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Find video protocols related to scientific articles indexed in Pubmed.
Effect of xanthone derivatives on animal models of depression.
Curr Ther Res Clin Exp
PUBLISHED: 12-01-2014
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Extracts of the plant Hypericum perforatum L. have been traditionally used in folk medicine for the treatment of depressive disorders. Xanthone, a component of Hypericum perforatum L., has been shown to be effective in animal models of depression.
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C-C Stretching Raman Spectra and Stabilities of Hydrocarbon Molecules in Natural Gas Hydrates - A Quantum Chemical Study.
J Phys Chem A
PUBLISHED: 11-19-2014
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The presence of specific hydrocarbon gas molecules in various types of water cavities in natural gas hydrates (NGHs) are governed by the relative stabilities of these encapsulated guest molecule ? water cavity combinations. Using molecular quantum-chemical dispersion-corrected hybrid density functional computations, the interaction energies (?Ehost-guest) and cohesive energies (?Ecoh), enthalpies and Gibbs free energies for the complexes of host water cages and hydrocarbon guest molecules are calculated at the ?B97X-D/6-311++G(2d,2p) level of theory. The zero point energy effect of ?Ehost-guest and ?Ecoh is found to be quite substantial. The energetically optimal host-guest combinations for seven hydrocarbon gas molecules (CH4, C2H6, C3H6, C3H8, C4H8, i-C4H10, and n-C4H10) and various water cavities (D, ID, T, P, H and I) in NGHs are found to be CH4@D, C2H6@T, C3H6@T, C3H8@T, C4H8@T/P/H, i-C4H10@H, and n-C4H10@H, as the largest cohesive energy magnitudes will be obtained with these host-guest combinations. The stabilities of various water cavities enclosing hydrocarbon molecules are evaluated from the computed cohesive Gibbs free energies: CH4 prefer to be trapped in a ID cage; C2H6 prefer T cages; C3H6 and C3H8 prefer T and H cages; C4H8 and i-C4H10 prefer H cages; and n-C4H10 prefer I cages. The vibrational frequencies and Raman intensities of the C-C stretching vibrational modes for these seven hydrocarbon molecules enclosed in each water cavity are computed. A blue shift results after the guest molecule is trapped from gas phase into various water cages due to the host-guest interactions between the water cage and hydrocarbon molecule. The frequency shifts to the red as the radius of water cages increases. The model calculations support the view that C-C stretching vibrations of hydrocarbon molecules in the water cavities can be used as a tool to identify the types of crystal phases and guest molecules in NGHs.
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Protein Tyrosine Phosphatase 1B Impairs Diabetic Wound Healing Through Vascular Endothelial Growth Factor Receptor 2 Dephosphorylation.
Arterioscler. Thromb. Vasc. Biol.
PUBLISHED: 11-15-2014
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Impaired wound healing is a major complication of diabetes mellitus. The mechanisms that govern wound healing, however, are complex and incompletely understood. In the present study, we determined the inhibitory role of protein tyrosine phosphatase 1B (PTP1B) in the process of diabetic wound healing.
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Post-Operative Radiotherapy (PORT) is Associated with Better Survival in Non-Small Cell Lung Cancer with Involved N2 Lymph Nodes: Results of an Analysis of the National Cancer Data Base.
J Thorac Oncol
PUBLISHED: 11-11-2014
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Use of post-operative radiotherapy (PORT) in non-small cell lung cancer (NSCLC) remains controversial. Limited data indicate that PORT may benefit patients with involved N2 nodes. This study evaluates this hypothesis in a large retrospective cohort treated with chemotherapy and contemporary radiation techniques.
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Amide Groups Switch Selectivity: C-H Trifluoromethylation of ?,?-Unsaturated Amides and Subsequent Asymmetric Transformation.
Org. Lett.
PUBLISHED: 11-10-2014
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The first direct C-H ?-trifluoromethylation of unsubstituted or ?-alkyl-substituted ?,?-unsaturated carbonyl compounds under metal-free conditions was realized with excellent regio- and stereoselectivity as well as a very broad substrate scope. Both olefinic and allylic trifluoromethylation products are accessible with high selectivities by altering the substrate substitutions. The resultant olefinic products, namely (E)-?-trifluoromethyl (CF3) ?,?-unsaturated hydroxamic acid derivatives, served as acceptors in organocatalytic asymmetric Michael addition reactions to give hydroxamic acid derivatives bearing a chiral CF3-substituted stereocenter with high enantioselectivities.
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Loss of BRMS1 Promotes a Mesenchymal Phenotype through NF-?B-Dependent Regulation of Twist1.
Mol. Cell. Biol.
PUBLISHED: 11-05-2014
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Breast cancer metastasis suppressor 1 (BRMS1) is downregulated in non-small cell lung cancer (NSCLC), and its reduction correlates with disease progression. Herein, we investigate the mechanisms through which loss of BRMS1 contributes to epithelial-to-mesenchymal transition (EMT). Using an shRNA system, we show that loss of BRMS1 promotes basal and transforming growth factor beta-induced EMT in NSCLC cells. NSCLC cells expressing BRMS1 shRNAs (BRMS1(KD)) display mesenchymal characteristics, including enhanced cell migration and differential regulation of the EMT markers. Mesenchymal phenotypes observed in BRMS1(KD) cells are dependent on RelA/p65, the transcriptionally active subunit of nuclear factor-kappa B (NF-?B). In addition, chromatin immunoprecipitation analysis demonstrates that loss of BRMS1 increases Twist1 promoter occupancy of RelA/p65 K310-a key histone modification associated with increased transcription. Knockdown of Twist1 results in reversal of BRMS1(KD)-mediated EMT phenotypic changes. Moreover, in our animal model, double-knockdown BRMS1(KD)/Twist1(KD) cells were less efficient in establishing lung tumors, compared with BRMS1(KD) cells. Collectively, this study demonstrates that loss of BRMS1 promotes malignant phenotypes that are dependent on NF-?B-dependent regulation of Twist1. These observations offer fresh insight into the mechanisms through which BRMS1 regulates the development of metastases in NSCLC.
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Rapid diversification of five Oryza AA genomes associated with rice adaptation.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 11-03-2014
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Comparative genomic analyses among closely related species can greatly enhance our understanding of plant gene and genome evolution. We report de novo-assembled AA-genome sequences for Oryza nivara, Oryza glaberrima, Oryza barthii, Oryza glumaepatula, and Oryza meridionalis. Our analyses reveal massive levels of genomic structural variation, including segmental duplication and rapid gene family turnover, with particularly high instability in defense-related genes. We show, on a genomic scale, how lineage-specific expansion or contraction of gene families has led to their morphological and reproductive diversification, thus enlightening the evolutionary process of speciation and adaptation. Despite strong purifying selective pressures on most Oryza genes, we documented a large number of positively selected genes, especially those genes involved in flower development, reproduction, and resistance-related processes. These diversifying genes are expected to have played key roles in adaptations to their ecological niches in Asia, South America, Africa and Australia. Extensive variation in noncoding RNA gene numbers, function enrichment, and rates of sequence divergence might also help account for the different genetic adaptations of these rice species. Collectively, these resources provide new opportunities for evolutionary genomics, numerous insights into recent speciation, a valuable database of functional variation for crop improvement, and tools for efficient conservation of wild rice germplasm.
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Solution processable colloidal nanoplates as building blocks for high-performance electronic thin films on flexible substrates.
Nano Lett.
PUBLISHED: 11-03-2014
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Low-temperature solution-processed electronic materials on plastic substrates are of considerable interest for flexible electronics. Solution dispersible inorganic nanostructures (e.g., zero-dimensional (0D) quantum dots or one-dimensional (1D) nanowires) have emerged as interesting ink materials for low-temperature solution processing of electronic thin films on flexible substrates, but usually with limited performance due to the large number of grain boundaries (0D) or incomplete surface coverage (1D). Here, we report two-dimensional (2D) colloidal nanoplates of layered materials as a new ink material for solution assembly of high-performance electronic thin films. The 2D colloidal nanoplates exhibit few dangling bonds and represent an ideal geometry for the assembly of highly uniform continuous thin films with greatly reduced grain boundaries dictated by large-area conformal plane-plane contact with atomically flat/clean interfaces. It can therefore promise efficient charge transport across neighboring nanoplates and throughout the entire thin film to enable unprecedented electronic performance. We show that Bi2Se3 and Bi2Te3 nanoplates can be synthesized with well-controlled thickness (6-15 nm) and lateral dimension (0.5-3 ?m) and can be used for the assembly of highly uniform continuous thin films with a full surface coverage and an excellent room temperature carrier mobility >100 cm(2)·V(-1)·s(-1), approaching that of chemical vapor deposition grown materials. Our study demonstrates a general strategy to using 2D nanoplates as a unique building block for the construction of high-performance electronic thin films on plastic substrates for future flexible electronics and optoelectronics.
