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Find video protocols related to scientific articles indexed in Pubmed.
Catalyst engineering for lithium ion batteries: the catalytic role of Ge in enhancing the electrochemical performance of SnO2(GeO2)0.13/G anodes.
Nanoscale
PUBLISHED: 11-04-2014
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The catalytic role of germanium (Ge) was investigated to improve the electrochemical performance of tin dioxide grown on graphene (SnO2/G) nanocomposites as an anode material of lithium ion batteries (LIBs). Germanium dioxide (GeO2) and SnO2 nanoparticles (<10 nm) were uniformly anchored on the graphene sheets via a simple single-step hydrothermal method. The synthesized SnO2(GeO2)0.13/G nanocomposites can deliver a capacity of 1200 mA h g(-1) at a current density of 100 mA g(-1), which is much higher than the traditional theoretical specific capacity of such nanocomposites (?702 mA h g(-1)). More importantly, the SnO2(GeO2)0.13/G nanocomposites exhibited an improved rate, large current capability (885 mA h g(-1) at a discharge current of 2000 mA g(-1)) and excellent long cycling stability (almost 100% retention after 600 cycles). The enhanced electrochemical performance was attributed to the catalytic effect of Ge, which enabled the reversible reaction of metals (Sn and Ge) to metals oxide (SnO2 and GeO2) during the charge/discharge processes. Our demonstrated approach towards nanocomposite catalyst engineering opens new avenues for next-generation high-performance rechargeable Li-ion batteries anode materials.
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Role of Transient Receptor Potential Vanilloid Type 1 and C-C Chemokine Receptor 2 in Renal Injury Induced by Salt-sensitive Hype.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao
PUBLISHED: 11-01-2014
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Objective To determine the effects of transient receptor potential vanilloid type 1(TRPV1)channel ablation and a chemokine receptor 2(CCR2)antagonist on salt-sensitive hypertension-induced renal injury. Methods Wild-type(WT)and TRPV1-null mutant(TRPV1(-/-))mice were subjected to uninephrectomy and deoxycorticosterone acetate(DOCA)-salt treatment for 4 weeks with or without a CCR2 antagonist,RS504393(n=8 for all the 4 groups). Sham WT and TRPV1(-/-)mice(both n=7)underwent uninephrectomy without receiving DOCA and saline. Systolic blood pressure,urinary excretion of albumin,8-isoprostane and creatinine clearance for 24 hours were assayed during the experimental period and at the end of the 4-week treatment. The morphological analysis was performed in renal histological sections,including glomerulosclerosis,tubulointerstitial injury,and monocyte/macrophage infiltration. Results Compared to the corresponding control mice,DOCA-salt treatment in both WT and TRPV1(-/-)mice led to increased systolic blood pressure(SBP),enhanced urinary excretion of albumin and 8-isoprostane,decreased creatinine clearance,increased glomerulosclerosis and tubulointerstitial injury associated with enhanced monocyte/macrophage infiltration(all P<0.05),all of which were much more severe in TRPV1(-/-)mice compared to WT mice with the exception of blood pressure(all P<0.05). RS5043943 attenuated DOCA-salt-induced changes in renal function and morphology in WT and TRPV1(-/-)mice(all P<0.05). There was no difference in blood pressure among DOCA-salt WT and TRPV1(-/-)mice with or without RS505393 with the exception of sham WT and TRPV1(-/-)mice(all P>0.05). Conclusions CCR2 antagonist inhibits DOCA-salt-induced renal injury and monocyte/macrophage infiltration in WT and TRPV1(-/-)mice with the greater in the latter strain. Activation of TRPV1 attenuates salt-sensitive hypertension-induced renal injury possibly via inhibition of CCR2-induced monocyte/macrophage infiltration.
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Spectral Unmixing via Data-guided Sparsity.
IEEE Trans Image Process
PUBLISHED: 10-21-2014
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Hyperspectral unmixing, the process of estimating a common set of spectral bases and their corresponding composite percentages at each pixel, is an important task for hyperspectral analysis, visualization and understanding. From an unsupervised learning perspective, this problem is very challenging-both the spectral bases and their composite percentages are unknown, making the solution space too large. To reduce the solution space, many approaches have been proposed by exploiting various priors. In practice, these priors would easily lead to some unsuitable solution. This is because they are achieved by applying an identical strength of constraints to all the factors, which does not hold in practice. To overcome this limitation, we propose a novel sparsity based method by learning a data-guided map to describe the individual mixed level of each pixel. Through this data-guided map, the `p (0 < p < 1) constraint is applied in an adaptive manner. Such implementation not only meets the practical situation, but also guides the spectral bases toward the pixels under highly sparse constraint. What's more, an elegant optimization scheme as well as its convergence proof have been provided in this paper. Extensive experiments on several datasets also demonstrate that the data-guided map is feasible, and high quality unmixing results could be obtained by our method.
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Three-dimensional Cephalometric Analysis of Adolescents With Cleft Lip and Palate Using Computed Tomography-Guided Imaging.
J Craniofac Surg
PUBLISHED: 10-21-2014
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To propose landmarks and a new coordinate system to aid three-dimensional cephalometric analysis of adolescent cleft lip and palate (CLP) using computed tomography (CT) imaging.
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Influence of atmospheric turbulence on the transmission of orbital angular momentum for Whittaker-Gaussian laser beams.
Opt Express
PUBLISHED: 10-17-2014
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We analyze the effects of turbulence on the detection probability spectrum and the mode weight of the orbital angular momentum (OAM) for Whittaker-Gaussian (WG) laser beams in weak non-Kolmogorov turbulence channels. Our numerical results show that WG beam is a better light source for mitigating the effects of turbulence with several adjustable parameters. The real parameters of WG beams ? and W0, which have significant effects on the mode weight, have no influence on the detection probability spectrum. Larger signal OAM quantum number, shorter wavelength, smaller beamwidth and coherence length will lead to the lower detection probability of the signal OAM mode.
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A double-blind, randomized phase II study of dicycloplatin plus paclitaxel versus carboplatin plus paclitaxel as first-line therapy for patients with advanced non-small-cell lung cancers.
Arch Med Sci
PUBLISHED: 10-03-2014
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The aim of this study was to compare the efficacy and toxicity of dicycloplatin plus paclitaxel with those of carboplatin plus paclitaxel as first-line treatment for patients with advanced non-small-cell lung cancer (NSCLC).
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[Research of bimingan granule on dendritic cell in allergic rhinitis mice].
Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi
PUBLISHED: 09-25-2014
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To investigate the mechanism.
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[Treating lupus nephritis by a drug pair of radix astragali and rehmanniae radix combined with glucocorticoid: a preliminary clinical study].
Zhongguo Zhong Xi Yi Jie He Za Zhi
PUBLISHED: 09-17-2014
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To observe the therapeutic effect of a drug pair of Radix Astragali and Rehmanniae Radix combined with glucocorticoid (GC) in treating lupus nephritis (LN) patients and its influence on some experimental indices.
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[The key points to the successful repair of cerebrospinal fluid rhinorrhea].
Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi
PUBLISHED: 09-09-2014
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To summarize the clinical experience of endoscopic repair for cerebrospinal fluid (CSF) rhinorrhea in our department in the last 4 years.
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[An overview of surveillance of avian influenza viruses in wild birds].
Bing Du Xue Bao
PUBLISHED: 08-15-2014
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Wild birds (mainly Anseriformes and Charadriiformes) are recognized as the natural reservoir of avian influenza viruses (AIVs). The long-term surveillance of AIVs in wild birds has been conducted in North America and Europe since 1970s. More and more surveillance data revealed that all the HA and NA subtypes of AIVs were identified in the wild ducks, shorebirds, and gulls, and the AIVs circulating in wild birds were implicated in the outbreaks of AIVs in poultry and humans. Therefore, the AIVs in wild birds pose huge threat to poultry industry and human health. To gain a better understanding of the ecology and epidemiology of AIVs in wild birds, we summarize the transmission of AIVs between wild birds, poultry, and humans, the main results of surveillance of AIVs in wild birds worldwide and methods for surveillance, and the types of samples and detection methods for AIVs in wild birds, which would be vital for the effective control of avian influenza and response to possible influenza pandemic.
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Association between fetuin-A levels with insulin resistance and carotid intima-media thickness in patients with new-onset type 2 diabetes mellitus.
