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Find video protocols related to scientific articles indexed in Pubmed.
Detection of posteriorly located breast tumors using gold nanoparticles: A breast-mimicking phantom study.
J Xray Sci Technol
PUBLISHED: 11-20-2014
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Accurately depicting breast tumors located posteriorly, close to the chest wall musculature, with conventional mammography is a technical challenge.OBJECTIVE: This study demonstrates the proof of concept of an x-ray fluorescence mapping (XFM) technique to address this issue.METHODS: A tissue-equivalent gel phantom is designed to mimic structures in the central part of a compressed breast. The posterior aspect of the breast and adjacent pectoralis major muscle are represented by another 10-mm-thickness breast tissue simulation phantom (BR12) that is attached to the back of the gel phantom as a region of interest (ROI). Two gold nanoparticle (GNP) solutions are embedded into the ROI to simulate varying GNP uptake within breast lesions. The ROI is imaged through performing the XFM technique with an x-ray pencil-beam and a single spectrometer.RESULTS: A 2D mapping of the middle plane in the ROI demonstrates feasibility and matches well the known spatial distribution and different GNP concentrations. 3D reconstruction of the ROI is easily rendered by repeating the 2D mapping process.CONCLUSION: XFM system geometry and its insensitivity to attenuation coefficients of breast tissue components are unique characteristics that may complement conventional mammography and improve the detection of breast cancers located posteriorly, adjacent to or overlying the chest wall musculature.
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Construction of dentate bonded TiO2-CdSe heterostructures with enhanced photoelectrochemical properties: versatile labels toward photoelectrochemical and electrochemical sensing.
Dalton Trans
PUBLISHED: 11-20-2014
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A facile synthetic route for TiO2-CdSe heterostructures was proposed based on dentate binding of TiO2 to carboxyl. Carboxyl functionalized CdSe quantum dots (CF-CdSe QDs) were successfully bonded onto TiO2 nanoparticles (NPs), which could significantly improve the photoelectrochemical (PEC) properties of TiO2 NPs. This is ascribed to the fact that CdSe QDs with a narrow band gap could be stimulated under visible light irradiation, and the energy levels of TiO2 NPs and CF-CdSe QDs are aligned with an electrolyte solution. High resolution transmission electron microscopy images revealed the heterostructures of the TiO2-CdSe composites. Ultraviolet visible spectroscopy, photoluminescence emission spectroscopy and electrochemical impedance spectroscopy analysis exhibited that the prepared TiO2-CdSe heterostructures have improved light absorption, charge separation efficiency and electron transfer ability in the visible light region. TiO2-CdSe heterostructures were used as versatile labels for fabrication of PEC and electrochemical immunosensors, and human immune globulin G (HIgG) was used as a model analyte. The immunosensor showed high sensitivity, a low detection limit and a wide linear range, which could be applied in practical serum sample analysis. The constructed TiO2-CdSe heterostructures would have potential applications in photocatalysis, aptasensors, cytosensors and other areas of nanotechnology.
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Deep localized distortion of alternating bonds and reduced transport of charged carriers in conjugated polymers under photoexcitation.
Nanoscale
PUBLISHED: 11-20-2014
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In a real bulk heterojunction polymer solar cell, after exciton separation in the heterojunction, the resulting negatively-charged carrier, a polaron, moves along the polymer chain of the acceptor, which is believed to be of significance for the charged carrier transport properties in a polymer solar cell. During the negative polaron transport, due to the external light field, the polaron, which is re-excited and induces deep localization, also forms a new local distortion of the alternating bonds. It is revealed that the excited polaron moves more slowly than the ground-state polaron. Furthermore, the velocity of the polaron moving along the polymer chain is crucially dependent on the photoexcitation. With an increase in the intensity of the optical field, the localization of the excited polaron will be deepened, with a decrease of the polaron's velocity. It is discovered that, for a charged carrier, photoexcitation is a significant factor in reducing the efficiency during the charged carrier transport in polymer solar cells. Mostly, the deep trapping effect of charged carrier in composite conjugated polymer solar cell presents an opportunity for the future application in nanoscale memory and imaging devices.
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Effect of deoxycholic acid on Ca(2+) movement, cell viability and apoptosis in human gastric cancer cells.
Toxicol. Mech. Methods
PUBLISHED: 11-20-2014
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Abstract Deoxycholic acid (DOA) is one of the secondary bile acids used as a mild detergent for the isolation of membrane associated proteins. This study examined whether the secondary bile acid, DOA, altered Ca(2+) movement, cell viability and apoptosis in SCM1 human gastric cancer cells. The Ca(2+)-sensitive fluorescent dye fura-2 was used to measure [Ca(2+)]i. DOA evoked [Ca(2+)]i rises concentration-dependently. The response was reduced by removing extracellular Ca(2+). DOA-evoked Ca(2+) entry was inhibited by store-operated Ca(2+) channel inhibitors (nifedipine, econazole and SKF96365), the protein kinase C (PKC) activator phorbol 12-myristate 13 acetate (PMA) and the PKC inhibitor GF109203X. In Ca(2+)-free medium, treatment with the endoplasmic reticulum Ca(2+) pump inhibitor thapsigargin (TG) abolished DOA-evoked [Ca(2+)]i rises. Conversely, treatment with DOA abolished TG-evoked [Ca(2+)]i rises. Inhibition of phospholipase C with U73122 abolished DOA-evoked [Ca(2+)]i rises. At 100-500 ?M, DOA decreased cell viability, which was not changed by chelating cytosolic Ca(2+) with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester (BAPTA/AM). DOA between 100 ?M and 300 ?M also induced apoptosis. Collectively, in SCM1 cells, DOA induced [Ca(2+)]i rises by evoking phospholipase C-dependent Ca(2+) release from the endoplasmic reticulum and Ca(2+) entry via store-operated Ca(2+) channels. DOA also caused Ca(2+)-independent apoptosis.
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Endovascular embolization for managing anastomotic bleeding after stapled digestive tract anastomosis.
Acta Radiol
PUBLISHED: 11-20-2014
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Anastomotic bleeding is an infrequent but life-threatening complication after stapled digestive tract anastomosis. Endovascular embolization is one of the available treatments, but precise clinical outcomes are yet to be evaluated.
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Deficient Autophagy Results in Mitochondrial Dysfunction and FSGS.
J. Am. Soc. Nephrol.
PUBLISHED: 11-20-2014
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FSGS is a heterogeneous fibrosing disease of the kidney, the cause of which remains poorly understood. In most cases, there is no effective treatment to halt or retard progression to renal failure. Increasing evidence points to mitochondrial dysfunction and the generation of reactive oxygen species in the pathogenesis of CKD. Autophagy, a major intracellular lysosomal degradation system, performs homeostatic functions linked to metabolism and organelle turnover. We prevented normal autophagic pathways in nephrons of mice by mutating critical autophagy genes ATG5 or ATG7 during nephrogenesis. Mutant mice developed mild podocyte and tubular dysfunction within 2 months, profound glomerular and tubular changes bearing close similarity to human disease by 4 months, and organ failure by 6 months. Ultrastructurally, podocytes and tubular cells showed vacuolization, abnormal mitochondria, and evidence of endoplasmic reticulum stress, features that precede the appearance of histologic or clinical disease. Similar changes were observed in human idiopathic FSGS kidney biopsy specimens. Biochemical analysis of podocytes and tubules of 2-month-old mutant mice revealed elevated production of reactive oxygen species, activation of endoplasmic reticulum stress pathways, phosphorylation of p38, and mitochondrial dysfunction. Furthermore, cultured proximal tubule cells isolated from mutant mice showed marked mitochondrial dysfunction and elevated mitochondrial reactive oxygen species generation that was suppressed by a mitochondrial superoxide scavenger. We conclude that mitochondrial dysfunction and endoplasmic reticulum stress due to impaired autophagic organelle turnover in podocytes and tubular epithelium are sufficient to cause many of the manifestations of FSGS in mice.
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Natribaculum breve gen. nov., sp. nov. and Natribaculum longum sp. nov., two novel halophilic archaea isolated from Lop Nur, China.
Int. J. Syst. Evol. Microbiol.
PUBLISHED: 11-20-2014
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Two halophilic archaeal strains TRM20010T and TRM20345T were isolated from saline soil of Lop Nur region in Xinjiang, Northwest of China. Cells from the two strains were observed to be pleomorphic rods, stain Gram-negative, and produce red-pigmented colonies. Strains TRM20010T and TRM20345T were able to grow at 30-62 °C (optimum 37 °C), 0.9-5.1 M NaCl (optimum 2.6 M and 3.4 M, respectively), pH 6.0-10.0 (optimum pH 7.0 -7.5) and neither strain required Mg2+ for growth. The major polar lipids of the two strains were phosphatidylglycerol (PG), phosphatidylglycerol phosphate methyl ester (PGP-Me), two glycolipids chromatographically identical to galactosyl mannosyl glucosyl diether (TGD-1) and disulfated mannosyl glucosyl diether (S2-DGD). Phylogenetic tree construction based on 16S rRNA and rpoB' genes revealed that strains TRM20010T and TRM20345T clustered together and formed a distinct clade separted from the related genera, Halovivax, Haloterrigena, Halostagnicola, Natronolimnobius and Natrinema. The DNA G+C content of strains TRM20010T and TRM20345T were 63.9 and 63.8 mol%, respectively. The DNA-DNA hybridization value between strain TRM20010T and strain TRM20345T was 42.8 %. The phenotypic, chemotaxonomic and phylogenetic properties suggested that strain TRM20010T and strain TRM20345T represented two novel species in a new genus within the family Halobacteriaceae, Natribaculum breve gen. nov., sp. nov. (type strain TRM20010T = CCTCC AB2013112T = NRRL B-59996T) and Natribaculum longum sp. nov. are proposed (type strain TRM20345T = CCTCC AB2013113T = NRRL B-59997T).