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[Characterization of recombinant L-isoleucine-4-hydroxylase from Bacillus thuringiensis and its application in 4hydroxyisoleucine biosynthesis].
Wei Sheng Wu Xue Bao
PUBLISHED: 10-28-2014
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L-isoleucine-4-hydroxylase (IDO) encoding gene ido from Bacillus thuringiensis TCCC 11826 was cloned and expressed, followed by enzyme characterization. In addition, recombinant strain was tested for its 4-Hydroxyisoleucine (4-HIL) biotransformation.
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[Low fat milk powder containing esterified plant sterols improves the blood lipid profile of adults with hypercholesterolemia].
Zhonghua Xin Xue Guan Bing Za Zhi
PUBLISHED: 10-21-2014
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To observe the impact of plant sterol esters (PSE) mixed in low fat milk powder (2.5 g of PSE/day) on plasma cholesterol levels in hypercholesterolemic subjects during a 6-week intervention period.
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Optical parametrically gated microscopy in scattering media.
Opt Express
PUBLISHED: 10-17-2014
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High-resolution imaging in turbid media has been limited by the intrinsic compromise between the gating efficiency (removal of multiply-scattered light background) and signal strength in the existing optical gating techniques. This leads to shallow depths due to the weak ballistic signal, and/or degraded resolution due to the strong multiply-scattering background - the well-known trade-off between resolution and imaging depth in scattering samples. In this work, we employ a nonlinear optics based optical parametric amplifier (OPA) to address this challenge. We demonstrate that both the imaging depth and the spatial resolution in turbid media can be enhanced simultaneously by the OPA, which provides a high level of signal gain as well as an inherent nonlinear optical gate. This technology shifts the nonlinear interaction to an optical crystal placed in the detection arm (image plane), rather than in the sample, which can be used to exploit the benefits given by the high-order parametric process and the use of an intense laser field. The coherent process makes the OPA potentially useful as a general-purpose optical amplifier applicable to a wide range of optical imaging techniques.
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Noise characterization of broadband fiber Cherenkov radiation as a visible-wavelength source for optical coherence tomography and two-photon fluorescence microscopy.
Opt Express
PUBLISHED: 10-17-2014
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Optical sources in the visible region immediately adjacent to the near-infrared biological optical window are preferred in imaging techniques such as spectroscopic optical coherence tomography of endogenous absorptive molecules and two-photon fluorescence microscopy of intrinsic fluorophores. However, existing sources based on fiber supercontinuum generation are known to have high relative intensity noise and low spectral coherence, which may degrade imaging performance. Here we compare the optical noise and pulse compressibility of three high-power fiber Cherenkov radiation sources developed recently, and evaluate their potential to replace the existing supercontinuum sources in these imaging techniques.
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Optimizing high performance computing workflow for protein functional annotation.
Concurr Comput
PUBLISHED: 10-15-2014
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Functional annotation of newly sequenced genomes is one of the major challenges in modern biology. With modern sequencing technologies, the protein sequence universe is rapidly expanding. Newly sequenced bacterial genomes alone contain over 7.5 million proteins. The rate of data generation has far surpassed that of protein annotation. The volume of protein data makes manual curation infeasible, whereas a high compute cost limits the utility of existing automated approaches. In this work, we present an improved and optmized automated workflow to enable large-scale protein annotation. The workflow uses high performance computing architectures and a low complexity classification algorithm to assign proteins into existing clusters of orthologous groups of proteins. On the basis of the Position-Specific Iterative Basic Local Alignment Search Tool the algorithm ensures at least 80% specificity and sensitivity of the resulting classifications. The workflow utilizes highly scalable parallel applications for classification and sequence alignment. Using Extreme Science and Engineering Discovery Environment supercomputers, the workflow processed 1,200,000 newly sequenced bacterial proteins. With the rapid expansion of the protein sequence universe, the proposed workflow will enable scientists to annotate big genome data.
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[Three new records of medical plant in Hubei, China].
Zhongguo Zhong Yao Za Zhi
PUBLISHED: 10-03-2014
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In order to have a better understanding of the species diversity of medical plants in Enshi, Hubei of China, extensive field investigations and specimen collections were conducted in Enshi and adjacent regions. Based on field observations of plants in their living habitats and comparative morphological studies on specimens in herbarium of Hubei minzu University and other available herbaria as well, three new records of medical plants in Hubei, Scutellaria yunnanensis, Alangium faberi var. heterophyllum, and Drymaria diandra, were reported in this paper.
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[UPLC fingerprint spectra for discrimination of Aucklandiae radix and Vladimiriae radix].
Zhongguo Zhong Yao Za Zhi
PUBLISHED: 10-03-2014
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It's difficult to identify Aucklandiae Radix and Vladimiriae Radix because of their similar composition. In this paper, UPLC method was used to establish their UPLC fingerprint to identify them with the mobile of acetonitrile -0. 05% phosphoric acid water solution by gradient elution at the detection wavelength of 238 nm. Clustering analysis and principal components analysis showed that Vladimiriae Radix was significantly different from Aucklandiae Radix. Eight common peaks and twelve common peaks were defined respectively in Aucklandiae Radix and Vladimiriae Radix herbs by fingerprint analysis. Six of them were identified as syringoside, chlorogenic acid, isochlorogenic acid A, isochlorogenic acid B, costunolide and dehydrocostuslactone by comparing with standard references. There are four peaks in all of Vladimiriae Radix samples and in none of Aucklandiae Radix samples. So UPLC fingerprint can be used to identify these two herbs.
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Validity of 18F-fluorodeoxyglucose Positron Emission Tomography/Computed Tomography for Pretreatment Evaluation of Patients With Cervical Carcinoma: A Retrospective Pathology-Matched Study.
Int. J. Gynecol. Cancer
PUBLISHED: 10-01-2014
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The aim of this study was to evaluate the validity of F-fluorodeoxyglucose (F-FDG) positron emission tomography (PET)/computed tomography (CT) for pretreatment evaluation of patients with cervical carcinoma.
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Total Synthesis and Structural Revision of (+)-Uprolide G Acetate.
Angew. Chem. Int. Ed. Engl.
PUBLISHED: 09-30-2014
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The first, asymmetric total synthesis of the proposed structure of (+)-uprolide G acetate (UGA) is reported, and the spectral properties of the synthetic compound clearly differed from those reported for natural UGA. On the basis of comprehensive analysis of the NMR data, two possible structures for the natural UGA were proposed and their total synthesis achieved, thus leading to the identification and confirmation of the correct structure and absolute configuration of the natural UGA. This synthesis was enabled by development of a novel synthetic strategy, which revolved around three key cyclization reactions: an Achmatowicz rearrangement, Sharpless asymmetric dihydroxylation/lactonization, and ring-closing metathesis. These synthetic studies pave the way for further studies on this class of structurally unusual cytotoxic cembranolides.
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Injectable Dopamine-Modified Poly(ethylene glycol) Nanocomposite Hydrogel with Enhanced Adhesive Property and Bioactivity.
ACS Appl Mater Interfaces
PUBLISHED: 09-26-2014
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A synthetic mimic of mussel adhesive protein, dopamine-modified four-armed poly(ethylene glycol) (PEG-D4), was combined with a synthetic nanosilicate, Laponite (Na(0.7+)(Mg5.5Li0.3Si8)O20(OH)4)(0.7-)), to form an injectable naoncomposite tissue adhesive hydrogel. Incorporation of up to 2 wt % Laponite significantly reduced the cure time while enhancing the bulk mechanical and adhesive properties of the adhesive due to strong interfacial binding between dopamine and Laponite. The addition of Laponite did not alter the degradation rate and cytocompatibility of PEG-D4 adhesive. On the basis of subcutaneous implantation in rat, PEG-D4 nanocomposite hydrogels elicited minimal inflammatory response and exhibited an enhanced level of cellular infiltration as compared to Laponite-free samples. The addition of Laponite is potentially a simple and effective method for promoting bioactivity in a bioinert, synthetic PEG-based adhesive while simultaneously enhancing its mechanical and adhesive properties.
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Straightforward installation of carbon-halogen, carbon-oxygen and carbon-carbon bonds within metal-organic frameworks (MOF) via palladium-catalysed direct C-H functionalization.
Chem. Commun. (Camb.)
PUBLISHED: 09-18-2014
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The straightforward C-H functionalization of UiO-67-dcppy materials was realized by a Pd-catalysed PSM. This novel protocol provides an efficient method for the synthesis of various functionalized MOFs, which have shown promising adsorbent ability in removing phenolic contaminates from water.
