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Find video protocols related to scientific articles indexed in Pubmed.
Delayed rearterialization unlikely leads to non-anastomotic stricture but causes temporary injury on bile duct after liver transplantation.
Transpl. Int.
PUBLISHED: 11-20-2014
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Non-anastomotic strictures (NAS) are common biliary complications after liver transplantation (LT). Delayed rearterialization induces biliary injury in several hours. However, whether this injury can be prolonged remains unknown. The correlation of this injury with NAS occurrence remains obscure.
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[Transnasal endoscopic management of foreign body injuries at orbital-skull base].
Zhonghua Yi Xue Za Zhi
PUBLISHED: 11-18-2014
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To explore the feasibility and methods of transnasal endoscope for removing foreign bodies at orbital-skull base.
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Total Synthesis of Rubriflordilactone A.
J. Am. Chem. Soc.
PUBLISHED: 11-01-2014
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The first and asymmetric total synthesis of rubriflordilactone A, a bisnortriterpenoid isolated from Schisandra rubriflora, has been accomplished in a convergent manner. Two enantioenriched fragments were forged together to give a functionalized cis-triene. A 6?-electrocyclization/aromatization sequence assembled the penta-substituted arene, and a formal vinylogous Mukaiyama aldol reaction introduced the butenolide side chain.
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Maternal histone variants and their chaperones promote paternal genome activation and boost somatic cell reprogramming.
Bioessays
PUBLISHED: 10-21-2014
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The mammalian egg employs a wide spectrum of epigenome modification machinery to reprogram the sperm nucleus shortly after fertilization. This event is required for transcriptional activation of the paternal/zygotic genome and progression through cleavage divisions. Reprogramming of paternal nuclei requires replacement of sperm protamines with canonical and non-canonical histones, covalent modification of histone tails, and chemical modification of DNA (notably oxidative demethylation of methylated cytosines). In this essay we highlight the role maternal histone variants play during developmental reprogramming following fertilization. We discuss how reduced maternal histone variant incorporation in somatic nuclear transfer experiments may explain the reduced viability of resulting embryos and how knowledge of repressive and activating maternal factors may be used to improve somatic cell reprogramming.
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Racemosin C, a novel minor bisindole alkaloid with protein tyrosine phosphatase-1B inhibitory activity from the green alga Caulerpa racemosa.
J Asian Nat Prod Res
PUBLISHED: 10-09-2014
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A novel minor bisindole alkaloid, racemosin C (1), characterized by a naturally unprecedented 8-hydroxy-2,4,6-cyclooctatrienone ring fused with two indole systems, was isolated from the green alga Caulerpa racemosa, together with one known related metabolite, caulersin (2). The structure of 1 was elucidated on the basis of extensive spectroscopic analysis, and by comparison with the data of related known compounds. A plausible biosynthetic pathway of 1 was proposed. Compounds 1 and 2 exhibited significant PTP1B inhibitory activity with IC50 values of 5.86 ± 0.57 and 7.14 ± 1.00 ?M, respectively, compared with the positive control oleanolic acid (IC50 = 3.03 ± 0.20 ?M). On the basis of the data obtained, the Caulerpa bisindole alkaloids may be considered as a new class of PTP1B inhibitors.
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Learning Multiscale Active Facial Patches for Expression Analysis.
IEEE Trans Cybern
PUBLISHED: 10-08-2014
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In this paper, we present a new idea to analyze facial expression by exploring some common and specific information among different expressions. Inspired by the observation that only a few facial parts are active in expression disclosure (e.g., around mouth, eye), we try to discover the common and specific patches which are important to discriminate all the expressions and only a particular expression, respectively. A two-stage multitask sparse learning (MTSL) framework is proposed to efficiently locate those discriminative patches. In the first stage MTSL, expression recognition tasks are combined to located common patches. Each of the tasks aims to find dominant patches for each expression. Secondly, two related tasks, facial expression recognition and face verification tasks, are coupled to learn specific facial patches for individual expression. The two-stage patch learning is performed on patches sampled by multiscale strategy. Extensive experiments validate the existence and significance of common and specific patches. Utilizing these learned patches, we achieve superior performances on expression recognition compared to the state-of-the-arts.
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A Gain-of-Function Mutation in Tnni2 Impeded Bone Development through Increasing Hif3a Expression in DA2B Mice.
PLoS Genet.
PUBLISHED: 10-01-2014
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Distal arthrogryposis type 2B (DA2B) is an important genetic disorder in humans. However, the mechanisms governing this disease are not clearly understood. In this study, we generated knock-in mice carrying a DA2B mutation (K175del) in troponin I type 2 (skeletal, fast) (TNNI2), which encodes a fast-twitch skeletal muscle protein. Tnni2K175del mice (referred to as DA2B mice) showed typical DA2B phenotypes, including limb abnormality and small body size. However, the current knowledge concerning TNNI2 could not explain the small body phenotype of DA2B mice. We found that Tnni2 was expressed in the osteoblasts and chondrocytes of long bone growth plates. Expression profile analysis using radii and ulnae demonstrated that Hif3a expression was significantly increased in the Tnni2K175del mice. Chromatin immunoprecipitation assays indicated that both wild-type and mutant tnni2 protein can bind to the Hif3a promoter using mouse primary osteoblasts. Moreover, we showed that the mutant tnni2 protein had a higher capacity to transactivate Hif3a than the wild-type protein. The increased amount of hif3a resulted in impairment of angiogenesis, delay in endochondral ossification, and decrease in chondrocyte differentiation and osteoblast proliferation, suggesting that hif3a counteracted hif1a-induced Vegf expression in DA2B mice. Together, our data indicated that Tnni2K175del mutation led to abnormally increased hif3a and decreased vegf in bone, which explain, at least in part, the small body size of Tnni2K175del mice. Furthermore, our findings revealed a new function of tnni2 in the regulation of bone development, and the study of gain-of-function mutation in Tnni2 in transgenic mice opens a new avenue to understand the pathological mechanism of human DA2B disorder.
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Improving Estimation of Distribution Algorithm on Multimodal Problems by Detecting Promising Areas.
IEEE Trans Cybern
PUBLISHED: 09-24-2014
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In this paper, a novel multiple sub-models maintenance technique, named maintaining and processing sub-models (MAPS), is proposed. MAPS aims to enhance the ability of estimation of distribution algorithms (EDAs) on multimodal problems. The advantages of MAPS over the existing multiple sub-models based EDAs stem from the explicit detection of the promising areas, which can save many function evaluations for exploration and thus accelerate the optimization speed. MAPS can be combined with any EDA that adopts a single Gaussian model. The performance of MAPS has been assessed through empirical studies where MAPS is integrated with three different types of EDAs. The experimental results show that MAPS can lead to much faster convergence speed and obtain more stable solutions than the compared algorithms on 12 benchmark problems.
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GRP78 secreted by colon cancer cells facilitates cell proliferation via PI3K/Akt signaling.
Asian Pac. J. Cancer Prev.
PUBLISHED: 09-18-2014
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Glucose regulated protein 78 (GRP78) is usually recognized as a chaperone in the endoplasmic reticulum. However, increasing evidence indicates that GRP78 can be translocated to the cell surface, acting as a signaling receptor for a variety of ligands. Since little is known about the secretion of GRP78 and its role in the progression of colon cancer we here focused on GRP78 from colon cancer cells, and purified GRP78 protein mimicking the secreted GRP78 was able to utilize cell surface GRP78 as its receptor, activating downstream PI3K/Akt and Wnt/?-catenin signaling and promote colon cancer cell proliferation. Our study revealed a new mode of action of autocrine GRP78 in cancer progression: secreted GRP78 binds to cell surface GRP78 as its receptor and activates intracellular proliferation signaling.
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Modeling, molecular dynamics simulation, and mutation validation for structure of cannabinoid receptor 2 based on known crystal structures of GPCRs.
J Chem Inf Model
PUBLISHED: 09-05-2014
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The cannabinoid receptor 2 (CB2) plays an important role in the immune system. Although a few of GPCRs crystallographic structures have been reported, it is still challenging to obtain functional transmembrane proteins and high resolution X-ray crystal structures, such as for the CB2 receptor. In the present work, we used 10 reported crystal structures of GPCRs which had high sequence identities with CB2 to construct homology-based comparative CB2 models. We applied these 10 models to perform a prescreen by using a training set consisting of 20 CB2 active compounds and 980 compounds randomly selected from the National Cancer Institute (NCI) database. We then utilized the known 170 cannabinoid receptor 1 (CB1) or CB2 selective compounds for further validation. Based on the docking results, we selected one CB2 model (constructed by ?1AR) that was most consistent with the known experimental data, revealing that the defined binding pocket in our CB2 model was well-correlated with the training and testing data studies. Importantly, we identified a potential allosteric binding pocket adjacent to the orthosteric ligand-binding site, which is similar to the reported allosteric pocket for sodium ion Na(+) in the A2AAR and the ?-opioid receptor. Our studies in correlation of our data with others suggested that sodium may reduce the binding affinities of endogenous agonists or its analogs to CB2. We performed a series of docking studies to compare the important residues in the binding pockets of CB2 with CB1, including antagonist, agonist, and our CB2 neutral compound (neutral antagonist) XIE35-1001. Then, we carried out 50 ns molecular dynamics (MD) simulations for the CB2 docked with SR144528 and CP55940, respectively. We found that the conformational changes of CB2 upon antagonist/agonist binding were congruent with recent reports of those for other GPCRs. Based on these results, we further examined one known residue, Val113(3.32), and predicted two new residues, Phe183 in ECL2 and Phe281(7.35), that were important for SR144528 and CP55940 binding to CB2. We then performed site-directed mutation experimental study for these residues and validated the predictions by radiometric binding affinity assay.