Biomed Rep
PUBLISHED: 07-24-2014
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Fetuin-A, which is known to inhibit insulin signaling and pathological calcification, has emerged as a diabetes risk biomarker. In the present study, the association between the fetuin-A levels with insulin resistance (IR) and carotid intima-media thickness (CIMT) was investigated in patients with new-onset type 2 diabetes mellitus (nT2DM). A total of 100 patients with nT2DM (nT2DM group) and 100 normal glucose tolerance (NGT group) controls were evaluated. The serum fetuin-A level was measured by a commercial solid-phase ELISA kit. The estimate of IR was calculated by homeostasis model assessment (HOMA-IR). CIMT was measured by B-mode ultrasound. The association between the serum fetuin-A levels and the metabolic parameters was also analyzed. The serum fetuin-A levels were increased significantly in the nT2DM group compared to the NGT group (368.5±15.6 mg/ml vs. 152.7±7.1 mg/ml, P<0.01). Fetuin-A was positively correlated with HOMA-IR, CIMT, glycated hemoglobin, triglyceride, low-density lipoprotein cholesterol, body mass index, systolic blood pressure, fasting blood glucose and 2 h post-glucose load blood glucose (P<0.05 and P<0.01), but negatively correlated with fasting plasma insulin, 2 h plasma insulin after glucose overload, high-density lipoprotein cholesterol and HOMA-?-cell insulin secretion index (P<0.05 and P<0.01). To the best of our knowledge, the study demonstrated for the first time that there is a significant association between the serum fetuin-A levels with IR and CIMT in nT2DM. These results indicate that serum fetuin-A levels can be used as independent markers in the diagnosis of macroangiopathies in nT2DM.
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3D graphene supported MoO2 for high performance binder-free lithium ion battery.
Nanoscale
PUBLISHED: 07-17-2014
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In this work, we report the synthesis of MoO2 nanoparticles grown on three dimensional graphene (3DG) via the reduction of ?-MoO3 nanobelts through a facile chemical vapor deposition (CVD) approach under argon protection gas environment. In this synthesis approach, the presence of hydrophobic 3DG promoted the Volmer-Weber growth of MoO2 nanoparticles (30-60 nm). The as-prepared MoO2-3DG nanocomposite was directly used as a binder-free anode electrode for lithium ion batteries (LIBs) without additives and exhibited excellent electrochemical performance. It delivered high reversible capacities of 975.4 mA h g(-1) and 537.3 mA h g(-1) at the current densities of 50 and 1000 mA g(-1), respectively. Moreover, the electrode also showed an increased capacity from 763.7 mA h g(-1) to 986.9 mA h g(-1) after 150 discharge and charge cycles at a current density of 200 mA g(-1). The enhanced electrochemical performance of MoO2-3DG nanocomposite electrode may be attributed to the synergistic effects of MoO2 nanoparticles and 3DG layers. This facile CVD synthesis process presents a feasible route for large-scale production of high performance, environmentally friendly electrode. In addition, this process also has the potential of being utilized in other materials for energy storage devices application.
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Experience with percardiac interventions for multiple congenital heart diseases in children.
Interact Cardiovasc Thorac Surg
PUBLISHED: 07-16-2014
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To report our experience with percardiac interventions for multiple congenital heart diseases in children.
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UV-B irradiation alleviates the deterioration of cold-stored mangoes by enhancing endogenous nitric oxide levels.
Food Chem
PUBLISHED: 06-22-2014
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Effects of UV-B radiation on chilling injury, ripening and endogenous nitric oxide (NO) levels in mango fruit were evaluated. Chilling injury index, ion leakage, and malondialdehyde (MDA) content of the fruit pretreated with 5kJm(-2) UV-B for 4h were significantly lower than those of the control during fruit ripening at ambient temperature following cold storage at 6°C for 10days. Fruit firmness of the mangoes irradiated with UV-B was significantly higher than the control during the ripening period. Endogenous NO levels of the UV-B-irradiated fruit were rapidly increased after UV-B treatment. Pre-treatment of mangoes with the NO specific scavenger, not only abolished UV-B-triggered NO accumulation, but also suppressed the UV-B-reduced chilling injury, oxidative damage, and ripening delay of the fruit. Together, the results suggest that UV-B treatment may enhance chilling tolerance and delay fruit ripening of mangoes by triggering endogenous NO generation in the fruit.
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CTLA-4 SNPs (CT60A/G, -1722T/C, -1661G/A, and -318C/T) and systemic lupus erythematosus: a meta-analysis.
Crit. Rev. Eukaryot. Gene Expr.
PUBLISHED: 06-19-2014
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In this meta-analysis, we investigated the association between CTLA-4 polymorphisms (CT60A/G, -1722T/C, -1661G/A, and -318C/T) and SLE susceptibility. Data were extracted independently by two reviewers. The odds ratios (ORs) with 95% confidence intervals (CIs) were calculated in fixed or random effects models. Seventeen studies involving of 3931 cases and 4619 controls were identified. Significant association of promoter -1722T/C polymorphism and SLE was observed for TT vs. CC (OR=1.63, 95% CI 1.63-2. 30, P<0.05) in the overall study population and in the Asians subgroups (OR=2. 18, 95% CI 1.70-2. 81, P<0.05); the OR for the allele T vs. C in Asians was 1.66 (95% CI 1.33-2. 07, P<0.05). For the CT60A/G polymorphism, significant association was observed for AA vs. AG (OR=0.64, 95% CI 0.46-0.88, P<0.05) in Asians. These results suggest that -1722T/C and CT60A/G polymorphisms in CTLA-4 are associated with SLE, particularly in Asians.
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Super-resolution imaging and tracking of protein-protein interactions in sub-diffraction cellular space.
Nat Commun
PUBLISHED: 06-18-2014
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Imaging the location and dynamics of individual interacting protein pairs is essential but often difficult because of the fluorescent background from other paired and non-paired molecules, particularly in the sub-diffraction cellular space. Here we develop a new method combining bimolecular fluorescence complementation and photoactivated localization microscopy for super-resolution imaging and single-molecule tracking of specific protein-protein interactions. The method is used to study the interaction of two abundant proteins, MreB and EF-Tu, in Escherichia coli cells. The super-resolution imaging shows interesting distribution and domain sizes of interacting MreB-EF-Tu pairs as a subpopulation of total EF-Tu. The single-molecule tracking of MreB, EF-Tu and MreB-EF-Tu pairs reveals intriguing localization-dependent heterogonous dynamics and provides valuable insights to understanding the roles of MreB-EF-Tu interactions.
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C-kit and PDGFRA gene mutations in triple negative breast cancer.
Int J Clin Exp Pathol
PUBLISHED: 06-15-2014
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In this study, we evaluated C-kit immunohistochemical expression and C-kit and platelet derived growth factor receptor A (PDGFRA) gene mutations in triple negative breast cancer. 171 cases were analyzed by immunohistochemical staining for the expression of C-kit and 45 cases, including 10 C-kit negative cases and 35 C-kit positive cases, were performed for C-kit gene mutations in exons 9, 11, 13 and 17 and PDGFRA gene mutations in exons 12 and 18. C-kit expression was detected in 42.1% of triple negative breast cancers. Only 1 activating mutation was detected in exon 11 of C-kit gene in 1 case. No activating mutations were found in the other 44 cases. C-kit expression is a frequent finding in triple negative breast cancers; 1 activating mutation which was also found in gastrointestinal stromal tumors was detected; a few cases might benefit from imatinib.
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Important impacts of intestinal bacteria on utilization of dietary amino acids in pigs.
