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Find video protocols related to scientific articles indexed in Pubmed.
CNV instability associated with DNA replication dynamics: evidence for replicative mechanisms in CNV mutagenesis.
Hum. Mol. Genet.
PUBLISHED: 11-16-2014
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Copy number variation (CNV) in the human genome is of vital importance to genomic disorders, human health and evolution of our species. However, much of the molecular basis of CNV mutagenesis remains to be elucidated. Considering the DNA replication model of 'fork stalling and template switching' for CNV formation, we hypothesized that replication fork progression could be important to CNV mutagenesis. However, molecular assays of replication fork progression at the genome level are technically challenging. Instead, we conducted an estimation of DNA replication dynamics, as the statistic R, using the readily available data of replication timing. Small R values can reflect 'slowed' replication, which could result from less fork initiation, reduced fork speed, or fork barriers. We generated genome-wide profiles of R in the genomes of human, mouse and Drosophila. Intriguingly, the CNV breakpoints in all three genomes show significantly biased distributions toward the genomic regions with small R values, suggesting potential replication stress-induced CNV instability. Notably, among the human CNVs with distinct breakpoint junction characteristics, the homology-mediated and VNTR-mediated CNVs contribute mostly to the correlation between CNV instability and the statistic R, consistent with the recent findings in the C. elegans and yeast genomes of repeat-induced DNA replication error and consequent CNV formation. The statistic R may reflect both replication stress and the effect of local genome architecture on fork progression. Our concordant observations suggest an important role for DNA replicative mechanisms in CNV mutagenesis and genome instability.
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Traditional Chinese medication for cardiovascular disease.
Nat Rev Cardiol
PUBLISHED: 11-12-2014
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Traditional Chinese medication (TCM) is increasingly used to treat cardiovascular disease (CVD) in China and some other Asian countries. However, therapeutic efficacy and adverse effects of TCM are difficult to evaluate because few large-scale, randomized controlled trials (RCTs) enrolling patients with CVD have been performed. In this Review, we critically examine the current evidence on the cardiovascular effects of TCM. We reviewed 68 RCTs that included a total of 16,171 patients. The methodological quality of the trials was generally low. Only three reports described adverse cardiovascular events specifically, although in most studies TCM was associated with significant improvements in surrogate end points for hypertension, coronary heart disease, cardiac arrhythmias, and heart failure. The risk of adverse effects was not increased compared with no intervention, placebo, or Western medications. However, whether TCM is effective in reducing the all-cause or cardiovascular mortality in patients with CVD remains unknown and must be tested in large-scale RCTs with adverse cardiovascular events as primary end points.
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The association of mannose-binding lectin genetic polymorphisms with the risk of rheumatoid arthritis: a meta-analysis.
J. Recept. Signal Transduct. Res.
PUBLISHED: 10-29-2014
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Abstract Objective: To better understand the risks of rheumatoid arthritis (RA) and certain subsets conferred by mannose-binding lectin (MBL2) polymorphisms in different races. Materials and methods: Eighteen articles (4810 cases and 4585 controls) were identified from the latest literature search carried out in May 2014 using PubMed, Web of Science, Wanfang Database (Chinese) and Chinese National Knowledge Infrastructure. Three single nucleotide polymorphisms of codon 52, 54 and 57, exonic and extended genotypic variance in MBL2 were synthesized. Results: Codon 54 mutation of MBL2 was unlikely to be a risk factor for RA in overall population, but turned out to be deleterious in East Asian (four studies with 523 cases and 647 controls, pooled OR:1.63, 95% CI: 1.23-2.17). Codon 54 mutation increased the risk of seropositive and erosive RA by 44% and 162%, respectively (three studies with 281 cases and 358 controls, 95% CI: 1.01-2.05; 3 studies with 180 cases and 499 controls, 95% CI: 1.77-3.88). Furthermore, those risks were relatively stronger when restricted in East Asian (two studies with 147 cases and 244 controls, pooled OR: 1.85, 95% CI: 1.19-2.87; 2 studies with 170 cases and 291 controls, pooled OR: 2.78, 95% CI: 1.85-4.20). No remarkable associations were detected regarding codon 52, 57, exon 1 and extended genotype of MBL2. Conclusions: Polymorphism of codon 54 in MBL2 may predispose to RA, especially seropositive or erosive RA, which East Asian appears to be more vulnerable.
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Two-Dimensional ?-Expanded Quinoidal Terthiophenes Terminated with Dicyanomethylenes as n-Type Semiconductors for High-Performance Organic Thin-Film Transistors.
J. Am. Chem. Soc.
PUBLISHED: 10-29-2014
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Quinoidal oligothiophenes (QOT), as classical n-type semiconductors, have been well-known for a long time but with non-optimal semiconducting properties. We report here the design and selective synthesis of new two-dimensional (2D) ?-expanded quinoidal terthiophenes, 2DQTTs, with proximal (2DQTT-i) and distal (2DQTT-o) regiochemistry for high-performance n-channel organic thin-film transistors (n-OTFTs) featuring high electron mobility, solution processability, and ambient stability. The elegant combination of thieno[3,4-b]thiophene [TT, donor (D)] and 5-alkyl-4H-thieno[3,4-c]pyrrole-4,6(5H)-dione [TPD, acceptor (A)] units with relatively large ?-surface endows these 2DQTTs with distinctive 2D structural characteristics and flat configuration stabilized by weak intramolecular S-O/S weak interactions. Furthermore, the A-D-A-D-A electronic structure maintains an adequately low LUMO energy level. These 2DQTTs are shown to exhibit outstanding semiconducting properties with electron mobilities of up to 3.0 cm(2) V(-1) s(-1) and on/off ratios of up to 10(6) (2DQTT-o) in ambient- and solution-processed OTFTs. Investigations on thin-film morphology reveal that the microstructure of 2DQTTs is highly dependent on the orientation of the fused thiophene subunits, leading to differences in electron mobilities of 1 order of magnitude. X-ray diffraction studies in particular reveal increased crystallinity, crystalline coherence, and orientational order in 2DQTT-o compared to 2DQTT-i, which accounts for the superior electron transport property of 2DQTT-o.
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[Reversal Effect of Cinobufacini on Multidrug Resistance of Raji/ADR Cells and Its Mechanisms].
Zhongguo Shi Yan Xue Ye Xue Za Zhi
PUBLISHED: 10-24-2014
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The aim of this study was to explore the reversing effect of cinobufacini on multidrug resistance of Raji/ADR cells and its mechanisms. The growth inhibitory rate, half inhibitory concentration (IC50), reversing multiples to adriamycin- resistance were detected by MTT, and the curve of growth inhibitory rate was drawn; the MDR-1 and MRP-1 gene transcription was determined by RT-PCR; the expressions of P-gp and MRP-1 proteins were assayed by Western blot and flow cytometry. The results showed that the inhibitory rates of cinobufacini on Raji and Raji/ADR cells at 72 h were 75.6% and 69.3% respectively, the IC50 were 3.9 mmol/L and 4.6 mmol/L without significant difference (P > 0.05). The reversing multiples to adriamycin-resistance were 255.7 multiples, the transcription of mdr-1 and mrp-1 genes and the expression of P-gp and MRP-1 proteins significantly decreased (P < 0.05) in Raji/ADR cells after the treatment with cinobufotalin. It is concluded that cinobufotalin can reverse the adriamycin-resistance in Raji/ADR cells and the expression of P-gp and MRP-1 proteins were down-regulated through the transcriptional pathway. The cinobufotalin is an effective reversal agent for the multidrug resistance of tumors.
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[Preliminary research on the feature of dissolved inorganic carbon in Wulixia Reservoir in summer, Guangxi, China].
Huan Jing Ke Xue
PUBLISHED: 10-24-2014
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To gain more knowledge on the transformation process of dissolved inorganic carbon in a karst reservoir, in situ monitoring, sampling and lab experiments of water columns were carried out at various sampling sites along the flow line in Wulixia Reservoir, Guangxi, China during early July, 2013. Results showed that: (1) The hydrochemical characteristics of study areas were controlled by the carbonate equilibrium system and the hydrochemical type of all water samples was HCO3-Ca + Mg. (2) The DIC concentration decreased gradually (DIC(Average) : from 1.03 to 0.78 mmol x L(-1)) and the delta13C(DIC) increased gradually (delta13C(DIC(Average) : from -10.21per thousand to -6.62 per thousand) from the reservoir end area to dam area. Meanwhile, with the depth increase in water column, the DIC concentration increased gradually (DIC(Average) : from 0.86 to 1.05 mmol x L(-1)) and the delta13C(DIC) decreased gradually (delta13C(DIC(Average) : from -7.88 per thousand to -13.39 per thousand) from the surface to the bottom of the reservoir. Possible reasons for these research results were found as follows: (1) Dissolution-precipitation process of carbonate substance could be inhibited by other processes such as biogeochemical processes, which played little role in delta13C(DIC) variations. (2) Thermal stratification existed in the study areas which could influence the distribution of DIC and delta13C(DIC) by affecting the distribution of plankton and its orientation and strength of metabolism process, and the extent of organic matter decomposition, and so on.
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[Diel variations of hydrochemistry and influencing factors in a surface stream in subtropical karst area, SW China].
Huan Jing Ke Xue
PUBLISHED: 10-24-2014
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In order to understand the diel variation and influencing factors of hydrochemistry in a surface creek fed by karst subterranean river in a subtropical area, where is located at Guancun Village, Daliang Township, Rong'an County of Guangxi Zhuang Autonomous Region, China, two monitoring sites were set simultaneously to launch Guancun subterranean river outlet (G1) and surface creek mouth (G2), respectively. Physical and hydrochemical parameters including pH, dissolved oxygen (DO), water temperature (T) and specific conductivity (Spc) were measured at 15-minute intervals and water samples for analyzing major ions such as Ca2+, HCO3- and NO3- as well as delta3C(DIC) were collected at 2-hour intervals. The results showed that: (1) G1 and G2 sites were both HCO3- Ca type water, however the two monitoring sites showed different diel variations of hydrogeochemical process; (2) The physical and hydrochemical parameters (T, DO, pH, Spc) and major ions (Ca2+, Mg2+, Na+, K+, HCO3-, SO4(2-), NO3-, Cl- in G1 site were basically stable, while the physical and hydrochemical parameters (T, DO, pH, Spc) and major ions (Ca2+, HCO3- and NO3-) in G2 site displayed regular diel variation during monitoring; (3) The dissolved inorganic carbon (DIC) and delta13C values in G2 monitoring site showed reverse characteristics in diurnal fluctuations, where DIC decreased in daylight and increased at night while the delta13C value increased in daylight and decreased at night, DIC also showed a negative correlation with the delta13C value (correlation coefficient is -0. 87, P < 0.01) in G2 site. These results indicated that photosynthesis and respiration of aquatic plants, water temperature and degassing jointly affected diurnal variation of hydrochemistry and controlled the cycling process of internal matter in this surface creek fed by karst subterranean river.
