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Find video protocols related to scientific articles indexed in Pubmed.
Parity-time symmetric Bragg structure in atomic vapor.
Opt Express
PUBLISHED: 11-18-2014
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We propose an efficient scheme in helium or alkaline earth atomic vapor to achieve a parity-time symmetric Bragg structure using coherent lights. Unidirectional invisibility can be realized in this scheme, i.e., the atomic vapor shows total transparency for probe light incident from one particular direction, but exhibits enhanced Bragg reflection for probe from the opposite side. By changing the relative phase between the coherent lights, this direction can easily be manipulated, providing a convenient way for investigating special properties of ???????? -symmetric Bragg structures.
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Structure-Function Analysis of the Conserved Tyrosine and Diverse ?-Stacking among Class I Histone Deacetylases: A QM (DFT)/MM MD Study.
J Chem Inf Model
PUBLISHED: 11-06-2014
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Discovery of the isoform-selective histone deacetylases (HDACs) inhibitors is of great medical importance and still a challenge. The comparison studies on the structure-function relationship of the conserved residues, which are located in the linker binding channel among class I HDACs (including 4 isoforms: HDAC1/2/3/8), have been carried out by using ab initio QM/MM MD simulations, a state-of-the-art approach to simulate metallo-enzymes. We found that the conserved tyrosine (Y303/308/286/306 in HDAC1/2/3/8, respectively) could modulate the zinc-inhibitor chelation among all class I HDACs with different regulatory mechanisms. For HDAC1/2/3 selective-inhibitor benzamide, the conserved tyrosine could modulate the coordinative ability of the central atom (Zn(2+)), while for pan-inhibitor SAHA, the conserved tyrosine could increase the chelating ability of the ligand (SAHA). Moreover, it is first found that the conserved tyrosine is correlated with the intertransformation of ?-? stacking styles (parallel shift vs T-shaped) by the aromatic ring in benzamide and the two conserved phenylalanine residues of HDACs. In addition, the catalytic roles of the conserved tyrosine in stabilizing the transition state and intermediate are further revealed. These findings provide useful molecular basis knowledge for further isoform-selective inhibitor design among class I HDACs.
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SUMOylation at K340 inhibits tau degradation through deregulating its phosphorylation and ubiquitination.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 11-05-2014
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Intracellular accumulation of the abnormally modified tau is hallmark pathology of Alzheimer's disease (AD), but the mechanism leading to tau aggregation is not fully characterized. Here, we studied the effects of tau SUMOylation on its phosphorylation, ubiquitination, and degradation. We show that tau SUMOylation induces tau hyperphosphorylation at multiple AD-associated sites, whereas site-specific mutagenesis of tau at K340R (the SUMOylation site) or simultaneous inhibition of tau SUMOylation by ginkgolic acid abolishes the effect of small ubiquitin-like modifier protein 1 (SUMO-1). Conversely, tau hyperphosphorylation promotes its SUMOylation; the latter in turn inhibits tau degradation with reduction of solubility and ubiquitination of tau proteins. Furthermore, the enhanced SUMO-immunoreactivity, costained with the hyperphosphorylated tau, is detected in cerebral cortex of the AD brains, and ?-amyloid exposure of rat primary hippocampal neurons induces a dose-dependent SUMOylation of the hyperphosphorylated tau. Our findings suggest that tau SUMOylation reciprocally stimulates its phosphorylation and inhibits the ubiquitination-mediated tau degradation, which provides a new insight into the AD-like tau accumulation.
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[Revealing the chemical changes of tea cell wall induced by anthracnose with confocal Raman microscopy].
Guang Pu Xue Yu Guang Pu Fen Xi
PUBLISHED: 11-01-2014
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Healthy tea and tea infected by anthracnose were first studied by confocal Raman microscopy to illustrate chemical changes of cell wall in the present paper. Firstly, Raman spectra of both healthy and infected sample tissues were collected with spatial resolution at micron-level, and ultrastructure of healthy and infected tea cells was got from scanning electron microscope. These results showed that there were significant changes in Raman shift and Raman intensity between healthy and infected cell walls, indicating that great differences occurred in chemical compositions of cell walls between healthy and infected samples. In details, intensities at many Raman bands which were closely associated with cellulose, pectin, esters were reduced after infection, revealing that the content of chemical compounds such as cellulose, pectin, esters was decreased after infection. Subsequently, chemical imaging of both healthy and infected tea cell walls were realized based on Raman fingerprint spectra of cellulose and microscopic spatial structure. It was found that not only the content of cellulose was reduced greatly after infection, but also the ordered structure of cellulose was destroyed by anthracnose infection. Thus, confocal Raman microscopy was shown to be a powerful tool to detect the chemical changes in cell wall of tea caused by anthracnose without any chemical treatment or staining. This research firstly applied confocal Raman microscopy in phytopathology for the study of interactive relationship between host and pathogen, and it will also open a new way for intensive study of host-pathogen at cellular level.
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Palladium-catalyzed oxidative C-H bond acylation of N-nitrosoanilines with toluene derivatives: a traceless approach to synthesize N-alkyl-2-aminobenzophenones.
Chem. Commun. (Camb.)
PUBLISHED: 10-28-2014
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A palladium-catalyzed cascade cross-coupling of N-nitroso-anilines and toluene derivatives for the direct synthesis of N-alkyl-2-aminobenzophenones is described. N-nitroso groups in anilines can act as the traceless directing groups while toluene derivatives can serve as effective acyl precursors under mild reaction conditions.
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The impact of IKZF1 deletion on the prognosis of acute lymphoblastic leukemia: An updated meta-analysis.
Cancer Biomark
PUBLISHED: 10-23-2014
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Various studies have reported that IKZF1 deletion (IKZF1-d) is a poor prognostic factor for acute lymphoblastic leukemia (ALL) patients, however they do not agree on the level of significance for this deletion.
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Molecular dynamics-based discovery of novel phosphodiesterase-9A inhibitors with non-pyrazolopyrimidinone scaffolds.
Mol Biosyst
PUBLISHED: 10-21-2014
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Phosphodiesterase-9A (PDE9A) is a promising therapeutic target for the treatment of diabetes and Alzheimer's disease (AD). The Pfizer PDE9A inhibitor PF-04447943 has completed Phase II clinical trials in subjects with mild to moderate AD in 2013. However, most of the reported PDE9A inhibitors share the same scaffold as pyrazolopyrimidinone, which lacks structural diversity and is unfavorable for the development of novel PDE9A inhibitors. In the present study, a combinatorial method including pharmacophores, molecular docking, molecular dynamics simulations, binding free energy calculations, and bioassay was used to discover novel PDE9A inhibitors with new scaffolds rather than pyrazolopyrimidinones from the SPECS database containing about 200?000 compounds. As a result, 15 hits out of 29 molecules (a hit rate of 52%) with five novel scaffolds were identified to be PDE9A inhibitors with inhibitory affinities no more than 50 ?M to enrich the structural diversity, different from the pyrazolopyrimidinone-derived family. The high hit ratio of 52% for this virtual screening method indicated that the combinatorial method is a good compromise between computational cost and accuracy. Binding pattern analyses indicate that those hits with non-pyrazolopyrimidinone scaffolds can bind the same active site pocket of PDE9A as classical PDE9A inhibitors. In addition, structural modification of compound AG-690/40135604 (IC50 = 8.0 ?M) led to a new one, , with an improved inhibitory affinity of 2.1 ?M as expected. The five novel scaffolds discovered in the present study can be used for the rational design of PDE9A inhibitors with higher affinities.
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Phase fluctuation cancellation of anonymous microwave signal transmission in passive systems.
Opt Express
PUBLISHED: 10-17-2014
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A phase fluctuation cancellation approach for anonymous microwave signal transmission over fiber link is proposed and demonstrated. Unlike most previous schemes that used for active systems, our proposal is suitable for passive systems by utilizing the optical signal feedback and electrical signal phase-locking. Experimental results show that phase drifts of 7.7-ps, 54-ps and 96-ps (RMS value) for 2.45-GHz signals could be reduced to 3.1-ps, 3.8-ps and 8.5-ps after 1-km, 10-km and 25-km SMF transmission over an eight-hour period, respectively. Overall system performance is limited by the coherent Rayleigh noise and could be further optimized.
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Similarity Learning of Manifold Data.
IEEE Trans Cybern
PUBLISHED: 10-15-2014
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Without constructing adjacency graph for neighborhood, we propose a method to learn similarity among sample points of manifold in Laplacian embedding (LE) based on adding constraints of linear reconstruction and least absolute shrinkage and selection operator type minimization. Two algorithms and corresponding analyses are presented to learn similarity for mixsignedand nonnegative data respectively. The similarity learning method is further extended to kernel spaces. The experiments on both synthetic and real world benchmark data sets demonstrate that the proposed LE with new similarity has better visualization and achieves higher accuracy in classification.
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Robust feature point matching with sparse model.
IEEE Trans Image Process
PUBLISHED: 10-09-2014
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Feature point matching that incorporates pairwise constraints can be cast as an integer quadratic programming (IQP) problem. Since it is NP-hard, approximate methods are required. The optimal solution for IQP matching problem is discrete, binary, and thus sparse in nature. This motivates us to use sparse model for feature point matching problem. The main advantage of the proposed sparse feature point matching (SPM) method is that it generates sparse solution and thus naturally imposes the discrete mapping constraints approximately in the optimization process. Therefore, it can optimize the IQP matching problem in an approximate discrete domain. In addition, an efficient algorithm can be derived to solve SPM problem. Promising experimental results on both synthetic points sets matching and real-world image feature sets matching tasks show the effectiveness of the proposed feature point matching method.