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Nerve fiber layer thinning lags retinal ganglion cell density following crush axonopathy.
Invest. Ophthalmol. Vis. Sci.
PUBLISHED: 09-18-2014
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We investigated the progressive nature of neurodegenerative structural changes following injury to retinal ganglion cell (RGC) axons using quantifiable and noninvasive in vivo imaging techniques.
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High-performance supercapacitor electrode based on the unique ZnO@Co?O4? core/shell heterostructures on nickel foam.
ACS Appl Mater Interfaces
PUBLISHED: 09-09-2014
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Currently, tremendous attention has been paid to the rational design and synthesis of unique core/shell heterostructures for high-performance supercapacitors. In this work, the unique ZnO@Co3O4 core/shell heterostructures on nickel foam are successfully synthesized through a facile and cost-effective hydrothermal method combined with a short post annealing treatment. Mesoporous Co3O4 nanowires are multidirectional growing on the rhombus-like ZnO nanorods. In addition, the growth mechanism for such unique core/shell heterostructures is also proposed. Supercapacitor electrodes based on the ZnO@Co3O4 and Co3O4 heterostructures on nickel foam are thoroughly characterized. The ZnO@Co3O4 electrode exhibits high capacitance of 1.72 F cm(-2) (857.7 F g(-1)) at a current density of 1 A g(-1), which is higher than that of the Co3O4 electrode. Impressively, the capacitance of the ZnO@Co3O4 electrode increases gradually from 1.29 to 1.66 F cm(-2) (830.8 F g(-1)) after 6000 cycles at a high current density of 6 A g(-1), indicating good long-term cycling stability. These results indicate the unique ZnO@Co3O4 electrode would be a promising electrode for high-performance supercapacitor applications.
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Electroluminescence and Photocurrent Generation from Atomically Sharp WSe2/MoS2 Heterojunction p-n Diodes.
Nano Lett.
PUBLISHED: 09-08-2014
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The p-n diodes represent the most fundamental device building blocks for diverse optoelectronic functions, but are difficult to achieve in atomically thin transition metal dichalcogenides (TMDs) due to the challenges in selectively doping them into p- or n-type semiconductors. Here, we demonstrate that an atomically thin and sharp heterojunction p-n diode can be created by vertically stacking p-type monolayer tungsten diselenide (WSe2) and n-type few-layer molybdenum disulfide (MoS2). Electrical measurements of the vertically staked WSe2/MoS2 heterojunctions reveal excellent current rectification behavior with an ideality factor of 1.2. Photocurrent mapping shows rapid photoresponse over the entire overlapping region with a highest external quantum efficiency up to 12%. Electroluminescence studies show prominent band edge excitonic emission and strikingly enhanced hot-electron luminescence. A systematic investigation shows distinct layer-number dependent emission characteristics and reveals important insight about the origin of hot-electron luminescence and the nature of electron-orbital interaction in TMDs. We believe that these atomically thin heterojunction p-n diodes represent an interesting system for probing the fundamental electro-optical properties in TMDs and can open up a new pathway to novel optoelectronic devices such as atomically thin photodetectors, photovoltaics, as well as spin- and valley-polarized light emitting diodes, on-chip lasers.
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Cascade Michael addition/cycloketalization of cyclic 1,3-dicarbonyl compounds: important role of the tethered alcohol of ?,?-unsaturated carbonyl compounds on reaction rate and regioselectivity.
J. Org. Chem.
PUBLISHED: 09-04-2014
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Reactions of ?,?-unsaturated aldehydes and cyclic 1,3-dicarbonyl compounds proceed primarily by cascade Knoevenagel condensation/six-?-electron electrocyclization (K6EC, formal [3 + 3] cycloaddition), while ?,?-unsaturated ketones usually react with cyclic 1,3-dicarbonyl compounds in a 1,4-addition manner. This paper discloses our findings that under acidic conditions, ?,?-unsaturated carbonyl compounds (ketones and aldehydes) with a tethered alcohol react with cyclic 1,3-dicarbonyl compounds in a highly regioselective 1,4-addition fashion via in situ generation of a hypothetical ?-methylene cyclic oxonium ion as the reactive Michael acceptor. Our studies uncovered the important effect of the tethered alcohol on the reaction rate and/or efficiency and some new mechanistic aspects of the cascade Michael addition/cycloketalization. Finally, the substrate scope was examined, and 43 analogues of penicipyrone and tenuipyrone were prepared in good to excellent yields.
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[A preliminary assessment of the clinical utility of measuring hepatitis C virus antibody to evaluate infection status].
Zhonghua Gan Zang Bing Za Zhi
PUBLISHED: 09-01-2014
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To investigate the potential of hepatitis C virus (HCV) antibody measurement as a clinical approach to determine the infection status and potential for spontaneous-resolution among patients with HCV mono-infection and HCV/human immunodeficiency virus (HIV) co-infection.
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Facile surface functionalization of hydrophobic magnetic nanoparticles.
J. Am. Chem. Soc.
PUBLISHED: 08-28-2014
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Nonpolar phase synthesized hydrophobic nanocrystals show attractive properties and have demonstrated prominent potential in biomedical applications. However, the preparation of biocompatible nanocrystals is made difficult by the presence of hydrophobic surfactant stabilizer on their surfaces. To address this limitation, we have developed a facile, high efficiency, single-phase and low-cost method to convert hydrophobic magnetic nanoparticles (MNPs) to an aqueous phase using tetrahydrofuran, NaOH and 3,4-dihydroxyhydrocinnamic acid without any complicated organic synthesis. The as-transferred hydrophilic MNPs are water-soluble over a wide pH range (pH = 3-12), and the solubility is pH-controllable. Furthermore, the as-transferred MNPs with carboxylate can be readily adapted with further surface functionalization, varying from small molecule dyes to oligonucleotides and enzymes. Finally, the strategy developed here can easily be extended to other types of hydrophobic nanoparticles to facilitate biomedical applications of nanomaterials.
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Detection of autoantibodies to multiple tumor-associated antigens (TAAs) in the immunodiagnosis of breast cancer.
Tumour Biol.
PUBLISHED: 08-22-2014
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We aimed to evaluate the immunodiagnostic values of autoantibodies to a panel of six tumor-associated antigens (TAAs) in the detection of patients with breast cancer. This study determines whether a panel of multiple TAAs would enhance antibody detection and be a useful approach in breast cancer detection and diagnosis. The panel of multiple TAAs was composed of six TAAs including Imp1, p16, Koc, survivin, cyclin B1, and c-myc full-length recombinant proteins. Enzyme-linked immunosorbent assay (ELISA) was used to detect antibodies against these six TAAs in 49 sera from patients with breast cancer, 35 sera from patients with benign breast tumor, and 38 sera from normal individuals. Antibody frequency to any individual TAA in breast cancer was variable and ranged from 12.2 to 18.4 %. With the successive addition of TAAs to a final total of six antigens, there was a stepwise increase of positive antibody reactions reaching a sensitivity of 67.3 % and a specificity of 92.2 % in breast cancer. Positive and negative likelihood ratios were 8.52 and 0.36, respectively, which showed that the clinical diagnostic value of a parallel assay of six TAAs was high. Positive and negative predictive values were, respectively, 91.7 and 68.6 %, indicating that the parallel assay of six TAAs raised the diagnostic accuracy greatly. Agreement rate and kappa value were 78.1 % and 0.57, respectively, which indicated that the observed value of this assay had a middle range of coincidence with the actual value. The data from this study further support our previous hypothesis that the detection of autoantibodies for diagnosis of a certain type of cancer can be enhanced by using a panel of several carefully selected TAAs as target antigens and a panel of multiple TAAs would be a useful approach in the detection and diagnosis of breast cancer.
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The expression of GLTSCR2 in cervical intra-epithelial lesion and cancer.
Arch. Gynecol. Obstet.
PUBLISHED: 08-14-2014
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GLTSCR2 was originally identified as a candidate tumor suppressor in several types of cancers. The present study was to investigate the expression pattern of GLTSCR2 in different cervical lesion tissues, appraise its potential role in cervical cancerogenesis.
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Improving quality of surgical care and outcomes: factors impacting surgical site infection after colorectal resection.
Am Surg
PUBLISHED: 08-09-2014
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Surgical site infections (SSIs) result in patient morbidity and increased costs. The purpose of this study was to determine reasons underlying SSI to enable interventions addressing identified factors. Combining data from the American College of Surgeons National Surgical Quality Improvement Project with medical record extraction, we evaluated 365 patients who underwent colon resection from January 2009 to December 2012 at a single institution. Of the 365 patients, 84 (23%) developed SSI. On univariate analysis, significant risk factors included disseminated cancer, ileostomy, patient temperature less than 36°C for greater than 60 minutes, and higher glucose level. The median number of cases per surgeon was 36, and a case volume below the median was associated with a higher risk of SSI. On multivariate analysis, significant risks associated with SSI included disseminated cancer (odds ratio [OR], 4.31; P < .001); surgery performed by a surgeon with less than 36 cases (OR, 2.19; P = .008); higher glucose level (OR, 1.06; P = .017); and transfusion of five units or more of blood (OR, 3.26; P = .029). In this study we found both modifiable and unmodifiable factors associated with increased SSI. Identifying modifiable risk factors enables targeting specific areas to improve the quality of care and patient outcomes.
