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Find video protocols related to scientific articles indexed in Pubmed.
New Benzo[1,2-b:4,5-b']dithiophene-Based Small Molecules Containing Alkoxyphenyl Side Chains for High Efficiency Solution-Processed Organic Solar Cells.
ChemSusChem
PUBLISHED: 08-20-2014
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A new acceptor-donor-acceptor (A-D-A) small molecule, namely, BDT-PO-DPP, based on the alkoxyphenyl (PO)-substituted benzo[1,2-b:4,5-b']dithiophene (BDT) derivative and the diketopyrrolopyrrole (DPP) unit was synthesized as an electron donor for solution-processed small-molecule organic solar cells (SMOSCs). BDT-PO-DPP exhibited good thermal stability, with a 5?% weight-lost temperature at 401?°C under a nitrogen atmosphere. BDT-PO-DPP exhibited a lower HOMO energy level of -5.25?eV and a weaker aggregation ability than alkoxy-substituted BDT-O-DPP. A bulk heterojunction SMOSC device based on BDT-PO-DPP and [6,6]-phenyl-C61 -butyric acid methyl ester was prepared, and it showed a power conversion efficiency up to 5.63?% with a high open-circuit voltage of 0.83?V, a short circuit current density of 11.23?mA?cm(-2) , and a fill factor of 60.37?% by using 1,2-dichlorobenzene as the co-solvent after thermal annealing at 110?°C. The results indicate that the alkoxyphenyl-substituted BDT derivative is a promising electron-donor building block for constructing highly efficient solution-processed SMOSCs.
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An integrated approach to blood-based cancer diagnosis and biomarker discovery.
Pac Symp Biocomput
PUBLISHED: 08-15-2014
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Disrupted or abnormal biological processes responsible for cancers often quantitatively manifest as disrupted additive and multiplicative interactions of gene/protein expressions correlating with cancer progression. However, the examination of all possible combinatorial interactions between gene features in most case-control studies with limited training data is computationally infeasible. In this paper, we propose a practically feasible data integration approach, QUIRE (QUadratic Interactions among infoRmative fEatures), to identify discriminative complex interactions among informative gene features for cancer diagnosis and biomarker discovery directly based on patient blood samples. QUIRE works in two stages, where it first identifies functionally relevant gene groups for the disease with the help of gene functional annotations and available physical protein interactions, then it explores the combinatorial relationships among the genes from the selected informative groups. Based on our private experimentally generated data from patient blood samples using a novel SOMAmer (Slow Off-rate Modified Aptamer) technology, we apply QUIRE to cancer diagnosis and biomarker discovery for Renal Cell Carcinoma (RCC) and Ovarian Cancer (OVC). To further demonstrate the general applicability of our approach, we also apply QUIRE to a publicly available Colorectal Cancer (CRC) dataset that can be used to prioritize our SOMAmer design. Our experimental results show that QUIRE identifies gene-gene interactions that can better identify the different cancer stages of samples, as compared to other state-of-the-art feature selection methods. A literature survey shows that many of the interactions identified by QUIRE play important roles in the development of cancer.
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Enhanced expression of SAM-pointed domain-containing Ets-like factor in Chronic rhinosinusitis with nasal polyps.
Laryngoscope
PUBLISHED: 07-11-2014
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Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by significant goblet hyperplasia and mucus hypersecretion. However, the molecular mechanism underlying mucin overexpression in CRSwNP has not been well characterized. This study sought to assess the expression of SAM-pointed domain-containing Ets-like factor (SPDEF) and its regulation of mucin production in CRSwNP patients.
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Antioxidant activity of carboxymethyl (1?3)-?-d-glucan (from the sclerotium of Poria cocos) sulfate (in vitro).
Int. J. Biol. Macromol.
PUBLISHED: 05-13-2014
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(1?3)-?-d-glucan derived from Poria cocos hardly exhibits bioactivities. To extend its use, three types of (1?3)-?-d-glucan derivatives, which were sulfated (1?3)-?-d-glucan (S-P), carboxymethyl (1?3)-?-d-glucan (CMP) and carboxylmethyl (1?3)-?-d-glucan sulfate (S-CMP), were synthesized. Potential antioxidant activities of S-P, CMP and S-CMP were evaluated in vitro. The experiments of scavenging abilities of free radicals were carried out, such as 1,1-diphenyl-2-picrylhydrazyl (DPPH), superoxide anion and hydroxyl. Deeply study of the derivatives' inhibitory effect for lipid peroxidation, DNA oxidative damage, erythrocyte hemolysis, and malondialdehyde (MDA) production were determined. And S-CMP significantly (P<0.01) increased the antioxidant activity of ?-glucan. These results showed that multiple modifications of polysaccharides may bring the derivatives with excellent properties and various applications.
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Development of new two-dimensional small molecules based on benzodifuran for efficient organic solar cells.
Chem Asian J
PUBLISHED: 05-02-2014
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A new organic small molecule, DCA3TBDF, with a 2D benzo[1,2-b:4,5-b']difuran (BDF) moiety as the central core and octyl cyanoacetate units as the end-capped blocks, was designed and synthesized for solution-processed bulk heterojunction solar cells. DCA3TBDF possesses good solubility in common organic solvents such as toluene, CH2Cl2, chlorobenzene, and CHCl3 and good thermal stability with an onset decomposition temperature with 5% weight-loss occurring at 361?°C. The DCA3TBDF thin film showed a broad absorption at ?=320-700?nm and high crystallinity. Small-molecule organic solar cells based on DCA3TBDF and [6,6]-phenyl-C61-butyric acid methyl ester demonstrated promising power conversion efficiency with a high fill factor under the illumination of AM?1.5G (100?mW?cm(-2)).
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Identification and characterization of a cathepsin-L-like peptidase in Eimeria tenella.
Parasitol. Res.
