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Find video protocols related to scientific articles indexed in Pubmed.
Analytic model for light guidance in single-wall hollow-core anti-resonant fibers.
Opt Express
PUBLISHED: 11-18-2014
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We report an analytic model for quantitatively calculating the transmission attenuation of single-wall hollow-core anti-resonant fibers. Our calculations unveil the light leakage dependences on azimuthal angle, polarization, and geometrical shape and have been examined in a variety of fiber geometries. Based on our model, a simple and clear picture about light guidance in hollow-core lattice fibers is presented. Formation of equiphase surface at fiber's outermost boundary and light emission ruled by Helmholtz equation in transverse plane constitute the basis of this picture. Using this picture, we explain how the geometrical shape of a single-wall hollow-core fiber influences its transmission properties.
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[Clinicopathological features associated with EGFR gene mutation in non-small cell lung cancer patients].
Zhonghua Yi Xue Za Zhi
PUBLISHED: 11-18-2014
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To explore the clinicopathological features associated with epidermal growth factor receptor (EGFR) gene mutation in non-small cell lung cancer (NSCLC) patients.
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Existence and stability of periodic solution of impulsive neural systems with complex deviating arguments.
J Biol Dyn
PUBLISHED: 11-15-2014
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This paper discusses a class of impulsive neural networks with the variable delay and complex deviating arguments. By using Mawhin's continuation theorem of coincidence degree and the Halanay-type inequalities, several sufficient conditions for impulsive neural networks are established for the existence and globally exponential stability of periodic solutions, respectively. Furthermore, the obtained results are applied to some typical impulsive neural network systems as special cases, with a real-life example to show feasibility of our results.
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[Changes in mitochondria fusion protein-2 hepatic expression in conditions of liver cirrhosis and acute on chronic liver failure].
Zhonghua Gan Zang Bing Za Zhi
PUBLISHED: 11-05-2014
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To determine the differential protein and mRNA expressions of mitochondria fusion protein-2 (Mfn2) in hepatic tissues in conditions of cirrhosis and acute on chronic liver failure using rat model systems,and to determine the correlative effects on production of adenosine triphosphate (ATP) and reactive oxygen species (ROS).
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Cobalt carbonate hydroxide/C: an efficient dual electrocatalyst for oxygen reduction/evolution reactions.
Chem. Commun. (Camb.)
PUBLISHED: 10-30-2014
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A novel bi-functional cobalt carbonate hydroxide supported on a carbon (CCH/C) catalyst has been synthesized via a facile hydrothermal method to meet the demand for the widespread commercialization of the energy conversion and storage technologies, which was used for the first time in ORR and OER. Furthermore, the newly discovered phase-dependent electrocatalytic ORR/OER characteristics of CCH/C are demonstrated.
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Pt/C trapped in activated graphitic carbon layers as a highly durable electrocatalyst for the oxygen reduction reaction.
Chem. Commun. (Camb.)
PUBLISHED: 10-29-2014
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A thin nitrogen-doped graphitic carbon layer is elaborately introduced into the Pt/C surface to not only inhibit migration and dissolution of Pt nanoparticles, but also impart activity to the integral catalyst without blocking the inner Pt catalytic active sites. The corrosion of the carbon support can also be alleviated due to the outer graphitic coverage.
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Bipart: Learning Block Structure for Activity Detection.
IEEE Trans Knowl Data Eng
PUBLISHED: 10-21-2014
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Physical activity consists complex behavior, typically structured in bouts which can consist of one continuous movement (e.g. exercise) or many sporadic movements (e.g. household chores). Each bout can be represented as a block of feature vectors corresponding to the same activity type. This paper introduces a general distance metric technique to use this block representation to first predict activity type, and then uses the predicted activity to estimate energy expenditure within a novel framework. This distance metric, dubbed Bipart, learns block-level information from both training and test sets, combining both to form a projection space which materializes block-level constraints. Thus, Bipart provides a space which can improve the bout classification performance of all classifiers. We also propose an energy expenditure estimation framework which leverages activity classification in order to improve estimates. Comprehensive experiments on waist-mounted accelerometer data, comparing Bipart against many similar methods as well as other classifiers, demonstrate the superior activity recognition of Bipart, especially in low-information experimental settings.
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Early markers of obesity-related renal injury in childhood.
Pediatr. Nephrol.
PUBLISHED: 09-23-2014
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Childhood obesity has become a global epidemic. Recent epidemiological data suggest that obesity is associated with increased risk of renal injury in children. The onset of obesity-associated renal disease is insidious and asymptomatic, so early markers will be extremely useful in its prevention and treatment. Biomarker discovery can be focused on unbiased or biased (candidate) approaches. Unbiased approaches using innovative technologies, such as proteomics and metabolomics, have uncovered candidates that are emerging as plausible biomarkers for such renal disorders as obstructive uropathy and diabetic nephropathy. Biased approaches are based on hypotheses related to glomerular or tubular injury pathophysiology in obesity. Goknar et al. (Pediatric Nephrology 2014; doi: 10.1007/s00467-014-2829-0 ) recently evaluated early urine renal injury markers, namely, microalbuminuria, N-acetyl-beta-D-glucosaminidase (NAG), neutrophil gelatinase-associated lipocalin, and kidney injury molecule (KIM)-1, in obese children. They reported that obese children had higher urinary NAG and KIM-1 levels than healthy controls. Longitudinal observation studies are needed to evaluate whether these tubular damage markers are useful as early markers of renal injury in obese children.
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Network Modeling of TGF? Signaling in Hepatocellular Carcinoma Epithelial-to-Mesenchymal Transition Reveals Joint Sonic Hedgehog and Wnt Pathway Activation.
Cancer Res.
PUBLISHED: 09-04-2014
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Epithelial-to-mesenchymal transition (EMT) is a developmental process hijacked by cancer cells to leave the primary tumor site, invade surrounding tissue, and establish distant metastases. A hallmark of EMT is the loss of E-cadherin expression, and one major signal for the induction of EMT is TGF?, which is dysregulated in up to 40% of hepatocellular carcinoma (HCC). We have constructed an EMT network of 70 nodes and 135 edges by integrating the signaling pathways involved in developmental EMT and known dysregulations in invasive HCC. We then used discrete dynamic modeling to understand the dynamics of the EMT network driven by TGF?. Our network model recapitulates known dysregulations during the induction of EMT and predicts the activation of the Wnt and Sonic hedgehog (SHH) signaling pathways during this process. We show, across multiple murine (P2E and P2M) and human HCC cell lines (Huh7, PLC/PRF/5, HLE, and HLF), that the TGF? signaling axis is a conserved driver of mesenchymal phenotype HCC and confirm that Wnt and SHH signaling are induced in these cell lines. Furthermore, we identify by network analysis eight regulatory feedback motifs that stabilize the EMT process and show that these motifs involve cross-talk among multiple major pathways. Our model will be useful in identifying potential therapeutic targets for the suppression of EMT, invasion, and metastasis in HCC. Cancer Res; 74(21); 5963-77. ©2014 AACR.
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Surface Al leached Ti3AlC2 as a substitute for carbon for use as a catalyst support in a harsh corrosive electrochemical system.
Nanoscale
PUBLISHED: 08-22-2014
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Surface Al leached Ti3AlC2 particles (e-TAC) with high corrosion resistance and excellent electrical conductivity were developed as an advanced support material for Pt catalysts. Electrochemical measurements confirm that the supported Pt/e-TAC electrocatalyst shows much improved activity and enhanced durability toward the oxygen reduction reaction when compared with the commercial Pt/C catalyst.
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Penguins significantly increased phosphine formation and phosphorus contribution in maritime Antarctic soils.
Sci Rep
PUBLISHED: 07-29-2014
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Most studies on phosphorus cycle in the natural environment focused on phosphates, with limited data available for the reduced phosphine (PH3). In this paper, matrix-bound phosphine (MBP), gaseous phosphine fluxes and phosphorus fractions in the soils were investigated from a penguin colony, a seal colony and the adjacent animal-lacking tundra and background sites. The MBP levels (mean 200.3?ng kg(-1)) in penguin colony soils were much higher than those in seal colony soils, animal-lacking tundra soils and the background soils. Field PH3 flux observation and laboratory incubation experiments confirmed that penguin colony soils produced much higher PH3 emissions than seal colony soils and animal-lacking tundra soils. Overall high MBP levels and PH3 emissions were modulated by soil biogeochemical processes associated with penguin activities: sufficient supply of the nutrients phosphorus, nitrogen, and organic carbon from penguin guano, high soil bacterial abundance and phosphatase activity. It was proposed that organic or inorganic phosphorus compounds from penguin guano or seal excreta could be reduced to PH3 in the Antarctic soils through the bacterial activity. Our results indicated that penguin activity significantly increased soil phosphine formation and phosphorus contribution, thus played an important role in phosphorus cycle in terrestrial ecosystems of maritime Antarctica.