Amino Acids
PUBLISHED: 05-26-2014
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Bacteria in pig intestine can actively metabolize amino acids (AA). However, little research has focused on the variation in AA metabolism by bacteria from different niches. This study compared the metabolism of AA by microorganisms derived from the lumen and epithelial wall of the pig small intestine, aiming to test the hypothesis that the metabolic profile of AA by gut microbes was niche specific. Samples from the digesta, gut wall washes and gut wall of the jejunum and ileum were used as inocula. Anaerobic media containing single AA were used and cultured for 24 h. The 24-h culture served as inocula for the subsequent 30 times of subcultures. Results showed that for the luminal bacteria, all AA concentrations except phenylalanine in the ileum decreased during the 24-h in vitro incubation with a increase of ammonia concentration, while 4 AA (glutamate, glutamine, arginine and lysine) in the jejunum decreased, with the disappearance rate at 60-95 %. For tightly attached bacteria, all AA concentrations were generally increased during the first 12 h and then decreased coupled with first a decrease and then an increase of ammonia concentration, suggesting a synthesis first and then a catabolism pattern. Among them, glutamate in both segments, histidine in the jejunum and lysine in the ileum increased significantly during the first 12 h and then decreased at 24 h. The concentrations of glutamine and arginine did not change during the first 12 h, but significantly decreased at 24 h. Jejunal lysine and ileal threonine were increased for the first 6 or 12 h. For the loosely attached bacteria, there was no clear pattern for the entire AA metabolism. However, glutamate, methionine and lysine in the jejunum decreased after 24 h of cultivation, while glutamine and threonine in the jejunum and glutamine and lysine in the ileum increased in the first 12 h. During subculture, AA metabolism, either utilization or synthesis, was generally decreased with disappearance rate around 20-40 % for most of AA and negligible for branch chained AA (BCAA). However, the disappearance rate of lysine in each group was around 90 % throughout the subculture, suggesting a high utilization of lysine by bacteria from all three compartments. Analysis of the microbial community during the 24-h in vitro cultivation revealed that bacteria composition in most AA cultures varied between different niches (lumen and wall-adherent fractions) in the jejunum, while being relatively similar in the ileum. However, for isoleucine and leucine cultures, bacteria diversity was similar between the luminal fraction and tightly attached fraction, but significantly higher than in the loosely attached fraction. For glutamine and valine cultures, bacteria diversity was similar between the luminal and loosely attached fractions, but lower than that of tightly attached bacteria. After 30 subcultures, bacteria diversity in arginine, valine, glutamine, and leucine cultures varied between niches in the jejunum while being relatively stable in the ileum, consistent with those in the 24-h in vitro cultures. The findings may suggest that luminal bacteria tended to utilize free AA, while tightly attached adherent bacteria seemed in favor of AA synthesis, and that small intestinal microbes contributed little to BCAA metabolism.
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Inhibition of SATB1 expression in regulatory T cells contributes to hepatitis B virus-related chronic liver inflammation.
Mol Med Rep
PUBLISHED: 05-13-2014
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Regulatory T cells (Tregs) contribute to the pathogenesis of chronic hepatitis B (CHB). Special AT-rich sequence-binding protein 1 (SATB1) may be a key component of this process. In the present study, Tregs and conventional T cells (Tconvs) were isolated by magnetic cell sorting of peripheral blood from CHB patients (n=57), individuals with resolved hepatitis B virus (HBV) infections (n=15), and healthy controls (n=29). SATB1 expression was studied by reverse transcription?quantitative PCR, flow cytometry and immunofluorescence microscopy, and the correlation of SATB1 expression to the expression of liver inflammation serum markers and the HBV DNA load was assessed. CHB patients showed significantly reduced SATB1 expression in Tregs than healthy controls and individuals with resolved HBV infections. Moreover, SATB1 expression in Tregs was significantly lower than in Tconvs of patients with chronic HBV infection. Serum HBV DNA and liver inflammation markers were inversely correlated to the SATB1 mRNA level in Tregs. Antiviral treatment was accompanied by increased expression of the SATB1 gene in Tregs. Thus, Tregs from CHB patients have reduced levels of SATB1, which is resolved with antiviral therapy. Inhibition of SATB1 expression may impair the hepatic inflammatory response and contribute to HBV persistence.
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Metabolic profiles of biological aging in American Indians: the strong heart family study.
Aging (Albany NY)
PUBLISHED: 05-07-2014
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Short telomere length, a marker of biological aging, has been associated with age-related metabolic disorders. Telomere attrition induces profound metabolic dysfunction in animal models, but no study has examined the metabolome of telomeric aging in human. Here we studied 423 apparently healthy American Indians participating in the Strong Family Heart Study. Leukocyte telomere length (LTL) was measured by qPCR. Metabolites in fasting plasma were detected by untargeted LC/MS. Associations of LTL with each metabolite and their combined effects were examined using generalized estimating equation adjusting for chronological age and other aging-related factors. Multiple testing was corrected using the q-value method (q<0.05). Of the 1,364 distinct m/z features detected, nineteen metabolites in the classes of glycerophosphoethanolamines, glycerophosphocholines, glycerolipids, bile acids, isoprenoids, fatty amides, or L-carnitine ester were significantly associated with LTL, independent of chronological age and other aging-related factors. Participants with longer (top tertile) and shorter (bottom tertile) LTL were clearly separated into distinct groups using a multi-marker score comprising of all these metabolites, suggesting that these newly detected metabolites could be novel metabolic markers of biological aging. This is the first study to interrogate the human metabolome of telomeric aging. Our results provide initial evidence for a metabolic control of LTL and may reveal previously undescribed new roles of various lipids in the aging process.
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Changes of major tea polyphenols and production of four new B-ring fission metabolites of catechins from post-fermented Jing-Wei Fu brick tea.
Food Chem
PUBLISHED: 04-18-2014
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HPLC analysis of samples from four major fermentation procedures of Jing-Wei Fu brick tea showed that the level of major tea catechins epigallocatechin gallate (EGCG) and epicatechin gallate (ECG) dropped increasingly to about 1/3 in the final product. Phytochemical study of the final product led to the discovery of four new B-ring fission metabolites of catechins (BRFCs) Fuzhuanin C-F (1-4) together with three known BRFCs (5-7), six known catechins (8-13), five simple phenols (14-18), seven flavones and flavone glycosides (19-25), two alkaloids (26, 27), three triterpenoids (28-30) and one steroid (31). The structures were elucidated by spectroscopic methods including 1D and 2D NMR, LC-HR-ESI-MS, IR, and CD spectra. Five compounds (16-18, 28, 29) were reported for the first time in tea. Possible pathways for the degradation of major tea catechins and the generation of BRFCs were also provided.
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Clinical classification of Caroli's disease: an analysis of 30 patients.
HPB (Oxford)
PUBLISHED: 04-15-2014
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Caroli's disease (CD) is a rare congenital disorder. The early diagnosis of the disease and differentiation of types I and II are of extreme importance to patient survival. This study was designed to review and discuss observations in 30 patients with CD and to clarify the clinical characteristics of the disease.
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Large dosage of chishao in formulae for cholestatic hepatitis: a systematic review and meta-analysis.
Evid Based Complement Alternat Med
PUBLISHED: 04-03-2014
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Objective. To evaluate the efficacy and safety of large dosage of Chishao in formulae for treatment of cholestatic hepatitis. Methods. The major databases (PubMed, Embase, Cochrane Library, Chinese Biomedical Database Wanfang, VIP medicine information system, and China National Knowledge Infrastructure) were searched until January 2014. Randomized controlled trials (RCTs) of large dosage of Chishao in formulae that reported on publications in treatment of cholestatic hepatitis with total efficacy rate, together with the biochemical indices including alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), and direct bilirubin (DBIL), were extracted by two reviewers. The Cochrane tool was used for the assessment of risk of bias included trials. Data were analyzed with RevMan 5.2.7 software. Results. 11 RCTs involving 1275 subjects with cholestatic hepatitis were included. Compared with essential therapy, large dosage of Chishao in formulae demonstrated more efficiently with down regulation of serum ALT, AST, TBIL, DBIL. Meanwhile, there were no obvious adverse events. Conclusion. As a promising novel treatment approach, widely using large dosage of Chishao in formulae may enhance the curative efficacy for cholestatic hepatitis. Considering being accepted by more and more practitioners, further rigorously designed clinical studies are required.
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Pathway analysis with next-generation sequencing data.
Eur. J. Hum. Genet.
PUBLISHED: 03-29-2014
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Although pathway analysis methods have been developed and successfully applied to association studies of common variants, the statistical methods for pathway-based association analysis of rare variants have not been well developed. Many investigators observed highly inflated false-positive rates and low power in pathway-based tests of association of rare variants. The inflated false-positive rates and low true-positive rates of the current methods are mainly due to their lack of ability to account for gametic phase disequilibrium. To overcome these serious limitations, we develop a novel statistic that is based on the smoothed functional principal component analysis (SFPCA) for pathway association tests with next-generation sequencing data. The developed statistic has the ability to capture position-level variant information and account for gametic phase disequilibrium. By intensive simulations, we demonstrate that the SFPCA-based statistic for testing pathway association with either rare or common or both rare and common variants has the correct type 1 error rates. Also the power of the SFPCA-based statistic and 22 additional existing statistics are evaluated. We found that the SFPCA-based statistic has a much higher power than other existing statistics in all the scenarios considered. To further evaluate its performance, the SFPCA-based statistic is applied to pathway analysis of exome sequencing data in the early-onset myocardial infarction (EOMI) project. We identify three pathways significantly associated with EOMI after the Bonferroni correction. In addition, our preliminary results show that the SFPCA-based statistic has much smaller P-values to identify pathway association than other existing methods.European Journal of Human Genetics advance online publication, 2 July 2014; doi:10.1038/ejhg.2014.121.
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Screening for voltage-gated sodium channel interacting peptides.