PUBLISHED: 04-20-2014
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Avian coccidiosis, caused by Eimeria spp., is one of the major parasitic diseases in birds. Cysteine protease is a major virulence factor in parasitic protozoa, and it may be a suitable chemotherapeutic target and vaccine candidate molecule. A 100 amino acid (aa.) partial sequence of cathepsin L, which is a cysteine protease, was reported by Katrib et al. (Ac. No. CDJ41293) (2012). A 219 aa. sequence was reported by Reid et al. (Ac. No. AFV92863) (2013). However, the open reading frame (ORF) was not reported. In this study, a full sequence of a cathepsin-L-like peptidase in Eimeria tenella (EtcatL) was obtained and its biochemical characterizations and expression profiles were analyzed across different stages of the parasite's life cycle. Results showed that the EtcatL gene encodes a protein 470 aa. in length, with 47 and 49 % identity to Toxoplasma gondii and Eimeria acervulina. Considering the close phylogenetic relationship, TgcatL (PDB. ID 3F75) was selected for use as a template for homology modeling with quality factors of 90.9. Gelatin SDS-PAGE showed it to exert protease activity at ?38 and ?26 kDa. Further analysis showed the kinetic parameters of the recombinant peptidase to be K m ?=?8.9 ?M and V max?=?5.7 RFU/s ?M at pH 5.5 containing 10 mM dithiothreitol (DTT) in the reaction matrix, and the IC50 value of E64 was 65.32?±?3.02 nM. The recombinant protein was active from 25 to 50 °C, with optimal activity at 42 °C. The RT-PCR and Western blot results showed it to be expressed mainly at the endogenous stages and the initial phase of the sporulation. The protective experiment showed that chickens immunized with 100 and 200 ?g rEtcatL had reduction of weight loss values 48.7 and 57.9 % those of infected controls, respectively. Their reduction of lesion scores (RLS) were 25.0 and 47.2 % that of control chickens, and relative oocyst production (ROP) was 39.6 and 15.5 % that of control chickens. These results indicate that the EtcatL can be used as an effective immunogen, and further studies are needed to enhance its potential as a vaccine candidate molecule.
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Azelastine enhances the clinical efficacy of glucocorticoid by modulating MKP-1 expression in allergic rhinitis.
Eur Arch Otorhinolaryngol
PUBLISHED: 04-17-2014
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Azelastine was suggested as a supplementary choice of glucocorticoid for the control of moderate to severe allergic rhinitis (AR). However, the underlying mechanism has not been completely understood. In this study, primary cultured nasal epithelial cells and bronchial epithelial cells were stimulated with proinflammatory cytokines (IL-1? and IL-17A) and anti-inflammatory agents (azelastine and budesonide) in vitro. The expression of intercellular adhesion molecule 1 (ICAM-1) and mitogen-activated protein kinase phosphatase-1 (MKP-1) was examined using qPCR and ELISA, respectively. Moreover, the additive effects of azelastine and budesonide nasal spray on nasal ICAM-1 level and total nasal symptom scores were evaluated in six uncontrolled severe AR patients by budesonide nasal spray alone. We found azelastine significantly inhibited cytokine-induced ICAM-1 upregulation, which is reversed by MKP-1 silencing. Azelastine and budesonide additively increased MKP-1 expression and inhibited ICAM-1 expression in vitro. After treatment for two consecutive weeks, combined azelastine and budesonide nasal spray significantly decreased nasal ICAM-1 level and TNSS in six uncontrolled AR patients. Our findings suggested that azelastine is able to additively enhance the anti-inflammatory effect of budesonide by modulating MKP-1 expression, which may implicate in the treatment of uncontrolled severe AR.
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Self-assembly of silver nanoparticles illuminated by a visible-near-infrared lamp.
J Nanosci Nanotechnol
PUBLISHED: 04-17-2014
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Silver nanoparticles (NPs) with diameters of 5-10 nm were synthesized by using formaldehyde (HCHO) to reduce silver nitrate (AgNO3) and polyethylenemine (PEI) as a stabilizer. It was found that on the carbon-supported cupper grid (Cu/polyvinylformal (PVF)/C) and under a visible-near-infrared (VIS-NIR, 400-860 nm) lamp illuminating at about 75 degrees C for six minutes, the spherical Ag NPs self-assembled into bigger NPs, triangular nanoprisms, or structures like clock hands. On the glass slides, the NPs firstly self-assembled into spherical particles with 3-6 microm in sizes, then assembled into chain structures comprised of 3-20 spherical particles after being illuminated by the VIS-NIR lamp for about nine minutes. The violent thermal motion of the NPs after being illuminated by the VIS-NIR lamp leads to the self-assembly and the shapes of the self-assembled particles are related to the interactions between the substrates and the samples.
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Novel donor-acceptor polymer containing 4,7-bis(thiophen-2-yl)benzo[c][1,2,5]thiadiazole for polymer solar cells with power conversion efficiency of 6.21%.
Macromol Rapid Commun
PUBLISHED: 01-18-2014
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In order to improve the solution processability of 4,7-bis(thiophen-2-yl)benzo[c][1,2,5]thiadiazole (DTBT)-based polymers, novel donor-acceptor polymer PTOBDTDTBT containing DTBT and benzo[1,2-b:4,5-b']dithiophene (BDT) with conjugated side chain is designed and synthesized with narrow band gap 1.67 eV and low lying HOMO energy level -5.4 eV. The blend film of PTOBDTDTBT and PC71 BM exhibits uniform and smooth film with root-mean-square (RMS) surface roughness 1.15 nm because of the excellent solubility of PTOBDTDTBT when six octyloxy side chains are introduced. The hole mobility of the blend film is measured to be 4.4 × 10(-5) cm(2) V(-1) s(-1) by the space-charge-limited current (SCLC) model. The optimized polymer solar cells (PSCs) based on PTOBDTDTBT/PC71 BM exhibits an improved PCE of 6.21% with Voc = 0.80 V, Jsc = 11.94 mA cm(-2) and FF = 65.10%, one of the highest PCE in DTBT containing polymers.
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Gene expression profiling associated with angiotensin II type 2 receptor-induced apoptosis in human prostate cancer cells.