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Exogenous abscisic acid alleviates zinc uptake and accumulation in Populus?×?canescens exposed to excess zinc.
Plant Cell Environ.
PUBLISHED: 08-27-2014
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A greenhouse experiment was conducted to study whether exogenous abscisic acid (ABA) mediates the responses of poplars to excess zinc (Zn). Populus?×?canescens seedlings were treated with either basal or excess Zn levels and either 0 or 10 ?m ABA. Excess Zn led to reduced photosynthetic rates, increased Zn accumulation, induced foliar ABA and salicylic acid (SA), decreased foliar gibberellin (GA3 ) and auxin (IAA), elevated root H2 O2 levels, and increased root ratios of glutathione (GSH) to GSSG and foliar ratios of ascorbate (ASC) to dehydroascorbate (DHA) in poplars. While exogenous ABA decreased foliar Zn concentrations with 7?d treatments, it increased levels of endogenous ABA, GA3 and SA in roots, and resulted in highly increased foliar ASC accumulation and ratios of ASC to DHA. The transcript levels of several genes involved in Zn uptake and detoxification, such as yellow stripe-like family protein 2 (YSL2) and plant cadmium resistance protein 2 (PCR2), were enhanced in poplar roots by excess Zn but repressed by exogenous ABA application. These results suggest that exogenous ABA can decrease Zn concentrations in P.?×?canescens under excess Zn for 7?d, likely by modulating the transcript levels of key genes involved in Zn uptake and detoxification.
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Prostaglandin Derivatives: Nonaromatic Phosphodiesterase-4 Inhibitors from the Soft Coral Sarcophyton ehrenbergi.
J. Nat. Prod.
PUBLISHED: 07-31-2014
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Ten new prostaglandin derivatives (PGs), sarcoehrendins A-J (1-10), together with five known analogues (11-15) were isolated from the soft coral Sarcophyton ehrenbergi. Compounds 4-8 represented the first examples of PGs featuring an 18-ketone group. The structures including the absolute configurations were elucidated on the basis of spectroscopic analysis and chemical evidence. All of the isolates and six synthetic analogues (3a, 3b, 4a, and 11a-11c) were screened for inhibitory activity against phosphodiesterase-4 (PDE4), which is a drug target for the treatment of asthma and chronic obstructive pulmonary disease. Compounds 2, 10, 11a, 11b, and 13-15 exhibited inhibition with IC50 values less than 10 ?M, and compound 15 (IC50 = 1.4 ?M) showed comparable activity to the positive control rolipram (IC50 = 0.60 ?M). The active natural PGs (2, 10, and 13-15) represent the first examples of PDE4 inhibitors without an aromatic moiety, and a preliminary structure-activity relationship is also proposed.
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Characterization of a novel CYP2C9 mutation (1009C>A) detected in a warfarin-sensitive patient.
J. Pharmacol. Sci.
PUBLISHED: 07-31-2014
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Warfarin is the most frequently prescribed anticoagulant for the long-term treatment in the clinic. Recent studies have shown that polymorphic alleles within the CYP2C9, VKORC1, and CYP4F2 genes are related to the warfarin dosage requirement. In this study, a novel non-synonymous mutation (1009C>A) in CYP2C9 was detected in a warfarin-hypersensitive patient, while the other two candidate genes were both found to be homozygous for the wild-type alleles. The newly identified point mutation results in an amino acid substitution at position 337 of the CYP2C9 protein (P337T) and has been designated as the novel allele CYP2C9*58. When expressed in insect cell microsomes, the relative intrinsic clearance values of the CYP2C9.58 variant for tolbutamide and losartan were quite similar to those of the typical defective variant CYP2C9.3, whereas the clearance value of CYP2C9.58 for diclofenac was slightly higher than that of another typical defective variant CYP2C9.2. These data suggested that when compared with wild-type CYP2C9.1, the enzymatic activity of the novel allelic variant has been greatly reduced by the 1009C>A mutation. If patients carrying this allele take drugs metabolized by CYP2C9, their metabolic rate might be slower than that of wild-type allele carriers and thus much more attention should be paid to their clinical care.
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Absorption-free Bragg reflector using Zeeman sublevels in atomic vapor.
Opt Express
PUBLISHED: 07-01-2014
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Absorption-free Bragg reflector has been studied in ions doped in crystals. We propose a new scheme using Zeeman sublevels of atoms to construct an absorption-free Bragg reflector with practical laser power. Its spatial period of refractive index equals half of the wavelength of the incident standing-wave coupling light. The proposal is simulated in a helium atom scheme, and can be extended to alkali earth atoms.
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Proteomic analysis of mouse testis reveals perfluorooctanoic acid-induced reproductive dysfunction via direct disturbance of testicular steroidogenic machinery.
J. Proteome Res.
PUBLISHED: 06-25-2014
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Perfluorooctanoic acid (PFOA) is a ubiquitous environmental pollutant suspected of being an endocrine disruptor; however, mechanisms of male reproductive disorders induced by PFOA are poorly understood. In this study, male mice were exposed to 0, 0.31, 1.25, 5, and 20 mg PFOA/kg/day by oral gavage for 28 days. PFOA significantly damaged the seminiferous tubules and reduced testosterone and progesterone levels in the testis in a dose-dependent manner. Furthermore, PFOA exposure reduced sperm quality. We identified 93 differentially expressed proteins between the control and the 5 mg/kg/d PFOA treated mice using a quantitative proteomic approach. Among them, insulin like-factor 3 (INSL3) and cytochrome P450 cholesterol side-chain cleavage enzyme (CYP11A1) as Leydig-cell-specific markers were significantly decreased. We examined in detail the expression patterns of CYP11A1 and associated genes involved in steroidogenesis in the mouse testis. PFOA inhibited the mRNA and protein levels of CYP11A1 and the mRNA levels of 17?-hydroxysteroid dehydrogenase (17?-HSD) in a dose-dependent manner. Moreover, in vitro study showed the reduction in progesterone levels was accompanied by decreased expression of CYP11A1 in cAMP-stimulated mLTC-1 cells. Our findings indicate that PFOA exposure can impair male reproductive function, possibly by disturbing testosterone levels, and CPY11A1 may be a major steroidogenic enzyme targeted by PFOA.
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Differential expression of miR-125a-5p and let-7e predicts the progression and prognosis of non-small cell lung cancer.
Cancer Invest.
PUBLISHED: 06-19-2014
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Aberrant expression of various microRNAs (miRNA) has shown diagnostic and prognostic significance in non-small cell lung cancer (NSCLC). qRT-PCR analysis confirmed altered expression of miR-125a-5p, let-7e, miR-30a, miR-30e and miR-30e-3p in 70 paired tissue and serum samples from NSCLC patients. The reduced expression of miR-125a-5p, let-7e and miR-30e was strongly associated with NSCLC dedifferentiation. The lost expression of miR-125a-5p and let-7e was associated with shorter overall survival and let-7e was an independent prognostic factor for NSCLC patients. These five miRNA expressions should be further evaluated as biomarkers for the early detection and prognosis of NSCLC patients.
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Electrocution-related mortality: a review of 71 deaths by low-voltage electrical current in Guangdong, China, 2001-2010.
Am J Forensic Med Pathol
PUBLISHED: 06-17-2014
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The aim of this study was to investigate the epidemiological characteristics of low-voltage electrocution deaths in Guangdong, China. Three thousand three hundred seventy autopsy reports from the Department of Forensic Pathology, Zhongshan School of Medicine, Sun Yat-Sen University, over a period of 10 years (2001-2010) were reviewed, of which 71 low-voltage electrocution cases were identified. The descriptive statistical analyses were carried out with the application of SPSS 19.0 software. Electrocution accounted for 2.11% of all autopsied cases. The age range was 3 to 57 years with a mean age of 31.77 ± 11.0 years. The average age of male victims was 33.08 ± 10.77 years, and that of female victims was 22.63 ± 11.06 years. The majority of the victims (87.33%) were male. Among the circumstances leading to electrocution, most of them occurred in factory and in the street. Considering the contact details, deaths were caused most frequently by touching electrical wires (n = 27, 38.02%), followed by touching charged machine (n = 20, 28.17%). There were no suicide and homicide cases. Of all electrocution cases, 50.70% occurred during the summer period from June through August. The upper extremity was the most frequently involved contact site (59.72%). No electrical burn marks were present in 14 cases (19.72%). Our results indicated that most deaths from electrocution occur more often in factories, in summer seasons, and to young male workers, which can help in the development of a differentiated strategy for the prevention of electrocution, while taking into consideration sex, age, occupation, and season of the year.
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Overexpression of MAGE-D4 in colorectal cancer is a potentially prognostic biomarker and immunotherapy target.