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Development of a sensitive ultra high performance liquid chromatography with tandem mass spectrometry method for the simultaneous quantification of nine active compounds in rat plasma and its application to a pharmacokinetic study after administration of Viscum coloratu
J Sep Sci
PUBLISHED: 07-24-2014
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A simple, specific, and sensitive ultra high performance liquid chromatography with tandem mass spectrometry method was developed and validated for the simultaneous quantification of nine compounds including a new compound, rhamnazin-3-?-?-d-(6''-?-hydroxy-?-methyglutaryl)-?-d-glucoside-4'-?-?-d-glucoside, in rat plasma using baicalin as an internal standard. The plasma samples were pretreated and extracted by protein precipitation with 0.2% formic acid in acetonitrile. The analytes were separated on a Thermo Syncronis C18 column by gradient elution with a mobile phase consisting of acetonitrile and 0.1% aqueous formic acid at a flow rate of 0.25 mL·min(-1) . The detection of the analytes was performed on an electrospray ionization interface operating in positive ion and multiple reaction-monitoring acquisition modes. The calibration curves of these analytes showed good linearity (r > 0.99) within the test ranges. The lower limit of quantification ranged from 0.4 to 20.1 ng·mL(-1) for the analytes. The intra- and inter-day precision and accuracy were all within ±15%, and the recoveries were higher than 80.0%. The validated method was successfully applied to a pharmacokinetic study of the nine flavonoids after administration of the Viscum coloratum extracts by intravenous injection. This article is protected by copyright. All rights reserved.
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Molecular cloning and expression of glutathione S-transferases involved in propargite resistance of the carmine spider mite, Tetranychus cinnabarinus (Boisduval).
Pestic Biochem Physiol
PUBLISHED: 07-24-2014
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The carmine spider mite (CSM) Tetranychus cinnabarinus has become a serious pest in China and has developed resistance to acaricide propargite as it is used to control mites worldwide including T. cinnabarinus. In this study, a resistant colony of T. cinnabarinus, PRR34 (37.78-fold resistant ratio), was established after 34 generations of propargite selection, and cross-resistance patterns of 7 other acaricides were determined in comparison with a susceptible strain (SS). The contribution of detoxification enzymes to propargite tolerance were investigated using biological, biochemical and molecular approaches. Enzyme inhibitor synergist tests suggested glutathione S-transferases (GST) involvement in propargite-resistance of PRR34, and GST activity against 1-chloro-2,4-dinitrobenzene (CDNB) was correlated with the development of resistance. Eight novel GST genes (TcGSTd1, TcGSTd2, TcGSTm1, TcGSTm2, TcGSTm3, TcGSTm4 and TcGSTm5) were cloned, and phylogenetic analysis showed that the eight GST genes were most closely related to GST family delta and mu from Tetranychusurticae. Quantitative RT-PCR revealed that the expression level of GSTs in PPR34 strain increased in larvae, nymphs and adults, while decreased in eggs compared with that of SS. Collectively, these results support a role of GSTs in mediating resistance to propargite in the PRR34 strain. TcGSTd1,TcGSTd2 and TcGSTm2 genes might play significant roles in propargite resistance of CSM, especially at adult stage. This is the first attempt to define specific genes involved in GST mediated propargite resistance of T. cinnabarinus at the transcriptional level.
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The rheological properties of tara gum (Caesalpinia spinosa).
Food Chem
PUBLISHED: 07-23-2014
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The rheological properties of tara gum, as affected by concentration, temperature, pH and the presence of salts and sucrose, were investigated by using steady and dynamic shear measurements and atomic force microscope observation. Tara gum exhibited non-Newtonian, pseudoplastic behaviour without thixotropy at tested concentrations (0.2-1.0%, w/v). Salts (CaCl2 and NaCl) led to a viscosity reduction, which was more sensitive to Ca(2+) than to Na(+). The gum had stable viscosity over a wide pH range (pH 3-11), and the influence of sucrose was concentration dependent. Increasing temperature from 20°C to 80°C decreased the gum viscosity. Frequency sweeps indicated that tara gum (1.0% w/v) behaved as a liquid at low frequency, and acted more like a gel at high frequency. With the decrease of concentration, tara gum may show a viscous property rather than an elastic one. These results are potentially useful for the application of tara gum in food processing.
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[Clinicopathological characteristics and imaging features of pulmonary adenocarcinoma with micropapillary pattern].
Zhonghua Zhong Liu Za Zhi
PUBLISHED: 07-04-2014
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To explore the clinicopathological characteristics and imaging features of lung adenocarcinoma with a micropapillary pattern (MPP).
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In vivo genotoxicity of estragole in male F344 rats.
Environ. Mol. Mutagen.
PUBLISHED: 06-24-2014
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Estragole, a naturally occurring constituent of various herbs and spices, is a rodent liver carcinogen which requires bio-activation. To further understand the mechanisms underlying its carcinogenicity, genotoxicity was assessed in F344 rats using the comet, micronucleus (MN), and DNA adduct assays together with histopathological analysis. Oxidative damage was measured using human 8-oxoguanine-DNA-N-glycosylase (hOGG1) and EndonucleaseIII (EndoIII)-modified comet assays. Results with estragole were compared with the structurally related genotoxic carcinogen, safrole. Groups of seven-week-old male F344 rats received corn oil or corn oil containing 300, 600, or 1,000 mg/kg bw estragole and 125, 250, or 450 mg/kg bw safrole by gavage at 0, 24, and 45 hr and terminated at 48 hr. Estragole-induced dose-dependent increases in DNA damage following EndoIII or hOGG1 digestion and without enzyme treatment in liver, the cancer target organ. No DNA damage was detected in stomach, the non-target tissue for cancer. No elevation of MN was observed in reticulocytes sampled from peripheral blood. Comet assays, both without digestion or with either EndoIII or hOGG1 digestion, also detected DNA damage in the liver of safrole-dosed rats. No DNA damage was detected in stomach, nor was MN elevated in peripheral blood following dosing with safrole suggesting that, as far both safrole and estragole, oxidative damage may contribute to genotoxicity. Taken together, these results implicate multiple mechanisms of estragole genotoxicity. DNA damage arises from chemical-specific interaction and is also mediated by oxidative species. Environ. Mol. Mutagen., 2014. © 2014 Crown copyright.
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A Novel Route to Recognizing Quaternary Ammonium Cations Using Electrospray Mass Spectrometry.
J. Am. Soc. Mass Spectrom.
PUBLISHED: 06-10-2014
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Characterizing and elucidating structures is a commonplace and necessary activity in the pharmaceutical industry with mass spectrometry and NMR being the primary tools for analysis. Although many functional groups are readily identifiable, quaternary ammonium cations have proven to be difficult to unequivocally identify using these techniques. Due to the lack of an N-H bond, quaternary ammonium groups can only be detected in the (1)H NMR spectra by weak signals generated from long-range (14)N-H coupling, which by themselves are inconclusive evidence of a quaternary ammonium functional group. Due to their low intensity, these signals are frequently not detected. Additionally, ions cannot be differentiated in a mass spectrum as an M(+) or [M + H](+) ion without prior knowledge of the compound's structure. In order to utilize mass spectrometry as a tool for determining this functionality, ion cluster formation of quaternary ammonium cations and non-quaternary amines was studied using electrospray ionization. Several mobile phase modifiers were compared; however, the addition of small amounts of trifluoroacetic acid proved superior in producing characteristic and intense [M +2TFA](-) clusters for compounds containing quaternary ammonium cations when using negative electrospray. By fragmenting this characteristic ion using CID, nearly all compounds studied could be unambiguously identified as containing a quaternary ammonium cation or a non-quaternary amine attributable to the presence (non-quaternary amine) or absence (quaternary ammonium cation) of the resulting [2TFA + H](-) ion in the product spectra. This method of analysis provides a rapid, novel, and reliable technique for indicating the presence of quaternary ammonium cations in order to aid in structural elucidation.
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Population activity changes during a trial-to-trial adaptation of bullfrog retinal ganglion cells.
Neuroreport
PUBLISHED: 05-23-2014
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A 'trial-to-trial adaptation' of bullfrog retinal ganglion cells in response to a repetitive light stimulus was investigated in the present study. Using the multielectrode recording technique, we studied the trial-to-trial adaptive properties of ganglion cells and explored the activity of population neurons during this adaptation process. It was found that the ganglion cells adapted with different degrees: their firing rates were decreased in different extents from early-adaptation to late-adaptation stage, and this was accompanied by a decrease in cross-correlation strength. In addition, adaptation behavior was different for ON-response and OFF-response, which implied that the mechanism of the trial-to-trial adaptation might involve bipolar cells and/or their synapses with other neurons and the stronger adaptation in the ganglion cells' OFF-responses might reflect the requirement to avoid possible saturation in the OFF circuit.