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Validation of a Non-Rigid Registration Error Detection Algorithm using Clinical MRI Brain Data.
IEEE Trans Med Imaging
PUBLISHED: 08-06-2014
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Identification of error in non-rigid registration is a critical problem in the medical image processing community. We recently proposed an algorithm that we call "Assessing Quality Using Image Registration Circuits" (AQUIRC) to identify non-rigid registration errors and have tested its performance using simulated cases. In this article, we extend our previous work to assess AQUIRC's ability to detect local non-rigid registration errors and validate it quantitatively at specific clinical landmarks, namely the Anterior Commissure (AC) and the Posterior Commissure (PC). To test our approach on a representative range of error we utilize 5 different registration methods and use 100 target images and 9 atlas images. Our results show that AQUIRC's measure of registration quality correlates with the true target registration error (TRE) at these selected landmarks with an R² = 0.542. To compare our method to a more conventional approach, we compute Local Normalized Correlation Coefficient (LNCC) and show that AQUIRC performs similarly. However, a multi-linear regression performed with both AQUIRC's measure and LNCC shows a higher correlation with TRE than correlations obtained with either measure alone, thus showing the complementarity of these quality measures. We conclude the article by showing that the AQUIRC algorithm can be used to reduce registration errors for all five algorithms.
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Post-traumatic psychological changes among survivors of the Lushan earthquake living in the most affected areas.
Psychiatry Res
PUBLISHED: 08-01-2014
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The primary objective of our study was to investigate both the negative and positive psychological changes following the Lushan earthquake, and to explore the factors associated with psychological changes. Multi-stage random sampling was used to select respondents from Lushan County, Sichuan Province, China. A simplified Chinese version of the short form of Changes in Outlook Questionnaire (CiOQ-S) was used to assess psychological changes in earthquake survivors. Descriptive statistics, t-tests, ANOVA and stepwise linear regression analysis were used for data analysis. A total of 4972 respondents were investigated in the cross-sectional study. The mean scores of the positive and negative psychological changes were 26.61 and 8.12, respectively. The factors associated with positive psychological changes included ethnic minority, high level of education, high household income, not injured in the earthquake, not trapped during the earthquake, and having experienced the Wenchuan earthquake. The factors associated with negative psychological changes included female gender, ethnic minority, low household income, history of diseases, injured during the earthquake, and trapped during the earthquake. The current analysis helps expand our knowledge of the negative and positive psychological changes that may occur following an earthquake experience.
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Association between retinol-binding protein 4 and polycystic ovary syndrome: A meta-analysis.
Endocr. J.
PUBLISHED: 07-25-2014
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Studies have examined the association between retinol-binding protein 4 (RBP4) and polycystic ovary syndrome (PCOS). However, the results have been inconsistent. To investigate the association between RBP4 and PCOS, we performed a meta-analysis. The Cochrane Library, MEDLINE, the ISI Web of Science, and EMBASE were searched to identify all of the studies that examined the relationship between circulating RBP4 levels and PCOS. Standard mean difference (SMD) values and 95% confidence interval (CI) were estimated and pooled using meta-analysis methodology. A total of seven studies were involved in the meta-analysis, which included a total of 636 subjects (260 controls and 376 patients with PCOS). The RBP4 level was higher in PCOS patients than in non-PCOS patients (random effects MD (95% CI)=0.69, [0.20, 1.18], P=0.006). However, the RBP4 level was not higher in nonobese PCOS patients than in nonobese controls (random effects MD (95% CI)=0.38, [-0.21, 0.98], P=0.20). The effect size revealed that the RBP4 level was higher in overweight or obese PCOS patients than weight-matched controls (fixed effects MD (95% CI)=7.95, [5.96, 9.93], P<0.05). In the subgroup analysis by region, the RBP4 level was higher in PCOS patients in Asia than controls (random effects MD (95% CI)=0.85, [0.54, 1.15], P<0.05), but not in European PCOS patients compared with controls (random effects MD (95% CI)=0.34, [-1.12, 1.80], P=0.65). This subgroup analysis also showed that nonobese PCOS patients have higher RBP4 levels than controls in Asia. Our meta-analysis results indicated that RBP4 might be a useful tool for identifying PCOS women.
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Differential expression and regulation of Ido2 in the mouse uterus during peri-implantation period.
In Vitro Cell. Dev. Biol. Anim.
PUBLISHED: 07-22-2014
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Ido2 is involved in tryptophan catabolism and immunity, but its physiological functions remain poorly understood. This study was undertaken to examine the expression and regulation of Ido2 gene in mouse uterus during the peri-implantation period. The results showed that Ido2 mRNA was highly expressed on day 4 of pregnancy and in the delayed implantation uterus. On days 5-8 of pregnancy, a low level of Ido2 expression was observed in the uteri. Simultaneously, Ido2 mRNA was also lowly expressed in the decidualized uterus. In the uterine stromal cells, 8-Br-cAMP could inhibit the expression of Ido2 mRNA. Moreover, Ido2 mRNA expression was gradually decreased after the stromal cells were treated with estrogen and progesterone and reached a nadir at 96 h. Further study found that overexpression of Ido2 could downregulate the expression of decidualization marker genes PRL, IGFBP1, and Dtprp under in vitro decidualization, while inhibition of Ido2 with devo-1-methyl-tryptophan (D-1-MT) could upregulate the expression of these marker genes. Under in vitro decidualization, overexpression of Ido2 could suppress the proliferation of uterine stromal cells and elevate the expression of Bax and MMP2 genes. On the contrary, Ido2 inhibitor D-1-MT could enhance the proliferation of stromal cells and expression of Bcl2 gene but decline the Bax/Bcl2 ratio. In the uterine stromal cells, estrogen and progesterone could induce the expression of Ido2 mRNA. These data indicate that Ido2 may be important for mouse embryo implantation and decidualization.
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Long-term effect of the antibiotic cefalexin on methane production during waste activated sludge anaerobic digestion.
Bioresour. Technol.
PUBLISHED: 07-21-2014
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Long-term experiments herein were conducted to investigate the effect of cefalexin (CLX) on methane production during waste activated sludge (WAS) anaerobic digestion. CLX exhibited a considerable inhibition in methane production during the initial 25 days while the negative effect attenuated subsequently and methane production recovered depending on CLX doses used (600 and 1000 mg/L). The highest methane yield reached 450 mL at 1000 mg-CLX/L after 157 days of digestion, 63.8% higher than CLX-free one. Stimulated excretion of extracellular polymeric substances (EPS) by CLX served as microbial protecting layers, creating a suitable environment for microbes' growth and fermentation. Further examination via ultraviolet visible (UV-Vis) spectra also verified the elevated slime EPS, LB-EPS and TB-EPS indicated by UV-254 in the presence of CLX. Unlike the commonly accepted adverse effect, this study demonstrated the beneficial role of CLX in methane production, providing new insights into its true environmental impacts.
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Copper-catalyzed aminotrifluoromethylation of unactivated alkenes with (TMS)CF3: construction of trifluoromethylated azaheterocycles.
J. Org. Chem.
PUBLISHED: 07-16-2014
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The first example of a copper(I)-catalyzed intramolecular aminotrifluoromethylation of unactivated alkenes using (TMS)CF3 (trimethyl(trifluoromethyl)silane) as the CF3 source is described. A broad range of electronically and structurally varied substrates undergo convenient and step-economical transformations for the concurrent construction of a five- or six-membered ring and a C-CF3 bond toward different types of trifluoromethyl azaheterocycles. The methodology not only circumvents use of expensive electrophilic CF3 reagents or the photoredox strategy but also expands the scope to substrates that are difficult to access by the existing methods. Mechanistic studies are conducted, and a plausible mechanism is proposed.
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Enhancement of optical coherence microscopy in turbid media by an optical parametric amplifier.
J Biophotonics
PUBLISHED: 07-07-2014
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We report the enhancement in imaging performance of a spectral-domain optical coherence microscope (OCM) in turbid media by incorporating an optical parametric amplifier (OPA). The OPA provides a high level of optical gain to the sample arm, thereby improving the signal-to-noise ratio of the OCM by a factor of up to 15 dB. A unique nonlinear confocal gate is automatically formed in the OPA, which enables selective amplification of singly scattered (ballistic) photons against the multiply-scattered light background. Simultaneous enhancement in both imaging depth and spatial resolution in imaging microstructures in highly light-scattering media are demonstrated with the combined OPA-OCM setup. Typical OCM inteferograms (left) and images (right) without and with OPA.