Int J Clin Exp Pathol
PUBLISHED: 06-15-2014
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Melanoma-associated antigen D4 (MAGE-D4) is a novel member of MAGE family. This study aimed to examine the expression and immunogenicity of MAGE-D4 in colorectal cancer (CRC) to determine its potential as a prognosis and immunotherapeutic target. The expression of MAGE-D4 mRNA and protein was determined by RT-PCR and immunohistochemistry (IHC) in CRCs with paired adjacent non-tumor tissues, colorectal adenomas and normal colorectal tissues, respectively. Sera from 64 CRC patients were tested for MAGE-D4 antibody by ELISA. MAGE-D4 mRNA was more frequently expressed in CRCs (76.7%, 46/60) than in adjacent non-tumor tissues (15.0%, 9/60). MAGE-D4 protein was detected in all the CRC tissues tested, 70.0% of which showed high expression. There was no MAGE-D4 protein detected in any paired adjacent non-tumor tissue. No MAGE-D4 expression was found in colorectal adenomas and normal colorectal tissues by either RT-PCR or immunohistochemistry. Patients with high MAGE-D4 protein expression had significantly shorter overall survival than those with low MAGE-D4 protein expression (median, 68.6 vs 122.2 months; P=0.030). Furthermore, multivariate analysis exhibited high MAGE-D4 protein expression had a trend toward an independent prognostic factor (hazard ratio: 6.124; P=0.050). Humoral immunity to MAGE-D4 was detected in 12 of 64 (18.8%) CRC patients' sera but not in 77 healthy donors. There was no correlation between MAGE-D4 expression, serum antibody and clinicopathological parameters. These findings suggest MAGE-D4 may serve as a potentially prognostic biomarker and an attractive target of immunotherapy in CRC.
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Optical length change measurement via RF frequency shift analysis of incoherent light source based optoelectronic oscillator.
Opt Express
PUBLISHED: 06-13-2014
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Radio-frequency (RF) frequency shift of incoherent light source based optoelectronic oscillator (OEO) is employed to measure the optical length change. In the proposed OEO using an incoherent light source, the optical length under test is inserted in the optoelectronic hybrid loop. The frequency shift of RF oscillation modes at the output of the OEO reflects the optical length change, with the change being measured via frequency shift analysis. Two OEO configurations are theoretically designed and experimentally performed, while an amplified spontaneous emission (ASE) source serves as the incoherent light source. A linear relationship between the frequency shift and the optical length change has been confirmed for measurement, and a reconfigurable measurement sensitivity is available by selecting different oscillation modes. Moreover, the use of ASE greatly reduces the complexity and the cost for stabilization control on light source, while the derived results are consistent with that obtained in a laser source based OEO both in the measured optical length changes and the phase noise performance. A sensitivity of -28 KHz/cm, -480 KHz/cm or higher, and a resolution of nano-meter scale are obtained, which can be used to monitor the displacement, the changes in refractive index, temperature.
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MAGED4 expression in glioma and upregulation in glioma cell lines with 5-aza-2'-deoxycytidine treatment.
Asian Pac. J. Cancer Prev.
PUBLISHED: 05-30-2014
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Melanoma-associated antigen (MAGE) family genes have been considered as potentially promising targets for anticancer immunotherapy. MAGED4 was originally identified as a glioma-specific antigen. Current knowledge about MAGED4 expression in glioma is only based on mRNA analysis and MAGED4 protein expression has not been elucidated. In the present study, we investigated this point and found that MAGED4 mRNA and protein were absent or very lowly expressed in various normal tissues and glioma cell line SHG44, but overexpressed in glioma cell lines A172,U251,U87-MG as well as glioma tissues, with significant heterogeneity. Furthermore, MAGED4 protein expression was positively correlated with the glioma type and grade. We also found that the expression of MAGED4 inversely correlated with the overall methylation status of the MAGED4 promoter CpG island. Furthermore, when SHG44 and A172 with higher methylation were treated with the DNA demethylating agent 5-aza-2'-deoxycytidine (5-AZA-CdR) reactivation of MAGED4 mRNA was mediated by significant demethylation in SHG44 instead of A172. However, 5-AZA-CdR treatment had no effect on MAGED4 protein in both SHG44 and A172 cells. In conclusion, MAGED4 is frequently and highly expressed in glioma and is partly regulated by DNA methylation. The results suggest that MAGED4 might be a promising target for glioma immunotherapy combined with 5-AZA-CdR to enhance its expression and eliminate intratumor heterogeneity.
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[Correlation of NOS1AP gene polymorphisms with sudden unexpected death in Chinese Han population].
Fa Yi Xue Za Zhi
PUBLISHED: 05-09-2014
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To investigate the single nucleotide polymorphism of NOS1AP gene with sudden unexpected death (SUD) during daily activities.
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Au@MnO2 Core-Shell Nanomesh Electrodes for Transparent Flexible Supercapacitors.
Small
PUBLISHED: 05-07-2014
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A novel Au@MnO2 supercapacitor is presented. The sophisticated core-shell architecture combining an Au nanomesh core with a MnO2 shell on a flexible polymeric substrate is demonstrated as an electrode for high performance transparent flexible supercapacitors (TFSCs). Due to their unique structure, high areal/gravimetric capacitance and rate capability for TFSCs are achieved.
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Improved linearity in down-converted analog photonic link by polarization manipulation.
Opt Lett
PUBLISHED: 05-03-2014
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A method to improve the linearity of the down-converted analog photonic link is proposed and experimentally demonstrated, consisting of two phase modulators, a polarizer, and an optical filter. Down-conversion of a 10-GHz microwave signal to 100-MHz intermediate frequency is successfully achieved. By carefully optimizing the angles between the transverse-electric and transverse-magnetic modes, the third-order inter-modulation distortion (IMD3) is suppressed. The linearization method leads to a suppression of the IMD3 by more than 14 and 13 dB improvement of spurious-free dynamic range.
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An atomic optical filter working at 1.5 ?m based on internal frequency stabilized laser pumping.
Opt Express
PUBLISHED: 04-11-2014
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An excited state Faraday anomalous dispersion optical filter (ES-FADOF) working at the optical communication wavelength (1.5 ?m) is realized. Unlike the usual ES-FADOF schemes using an external frequency stabilization, an internal frequency stabilization scheme is proposed and the working atoms inside the filter are adopted as the reference. A particular cross line of multiple transitions is used for the frequency stabilization for the pump laser and thus, a higher pump efficiency is achieved. For example, compared with previous ES-FADOF schemes, this method can increase the transmittance from 10% to 60% at 100 °C. Moreover, in this scheme, the external frequency stabilization is not necessary and the volume of the atomic filter can be reduced. This simplifies the whole structure and a compact ES-FADOF can thus be realized.
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The up-regulation of endothelin-1 and down-regulation of miRNA-125a-5p, -155, and -199a/b-3p in human atherosclerotic coronary artery.
Cardiovasc. Pathol.
PUBLISHED: 03-31-2014
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Previous studies have reported important roles of endothelin-1 (ET-1) and angiotensin II (Ang II) in the pathogenesis of atherosclerosis. However, the expression of these two proteins and the underlying mechanisms in human atherosclerotic coronary arteries are largely unknown.
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Poloxamer-188 Can Attenuate Blood-Brain Barrier Damage to Exert Neuroprotective Effect in Mice Intracerebral Hemorrhage Model.
J. Mol. Neurosci.
PUBLISHED: 03-27-2014
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Blood-brain barrier (BBB) disruption and brain edema formation play important roles in the secondary neuronal death and neurological dysfunction induced by intracerebral hemorrhage (ICH). Poloxamer 188 (P188), a multiblock copolymer surfactant, has been shown to be capable of sealing damaged cell membranes and decrease neuronal cell death. In this study, we explored whether P188 had a protective effect against ICH and its underlying mechanisms. Male ICR mice were subjected to infusion of type IV collagenase (to induce ICH) of saline (for shams) into the left striatum. The results showed that P188-12 mg post-treatment by tail intravenous injection significantly ameliorated the neurological symptoms and brain edema, attenuated BBB permeability, and decreased cell insults and injury volume at 24 and 72 h after ICH. Furthermore, P188 maintained the protein levels of tight junction (TJ) proteins including claudin-5, occludin, and zonula occludens-1, and reversed the increases of nuclear factor-kappaB (NF-?B), matrix metalloproteinase (MMP)-2, and MMP-9 protein expression at 72 h post ICH. Immunofluorescence showed P188 treatment rearranged the structure of TJ proteins in a continuous and linear pattern. Therefore, the present study concludes that P188 can protect against ICH, and the protective effect was associated with preventing BBB disruption through NF-?B-MMPs-mediated TJ proteins degradation.
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Prenylated coumarins: natural phosphodiesterase-4 inhibitors from Toddalia asiatica.
J. Nat. Prod.
PUBLISHED: 03-05-2014
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Bioassay-guided fractionation of the ethanolic extract of the roots of Toddalia asiatica led to the isolation of seven new prenylated coumarins (1-7) and 14 known analogues (8-21). The structures of 1-7 were elucidated by spectroscopic analysis, and their absolute configurations were determined by combined chemical methods and chiral separation analysis. Compounds 1-5, named toddalin A, 3?-O-demethyltoddalin A, and toddalins B-D, represent an unusual group of phenylpropenoic acid-coupled prenylated coumarins. Compounds 1-21 and four modified analogues, 10a, 11a, 13a, and 17a, were screened by using tritium-labeled adenosine 3',5'-cyclic monophosphate ([3H]-cAMP) as substrate for their inhibitory activity against phosphodiesterase-4 (PDE4), which is a drug target for the treatment of asthma and chronic obstructive pulmonary disease. Compounds 3, 8, 10, 10a, 11, 11a, 12, 13, 17, and 21 exhibited inhibition with IC50 values less than 10 ?M. Toddacoumalone (8), the most active compound (IC50=0.14 ?M), was more active than the positive control, rolipram (IC50=0.59 ?M). In addition, the structure-activity relationship and possible inhibitory mechanism of the active compounds are also discussed.