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Inhibition of endothelial lipase activity by sphingomyelin in the lipoproteins.
Lipids
PUBLISHED: 08-29-2014
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Endothelial lipase (EL) is a major determinant of plasma HDL concentration, its activity being inversely proportional to HDL levels. Although it is known that it preferentially acts on HDL compared to LDL and VLDL, the basis for this specificity is not known. Here we tested the hypothesis that sphingomyelin, a major phospholipid in lipoproteins is a physiological inhibitor of EL, and that the preference of the enzyme for HDL may be due to low sphingomyelin/phosphatidylcholine (PtdCho) ratio in HDL, compared to other lipoproteins. Using recombinant human EL, we showed that sphingomyelin inhibits the hydrolysis of PtdCho in the liposomes in a concentration-dependent manner. While the enzyme showed lower hydrolysis of LDL PtdCho, compared to HDL PtdCho, this difference disappeared after the degradation of lipoprotein sphingomyelin by bacterial sphingomyelinase. Analysis of molecular species of PtdCho hydrolyzed by EL in the lipoproteins showed that the enzyme preferentially hydrolyzed PtdCho containing polyunsaturated fatty acids (PUFA) such as 22:6, 20:5, 20:4 at the sn-2 position, generating the corresponding PUFA-lyso PtdCho. This specificity for PUFA-PtdCho species was not observed after depletion of sphingomyelin by sphingomyelinase. These results show that sphingomyelin not only plays a role in regulating EL activity, but also influences its specificity towards PtdCho species.
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RAR?-C-Fos-PPAR?2 signaling rather than ROS generation is critical for all-trans retinoic acid-inhibited adipocyte differentiation.
Biochimie
PUBLISHED: 08-28-2014
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Obesity has become a worldwide public health problem, which is mainly determined by excess energy intake and adipose tissue expansion. Adipose tissue expansion can occur through hyperplasia (adipocyte differentiation) or hypertrophy. Retinoic acid was shown to inhibit adipocyte differentiation. However, the molecular mechanism is unclear. In the study, we found that all-trans-retinoic acid (ATRA) inhibited 3T3-L1 adipocyte differentiation. We did not observe significant apoptosis in differentiated adipocytes treated by ATRA. ATRA increased ROS generation and disturbed redox balance. However, antioxidant treatment did not ameliorate the reduction of lipid accumulation induced by ATRA, indicating that ROS generation was not involved in ATRA-inhibited adipocyte differentiation. ATRA reduced C/EBP?, PPAR? and its target gene expression. In the presence of ATRA, retinoic acid receptor (RAR) ?/? expression was increased. Inhibition of RAR?, but not RAR?, blocked ATRA-induced reduction of PPAR?2 expression. ATRA induced a profound interaction between RAR? and C-Fos protein, reflected by Co-IP results. C-Fos was found to exhibit a differentiation-dependent DNA binding activity to PPAR?2 promoter. RAR? inhibitor significantly suppressed ATRA-inhibited DNA binding activity of C-Fos to PPAR?2 promoter, indicating that downregulation of C-Fos activity mediated activation of RAR?-exerted reduction of PPAR?2 expression and thus inhibition of adipocyte differentiation induced by ATRA. Taken together, these data demonstrates that RAR?-C-Fos-PPAR?2 signaling rather than ROS generation is critical for ATRA-inhibited adipocyte differentiation.
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Examining the critical roles of human CB2 receptor residues Valine 3.32 (113) and Leucine 5.41 (192) in ligand recognition and downstream signaling activities.
Biochem. Biophys. Res. Commun.
PUBLISHED: 08-19-2014
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We performed molecular modeling and docking to predict a putative binding pocket and associated ligand-receptor interactions for human cannabinoid receptor 2 (CB2). Our data showed that two hydrophobic residues came in close contact with three structurally distinct CB2 ligands: CP-55,940, SR144528 and XIE95-26. Site-directed mutagenesis experiments and subsequent functional assays implicated the roles of Valine residue at position 3.32 (V113) and Leucine residue at position 5.41 (L192) in the ligand binding function and downstream signaling activities of the CB2 receptor. Four different point mutations were introduced to the wild type CB2 receptor: V113E, V113L, L192S and L192A. Our results showed that mutation of Val113 with a Glutamic acid and Leu192 with a Serine led to the complete loss of CB2 ligand binding as well as downstream signaling activities. Substitution of these residues with those that have similar hydrophobic side chains such as Leucine (V113L) and Alanine (L192A), however, allowed CB2 to retain both its ligand binding and signaling functions. Our modeling results validated by competition binding and site-directed mutagenesis experiments suggest that residues V113 and L192 play important roles in ligand binding and downstream signaling transduction of the CB2 receptor.
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[Chemical constituents from flowers of Paeonia lactiflora].
Zhong Yao Cai
PUBLISHED: 08-06-2014
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To study the chemical constituents of Paeonia lactiflora flowers.
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Investigation of data representation issues in computerizing clinical practice guidelines in china.
Healthc Inform Res
PUBLISHED: 07-31-2014
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From the point of view of clinical data representation, this study attempted to identify obstacles in translating clinical narrative guidelines into computer interpretable format and integrating the guidelines with data in Electronic Health Records in China.
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Nickel-Catalyzed Asymmetric Transfer Hydrogenation of Olefins for the Synthesis of ?- and ?-Amino Acids.
Angew. Chem. Int. Ed. Engl.
PUBLISHED: 07-30-2014
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The field of asymmetric (transfer) hydrogenation of prochiral olefins has been dominated by noble metal catalysts based on rhodium, ruthenium, and iridium. Herein we report that a simple nickel catalyst is highly active in the transfer hydrogenation using formic acid. Chiral ?- and ?-amino acid derivatives were obtained in good to excellent enantioselectivity. The key toward success was the use of the strongly donating and sterically demanding bisphosphine Binapine.
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Rational design of magnetic nanorattles as contrast agents for ultrasound/magnetic resonance dual-modality imaging.
ACS Appl Mater Interfaces
PUBLISHED: 07-24-2014
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Nanorattles, as promising functional hollow nanomaterials, show considerable advantages in a variety of applications for drug delivery, biosensors, and biomedical imaging because of their tailored ability in both the movable core and shell. In this study, we formulate a facile controllable route to synthesize a monodisperse magnetic nanorattle with an Fe3O4 superparticle as the core and poly(vinylsilane) (PVS) as the outer shell (Fe3O4@air@PVS) using the polymer-backbone-transition strategy. In the process of synthesis, besides acting as the precursor for the PVS shells of nanorattles, organosilica (o-SiO2) plays the role of template for the middle cavities. The structures of nanorattles can be easily formed via etching treatment of NaOH solution. Through encapsulating sensitive perfluorohexane (PFH) in the cavities of Fe3O4@air@PVS, the biocompatible magnetic nanosystem shows a relatively stable ultrasound signal intensity and a high r2 value of 62.19 mM(-1) s(-1) for magnetic resonance imaging (MRI). After intravenous administration of nanorattles to a healthy rat, dramatically positively enhanced ultrasound imaging and negatively enhanced T2-weighted MRI are detected in the liver. Furthermore, when the Fe3O4@PFH@PVS nanorattles are administered to tumor-bearing mice, a significant passive accumulation in the tumor via an electron paramagnetic resonance effect is detected by both ultrasound imaging and MRI. In vivo experiments indicate that the obtained Fe3O4@PFH@PVS nanorattles can be used as dual-modality contrast agents for simultaneous ultrasound and MRI detection.
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[Recognition of walking stance phase and swing phase based on moving window].
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi
PUBLISHED: 07-22-2014
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Wearing transfemoral prosthesis is the only way to complete daily physical activity for amputees. Motion pattern recognition is important for the control of prosthesis, especially in the recognizing swing phase and stance phase. In this paper, it is reported that surface electromyography (sEMG) signal is used in swing and stance phase recognition. sEMG signal of related muscles was sampled by Infiniti of a Canadian company. The sEMG signal was then filtered by weighted filtering window and analyzed by height permitted window. The starting time of stance phase and swing phase is determined through analyzing special muscles. The sEMG signal of rectus femoris was used in stance phase recognition and sEMG signal of tibialis anterior is used in swing phase recognition. In a certain tolerating range, the double windows theory, including weighted filtering window and height permitted window, can reach a high accuracy rate. Through experiments, the real walking consciousness of the people was reflected by sEMG signal of related muscles. Using related muscles to recognize swing and stance phase is reachable. The theory used in this paper is useful for analyzing sEMG signal and actual prosthesis control.