Sci Rep
PUBLISHED: 03-18-2014
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The voltage-gated sodium channel (VGSC) interacting peptide is of special interest for both basic research and pharmaceutical purposes. In this study, we established a yeast-two-hybrid based strategy to detect the interaction(s) between neurotoxic peptide and the extracellular region of VGSC. Using a previously reported neurotoxin JZTX-III as a model molecule, we demonstrated that the interactions between JZTX-III and the extracellular regions of its target hNav1.5 are detectable and the detected interactions are directly related to its activity. We further applied this strategy to the screening of VGSC interacting peptides. Using the extracellular region of hNav1.5 as the bait, we identified a novel sodium channel inhibitor SSCM-1 from a random peptide library. This peptide selectively inhibits hNav1.5 currents in the whole-cell patch clamp assays. This strategy might be used for the large scale screening for target-specific interacting peptides of VGSCs or other ion channels.
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[Overexpression of mouse IRF8 inhibits the differentiation of RAW264.7 cells into osteoclast-like cells].
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi
PUBLISHED: 03-11-2014
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To construct and identify recombinant adenovirus Ad-IRF8 carrying mouse interferon regulatory factor-8 (IRF8) and observe the influence of the over-expressed IRF8 on the differentiation of osteoclast precursor cells (RAW264.7) induced by soluble receptor activator of nuclear factor ?B ligand (sRANKL).
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A high-grain diet alters the omasal epithelial structure and expression of tight junction proteins in a goat model.
Vet. J.
PUBLISHED: 03-09-2014
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The omasal epithelial barrier plays important roles in maintaining nutrient absorption and immune homeostasis in ruminants. However, little information is currently available about the changes in omasal epithelial barrier function at the structural and molecular levels during feeding of a high-grain (HG) diet. Ten male goats were randomly assigned to two groups, fed either a hay diet (0% grain; n?=?5) or HG diet (65% grain; n?=?5). Changes in omasal epithelial structure and expression of tight junction (TJ) proteins were determined via electron microscopy and Western blot analysis. After 7 weeks on each diet, omasal contents in the HG group showed significantly lower pH (P?<0.001) and significantly higher concentrations of free lipopolysaccharides (LPS; P?=?0.001) than the hay group. The goats fed a HG diet showed profound alterations in omasal epithelial structure and TJ proteins, corresponding to depression of thickness of total epithelia, stratum granulosum, and the sum of the stratum spinosum and stratum basale, marked epithelial cellular damage, erosion of intercellular junctions and down-regulation in expression of the TJ proteins, claudin-4 and occludin. The study demonstrates that feeding a HG diet is associated with omasal epithelial cellular damage and changes in expression of TJ proteins. These research findings provide an insight into the possible significance of diet on the omasal epithelial barrier in ruminants.
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Genetic variants in nicotinic acetylcholine receptor genes jointly contribute to kidney function in American Indians: the Strong Heart Family Study.
J. Hypertens.
PUBLISHED: 02-27-2014
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Cigarette smoking negatively affects kidney function. Genetic variants in the nicotinic acetylcholine receptor (nAChR) genes have been associated with nicotine dependence, and are likely to influence renal function and related traits. Whereas each single variant may only exert a small effect, the joint contribution of multiple variants to the risk of disease could be substantial.
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Full Genome Sequence of a Recombinant H1N2 Avian Influenza Virus Isolated from Wild Waterfowl in the East Dongting Lake Wetland.
Genome Announc
PUBLISHED: 02-22-2014
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Here, we report the full genome sequence of an H1N2 avian influenza virus (AIV) isolated from wild waterfowl in Dongting Lake. Phylogenetic analysis showed that it was a novel recombinant AIV between domestic ducks and wild waterfowl. Investigation of this virus is helpful for our understanding of the ecology of AIV in this region.
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Development of pathological diagnostics of human kidney cancer by multiple staining using new fluorescent Fluolid dyes.
Biomed Res Int
PUBLISHED: 02-16-2014
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New fluorescent Fluolid dyes have advantages over others such as stability against heat, dryness, and excess light. Here, we performed simultaneous immunostaining of renal tumors, clear cell renal cell carcinoma (RCC), papillary RCC, chromophobe RCC, acquired cystic disease-associated RCC (ACD-RCC), and renal angiomyolipoma (AML), with primary antibodies against Kank1, cytokeratin 7 (CK7), and CD10, which were detected with secondary antibodies labeled with Fluolid-Orange, Fluolid-Green, and Alexa Fluor 647, respectively. Kank1 was stained in normal renal tubules, papillary RCC, and ACD-RCC, and weakly or negatively in all other tumors. CK7 was positive in normal renal tubules, papillary RCC, and ACD-RCC. In contrast, CD10 was expressed in renal tubules and clear cell RCC, papillary RCC, AML, and AC-RCC, and weakly in chromophobe RCC. These results may contribute to differentiating renal tumors and subtypes of RCCs. We also examined the stability of fluorescence and found that fluorescent images of Fluolid dyes were identical between a tissue section and the same section after it was stored for almost three years at room temperature. This indicates that tissue sections can be stored at room temperature for a relatively long time after they are stained with multiple fluorescent markers, which could open a door for pathological diagnostics.
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Chimera states on complex networks.
Phys Rev E Stat Nonlin Soft Matter Phys
PUBLISHED: 02-14-2014
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The model of nonlocally coupled identical phase oscillators on complex networks is investigated. We find the existence of chimera states in which identical oscillators evolve into distinct coherent and incoherent groups. We find that the coherent group of chimera states always contains the same oscillators no matter what the initial conditions are. The properties of chimera states and their dependence on parameters are investigated on both scale-free networks and Erdös-Rényi networks.
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Efficient gene carriers composed of 2-hydroxypropyl-?-cyclodextrin, ethanolamine-functionalized poly(glycidyl methacrylate), and poly((2-dimethyl amino)ethyl methacrylate) by combination of ATRP and click chemistry.
Macromol Biosci
PUBLISHED: 01-31-2014
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In this work, a simple one-step method is first employed to produce the bromoisobutyryl-terminated 2-hydroxypropyl-?-cyclodextrin (HPCD-Br). The pendant epoxy groups of poly(glycidyl methacrylate) block prepared via ATRP from HPCD-Br can be reacted with ethanolamine to produce HPCD-PGEA which exhibits much lower cytotoxicity and better gene transfection yield than polyethylenimine (25?kDa) in COS7 and HepG2 cell lines. Moreover, poly((2-dimethyl amino)ethyl methacrylate) blocks can be incorporated into low-molecular-weight HPCD-PGEA via "click" reaction to further enhance the gene transfection efficiency in HepG2 cell lines.
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A histone methylation network regulates transgenerational epigenetic memory in C. elegans.
Cell Rep
PUBLISHED: 01-30-2014
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How epigenetic information is transmitted from generation to generation remains largely unknown. Deletion of the C. elegans histone H3 lysine 4 dimethyl (H3K4me2) demethylase spr-5 leads to inherited accumulation of the euchromatic H3K4me2 mark and progressive decline in fertility. Here, we identified multiple chromatin-modifying factors, including H3K4me1/me2 and H3K9me3 methyltransferases, an H3K9me3 demethylase, and an H3K9me reader, which either suppress or accelerate the progressive transgenerational phenotypes of spr-5 mutant worms. Our findings uncover a network of chromatin regulators that control the transgenerational flow of epigenetic information and suggest that the balance between euchromatic H3K4 and heterochromatic H3K9 methylation regulates transgenerational effects on fertility.
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Structure-based discovery of Middle East respiratory syndrome coronavirus fusion inhibitor.
Nat Commun
PUBLISHED: 01-30-2014
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A novel human coronavirus, Middle East respiratory syndrome coronavirus (MERS-CoV), has caused outbreaks of a SARS-like illness with high case fatality rate. The reports of its person-to-person transmission through close contacts have raised a global concern about its pandemic potential. Here we characterize the six-helix bundle fusion core structure of MERS-CoV spike protein S2 subunit by X-ray crystallography and biophysical analysis. We find that two peptides, HR1P and HR2P, spanning residues 998-1039 in HR1 and 1251-1286 in HR2 domains, respectively, can form a stable six-helix bundle fusion core structure, suggesting that MERS-CoV enters into the host cell mainly through membrane fusion mechanism. HR2P can effectively inhibit MERS-CoV replication and its spike protein-mediated cell-cell fusion. Introduction of hydrophilic residues into HR2P results in significant improvement of its stability, solubility and antiviral activity. Therefore, the HR2P analogues have good potential to be further developed into effective viral fusion inhibitors for treating MERS-CoV infection.
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[Therapeutic effect of sorafenib on portal hypertension: research progress and mechanisms].