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Overexpression of bacterial ?-glutamylcysteine synthetase mediates changes in cadmium influx, allocation and detoxification in poplar.
New Phytol.
PUBLISHED: 02-27-2014
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Overexpression of bacterial ?-glutamylcysteine synthetase in the cytosol of Populus tremula × P. alba produces higher glutathione (GSH) concentrations in leaves, thereby indicating the potential for cadmium (Cd) phytoremediation. However, the net Cd(2+) influx in association with H(+) /Ca(2+) , Cd tolerance, and the underlying molecular and physiological mechanisms are uncharacterized in these poplars. We assessed net Cd(2+) influx, Cd tolerance and the transcriptional regulation of several genes involved in Cd(2+) transport and detoxification in wild-type and transgenic poplars. Poplars exhibited highest net Cd(2+) influxes into roots at pH 5.5 and 0.1 mM Ca(2+) . Transgenics had higher Cd(2+) uptake rates and elevated transcript levels of several genes involved in Cd(2+) transport and detoxification compared with wild-type poplars. Transgenics exhibited greater Cd accumulation in the aerial parts than wild-type plants in response to Cd(2+) exposure. Moreover, transgenic poplars had lower concentrations of O2 ?(-) and H2 O2 ; higher concentrations of total thiols, GSH and oxidized GSH in roots and/or leaves; and stimulated foliar GSH reductase activity compared with wild-type plants. These results indicate that transgenics are more tolerant of 100 ?M Cd(2+) than wild-type plants, probably due to the GSH-mediated induction of the transcription of genes involved in Cd(2+) transport and detoxification.
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Excited state Faraday anomalous dispersion optical filters based on indirect laser pumping.
Opt Lett
PUBLISHED: 02-25-2014
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The direct pump method now used in excited state Faraday anomalous dispersion optical filters (ES-FADOFs) requires that the transition between the target and the ground state is an electric dipole allowed transition and that a laser that operates at the exact pump wavelength is available. This is not always satisfied in practice. An indirect laser pump method for ES-FADOF is proposed and experimentally realized. Compared with the commonly used direct pump method, this indirect pump method can reach the same performance using lasers at very different wavelengths. This method can greatly extend the wavelength range of FADOF and provide a novel scheme for ES-FADOF design.
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Separable and error-free reversible data hiding in encrypted image with high payload.
ScientificWorldJournal
PUBLISHED: 02-24-2014
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This paper proposes a separable reversible data-hiding scheme in encrypted image which offers high payload and error-free data extraction. The cover image is partitioned into nonoverlapping blocks and multigranularity encryption is applied to obtain the encrypted image. The data hider preprocesses the encrypted image and randomly selects two basic pixels in each block to estimate the block smoothness and indicate peak points. Additional data are embedded into blocks in the sorted order of block smoothness by using local histogram shifting under the guidance of the peak points. At the receiver side, image decryption and data extraction are separable and can be free to choose. Compared to previous approaches, the proposed method is simpler in calculation while offering better performance: larger payload, better embedding quality, and error-free data extraction, as well as image recovery.
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Natural phosphodiesterase-4 (PDE4) inhibitors from Crotalaria ferruginea.
Fitoterapia
PUBLISHED: 02-20-2014
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Bioassay-guided fractionation of the ethanol extract of the Chinese folk medicine Crotalaria ferruginea led to the isolation of a new isoflavonoid, 4'-hydroxy-2'-methylalpinum-isoflavone (1), and eight known analogs (2-9). Their structures were elucidated by spectroscopic analysis. Compounds 1, 2, 5, and 8 showed inhibitory activities against phosphodiesterase-4 (PDE4), a therapeutic target of asthma, with IC50 values ranging from 2.57 to 8.94 ?M. The possible action mechanism and the structure-activity relationship (SAR) of the active isoflavonoids were explored by using molecular docking and molecular dynamics (MD) simulation methods. Our study herein may explain the anti-inflammatory function of this plant in Chinese folk medicine.
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On some classes of sequential spiking neural p systems.
Neural Comput
PUBLISHED: 02-20-2014
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Spiking neural P systems (SN P systems) are a class of distributed parallel computing devices inspired by the way neurons communicate by means of spikes; neurons work in parallel in the sense that each neuron that can fire should fire, but the work in each neuron is sequential in the sense that at most one rule can be applied at each computation step. In this work, with biological inspiration, we consider SN P systems with the restriction that at each step, one of the neurons (i.e., sequential mode) or all neurons (i.e., pseudo-sequential mode) with the maximum (or minimum) number of spikes among the neurons that are active (can spike) will fire. If an active neuron has more than one enabled rule, it nondeterministically chooses one of the enabled rules to be applied, and the chosen rule is applied in an exhaustive manner (a kind of local parallelism): the rule is used as many times as possible. This strategy makes the system sequential or pseudo-sequential from the global view of the whole network and locally parallel at the level of neurons. We obtain four types of SN P systems: maximum/minimum spike number induced sequential/pseudo-sequential SN P systems with exhaustive use of rules. We prove that SN P systems of these four types are all Turing universal as number-generating computation devices. These results illustrate that the restriction of sequentiality may have little effect on the computation power of SN P systems.
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Determination of protein phosphatase type 2A in monocytes from multiple trauma patients: a potential biomarker for sepsis.
J. Surg. Res.
PUBLISHED: 02-17-2014
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Protein phosphatase type 2A (PP2A) can downregulate c-Jun N-terminal kinase (JNK) expression in monocytes stimulated by lipopolysaccharide. However, this effect has not been evaluated in patients with sepsis. We sought to determine whether PP2A/JNK pathway is involved in sepsis and whether PP2A expression can be associated with patient outcome.
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Discovery of 3-(4-hydroxybenzyl)-1-(thiophen-2-yl)chromeno[2,3-c]pyrrol-9(2H)-one as a phosphodiesterase-5 inhibitor and its complex crystal structure.
Biochem. Pharmacol.
PUBLISHED: 02-12-2014
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Phosphodiesterase-5 (PDE5) inhibitors have been approved for the treatment of erectile dysfunction and pulmonary hypertension, but enthusiasm on discovery of PDE5 inhibitors continues for their potential new applications. Reported here is discovery of a series of new PDE5 inhibitors by structure-based design, molecular docking, chemical synthesis, and enzymatic characterization. The best compound, 3-(4-hydroxybenzyl)-1-(thiophen-2-yl)chromeno[2,3-c]pyrrol-9(2H)-one (57), has an IC?? of 17 nM against the PDE5 catalytic domain and good selectivity over other PDE families. The crystal structure of the PDE5 catalytic domain in complex with 57 was determined at 2? resolution and showed that 57 occupies the same pocket as other PDE5 inhibitors, but has a different binding pattern in detail. On the basis of the binding pattern of 57, a novel scaffold can be proposed as a candidate of PDE inhibitors.
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AG-690/11026014, a novel PARP-1 inhibitor, protects cardiomyocytes from AngII-induced hypertrophy.
Mol. Cell. Endocrinol.
PUBLISHED: 01-28-2014
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Poly(ADP-ribose) polymerase-1 (PARP-1) enzyme, as a sensor of DNA damage, could convert nicotinamide adenine dinucleotide (NAD) into long poly(ADP-ribose) chains and regulate many cellular processes, including DNA repair, gene transcription, cell survival and chromatin remodeling. However, excessive activation of PARP-1 depletes its substrate NAD and leads to cell death. Mounting evidences have shown that PARP-1 overactivation plays a pivotal role in the pathogenesis of cardiac hypertrophy and heart failure. In present study, a novel PARP-1 inhibitor AG-690/11026014 (6014) was identified based on virtual screening and validated by bioassay. Our results further showed that 6014 prevented the cardiomyocytes from AngII-induced hypertrophy, accompanying attenuation of the mRNA and protein expressions of atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP), and reduce in the cell surface area. Additionally, 6014 reversed the depletion ofcellular NAD and SIRT6 deacetylase activity induced by AngII in cardiomyocytes. These observations suggest that anti-hypertrophic effect of 6014 might be partially attributed to the rescue of NAD depletion and subsequent restoring of SIRT6 activity by inhibition of PARP-1. Moreover, 6014 attenuated the generation of oxidative stress via suppression of NADPH oxidase 2 and 4, which might probably contribute to the inhibition of PARP-1.
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Six new tetraprenylated alkaloids from the South China Sea gorgonian Echinogorgia pseudossapo.
Mar Drugs
PUBLISHED: 01-13-2014
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Six new tetraprenylated alkaloids, designated as malonganenones L-Q (1-6), were isolated from the gorgonian Echinogorgia pseudossapo, collected in Daya Bay of Guangdong Province, China. The structures of 1-6 featuring a methyl group at N-3 and a tetraprenyl chain at N-7 in the hypoxanthine core were established by extensive spectroscopic analyses. Compounds 1-6 were tested for their inhibitory activity against the phosphodiesterases (PDEs)-4D, 5A, and 9A, and compounds 1 and 6 exhibited moderate inhibitory activity against PDE4D with IC?? values of 8.5 and 20.3 µM, respectively.
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The association of interleukin-21 polymorphisms with interleukin-21 serum levels and risk of systemic lupus erythematosus.