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Synthetic-Method-Dependent Magnetic Relaxation in a Cobalt(II) Phosphonate Chain Compound.
Inorg Chem
PUBLISHED: 11-14-2014
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A polar cobalt(II) phosphonate Co(bamdpH2)(H2O) (1) [bamdpH4 = (benzylazanediyl)bis(methylene)diphosphonic acid] is reported. It shows a linear chain structure. The neighboring chains are connected by moderately strong hydrogen bonds forming a supramolecular layer. The interlayer spaces are filled with the organic groups of the phosphonate ligands. Compound 1 displays the coexistence of single-chain magnet behavior and canted antiferromagnetism below 2.8 K. Moreover, the magnetic dynamics is strongly dependent on the synthetic methods, a phenomenon that has not been documented before.
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EGR2 is critical for peripheral naïve T-cell differentiation and the T-cell response to influenza.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 11-03-2014
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Early growth response 2 (EGR2) transcription factor negatively regulates T-cell activation, in contrast to the positive regulation of this process by EGR1. Here, we unexpectedly found that EGR2 promotes peripheral naïve T-cell differentiation, with delayed T-cell receptor-induced proliferation in naïve T cells from Egr2 conditional knockout (CKO) mice and decreased production of IFN-?, IL-4, IL-9, and IL-17A in cells subjected to T-helper differentiation. Moreover, genes that promote T-cell activation, including Tbx21 and Notch1, had decreased expression in Egr2 CKO T cells and are direct EGR2 target genes. Following influenza infection, Egr2 CKO mice had delayed viral clearance, more weight loss, and more severe pathological changes in the lung than did WT and Egr1 KO mice, with decreased production of effector cytokines, increased infiltration of antigen-specific memory-precursor CD8(+) T cells, and lower numbers of lung-resident memory CD8(+) T cells. Thus, unexpectedly, EGR2 can function as a positive regulator that is essential for naïve T-cell differentiation and in vivo T-cell responses to a viral infection.
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Copper-Mediated Direct Alkoxylation of Arenes Using an N,O-Bidentate Directing System.
J. Org. Chem.
PUBLISHED: 10-22-2014
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Highly effective CuCl-mediated C-H alkoxylation of arenes and heteroarenes has been developed by using a 2-aminopyridine 1-oxide moiety as an N,O-bidentate directing group. The reaction proceeds smoothly using a broad range of substrates to afford o-alkoxylated benzoic and heteroaromatic amide products. Moreover, the reaction system shows remarkable compatibility when hexafluoroisopropanol is used as a coupling parter; halogen, nitro, ether, alkoxy, ester, and sulfonyl functional groups are all tolerated. The directing group can be easily removed by base hydrolysis, affording o-alkoxylated benzoic acids.
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Monotone spline regression for accurate MTF measurement at low frequencies.
Opt Express
PUBLISHED: 10-17-2014
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The modulation transfer function (MTF) of radiographic systems is frequently evaluated by the system's line spread function (LSF) using narrow slits. The conventional slit method requires LSF tail approximation, which is achieved by exponentially extrapolating the LSF tails beyond 1% of peak value. However, the estimated MTF at low frequencies from extrapolation may not reflect the true performance of the system. In this study, a monotone spline regression technique for LSF tail approximation is developed to improve the accuracy of MTF estimation at low frequencies. This technique is based on the underlying physical principles of the system response. The advantages of this technique are demonstrated with simulated examples of which the true MTFs are known. The application of this measurement technique is also demonstrated.
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Method for determining the modulation transfer function of X-ray fluorescence mapping system.
Opt Express
PUBLISHED: 10-17-2014
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A method for determining the modulation transfer function (MTF) in direct X-ray fluorescence mapping (XFM) system is reported. With a standard container filled with homogeneous gold nanoparticle (GNP) solution (1% by weight), sharp edges are made and utilized to acquire the data for edge spread function (ESF). Through necessary data processing such as signal extraction, attenuation correction and curve fitting and proper calculations of differentiating and Fourier transform, MTF can be determined. Influencing factors of MTF determination in XFM system are thoroughly discussed in theory and validated by experiments. The results show that different mapping steps do not noticeably affect the measured MTF, while MTF is greatly degraded as the collimator-to-object distance increases. The theoretical analyses and experimental validations of the MTF determination are useful and helpful for imaging performance evaluation, system design and optimal operations. The presented methodology could be applied in other XRF based systems with modified imaging trajectories.
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Candidate Pathway-Based GWAS Identifies Novel Associations of Genomic Variants in the Complement System Associated with Coronary Artery Disease.
Circ Cardiovasc Genet
PUBLISHED: 09-25-2014
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-Genomic variants identified by genome-wide association studies (GWAS) explain <20% of heritability of coronary artery disease (CAD), thus many risk variants remain missing for CAD. Identification of new variants may unravel new biological pathways and genetic mechanisms for CAD. To identify new variants associated with CAD, we developed a candidate pathway-based GWAS by integrating expression quantitative loci (eQTL) analysis and mining of GWAS data with variants in a candidate pathway.
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Effect of Fluoxetine on [Ca²?]i and Cell Viability in OC2 Human Oral Cancer Cells.
Chin J Physiol
PUBLISHED: 09-23-2014
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Fluoxetine is a serotonin-specific reuptake inhibitor that has been used as an antidepressant. This study examined the effect of fluoxetine on cytosolic free Ca²? concentrations ([Ca2?]i) and viability in OC2 human oral cancer cells. The Ca²?-sensitive fluorescent dye fura-2 was used to measure [Ca²?]i, and the water soluble tetrazolium (WST-1) regent was used to measure viability. Fluoxetine induced [Ca²?]i rises concentration-dependently. The response was reduced by half by removing extracellular Ca²?. Fluoxetine-induced Ca²? entry was enhanced by activation of protein kinase C (PKC) with phorbol 12-myristate 13 acetate (PMA) but was inhibited by inhibition of the enzyme with GF109203X. In Ca²?-free medium, treatment with the endoplasmic reticulum Ca²? pump inhibitor 2,5-di-tert-butylhydroquinone (BHQ) or thapsigargin abolished fluoxetine-evoked [Ca²?]i rise. Conversely, treatment with fluoxetine inhibited BHQ/thapsigargin-evoked [Ca²?]i rise. Inhibition of phospholipase C (PLC) with U73122 abolished fluoxetine-induced [Ca²?]i rise. At 20-80 ?M, fluoxetine decreased cell viability concentration-dependently, which was not altered by chelating cytosolic Ca²? with 1,2-bis(2- aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester (BAPTA/AM). At 20-60 ?M, fluoxetine induced apoptosis as detected by annexin V/propidium iodide (PI) staining. Together, in OC2 cells, fluoxetine induced [Ca²?]i rises by evoking PLC-dependent Ca²? release from the endoplasmic reticulum and Ca²? entry via PKC-regulated mechanisms. Fluoxetine also caused Ca²?-independent apoptosis.
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Chemical Modifications of Therapeutic Proteins Induced by Residual Ethylene Oxide.
J Pharm Sci
PUBLISHED: 09-10-2014
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Ethylene oxide (EtO) is widely used in sterilization of drug product primary containers and medical devices. The impact of residual EtO on protein therapeutics is of significant interest in the biopharmaceutical industry. The potential for EtO to modify individual amino acids in proteins has been previously reported. However, specific identification of EtO adducts in proteins and the effect of residual EtO on the stability of therapeutic proteins has not been reported to date. This paper describes studies of residual EtO with two therapeutic proteins, a PEGylated form of the recombinant human granulocyte colony-stimulating factor (Peg-GCSF) and recombinant human erythropoietin (EPO) formulated with human serum albumin (HSA). Peg-GCSF was filled in an EtO sterilized delivery device and incubated at accelerated stress conditions. Glu-C peptide mapping and LC-MS analyses revealed residual EtO reacted with Peg-GCSF and resulted in EtO modifications at two methionine residues (Met-127 and Met-138). In addition, tryptic peptide mapping and LC-MS analyses revealed residual EtO in plastic vials reacted with HSA in EPO formulation at Met-328 and Cys-34. This paper details the work conducted to understand the effects of residual EtO on the chemical stability of protein therapeutics. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci.
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[Viral etiologies of hospitalized pneumonia patients aged less than five years in six provinces, 2009-2012].
Zhonghua Liu Xing Bing Xue Za Zhi
PUBLISHED: 09-02-2014
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To analyze the viral etiologies of hospitalized pneumonia patients aged less than five years in six provinces during 2009-2012, and to describe the seasonality of the detected viral etiologies.
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Fission yeast Pxd1 promotes proper DNA repair by activating Rad16XPF and inhibiting Dna2.
PLoS Biol.
PUBLISHED: 09-01-2014
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Structure-specific nucleases play crucial roles in many DNA repair pathways. They must be precisely controlled to ensure optimal repair outcomes; however, mechanisms of their regulation are not fully understood. Here, we report a fission yeast protein, Pxd1, that binds to and regulates two structure-specific nucleases: Rad16XPF-Swi10ERCC1 and Dna2-Cdc24. Strikingly, Pxd1 influences the activities of these two nucleases in opposite ways: It activates the 3' endonuclease activity of Rad16-Swi10 but inhibits the RPA-mediated activation of the 5' endonuclease activity of Dna2. Pxd1 is required for Rad16-Swi10 to function in single-strand annealing, mating-type switching, and the removal of Top1-DNA adducts. Meanwhile, Pxd1 attenuates DNA end resection mediated by the Rqh1-Dna2 pathway. Disabling the Dna2-inhibitory activity of Pxd1 results in enhanced use of a break-distal repeat sequence in single-strand annealing and a greater loss of genetic information. We propose that Pxd1 promotes proper DNA repair by differentially regulating two structure-specific nucleases.