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Structural and biochemical characterization reveals LysGH15 as an unprecedented "EF-hand-like" calcium-binding phage lysin.
PLoS Pathog.
PUBLISHED: 05-01-2014
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The lysin LysGH15, which is derived from the staphylococcal phage GH15, demonstrates a wide lytic spectrum and strong lytic activity against methicillin-resistant Staphylococcus aureus (MRSA). Here, we find that the lytic activity of the full-length LysGH15 and its CHAP domain is dependent on calcium ions. To elucidate the molecular mechanism, the structures of three individual domains of LysGH15 were determined. Unexpectedly, the crystal structure of the LysGH15 CHAP domain reveals an "EF-hand-like" calcium-binding site near the Cys-His-Glu-Asn quartet active site groove. To date, the calcium-binding site in the LysGH15 CHAP domain is unique among homologous proteins, and it represents the first reported calcium-binding site in the CHAP family. More importantly, the calcium ion plays an important role as a switch that modulates the CHAP domain between the active and inactive states. Structure-guided mutagenesis of the amidase-2 domain reveals that both the zinc ion and E282 are required in catalysis and enable us to propose a catalytic mechanism. Nuclear magnetic resonance (NMR) spectroscopy and titration-guided mutagenesis identify residues (e.g., N404, Y406, G407, and T408) in the SH3b domain that are involved in the interactions with the substrate. To the best of our knowledge, our results constitute the first structural information on the biochemical features of a staphylococcal phage lysin and represent a pivotal step forward in understanding this type of lysin.
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[Temporal rotation skin flap combined with cartilage plasty for correcting cryptotia].
Zhonghua Zheng Xing Wai Ke Za Zhi
PUBLISHED: 04-24-2014
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To explore the therapeutic effect of the temporal rotation flap combined with cartilage plasty for cryptotia correction.
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Enhancement and electric charge-assisted tuning of nonlinear light generation in bipolar plasmonics.
Nano Lett.
PUBLISHED: 04-24-2014
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We propose and experimentally demonstrate a new plasmonic nonlinear light generation (NLG) structure, termed plasmonic-enhanced, charge-assisted second-harmonic generator (p-CASH), that not only achieves high second-harmonic generation (SHG) enhancement (76-fold), large SHG tunability by bias (8%/V), wide tuning range (280%), 7.8 × 10(-9) conversion efficiency, and high stability but also exhibits a SHG tuning, that is bipolar rather than unipolar, not due to the third-order nonlinear polarization term, hence fundamentally different from the classic electric field induced SHG-tuning (EFISH). We propose a new SHG tuning mechanism: the second-order nonlinear polarization term enhanced by plasmonic effects, changed by charge injection and negative oxygen vacancies movement, and is nearly 3 orders of magnitude larger than EFISH. p-CASH is a bipolar parallel-plate capacitor with thin layers of plasmonic nanostructures, a TiOx (semiconductor and nonlinear) and a SiO2 (insulator) sandwiched between two electrodes. Fabrication of p-CASH used nanoimprint on 4? wafer and is scalable to wallpaper-sized areas. The new structure, new properties, and new understanding should open up various new designs and applications of NLG in various fields.
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E2F3a gene expression has prognostic significance in childhood acute lymphoblastic leukemia.
Eur. J. Haematol.
PUBLISHED: 04-10-2014
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To study E2F3a expression and its clinical significance in children with acute lymphoblastic leukemia (ALL).
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Matrix-bound phosphine, phosphorus fractions and phosphatase activity through sediment profiles in Lake Chaohu, China.
Environ Sci Process Impacts
PUBLISHED: 04-08-2014
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The distribution patterns of matrix-bound phosphine (MBP), phosphorus (P) fractions and neutral phosphatase activity (NPA) were investigated through five sediment profiles in Lake Chaohu, China. MBP was discovered in all sediment profiles within the concentration range of 1.58-50.34 ng kg(-1). These concentrations exhibited a consistent vertical distribution pattern in all profiles, and higher concentrations generally occurred in surface sediments. MBP concentrations showed a significant positive correlation with P fractions, total nitrogen (TN), Cu and Zn under lower levels of inorganic phosphorus (<0.6 g kg(-1)), organic phosphorus (<0.2 g kg(-1)), TN (<0.13%), Cu (<25 mg kg(-1)) and Zn (<150 mg kg(-1)), but no statistically significant correlations were obtained under higher levels. A multiple stepwise regression model ([MBP]=1.36[NPA]-6.21[pH]-0.06[Zn]+0.75[Cu]+49.86) was obtained between MBP concentrations and environmental variables, and MBP concentrations showed a strong positive correlation with NPA (P<0.0001). This indicates that the production of sediment MBP was controlled by microbially mediated processes in Lake Chaohu. This model could be used to predict MBP levels in the sediments. Our results indicate that MBP levels could not be used as indicators for the degree of lake eutrophication. The study of sediment MBP, P factions and NPA will improve our understanding of P cycling and their environmental significance in the eutrophic Lake Chaohu.
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Demonstration of broad photonic crystal stop band in a freely-suspended microfiber perforated by an array of rectangular holes.
Opt Express
PUBLISHED: 03-26-2014
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It is shown that photonic crystal (PhC) optical reflectors with reflectance in excess of 60% and fractional bandwidths greater than 10% can be fabricated by ion beam milling of fewer than ten periods of rectangular cross section through-holes in micron-scale tapered fibers. The optical characteristics agree well with numerical simulations when allowance is made for fabrication artefacts and we show that the radiation loss, which is partly determined by optical interference, can be suppressed by design. The freely-suspended devices are compact and robust and could form the basic building block of optical cavities and filters.
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Structural and functional analyses of human tryptophan 2,3-dioxygenase.
Proteins
PUBLISHED: 03-19-2014
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Tryptophan 2,3-dioxygenase (TDO), one of the two key enzymes in the kynurenine pathway, catalyzes the indole ring cleavage at the C2-C3 bond of l-tryptophan. This is a rate-limiting step in the regulation of tryptophan concentration in vivo, and is thus important in drug discovery for cancer and immune diseases. Here, we report the crystal structure of human TDO (hTDO) without the heme cofactor to 2.90 Å resolution. The overall fold and the tertiary assembly of hTDO into a tetramer, as well as the active site architecture, are well conserved and similar to the structures of known orthologues. Kinetic and mutational studies confirmed that eight residues play critical roles in l-tryptophan oxidation. Proteins 2014; 82:3210-3216. © 2014 Wiley Periodicals, Inc.
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Genetic diversity and population structure of black Dahe pig based on DNA sequences analyses of mitochondrial and nuclear genes.
Mitochondrial DNA
PUBLISHED: 03-13-2014
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Abstract To investigate the genetic diversity and population structure of black Dahe pigs, we collected 175 samples from 5 local populations and sequenced them using a combination of two selected molecular markers for mitochondrial cytochrome b and Major Histocompatibility Complex (MHC) DRB. Overall, the results of AMOVA and phylogenetic tree and gene flow analyses detected high levels of gene flow among the five populations, particularly individual pigs from Dahe town (Pop1) or Yingshang town (Pop2) to other populations (Pop3, Pop4, and Pop5). The genetic diversity analyses showed that the diversity indices of the five populations did not vary significantly, but they were much lower than those of other Chinese pig species. These results suggest that distinct gene flow, unstable population pattern, and lower genetic diversity have been influenced mainly by human introductions for economic ends. These findings provide genetic information that could be used for the preservation and further genetic improvement of the black Dahe pig, as well as an important reference for the evaluation, conservation, and utilization of the genetic resources of this breed.
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Calpain: a molecule to induce AIF-mediated necroptosis in RGC-5 following elevated hydrostatic pressure.
BMC Neurosci
PUBLISHED: 03-12-2014
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RIP3 (Receptor-interacting protein 3) pathway was mainly described as the molecular mechanism of necroptosis (programmed necrosis). But recently, non-RIP3 pathways were found to mediate necroptosis. We deliberate to investigate the effect of calpain, a molecule to induce necroptosis as reported (Cell Death Differ 19:245-256, 2012), in RGC-5 following elevated hydrostatic pressure.
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Contributions of endoplasmic reticulum stress and reactive oxygen species to renal injury in aldosterone/salt-induced rats.
Nephron Exp. Nephrol.
PUBLISHED: 03-07-2014
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Recent studies have suggested that aldosterone (Aldo) plays a key role in the pathogenesis of renal injury; however, the molecular mechanisms of Aldo-induced renal injury have not been characterized. This study was performed to test the hypothesis that reactive oxygen species (ROS) and endoplasmic reticulum (ER) stress contribute to the pathogenesis of Aldo- and salt-induced renal injury.