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Multiple injections of human umbilical cord-derived mesenchymal stromal cells through the tail vein improve microcirculation and the microenvironment in a rat model of radiation myelopathy.
J Transl Med
PUBLISHED: 07-05-2014
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BackgroundAt present, no effective clinical treatment is available for the late effects of radiation myelopathy. The aim of the present study was to assess the therapeutic effects of human umbilical cord-derived mesenchymal stromal cells (UC-MSCs) in a rat model of radiation myelopathy.MethodsAn irradiated cervical spinal cord rat model was generated. UC-MSCs were injected through the tail vein at 90, 97, 104 and 111 days post-irradiation. Behavioral tests were performed using the forelimb paralysis scoring system, and histological damage was examined using Nissl staining. The microcirculation in the spinal cord was assessed using von Willebrand factor (vWF) immunohistochemical analysis and laser-Doppler flowmetry. The microenvironment in the spinal cord was determined by measuring the pro-inflammatory cytokines interleukin-1ß (IL-1ß) and tumor necrosis factor-¿ (TNF-¿) in the serum and the anti-inflammatory cytokines brain-derived neurotrophic factor (BDNF) and glial cell-derived neurotrophic factor (GDNF) in the spinal cord.ResultsMultiple injections of UC-MSCs through the tail veil decreased the forelimb paralysis, decreased spinal cord histological damage, increased the number of neurons in the anterior horn of the spinal cord, increased the endothelial cell density and the microvessel density in the white matter and gray matter of the spinal cord, increased the relative magnitude of spinal cord blood flow, down-regulated pro-inflammatory cytokine expression in the serum, and increased anti-inflammatory cytokine expression in the spinal cord.ConclusionMultiple injections of UC-MSCs via the tail vein in a rat model of radiation myelopathy significantly improved the microcirculation and microenvironment through therapeutic paracrine effects.
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Effect of ammonium pyrrolidine dithiocarbamate (PDTC) on NF-?B activation and CYP2E1 content of rats with immunological liver injury.
Pharm Biol
PUBLISHED: 06-25-2014
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Abstract Context: Ammonium pyrrolidine dithiocarbamate (PDTC) is a potent inhibitor of nuclear factor-?B (NF-?B). Recent studies have shown that NF-?B plays an essential role in the regulation of genes whose products are involved in the pathogenesis of immunological liver injury.
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Preoperative quantification of perceptions of surgical frailty.
J. Surg. Res.
PUBLISHED: 06-23-2014
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Frailty has gained recognition as an objective measure of a patient's physiologic reserve that ideally can replace the subjective biases of surgeons. In this study, we sought to examine the concordance between patient and attending surgeon perceptions of the patient's "fitness" before surgery. We then correlated these ratings with the patient's objective frailty scores.
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Few-layer molybdenum disulfide transistors and circuits for high-speed flexible electronics.
Nat Commun
PUBLISHED: 06-04-2014
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Two-dimensional layered materials, such as molybdenum disulfide, are emerging as an exciting material system for future electronics due to their unique electronic properties and atomically thin geometry. Here we report a systematic investigation of MoS2 transistors with optimized contact and device geometry, to achieve self-aligned devices with performance including an intrinsic gain over 30, an intrinsic cut-off frequency fT up to 42?GHz and a maximum oscillation frequency fMAX up to 50?GHz, exceeding the reported values for MoS2 transistors to date (fT~0.9?GHz, fMAX~1?GHz). Our results show that logic inverters or radio frequency amplifiers can be formed by integrating multiple MoS2 transistors on quartz or flexible substrates with voltage gain in the gigahertz regime. This study demonstrates the potential of two-dimensional layered semiconductors for high-speed flexible electronics.
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Cholecystokinin octapeptide antagonizes apoptosis in human retinal pigment epithelial cells.
Neural Regen Res
PUBLISHED: 05-24-2014
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Although cholecystokinin octapeptide-8 is important for neurological function, its neuroprotective properties remain unclear. We speculated that cholecystokinin octapeptide-8 can protect human retinal pigment epithelial cells against oxidative injury. In this study, retinal pigment epithelial cells were treated with peroxynitrite to induce oxidative stress. Peroxynitrite triggered apoptosis in these cells, and increased the expression of Fas-associated death domain, Bax, caspa-se-8 and Bcl-2. These changes were suppressed by treatment with cholecystokinin octapeptide-8. These results suggest that cholecystokinin octapeptide-8 can protect human retinal pigment epithelial cells against apoptosis induced by peroxynitrite.
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Immunohistochemical and histochemical analysis of newly formed tissues in root canal space transplanted with dental pulp stem cells plus platelet-rich plasma.
J Endod
PUBLISHED: 05-19-2014
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Tissue regeneration in root canals after pulpectomy can be achieved by transplantation of autologous dental pulp stem cells and/or platelet-rich plasma. However, the identity of the newly formed tissue in the pulp space has been only examined by histologic analysis. This study aimed to apply immunohistochemistry and histochemistry to detect specific markers in the newly generated tissues after root canal regenerative treatment.
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Enantioselective c?h bond functionalization triggered by radical trifluoromethylation of unactivated alkene.
Angew. Chem. Int. Ed. Engl.
PUBLISHED: 05-19-2014
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An asymmetric unactivated alkene/C?H bond difunctionalization reaction for the concomitant construction of C?CF3 and C?O bonds was realized by using a Cu/Brønsted acid cooperative catalytic system, thus providing facile access to valuable chiral CF3 -containing N,O-aminals with excellent regio-, chemo-, and enantioselectivity. Mechanistic studies revealed that this reaction may proceed by an unprecedented 1,5-hydride shift involving activation of unactivated alkenes and a radical trifluoromethylation to initiate subsequent enantioselective functionalization of C?H bonds. Control experiments also suggested that chiral Brønsted acid plays multiple roles and not only controls the stereoselectivity but also increases the reaction rate through activation of Togni's reagent.
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Alkenyl/Thiol-Derived Metal-Organic Frameworks (MOFs) by Means of Postsynthetic Modification for Effective Mercury Adsorption.
Chemistry
PUBLISHED: 05-04-2014
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The synthesis of new functionally diverse alkenyl-derived Cr-MIL-101s (MIL=material of Institute Lavoisier) was realized by a novel and convenient postsynthetic modification (PSM) protocol by means of the carbon?carbon bond-forming Mizoroki-Heck reaction. The new PSM protocol demonstrates a broad scope of substrates with excellent tolerance of functionality under mild reaction conditions. Moreover, a new metal-organic framework (MOF) that bears both alkenyl and thiol side chains prepared by means of the tandem PSM method has shown excellent adsorbent ability in removing mercury ions from water.
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Heat shock protein 90 (HSP90) is overexpressed in p16-negative oropharyngeal squamous cell carcinoma, and its inhibition in vitro potentiates the effects of chemoradiation.
Cancer Chemother. Pharmacol.
PUBLISHED: 05-02-2014
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Cisplatin and radiation therapy remain the current standard for treating locally advanced SCCHN. Novel treatment approaches are needed, especially in patients with human papilloma virus (HPV)-negative disease who have worse outcomes despite multimodality therapy.
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Resveratrol protects against arsenic trioxide-induced oxidative damage through maintenance of glutathione homeostasis and inhibition of apoptotic progression.
Environ. Mol. Mutagen.
PUBLISHED: 05-01-2014
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Arsenic trioxide (As2 O3 ) is commonly used to treat acute promyelocytic leukemia and solid tumors. However, the clinical application of the agent is limited by its cyto- and genotoxic effects on normal cells. Thus, relief of As2 O3 toxicity in normal cells is essentially necessary for improvement of As2 O3 -mediated chemotherapy. In this study, we have identified a series of protective effects of resveratrol against As2 O3 -induced oxidative damage in normal human bronchial epithelial (HBE) cells. We showed that treatment of HBE cells with resveratrol significantly reduced cellular levels of DNA damage, chromosomal breakage, and apoptosis induced by As2 O3 . The effect of resveratrol against DNA damage was associated with a decreased level of reactive oxygen species and lipid peroxidation in cells treated by As2 O3 , suggesting that resveratrol protects against As2 O3 toxicity via a cellular anti-oxidative stress pathway. Further analysis of the roles of resveratrol demonstrated that it modulated biosynthesis, recycling, and consumption of glutathione (GSH), thereby promoting GSH homeostasis in HBE cells treated by As2 O3 . This was further supported by results showing that resveratrol prevented an increase in the activities and levels of caspases, Fas, Fas-L, and cytochrome c proteins induced by As2 O3 . Our study indicates that resveratrol relieves As2 O3 -induced oxidative damage in normal human lung cells via maintenance of GSH homeostasis and suppression of apoptosis. Environ. Mol. Mutagen., 2014. © 2014 Wiley Periodicals, Inc.