Nan Fang Yi Ke Da Xue Xue Bao
PUBLISHED: 01-28-2014
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Portal hypertension, as one of the major complications of liver cirrhosis, is a common clinical syndrome characterized by an increased portal pressure and the formation of portal-systemic collaterals. Currently no ideal therapeutic agent has been available for portal hypertension. Sorafenib is an oral tyrosine kinase inhibitor that has been shown to significantly improve blood flow dynamics, inhibit angiogenesis, reduce liver fibrosis and decrease portal pressure in the treatment of portal hypertension. The authors review the progress in the research of sorafenib in the treatment of portal hypertension and the mechanisms of its actions.
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Reconstitution of a 10-gene pathway for synthesis of the plant alkaloid dihydrosanguinarine in Saccharomyces cerevisiae.
Nat Commun
PUBLISHED: 01-20-2014
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Benzylisoquinoline alkaloids (BIAs) represent a large class of plant secondary metabolites, including pharmaceuticals such as morphine, codeine and their derivatives. Large-scale production of BIA-based pharmaceuticals is limited to extraction and derivatization of alkaloids that accumulate in planta. Synthesis of BIAs in microbial hosts could bypass such limitations and transform both industrial production of BIAs with recognized value and research into uncharacterized BIAs. Here we reconstitute a 10-gene plant pathway in Saccharomyces cerevisiae that allows for the production of dihydrosanguinarine and its oxidized derivative sanguinarine from (R,S)-norlaudanosoline. Synthesis of dihydrosanguinarine also yields the side-products N-methylscoulerine and N-methylcheilanthifoline, the latter of which has not been detected in plants. This work represents the longest reconstituted alkaloid pathway ever assembled in yeast and demonstrates the feasibility of the production of high-value alkaloids in microbial systems.
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Raman enhancement by graphene-Ga2O3 2D bilayer film.
Nanoscale Res Lett
PUBLISHED: 01-19-2014
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2D ?-Ga2O3 flakes on a continuous 2D graphene film were prepared by a one-step chemical vapor deposition on liquid gallium surface. The composite was characterized by optical microscopy, scanning electron microscopy, Raman spectroscopy, energy dispersive spectroscopy, and X-ray photoelectron spectroscopy (XPS). The experimental results indicate that Ga2O3 flakes grew on the surface of graphene film during the cooling process. In particular, tenfold enhancement of graphene Raman scattering signal was detected on Ga2O3 flakes, and XPS indicates the C-O bonding between graphene and Ga2O3. The mechanism of Raman enhancement was discussed. The 2D Ga2O3-2D graphene structure may possess potential applications.
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Combined use of non-biological artificial liver treatments for patients with acute liver failure complicated by multiple organ dysfunction syndrome.
World J Emerg Med
PUBLISHED: 01-11-2014
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Acute liver failure (ALF) caused by viral and non-viral hepatitis is often accompanied with severe metabolic disorders, the accumulation of toxic substances and continuous release and accumulation of a large number of endogenous toxins and inflammatory mediators. The present study aimed to investigate the effects of various combined non-biological artificial liver treatments for patients with acute liver failure (ALF) complicated by multiple organ dysfunction syndrome (MODS).
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Alkaloids from the bulbs of Lycoris longituba and their neuroprotective and acetylcholinesterase inhibitory activities.
Arch. Pharm. Res.
PUBLISHED: 01-11-2014
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Three novel alkaloids (1-3), together with nineteen known ones (4-22), were isolated from the bulbs of Lycoris longituba. Their structures were elucidated on the basis of extensive spectroscopic analyses, which belong to several Amaryllidaceae alkaloid skeletons. Among them, the harmane-type alkaloids (the new compound 1 and the known compounds 5, 6 and 7) were found for the first time from Lycoris genus. The isolates were tested for their neuroprotective activities against CoCl2, H2O2 and A?25-35-induced SH-SY5Y cell injuries, and the majority of them exhibited neuroprotective activities of different degrees. The acetylcholinesterase (AChE) inhibitory activities of the isolated alkaloids were also evaluated, while compounds 12, 14-20 and 22 exhibited extremely significant AChE inhibitory activities.
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DNA microarray-based gene expression profiling of estrogenic chemicals.
Cell. Mol. Life Sci.
PUBLISHED: 01-08-2014
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We summarize updated information about DNA microarray-based gene expression profiling by focusing on its application to estrogenic chemicals. First, estrogenic chemicals, including natural/industrial estrogens and phytoestrogens, and the methods for detection and evaluation of estrogenic chemicals were overviewed along with a comprehensive list of estrogenic chemicals of natural or industrial origin. Second, gene expression profiling of chemicals using a focused microarray containing estrogen-responsive genes is summarized. Third, silent estrogens, a new type of estrogenic chemicals characterized by their estrogenic gene expression profiles without growth stimulative or inhibitory effects, have been identified so far exclusively by DNA microarray assay. Lastly, the prospect of a microarray assay is discussed, including issues such as commercialization, future directions of applications and quality control methods.
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Candida glabrata infection following total hip arthroplasty: A case report.
Exp Ther Med
PUBLISHED: 01-08-2014
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Candida glabrata infection following total hip arthroplasty is rare and, due to the insufficiency of standardized clinical and evidence-based guidelines, there is no appropriate therapeutic schedule. The present study reports the case of a 44-year-old patient with Candida glabrata infection following a total hip arthroplasty. The patient was successfully treated by administration of intravenous and oral voriconazole without removal of the prosthesis. This case illustrates the significance of postoperative follow-up, clinician experience and the choice of the correct antifungal agent. In this case, we found in the early stage of Candida glabrata infection, we were able to control the infection without surgery through thorough irrigation. This reduces patient suffering and economic burden.
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Phylogenetic and antigenic characterization of reassortant H9N2 avian influenza viruses isolated from wild waterfowl in the East Dongting Lake wetland in 2011-2012.
Virol. J.
PUBLISHED: 01-07-2014
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Wild waterfowl are recognized as the natural reservoir for influenza A viruses. Two distinct lineages, the American and Eurasian lineages, have been identified in wild birds. Gene flow between the two lineages is limited. The H9N2 virus has become prevalent in poultry throughout Eurasia, and mainly circulates in wild ducks and shorebirds in North America.
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Joint association of nicotinic acetylcholine receptor variants with abdominal obesity in American Indians: the Strong Heart Family Study.
PLoS ONE
PUBLISHED: 01-01-2014
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Cigarette smoke is a strong risk factor for obesity and cardiovascular disease. The effect of genetic variants involved in nicotine metabolism on obesity or body composition has not been well studied. Though many genetic variants have previously been associated with adiposity or body fat distribution, a single variant usually confers a minimal individual risk. The goal of this study is to evaluate the joint association of multiple variants involved in cigarette smoke or nicotine dependence with obesity-related phenotypes in American Indians. To achieve this goal, we genotyped 61 tagSNPs in seven genes encoding nicotine acetylcholine receptors (nAChRs) in 3,665 American Indians participating in the Strong Heart Family Study. Single SNP association with obesity-related traits was tested using family-based association, adjusting for traditional risk factors including smoking. Joint association of all SNPs in the seven nAChRs genes were examined by gene-family analysis based on weighted truncated product method (TPM). Multiple testing was controlled by false discovery rate (FDR). Results demonstrate that multiple SNPs showed weak individual association with one or more measures of obesity, but none survived correction for multiple testing. However, gene-family analysis revealed significant associations with waist circumference (p?=?0.0001) and waist-to-hip ratio (p?=?0.0001), but not body mass index (p?=?0.20) and percent body fat (p?=?0.29), indicating that genetic variants are jointly associated with abdominal, but not general, obesity among American Indians. The observed combined genetic effect is independent of cigarette smoking per se. In conclusion, multiple variants in the nAChR gene family are jointly associated with abdominal obesity in American Indians, independent of general obesity and cigarette smoking per se.
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Investigation of avian influenza infections in wild birds, poultry and humans in Eastern Dongting Lake, China.
PLoS ONE
PUBLISHED: 01-01-2014
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We investigated avian influenza infections in wild birds, poultry, and humans at Eastern Dongting Lake, China. We analyzed 6,621 environmental samples, including fresh fecal and water samples, from wild birds and domestic ducks that were collected from the Eastern Dongting Lake area from November 2011 to April 2012. We also conducted two cross-sectional serological studies in November 2011 and April 2012, with 1,050 serum samples collected from people exposed to wild birds and/or domestic ducks. Environmental samples were tested for the presence of avian influenza virus (AIV) using quantitative PCR assays and virus isolation techniques. Hemagglutination inhibition assays were used to detect antibodies against AIV H5N1, and microneutralization assays were used to confirm these results. Among the environmental samples from wild birds and domestic ducks, AIV prevalence was 5.19 and 5.32%, respectively. We isolated 39 and 5 AIVs from the fecal samples of wild birds and domestic ducks, respectively. Our analysis indicated 12 subtypes of AIV were present, suggesting that wild birds in the Eastern Dongting Lake area carried a diverse array of AIVs with low pathogenicity. We were unable to detect any antibodies against AIV H5N1 in humans, suggesting that human infection with H5N1 was rare in this region.
