering the spatial information in image segmentation. This paper introduces medium mathematics system which is employed to process fuzzy information for image segmentation. It establishes the medium similarity measure based on the measure of medium truth degree (MMTD) and uses the correlation of the pixel and its neighbors to define the medium membership function. An improved FCM medical image segmentation algorithm based on MMTD which takes some spatial features into account is proposed in this paper. The experimental results show that the proposed algorithm is more antinoise than the standard FCM, with more certainty and less fuzziness. This will lead to its practicable and effective applications in medical image segmentation.
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Structural damage and functional reorganization in ipsilesional m1 in well-recovered patients with subcortical stroke.
Stroke
PUBLISHED: 02-04-2014
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Both structural atrophy and functional reorganization of the primary motor cortex (M1) have been reported in patients with subcortical infarctions affecting the motor pathway. However, the relationship between structural impairment and functional reorganization in M1 remains unclear.
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Transcriptome and gene expression analysis during flower blooming in Rosa chinensis 'Pallida'.
Gene
PUBLISHED: 01-29-2014
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Rosa chinensis 'Pallida' (Rosa L.) is one of the most important ancient rose cultivars originating from China. It contributed the 'tea scent' trait to modern roses. However, little information is available on the gene regulatory networks involved in scent biosynthesis and metabolism in Rosa. In this study, the transcriptome of R. chinensis 'Pallida' petals at different developmental stages, from flower buds to senescent flowers, was investigated using Illumina sequencing technology. De novo assembly generated 89,614 clusters with an average length of 428bp. Based on sequence similarity search with known proteins, 62.9% of total clusters were annotated. Out of these annotated transcripts, 25,705 and 37,159 sequences were assigned to gene ontology and clusters of orthologous groups, respectively. The dataset provides information on transcripts putatively associated with known scent metabolic pathways. Digital gene expression (DGE) was obtained using RNA samples from flower bud, open flower and senescent flower stages. Comparative DGE and quantitative real time PCR permitted the identification of five transcripts encoding proteins putatively associated with scent biosynthesis in roses. The study provides a foundation for scent-related gene discovery in roses.
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Perirenal fat associated with microalbuminuria in obese rats.
Int Urol Nephrol
PUBLISHED: 01-28-2014
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To determine whether perirenal fat is associated with increased urinary albumin excretion and whether perirenal fat affects renal vascular endothelial function in obese rats.
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Ethanol fermentation of energy beets by self-flocculating and non-flocculating yeasts.
Bioresour. Technol.
PUBLISHED: 01-28-2014
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Specialized varieties of sugar beets (Energy Beets™) are being developed for producing industrial sugars in Arkansas' Mississippi River Delta. To evaluate their suitability for producing regional fermentation feedstocks, we report initial cultivation trials and ethanol fermentation of raw beet juice and combined juice with pulp mash (JPM) liquefied with enzymes, comparing ethanol yields under different regimes by self-flocculating and non-flocculating yeasts. Nine varieties produced root yields averaging 115Mg/ha and 18.5% sucrose contents. Raw beet juice fermentation yielded ethanol up to 0.48g/g (sugar). JPM was directly fermented through either a sequential (SeqSF) or simultaneous saccharification and fermentation (SSF) process. For both yeast types, SSF was a more efficient process than SeqSF, with ethanol yields up to 0.47g/g (sugar) and volumetric productivity up to 7.81g/L/h. These results indicate the self-flocculating yeast is suitable for developing efficient bioprocesses to ferment industrial sugar from energy beets.
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Antiangiogenesis therapy of endometriosis using PAMAM as a gene vector in a noninvasive animal model.
Biomed Res Int
PUBLISHED: 01-27-2014
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To evaluate the characteristics and antiangiogenic effects of endostatin-loaded PAMAM on endometriosis in a noninvasive animal model.
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Mutation of the RDR1 gene caused genome-wide changes in gene expression, regional variation in small RNA clusters and localized alteration in DNA methylation in rice.
BMC Plant Biol.