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Direct sp(3)C-H acroleination of N-aryl-tetrahydroisoquinolines by merging photoredox catalysis with nucleophilic catalysis.
Org. Biomol. Chem.
PUBLISHED: 02-20-2014
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Sequence catalysis merging photoredox catalysis (PC) and nucleophilic catalysis (NC) has been realized for the direct sp(3) C-H acroleination of N-aryl-tetrahydroisoquinoline (THIQ). The reaction was performed under very mild conditions and afforded products in 50-91% yields. A catalytic asymmetric variant was proved to be successful with moderate enantioselectivities (up to 83?:?17 er).
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Structures of the Ca2+-regulated photoprotein obelin Y138F mutant before and after bioluminescence support the catalytic function of a water molecule in the reaction.
Acta Crystallogr. D Biol. Crystallogr.
PUBLISHED: 02-15-2014
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Ca(2+)-regulated photoproteins, which are responsible for light emission in a variety of marine coelenterates, are a highly valuable tool for measuring Ca(2+) inside living cells. All of the photoproteins are a single-chain polypeptide to which a 2-hydroperoxycoelenterazine molecule is tightly but noncovalently bound. Bioluminescence results from the oxidative decarboxylation of 2-hydroperoxycoelenterazine, generating protein-bound coelenteramide in an excited state. Here, the crystal structures of the Y138F obelin mutant before and after bioluminescence are reported at 1.72 and 1.30?Å resolution, respectively. The comparison of the spatial structures of the conformational states of Y138F obelin with those of wild-type obelin gives clear evidence that the substitution of Tyr by Phe does not affect the overall structure of both Y138F obelin and its product following Ca(2+) discharge compared with the corresponding conformational states of wild-type obelin. Despite the similarity of the overall structures and internal cavities of Y138F and wild-type obelins, there is a substantial difference: in the cavity of Y138F obelin a water molecule corresponding to W2 in wild-type obelin is not found. However, in Ca(2+)-discharged Y138F obelin this water molecule now appears in the same location. This finding, together with the observed much slower kinetics of Y138F obelin, clearly supports the hypothesis that the function of a water molecule in this location is to catalyze the 2-hydroperoxycoelenterazine decarboxylation reaction by protonation of a dioxetanone anion before its decomposition into the excited-state product. Although obelin differs from other hydromedusan Ca(2+)-regulated photoproteins in some of its properties, they are believed to share a common mechanism.
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Bone marrow-derived mesenchymal stem cells protect against lung injury in a mouse model of bronchopulmonary dysplasia.
Mol Med Rep
PUBLISHED: 02-14-2014
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The aim of the present study was to investigate the effect of bone marrow?derived mesenchymal stem cells (BMSCs) in the treatment of lung injury in a mouse model of bronchopulmonary dysplasia (BPD) and examine the underlying mechanisms. A mouse model of BPD was created using continuous exposure to high oxygen levels for 14 days. BMSCs were isolated, cultured and then labeled with green fluorescent protein. Cells (1x106) were subsequently injected intravenously 1 h prior to high oxygen treatment. Animals were randomly divided into three groups (n=5 in each): Control group, BPD model group and BMSC injection group. At two weeks post?treatment, the expression of transforming growth factor??1 (TGF??1), vascular endothelial growth factor (VEGF) and von Willebrand factor (vWF) was detected using immunohistochemical staining and immunofluorescence. Compared with the BPD model group, the body weight, airway structure and levels of TGF??1 and VEGF were significantly improved in the BMSC?treated group. Immunofluorescence observations indicated that BMSCs were able to differentiate into cells expressing vWF and VEGF, which are markers of vascular tissues. The present study demonstrated that intravenous injection of BMSCs significantly improved lung damage in a neonatal mouse model of BPD at 14 days following hyperoxia?induced injury. This provides novel information which may be used to guide further investigation into the use of stem cells in BPD.
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Synthesis of CF3-containing 3,3'-cyclopropyl spirooxindoles by sequential [3 + 2] cycloaddition/ring contraction of ylideneoxindoles with 2,2,2-trifluorodiazoethane.
J. Org. Chem.
PUBLISHED: 02-13-2014
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A [3 + 2] cycloaddition/ring contraction sequence of ylideneoxindoles with in situ-generated 2,2,2-trifluorodiazoethane without the use of any transition-metal catalyst has been developed. The reaction provides efficient access to biologically important and synthetically useful CF3-containing 3,3'-cyclopropyl spirooxindoles in high yield (74-99%) with high diastereoselectivity (>95:5 d.r.).
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Predictive and prognostic value of ER-?36 expression in breast cancer patients treated with chemotherapy.
Steroids
PUBLISHED: 02-07-2014
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This study is to investigate the predictive and prognostic value of ER-?36 expression in breast cancer patients treated with chemotherapy.
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Crystallization, preliminary X-ray crystallographic and cryo-electron microscopy analysis of a bifunctional enzyme fucokinase/L-fucose-1-P-guanylyltransferase from Bacteroides fragilis.
Acta Crystallogr F Struct Biol Commun
PUBLISHED: 02-04-2014
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Fucokinase/L-fucose-1-P-guanylyltransferase (FKP) is a bifunctional enzyme which converts L-fucose to Fuc-1-P and thence to GDP-L-fucose through a salvage pathway. The molecular weights of full-length FKP (F-FKP) and C-terminally truncated FKP (C-FKP, residues 300-949) are 105.7 and 71.7?kDa, respectively. In this study, both recombinant F-FKP and C-FKP were expressed and purified. Size-exclusion chromatography experiments and analytical ultracentrifugation results showed that both F-FKP and C-FKP are trimers. Native F-FKP protein was crystallized by the vapour-diffusion method and the crystals belonged to space group P212121 and diffracted synchrotron X-rays to 3.7?Å resolution. The crystal unit-cell parameters are a = 91.36, b = 172.03, c = 358.86?Å, ? = ? = ? = 90.00°. The three-dimensional features of the F-FKP molecule were observed by cryo-EM (cryo-electron microscopy). The preliminary cryo-EM experiments showed the F-FKP molecules as two parallel disc-shaped objects stacking together. Combining all results together, it is assumed that there are six FKP molecules in one asymmetric unit, which corresponds to a calculated Matthews coefficient of 2.19?Å(3)?Da(-1) with 43.83% solvent content. These preliminary crystallographic and cryo-EM microscopy analyses provide basic structural information on FKP.
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Effect of microRNA-210 on prognosis and response to chemotherapeutic drugs in pediatric acute lymphoblastic leukemia.
Cancer Sci.
PUBLISHED: 01-29-2014
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Many studies have demonstrated that microRNA-210 (miR-210) expression is intensively upregulated in hypoxic states and differentially regulated in most types of cancer cells. However, the clinical significance of miR-210 and its effects on the response of leukemic cells to chemotherapeutic drugs in childhood acute lymphoblastic leukemia (ALL) remain unknown. In the current study, using real-time qRT-PCR to detect miR-210 expression in bone marrow samples from 114 children at initial diagnosis of ALL, we investigated the prognostic significance of miR-210 and determined its associations with common clinical characteristics and treatment outcome. We further examined its effect on the response to chemotherapeutic drugs in the Reh and RS4;11 cell lines. Results showed that miR-210 expression was significantly lower in patients suffering from relapse and induction failure than in other patients (P < 0.001). Using the receiver operating characteristic curve, 3.8243 was selected as the cut-off value of miR-210 expression in our test cohort (38 cases). A significantly poorer treatment outcome (P < 0.05) was found in the low-expression group and verified in the validation cohort (76 cases, P < 0.05). Patients with low expression of miR-210 and positive minimal residual disease at the end of induction had a much higher rate of relapse or induction failure (P = 0.001). Increasing/decreasing miR-210 expression using agomir/antagomir could enhance or reduce the response of Reh cells and RS4;11 cells to daunorubicin/dexamethasone/L-asparaginase and daunorubicin/dexamethasone/vincristine, respectively. In conclusion, miR-210 may be a good prognostic factor and a useful predictor of drug sensitivity, and is a potential therapeutic target for pediatric ALL.
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Phytophthora parasitica: a model oomycete plant pathogen.
Mycology
PUBLISHED: 01-25-2014
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Oomycetes are eukaryotic microorganisms morphologically similar to but phylogenetically distant from true fungi. Most species in the genus Phytophthora of oomycetes are devastating plant pathogens, causing damages to both agricultural production and natural ecosystems. Tremendous progress has been achieved in recent years in diversity, evolution and lifestyles of oomycete plant pathogens, as well as on the understanding of genetic and molecular basis of oomycete-plant interactions. Phytophthora parasitica is a soilborne pathogen with a wide range of host plants and represents most species in the genus Phytophthora. In this review, we present some recent progress of P. parasitica research by highlighting important features that make it emerge as a model species of oomycete pathogens. The emerged model pathogen will facilitate improved understanding of oomycete biology and pathology that are crucial to the development of novel disease-control strategies and improved disease-control measures.