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The Top 10 oomycete pathogens in molecular plant pathology.
Mol. Plant Pathol.
PUBLISHED: 09-01-2014
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Oomycetes form a deep lineage of eukaryotic organisms that includes a large number of plant pathogens that threaten natural and managed ecosystems. We undertook a survey to query the community for their ranking of plant pathogenic oomycete species based on scientific and economic importance. In total, we received 263 votes from 62 scientists in 15 countries for a total of 33 species. The Top 10 species and their ranking are: (1) Phytophthora infestans; (2, tied) Hyaloperonospora arabidopsidis; (2, tied) Phytophthora ramorum; (4) Phytophthora sojae; (5) Phytophthora capsici; (6) Plasmopara viticola; (7) Phytophthora cinnamomi; (8, tied) Phytophthora parasitica; (8, tied) Pythium ultimum; and (10) Albugo candida. The article provides an introduction to these 10 taxa and a snapshot of current research. We hope that the list will serve as a benchmark for future trends in oomycete research.
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Plasma and tissue free amino acid profiles and their concentration correlation in patients with lung cancer.
Asia Pac J Clin Nutr
PUBLISHED: 08-29-2014
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Variation of plasma free amino acids (PFAAs) is an essential feature of protein metabolic abnormalities in cancer patients. But there still little data about the cancer tissue free amino acid (TFAAs) profiles, including their patterns and correlations with PFAAs. To evaluate the variation in PFAAs and cancer TFAAs in patients with lung cancer, including their patterns and correlations, we investigated the concentrations of free amino acids in lung cancer tissues (n=27), paired lung paracarcinomous tissues (n=27) and plasma (n=27) using an automatic amino acid analyzer after pre-treatment. Within the PFAAs, the concentrations of five amino acids (tryptophan, glycine, citrulline, ornithine and proline) were significantly decreased, while that of phenylalanine was markedly increased compared with control subjects. Within the TFAAs, the concentrations of three amino acids (taurine, glutamic acid and glycine) were increased, while the concentrations of two amino acids (lysine and ornithine) were decreased significantly in lung cancer tissues compared with the paracarcinomous tissues. The amino acid patterns in PFAAs and TFAAs had similar trends, but percentage variations were diverse. Additionally, the concentrations of five amino acids (lysine, phenylalanine, threonine, serine, and alanine) in PFAAs correlated with those in lung cancer TFAAs, but no amino acids in PFAAs were correlated with those in lung paracarcinomous TFAAs. Thus, PFAA profiles may reflect the status of cancer tissues, which may provide more information about the metabolic statuses and prognoses of patients with lung cancer.
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[Altered effective connectivity of insula in nicotine addiction].
Zhonghua Yi Xue Za Zhi
PUBLISHED: 08-26-2014
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To explore the changes of effective connectivity associated with insula in different nicotine addiction sessions so as to understand its role and function.
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Proteomics analysis of altered cellular metabolism induced by insufficient copper level.
J. Biotechnol.
PUBLISHED: 08-20-2014
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Insufficient copper level in the mammalian cell culture medium resulted in lactate accumulation while maintaining similar growth and culture viability profiles. Label-free, LC-MS/MS-based shotgun proteomics method was applied to compare the protein expression profiles obtained from the cultures exposed to suboptimal copper level to those provided with sufficient amount of copper. Under copper deficient condition, a substantial reduction of the protein levels of the multiple subunits of Complex IV, also known as cytochrome c oxidase, of the mitochondrial electron transport chain was observed for all three different Chinese Hamster Ovary (CHO) cell lines expressing therapeutic monoclonal antibodies tested. Additional proteins affected by suboptimal copper level included peroxiredoxin (PRDX) and hepatocyte-derived growth factor (HDGF), which were affected during early phase of the fed-batch production, several days prior to initiation of lactate accumulation. In contrast, proteins such as syntenin (SDCBP) and integral membrane 2C (ITM2C) showed altered expression patterns toward the end of culture duration, after lactate divergence had occurred. For all conditions tested, time was the most predominant factor facilitating the direction of global protein expression trend, with substantial number of proteins subjected to time-dependent changes in expression, independent of copper.
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Process optimization and kinetic evaluation for biosynthesis of D-isoascorbyl stearate.
Bioprocess Biosyst Eng
PUBLISHED: 08-17-2014
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The synthesis of D-isoascorbyl stearate from D-isoascorbic acid and stearic acid with immobilized lipase (Novozym(®)435) as catalyst was studied. Response surface methodology and Box-Behnken design with six variables and three levels were employed to evaluate the effects of processing conditions on the conversion of D-isoascorbic acid. The results confirmed that the response surface method and statistical analysis were proved to be useful in developing optimal conditions for D-isoascorbyl stearate synthesis. The optimum conditions were predicted as follows: reaction temperature 48 °C, reaction time 17.7 h, immobilized lipase amount 50.0 % (w/w, of D-isoascorbic acid), substrate molar ratio 9:1 (stearic acid to D-isoascorbic acid), D-isoascorbic acid concentration 0.14 mol/L (based on solvent), 4A molecular sieve addition 200 g/L (based on solvent), and the optimal conversion was 90.6 %. Through the kinetics model fitting of the esterification, it was considered that the esterification conformed to a Ping-Pong bi-bi kinetic model with D-isoascorbic acid inhibition, and the obtained kinetic constants showed that the inhibition of D-isoascorbic acid and the enzyme affinity to substrate were abate with the increase of the reaction temperature.
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Control of the single-molecule magnet behavior of lanthanide-diarylethene photochromic assemblies by irradiation with light.
Chemistry
PUBLISHED: 08-11-2014
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Lanthanide-based extended coordination frameworks showing photocontrolled single-molecule magnet (SMM) behavior were prepared by combining highly anisotropic Dy(III) and Ho(III) ions with the carboxylato-functionalized photochromic molecule 1,2-bis(5-carboxyl-2-methyl-3-thienyl)perfluorocyclopentene (H2 dae), which acts as a bridging ligand. As a result, two new compounds of the general formula [{Ln(III) 2 (dae)3 (DMSO)3 (MeOH)}?10?MeOH]n (M=Dy for 1?a and Ho for 2) and two additional pseudo-polymorphs [{Dy(III) 2 (dae)3 (DMSO)3 (H2 O)}?x?MeOH]n (1?b) and [{Dy(III) 2 (dae)3 (DMSO)3 (DMSO)}?x?MeOH]n (1?c) were obtained. All four compounds have 2D coordination-layer topologies, in which carboxylate-bridged Ln2 units are linked together by dae(2-) anions into grid-like frameworks. All four compounds exhibited a strong reversible photochromic response to UV/Vis light. Moreover, both 1?a and 2 show field-induced SMM behavior. The slow magnetic relaxation of 1?a is influenced by the photoisomerization reaction leading to the observation of the cross-effect: photocontrolled SMM behavior.
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The mechanism of honokiol-induced intracellular Ca(2+) rises and apoptosis in human glioblastoma cells.
Chem. Biol. Interact.
PUBLISHED: 08-07-2014
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Honokiol, an active constituent of oriental medicinal herb Magnolia officinalis, caused Ca(2+) mobilization and apoptosis in different cancer cells. In vivo, honokiol crossed the blood-brain or -cerebrospinal fluid barrier, suggesting that it may be an effective drug for the treatment of brain tumors, including glioblastoma. This study examined the effect of honokiol on intracellular Ca(2+) concentration ([Ca(2+)]i) and apoptosis in DBTRG-05MG human glioblastoma cells. Honokiol concentration-dependently induced a [Ca(2+)]i rise. The signal was decreased partially by removal of extracellular Ca(2+). Honokiol-triggered [Ca(2+)]i rise was not suppressed by store-operated Ca(2+) channel blockers (nifedipine, econazole, SK&F96365) and the protein kinase C (PKC) activator phorbol 12-myristate 13 acetate (PMA), but was inhibited by the PKC inhibitor GF109203X. GF109203X-induced inhibition was not altered by removal of extracellular Ca(2+). In Ca(2+)-free medium, pretreatment with the endoplasmic reticulum Ca(2+) pump inhibitor thapsigargin (TG) or 2,5-di-tert-butylhydroquinone (BHQ) abolished honokiol-induced [Ca(2+)]i rise. Conversely, incubation with honokiol abolished TG or BHQ-induced [Ca(2+)]i rise. Inhibition of phospholipase C (PLC) with U73122 abolished honokiol-induced [Ca(2+)]i rise. Honokiol (20-80?M) reduced the cell viability, which was not reversed by prechelating cytosolic Ca(2+) with BAPTA-AM (1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester). Honokiol (20-60?M) enhanced reactive oxygen species (ROS) production, decreased mitochondrial membrane potential, released cytochrome c, and activated caspase-9/caspase-3. Together, honokiol induced a [Ca(2+)]i rise by inducing PLC-dependent Ca(2+) release from the endoplasmic reticulum and Ca(2+) entry via PKC-dependent, non store-operated Ca(2+) channels. Moreover, honokiol activated the mitochondrial pathway of apoptosis in DBTRG-05MG human glioblastoma cells.
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Homochiral Cobalt Phosphonates Containing ?-type Chains with a Tunable Interlayer Distance and a Field-Induced Phase Transition.