PUBLISHED: 01-24-2014
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Endogenous small (sm) RNAs (primarily si- and miRNAs) are important trans/cis-acting regulators involved in diverse cellular functions. In plants, the RNA-dependent RNA polymerases (RDRs) are essential for smRNA biogenesis. It has been established that RDR2 is involved in the 24 nt siRNA-dependent RNA-directed DNA methylation (RdDM) pathway. Recent studies have suggested that RDR1 is involved in a second RdDM pathway that relies mostly on 21 nt smRNAs and functions to silence a subset of genomic loci that are usually refractory to the normal RdDM pathway in Arabidopsis. Whether and to what extent the homologs of RDR1 may have similar functions in other plants remained unknown.
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Recyclable removal of bisphenol A from aqueous solution by reduced graphene oxide-magnetic nanoparticles: adsorption and desorption.
J Colloid Interface Sci
PUBLISHED: 01-14-2014
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Reduced graphene oxide (rGO) nanosheets decorated with tunable magnetic nanoparticles (MNPs) were synthesized by a simple co-precipitation method and employed for recyclable removal of bisphenol A (BPA) from aqueous solution. The morphological characterization shows that Fe3O4 nanoparticles are uniformly deposited on rGO sheets. The magnetic characterization demonstrates that composites with various amounts of Fe3O4 nanoparticles are superparamagnetic. Due to the superparamagnetism, rGO-MNPs were used as recyclable adsorbents for BPA removal in aqueous solution. The kinetics of the adsorption process and the adsorption isotherm were investigated. The results indicate that the adsorption process is fitted to Langmuir model and the composites with lower density of MNPs represent better adsorption ability. In addition, its kinetics follows pseudo-second-order rate equation. Moreover, the adsorbents could be recovered conveniently by magnetic separation and recyclable used because of the easy desorption of BPA.
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Overexpression of UDP-glucose pyrophosphorylase from Larix gmelinii enhances vegetative growth in transgenic Arabidopsis thaliana.
Plant Cell Rep.
PUBLISHED: 01-10-2014
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A UDP-glucose pyrophosphorylase gene ( LgUGPase ) was identified from Larix gmelinii, and its function in enhancing vegetative growth and cellulose biosynthesis was confirmed by analyzing transgenic Arabidopsis thaliana overexpressed LgUGPase . UDP-glucose pyrophosphorylase (UGPase), an important regulatory enzyme in carbohydrate metabolism, catalyzes the reversible production of glucose 1-phosphate and the conversion of uridine triphosphate to uridine diphosphate glucose and pyrophosphate. In this study, a larch UGPase (LgUGPase) gene was isolated from Larix gmelinii. The 1,443-bp open reading frame encodes a protein of 480 amino acids with a predicted molecular weight of 53.7 kDa and shows striking sequence similarity to UGPase proteins from Pinus taeda and Picea sitchensis. Semiquantitative reverse transcription-polymerase chain reaction showed that the LgUGPase gene was expressed primarily in the larch stem in addition to its root and leaf. Southern blot analysis indicated that LgUGPase is encoded by two genes in the L. gmelinii genome. Overexpression of LgUGPase enhanced vegetative growth in transgenic Arabidopsis and increased the contents of soluble sugars and cellulose, and thickened parenchyma cell walls. These results revealed that L. gmelinii UGPase participates in sucrose/polysaccharide metabolism and cell wall biosynthesis, suggesting that LgUGPase may be a good candidate gene for improvement of fiber cell development in plants.
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A new rapid colorimetric detection method of Al³? with high sensitivity and excellent selectivity based on a new mechanism of aggregation of smaller etched silver nanoparticles.