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[Analysis of phenotype and genotype in a family with late infantile metachromatic leukodystrophy].
Zhonghua Yi Xue Yi Chuan Xue Za Zhi
PUBLISHED: 10-10-2014
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To study genotype-phenotype correlation of a family with late infantile metachromatic leukodystrophy(MLD).
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Characterization of ATP Alternations in an Alzheimer's Disease Transgenic Mouse Model.
J. Alzheimers Dis.
PUBLISHED: 09-28-2014
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Mitochondrial impairment as evidenced by decline in adenosine 5'-triphosphate (ATP) is associated with oxidative stress in Alzheimer's disease neuropathology and suggests that mitochondria may fail to maintain cellular energy, through reduced ATP production in neurons. To gain insights into the ATP characteristics of Alzheimer's disease transgenic (Tg) mice, we investigated ATP contents in the brain and whole blood of Tg mice at three ages (1-, 5-, and 24-months old). Overall, our results demonstrate that tissue ATP contents in Tg mice are significantly reduced, suggesting a decrease of tissue ATP production and mitochondrial dysfunction.
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[Release of mercury from soil and plant in water-level-fluctuating zone of the Three Gorges Reservoir area and its accumulation in zebrafish].
Huan Jing Ke Xue
PUBLISHED: 09-24-2014
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To investigate the production, distribution and bioavailability of methylmercury (MMHg) in soil and plants of the water-level-fluctuating zone (WLFZ) of the Three Gorges Reservoir area, simulation experiments were conducted in laboratory. Results indicated that the level of total mercury (THg) in soil decreased with the lengthening of submerging time while that in water increased obviously. The level of MMHg in inundated soil and water increased, especially in the water treated by Echinochloa crusgalli and soils. And the MMHg level in that treatment was 2.52 times higher than that treated only by soils for 21 days. This indicated that soil and plants of WLFZ were important sources of mercury in the water of the reservoir. Echinochloa crusgalli as the tested plant was decomposed after being submerged, leading to lower pH and DO and higher DOC, which had little effect on MMHg in soil but significant effect on MMHg in water. The level of THg in the head, viscera and muscle of zebrafish increased obviously, which had a significant correlation with that in water (P < 0.01). MMHg levels accumulated in the head, viscera and muscle of zebrafish differed to some degree, particularly in the head and muscle. After treated in the soils for 21 days, MMHg levels in the head, viscera and muscle of zebrafish were 1.75-6.25, 3.53-8.38 and 2.22-3.36 times higher than those in the control groups, respectively. While for the treatment of Echinochloa crusgalli and soil, MMHg levels in zebrafish's head, viscera and muscle were 3.57, 2.37 and 1.52 times higher than those treated only by soil, respectively. Therefore, submerged soil was the main source of MMHg in fish. And submerged plants changed the water condition and affected the release of mercury to water so as to cause elevated levels of MMHg in fish.
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Multicolored-Fluorescence Switching of ICT-Type Organic Solids with Clear Color Difference: Mechanically Controlled Excited State.
Chemistry
PUBLISHED: 09-23-2014
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A donor-acceptor-type fluorophore containing a twisted diphenylacrylonitrile and triphenylamine has been developed by using the Suzuki reaction. The system indicates typical intramolecular charge-transfer properties. Upon mechanical grinding or hydrostatic pressure, the fluorophore reveals a multicolored fluorescence switching. Interestingly, a fluorescence color transition from green to red was clearly observed, and the change of photoluminescent (PL) wavelength gets close to 111?nm. The mechanisms of high-contrast mechanochromic behavior are fully investigated by techniques including powder XRD, PL lifetime, high-pressure PL lifetime, and Raman spectra analysis. The tremendous PL wavelength shift is attributed to gradual transition of excited states from the local excited state to the charge-transfer state.
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Simulation of injury potential compensation by direct current stimulation in rat spinal cord.
Biomed Mater Eng
PUBLISHED: 09-18-2014
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Injury potential, a significant index of spinal cord injury (SCI), is generated by the movement of extracellular ions. It can be compensated through applied direct current (DC) stimulation, which prevents the influx of the free calcium, and eventually reduces the development of secondary injury. Therefore, the compensation of injury potential is beneficial to the repairing of the function of spinal cord. The compensation effect can be evaluated by whether the magnitudes of longitudinal electric fields (EFs) are compensated to zero. However, there have been no established criteria to determine the distribution and shape of stimulating electrodes. In this study, in order to optimize the stimulating electrodes, a finite element model (FEM) of rat spinal cord was developed, and the EFs changes induced by electrodes of different sizes, shapes and locations after SCI were calculated. All the designed configurations of electrodes were able to compensate injury potential, but the resultant compensation effects vary. Pin and disc electrodes produced uneven EFs, while ring electrodes produced uniformly distributed EFs. Moreover, large ring electrodes can compensate the longitudinal EFs almost to zero with relatively low current density (0.55 ?A/mm(2)) applied. These results provide a basis for the determination of electrical stimulation parameters in the compensation of injury potential.
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A bioelectrical impedance phase angle measuring system for assessment of nutritional status.
Biomed Mater Eng
PUBLISHED: 09-18-2014
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Bioelectrical impedance phase angle has been recommended as a tool to assess nutrition state, but there are no measuring devices have been specially designed for hospital residents. In this study, a system was established for the measurement of bioelectrical impedance phase angle. The electrical composition, calculation method and measuring method of this system are presented in this paper. Experiments showed excellent performance of this system in measuring impedance made of resistors and capacitors. The designed system was also used to measure the bioelectrical impedance phase angle of both healthy subjects and patients with malnutrition, and the results demonstrated that the phase angle of patients with malnutrition is lower than that of healthy subjects (P < 0.01 for male and P < 0.05 for female). These results suggest that phase angle has the potential to be a useful tool for the quantitative assessment of nutritional status.
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Oscillating field stimulation promotes spinal cord remyelination by inducing differentiation of oligodendrocyte precursor cells after spinal cord injury.
Biomed Mater Eng
PUBLISHED: 09-18-2014
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Demyelination is part of the cascading secondary injury after the primary insult and contributes to the loss of function after spinal cord injury (SCI). Oligodendrocyte precursor cells (OPCs) are the main remyelinating cells in the central nervous system (CNS). We explored whether oscillating field stimulation (OFS) could efficiently promote OPC differentiation and improve remyelination after SCI. SD rats with SCI induced by the Allen method were randomly divided into two groups, the SCI+OFS group and SCI group. The former group received active stimulator units and the latter group received sham (inoperative) stimulator units. Additionally, rats that only received laminectomy were referred as the sham group. The electric field intensity was 600 ?V/mm, and the polarity was alternated every 15 minutes. The results showed that the SCI+OFS rats had significantly less demyelination and better locomotor function recovery after 12-weeks treatment. The OFS treatment significantly increased the number of Gal C-positive OPCs after 2-weeks treatment. Furthermore, these rats had higher protein expression of oligodendroglial transcription factors Olig2 and NKx2.2. These findings suggest OFS can promote locomotor recovery and remyelination in SCI rats and this effect may be related to the improved differentiation of OPCs in the spinal cord.
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[Genetics and pedigree analysis of primary carnitine deficiency cardiomyopathy in 6 cases].
Zhonghua Er Ke Za Zhi
PUBLISHED: 09-17-2014
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To investigate the mutation and background of SLC22A5 in 6 patients with primary carnitine deficiency (PCD) who only presented as cardiomyopathy.
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Ultrasmooth and thermally stable silver-based thin films with subnanometer roughness by aluminum doping.
ACS Nano
PUBLISHED: 09-17-2014
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Rough surface and poor stability of ultrathin Ag films limit their applications in nanophotonic and optoelectronic devices. Here, we report an approach for fabricating ultrasmooth and thermally stable Ag-based thin films on SiO2/Si substrates by Al-doping. The effect of Al-doping on the surface morphology and stability of ultrathin Ag films at room temperature and elevated temperature was investigated. The 15 nm Al-doped Ag films with an Al atomic concentration of 4% have a root-mean-square roughness as low as 0.4 nm. The smooth surface morphology is maintained even after 300 °C annealing in N2. Al-doping enhances the nuclei density of films. Moreover, a capping layer spontaneously formed over the Al-doped Ag films restrains the surface diffusion and mass transportation of Ag atoms. Therefore, Al-doping induces ultrathin Ag films with highly stable and ultrasmooth surface morphology.
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HPS6 interacts with dynactin p150Glued to mediate retrograde trafficking and maturation of lysosomes.
J. Cell. Sci.
PUBLISHED: 09-04-2014
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HPS6 was originally identified as a subunit of the BLOC-2 protein complex which is involved in the biogenesis of lysosome-related organelles (LRO). Here, we demonstrate that HPS6 directly interacts with the p150(Glued) subunit of the dynein-dynactin motor complex and acts as cargo adaptor for the retrograde motor to mediate transport of lysosomes from the cell periphery to the perinuclear region. Small interference RNA (siRNA)-mediated knockdown of HPS6 in HeLa cells not only partially blocks centripetal movement of lysosomes but also causes delay in lysosome-mediated protein degradation. Moreover, lysosomal acidification and degradative capacity as well as fusion between LE/MVB and lysosome are also impaired when HPS6 is depleted, suggesting that dynein-dynactin-mediated perinuclear positioning is required for lysosome maturation and activity. Our results have uncovered a novel specific role for HPS6 in the spatial distribution of the lysosomal compartment.
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Treatment outcome of radiotherapy alone versus radiochemotherapy in IE/IIE extranodal nasal-type natural killer/T cell lymphoma: a meta-analysis.
PLoS ONE
PUBLISHED: 09-03-2014
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Previous studies have revealed conflicting findings concerning the efficacy of radiotherapy (RT) and radiochemotherapy (RCT) in IE/IIE extranodal nasal-type natural killer/T cell lymphoma (ENKTL). In this study, we conducted a comprehensive meta-analysis to address this issue.
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Protein kinase LKB1 promotes RAB7-mediated neuropilin-1 degradation to inhibit angiogenesis.
J. Clin. Invest.
PUBLISHED: 09-02-2014
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After internalization, transmembrane receptors (TMRs) are typically recycled back to the cell surface or targeted for degradation. Efficient TMR trafficking is critical for regulation of several processes, including signal transduction pathways, development, and disease. Here, we determined that trafficking of the angiogenic receptor neuropilin-1 (NRP-1) is abrogated by the liver kinase B1 (LKB1), a serine-threonine kinase of the calcium calmodulin family. We found that aberrant NRP-1 expression in tumor cells from patients with lung adenocarcinoma is associated with decreased levels of LKB1. In cultured lung cells, LKB1 accentuated formation of a complex between NRP-1 and RAB7 in late endosomes. LKB1 specifically bound GTP-bound RAB7, but not a dominant-negative GDP-bound form of RAB7, promoting rapid transfer and lysosome degradation of NRP-1. siRNA-mediated depletion of RAB7 disrupted the transfer of NRP-1 to the lysosome, resulting in recovery of the receptor as well as increased tumor growth and angiogenesis. Together, our findings indicate that LKB1 functions as a RAB7 effector and suppresses angiogenesis by promoting the cellular trafficking of NRP-1 from RAB7 vesicles to the lysosome for degradation. Furthermore, these data suggest that LKB1 and NRP-1 have potential as therapeutic targets for limiting tumorigenesis.