Chemistry
PUBLISHED: 07-27-2014
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Two pairs of enantiomeric Co(II) compounds with formulas [Co2 (?3 -OH)(cyamp)(Cn H2n+1 COO)] (cyampH2 =(S)- or (R)-[(1-cyclohexylethyl)amino]methylphosphonic acid; n=1 (1); n=7 (2)) were synthesized. The structures of S-1 and S-2 were determined by single-crystal structural analyses. Both crystallize in a monoclinic chiral space group P21 , and exhibit layered structures in which the ?-type chains of corner-sharing Co3 (?3 -OH) triangles are connected by the phosphonate groups. The interlayer spaces are filled with the organic groups of the phosphonate and carboxylate ligands. Therefore, the distances between the layers can be manipulated by the length of the alkyl chain of the carboxylate ligands, from 14.6?Å in 1 to 20.0?Å in 2. Magnetic studies were carried out for compounds S-1 and S-2. Both show metamagnetism at low temperature. The critical field decreases with increasing interlayer distance from 8.18?kOe for S-1 to 7.01?kOe for S-2 at 1.8?K. The optical properties were also studied.
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Effect of rifampicin on the pharmacokinetics of lenvatinib in healthy adults.
Clin Drug Investig
PUBLISHED: 07-16-2014
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Lenvatinib is an oral, multitargeted tyrosine kinase inhibitor under clinical investigation in solid tumours. This study evaluated the influence of P-glycoprotein (P-gp) inhibition (single-dose rifampicin) and simultaneous cytochrome P450 3A4 (CYP3A4)/P-gp induction (multiple-dose rifampicin) on lenvatinib pharmacokinetics.
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Design, fabrication, and characterization of archaeal tetraether free-standing planar membranes in a PDMS- and PCB-based fluidic platform.
ACS Appl Mater Interfaces
PUBLISHED: 06-30-2014
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The polar lipid fraction E (PLFE) isolated from the thermoacidophilic archaeon Sulfolobus acidocaldarius contains exclusively bipolar tetraether lipids, which are able to form extraordinarily stable vesicular membranes against a number of chemical, physical, and mechanical stressors. PLFE liposomes have thus been considered appealing biomaterials holding great promise for biotechnology applications such as drug delivery and biosensing. Here we demonstrated that PLFE can also form free-standing "planar" membranes on micropores (?100 ?m) of polydimethylsiloxane (PDMS) thin films embedded in printed circuit board (PCB)-based fluidics. To build this device, two novel approaches were employed: (i) an S1813 sacrificial layer was used to facilitate the fabrication of the PDMS thin film, and (ii) oxygen plasma treatment was utilized to conveniently bond the PDMS thin film to the PCB board and the PDMS fluidic chamber. Using electrochemical impedance spectroscopy, we found that the dielectric properties of PLFE planar membranes suspended on the PDMS films are distinctly different from those obtained from diester lipid and triblock copolymer membranes. In addition to resistance (R) and capacitance (C) that were commonly seen in all the membranes examined, PLFE planar membranes showed an inductance (L) component. Furthermore, PLFE planar membranes displayed a relatively large membrane resistance, suggesting that, among the membranes examined, PLFE planar membrane would be a better matrix for studying channel proteins and transmembrane events. PLFE planar membranes also exhibited a sharp decrease in phase angle with the frequency of the input AC signal at ?1 MHz, which could be utilized to develop sensors for monitoring PLFE membrane integrity in fluidics. Since the stability of free-standing planar lipid membranes increases with increasing membrane packing tightness and PLFE lipid membranes are more tightly packed than those made of diester lipids, PLFE free-standing planar membranes are expected to be considerably stable. All these salient features make PLFE planar membranes particularly attractive for model studies of channel proteins and transmembrane events and for high-throughput drug screening and artificial photosynthesis. This work can be extended to nanopores of PDMS thin films in microfluidics and eventually aid in membrane-based new lab-on-a-chip applications.
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[Analysis of effect on infectious diseases outbreak detection performance by classifying provinces for moving percentile method].
Zhonghua Yu Fang Yi Xue Za Zhi
PUBLISHED: 06-28-2014
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Providing evidences for further modification of China Infectious Diseases Automated-alert and Response System (CIDARS) via analyzing the outbreak detection performance of Moving Percentile Method (MPM) by optimizing thresholds in different provinces.
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[Comparing the performance of temporal model and temporal-spatial model for outbreak detection in China Infectious Diseases Automated-alert and Response System, 2011-2013, China].
Zhonghua Yu Fang Yi Xue Za Zhi
PUBLISHED: 06-28-2014
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For providing evidences for further modification of China Infectious Diseases Automated-alert and Response System (CIDARS) by comparing the early-warning performance of the temporal model and temporal-spatial model in CIDARS.
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[The implement performance of China Infectious Diseases Automated-alert and Response System in 2011-2013].
Zhonghua Yu Fang Yi Xue Za Zhi
PUBLISHED: 06-28-2014
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To analyze the implement performance of China Infectious Diseases Automated-alert and Response System (CIDARS) of 31 provinces in mainland China, and to provide the evidences for further promoting the application and improvement of this system.
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Effect of melamine on [Ca(2+)]i and viability in PC3 human prostate cancer cells.
Environ. Toxicol. Pharmacol.
PUBLISHED: 06-20-2014
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Melamine is thought to be an endocrine disrupter that affects physiology in cells. This study examined the effect of melamine on cytosolic free Ca(2+) concentrations ([Ca(2+)]i) and viability in PC3 human prostate cancer cells. Melamine evoked [Ca(2+)]i rises concentration-dependently. Melamine-evoked Ca(2+) entry was inhibited by nifedipine, econazole, SKF96365, GF109203X and phorbol 12-myristate 13 acetate. In Ca(2+)-free medium, treatment with the endoplasmic reticulum Ca(2+) pump inhibitor thapsigargin inhibited melamine-evoked [Ca(2+)]i rise. Conversely, treatment with melamine abolished thapsigargin-evoked [Ca(2+)]i rise. Inhibition of phospholipase C with U73122 did not alter melamine-evoked [Ca(2+)]i rise. Melamine at 500-800?M decreased cell viability, which was not reversed by pretreatment with the Ca(2+) chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester (BAPTA/AM). Collectively, our data suggest that in PC3 cells, melamine induced [Ca(2+)]i rises by evoking phospholipase C-independent Ca(2+) release from the endoplasmic reticulum, and Ca(2+) entry via protein kinase C-regulated store-operated Ca(2+) entry. Melamine also caused Ca(2+)-independent cell death.
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A luminescent heptanuclear DyIr6 complex showing field-induced slow magnetization relaxation.
Chem. Commun. (Camb.)
PUBLISHED: 06-20-2014
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The first example of iridium/lanthanide phosphonates, i.e. [DyIr6(ppy)12(bpp)2(bppH)4](CF3SO3)·8H2O (1) (ppy(-) = 2-phenylpyridine, bpp(2-) = 2-pyridylphosphonate) is reported. It shows dual functions with the photoluminescence and field-induced slow magnetization relaxation originating from the Ir and Dy moieties, respectively.
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A layered erbium phosphonate in pseudo-D(5h) symmetry exhibiting field-tunable magnetic relaxation and optical correlation.
Chem. Commun. (Camb.)
PUBLISHED: 06-04-2014
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A layered erbium(III) phosphonate compound, [Er(notpH4)(H2O)]ClO4·3H2O (1), in which the Er(III) ion has a pseudo-D5h symmetry exhibits field tunable multiple magnetic relaxation. The near-IR emission spectrum of 1, excited at 1064 nm (Nd:YAG laser), provides a direct probe of the crystal field splitting correlated to the magnetic data.
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The mechanism of bifonazole-induced [Ca(2+)]i rises and non-Ca(2+)-triggered cell death in PC3 human prostate cancer cells.
J. Recept. Signal Transduct. Res.
PUBLISHED: 05-22-2014
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Abstract Bifonazole is an antifungal drug widely used for treating skin diseases. The effect of bifonazole on physiology of cancer cells is unclear. The effect of bifonazole on cytosolic free Ca(2+) concentrations ([Ca(2+)]i) and viability in PC3 human prostate cancer cells was explored. The Ca(2+)-sensitive fluorescent dye, fura-2, was applied to measure [Ca(2+)]i. Bifonazole at concentrations of 5-30?µM induced a [Ca(2+)]i rise in a concentration-dependent manner. The response was reduced by 50% by removing extracellular Ca(2+). Bifonazole-evoked [Ca(2+)]i rise was not altered by nifedipine, econazole, SK&F96365 and protein kinase C activator, but was inhibited by 75% by GF109203X, a protein kinase C inhibitor. In Ca(2+)-free medium, treatment with the endoplasmic reticulum Ca(2+) pump inhibitor 2,5-di-tert-butylhydroquinone (BHQ) nearly abolished bifonazole-evoked [Ca(2+)]i rise. Conversely, treatment with bifonazole abolished BHQ-evoked [Ca(2+)]i rise. Inhibition of phospholipase C with U73122 abolished bifonazole-induced [Ca(2+)]i rise. At 30-100?µM, bifonazole decreased cell viability concentration-dependently, which was not reversed by chelating cytosolic Ca(2+) with 1,2-bis(2-aminophenoxy)ethane-N,N,N?,N'-tetraacetic acid/acetoxy methyl. Annexin V/propidium iodide staining data suggest that bifonazole (30-100?µM) induced apoptosis concentration-dependently. Together, in PC3 human prostate cancer cells, bifonazole induced [Ca(2+)]i rises by inducing phospholipase C- and protein kinase C-dependent Ca(2+) release from the endoplasmic reticulum and Ca(2+) influx via non-store-operated pathways. Bifonazole induced cell death that might involve apoptosis.
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[Research progress of three-dimensional printing technique in joint surgery].
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi
PUBLISHED: 05-22-2014
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To summarize the application status of three-dimensional (3-D) printing technique in joint surgery and look forward to the future research directions.
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An analysis of women¿s and children¿s health professional requirements in China in 2010 based on workload.