PLoS ONE
PUBLISHED: 01-01-2014
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Increased expression of angiotensin II type 2 receptor (AT2R) induces apoptosis in numerous tumor cell lines, with either Angiotensin II-dependent or Angiotensin II-independent regulation, but its molecular mechanism remains poorly understood. Here, we used PCR Array analysis to determine the gene and microRNA expression profiles in human prostate cancer cell lines transduced with AT2R recombinant adenovirus. Our results demonstrated that AT2R over expression leads to up-regulation of 6 apoptosis-related genes (TRAIL-R2, BAG3, BNIPI, HRK, Gadd45a, TP53BP2), 2 cytokine genes (IL6 and IL8) and 1 microRNA, and down-regulation of 1 apoptosis-related gene TNFSF10 and 2 cytokine genes (BMP6, BMP7) in transduced DU145 cells. HRK was identified as an up-regulated gene in AT2R-transduced PC-3 cells by real-time RT-PCR. Next, we utilized siRNAs to silence the up-regulated genes to further determine their roles on AT2R overexpression mediated apoptosis. The results showed downregulation of Gadd45a reduced the apoptotic effect by ?30% in DU145 cells, downregulation of HRK reduced AT2R-mediated apoptosis by more than 50% in PC-3 cells, while downregulation of TRAIL-R2 enhanced AT2R-mediated apoptosis more than 4 times in DU145 cells. We also found that the effects on AT2R-mediated apoptosis caused by downregulation of Gadd45a, TRAIL-R2 and HRK were independent in activation of p38 MAPK, p44/42 MAPK and p53. Taken together, our results demonstrated that TRAIL-R2, Gadd45a and HRK may be novel target genes for further study of the mechanism of AT2R-mediated apoptosis in prostate cancer cells.
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Cluster subcutaneous allergen specific immunotherapy for the treatment of allergic rhinitis: a systematic review and meta-analysis.
PLoS ONE
PUBLISHED: 01-01-2014
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Although allergen specific immunotherapy (SIT) represents the only immune- modifying and curative option available for patients with allergic rhinitis (AR), the optimal schedule for specific subcutaneous immunotherapy (SCIT) is still unknown. The objective of this study is to systematically assess the efficacy and safety of cluster SCIT for patients with AR.
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[Trend analyses on the differences of lung cancer incidence between gender, area and average age in China during 1989-2008].
Zhongguo Fei Ai Za Zhi
PUBLISHED: 09-17-2013
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The lung cancer incidence was significantly increased in the past two decades in China. But the secular trend of lung cancer incidence difference between gender (male and female), area (urban and rural) and average age was not clear. The aim of this study is to analyze the trend of lung cancer incidence rate ratio between gender, area and average age in China during 1989-2008, and provide some inspiration for lung cancer prevention and control activities.
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Fluorine substitution enhanced photovoltaic performance of a D-A(1)-D-A(2) copolymer.
Chem. Commun. (Camb.)
PUBLISHED: 09-04-2013
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A new alternating donor-acceptor (D-A1-D-A2) copolymer containing two electron-deficient moieties, isoindigo and quinoxaline, was synthesized. The photovoltaic performance of this polymer could be improved by incorporating fluorine atoms into the quinoxaline units, resulting in an efficiency of 6.32%. This result highlights the attractive promise of D-A1-D-A2 copolymers for high-performance bulk heterojunction solar cells.
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Synthesis and characterization of functional thienyl-phosphine microporous polymers for carbon dioxide capture.
Macromol Rapid Commun
PUBLISHED: 04-09-2013
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A novel kind of functional organic microporous polymer is designed by introducing polar organic groups (P=O and P=S) and electron-rich heterocyclic into the framework to obtain high carbon dioxide capture capacity. The estimated Brunauer-Emmett-Teller (BET) surface areas of these polymers are about 600 m(2) g(-1) and the highest CO2 uptake is 2.26 mmol g(-1) (1.0 bar/273 K). Interestingly, the polymer containing P=O groups shows greater CO2 capture capacity than that containing P=S groups at the same temperature. In addition, these polymers show high isosteric heats of CO2 adsorption (28.6 kJ mol(-1) ), which can be competitive with some nitrogen-rich networks. Therefore, these microporous polymers are promising candidates for carbon dioxide capture.
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Prion protein (PrP(c)) interacts with histone H3 confirmed by affinity chromatography.
J. Chromatogr. B Analyt. Technol. Biomed. Life Sci.
PUBLISHED: 02-14-2013
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The histones including H2a, H2b, H3 and H4 purified from pig liver tissue were immobilized onto Sepharose 4B to create a histone-Sepharose column. During chromatography of cow milk casein by histone-Sepharose column, two isoforms of prion protein (PrP(c)) with 34 and 30kDa molecular mass corresponding to diglycosylated and monoglycosylated PrP(c) respectively were found to be captured by histone ligands. To further verify the interaction between histones and PrP(c), the PrP(c)-Sepharose column was prepared and used to separate the histones. Two chromatography processes and SDS-PAGE demonstrated that only H3 in the histones was found to interact with PrP(c). This study suggested H3 could be the target molecule of PrP(C) in nuclei, which might be useful for understanding the prion disease.
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Increased expression of aldehyde dehydrogenase 1 A1 in nasopharyngeal carcinoma is associated with enhanced invasiveness.