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Incidence of chronic lymphocytic leukemia and high-count monoclonal B-cell lymphocytosis using the 2008 guidelines.
Cancer
PUBLISHED: 01-16-2014
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The 1996 National Cancer Institute Working Group (NCI-WG 96) guidelines classified disease in individuals who had a B-cell clone with chronic lymphocytic leukemia (CLL) immunophenotype as CLL if their absolute lymphocyte count was ?5?×?10(9)/L. The 2008 International Workshop on CLL guidelines (IWCLL 2008) classified disease as CLL if the absolute B-cell count was ?5?×?10(9)/L or as monoclonal B-cell lymphocytosis (MBL) if the absolute B-cell count was <5?×?10(9)/L. The objective of the current study of Olmsted County, Minnesota, was to assess the effects of these changes on incidence rates and presentation from 2000 to 2010.
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Structural analysis of asparaginyl endopeptidase reveals the activation mechanism and a reversible intermediate maturation stage.
Cell Res.
PUBLISHED: 01-10-2014
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Asparaginyl endopeptidase (AEP) is an endo/lysosomal cysteine endopeptidase with a preference for an asparagine residue at the P1 site and plays an important role in the maturation of toll-like receptors 3/7/9. AEP is known to undergo autoproteolytic maturation at acidic pH for catalytic activation. Here, we describe crystal structures of the AEP proenzyme and the mature forms of AEP. Structural comparisons between AEP and caspases revealed similarities in the composition of key residues and in the catalytic mechanism. Mutagenesis studies identified N44, R46, H150, E189, C191, S217/S218 and D233 as residues that are essential for the cleavage of the peptide substrate. During maturation, autoproteolytic cleavage of AEP's cap domain opens up access to the active site on the core domain. Unexpectedly, an intermediate autoproteolytic maturation stage was discovered at approximately pH 4.5 in which the partially activated AEP could be reversed back to its proenzyme form. This unique feature was confirmed by the crystal structure of AEPpH4.5 (AEP was matured at pH 4.5 and crystallized at pH 8.5), in which the broken peptide bonds were religated and the structure was transformed back to its proenzyme form. Additionally, the AEP inhibitor cystatin C could be digested by the fully activated AEP, but could not be digested by activated cathepsins. Thus, we demonstrate for the first time that cystatins may regulate the activity of AEP through substrate competition for the active site.
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Feasible Method to enable clear visualization of suspected bladder cancer with 18F-FDG PET/CT.
Clin Imaging
PUBLISHED: 01-09-2014
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To evaluate value of a new method in detecting bladder lesion with (18)F-FDG PET/CT.
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DNA logic gate based on metallo-toehold strand displacement.
PLoS ONE
PUBLISHED: 01-01-2014
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DNA is increasingly being used as an ideal material for the construction of nanoscale structures, circuits, and machines. Toehold-mediated DNA strand displacement reactions play a very important role in these enzyme-free constructions. In this study, the concept of metallo-toehold was utilized to further develop a mechanism for strand displacement driven by Ag+ ions, in which the intercalation of cytosine-cytosine mismatched base pairs on the toeholds provides additional control by varying of the concentration of Ag+ ions. The characteristics of displacement reaction in response to different concentration of Ag+ ions are investigated by fluorescence spectral and non-denaturing polyacrylamide gel electrophoresis. The reaction can successfully occur when the concentration of Ag+ ions is suitabe; excess Ag+ ions block the reaction. Furthermore, the displacement reaction can be tuned and controlled most efficiently under the condition of two C:C mismatched base pairs placed on the six-nt toehold. Based on our research, a mechanism was developed to construct Boolean logic gate AND and OR by employing strand displacement reaction as a tool, Ag+ and Hg2+ as input.
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Sox9 gene transfer enhanced regenerative effect of bone marrow mesenchymal stem cells on the degenerated intervertebral disc in a rabbit model.
PLoS ONE
PUBLISHED: 01-01-2014
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The effect of Sox9 on the differentiation of bone marrow mesenchymal stem cells (BMSCs) to nucleus pulposus (NP)-like (chondrocyte-like) cells in vitro has been demonstrated. The objective of this study is to investigate the efficacy and feasibility of Sox9-transduced BMSCs to repair the degenerated intervertebral disc in a rabbit model.
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Accurate and economical detection of ALK positive lung adenocarcinoma with semiquantitative immunohistochemical screening.
PLoS ONE
PUBLISHED: 01-01-2014
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Right detection of anaplastic lymphoma kinase (ALK) gene rearrangement is pivotal to selection of patients with lung adenocarcinoma for ALK-targeted therapy. We explored the potential of combination of immunohistochemistry (IHC) screening and fluorescence in situ hybridization (FISH) as an affordable practice. We analyzed 410 unselected lung adenocarcinomas by ALK IHC (D5F3 clone) and FISH. Some equivocal cases were further analyzed by RT-PCR. The EGFR mutation was detected by pyrosequencing assay. In total 368 cases which got all IHC, FISH, EGFR mutation results were eligible for analysis. Cases were evaluated as IHC score 3+ (n = 26), score 2+ (n = 9), score 1+ (n = 51), and score 0 (n = 282), respectively. 23 of 26 IHC 3+ and 5 of 9 IHC 2+ cases were FISH positive, whereas 3 of 26 IHC 3+, 4 of 9 IHC 2+ and all 333 IHC 1+/0 cases were FISH negative. If considering FISH as the standard, the sensitivity and specificity of ALK IHC 3+/2+ as ALK positive were 100% and 97.9%, respectively. Three IHC 3+ cases reported as FISH "negative" were actually ALK positive confirmed by ALK RT-PCR or re-detected. Based on the final classify, ALK IHC 3+/2+ was 100% sensitive and 98.8% specific. However, FISH was 90.3% sensitive and 100% specific. IHC 2+ was regarded as equivocal and need to be confirmed by FISH or RT-PCR. In the 368 cases, 8.4% cases had ALK positive, 52.2% cases had EGFR mutation, and only one case had a coexisting. Manually semiquantitative ALK IHC (primary antibody D5F3 coupled with secondary DAKO Envision system) used as the initial screening combined with auxiliary FISH confirmation is a reliable, economical approach to identify ALK positive lung adenocarcinoma. The IHC can find some ALK positive cases which would be missed by FISH only.
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Proteomic approach to reveal the regulatory function of aconitase AcnA in oxidative stress response in the antibiotic producer Streptomyces viridochromogenes Tü494.
PLoS ONE
PUBLISHED: 01-01-2014
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The aconitase AcnA from the phosphinothricin tripeptide producing strain Streptomyces viridochromogenes Tü494 is a bifunctional protein: under iron-sufficiency conditions AcnA functions as an enzyme of the tricarboxylic acid cycle, whereas under iron depletion it is a regulator of iron metabolism and oxidative stress response. As a member of the family of iron regulatory proteins (IRP), AcnA binds to characteristic iron responsive element (IRE) binding motifs and post-transcriptionally controls the expression of respective target genes. A S. viridochromogenes aconitase mutant (MacnA) has previously been shown to be highly sensitive to oxidative stress. In the present paper, we performed a comparative proteomic approach with the S. viridochromogenes wild-type and the MacnA mutant strain under oxidative stress conditions to identify proteins that are under control of the AcnA-mediated regulation. We identified up to 90 differentially expressed proteins in both strains. In silico analysis of the corresponding gene sequences revealed the presence of IRE motifs on some of the respective target mRNAs. From this proteome study we have in vivo evidences for a direct AcnA-mediated regulation upon oxidative stress.
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Long-term exposure of mice to nucleoside analogues disrupts mitochondrial DNA maintenance in cortical neurons.
PLoS ONE
PUBLISHED: 01-01-2014
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Nucleoside analogue reverse transcriptase inhibitor (NRTI), an integral component of highly active antiretroviral therapy (HAART), was widely used to inhibit HIV replication. Long-term exposure to NRTIs can result in mitochondrial toxicity which manifests as lipoatrophy, lactic acidosis, cardiomyopathy and myopathy, as well as polyneuropathy. But the cerebral neurotoxicity of NRTIs is still not well known partly due to the restriction of blood-brain barrier (BBB) and the complex microenvironment of the central nervous system (CNS). In this study, the Balb/c mice were administered 50 mg/kg stavudine (D4T), 100 mg/kg zidovudine (AZT), 50 mg/kg lamivudine (3TC) or 50 mg/kg didanosine (DDI) per day by intraperitoneal injection, five days per week for one or four months, and primary cortical neurons were cultured and exposed to 25 µM D4T, 50 µM AZT, 25 µM 3TC or 25 µM DDI for seven days. Then, single neuron was captured from mouse cerebral cortical tissues by laser capture microdissection. Mitochondrial DNA (mtDNA) levels of the primary cultured cortical neurons, and captured neurons or glial cells, and the tissues of brains and livers and muscles were analyzed by relative quantitative real-time PCR. The data showed that mtDNA did not lose in both NRTIs exposed cultured neurons and one month NRTIs treated mouse brains. In four months NRTIs treated mice, brain mtDNA levels remained unchanged even if the mtDNA levels of liver (except for 3TC) and muscle significantly decreased. However, mtDNA deletion was significantly higher in the captured neurons from mtDNA unchanged brains. These results suggest that long-term exposure to NRTIs can result in mtDNA deletion in mouse cortical neurons.