BMC Health Serv Res
PUBLISHED: 05-19-2014
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BackgroundTo make health services more equitable and accessible for women and children and to achieve a universal coverage, human resources for women and children¿s health (WCH) should be evaluated. However, since there is still no consensus on the real situation of Chinese WCH professionals, we aim with this study to compare the actual and required amount of WCH professionals for China.MethodsThe data of the actual number of WCH professionals and workload of each service type was obtained by a national institution-based sampling survey. We then estimated the time that a WCH professional spends at work (annually), the time norm of each service schedule and the required number of WCH professionals based on workload. We evaluated the situation of Chinese WCH professionals in 2010 by comparing the actual and required WCH professionals and by calculating the ratios of the actual-to-required number of staff.ResultsThere were 515,778 health professionals providing WCH services in the investigated 5,168 medical/health institutions in 2010. Workloads of most WCH services in east areas were larger than that in the central and the west. For women¿s health, the numbers of required WCH professionals were 48510, 43992, 40571 and 133073 for the east, the central, the west areas and the whole nation respectively. For children¿s health professionals, the corresponding numbers were 56241, 36818, 40618 and 133677 for the east, the central, the west and the whole nation.ConclusionsThe WCH professionals in China were sufficient for workload in 2010, there were still lots of potential capacities to provide better services, especially for women. Strategies should be taken to improve the quality of WCH professionals or their working motivation.
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The Mechanism of NPC-14686-Induced [Ca²?]i Rises and Non-Ca²?-Triggered Cell Death in MG63 Human Osteosarcoma Cells.
Chin J Physiol
PUBLISHED: 05-16-2014
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NPC-14686 has been shown to have anti-inflammatory effect in previous studies, but the mechanisms are unclear. The effect of NPC-14686 on cytosolic Ca²? concentrations ([Ca²?]i) and viability in MG63 human osteosarcoma cells was explored. The Ca²?-sensitive fluorescent dye fura-2 was applied to measure [Ca²?]i. NPC-14686 at concentrations of 100-500 ?M induced a [Ca²?]i rise in a concentrationdependent manner. The response was reduced by 80% by removing Ca²?. NPC-14686 induced Mn²? influx leading to quenching of fura-2 fluorescence. NPC-14686-evoked Ca²? entry was suppressed by nifedipine, econazole, SK&F96365, and protein kinase C inhibitor. Inhibition of phospholipase C with U73122 abolished NPC-14686-induced [Ca²?]i rise. At 20-50 ?M, NPC-14686 decreased cell viability, which was not reversed by chelating cytosolic Ca²? with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid/acetoxy methyl (BAPTA/AM). Annexin V/propidium iodide staining data suggest that NPC-14686 (30-50 ?M) induced apoptosis in a concentration-dependent manner. NPC-14686 also increased levels of reactive oxygen species. Together, in human osteosarcoma cells, NPC-14686 induced a [Ca²?]i rise by inducing phospholipase C-dependent Ca²? release from the endoplasmic reticulum and Ca²? entry via protein kinase C-sensitive store-operated Ca²? channels. NPC-14686 induced cell death that might involve apoptosis via mitochondrial pathways.
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Discovery and characterization of a photo-oxidative histidine-histidine cross-link in IgG1 antibody utilizing ¹?O-labeling and mass spectrometry.
Anal. Chem.
PUBLISHED: 05-02-2014
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A novel photo-oxidative cross-linking between two histidines (His-His) has been discovered and characterized in an IgG1 antibody via the workflow of XChem-Finder, (18)O labeling and mass spectrometry (Anal. Chem. 2013, 85, 5900-5908). Its structure was elucidated by peptide mapping with multiple proteases with various specificities (e.g., trypsin, Asp-N, and GluC combined with trypsin or Asp-N) and mass spectrometry with complementary fragmentation modes (e.g., collision-induced dissociation (CID) and electron-transfer dissociation (ETD)). Our data indicated that cross-linking occurred across two identical conserved histidine residues on two separate heavy chains in the hinge region, which is highly flexible and solvent accessible. On the basis of model studies with short peptides, it has been proposed that singlet oxygen reacts with the histidyl imidazole ring to form an endoperoxide and then converted to the 2-oxo-histidine (2-oxo-His) and His+32 intermediates, the latter is subject to a nucleophilic attack by the unmodified histidine; and finally, elimination of a water molecule leads to the final adduct with a net mass increase of 14 Da. Our findings are consistent with this mechanism. Successful discovery of cross-linked His-His again demonstrates the broad applicability and utility of our XChem-Finder approach in the discovery and elucidation of protein cross-linking, particularly without a priori knowledge of the chemical nature and site of cross-linking.
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QPEEG analysis of the effects of sodium valproate on adult Chinese patients with generalized tonic-clonic seizures.
Metab Brain Dis
PUBLISHED: 04-30-2014
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Objectives EEG effects of the sustained-release form of sodium valproate (SR-VPA) are unknown, although it is widely used in Chinese patients with generalized tonicclonic seizures (GTCS). Methods Fourteen newly diagnosed, untreated GTCS patients were recruited and treated with SR-VPA. Waking EEG was recorded and analyzed by way of quantitative pharmaco-electroencephalogram (QPEEG) analysis during the three-month follow-up. Results There was a statistically significant decrease in the absolute power of the delta band (P?
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Ultrasensitive dual amplification sandwich immunosensor for breast cancer susceptibility gene based on sheet materials.
Analyst
PUBLISHED: 04-29-2014
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A new electrochemical dual amplification sandwich immunosensor (DASI) was designed for ultrasensitive and accurate detection of the breast cancer susceptibility gene based on the combination of N-doped graphene, hydroxypropyl chitosan and Co3O4 mesoporous nanosheets. N-doped graphene has better electroconductibility than traditional graphene. It is an ideal electrochemical material with a large specific surface area and low resistance. Hydroxypropyl chitosan replaces the pure chitosan in immobilization of the sensor to achieve the sensitivity increase. Co3O4 mesoporous nanosheets can enhance the effective area of the immunoreaction. This kind of dual amplification sandwich immunosensor was first used for the detection of the breast cancer susceptibility gene. It has a wide linear response range of 0.001-35 ng mL(-1) and a minimum detection limit of 0.33 pg mL(-1). It was demonstrated that the stability, selectivity and reproducibility of the sensor were acceptable. The fabricated immunosensor shows great potential applications in early disease diagnosis.
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Influence of hepatic impairment on lenvatinib pharmacokinetics following single-dose oral administration.
J Clin Pharmacol
PUBLISHED: 04-04-2014
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This open-label, single-dose study assessed lenvatinib pharmacokinetics (PK) in subjects with normal hepatic function (n?=?8) and mild, moderate, or severe hepatic impairment (n?=?6 each). Subjects received 10?mg oral lenvatinib, except those with severe hepatic impairment (5?mg). Plasma and urine samples were collected over 14 days; free and total lenvatinib and its metabolites were analyzed using validated chromatography/spectrometry. PK parameters were estimated using noncompartmental analysis. There were no clinically meaningful effects of mild or moderate hepatic impairment on lenvatinib PK. Dose-normalized Cmax for free lenvatinib was 7.0, 3.7, 5.7, and 5.6?ng/mL in subjects with normal hepatic function, mild, moderate, and severe hepatic impairment, respectively. There was no consistent trend, although dose-normalized Cmax was lower for all subjects with hepatic impairment. AUCs increased 170% and t1/2 increased (37 versus 23?hours) in subjects with severe hepatic impairment. Changes in exposure based on total plasma concentrations were generally less than those based on free concentrations, suggesting changes in plasma protein binding in subjects with severe hepatic impairment. Lenvatinib was generally well tolerated. Subjects with severe hepatic impairment should begin lenvatinib treatment at a reduced dose of 14?mg versus 24?mg for subjects with normal liver function and subjects with mild or moderate hepatic impairment.
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Effects of Thymol on Ca²? Homeostasis and Apoptosis in MDCK Renal Tubular Cells.
Chin J Physiol
PUBLISHED: 04-04-2014
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Thymol is a natural essential oil present in many plants and has many different effects in various cell types. However, the effect of thymol on the physiology of MDCK renal tubular cells is unknown. The action of the phytochemical thymol on cytosolic Ca²? concentrations ([Ca²?]i) and apoptosis in Madin-Darby canine kidney (MDCK) renal tubular cells was explored. Fura-2, a Ca²?-sensitive fluorescent dye, was used to assess [Ca²?]i. Thymol at concentrations of 200-500 ?M caused a [Ca²?]i rise in a concentration-dependent manner. Removal of extracellular Ca²? partially reduced the effects of thymol. Thymol-induced Ca²? entry was inhibited by nifedipine, econazole, SK&F96365 and protein kinase C modulators. In a Ca²?-free medium, treatment with the endoplasmic reticulum Ca²? pump inhibitor thapsigargin inhibited thymol-induced [Ca²?]i increases. Treatment with thymol also inhibited thapsigargin-induced [Ca²?]i rise. Thymol killed cells at concentrations of 300-500 ?M in a concentrationdependent fashion. Chelating cytosolic Ca²? with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid/AM (BAPTA/AM) did not prevent thymol cytotoxicity. Thymol (400 and 500 ?M) induced apoptosis detected by using Annexin V/propidium iodide staining. At 400 or 500 ?M, thymol increased levels of reactive oxygen species. Together, in MDCK cells, thymol induced a [Ca²?]i rise by inducing Ca²? release from the endoplasmic reticulum and Ca²? entry via protein kinase C-sensitive store-operated Ca²? channels. Our data suggest that thymol-induced apoptosis might involve reactive oxygen species (ROS) production.
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Transcriptomic analysis of the phytopathogenic oomycete Phytophthora cactorum provides insights into infection-related effectors.
BMC Genomics
PUBLISHED: 03-31-2014
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Phytophthora cactorum, a hemibiotrophic oomycete pathogen, can cause destructive diseases on numerous crops worldwide, leading to essential economic losses every year. However, little has been known about its molecular pathogenicity mechanisms. To gain insight into its repertoire of effectors, the P. cactorum transcriptome was investigated using Illumina RNA-seq.