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Acetylcholinesterase overexpression mediated by oncolytic adenovirus exhibited potent anti-tumor effect.
BMC Cancer
PUBLISHED: 04-30-2014
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Acetylcholinesterase (AChE) mainly functions as an efficient terminator for acetylcholine signaling transmission. Here, we reported the effect of AChE on gastric cancer therapy.
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Targeting the raft-associated Akt signaling in hepatocellular carcinoma.
Biomed Res Int
PUBLISHED: 04-29-2014
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Caveolin-1 and flotillin-1 are considered as markers of lipid rafts which can be regarded as sorting platforms for targeted transport of transmembrane proteins and are involved in fundamental cellular events such as signal transduction, cell adhesion, lipid/protein sorting, and human cancer. We addressed caveolin-1 and flotillin-1 expression in 90 human hepatocellular carcinoma (HCC) and adjacent noncancerous tissues (ANT) samples by SDS-PAGE and immunoblotting with specific antibodies. Significant caveolin-1 and flotillin-1 overexpression was found in HCC tissues compared to ANT and was confirmed by immunohistochemistry. Raft-associated Akt signaling pathway components involved in the regulation of cell survival were altered by western blotting in HCC microdomain-enriched subcellular fractions purified from paired HCC and ANT samples. Our results demonstrated that the activity of raft-associated but not total membrane Akt determines its cellular functions. Lipid rafts differ in different types of tissues, which allows for the possibility of tissue-type-specific targeting for cell survival.
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Critical role of cellular glutathione homeostasis for trivalent inorganic arsenite-induced oxidative damage in human bronchial epithelial cells.
Mutat Res Genet Toxicol Environ Mutagen
PUBLISHED: 04-28-2014
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Trivalent inorganic arsenic (iAs(3+)) is a powerful carcinogen that enhances the risk of lung cancer. Paradoxically, iAs(3+) also shows substantial efficacy in the treatment of lung tumors. However, the exact molecular mechanisms underlying iAs(3+)-induced toxicity and therapeutic effect in lung remain unclear. In this study, the effects of iAs(3+), sodium arsenite (NaAsO2) and arsenic trioxide (As2O3), on cell viability, apoptosis, genotoxicity and oxidative stress in cultured human bronchial epithelial cells were observed. Our results showed that NaAsO2 and As2O3 exposure could result in defects in cell proliferation and greatly enhance the level of oxidative damage. To clarify the critical role of glutathione (GSH) homeostasis in oxidative damage induced by iAs(3+), we further measured the content of GSH, ratio of GSH to GSSG, and the activities of GSH-related enzymes involved in the process of GSH synthesis, recycling and utilization. Our data demonstrated that NaAsO2 and As2O3 disrupted the balance of GSH homeostasis, and NaAsO2- and As2O3-induced oxidative damage was closely associated with the imbalance in GSH synthesis, recycling and utilization. To better understand the physiologic significance of Nrf2 in maintaining GSH-homeostasis, the expression level of Nrf2 was measured after iAs(3+) exposure. We found that the protein expression levels of Nrf2 were increased in both NaAsO2- and As2O3-treated cells. Collectively, our findings suggest that disturbed Nrf2-regulated GSH-homeostasis is associated with the oxidative damage triggered by iAs(3+), and loss of GSH homeostasis might implicate in both the pathogenesis of iAs(3+)-induced lung diseases and anticancer activity of iAs(3+).
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Thiol-based redox proteomics in cancer research.
Proteomics
PUBLISHED: 04-25-2014
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Cancer cells maintain their intracellular reactive oxygen species (ROS) concentrations at required levels for their survival. Changes in ROS concentrations can regulate biochemical signaling mechanisms that control cell function. It has been demonstrated that ROS regulate the cellular events through redox regulation of redox-sensitive proteins (redox sensors). Upon oxidative stress, redox sensors undergo redox modifications that cause the allosteric changes of these proteins and endows them with different functions. Understanding the altered functions of redox sensors and the underlying mechanisms is critical for the development of novel cancer therapeutics. Recently, a series of high throughput proteomics approaches have been developed for screening redox processes. In this manuscript, we review these methodologies and discuss the important redox sensors recently identified that are related to cancer. This article is protected by copyright. All rights reserved.
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Network anomaly detection system with optimized DS evidence theory.
ScientificWorldJournal
PUBLISHED: 04-24-2014
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Network anomaly detection has been focused on by more people with the fast development of computer network. Some researchers utilized fusion method and DS evidence theory to do network anomaly detection but with low performance, and they did not consider features of network-complicated and varied. To achieve high detection rate, we present a novel network anomaly detection system with optimized Dempster-Shafer evidence theory (ODS) and regression basic probability assignment (RBPA) function. In this model, we add weights for each sensor to optimize DS evidence theory according to its previous predict accuracy. And RBPA employs sensor's regression ability to address complex network. By four kinds of experiments, we find that our novel network anomaly detection model has a better detection rate, and RBPA as well as ODS optimization methods can improve system performance significantly.
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Ultrasound-modulated fluorescence based on fluorescent microbubbles.
J Biomed Opt
PUBLISHED: 04-15-2014
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Ultrasound-modulated fluorescence (UMF) imaging has been proposed to provide fluorescent contrast while maintaining ultrasound resolution in an optical-scattering medium (such as biological tissue). The major challenge is to extract the weakly modulated fluorescent signal from a bright and unmodulated background. UMF was experimentally demonstrated based on fluorophore-labeled microbubble contrast agents. These contrast agents were produced by conjugating N-hydroxysuccinimide (NHS)-ester-attached fluorophores on the surface of amine-functionalized microbubbles. The fluorophore surface concentration was controlled so that a significant self-quenching effect occurred when no ultrasound was applied. The intensity of the fluorescent emission was modulated when microbubbles were oscillated by ultrasound pulses, presented as UMF signal. Our results demonstrated that the UMF signals were highly dependent on the microbubbles' oscillation amplitude and the initial surface fluorophore-quenching status. A maximum of ?42% UMF modulation depth was achieved with a single microbubble under an ultrasound peak-to-peak pressure of 675 kPa. Further, UMF was detected from a 500-?m tube filled with contrast agents in water and scattering media with ultrasound resolution. These results indicate that ultrasound-modulated fluorescent microbubble contrast agents can potentially be used for fluorescence-based molecular imaging with ultrasound resolution in the future.
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Effects of combinations of Xiexin decoction constituents on diabetic nephropathy in rats.
J Ethnopharmacol
PUBLISHED: 04-10-2014
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Xiexin decoction (XXD) has been used as a treatment for diabetes mellitus for more than 1300 years. XXD constituents with protective effects against diabetic nephropathy (DN) include Rhizoma Coptidis alkaloids (RA), Radix et Rhizoma Rhei polysaccharides (RP), and Radix Scutellaria flavones (RF). The aim of the study is to investigate the effects of combinations of RA, RP, and RF on DN and their mechanisms of action.
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In situ generation of electrophilic trifluoromethylthio reagents for enantioselective trifluoromethylthiolation of oxindoles.
Org. Lett.
PUBLISHED: 04-03-2014
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An organocatalytic asymmetric trifluoromethylthiolation reaction via in situ generation of active electrophilic trifluoromethylthio species involving trichloroisocyanuric acid and AgSCF3 as a practical and easily handled electrophilic SCF3 source for CSP(3)-SCF3 bond formation was developed. Reactions with this one-pot version strategy occurred in good yields and excellent stereoselectivities to access enantiopure oxindoles bearing a SCF3-substituted quaternary chiral center. The straightforward process described here makes use of simple starting materials and proceeds under mild conditions, which will be useful in medicinal chemistry and diversity-oriented syntheses.
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The use of biologic therapies in the treatment of rheumatoid arthritis.
Curr Pharm Biotechnol
PUBLISHED: 03-30-2014
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The use of biologic agents has revolutionized the management of rheumatoid arthritis (RA) in the past two decades. These biologic agents directly target molecules and cells involved in the pathogenesis of RA. Biologic agents indeed lead to a better prognosis and clinical remission in patients with RA, especially in patients who are not well-controlled with traditional disease-modifying anti-rheumatic drugs (DMARDs). Currently, five TNF inhibitors (infliximab, etanercept, adalimumab, golimumab and certolizumab pegol), an IL-6 receptor antagonist (tocilizumab), an IL-1 receptor antagonist (anakinra), a B cell depleting agent (rituximab) and a T cell co-stimulation inhibitor (abatacept) have been approved for the treatment of RA. With the increased understanding of the pathogenic mechanisms of RA and advantages in manufacturing biotechnology of pharmaceutical companies, a series of novel biologic therapeutic approaches are being developed. In the present paper, we will summarize the biologic agents currently available to treat RA, and the prospective biologic therapies that might be used in the management of RA in future.