Talanta
PUBLISHED: 01-07-2014
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As a pathogenic factor of the Alzheimer?s disease, aluminum has been associated with the damage of the central nervous system in humans. In this study, we propose a new facile and rapid colorimetric detection method of Al(3+) with excellent selectivity and high sensitivity based on silver nanoparticles (AgNPs) stabilized by reduced glutathione (GSH) in the presence of l-cysteine (Cys). The new mechanism of our Al(3+) detection system based on GSH-AgNPs, i.e., aggregation of smaller etched GSH-AgNPs, are confirmed by TEM, EDS and DLS. The aggregation of smaller etched GSH-AgNPs results in obvious color change of the nanoparticle dispersion from yellow to reddish brown, and red shift and intensity decrease of the surface plasmon resonance (SPR) absorption. The GSH concentration, Cys concentration and pH value of the GSH-AgNPRs-based detection system are respectively optimized to be 10.0 mM, 50.0 mM and 6.0 according to the sensing effect of Al(3+). At the optimized conditions, the selectivity of the GSH-AgNPs detection system for Al(3+) is excellent compared with other ions including K(+), Mg(2+), Fe(3+), Co(2+), Mn(2+), Zn(2+), Cd(2+), Pb(2+), Ca(2+), Ba(2+), Cu(2+), Cr(3+), Hg(2+), Ni(2+), [Formula: see text] , [Formula: see text] , [Formula: see text] , [Formula: see text] and [Formula: see text] . Furthermore, this detection system is very sensitive for Al(3+). The limit of detection (LOD) is 1.2 µM by the naked eyes and 0.16 µM by UV-vis spectra, which are both much lower than the national drinking water standards (7.4 µM). Furthermore, the UV-vis detection offers a good linear detection range from 0.4 to 4.0 µM (R(2)=0.9924), which indicates that our developed detection system can also be used for the quantitative analysis of Al(3+). The detection results of real water samples indicate that this method can be used for real water detection.
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Verbascoside promotes apoptosis by regulating HIPK2-p53 signaling in human colorectal cancer.
BMC Cancer
PUBLISHED: 01-06-2014
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We investigated the role of the HIPK2-p53 signaling pathway in tumorigenesis and resistance to the drug Verbascoside (VB) in colorectal cancer (CRC), using in vivo and in vitro experiments.
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Serum estradiol level change after human chorionic gonadotropin administration had no correlation with live birth rate in IVF cycles.
Eur. J. Obstet. Gynecol. Reprod. Biol.
PUBLISHED: 01-05-2014
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To investigate the correlation between the estradiol (E2) level change after hCG administration and the live birth rate in GnRH agonist long or short protocols, and to explore the possible factors related to E2 dynamics after hCG administration during controlled ovarian hyperstimulation (COH).
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Coordinated Actions of FXR and LXR in Metabolism: From Pathogenesis to Pharmacological Targets for Type 2 Diabetes.
Int J Endocrinol
PUBLISHED: 01-02-2014
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Type 2 diabetes (T2D) is the most prevalent metabolic disease, and many people are suffering from its complications driven by hyperglycaemia and dyslipidaemia. Nuclear receptors (NRs) are ligand-inducible transcription factors that mediate changes to metabolic pathways within the body. As metabolic regulators, the farnesoid X receptor (FXR) and the liver X receptor (LXR) play key roles in the pathogenesis of T2D, which remains to be clarified in detail. Here we review the recent progress concerning the physiological and pathophysiological roles of FXRs and LXRs in the regulation of bile acid, lipid and glucose metabolism and the implications in T2D, taking into account that these two nuclear receptors are potential pharmaceutical targets for the treatment of T2D and its complications.
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?5 Nicotinic acetylcholine receptor mediates nicotine-induced HIF-1? and VEGF expression in non-small cell lung cancer.
Toxicol. Appl. Pharmacol.