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[Effects of low molecular weight organic acids on redox reactions of mercury].
Huan Jing Ke Xue
PUBLISHED: 08-28-2014
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To study the effects of the main component of vegetation root exudates-low molecular weight organic acids on the redox reactions of mercury, laboratory experiments were conducted to investigate the roles of tartaric, citric, and succinic acid in the redox reactions of mercury, and to analyze their interaction mechanism. The results indicated that tartaric acid significantly stimulated the mercury reduction reaction, while citric acid had inhibitory effect. Succinic acid improved the reduction rate at low concentration, and inhibited the reaction at high concentration. The mercury reduction rate by tartaric acid treatment was second-order with respect to Hg2+ concentration, ranging from 0.0014 L x (ng x min)(-1) to 0.005 6 L x (ng x min)(-1). All three organic acids showed a capacity for oxidating Hg(0) in the early stage, but the oxidized Hg(0) was subsequently reduced. The oxidation capacity of the three organic acids was in the order of citric acid > tartaric acid > succinic acid.
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Diurnal characteristics of migration and transformation of mercury and effects of nitrate in Jialing River, Chongqing, China.
Chemosphere
PUBLISHED: 08-19-2014
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Laboratory incubation experiments were performed to identify diurnal characteristics of migration and transformation of mercury (Hg) and effects of nitrate (NO3(-), a hydroxyl radical donor by photolysis) in Jialing River, Chongqing, China. It is found that there are strong diurnal signals of [monomethylmercury (MMHg)] and [reactive Hg (RHg)] in sediment, pore water and overlying water, which suggest that solar radiation may be an important variable that involved in aquatic Hg cycling. Photo-degradation (PD) of MMHg plays a key role in Hg cycling in water systems, and the rates are measured to be 38.22% in March, 2012. The presence of NO3(-) has a marked effect on MMHg PD under solar radiation, and affects inorganic species reducting to Hg(0), resulting in more Hg species available for methylation. So NO3(-) is an important factor for Hg cycling in water systems. Diffusive flux of MMHg, RHg and dissolved Hg (DHg) are 1.92-2.34, 3.43-3.64 and 3.04-5.71ngm(-2)d(-1) at daytime, and 6.04-6.92, 3.22-3.25 and 7.79-8.37ngm(-2)d(-1) at nighttime, respectively, implying that sediment is a major Hg source for shallow-water area in Jialing River at springtime. These results show great importance for understanding Hg biogeochemical processes in clear, oligotrophic, shallow, sluggish, and agriculturally-impacted waters.
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NLRP3 gene silencing ameliorates diabetic cardiomyopathy in a type 2 diabetes rat model.
PLoS ONE
PUBLISHED: 08-19-2014
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Nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome is associated with metabolic disorder and cell death, which are important triggers in diabetic cardiomyopathy (DCM). We aimed to explore whether NLRP3 inflammasome activation contributes to DCM and the mechanism involved.
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High NR2F2 transcript level is associated with increased survival and its expression inhibits TGF-?-dependent epithelial-mesenchymal transition in breast cancer.
Breast Cancer Res. Treat.
PUBLISHED: 08-17-2014
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NR2F2, a member of nuclear receptor subfamily 2, was shown to be associated with cancer, but its role in breast malignancy remains unclear. In this study, we aimed to explore the function of NR2F2 in breast cancer. We browsed GEO and TCGA databases and used Kaplan-Meier survival analysis to explore the association between NR2F2 transcript level and patient survival in breast cancer. NR2F2 expression in breast cancer tissues was evaluated by immunohistochemistry staining. NR2F2-related functions and its role in Epithelial-Mesenchymal Transition (EMT) were predicted by Gene Set Enrichment Analysis (GSEA) and validated by in vitro assays with NR2F2 knockdown MDA-MB231 and MCF7 cells. We found high NR2F2 transcript level was correlated with favorable overall survival and distant metastasis-free survival. Positive rate of NR2F2 protein tended to be decreased with the progression of malignancy. Results of in vitro migration and invasion assays suggested NR2F2's potential in inhibiting invasiveness. NR2F2 was predicted to be negatively linked with EMT and TGF-?-pathway related genes, which was supported by observation of EMT-like morphology and changes in EMT-markers E-cadherin and Slug. Additionally, we found TGF-? inhibited the expression of NR2F2. GSEA also predicted that NR2F2 could be inversely associated with chemoresistance, which was verified by results of in vitro growth inhibition assays using chemotherapeutic agents. Our results demonstrated high NR2F2 transcript level was associated with favorable clinical outcome, which might be due to NR2F2's inhibitory effect on TGF-?-dependent EMT and its role in inhibiting chemoresistance.
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Effects of Tirofiban on Platelet Activation and Endothelial Function in Patients with ST-Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention.
Cell Biochem. Biophys.
PUBLISHED: 08-15-2014
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This pilot study examined, for the first time, the effect of intracoronary administration of tirofiban, an inhibitor of platelet aggregation, on platelet activation and endothelial dysfunction in patients with ST-segment-elevated myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI). A total of 119 STEMI patients were randomized into either tirofiban group (n = 72, intracoronary injection of 10 ?g/kg tirofiban prior to PCI, followed by intravenous infusion at 0.15 ?g/kg min) or a control group (n = 47), which did not receive tirofiban. Periprocedural administration of tirofiban was associated with significantly reduced levels of platelet activation (lower levels of CD62P and PAC-1) and endothelial dysfunction (reduced levels of endothelial microparticles, VCAM-1, and ICAM-1) 48 h after PCI. At 10 days after PCI, patients in the tirofiban group had a higher incidence of complete STR (78.7 vs. 65.0 %) and higher left ventricular ejection fractions (47.8 vs. 44.2) compared to those in the control group. The clinical outcomes between two groups did not differ significantly two weeks after treatment. The results demonstrated that periprocedural administration of tirofiban is associated with significantly attenuated platelet activation and endothelial dysfunction in STEMI patients undergoing PCI. This may have contributed to the improved myocardial reperfusion and preservation of left ventricular systolic function in these patients.
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Fluorescence in situ hybridization of chromosome 17 polysomy in breast cancer using thin tissue sections causes the loss of CEP17 and HER2 signals.
Oncol. Rep.
PUBLISHED: 08-13-2014
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Human epidermal growth factor receptor 2 (HER2 gene) and chromosome 17 polysomy are associated with breast cancer prognosis, chemotherapy and hormone therapy. HER2 gene analysis using fluorescence in situ hybridization (FISH) with 4-µm sections assuming a nuclear diameter of 6 µm caused the loss of genetic DNA. Using intact whole nuclei FISH (WNFISH) and thin tissue section FISH (TTFISH), 109 cases of invasive breast cancer were examined to observe correlations among HER2 gene ampli?cation, CEP17 polysomy and the HER2/CEP17 ratio. The results showed significant differences in the mean copy number of HER2 and the HER2/CEP17 ratios between the WNFISH and TTFISH groups. No significant differences were observed in HER2 amplified, equivocal and non-amplified HER2 samples. Thirty-seven cases of CEP17 polysomy and 72 cases of non?polysomy were detected by WNFISH. Twenty-nine cases of CEP17 polysomy and 72 cases of non-polysomy were detected by TTFISH. Significant differences were observed between the two methods using the McNemar test (P=0.039). In conclusion, detection of chromosome 17 polysomy in breast cancer with fluorescence in situ hybridization using thin tissue sections may cause the loss of CEP17 and HER2 signals.
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Design, synthesis, and fungicidal evaluation of a series of novel 5-methyl-1H-1,2,3-trizole-4-carboxyl amide and ester analogues.
Eur J Med Chem
PUBLISHED: 08-12-2014
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Succinate dehydrogenase inhibitors (SDHIs) are efficient fungicides that are widely used to control plant diseases caused by phytopathogenic fungi, although their effectiveness is undermined by the development of resistance across a range of different fungi. One of the most common structural features of SDHIs is their amide bond. The introduction of greater structural diversity to SDHIs is a promising strategy to delay the onset of resistance. A series of novel SDHIs containing a bioactive 1,2,3-triazole moiety have been designed and synthesized and their fungicidal and insecticidal activities evaluated. The results of these analyses show that most of the newly synthesized 1,2,3-trizole-4-carboxyl amide (ester) analogues exhibit good fungicidal activities, especially towards Sclerotinia sclerotiorum, and a structure-activity relationship study confirmed that the replacement of the amide group with an ester group had little effect on fungicidal activity, which could be provideous in terms of issues and metabolism. 1,6-Dimethyl phenyl was confirmed as the most efficient substituent of the current study when it was placed on both the amide and ester compounds. Interestingly, some of the newly synthesized compounds displayed good insecticidal activities against Culex pipiens pallens. The results of the current study show that these 1,2,3-triazole-4-carboxyl amide and ester analogues represent a new type of SDHI that could be used for the development of novel pesticides.
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Logic nanoparticle beacon triggered by the binding-induced effect of multiple inputs.
ACS Appl Mater Interfaces
PUBLISHED: 08-12-2014
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Recently, the toehold-mediated DNA strand displacement reaction has been widely used in detecting molecular signals. However, traditional strand displacement, without cooperative signaling among DNA inputs, is insufficient for the design of more complicated nanodevices. In this work, a logic computing system is established using the cooperative "binding-induced" mechanism, based on the AuNP-based beacons, in which five kinds of multiple-input logic gates have been constructed. This system can recognize DNA and protein streptavidin simultaneously. Finally, the manipulations of the logic system are also demonstrated by controlling programmed conjugate DNA/AuNP clusters. This study provides the possibility of detecting multiple input signals and designing complex nanodevices that can be potentially applied to the detection of multiple molecular targets and the construction of large-scale DNA-based computation.
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Analgesic effect of different moxibustion durations in rheumatoid arthritis rats.
J Tradit Chin Med
PUBLISHED: 08-09-2014
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To observe the influence of different moxibustion durations on hypothalamic pro-opiomelanocortin (POMC) and prodynorphin (PDYN) mRNA expressions and plasma beta-endorphin (beta-EP) content in rheumatoid arthritis (RA) rats, to understand the mechanism of moxibustion analgesia and its dose-effect relationship.
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Effects of Priming with Recombinant Human Granulocyte Colony-Stimulating Factor on Conditioning Regimen for High-Risk Acute Myeloid Leukemia Patients Undergoing Human Leukocyte Antigen-Haploidentical Hematopoietic Stem Cell Transplantation: A Multicenter Randomized Cont
Biol. Blood Marrow Transplant.