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Rise of [Ca²?]i and apoptosis induced by M-3M3FBS in SCM1 human gastric cancer cells.
Chin J Physiol
PUBLISHED: 03-14-2014
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M-3M3FBS (2,4,6-trimethyl-N-(meta-3-trifluoromethyl-phenyl)-benzenesulfonamide is a presumed phospholipase C activator which induced Ca²? movement and apoptosis in different cell models. How- ever, the effect of m-3M3FBS on cytosolic free Ca²? concentrations ([Ca²?]i) and apoptosis in SCM1 human gastric cancer cells is unclear. This study explored whether m-3M3FBS elevated basal [Ca²?]i levels in suspended cells by using fura-2 as a Ca²?-sensitive fluorescent dye. M-3M3FBS at concentrations between 5-50 ?M increased [Ca²?]i in a concentration-dependent manner. The Ca²? signal was reduced by half by removing extracellular Ca²?. M-3M3FBS-induced Ca²? influx was inhibited by nifedipine, econazole, SK&F96365, aristolochic acid, and GF109203X. In Ca²?-free medium, 50 ?M m-3M3FBS pretreatment inhibited the [Ca²?]i rise induced by the endoplasmic reticulum Ca²? pump inhibitor thapsigargin. Conversely, pretreatment with thapsigargin partly reduced m-3M3FBS-induced [Ca²?]i rise. Suppression of inositol 1,4,5-trisphosphate production with U73122 did not change m-3M3FBS- induced [Ca²?]i rise. At concentrations between 25 and 50 ?M m-3M3FBS killed cells in a concentration- dependent manner. The cytotoxic effect of m-3M3FBS was not reversed by prechelating cytosolic Ca²? with acetoxy-methyl ester of bis-(o-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid (BAPTA/AM). Annexin V/propidium iodide staining data suggest that m-3M3FBS induced apoptosis at 25 and 50 ?M. M-3M3FBS also increased levels of superoxide. Together, in human gastric cancer cells, m-3M3FBS induced a [Ca²?]i rise by inducing phospholipase C-independent Ca²? release from the endoplasmic reticulum and Ca²? entry via protein kinase C-sensitive store-operated Ca²? channels. M-3M3FBS induced cell death that might involve apoptosis via reactive oxygen species production.
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Three-dimensional x-ray fluorescence mapping of a gold nanoparticle-loaded phantom.
Med Phys
PUBLISHED: 03-06-2014
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X-ray fluorescence (XRF) is a promising technique with sufficient specificity and sensitivity for identifying and quantifying features in small samples containing high atomic number (Z) materials such as iodine, gadolinium, and gold. In this study, the feasibility of applying XRF to early breast cancer diagnosis and treatment is studied using a novel approach for three-dimensional (3D) x-ray fluorescence mapping (XFM) of gold nanoparticle (GNP)-loaded objects in a physical phantom at the technical level.
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Nanosheet Au/Co3O4-based ultrasensitive nonenzymatic immunosensor for melanoma adhesion molecule antigen.
Biosens Bioelectron
PUBLISHED: 03-04-2014
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Highly sensitive and enzyme-free detection of melanoma adhesion molecule antigen (CD146) remains a challenge in clinical diagnosis. The prepared immunosensor, based on amination graphene (GS-NH2) and mesoporous nano-Co3O4 sheet combined with gold nanoparticles (Au/Co3O4), exhibited significantly increased electron transfer, high sensitivity and stability to CD146. Au/Co3O4 can increase the contact surface between the antibody and Au nanoparticles attached on Co3O4 than mesoporous Co3O4 only. And the mesoporous Co3O4 nanosheet can capture more biomolecules to enhance the sensitivity due to the large effective specific area. Amperometric i-t curve and electrochemical impedance spectroscopy (EIS) were used to characterize the recognition of CD146. This novel immunosensor, works well over a broad linear range of 0.01-15ng/mL, with a low detection limit of 3.4pg/mL (S/N=3). The immunosensor was evaluated for the determination of human serum sample, and received a satisfactory result. The developed immunosensor provides a promising approach for clinical research and diagnostic applications.
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Simultaneous electrochemical immunosensor based on water-soluble polythiophene derivative and functionalized magnetic material.
Anal. Chim. Acta
PUBLISHED: 03-03-2014
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A novel, sensitive electrochemical immunosensor for simultaneous determination of squamous cell carcinoma associated antigen (SCC-Ag) and carcinoembryonic antigen (CEA) for the combined diagnosis of cervical cancer was designed. The amplification strategy for electrochemical immunoassay was based on poly[3-(1,1'-dimethyl-4-piperidine-methylene) thiophene-2,5-diylchloride] (PDPMT-Cl) and functionalized mesoporous ferroferric oxide nanoparticles (Fe3O4 NPs). PDPMT-Cl dispersed in chitosan solution with enhanced electrical conductivity and solubility was used as matrices to immobilize the first antibodies. Different redox probes (thionine (Th) and ferrocenecarboxylic acid (Fca)) functionalized Fe3O4 NPs incubated with two kinds of secondary antibodies to fabricate the labels. Using an electrochemical analysis technique, two well-separated peaks were generated by Th and Fca, making the simultaneous detection of two analytes on the electrode possible. Under optimized conditions, this method showed wide linear ranges of three orders of magnitude with the detection limits of 4 pg mL(-1) and 5 pg mL(-1), respectively. The disposable immunosensor possessed excellent clinical value in cervical cancer screening as well as convenient point-of-care diagnostics.
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Copper-mediated direct aryloxylation of benzamides assisted by an N,O-bidentate directing group.
Org. Lett.
PUBLISHED: 02-06-2014
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Copper-mediated selective mono- or diaryloxylation of benzamides has been achieved by using 2-aminopyridine 1-oxide as a new and removable N,O-bidentate directing group. The reaction system shows a broad substrate scope and provides a straightforward way for the synthesis of mono- and diaryloxylated benzoic acids.
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Extracellular lipase of an entomopathogenic fungus effecting larvae of a scale insect.
J. Basic Microbiol.
PUBLISHED: 01-10-2014
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Lipases play an important role in the infection process of entomopathogenic fungi by hydrolyzing the ester bonds of lipoproteins, fats and waxes present on the insect surface and in the body. Here we report the purification and characterization of an extracellular lipase from Isaria fumosorosea. The enzyme was purified (138.46-fold) in three steps using (NH4 )2 SO4 precipitation followed by DEAE-cellulose and Sephadex G-100 column chromatography. The molecular weight of purified enzyme was determined to be 31?KDa by SDS-PAGE. The optimum temperature and pH for enzyme activity were 35?°C and 7.0, respectively, using p-nitrophenylpalmitate as the substrate. Lipolytic activity was enhanced in the presence of Ca(+2) , Mg(+2) , Na(+) , and NH4 (+) salts, while Zn(+2) , Fe(+2) , and Cu(+2) inhibited enzyme activity. The enzyme displayed broad substrate specificity with the highest activity observed for coconut oil and p-nitrophenyl carprate. Topical co-application of purified lipase with fungal conidial suspensions decreased the median survival time (ST50 ) of Dysmicoccus neobrevipes nymphs as compared to the fungus alone. Our results indicate that an extracellular lipase produced by I. fumosorosea can be exploited for development of enzyme-based insect management.
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Regulation of CARD8 expression by ANRIL and association of CARD8 single nucleotide polymorphism rs2043211 (p.C10X) with ischemic stroke.
Stroke
PUBLISHED: 01-02-2014
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ANRIL has long been considered as the strongest candidate gene at the 9p21 locus, robustly associated with stroke and coronary artery disease. However, the underlying molecular mechanism remains unknown. The present study works to elucidate such a mechanism.
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Myocardial Injury after Surgery Is a Risk Factor for Weaning Failure from Mechanical Ventilation in Critical Patients Undergoing Major Abdominal Surgery.
PLoS ONE
PUBLISHED: 01-01-2014
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Myocardial injury after noncardiac surgery (MINS) is a newly proposed concept that is common among adults undergoing noncardiac surgery and associated with substantial mortality. We analyzed whether MINS was a risk factor for weaning failure in critical patients who underwent major abdominal surgery.
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A new species and first record of the genus Cynegetis Chevrolat (Coleoptera, Coccinellidae, Epilachnini) from China.
Zookeys
PUBLISHED: 01-01-2014
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The first species of the genus Cynegetis Chevrolat is recorded from China. Cynegetischinensis Wang & Ren, sp. n. is described from the Ningxia Province in North China. A key to the known species of Cynegetis is given. Diagnostic similarities and differences between Cynegetis and Subcoccinella Agassiz & Erichson are discussed and illustrated.
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RNAi-mediated knockdown of serine protease inhibitor genes increases the mortality of Plutella xylostella challenged by destruxin A.
PLoS ONE
PUBLISHED: 01-01-2014
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Destruxin A is a mycotoxin that is secreted by entomopathogenic fungi which has a broad-spectrum insecticidal effect. Previous transcript and protein profiling analysis showed that destruxin A has significant effects on the expression of serine protease inhibitor genes (serpin-2, 4, 5) in the larvae of Plutella xylostella. In the current study, we aimed to understand the role of serpins under application of destruxin A. We obtained two full-length cDNA sequences of P. xylostella serpins, named serpin-4 and serpin-5, and cloned the serpin-2 gene whose full-length has already been published. Phylogenetic analysis indicated that these two serpin genes were highly clustered with other serpins associated with the immune response in other insects. The temporal and spatial expression of serpin-2, serpin-4 and serpin-5 were determined to be the highest in the fat body and hemolymph of 4th larval stage using qRT-PCR and western blot detection techniques. RNA interference (RNAi) mediated knockdown of P. xylostella serpin genes was carried out by microinjection of double-stranded RNA (dsRNA). The expression levels of serpins decreased significantly after RNAi. Results showed that the depletion of serpins induced cecropins expression, increased phenoloxidase (PO) activity, body melanization and mortality in the larvae of P. xylostella under the same lethal concentration of destruxin A. The superimposed effects of serpins RNAi were similar with the destruxin A treatment upon mortality of P. xylostella larvae. We discovered for the first time that serpins play indispensable role in P. xylostella when challenged by destruxin A and deduced the possible function mechanism of destruxin A. Our findings are conducive to fully understanding the potential insecticidal mechanism of destruxin A and constitute a well-defined potential molecular target for novel insecticides.