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Anti-CD20 antibody in primary Sjögren's syndrome management.
Curr Pharm Biotechnol
PUBLISHED: 03-30-2014
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Primary Sjogren's Syndrome (pSS) is a systemic inflammatory autoimmune of unknown aetiology affecting exocrine glands, particularly the lacrimal and salivary glands. Growing evidence that B-cell depletion therapies are remarkably efficacious in the disorder indicate a major role for B-cell in the immunopathogenesis of pSS. B cell-targeted therapies have raised new therapy promise for they interact with B-cell homeostasis. Anti-CD20 therapy is the unique effective non-symptomatic therapy used in pSS. Growing data suggest Rituximab a promising candidate for pSS therapy. We performed a search for publications on Rituximab in the treatment of pSS to explicate pathogenetic function of B cells and assesse the efficacy in glandular symptoms, systemic manifestations and laboratory parameters in pSS patients. However, the efficiency on glandular manifestations is rather disappointing and controversial. Whether pSS patients with a reasonable residual salivary flow and/or with shorter disease duration will benefit most from Rituximab treatment still remains unclear. Fatigue is the symptom that responds best to Rituximab therapy compared with other systematical involvements. The efficiency in laboratory parameters is unsatisfactory.
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Biologics in polymyositis and dermatomyositis-associated interstitial lung disease.
Curr Pharm Biotechnol
PUBLISHED: 03-30-2014
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Interstitial lung disease (ILD) is one of the most common complications of polymyositis (PM) and dermatomyositis (DM). It is always progressive and does not respond to conventional immunosuppressive agent treatment. Biologics are commonly used in treatment of rheumatic diseases. They are also used in polymyositis and dermatomyositis associated interstitial lung disease. This review will focus on the updated use of biologics in PM/DM-ILD.
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Re-evaluation of biotin-streptavidin conjugation in Förster resonance energy transfer applications.
J Biomed Opt
PUBLISHED: 03-30-2014
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Bioaffinity conjugation between streptavidin (SA) and biotin has been widely used to link donors and acceptors for investigating the distance-dependent Förster resonance energy transfer (FRET). When studying a commonly used FRET system of (QD-SA)-(biotin-DNA-dye) [donor: quantum dot (QD); acceptor: small organic fluorescent dye; and linker: deoxyribose nucleic acid (DNA) molecule via SA-biotin conjugation], however, a contradictory finding was recently reported in the literature. It was found that the FRET lost its dependence on the number of DNA base pairs when using a phosphate-buffered saline (PBS) solution. We found that the conflicted results were caused by the ionic strength of the adopted buffer solutions. Our results suggest that the dependent FRET on the number of DNA bases is favorable in a low-ionic-strength buffer, whereas in relatively high-ionic-strength buffers, the FRET loses the DNA length dependence. We propose that the independence is mainly caused by the conformational change of DNA molecules from a stretched to a coiled mode when the cations in the high-ionic-strength buffer neutralize the negatively charged backbone of DNA molecules, thereby bringing the acceptors close to the donors.
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Reduction in dynamin-2 is implicated in ischaemic cardiac arrhythmias.
J. Cell. Mol. Med.
PUBLISHED: 03-29-2014
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Ischaemic cardiac arrhythmias cause a large proportion of sudden cardiac deaths worldwide. The ischaemic arrhythmogenesis is primarily because of the dysfunction and adverse remodelling of sarcolemma ion channels. However, the potential regulators of sarcolemma ion channel turnover and function in ischaemic cardiac arrhythmias remains unknown. Our previous studies indicate that dynamin-2 (DNM2), a cardiac membrane-remodelling GTPase, modulates ion channels membrane trafficking in the cardiomyocytes. Here, we have found that DNM2 plays an important role in acute ischaemic arrhythmias. In rat ventricular tissues and primary cardiomyocytes subjected to acute ischaemic stress, the DNM2 protein and transcription levels were markedly down-regulated. This DNM2 reduction was coupled with severe ventricular arrhythmias. Moreover, we identified that the down-regulation of DNM2 within cardiomyocytes increases the action potential amplitude and prolongs the re-polarization duration by depressing the retrograde trafficking of Nav1.5 and Kir2.1 channels. These effects are likely to account for the DNM2 defect-induced arrhythmogenic potentials. These results suggest that DNM2, with its multi-ion channel targeting properties, could be a promising target for novel antiarrhythmic therapies.
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The problem of unreasonably high pharmaceutical fees for patients in Chinese hospitals: a system dynamics simulation model.
Comput. Biol. Med.
PUBLISHED: 02-22-2014
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The social problem of unreasonably high pharmaceutical costs for patients in Chinese hospitals damages the interests of patients and it has a highly negative impact on the long-term development of the Chinese health service. We constructed a system dynamics model to address two problems, i.e., the unreasonably high prices of drugs and the high level of pharmaceutical fees relative to the medical costs of patients, and we suggest countermeasures and possible solutions. The program Vensim DSS was used to construct a system dynamics model to represent the problem of high pharmaceutical fees for patients in Chinese hospitals. If hospital and medical staff receive a higher kickback rate, they are more likely to prescribe unnecessary expensive drugs to make greater profits, which results in unnecessary drug consumption and irrational drug use, eventually leading to unreasonably high pharmaceutical fees. The benefit chain of the main drug suppliers should be cut off. It is necessary to break the link between the profits from pharmaceutical sales and the prescribing behavior of physicians, and hospital incomes, to avoid any conflicts of interest over how medicines are prescribed. Thus, cost-containment measures and a reformed pharmaceutical distribution system are needed to regulate physicians and hospital interaction.
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High Pathologic Complete Response in Her2-Positive, Early-Stage Breast Cancer to a Novel Nonanthracycline Neoadjuvant Chemotherapy.
Clin. Breast Cancer
PUBLISHED: 02-20-2014
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Neoadjuvant chemotherapy is widely used to downstage breast cancers before surgery and is an accepted standard of care among patients with early-stage breast cancer in whom adjuvant chemotherapy would be recommended. Pathologic complete response (pCR) rate is a robust predictor of outcome for certain breast cancer subtypes, including Her2-overexpressing breast cancer. The incorporation of Her2-targeted therapies has significantly increased the pCR rate in the neoadjuvant setting. Although regimens composed of trastuzumab, nab-paclitaxel, and vinorelbine have demonstrated clinical efficacy in patients with metastatic breast cancer, few studies have examined this combination in early-stage Her2+ breast cancer. We hypothesized that the combination of neoadjuvant nab-paclitaxel followed by vinorelbine could represent a nonanthracycline-based treatment option for early-stage Her2-overexpressing breast cancer.
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Modifications to the endoscopic approach for anterior skull base lesions improve postoperative sinonasal symptoms.
J Neurol Surg B Skull Base
PUBLISHED: 02-06-2014
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Background/Objective?Our institution previously showed that patients experience significant postoperative sinonasal symptoms for the first few months after endoscopic transnasal transsphenoidal skull base surgery (eTNTS). Since our initial study we have modified our technique, discontinuing routine resection of the middle turbinate, maxillary antrostomies, and nasoseptal flaps. In this study, we analyze whether these technical modifications decrease postoperative sinonasal morbidity after eTNTS. Methods?A retrospective review was performed of 93 consecutive patients who underwent eTNTS at a tertiary academic medical center from August 2011 to August 2012. Main Outcome Measures? Sino-Nasal Outcome Test (SNOT)-20 and SNOT-22 scores preoperatively and after surgery. Results?Compared with our previous study, our new cohort experienced a significant improvement (p?
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Epidemiological studies of esophageal cancer in the era of genome-wide association studies.
World J Gastrointest Pathophysiol
PUBLISHED: 01-27-2014
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Esophageal cancer (EC) caused about 395000 deaths in 2010. China has the most cases of EC and EC is the fourth leading cause of cancer death in China. Esophageal squamous cell carcinoma (ESCC) is the predominant histologic type (90%-95%), while the incidence of esophageal adenocarcinoma (EAC) remains extremely low in China. Traditional epidemiological studies have revealed that environmental carcinogens are risk factors for EC. Molecular epidemiological studies revealed that susceptibility to EC is influenced by both environmental and genetic risk factors. Of all the risk factors for EC, some are associated with the risk of ESCC and others with the risk of EAC. However, the details and mechanisms of risk factors involved in the process for EC are unclear. The advanced methods and techniques used in human genome studies bring a great opportunity for researchers to explore and identify the details of those risk factors or susceptibility genes involved in the process of EC. Human genome epidemiology is a new branch of epidemiology, which leads the epidemiology study from the molecular epidemiology era to the era of genome wide association studies (GWAS). Here we review the epidemiological studies of EC (especially ESCC) in the era of GWAS, and provide an overview of the general risk factors and those genomic variants (genes, SNPs, miRNAs, proteins) involved in the process of ESCC.