PUBLISHED: 08-08-2014
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HLA-haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is an effective and immediate treatment for high-risk acute myeloid leukemia (HR-AML) patients lacking matched donors. Relapse remains the leading cause of death for HR-AML patients after haplo-HSCT. Accordingly, the prevention of relapse remains a challenge in the treatment of HR-AML. In a multicenter randomized controlled trial in southwestern China, 178 HR-AML patients received haplo-HSCT with conditioning regimens involving recombinant human granulocyte colony-stimulating factor (rhG-CSF) or non-rhG-CSF. The cumulative incidences of relapse and graft-versus-host disease (GVHD), 2-year leukemia-free survival (LFS), and overall survival (OS) were evaluated. HR-AML patients who underwent the priming conditioning regimen with rhG-CSF had a lower relapse rate than those who were treated with non-rhG-CSF (38.2%; 95% confidence interval [CI], 28.1% to 48.3% versus 60.7%, 95% CI, 50.5% to 70.8%; P < .01). The cumulative incidences of acute GVHD, chronic GVHD, transplantation-related toxicity, and infectious complications appeared to be equivalent. In total, 53 patients in the rhG-CSF-priming group and 31 patients in the non-rhG-CSF-priming group were still alive at the median follow-up time of 42 months (range, 24 to 80 months). The 2-year probabilities of LFS and OS in the rhG-CSF-priming and non-rhG-CSF-priming groups were 55.1% (95% CI, 44.7% to 65.4%) versus 32.6% (95% CI, 22.8% to 42.3%) (P < .01) and 59.6% (95% CI, 49.4% to 69.7%) versus 34.8% (95% CI, 24.9% to 44.7%) (P < .01), respectively. Multivariate analyses indicated that the 2-year probability of LFS of patients who achieved complete remission (CR) before transplantation was better than that of patients who did not achieve CR. The 2-year probability of LFS of patients with no M4/M5/M6 subtype was better than that of patients with the M4/M5/M6 subtype in the G-CSF-priming group (67.4%; 95% CI, 53.8% to 80.9% versus 41.9%; 95% CI, 27.1% to 56.6%; P < .05). This study suggests that the rhG-CSF-priming conditioning regimen is an acceptable choice for HR-AML patients, especially for the patients with no M4/M5/M6 subtype who achieved CR before transplantation.
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Role of C5a-C5aR axis in the development of atherosclerosis.
Sci China Life Sci
PUBLISHED: 08-08-2014
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Complement component 5a (C5a) is a 74 amino acid glycoprotein and an important proinflammatory mediator that is cleaved enzymatically from its precursor, C5, on activation of the complement cascade. C5a is quickly metabolised by carboxypeptidases, forming the less-potent C5a desArg. C5a and C5a desArg interact with their receptors (C5aR and C5L2), which results in a number of effects which are essential to the immune response. C5a has a broad range of biological effects throughout the human body because the widespread expression of C5a receptors throughout the human organs enables C5a and C5a desArg to elicit a broad range of biological effects. Recently, accumulating evidence in humans and experimental animal models shows that the C5a-C5aR axis is involved in the development of atherosclerosis lesions. The absence or blockade of C5aRs greatly reduces the formation of atherosclerotic lesions or wire-injury-induced neointima formation in atherosclerosis-prone mice. Serum C5a level was related to the major adverse cardiovascular events in patients with advanced atherosclerosis and those with drug-eluting stent implantation. Thus, the C5a-C5aR axis may be a significant pathogenic driver of arteriosclerotic vascular disease, making C5a-C5aR inhibition an attractive therapeutic strategy.
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Pro-angiogenic effects of Carthami Flos whole extract in human microvascular endothelial cells in vitro and in zebrafish in vivo.
Phytomedicine
PUBLISHED: 07-25-2014
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Carthami Flos (CF) is a Chinese herb traditionally used for cardiovascular disease and bone injury in China with pharmacological effects on improving blood circulation. The aim of this study was to investigate the angiogenic potential of CF whole extract (extracted by boiling with water, followed by ethanol) and the underlying mechanisms in human microvascular endothelial cells (HMEC-1) in vitro and in transgenic TG(fli1:EGFP)(y1)/+(AB) zebrafish with transgenic endothelial cells expressing EGFP (Enhanced Green Fluorescent Protein) in vivo.
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Highly selective and ultra fast solid-phase extraction of N-glycoproteome by oxime click chemistry using aminooxy-functionalized magnetic nanoparticles.
Anal. Chem.
PUBLISHED: 07-25-2014
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For the highly efficient extraction of the N-glycoproteome, a novel solid-phase extraction method based on oxime click chemistry has been developed. With the use of a newly synthesized aminooxy-functionalized magnetic nanoparticle, the oxidized glycan chains on glycopeptides readily react with the aminooxy groups through oxime click chemistry, resulting in the highly selective extraction of glycopeptides. Compared to the traditional hydrazide chemistry-based method, which takes 12-16 h of coupling time, this new method renders excellent enrichment performance within 1 h. Furthermore, the enrichment sensitivity (fmol level), selectivity (extracting glycopeptides from mixtures of nonglycopeptides at a 1:100 molar ratio), and reproducibility (CVs < 20%) are also dramatically improved. We have successfully profiled the N-glycoproteome from only 1 ?L of human colorectal cancer serum using this innovative protocol, which offers a more efficient alternative N-glycoproteome extraction method.
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Long-Term Electrophysiological and Behavioral Analysis on the Improvement of Visual Working Memory Load, Training Gains, and Transfer Benefits.
J Behav Brain Sci
PUBLISHED: 07-22-2014
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Recent evidence demonstrates that with training, one can enhance visual working memory (VWM) capacity and attention over time in the near transfer tasks. Not only do these studies reveal the characteristics of VWM load and the influences of training, they may also provide insights into developing effective rehabilitation for patients with VWM deficiencies. However, few studies have investigated VWM over extended periods of time and evaluated transfer benefits on non-trained tasks. Here, we combined behavioral and electroencephalographical approaches to investigate VWM load, training gains, and transfer benefits. Our results reveal that VWM capacity is directly correlated to the difference of event-related potential waveforms. In particular, the "magic number 4" can be observed through the contralateral delay amplitude and the average capacity is 3.25-item over 15 participants. Furthermore, our findings indicate that VWM capacity can be improved through training; and after training exercises, participants from the training group are able to dramatically improve their performance. Likewise, the training effects on non-trained tasks can also be observed at the 12th week after training. Therefore, we conclude that participants can benefit from training gains, and augmented VWM capacity sustained over long periods of time on specific variety of tasks.
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[Preliminary research on multi-neurotransmitters' change regulation in 120 depression patients' brains].
Zhongguo Zhong Yao Za Zhi
PUBLISHED: 07-22-2014
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In view of the effective traditional Chinese medicine (TCM) in the treatment of clinical depression, the mechanism is not clear, this study attempts to research the cause of depression in a complex situation to lay the foundation for the next step of TCM curative effect evaluation. Based on the brain wave of 120 depression patients and 40 ordinary person, the change regulation of acetylcholine, dopamine, norepinephrine, depression neurotransmitters and excited neurotransmitters in the whole and various encephalic regions' multi-neurotransmitters of depression patients-serotonin are analysed by search of encephalo-telex (SET) system, which lays the foundation for the diagnosis of depression. The result showed that: contrased with the normal person group, the mean value of the six neurotransmitters in depression patients group are: (1) in the whole encephalic region of depression patients group the dopamine fall (P < 0.05), and in the double centralregions, right temporal region and right parietal region distinct fall (P < 0.01); (2) in the right temporal region of depression patients group the serotonin rise (P < 0.05); (3) in the right central region, left parietal region of depression patients group the acetylcholine fall (P < 0.05), left rear temporal region fall obviously (P < 0.01). The correlation research between antagonizing pairs of neurotransmitters and neurotransmitters: (1) the three antagonizing pairs of neurotransmitters-serotonin and dopamine, acetylcholine and norepinephrine, depression neurotransmitters and excited neurotransmitters, in ordinary person group and depression patients group are characterizeed by middle or strong negative correlation. Serotonin and dopamine, which are characterized by weak negative correlation in the right rear temporal region of ordinary person group, are characterized by strong negative correlation in the other encephalic regions and the whole encephalic (ordinary person group except the right rear temporal region: the range of [r] is [0.82, 0.92], P < 0.01)/(depression patients group:the range of [r] is [0.88, 0.94], P < 0.01); acetylcholine and norepinephrine, in the whole and various encephalic region are characterized by middle negative correlation(ordinary person group:the range of [r] is [0.39, 0.76], P < 0.01 or P < 0.05)/(depression patients group: the range of [Ir] is [0.56, 0.64], P < 0.01); depression neurotransmitters and excited neurotransmitters are characterized by middle strong negative correlation (ordinary person group: the range of [r] is [0.57, 0.80], P < 0.01)/(depression patients group: the range of [r] is [0.68, 0.78], P < 0.01). (2) The two neurotransmitters which are not antagonizing pairs of neurotransmitters, serotonin and excited neurotransmitters, or acetylcholine and depression neurotra-nsmitters, or dopamine and depression neurotransmitters in the various encephalic regions are characterized by weak negative correlation. Serotonin and excited neurotransmitters are characterizeed by weak negative correlation (ordinary person group: in the right central region, left parietal region, double front temporal regions, right rear temporal region, the range of [r] is [0.25, 0.50], P < 0.01 or P < 0.05)/(depression patients group: in the whole encephalic regions, double parietal regions, double occipital regions, right front temporal region, left central region, left frontal region, the range of [r] is [0.18, 0.37], P < 0.01 or P < 0.05); acetylcholine and depression, neurotransmitters are characterized by weak negative correlation (ordinary person group: in the double frontal regions, left parietal region, left front temporal region, right rear temporal region, the range of [r] is [0.31, 0.46], P < 0.01 or P < 0.05)/(depression patients group: in double rear temporal regions, right front temporal region, double occipital regions, left central region, the range of [r] is [0.20, 0.32] , P < 0.01 or P < 0.05); do-pamine and depression neurotransmitters are characterized by weak middle negative correlation (ordinary person group: in left parietal region, right central region, left frontal region, left occipital region, double front temporal regions, the range of [r] is [0.33, 0.68], P < 0.01 or P < 0.05)/(depression patients group: in the whole region and other various regions except the left frontal region, right central region, the range of Irl is [0.21, 0.34], P < 0.01 or P < 0.05). Dopamine and acetylcholine or norepinephrine and serotonin are characterized by weak positive correlation in all encephalic regions. Dopamine and acetylcholine are characterized by weak positive correlation (ordinary person group: in left frontal region, right parietal region, left front temporal region and left rear temporal region, the range of [r] is [0.37, 0.46], P < 0.01)/(depression patients group: in the whole region and the orther various regions except the double central regions, the range of [r] is [0.23, 0.5], P < 0.01 or P < 0.05); norepinephrine and serotonin are characterized by weak positive correlation (ordinary person group: in double front temporal regions, double rear temporal regions, right frontal region and left parietal region, the range of [r] is [0.34, 0.48], P < 0.01 or P < 0.05)/(depression patients group: in the whole and various regions, the range of [r] is [0.18, 0.42], P < 0.01). The main differences between the depression patients group and ordinary person group are: (1) In the whole regin, left frontal region and right central region of depression patients group, the six neurotransmitters all fall normally (P < 0.05). (2) The percent of dopamine falling or including dopamine falling, or including dopamine falling and serotonin rising in depression patients group increases. The percent of dopamine falling or including dopamine falling in the whole region, right frontal region, right central region increases (P < 0.01), such as dopamine decreasing, serotonin increasing dopamine decreasing, serotonin increasing acetylcholine decreasing dopamine decreasing, dopamine decreasing norepinephrine increasing depression neurotransmitters decreasing, serotonin increasing acetylcholine decreasing dopamine decreasing neurotransmitters increasing and so on. (3) The percent of acetylcholine falling, or including acetylcholine falling, or including acetylcholine falling and neurotransmitters (beta)-receptor)rising in depression patients group increases. The percent of acetylcholine falling, or including acetylcholine falling in the right temporal region, double central regions increases (P < 0.05 or P < 0.01), such as acetylcholine decreasing, acetylcholine decreasing neurotransmitters increaseng, acetylcholine decreasing neurotransmitters increasing depression neurotransmitters decreasing, serotonin increasing acetylcholine decreasing dopamine decreasing neurotransmitters increasing and so on. It's showed in research that depression patients' brain are characterized by multi-neurotransmitters abnormal, the synchronous change of multi-neurotransmitters has some certain regularities, which are not the simple linear relation. It's conformed that the three antagonizing pairs, neurotransmitters-serotonin and dopamine, acetylcholine and norepinephrine, depression eurotransmitters and excited neurotransmitters of ordinary person group and depression patients group, are both characterized by strong antagonizing relation, that the two neurotransmitters which are not antagonizing pairs of neurotransmitters are characterized by weak positive correlation or negative correlation, prompt maybe has the indirect causal relationship. And the change of six neurotransmitters in depression patients' various encephalic regions is rather complex. It's conformed preliminarily that the right frontal region and right central region are characterized by dopamine decreasing, acetylcholine decreasing, serotonin increasing dopamine decreasing, serotonin increasing acetylcholine decreasing dopamine decreasing, dopamine decreasing norepinephrine increasing excited neurotransmitters decreasing, serotonin increasing acetylcholine decreasing dopamine decreasing neurotransmitters increasing, acetylchoine decreasing neurotransmitters increasing, acetylcholine decreasing neurotransmitters increasing excited neurotransmitters decreasing and so on. Contrasted with the ordinary person group, the depression patients group have the notable difference.