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Expression and function of kisspeptin during mouse decidualization.
PLoS ONE
PUBLISHED: 01-01-2014
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Plasma kisspeptin levels dramatically increased during the first trimester of human pregnancy, which is similar to pregnancy specific glycoprotein-human chorionic gonadotropin. However, its particular role in the implantation and decidualization has not been fully unraveled. Here, the study was conducted to investigate the expression and function of kisspeptin in mouse uterus during early pregnancy and decidualization.
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Endovascular Treatment of an Unusual Primary Arterioportal Fistula Complicated by Cavernous Transformation of the Portal Vein Caused by Portal Thrombosis.
Ann Vasc Surg
PUBLISHED: 12-22-2013
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We describe an elderly woman who presented with an unusual primary arterioportal fistula and cavernous transformation of the portal vein caused by portal thrombosis, which were subsequently managed with endovascular coil embolization and transjugular intrahepatic portosystemic shunt using 2 stents after balloon remodeling. This case shows a rarely seen condition in the elderly and a novel management strategy that should be considered in the management of this complex disease.
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[Clinical value of iodine [131I] metuximab infusion combined with TACE for treatment of patients with post-intervention relapse of mid or advanced stage hepatocellular carcinoma].
Zhonghua Gan Zang Bing Za Zhi
PUBLISHED: 12-17-2013
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To evaluate the clinical value of iodine[131I] metuximab infusion combined with transcatheter arterial chemoembolization (TACE) for treating cases of post-intervention relapse of mid or advanced stage hepatocellular carcinoma (HCC).
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Twenty-year trends in major cardiovascular risk factors in hospitalized patients with acute myocardial infarction in Beijing.
Chin. Med. J.
PUBLISHED: 11-19-2013
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Hypertension, diabetes mellitus, hypercholesterolaemia and current smoking are the strongest modifiable cardiovascular risk factors for acute myocardial infarction (AMI). We examined their changing trends over the last 20 years.
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Assessment of 64-row computed tomographic angiography for diagnosis and pretreatment planning in pulmonary sequestration.
Radiol Med
PUBLISHED: 11-15-2013
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This study was done to evaluate the clinical implications and results of a prospective protocol using 64-row computed tomographic angiography (CTA) for diagnosis and pre-treatment planning in pulmonary sequestration (PS).
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Influenza vaccination acceptance among diverse pregnant women and its impact on infant immunization.
Hum Vaccin Immunother
PUBLISHED: 10-30-2013
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Objective: We examined pregnant womens likelihood of vaccinating their infants against seasonal influenza via a randomized message framing study. Using Prospect Theory, we tested gain- and loss-frame message effects and demographic and psychosocial correlates of influenza immunization intention. We also explored interactions among pregnant women who viewed "Contagion" to understand cultural influences on message perception. Methods: Pregnant women ages 18-50 participated in a randomized message framing study from September 2011 through May 2012 that included exposure to intervention or control messages, coupled with questionnaire completion. Venue-based sampling was used to recruit racial and ethnic minority female participants at locations throughout Atlanta, Georgia. Bivariate and multivariate analyses were conducted to evaluate key outcomes. Results: The study population (n = 261) included many lower income (? $20?000/yearly household earnings) pregnant participants (69.2%, n = 171) inclusive of Black/African Americans (88.5%, n = 230), Hispanic/Latinas (7.3%, n = 19), and Other/Multicultural women (4.2%, n = 11). Both gain [OR = 2.13, 90% CI: (1.120, 4.048)] and loss-frame messages [OR = 2.02, 90% CI: (1.083, 3.787)] were significantly associated with infant influenza vaccination intention compared with the control condition. Intention to immunize against influenza during pregnancy had a strong effect on intent to immunize infants [OR = 10.83, 90%CI: (4.923, 23.825)]. Those who had seen the feature film "Contagion" (n = 54, 20.69%) viewed gain- and loss-framed messages as appealing (x (2) = 6.03, p = 0.05), novel (x (2) = 6.24, p = 0.03), and easy to remember (x (2) = 16.33, p = 0.0003). Conclusions: In this population, both gain- and loss-framed messages were positively associated with increased maternal intent to immunize infants against influenza. Message resonance was enhanced among those who saw the film "Contagion." Additionally, history of immunization was strongly associated with infant immunization intention. :
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Cobalt phosphonates based on 4-(ethoxycarbonyl)naphthalen-1-yl)phosphonic acid.
Dalton Trans
PUBLISHED: 09-26-2013
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The first examples of metal phosphonates based on 4-(ethoxycarbonyl)naphthanen-1-yl)phosphonic acid (4-cnppH2) are reported, namely, Co(4-cnpp) (1), Co2(4-cnpp)2(dptz) (2) and Co2(4-cnpp)2(4,4-bpy)(H2O) (3) (dptz = 3,6-di(pyridin-3-yl)-1,2,4,5-tetrazine, 4,4-bpy = 4,4-bipyridine). The cobalt atoms are four-coordinated with distorted tetrahedral geometries in both 1 and 2, while five-coordinated with a distorted trigonal bipyramidal environment in compound 3. Compound 1 shows a layer structure in which the inorganic layers made up of edge-sharing {CoNO3} dimers and {PO3C} linkages are separated by the organic groups of the 4-cnpp(2-) ligands. Compound 2 displays a different type of layer structure, where the ladder-like chains composed of corner-sharing {CoNO3} and {PO3C} tetrahedra are connected by dptz ligands with the organic groups of the 4-cnpp(2-) ligands pendent on the two sides of the layer. In 3, similar ladder-like chains of corner-sharing {CoNO4} and {PO3C} are also found except that the cobalt atoms within the chain are further bridged by a coordinated water molecule. The chains are cross-linked by 4,4-bpy, leading to a three-dimensional open-framework structure. Magnetic studies reveal that dominant antiferromagnetic interactions are mediated between the Co(II) ions in all three cases.
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Pathways of [Ca(2+)]i rise evoked by angiotensin II in MDCK renal tubular cells.
J. Recept. Signal Transduct. Res.
PUBLISHED: 09-25-2013
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Abstract The effect of angiotensin II (Ang II) on cytosolic Ca(2+) concentrations ([Ca(2+)]i) in MDCK renal tubular cells was explored. The Ca(2+)-sensitive fluorescent dye fura-2 was applied to measure [Ca(2+)]i. Ang II at concentrations of 5-40?µM induced a [Ca(2+)]i rise in a concentration-dependent manner. The response was reduced partly by removing Ca(2+). Ang II evoked store-operated Ca(2+) entry that was inhibited by La(3+) and Gd(3+). In the absence of extracellular Ca(2+), incubation with the endoplasmic reticulum Ca(2+) pump inhibitor 2,5-di-tert-butylhydroquinone (BHQ) or thapsigargin abolished Ang II-induced Ca(2+) release. Inhibition of phospholipase C with U73122 abolished Ang II-induced [Ca(2+)]i rise. Three Ang II analogues [(ASN1,VAL5)-Ang II acetate, (SAR1,THR8)-Ang II acetate, (VAL5)-Ang II acetate] failed to induce a [Ca(2+)]i rise. Together, in MDCK cells, Ang II induced a [Ca(2+)]i rise via Ca(2+) entry through store-operated Ca(2+) channels and phospholipase C-dependent Ca(2+) release from the endoplasmic reticulum. Moreover, Ang IIs amino acid sequence is important in its stimulatory effect on [Ca(2+)]i.
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Cysteamine Modulates Oxidative Stress and Blocks Myofibroblast Activity in CKD.
J. Am. Soc. Nephrol.
PUBLISHED: 09-05-2013
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Therapy to slow the relentless expansion of interstitial extracellular matrix that leads to renal functional decline in patients with CKD is currently lacking. Because chronic kidney injury increases tissue oxidative stress, we evaluated the antifibrotic efficacy of cysteamine bitartrate, an antioxidant therapy for patients with nephropathic cystinosis, in a mouse model of unilateral ureteral obstruction. Fresh cysteamine (600 mg/kg) was added to drinking water daily beginning on the day of surgery, and outcomes were assessed on days 7, 14, and 21 after surgery. Plasma cysteamine levels showed diurnal variation, with peak levels similar to those observed in patients with cystinosis. In cysteamine-treated mice, fibrosis severity decreased significantly at 14 and 21 days after unilateral ureteral obstruction, and renal oxidized protein levels decreased at each time point, suggesting reduced oxidative stress. Consistent with these results, treatment of cultured macrophages with cysteamine reduced cellular generation of reactive oxygen species. Furthermore, treatment with cysteamine reduced ?-smooth muscle actin-positive interstitial myofibroblast proliferation and mRNA levels of extracellular matrix proteins in mice and attenuated myofibroblast differentiation and proliferation in vitro, but did not augment TGF-? signaling. In a study of renal ischemia reperfusion, cysteamine therapy initiated 10 days after injury and continued for 14 days decreased renal fibrosis by 40%. Taken together, these data suggest previously unrecognized antifibrotic actions of cysteamine via TGF-?-independent mechanisms that include oxidative stress reduction and attenuation of the myofibroblast response to kidney injury and support further investigation into the potential benefit of cysteamine therapy in the treatment of CKD.
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Qindan capsule changes adventitial collagen synthesis in spontaneously hypertensive rats.