Gene
PUBLISHED: 01-03-2014
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Systemic lupus erythematosus (SLE) is one of the common autoimmune diseases, with complex genetic components. Interleukin-21 (IL-21) is the most recently discovered member of the type-I cytokine family, which has a variety of effects on the immune system, including B cell activation, plasma cell differentiation, and immunoglobulin production. Previous studies have identified that IL-21 was associated with different autoimmune and inflammatory diseases, such as rheumatoid arthritis, multiple sclerosis and SLE. Variations in the DNA sequence in the IL-21 gene may lead to altered IL-21 production and/or activity, and thus this can modulate an individual's susceptibility to SLE. To test this hypothesis, we investigated the association of the IL-21 polymorphisms and its serum levels with the risk of SLE in a Chinese population. We analyzed three single nucleotide polymorphisms of IL-21 gene rs907715 C/T, rs2221903 T/C and rs2055979 C/A in 175 patients with SLE and 190 age- and sex-matched controls, using Snapshot SNP genotyping assays and DNA sequencing method. Soluble IL-21 (sIL-21) levels were measured by ELISA. There were significant differences in the genotype and allele frequencies of IL-21 gene rs2055979 C/A polymorphism between the group of patients with SLE and the control group (P<0.05). sIL-21 levels were increased in patients with SLE compared with controls (P<0.01). Moreover, genotypes carrying the IL-21 rs2055979 A variant allele were associated with increased IL-21 levels compared to the homozygous wild-type genotype in patients with SLE. The rs2055979 C/A polymorphism of IL-21 and its sIL-21 levels were associated with SLE in the Chinese population. Our data suggests that IL-21 gene may play a role in the development of SLE.
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LIN28B Promotes Colon Cancer Migration and Recurrence.
PLoS ONE
PUBLISHED: 01-01-2014
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LIN28B is involved in "stemness" and tumourigenesis by negatively regulating the maturation of let-7 microRNA family members. In this study, we showed that LIN28B expression promotes migration and recurrence of colon cancer. Immunohistochemistry and reverse-transcription polymerase chain reactions were performed to detect LIN28B expression in colon cancer tissue microarrays, paraffin-embedded surgical resected tissues and cancer cells. Loss-of-function, migration and proliferation analyses were performed to delineate the potential roles of LIN28B in colon cancer. LIN28B was upregulated in colon cancer tissue compared to normal mucosa, and its overexpression correlated with reduced patient survival and increased tumour recurrence. LIN28B suppression inhibited the migration of SW480 colon cancer cells and facilitated the cytotoxicity induced by oxaliplatin in SW480 and HCT116 colon cancer cells. In conclusion, LIN28B overexpression contributes to colon tumourigenesis, and LIN28B may serve as a diagnostic tool and therapeutic target for colon cancer.
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High expression and frequently humoral immune response of melanoma-associated antigen D4 in glioma.
Int J Clin Exp Pathol
PUBLISHED: 01-01-2014
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MAGE-D4 is a novel member of MAGE super-family. It has preliminarily been demonstrated that MAGE-D4 mRNA is not expressed in majority of normal tissues except for brain and ovary in which only trace amount of MAGE-D4 mRNA can be detected, but predominantly expressed in glioma. MAGE-D4 protein expression and its immunogenicity in glioma have not been elucidated well. This study was designed to analyze MAGE-D4 expression both at mRNA and protein level, characteristic of humoral immune response, and their relationships with glioma patients' clinicopathological parameters. Recombinant MAGE-D4 protein and antiserum were generated. Quantitative RT-PCR analysis revealed that MAGE-D4 mRNA expression was overall up-regulated in 41 glioma specimens compared with that in 14 normal brain tissues. Immunohistochemistry analysis showed that 78% (21/27) glioma tissues expressed MAGE-D4 protein, which was predominantly located in the cytoplasm of tumor cells, but absent in any neuroglia cell of normal brain tissues. ELISA analysis demonstrated that humoral response against MAGE-D4 was detected in 17% (7/41) of glioma patients' sera but not in 77 healthy donors. No apparent correlation was observed between the expression and immunogenicity of MAGE-D4 with clinicopathological parameters of glioma. In summary, these results indicate that MAGE-D4 is highly expressed in glioma and can develop specifically humoral response in glioma patients, which supports that it may be a promising biomarker for glioma diagnosis and immunotherapy.
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Selaginpulvilins A-D, New Phosphodiesterase-4 Inhibitors with an Unprecedented Skeleton from Selaginella pulvinata.
Org. Lett.
PUBLISHED: 12-12-2013
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Selaginpulvilins A-D (1-4), four new phenols with an unprecedented 9,9-diphenyl-1-(phenylethynyl)-9H-fluorene skeleton, together with four known selaginellins (5-8) were isolated from Selaginella pulvinata. Their structures were elucidated by spectroscopic analysis and chemical correlation. The structure of 1 was confirmed by single-crystal X-ray diffraction. Compounds 1-8 exhibited remarkable inhibitory activities (IC50 values in the range of 0.11-5.13 ?M) against phosphodiesterase-4 (PDE4), a drug target for the treatment of asthma and chronic obstructive pulmonary disease.
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[Expression of VCAM-1 and caspase-3 in myocardium of persons who died from viral myocarditis].
Fa Yi Xue Za Zhi
PUBLISHED: 12-06-2013
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To observe the expression and distribution of vascular cell adhesion molecule-1 (VCAM-1) and caspase-3 in myocardium of persons who died from viral myocarditis and to explore its pathogenesis and death mechanism.
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The Molecular Basis for the Selectivity of Tadalafil toward Phosphodiesterase 5 and 6: A Modeling Study.
J Chem Inf Model
PUBLISHED: 11-12-2013
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Great attention has been paid to the clinical significance of phosphodiesterase 5 (PDE5) inhibitors, such as sildenafil, tadalafil, and vardenafil widely used for erectile dysfunction. However, sildenafil causes side effects on visual functions since it shows similar potencies to inhibit PDE5 and PDE6, whereas tadalafil gives a high selectivity of 1020-fold against PDE6. Till now, their molecular mechanisms of selectivity of PDE5 versus PDE6 have remained unknown in the absence of the crystal structure of PDE6. In order to elucidate its isoform-selective inhibitory mechanism, a 3D model of PDE6 was constructed by homology modeling, and its interaction patterns with tadalafil plus sildenafil were exploited by molecular docking, molecular dynamics (MD) simulations, and binding free energy calculations. The present work reveals that tadalafil exhibits a less negative predicted binding free energy of -35.21 kcal/mol with PDE6 compared with the value of -41.12 kcal/mol for PDE5, which suggests that tadalafil prefers PDE5 rather than PDE6 and confers a high selectivity for PDE5 versus PDE6. The binding free energy results for tadalafil were consistent with external bioassay studies (IC50 = 5100 and 5 nM toward PDE6 and PDE5, respectively). Two important residues from the Q2 pockets (Val782 and Leu804 in PDE5 and their corresponding Val738 and Met760 in PDE6) were further identified to account for the high selectivity of tadalafil for PDE5 versus PDE6. These findings have shed light on the continuous puzzle of why sildenafil (IC50 = 74 and 6 nM toward PDE6 and PDE5, respectively) causes visual disorders because of its poor selectivity but tadalafil does not. In addition, the homology model of PDE6 can be used to design more potent and selective second-generation PDE5 inhibitors with less inhibitory potency against PDE6.
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Synthesis and Evaluation of Multi-Target-Directed Ligands against Alzheimers Disease Based on the Fusion of Donepezil and Ebselen.
J. Med. Chem.
PUBLISHED: 11-12-2013
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A novel series of compounds obtained by fusing the cholinesterase inhibitor donepezil and the antioxidant ebselen were designed as multi-target-directed ligands against Alzheimers disease. An in vitro assay showed that some of these molecules did not exhibit highly potent cholinesterase inhibitory activity but did have various other ebselen-related pharmacological effects. Among the molecules, compound 7d, one of the most potent acetylcholinesterase inhibitors (IC50 values of 0.042 ?M for Electrophorus electricus acetylcholinesterase and 0.097 ?M for human acetylcholinesterase), was found to be a strong butyrylcholinesterase inhibitor (IC50 = 1.586 ?M), to possess rapid H2O2 and peroxynitrite scavenging activity and glutathione peroxidase-like activity (?0 = 123.5 ?M min(-1)), and to be a substrate of mammalian TrxR. A toxicity test in mice showed no acute toxicity at doses of up to 2000 mg/kg. According to an in vitro blood-brain barrier model, 7d is able to penetrate the central nervous system.
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High volumetric capacity silicon-based lithium battery anodes by nanoscale system engineering.
Nano Lett.
PUBLISHED: 10-30-2013
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The nanostructuring of silicon (Si) has recently received great attention, as it holds potential to deal with the dramatic volume change of Si and thus improve lithium storage performance. Unfortunately, such transformative materials design principle has generally been plagued by the relatively low tap density of Si and hence mediocre volumetric capacity (and also volumetric energy density) of the battery. Here, we propose and demonstrate an electrode consisting of a textured silicon@graphitic carbon nanowire array. Such a unique electrode structure is designed based on a nanoscale system engineering strategy. The resultant electrode prototype exhibits unprecedented lithium storage performance, especially in terms of volumetric capacity, without the expense of compromising other components of the battery. The fabrication method is simple and scalable, providing new avenues for the rational engineering of Si-based electrodes simultaneously at the individual materials unit scale and the materials ensemble scale.