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iTRAQ-based quantitative proteomics analysis of Brassica napus leaves reveals pathways associated with chlorophyll deficiency.
J Proteomics
PUBLISHED: 07-21-2014
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Photosynthesis, the primary source of plant biomass, is important for plant growth and crop yield. Chlorophyll is highly abundant in plant leaves and plays essential roles in photosynthesis. We recently isolated a chlorophyll-deficient mutant (cde1) from ethyl methanesulfonate (EMS) mutagenized Brassica napus. Herein, quantitative proteomics analysis using the iTRAQ approach was conducted to investigate cde1-induced changes in the proteome. We identified 5069 proteins from Brassica napus leaves, of which 443 showed differential accumulations between the cde1 mutant and its corresponding wild-type. The differentially accumulated proteins were found to be involved in photosynthesis, porphyrin and chlorophyll metabolism, biosynthesis of secondary metabolites, carbon fixation, spliceosome, mRNA surveillance and RNA degradation. Our results suggest that decreased abundance of chlorophyll biosynthetic enzymes and photosynthetic proteins, impaired carbon fixation efficiency and disturbed redox homeostasis might account for the reduced chlorophyll contents, impaired photosynthetic capacity and increased lipid peroxidation in this mutant. Epigenetics was implicated in the regulation of gene expression in cde1, as proteins involved in DNA/RNA/histone methylation and methylation-dependent chromatin silencing were up-accumulated in the mutant. Biological significance Photosynthesis produces more than 90% of plant biomass and is an important factor influencing potential crop yield. The pigment chlorophyll plays essential roles in light harvesting and energy transfer during photosynthesis. Mutants deficient in chlorophyll synthesis have been used extensively to investigate the chlorophyll metabolism, development and photosynthesis. However, limited information is available with regard to the changes of protein profiles upon chlorophyll deficiency. Here, a combined physiological, histological, proteomics and molecular analysis revealed several important pathways associated with chlorophyll deficiency. This work provides new insights into the regulation of chlorophyll biosynthesis and photosynthesis in higher plants and these findings may be applied to genetic engineering for high photosynthetic efficiency in crops.
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Integrative expression vectors for overexpression of xylitol dehydrogenase (XYL2) in Osmotolerant yeast, Candida glycerinogenes WL2002-5.
J. Ind. Microbiol. Biotechnol.
PUBLISHED: 07-18-2014
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Yeasts are excellent hosts for the production of recombinant proteins. Candida glycerinogenes WL2002-5, an osmotolerant yeast with extremely high glycerol productivity, provides an attractive eukaryotic expression platform. The integrative vectors PURGAP-gfp and PURGPD-gfp harbouring phleomycin-resistance coding sequence and GFP coding sequence with PCgGAP, PCgGPD promoter, respectively, were constructed. The recombinant plasmid PURPpGAP-gfp with the promoter PPpGAP based on the sequence of Pichia pastoris GAPDH gene and the plasmid PURScGAP-gfp with the promoter PScGAP from Saccharomyces cerevisiae were constructed. After transformation, the copy number of gfp gene, which determined using fluorescent quantitative real-time polymerase chain reaction (FQ-RTPCR) in genome of C. glycerinogenes is 1. Expressions of gfp at different levels were conducted using different promoters by osmotic stress containing NaCl or glucose for the recombinant strains. In this study, C. glycerinogenes WL2002-5, expressing xylitol dehydrogenase (XYL2) gene from Pichia stipitis, has the ability to produce glycerol from xylose entered into pentose phosphate pathway. Two recombinant strains of PURGAPX, PURGPDX with XYL2 overexpression were constructed to ferment a mixture of glucose and xylose simultaneously in batch fermentation. Compared to C. glycerinogenes WL2002-5 strain, glycerol production from xylose in strains PURGAPX, PURGPDX were increased by 95.9 and 121.1 %, respectively.
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Regulatory T cells prevent angiotensin II-induced abdominal aortic aneurysm in apolipoprotein E knockout mice.
Hypertension
PUBLISHED: 07-14-2014
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To test the hypothesis that adoptive transfer of regulatory T cells (Tregs) may dose-dependently inhibit the formation of angiotensin II-induced abdominal aortic aneurysm in apolipoprotein E knockout mice, we established an animal model of abdominal aortic aneurysm by angiotensin II infusion in apolipoprotein E knockout mice. Then mice received different treatment with PBS, low-dose Tregs, high-dose Tregs, or CD25-depleting PC61 antibody. Histopathologic analysis showed that the incidence of abdominal aortic aneurysm was 80%, 76%, 27%, and 71% in the PBS, low-dose Tregs, high-dose Tregs, and PC61 groups, respectively. Tregs treatment markedly decreased macrophage and CD4+ T-cell infiltration and preserved the medial smooth muscle cells. Furthermore, Tregs decreased the levels of proinflammatory cytokines, matrix metalloproteinase-2 (MMP-2) and MMP-9, increased the expression of anti-inflammatory interleukin-10 and transforming growth factor-?, and suppressed apoptosis and oxidative stress. In vitro, Tregs inhibited the response of human aortic smooth muscle cells to angiotensin II and reduced the expression of proinflammatory cytokines, MMP-2 and MMP-9, possibly by inhibiting the activation of nuclear factor-?B and extracellular signal-regulate kinase 1/2. In addition, Tregs downregulated macrophage type 1-related genes and upregulated macrophage type 2-related genes. However, Tregs-mediated effects were largely reversed by disrupting cell-cell contact or using neutralizing antibodies against interleukin-10 and transforming growth factor-?. Adoptive transfer of Tregs dose-dependently prevents angiotensin II-induced abdominal aortic aneurysm in apolipoprotein E knockout mice. The mechanisms may involve declined proinflammatory cytokine expression and MMP-2 and MMP-9 levels and enhanced anti-inflammatory cytokine expression, which is mediated by direct cell-cell contact and soluble mediators.
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Large-area binary blazed grating coupler between nanophotonic waveguide and LED.
ScientificWorldJournal
PUBLISHED: 07-13-2014
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A large-area binary blazed grating coupler for the arrayed waveguide grating (AWG) demodulation integrated microsystem on silicon-on-insulator (SOI) was designed for the first time. Through the coupler, light can be coupled into the SOI waveguide from the InP-based C-band LED for the AWG demodulation integrated microsystem to function. Both the length and width of the grating coupler are 360 ?m, as large as the InP-based C-band LED light emitting area in the system. The coupler was designed and optimized based on the finite difference time domain method. When the incident angle of the light source is 0°, the coupling efficiency of the binary blazed grating is 40.92%, and the 3 dB bandwidth is 72 nm at a wavelength of 1550 nm.
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[The expression of SIRT1 in brainstem of rats in different types of hypoxia and its significance].
Zhonghua Jie He He Hu Xi Za Zhi
PUBLISHED: 07-12-2014
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To explore the correlation between SIRT1 expression in brainstem and apnea hypopnea index and the effect of hypoxia on SIRT1 expression in rats.
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miR-193a-3p regulates the multi-drug resistance of bladder cancer by targeting the LOXL4 gene and the Oxidative Stress pathway.
Mol. Cancer
PUBLISHED: 07-10-2014
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Chemoresistance is a major obstacle to the curative cancer chemotherapy and presents one of the most formidable challenges in both research and management of cancer.
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High performance bianisotropic metasurfaces: asymmetric transmission of light.
Phys. Rev. Lett.
PUBLISHED: 07-10-2014
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It is experimentally shown that bianisotropic metasurfaces allow for extreme polarization control of light with high performance. A metasurface providing asymmetric transmission (i.e., polarization conversion) of circularly polarized light is reported at a wavelength of 1.5???m. The experimental transmittance and extinction ratio are 50% and 20:1, which represents an order of magnitude improvement over previous optical structures exhibiting asymmetric transmission. The metasurface consists of patterned gold sheets that are spaced at a subwavelength distance from each other. The same design and fabrication processes can be used in the future to completely control the phase, amplitude, and polarization of light.