Eur Arch Otorhinolaryngol
PUBLISHED: 01-19-2013
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Increased expression of aldehyde dehydrogenase 1 (ALDH1) has recently been reported in several cancers. However, whether member A1 of aldehyde dehydrogenase 1 (ALDH1A1) is involved in the formation of nasopharyngeal carcinoma (NPC) remains unknown. To investigate the expression of ALDH1A1 in NPC and its association with the tumorigenesis of NPC, we examined the expression of ALDH1A1 in NPC specimens using immunohistochemistry (IHC), quantitative RT-PCR (qRT-PCR) and Western blot. Moreover, we sorted ALDH1A1(high) cells from NPC cell line CNE-2 by flow cytometry and examined the expression of primitive embryonic stem cell markers OCT4, SOX2 and Nanog. Finally, we investigated the capacities of growth, proliferation, colony- formation and tumorigenesis of ALDH1A1(high) cells in vitro and in vivo. We found ALDH1A1 was significantly increased in human NPC samples via IHC, qRT-PCR and Western blot (p < 0.05). ALDH1A1(high) cells sorted from NPC cell line CNE-2 by flow cytometry had higher expression of primitive embryonic stem cell markers OCT4, SOX2 and Nanog, and showed enhanced capacities of growth, proliferation, colony formation and tumorigenesis in vitro and in vivo when compared with ALDH1A1(low) cells (p < 0.05). Our findings indicated that increased expression of ALDH1A1 in NPC was associated with enhanced invasiveness.
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Ratiometric fluorescent ion detection in water with high sensitivity via aggregation-mediated fluorescence resonance energy transfer using a conjugated polyelectrolyte as an optical platform.
Macromol Rapid Commun
PUBLISHED: 01-12-2013
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A cationic conjugated polyelectrolyte was designed and synthesized based on poly(fluorene-co-phenylene) containing 5 mol% benzothiadiazole (BT) as a low energy trap and 15-crown-5 as a recognizing group for potassium ions. A potassium ion can form a sandwich-type 2:1 Lewis acid-based complex with 15-crown-5, to cause the intermolecular aggregation of polymers. This facilitates inter-chain fluorescence resonance energy transfer (FRET) to a low-energy BT segment, resulting in fluorescent signal amplification, even at dilute analyte concentrations. Highly sensitive and selective detection of K(+) ions was demonstrated in water. The linear response of ratiometric fluorescent signal as a function of [K(+) ] allows K(+) quantification in a range of nanomolar concentrations with a detection limit of ?0.7 × 10(-9) M.
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Inhibition of GSK 3? activity is associated with excessive EZH2 expression and enhanced tumour invasion in nasopharyngeal carcinoma.
PLoS ONE
PUBLISHED: 01-01-2013
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Enhancer of zeste homolog 2 (EZH2) has been shown to contribute to tumour development and/or progression. However, the signalling pathway underlying the regulation of EZH2 in nasopharyngeal carcinoma (NPC) remains unclear. Since EZH2 contains the putative Glycogen synthase kinase 3 beta (GSK3?) phosphorylation motif ADHWDSKNVSCKNC (591) and may act as a possible substrate of GSK-3?, it is possible that inactivation of GSK3? may lead to excessive EZH2 expression in NPC.
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The anti-apoptotic effect of PI3K-Akt signaling pathway after subarachnoid hemorrhage in rats.
Ann. Clin. Lab. Sci.
PUBLISHED: 12-15-2011
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The serine-threonine kinase Akt plays an important role in survival pathways by inactivating downstream apoptogenic factors in many cell systems. In the following study, we investigated whether or not the activation of the Phosphatidylinositol 3-kinase (PI3K)-Akt pathway could reduce neuronal apoptosis following subarachnoid hemorrhage (SAH). Rats were randomly divided into 6 groups: control group, SAH group, SAH+ saline group, SAH+ vehicle group, SAH+ Insulin-like Growth Factor 1 (IGF-1) group, and SAH+Ly294002 (PI3K pathway inhibitor) group. All SAH animals were subjected to injection of autologous blood into the cisterna magna twice (on day 0 and on day 1). The administration was executed via cerebral ventricle 30 minutes before the induced SAH on day 0 and was continued every 24 hours for 72 hours. Whole brains were obtained on day 2. Phospho-Akt (pAkt) expression was analyzed by immunohistochemistry and western blotting. The neuronal apoptosis was evaluated by terminal deoxynucleotidyl transferase-mediated uridine 5-triphosphate-biotin nick end-labeling (TUNEL). We found that the PI3K-Akt pathway was activated in the brain after experimental SAH. Moreover, administration of IGF-1 significantly elevated pAkt expression and decreased the percentage of apoptotic neurons following SAH, while administration of Ly294002 suppressed pAkt expression and induced increased neuronal apoptosis following SAH. Taken as a whole, our results suggested that the activation of PI3K-Akt pathway could mediate the protective effect against neuronal apoptosis after SAH.
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TIP: a probabilistic method for identifying transcription factor target genes from ChIP-seq binding profiles.
Bioinformatics
PUBLISHED: 10-29-2011
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ChIP-seq and ChIP-chip experiments have been widely used to identify transcription factor (TF) binding sites and target genes. Conventionally, a fairly simple approach is employed for target gene identification e.g. finding genes with binding sites within 2 kb of a transcription start site (TSS). However, this does not take into account the number of sites upstream of the TSS, their exact positioning or the fact that different TFs appear to act at different characteristic distances from the TSS.
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Organ dose evaluation for multi-slice spiral CT scans based on China Sichuan chest anthropomorphic phantom measurements.
Radiat Prot Dosimetry
PUBLISHED: 10-27-2011
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The authors measured organ radiation doses during multi-slice computed tomography (MSCT) chest scans using a China Sichuan anthropomorphic phantom (CDP-1C). Chest CT images from live volunteers based on automatic tube current modulation (ATCM) techniques were similar to those obtained using the CDP-1C phantom, indicating that the phantom accurately modelled the anatomic structure and X-ray absorbance of the human torso. Indeed, attenuation values differed by <5%. Organ radiation doses were measured using thermoluminescence dosemeters in the CDP-1C. With increased noise index, the CT dose index, the dose-length product and the average organ dose all decreased. Thus, the CDP-1C phantom can also assess dose levels during CT examinations in Chinese patients. The noise index (based on ATCM techniques) should be set to 8.5 or higher to reduce X-ray exposure while maintaining appropriate resolution for diagnosis.
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PhenoM: a database of morphological phenotypes caused by mutation of essential genes in Saccharomyces cerevisiae.
Nucleic Acids Res.