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Matrix-bound phosphine and phosphorus fractions in surface sediments of Arctic Kongsfjorden, Svalbard: Effects of glacial activity and environmental variables.
Chemosphere
PUBLISHED: 11-26-2013
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The surface sediments were collected from the glacial bay (GLAC), the central basin (CENTR) and their transition area (TRANS) along the fjord Kongsfjorden axis on Svalbard, Arctic, and matrix-bound phosphine (MBP), phosphorus fractions and alkaline phosphatase activity (APA) were analyzed. MBP was found in all the sediments with the concentration range of 8.93-59.45ngkg(-1)dw. The MBP levels in the CENTR sediments were two times higher than those in the GLAC and TRANS sediments, and the yield of phosphine (PH3) as a fraction of total phosphorus ranged from 1.78×10(-8) to 3.53×10(-8)mgPH3mg(-1)P. The CENTR and TRANS sediments showed higher concentrations of total phosphorus (TP), organic phosphorus (OP) and APA than the GLAC sediments, indicating that glacial activity had an important effect on the spatial variability in the concentrations of MBP and phosphorus fractions. There existed a significant positive correlation (p<0.01) between MBP and seawater depths, OP, TP, APA, total organic matter, total nitrogen and total sulfur. The multiple stepwise regression model ([MBP]=16.1[OP]+18.6[APA]-26.1pH+221.3) was obtained between MBP concentrations and environmental variables. This model could be used to predict MBP levels in the sediments. Our results indicated that the production of MBP was associated with OP decomposition and microbially mediated factors in the sediments of Kongsfjorden in Arctic.
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Cytotoxicity and genotoxicity assessment of silver nanoparticles in mouse.
Nanotoxicology
PUBLISHED: 11-22-2013
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Abstract Silver nanoparticles (AgNPs) are among the most commercially used nanomaterials and their toxicity and genotoxicity are controversial. Although many in vitro studies have been conducted to evaluate the genotoxicity of AgNPs, in vivo genotoxicity studies on the nanomaterials are limited. Given the unique physicochemical properties and complex pharmacokinetics behavior of nanoparticles (NPs), in vivo genotoxicity assessment of AgNPs is badly needed. In this study, the clastogenicity and mutagenicity of AgNPs with different sizes and coatings were evaluated using mouse micronucleus (MN) assay, Pig-a assay and Comet assay. Five 7-week-old male B6C3F1 mice per group were treated with 5?nm polyvinylpyrrolidone (PVP)-coated AgNPs at a single dose of 0.5, 1.0, 2.5, 5.0, 10.0 or 20.0?mg/kg body weight (bw) via intravenous injection for both the MN and Pig-a assays; or with 15-100?nm PVP- or 10-80?nm silicon-coated AgNPs at a single or 3-day repeated dose of 25.0?mg/kg bw for the MN assay and Comet assay in mouse liver. Inductively coupled plasma mass spectrometry (ICP-MS) and transmission electron microscopy (TEM) analyses indicated that AgNPs reached the testing tissues (bone marrow for the MN and Pig-a assays and liver for the Comet assay). Although there was a reduction of reticulocytes in the PVP-coated AgNPs-treated animals, indicating cytotoxicity of the AgNPs, none of the treatments resulted in a significant increase of either mutant frequencies in the Pig-a gene or the percent of micronucleated reticulocyte over the concurrent controls. However, both the PVP- and silicon-coated AgNPs induced oxidative DNA damage in mouse liver. These results demonstrate that the AgNPs can reach mouse bone marrow and liver, and generate cytotoxicity to the reticulocytes and oxidative DNA damage to the liver.
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Hypertrophy and Fibrosis of the Ligamentum Flavum in Lumbar Spinal Stenosis is Associated with Increased Expression of LPA and LPAR1.
J Spinal Disord Tech
PUBLISHED: 11-20-2013
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Histological, immunohistochemical, and ELISA analysis of the human ligamentum flavum (LF).
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A Pegylated Leptin Antagonist Ameliorates CKD-Associated Cachexia in Mice.
J. Am. Soc. Nephrol.
PUBLISHED: 10-10-2013
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Elevated serum leptin levels correlate with inflammation and predict changes in lean body mass in patients with CKD, and activation of the melanocortin system by leptin signaling mediates the pathophysiology of CKD-associated cachexia. We tested whether treatment with a pegylated leptin receptor antagonist (PLA) attenuates cachexia in mice with CKD. CKD and Sham mice received vehicle or PLA (2 or 7 mg/kg per day). At these doses, PLA did not influence serum leptin levels in mice. Treatment with 7 mg/kg per day PLA stimulated appetite and weight gain, improved lean mass and muscle function, reduced energy expenditure, and normalized the levels of hepatic TNF-? and IL-6 mRNA in mice with CKD. Furthermore, treatment with 7 mg/kg per day PLA attenuated the CKD-associated increase in the transcriptional and protein abundance of uncoupling proteins that mediates thermogenesis, and it normalized the molecular signatures of processes associated with muscle wasting in CKD, including proteolysis, myogenesis and muscle regeneration, and expression of proinflammatory muscle cytokines, such as IL-1?, -1?, and -6 and TNF-?. Our results suggest that leptin antagonism may represent a viable therapeutic strategy for cachexia in CKD.
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An extraordinarily stable catalyst: Pt NPs supported on two-dimensional Ti3C2X2 (X = OH, F) nanosheets for oxygen reduction reaction.
Chem. Commun. (Camb.)
PUBLISHED: 09-18-2013
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High dispersion Pt nanoparticles supported on 2D Ti3C2X2 (X = OH, F) nanosheets are presented and electro-chemical measurements confirm that the Pt/Ti3C2X2 catalyst shows enhanced durability and improved ORR activity compared with the commercial Pt/C catalyst.
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Metallo-toeholds: controlling DNA strand displacement driven by Hg(II) ions.
Chem. Commun. (Camb.)
PUBLISHED: 09-16-2013
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Toehold-mediated strand displacement is a powerful tool that permits programmable control over DNA hybridization. Here, we developed a mechanism for strand displacement driven by Hg(2+) ions, in which the insertion of thymine-thymine mismatched base pairs on the toeholds provides additional control through variation of the concentration of Hg(2+) ions.
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Chronic lymphocytic leukemia in young (less than 55 years) patients: a comprehensive analysis of prognostic factors and outcomes.
Haematologica
PUBLISHED: 08-02-2013
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The clinical characteristics and outcomes of younger (?55 years) patients with chronic lymphocytic leukemia in the era of modern prognostic biomarkers and chemoimmunotherapy are not well understood. Baseline characteristics and outcomes of patients with chronic lymphocytic leukemia ?55 years who were seen at Mayo Clinic between 1/1995 and 4/2012 were compared with those >55 years. Overall survival of patients ?55 was compared to age- and sex-matched normal population. The characteristics of 844 newly diagnosed chronic lymphocytic leukemia patients ?55 years (median, 50 years) were compared to 2324 patients >55 years (median, 67 years). Younger patients were more likely to be Rai stage I or II (p<0.0001), IGHV unmutated (p=0.002) and ZAP-70 positive (p=0.009). These differences became more pronounced when ?55 age group was sub-stratified into age ?45, 46-50 and 51-55 years. After a median follow-up of 5.5 years, 426 (51%) patients ?55 received treatment, and 192 (23%) had died. Patients ?55 had a shorter time to first treatment (4.0 years vs. 5.2 years; p=0.001) but longer survival (12.5 years vs. 9.5 years; p<0.0001) compared to patients >55 yrs. However, patients ?55 had significantly shorter survival than age- and sex-matched normal population (12.5 years vs. not reached; p<0.0001). Our study is the first comprehensive analysis of younger chronic lymphocytic leukemia patients in the modern era. Adverse prognostic markers appear more common among young patients. Although the survival of young chronic lymphocytic leukemia patients is longer than those >55, their survival relative to the age- and sex-matched normal population is profoundly shortened.
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Genotoxicity of doxorubicin in F344 rats by combining the comet assay, flow-cytometric peripheral blood micronucleus test, and pathway-focused gene expression profiling.