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Covalent agonists for studying G protein-coupled receptor activation.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 07-08-2014
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Structural studies on G protein-coupled receptors (GPCRs) provide important insights into the architecture and function of these important drug targets. However, the crystallization of GPCRs in active states is particularly challenging, requiring the formation of stable and conformationally homogeneous ligand-receptor complexes. Native hormones, neurotransmitters, and synthetic agonists that bind with low affinity are ineffective at stabilizing an active state for crystallogenesis. To promote structural studies on the pharmacologically highly relevant class of aminergic GPCRs, we here present the development of covalently binding molecular tools activating Gs-, Gi-, and Gq-coupled receptors. The covalent agonists are derived from the monoamine neurotransmitters noradrenaline, dopamine, serotonin, and histamine, and they were accessed using a general and versatile synthetic strategy. We demonstrate that the tool compounds presented herein display an efficient covalent binding mode and that the respective covalent ligand-receptor complexes activate G proteins comparable to the natural neurotransmitters. A crystal structure of the ?2-adrenoreceptor in complex with a covalent noradrenaline analog and a conformationally selective antibody (nanobody) verified that these agonists can be used to facilitate crystallogenesis.
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Characteristics of stem cells derived from rat fascia: In vitro proliferative and multilineage potential assessment.
Mol Med Rep
PUBLISHED: 07-01-2014
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Fascia?derived stem cells (FDSCs) were previously isolated from the fascia of the gluteus maximus of the rat. However, the use of FDSCs as a cell source for musculoskeletal tissue engineering has not been compared with that of adipose?derived stem cells (ADSCs) and bone marrow?derived mesenchymal stem cells (BMSCs). Therefore, the present study aimed to compare the mesenchymal stem cell (MSC) and self?renewal stem cell markers, proliferative capacity and multilineage differentiation potential of these stem cells in vitro. The MSC and embryonic stem cell (ESC) marker profiles were compared using flow cytometry and quantitative polymerase chain reaction (qPCR). Their proliferative capacities were compared using 5?bromo?2'?deoxyuridine and MTT assays. Their osteogenic, adipogenic and chondrogenic differentiation potentials were compared using standard staining assays and qPCR. The FDSCs possessed similar cell morphology and immunophenotypic profiles with BMSCs and ADSCs. FDSCs demonstrated a similar expression pattern of ESC markers with ADSCs, which has higher expression of sex determining region Y?box (Sox)2 and octamer?binding transcription factor 4, and lower expression of Krüppel?like factor 4, when compared with BMSCs. FDSCs exhibited higher proliferation under serum?deprived conditions (0.5% FBS growth medium), and attained higher expression levels of collagen type I, ? 2 and type II, ? 1 as well as Sox9 mRNA than ADSCs and BMSCs upon chondrogenic induction. An increased amount of proteoglycan deposition was also observed in the FDSC group. However, lower levels of adipogenic and osteogenic marker expression in FDSCs were detected compared with ADSCs and BMSCs upon adipogenic and osteogenic induction, respectively. FDSCs possessed high chondrogenic potential, low osteogenic and adipogenic differentiation potential and were responsive to the induction signals for collagen?rich fascial structure regeneration. Therefore, FDSCs may represent an improved alternative cell source to conventional ADSCs and BMSCs for musculoskeletal tissue repair and tissue engineering, particularly for collagen?rich structures with poor vasculature.
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[Higher procalcitonin level in diabetic nephropathy patients compared with healthy volunteers].
Sichuan Da Xue Xue Bao Yi Xue Ban
PUBLISHED: 06-20-2014
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To investigate the difference of procalcitonin (PCT) level between uninfected diabetic nephropathy patients and healthy volunteers.
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Angiotensin(1-7) attenuates the progression of streptozotocin-induced diabetic renal injury better than angiotensin receptor blockade.
Kidney Int.
PUBLISHED: 06-16-2014
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To explore the potential therapeutic effects of angiotensin(1-7) (Ang(1-7)), an endogenous ligand of the Mas receptor, on streptozotocin-induced diabetic nephropathy, male Wistar rats were randomly divided into two groups: a control group and a diabetic model group. After 12 weeks, the diabetic rats were divided into subgroups for 4-week treatments consisting of no-treatment group, small-, moderate-, and large-dose Ang(1-7) groups, a valsartan group, a large-dose Ang(1-7) plus valsartan group, and an A779 (antagonist of the Mas receptor) group, each with 15 rats. Ang(1-7) improved renal function, attenuated glomeruli sclerosis, oxidative stress, and cell proliferation, decreased the expression of collagen IV, TGF-?1, VEGF, NOX4, p47phox, PKC?, and PKC?1, and the phosphorylation of Smad3. In the rat mesangial HBZY-1 cell line, Ang(1-7) decreased high-glucose-induced oxidative stress, the proliferation and expression of NOX4, p47phox, and TGF-?1, the phosphorylation of Smad3, collagen IV, and VEGF, and the membrane translocation of PKC? and PKC?1. A779 blocked the effects of Ang(1-7) both in vivo and in vitro. The effects of large-dose Ang(1-7) alone and in combination with valsartan were superior to valsartan alone, but the combination had no significant synergistic effect compared with Ang(1-7) alone. Thus, Ang(1-7) ameliorated streptozotocin-induced diabetic renal injury. Large-dose treatment was superior to valsartan in reducing oxidative stress and inhibiting TGF?1/Smad3- and VEGF-mediated pathways.Kidney International advance online publication, 30 July 2014; doi:10.1038/ki.2014.274.
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PQ-69, a novel and selective adenosine A1 receptor antagonist with inverse agonist activity.
Purinergic Signal.
PUBLISHED: 06-15-2014
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Potent and selective adenosine A1 receptor (A1AR) antagonists with favourable pharmacokinetic properties used as novel diuretics and antihypertensives are desirable. Thus, we designed and synthesized a series of novel 4-alkylamino substitution-2-arylpyrazolo[4,3-c]quinolin-3-one derivatives. The aim of the present study is to characterize the biological profiles of the optimized compound, PQ-69. In vitro binding assay revealed a K i value of 0.96 nM for PQ-69 in cloned hA1 receptor, which was 217-fold more selective compared with hA2A receptors and >1,000-fold selectivity for hA1 over hA3 receptor. The results obtained from [(35)S]-GTP?S binding and cAMP concentration assays indicated that PQ-69 might be an A1AR antagonist with inverse agonist activity. In addition, PQ-69 displayed highly inhibitory activities on isolated guinea pig contraction (pA2 value of 8.99) induced by an A1AR agonist, 2-chloro-N6-cyclopentyl adenosine. Systemic administration of PQ-69 (0.03, 0.3, 3 mg/kg) increased urine flow and sodium excretion in normal rats. Furthermore, PQ-69 displayed better metabolic stability in vitro and longer terminal elimination half-life (t 1/2) in vivo compared with 1,3-dipropyl-8-cyclopentylxanthine. These findings suggest that PQ-69 exhibits potent antagonist effects on A1AR in vitro, ex vivo and in vivo, it might be a useful research tool for investigating A1AR function, and it could be developed as a potential therapeutic agent.
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[Characterization of muscular involvement in patients with Duchenne muscular dystrophy by magnetic resonance imaging].
Zhonghua Yi Xue Yi Chuan Xue Za Zhi
PUBLISHED: 06-15-2014
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To study the order and degree of muscular affection in patients with Duchenne muscular dystrophy (DMD) during the course of disease.
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A simulation study of mercury release fluxes from soils in wet-dry rotation environment.
J Environ Sci (China)
PUBLISHED: 06-13-2014
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A simulative mesocosm study was conducted to evaluate the influence of wet-dry rotation on mercury (Hg) flux from soil/water to air and the distribution of Hg species in water as well as Hg chemical fractions in soil. Three types of soil were employed including two kinds of paddy soil, Typic Purpli-Udic Cambosols (TPUC) and Xanthi-Udic Ferralosols (XUF), as well as the Alluvial Soil (AS) from Three Gorge reservoir area in Chongqing, China. The results showed that Hg fluxes in wetting periods were significantly higher than that in drying periods. It might be due to the formation of a layer of stable air over the water surface in which some redox reactions promote evasion processes over the water surface. This result indicated that more Hg would be evaporated from the Three Gorge reservoir and paddy soil field during the flooding season. Hg fluxes were positively correlated with air temperature and solar irradiation, while negatively correlated with air humidity and the electronic conductivity of water. Hg fluxes from AS and TPUC were significantly higher than that from XUF, which might be due to the higher organic matter (OM) contents in XUF than TPUC and AS. The reduction processes of oxidized Hg were restrained due to the strong binding of Hg to OM, resulting in the decrease in Hg flux from the soil.
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Comprehensive proteomic analysis of a Chinese 2-herb formula (Astragali Radix and Rehmanniae Radix) on mature endothelial cells.
Proteomics
PUBLISHED: 06-08-2014
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Endothelial cells are crucially involved in wound healing angiogenesis, restoring blood flow to wound tissues. Our previous study demonstrated that the Chinese 2-herb formula (NF3) possesses significant wound healing effect in diabetic foot ulcer rats with promising in vitro proangiogenic effects on human umbilical vein endothelial cells (HUVEC). Here, we present the comparative global proteome analysis of NF3-treated HUVEC in static or scratch conditions, screening the comprehensive molecular targets in governing the proangiogenic response in wound healing. Our results suggest plasminogen activator inhibitor-1, specifically down-regulated in static condition and Annexin A1 and Annexin A2, up-regulated in scratch condition, as principal proteins responsible for the proangiogenesis in wound healing. We also identified a panel of cytoskeleton regulatory proteins in static and scratch condition, mediating the migratory behavior of NF3-treated HUVEC. The key proteins in static state include myosin regulatory light polypeptide 9, SPAST, tropomyosin (TPM)2, and Vimentin while that in scratch state contained prelamin-A/C, TPM1, TPM2, and Vimentin. In addition, NF3 was shown to regulate transcription and translation, cell-cell interaction, and ROS defense in HUVEC. Proliferation and migration assays further confirmed the identified principal proteins plasminogen activator inhibitor-1 and Annexin A2 which are responsible for NF3-induced proangiogenesis of HUVEC in wound healing. This is the first study on the global proteome expression of NF3-treated HUVEC with the identification of the differences at the molecular level, between static and scratch conditions involved in wound healing angiogenesis.
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Effects of gonadotropin on Fas and/or FasL expression and proliferation in rat ovary.