PUBLISHED: 10-18-2011
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About one-fifth of the genes in the budding yeast are essential for haploid viability and cannot be functionally assessed using standard genetic approaches such as gene deletion. To facilitate genetic analysis of essential genes, we and others have assembled collections of yeast strains expressing temperature-sensitive (ts) alleles of essential genes. To explore the phenotypes caused by essential gene mutation we used a panel of genetically engineered fluorescent markers to explore the morphology of cells in the ts strain collection using high-throughput microscopy. Here, we describe the design and implementation of an online database, PhenoM (Phenomics of yeast Mutants), for storing, retrieving, visualizing and data mining the quantitative single-cell measurements extracted from micrographs of the ts mutant cells. PhenoM allows users to rapidly search and retrieve raw images and their quantified morphological data for genes of interest. The database also provides several data-mining tools, including a PhenoBlast module for phenotypic comparison between mutant strains and a Gene Ontology module for functional enrichment analysis of gene sets showing similar morphological alterations. The current PhenoM version 1.0 contains 78,194 morphological images and 1,909,914 cells covering six subcellular compartments or structures for 775 ts alleles spanning 491 essential genes. PhenoM is freely available at http://phenom.ccbr.utoronto.ca/.
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Systematic exploration of essential yeast gene function with temperature-sensitive mutants.
Nat. Biotechnol.
PUBLISHED: 01-13-2011
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Conditional temperature-sensitive (ts) mutations are valuable reagents for studying essential genes in the yeast Saccharomyces cerevisiae. We constructed 787 ts strains, covering 497 (?45%) of the 1,101 essential yeast genes, with ?30% of the genes represented by multiple alleles. All of the alleles are integrated into their native genomic locus in the S288C common reference strain and are linked to a kanMX selectable marker, allowing further genetic manipulation by synthetic genetic array (SGA)-based, high-throughput methods. We show two such manipulations: barcoding of 440 strains, which enables chemical-genetic suppression analysis, and the construction of arrays of strains carrying different fluorescent markers of subcellular structure, which enables quantitative analysis of phenotypes using high-content screening. Quantitative analysis of a GFP-tubulin marker identified roles for cohesin and condensin genes in spindle disassembly. This mutant collection should facilitate a wide range of systematic studies aimed at understanding the functions of essential genes.
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Climate change induced range shifts of Galliformes in China.
Integr Zool
PUBLISHED: 12-17-2010
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Climate change will cause range shifts of many species in the future. Galliformes might be particularly vulnerable to climate change, as they have low dispersal ability. Little is known about their possible responses to the future climate. We used a generalized additive model to predict the current and future ranges of all 63 Galliformes in China, based on a comprehensive species occurrence database and a combination of climate variables. Other environmental variables (e.g. elevation and human footprint index) were also considered, as well as the latitude and longitude of the occurrences. Principal component analysis was conducted to illustrate the association between environmental variables and Galliformes distributions. Using the Special Report on Emissions Scenarios (SRES) A2 climate change scenario for 2071-2100, we projected that 29 species would have range shifts over 50%, including 13 endemic species. Galliformes at higher elevation face greater range shifts. Northward shifts are greater than those in other directions. We suggest conservationists pay special attention to the 29 Galliformes that face extensive range shifts, especially the endemic species among them.
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Label-free, dual-analyte electrochemical biosensors: a new class of molecular-electronic logic gates.
J. Am. Chem. Soc.
PUBLISHED: 06-10-2010
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An "XOR" gate built using label-free, dual-analyte electrochemical sensors and the activation of this logic gate via changing concentrations of cocaine and the relevant cDNA as inputs are described.
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Colorimetric detection of DNA, small molecules, proteins, and ions using unmodified gold nanoparticles and conjugated polyelectrolytes.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 06-01-2010
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We have demonstrated a novel sensing strategy employing single-stranded probe DNA, unmodified gold nanoparticles, and a positively charged, water-soluble conjugated polyelectrolyte to detect a broad range of targets including nucleic acid (DNA) sequences, proteins, small molecules, and inorganic ions. This nearly "universal" biosensor approach is based on the observation that, while the conjugated polyelectrolyte specifically inhibits the ability of single-stranded DNA to prevent the aggregation of gold-nanoparticles, no such inhibition is observed with double-stranded or otherwise "folded" DNA structures. Colorimetric assays employing this mechanism for the detection of hybridization are sensitive and convenient--picomolar concentrations of target DNA are readily detected with the naked eye, and the sensor works even when challenged with complex sample matrices such as blood serum. Likewise, by employing the binding-induced folding or association of aptamers we have generalized the approach to the specific and convenient detection of proteins, small molecules, and inorganic ions. Finally, this new biosensor approach is quite straightforward and can be completed in minutes without significant equipment or training overhead.
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Exploiting the determinants of stochastic gene expression in Saccharomyces cerevisiae for genome-wide prediction of expression noise.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 05-20-2010
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Gene regulation is a process with many steps allowing for stochastic biochemical reactions, which leads to expression noise-i.e., the cell-to-cell stochastic fluctuation in protein abundance. Such expression noise can give rise to drastically diverse phenotypes, even within isogenic cell populations. Although numerous biophysical approaches had been proposed to model the origin and propagation of expression noise in biological networks, these models essentially characterize the innate stochastic dynamics in gene regulation in a mechanistic way. In this work, by investigating expression noise in the context of yeast cellular networks, we place the biophysical formulism onto solid genetic ground. At the sequence level, we show that extremely noisy genes are highly conserved in their coding sequences. At the level of cellular networks where natural selection is manifested by the topological constraints, we show that genes with varying expression noise are modularly organized in the protein interaction network and are positioned orderly in the gene regulatory network. We demonstrate that these topological constraints are highly predictive of stochastic gene expression, with which we were able to confidently predict stochastic expression for more than 2,000 yeast genes whose expression noise was previously not known. We validated the predictions by high-content cell imaging. Our approach makes feasible genome-wide prediction of stochastic gene expression, and such predictability in turn suggests that expression noise is an evolvable genetic trait.