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Alkaline Earth Guests in Polyoxopalladate Chemistry: From Nanocube to Nanostar via an Open-Shell Structure.
Angew. Chem. Int. Ed. Engl.
PUBLISHED: 07-10-2014
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The three novel, discrete palladium(II)-oxo clusters [CaPd12 O8 (PhAsO3 )8 ](6-) (CaPd12 ), [SrPd12 O6 (OH)3 (PhAsO3 )6 (OAc)3 ](4-) (SrPd12 ), and [BaPd15 O10 (PhAsO3 )10 ](8-) (BaPd15 ) encapsulating alkaline earth metal ions were prepared and fully characterized by a multitude of solution and solid-state physicochemical techniques. We have discovered a structure-directing template effect induced by the respective size of the alkaline earth guest ion, which determines the detailed condensation arrangement of the peripheral Pd(II) -oxo shell. The unprecedented SrPd12 with an open-shell type structure is of particular importance and reflects a successful strategy for deliberate design of new structural classes of polyoxo-noble-metalates. Furthermore, the unusual acetate-water ligand exchange phenomenon renders SrPd12 as a promising candidate for noble-metal-based catalysis.
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ATP Synthase ?-Chain Overexpression in SR-BI Knockout Mice Increases HDL Uptake and Reduces Plasma HDL Level.
Int J Endocrinol
PUBLISHED: 07-10-2014
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HDL cholesterol is known to be inversely correlated with cardiovascular disease due to its diverse antiatherogenic functions. SR-BI mediates the selective uptake of HDL-C. SR-BI knockout diminishes but does not completely block the transport of HDL; other receptors may be involved. Ectopic ATP synthase ?-chain in hepatocytes has been previously characterized as an apoA-I receptor, triggering HDL internalization. This study was undertaken to identify the overexpression of ectopic ATP synthase ?-chain on DIL-HDL uptake in primary hepatocytes in vitro and on plasma HDL levels in SR-BI knockout mice. Human ATP synthase ?-chain cDNA was delivered to the mouse liver by adenovirus and GFP adenovirus as control. The adenovirus-mediated overexpression of ?-chain was identified at both mRNA and protein levels on mice liver and validated by its increasing of DiL-HDL uptake in primary hepatocytes. In response to hepatic overexpression of ?-chain, plasma HDL-C levels and cholesterol were reduced in SR-BI knockout mice, compared with the control. The present data suggest that ATP synthase ?-chain can serve as the endocytic receptor of HDL, and its overexpression can reduce plasma HDL-C.
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Direct contacts with colon cancer cells regulate the differentiation of bone marrow mesenchymal stem cells into tumor associated fibroblasts.
Biochem. Biophys. Res. Commun.
PUBLISHED: 07-09-2014
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Tumor-stroma interactions are referred to as essential events in tumor progression. There has been growing attention that bone marrow-derived mesenchymal stem cells (BMSCs) can travel to tumor stroma, where they differentiate into tumor-associated fibroblast (TAF)-like cells, a predominant tumor-promoting stromal cell. However, little is definitively known about the contributors for this transition. Here, using an in vitro direct co-culture model of colon cancer cells and BMSCs, we identify that colon cancer cells can induce adjoining BMSCs to exhibit the typical characteristic of TAFs, with increased expression of ?-smooth muscle actin (?-SMA). Importantly, the present data also reveals that activated Notch signaling mediates transformation of BMSCs to TAFs through the downstream TGF-?/Smad signaling pathway.
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GRP78 enhances the glutamine metabolism to support cell survival from glucose deficiency by modulating the ?-catenin signaling.
Oncotarget
PUBLISHED: 07-01-2014
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To support the high rates of proliferation, cancer cells undergo the metabolic reprogramming: aerobic glycolysis and glutamine addiction. Though glucose regulated protein 78 (GRP78) is a glucose-sensing protein and frequently highly expressed in tumor cells, its roles in glucose and glutamine metabolic regulation remain poorly unknown. We report here that glucose deficiency-induced GRP78 enhances ?-catenin signaling and consequently promotes its downstream c-Myc-mediated glutamine metabolism in colorectal cancer cells. Mechanistically, GRP78 elevates intracellular free ?-catenin level via disruption of adenomatous polyposis coli (APC)-?-catenin and E-cadherin-?-catenin protein complexes. Notably, overexpression of GRP78 causes APC protein downregulation in proteasome- and lysosome-independent manners. Further mechanistic studies reveal that GRP78 facilitates the extracellular release of APC, thereby rendering the liberation of ?-catenin from APC. Furthermore, GRP78 acts through both hindering E-cadherin expression and impairing the interaction of E-cadherin with ?-catenin to indirectly and directly influence E-cadherin-?-catenin complex stability. Our study reveals that GRP78 is a novel molecular link between metabolic alterations and signal transduction during tumor progression.
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Ethyl 2,6-bis-(4-chloro-phen-yl)-1-iso-cyano-4-oxo-cyclo-hexa-necarboxyl-ate.
Acta Crystallogr Sect E Struct Rep Online
PUBLISHED: 06-21-2014
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In the title compound, C22H19Cl2NO3, the central six-membered ring is in a twist-boat conformation. The two aryl groups are in equatorial positions, trans to each other and with a dihedral angle of 77.50?(2)° between them. One of the least hindered -CH2- groups and one of the aryl-substituted C atoms, with its axial H atom, are in the flagpole positions. The eth-oxy-carbonyl group is in an equatorial position and is cis to the second aryl group. In the crystal, molecules are linked via weak C-H?O hydrogen bonds, forming chains along [010].
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PKM2 depletion induces the compensation of glutaminolysis through ?-catenin/c-Myc pathway in tumor cells.
Cell. Signal.
PUBLISHED: 06-21-2014
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The metabolic activity in cancer cells primarily rely on aerobic glycolysis. Besides glycolysis, some tumor cells also exhibit excessive addition to glutamine, which constitutes an advantage for tumor growth. M2-type pyruvate kinase (PKM2) plays a pivotal role in sustaining aerobic glycolysis, pentose phosphate pathway and serine synthesis pathway. However, the participation of PKM2 in glutaminolysis is little to be known. Here we demonstrated that PKM2 depletion could provoke glutamine metabolism by enhancing the ?-catenin signaling pathway and consequently promoting its downstream c-Myc-mediated glutamine metabolism in colon cancer cells. Treatment with 2-deoxy-d-glucose (2-DG), a glycolytic inhibitor, got consistent results with the above. In addition, the dimeric form of PKM2, which lacks the pyruvate kinase activities, plays a critical role in regulating ?-catenin. Moreover, we found that overexpression of PKM2 negatively regulated ?-catenin through miR-200a. These insights supply evidence that glutaminolysis plays a compensatory role for cell survival upon glucose metabolism impaired.
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The multifaceted regulation and functions of PKM2 in tumor progression.
Biochim. Biophys. Acta
PUBLISHED: 06-16-2014
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Tumor cells undergo metabolic rewiring from oxidative phosphorylation towards aerobic glycolysis to maintain the increased anabolic requirements for cell proliferation. It is widely accepted that specific expression of the M2 type pyruvate kinase (PKM2) in tumor cells contributes to this aerobic glycolysis phenotype. To date, researchers have uncovered myriad forms of functional regulation for PKM2, which confers a growth advantage on the tumor cells to enable them to adapt to various microenvironmental signals. Here the richness of our understanding on the modulations and functions of PKM2 in tumor progression is reviewed, and some new insights into the paradoxical expression and functional differences of PKM2 in distinct cancer types are offered.
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[Study on the distribution of superantigen of group A streptococcus isolated from children in Beijing, 2011].
Zhonghua Liu Xing Bing Xue Za Zhi
PUBLISHED: 05-17-2014
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To analyze the prevalence of super-antigens (SAgs) of group A streptococcus (GAS)isolated from Beijing pediatric patients in 2011, and to explore the relationship between emm types, characteristics of patients and SAgs.
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Metabolic engineering of Escherichia coli for poly(3-hydroxypropionate) production from glycerol and glucose.
Biotechnol. Lett.
PUBLISHED: 05-13-2014
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A new poly(3-hydroxypropionate) (P3HP) biosynthetic pathway employing ?-alanine as an intermediate from an inexpensive carbon source was developed in recombinant Escherichia coli. After a series of systematic optimization, the genes for L-aspartate decarboxylase and its maturation factor (panD and panM, from E. coli), ?-alanine-pyruvate transaminase (pp0596, from Pseudomonas putida), 3-hydroxy acid dehydrogenase and 3-hydroxypropionyl-CoA synthase (ydfG and prpE respectively, from E. coli), and polyhydroxyalkanoate synthase (phaC1, from Cupriavidus necator) were cloned and expressed in E. coli. Under shake-flask conditions, the recombinant strain produced 0.5 g P3HP l(-1) from glycerol and glucose, up to 10.2 % of CDW. Though the content of P3HP was low, this pathway has some advantages over other reported pathways, such as being redox neutral, does not require any coenzyme, and can use a wide range of carbon sources.