Environ. Mol. Mutagen.
PUBLISHED: 07-25-2013
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Doxorubicin (DOX) is an antineoplastic drug effective against many human malignancies. DOXs clinical efficacy is greatly limited because of severe cardiotoxicity. To evaluate if DOX is genotoxic in the heart, ~7-week-old, male F344 rats were administered intravenously 1, 2, and 3 mg/kg bw DOX at 0, 24, 48, and 69 hr and the Comet assays in heart, liver, kidney, and testis and micronucleus (MN) assay in the peripheral blood (PB) erythrocytes using flow cytometry were conducted. Rats were euthanized at 72 hr and PB was removed for the MN assay and single cells were isolated from multiple tissues for the Comet assays. None of the doses of DOX induced a significant DNA damage in any of the tissues examined by the alkaline Comet assay. Contrastingly, the glycosylase enzymes-modified Comet assay showed a significant dose dependent increase in the oxidative DNA damage in the cardiac tissue (P ? 0.05). In the liver, only the top dose induced significant increase in the oxidative DNA damage (P ? 0.05). The histopathology showed no severe cardiotoxicity but non-neoplastic lesions were present in both untreated and treated samples. A severe toxicity likely occurred in the bone marrow because no viable reticulocytes could be screened for the MN assay. Gene expression profiling of the heart tissues showed a significant alteration in the expression of 11 DNA damage and repair genes. These results suggest that DOX is genotoxic in the heart and the DNA damage may be induced primarily via the production of reactive oxygen species. Environ. Mol. Mutagen. 55:24-34, 2014. © 2013 Wiley Periodicals, Inc.(†)
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Protective Effects of Angiotensin-(1-7) Administered with an Angiotensin Receptor Blocker in a Rat Model of Chronic Kidney Disease.
Nephrology (Carlton)
PUBLISHED: 07-24-2013
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Angiotensin-(1-7) [Ang-(1-7)] opposes angiotensin II-induced cell growth, matrix accumulation and fibrosis in cardiac tissue. However, the role of Ang-(1-7) in the pathogenesis of renal fibrosis is uncertain. This study observed the effects of Ang-(1-7), on its own or in combination with Losartan, an angiotensin receptor blocker, on five-sixths nephrectomized rats.
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Structural biology study of human TNF receptor associated factor 4 TRAF domain.
Protein Cell
PUBLISHED: 07-04-2013
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TRAF4 is a unique member of TRAF family, which is essential for innate immune response, nervous system and other systems. In addition to be an adaptor protein, TRAF4 was identified as a regulator protein in recent studies. We have determined the crystal structure of TRAF domain of TRAF4 (residues 292-466) at 2.60 Å resolution by X-ray crystallography method. The trimericly assembled TRAF4 resembles a mushroom shape, containing a super helical "stalk" which is made of three right-handed intertwined ? helixes and a C-terminal "cap", which is divided at residue L302 as a boundary. Similar to other TRAFs, both intermolecular hydrophobic interaction in super helical "stalk" and hydrogen bonds in "cap" regions contribute directly to the formation of TRAF4 trimer. However, differing from other TRAFs, there is an additional flexible loop (residues 421-426), which contains a previously identified phosphorylated site S426 exposing on the surface. This S426 was reported to be phosphorylated by IKK? which is the pre-requisite for TRAF4-NOD2 complex formation and thus to inhibit NOD2-induced NF-?B activation. Therefore, the crystal structure of TRAF4-TRAF is valuable for understanding its molecular basis for its special function and provides structural information for further studies.
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Abnormal hypermethylation and clinicopathological significance of FBLN1 gene in cutaneous melanoma.
Tumour Biol.
PUBLISHED: 07-04-2013
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Fibulin-1 (FBLN1) is involved in the progression of some types of cancer. However, the role of FBLN1 in cutaneous melanoma (CM) has not been examined. The purpose of this study was to understand the molecular mechanisms and clinical significance of FBLN1 inactivation in CM. The expression of FBLN1 mRNA in CM tissues and adjacent normal skin tissues was analyzed by quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR). Methylation-specific polymerase chain reaction was performed to examine the methylation status of the FBLN1 gene promoter. Furthermore, the methylation status of FBLN1 was analyzed with the clinicopathological characteristics and overall survival. qRT-PCR showed FBLN1 mRNA levels in cancerous tissues to be significantly decreased compared with that in adjacent normal skin tissues. The rate of FBLN1 promoter methylation was significantly higher in CM tissues than in adjacent normal skin tissues (P?
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Unilateral versus bilateral instrumented transforaminal lumbar interbody fusion in two-level degenerative lumbar disorders: a prospective randomised study.
Int Orthop
PUBLISHED: 06-14-2013
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The aim of this study was to analyse the clinical and radiological outcomes of unilateral versus bilateral instrumented TLIF in two-level degenerative lumbar disorders.
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Priorities for research and control of cestode zoonoses in Asia.
Infect Dis Poverty
PUBLISHED: 06-13-2013
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Globally, cestode zoonoses cause serious public health problems, particularly in Asia. Among all neglected zoonotic diseases, cestode zoonoses account for over 75% of global disability adjusted life years (DALYs) lost. An international symposium on cestode zoonoses research and control was held in Shanghai, China between 28th and 30th October 2012 in order to establish joint efforts to study and research effective approaches to control these zoonoses. It brought together 96 scientists from the Asian region and beyond to exchange ideas, report on progress, make a gap analysis, and distill prioritizing settings with a focus on the Asian region. Key objectives of this international symposium were to agree on solutions to accelerate progress towards decreasing transmission, and human mortality and morbidity caused by the three major cestode zoonoses (cystic echinococcosis, alveolar echinococcosis, and cysticercosis); to critically assess the potential to control these diseases; to establish a research and validation agenda on existing and new approaches; and to report on novel tools for the study and control of cestode zoonoses.
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High levels of divergent HIV-1 quasispecies in patients with neurological opportunistic infections in China.
J. Neurovirol.
PUBLISHED: 06-05-2013
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Despite the fact that the survival of people infected with human immunodeficiency virus (HIV) has improved worldwide because of the increasingly powerful and highly active antiretroviral therapy, opportunistic infections (OIs) of the central nervous system (CNS) remain a serious burden. HIV-1 is capable of entering the CNS through infected peripheral monocytes, but its effect on OIs of CNS remains unclear. In this study, we investigated the characteristics of HIV-1 in acquired immunodeficiency syndrome (AIDS) patients with CNS OIs. A total of 24 patients with CNS OIs and 16 non-CNS OIs (control) cases were selected. These AIDS patients were infected with HIV-1 by paid blood donors in China. HIV-1 loads in plasma and cerebrospinal fluid (CSF) were detected using RT-PCR, and the C2-V5 region of HIV-1 envelope gene was amplified from viral quasispecies isolated from CSF using nested PCR. The CSF HIV-1 load of CNS OIs was higher than that of non-CNS OIs, but plasma HIV-1 load of CNS OIs was not higher than that of non-CNS OIs. The nucleotide sequence of C2-V5 region of the HIV-1 quasispecies isolated from the CSF of CNS OIs had a high diversity, and the HIV-1 quasispecies isolated from the CSF of CNS OIs revealed R5 tropism as 11/25 charge rule. These results suggest that high levels of divergent HIV-1 quasispecies in the CNS probably contribute to opportunistic infections.
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[Lethal effects of scopoletin and bisdemethoxycurcumin against Tetranychus cinnabarinus Boisd. (Acari: Tetranychidae): a simulation study].
Ying Yong Sheng Tai Xue Bao
PUBLISHED: 05-31-2013
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By using slide-dip bioassay method under laboratory condition, an investigation was made on the lethal effects of scopoletin, bisdemethoxycurcumin (BDMC), and their combination at an optimal mass ratio (7:6) of scopoletin to BDMC against the adult females of Tetranychus cinnabarinus Boisd. A time-dose mortality model (TDM) was established, which passed the Hosmer-Lemeshow test. The sensitivity of the adult females to the concentration change of the acaricides was in the sequence of scopoletin > optimal mass ratio of scopoletin to BDMC > BDMC. The peak mortality of the female adults was found at 32, 28 and 32 h after treated with BDMC, scopoletin, and their combination at the optimal mass ratio, respectively. The values of the LC50 and LC90 at 48 h after treated with BDMC, scopoletin, and their combination at the optimal mass ratio were 0.3324, 0.2035 and 0.2195 mg x mL(-1), and 2.1198, 0.9521 and 1.1617 mg x mL(-1), and the median lethal time (LT50) of BDMC, scopoletin, and their combination at the optimal mass ratio was 7.4, 6.0 and 6.1 h at the concentration 1.0 mg x mL(-1), and 6.4, 4.8 and 5.0 h at the concentration 2.0 mg x mL(-1), respectively. The acaricidal activity and time-dose response of the optimal combination of scopoletin and BDMC were closer to those of scopoletin, suggesting a synergistic acaricidal activity of the combination of scopoletin and BDMC, which was worthy to be developed for application.