Theriogenology
PUBLISHED: 06-05-2014
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Although gonadotropin is a dominant hormone involved in promoting ovarian follicle development in females, the mechanism by which gonadotropin regulates follicular development is still unknown. To systematically evaluate the effectiveness of the gonadotropin on apoptosis and proliferation of ovarian cells in vivo, rats were injected subcutaneously with eCG and/or anti-eCG antiserum. Equine chorionic gonadotropin treatment increased ovarian cell proliferation and expression of FSH receptors (FSHR) as revealed by increased immunostaining of proliferating cell nuclear antigen and FSHR in rat ovary. These effects did not occur in a follicular stage-dependent manner. Moreover, these actions were abolished by anti-eCG antiserum. However, granulosa cells exhibited more intense Fas- and FasL-positive immunostaining during all follicular stages in the anti-eCG antiserum group. We used Western blot analysis to confirm these results; Fas and FasL protein contents in rat ovaries were decreased by eCG. Meanwhile, proliferating cell nuclear antigen and FSHR expression were upregulated by eCG. However, all these eCG-induced regulations were reversed by anti-eCG antiserum treatment. Furthermore, there were no significant differences between the anti-eCG antiserum and control groups. These results indicate that eCG promotes follicular development via downregulation of death-inducer Fas/FasL expression and promotion of ovarian cell proliferation, which is partially mediated by FSHR.
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[Distribution and risk assessment of mercury species in soil of the water-level-fluctuating zone in the Three Gorges Reservoir].
Huan Jing Ke Xue
PUBLISHED: 06-03-2014
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To investigate pollution level and ecological risk of mercury in soils of the water-level-fluctuating zone in the Three Gorges Reservoir Region, 192 surface soil samples from 14 counties (districts) in Chongqing were obtained. Concentrations of THg and Hg species, bioavailable Hg were analyzed and discussed. Geoaccumulation index (I(geo)) and Håkanson potential ecological risk index (E(r)) were applied to assess the pollution status and potential ecological risk of THg and Hg species, respectively. The results showed that significant differences in the concentration of THg were found in soils of water-level-fluctuating zone in the Three Gorges Reservoir. The THg concentration ranged from 22.4 to 393.5 microg x kg(-1), with an average of (84.2 +/- 54.3) microg x kg(-1). 76.6% of the samples' THg content was higher than the soil background value in the Three Gorges Reservoir Region. The percentage of five mercury species (water-soluble Hg, HCl-soluble Hg, KOH-soluble Hg, H2O2-soluble Hg, residue Hg) in soils were 4.1%, 15.5%, 18.3%, 10.9%, 51.3%, respectively. The average concentrations of bioavailable mercury varied between 19.7-36.6 microg x kg(-1), and the percentage of bioavailable Hg was 22.1%-51.6% of THg. According to the geoaccumulation index, the soils were lightly polluted by Hg. Håkanson single potential ecological risk index evaluation showed that Hg species had a low potential ecological risk, moreover, soils of water-level-fluctuating zone in the Three Gorges Reservoir were at low ecological risk levels as evaluated by bioavailable Hg. While, the assessment results based on THg of soils was much higher than that based on the Hg species. Two methods of evaluation showed that the I(geo) and E(r) values calculated based on the Hg species better reflected the actual pollution levels of soils and its hazard to aquatic organisms.
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Magnetic MSP@ZrO? microspheres with yolk-shell structure: designed synthesis and application in highly selective enrichment of phosphopeptides.
Langmuir
PUBLISHED: 05-29-2014
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Magnetic yolk-shell MSP@ZrO2 microspheres consisting of a movable magnetic supraparticle (MSP) core and a crystalline ZrO2 shell were synthesized via a two-step controlled "sol-gel" approach for the first time. First, a large amount of the generated hydrolyzate Zr(OH)4 was firmly fixed onto the surface of the cross-linked polymethylacrylic acid matrix via a strong hydrogen-bonding interaction between Zr(OH)4 and the carboxyl groups. Then a calcination process was adopted to convert the Zr(OH)4 into a continuous ZrO2 shell and simultaneously make the ZrO2 shell crystallized. At the same time, the polymer matrix could be selectively removed to form a yolk-shell structure, which has better dispersibility and higher adsorbing efficiency of phosphopeptides than its solid counterpart. The formation mechanism of such yolk-shell microspheres could be reasonably proved by the results of TEM, TGA, VSM, XRD, and FT-IR characterization. By taking advantage of the unique properties, the yolk-shell MSP@ZrO2 exhibited high specificity and great capability in selective enrichment of phosphopeptides, and a total of 33 unique phosphopeptides mapped to 33 different phosphoproteins had been identified from 1 mL of human saliva. This result clearly demonstrated that the yolk-shell MSP@ZrO2 has great performance in purifying and identifying the low-abundant phosphopeptides from real complex biological samples. Moreover, the synthetic method can be used to produce hybrid yolk-shell MSP@ZrO2-TiO2.
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Observations of a Metal-Insulator Transition and Strong Surface States in Bi2-x Sbx Se3 Thin Films.
Adv. Mater. Weinheim
PUBLISHED: 05-22-2014
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High-quality thin films of the topological insulator Bi2-x Sbx Se3 are grown by molecular beam epitaxy. A metal-insulator transition along with strong surface states - revealed by Shubnikov-de Haas oscillations - is observed as the Sb concentration is increased. This system represents a widely tunable platform for achieving high surface conduction, suppressing the bulk influence, and manipulating the band structure of topological insulators.
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An ultrathin, smooth, and low-loss Al-doped Ag film and its application as a transparent electrode in organic photovoltaics.
Adv. Mater. Weinheim
PUBLISHED: 05-17-2014
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An ultrathin, smooth, and low-loss Ag film without a wetting layer is achieved by co-depositing a small amount of Al into Ag. The film can be as thin as 6 nm, with a roughness below 1 nm and excellent mechanical flexibility. Organic photovoltaics that use these thin films as transparent electrode show superior efficiency to their indium tin oxide (ITO) counterparts because of improved photon management.
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Association between LGALS2 3279C>T and coronary artery disease: A case-control study and a meta-analysis.
Biomed Rep
PUBLISHED: 04-22-2014
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Coronary artery disease (CAD) has become the main cause of mortality worldwide. Lectin galactoside-binding soluble-2 (LGALS2) is involved in the cytokine lymphotoxin-? (LTA) cascade that may influence the progress of CAD. The aim of the present study was to assess the association between the LGALS2 3279C>T (rs7291467) polymorphism and CAD. A total of 562 cases and 572 controls were recruited to examine the association. A systematic meta-analysis was performed to evaluate the contribution of LGALS2 3279C>T polymorphism to the risk of CAD among 12,093 cases and 11,020 controls. There was no significant association found in the present case-control study. However, the meta-analysis showed that LGALS2 3279C>T played a protective role in CAD [P=0.008, odds ratio (OR), 0.90; 95% confidence interval (95% CI), 0.82-0.97] and particularly in the Asian population (P=0.006; OR, 0.82; 95% CI, 0.71-0.94). The present case-control study did not find a significant association between LGALS2 3279C>T and CAD in the Eastern Han Chinese population. However, the meta-analysis indicated that LGALS2 3279C>T played a protective role in CAD, suggesting an ethnic difference in the association of the locus with CAD.
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Diagnostic value of microRNA-21 in the diagnosis of lung cancer: evidence from a meta-analysis involving 11 studies.
Tumour Biol.
PUBLISHED: 03-12-2014
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Molecular biomarkers that can be detected in easily accessible body fluids have been proposed as non-invasive, cost-effective, and useful tools for cancer diagnosis. Recently, extensive research has explored the involvement of the aberrant expression of microRNA-21 (miRNA-21, miR-21) in lung cancer. Inconsistent results, however, have prevented its widespread use in diagnosis. In light of this situation, our meta-analysis aimed to systematically determine whether aberrant miR-21 expression can distinguish patients with lung cancer from cancer-free controls with a high level of diagnostic accuracy. A comprehensive literature search for relevant studies published before December 23, 2013 was conducted in the MEDLINE, EMBASE, the Cochrane Library, and three Chinese databases. The pooled sensitivity, specificity and other parameters were used to assess the overall performance of miR-21-based assays. Statistical analysis was conducted using the STATA 11.0 software. Eleven research articles involving 676 patients with lung cancer and 529 healthy controls were considered eligible for inclusion in the present meta-analysis. The following summary parameters were calculated from all the included studies: sensitivity of 0.66 (95 % confidence interval [CI]: 0.57-0.74), specificity of 0.82 (95 % CI: 0.74-0.88), positive likelihood ratio (PLR) of 3.70 (95 % CI: 2.50-5.60), negative likelihood ratio (NLR) of 0.42 (95 % CI: 0.32-0.54); diagnostic odds ratio (DOR) of 9.00 (95 % CI: 5.00-16.00), and area under the curve (AUC) of 0.81 (95 % CI: 0.77-0.84). In addition, we added two pre-specified covariates (ethnicity and specimen types) to the bivariate model to assess their impact on the diagnostic value of miR-21 for lung cancer. Similar results were also observed in subgroup analyses, indicating a relatively low level of accuracy. The current meta-analysis indicates that a single miR-21 may not be sufficient to identify lung cancer and that more miRNAs should be used to detect lung carcinoma.
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Prevalence of and risk factors for gallstones in Uighur and Han Chinese.
World J. Gastroenterol.
PUBLISHED: 03-08-2014
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To perform a single-centre survey of the prevalence of and possible risk factors for gallstones in Uighur and Han Chinese.
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Nickel-catalyzed decarboxylative acylation of heteroarenes by sp2 C-H functionalization.
Chemistry
PUBLISHED: 03-07-2014
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Nickel-catalyzed ligand-free decarboxylative cross-coupling of azole derivatives with ?-oxoglyoxylic acids has been developed. This work represents the first example of decarboxylative cross-coupling reactions, in a C-H bond functionalization manner, through nickel catalysis, and tolerates various functional groups. Additionally, this approach provides an efficient access to azole ketones, an important structural motif in many medicinal compounds with a broad range of biological activities.
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Pneumocystis jirovecii dihydropteroate synthase gene mutations in a group of HIV-negative immunocompromised patients with Pneumocystis pneumonia.
Exp Ther Med
PUBLISHED: 03-05-2014
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The purpose of this study was to investigate dihydropteroate synthase (DHPS) mutations and their clinical context in non-HIV-infected patients with Pneumocystis pneumonia (PCP). DHPS genes in respiratory samples collected from HIV-negative patients with PCP presented between January 2008 and April 2011 were amplified by polymerase chain reaction (PCR) and sequenced. Basic clinical data from the medical records of the patients were also reviewed. The most common point mutations, which result in Thr55Ala and Pro57Ser amino acid substitutions, were not detected in the Pneumocystis jirovecii sampled from the HIV-negative patients. Two other point mutations, which result in nonsynonymous mutation, Asp90Asn and Glu98Lys, were identified in P. jirovecii from two patients. Among the patients, the levels of lactate dehydrogenase (LDH), C-reactive protein (CRP) and plasma (1-3) ?-D-glucan were elevated in 75, 92.31 and 42.86% of patients, respectively. The percentage of circulating lymphocytes was significantly lower in non-survivors than in survivors [4.2%, interquartile range (IQR) 2.4-5.85 versus 10.1%, IQR 5.65-23.4; P=0.019]. The neutrophil proportion in bronchoalveolar lavage fluid (BALF) was significantly higher in non-survivors than in survivors (49.78±27.67 versus 21.33±15.03%; P=0.047). Thirteen patients had received adjunctive corticosteroids (1 mg/kg/day prednisone equivalent) and nine (69.23%) of them eventually experienced treatment failure. No common DHPS gene mutations of P. jirovecii were detected in the HIV-negative PCP patients. However, other mutations did exist, the significance of which remains to be further identified. The elevation of neutrophil counts in BALF and reduction of the number of lymphocytes in peripheral blood may be associated with poor outcome. The efficacy of adjunctive steroid therapy in HIV-negative patients with P. jirovecii infection requires further investigation.