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A combination of serological assays to detect human antibodies to the avian influenza A H7N9 virus.
PLoS ONE
PUBLISHED: 01-01-2014
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Human infection with avian influenza A H7N9 virus was first identified in March 2013 and represents an ongoing threat to public health. There is a need to optimize serological methods for this new influenza virus. Here, we compared the sensitivity and specificity of the hemagglutinin inhibition (HI), microneutralization (MN), and Western blot (WB) assays for the detection of human antibodies against avian influenza A (H7N9) virus. HI with horse erythrocytes (hRBCs) and a modified MN assay possessed greater sensitivity than turkey erythrocytes and the standard MN assay, respectively. Using these assays, 80% of tested sera from confirmed H7N9 cases developed detectable antibody to H7N9 after 21 days. To balance sensitivity and specificity, we found serum titers of ?20 (MN) or 160 (HI) samples were most effective in determining seropositive to H7N9 virus. Single serum with HI titers of 20-80 or MN titer of 10 could be validated by each other or WB assay. Unlike serum collected from adult or elderly populations, the antibody response in children with mild disease was low or undetectable. These combinations of assays will be useful in case diagnosis and serologic investigation of human cases.
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Cyclin D1 overexpression is associated with poor clinicopathological outcome and survival in oral squamous cell carcinoma in Asian populations: insights from a meta-analysis.
PLoS ONE
PUBLISHED: 01-01-2014
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The clinicopathological significance of cyclin D1 overexpression and prognosis of oral squamous cell carcinoma has not been fully quantified. We performed a comprehensive meta-analysis for evaluation of cyclin D1 overexpression in oral squamous cell carcinoma to determine the strength of this association.
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A conformational restriction in influenza A virus neuraminidase binding site by R152 caused the combinational effect of I222T with H274Y on oseltamivir resistance.
Antimicrob. Agents Chemother.
PUBLISHED: 12-23-2013
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The I222K, I222R and I222T substitutions in neuraminidase (NA) were currently found in clinically-derived 2009 pandemic H1N1 viruses with altered susceptibilities to NA inhibitors (NAIs). The effects of these substitutions together with the most frequently observed resistance related substitution, H274Y, on viral fitness and resistance mechanism were further investigated in this study. Reduced sensitivities to oseltamivir were observed in all three mutants. Furthermore, I222K and I222T substitutions had combinational effect of further increasing resistance in the presence of H274Y, which might result from a conformational restriction in NA binding-site. Especially, by using the molecular dynamics simulation, R152, the neighbor of T222, was observed to translate to a closer position to T222 and resulted in the narrowing down of binding pocket, which just subtended the residue substitution of H274Y. Moreover, significantly attenuated NA function and viral growth abilities were found in I222K+H274Y mutant, while I222T+H274Y mutant exhibited a slightly delayed growth but with similar peak viral titer as that of wild-type virus in MDCK cells. Relatively growth advantage of I222T mutant versus I222K and higher frequency of I222T emerging in N1 subtype influenza viruses raised the concerns to closely monitoring the dual substitutions of I222T and H274Y.
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Two new alkaloids from the bulbs of Lycoris sprengeri.
J Asian Nat Prod Res
PUBLISHED: 12-06-2013
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Two new alkaloids, lycosprenine (1) and 2?-methoxy-6-O-methyllycorenine (2), along with 22 known alkaloids (3-23b), were isolated from the bulb of Lycoris sprengeri. Their structures were elucidated on the basis of spectral analysis and by comparison of the spectroscopic data with those of known compounds. Selected compounds (1-3 and 6-9) were tested for their neuroprotective activities against H2O2-, CoCl2- and A?25-35-induced SH-SY5Y cell injury, most of which exhibited neuroprotective effects of different degrees.
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[Comparative study on pharmacokinetics of gentiopicroside and gentianae radix extract in rats].
Zhong Yao Cai
PUBLISHED: 11-14-2013
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To compare the pharmacokinetics of gentiopicroside and Gentianae Radix extract in rats and assess the effect of other components in Gentianae Radix on the pharmacokinetics of gentiopicroside.
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Complete Genome Sequence of an H12N8 Avian Influenza Virus Isolated from Wild Bird Feces in Hunan East Dongting Lake National Nature Reserve.
Genome Announc
PUBLISHED: 10-26-2013
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An H12N8 subtype avian influenza virus (AIV) was isolated from a wild bird in China in 2011. It is the first report of isolation of the H12N8 subtype AIV in Asia. Phylogenetic analysis results suggested it is a reassortant, and all eight gene segments belong to the Eurasian gene pool.
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Dietary N-nitroso compounds and risk of colorectal cancer: a case-control study in Newfoundland and Labrador and Ontario, Canada.
Br. J. Nutr.
PUBLISHED: 10-25-2013
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Several N-nitroso compounds (NOC) have been shown to be carcinogenic in a variety of laboratory animals, but evidence of their carcinogenicity in humans is lacking. We aimed to examine the association between NOC intake and colorectal cancer (CRC) risk and possible effect modification by vitamins C and E and protein in a large case-control study carried out in Newfoundland and Labrador and Ontario, Canada. A total of 1760 case patients with pathologically confirmed adenocarcinoma and 2481 population controls were asked to complete a self-administered FFQ to evaluate their dietary intakes 1 year before diagnosis (for cases) or interview (for controls). Adjusted OR and 95 % CI were calculated across the quintiles of NOC (measured by N-nitrosodimethylamine (NDMA)) intake and relevant food items using unconditional logistic regression. NDMA intake was found to be associated with a higher risk of CRC (highest v. lowest quintiles: OR 1·42, 95 % CI 1·03, 1·96; P for trend = 0·005), specifically for rectal carcinoma (OR 1·61, 95 % CI 1·11, 2·35; P for trend = 0·01). CRC risk also increased with the consumption of NDMA-containing meats when the highest tertile was compared with the lowest tertile (OR 1·47, 95 % CI 1·03, 2·10; P for trend = 0·20). There was evidence of effect modification between dietary vitamin E and NDMA. Individuals with high NDMA and low vitamin E intakes had a significantly increased risk than those with both low NDMA and low vitamin E intakes (OR 3·01, 95 % CI 1·43, 6·51; P for interaction = 0·017). The present results support the hypothesis that NOC intake may be positively associated with CRC risk in humans. Vitamin E, which inhibits nitrosation, could modify the effect of NDMA on CRC risk.
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miR-138 protects cardiomyocytes from hypoxia-induced apoptosis via MLK3/JNK/c-jun pathway.
Biochem. Biophys. Res. Commun.
PUBLISHED: 10-22-2013
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Cardiomyocytes experience a series of complex endogenous regulatory mechanisms against apoptosis induced by chronic hypoxia. MicroRNAs are a class of endogenous small non-coding RNAs that regulate cellular pathophysiological processes. Recently, microRNA-138 (miR-138) has been found related to hypoxia, and beneficial for cell proliferation. Therefore, we intend to study the role of miR-138 in hypoxic cardiomyocytes and the main mechanism. Myocardial samples of patients with congenital heart disease (CHD) were collected to test miR-138 expression. Agomir or antagomir of miR-138 was transfected into H9C2 cells to investigate its effect on cell apoptosis. Higher miR-138 expression was observed in patients with cyanotic CHD, and its expression gradually increased with prolonged hypoxia time in H9C2 cells. Using MTT and LDH assays, cell growth was significantly greater in the agomir group than in the negative control (NC) group, while antagomir decreased cell survival. Dual luciferase reporter gene and Western-blot results confirmed MLK3 was a direct target of miR-138. It was found that miR-138 attenuated hypoxia-induced apoptosis using TUNEL, Hoechst staining and Annexin V-PE/7-AAD flow cytometry analysis. We further detected expression of apoptosis-related proteins. In the agomir group, the level of pro-apoptotic proteins such as cleaved-caspase-3, cleaved-PARP and Bad significantly reduced, while Bcl-2 and Bcl-2/Bax ratio increased. Opposite changes were observed in the antagomir group. Downstream targets of MLK3, JNK and c-jun, were also suppressed by miR-138. Our study demonstrates that up-regulation of miR-138 plays a protective role in myocardial adaptation to chronic hypoxia, which is mediated mainly by MLK3/JNK/c-jun signaling pathway.