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Depending on the stage of hepatosteatosis, p53 causes apoptosis primarily through either DRAM-induced autophagy or BAX.
Liver Int.
PUBLISHED: 05-23-2013
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Apoptosis mediated by p53 plays a pathological role in the progression of hepatosteatosis. It is noteworthy that p53 can promote the expression of damage-regulated autophagy modulator (DRAM), an inducer of autophagy-mediated apoptosis. However, the relationship between p53-mediated apoptosis and autophagy in hepatosteatosis remains elusive. This study aimed to examine how p53 orchestrates autophagy and apoptosis to affect hepatosteatosis.
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Quantitative T2 mapping to characterize the process of intervertebral disc degeneration in a rabbit model.
BMC Musculoskelet Disord
PUBLISHED: 05-21-2013
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To investigate the potential of T2 mapping for characterizing the process of intervertebral disc degeneration (IDD) in a rabbit model.
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Space-Confinement-Induced Synthesis of Pyridinic- and Pyrrolic-Nitrogen-Doped Graphene for the Catalysis of Oxygen Reduction.
Angew. Chem. Int. Ed. Engl.
PUBLISHED: 05-08-2013
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Forced obedience: Layer-structured montmorillonite (MMT) was used as a nanoreactor for the generation of planar pyridinic and pyrrolic N sites in nitrogen-doped graphene (NG; see picture). The selectivity for the formation of planar N sites was inversely proportional to the interspace width (?) of the MMT and reached a maximum of 90.27?%. The NG catalyst exhibited low electrical resistance, high electrocatalytic activity, and good stability.
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Leptin induces terminal differentiation of rat annulus fibrosus cells via activation of MAPK signaling.
Anat Rec (Hoboken)
PUBLISHED: 05-02-2013
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Both leptin and its receptor are expressed in rat annulus fibrosus (AF) cells. However, little is known about their role and mechanism during disc degeneration. The mitogen activating protein kinase (MAPK) pathway which mediates leptin-induced terminal differentiation of rat AF cells was analyzed using PCR, Western-blot and immunocytochemistry. It was found that leptin-induced AF cells terminal differentiation, which may be attributed to upregulated p38 and ERK1/2 phosphorylation, however, JNK phosphorylation was not observed. Specific inhibitors of p38 or ERK1/2, but not JNK, could inhibit the stimulative activity of leptin on collagen X and MMP-13 protein levels. This study, for the first time, shows that the MAPK pathway, especially p38 and ERK1/2 signaling, plays a distinct role in leptin-induced AF cells terminal differentiation.
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Mechanism of the hairpin folding transformation of thymine-cytosine-rich oligonucleotides induced by Hg(II) and Ag(I) ions.
Eur Phys J E Soft Matter
PUBLISHED: 04-23-2013
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The metal-induced folding of thymine-cytosine-rich oligonucleotides into hairpin-like structures was characterised by isothermal titration calorimetry, secondary structure analysis, equilibrium titrations, and fluorescence study. We find that designed thymine-cytosine-rich oligonucleotides can specifically bind with Hg(II) or Ag(I) ions to generate metal-mediated base pairs in a hairpin-like structure from a random coil structure. Isothermal titration calorimetry experiments were performed to reveal the detail of the whole binding process. The thermodynamic result exhibits two possible pathways of significant change upon the addition of Hg(II) ions. Furthermore, this transformation can be enhanced by the presence of Ag(I) ions. The fluorescence decreases through fluorescence resonance energy transfer (FRET) between the fluorophore and quencher confirms the process of formation of the hairpin-like structure. The analysis of optical titration data demonstrates that the saturated binding stoichiometries are 12:1 and 4:1 for Hg(II) and Ag(I) ions, respectively. Our result provides a promising strategy for the investigation of the mechanism of structural transformation of oligonucleotides influenced by metal-mediated base pairs, which may eventually lead to progress in constructing a metal-triggered DNA origami system and metal-containing DNA nanotechnology.
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Chromobox homolog 4 is correlated with prognosis and tumor cell growth in hepatocellular carcinoma.
Ann. Surg. Oncol.
PUBLISHED: 04-17-2013
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Chromobox homolog 4 (CBX4) is a member of the chromobox family of Polycomb group proteins involved in the chromatin remodeling and transcriptional regulation. However, its clinical relevance in hepatocellular carcinoma (HCC) has not yet been explored.
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Structure of severe fever with thrombocytopenia syndrome virus nucleocapsid protein in complex with suramin reveals therapeutic potential.
J. Virol.
PUBLISHED: 04-10-2013
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Severe fever with thrombocytopenia syndrome is an emerging infectious disease caused by a novel bunyavirus (SFTSV). Lack of vaccines and inadequate therapeutic treatments have made the spread of the virus a global concern. Viral nucleocapsid protein (N) is essential for its transcription and replication. Here, we present the crystal structures of N from SFTSV and its homologs from Buenaventura (BUE) and Granada (GRA) viruses. The structures reveal that phleboviral N folds into a compact core domain and an extended N-terminal arm that mediates oligomerization, such as tetramer, pentamer, and hexamer of N assemblies. Structural superimposition indicates that phleboviral N adopts a conserved architecture and uses a similar RNA encapsidation strategy as that of RVFV-N. The RNA binding cavity runs along the inner edge of the ring-like assembly. A triple mutant of SFTSV-N, R64D/K67D/K74D, almost lost its ability to bind RNA in vitro, is deficient in its ability to transcribe and replicate. Structural studies of the mutant reveal that both alterations in quaternary assembly and the charge distribution contribute to the loss of RNA binding. In the screening of inhibitors Suramin was identified to bind phleboviral N specifically. The complex crystal structure of SFTSV-N with Suramin was refined to a 2.30-Å resolution. Suramin was found sitting in the putative RNA binding cavity of SFTSV-N. The inhibitory effect of Suramin on SFTSV replication was confirmed in Vero cells. Therefore, a common Suramin-based therapeutic approach targeting SFTSV-N and its homologs could be developed for containing phleboviral outbreaks.
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Structure of the Leanyer orthobunyavirus nucleoprotein-RNA complex reveals unique architecture for RNA encapsidation.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 04-08-2013
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Negative-stranded RNA viruses cover their genome with nucleoprotein (N) to protect it from the human innate immune system. Abrogation of the function of N offers a unique opportunity to combat the spread of the viruses. Here, we describe a unique fold of N from Leanyer virus (LEAV, Orthobunyavirus genus, Bunyaviridae family) in complex with single-stranded RNA refined to 2.78 Å resolution as well as a 2.68 Å resolution structure of LEAV N-ssDNA complex. LEAV N is made up of an N- and a C-terminal lobe, with the RNA binding site located at the junction of these lobes. The LEAV N tetramer binds a 44-nucleotide-long single-stranded RNA chain. Hence, oligomerization of N is essential for encapsidation of the entire genome and is accomplished by using extensions at the N and C terminus. Molecular details of the oligomerization of N are illustrated in the structure where a circular ring-like tertiary assembly of a tetramer of LEAV N is observed tethering the RNA in a positively charged cavity running along the inner edge. Hydrogen bonds between N and the C2 hydroxyl group of ribose sugar explain the specificity of LEAV N for RNA over DNA. In addition, base-specific hydrogen bonds suggest that some regions of RNA bind N more tightly than others. Hinge movements around F20 and V125 assist in the reversal of capsidation during transcription and replication of the virus. Electron microscopic images of the ribonucleoprotein complexes of LEAV N reveal a filamentous assembly similar to those found in phleboviruses.
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Online feature selection with streaming features.
IEEE Trans Pattern Anal Mach Intell
PUBLISHED: 03-23-2013
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We propose a new online feature selection framework for applications with streaming features where the knowledge of the full feature space is unknown in advance. We define streaming features as features that flow in one by one over time whereas the number of training examples remains fixed. This is in contrast with traditional online learning methods that only deal with sequentially added observations, with little attention being paid to streaming features. The critical challenges for Online Streaming Feature Selection (OSFS) include 1) the continuous growth of feature volumes over time, 2) a large feature space, possibly of unknown or infinite size, and 3) the unavailability of the entire feature set before learning starts. In the paper, we present a novel Online Streaming Feature Selection method to select strongly relevant and nonredundant features on the fly. An efficient Fast-OSFS algorithm is proposed to improve feature selection performance. The proposed algorithms are evaluated extensively on high-dimensional datasets and also with a real-world case study on impact crater detection. Experimental results demonstrate that the algorithms achieve better compactness and higher prediction accuracy than existing streaming feature selection algorithms.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.