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Direct access to ?-trifluoromethyl enones via efficient copper-catalyzed trifluoromethylation of Meyer-Schuster rearrangement.
Org. Lett.
PUBLISHED: 01-27-2014
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A novel domino copper-catalyzed trifluoromethylated Meyer-Schuster rearrangement reaction with Togni's reagent was developed, leading to ?-trifluormethyl (CF3) enone products with moderate to good yields. Furthermore, ?-CF3 enones can be transformed toward important trifluoromethyl heterocyclic motifs in a one-pot version.
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Efficient copper-catalyzed direct intramolecular aminotrifluoromethylation of unactivated alkenes with diverse nitrogen-based nucleophiles.
Chemistry
PUBLISHED: 01-25-2014
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A mild, convenient, and step-economical intramolecular aminotrifluoromethylation of unactivated alkenes with a variety of electronically distinct, nitrogen-based nucleophiles in the presence of a simple copper salt catalyst, in the absence of extra ligands, is described. Many different nitrogen-based nucleophiles (e.g., basic primary aliphatic and aromatic amines, sulfonamides, carbamates, and ureas) can be employed in this new aminotrifluoromethylation reaction. The aminotrifluoromethylation process allows straightforward access to diversely substituted CF3-containing pyrrolidines or indolines, in good to excellent yields, through a direct difunctionalization strategy from the respective acyclic starting materials. Mechanistic studies were conducted and a plausible mechanism was proposed.
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Highly enantioselective kinetic resolution of axially chiral BINAM derivatives catalyzed by a Brønsted acid.
Angew. Chem. Int. Ed. Engl.
PUBLISHED: 01-18-2014
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A highly efficient strategy for the kinetic resolution of axially chiral BINAM derivatives involving a chiral Brønsted acid-catalyzed imine formation and transfer hydrogenation cascade process was developed. The kinetic resolution provides a convenient route to chiral BINAM derivatives in high yields with excellent enantioselectivities.
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Integrative genomic analysis reveals a high frequency of LKB1 genetic alteration in Chinese lung adenocarcinomas.
J Thorac Oncol
PUBLISHED: 01-15-2014
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Liver kinase B1 (LKB1) genetic alteration in lung cancer involves not only point mutations and small deletion of several base pairs but also exonic loss. However, most of recent studies in LKB1 gene status only focus on point mutations and small deletion, and thus may underestimate the actual frequency of LKB1 genetic alteration in lung cancer. Thus, an integrative analysis of LKB1 genetic alteration is timely and important for providing a better estimate for the incidence of genetic alterations in this important tumor suppressor gene. One hundred and seven lung adenocarcinomas with more than 70% tumor have been analyzed for mutation of LKB1 as well as LKB1 large deletions detection by using multiplex ligation-dependent probe amplification analysis. These samples were also analyzed for EGFR, KRAS, HER2, BRAF, ALK, ROS1, and RET status in stepwise method. Among 107 lung adenocarcinomas analyzed, 29 (27.1%) harbored LKB1 genetic alteration. Twenty-three (21.5%) harbored LKB1 large exonic deletions and eight (7.48%) had LKB1 points mutations, two samples harbored both LKB1 large exonic deletions and point mutations. Eighty-seven samples (81.31%) harbored known driver mutations and 20 samples (18.69%) had no identifiable driver mutations. A high rate of LKB1 genetic alteration in Chinese lung adenocarcinomas is revealed by the integrative analysis of point mutation and exonic deletion. Moreover, LKB1 genetic alterations are concurrent with EGFR, KRAS, HER2, and CD74-ROS fusions.
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Gram-scale synthesis of single-crystalline graphene quantum dots with superior optical properties.
Nat Commun
PUBLISHED: 01-06-2014
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Graphene quantum dots (GQDs) have various alluring properties and potential applications, but their large-scale applications are limited by current synthetic methods that commonly produce GQDs in small amounts. Moreover, GQDs usually exhibit polycrystalline or highly defective structures and thus poor optical properties. Here we report the gram-scale synthesis of single-crystalline GQDs by a facile molecular fusion route under mild and green hydrothermal conditions. The synthesis involves the nitration of pyrene followed by hydrothermal treatment in alkaline aqueous solutions, where alkaline species play a crucial role in tuning their size, functionalization and optical properties. The single-crystalline GQDs are bestowed with excellent optical properties such as bright excitonic fluorescence, strong excitonic absorption bands extending to the visible region, large molar extinction coefficients and long-term photostability. These high-quality GQDs can find a large array of novel applications in bioimaging, biosensing, light emitting diodes, solar cells, hydrogen production, fuel cells and supercapacitors.
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Diabetes mellitus and risk of age-related macular degeneration: a systematic review and meta-analysis.
PLoS ONE
PUBLISHED: 01-01-2014
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Age-related macular degeneration (AMD) is a major cause of severe vision loss in elderly people. Diabetes mellitus is a common endocrine disorder with serious consequences, and diabetic retinopathy (DR) is the main ophthalmic complication. DR and AMD are different diseases and we seek to explore the relationship between diabetes and AMD. MEDLINE, EMBASE, and the Cochrane Library were searched for potentially eligible studies. Studies based on longitudinal cohort, cross-sectional, and case-control associations, reporting evaluation data of diabetes as an independent factor for AMD were included. Reports of relative risks (RRs), hazard ratios (HRs), odds ratio (ORs), or evaluation data of diabetes as an independent factor for AMD were included. Review Manager and STATA were used for the meta-analysis. Twenty four articles involving 27 study populations were included for meta-analysis. In 7 cohort studies, diabetes was shown to be a risk factor for AMD (OR, 1.05; 95% CI, 1.00-1.14). Results of 9 cross-sectional studies revealed consistent association of diabetes with AMD (OR, 1.21; 95% CI, 1.00-1.45), especially for late AMD (OR, 1.48; 95% CI, 1.44-1.51). Similar association was also detected for AMD (OR, 1.29; 95% CI, 1.13-1.49) and late AMD (OR, 1.16; 95% CI, 1.11-1.21) in 11 case-control studies. The pooled ORs for risk of neovascular AMD (nAMD) were 1.10 (95% CI, 0.96-1.26), 1.48 (95% CI, 1.44-1.51), and 1.15 (95% CI, 1.11-1.21) from cohort, cross-sectional and case-control studies, respectively. No obvious divergence existed among different ethnic groups. Therefore, we find diabetes a risk factor for AMD, stronger for late AMD than earlier stages. However, most of the included studies only adjusted for age and sex; we thus cannot rule out confounding as a potential explanation for the association. More well-designed prospective cohort studies are still warranted to further examine the association.
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Abundance, composition and activity of ammonia oxidizer and denitrifier communities in metal polluted rice paddies from South China.
PLoS ONE
PUBLISHED: 01-01-2014
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While microbial nitrogen transformations in soils had been known to be affected by heavy metal pollution, changes in abundance and community structure of the mediating microbial populations had been not yet well characterized in polluted rice soils. Here, by using the prevailing molecular fingerprinting and enzyme activity assays and comparisons to adjacent non-polluted soils, we examined changes in the abundance and activity of ammonia oxidizing and denitrifying communities of rice paddies in two sites with different metal accumulation situation under long-term pollution from metal mining and smelter activities. Potential nitrifying activity was significantly reduced in polluted paddies in both sites while potential denitrifying activity reduced only in the soils with high Cu accumulation up to 1300 mg kg-1. Copy numbers of amoA (AOA and AOB genes) were lower in both polluted paddies, following the trend with the enzyme assays, whereas that of nirK was not significantly affected. Analysis of the DGGE profiles revealed a shift in the community structure of AOA, and to a lesser extent, differences in the community structure of AOB and denitrifier between soils from the two sites with different pollution intensity and metal composition. All of the retrieved AOB sequences belonged to the genus Nitrosospira, among which species Cluster 4 appeared more sensitive to metal pollution. In contrast, nirK genes were widely distributed among different bacterial genera that were represented differentially between the polluted and unpolluted paddies. This could suggest either a possible non-specific target of the primers conventionally used in soil study or complex interactions between soil properties and metal contents on the observed community and activity changes, and thus on the N transformation in the polluted rice soils.
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