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On the binding of cationic, water-soluble conjugated polymers to DNA: electrostatic and hydrophobic interactions.
J. Am. Chem. Soc.
PUBLISHED: 01-12-2010
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Water-soluble, cationic conjugated polymer binds single-stranded DNA with higher affinity than it binds double-stranded or otherwise "folded" DNA. This stronger binding results from the greater hydrophobicity of single-stranded DNA. Upon reducing the strength of the hydrophobic interactions, the electrostatic attraction becomes the important interaction that regulates the binding between the water-soluble conjugated polymer and DNA. The different affinities between the cationic conjugated polymer and various forms of DNA (molecular beacons and its open state; single-stranded DNA and double-stranded DNA and single-stranded DNA and complex DNA folds) can be used to design a variety of biosensors.
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Gene expression variability within and between human populations and implications toward disease susceptibility.
PLoS Comput. Biol.
PUBLISHED: 01-10-2010
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Variations in gene expression level might lead to phenotypic diversity across individuals or populations. Although many human genes are found to have differential mRNA levels between populations, the extent of gene expression that could vary within and between populations largely remains elusive. To investigate the dynamic range of gene expression, we analyzed the expression variability of ?18, 000 human genes across individuals within HapMap populations. Although ?20% of human genes show differentiated mRNA levels between populations, our results show that expression variability of most human genes in one population is not significantly deviant from another population, except for a small fraction that do show substantially higher expression variability in a particular population. By associating expression variability with sequence polymorphism, intriguingly, we found SNPs in the untranslated regions (5 and 3UTRs) of these variable genes show consistently elevated population heterozygosity. We performed differential expression analysis on a genome-wide scale, and found substantially reduced expression variability for a large number of genes, prohibiting them from being differentially expressed between populations. Functional analysis revealed that genes with the greatest within-population expression variability are significantly enriched for chemokine signaling in HIV-1 infection, and for HIV-interacting proteins that control viral entry, replication, and propagation. This observation combined with the finding that known human HIV host factors show substantially elevated expression variability, collectively suggest that gene expression variability might explain differential HIV susceptibility across individuals.
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Improved injection in n-type organic transistors with conjugated polyelectrolytes.
J. Am. Chem. Soc.
PUBLISHED: 12-09-2009
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To improve injection in n-type organic thin film transistors (OTFTs), a thin conjugated polyelectrolyte (CPE) layer was interposed between electrodes and the semiconductor layer. OTFTs were fabricated with [6,6]-phenyl-C(61) butyric acid methyl ester (PCBM) and Au source and drain contacts. We demonstrate that the insertion of CPEs beneath top-contact Au source/drain electrodes can be a very effective strategy for improving the carrier injection and reducing turn-on threshold voltages of n-channel OTFTs. Ultraviolet photoemission spectroscopy (UPS) indicates that the decrease of the electron injection barrier is consistent with organized dipoles at the metal/organic interface.
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Comparing the properties of electrochemical-based DNA sensors employing different redox tags.
Anal. Chem.
PUBLISHED: 10-09-2009
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Many electrochemical biosensor approaches developed in recent years utilize redox-labeled (most commonly methylene blue or ferrocene) oligonucleotide probes site-specifically attached to an interrogating electrode. Sensors in this class have been reported that employ a range of probe architectures, including single- and double-stranded DNA, more complex DNA structures, DNA and RNA aptamers, and, most recently, DNA-small molecule chimeras. Signaling in this class of sensors is generally predicated on binding-induced changes in the efficiency with which the covalently attached redox label transfers electrons with the interrogating electrode. Here we have investigated how the properties of the redox tag affect the performance of such sensors. Specifically, we compare the differences in signaling and stability of electrochemical DNA sensors (E-DNA sensors) fabricated using either ferrocene or methylene blue as the signaling redox moiety. We find that while both tags support efficient E-DNA signaling, ferrocene produces slightly improved signal gain and target affinity. These small advantages, however, come at a potentially significant price: the ferrocene-based sensors are far less stable than their methylene blue counterparts, particularly with regards to stability to long-term storage, repeated electrochemical interrogations, repeated sensing/regeneration iterations, and employment in complex sample matrices such as blood serum.
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A probabilistic framework to improve microrna target prediction by incorporating proteomics data.
J Bioinform Comput Biol
PUBLISHED: 07-16-2009
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Due to the difficulties in identifying microRNA (miRNA) targets experimentally in a high-throughput manner, several computational approaches have been proposed. To this date, most leading algorithms are based on sequence information alone. However, there has been limited overlap between these predictions, implying high false-positive rates, which underlines the limitation of sequence-based approaches. Considering the repressive nature of miRNAs at the mRNA translational level, here we describe a probabilistic model to make predictions by combining sequence complementarity, miRNA expression level, and protein abundance. Our underlying assumption is that, given sequence complementarity between a miRNA and its putative mRNA targets, the miRNA expression level should be high and the protein abundance of the mRNA should be low. Having identified a set of confident predictions, we then built a second probabilistic model to trace back to the mRNA expression of the confident targets to investigate the mechanisms of the miRNA-mediated post-transcriptional regulation. Our results suggest that translational repression (which has no effect on mRNA level), instead of mRNA degradation, is the dominant mechanism in miRNA regulation. This observation explained the previously observed discordant correlation between mRNA expression and protein abundance.
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New seco-anthraquinone glucosides from Rumex nepalensis.
Planta Med.
PUBLISHED: 03-16-2009
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Investigation of the N-BuOH extract of the roots of Rumex nepalensis afforded two new seco-anthraquinone glucosides, nepalensides A and B, along with nine known compounds, torachrysone ( 3), rumexoside, orientaloside, orcinol glucoside, aloesin, lyoniresinol 3 alpha- O- beta- D-glucopyranoside, (-)-epicatechin-3- O-gallate, (3,5-dimethoxy-4-hydroxyphenol)-1- O- beta- D-(6- O-galloyl) glucose, and (-)-epicatechin. Their structures were elucidated on the basis of spectroscopic methods. The possible formation of nepalensides A and B is briefly discussed.