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Enhanced photoelectrochemical water splitting performance of TiO2 nanotube arrays coated with an ultrathin nitrogen-doped carbon film by molecular layer deposition.
Nanoscale
PUBLISHED: 05-13-2014
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Vertically oriented TiO2 nanotube arrays (TNTAs) were conformally coated with an ultrathin nitrogen-doped (N-doped) carbon film via the carbonization of a polyimide film deposited by molecular layer deposition and simultaneously hydrogenated, thereby creating a core/shell nanostructure with a precisely controllable shell thickness. The core/shell nanostructure provides a larger heterojunction interface to substantially reduce the recombination of photogenerated electron-hole pairs, and hydrogenation enhances solar absorption of TNTAs. In addition, the N-doped carbon film coating acts as a high catalytic active surface for oxygen evolution reaction, as well as a protective film to prevent hydrogen-treated TiO2 nanotube oxidation by electrolyte or air. As a result, the N-doped carbon film coated TNTAs displayed remarkably improved photocurrent and photostability. The TNTAs with a N-doped carbon film of ? 1 nm produces a current density of 3.6 mA cm(-2) at 0 V vs. Ag/AgCl under the illumination of AM 1.5 G (100 mW cm(-2)), which represents one of the highest values achieved with modified TNTAs. Therefore, we propose that ultrathin N-doped carbon film coating on materials is a viable approach to enhance their PEC water splitting performance.
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Detecting temporal protein complexes from dynamic protein-protein interaction networks.
BMC Bioinformatics
PUBLISHED: 05-10-2014
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Proteins dynamically interact with each other to perform their biological functions. The dynamic operations of protein interaction networks (PPI) are also reflected in the dynamic formations of protein complexes. Existing protein complex detection algorithms usually overlook the inherent temporal nature of protein interactions within PPI networks. Systematically analyzing the temporal protein complexes can not only improve the accuracy of protein complex detection, but also strengthen our biological knowledge on the dynamic protein assembly processes for cellular organization.
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Size-selective catalytic growth of nearly 100% pure carbon nanocoils with copper nanoparticles produced by atomic layer deposition.
ACS Nano
PUBLISHED: 05-05-2014
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In this paper, Cu nanoparticles with narrow size distribution are synthesized by reduction of CuO films produced by atomic layer deposition (ALD), which are used as catalysts for the catalytic growth of carbon nanostructures. By properly adjusting the ALD cycle numbers, the size of produced Cu nanoparticles can be well controlled. Uniform carbon nanocoils with near 100% purity can be obtained by using 50-80 nm Cu nanoparticles, while thin straight fibers and thick straight fibers are produced by applying 5-35 and 100-200 nm Cu nanoparticles, respectively. The mechanism of the particle size-dependent growth of the carbon nanostructure was analyzed based on the experimental results and theoretical simulation. Our results can provide important information for the preparation of helical carbon nanostructures with high purity. Moreover, this work also demonstrates that ALD is a viable technique for synthesizing nanoparticles with highly controllable size and narrow size distribution suitable for studying particle size-dependent catalytic behavior and other applications.
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Influenza vaccine effectiveness against medically-attended influenza illness during the 2012-2013 season in Beijing, China.
Vaccine
PUBLISHED: 04-28-2014
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Influenza vaccine coverage remains low in China, and there is limited information on the preventive value of local vaccination programs.
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Modification of indium tin oxide with persulfate-based photochemistry toward facile, rapid, and low-temperature interface-mediated multicomponent assembling.
Langmuir
PUBLISHED: 04-21-2014
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The well-controlled material assembly and patterning on indium tin oxide (ITO) coating layer is of great importance for the practical fabrication of a functional device. Nonetheless, the conventional way to achieve this aim is still mainly based on the combination of photolithography with pattern transfer techniques (e.g., wet/dry etching, ?CP) due to the lack of one method that is able to directly afford site-selective ITO surface tailoring and subsequent templating for material assembly. Herein, we reported a novel, fast, and efficient photochemical reaction to accurately tailor the surface property of ITO with light-controlled site-selectivity, thus resulting in direct photoresist-free and etching/contact-free lithographic patterning of building blocks, e.g., ZnO, BaTiO3, CdS, lipid membrane, conductive polymers, colloids, and liquid crystals. The entire process reveals new interfacial chemistry suitable for inorganic metal oxide and its important versatile implications for low-cost fabrication of large-area flat and flexible optical/electronic/biorelated devices.
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Risk of bone fractures associated with glucagon-like peptide-1 receptor agonists' treatment: a meta-analysis of randomized controlled trials.
Endocrine
PUBLISHED: 04-19-2014
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Traditional anti-diabetic drugs may have negative or positive effects on risk of bone fractures. Yet the relationship between the new class glucagon-like peptide-1 receptor agonists (GLP-1 RA) and risk of bone fractures has not been established. We performed a meta-analysis including randomized controlled trials (RCT) to study the risk of bone fractures associated with liraglutide or exenatide, compared to placebo or other active drugs. We searched MEDLINE, EMBASE, and clinical trial registration websites for published or unpublished RCTs comparing the effects of liraglutide or exenatide with comparators. Only studies with disclosed bone fracture data were included. Separate pooled analysis was performed for liraglutide or exenatide, respectively, by calculating Mantel-Haenszel odds ratio (MH-OR). 16 RCTs were identified including a total of 11,206 patients. Liraglutide treatment was associated with a significant reduced risk of incident bone fractures (MH-OR = 0.38, 95 % CI 0.17-0.87); however, exenatide treatment was associated with an elevated risk of incident bone fractures (MH-OR = 2.09, 95 % CI 1.03-4.21). Publication bias and heterogeneity between studies were not observed. Our study demonstrated a divergent risk of bone fractures associated with different GLP-1 RA treatments. The current findings need to be confirmed by future well-designed prospective or RCT studies.
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Effect of HbA1C detection on the diagnostic screening for glucose metabolic disorders in polycystic ovary syndrome.
Clin Exp Obstet Gynecol
PUBLISHED: 04-09-2014
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This study aimed to assess the effect of hemoglobin A1C (HbA1C) detection on the diagnostic screening for glucose metabolic disorders in women with polycystic ovary syndrome (PCOS).
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The effect of electronic medical record application on the length of stay in a Chinese general hospital: a department- and disease-focused interrupted time-series study.
J Med Syst
PUBLISHED: 04-07-2014
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A key purpose of electronic medical records (EMR) introduced in medical institutions is to improve work efficiency. The average length of stay (LOS) is just an important indicator to evaluate work efficiency of medical care in hospitals. Recently, there have been reports about effects of EMR application on LOS in medical institutions, but they have been mostly based on the overall analysis of a region or a hospital and not of specific clinical departments and diseases or based on longer time periods. Therefore, in this study, we selected four clinical departments and four diseases with the largest number of inpatients from January 2004 to December 2012 in a Chinese 3A general hospital and used an interrupted time-series method by the departments and diseases to analyze the relationship of EMR application and LOS. Through our analyses, we concluded that, under unadjusted condition, LOS were all reduced (P?
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Inflammatory myofibroblastic tumor of the thigh without bone involvement: a case report.
World J Surg Oncol
PUBLISHED: 03-30-2014
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Inflammatory myofibroblastic tumors are rare, and those located in the extremities without bone involvement are even rarer. We present the case of a 61-year-old Chinese male patient with an inflammatory myofibroblastic tumor of the right thigh. It was excised and a histopathologic examination revealed an inflammatory myofibroblastic tumor. This case is presented by virtue of its rare location.
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Chemoselective phototransformation of C-H bonds on a polymer surface through a photoinduced cerium recycling redox reaction.
Chemistry
PUBLISHED: 03-26-2014
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It is generally accepted that Ce(4+) is unable to directly oxidize unreactive alkyl C-H bonds without the assistance of adjacent polar groups. Herein, we demonstrate in our newly developed confined photochemical reaction system that this recognized issue may be challenged. As we found, when a thin layer of a CeCl(3)/HCl aqueous solution was applied to a polymeric substrate and the substrate subjected to UV irradiation, Ce(3+) was first photooxidized to form Ce(4+) in the presence of H(+), and the in situ formed Ce(4+) then performs an oxidation reaction on the C-H bonds of the polymer surface to form surface-carbon radicals for radical graft polymerization reactions and functional-group transformations, while reducing to Ce(3+) and releasing H(+) in the process. This photoinduced cerium recycling redox (PCRR) reaction behaved as a biomimetic system in an artificial recycling reaction, leading to a sustainable chemical modification strategy for directly transforming alkyl C-H bonds on polymer surfaces into small-molecule groups and polymer brushes. This method is expected to provide a green and economical tool for industrial applications of polymer-surface modification.
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Hydroxylation of organic polymer surface: method and application.