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SFDR enhancement in analog photonic links by simultaneous compensation for dispersion and nonlinearity.
Opt Express
PUBLISHED: 10-10-2013
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A method to improve the spurious-free dynamic range (SFDR) of analog photonic links has been proposed and experimentally demonstrated, which only consists of a phase modulator (PM), a polarizer and an optical filter. Such structure could compensate for the chromatic dispersion and the nonlinearity of the modulator simultaneously. In addition, by adjusting the states of polarization (SOPs) launching into the PM and the polarizer, the proposed scheme could also be reconfigured to mitigate the second harmonic nonlinearity induced by the photodetector. Experimental results show that the suppressions of the second-order and third-order intermodulation distortions (IMD2 & IMD3) are larger than 14-dB and 25.4-dB, respectively. Furthermore, the SFDR can achieve ~110-dB · Hz(4/5) for 40-km fiber transmission, which is 26-dB higher than that of the link without compensation.
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Assessment of the associations between three VEGF polymorphisms and risk of prostate cancer.
Tumour Biol.
PUBLISHED: 08-22-2013
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Vascular endothelial growth factor (VEGF) plays a crucial role in the regulation of angiogenesis and is involved in the development and metastasis of common cancers. There were several case-controls studies published to assess the associations of VEGF polymorphisms with risk of prostate cancer, but the findings were inconsistent. We performed a meta-analysis to provide a comprehensive assessment of the associations of three VEGF polymorphisms with risk of prostate cancer. The pooled odds ratio (OR) with 95 % confidence interval (95 % CI) was calculated to assess the associations. Eleven individual case-control studies with a total of 5,209 cases of prostate cancer and 5,233 controls were finally included into our meta-analysis. Overall, VEGF rs833061 polymorphism was not associated with risk of prostate cancer (T versus C, OR?=?1.14, 95 % CI 0.91-1.44, P?=?0.26; TT versus CC, OR?=?1.09, 95 % CI 0.67-1.76, P?=?0.74; TT versus CC/CT: OR?=?1.46, 95 % CI 0.67-3.18, P?=?0.34; TT/CT versus CC, OR?=?1.08, 95 % CI 0.82-1.43, P?=?0.59). VEGF rs3025039 polymorphism was also not associated with risk of prostate cancer (T versus C, OR?=?1.03, 95 % CI 0.91-1.16, P?=?0.66; TT versus CC, OR?=?1.82 95 % CI 0.16-20.53, P?=?0.63; TT versus CC/CT, OR?=?2.00, 95 % CI 0.18-22.41, P?=?0.57; TT/CT versus CC, OR?=?0.72, 95 % CI 0.38-1.36, P?=?0.31). VEGF rs2010963 polymorphism was not associated with risk of prostate cancer under three models (C versus G, OR?=?1.17, 95 % CI 0.92-1.48, P?=?0.20; CC versus GG, OR?=?2.28, 95 % CI 0.90-5.75, P?=?0.08; CC versus GG/GC, OR?=?1.57, 95 % CI 0.67-3.68, P?=?0.30). In conclusison, current data suggest that those three VEGF polymorphisms are not obviously associated with risk of prostate cancer.
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Nitrogen metabolism of two contrasting poplar species during acclimation to limiting nitrogen availability.
J. Exp. Bot.
PUBLISHED: 08-20-2013
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To investigate N metabolism of two contrasting Populus species in acclimation to low N availability, saplings of slow-growing species (Populus popularis, Pp) and a fast-growing species (Populus alba × Populus glandulosa, Pg) were exposed to 10, 100, or 1000 ?M NH4NO3. Despite greater root biomass and fine root surface area in Pp, lower net influxes of NH4(+) and NO3(-) at the root surface were detected in Pp compared to those in Pg, corresponding well to lower NH4(+) and NO3(-) content and total N concentration in Pp roots. Meanwhile, higher stable N isotope composition (?(15)N) in roots and stronger responsiveness of transcriptional regulation of 18 genes involved in N metabolism were found in roots and leaves of Pp compared to those of Pg. These results indicate that the N metabolism of Pp is more sensitive to decreasing N availability than that of Pg. In both species, low N treatments decreased net influxes of NH4(+) and NO3(-), root NH4(+) and foliar NO3(-) content, root NR activities, total N concentration in roots and leaves, and transcript levels of most ammonium (AMTs) and nitrate (NRTs) transporter genes in leaves and genes involved in N assimilation in roots and leaves. Low N availability increased fine root surface area, foliar starch concentration, ?(15)N in roots and leaves, and transcript abundance of several AMTs (e.g. AMT1;2) and NRTs (e.g. NRT1;2 and NRT2;4B) in roots of both species. These data indicate that poplar species slow down processes of N acquisition and assimilation in acclimation to limiting N supply.
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Improvement of linearity in phase-modulated analog photonic link.
Opt Lett
PUBLISHED: 08-14-2013
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A method to improve the linearity of the analog photonic link is proposed and experimentally demonstrated, which consists of a phase modulator and an optical tunable bandpass filter. By carefully optimizing the bandwidth and center wavelength of the filter, we can significantly suppress the third-order intermodulation distortion by ~32 dB. Subsequently the spurious-free dynamic range of the link is improved by ~14 dB.
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[Research on the application of principal component analysis and improved BP neural network to the determination of Fe and Ti contents in geological samples].
Guang Pu Xue Yu Guang Pu Fen Xi
PUBLISHED: 08-03-2013
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Aiming at forecasting elemental contents in geological samples accurately, a principal component analysis and improved BP (PCA-BP) neural network theory is proposed in the present work. The samples from west Tianshan were measured through X-ray fluorescence measurement method, and the X-Ray fluorescence counts of each element such as Fe, Ti, V, Pb, Zn, etc. were input to the PCA-BP neural network as input variables to forecast Fe and Ti contents in uncertified geological samples quantitatively. The results show that the PCA-BP neural network can give an ideal result, and the relative error between the forecast data and chemical analysis data is less than 3%. This method provides a new and effective approach to forecasting elemental contents in geological samples.
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Design, synthesis, and evaluation of multitarget-directed resveratrol derivatives for the treatment of Alzheimers disease.
J. Med. Chem.
PUBLISHED: 07-08-2013
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A series of multitarget-directed resveratrol derivatives was designed and synthesized for the treatment of Alzheimers disease (AD). In vitro studies indicated that most of the target compounds exhibit significant inhibition of self-induced ?-amyloid (A?) aggregation and Cu(II)-induced A?1-42 aggregation and acted as potential antioxidants and biometal chelators. In particular, compounds 5d and 10d are potential lead compounds for AD therapy (5d, IC50 = 7.56 ?M and 10d, IC50 = 6.51 ?M for self-induced A? aggregation; the oxygen radical absorbance capacity assay using fluorescein (ORAC-FL) values are 4.72 and 4.70, respectively). Moreover, these compounds are capable of disassembling the highly structured A? fibrils generated by self- and Cu(II)-induced A? aggregation. Furthermore, 5d crossed the blood-brain barrier (BBB) in vitro and did not exhibit any acute toxicity in mice at doses of up to 2000 mg/kg. Taken together, the data indicate that 5d is a very promising lead compound for AD.
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Intertwined network of Si/C nanocables and carbon nanotubes as lithium-ion battery anodes.
ACS Appl Mater Interfaces
PUBLISHED: 07-02-2013
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We demonstrate a new kind of Si-based anode architectures consisting of silicon nanowire/overlapped graphene sheet core-sheath nanocables (SiNW@G) intertwined with carbon nanotubes (CNTs). In such a hybrid structure, the CNTs, mechanically binding SiNW@G nanocables together, act as a buffer matrix to accommodate the volume change of SiNW@G, and overlapped graphene sheets (that is, G sheaths) effectively prevent the direct contact of silicon with the electrolyte during cycling, both of which enable the structural integrity and interfacial stabilization of such hybrid electrodes. Furthermore, the one-dimensional nature of both components affords the creation of a three-dimensional interpenetrating network of lithium ion and electron pathways in the resultant hybrids, thereby enabling efficient transport of both electrons and lithium ions upon charging/discharging. As a result, the hybrids exhibit much-improved lithium storage performance.
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Optical quasi logic gates based on polarization-dependent four-wave mixing in subwavelength metallic waveguides.
Opt Express
PUBLISHED: 06-22-2013
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All-optical quasi logic gates are demonstrated by means of polarization-dependent four-wave mixing (FWM) in metal-insulator-metal (MIM) waveguides filled with a Kerr nonlinear medium. By using finite-difference-time-domain (FDTD) methods, we perform a quantitative comparison of the FWM efficiency associated with different pump polarization states. By manipulating the core thickness and the polarization properties of the pump and signals, all-optical NOT, NAND, NOR, and NXOR logical functions are obtained.
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Electroversion in treatment of arrhythmia in a patient with Wolff-Parkinson-White syndrome and cervical spinal cord injury.
Chin. J. Traumatol.
PUBLISHED: 06-06-2013
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We report electroversion in treatment of atrial fibrillation (AF) and atrioventricular nodal reentry tachycardia (AVNRT) in a patient with Wolff-Parkinson-White syndrome and cervical spinal cord injury. At first, the patient sustained respiratory failure and weak cough reflex, thereafter repeated bronchoscopy was used to aspirate the sputum as well as control the pneumonia, which resulted in arrhythmia (AF and AVNRT). Two doses of intravenous amiodarone failed to correct the arrhythmia. After restoration of sinus rhythm by electroversion, he was successfully weaned from mechanical ventilation and discharged from the intensive care unit without recurrent arrhythmia.