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Learned random-walk kernels and empirical-map kernels for protein sequence classification.
J. Comput. Biol.
PUBLISHED: 03-04-2009
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Biological sequence classification (such as protein remote homology detection) solely based on sequence data is an important problem in computational biology, especially in the current genomics era, when large amount of sequence data are becoming available. Support vector machines (SVMs) based on mismatch string kernels were previously applied to solve this problem, achieving reasonable success. However, they still perform poorly on difficult protein families. In this paper, we propose two approaches to solve the protein remote homology detection problem: one uses a convex combination of random-walk kernels to approximate the random-walk kernel with the optimal random steps, and the other constructs an empirical-map kernel using a profile kernel. Both resulting kernels make use of a large number of pairwise sequence similarity information and unlabeled data; and have much better prediction performance than the best profile kernel directly derived from protein sequences. On a competitive Structural Classification Of Proteins (SCOP) benchmark dataset, the overall mean ROC(50) scores on 54 protein families we obtained using both approaches are above 0.90, which significantly outperform previous published results.
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[Purification of immunoglobulin and serum albumin from serum via strong anion exchange chromatography coupled with molecular exclusion chromatography].
Se Pu
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The isoelectric points of immunoglobulin (Ig) and serum albumin (SA) in animal serum are about 7.8 and 4.8, respectively. Based on their larger difference of isoelectric points, Q Sepharose-XL strong anion exchange chromatography coupled with molecular exclusion chromatography was used to purify Ig and SA simultaneously from the high immune rabbit serum. After the Q Sepharose-XL strong anion exchange column was equilibrated with 0.02 mol/L Tris-HCl buffer of pH 8.0, a 10-fold dilution sample of rabbit serum was loaded onto the column and the pH gradient elution was performed. With the low flow rate of elution of 0.3 mL/min, the high-purity Ig was obtained when the elution pH was at 6.0. Continuously eluted at pH 4.0 with the same flow rate of elution, the SA was obtained and its purity was greater than 95% after molecular exclusion chromatography through Sephadex G-75. The purified Ig and SA were demonstrated to maintain normal activities by activity analysis. The results of protein content showed that the purification recoveries of Ig and SA were over 95% and 90%, respectively. The method has the advantages of simple operation and rapidity, and the Ig and SA purified simultaneously from the animal serum could maintain normal activities.
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Eimeria tenella: interleukin 17 contributes to host immunopathology in the gut during experimental infection.
Exp. Parasitol.
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Although IL-17 is a key factor in Th17 lineage host responses and plays critical roles in immunological control of a variety of infectious diseases, the contribution of IL-17 to immune function during Eimeria tenella infection is unknown. In the present study, we used an experimental E. tenella infection model to clarify the role of Th17-associated response in the resulting immune response by quantitative real-time PCR assays. We observed robust production of STAT-3 (the transcription factors), IL-1?, IL-6 and IL-17 in cecal intraepithelial lymphocytes during the early infection, peaking at 6h p.i. and declining thereafter. The expression of TGF-? was moderately upregulated and had 2 peaks at 6 and 72h p.i. during the early infection. To further investigate the role of chIL-17 during the infection, we treated the infected chickens with IL-17 and its neutralized antibody. As a result, the reduced fecal oocyst shedding and cecal lesion scores, but enhanced body weight gains were observed in IL-17 neutralized chickens. The results of histopathology showed that the neutrophils recruitment diminished and the parasite burden in IL-17 neutralized chickens decreased. These results may be due to the significant decrease in the production of IL-17, IL-6 and TGF-?, but enhanced IL-12 and IFN-? expression in IL-17 neutralized chickens. The converse results were shown in IL-17 treated infected-chickens in which chickens showed increased fecal oocyst shedding, exacerbated lesion scores, and reduced body weight gains. These results suggested that chicken IL-17 might mediate E. tenella - induced immunopathology during the infection.
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An expedient synthesis of fused heteroacenes bearing a pyrrolo[3,2-b]pyrrole core.
Chem. Commun. (Camb.)
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Two linear fused heteroacenes bearing a pyrrolo[3,2-b]pyrrole core have been synthesized via a novel reductive ring closure methodology in three steps and in good overall yield. Preliminary OFET results showed that dinaphtho[2,3-b:2,3-f]pyrrolo[3,2-b]pyrrole (DNPP) is a potential candidate for organic electronics.
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Experimental study of detection of nodules showing ground-glass opacity and radiation dose by using anthropomorphic chest phantom: digital tomosynthesis and multidetector CT.
J Comput Assist Tomogr
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The purpose of this study was to compare chest digital tomosynthesis (DTS) and multidetector computed tomography (MDCT) for the detection of pulmonary ground-glass opacity (GGO) nodules and estimation of radiation dose using an anthropomorphic chest phantom and simulated nodules.
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Understanding transcriptional regulation by integrative analysis of transcription factor binding data.
Genome Res.
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Statistical models have been used to quantify the relationship between gene expression and transcription factor (TF) binding signals. Here we apply the models to the large-scale data generated by the ENCODE project to study transcriptional regulation by TFs. Our results reveal a notable difference in the prediction accuracy of expression levels of transcription start sites (TSSs) captured by different technologies and RNA extraction protocols. In general, the expression levels of TSSs with high CpG content are more predictable than those with low CpG content. For genes with alternative TSSs, the expression levels of downstream TSSs are more predictable than those of the upstream ones. Different TF categories and specific TFs vary substantially in their contributions to predicting expression. Between two cell lines, the differential expression of TSS can be precisely reflected by the difference of TF-binding signals in a quantitative manner, arguing against the conventional on-and-off model of TF binding. Finally, we explore the relationships between TF-binding signals and other chromatin features such as histone modifications and DNase hypersensitivity for determining expression. The models imply that these features regulate transcription in a highly coordinated manner.