ACS Appl Mater Interfaces
PUBLISHED: 03-06-2014
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It may be hardly believable that inert C-H bonds on a polymeric material surface could be quickly and efficiently transformed into C-OH by a simple and mild way. Thanks to the approaches developed recently, it is now possible to transform surface H atoms of a polymeric substrate into monolayer OH groups by a simple/mild photochemical reaction. Herein the method and application of this small-molecular interfacial chemistry is highlighted. The existence of hydroxyl groups on material surfaces not only determines the physical and chemical properties of materials but also provides effective reaction sites for postsynthetic sequential modification to fulfill the requirements of various applications. However, organic synthetic materials based on petroleum, especially polyolefins comprise mainly C and H atoms and thus present serious surface problems due to low surface energy and inertness in reactivity. These limitations make it challenging to perform postsynthetic surface sequential chemical derivatization toward enhanced functionalities and properties and also cause serious interfacial problems when bonding or integrating polymer substrates with natural or inorganic materials. Polymer surface hydroxylation based on direct conversion of C-H bonds on polymer surfaces is thus of significant importance for academic and practical industrial applications. Although highly active research results have reported on small-molecular C-H bond activation in solution (thus homogeneous), most of them, featuring the use of a variety of transition metals as catalysts, present a slow reaction rate, a low atom economy and an obvious environmental pollution. In sharp contrast to these conventional C-H activation strategies, the present Spotlight describes a universal confined photocatalytic oxidation (CPO) system that is able to directly convert polymer surface C-H bonds to C-OSO3(-) and, subsequently, to C-OH through a simple hydrolysis. Generally speaking, these newly implanted hydroxyl groups preserve their own reactivity toward other complementary compounds, thus creating a novel base with distinct surface properties. Thanks to this functionalized platform, a wide range of organic, inorganic and metal materials have been attached to conventional organic polymer substrates through the rational engineering of surface molecular templates from small functional groups to macromolecules. It is expected that the proposed novel CPO method and its versatile usages in advanced material applications will offer new opportunities for a variety of scientific communities, especially for those working on surface/interface modulation.
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Biofeedback-guided pelvic floor exercise therapy for obstructive defecation: an effective alternative.
World J. Gastroenterol.
PUBLISHED: 02-26-2014
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To compare biofeedback-guided pelvic floor exercise therapy (BFT) with the use of oral polyethylene glycol (PEG) for the treatment of obstructive defecation.
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Pyruvate kinase M2 facilitates colon cancer cell migration via the modulation of STAT3 signalling.
Cell. Signal.
PUBLISHED: 02-14-2014
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Understanding the mechanisms of colorectal cancer (CRC) metastatic progression is essential to reducing its morbidity and mortality. Pyruvate kinase (PK) catalyses the final step of glycolysis and has been identified as a critical regulator of glucose consumption. However, the mechanisms and roles of PKM1 and PKM2 in the regulation of CRC cell migration and cell adhesion remain elusive. Here, we report that PKM2 rather than PKM1 drives CRC cell migration and cell adhesion, whereas PKM attenuation reverses these phenomena. Furthermore, the overexpression of PKM2 significantly increases the expression of N-cadherin, MMP-2, MMP-9, STAT3, Snail-2, pFAK and active ?1-integrin, while E-cadherin expression is suppressed. More importantly, the results indicated that PKM2 overexpression facilitates STAT3 nuclear translocation, and it is required for PKM2 function in the regulation of migration and adhesion associated signalling. In addition, the dimeric form of PKM2, which lacks the pyruvate kinase activities but possesses protein kinase activity, is critical for CRC cell migration and cell adhesion. Overall, this study suggests that PKM2 overexpression promotes CRC cell migration and cell adhesion by regulating STAT3-associated signalling and that PKM2 may serve as a therapeutic target for CRC metastasis.
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Molecular mechanism of inhibitory effects of C-phycocyanin combined with all-trans-retinoic acid on the growth of HeLa cells in vitro.
Tumour Biol.
PUBLISHED: 02-10-2014
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We studied the effects of all-trans-retinoic acid (ATRA), C-phycocyanin (C-PC), or ATRA+C-PC on the growth of cervical cells (HeLa cells), cell cycle distribution, and apoptosis. The anticancer mechanism of the drug combination was revealed. MTT assay was adopted to determine the effects of C-PC and ATRA on the growth of HeLa cells. The expression quantities of cyclin-dependent kinase (CDK) 4, cyclin D1, Bcl-2, caspase-3, and CD59 were determined by in situ hybridization, immunofluorescence, immunohistochemistry staining, Western blot, and RT-PCR. TUNEL assay was adopted to determine the cellular apoptosis levels. Both C-PC and ATRA could inhibit the growth of HeLa cells, and the combination of ATRA+C-PC functioned cooperatively to induce apoptosis in HeLa cells. The dosage of ATRA was reduced when it cooperated with C-PC to reduce the toxicity. ATRA treated with C-PC could induce more cell cycle arrests than the single drug used by decrease in cyclin D1 and CDK4 expression. The combination of the two drugs could upregulate caspase-3 and downregulate the Bcl-2 gene and induce cell apoptosis. Moreover, the combination therapy has an important immunological significance in decreased expression of the CD59 protein. Singly, C-PC or ATRA could inhibit the growth of HeLa cells, and the effects of treatment were further enhanced in the combination group. In combination with C-PC, the dosage of ATRA was effectively reduced. The C-PC?+?ATRA combination might take effect by inhibiting the progress of the cell cycle, inducing cell apoptosis and promoting complement-mediated cytolysis.
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Improved cognitive outcome after progesterone administration is associated with protecting hippocampal neurons from secondary damage studied in vitro and in vivo.
Behav. Brain Res.
PUBLISHED: 01-28-2014
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Previous studies reported that progesterone could improve cognitive outcome following TBI. Moreover, some evidence implied that the hippocampus is associated with cognitive function. The aim of this study was to investigate the neuroprotective effects of progesterone on hippocampal neurons in vitro and in vivo, and its in?uence on the cognitive outcome. In vitro, the model of primary cultured hippocampal neurons against glutamate-induced excitotoxic damage was used. After 10-day culture, neurons were pretreated with progesterone in a concentration 10 ng/ml, 48 h before a 5-min exposure to 200 ?mol/l glutamate. Then 24h after glutamate exposure, the nerve cells were observed and LDH was detected. The results showed progesterone protected the cultured hippocampal neurons morphology and significantly reduced the amount of LDH. In vivo, the model of TBI was established by modified Feeney's weight-dropping method. The progesterone was given in a dose of 16 mg/kg by intraperitoneal injection 1h post injury and subsequent injections subcutaneously at 6h and 12h after TBI. Brain samples were extracted at 24h after injury. Histology and the iNOS expression were examined by Nissl stain, immunohistochemistry and Western blot. The cognitive outcome was assessed by Morris water maze test (MWM). The results revealed that the neuronal cell damage and the expression of iNOS in the hippocampus CA1 were significantly decreased after progesterone administration. Progesterone significantly improved cognitive outcome after TBI. The results suggest that the positive effects of progesterone on cognitive outcome may be linked to protecting hippocampal neurons from secondary damage.
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LDsplit: screening for cis-regulatory motifs stimulating meiotic recombination hotspots by analysis of DNA sequence polymorphisms.
BMC Bioinformatics
PUBLISHED: 01-27-2014
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As a fundamental genomic element, meiotic recombination hotspot plays important roles in life sciences. Thus uncovering its regulatory mechanisms has broad impact on biomedical research. Despite the recent identification of the zinc finger protein PRDM9 and its 13-mer binding motif as major regulators for meiotic recombination hotspots, other regulators remain to be discovered. Existing methods for finding DNA sequence motifs of recombination hotspots often rely on the enrichment of co-localizations between hotspots and short DNA patterns, which ignore the cross-individual variation of recombination rates and sequence polymorphisms in the population. Our objective in this paper is to capture signals encoded in genetic variations for the discovery of recombination-associated DNA motifs.
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A quantitative chemical proteomics approach to profile the specific cellular targets of andrographolide, a promising anticancer agent that suppresses tumor metastasis.
Mol. Cell Proteomics
PUBLISHED: 01-20-2014
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Drug target identification is a critical step toward understanding the mechanism of action of a drug, which can help one improve the drug's current therapeutic regime and expand the drug's therapeutic potential. However, current in vitro affinity-chromatography-based and in vivo activity-based protein profiling approaches generally face difficulties in discriminating specific drug targets from nonspecific ones. Here we describe a novel approach combining isobaric tags for relative and absolute quantitation with clickable activity-based protein profiling to specifically and comprehensively identify the protein targets of andrographolide (Andro), a natural product with known anti-inflammation and anti-cancer effects, in live cancer cells. We identified a spectrum of specific targets of Andro, which furthered our understanding of the mechanism of action of the drug. Our findings, validated through cell migration and invasion assays, showed that Andro has a potential novel application as a tumor metastasis inhibitor. Moreover, we have unveiled the target binding mechanism of Andro with a combination of drug analog synthesis, protein engineering, and mass-spectrometry-based approaches and determined the drug-binding sites of two protein targets, NF-?B and actin.