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Transmission of multi-polarization-multiplexed signals: another freedom to explore?
Opt Express
PUBLISHED: 05-15-2013
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We propose a configuration of signal multiplexing with four polarization states, and investigate its transmission performance over single-mode-fiber links. Assisted by coherent detection and digital signal processing (DSP), the demodulation of four-polarization multiplexed (4PM) on-off-keying (OOK) and phase-shift-keying (PSK) signals are achieved. We then discuss the impact of the crosstalk from polarization mode dispersion (PMD) on 4PM systems. The transmission distance is extended from ~50-km to ~80 km by employing feedback-decision-equalizers. We also compare the back-to-back characteristics of the 40-Gbit/s 4PM-OOK system and 40-Gbit/s PDM-QPSK system with the same spectral efficiency. The results show that the performance of 4PM systems is comparable to that of PDM-QPSK systems, which indicates that the proposed scheme is a potentially promising candidate for future optical networks.
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The molecular basis for the inhibition of phosphodiesterase-4D by three natural resveratrol analogs. Isolation, molecular docking, molecular dynamics simulations, binding free energy, and bioassay.
Biochim. Biophys. Acta
PUBLISHED: 05-10-2013
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The phosphodiesterase-4 (PDE4) enzyme is a promising therapeutic target for several diseases. Our previous studies found resveratrol and moracin M to be natural PDE4 inhibitors. In the present study, three natural resveratrol analogs [pterostilbene, (E)-2,3,5,5-tetrahydroxystilbene (THSB), and oxyresveratrol] are structurally related to resveratrol and moracin M, but their inhibition and mechanism against PDE4 are still unclear. A combined method consisting of molecular docking, molecular dynamics (MD) simulations, binding free energy, and bioassay was performed to better understand their inhibitory mechanism. The binding pattern of pterostilbene demonstrates that it involves hydrophobic/aromatic interactions with Phe340 and Phe372, and forms hydrogen bond(s) with His160 and Gln369 in the active site pocket. The present work also reveals that oxyresveratrol and THSB can bind to PDE4D and exhibits less negative predicted binding free energies than pterostilbene, which was qualitatively validated by bioassay (IC50=96.6, 36.1, and 27.0?M, respectively). Additionally, a linear correlation (R(2)=0.953) is achieved for five PDE4D/ligand complexes between the predicted binding free energies and the experimental counterparts approximately estimated from their IC50 values (?RT ln IC50). Our results imply that hydrophobic/aromatic forces are the primary factors in explaining the mechanism of inhibition by the three products. Results of the study help to understand the inhibitory mechanism of the three natural products, and thus help the discovery of novel PDE4 inhibitors from resveratrol, moracin M, and other natural products.
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Enhanced transparent conductive properties of graphene/carbon nano-composite films.
J Nanosci Nanotechnol
PUBLISHED: 05-08-2013
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Transparent conductive graphene/carbon nano-composite films are produced based on graphene oxide (GO) sheets and phenolic resins that are layer-by-layer deposited on a quartz substrate using a spin coating technique. The graphene/carbon nano-composite films with high graphitization degree and high crystallization exhibit exceptionally high electrical conductivity and transparency after thermal reduction. A remarkable sheet resistance of 1.98 komega/square at 81.3% transparency in the wavelength of 550 nm is obtained, which significantly outperforms that (3.29 komega/square at 81.7% transparency) of the film produced from pure GO sheets after thermal reduction.
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The association of SNPs in Hsp90? gene 5 flanking region with thermo tolerance traits and tissue mRNA expression in two chicken breeds.
Mol. Biol. Rep.
PUBLISHED: 04-30-2013
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Thermo stress induces heat shock proteins (HSPs) expression and HSP90 family is one of them that has been reported to involve in cellular protection against heat stress. But whether there is any association of genetic variation in the Hsp90? gene in chicken with thermo tolerance is still unknown. Direct sequencing was used to detect possible SNPs in Hsp90? gene 5 flanking region in 3 chicken breeds (n = 663). Six mutations, among which 2 SNPs were chosen and genotypes were analyzed with PCR-RFLP method, were found in Hsp90? gene in these 3 chicken breeds. Association analysis indicated that SNP of C.-141G>A in the 5 flanking region of the Hsp90? gene in chicken had some effect on thermo tolerance traits, which may be a potential molecular marker of thermo tolerance, and the genotype GG was the thermo tolerance genotype. Hsp90? gene mRNA expression in different tissues detected by quantitative real-time PCR assay were demonstrated to be tissue dependent, implying that different tissues have distinct sensibilities to thermo stress. Besides, it was shown time specific and varieties differences. The expression of Hsp90? mRNA in Lingshan chickens in some tissues including heart, liver, brain and spleen were significantly higher or lower than that of White Recessive Rock (WRR). In this study, we presume that these mutations could be used in marker assisted selection for anti-heat stress chickens in our breeding program, and WRR were vulnerable to tropical thermo stress whereas Lingshan chickens were well adapted.
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Covalently stabilized Pd clusters in microporous polyphenylene: an efficient catalyst for Suzuki reactions under aerobic conditions.
Small
PUBLISHED: 04-19-2013
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A novel catalyst composed of a microporous polyphenylene network and covalently stabilized Pd clusters (Pd/MPP) for highly efficient Suzuki-Miyaura coupling is synthesized with an in-situ one-pot chemical approach, through the catalytic trimerization of 1,3,5-triethynylbenzene. The unique Pd/MPP cluster exhibits very high catalytic activity for a broad scope of Suzuki-Miyaura reactions with short reaction time, good yield, and high turnover number and turnover frequency values, even in aqueous media under aerobic conditions. The strong covalent interaction between Pd and MPP network prevents the agglomeration or leaching of Pd clusters and enables the catalyst to remain highly active, even after a number of cycles.
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Biophysical analysis of the putative acetyltransferase SACOL2570 from methicillin-resistant Staphylococcus aureus.
J. Struct. Funct. Genomics
PUBLISHED: 04-12-2013
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Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of a myriad of insidious and intractable infections in humans, especially in patients with compromised immune systems and children. Here, we report the apo- and CoA-bound crystal structures of a member of the galactoside acetyltransferase superfamily from methicillin-resistant S. aureus SACOL2570 which was recently shown to be down regulated in S. aureus grown in the presence of fusidic acid, an antibiotic used to treat MRSA infections. SACOL2570 forms a homotrimer in solution, as confirmed by small-angle X-ray scattering and dynamic light scattering. The protein subunit consists of an N-terminal alpha-helical domain connected to a C-terminal L?H domain. CoA binds in the active site formed by the residues from adjacent L?H domains. After determination of CoA-bound structure, molecular dynamics simulations were performed to model the binding of AcCoA. Binding of both AcCoA and CoA to SACOL2570 was verified by isothermal titration calorimetry. SACOL2570 most likely acts as an acetyltransferase, using AcCoA as an acetyl group donor and an as-yet-undetermined chemical moiety as an acceptor. SACOL2570 was recently used as a scaffold for mutations that lead the generation of cage-like assemblies, and has the potential to be used for the generation of more complex nanostructures.
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Vorinostat, a HDAC inhibitor, showed anti-osteoarthritic activities through inhibition of iNOS and MMP expression, p38 and ERK phosphorylation and blocking NF-?B nuclear translocation.
Int. Immunopharmacol.
PUBLISHED: 04-10-2013
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Overproduction of nitric oxide (NO) and matrix metalloproteinases (MMPs) plays an important role in the pathogenesis of osteoarthritis (OA). In present study, we investigated whether vorinostat can inhibit the catabolic effects of IL-1? in vitro, especially the inhibition of MMPs and inducible nitric oxide synthase (iNOS) through the attenuation of nuclear factor kappa-B (NF-?B) and mitogen activated protein kinase (MAPK) pathways in human chondrocytes. Human OA chondrocytes were either left untreated or treated with various concentrations of vorinostat followed by incubation with IL-1? (5ng/mL). Effects of vorinostat on IL-1?-induced gene and protein expression of iNOS, MMP-1, MMP-13 and tissue inhibitors of metalloproteinase-1 (TIMP-1) were verified by quantitative real time-PCR and Western blot analysis. Production of NO, MMP-1, MMP-13 and TIMP-1 released in culture supernatant was estimated using commercially available kits. The roles of NF-?B and MAPK pathways in the regulation of targeted genes and the mechanism involved in vorinostat mediated modulation of these genes were determined by Western blot using specific antibodies. We found that vorinostat down-regulated iNOS, MMP-1 and MMP-13 expression and up-regulated TIMP-1 expression in human OA chondrocytes. In addition, the release of NO, MMP-1 and MMP-13 secreted from IL-1? stimulated chondrocytes was also suppressed by vorinostat. Interestingly, vorinostat selectively inhibited IL-1?-induced p38 and ERK1/2 activation without affecting JNK activation. Furthermore, we observed that vorinostat inhibited NF-?B pathway by suppressing the degradation of I-?B? and attenuating NF-?B p65 translocation to the nucleus. These results suggest that vorinostat may be a promising therapeutic agent for the prevention and treatment of OA.
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Identification of novel phosphodiesterase-4D inhibitors prescreened by molecular dynamics-augmented modeling and validated by bioassay.