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Evaluation of chromosome 17 polysomy in breast cancer by FISH analysis of whole nuclei, and its clinicopathological significance.
Oncol Lett
PUBLISHED: 02-26-2014
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Human epidermal growth factor receptor 2 (HER2) amplification and overexpression are associated with poor prognosis and resistance to cytotoxic drugs in patients with breast cancer. Increases in the number of HER2 gene copies have been shown to be associated with chromosome 17 polysomy. The use of whole, intact nuclei for fluorescence in situ hybridization (FISH) assay improves the accuracy of the results. FISH analysis of whole nuclei (WNFISH) and immunohistochemistry (IHC) were used to analyze HER2 gene amplification and HER2 protein expression in 109 breast cancer specimens. Chromosome 17 polysomy and its correlations with HER2 gene amplification, HER2 protein expression and the clinicopathological outcomes of the patients were also investigated. Among the 109 cases, WNFISH detected HER2 amplification in 30 cases, equivocal amplification in 19 cases and no amplification in 60 cases. WNFISH detected chromosome 17 centromere (CEP17) polysomy in 37 cases and no polysomy in 72 cases. Among the 109 cases assessed by tissue microarray and IHC, 31 cases were HER2-negative, 14 cases were scored 1+, 23 cases were scored 2+ and 41 cases were scored 3+. The results demonstrated that in the cases with chromosome 17 polysomy, the HER2 gene was amplified, HER2 protein expression was increased and the incidences of nuclear atypia and lymph node metastases were higher compared with those in the cases without chromosome 17 polysomy. Chromosome 17 polysomy may correlate with increased malignant potential and metastatic spread in breast cancer.
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HMGB1 mediates hyperglycaemia-induced cardiomyocyte apoptosis via ERK/Ets-1 signalling pathway.
J. Cell. Mol. Med.
PUBLISHED: 02-22-2014
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Apoptosis is a key event involved in diabetic cardiomyopathy. The expression of high mobility group box 1 protein (HMGB1) is up-regulated in diabetic mice. However, the molecular mechanism of high glucose (HG)-induced cardiomyocyte apoptosis remains obscure. We aimed to determine the role of HMGB1 in HG-induced apoptosis of cardiomyocytes. Treating neonatal primary cardiomyocytes with HG increased cell apoptosis, which was accompanied by elevated levels of HMGB1. Inhibition of HMGB1 by short-hairpin RNA significantly decreased HG-induced cell apoptosis by reducing caspase-3 activation and ratio of Bcl2-associated X protein to B-cell lymphoma/leukemia-2 (bax/bcl-2). Furthermore, HG activated E26 transformation-specific sequence-1 (Ets-1), and HMGB1 inhibition attenuated HG-induced activation of Ets-1 via extracellular signal-regulated kinase 1/2 (ERK1/2) signalling. In addition, inhibition of Ets-1 significantly decreased HG-induced cardiomyocyte apoptosis. Similar results were observed in streptozotocin-treated diabetic mice. Inhibition of HMGB1 by short-hairpin RNA markedly decreased myocardial cell apoptosis and activation of ERK and Ets-1 in diabetic mice. In conclusion, inhibition of HMGB1 may protect against hyperglycaemia-induced cardiomyocyte apoptosis by down-regulating ERK-dependent activation of Ets-1.
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An electrochemical DNA sensor for sequence-specific DNA recognization in a homogeneous solution.
Biosens Bioelectron
PUBLISHED: 02-01-2014
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In this work, a sensitive electrochemical DNA sensor based on an avidin modified electrode and a DNA-functionalized Au nanoparticle (DFNP) was developed. The DNA-functionalized Au nanoparticle contained two kinds of DNA, one is hairpin probe DNA with a biotin at the 3' terminal and a thiol at the 5' terminal, the other is methylene blue (MB)-labeled linear signal DNA. Without hybridizing with the target DNA, the loop of the hairpin impeded biotin linked with avidin on electrode. However, after target hybridization, the hairpin was opened and biotin was recognized by avidin which resulted in a DNA-functionalized Au nanoparticle brought on the electrode surface. Electrochemical signals of MB bound to signal DNA were measured by differential pulse voltammetry (DPV). Taking advantage of amplification effects of the AuNP and binding specificity of the hairpin probe, this DNA biosensor greatly simplified the electrochemical DNA detection method and displayed high specificity in DNA detection. By using this new method, we demonstrate that this prototype sensor has been able to detect as low as picomolar DNA targets with excellent differentiation ability even for a single mismatch.
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Control of gold nanoparticles based on circular DNA strand displacement.
J Colloid Interface Sci
PUBLISHED: 01-28-2014
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In this study, DNA strand displacement is utilized to control the aggregation of DNA/gold nanoparticles (AuNPs) based on circular DNA, in which DNA/AuNP conjugates are captured and released by adding different DNA signal strands. Using this strategy, single DNA/nanoparticle building blocks are capable of assembling into complex structures of two and three circular DNA/nanoparticles. The existence of these structures is demonstrated by gel electrophoresis and transmission electron microscopy (TEM) analysis. This advance has potential applications in controlling, transporting and detecting DNA/AuNP conjugates with subsequent manipulation of the structure and function of these assemblies.
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Human umbilical cord blood-derived stromal cells: A new source of stromal cells in hematopoietic stem cell transplantation.
Crit. Rev. Oncol. Hematol.
PUBLISHED: 01-14-2014
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The hematopoietic inductive microenvironment (HIM), which is composed of stromal cells, extracellular matrix and cytokines, plays a vital role in hematopoietic stem cell transplantation (HSCT). Bone marrow stromal cells (BMSCs), as the main component of HIM, have been well studied. However, the highly invasive procedure of bone marrow (BM) collection limits the clinical application of BMSCs. Human umbilical cord blood-derived stromal cells (hUCBDSCs) isolated and cultured in our laboratory have attracted much attention for their ease collection and low probability of pathophoresis. Previous research demonstrated that hUCBDSCs have numerous functions that are identical to those of BMSCs, for example, hUCBDSCs can support the growth of hematopoietic stem and progenitor cells, especially during the expansion of megakaryocyte colony-forming units (CFU-Mk), promote engraftment after hematopoietic stem cell transplantation (HSCT), exert immunosuppressive effects on xenogenic T cells in vitro and suppress acute graft-versus-host disease (aGVHD) in vivo. Although hUCBDSCs, as new stromal cells, have not been used in clinical practice, they have great practical significance because of their superiority in hematopoiesis and the regulation of immunity.
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Design of dual-diameter nanoholes for efficient solar-light harvesting.
Nanoscale Res Lett
PUBLISHED: 01-01-2014
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A dual-diameter nanohole (DNH) photovoltaic system is proposed, where a top (bottom) layer with large (small) nanoholes is used to improve the absorption for the short-wavelength (long-wavelength) solar incidence, leading to a broadband light absorption enhancement. Through three-dimensional finite-element simulation, the core device parameters, including the lattice constant, nanohole diameters, and nanohole depths, are engineered in order to realize the best light-matter coupling between nanostructured silicon and solar spectrum. The designed bare DNH system exhibits an outstanding absorption capability with a photocurrent density (under perfect internal quantum process) predicted to be 27.93 mA/cm(2), which is 17.39%, 26.17%, and over 100% higher than the best single-nanohole (SNH) system, SNH system with an identical Si volume, and equivalent planar configuration, respectively. Considering the fabrication feasibility, a modified DNH system with an anti-reflection coating and back silver reflector is examined by simulating both optical absorption and carrier transport in a coupled way in frequency and three-dimensional spatial domains, achieving a light-conversion efficiency of 13.72%.
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Maternal LPS exposure during pregnancy impairs testicular development, steroidogenesis and spermatogenesis in male offspring.
PLoS ONE
PUBLISHED: 01-01-2014
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Lipopolysaccharide (LPS) is associated with adverse developmental outcomes including embryonic resorption, fetal death, congenital teratogenesis and fetal growth retardation. Here, we explored the effects of maternal LPS exposure during pregnancy on testicular development, steroidogenesis and spermatogenesis in male offspring. The pregnant mice were intraperitoneally injected with LPS (50 µg/kg) daily from gestational day (GD) 13 to GD 17. At fetal period, a significant decrease in body weight and abnormal Leydig cell aggregations were observed in males whose mothers were exposed to LPS during pregnancy. At postnatal day (PND) 26, anogenital distance (AGD), a sensitive index of altered androgen action, was markedly reduced in male pups whose mothers were exposed to LPS daily from GD13 to GD 17. At PND35, the weight of testes, prostates and seminal vesicles, and serum testosterone (T) level were significantly decreased in LPS-treated male pups. At adulthood, the number of sperm was significantly decreased in male offspring whose mothers were exposed to LPS on GD 13-17. Maternal LPS exposure during gestation obviously diminished the percent of seminiferous tubules in stages I-VI, increased the percent of seminiferous tubules in stages IX-XII, and caused massive sloughing of germ cells in seminiferous tubules in mouse testes. Moreover, maternal LPS exposure significantly reduced serum T level in male mice whose mothers were exposed to LPS challenge during pregnancy. Taken together, these results suggest that maternal LPS exposure during pregnancy disrupts T production. The decreased T synthesis might be associated with LPS-induced impairments for spermatogenesis in male offspring.
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Risk factors for long-term outcome of drug-eluting stenting in adults with early-onset coronary artery disease.
Int J Med Sci
PUBLISHED: 01-01-2014
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We lack data on the long-term outcome of drug-eluting stenting in patients with early-onset coronary artery disease (CAD). Here, we investigated the association of traditional risk factors and major adverse cardiovascular events (MACEs) after drug-eluting stenting in patients with CAD who were < 50 years old.
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Association between low serum magnesium level and major adverse cardiac events in patients treated with drug-eluting stents for acute myocardial infarction.
PLoS ONE
PUBLISHED: 01-01-2014
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We investigated the association of serum magnesium (Mg) levels and major adverse cardiac events (MACEs) after drug-eluting stent (DES) implantation.
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The association between the phenotype of excessive daytime sleepiness and blood pressure in patients with obstructive sleep apnea-hypopnea syndrome.
Int J Med Sci
PUBLISHED: 01-01-2014
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Investigate the clinical features and the blood pressure (BP) pattern of the phenotype of excessive daytime sleepiness (EDS) in OSAHS.
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