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Efficacy of face masks and respirators in preventing upper respiratory tract bacterial colonization and co-infection in hospital healthcare workers.
Prev Med
PUBLISHED: 01-15-2014
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We compared the efficacy of medical masks (MM) and N95 respirators (N95) in preventing bacterial colonization/infection in healthcare workers (HCWs).
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Behavioural factors associated with diarrhea among adults over 18 years of age in Beijing, China.
BMC Public Health
PUBLISHED: 01-14-2014
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To date, a large proportion of people still suffer from diarrhea diseases. In addition to the burden of diarrhea, there are substantial social and economic costs caused by the high incidence of diarrheal diseases. Therefore, the purpose of this study was to explore the self-reported prevalence of diarrhea and associated risk factors of diarrhea among adults in Beijing, China.
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Post-pandemic assessment of public knowledge, behavior, and skill on influenza prevention among the general population of Beijing, China.
Int. J. Infect. Dis.
PUBLISHED: 01-05-2014
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The aim of this study was to assess the knowledge, behavioral, and skill responses toward influenza in the general population of Beijing after pandemic influenza A (H1N1) 2009.
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Transcriptome Sequencing and De Novo Analysis of Cytoplasmic Male Sterility and Maintenance in JA-CMS Cotton.
PLoS ONE
PUBLISHED: 01-01-2014
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Cytoplasmic male sterility (CMS) is the failure to produce functional pollen, which is inherited maternally. And it is known that anther development is modulated through complicated interactions between nuclear and mitochondrial genes in sporophytic and gametophytic tissues. However, an unbiased transcriptome sequencing analysis of CMS in cotton is currently lacking in the literature. This study compared differentially expressed (DE) genes of floral buds at the sporogenous cells stage (SS) and microsporocyte stage (MS) (the two most important stages for pollen abortion in JA-CMS) between JA-CMS and its fertile maintainer line JB cotton plants, using the Illumina HiSeq 2000 sequencing platform. A total of 709 (1.8%) DE genes including 293 up-regulated and 416 down-regulated genes were identified in JA-CMS line comparing with its maintainer line at the SS stage, and 644 (1.6%) DE genes with 263 up-regulated and 381 down-regulated genes were detected at the MS stage. By comparing the two stages in the same material, there were 8 up-regulated and 9 down-regulated DE genes in JA-CMS line and 29 up-regulated and 9 down-regulated DE genes in JB maintainer line at the MS stage. Quantitative RT-PCR was used to validate 7 randomly selected DE genes. Bioinformatics analysis revealed that genes involved in reduction-oxidation reactions and alpha-linolenic acid metabolism were down-regulated, while genes pertaining to photosynthesis and flavonoid biosynthesis were up-regulated in JA-CMS floral buds compared with their JB counterparts at the SS and/or MS stages. All these four biological processes play important roles in reactive oxygen species (ROS) homeostasis, which may be an important factor contributing to the sterile trait of JA-CMS. Further experiments are warranted to elucidate molecular mechanisms of these genes that lead to CMS.
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Discoidin Domain Receptor 1 Contributes to Tumorigenesis through Modulation of TGFBI Expression.
PLoS ONE
PUBLISHED: 01-01-2014
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Discoidin domain receptor 1 (DDR1) is a member of the receptor tyrosine kinase family. The receptor is activated upon binding to its ligand, collagen, and plays a crucial role in many fundamental processes such as cell differentiation, adhesion, migration and invasion. Although DDR1 is expressed in many normal tissues, upregulated expression of DDR1 in a variety of human cancers such as lung, colon and brain cancers is known to be associated with poor prognosis. Using shRNA silencing, we assessed the oncogenic potential of DDR1. DDR1 knockdown impaired tumor cell proliferation and migration in vitro and tumor growth in vivo. Microarray analysis of tumor cells demonstrated upregulation of TGFBI expression upon DDR1 knockdown, which was subsequently confirmed at the protein level. TGFBI is a TGF?-induced extracellular matrix protein secreted by the tumor cells and is known to act either as a tumor promoter or tumor suppressor, depending on the tumor environment. Here, we show that exogenous addition of recombinant TGFBI to BXPC3 tumor cells inhibited clonogenic growth and migration, thus recapitulating the phenotypic effect observed from DDR1 silencing. BXPC3 tumor xenografts demonstrated reduced growth with DDR1 knockdown, and the same xenograft tumors exhibited an increase in TGFBI expression level. Together, these data suggest that DDR1 expression level influences tumor growth in part via modulation of TGFBI expression. The reciprocal expression of DDR1 and TGFBI may help to elucidate the contribution of DDR1 in tumorigenesis and TGFBI may also be used as a biomarker for the therapeutic development of DDR1 specific inhibitors.
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Efficiency of individual dosage of digoxin with calculated concentration.
Clin Interv Aging
PUBLISHED: 01-01-2014
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Digoxin is a frequently prescribed drug, particularly in the elderly population, in which there is an increased prevalence of atrial fibrillation and cardiac failure. With its complex pharmacokinetic profile and narrow therapeutic index, use of digoxin requires regular monitoring of blood levels. Recent evidence suggests that a lower concentration range (0.4-1.0 ng/mL) is preferable in patients with congestive heart failure and a higher range (0.8-2.0 ng/mL) is needed in patients with atrial tachyarrhythmia. The Konishi equation is widely used to predict the serum digoxin concentration (SDC) in Japan. This study assessed the correlation between SDC predicted by the Konishi equation and that actually measured in Chinese patients and investigated the impact of renal function on SDC.
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Differences in meiotic recombination rates in childhood acute lymphoblastic leukemia at an MHC class II hotspot close to disease associated haplotypes.
PLoS ONE
PUBLISHED: 01-01-2014
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Childhood Acute Lymphoblastic Leukemia (ALL) is a malignant lymphoid disease of which B-cell precursor- (BCP) and T-cell- (T) ALL are subtypes. The role of alleles encoded by major histocompatibility loci (MHC) have been examined in a number of previous studies and results indicating weak, multi-allele associations between the HLA-DPB1 locus and BCP-ALL suggested a role for immunosusceptibility and possibly infection. Two independent SNP association studies of ALL identified loci approximately 37 kb from one another and flanking a strong meiotic recombination hotspot (DNA3), adjacent to HLA-DOA and centromeric of HLA-DPB1. To determine the relationship between this observation and HLA-DPB1 associations, we constructed high density SNP haplotypes of the 316 kb region from HLA-DMB to COL11A2 in childhood ALL and controls using a UK GWAS data subset and the software PHASE. Of four haplotype blocks identified, predicted haplotypes in Block 1 (centromeric of DNA3) differed significantly between BCP-ALL and controls (P?=?0.002) and in Block 4 (including HLA-DPB1) between T-ALL and controls (P?=?0.049). Of specific common (>5%) haplotypes in Block 1, two were less frequent in BCP-ALL, and in Block 4 a single haplotype was more frequent in T-ALL, compared to controls. Unexpectedly, we also observed apparent differences in ancestral meiotic recombination rates at DNA3, with BCP-ALL showing increased and T-ALL decreased levels compared to controls. In silico analysis using LDsplit sotware indicated that recombination rates at DNA3 are influenced by flanking loci, including SNPs identified in childhood ALL association studies. The observed differences in rates of meiotic recombination at this hotspot, and potentially others, may be a characteristic of childhood leukemia and contribute to disease susceptibility, alternatively they may reflect interactions between ALL-associated haplotypes in this region.
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Total osteocalcin in serum predicts testosterone level in male type 2 diabetes mellitus.
Int J Clin Exp Med
PUBLISHED: 01-01-2014
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To investigate the relationship between total osteocalcin (total OC) and testosterone level in the serum of male patients with type 2 diabetes mellitus (T2DM).
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Luteolin inhibits behavioral sensitization by blocking methamphetamine-induced MAPK pathway activation in the caudate putamen in mice.
PLoS ONE
PUBLISHED: 01-01-2014
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To investigate the effect of luteolin on methamphetamine (MA)-induced behavioral sensitization and mitogen-activated protein kinase (MAPK) signal transduction pathway activation in mice.
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Ensemble positive unlabeled learning for disease gene identification.
PLoS ONE
PUBLISHED: 01-01-2014
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An increasing number of genes have been experimentally confirmed in recent years as causative genes to various human diseases. The newly available knowledge can be exploited by machine learning methods to discover additional unknown genes that are likely to be associated with diseases. In particular, positive unlabeled learning (PU learning) methods, which require only a positive training set P (confirmed disease genes) and an unlabeled set U (the unknown candidate genes) instead of a negative training set N, have been shown to be effective in uncovering new disease genes in the current scenario. Using only a single source of data for prediction can be susceptible to bias due to incompleteness and noise in the genomic data and a single machine learning predictor prone to bias caused by inherent limitations of individual methods. In this paper, we propose an effective PU learning framework that integrates multiple biological data sources and an ensemble of powerful machine learning classifiers for disease gene identification. Our proposed method integrates data from multiple biological sources for training PU learning classifiers. A novel ensemble-based PU learning method EPU is then used to integrate multiple PU learning classifiers to achieve accurate and robust disease gene predictions. Our evaluation experiments across six disease groups showed that EPU achieved significantly better results compared with various state-of-the-art prediction methods as well as ensemble learning classifiers. Through integrating multiple biological data sources for training and the outputs of an ensemble of PU learning classifiers for prediction, we are able to minimize the potential bias and errors in individual data sources and machine learning algorithms to achieve more accurate and robust disease gene predictions. In the future, our EPU method provides an effective framework to integrate the additional biological and computational resources for better disease gene predictions.