J Chem Inf Model
PUBLISHED: 03-29-2013
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Phosphodiesterase-4D (PDE4D) has been proved to be a potential therapeutic target against strokes. In the present study, a procedure of integrating pharmacophore, molecular docking, molecular dynamics (MD) simulations, binding free energy calculations, and finally validation with bioassay was developed and described to search for novel PDE4D inhibitors from the SPECS database. Among the 29 compounds selected by our MD-augmented strategy, 15 hits were found with IC50 between 1.9 and 50 ?M (a hit rate of 52%) and 6 potent hits showed IC50 less than 10 ?M, which suggested that MD simulations can explore the intermolecular interactions of PDE4D-inhibitor complexes more precisely and thus significantly enhanced the hit rate of this screening. The effective and efficient integrated procedures described in this study could be readily applied to screening studies toward other drug targets.
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A transcriptomic network underlies microstructural and physiological responses to cadmium in Populus x canescens.
Plant Physiol.
PUBLISHED: 03-25-2013
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Bark tissue of Populus × canescens can hyperaccumulate cadmium, but microstructural, transcriptomic, and physiological response mechanisms are poorly understood. Histochemical assays, transmission electron microscopic observations, energy-dispersive x-ray microanalysis, and transcriptomic and physiological analyses have been performed to enhance our understanding of cadmium accumulation and detoxification in P. × canescens. Cadmium was allocated to the phloem of the bark, and subcellular cadmium compartmentalization occurred mainly in vacuoles of phloem cells. Transcripts involved in microstructural alteration, changes in nutrition and primary metabolism, and stimulation of stress responses showed significantly differential expression in the bark of P. × canescens exposed to cadmium. About 48% of the differentially regulated transcripts formed a coregulation network in which 43 hub genes played a central role both in cross talk among distinct biological processes and in coordinating the transcriptomic regulation in the bark of P. × canescens in response to cadmium. The cadmium transcriptome in the bark of P. × canescens was mirrored by physiological readouts. Cadmium accumulation led to decreased total nitrogen, phosphorus, and calcium and increased sulfur in the bark. Cadmium inhibited photosynthesis, resulting in decreased carbohydrate levels. Cadmium induced oxidative stress and antioxidants, including free proline, soluble phenolics, ascorbate, and thiol compounds. These results suggest that orchestrated microstructural, transcriptomic, and physiological regulation may sustain cadmium hyperaccumulation in P. × canescens bark and provide new insights into engineering woody plants for phytoremediation.
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Ectomycorrhizas with Paxillus involutus enhance cadmium uptake and tolerance in Populus?×?canescens.
Plant Cell Environ.
PUBLISHED: 03-20-2013
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Ectomycorrhizas (EMs), which are symbiotic organs formed between tree roots and certain fungi, can mediate cadmium (Cd) tolerance of host plants, but the underlying physiological and molecular mechanisms are not fully understood. To investigate EMs mediated Cd tolerance in woody plants, Populus?×?canescens was inoculated with Paxillus involutus (strain MAJ) to establish mycorrhizal roots. Mycorrhizal poplars and non-mycorrhizal controls were exposed to 0 or 50??M CdSO4 . EMs displayed higher net Cd(2+) influx than non-mycorrhizal roots. Net Cd(2+) influx was coupled with net H(+) efflux and inactivation of plasma membrane (PM) H(+) -ATPases reduced Cd(2+) uptake of EMs less than of non-mycorrhizal roots. Consistent with higher Cd(2+) uptake in EMs, in most cases, transcript levels of genes involved in Cd(2+) uptake, transport and detoxification processes were increased in EMs compared to non-mycorrhizal roots. Higher CO2 assimilation, improved nutrient and carbohydrate status, and alleviated oxidative stress were found in mycorrhizal compared to non-mycorrhizal poplars despite higher Cd(2+) accumulation. These results indicate that mycorrhizas increase Cd(2+) uptake, probably by an enlarged root volume and overexpression of genes involved in Cd(2+) uptake and transport, and concurrently enhance Po.?×?canescens?Cd tolerance by increased detoxification, improved nutrient and carbohydrate status and defence preparedness.
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Observation and optimization of 4He atomic polarization spectroscopy.
Opt Lett
PUBLISHED: 03-19-2013
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Polarization spectroscopy in (4)He around 1083 nm is observed and optimized with a distributed feedback fiber laser and is applied for frequency stabilization. In order to improve the accuracy and long-term stability of the frequency-locking performance, a power stabilization module is added, and the dependences of the peak-to-peak amplitude and frequency difference (width) of the polarization spectroscopy signal on various pump and probe powers are investigated.
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Hybrid chaos-based communication system consisting of three chaotic semiconductor ring lasers.
Appl Opt
PUBLISHED: 03-06-2013
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We report on the realization of a hybrid chaos-based communication scheme using three chaotic semiconductor ring lasers (SRLs). In this scheme, two slave SRLs (S-SRLs) are identically driven by a master SRL (M-SRL) subject to delayed optical feedback. Under proper conditions, the S-SRLs are completely synchronized with each other due to the symmetric operation, and they are also synchronized with the M-SRL through the injection-locking effect. The results also show that a message encrypted through chaos shift keying at the M-SRL end can be successfully decrypted by the two S-SRLs, while the two uncoupled S-SRLs allow for dual-channel chaos communication when both counterpropagating modes of one S-SRL are encoded with a message.
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Pyrolyzed bacterial cellulose: a versatile support for lithium ion battery anode materials.
Small
PUBLISHED: 03-05-2013
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A scalable, low-cost and environmentally benign strategy is developed for the facile construction of a unique kind of three-dimensional porous electrode architecture for high-performance lithium ion batteries. The methodology is based on the employment of pyrolyzed bacterial cellulose as a new three-dimensional porous scaffold to support various nanostructured active electrode materials, such as SnO2 and Ge.
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Contact-engineered and void-involved silicon/carbon nanohybrids as lithium-ion-battery anodes.
Adv. Mater. Weinheim
PUBLISHED: 02-22-2013
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A novel anode structure composed of silicon nanowires dwelling in graphitic tubes is developed. The thus-fabricated 1D/1D hybrid structure exhibits good rate capability and remarkable cycling stability, which mainly originates from their structural advantages including the built-in void spaces and the robust line-to-line contact mode between the components.
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3D-QSAR studies of azaoxoisoaporphine, oxoaporphine, and oxoisoaporphine derivatives as anti-AChE and anti-AD agents by the CoMFA method.
J. Mol. Graph. Model.
PUBLISHED: 02-04-2013
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In the present study, a series of novel azaoxoisoaporphine derivatives were reported and their inhibitory activities toward acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), and A? aggregation were evaluated. The new compounds remained high inhibitory potency on A? aggregation, with inhibitory activity from 29.42% to 89.63% at a concentration of 10?M, but had no action on AChE or BuChE, which was very different from our previously reported oxoaporphine and oxoisoaporphine derivatives. By 3D-QSAR studies, we constructed a reliable CoMFA model (q(2)=0.856 and r(2)=0.986) based on the inhibitory activities toward AChE and discovered key information on structure and anti-AChE activities among the azaoxoisoaporphine, oxoaporphine, and oxoisoaporphine derivatives. The model was further confirmed by the test-set validation (q(2)=0.873, r(2)=0.937, and slope k=0.902) and Y-randomization examination. The statistically significant and physically meaningful 3D-QSAR/CoMFA model provided better insight into understanding the inhibitory behaviors of those chemicals, which may provide useful information for the rational molecular design of azaoxoisoaporphine derivatives anti-AChE and anti-AD agents.
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Effects of different cold-air exposure intensities on the risk of cardiovascular disease in healthy and hypertensive rats.
Int J Biometeorol
PUBLISHED: 01-31-2013
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Ten-week-old male Wistar rats (systolic blood pressure, 106-116 mmHg; body weight, 300-320 g) and spontaneously hypertensive rats (systolic blood pressure, 160-176 mmHg; body weight, 210.9-244.9 g) were used as healthy and hypertensive subjects to determine the effects of varying degrees of cold-air exposure in a climate chamber box. The three cold-air ranks were cold air I [minimum temperature (TMIN) 6.4 °C, ??T(48) 8.6 °C], cold air II (TMIN 3.8 °C, ??T(48) 11.2 °C), and cold air III (TMIN -0.3 °C, ??T(48) 15.3 °C), as established from the cold-air data of Zhangye City, China. Each cold-air rank consisted of a temperature drop and a temperature increase with the same initial and terminal temperatures (15 °C). After cold-air exposure, the risk factors for cardiovascular disease (CVD) such as systolic blood pressure, whole blood viscosity (10/s and 150/s), plasma fibrinogen, and blood lipids of the rats were determined. The results indicated that the CVD risk factors of the healthy and hypertensive rats increased significantly with cold-air exposure intensities. The increase in systolic blood pressure was greater during temperature drops, whereas the increases in whole blood viscosity and plasma fibrinogen were greater after cold-air exposure. The effects of cold-air exposure on the CVD risk factors of healthy rats, particularly the systolic blood pressure, whole blood viscosity (150/s), and LDL/HDL, were greater than those in hypertensive rats. In conclusion, CVD risk may increase with cold-air ranks. Blood pressure-induced CVD risk may be greater during cold-air temperature drop, whereas atherosclerosis-induced CVD risk may be greater after cold-air exposure. The effect of cold air on the CVD risk factors in healthy subjects may be more significant than those in hypertensive subjects.
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