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Architecture of the human regulatory network derived from ENCODE data.
Nature
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Transcription factors bind in a combinatorial fashion to specify the on-and-off states of genes; the ensemble of these binding events forms a regulatory network, constituting the wiring diagram for a cell. To examine the principles of the human transcriptional regulatory network, we determined the genomic binding information of 119 transcription-related factors in over 450 distinct experiments. We found the combinatorial, co-association of transcription factors to be highly context specific: distinct combinations of factors bind at specific genomic locations. In particular, there are significant differences in the binding proximal and distal to genes. We organized all the transcription factor binding into a hierarchy and integrated it with other genomic information (for example, microRNA regulation), forming a dense meta-network. Factors at different levels have different properties; for instance, top-level transcription factors more strongly influence expression and middle-level ones co-regulate targets to mitigate information-flow bottlenecks. Moreover, these co-regulations give rise to many enriched network motifs (for example, noise-buffering feed-forward loops). Finally, more connected network components are under stronger selection and exhibit a greater degree of allele-specific activity (that is, differential binding to the two parental alleles). The regulatory information obtained in this study will be crucial for interpreting personal genome sequences and understanding basic principles of human biology and disease.
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Construction of logic gates with the fluorene-based small molecule/DNA probes.
Mol Biosyst
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Fluorene-based small molecules (FSMs) have optical properties and can interact with DNA. In this paper, the integrated "INH" and "AND" gates operating in parallel are developed with the fluorene-based small molecule (FSM)/DNA probe. They are activated by taking advantage of the two-step fluorescence resonance energy transfer (FRET) process and the sequence-recognition mechanism of DNA. Then, a "NOT" gate is obtained with a molecular beacon-like probe (FSM-MB) by using the FSM as the fluorophore. Moreover, the "NOT" gate based on the FSM-MB probe can be used as a biosensor and has potential applications in label-free detection of target molecules.
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Eimeria tenella heat shock protein 70 enhances protection of recombinant microneme protein MIC2 subunit antigen vaccination against E. tenella challenge.
Vet. Parasitol.
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Heat shock proteins have been reported to stimulate the immune system via innate receptors. Our study found that the novel immunopotentiator, Eimeria tenella (E. tenella) heat shock protein 70 (HSP70), enhanced protective immunity elicited by E. tenella antigen microneme protein 2 (EtMIC2) against avian coccidiosis. It demonstrated that the expression of TLR2 and TLR4 were strongly upregulated in EtHSP70 and EtMIC2 plus EtHSP70 stimulated chicken embryo fibroblasts (CEF) compared with untreated controls and EtMIC2 alone. In addition, the same treatment induced high levels of interleukin (IL)-12 and interferon (IFN)-? that are critical cytokines of innate immunity. In vivo experiments involved using broiler chickens subcutaneously immunized with EtMIC2 alone or EtMIC2 plus EtHSP70 at 7 and 14 days post-hatch, which were then orally challenged with live E. tenella at 7 days following secondary immunization. Body weight gains, cecal lesion scores, fecal oocyst shedding, serum antibody responses against MIC2, and intestinal cytokine transcript levels were assessed as measures of protective immunity. Chickens immunized with EtMIC2 plus EtHSP70 showed increased body weight gains, decreased oocyst shedding, increased serum antibody responses, and high levels of IL-12, IFN-?, and IL-17 compared with the EtMIC2 only or control groups. Moreover, chickens immunized with EtHSP70 alone showed significantly protective effect against E. tenella infection. In summary, this study provides the first evidence of the immunoenhancing activities of EtHSP70 in poultry.
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Eimeria tenella: expression profiling of toll-like receptors and associated cytokines in the cecum of infected day-old and three-week old SPF chickens.
Exp. Parasitol.
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Coccidiosis is an economically important protozoan disease worldwide caused by Eimeria parasites. Toll-like receptors (TLRs), a family of highly conserved proteins, are involved in pathogen detection by initiating host responses, and play important roles in the reduction and clearance of pathogens. Little is known about the roles of chicken TLRs during Eimeria tenella infection. We detected the dynamic changes in the expression of TLRs and associated cytokines in the cecum of E. tenella-infected chickens during the early stage of infection. Day-old (Experiment 1) and three-week-old (Experiment 2) chickens were orally gavaged with 10,000 oocysts (30 chickens each experiment), and their cecum intraepithelial lymphocytes were collected at 3, 6, 12, 24, 48, and 72h post-infection (hpi). Expression profiling of TLR1LA, TLR4, TLR5, TLR7, TLR21, and IFN-?, IFN-?, IFN-?, IL-1?, IL-12 genes were analyzed using quantitative real-time polymerase chain reaction. Almost all TLR transcripts were transiently increased at 3hpi in Experiment 1. In three-week-old chickens, TLR1LA, TLR4, TLR5, TLR7, and TLR21 expression was upregulated at 12hpi, and TLR1LA, TLR5, and TLR21 were highly expressed at 72hpi. In day-old chickens, IFN-?, IFN-?, IFN-?, IL-1?, and IL-12 expression was significantly upregulated at 3hpi (156.1-1117.1-fold change), in comparison to the different peak level times and relatively small changes for these cytokines in the three-week-old chickens. Our results provide a valuable overview for the expression pattern of TLRs and associated cytokines during the early stage of E. tenella infection in chickens.
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An OR logic gate based on two molecular beacons.
Mol Biosyst
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Design of elementary molecular logic gates is the key and the fundamental of performing complicated Boolean calculations. Herein, we report a strategy for constructing a DNA-based OR gate by using the mechanism of sequence recognition and the principle of fluorescence resonance energy transfer (FRET). In this system, the gate is entirely composed of a single strand of DNA (A, B and C) and the inputs are the molecular beacon probes (MB1 and MB2). Changes in fluorescence intensity confirm the realization of the OR logic operation and electrophoresis experiments verify these results. Our successful application of DNA to perform the binary operation represents that DNA can serve as an efficient biomaterial for designing molecular logic gates and devices.
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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.