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[Hepatitis B virus X promotes HepG2 cell cycle progression and growth via downregulation expression of p16 protein].
Zhonghua Gan Zang Bing Za Zhi
PUBLISHED: 10-15-2013
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To investigate the effects and related mechanisms of hepatitis B virus X (HBx) protein on cell cycle and growth in hepatocellular carcinoma.
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STAR: an integrated solution to management and visualization of sequencing data.
Bioinformatics
PUBLISHED: 09-27-2013
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Easily visualization of complex data features is a necessary step to conduct studies on next-generation sequencing (NGS) data. We developed STAR, an integrated web application that enables online management, visualization and track-based analysis of NGS data.
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Evolution after whole-genome duplication: a network perspective.
G3 (Bethesda)
PUBLISHED: 09-20-2013
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Gene duplication plays an important role in the evolution of genomes and interactomes. Elucidating how evolution after gene duplication interplays at the sequence and network level is of great interest. In this work, we analyze a data set of gene pairs that arose through whole-genome duplication (WGD) in yeast. All these pairs have the same duplication time, making them ideal for evolutionary investigation. We investigated the interplay between evolution after WGD at the sequence and network levels and correlated these two levels of divergence with gene expression and fitness data. We find that molecular interactions involving WGD genes evolve at rates that are three orders of magnitude slower than the rates of evolution of the corresponding sequences. Furthermore, we find that divergence of WGD pairs correlates strongly with gene expression and fitness data. Because of the role of gene duplication in determining redundancy in biological systems and particularly at the network level, we investigated the role of interaction networks in elucidating the evolutionary fate of duplicated genes. We find that gene neighborhoods in interaction networks provide a mechanism for inferring these fates, and we developed an algorithm for achieving this task. Further epistasis analysis of WGD pairs categorized by their inferred evolutionary fates demonstrated the utility of these techniques. Finally, we find that WGD pairs and other pairs of paralogous genes of small-scale duplication origin share similar properties, giving good support for generalizing our results from WGD pairs to evolution after gene duplication in general.
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QTL mapping of leukocyte telomere length in American Indians: the Strong Heart Family Study.
Aging (Albany NY)
PUBLISHED: 09-17-2013
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Telomeres play a central role in cellular senescence and are associated with a variety of age-related disorders such as dementia, Alzheimers disease and atherosclerosis. Telomere length varies greatly among individuals of the same age, and is heritable. Here we performed a genome-wide linkage scan to identify quantitative trait loci (QTL) influencing leukocyte telomere length (LTL) measured by quantitative PCR in 3,665 American Indians (aged 14-93 years) from 94 large, multi-generational families. All participants were recruited by the Strong Heart Family Study (SHFS), a prospective study to identify genetic factors for cardiovascular disease and its risk factors in American Indians residing in Oklahoma, Arizona and Dakota. LTL heritability was estimated to be between 51% and 62%, suggesting a strong genetic predisposition to interindividual variation of LTL in this population. Significant QTLs were localized to chromosome 13 (Logarithm of odds score (LOD)=3.9) at 13q12.11, to 18q22.2 (LOD=3.2) and to 3p14.1 (LOD=3.0) for Oklahoma. This is the first study to identify susceptibility loci influencing leukocyte telomere variation in American Indians, a minority group suffering from a disproportionately high rate of type 2 diabetes and other age-related disorders.
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Predicting enhancer transcription and activity from chromatin modifications.
Nucleic Acids Res.
PUBLISHED: 09-12-2013
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Enhancers play a pivotal role in regulating the transcription of distal genes. Although certain chromatin features, such as the histone acetyltransferase P300 and the histone modification H3K4me1, indicate the presence of enhancers, only a fraction of enhancers are functionally active. Individual chromatin marks, such as H3K27ac and H3K27me3, have been identified to distinguish active from inactive enhancers. However, the systematic identification of the most informative single modification, or combination thereof, is still lacking. Furthermore, the discovery of enhancer RNAs (eRNAs) provides an alternative approach to directly predicting enhancer activity. However, it remains challenging to link chromatin modifications to eRNA transcription. Herein, we develop a logistic regression model to unravel the relationship between chromatin modifications and eRNA synthesis. We perform a systematic assessment of 24 chromatin modifications in fetal lung fibroblast and demonstrate that a combination of four modifications is sufficient to accurately predict eRNA transcription. Furthermore, we compare the ability of eRNAs and H3K27ac to discriminate enhancer activity. We demonstrate that eRNA is more indicative of enhancer activity. Finally, we apply our fibroblast trained model to six other cell-types and successfully predict eRNA synthesis. Thus, we demonstrate the learned relationships are general and independent of cell-type. We provided a powerful tool to identify active enhancers and reveal the relationship between chromatin modifications, eRNA production and enhancer activity.
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[Effects of different stimulatory factors on functions of CIK cells].
Zhongguo Shi Yan Xue Ye Xue Za Zhi
PUBLISHED: 09-04-2013
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This study was aimed to investigate the effects of different stimulatory factors on proliferation and function of cytokine induced killer (CIK) cells.Peripheral blood mononuclear cells (PBMNC) were separated by Ficoll-Hypacue gradient. According to supplement of different stimulatory factors (CD28 mAb,IL-15 and IL-21), the experiment was divided into five groups:control group (CIK), CB28+IL-15+IL-21 group, IL-15+IL-21 group, CD28+IL-15 group and CD28+IL-21 group.Effects of different stimulatory factors on the proliferation of CIK cells were assayed by an automated hematology analyzer.Changes of granzyme B,perforin and CD107a were detected by flow cytometry. IL-10, IL-12, INF-? and TNF-? were quantified by ELISA. Cytotoxicities on lung cancer cell line A549, breast adenocarcinoma cell line MFC-7 and human melanoma cell line HME1 were examined by lactate dehydrogenase release method.The results showed that there were significant differences among different groups. The highest proliferation index on days 10 was observed in group CD28mAb, IL-15 and IL-21(255.3 ± 6.3), which was higher than control group, IL-21+IL-15 group and CD28 mAb+IL-21 group (166.6 ± 13.5, 199.4 ± 15.0 and 228.8 ± 16.6) (P < 0.05). The expression of perforin in CD28 mAb+IL-15 group was higher than the other groups. The expression of perforin,GranB and CD107a of costimulatory groups was higher than control group. The cytotoxicities of CD28 mAb+IL-15 group on A549, MFC-7 and HME1 cells (82.2%, 59.3% and 70.6%) were much higher than that of control group (60.9%, 49.6% and 48.4%) (P < 0.05). The highest IFN-?secretion was found in CD28 mAb, IL-15 and IL-21 groups. It is concluded that there are significant difference of proliferative capacity, cytokine secretion and cytotoxicity after being activated by different stimulatory factors. Adding corresponding stimulatory factors into the culture system displays a great value for target cells culture.
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Imbalance of interleukin-17-producing CD4 T cells/regulatory T cells axis occurs in remission stage of patients with hepatitis B virus-related acute-on-chronic liver failure.
J. Gastroenterol. Hepatol.
PUBLISHED: 08-27-2013
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Although regulatory T cells (Treg) and interleukin-17-producing CD4 T cells (Th17) have been demonstrated to play opposing roles in inflammation-associated diseases, their frequency and balance in different stages of hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF) remain unknown.
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Short leukocyte telomere length predicts risk of diabetes in american indians: the strong heart family study.
Diabetes
PUBLISHED: 08-15-2013
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Telomeres play a central role in cellular aging, and shorter telomere length has been associated with age-related disorders including diabetes. However, a causal link between telomere shortening and diabetes risk has not been established. In a well-characterized longitudinal cohort of American Indians participating in the Strong Heart Family Study, we examined whether leukocyte telomere length (LTL) at baseline predicts incident diabetes independent of known diabetes risk factors. Among 2,328 participants free of diabetes at baseline, 292 subjects developed diabetes during an average 5.5 years of follow-up. Compared with subjects in the highest quartile (longest) of LTL, those in the lowest quartile (shortest) had an almost twofold increased risk of incident diabetes (hazard ratio [HR] 1.83 [95% CI 1.26-2.66]), whereas the risk for those in the second (HR 0.87 [95% CI 0.59-1.29]) and the third (HR 0.95 [95% CI 0.65-1.38]) quartiles was statistically nonsignificant. These findings suggest a nonlinear association between LTL and incident diabetes and indicate that LTL could serve as a predictive marker for diabetes development in American Indians, who suffer from disproportionately high rates of diabetes.