PUBLISHED: 01-02-2014
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By binding to nicotinic acetylcholine receptors (nAChRs), nicotine induces the proliferation and apoptosis of non-small cell lung cancer (NSCLC). Previous studies have indicated that ?5-nAChR is highly associated with lung cancer risk and nicotine dependence. However, the mechanisms through which ?5-nAChRs may influence lung carcinogenesis are far from clear. In the present study, we investigated the roles of ?5-nAChR in the nicotine-induced expression of hypoxia-inducible factor-1? (HIF-1?) and vascular endothelial growth factor (VEGF). Immunohistochemistry was used to detect the expression of ?5-nAChR and HIF-1? in 60 specimens of lung cancer and para-carcinoma tissue. The correlations between the expression levels of ?5-nAChR and HIF-1? and other clinicopathological data were analyzed. In a cell line that highly expressed ?5-nAChR, the loss of ?5-nAChR function by siRNA was used to study whether ?5-nAChR is involved in the nicotine-induced expression of HIF-1? and VEGF through the activation of the ERK1/2 and PI3K/Akt signaling pathways. Cell growth was detected using the cell counting kit-8 (CCK-8). ?5-nAChR (78.3%) and HIF-1? (88.3%) were both overexpressed in NSCLC, and their expression levels were found to be correlated with each other (P<0.05). In the A549 cell line, ?5-nAChR and HIF-1? were found to be expressed under normal conditions, and their expression levels were significantly increased in response to nicotine treatment. The silencing of ?5-nAChR significantly inhibited the nicotine-induced cell proliferation compared with the control group and attenuated the nicotine-induced upregulation of HIF-1? and VEGF, and these effects required the cooperation of the ERK1/2 and PI3K/Akt signaling pathways. These results show that the ?5-nAChR/HIF-1?/VEGF axis is involved in nicotine-induced tumor cell proliferation, which suggests that ?5-nAChR may serve as a potential anticancer target in nicotine-associated lung cancer.
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Role of hypoxia-inducible factor-1? and survivin in oxygen-induced retinopathy in mice.
Int J Clin Exp Pathol
PUBLISHED: 01-01-2014
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Survivin, an inhibitor of apoptosis protein family, appears to be involved in tumor progression and angiogenesis. The current study contains rare reports on the transcriptional regulation of survivin expression in retinal neovascularization (NV). The aim of this study was to investigate hypoxia-inducible factor-1? (HIF-1?) and survivin expression in pathologic ocular angiogenesis and to determine their correlation and cellular location. The model of oxygen-induced retinopathy (OIR) was induced in C57BL/6 mice by exposing 75% oxygen from postnatal day 7 (p7) to p12 and then followed by room air. Fluorescence angiography, immunostaining and HE staining were used to assess the visualization of retinal vascularization and the expression of HIF-1? and survivin protein in retina oxygen-induced retinopathy was characterized by clusters of neovascularization and regions of non-perfusion. HIF-1? and survivin were both highly expressed in OIR and a positive correlation existed between HIF-1? and survivin expression. In OIR, there was more HIF1-? protein expression in the inner nuclear layer (INL), the ganglion cell layer (GCL), and more neovascularization breaking through the inner retina and survivin protein was detected in GCL, and more neovascularization breaking through the inner retina. Our study had shown that both HIF1-? and survivin are involved in the retinal neovaccularization. Meanwhile HIF1-? and survivin have differential cellular location in retinal ischemia, and HIF1-? might be a critical transcription factor involved in the regulation of survivin expression.
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Protocatechuic Acid, a Novel Active Substance against Avian Influenza Virus H9N2 Infection.
PLoS ONE
PUBLISHED: 01-01-2014
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Influenza virus H9N2 subtype has triggered co-infection with other infectious agents, resulting in huge economical losses in the poultry industry. Our current study aims to evaluate the antiviral activity of protocatechuic acid (PCA) against a virulent H9N2 strain in a mouse model. 120 BALB/c mice were divided into one control group, one untreated group, one 50 mg/kg amantadine hydrochloride-treated group and three PCA groups treated 12 hours post-inoculation with 40, 20 or 10 mg/kg PCA for 7 days. All the infected animals were inoculated intranasally with 0.2 ml of a A/Chicken/Hebei/4/2008(H9N2) inoculum. A significant body weight loss was found in the 20 mg/kg and 40 mg/kg PCA-treated and amantadine groups as compared to the control group. The 14 day survivals were 94.4%, 100% and 95% in the PCA-treated groups and 94.4% in the amantadine hydrochloride group, compared to less than 60% in the untreated group. Virus loads were less in the PCA-treated groups compared to the amantadine-treated or the untreated groups. Neutrophil cells in BALF were significantly decreased while IFN-?, IL-2, TNF-? and IL-6 decreased significantly at days 7 in the PCA-treated groups compared to the untreated group. Furthermore, a significantly decreased CD4+/CD8+ ratio and an increased proportion of CD19 cells were observed in the PCA-treated groups and amantadine-treated group compared to the untreated group. Mice administered with PCA exhibited a higher survival rate and greater viral clearance associated with an inhibition of inflammatory cytokines and activation of CD8+ T cell subsets. PCA is a promising novel agent against bird flu infection in the poultry industry.