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Transcriptome profiling of a multiple recurrent muscle-invasive urothelial carcinoma of the bladder by deep sequencing.
PLoS ONE
PUBLISHED: 01-01-2014
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Urothelial carcinoma of the bladder (UCB) is one of the commonly diagnosed cancers in the world. The UCB has the highest rate of recurrence of any malignancy. A genome-wide screening of transcriptome dysregulation between cancer and normal tissue would provide insight into the molecular basis of UCB recurrence and is a key step to discovering biomarkers for diagnosis and therapeutic targets. Compared with microarray technology, which is commonly used to identify expression level changes, the recently developed RNA-seq technique has the ability to detect other abnormal regulations in the cancer transcriptome, such as alternative splicing. In this study, we performed high-throughput transcriptome sequencing at ?50× coverage on a recurrent muscle-invasive cisplatin-resistance UCB tissue and the adjacent non-tumor tissue. The results revealed cancer-specific differentially expressed genes between the tumor and non-tumor tissue enriched in the cell adhesion molecules, focal adhesion and ECM-receptor interaction pathway. Five dysregulated genes, including CDH1, VEGFA, PTPRF, CLDN7, and MMP2 were confirmed by Real time qPCR in the sequencing samples and the additional eleven samples. Our data revealed that more than three hundred genes showed differential splicing patterns between tumor tissue and non-tumor tissue. Among these genes, we filtered 24 cancer-associated alternative splicing genes with differential exon usage. The findings from RNA-Seq were validated by Real time qPCR for CD44, PDGFA, NUMB, and LPHN2. This study provides a comprehensive survey of the UCB transcriptome, which provides better insight into the complexity of regulatory changes during recurrence and metastasis.
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In vitro and in vivo evaluation of cysteine and site specific conjugated herceptin antibody-drug conjugates.
PLoS ONE
PUBLISHED: 01-01-2014
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Antibody drug conjugates (ADCs) are monoclonal antibodies designed to deliver a cytotoxic drug selectively to antigen expressing cells. Several components of an ADC including the selection of the antibody, the linker, the cytotoxic drug payload and the site of attachment used to attach the drug to the antibody are critical to the activity and development of the ADC. The cytotoxic drugs or payloads used to make ADCs are typically conjugated to the antibody through cysteine or lysine residues. This results in ADCs that have a heterogeneous number of drugs per antibody. The number of drugs per antibody commonly referred to as the drug to antibody ratio (DAR), can vary between 0 and 8 drugs for a IgG1 antibody. Antibodies with 0 drugs are ineffective and compete with the ADC for binding to the antigen expressing cells. Antibodies with 8 drugs per antibody have reduced in vivo stability, which may contribute to non target related toxicities. In these studies we incorporated a non-natural amino acid, para acetyl phenylalanine, at two unique sites within an antibody against Her2/neu. We covalently attached a cytotoxic drug to these sites to form an ADC which contains two drugs per antibody. We report the results from the first direct preclinical comparison of a site specific non-natural amino acid anti-Her2 ADC and a cysteine conjugated anti-Her2 ADC. We report that the site specific non-natural amino acid anti-Her2 ADCs have superior in vitro serum stability and preclinical toxicology profile in rats as compared to the cysteine conjugated anti-Her2 ADCs. We also demonstrate that the site specific non-natural amino acid anti-Her2 ADCs maintain their in vitro potency and in vivo efficacy against Her2 expressing human tumor cell lines. Our data suggests that site specific non-natural amino acid ADCs may have a superior therapeutic window than cysteine conjugated ADCs.
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Surveillance for Avian Influenza A(H7N9), Beijing, China, 2013.
Emerging Infect. Dis.
PUBLISHED: 11-27-2013
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During surveillance for pneumonia of unknown etiology and sentinel hospital-based surveillance in Beijing, China, we detected avian influenza A(H7N9) virus infection in 4 persons who had pneumonia, influenza-like illness, or asymptomatic infections. Samples from poultry workers, associated poultry environments, and wild birds suggest that this virus might not be present in Beijing.
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An optical sensing strategy leading to in situ monitoring of the degradation of mesoporous magnetic supraparticles in cells.
ACS Appl Mater Interfaces
PUBLISHED: 11-27-2013
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Mesoporous magnetic supraparticles (meso-MSPs) as multifunctional targeted drug carriers have attracted much attention, because of their easy magnetic-field manipulation and in situ sensing functionality. In this paper, a Fe(3+)-selective chemodosimeter fluorescent probe (FP-1) was synthesized and loaded inside of the meso-MSPs (meso-MSPs/probe); the meso-MSPs/probe nanocomposites were then used to monitor the degradation of meso-MSPs in cells. In our experiments, strong fluorescence intensity was observed in HeLa cells, because of their acidic intracellular environment, which can quickly degrade the meso-MSPs and then release Fe(3+) ions in cells that, in turn, activate the fluorescence of FP-1. Meanwhile, a very weak fluorescence signal was detected in HEK 293T cells due to the relative neutral intracellular environment of HEK 293T cells, which prevented the Fe(3+) ion from leaching out of meso-MSPs. Moreover, this degradation-luminescence relationship of the meso-MSPs/probe nanocomposites not only assisted us to understand the degradation status of meso-MSPs in cells, but also allowed us to recognize the peculiarity of different cells with various intracellular environments.
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A cross-sectional study of factors associated with uptake of vaccination against influenza among older residents in the postpandemic season in Beijing, China.
BMJ Open
PUBLISHED: 11-22-2013
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Annually, influenza epidemics are associated with high mortality rates, notably among elderly persons. The aim of the study was to examine the level of influenza vaccine coverage among Chinese residents aged 60 years and older and to examine the demographic, behavioural and lifestyle health factors associated with vaccine receipt.
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Seven novel coordination polymers constructed by rigid 4-(4-carboxyphenyl)-terpyridine ligands: synthesis, structural diversity, luminescence and magnetic properties.
Dalton Trans
PUBLISHED: 11-08-2013
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Seven coordination polymers, namely [Mn(4-cptpy)2]n (1), [Co(4-cptpy)2]n (2), [Mn3(4-cptpy)6(H2O)]n·2nH2O (3), [Co(4-cptpy)(HCOO)(H2O)]n·nDMF (4), [Zn2(4-Hcptpy)2Cl4]n·2nC2H5OH·nH2O (5), [Co4(3-cptpy)4(HCOO)4(H2O)2]n (6), and [Mn(3-cptpy)2]n (7) (4-Hcptpy = 4-(4-carboxyphenyl)-4,2:6,4-terpyridine; 3-Hcptpy = 4-(4-carboxyphenyl)-3,2:6,3-terpyridine), have been synthesized under hydro(solvo)thermal conditions and structurally characterized. A general solvothermal method is proposed for preparing carboxylate complexes in DMF solution without any basic additive. 1 and 2 possess isostructural 3D metal-organic frameworks containing nanosized cavities. 3 is a beautiful 2D coordination polymer assembled by flower-like Mn3(4-cptpy)6(H2O) subunits. 4 and 6 both display 2D polymeric networks constructed from 4/3-cptpy(-) ligands, in which the formate ligands originate from the hydrolysis of DMF. 5 is a 1D 21 helical chain polymer. 7 shows a 2D network with a (3.6) two-nodal kgd topology. 4/3-Hcptpy ligands display seven types of coordination modes. The zinc complex 5 emits strong violet luminescence. 1 and 2 are both thermally stable below 440 °C and exhibit antiferromagnetic interactions.
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Stimuli-responsive biodegradable poly(methacrylic acid) based nanocapsules for ultrasound traced and triggered drug delivery system.
Biomaterials
PUBLISHED: 10-30-2013
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Ultrasound contrast agents (UCAs) have been investigated for echogenic intravenous drug delivery system. Due to the traditional UCAs with overlarge size (micro-scale), their reluctant accumulation in target organs and the instability have presented severe obstacles to the accurate response to the ultrasound and severely limited their further clinical application. Furthermore, elimination of drug carriers from the biologic system after their carrying out the diagnostic or therapeutic functions is one important aspect to be considered. The drug carriers with large sizes, avoiding renal filtration, will lead to increasing toxicity. In this present paper, we design and develop a new type of triple-stimuli responsive (ultrasound/pH/GSH) biodegradable nanocapsules, in which fill up with perfluorohexane, and the DOX-loaded PMAA with disulfide crosslinking forms the wall. These soft nanocapsules with uniform size of 300 nm can easily enter the tumor tissues via EPR effects. The PMAA shell has high DOX-loading content (36 wt%) and great drug loading efficiency (93.5%), the PFH filled can effectively enhance US imaging signal through acoustic droplet vaporization (ADV), ensuring diagnostic and image-guided therapeutic applications. What is more, the disulfide-crosslinked PMAA shell is biodegradable and thus safe for normal organisms. These merits enabled us optimize the balance of diagnostic, therapeutic and biodegradable functionalities in a multifunctional theranostic nanoplatform.