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[A review of H7 subtype avian influenza virus].
Bing Du Xue Bao
PUBLISHED: 08-03-2013
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Since 2002, H7 subtype avian influenza viruses (AIVs) have caused more than 100 human infection cases in the Netherlands, Italy, Canada, the United States, and the United Kingdom, with clinical illness ranging from conjunctivitis to mild upper respiratory illness to pneumonia. On March 31st, three fatal cases caused by infection of a novel reassortant H7N9 subtype were reported in Shanghai City and Anhui Province in China. With the ability of H7 subtype to cause severe human disease and the increasing isolation of subtype H7 AIVs, we highlighted the need for continuous surveillance in both humans and animals and characterization of these viruses for the development of vaccines and anti-viral drugs.
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[Blejiajian pill inhibited the proliferation, adhesion, and invasion of hepatoma carcinoma cells: an experimental research].
Zhongguo Zhong Xi Yi Jie He Za Zhi
PUBLISHED: 08-03-2013
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To investigate effects of biejiajian pill (BP) on the proliferation, adhesion, and invasion of hepatoma carcinoma cells (HepG2), and to primarily explore the mechanisms for fighting against metastasis and invasion.
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A novel reassortant H3N8 influenza virus isolated from drinking water for duck in a domestic duck farm in Poyang Lake area.
Biomed. Environ. Sci.
PUBLISHED: 07-31-2013
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To conduct a full genome sequence analysis for genetic characterization of an H3N8 influenza virus isolated from drinking water of a domestic duck farm in Poyang Lake area in 2011.
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The pluripotent genome in three dimensions is shaped around pluripotency factors.
Nature
PUBLISHED: 06-26-2013
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It is becoming increasingly clear that the shape of the genome importantly influences transcription regulation. Pluripotent stem cells such as embryonic stem cells were recently shown to organize their chromosomes into topological domains that are largely invariant between cell types. Here we combine chromatin conformation capture technologies with chromatin factor binding data to demonstrate that inactive chromatin is unusually disorganized in pluripotent stem-cell nuclei. We show that gene promoters engage in contacts between topological domains in a largely tissue-independent manner, whereas enhancers have a more tissue-restricted interaction profile. Notably, genomic clusters of pluripotency factor binding sites find each other very efficiently, in a manner that is strictly pluripotent-stem-cell-specific, dependent on the presence of Oct4 and Nanog protein and inducible after artificial recruitment of Nanog to a selected chromosomal site. We conclude that pluripotent stem cells have a unique higher-order genome structure shaped by pluripotency factors. We speculate that this interactome enhances the robustness of the pluripotent state.
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A high-grain diet causes massive disruption of ruminal epithelial tight junctions in goats.
Am. J. Physiol. Regul. Integr. Comp. Physiol.
PUBLISHED: 06-05-2013
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Alterations in rumen epithelial tight junctions (TJs) at the tissue and molecular levels during high-grain (HG) diet feeding are unknown. Here, 10 male goats were randomly assigned to either a hay diet (0% grain; n = 5) or HG diet group (65% grain; n = 5) to characterize the changes in ruminal epithelial structure and TJ protein expression and localization using scanning and transmission electron microscopy, quantitative real-time PCR, Western blot analysis, and immunofluorescence. After 7 wk of feeding, ruminal free LPS in HG group increased significantly (P < 0.001) compared with the hay group, and free LPS in the peripheral blood was detectable with concentrations of 0.8 ± 0.20 EU/ml, while not detectable in the control, suggesting a leakage of LPS into the blood in the HG group. Correspondingly, the HG-fed goats showed profound alterations in ruminal epithelial structure and TJ proteins, depicted by marked epithelial cellular damage and intercellular junction erosion, down-regulation of TJ proteins claudin-4, occludin, and zonula occludens-1 mRNA and protein expression, as well as redistribution of claudin-1, claudin-4, and occludin. Furthermore, these changes in TJ proteins in the HG group were coupled with the upregulation of mRNA levels for the cytokines TNF-? and IFN-? in the ruminal epithelia. These results demonstrated for the first time that the HG diet feeding caused disruption of ruminal epithelial TJs that was associated with a local inflammatory response in the rumen epithelium. These findings may provide new insights into understanding the role of TJ proteins in the ruminal epithelial immune homeostasis of ruminants.
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Continuous graphene films synthesized at low temperatures by introducing coronene as nucleation seeds.
Nanoscale
PUBLISHED: 05-14-2013
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In this paper, we systematically studied the effects of coronene as nucleation seeds for graphene synthesis at low temperatures by chemical vapor deposition. Naphthalene was used as a solid carbon source which is capable of producing graphene at temperatures down to 300 °C. The experimental results showed clear evidence that coronene seeds work as preferred nucleation sites, through which the nucleation density and graphene domain size could be modulated. The introduction of the seeds greatly improved the homogeneity of monolayer graphene by suppressing uncontrolled nucleation and multilayer growth of graphene domains. The obtained carrier mobility of graphene fabricated at 400 °C by the seed-assisted process reached ~912 cm(2) V(-1) s(-1), which is considerably higher than that of ~300 cm(2) V(-1) s(-1) measured on graphene prepared without seeding. Besides offering cost advantages for large scale application, the technique proposed in this study may find significant applications in graphene/copper hybrid interconnects and graphene based flexible electronics.
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Human infection with a novel avian-origin influenza A (H7N9) virus.
N. Engl. J. Med.
PUBLISHED: 04-11-2013
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Infection of poultry with influenza A subtype H7 viruses occurs worldwide, but the introduction of this subtype to humans in Asia has not been observed previously. In March 2013, three urban residents of Shanghai or Anhui, China, presented with rapidly progressing lower respiratory tract infections and were found to be infected with a novel reassortant avian-origin influenza A (H7N9) virus.
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Pegylated filgrastim is comparable with filgrastim as support for commonly used chemotherapy regimens: a multicenter, randomized, crossover phase 3 study.
Anticancer Drugs
PUBLISHED: 04-11-2013
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The purpose of this study was to compare the efficacy and safety of a single subcutaneous injection of pegylated filgrastim with daily filgrastim as a prophylaxis for neutropenia induced by commonly used chemotherapy regimens. Fifteen centers enrolled 337 chemotherapy-naive cancer patients with normal bone marrow function. All patients randomized into AOB and BOA arms received two cycles of chemotherapy. Patients received a single dose of pegylated filgrastim 100 µg/kg in cycle 1 (AOB) or cycle 2 (BOA) and daily doses of filgrastim 5 µg/kg/day in cycle 1 (BOA) or cycle 2 (AOB). Efficacy and safety parameters were recorded. The primary end point was the rate of protection against grade 4 neutropenia after chemotherapy [defined as the rate at which the absolute neutrophil count (ANC) remained >0.5×10(9)/l throughout the entire cycle]. Ninety-four percent of patients receiving pegylated filgrastim or filgrastim did not develop grade 4 neutropenia. The incidence of ANC<1.0×10(9)/l was 16.0% (50/313) after support with either pegylated filgrastim or filgrastim. The incidences of febrile neutropenia and antibiotic administration were similar in both groups. Notably, faster ANC recovery was observed with pegylated filgrastim support. The ANC nadir was also earlier with pegylated filgrastim (day 7) support than with filgrastim support (day 9), although the depth of nadir was not significantly different. A single subcutaneous injection of pegylated filgrastim 100 ?g/kg provided adequate and safe neutrophil support comparable with daily subcutaneous injections of unmodified filgrastim 5 ?g/kg/day in patients receiving commonly used standard-dose mild-to-moderate myelosuppressive chemotherapy regimens.
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Direct growth of graphene film on germanium substrate.
Sci Rep
PUBLISHED: 04-10-2013
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Graphene has been predicted to play a role in post-silicon electronics due to the extraordinary carrier mobility. Chemical vapor deposition of graphene on transition metals has been considered as a major step towards commercial realization of graphene. However, fabrication based on transition metals involves an inevitable transfer step which can be as complicated as the deposition of graphene itself. By ambient-pressure chemical vapor deposition, we demonstrate large-scale and uniform depositon of high-quality graphene directly on a Ge substrate which is wafer scale and has been considered to replace conventional Si for the next generation of high-performance metal-oxide-semiconductor field-effect transistors (MOSFETs). The immiscible Ge-C system under equilibrium conditions dictates graphene depositon on Ge via a self-limiting and surface-mediated process rather than a precipitation process as observed from other metals with high carbon solubility. Our technique is compatible with modern microelectronics technology thus allowing integration with high-volume production of complementary metal-oxide-semiconductors (CMOS).
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