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Tissue culture-induced heritable genomic variation in rice, and their phenotypic implications.
PLoS ONE
PUBLISHED: 01-01-2014
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Somaclonal variation generally occurs in plants regenerated from tissue culture. However, fundamental issues regarding molecular characteristics, mutation rates and mutation spectra of plant somatic variation as well as their phenotypic relevance have been addressed only recently. Moreover, these studies have reported highly discrepant results in different plant species and even in the same plant genotype.
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Similar metabolic changes induced by HIPVs exposure as herbivore in Ammopiptanthus mongolicus.
PLoS ONE
PUBLISHED: 01-01-2014
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Herbivore-induced plant volatiles (HIPVs) are important compounds to prim neighboring undamaged plants; however, the mechanism for this priming process remains unclear. To reveal metabolic changes in plants exposed to HIPVs, metabolism of leaves and roots of Ammopiptanthus mongolicus seedlings exposed to HIPVs released from conspecific plants infested with larvae of Orgyia ericae were analyzed together with control and infested seedlings using nuclear magnetic resonance (NMR)-based metabolic technology and multi variate data analysis. Results presented showed that HIPVs exposure led to similar but specific metabolic changes compared with those induced by infestation in both leaves and roots. Furthermore, both HIPVs exposure and herbivore attack resulted in metabolic changes involving a series of primary and secondary metabolites in both leaves and roots. Taken together, these results suggested that priming of yet-damaged plants may be achieved by reconfiguring metabolic pathways in leaves and roots to make similar concentrations for all metabolites as those in seedlings infested. Therefore, we propose that improved readiness of defense induction of primed plants toward subsequent herbivore attack may be based on the similar metabolic profiling induced by HIPVs exposure as those caused by herbivore.
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Novel mutations of CRB1 in Chinese families presenting with retinal dystrophies.
Mol. Vis.
PUBLISHED: 01-01-2014
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To identify disease-causing mutations in Chinese families who presented with retinitis pigmentosa (RP) and Leber congenital amaurosis (LCA).
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Microtubule stabilization by Mdp3 is partially attributed to its modulation of HDAC6 in addition to its association with tubulin and microtubules.
PLoS ONE
PUBLISHED: 01-01-2014
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Microtubule-mediated cellular events such as intracellular transport and the maintenance of cell polarity are highly dependent upon microtubule stability, which is controlled by a repertoire of microtubule-associated proteins (MAPs) in the cell. MAP7 domain-containing protein 3 (Mdp3) has recently been identified as a critical regulator of microtubule stability. However, it remains elusive how Mdp3 carries out this function. In this study, by examination of tubulin partitioning between the polymer and soluble dimer forms, we found that Mdp3 could protect microtubules from cold- or nocodazole-induced depolymerization. Immunoblotting and immunofluorescence microscopy showed that knockdown of Mdp3 expression significantly reduced the level of tubulin acetylation. In vitro tubulin polymerization assays revealed that the amino-terminal region of Mdp3 was necessary for its ability to stabilize microtubules. Immunoprecipitation and pulldown experiments showed that the amino-terminal region mediated the interaction of Mdp3 with histone deacetylase 6 (HDAC6), in addition to its association with tubulin and microtubules. Immunofluorescence microscopy further demonstrated that endogenous Mdp3 and HDAC6 colocalized in the cytoplasm. Moreover, depletion of Mdp3 dramatically increased the activity of HDAC6 toward tubulin deacetylation. These findings suggest that Mdp3 controls microtubule stability through its binding to tubulin and microtubules as well as its regulation of HDAC6 activity.
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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.