Chin J Integr Med
PUBLISHED: 08-24-2013
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To investigate the effect of Qindan capsule (QC) on collagen synthesis and the mechanism underlying the process in spontaneously hypertensive rats (SHRs).
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A mononuclear cobalt(II)-dithienylethene complex showing slow magnetic relaxation and photochromic behavior.
Chem. Commun. (Camb.)
PUBLISHED: 08-22-2013
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Mononuclear complex Co(hpbdti)2·3CH3OH (1) was synthesized [hpbdtiH = 2-(2-hydroxyphenyl)-4,5-bis(2,5-dimethyl(3-thienyl))-1H-imidazole], showing multiple-step field-induced slow magnetic relaxation behaviors, and photochromic properties in CH2Cl2-CH3CN solution.
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BRG1 variant rs1122608 on chromosome 19p13.2 confers protection against stroke and regulates expression of pre-mRNA-splicing factor SFRS3.
Hum. Genet.
PUBLISHED: 08-10-2013
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A single nucleotide polymorphism (SNP) rs1122608 on chromosome 19p13.2 and in the BRG1/SMARCA4 gene was previously associated with coronary artery disease (CAD). CAD and ischemic stroke are both associated with atherosclerosis. Thus, we tested the hypothesis that rs1122608 is associated with ischemic stroke. Further studies were used to identify the most likely mechanism by which rs1122608 regulates atherosclerosis. For case-control association studies, two independent Chinese Han GeneID cohorts were used, including a Central cohort with 1,075 cases and 2,685 controls and the Northern cohort with 1,208 cases and 824 controls. eQTL and real-time RT-PCR analyses were used to identify the potential candidate gene(s) affected by rs1122608. The minor allele T of SNP rs1122608 showed significant association with a decreased risk of ischemic stroke in the Central GeneID cohort (adjusted P adj = 2.1 × 10(-4), OR 0.61). The association was replicated in an independent Northern GeneID cohort (P adj = 6.00 × 10(-3), OR 0.69). The association became more significant in the combined population (P adj = 7.86 × 10(-5), OR 0.73). Allele T of SNP rs1122608 also showed significant association with a decreased total cholesterol level (P adj = 0.013). Allele T of rs1122608 was associated with an increased expression level of SFRS3 encoding an mRNA splicing regulator, but not with the expression of BRG1/SMARCA4 or LDLR (located 36 kb from rs1122608). Increased expression of SFSR3 may decrease IL-1? expression and secretion, resulting in reduced risk of atherosclerosis and stroke. This is the first study that demonstrates that rs1122608 confers protection against ischemic stroke and implicates splicing factor SFSR3 in the disease process.
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Facile decoration of Au nanoparticles on CdS nanorods by polyoxometalate with enhanced photocatalytic activities toward hydrogen evolution.
J Nanosci Nanotechnol
PUBLISHED: 08-02-2013
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The tri-component hybrid CdS nanorods (NRs)/Au nanoparticles (NPs)@polyoxometalate (POM) was successfully prepared by a facile, efficient and green method. The structural properties and component analysis were studied by Transmission electron microscopy (TEM), X-ray Diffraction (XRD) and UV-Vis spectra. The POMs sever as not only reductant and bridge molecules, but also as co-catalyst to play an important role in the photocatalytic process. The as-prepared nanohybrid shows obviously enhanced photocatalytic activity toward photocatalytic evolution of hydrogen.
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Mechanisms of resveratrol-induced changes in [Ca(2+)]i and cell viability in PC3 human prostate cancer cells.
J. Recept. Signal Transduct. Res.
PUBLISHED: 07-30-2013
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Resveratrol is a natural compound that affects cellular Ca(2+) homeostasis and viability in different cells. This study examined the effect of resveratrol on cytosolic free Ca(2+) concentrations ([Ca(2+)]i) and viability in PC3 human prostate cancer cells. The Ca(2+)-sensitive fluorescent dye fura-2 was used to measure [Ca(2+)]i and WST-1 was used to measure viability. Resveratrol-evoked [Ca(2+)]i rises concentration-dependently. The response was reduced by removing extracellular Ca(2+). Resveratrol-evoked Ca(2+) entry was not inhibited by nifedipine, econazole, SKF96365 and the protein kinase C inhibitor GF109203X, but was nearly abolished by the protein kinase C activator phorbol 12-myristate 13 acetate. In Ca(2+)-free medium, treatment with the endoplasmic reticulum Ca(2+) pump inhibitor 2,5-di-tert-butylhydroquinone decreased resveratrol-evoked rise in [Ca(2+)]i. Conversely, treatment with resveratrol inhibited BHQ-evoked rise in [Ca(2+)]i. Inhibition of phospholipase C with U73122 did not alter resveratrol-evoked rise in [Ca(2+)]i. Previous studies showed that resveratrol between 10 and 100?µM induced cell death in various cancer cell types including PC3 cells. However, in this study, resveratrol (1-10??M) increased cell viability, which was abolished by chelating cytosolic Ca(2+) with 1,2-bis(2-aminophenoxy)ethane-N,N,N,N-tetra-acetic acid-acetoxymethyl ester (BAPTA/AM). Therefore, it is suggested that in PC3 cells, resveratrol had a dual effect on viability: at low concentrations (1-10?µM) it induced proliferation, whereas at higher concentrations it caused cell death. Collectively, our data suggest that in PC3 cells, resveratrol-induced rise in [Ca(2+)]i by evoking phospholipase C-independent Ca(2+) release from the endoplasmic reticulum and Ca(2+) entry, via protein kinase C-regulated mechanisms. Resveratrol at 1-10?µM also caused Ca(2+)-dependent cell proliferation.
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Effect of the pesticide, deltamethrin, on Ca(2+) signaling and apoptosis in OC2 human oral cancer cells.
Drug Chem Toxicol
PUBLISHED: 07-05-2013
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Abstract Deltamethrin is a synthetic pyrethroid insecticide used extensively in pest control. Although deltamethrin has been shown to induce cytosolic free Ca(2+) concentration ([Ca(2+)]i) rises and apoptosis in different cancer cells, there is no information concerning the effects of deltamethrin on oral cancer. This study explored the effects of deltamethrin on [Ca(2+)]i and viability in OC2 human oral cancer cells. Deltamethrin, at concentrations of 5-10??M, increased [Ca(2+)]i in a concentration-dependent manner. The Ca(2+) signal was reduced partly by removing extracellular Ca(2+). Deltamethrin-induced [Ca(2+)]i rise was not inhibited by econazole, SK&F96365, phorbol 12-myristate 13 acetate (PMA) or GF109203X, but was inhibited by nifedipine. In Ca(2+)-free medium, 10-?M deltamethrin pretreatment inhibited the [Ca(2+)]i rise induced by the endoplasmic reticulum Ca(2+) pump inhibitor, 2,5-di-tert-butylhydroquinone (BHQ). Conversely, pretreatment with BHQ inhibited deltamethrin-induced [Ca(2+)]i rise. Inhibition of inositol 1,4,5-trisphosphate formation with phospholipase C (PLC) inhibitor U73122 did not suppress deltamethrin-induced Ca(2+) release. At concentrations between 20 and 100??M, deltamethrin killed cells in a concentration-dependent manner. The cytotoxic effect of deltamethrin was not reversed by prechelating cytosolic Ca(2+) with 1,2-bis(2-aminophenoxy)ethane-N,N,N,N-tetraacetic acid/acetoxymethyl. Deltamethrin-induced cell death was not caused by a preceding [Ca(2+)]i rise. Annexin V/propidium iodide staining data suggest that deltamethrin (40-60??M) induced apoptosis in a concentration-dependent manner. To conclude, in OC2 cells, deltamethrin evoked a [Ca(2+)]i rise by inducing PLC-independent Ca(2+) release from the endoplasmic reticulum and Ca(2+) entry by nifedipine-sensitive Ca(2+) channels. Further, deltamethrin induced Ca(2+)-independent cell death might involve apoptosis.
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The IL-33-ST2L pathway is associated with coronary artery disease in a Chinese Han population.
Am. J. Hum. Genet.
PUBLISHED: 06-27-2013
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The effects of interleukin-33 (IL-33) on the immune system have been clearly demonstrated; however, in cardiovascular diseases, especially in coronary artery disease (CAD), these effects have not yet been clarified. In this study, we investigate the genetic role of the IL-33-ST2L pathway in CAD. We performed three-stage case-control association analyses on a total of 4,521 individuals with CAD and 4,809 controls via tag SNPs in the genes encoding IL-33 and ST2L-IL-1RL1. One tag SNP in each gene was significantly associated with CAD (rs7025417(T) in IL33, padj = 1.19 × 10(-28), OR = 1.39, 95% CI: 1.31-1.47; rs11685424(G) in IL1RL1, padj = 6.93 × 10(-30), OR = 1.40, 95% CI: 1.32-1.48). Combining significant variants in two genes, the risk for CAD increased nearly 5-fold (padj = 8.90 × 10(-21), OR = 4.98, 95% CI: 3.56-6.97). Traditional risk factors for CAD were adjusted for the association studies by SPSS with logistic regression analysis. With the two variants above, both located within the gene promoter regions, reporter gene analysis indicated that the rs7025417 C>T and rs11685424 A>G changes resulted in altered regulation of IL33 and IL1RL1 gene expression, respectively (p < 0.005). Further studies revealed that the rs7025417 genotype was significantly associated with plasma IL-33 levels in the detectable subjects (n = 227, R(2) = 0.276, p = 1.77 × 10(-17)): the level of IL-33 protein increased with the number of rs7025417 risk (T) alleles. Based on genetic evidence in humans, the IL-33-ST2L pathway appears to have a causal role in the development of CAD, highlighting this pathway as a valuable target for the prevention and treatment of CAD.
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