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Reliable and Fast Estimation of Recombination Rates by Convergence Diagnosis and Parallel Markov Chain Monte Carlo.
IEEE/ACM Trans Comput Biol Bioinform
PUBLISHED: 10-30-2013
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Genetic recombination is an essential event during the process of meiosis resulting in an exchange of segments between paired chromosomes. Estimating recombination rate is crucial for understanding evolution. Experimental methods are normally difficult and limited to small scale estimations. Thus statistical methods using population genetic data are important for large-scale analysis. LDhat is an extensively used statistical method using rjMCMC algorithm to predict recombination rates. Due to the complexity of rjMCMC scheme, LDhat may take a long time to generate results for large SNP data. In addition, rjMCMC parameters should be manually defined in the original program that directly impact results. To address these issues, we designed an improved algorithm based on LDhat implementing MCMC convergence diagnostic algorithms to automatically predict values of parameters and monitor the mixing process. Then parallel computation methods were employed to further accelerate the new program. The new algorithms have been tested on ten samples from HapMap phase 2 datasets. The results were compared with previous code and showed nearly identical outputs, however our new methods achieved significant acceleration proving that they are more efficient and reliable for the estimation of recombination rates. The stand-alone package is freely available for download at http://www.ntu.edu.sg/home/zhengjie/software/CPLDhat/.
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[Early detection on the onset of scarlet fever epidemics in Beijing, using the Cumulative Sum].
Zhonghua Liu Xing Bing Xue Za Zhi
PUBLISHED: 09-11-2013
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Based on data related to scarlet fever which was collected from the Disease Surveillance Information Reporting System in Beijing from 2005 to 2011, to explore the efficiency of Cumulative Sum (CUSUM) in detecting the onset of scarlet fever epidcmics. Models as C1-MILD (C1), C2-MEDIUM (C2) and C3-ULTRA (C3) were used. Tools for evaluation as Youdens index and detection time were calculated to optimize the parameters and optimal model. Data on 2011 scarlet fever surveillance was used to verify the efficacy of these models. C1 (k = 0.5, H = 2?), C2 (k = 0.7, H = 2?), C3 (k = 1.1, H = 2?) appeared to be the optimal parameters among these models. Youdens index of C1 was 83.0% and detection time being 0.64 weeks, Youdens index of C2 was 85.4% and detection time being 1.27 weeks, Youdens index of C1 was 85.1% and detection time being 1.36 weeks. Among the three early warning detection models, C1 had the highest efficacy. Three models all triggered the signals within 4 weeks after the onset of scarlet fever epidemics. The early warning detection model of CUSUM could be used to detect the onset of scarlet fever epidemics, with good efficacy.
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Effects of FMN riboswitch on antioxidant activity in Deinococcus radiodurans under H2O2 stress.
Microbiol. Res.
PUBLISHED: 08-06-2013
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The flavin mononucleotide (FMN) riboswitch is structured noncoding RNA domains that control gene expression by selectively binding FMN or sensing surrounding changes without protein factors, which are involved in the biosynthesis and transport of riboflavin and related compounds. We constructed the deletion mutant of FMN riboswitch to investigate its possible role in response to H2O2 stress in Deinococcus radiodurans. The results showed that the deletion of FMN riboswitch resulted in an obvious growth delay in D. radiodurans. Compared with the survival rate of 56% of D. radiodurans, only 40% of the mutant survived after treated with 50mM of H2O2, indicating that deletion of FMN riboswitch obviously increased the susceptibility to H2O2. Compared with the wild type R1 strain of D. radiodurans, FMN riboswitch knockout cells accumulated a higher level of intracellular reactive oxygen species (ROS) while their total catalase activity reduced significantly. Results from quantitative real-time PCR analysis implies structural alterations of in response to H2O2 challenge. Our data suggest a critical role of FMN riboswitch in the oxidation tolerance system of D. radiodurans.
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A novel whole-phase succinate fermentation strategy with high volumetric productivity in engineered Escherichia coli.
Bioresour. Technol.
PUBLISHED: 07-30-2013
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The strategic design of this study aims at fermentative succinate production with high volumetric productivity in engineered Escherichia coli. An E. coli YL106/pSCsfcA was engineered to produce succinate under aerobic, microaerobic and anaerobic conditions by derepressing the inhibition of low dissolved oxygen, eliminating the NADH competitive pathways, modulating the redistribution of metabolic flux, and increasing the transport rate of the sole carbon source glucose. Based on this strain, a novel "whole-phase" succinate production strategy was further developed, in which the engineered strain was first cultivated aerobically, then shifted to microaerobic phase at the end of exponential growth, and finally kept in anaerobic phase until the end of fermentation. Employing this strategy, the engineered E. coli YL106/pSCsfcA was able to produce 85.30 g l(-1) succinate with an overall volumetric productivity of 2.13 g l(-1)h(-1). This process offers an efficiently fermentative method for industrial succinate production in metabolically engineered E. coli.
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A catalyst-free one-pot construction of skeletons of 5-methoxyseselin and alloxanthoxyletin in water.
Org. Lett.
PUBLISHED: 07-19-2013
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In refluxing water and without an additional catalyst, electron-rich phenols could react with alkynoic acids or alkynoates to provide coumarin structures. The skeletons of two natural pyranocoumarins, 5-methoxyseselin and alloxanthoxyletin, could be constructed (total yield up to 76%) in an aqueous multicomponent reaction in which isoprenyl acetate, propiolic acid, and phloroglucinol were simply mixed and refluxed in water.
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Influenza vaccination coverage rates among adults before and after the 2009 influenza pandemic and the reasons for non-vaccination in Beijing, China: a cross-sectional study.
BMC Public Health
PUBLISHED: 07-05-2013
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To optimize the vaccination coverage rates in the general population, the status of coverage rates and the reasons for non-vaccination need to be understood. Therefore, the objective of this study was to assess the changes in influenza vaccination coverage rates in the general population before and after the 2009 influenza pandemic (2008/2009, 2009/2010, and 2010/2011 seasons), and to determine the reasons for non-vaccination.
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Characteristics of group A Streptococcus strains circulating during scarlet fever epidemic, Beijing, China, 2011.
Emerging Infect. Dis.
PUBLISHED: 06-06-2013
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Scarlet fever is one of a variety of diseases caused by group A Streptococcus (GAS). During 2011, a scarlet fever epidemic characterized by peak monthly incidence rates 2.9-6.7 times higher than those in 2006-2010 occurred in Beijing, China. During the epidemic, hospital-based enhanced surveillance for scarlet fever and pharyngitis was conducted to determine characteristics of circulating GAS strains. The surveillance identified 3,359 clinical cases of scarlet fever or pharyngitis. GAS was isolated from 647 of the patients; 76.4% of the strains were type emm12, and 17.1% were emm1. Almost all isolates harbored superantigens speC and ssa. All isolates were susceptible to penicillin, and resistance rates were 96.1% to erythromycin, 93.7% to tetracycline, and 79.4% to clindamycin. Because emm12 type GAS is not the predominant type in other countries, wider surveillance for the possible spread of emm12 type GAS from China to other countries is warranted.
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Time-Course of Attentional Bias for Positive Social Words in Individuals with High and Low Social Anxiety.
Behav Cogn Psychother
PUBLISHED: 05-17-2013
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Background: Although accumulating research demonstrates the association between attentional bias and social anxiety, the bias for positive stimuli has so far not been adequately studied. Aims: The aim is to investigate the time-course of attentional bias for positive social words in participants with high and low social anxiety. Method: In a modified dot-probe task, word-pairs of neutral and positive social words were randomly presented for 100, 500, and 1250 milliseconds in a nonclinical sample of students to test their attentional bias. Results: Non-significant interaction of Group × Exposure Duration was found. However, there was a significant main effect of group, with significantly different response latencies between the high social anxiety (HSA) and low social anxiety (LSA) groups in the 100 ms condition, without for 500 or 1250 ms. With respect to attentional bias, the LSA group showed enhanced preferential attention for positive social words to which the HSA group showed avoidance in the 100 ms condition. In the 500 ms condition, preferential attention to positive social words was at trend in the LSA group, relative to the HSA group. Neither group showed attentional bias in the 1250 ms condition. Conclusions: These findings extend recent research about the attention training program and add to the empirical literature suggesting that the initial avoidance of positive stimuli may contribute to maintaining social anxiety.
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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.

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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.